The Netter Collection of Medical Illustrations VOLUME 7 PART l

P late 8-1 Brain: PART I

Posterior view Habenular trigone
3rd ventricle
Pulvinar Lateral Geniculate bodies
of thalamus Medial

Pineal body Dorsal median sulcus
Superior colliculus Superior cerebellar peduncle
Locus caeruleus
Inferior colliculus Medial eminence
Trochlear nerve (IV) Facial colliculus
Vestibular area
Superior medullary velum

Cerebellum and the Cerebellar Superior
Fourth Ventricle peduncles Middle
Inferior
The fourth ventricle lies posterior to the pons and
upper half of the medulla oblongata and anterior to Lateral recess Lateral funiculus Dentate nucleus
the cerebÂ

Plate 8-2 Cerebellum and Ataxia

Cerebellum Gross Anatomy Superior vermis Superior surface Anterior lobe
Lobule III (Central) Anterior cerebellar notch
The cerebellum, from the Latin meaning little brain, is Lobule IV-V (Quadrangular)
the largest part of the hindbrain occupying most of the Preculminate fissure Primary fissure
posterior fossa. In the adult human brain, the cerebel­ Horizontal fissure
lum’s volume is about 144 cm3, weighing 150 grams Lobules IV-V (Culmen) Posterior lobe
(10% total brain weight). However, its surface area is Intraculminate fissure
40% of the cerebral cortex, containing half the total
number of intracerebral neurons. The cerebellum, con­ Paravermian sulcus Lobule VI (Simple)
sisting of two hemispheres situated contiguously with the Primary fissure Superior
midline vermis, is separated from the overlying cere­ Lobule VI (Declive) posterior
brum by the tentorium cerebelli. The vermis (i.e., from fissure
the Latin, meaning worm) is visible posteriorly and Lobule VIIAf (Folium)
inferiorly in the vallecula, the deep groove separating Lobule VIIA Crus I
the two cerebellar hemispheres. Superiorly, in contrast, (Superior semilunar)
the vermis appears as a low ridge straddling the midline,
extending up 10╯mm bilaterally. Horizontal fissure

A wide hollow within the anterior cerebellum is Superior vermis Posterior cerebellar notch Lobule VIIA Crus II
occupied by the pons and upper medulla oblongata, Lobule III (Central) Inferior surface (Inferior semilunar)
which are separated from the cerebellum by the fourth Anterior lobe
ventricle. Posteriorly, there is a narrow median notch, Lobules I-II (Lingula)
lodging the falx cerebelli. The cerebellum is connected Lobules III, IV, V
to the brainstem by three white matter tracts: the supe­ 4th ventricle Sup Med Cerebellar peduncles
rior, middle, and inferior cerebellar peduncles (described Inf
more fully in Plate 8-3). The cerebellum’s superior and Inferior vermis Flocculonodular lobe
inferior surfaces meet within the caudal aspect of lobule Lobule X (Nodule) Lobule X (Flocculus)
crus I. The cerebellum forms a sphere, and therefore Posterolateral
the vermal lobule I/II is separated anteriorly from Lobule IX (Uvula) fissure
lobule X by the fourth ventricle. Secondary fissure Posterior lobe
Lobule IX (Tonsil)
The cerebellum surfaces include numerous narrow folia
separated by parallel, curved, deeply penetrating fis­ Lobule VIII Lobule VIIIA-B
sures. Each folium further consists of multiple, small (Pyramid) (Biventer)
subfolia. The folia are grouped into ten lobules divided
by named fissures. These ten lobules form three lobes: Lobule VIIAt-VIIB Posterior cerebellar notch Horizontal fissure
the anterior, posterior, and flocculonodular lobes. Lobules I to (Tuber) Lobule VIIB
V are the anterior lobe, lobules VI to IX are the posterior (Inferior semilunar)
lobe, and lobule X is the flocculonodular lobe, including the Prepyramidal
flocculus, which is a small, semidetached portion lying fissure Ansoparamedian fissure
close to the middle cerebellar peduncle. Earlier cerebel­ Lobule VIIA Crus II
lum nomenclatures were not uniform (one version is in Decussation of (Inferior semilunar)
the diagrams for comparison). These are replaced by superior cerebellar peduncles
a simplified, coherent numeric system existing across Cerebral peduncle
different species’ brains. All lobules are identifiable at Cerebellar nuclei 4th ventricle
the vermis; lobules III to X are continuous across the Fastigial Superior cerebellar peduncle
hemispheres.
Globose Lobule I (Lingula)
The primary fissure separating the anterior from the Emboliform
posterior lobe is deepest and most evident in the mid­ Dentate Hilum of
sagittal plane but not as readily identifiable externally. dentate
The superior posterior fissure separating lobule VI from Medullary core nucleus
lobule VII is well seen on the posterior superior surface. Vermis
The horizontal fissure, prominent on the posterior, infe­ Folium Subfolium White matter
rior, and lateral hemisphere aspects divides lobule VIIA lamina
into two major components: lobule VIIAf at the vermis/
crus I in the hemisphere, and lobule VIIAt at the Cerebellar fissure Cerebellar
vermis/crus II in the hemisphere. The paravermian cortex
sulcus on each side of the superior cerebellum surface is
an indentation formed by the superior cerebellar artery Section in plane of superior cerebellar peduncle
medial branch. The retrotonsillar groove at the inferior â•…
and medial aspect of the cerebellum is caused by the
rim of the foramen magnum and delineates the tonsil, a largely of mossy and climbing fibers entering the cerebel­ cerebellar cortex serving as the cerebellum’s functional
gross morphologic feature comprising lobule IX and lum, and axons of Purkinje cells leaving the cerebellar unit, namely, the corticonuclear microcomplex. Except for
part of lobule VIIIB that becomes clinically relevant cortex to the nuclei. There are no association fibers in the vestibulocerebellum, these nuclei are the primary
with herniation syndromes. the cerebellum linking cerebellar cortical areas with source of cerebellar efferents. These have highly orga­
each other. The cerebellar nuclei within the medullary core nized connections with extracerebellar structures. The
The interior of the cerebellum contains a central mass include, medial to lateral, the fastigial, globose, emboli- large, folded dentate nucleus is U-shaped. Its open end,
of white matter, the medullary core, surrounded by the form, and dentate. These nuclei, together with other or hilus, points medially, conveying fibers that, together
deeply folded cerebellar folia. The relationship of the minor nuclei in the medullary core and vestibular nuclei with those from the fastigial, globose, and emboliform
folia to the white matter has a tree branch appearance, in the posterior pons and medulla, are linked with the nuclei, form the superior cerebellar peduncle.
hence arbor vitae. The white matter core extends into
the folia as narrow laminae, surrounded by the three-
layered cerebellar cortex. The white matter consists

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 179

P late 8-3 Brain: PART I

Cerebellar Peduncles Peduncle Input (afferents) Output (efferents)
Inferior
The cerebellum is linked with the spinal cord, brain­ Level of (restiform body) Spinocerebellar Fastigiobulbar, To vestibular
stem, and cerebral hemispheres by three major fiber section Dorsal Uncinate and reticular
tracts—the inferior, middle, and superior cerebellar Rostral fasciculus nuclei
peduncles. These convey axons into the cerebellum Cuneocerebellar
(afferent) or away from it (efferent). Direct cerebellovestibular
Olive-cerebellar (to LVN)
The inferior cerebellar peduncle (ICP) has two compo­ Reticulocerebellar
nents. The larger is the restiform body, a purely afferent Superior Trigeminocerebellar
system, whereas the smaller juxtarestiform body carries Raphe-cerebellar
both afferent and efferent fibers.
Middle cerebellar cerebellar Juxtarestiform Vestibulospinal
The restiform body (or ICP proper) is located in the peduncle peduncle body (primary, secondary)
dorsolateral medulla, lateral to the vestibular nuclei.
Entering the cerebellum, it is situated medial to the Middle Pontocerebellar Dentatothalamic
middle cerebellar peduncle, conveying uncrossed mossy (brachium pontis) Ventral Dentatorubral
fiber afferents to cerebellum from the ipsilateral spinal Superior Dentatoreticular
cord and brainstem, and crossed climbing fiber inputs (brachium spinocerebellar Interpositus-rubral
from the contralateral inferior olivary nucleus. Spinal conjunctivum) Trigeminocerebellar
cord inputs in the ICP are from the dorsal (posterior) Tectocerebellar connections
spinocerebellar tract (DSCT), conveying information (globose, emboliform)
from the trunk and lower limbs. The rostral spinocerebel- Superior colliculus
lar tract carries information from the upper limbs and Inferior colliculus
the central cervical tract arising from upper cervical seg­ Coeruleo-cerebellar
ments. From the brainstem, the ICP conveys the cuneo-
cerebellar tract arising in the external cuneate nucleus Reprinted with permission from Takahashi E, Song JW, Folkerth RD, Grant PE,
(also known as the lateral or accessory cuneate nucleus),
which conveys information from the upper limb and the Schmahmann JD. Detection of Postmortem Human Cerebellar Cortex and
reticular formation (reticulocerebellar fibers), the tri­
geminal principal sensory nucleus (trigeminocerebellar Corticospinal Inferior cerebellar White Matter Pathways Using High Angular Resolution Diffusion Tractography:
fibers), and the midline raphe. Climbing fibers arise in tract
the inferior olive, cross in the medulla, and course peduncle A feasibility study. NeuroImage, in press.
within the ICP to reach the contralateral cerebellar
hemisphere. Fastigial Superior cerebellar
Globose nucleus Cerebellum peduncle Inferior cerebellar
The juxtarestiform body is a small aggregation of fibers nucleus peduncle
situated medial to the restiform body that enters the
cerebellum passing through the vestibular nuclei. It Emboliform Middle cerebellar
conveys afferent fibers to vermal lobule IX (uvula) and nucleus peduncle
lobule X (the flocculonodular lobe). Primary vestibular
afferents arise from the vestibular sense organs (the Dentate
saccule and utricle) and terminate ipsilaterally; second­ nucleus
ary vestibular fibers from the vestibular nuclei termi­
nate bilaterally. Efferent fibers in the juxtarestiform Fourth
body arise from the cerebellar cortex and fastigial ventricle
nucleus. Cerebellar cortical axons in the juxtarestiform
body emanating from Purkinje cells in the vestibulocer­ Lateral vestibular Medial
ebellum (part of lobule IX, and lobule X) terminate in nucleus longitudinal
Deiters lateral vestibular nucleus, and, together with Genu of CN VII fasciculus
efferents from the anterior vermis, are the only instance Nucleus CN VI Tectospinal tract
of projections from cerebellar cortex bypassing the deep Nucleus CN VII
cerebellar nuclei to terminate on a target outside the Medial lemniscus
cerebellum. Juxtarestiform body fibers arising from the
fastigial nuclei lead to the vestibular and the reticular Corticospinal tract
nuclei. Axons from the rostral half of the fastigial Pontine nuclei
nucleus course to the ipsilateral brainstem in the fasti-
giobulbar tract. Axons from the caudal half of the fasti­ Pons
gial nucleus cross to the contralateral cerebellum in the
uncinate bundle, that is, the hook bundle of Russell, â•…
before traveling to the brainstem in the contralateral
juxtarestiform body (see Plate 8-10). the posterolateral wall of the fourth ventricle, ascends (anterior) spinocerebellar tract fibers conveying infor­
as the brachium conjunctivum to the midbrain, where mation concerning the contralÂ

P late 8-4 Deep Cerebellum and Ataxia
nucleus
Cerebellar Cortex Medullary core CEREBELLAR CORTEX AND NUCLEI: NEURONAL ELEMENTS
and Nuclei (cerebellar Sections of human cerebellar cortex
white matter) stained for Nissl substance at progressively
higher levels of magnification (0.5x, 2x,
4x, and 20x)

The histology of the cerebellar cortex differs funda­ Folium Subfolium
mentally from that of the cerebral cortex in that it has Molecular layer
essentially the same paracrystalline structure through­ White matter
out. The trilaminate cortex, the Purkinje cell layer lying Granule cells lamina
between the innermost granular layer and the outermost Granule cell Cortex
molecular layer, is apposed on each side of a white matter Purkinje cell layer
lamella conveying fibers to and from the cortex (see glomeruli Granule cell layer
Plates 8-4 and 8-5). stellate cells in the middle part of the molecular layer White matter lamina
have long axons up to 450╯µm in the parasagittal plane, Molecular layer
The Purkinje cell (PC) layer is a monolayer composed providing ascending and descending collaterals early in Stellate cells,
entirely of PCs, a 100╯µm-thick sheet of 15 million their course, but they rarely enter the pericellular PC glial cells
neurons situated between the molecular and granular plexus and do not participate in the pinceau. Purkinje cells
layers. The PC is the defining neuron of the cerebel­
lum. It is among the largest cells in the nervous system, The granular layer is 200╯µm to 300╯µm deep and â•…
with a pear-shaped soma (35 × 70╯µm) and a fanlike contains granule, Golgi, Lugaro, and unipolar brush
appearance of its dendritic tree. The proximal dendrite cells. Granule cells number about 50 billion, 3,000 per the granule cell glomerulus, pale islands between the
divides into two major dendrites that branch multiple single PC. They have minimal cytoplasm, are among granule cells containing a complex articulation between
times to form a flattened plate (400 × 20╯µm) in the the smallest neurons in the brain (6-8╯µm diameter), terminal rosettes of mossy fiber afferents, arborizations
parasagittal plane oriented perpendicular to the long and are the most numerous. Their density renders the of granule cell dendrites, and Golgi cell axons. The
axis of the folium. Each PC has over 150,000 spines, granule cell layer a deep blue on stains such as Nissl, granule cell axon ascends into the molecular layer
with a density 25 times higher on distal dendrites, which label nuclear material. The granule cell has three where its PFs provide excitatory input to the PCs.
where parallel fibers (PFs) synapse, than on proximal to five clawlike branched dendrites that participate in
dendrites, where climbing fibers (CFs) synapse. The Golgi cells are irregularly rounded or polygonal inhib­
PC is the only neuron with axons leaving the cerebellar itory interneurons numbering approximately 1 per 1.5
cortex. The axon descends through a constricted region PCs. In contrast to the PC, basket, and stellate cells,
surrounded by the pinceau of basket cell axon terminals, the Golgi cell dendritic tree has a three-dimensional
acquires a myelin sheath, and descends to the deep configuration. Large Golgi cells, 10 to 24╯µm in diam­
cerebellar nuclei or vestibular nuclei. Recurrent col­ eter, lie in the upper half of the granular layer, their
laterals course back toward the molecular layer, inhibit­ dendrites arising as one or two main trunks with sub­
ing interneurons as well as the soma and proximal sidiary branches that ascend to the outer zone of the
dendrites of neighboring PCs.

The molecular layer is 300╯µm thick. It contains granule
cell axons and PFs, dendritic arborizations of PCs and
Golgi interneurons, and cell bodies of basket, stellate, and
supporting glial cells.

Parallel fibers are formed when the granule cell axon
ascends through the PC layer into the molecular layer
and branches in the shape of a T to form the PF, one
of the thinnest vertebrate axons. It travels parallel to the
long axis of the folium for 1 to 3╯mm in the rat and cat,
and possibly 6 to 8╯mm in primates.

The basket cell lies in the lower third of the molecular
layer just above the PCs. Its dendrites extend up into
the molecular layer in a fan-shaped field 30╯µm wide in
the parasagittal plane (the same plane as the PC den­
dritic tree), giving off relatively few branches, interdigi­
tating with the dendritic fields of the PCs, and contacted
by the PFs. Its axon courses in the parasagittal plane
among the lower dendrites of 9 or 10 PCs. It emits a
succession of descending branches that envelope the
PC somata in an axonal sheath with numerous synaptic
contacts, giving the basket cell its name. Terminal
axonal branches surround the initial segment of the PC
axon in a dense fiber plexus with the appearance of
an old paintbrush (French, pinceau). This axo-axonic
complex is unique in the mammalian nervous system.
Sparse ascending collaterals from the basket cell axon
synapse on secondary and tertiary PC dendrites.

Stellate cells are small, 5 to 10╯µm in diameter, with
short, profusely branching dendrites contacted by par­
allel fibers and axons that terminate on PC dendrites.
Superficial stellate cells in the upper molecular layer have
short axons oriented in the parasagittal plane. Deep

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 181

P late 8-5 Brain: PART I

CEREBELLAR CORTEX: NEURONAL ELEMENTS
Glial cell

Cerebellar Cortex and Stellate cell Brainbow image of Purkinje
Nuclei (Continued) cells and granule cells in
Basket mouse, derived by mapping
molecular layer. Smaller Golgi cells, 9 to 18╯µm, are in cell the differential expression
the depths of the granular layer, with dendrites that axons of multiple fluorescent
radiate out from the soma. One to three axons emerge proteins in individual
from the Golgi cell body or from proximal dendrites PC nucleus neurons Courtesy of Tamily
and divide repeatedly, resulting in a multitude of fine PC nucleolus
branches that form an elaborate, dense plexus extending Basket Weissman, PhD. The Brainbow
throughout the granular layer and participating in the Pinceau mouse was produced by Livet J,
granule cell glomerulus. Granule cell Weissman TA, Kang H, Draft RW,
glomerulus Lu J, Bennis RA, Sanes JR, Lichtman
The Lugaro cell is a fusiform inhibitory interneuron Granule cell JW. Nature 2007;450:56-62.
measuring 10 × 30╯µm, lying horizontally or obliquely Cerebellar cortex studied with Bielschowsky silver stain (20x)
in the outer third of the granular layer. Its dendrites 3D reconstruction of
originate from the tapering extremities at the two poles Courtesy Dr. Matthew P. Frosch. Lucifer yellow-filled PC
and extend horizontally for up to 600╯µm at the level viewed perpendicular to
of the PC bodies in the infraganglionic plexus formed Distal dendrite (left) and parallel to (right)
by the PC recurrent axon collaterals. It receives excit­ the long axis of the folium.
atory input from the granule cell axon and serotonin­ Stellate cell
ergic modulation acting through volume transmission. Reprinted with permission from
Its axon arises from the cell body or large proximal Proximal dendrite Rossi DJ, Alford S, Mugnaini E,
dendrite, forming two types of axonal plexuses. One Slater NT. Properties of transmission
parasagittal axon contacts the soma and dendrites of Glial cell at a giant glutamatergic synapse in
stellate and basket cells in the molecular layer; the Dendritic shaft cerebellum: the mosssy
other is transverse and contacts Golgi cells in the fiber-unipolar brush cell synapse.
granular layer. Soma J Neurophysiol 1995;74:24-42.
Nucleus
The unipolar brush cell (UBC) is the only excitatory Nucleolus
interneuron in the cerebellum. The soma is 9 to 12╯µm
in diameter, with a single dendrite ending in a tight Axon
brushlike tip of dendrioles that have extensive synaptic
contact with the mossy fiber rosette. Its axon synapses Purkinje cell and adjacent cortex (20x) Cerebellar cortex
on granule and Golgi cells. The UBC is found in stained with hematoxylin and eosin immunostained with
the vestibulocerebellum, vermis, and dorsal cochlear calbindin (10x)
nucleus, and it is thought to amplify vestibular signals Courtesy Dr. Matthew P. Frosch. CEREBELLAR NUCLEI
and provide feed-forward excitation to granule cells.

Glial cells in the cerebellum include protoplasmic
astrocytes that envelope the PC perikaryon in a neuro­
glial sheath; Bergmann glial cells in the PC layer that
are involved in neural migration and development of
the cerebellar cortex, and that play a role in regulating
glutamatergic neural transmission in the mature cere­
bellum; and oligodendroglia in cerebellar white matter
and in the granular layer.

CEREBELLAR NUCLEI Left: Coronal section of cerebellum stained for Nissl substance shows the fastigial (F), globose (G),
The fastigial, globose, emboliform, and dentate nuclei emboliform (E), and dentate (D) nuclei. Right: Similar section stained for myelin. Reprinted with permission from
are together termed the deep cerebellar nuclei (DCN)
to differentiate them from the precerebellar nuclei. The Schmahmann J, Doyon J, Toga A, Petrides M, Evans A. MRI atlas of the human cerebellum. San Diego: Academic Press, Elsevier; 2000.
fastigial nucleus is the homologue of the medial nucleus
in lower primates, whereas the posterior and anterior â•…
interpositus nuclei are homologous with the globose
and emboliform nuclei, respectively. Among the cere­ The neurons of the DCN are outnumbered by the convey excitatory output to the thalamus and brainstem,
bellar nuclei, the dentate, or lateral nucleus in lower PCs of the cerebellar cortex by about 26 to 1. Each PC and nucleocortical projections back to the cerebellar
vertebrates, has evolved most. The posterior (dorsal) contacts approximately 35 nuclear neurons, and each cortex; small γ-aminobutyric acid (GABA)ergic neurons are
part with small narrow folds (microgyric) contains large DCN neuron receives inputs from more than 800 PCs. inhibitory to the inferior olivary nucleus; and small gly-
cells and is phylogenetically older. The macrogyric The cytologic features of the DCN suggest anatomic cinergic neurons in the DCN are thought to be inhibitory
anterior (ventral) and lateral part contains smaller subdivisions that may have connectional and functional intranuclear interneurons. It is now possible to identify
neurons and has expanded greatly in concert with the relevance, but these are not sufficiently definitive to the DCN on magnetic resonance imaging (MRI) by
association cortex of the cerebral hemispheres. This is formally subdivide the nuclei further. Neurons in the taking advantage of their iron content, although detailed
important from the perspective of anthropology as well DCN are of three types. Large glutamatergic neurons organization is not apparent with available technology.
as cognitive neurosÂ

Plate 8-6 Cerebellum and Ataxia

Excitatory endings CEREBELLAR NEURONAL CIRCUITRY Molecular
Inhibitory endings layer
Golgi cell (inhibitory) Purkinje cell layer
Granule cells (excitatory)
Granular
Parallel fibers (axons of granule cells) layer
Parallel fibers (cut)

Purkinje cells (inhibitory)

Dendrites of Purkinje cell
Outer stellate cell (inhibitory)

Basket cell White
(inhibitory) matter

To deep Glomeruli
cerebellar Purkinje cell axon
Climbing fiber (excitatory)
nuclei Mossy fibers (excitatory)

Purkinje cell axon

Climbing fiber (excitatory)
â•…

Cerebellar Cortical and dendritic trees of stellate and Golgi cells. The olivocer­ in the granular layer and spines of the proximal den­
Corticonuclear Circuitry ebellar projection is organized according to a strict drites of PCs in the molecular layer. Upon reaching the
mediolateral parasagittal zonal pattern (see Plate 8-12). molecular layer, the granule cell axon divides to form
The neurons of the cerebellar cortex and nuclei parallel fibers (PFs), the two branches traveling in
are linked together in multiple repeating anatomic Mossy fibers (MFs) are named for their thickened opposite directions along the folium. The PFs make
microcircuits—corticonuclear microcomplexes—that terminals that have thick, short, divergent, varicose synaptic contact with one or two spiny branchlets on
serve as the essential functional unit of the cerebellum. branches resembling moss. Their synaptic arborizations intermediate and distal regions of the dendritic trees of
The key to their elucidation is the dual nature of the are termed rosettes, have a variety of shapes, and are up to 300 PCs along the folium.
cerebellar inputs—the mossy fiber and climbing fiber located along the course of the MF in the granular layer
systems. Monoaminergic fibers from the brainstem are at the branch points and at their sites of terminations. Each PC receives synaptic inputs from approximately
an additional minor source of cerebellar afferents. MFs are heavily myelinated and convey excitatory affer- 200,000 parallel fibers. In addition to excitatory inputs
ents to the cerebellar cortex from the spinal cord, brain­ to the PCs from MFs and CFs, the PCs participate in
Climbing fibers (CFs) arise exclusively from the infe- stem (except the olive), and the cerebral hemispheres. a bidirectional corticonuclear projection, receiving
rior olive. Axons of olivary neurons branch to form 7 to They enter through all three cerebellar peduncles, excitatory feedback back from those regions of the
10 CFs. Each CF provides extensive excitatory synaptic giving off 20 to 30 collateral branches in the white DCN and vestibular nuclei to which the PC inhibitory
contact with the dendritic tree of a single PC (between matter of the folium as they course toward the granular projection is directed. The PCs receive inhibitory
1,000 and 1,500 synaptic contacts between a CF and its layer. They also provide collaterals to the deep cerebel­ inputs from interneurons in the molecular layer—
PC). Climbing fibers enter the cerebellum through the lar nuclei. Many MFs terminate bilaterally in the cer­ stellate cells, basket cells, and Lugaro cells, all of which
inferior cerebellar peduncle (ICP), branch in the white ebellum after crossing in the cerebellar white matter. receive excitatory afferents from the ascending granule
matter, where they emit collaterals to the deep cerebel­ Unlike the CF, the MF provides excitatory input to the cell axon and the PFs. Recurrent axon collaterals of the
lar nuclei (DCN), and ascend to the molecular layer. In PC indirectly. The MF rosette is the central component PCs are also inhibitory. The dendrites of the unipolar
the lower two thirds of the molecular layer the CF is of the granule cell glomerulus, the complex articulation brush cell (UBC) in the vestibulocerebellum, the only
tightly wound around the trunk and major proximal between MF rosettes and the terminal arborizations of excitatory cerebellar interneuron, receive MF inputs
branches of the PC dendritic tree. Each varicosity of a granule cell dendrites. Each MF rosette makes excit­ within the granule cell glomerulus. The net effect of these
CF synapses with several dendritic spines arising from atory synaptic contact with 50 to 100 dendritic termi­ finely balanced interactions is that inputs to cerebellum are
the same dendritic branch. Fine tendrils that branch off nals from up to 20 granule cells and receives inhibitory excitatory, output from the cortex via the PC is inhibi­
from the CF in the molecular layer synapse with feedback from the descending axons of Golgi cells. The tory, and output from the cerebellum via the DCN is
ascending branches of the basket cell axon and with the granule cell axon ascends toward the molecular layer, excitatory to thalamus and brainstem but inhibitory to
making synaptic contact with dendrites of Golgi cells the inferior olive.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 183

P late 8-7 Brain: PART I
CIRCUIT DIAGRAM OF AFFERENT CONNECTIONS IN THE CEREBELLUM

Stellate cell

Parallel Basket Parallel
fiber (PF) cell (BC) fiber (PF)

Cerebellar Cortical and Purkinje
Corticonuclear Circuitry cell (PC)

(Continued) Ascending Climbing Purkinje
axon (AA) fiber cell
The output from the cerebellar cortex is derived Golgi cell (Go)
exclusively from PCs, precisely organized, and directed Orientation of
toward the DCN and precerebellar nuclei. PCs in each Granule cerebellar neurons
lobule project to those parts of the deep cerebellar cell (Gr)
nuclei closest to them. Thus the vermis projects to the
fastigial nucleus, the intermediate cortex to the globose SC BC AA PF
and emboliform nuclei, and much of the lateral hemi­ PC
spheres project to the dentate nucleus. More detail on Go
cerebellar corticonuclear circuits, modules, and micro­
zones is presented in Plate 8-12. Gr

The two major neurotransmitters in the cerebellum Reciprocal to CF MF
are glutamate and γ-aminobutyric acid (GABA). Gluta- cerebellar cortex Cerebellar
mate is excitatory and is found in the MFs, PFs, CFs,
UBCs, and deep cerebellar nuclear neurons that project nuclei
to thalamus, brainstem, and cerebellar cortex. GABA is
inhibitory and is utilized by the PCs, all remaining Cerebellar Thalamus
cerebellar interneurons (stellate, basket, Golgi, Lugaro), nuclei to cerebral
and the DCN neurons that project to the inferior olive. cortex
Glycine is present in inhibitory interneurons in the DCN. Reciprocal
A number of other peptide neurotransmitters are to inferior olive
present also in the afferent fibers and neurons of the
cerebellar cortex. Brainstem to
spinal cord
The PC generates two different classes of action potentials
in response to its principal afferents. The input of hun­ A. Impagliazzo
dreds of MFs produces a brief burst of repetitive simple
spikes, 50 to 150 per second. The inhibitory basket and Mossy Climbing â•…
stellate cell interneurons produce inhibition of PCs locally fiber (MF) fiber (CF)
and for some distance lateral to the longitudinal strip
of active parallel fibers. Therefore MF-induced PC These corticonuclear circuits and physiology are the a universal cerebellar transform, which is applied to mul-
activity consists of a brief burst of action potentials basis of theories that the cerebellum functions as an adap- tiple domains of neurologic function. The role of the cereÂ

P late 8-8 Cerebellum and Ataxia

Cerebellum Subdivisions and CEREBELLAR AFFERENT PATHWAYS
Afferent Pathways
Middle cerebellar peduncle
The cerebellum is divided into three lobes: anterior, Superior cerebellar peduncle
posterior, and flocculonodular (see also Plate 8-2). It is
also divided into three mediolateral subregions on the To contralateral cerebellar cortex
basis of phylogeny and function. The archicerebellum, or
vestibulocerebellum, includes vermal and hemispheric Cortical input Leg Arm Face Primary fissure
parts of lobule X (flocculonodular lobe), parts of vermal
lobule IX (uvula), and lobule I/ II (lingula); it is linked Nucleus Vestibular To lobule X (nodule and flocculus)
with the vestibular nuclei and is concerned with eye reticularis nuclei Inferior cerebellar peduncle
movements and equilibrium. The paleocerebellum, or tegmenti
spinocerebellum, in vermal and paravermal lobules III pontis
through VI and lobule VIII, receives cutaneous and
kinesthetic afferents from spinal cord, brainstem, and Pontine nuclei
cerebral hemispheres. The anterior vermis is linked with (contralateral)
the rostral fastigial nucleus, influences the medial motor
system through brainstem vestibulospinal and reticulo­ Spinal input
spinal projections, and controls trunk and girdle muscles
enabling balance and gait. Paravermal areas are linked Inferior olive
with the interpositus nuclei, the posterior part of the
dentate nucleus, red nucleus, and primary motor cortex, Upper part
influencing descending lateral motor systems and con­ of medulla
trolling distal limb movements. The neocerebellum (pon­ oblongata
tocerebellum) includes lobules VI and VII at the vermis
and hemispheres. It receives afferents from cerebral Spinal input
cortex through the pons. Lateral cerebellar hemispheres
project via the ventral dentate nucleus to thalamus and Vestibular nerve Reticulocerebellar Functional Subdivisions of Cerebellum
cerebral association areas; the posterior vermis is linked and ganglion tract Hemisphere Vermis
through the caudal fastigial nucleus with limbic areas.
It appears that the neocerebellum is involved in cogni­ Lower part Cuneocerebellar Inter- Anterior lobe
tion and emotion. of medulla tract Lateral mediate Primary
oblongata part part fissure
Knowledge of cerebellar connections with extracer­ Gracile nucleus
ebellar structures is critical to understanding the diverse Cortical input Leg zone
roles of the cerebellum and the consequences of Main cuneate Arm zone
cerebellar injury. Afferents to cerebellum are conveyed Lateral reticular nucleus (relay Face zone
predominantly by mossy fibers and climbing fibers that nucleus for cutaneous
are organized in a fundamentally different manner information) 2nd spinal Posterior
(see Plates 8-6 and 8-7). Spinal input projection lobe
MOSSY FIBER PATHWAYS External cuneate
Spinocerebellar Pathways. Sensory afferents from the Cervical part nucleus (relay for area (gracile Posterolateral
spinal cord terminate in a somatotopic fashion in the of spinal cord proprioceptive
primary sensorimotor representation in lobules III information) lobule) fissure
through V and the secondary sensorimotor representa­ Motor interneuron
tion in lobule VIII, with collateral inputs to the deep From skin (touch Archi- Lobule I,II Flocculo-
cerebellar nuclei (DCN). The trunk and lower limbs Rostral and pressure) cerebellum Lobule X nodular lobe
are subserved by the dorsal and ventral spinocerebellar spinocerebellar (vestibulo-
tracts, and the head, neck, and upper extremities by the tract From muscle
cuneocerebellar, rostral spinocerebellar, and central (spindles and cerebellum) Lobule IX
cervical tracts. These are all uncrossed, ascending in the Spinal border cells Golgi tendon VIIIA-B
ipsilateral spinal cord, except for the ventral (anterior) organs) Paleocerebellum III-V
spinocerebellar tract (VSCT), which decussates and Motor interneuron (spinocerebellum)
ascends on the contralateral side. From skin and
Lumbar part deep tissues Neocerebellum Lobule VI,
The dorsal (posterior) spinocerebellar tract (DSCT) of spinal cord (pain and Golgi (pontocerebellum) Lobule VIIA (Crus I and II), Lobule VIIB
and the cuneocerebellar tract (CCT) convey analogous tendon organs)
proprioceptive and exteroceptive information from the Clarke’s column Theoretic
hindlimb and forelimb, respectively. Both enter cere­ From skin (touch “unfolding”
bellum via the inferior cerebellar peduncle (ICP). Pro- Ventral and pressure) of cerebellar
prioceptive information comes from (1) muscle spindle (anterior) spino- and from muscle surface in
afferents that signal muscle length (groups Ia and II fibers) cerebellar tract (spindles and derivation of
and (2) Golgi tendon organs that signal muscle tension Golgi tendon above diagram
(group Ib fibers). DSCT or CCT neurons convey infor­ organs)
mation regarding closely related muscles; some relay â•…
information from joint receptors. Exteroceptive signals Dorsal (posterior)
provide the cerebellum with cutaneous afferents origi­ spinocerebellar tract
nating from touch and hair-movement receptors in
small areas of skin. The DSCT in the posterolateral funiculus conveys proprioceptive and exteroceptive pathways activated by cutaneous and high-threshold
afferents from the trunk and legs, arising in Clarke’s muscle afferents. The VSCT originates from spinal
column in lamina VII of the dorsal horn at spinal seg­ border cells, mostly in Rexed lamina VII at the postero­
ments C8 to L3. It terminates in hindlimb projection lateral aspect of the anterior horn of the lumbosacral
areas in the intermediate part of the ipsilateral anterior spinal cord. It decussates close to the cell bodies,
lobe and lobule VIII. The CCT ascends from the ascends in the contralateral anterolateral funiculus, and
medulla, conveying proprioceptive afferents from the enters the cerebellum through the superior cerebellar
arms, originating in the external cuneate nucleus, and peduncle (SCP). Most of its fibers cross to the other
exteroceptive fibers from the main cuneate nucleus. side, hence the double crossing. It terminates in longi­
tudinal zones in the hindlimb representations in the
The ventral (anterior) spinocerebellar tract and rostral anterior lobe and, to a lesser extent, in lobule VIII. The
spinocerebellar tract (RSCT) convey information to cer­ RSCT originates from neurons at the base of the pos­
ebellum regarding complex motor repertoires. Affer­ terior spinal horn in Rexed lamina VII at spinal cord
ents arise from (1) interneurons within spinal motor levels C4 to C8, ascends in the ipsilateral posterolateral
centers controlling the hindlimbs (VSCT) and fore­ funiculus, and enters the cerebellum via both the
limbs (RSCT), (2) group I muscle afferents from Golgi ICP and SCP, terminating bilaterally in primary and
tendon organs in groups of muscles involved in secondary forelimb sensorimotor representations. The
synchronized movements, and (3) multisynaptic spinal

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 185

Plate 8-9 Brain: PART I

Cerebellum Subdivisions and SOMATOSENSORY SYSTEM: SPINOCEREBELLAR PATHWAYS
Afferent Pathways (Continued)

corticospinal system facilitates excitatory or inhibitory Cerebellum
effects of cutaneous and muscle afferent fibers in the
VSCT and RSCT, whereas the reticulospinal system Superior cerebellar peduncle
inhibits them. The rubrospinal and propriospinal Pons
pathways produce excitation independent of spinal
afferents. Cerebellum

Sensory afferents from C1 through C4 are conveyed Medulla Cuneocerebellar tract
in the central cervical tract (CCT). This arises in the Inferior cerebellar peduncle
central cervical nucleus in Rexed layer VII, which inte­ Lateral (accessory) cuneate nucleus
grates information related to head rotation, such as
group I afferent input from neck muscles and vestibular Rostral spinocerebellar tract (RSCT)
input from semicircular canals. The CCT carries infor­
mation via the ICP and SCP to the anterior lobe and Upper Body Ia (to cuneocerebellar tract)
lobule VIII. (above T6) Ib (to RSCT)
Dorsal (posterior) spinocerebellar
Trigeminocerebellar projections from the principal tri­ Ventral spinocerebellar tract (VSCT) tract (DSCT)
geminal sensory nucleus travel in the ICP to the face
representation in caudal lobule V and lobule VI; in Lower Body
contrast, cerebellar projections from the mesencephalic (below T6)
trigeminal nucleus travel in the SCP. The tectocerebellar
tract from the superior and inferior colliculi bilaterally vermal and hemispheric components of cerebellar Ia (to DSCT)
projects to lobules VIII and IX (the posterior, or dorsal, lobule X (nodulus and flocculus) and the fastigial and Ib (to VSCT)
paraflocculus and uvula), and the vermal visual area in interposed nuclei. Anterior white commissure â•…
lobule VII. MCP to the cerebellar cortex. The organization,
Arcuate Cerebellar Tract. Fibers from the arcuate somatotopy, and functional relevance of the cortico­
Reticulocerebellar projections act over wide areas of the nucleus in the ventral medulla form the striae medullares pontocerebellar system are considered in Plate 8-13.
cerebellum and DCN. They originate from the lateral visible on the posterior surface of the medulla. They
reticular nucleus (LRN) and paramedian reticular nucleus enter cerebellum via the ICP and terminate in ipsilat­ CLIMBING FIBER PATHWAYS
in the medulla, the nucleus reticularis tegmenti pontis eral hemispheric lobule X. The arcuate nucleus is Climbing fibers from the inferior olives project via the
(NRTP) in the pons, and the medial (magnocellular) involved in central reflex chemosensitivity and cardio­ contralateral ICP to the cerebellar cortex. Climbing
reticular formation. Feedback projections arise from the respiratory activity. fiber anatomy, connections, and physiology are shown
DCN, particularly the fastigial nucleus. in Plates 8-6 and 8-7.
Vestibulocerebellar Pathways. Vestibular input to
The NRTP receives cerebral cortical afferents from cerebellum arises from primary vestibular afferent fibers MONOAMINERGIC FIBERS
sensorimotor, frontal lobe, and superior parietal and projections of neurons in the vestibular nuclei. Minor dopaminergic inputs to cerebellum arise in
regions, and subcortical afferents from vestibular and These fibers carry information from receptors of the the substantia nigra—noradrenergic inputs from the
visual- or eye-movement–related nuclei, including the vestibular labyrinth, which signal the position and locus coeruleus project diffusely to the vermis and
superior colliculus. Inputs from limbic-related struc­ motion of the head in space (see Plate 8-11). lateral hemispheres, and serotonergic fibers from raphe
tures include the cingulate gyrus and mammillary nuclei project diffusely to most regions of cerebellar
bodies. NRTP fibers enter cerebellum through the Pontocerebellar Pathways. Basis pontis neurons cortex.
middle cerebellar peduncle and project widely, with a receive input from multiple areas of the cerebral cortex
focus in vermal lobules VI and VII, and lobule X. The and project as pontocerebellar fibers via the contralateral
NRTP is involved in ocular vergence and accommoda­
tion and the visual guidance of eye movements. The
limbic relay provides cerebellum with emotionally
salient information (see Plate 8-15).

The lateral reticular nucleus (LRN) receives inputs
from the spinal cord, lateral vestibular nucleus, red
nucleus, superior colliculus, and cerebral cortex. Its
fibers enter the cerebellum through the ipsilateral ICP;
many cross to the contralateral side, providing collater­
als to the DCN and terminating in multiple parasagittal
zones. LRN connections are somatotopically arranged:
the ventrolateral parvicellular region conveys afferents
from the lumbar cord to primary and secondary hindlimb
representations bilaterally; the dorsomedial, magnocel­
lular part conveys inputs from the cervical cord to cer­
ebellar forelimb regions. LRN neurons resemble VSCT
or RSCT neurons but lack group I muscle input,
are excited by descending vestibulospinal fibers, and
respond to stimulation of larger body surface areas.

The paramedian reticular nucleus in the medulla
receives afferents from the vestibular nuclei and
somatosensory regions of the cerebral cortex and proj­
ects through the ICP to the vermis.

Perihypoglossal Nuclei. These medullary nuclei
related to the control of extraocular muscles receive
vertical and horizontal gaze information from midbrain
and pontine nuclei and face regions of the sensorimotor
cortex. They are reciprocally interconnected with

186 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

P late 8-10 Cerebellum and Ataxia

CEREBELLAR OUTPUT

Excitatory endings

Inhibitory endings
of Purkinje cells

Cerebral cortex

Internal
capsule

Cerebellar Efferent Anterior and Cerebral peduncle
Pathways anterolateral nuclei
of thalamus (and others) Decussation of superior cerebellar
Mesencephalic reticular formation peduncles

Red nucleus Descending fibers from superior
Fastigial nucleus cerebellar peduncles
Globose nuclei
Emboliform nucleus Hook bundle of Russell
Dentate nucleus
Cerebellar cortex Section A – B
viewed from
below

Efferent pathways from cerebellum originate in Pur- Vestibular nuclei Section B – C
kinje cells (PCs) that project to the deep cerebellar nuclei Inferior cerebellar viewed from
(DCN). DCN neurons then convey efferents from cer­ above
ebellum to extracerebellar areas in the spinal cord, peduncle
brainstem, and cerebral hemispheres. DCN neurons Lateral reticular nucleus A
receive inhibitory inputs from the PCs and from DCN
interneurons, and excitatory input from collaterals of Inferior olive B
mossy fibers and climbing fibers on their way to the Medulla oblongata
cerebellar cortex. The nature of DCN efferents is Pontomedullary reticular formation C
determined by the interaction of excitation and inhibi­
tion governed by the arrival of information in cerebellar The exception to the PC-DCN projection pattern Planes of section:
afferent pathways and by the processing of that infor­ throughout the cerebellum is the vestibulocerebellar red arrows indicate
mation by the cerebellar cortex. Glutamatergic projection cortex (vermal part of lobule IX [uvula], vermal direction of view
neurons of the DCN are excitatory to all extracerebellar [nodulus], and hemispheric parts [flocculus] of lobule â•…
areas, whereas γ-aminobutyric acid (GABA)-mediated X), which has direct reciprocal connections with
DCN projection neurons to the inferior olive are inhibi­ vestibular nuclei. In addition, PCs in zone B of the activation of descending spinal motor systems (see
tory. The PC-DCN interaction is the basis of the cor­ anterior vermis commit their axons directly to the Plates 8-11 and 8-12).
ticonuclear microcomplex, the essential component of lateral vestibular nucleus, the source of the lateral vestibu-
the parasagittal zones that form cerebellar cortical lospinal tract, by which the cerebellum regulates the FASTIGIAL NUCLEUS
modules (see Plate 8-12). The reciprocal nucleo-olivary Corticonuclear projections from the cerebellar vermis
connections are organized with exquisite precision in are directed to the fastigial nucleus. It has rostral and
a closed-loop circuit. The PC-DCN corticonuclear caudal parts with different connections and functional
microcomplex receives input from and sends DCN significance. The rostral part of the fastigial nucleus sends
output to essentially the identical cluster of neurons
within the inferior olivary complex. The exact pattern
of thalamic terminations varies according to the cere­
bellar module of origin, but the thalamocerebellar pro­
jections conform to a general arrangement, whereby
focal areas within the DCN project to rod-shaped
aggregates of thalamic neurons situated within curved,
longitudinally oriented, onion-like lamellae stacked in
a mediolateral direction.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 187

Brain: PART I

Cerebellar Efferent GLOBOSE AND EMBOLIFORM NUCLEI into a dorsal part with closely packed folds (polymicro­
Pathways (Continued) These nuclei are referred to in lower mammals as the gyric) and a ventral part that is less folded (macrogyric).
nucleus interpositus posterior (NIP) and nucleus inter­ The dorsal part (paleodentate, because of its relation­
efferents in the ipsilateral juxtarestiform body to the same positus anterior (NIA), respectively. They provide cer­ ship to the paleo-, or spinocerebellum) is linked with
side of the brainstem. Axons from its caudal part cross ebellar efferents in the superior cerebellar peduncle motor regions of the cerebral cortex. The ventral part
to the contralateral cerebellum in the hook bundle of from the predominantly motor-related spinocerebel­ (neodentate, interconnected with the more recently
Russell (the uncinate fasciculus) and project either to the lum that receives proprioceptive and exteroceptive evolved neocerebellum) is linked with cerebral associa­
contralateral brainstem in the juxtarestiform body or to inputs from the spinal cord and brainstem, and senso­ tion areas. Axons from dentate neurons course in the
the contralateral cerebral hemisphere in the superior rimotor information from the cerebral cortex. Fibers white matter hilum, enter the SCP, cross to the other
cerebellar peduncle (SCP). leave the interpositus nuclei and travel in the superior side in the decussation of the brachium conjunctivum,
cerebellar peduncle (SCP), also known as the brachium and terminate in the thalamus. Dorsal dentate nucleus
Both the rostral and caudal divisions of the fastigial conjunctivum, crossing to the contralateral side in the fibers terminate in motor-related thalamic nuclei,
nucleus project to nuclei of the pontomedullary reticular SCP decussation to course through the red nucleus, including the ventroposterolateral and ventral lateral
formation from which they receive inputs (see Reticular providing somatotopically arranged terminations in its nuclei, that then project to the primary motor and pre­
Afferents, Plate 8-9). They also both project to the caudal, magnocellular part. This red nucleus sector motor cerebral cortex. Middle and caudal thirds of the
vestibular nuclei; projections from the rostral fastigial provides the origin for rubrospinal fibers that act on the dentate nucleus are linked via the ventral anterior
nucleus are largely bilateral, those from the caudal fas­ spinal motor apparatus, particularly arm and hand nucleus of thalamus with the premotor cortex and
tigial nucleus are mostly contralateral. There are small, flexor muscles. with the frontal eye fields engaged in saccadic eye
crossed projections from the caudal part of the fastigial movements. Ventral and lateral parts of the dentate
nucleus to neurons in the posterolateral region of the Multiple other brainstem connections of the inter­ nucleus project via the dorsal sector of the ventral
basis pontis and to the medullary perihypoglossal positus nuclei include (1) the lateral reticular nucleus lateral nucleus and the medial dorsal nucleus to dorso­
nuclei. Crossed fastigiospinal projections terminate on and medullary reticular formation giving rise to reticu- lateral prefrontal, posterior parietal, and other cerebral
motor neurons in the upper cervical spinal cord. lospinal tracts, (2) the vestibular nuclei as source for association areas. Dentate nucleus projections to tha­
vestibulospinal tracts, (3) the superior colliculus giving lamic intralaminar nuclei provide widespread influence
Crossed axons from the caudal division of the fastigial rise to the tectospinal tract, (4) the oculomotor nuclei on cerebral cortical areas. These intralaminar nuclei
nucleus ascend in the superior cerebellar peduncle and ter­ (prepositus hypoglossi, Darkschewitsch, and posterior also project to the striatum, providing an indirect link
minate in the pretectal, superior colliculus, and posterior commissures), (5) the sensory (lateral/external cuneate between cerebellum and basal ganglia. The dentate
commissure midbrain nuclei concerned with oculomotor nucleus), and (6) the nociceptive systems (periaqueduc­ nucleus also projects to the small-celled (parvicellular)
and visual control. Connections with periaqueductal tal gray, medullary raphe). These rostrally directed part of the red nucleus that feeds back through the
gray, anterior tegmental, solitary tract, and interpeduncular fibers from the interpositus nuclei continue to the central tegmental tract to the inferior olive, which, in
as well as parabrachial nuclei impact autonomic, nocicep­ hypothalamus and zona incerta before reaching the turn, is linked with the cerebellum. Lesions in this tri­
tive, and limbic functions. Fastigial efferents also thalamus. Here they provide heavy terminations to angle of Guillain and Mollaret result in palatal tremor.
target the hypothalamus. Thalamic terminations occur nuclei linked with the precentral motor cortex, notably Dentate fibers in the descending limb of the superior
in motor-related anterolateral/anterior posterolateral the ventral posterolateral pars oralis (VPLo) and ven­ cerebellar peduncle (SCP) terminate in reticular nuclei
nuclei, the diffusely projecting midline nuclei, and the trolateral pars caudalis nuclei (VLc), and to the central in the pons.
intralaminar nuclei (central lateral and centromedian). lateral nucleus, which has widespread connections
Earlier physiologic and anatomic studies pointed to fas- beyond motor areas. Efferents from the interpositus The rostral and dorsomedial parts of the dentate
tigial nucleus connections with the septal region, hippocam- nuclei coursing within the descending limb of the SCP nucleus (the paleodentate) project to the dorsal lamina
pus, and amygdala. project back to the contralateral nucleus reticularis teg­ and bend of the principal olive. The ventral and caudal
menti pontis and to the dorsal and peduncular nuclei of parts of the dentate nucleus (the neodentate) project to
The fastigial nucleus connections with the contralateral the basis pontis. the ventral lamina of the principal olive.
inferior olivary nucleus are in the caudal part of the
medial accessory olive. The globose nucleus (NIP) is reciprocally linked with The complex and varied destinations of the projec­
the rostral half of the contralateral medial accessory tions from the DCN and vestibular nuclei underscore
Fastigial nucleus efferents influence multiple func­ olive, and the emboliform nucleus (NIA) with the ros­ the role of the cerebellum in multiple domains of neu­
tional domains: axial and limb girdle musculature (medial tromedial part of the dorsal accessory olive. rologic function. Lesions of these different pathways
motor system) via the vestibular and reticular nuclei; produce a wide array of impairments, motor and
oculomotor systems, including vertical and horizontal gaze DENTATE NUCLEUS otherwise. Damage to the DCN superimposed upon
centers in the midbrain and pons; autonomic centers The large and multiply folded dentate nucleus is the cerebellar cortical dysfunction appears to have adverse
through connections with brainstem and hypothala­ most lateral of the four major DCN. It is divided consequences on long-term recovery, as exemplified in
mus; and emotional modulation through links with patients with cerebellar stroke or tumor.
limbic-related circuits.

188 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 8-11 Vermis Cerebellum and Ataxia

Cerebellovestibular pathways Vestibulocerebellar pathways
Excitatory endings Fastigial nucleus
Inhibitory endings Globose nuclei
Emboliform nucleus
Dentate nucleus
Hook bundle of Russell

Vestibular nuclei Superior Flocculus
Lateral Mossy fibers
Medial Granule cell
Inferior Purkinje cell

Fibers from cristae

Vestibular
ganglion

Nodule Vestibular nerve Fibers from maculae

â•…
and to the anterior vermis. Together with the perihy­ Purkinje cells of the cerebellar vermis can depress the
Cerebellovestibular poglossal nucleus, they also project to the fastigial activity of neurons in the vestibular nuclei either by
Pathways nucleus as collaterals of vestibulocortical fibers. Axons direct inhibition or by inhibiting the discharge of
of both pathways terminate as diffusely projecting neurons in the fastigial nucleus, thereby decreasing the
The vestibular system is closely related to vermal lobule mossy fibers in granule cell glomeruli within the cere­ excitatory activity reaching vestibular neurons via fasti­
IX (uvula), vermal and hemispheric parts of lobule X bellar cortex. Tertiary vestibular afferents reach vermal giovestibular pathways, an example of disfacilitation.
(nodulus and flocculus, respectively), and vermal lobule lobules IX and X as climbing fibers derived from sub­
I/II (lingula)—phylogenetically ancient regions that regions of the medial accessory olive (beta subnucleus
are therefore referred to both as archicerebellum and dorsomedial cell column). These olivary nuclei FUNCTIONAL CONSIDERATIONS
and vestibulocerebellum. The vestibular system is
also related to the paleocerebellum (spinocerebellum) receive inhibitory input from the parasolitary nucleus The vestibular system is critical for the control of eye
through its connections with anterior lobe vermis and that, in turn, receives projections from the labyrinth. movements for orientation in intrapersonal and extra­
the fastigial nucleus. The olivocerebellar terminations are arranged in dis­ personal space and for control of the axial musculature,
VESTIBULOCEREBELLAR PROJECTIONS crete parasagittal zones, relaying information from the essential for balance. Vestibulocerebellar connections
There are five peripheral vestibular end organs; the vertical and anterior semicircular canals. provide the cerebellum with a topographic map of
cristae in the three orthogonally oriented semicircular space, serving as an anatomic substrate for modulation
canals detect movement in the sense of angular rotation of postural reflexes evoked by vestibular and optoki­
in the horizontal, pitch, and roll planes, and the maculae CEREBELLOVESTIBULAR PROJECTIONS netic stimulation. The vestibulocerebellum predicts
in the two otoliths that sense the effect of the linear
acceleration of gravity during roll-tilt (utricle) and pitch Projections from vermal and hemispheric parts of spatial environments and, by modulating the amplitude
(saccule). lobules IX and X are directed to all the vestibular nuclei. of movements produced by reflexes such as the
The anterior lobe vermis projects to the fastigial vestibulo-ocular reflex, compensates for head move­
Vestibular afferents from these end organs combine nucleus, and in addition, Purkinje cells in zone B of the ments to optimally guide behavior. The clinical rele­
in the vestibular nerve. One branch terminates in the anterior vermis project directly to the part of the lateral vance of these vestibulocerebellar circuits is exemplified
ipsilateral cerebellar cortex, providing profuse primary vestibular nucleus that is devoid of vestibular afferents by the loss of plastic changes in the horizontal vestibulo-
vestibular afferents from otoliths to vermal lobule IX and gives rise to the lateral vestibulospinal tract. Strong ocular reflex in individuals with damage to lobule X
and from semicircular canals to vermal lobule X. The topographically arranged projections to the vestibular (flocculus) and by the inability to remember postural
other branch terminates with varying degrees of inten­ nuclei are also derived from the fastigial nucleus. The adjustments to a previously maintained head position in
sity in different subregions of all four vestibular nuclei: rostral fastigial nucleus, linked with the spinal recipient space after damage to the vermal lobules IX and X.
medial, lateral, superior, and inferior. These nuclei, anterior vermis, projects to the medial, superior, and Acute injury to the vestibular system produces violent
with the exception of the posterior part of the lateral perihypoglossal nuclei. The caudoventral region of the nausea, vomiting, and vertigo. The paleocerebellum
vestibular nucleus (Deiters nucleus), provide choliner­ fastigial nucleus, devoted to oculomotor control, proj­ receives a modest amount of vestibular afferent input
gic secondary vestibular afferents bilaterally to the ects to the inferior vestibular nucleus and to the part of but extensive input from spinocerebellar tracts. The
vermal and hemispheric regions of lobules IX and X the lateral vestibular nucleus that receives zone B corti­ principal action of the paleocerebellum on the vestibu­
cal inputs. The projections of the rostral portion of the lar system is to regulate vestibular activity in relation to
fastigial nucleus are ipsilateral, whereas fibers from the proprioceptive and exteroceptive information about the
caudal fastigial nucleus cross in the hook bundle of head, trunk, and extremities. This is critical for posture,
Russell to excite contralateral vestibular neurons. Thus balance, and equilibrium.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 189

Plate 8-12 Brain: PART I

Cerebellum Modular CEREBELLUM MODULAR ORGANIZATION
Organization
Cuneate nuclei Solitary nucleus and tract
The cerebellar cortex and deep cerebellar nuclei (DCN) Dorsal motor nucleus of X
are linked anatomically in multiple repeating, parasagit­
tally arranged, and histochemically identifiable cortico- Choroid plexus
nuclear microcomplexes. These channel Purkinje cell (PC)
axons from longitudinal PC zones to focal regions Level of section Fourth ventricle
within the DCN. The zonal organization is reflected
also in the connections of the inferior olive with the Inferior cerebellar peduncle Nucleus CN XII
cerebellar cortex and DCN. Cerebellar zones are further
divided into microzones about 0.5╯mm wide (four to Spinal nucleus and tract, CN V
five PCs), extending many millimeters rostrocaudally.
Monoclonal antibody stains show alternating zebrin- CN X
positive and -negative stripes in the cortex that correlate Spinothalamic/
with corticonuclear and olivocerebellar connections. spinoreticular tract Medial longitudinal fasciculus

CEREBELLAR CORTICONUCLEAR Nucleus ambiguus CN XII Tectospinal tract
PROJECTION Principal olivary nucleus Pyramid Medial lemniscus
Output from the cerebellar cortex to the DCN is Dorsal accessory olivary nucleus Medial accessory olivary nucleus
derived exclusively from PCs and is inhibitory. The
vermis projects to the fastigial nucleus, the intermediate Hemispheric A X B C1 C2 Color-coded diagram of cat
cortex project to globose and emboliform nuclei, and lobules C3 parasagittal zonal arrangement of
lateral hemispheres project to the dentate nucleus cerebellar cortical connections
(DN). There is a reciprocal excitatory projection of the I-V I-V D1 (zones A through D2) with the
DCN neurons back onto the PCs (Plate 8-5). Y deep cerebellar nuclei and with
Coronal section through adult rat D2 the inferior olivary nuclear
INFERIOR OLIVARY NUCLEUS cerebellum immunostained for VI VI complex. Adapted from Voogd J.
This nuclear complex is a folded sheet of 1.5 millions VII
neurons in the medulla, situated between the pyramidal zebrin I shows Purkinje cells Crus I A2 Cerebellar zones - a personal history.
tract and the lateral reticular nucleus. The medial aligned in parasagittal bands in
accessory olive (MAO) and the dorsal accessory olive vermis and hemispheres Reprinted Crus II Cerebellum 2001; 10: 334-350.
(DAO) each have rostral and caudal components. The
principal olive (PO) has dorsal, lateral, ventral, and with permission from Leclerc N, Doré L, Deep cerebellar nuclei:
medial lamellae. Other subnuclei include the beta cell VIII F (fastigial)
group, dorsomedial cell column (DMCC), and dorsal Parent A, Hawkes R. The compartmentalization VIIIA
cap of Kooy. Proximal dendrites of olivary neurons have of the monkey and rat cerebellar cortex. AI (anterior interposed)
appendages that form the central core of a complex VIIIB
synaptic structure, the olivary glomerulus. These have Brain Res 1990;506:70.
gap junctions enabling electrotonic coupling between
groups of olivary neurons. Each olivary axon provides IX PI (posterior interposed)
7 to 10 climbing fibers to the cerebellar cortex and IX Dr (rostromedial dentate)
DCN; one CF per PC (see Plate 8-6). XX Dc (caudoventral dentate)
Minor nuclei:
OLIVARY AFFERENTS AND PROJECTIONS DLP ICG (interstitial cell group)
TO CEREBELLUM AI DLP (dorsolateral protuberance)
The olive receives multiple excitatory afferents, sends
excitatory CFs to discrete longitudinally oriented para­ F Dr Vest (vestibular nuclei)
sagittal microzones in the cerebellar cortex, and sends ICG PI Dc LV (lateral vestibular nucleus)
collaterals to focal areas within the DCN that are linked
to PCs in that cortical microzone. Olivary neurons LV Inferior olivary nuclear complex:
receive inhibitory feedback projections from those vest Dorsal PO (principal olive)
DCN neurons to which they project, forming a closed- Ventral lamina MAO (medial accessory olive)
loop system. Transverse section through anterior lamina DMCC (dorsomedial cell column)
lobe of monkey cerebellum stained
Spinal cord projections are conveyed directly to the for acetylcholinesterase shows DMCC r r DC (dorsal cap)
MAO and DAO in the crossed ventral spino-olivary parasagittal compartments within DAO (dorsal accessory olive)
tracts (SOT) and indirectly in the dorsal SOT that the white matter, from zone A
ascends in the ipsilateral dorsal column, synapses in the medially to zone D2 most laterally int Beta c r: rostral
gracile and cuneate nuclei, decussates to the contralat­ c DAO int: intermediate
eral olive, and decussates again in the olivocerebellar Reprinted with permission from Voogd J, c: caudal
projection, terminating in the cerebellum ipsilateral to Paxinos G, Mai JK. The human nervous system. DC
its spinal cord origin. Spino-olivary fibers terminate in London: Academic Press; 1990.
primary and secondary arm and leg representations in MAO PO
the spinocerebellum (zones A through C3).
â•…
The trigeminal sensory nucleus projects to the caudal
MAO and rostromedial DAO; these project to lobule VI in zones C1 and C3, with collaterals to the emboli­ DMCC and nucleus β to vermal and hemispheric
form nucleus. regions of lobules IX (uvula, paraflocculus) and X
(nodulus and flocculus).
Cerebral cortex projections are conveyed to the olive
and cerebellum via the parvocellular component of the Visual information from superior colliculus is relayed
red nucleus (RNpc). Primary motor and premotor cere­ through the caudal MAO to the vermal visual area in
bral cortex are linked somatotopically with the caudo­ lobule VII and fastigial nucleus. Other afferents origi­
lateral RNpc; this projects to the PO dorsal lamina and nate in midbrain regions concerned with oculomotor
bend, which sends efferents to the lateral cerebellar D2 control (nuclei of Darkschewitsch, Cajal, Edinger-
zone and dorsomedial dentate nucleus (paleodentate) Westphal, perihypoglossal) and are conveyed to vermal
and to the rostral MAO that targets cerebellar zone lobules IX and X. The lateral reticular nucleus, periaque­
C2 and the globose nucleus. Frontal eye fields, premo­ ductal gray, and zona incerta convey motor, nociceptive/
tor, and prefrontal areas project via the dorsomedial autonomic, and associative information to the olive.
RNpc and the PO ventral lamina to the medial cerebel­
lar D1 zone and the caudoventral dentate nucleus Together with their connections with the inferior
(neodentate). olive, the corticonuclear microcomplexes comprise cer­
ebellar modules that are also linked with pontine and
Optokinetic information from pretectal nuclei, includ­ other afferents and efferents. The paracrystalline archi­
ing the nucleus of the optic tract and accessory optic tectural uniformity of the modules likely supports a
nuclei, is conveyed to the dorsal cap and the ventrolat­ neural computation, the universal cerebellar transform,
eral outgrowth, and relayed to lobule X (flocculonodu­ common to all cerebellar areas, which can be applied to
lar lobe). multiple domains of neurologic function by virtue of
the precise connections of each module with extracer­
Vestibular information is conveyed to vestibular nuclei, ebellar structures.
including the parasolitary nucleus, which project via

190 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

P late 8-13 Cerebellum and Ataxia

Cerebrocerebellar CEREBROcEREBELLAR CONNECTIONS
Connections
Functional connectivity MRI mapping in the human cerebrocerebellar system

Cerebral cortex Cerebral cortex
(left hemisphere)
There are massive, reciprocal, topographically arranged
connections between the cerebral cortex and the cere­ Projection to Ipsilateral
bellum. Each cerebral hemisphere communicates pre­ ipsilateral (left) (left)
dominantly with the contralateral cerebellar hemisphere. pontine nuclei thalamus
The cerebrocerebellar circuit has a two-stage feed-
forward limb and a two-stage feedback limb. Ipsilateral Contralateral (right) SCP
corticopontine projections originate in cortical layer Vb decussates in midbrain
in sensorimotor areas as well as association and limbic-
related cortices concerned with cognition and emotion Decussation in right MCP Contralateral (right) IV
(posterior parietal, superior and middle temporal, dor­ cerebellum V
solateral and medial prefrontal and cingulate areas, and Corticopontocerebellar circuit in the monkey
posterior parahippocampal gyrus). Corticopontine pro­ (from anatomic tract tracing studies) Functional networks Cr I VI
jections terminate around neurons in the basis pontis. Visual Cr II
Pontocerebellar pathways decussate in the middle cer­ Cerebral cortical regions Sensorimotor
ebellar peduncle, conveying corticopontine afferents Basis pontis Dorsal attention VIIB X
to the contralateral cerebellum. Feedback to cerebral Upper Ventral attention VIIIA VIIIB IX
cortex is via crossed cerebellothalamic projections in Limbic
the superior cerebellar peduncle, and ipsilateral thala­ Frontoparietal VI V
mocortical projections to cortical areas from which the Default mode Cr I
feed-forward projections arose, thereby completing the
closed-loop systems. Middle Cerebellar terminations via thalamus Cr II VIIIB IX
Lower identi ed to date VIIB VI
In the cerebral peduncle, prefrontal fibers are most ( attened map)
medial, sensorimotor fibers intermediate, and fibers VIIIA
from the parietal, temporal, and occipital lobes are
lateral. In the monkey, terminations in the pons from Cr I
motor and association areas are topographically
arranged. The caudal pons preferentially receives senso­ Cr II VIIIA VIIIB
rimotor inputs and projects mostly to the cerebellar VIIB
anterior lobe and lobule VIII, containing primary and
secondary sensorimotor representations, respectively. Functional topography in the human cerebellum Right arm sensorimotor
Dorsolateral pons projects to visual areas in the vermal (derived from functional MRI) Executive / working memory
and hemispheric lobule IX. Medial parts of the rostral
pons project to crus I. Medial, anterior, and lateral pons IV V Language
project to crus II. By way of these projections, lobules Spatial
III through V of the anterior lobe and lobule VIII VI Limbic
receive sensorimotor afferents. In contrast, much of VI V VI VI VI
lobule VI, crus I and crus II of lobule VIIA, and lobule Cr I Cr I
VIIB receive inputs from association areas and limbic- VI Cr I Cr I
related regions of the cerebral cortex. L
Cr II R L Cr II R IX L Cr II R Cr II
Clinicopathologic studies in patients show that speech VIIB VIII VIIB VIII VIIB
is represented medially in the rostral pons, hand coordi- VIIB VIIB
nation medially and anteriorly in the rostral and
midpons, the arm anteriorly and laterally to the hand, Adapted from Schmahmann JD, Pandya DN. The cerebrocerebellar system. Int Rev Neurobiol 1997;41:31-60. Kelly RM, Strick PL. Cerebellar loops with
leg coordination mostly laterally in the caudal pons, and motor cortex and prefrontal cortex of a nonhuman primate. J Neurosc 2003;23:8432-8444. Middleton FA, Strick PL. Cerebellar output channels.
gait is distributed in medial and lateral locations Int Rev Neurobiol 1997;41:61-82. Buckner RL, Krienen FM, Castellanos A, Diaz JC, Yeo BT. The organization of the human cerebellum estimated by intrinsic
throughout. functional connectivity. J Neurophysiol 2011;106:2322-2345. Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis
of neuroimaging studies. NeuroImage 2009;44:489-501. Stoodley CJ, Valera EM, Schmahmann JD. Functional topography of the cerebellum for motor and
In the feedback system, primary motor cortex receives cognitive tasks: an fMRI study. NeuroImage 2012;59:1560-1570.
projections via thalamus from dorsal parts of the dentate â•…
nucleus and caudal portions of the anterior interpositus
nucleus, where neurons activate with arm movement. lobe and adjacent parts of lobule VI; the secondary hemispheres; lobule VI with a salience network; and
Premotor cortex receives input from midÂr

P late 8-14 Brain: PART I

Cerebellar Motor Brainstem and/or cerebellar manifestations
Examination

Cerebellar incoordination is characterized by disturbed Wide-based gait. Exaggerated,
rate, rhythm, and force of movements. This manifests Patient teeters repetitive
as impaired oculomotor control; articulation (dysar­ back and forth knee jerk.
thria); stance, equilibrium, and gait (ataxia); and motion and sideways.
of the limbs (dysmetria). Severity of involvement can be Finger-to-nose test.
graded using ataxia rating scales. Patient cannot direct
finger accurately.
Eye Movements. Cerebellar lesions produce unsteady
ocular fixation in primary position, microsaccadic oscilla- Patient cannot move Action tremor.
tions, square wave jerks, ocular flutter, ocular bobbing, heel down shin evenly. Hand unsteady on
and opsoclonus. Pursuit eye movements show saccadic attempting to hold
intrusions—jerkiness following a moving target. glass, write, etc.
Volitional gaze (saccades) is hypermetric (overshoot)
or hypometric (undershoot/catch-up). Gaze-evoked, Acute cerebellar lesions produce headache, nausea, vomiting,
direction-beating nystagmus has a fast phase in the and vertigo, along with gait ataxia, dysarthria, and sometimes
direction of eccentric gaze and slow phase in the oppo­ diplopia. Hiccups and tinnitus may also occur.
site direction. Downbeat nystagmus in primary gaze
points to lesions of the cervicomedullary junction, â•…
upbeat nystagmus to midline lesions or drug toxicity.
testing; the patient brings the index finger to his/her wheelchair-bound patients, the heel is brought to the
The vestibulo-ocular reflex (VOR) maintains visualized nose and then to the examiner’s finger held steady at knee of the opposite leg held parallel to the ground.
image stabilization on the retina during head move­ arm’s length. Tremor increases with proximity to the Proximal overshoot occurs as the heel is placed on the
ment. With passive trunk and head rotation while target; tremor direction is generally perpendicular to knee, and tremor occurs as the heel is maintained in
focusing on his or her own hand, the patient’s eyes direction of movement. The finger chase/mirror test that position. Slowing, jerking, or side-to-side move­
should not move relative to the head. Failure of this measures overshoot/undershoot. The patient points to the ments are noted as the heel moves down the shin. In
VOR cancellation from lesions of the vestibulocerebel­ examiner’s finger held at arm’s length, following his/her the draw-a-circle test, the supine patient traces a circle
lum manifests as saccadic eye movements. sequential moves horizontally and vertically. Dysdiado- in the air; decomposition manifests as irregular or
chokinesia is degradation of rapid alternating move­ chaotic motions.
Slowing of eye movements leading to ophthalmoplegia ments, tested by forearm pronation/supination. Tapping
occurs in spinocerebellar ataxias and mitochondrial dis­ the index finger on the crease of the thumb assesses fine Cerebellar tremor is large amplitude, 2 to 3╯Hz, and
orders. Patients with oculomotor apraxia cannot direct motor control. Dysrhythmia is an inability to generate may involve many body parts. Rubral tremor from red
gaze voluntarily and perform head thrusts to initiate normal rhythms, assessed by rapidly tapping the hand nucleus lesions and its connections involves multiple
these movements. on a surface or the heel on the ground. joints, direction changes, and is frequently rotatory.
Palatal tremor is slow and semirhythmic, resulting
Speech/Swallowing. Cerebellar dysarthria is The heel-to-shin test, performed with the patient from Guillain-Mollaret myoclonic triangle lesions of
described as “scanning speech.” Syllables are poorly artic­ supine, assesses leg coordination. The heel is placed on this neuronal brainstem/cerebellum network (dentate
ulated, cadence is slowed and irregular, and rapid or the opposite knee and moved down the shin. In nucleus to red nucleus and inferior olivary nucleus).
alternating buccal, palatal, and lingual consonants are
degraded. Dysarthria is compounded by deficient
volume control. Ataxic respiration affects quality of
speech. Impaired control of muscles of deglutition leads
to dysphagia and aspiration risk.

Motor Control. Resting tone in pure cerebellar
disease is generally decreased, or hypotonic. There may
be a spastic catch or frank spasticity when spinal cord
pathology is also present in some inherited ataxic dis­
orders. Cerebellar lesions do not produce weakness, but
there may be slowed initiation and generation of force.
Truncal ataxia occurs with midline lesions, including
titubation, that is, oscillations of the head and trunk.
The patient has a widened stance and is unable to stand
in tandem position or on one foot. Cerebellar ataxic gait
is staggering, uneven, irregular, and veers from side to
side. Unilateral lesions cause stumbling toward the
affected side.

Coordination of Arms and Legs. Dysmetria (Greek
dys, and metron [measure]) is the disordered ability to
regulate, judge, and control behavior, both with motor
and cognitive domains (see Plate 8-15). The cerebellar
motor syndrome causes difficulty judging distances,
trajectory of intended movements, and force required
for movements. Compound movements (across more than
one joint) are particularly affected. Visual guidance
improves outcome minimally.

Postural tremor is assessed with arms extended in pro­
nated position. Rebound is tested by the examiner dis­
placing the arm downward, observing for overshoot
above the starting point. Dysmetria characteristics
include end-point tremor, overshooting targets (hyper­
metria) or undershooting (hypometria), and oscillation
at the elbow. These are assessed with finger-to-nose

192 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

P late 8-15 Cerebellum and Ataxia

CEREBELLAR COGNITIVE AFFECTIVE SYNDROME

Cerebellar Cognitive CCAS Following Tumor Resection in Adult Post-Infectious Cerebellitis
Affective Syndrome Following Epstein-Barr
Virus Infection

The cerebellum is organized into a primary sensorimo­ MRI after resection
tor region in the anterior lobe and adjacent part of of ganglioglioma
lobule VI and a second sensorimotor region in lobule
VIII. Current evidence indicates that cognitive and limbic Patient writing sample Patient clock drawing reveals Patient’s copy of Rey diagram
regions are in the posterior lobe (lobule VI, lobule VIIA demonstrates agrammatism impaired visual-spatial showing poor visual-spatial
[which includes crus I and crus II], and lobule VIIB); (”twenty 3rd”), perseveration strategy and execution planning
lobule IX may also be part of this network. Cognitively (”the the”), and disinhibition
relevant areas are situated more laterally in these lobules, (underlining)
whereas the limbic cerebellum is represented in the
vermis. Lesions of the sensorimotor cerebellum result CCAS Following Resection of Left Cerebellar Cystic Astrocytoma in Child
in the cerebellar motor syndrome (see Plate 8-14).
Lesions of the cognitive and limbic cerebellum lead to Copy Immediate Delayed
the cerebellar cognitive affective syndrome (CCAS). This recall recall
constellation of deficits is characterized by impairments
in (1) executive function, (2) visual spatial processing, Severely impaired Rey diagrams
(3) linguistic deficits, and (4) affective dysregulation. CCAS Following Cerebellar Infarction
The CCAS occurs in adults and children after many
types of injury. It can be prominent after acute lesions, Axial and parasagittal MRI showing bilateral Perseverative copying
including stroke, hemorrhage, and infectious or postin­ PICA and left SCA infarcts respectively of a two-loop diagram
fectious cerebellitis but relatively subtle in late-onset
hereditary ataxias. From Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain 1998;121 (Pt 4):
561-579; and Levisohn L, Cronin-Golomb A, Schmahmann JD. Neuropsychological consequences of
Executive function deficits include problems with cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric
working memory, as tested with reverse digit span; population. Brain 2000;123 (Pt 5):1041-1050.
mental flexibility is tested using tasks of set shifting;
and perseveration is demonstrated using bedside tests â•…
of mental control. Patients may have concrete thinking,
poor problem-solving strategies, and impaired ability to Early evidence indicates that there are five domains nonmotor manifestations of cerebellar lesions can lead
multitask, with trouble planning, sequencing, and orga­ of behavioral dysregulation caused by cerebellar damage. to earlier diagnosis of cerebellar damage and facilitate
nizing their activities. These are impairments of attentional control, emo­ treatment of cognitive emotional consequences of dis­
tional control, autism spectrum disorders, psychosis rupted cerebellar modulation of higher function. The
Mental representation of visual spatial relationships spectrum disorders, and difficulties with the social skill nature of these deficits provides new avenues for con­
can be impaired. Visuospatial disintegration is apparent set. Within each of these domains, there are hypometric/ ceptualizing mental illnesses, including autism, schizo­
when attempting to copy or recall visual images. Iden­ diminished behaviors and hypermetric/exaggerated phrenia, bipolar disorder, attention deficit disorder,
tification of multiple features within a complex diagram behaviors, consistent with the dysmetria of thought and dyslexia. Appreciating the role of the cerebellum
(simultanagnosia) is difficult. theory of the cerebellar role in nervous system beyond motor control therefore has implications for
function. understanding and improving neuropsychiatric disor­
Expressive language can be abnormal, characterized by ders. This represents a radical departure from our pre­
long response latency, brief responses, reluctance to The intellectual and emotional impairments from vious understanding of the functions of the “little
engage in conversation, and word-finding difficulties. damage to the cognitive and limbic posterior lobe of brain” and is an area of active investigation in neurosci­
Verbal fluency is decreased affecting phonemic (letter) the cerebellum may be more disabling than motor defi­ ence. The neural substrates that support this nonmotor
more than semantic (category) naming. Mutism occurs cits, and when the anterior lobe is spared, these occur cerebellar role are discussed in Plate 8-13.
postoperatively for vermis tumors, particularly in in the absence of the motor syndrome. Recognizing the
children but also in adults subsequent to cerebellitis,
infarction, and hemorrhage. Speech may have abnormal
syntax, resulting in agrammatism. Degraded control of
volume, pitch, and tone can produce high-pitched, hypo-
phonic speech.

Short-term memory impairments include difficulty
learning and spontaneously recalling new information,
reflecting deficient strategies for organizing verbal or
visual-spatial material for encoding, and difficulty locat­
ing information in memory stores. Successful recall is
aided by a structured approach to the task, using clues
and other prompts. Conditional associative learning is
degraded, as shown in studies of classic conditioning
in cerebellar patients (as well as in animals). Mental
arithmetic is impaired. Ideational apraxia and hemi-
inattention have been reported.

The affective component of the CCAS occurs when
lesions involve the limbic cerebellum in the vermis and
fastigial nucleus. Patients exhibit difficulty modulating
behavior and personality style, have flattened affect or
disinhibition manifesting as overfamiliarity, and flam­
boyant or impulsive actions. Behavior may be regressive
and childlike, sometimes with obsessive-compulsive
traits. Patients can be irritable, with labile affect and
poor attentional and behavioral modulation. Acquired
panic disorder is described in this setting as well.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 193

P late 8-16 Brain: PART I

Cerebellar Disorders— *
Differential Diagnosis
Cerebellar hypoplasia. Underdeveloped cerebellum Idiopathic late onset cerebellar ataxia. Cerebellar volume
Diagnosing the cause of a cerebellar disorder can be seen on T2-weighted coronal MRI, with prominent loss with small vermis and prominent fissures seen on mid-
straightforward or require sleuthing and special tests. fissures (arrows) and fourth ventricle (asterisk). sagittal T1 MRI. The pons is largely spared.
The following principles guide the approach: (1) recog­
nize symptoms and signs of cerebellar disease; (2) deter­
mine whether peripheral nerves, spinal cord, brainstem,
or cerebral hemispheres are also affected; (3) character­
ize the timing of onset and progression, that is, the
temporal profile; (4) search for risk factors, that is, toxins
and drugs, recent infections, and systemic features of
neoplasms; (5) document family history and country of
origin, a critical feature when considering hereditary
disorders; (6) brain magnetic resonance imaging is essen­
tial; and (7) laboratory data may clinch the diagnosis.

ACUTE—MINUTES TO HOURS Cerebellar stroke. Acute infarction (arrow) in the Spinocerebellar ataxia type 2. Cerebellar volume loss and
Ischemic stroke and hemorrhage start abruptly. Both territory of the superior cerebellar artery seen on mild pontine volume loss seen on mid-sagittal T1 MRI.
worsen clinically over hours if cerebellar edema devel­ axial diffusion-weighted MRI.
ops. Note the “posterior fossa mantra” of acute cerebellar
and brainstem injury—headache, nausea, vomiting, and *
vertigo, with or without ataxia, dysarthria, diplopia, and
nystagmus. Neurologic examination lateralizes to side
of injury.

Acute cerebellitis occurs more commonly in children
than adults, starting more abruptly than postinfectious
cerebellitis; both produce a pancerebellar syndrome.

Thiamine deficiency produces Wernicke encephalopathy,
a triad of ataxia, confusion, and oculomotor distur­
bances that is a medical emergency requiring immedi­
ate repletion of vitamin B1.

SUBACUTE—DAYS TO WEEKS Multiple system atrophy, cerebellar type (MSAc). Axial T2 (left) and mid-sagittal T1 MRI (right), showing prominent
Paraneoplastic immune-mediated Purkinje cell attack from cerebellar volume loss including the white matter, enlarged fourth ventricle (asterisk), and marked pontine volume
remote tumors (lung, breast, ovary) may develop acutely loss with hot-cross-bun sign (arrow).
over days, producing a pancerebellar syndrome. â•…

Cerebellar tumors (benign or malignant) worsen over are more than 35 SCAs (NIH website - GeneTests, Hereditary spastic paraplegias are AD or AR. Myelopa­
weeks to months but occasionally present acutely with www.ncbi.nlm.nih.gov/sites/GeneTests). thy may be accompanied by ataxia and dysmetria.
obstructive hydrocephalus.
Episodic ataxias (EA) are AD. EA1, a potassium chan- Mitochondrial encephalomyopathies cause ataxia and
Other focal lesions include abscesses, multiple scle­ nelopathy starts in childhood, producing brief duration complex clinical constellations. Most are AR or obey
rosis, progressive multifocal leukoencephalopathy ataxic episodes and myokymia. EA2 is a calcium chan- mitochondrial maternal inheritance. Mitochondrial reces-
(PML), and rhombencephalitis. Alcoholic cerebellar nelopathy; attacks last for days, sometimes with migraine. sive ataxia syndromes (MIRAS) caused by mutations in
atrophy (anterior superior vermis) may present sub­ The gene causing EA2 is associated with familial hemi­ polymerase gamma cause ataxia, neuropathy, and hear­
acutely, as can cerebellar leukoencephalopathy from plegic migraine and SCA6. Both EAs improve with ing loss, particularly in Scandinavian families. Fragile
inhaled solvents and heroin, and Creutzfeldt-Jakob acetazolamide. X–associated tremor ataxia syndrome is an X-linked poly­
disease, with ataxia, dementia, and myoclonus. glutamine disorder causing ataxia, tremor, cognitive
Autosomal recessive disorders (AR) manifest in one failure, and erectile dysfunction.
INSIDIOUS, CHRONIC PROGRESSION— generation, usually in childhood. Parents are asymp­
MONTHS TO YEARS tomatic; nonsibling family history is unrevealing. Fried- Sporadic ataxias include multiple system atrophy, a
Neurodegenerative disorders start insidiously, progress­ reich ataxia is the most common AR cerebellar disorder, synucleinopathy with cerebellar ataxia or parkinson­
ing over years or decades. Autosomal dominant (AD) with ataxia, peripheral neuropathy, cardiomyopathy, ism, autonomic dysfunction (postural hypotension,
ataxic disorders pass down through generations. AD scoliosis, and diabetes. Hearing and visual impairment erectile dysfunction, urinary incontinence), and rapid
spinocerebellar ataxias (SCAs) typically manifest during occur late. Occasionally, it begins in adulthood, resem­ eye movement (REM) sleep behavior disorder. Idio-
adulthood. SCA 1 and SCA 3 have extrapyramidal, bling SCAs. Ataxia telangiectasia often manifests before pathic late-onset cerebellar ataxia (ILOCA) describes
corticospinal and peripheral nerve lesions. SCA 2 has telangiectasias develop; features include recurrent adults older than 50 years with isolated cerebellar
slowed eye movements, and extrapyramidal features in infections from immunoglobulin IgA deficiency and degeneration.
younger patients. SCA 3 is prevalent in Portuguese radiation sensitivity with risk of neoplasia. Ataxia with
Azorean communities; younger patients have dystonia. oculomotor apraxia types 1 and 2 include peripheral Isolated downbeat nystagmus points to lesions at the
SCA 5 and 6 are purely cerebellar. SCA 7 has visual neuropathy, choreiform movements, and cognitive cervicomedullary junction or lobules IX/X. Rarely, this
failure from rod-cone macular dystrophy. SCA 8 difficulties. French Canadians experience AR cerebellar heralds a neurodegenerative disorder. Palatal tremor
includes mild chorea. SCA 10 occurs associated with ataxia (ARCA) type 1 progressing over decades and AR occurs with SCA 20.
epilepsy in families with Native American ancestry. SCA spastic ataxia of Charlevoix-Saguenay starting in child­
17 resembles Huntington disease, with cognitive fail­ hood. ARCA-2 (ataxia with coenzyme Q10 deficiency) and Many disorders of infancy and childhood have
ure and choreoathetosis. Dentatorubropallidoluysian ataxia with vitamin E deficiency are treatable. cerebellar malformations or disruptions—hypoplasia,
atrophy causes myoclonus, dystonia, and cognitive agenesis, megacerebellum, Chiari, and Dandy-Walker
decline; it is uncommon outside Japan. Currently, there malformations.

194 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

P late 8-17 Cerebellum and Ataxia
B
A

Stage 1 Parkinson Stage 2 Parkinson Stage 3 Parkinson Typical wide-based
disease: unilateral disease: bilateral involve- disease: pronounced gait of alcohol intoxication
involvement; blank ment with early postural gait disturbances and
facies; affected arm changes; slow, shuffling moderate generalized
in semiflexed gait with decreased disability; postural
position with tremor; excursion of legs instability with
patient leans to tendency to fall
unaffected side

Gait Disorders—Differential CD EF
Diagnosis
Left hemiparesis with Wide-based gait of midline Apraxic gait of Characteristic posture in
Gait is a complex neurologic function that can be decreased arm swing cerebellar tumor or other lesion normal-pressure left-sided lower lumbar
degraded by lesions at multiple points in the nervous sometimes associated hydrocephalus disc herniation
and musculoskeletal systems. Identifying the location of with limited sensation
pathology is essential to establishing the diagnosis. secondary to a cortico-
Elicitation of the history is followed by observation of spinal tract lesion
the gait, which facilitates hypothesis-driven examina­
tion. Focused imaging and laboratory investigations â•…
confirm or refute the clinical impression.
or plexopathies produce weakness in multiple myo­ Cerebellum. Cerebellar gait is wide based, veers from
Muscle. Myopathy is proximally predominant in tomes, unilaterally or bilaterally, affecting walking. side to side, with a lurching, irregular cadence, and
inflammatory myopathies, steroid myopathy, and extra steps when turning or making sudden moves. The
Duchenne and limb girdle dystrophies. Waddling gait Spinal Cord. With myelopathies, lower-extremity earliest sign is inability to walk in tandem. Late-stage
results from dropping of the pelvis. Patients have dif­ hypertonicity causes spastic gait, scissoring (legs tending cerebellar disease destroys truncal stability, making
ficulty ascending stairs, arising from chairs, or arising to cross each other), stiff-legged motions, minimal knee gait impossible without a walker or bilateral support.
from a seated position on the floor. flexion, and circumduction. Strength may be pre­ Unilateral cerebellar lesions produce stumbling and/or
served. Reflexes are exaggerated with extensor plantar ipsilateral falling. Strength is preserved.
Neuromuscular Junction (NMJ). Of the various responses, but the jaw jerk is normal.
NMJ disorders Lambert-Eaton myasthenic syndrome
(LEMS) is most likely to present with a gait disorder.
Climbing stairs and arising from a chair is impaired.
Typically, myasthenia gravis presents with ocular symp­
toms; gait dysfunction usually does not occur until gen­
eralization later in the course. Both NMJ disorders
worsen with exertion.

Peripheral Nerve. Peroneal nerve palsy produces
foot drop because of tibialis anterior muscle weakness.
The leg is lifted high; the foot does not dorsiflex and is
slapped down with the ball of the foot hitting the
ground first. Femoral neuropathies affect the quadri­
ceps muscles, causing weakness or buckling when navi­
gating stairs, particularly descending as the quadriceps
needs to lock to support the after-coming leg.

Generalized peripheral neuropathies are symmetric
and length dependent, causing foot slapping because of
distal weakness and sensory deafferentation, particu­
larly proprioceptive impairment. The proprioceptive
loss contributes to increased difficulties in darkness; the
Romberg test is positive. Muscle stretch reflexes are
diminished or absent. Lumbosacral polyrÂ

P late 8-18 Brain: PART I
G HI

Patient walks gingerly due to Patient with lumbar spinal Patient with peripheral neuropathy
loss of position sense and/or stenosis with forward-flexed gait and loss of proprioception
painful dysesthesia
JK L

Gait Disorders—Differential
Diagnosis (Continued)

Brainstem. Ataxic hemiparesis results from lesions in Sudden occurrence of
the basis pontis, midbrain, thalamus, and corona radiata, foot drop while walking
involving corticospinal and cerebrocerebellar circuits. (peroneal nerve)
Mild weakness is accompanied by true cerebellar dys­
metria and dysrhythmia. The affected leg circumducts, Typical spastic gait, Severe myopathy or NMJ N
with inaccurate foot placement. scuffing toe of lesion with proximal
affected leg weakness
Basal Ganglia. Extrapyramidal movement disorders
affect gait, depending on the interplay of inhibition and M
disinhibition within the basal ganglia circuitry. Parkin­
sonian syndromes characteristically have small shuffling Sudden buckling of knee Muscle cramps from defect in energy
steps at initiation of stride and through all gait phases, while going down stairs metabolism (McArdle disease)
stooped posture, and festination, with the anteriorly (femoral nerve)
displaced center of gravity pulling the patient forward.
The patient festinates from one stationery object to â•…
another to prevent escalation of speed. Resting tremor
occurs in Parkinson disease (see Plate 7-4), anteflexed extension and the arm in flexion. The leg circumducts spine or disc disease, and podiatric conditions (bunions,
neck in multiple system atrophy, absent vertical gaze in because of poor flexion at the hip and knees. The tenosynovitis, neuromas).
progressive supranuclear palsy (see Plate 7-7), and limb plantar-flexed foot may have clonus, producing a
apraxia in corticobasal degeneration (see Plate 7-7). bouncing quality to the gait. Gait is sometimes irregular in primary psychiatric dis-
Chorea, dystonia, and athetosis characterize Hunting­ orders, with stereotypies and mannerisms or extrapyra­
ton disease (see Plate 7-13); dyskinesias occur with Non-neurologic Disorders. Elderly persons sometimes midal features from chronic psychotropic medications.
dopaminergic excess in treated Parkinson patients; have a slow cautious gait, reflecting slowing of neural Psychogenic gait disorders (astasia-abasia) are varying
hemiballism is seen after subthalamic lesions and in conduction and concern to prevent falls. Non- and inconstant, contravening recognized neurologic
Tourette syndrome. neurologic disorders producing limp or insecure gait patterns; this diagnosis is best made by neurologists
include arthritis, trochanteric bursitis, lumbosacral after careful investigation.
Cerebral Cortex and White Matter. Frontal lobe gait
disorders (gait apraxia) secondary to subcortical small
vessel lacunar disease are characterized by a magnetic
quality, as if glued to the floor, or slipping clutch.
Patients have difficulty initiating stride, taking small
repetitive steps before launching a gait that looks almost
normal. After stopping, the attempt to restart repro­
duces the pattern. Confined spaces are particularly
troublesome.

Normal-Pressure Hydrocephalus (see Plate 8-17).
Normal-pressure hydrocephalus produces a similar gait
disorder, together with urinary dysfunction, cognitive
decline, and ventriculomegaly on imaging. Hemiparesis
from upper motor neuron lesions produces increased tone
in the contralateral limbs, with the leg maintained in

196 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

P late 8-19 Cerebellum and Ataxia
Dorsal and ventral spinocerebellar
Child with tracts (ataxia)
progressive
ataxia, wide Lateral corticospinal (pyramidal) tract
gait, scoliosis (loss of motor power)

Paradoxical Posterior columns (loss of
Babinski’s sign, with position sense) Posterior root
loss of knee jerk
ganglion

Sites of spinal cord degeneration
(and resultant functional deficits)

Pes cavus with talipes varus and claw toes Death often caused by cardiac abnormalities (interstitial myocarditis,
fibrosis, enlargement, arrhythmias, murmurs, heart block)

â•…

Friedreich Ataxia not affected overall, the speed of information process­ delayed FDRA onset, the GAA expansion is generally
ing is often slowed, with increasing difficulty in complex smaller (100-600 repeats), but factors such as genetic
Friedreich ataxia (FRDA; [Online Mendelian Inheri­ reasoning. Scoliosis is present in virtually all individu­ background and environmental influences are impor­
tance in Man {OMIM}: phenotype 229300; gene/locus als, requiring constant surveillance for progression, tant variables. FRDA is due to abnormal expansion
606829]) is a unique disorder involving expansion of a bracing to retard progress, and surgical intervention in (equal or different lengths) in both alleles of FXN in
trinucleotide repeat (GAA) in the first intron of the up to 20%. approximately 98% of cases. The remainder represents
relevant gene, frataxin (FXN), leading to loss of func­ individuals with abnormal expansion in one allele and
tion in the unstable frataxin protein. FRDA is autoso­ Systemic involvement is also prominent in the form a point mutation or deletion inactivating the gene in
mal recessive unlike other trinucleotide repeat disorders, of cardiomyopathy and progressive cardiac conduction the other allele. No individual has been described
which are typically autosomal dominant or X-linked. It defects (arrhythmia and heart block), representing lacking an expansion in at least one FXN allele.
differs from CAG repeat disorders (Huntington disease, the most common cause of death. In addition, diabetes
the spinocerebellar ataxias, and Kennedy disease), mellitus and glucose intolerance, requiring glucose Diagnosis of FDRA depends on assessment of FXN
wherein expansion occurs in the coding region, leading monitoring, occur in at least one third of patients. in blood by deoxyribonucleic acid (DNA) sequencing
to toxic gain of function by increasing content of glu­ methodology capable of detecting GAA expansion and
tamine in the relevant protein. Assessment of neurologic function involves neuro­ direct assessment of inactivating mutations of nonex­
imaging, clinical electrophysiology (electromyography panded regions for the small percentage with a point
FRDA is a progressive spinocerebellar disorder typi­ [EMG]), radiologic evaluation for scoliosis, and testing mutation or deletion. Carrier detection and prenatal
cally having prepubertal onset between ages 5 and 15 for visual and audiometric function. Magnetic reso­ diagnosis is recommended for individuals in a family
years, although exceptions occur, with up to 25% nance imaging (MRI) of cerebral hemispheres is with known disease-producing expansion. Frataxin is a
having delayed onset into adulthood. Because of spinal normal, but atrophy of the spinal cord, brainstem, and relatively small (210 amino acids) protein that is preva­
cord, peripheral nerve, and, to a lesser extent, cerebellar cerebellum are progressive. Motor nerve conduction lent in the inner mitochondrial membrane. Required in
atrophy, the initial signs are principally ataxia involving velocities are generally normal, but sensory nerve the formation of iron-sulfur clusters that occur in respi­
gait and limb function (spinocerebellar tracts) and studies reveal reduced or absent function. Electrocar­ ratory chain complexes I to III and aconitase, frataxin
muscle weakness followed by progressive loss of muscle diogram (ECG) is recommended at diagnosis and annu­ deficiency results in defective mitochondrial function,
stretch reflexes at the knees and ankles, contrasting with ally thereafter, and echocardiography is recommended increased mitochondrial free iron, and abnormal energy
spasticity and extensor plantar responses (pyramidal with onset of cardiomyopathy. production in spinal cord and skeletal and cardiac
tracts). In addition, progressive diminution of proprio­ muscle. Differential diagnosis includes peripheral neu­
ception and vibratory sensation (posterior columns) FRDA has an incidence in Indo-European popula­ ropathy (Charcot-Marie-Tooth), spinocerebellar ataxia,
occurs. With steady progression of gait and lower limb tions of approximately 1â•:› â•5› 0,000, although isolates have ataxia telangiectasia, abetalipoproteinemia,╯mitochon­
dysfunction with foot deformities, that is, equinovarus, been described at 1â•:› â•2› 5,000. Lower frequencies are drial DNA mutations (myoclonus epilepsy with ragged-
pes cavus, and clawed toes, wheelchair dependency reported in Native Americans and residents of sub- red fibers [MERF]), and late-onset hexosaminidase
occurs as early 10 years after onset. Saharan Africa and Southeast Asia. deficiency.

Progressive dysarthria is typical. Abnormal visual and The normal range of GAA repeats in FXN is 5 to 33, In general, survival is significantly shortened in
auditory function occurs, particularly in later stages. with greater than 80% having less than 12. Affected FRDA, with an average longevity of 30 to 40 years after
Abnormal oculomotor function is quite common; optic individuals have at least 70 GAA repeats, although onset. Although no cure exists at present, a number of
atrophy occurs in 25%. Although cognitive function is expansions up to 1,700 are described. Most commonly, pharmacologic agents are under investigation. Specific
repeat length is 600 to 1,200. The intermediate range gene therapy is not currently available.
is regarded as a premutation, although the percentage
of affected individuals is less than 1%. In the 25% with

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 197

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SECTION 9â•…

CEREBROVASCULAR
CIRCULATION
AND STROKE

P late 9-1 Brain: PART I

ARTERIES TO BRAIN AND MENINGES

Overview and Approach to Posterior cerebral artery Left middle meningeal artery
Stroke Patient
Superior cerebellar artery Posterior communicating artery
ARTERIAL SUPPLY TO THE BRAIN
AND MENINGES Basilar artery Middle cerebral artery
Overview and Cervical Segments Anterior inferior cerebellar artery Anterior cerebral artery
The brain and meninges are supplied by branches that Left labyrinthine (internal acoustic) artery Anterior communicating artery
originate from the aorta. The brachiocephalic trunk Mastoid branch of Ophthalmic artery
(or innominate artery) divides behind the right sterno- left occipital artery
clavicular joint into a right common carotid artery Cavernous sinus
(CCA) and a right subclavian artery that supplies the
arm. The next aortic branches are the left common Posterior inferior Middle
carotid artery and the left subclavian artery, arising cerebellar artery meningeal
directly from the aortic arch. The vertebral arteries are Posterior meningeal artery
early branches of the subclavian arteries of each side. branch of left
The common carotid arteries bifurcate in the neck, ascending
usually opposite the upper border of the thyroid carti- pharyngeal artery
lage, most often at the level of the body of the fourth
cervical vertebra, into the internal carotid arteries, Left and right Maxillary
which are direct (nearly 180-degree extensions of the vertebral arteries artery
common carotid artery) and the external carotid arter- (intracranial part) Superficial
ies (ECAs), which course more anteriorly and laterally Posterior meningeal temporal
and supply branches to the face and its structures. branch of vertebral artery
artery External
Internal Carotid Artery Anterior meningeal carotid
The internal carotid arteries (ICAs) ascend vertically in branch of vertebral artery artery
the neck, posterior and slightly medial to the external Posterior auricular artery Facial artery
carotid artery. These arteries are positioned medial to Lingual artery
the sternocleidomastoid muscle and travel behind the Occipital artery Ascending pharyngeal artery
faucial pillars of the pharynx until they reach the carotid Internal carotid artery
canal at the skull base. They have no branches within Superior laryngeal artery
the neck. At the skull base, the carotid arteries lie Carotid sinus Superior thyroid artery
adjacent to the 9th to 12th cranial nerves, which exit Carotid body
the skull from the jugular and hypoglossal foramina. Vertebral artery Common carotid artery
The arteries then enter the skull through the carotid (cervical part) Inferior thyroid artery
canal within the petrous bone and form an S-shaped Transverse process of C6 Thyrocervical trunk
curve. The portion of the internal carotid arteries Deep cervical artery Brachiocephalic trunk
within this curve is referred to as the carotid siphon. Supreme intercostal
There are three divisions of the internal carotid arteries artery â•…
within the siphon: an intrapetrous portion, an intraÂ

P late 9-2 Cerebrovascular Circulation and Stroke
TERRITORIES OF THE CEREBRAL ARTERIES
Overview and Approach to
Stroke Patient (Continued)

anterior spinal artery branches, penetrating arteries to the carotid arteries on each side connect to the posterior Anterior cerebral artery
medulla, and the large posterior inferior cerebellar arteries. cerebral artery branches of the basilar artery, forming the Middle cerebral artery
lateral sides and posterior portion of the “circle.” Posterior cerebral artery
External Carotid Artery
The external carotid arteries give off many branches The superior hypophyseal arteries arise as the first â•…
that supply structures within the face and neck. They branches of the supraclinoid portion of the internal
extend from the upper border of the thyroid cartilage carotid arteries, giving off branches to the optic chiasm feed the optic tract and the posterior portion of the
to the neck of the mandible, where they divide into and participating in an anastomosis that supplies the optic chiasm, the posterior hypothalamus, and the walls
temporal and maxillary arteries. There are eight major pituitary gland, which is composed of arterial branches of the third ventricle. The tuberothalamic (polar) artery
branches. The superior thyroid, lingual, and facial from each side and branches of the right and left menin- most often arises from the middle third of the posterior
arteries arise from the anterior aspect of the ECAs and gohypophyseal trunk. communicating artery but may also arise from the
course medially. The occipital and posterior auricular proximal segment of the posterior cerebral artery. The
arteries arise from the posterior aspect of the artery. The posterior communicating artery (about 1.5╯cm in polar artery supplies the anteromedial and anterolateral
The temporal and mandibular artery branches arise length) proceeds posteriorly and medially to join the portions of the thalamus.
behind the neck of the mandible. There are the deep posterior cerebral arteries on each side about 1╯cm from Basilar Artery
and superficial temporal branches of the temporal artery. their origins from the basilar artery. Small branches The basilar artery is formed by the union of the two
intracranial vertebral arteries at the medullo-pontine
The ECAs have two branches that supply the face junction. It courses rostrally in a groove closely applied
and can provide collateral blood flow to the ICA system: to the anterior surface of the pons, where it is located
the facial arteries, which course along the cheek toward
the nasal bridge, where they are termed the angular
arteries, and the preauricular arteries, which terminate
as the superficial temporal arteries. The internal maxil-
lary artery and ascending pharyngeal branches of the
ECAs also can contribute to collateral circulation when
an ICA occludes. The internal maxillary arteries give
off the middle meningeal artery branches, which pene-
trate into the skull through the foramen spinosum.
Another important arterial supply of the face involves
the frontal and supratrochlear branches that originate
from the ophthalmic arteries that supply the medial
forehead above the brow. When an ICA occludes, these
ECA branches can be important sources of collateral
blood.

Anomalous Origins
The right common carotid artery and right subclavian
arteries may arise as separate branches directly from
the aortic arch. The right vertebral artery may arise
directly from the brachiocephalic trunk instead of the
right subclavian artery. The left vertebral artery may
also arise from the brachiocephalic trunk. The right
subclavian artery can arise from the aortic arch distal to
the left subclavian artery, in which case it then crosses
to the right side. Sometimes the left common carotid
and the left subclavian arteries arise from a common
(left brachiocephalic) trunk. Rarely, a VA can arise from
a common carotid artery.

Supratentorial Arteries to the Brain
The internal carotid (anterior) circulation supplies the
anterior and most of the lateral portions of the cerebral
hemispheres, while the vertebrobasilar (posterior) cir-
culation supplies the brainstem, cerebellum, and the
posterior portion of the cerebral hemispheres. About
40% of the brain’s blood flow comes through each
internal carotid artery, while 20% flows through the
vertebrobasilar arterial system.

Circle of Willis
This anastomosis at the base of the brain (more a
hexagon than a circle) serves to connect the major arter-
ies of the anterior and posterior circulations, and the
arteries from both sides. The horizontal portions of the
anterior cerebral artery branches of the internal carotid
arteries are connected to the anterior communicating
artery, forming the anterior portion of the circle. The
posterior communicating artery branches of the internal

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 201

Plate 9-3 Brain: PART I

ARTERIES OF BRAIN: LATERAL AND MEDIAL VIEWS

Overview and Approach to Anterior parietal (postcentral sulcal) artery* Posterior parietal artery
Stroke Patient (Continued) Central (rolandic) sulcal artery Branch to angular gyrus
Terminal
within the prepontine cistern behind the clivus. The Precentral (prerolandic) sulcal artery branches
distal segment enters the interpeduncular cistern, Prefrontal sulcal artery of posterior
where it is often separated from the basal surface of the cerebral artery
brainstem. The distal portion of the artery lies between Terminal branches
the cerebral peduncles and ends at the pontomesence- of anterior
phalic junction, just after passing between the two cerebral artery
oculomotor nerves, by dividing into the two posterior Lateral fronto-
cerebral arteries. The basilar artery is often curved and basal (orbito-
tortuous and may deviate from the midline. The basilar frontal) artery
artery averages about 33╯cm in length, and the diameter
usually is between 4 and 4.5╯mm. The main branches Left middle Occipitotemporal
of the artery are the anterior inferior and superior cer- cerebral artery branches
ebellar arteries, paramedian arteries that penetrate Left anterior Posterior temporal branch
directly into the pons, and short circumferential arteries cerebral artery Middle temporal branch
that course around the pons and give off lateral basal Anterior communicating artery Superior and inferior terminal branches (trunks)
and lateral tegmental penetrating arteries.
Posterior Cerebral Arteries Right anterior cerebral artery Anterior temporal branch
The posterior cerebral arteries originate from the terminal
bifurcation of the basilar artery rostral to the third Left internal carotid artery
cranial nerves and then encircle the midbrain above the Polar temporal artery
level of the tentorium cerebelli. As the posterior cere-
bral arteries course the dorsal surface of the midbrain, Medial Posterior Pericallosal artery
they divide into cortical branches. The arteries are frontal Intermediate Paracentral artery
divided into peduncular, ambient, and quadrigeminal branches Anterior Cingular branches
segments, named after the cisterns through which they Callosomarginal Right posterior cerebral artery
pass. The proximal portion of the arteries, before the artery
posterior communicating artery branch, is referred to Polar frontal artery Precuneal artery
as the precommunal, P1 segment, or the mesencephalic Dorsal branch to
artery. Right anterior corpus callosum
cerebral artery
Branches that supply the midbrain and thalamus arise Medial fronto- Parieto-occipital
from the proximal peduncular and ambient segments. basal (orbito- branch
Paramedian mesencephalic arteries arise from the first 3 frontal) artery
to 7╯mm of the arteries. The thalamic-subthalamic Calcarine
arteries (also called thalamoperforating) also arise proxi- branch
mally to supply the paramedian portions of the postero-
medial thalamus. The medial posterior choroidal arteries Anterior communicating Medial occipital artery
also arise proximally from the peduncular segments and artery (cut) Posterior temporal branch
supply the quadrigeminal plate in the midbrain and the Anterior temporal branch
choroid plexus of the third ventricle. More distally, Distal medial striate artery Posterior communicating artery
the peduncular perforating and thalamogeniculate arteries (recurrent artery of Heubner)
originate from the ambient segments. These supply the
basolateral midbrain and the anterolateral thalamus, Right internal carotid artery
respectively. Each consists of a fan of parallel arteries.
*Note: Anterior parietal (postcentral sulcal) artery also occurs
Further in their course, after the posterior cerebral as separate anterior parietal and postcentral sulcal arteries.
arteries have circled the midbrain, the lateral posterior
choroidal artery branches arise, which will supply the â•…
pulvinar, dorsal thalamus, and the lateral geniculate
bodies as well as the choroid plexus of the temporal Ophthalmic, Anterior Choroidal, and medially to supply a portion of the midbrain and the
horns of the lateral ventricles. There are four main Posterior Communicating Arteries thalamus. The anterior choroidal arteries end in the
cortical branches of the posterior cerebral arteries: the lateral geniculate body, where they join with lateral
anterior temporal, posterior temporal, parieto-occipital, The anterior choroidal arteries are relatively small arteries posterior choroidal artery branches of the posterior
and calcarine arteries. The anterior temporal arteries that originate from the internal carotid arteries after the cerebral arteries and in the choroid plexus of the lateral
arise first from the ambient segments, usually as single origins of the ophthalmic and posterior communicating ventricles near the temporal horns.
arterial trunks or as multiple branches to supply the arteries. The ophthalmic artery projects anteriorly into
inferior portion of the temporal lobe. The posterior tem- the back of the orbit, whereas the anterior choroidal and Anterior Cerebral Arteries
poral arteries course posteriorly on the inferior parietal posterior communicating arteries project posteriorly from The anterior cerebral arteries are the smaller of the two
and occipital lobes. The parieto-occipital and calcarine the internal carotid artery. The anterior choroidal arteries terminal branches of the internal carotid arteries. They
arteries are more variable, usually arising independently course posteriorly and laterally, running along the optic course medially until they reach the longitudinal fis-
from the ambient segments and supplying the occipital tract. They first give off penetrating artery branches to sures and then run posteriorly over the corpus callo-
and medial inferior parietal lobes. The posterior perical- the globus pallidus and posterior limb of the internal sum. The first portion of the ACA is sometimes
losal arteries that circle the posterior portion of the capsule and then supply branches that course laterally hypoplastic on one side, in which case the ACA from
corpus callosum to anastomose with the anterior peri- to the medial temporal lobe, and branches that course
callosal artery branches of the anterior cerebral arteries
usually arise from the parieto-occipital arteries within
the quadrigeminal cisterns.

202 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 9-4 Cerebrovascular Circulation and Stroke

ARTERIES OF BRAIN: FRONTAL VIEW AND SECTION

Overview and Approach to Corpus callosum Pericallosal artery
Stroke Patient (Continued) Paracentral artery
Anterolateral central Medial frontal branches
the other side supplies both medial frontal lobes. The (lenticulostriate) arteries Callosomarginal artery
anterior communicating artery connects the right and left Lateral frontobasal Polar frontal artery
anterior cerebral arteries and provides potential col- (orbitofrontal) artery Anterior cerebral
lateral circulation from the anterior circulation of the arteries
opposite side. Prefrontal artery Medial fronto-
Precentral (pre- basal (orbito-
The horizontal segment of the anterior cerebral rolandic) and central frontal) artery
artery gives rise to multiple branches. Some course (rolandic) Distal medial
inferiorly to supply the upper surface of the optic nerves sulcal arteries striate artery
and the optic chiasm. Dorsally directed branches pen- Anterior parietal (recurrent artery
etrate the orbital brain surface to supply the anterior (postcentral sulcal) of Heubner)
hypothalamus, the septum pellucidum, the medial part artery Internal carotid
of the anterior commissure, the columns of the fornix, artery
and the basal frontal lobe structures (called the anterior Posterior parietal Anterior
perforated substance or substantia innominata). The artery choroidal
largest horizontal segment branch is called the recurrent Branch to artery
artery of Heubner. It most often arises from the anterior angular gyrus Posterior cerebral
cerebral artery near its junction with the anterior com- artery
municating artery. Most often “Heubner’s artery” is a Temporal branches Superior cerebellar
group of parallel small arteries rather than a single (anterior, middle, artery
vessel. They supply the anteromedial portion of the and posterior) Basilar and
caudate nucleus and the anterior inferior portion of the Middle cerebral pontine arteries
anterior limb of the internal capsule. artery and branches Labyrinthine (internal
(deep in lateral cerebral acoustic) artery
The proximal interhemispheric portions of the ante- [sylvian] sulcus) Vertebral artery
rior cerebral arteries have medial orbitofrontal branches Posterior inferior cerebellar artery (PICA)
that travel anteriorly along the gyrus rectus to supply Posterior communicating artery
the medial part of the orbital gyri and the olfactory Anterior communicating artery Anterior spinal artery
bulbs and tracts, and frontopolar artery branches to the
superior frontal gyri. The anterior cerebral artery then Anterior inferior cerebellar artery (AICA)
passes around the genu of the corpus callosum and, in Posterior spinal artery
that general location, divides into callosomarginal and
pericallosal branches. The callosomarginal artery passes Corpus striatum (caudate and lentiform nuclei) Falx cerebri
over the cingulate gyrus to course posteriorly within the Callosomarginal arteries
cingulate sulcus. It supplies anterior, middle, and pos- Anterolateral central and
terior branches to the medial frontal lobes. The perical- (lenticulostriate) arteries Pericallosal arteries
losal artery courses posteriorly, below and parallel to the (branches of anterior
callosomarginal artery, in a sulcus between the corpus Insula (island of Reil) cerebral arteries)
callosum and the cingulate gyrus. It supplies branches Trunk of corpus callosum
to the precuneus and medial superior parietal lobes. Precentral (prerolandic), Internal capsule
The pericallosal artery anastomoses with the perical- central (rolandic) sulcal, Septum pellucidum
losal branch of the posterior cerebral artery variably, and parietal arteries Rostrum of corpus callosum
usually near the splenium of the corpus callosum. Lateral cerebral (sylvian) sulcus Anterior cerebral arteries
Middle Cerebral Arteries Distal medial striate artery
The middle cerebral arteries arise from the internal Temporal branches of (recurrent artery of Heubner)
carotid artery bifurcation just lateral to the optic chiasm. middle cerebral artery
The “mainstem” (M1) portion of the arteries courses Anterior communicating artery
horizontally in a lateral direction to enter the sylvian Temporal lobe Optic chiasm
fissure. Three to six medial and lateral lenticulostriate Middle cerebral artery
arteries arise from the mainstem middle cerebral artery â•…
and penetrate the anterior perforated substance to Internal carotid artery
supply the basal ganglia and deep portions of the cere-
bral hemispheres. The medial lenticulostriate arteries sylvian fissures. These main divisions turn upward Meningeal Arteries
supply the outer portion of the globus pallidus and the around the inferior portion of the insula of Reil to The meningeal arteries and veins are located along the
medial parts of the caudate nucleus and putamen. The continue upward and backward in the deepest part of outer portion of the dura, grooving the inner table of
lateral lenticulostriate arteries supply the lateral portion the sylvian fissure between the outer surface of the the skull. They supply the dura, the adjacent bony
of the caudate nucleus, the putamen, the anterior insula and the medial surface of the temporal lobe. The structures, and form anastomoses across both sides of
portion and genu of the internal capsule, and the adja- superior division of the middle cerebral artery has the skull and with cerebral arteries. Their major clinical
cent corona radiata. Anterior temporal and frontopolar lateral orbitoÂf

P late 9-5 Brain: PART I

Overview and Approach to Ischemic STROKE SUBTYPES Hemorrhagic
Stroke Patient (Continued)
Stroke

The middle meningeal artery, originating from the Thrombosis
external carotid system via the external maxillary artery, Infarct
is the largest of the meningeal arteries. It supplies the
major blood supply to the dura mater and arises from Clot in carotid artery Subarachnoid hemorrhage
the maxillary artery and ascends just lateral to the exter- extends directly to (ruptured aneurysm)
nal pterygoid muscle to enter the calvarium through the middle cerebral artery
foramen spinosum. The middle meningeal artery then
passes forward and laterally across the floor of the Embolism
middle cranial fossa and divides into two branches Infarct
below the pterion. The frontal (anterior) branch climbs
across the greater wing of the sphenoid and parietal Clot fragment carried
bone, forming a groove on the inner table of the cal- from heart or more
varia and then dividing into two branches that supply proximal artery
the outer surface of the dura from the frontoparietal
convexity to the vertex and as far posteriorly as the Hypoxia
occiput. The smaller parietal (posterior) branch curves
backward over the temporal region to supply the pos- Infarcts
terior part of the dura mater.
Intracerebral hemorrhage
The accessory meningeal artery may also arise from the (hypertensive)
maxillary artery or from the middle meningeal artery.
It ascends through the foramen ovale to supply the Hypotension and poor
trigeminal ganglion and the adjacent dura within the cerebral perfusion:
middle cranial fossa. border zone infarcts,
no vascular occlusion
The bone and dura of the posterior fossa are supplied
by (1) the meningeal branches of the ascending pharyngeal before its lateral bend at the level of the atlas. It ascends â•…
artery, which pass through the jugular foramen, foramen and passes anteromedially to supply the dura of the
lacerum, and the hypoglossal canal; (2) the meningeal anterior margin of the foramen magnum. The posterior inside the skull into the brain or cerebrospinal fluid or
branches of the occipital artery, which pass through the meningeal branch arises from the third segment of the membranes surrounding the brain. Brain ischemia refers
jugular foramen and the condylar canal; and (3) the vertebral artery between the atlas and the foramen to insufficient blood flow. Hemorrhage and ischemia
small mastoid branch of the occipital artery, which passes magnum. It passes between the dura and the calvaria, are polar opposites. Hemorrhage is characterized by
through the mastoid foramen. supplying the posterior rim of the foramen magnum, too much blood inside the skull, and in ischemia, there
the falx cerebelli, and the posteromedial portion of the is not enough blood supply to allow continued normal
Branches of the Internal Carotid System. The dura of the posterior fossa. functioning of the effected brain tissue. Brain ischemia
meningohypophyseal trunk has three major branches. is much more common than hemorrhage. About four
The tentorial branch enters the tentorium cerebelli at fifths of strokes are ischemic.
the apex of the petrous bone, supplying the anterolat-
eral free margin of the tentorial incisura and the base TYPES OF STROKE Hemorrhage
of the tentorium near the attachment to the petrous Strokes are divided into two broad categories: hemor- The four designations of hemorrhage are named for
bone. A dorsal branch supplies the dura mater of the rhage and ischemia. Hemorrhage refers to bleeding their locations. Hemorrhages within brain substance
dorsum sella and clivus, sending small twigs to supply (inside the pia mater) are called intracerebral hemorrhages;
the dura around the internal auditory canal. The artery
to the inferior portion of the cavernous sinus originates from
the lateral aspect of the cavernous segment of the inter-
nal carotid artery.

An anterior meningeal artery arises from the anterior
aspect of the cavernous carotid artery and passes over
the top of the lesser wing of the sphenoid to supply the
dura of the floor of the anterior fossa.

As the ophthalmic artery passes medially and then
above the optic nerve, it gives off a lacrimal branch. The
recurrent meningeal artery arises from this branch and
passes through the superior orbital fissure to supply the
dura of the anterior wall of the middle cranial fossa.

The ophthalmic artery also provides several eth-
moidal branches. The posterior ethmoidal artery leaves
the orbit to supply the posterior ethmoid air cells and
the dura of the planum sphenoidale and the posterior
half of the cribriform plate. The anterior ethmoidal
artery passes through the anterior ethmoidal canal to
supply the mucosa of the anterior and middle ethmoidal
air cells and the frontal sinus. It then enters the cranial
cavity, where it gives off an anterior meningeal branch
(anterior falx artery) to the dura mater and the anterior
portion of the falx cerebri.

Branches of the Vertebral Artery. The meningeal
branches enter the skull through the foramen magnum.
The anterior meningeal branch originates from the distal
part of the second segment of the vertebral artery just

204 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 9-6 Cerebrovascular Circulation and Stroke

Overview and Approach to TEMPORAL PROFILE OF TRANSIENT ISCHEMIC ATTACK (TIA) AND COMPLETED INFARCTION (CI)
Stroke Patient (Continued)

those between the pia mater and arachnoid are labeled TIA Sudden episode of focal weekness
subarachnoid hemorrhages. Hemorrhages outside the or numbness, aphasia, unilateral
arachnoid but inside the dura mater are called subdural 5MAY loss of vision (amaurosis, fugax),
hemorrhages, and hemorrhages outside the dura mater homonymous hemianopsia, or
but inside the skull are called epidural hemorrhages. The 11 12 1 Minutes symptoms from vertebrobasilar
different sites of bleeding have different causes. 10 2 artery TIA

Intracerebral hemorrhages develop gradually and are 93 May progress
located between normal brain tissues. The bleeding is 84 to severe focal
due to rupture of small blood vessels, arterioles, and neurologic
capillaries within the brain substance. The bleeding is 765 deficit and
most often due to uncontrolled hypertension. Bleeding eventually coma
disorders, vascular malformations, and fragility of blood Recovery Stroke
vessels, for example, due to infiltration with amyloid in
cerebral amyloid angiopathy, are other common causes. very narrow, blood flow is severely reduced, causing 20OCTOBER
The blood usually oozes into the brain under pressure localized stagnation of the blood column. This change
and forms a localized hematoma. The hematoma sepa- in flow causes blood to clot, resulting in total arterial Months
rates normal brain structures and interrupts brain path- occlusion. This is a local problem in one pipe; a plumber Variable
ways. Hematomas also exert pressure on brain regions would try to fix the damaged blocked pipe. Similarly, residual
adjacent to the collection of blood and can injure these treating physicians could try to open or bypass a ste- deficit
tissues. Large hemorrhages are often fatal because they notic or occluded artery.
increase pressure within the skull compressing the â•…
brainstem. Alternatively, blockage of that second floor sink pipe
could be due to debris in the water system that came to The source could be from the heart, the aorta, or from
Subarachnoid hemorrhages are usually caused by rest in that pipe rather than a local problem that began a major artery in the neck or head located before the
rupture of an aneurysm that breaks, spilling blood within the pipe. A neck or cranial artery supplying the blocked artery along the same circulatory pathway. The
instantly into the spinal fluid. The sudden release of brain can become blocked by thrombi or other particu- process of particles breaking loose and blocking a
blood under arterial pressure increases intracranial late matter that breaks loose from a downstream site. distant artery is known as embolism. The source of the
pressure, causing severe sudden-onset headache, often material is called the donor site, and the receiving vessel
with vomiting and often a lapse in brain function so that is called the recipient site. The material is called an
the patients may stare, drop to their knees, or become embolus, and the process is called embolism. Treatment
confused and unable to remember. The symptoms in of embolism could involve unblocking the recipient
patients with subarachnoid hemorrhage relate to diffuse artery but also trying to prevent further embolization.
abnormalities of brain function because usually there is
no bleeding into one part of the brain. In contrast, in Another reason for poor flow in the second floor sink
patients with intracerebral hemorrhages, the hematoma might be a general problem with the water tank, water
is localized and causes loss of function related to the pump, or water pressure. In that case, flow through all
area damaged by the local blood collection.

Subdural and epidural hemorrhages are most often
caused by head injuries that tear blood vessels. In sub-
dural hemorrhages, the bleeding is usually from veins
located between the arachnoid and the dura mater. In
epidural hemorrhages, the bleeding most often results in
tearing of meningeal arteries. The tear is often caused
by a skull fracture. Arterial bleeding develops faster
than venous bleeding so that symptoms develop sooner
after head injury in patients with epidural hemorrhages.
In subdural hemorrhages, the bleeding can be slow so
that symptoms may be delayed for weeks after head
injury.

Brain Ischemia
Insufficient blood supply to the brain is called ischemia.
When ischemia is prolonged, it leads to death of
tissue—infarction.

There are three different major categories of brain
ischemia—thrombosis, embolism, and systemic hypoperfu-
sion; each indicates a different mechanism of blood
vessel injury or reason for decreased blood flow. The
difference between these mechanisms is easiest to
understand by using an analogy to house plumbing.
Suppose, turning on the faucet in the second floor bath-
room results in no flow, or instead, water dribbles out.
The malfunctioning could be due to a local problem,
such as rust buildup in the pipe supplying that sink.
This is analogous to thrombosis, a term used to describe
a local problem that involves an artery supplying
the brain. Atherosclerosis or another condition often
narrows the arterial lumen. When the lumen becomes

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 205

Plate 9-7 Brain: PART I

Overview and Approach to CLINICAL EVALUATION AND THERAPEUTIC OPTIONS IN STROKE
Stroke Patient (Continued) History (from patient and family, with emphasis on onset and timing)

pipes in the house should be affected. Turning on the Fundoscopic examination Platelet fibrin emboli (arrow)
faucets elsewhere in the house will reveal the nature of with retinal ischemia (arrowhead)
the problem. In the body, this type of problem is called Hollenhorst plaque (arrow)
systemic hypoperfusion. Abnormal cardiac performance â•…
could lead to low pressure in the system. Abnormally Auscultation
slow or fast heart rhythms, cardiac arrest, and failure of sometimes a loved one or a colleague, with subsequent
the heart to pump blood adequately can all lead to cause and treating it is much more important than char- thoughtful vascular and neurologic examinations. The
diminished brain perfusion. Hypotension and hypoper- acterizing the time course. history is directed to answering what (the cause of the
fusion due to an inadequate amount of fluid in the condition—the pathology and pathophysiology) and
vascular compartment of the body are other causes. Therapeutic strategies relate to four different time where (brain and vascular location) queries. The neuro-
Bleeding, dehydration, and shock all lead to inadequate epochs. Prevention involves strategies of identifying and logic symptoms and signs and vascular examinations
brain perfusion. This would be akin to having a very controlling potential risk factors before a stroke occurs. yield information about the where question. The dif-
low water tank. Strategies during acute ischemia involve reperfusion of ferential diagnosis of the what question depends on
the ischemic area and neuroprotection (rendering the information from the history about (1) the time and
In patients with brain embolism and thrombosis, one ischemic area more resistant to infarction). After a activity at and before the onset of symptoms; (2) the
artery is usually blocked, leading to dysfunction of the stroke, recovery and rehabilitation are facilitated. course of the symptoms—transient, gradually proÂ

Plate 9-8 Cerebrovascular Circulation and Stroke

Overview and Approach to CLINICAL EVALUATION AND THERAPEUTIC OPTIONS IN STROKE (CONTINUED)
Stroke Patient (Continued) Electrocardiogram

vascular disease, and obesity; (4) past strokes; (5) the Atrial fibrillation Myocardial infarction
presence, nature, and timing of any transient ischemic MRI and CT scans (to rule out other diseases)
attacks; (6) headache before, at, or after stroke onset;
and (7) the occurrence of a seizure, vomiting, or change Subdural hematoma Metastatic cancer Meningioma Glioblastoma
in level of consciousness.
Blood analysis followed by angiography
All stroke suspects require blood tests with brain
and vascular imaging. A complete blood count (CBC), CBC Glucose level
including platelet count, blood sugar, blood urea nitro- Platelet count Calcium level
gen or creatinine with a glomerular filtration rate, and Sedimentation rate Serologic test for syphilis
a prothrombin time or international normalized ratio
(INR) are obtained. The brain and the arteries that Therapeutic options Medical
supply it and the veins that drain it can be imaged using Surgical
either computed tomography (CT) or MRI. The ques-
tions to be answered by brain and vascular imaging are Cardiac emboli
(1) Is/are the brain lesion(s) caused by ischemia or hem-
orrhage, or is it related to a nonvascular stroke mimic? Carotid artery stenosis Disease of Hypertension
(2) Where is/are the brain lesion(s), and what is/are its/ vertebro-
their size, shape, and extent? (3) What are the nature, basilar artery â•…
site, and severity of the vascular lesion(s), and how
does/do the vascular lesion(s) and brain perfusion which includes a B-mode image combined with a pulsed stenting, and intra-arterial thrombolysis or mechanical
abnormality(ies) relate to the brain lesion(s)? Doppler spectrum analysis, can accurately show occlu- clot extraction. In patients in whom strokes cause sei-
sive lesions within neck arteries. Transcranial Doppler zures, electroencephalography (EEG) can be helpful.
CT is readily available in most hospitals and reliably ultrasound (TCD) involves insonation of intracranial
demonstrates the presence or absence of intracerebral arteries by measuring blood flow velocities using a Treatment of acute stroke patients depends heavily on
hemorrhage. Immediately after the onset of bleeding, probe placed on the orbit, temporal bone, and foramen the type and cause of the stroke. In subarachnoid hemor-
intracerebral hematomas (ICHs) are seen on CT as magnum. Areas of narrowing or occlusion can be rhage patients, aneurysms and vascular malformations
well-circumscribed areas of high density with smooth detected; these probes also provide a means to monitor can be controlled by cranial surgical clipping or coiling
borders. Edema develops within the first days and is for embolic materials passing under them. Dye contrast through an intravenous interventional approach. The
seen as a dark rim around the white hematoma. Sub- digital angiography shows neck and intracranial arteries vasoconstriction that follows bleeding and surgery also
arachnoid bleeding is demonstrated by a high-density in more detail than CTA and MRA and is now used to is a target for therapy. In patients who have had an
signal within the cerebrospinal fluid and brain cisterns. clarify vascular lesions not shown well by these screen- intracerebral hemorrhage, blood pressure control, rever-
Early signs of brain infarction include obscuring of the ing techniques; it is also pursued at the time of intra- sal of bleeding diatheses, and drainage of space-taking
basal ganglia density, blurring of the distinction between vascular interventions, such as coiling of aneurysms, hematomas, especially those that are lobar and near the
the grey matter of the cerebral cortex and the underly- surface, are the major therapeutic strategies.
ing white matter, and loss of definition of the insular
cortex. Later, infarction appears as a low-density lesion.
Specific vascular abnormalities include hyperdense
arteries, indicating thrombosis or slow flow and calcific
emboli within arteries. The signs of infarction on CT
scans are often subtle when images are taken within
several hours of the onset of symptoms. Viewing images
on a computer with the ability to vary the contrast helps
identify subtle abnormalities and asymmetries.

Diffusion-weighted MRI images (DWI) and fluid-
attenuated inversion recovery (FLAIR) images are par-
ticularly useful and sensitive for detection of acute brain
infarcts. Infarcted areas appear bright on DWI and dark
on apparent diffusion coefficient (ADC) images. The
location, pattern, and multiplicity of DWI ischemic
lesions help to suggest the most likely causative stroke
mechanism. DWI positivity wanes during the first 7 to
10 days after stroke onset. Lesions seen on DWI images
(and confirmed by ADC) usually, but not always, cor-
respond to areas of infarction. T2-weighted scans show
established infarcts as bright. MRI can also accurately
show ICH, especially when echo-planar gradient-echo
susceptibility-weighted images (T2*) are performed.
These T2*-weighted (susceptibility) images can also
show thrombi within intracranial arteries and dural
sinuses and veins.

Vascular imaging can be performed using CT (CT
angiography [CTA]) or MR (MR angiography [MRA]),
or by using ultrasound. CTA and MRA images can be
obtained concurrently with the respective primary
brain imaging. CTA requires intravenous dye infusion.
The neck and intracranial arteries and veins can be
shown well by either technique. Duplex ultrasound,

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 207

Plate 9-9 Brain: PART I

Overview and Approach to UNCOMMON ETIOLOGIC MECHANISMS IN STROKE
Stroke Patient (Continued)

In patients with acute brain ischemia, attention is Cardiac
directed toward reperfusing ischemic zones. When a emboli
thromboembolus blocks an artery, intravenous or intra-
arterial thrombolysis can be pursued; alternatively, Myocardiopathy Mitral valve Atrial Marantic Patent fora-
mechanical devices or stenting of blocked arteries can with thrombi prolapse with myxomatous emboli men ovale
also lead to recanalization. Maximizing collateral blood clots tumor emboli transmitting
flow by attention to blood pressure and blood volume venous clots
can augment perfusion of the ischemic zone. AntiÂ

P late 9-10 Cerebrovascular Circulation and Stroke
COMMON SITES OF CEREBROVASCULAR OCCLUSIVE DISEASE

Middle cerebral Basilar artery
artery origin Fourth segment
of vertebral artery
Anterior cerebral
artery origin

Siphon portion
of internal

carotid artery

Carotid bifurcation

Anterior Circulation
Ischemia

ETIOLOGY First segment of â•…
The most common etiology of internal carotid artery vertebral artery
disease is atherosclerosis, predominantly occurring in Proximal subclavian occurring between the intima and media usually causes
Caucasians and the elderly. Other etiologies include stenosis or occlusion of the affected artery, whereas
arterial dissection, fibromuscular dysplasia, and giant artery dissection between the media and adventitia is associ-
cell arteritis. ated with aneurysmal dilation (see Plate 9-11, A and B).
red thrombus, however, can dislodge and embolize to Congenital abnormalities in the media or elastica of the
Atherosclerosis causes stenosis or occlusion of extra- distal arterial branches. arteries as seen in Marfan syndrome, fibromuscular
cranial and intracranial arteries and is directly respon- dysplasia, osteogenesis imperfecta, and cystic medial
sible for a significant percentage of cerebral ischemic The main risk factors for carotid artery atherosclerotic necrosis can predispose patients to arterial dissection.
events. Atheroma formation involves the progressive disease are arterial hypertension, diabetes, hypercholes- Although often associated with acute trauma, arterial
deposition of circulating lipids and ultimately fibrous terolemia, and smoking. Frequent sites for anterior dissection may result from seemingly innocuous inci-
tissue in the subintimal layer of the large and medium circulation atherosclerosis are the origin of the internal dents, such as a fall while hiking or skiing, sports activi-
arteries, occurring most frequently at branching points. carotid artery (ICA) , the carotid siphon, and the main- ties (particularly wrestling or diving into a wave), and
Plaque formation is enhanced by blood-associated stems of the middle cerebral artery (MCA) and anterior paroxysms of coughing that stretch the artery.
inflammatory factors as well as increased shear injury cerebral artery (ACA) (see Plate 9-10). The internal
from uncontrolled blood pressure. Intraplaque hemor- carotid artery at or around the bifurcation is usually Spontaneous intracranial ICA dissections are uncom-
rhage, subintimal necrosis with ulcer formation, and affected in Caucasians, whereas in Asian, Hispanic, and mon when compared with dissections of its cervical
calcium deposition can cause enlargement of the ath- African-American populations, intracranial atheroscle- portion. Although early reports described a very
erosclerotic plaque with consequent worsening of the rosis is more common than carotid artery disease in poor prognosis with extensive strokes and very high
degree of arterial narrowing. the neck.

Disruption of the endothelial surface triggers throm- Dissection of the extracranial ICA usually occurs in
bus formation within the arterial lumen through activa- patients between age 20 to 50 years and commonly
tion of nearby platelets by the subendothelial matrix. involves its pharyngeal and distal segments. Dissection
When platelets become activated, they release throm-
boxane A2, causing further platelet aggregation. The
development of a fibrin network stabilizes the platelet
aggregate, forming a “white thrombus.” In areas of
slowed or turbulent flow within or around the plaque,
the thrombus develops further, enmeshing red blood
cells (RBCs) in the platelet-fibrin aggregate to form a
“red thrombs.” This remains poorly organized and
friable for up to 2 weeks and presents a significant risk
of propagation and embolization. Either the white or

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 209

Plate 9-11 Brain: PART I

OTHER ETIOLOGIES OF CAROTID ARTERY DISEASE

AB
CTA of the neck shows a pseudoaneurysm (A) and a string sign of the internal carotid artery (B)

Anterior Circulation
Ischemia (Continued)

mortality, more recent studies have shown a relatively C D
better outcome, with patients surviving with few or T2-weighted MRI shows a right basal ganglia infarct (C) MRA of the head demonstrates a filling defect
moderate deficits. Imaging studies usually show nar- in the distal portion of the right ICA and
rowing of the supraclinoid ICA, with extension to the proximal MCA stem (D)
MCA or ACA and, less commonly, aneurysm formation
(see Plate 9-11, C to F). EF G
Cerebral angiography shows the presence of a double lumen in the right CTA of the head and neck
Fibromuscular dysplasia is a nonatherosclerotic nonin- MCA stem (E) and narrowing of the supraclinoid portion of the right ICA, demonstrates areas of fibro-
flammatory angiopathy characterized by fibrodysplastic suggestive of intracranial dissection (F) muscular dysplasia in both
changes of unclear etiology. It occurs predominantly in internal carotid arteries (G)
women of childbearing age and often affects the neck â•…
arteries, most often the pharyngeal portion of the inter-
nal carotid artery. Intracranial disease is much rarer.
The lesions have a characteristic beaded appearance
that can be detected on magnetic resonance angiogÂ

P late 9-12 Cerebrovascular Circulation and Stroke

CLINICAL MANIFESTATIONS OF CAROTID ARTERY DISEASE

Ocular

Internal carotid artery

Transient Ophthalmic artery

blindness in
one eye from
temporary
occlusion by
platelet-fibrin
or cholesterol Central retinal artery

emboli (on side Partial blindness may be detected
of involved artery) by covering one eye at a time to
determine if defect is monocular
Cerebral hemisphere or binocular

Occasional Homonymous (partial) visual field defects
headache (usually Language defect (partial or complete)
supraorbital only when dominant hemisphere is involved
or temporal)

Hemiparesis or hemiplegia On side opposite
(only arm or leg may be affected); involved artery
may be fleeting, transient, or
Anterior Circulation permanent and may appear with
Ischemia (Continued) or without sensory deficits

within the carotid artery territory. Rarely, with critical Patient may awaken
ipsilateral internal carotid stenosis, gradual dimming or from sleep unable
loss of vision when exposed to bright light, such as glare to move affected side
from snow on a sunlit background, can be reported and
is due to limited vascular flow in the face of increased Clinical symptoms in patients with border zone strokes
retinal metabolic demand.
Stroke location Clinical symptoms
Strokes from intra-arterial embolism from ICA
disease are usually cortically based (see Plate 9-12). Anterior border zone Contralateral weakness (proximal > distal), sparing face, transcortical motor
Symptoms depend on whether branches of the MCA, aphasia (left-sided infarcts), mood disturbances (right-sided infarcts)
ACA, or both are involved (see Plate 9-13). The poste-
rior cerebral artery (PCA) territory may rarely be Posterior border zone Homonymous hemianopsia, lower-quadrant anopsia, transcortical sensory
affected by intra-arterial emboli from ipsilateral ICA aphasia (left-sided infarcts), hemineglect, and anosognosia (right-sided infarcts)
stenosis or occlusion in patients with a persistent fetal
PCA originating from the ICA. Subcortical border zone Brachiofacial hemiparesis with or without sensory loss, subcortical aphasia
(left-sided infarcts)
Neurologic findings vary by the location of the occlu- â•…
sion and the adequacy of collateral circulation. A large
MCA territory stroke is usually seen in patients with as in patients with ICA disease and usually occur over syndrome are more frequently seen. Left-sided spatial
MCA mainstem occlusion without good collateral flow, a shorter period of hours or days. When strokes occur, neglect and mild speech difficulties may accompany
whereas deep or parasylvian strokes are the most initial symptoms are typically noticed on awakening and right- and left-sided lesions, respectively. Small vessel
common presentation when enough collateral flow is often fluctuate during the day, supporting a hemody- disease is the most common mechanism of anterior
present over the convexities. Contralateral motor weak- namic mechanism. choroidal strokes; however, large strokes in this terri-
ness involving the foot more than the thigh and shoul- tory have also been associated with cardioembolism and
der, with relative sparing of the hand and face, is the Isolated infarction of the anterior choroidal artery ipsilateral intracranial carotid artery disease.
typical manifestations of distal ACA branch occlusion. territory is not common. The classic clinical presenÂ

P late 9-13 Brain: PART I

OCCLUSION OF MIDDLE AND ANTERIOR CEREBRAL ARTERIES

Lesion Artery occluded Infarct, surface Infarct, Clinical manifestations
Entire coronal section
territory
Anterior cerebral Contralateral gaze palsy,
hemiplegia, hemisensory
Superior division loss, spatial neglect,
Lenticulostriate hemianopsia
Medial Lateral

Global aphasia (if on left side)

Middle cerebral May lead to coma secondary
to edema
Inferior division
Internal carotid

Middle cerebral artery Deep Contralateral hemiplegia,
hemisensory loss
Transcortical motor and/or
sensory aphasia (if on
left side)

Para- Contralateral weakness
sylvian and sensory loss of face
and hand
Conduction aphasia,
apraxia, and Gerstmann
syndrome (if on left side)
Constructional dyspraxia
(if on right side)

Anterior Circulation SuperiorAnterior cerebral artery Contralateral hemiplegia,
Ischemia (Continued) division hemisensory loss, gaze palsy,
Inferior spatial neglect
involvement of sympathetic fibers along the wall of the division Broca aphasia (if on left side)
internal carotid artery are common in patients with Entire
extracranial carotid dissection, and its presence helps territory Contralateral hemianopsia
with the clinical diagnosis. TIAs and/or strokes usually Distal or upper quadrant anopsia
occur several days after onset of symptoms and are dissection, fibromuscular dysplasia, or giant cell arteri- Wernicke aphasia (if on left side)
usually caused by intra-arterial embolism. tis is more limited because lesions often occur on its Constructional dyspraxia (if on
pharyngeal portions or distal to it, and only indirect right side)
Severe retro-orbital or temporal headaches are also signs of a distal carotid occlusion are found. Transcra-
frequent in patients with intracranial dissections; nial Doppler can assess the patency of the intracranial Incontinence
however, the neurologic signs, most commonly a con- arteries; patterns of collateral flow through the circle Contralateral hemiplegia
tralateral hemiparesis, tend to follow almost immedi- of Willis also can be used for emboli monitoring (see Abulia
ately the headache’s onset. Neurologic deficits tend to Plate 9-14). Transcortical motor aphasia
fluctuate within the first two weeks of onset of symp- or motor and sensory aphasia
toms, probably reflecting cerebral hypoperfusion. Left limb dyspraxia
DIAGNOSIS
The diagnosis of anterior circulation ischemia is often Contralateral weakness
made by noninvasive methods, including ultrasound of leg, hip, foot, and shoulder
techniques, computed tomography, and magnetic reso- Sensory loss in foot
nance imaging techniques (see Plates 9-14 and 9-15). Transcortical motor aphasia
Digital subtraction angiography remains the gold stan- or motor and sensory aphasia
dard for the evaluation of the supra-aortic vasculature. Left limb dyspraxia
However, due to its potential risks of neurologic com-
plications, this technique is usually reserved for select â•…
patients when the diagnosis is still not clear after non-
invasive testing. Advances in both CTA and contrast-enhanced MRA
have allowed assessment of the entire supra-aortic tree,
Ultrasound of the carotid arteries at their bifurcation from the aortic arch to the circle of Willis. Each of
in the neck can determine the presence of critically these techniques is extremely valuable in the evaluation
stenotic extracranial artery disease as well characteriza- of the degree of stenosis in patients with extra- and
tion of carotid plaques as “soft,” consisting of choles- intracranial atherosclerotic disease as well as with
terol deposits and clot. “Soft” plaques are more prone plaque characterization (see Plates 9-14 and 9-15).
to ulcerate and cause artery-to-artery emboli. “Hard” Recent studies have shown that multidetector CTA has
plaques are those that have fibrosed and calcified over
time; they are a less common source of emboli. The
role of ultrasound in detection of internal carotid artery

212 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

P late 9-14 Cerebrovascular Circulation and Stroke

DIAGNOSIS OF INTERNAL CAROTID DISEASE

c1m50000/s 24 54 10 P1
Ϫ50
DEPTH SAMPLE

0 46 MEAN SYS

POWER

Ϫc1m0550000/s 24 48 10 P1

DEPTH SAMPLE
46
0 MEAN SYS
POWER

sin1 %50
cos1 0

Ϫ50

csions22 5%0
0

Ϫ50

1350 1400 1450 1500 1550 msec

Transcranial Doppler (TCD). Shows intra-arterial CTA of the head demonstrates an
embolism in a patient with carotid artery stenosis. ulcerated plaque

Anterior Circulation
Ischemia (Continued)

a sensitivity of 98% to 100% and specificity of 96% to Computer tomographic angiography (CTA). Shows an ICA occlusion.
100% for detection of severe carotid stenosis compared
with angiography, whereas contrast-enhanced MRA has Computer tomography perfusion (CTP). Shows cerebral hypoperfusion on the right MCA
a sensitivity of 93% to 98% and a specificity of 96% to territory in a patient with severe right internal carotid artery (RICA) stenosis.
100%. Regarding plaque characterization, MRI is able
to qualitatively and quantitatively define carotid plaque â•…
morphology as well as identify vulnerable plaque fea-
tures, such as intraplaque hemorrhages, whereas CTA ICA disease. MRIs cannot be performed in patients TREATMENT
is able to identify with precision the presence of plaque with pacemakers, and renal failure is a contraindication
calcification and ulcerations. for both CTA and MRA with gadolinium. Gadolinium- Carotid Artery Atherosclerotic Disease
based contrast agents have been linked to the develop- All patients with carotid artery atherosclerotic disease,
In patients with anterior circulation dissection, MRI ment of nephrogenic systemic fibrosis and nephrogenic should be screened for modifiable risk factors, such as
and MRA of the neck can provide morphologic details fibrosing dermopathy, often with serious and irrevers- hypertension and diabetes, and appropriately treated
as well as document intraluminal blood flow, respec- ible skin or organ pathology in patients with moderate according to the 2011 AHA/ASA (American Heart
tively, and is frequently the first choice of imaging to end-stage renal disease. Association/American Stroke Association) guidelines,
studies in the workup. The typical MRI appearance of which include dietary changes, increased physical
a dissected artery in cross section is an increased diam-
eter of the artery with an eccentric narrowed lumen
caused by the presence of an intramural hematoma.
The hematoma can be detected on spin-echo T1- and
T2-weighted images and fat-suppressed T1-weighted
techniques (see Plate 9-15). The lumen containing a
flow void, indicating patency, is usually the true lumen.
Three-dimensional time-of-flight MRA can show the
presence of a double lumen, string sign, wall irregular-
ity, and aneurysmal dilation. Artifacts from swallowing,
the patient’s movement, tendency to overestimate the
degree of stenosis, and difficulties distinguishing slow
flow and intraluminal thrombus are the main limita-
tions of this technique. CTA is another noninvasive
alternative for the diagnosis of arterial dissection, and
because it is independent of flow phenomena, even a
small residual lumen and pseudoaneurysms causing
slow or turbulent flow can be detected (see Plate 9-11,
A and B). However, subtle intimal flaps and intramural
thrombi can escape detection with CTA.

The presence of pacemaker devices and renal failure
limit the imaging studies performed in patients with

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 213

Plate 9-15 Brain: PART I

DIAGNOSIS OF CAROTID ARTERY DISEASE

Fat-suppressed T1-weighted imaging showing eccentric narrowed lumen and the presence of an
intramural hematoma in both distal ICAs suggestive of bilateral ICA dissection

Anterior Circulation
Ischemia (Continued)

activity, and pharmacologic treatment. Smoking cessa- MRA of the neck shows stenosis of the distal left CCA Magnetic resonance imaging (MRI). Shows
tion is recommended, and avoidance of environmental just proximal to ICA and ECA bifurcation anterior border zone strokes, right greater
tobacco smoke for stroke prevention should be consid- than left, in a patient with bilateral carotid
ered in all patients. Statins have been approved for artery disease
prevention of ischemic strokes in hypercholesterolemic
patients with coronary artery disease and, more recently, MRA of the head demonstrates stenosis
since the publication of the SPARCL (Stroke Preven- of the right MCA and left ACA
tion by Aggressive Reduction in Cholesterol Levels)
trial, recommended by the 2011 AHA/ASA for patients â•…
with atherosclerotic ischemic stroke or TIA without
known coronary heart disease to reduce the risk of both For patients with asymptomatic internal carotid that CEA should be considered for patients with asymp-
subsequent stroke and cardiovascular events. This trial artery stenosis from 60% to 99%, evidence from the tomatic stenosis of 60% to 99% if the patients have a
showed a 5-year absolute risk reduction of 2.2% for Asymptomatic Carotid Atherosclerosis Study (ACAS) life expectancy of at least 5 years and the rate of peri-
the combination fatal and nonfatal stroke and of 3.5% and Asymptomatic Carotid Surgery Trial (ACST) operative stroke or death for the institution or particu-
absolute risk reduction for major cardiovascular events showed a modest benefit favoring CEA, with an abso- lar surgeon can be reliably kept to less than 3%. Since
in patients receiving 80╯mg of atorvastatin compared lute stroke risk reduction at 5 years of 5.9% and 5.4%, then, further studies have shown that more intensive
with placebo. respectively. The stroke risk reduction was more promi- medical treatment can decrease the ipsilateral stroke
nent in men and independent of the degree of stenosis risk to less than 1%. It is possible that the absolute
Antiplatelet treatments, such as aspirin, clopidogrel, or contralateral disease. Therefore it was concluded benefit from carotid endarterectomy is even smaller
and a combination of aspirin and dipyridamole, are
often used for TIA and stroke prevention in patients
with nonsignificant stenosis of the carotid arteries. Both
clopidogrel (Clopidogrel versus Aspirin in Patients at
Risk of Ischemic Events trial [CAPRIE]) and the com-
bination between aspirin and dipyridamole (European
Stroke Prevention Study 2 [ESPS-2]) have been shown
to be superior to aspirin for prevention of recurrent
cerebral ischemia, whereas no statistical difference was
seen between clopidogrel and the combination of aspirin
and dipyridamole (Prevention Regimen for Effectively
Avoiding Second Strokes trial [PROGRESS]).

Carotid endarterectomy (CEA) for prevention of
ischemic stroke has been performed since the early
1950s (see Plate 9-16), but it was only in the 1990s that
several large-scale trials were performed comparing this
type of surgery against best medical treatment in
patients with asymptomatic and symptomatic internal
carotid artery stenosis.

214 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

P late 9-16 Cerebrovascular Circulation and Stroke
CAROTID ENDARTERECTOMY

Internal carotid artery External carotid artery

Common carotid artery

Longitudinal incision to remove
atherosclerotic obstruction at
carotid bifurcation

Sloping cut through intima

Anterior Circulation Silastic tube inserted for shunt
Ischemia (Continued) during endarterectomy. T permits
clearance of air from tube.
than reported by the above trials. A subgroup of patients
with asymptomatic carotid artery disease and microem- Endarterectomy
bolism on transcranial Doppler monitoring or imaging performed
markers of a vulnerable plaque or reduced cerebral
blood flow reactivity may potentially benefit from vas- Angiogram (lateral view)
cular intervention; however, further studies will be showing moderately severe
required to answer this question. stenosis at origin of left
internal carotid artery, with
For patients with symptomatic internal carotid artery ulceration indicated by
disease, evidence from the North American Symptom- protrusion of contrast
atic Carotid Endarterectomy Trial (NASCET) and the medium (arrows). Such
European Carotid Surgery Trial (ECST) support CEA a case is suitable
for severe stenosis (70%–99%) over best medical treat- for endarterectomy.
ment. The NASCET showed an absolute stroke risk
reduction at 2 years of 17%, whereas the ECST showed Vein graft or Dacron velour Patient’s head turned to
an absolute benefit from surgery of 11.6%. For symp- patch used to widen vessel side; incision along
tomatic patients with stenosis between 50% and 69%, if necessary. Arteriotomy anterior margin of
CEA is moderately useful and can be considered in closed by direct suture. sternocleidomastoid
selected patients. The NASCET showed a 5-year rate muscle
of ipsilateral stroke of 15.7% in the surgical group com-
pared with 22.2% among those treated medically in this â•…
subgroup of patients. CEA is not indicated for patients
with stenosis less than 50%. difference in the occurrence of minor strokes. This This trial showed no difference between the risks of
finding was also supported by the results of a MRI stroke, death, and MI in patient treated with a stent
Stenting (see Plate 9-17) has been investigated as an substudy showing more diffusion-weighted imaging or CEA; however, periprocedural strokes and death
alternative therapy for patients with carotid artery lesions in patients submitted to a carotid stent than to in symptomatic patients were significantly higher in
disease. Two multicenter studies, the International a CEA. patients treated with stents (6%) versus CEA (3.2%,
Carotid Stenting Study (ICSS) and the North American P = .02), whereas MI was more frequent in patients
Carotid Revascularization Endarterectomy versus The CREST enrolled symptomatic patients with at treated with CEA.
Stenting Trial (CREST), have compared the efficacy of least 50% stenosis on angiography or 70% by ultra-
carotid endarterectomy versus carotid stents in patients sound as well as asymptomatic ones with at least 60% Stricter practitioner credentialing requirements and
with symptomatic and asymptomatic carotid artery stenosis by angiography or 70% stenosis by ultrasound. inclusion of lower-risk asymptomatic patients in the
disease and showed somewhat different results.

The ICSS was the first randomized trial for symp-
tomatic patients with at least 50% internal carotid ste-
nosis. This study showed that the risk of stroke, death,
and myocardial infarction (MI) in the carotid artery
stenting group was significantly higher than in the sur-
gical arm (8.5% versus 5.2%, P = .006) with a major

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 215

P late 9-17 Brain: PART I

ENDOVASULAR ICA ANGIOPLASTY AND STENTING USING A PROTECTIVE DEVICE

Cerebral vessels Protection device Distal blood
at risk for embolic deployed from flow occurs
debris created by catheter through
intervention at Micromesh fabric micropores
carotid level particle “net” in net

Catheter containing Wire loop
folded protection Plaque
device passed
beyond plaque

Plaque in Debris captured
internal in protection net
carotid
artery

Anterior Circulation Plaque fractured Bag containing
Ischemia (Continued) via balloon captured debris
angioplasty,
CREST probably explain some of the different results creating embolic Wire loop
between these two trials. Until further studies are done, debris passing At conclusion of
carotid endarterectomy is still the treatment of choice distally into procedure, the
for patients with symptomatic carotid artery disease. protection “net” protection net
Intracranial ACA/MCA Captured debris containing debris
Atherosclerotic Disease created by the
Warfarin has showed no advantage over aspirin for pre- After balloon dilation, angioplasty is
vention of ischemic stroke or vascular death in patients stent deployed across withdrawn into
with symptomatic intracranial artery stenosis (Warfarin- plaque bed, creating catheter and
Aspirin Symptomatic Intracranial Disease [WASID] further embolic debris removed
trial) and was associated with significantly higher rates captured in net
of adverse events. The current guidelines from the Catheter
Consensus Conference on Intracranial Atherosclerotic anterior circulation remains unclear. The 2011 AHA/
Disease recommend aspirin monotherapy, the combi- ASA guidelines recommend the use of antithrombotic â•…
nation of aspirin and extended-release dipyridamole, treatment for 3 to 6 months as a reasonable option but
and clopidogrel monotherapy as acceptable options in acknowledge that the relative efficacy of antiplatelet or progressive neurologic deficits secondary to hemo-
patients with noncardioembolic ischemic stroke and therapy compared with anticoagulation is unknown for dynamic insufficiency and may require more aggressive
TIA. Aggressive treatment of atherogenic risk factors is these patients. treatment with stent placement.
also beneficial in this group of patients.
Even though most cases of carotid artery dissection Although the number of reported patients with
The prospective randomized study SAMMPRIS have a good prognosis with conservative management, intracranial dissections treated with anticoagulation or
(Stenting and Aggressive Medical Management for a small proportion of patients can develop fluctuating antiplatelet treatment is too small for any type of con-
Preventing Recurrent Stroke in Intracranial Stenosis) clusion, both treatments seem to be relatively safe in
showed that aggressive medical management was supe- patients with intracranial dissections without subarach-
rior to stenting, both because the risk of early stroke noid hemorrhage.
after stenting was high and the risk of stroke with
aggressive medical therapy alone was lower than
expected.

Nevertheless, intracranial angioplasty, with or withÂ

P late 9-18 Cerebrovascular Circulation and Stroke

ARTERIAL DISTRUBUTION TO THE BRAIN: BASAL VIEW

Circle of Willis

Anterior communicating artery
Anterior cerebral artery

Vertebral Basilar Recurrent artery (of Heubner)
System Disorders Internal carotid artery

SUBCLAVIAN AND INNOMINATE ARTERIES Medial and lateral lenticulostriate arteries
The left subclavian artery is usually the last brachioce- Middle cerebral artery
phalic branch of the aortic arch, while the right
subcÂ

Plate 9-19 Brain: PART I

ARTERIES OF POSTERIOR CRANIAL FOSSA

Lateral and medial geniculate bodies of left thalamus

Thalamogeniculate arteries Posterior lateral
Anterior choroidal artery choroidal artery

Vertebral Basilar System Posterior Posterior medial
Disorders (Continued) communicating artery choroidal artery
Anterolateral central to choroid plexus
distal extracranial portion (V3) is the most common (lenticulostriate) arteries of 3rd ventricle
location for dissection. This segment is relatively Middle
mobile and so vulnerable to tearing by sudden motion cerebral artery Occipital (posterior) horn
and stretching as might occur during chiropractic Anterior of right lateral ventricle
manipulation. Distal vertebral artery dissections may cerebral artery
extend into the intracranial vertebral artery. The symp- Right posterior branch to corpus
toms and signs are attributable to lateral medullary and Anterior callosum (posterior pericallosal artery)
cerebellar ischemia and are the same as those found in cerebral arteries
patients with intracranial vertebral artery occlusive Parieto-occipital Branches of
disease. Distal extracranial vertebral artery dissections Calcarine right posterior
are often bilateral. cerebral artery

INTRACRANIAL VERTEBRAL Ophthalmic artery III IV Superior
ARTERY DISEASE V vermian
Thalamoperforating VI branch
There are three specific intracranial vertebral artery arteries VIII Lateral (marginal)
syndromes. branch
Left internal VII
Lateral Medullary Syndrome carotid artery IX Outline of 4th
Atherosclerosis of the intracranial vertebral arteries is X ventricle
most severe in the distal portion of the arteries, often Basilar artery (broken line)
at the vertebral-basilar artery junction, sometimes
extending into the proximal basilar artery. Stenosis is Pontine arteries XI Inferior vermian
also common just after dural penetration. Most often, artery (phantom)
patients with proximal intracranial vertebral artery Labyrinthine (internal acoustic) artery
occlusive disease present with features of the lateral Choroidal branch to 4th
medullary syndrome. The findings are understood best Posterior cerebral artery ventricle (phantom) and
by reviewing the structures in the lateral medullary Cerebellar tonsillar branch
tegmentum that are specifically involved. Superior cerebellar artery of posterior inferior
cerebellar artery
1. Nucleus and descending spinal tract of V. Sharp Anterior inferior cerebellar artery (AICA) Posterior meningeal branch
jabs of pain are found in the ipsilateral eye and face, of vertebral artery
and numbness of the face; examination confirms Anterior meningeal branch of vertebral artery Posterior inferior cerebellar artery (PICA)
decreased pinprick and temperature sensations on Temporal branches of posterior cerebral artery Left posterior spinal artery
the ipsilateral face. Left vertebral artery
Anterior spinal artery
2. Vestibular nuclei and their connections. Feelings of
dizziness or instability of the environment may â•…
be present; examination shows nystagmus with
coarse rotatory eye movements when looking to ipsilateral arm. On standing or sitting, patients 6. Nucleus ambiguus. When the infarct extends
the ipsilateral side and small-amplitude faster nys- often lean or tilt to the side of the lesion. medially, it often affects this nucleus, causing
tagmus when looking contralaterally. 5. Autonomic nervous system nuclei and tracts. hoarseness and dysphagia. The pharynx and palate
Descending sympathetic system axons traverse the are weak on the side of the lesion, sometimes
3. Spinothalamic tract. There is decreased pinprick lateral medulla in the lateral reticular formation; causing patients to retain food within the piriform
and temperature sensation in the contralateral dysfunction causes an ipsilateral Horner syn- recess of the pharynx. A crowlike cough repre-
limbs and body; a sensory level may be present on drome. The dorsal motor nucleus of the vagus is sents an attempt to extricate food from this area.
the contralateral trunk with pain and temperature sometimes affected, leading to tachycardia and a
loss on the trunk below that level and in the lower labile increased blood pressure. 7. At times, there is also ipsilateral facial weakness,
extremity. The pinprick and temperature loss can perhaps related to ischemia of the caudal part of
extend to the contralateral face when the crossed
quintothalamic tract that appends itself medially to
the spinothalamic tract is involved. Rarely, the
loss of pain and temperature sensation is totally
contralateral and involves the face, arm, trunk,
and leg.

4. Inferior cerebellar peduncle. There is veering
or leaning toward the side of the lesion and
clumsiness of the ipsilateral limbs; examination
shows hypotonia and exaggerated rebound of the

218 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 9-20 Cerebrovascular Circulation and Stroke
CLINICAL MANIFESTATIONS OF VERTEBROBASILAR TERRITORY ISCHEMIA

Motor and sensory deficits in face (cranial
nerves V and VII); unilateral, bilateral,
or alternating (cranial nerves V and VII)

Vertebral Basilar System
Disorders (Continued)

the seventh nerve nucleus, just rostral to the nucleus Vertigo, ataxia; motor Dysphagia (cranial nerves IX and X)
ambiguus, or involvement of corticobulbar fibers and sensory deficits,
going toward the seventh nerve nucleus. which may be unilateral,
8. Abnormal respiratory control may also be found, or alternating
especially in bilateral lateral medullary lesions.
Hypoventilation is probably related to involve- Dysphonia (cranial nerve X)
ment of the nucleus of the solitary tract, nucleus
ambiguus, nucleus retroambiguus, and nuclei par- Headache, vomiting
vocellularis and gigantocellularis.
Abnormal eye movements (cranial nerves III, IV, Hemianopsia (bilateral
Cerebellar Infarction and/or VI). Horner syndrome may be present. occipital lesions—
The other common clinical syndrome is cerebellar cortical blindness
infarction in the distribution of the posterior inferior and Balint syndrome)
cerebellar artery, a branch of the intracranial vertebral
artery. Cerebellar infarction is often difficult to diag-
nose. Symptoms can resemble labyrinthitis and can
appear deceptively slight. Gait ataxia and vomiting are
often accompanied by dizziness.

Medial Medullary Infarction
This third syndrome is much less common. The ante-
rior spinal artery supplying the medial medulla arises
from the distal intracranial vertebral artery. The medial
medullary syndrome is characterized by a hemiparesis
that affects the contralateral arm and leg attributable to
ischemia of the medullary pyramid, and ipsilateral
weakness of the tongue and contralateral loss of posi-
tion sense explained by involvement of the hypoglossal
nerve and the medial lemniscus. In some patients with
intracranial vertebral artery occlusion, ischemia of the
medial medulla accompanies lateral medullary infarc-
tion, forming a hemimedullary syndrome. This occurs
when an intracranial vertebral artery occlusion is exten-
sive and both the lateral medullary penetrators and
the anterior spinal artery branches are concomitantly
involved. Rarely, medial medullary infarction is bilat-
eral and can extend caudally into the rostral spinal cord,
causing a syndrome of quadriparesis difficult to separate
from basilar artery occlusion with pontine infarction.

PROXIMAL AND MIDBASILAR tegmentum on one or both sides. The most important Altered consciousness (partial or complete)
ARTERY OCCLUSION neurologic signs and symptoms that accompany basilar may be fleeting, transient, or of long duration
artery occlusion are: â•…
The basilar artery forms after merging of the two intra-
cranial vertebral arteries at the medullo-pontine junc- 1. Limb paralysis. Limb paralysis is usually bilateral 2. Bulbar or pseudobulbar paralysis. Infarction may
tion. The basilar artery ends at the junction of the pons but often asymmetric; stiffness, hyperreflexia, and affect cranial motor nuclei, causing paralysis of
and midbrain. The major territory of supply of the extensor plantar reflexes are found when examin- the face, palate, pharynx, neck, or tongue on one
basilar artery is the pons, especially the basis pontis. ing the weak limbs. Some patients present with a or both sides. The 9th- to 12th-nerve nuclei are
The tegmentum of the pons has a rich collateral supply hemiparesis, but examination shows weakness and located within the medullary tegmentum, which
of blood vessels. The superior cerebellar arteries at the reflex changes in the contralateral limbs. is usually below the level of infarction. Weakness
distal end of the basilar artery provide much supply to of the cranial musculature innervated by these
the pontine and midbrain tegmentum. Occlusion of nuclei causes dysarthria, dysphonia, hoarseness,
the basilar artery often causes ischemia in the pontine dysphagia, and tongue weakness. The pontine
base bilaterally, sometimes extending into the medial

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 219

Plate 9-21 Brain: PART I

INTRACRANIAL OCCLUSION OF VERTEBRAL ARTERY
Posterolateral medullary infarction and clinical manifestations

Vertebral Basilar System Cerebellum Headache, vomiting,
Disorders (Continued) Vestibular nuclei decreased
consciousness
lesion interrupts corticofugal descending fibers Inferior
destined for these cranial nerve nuclei. The cerebellar Dizziness, vertigo,
resulting weakness is referred to as pseudobulbar peduncle diplopia,
because it involves the descending pathways con- Solitary nystagmus
trolling the bulbar nuclei rather than the nuclei tract
themselves. Exaggerated jaw and facial reflexes, nucleus Hoarseness,
increased gag reflex, and easily induced emotional palatal paralysis,
incontinence with excessive laughing and/or Dorsal dysphagia
crying are found. The limb and bulbar paralysis vagal
may be so severe that the patient cannot com- nucleus Pain in eye, face,
municate verbally or by gesture. Such patients Descending forehead (at
have been referred to as having the locked-in syn- spinal tract onset); ipsilateral
drome because of their loss of motor function. and nucleus loss of pain and
3. Eye movement abnormalities. The sixth-nerve of trigeminal temperature
nuclei, medial longitudinal fasciculi (MLFs), and (V) nerve sensation in face;
pontine lateral gaze centers are located in the Hypoglossal diminished
paramedian pontine tegmentum, and are vulner- nucleus corneal reflex
able to ischemia in this region. Lesions of the Ataxia, staggering
sixth nerve or nucleus cause paralysis of abduction
of the eye. A MLF lesion results in loss of adduc- Lateral spino- Contralateral loss of
tion of the ipsilateral eye on gaze directed to the cerebellar tract pain and temperature
opposite side and nystagmus of the contralateral Lateral spino- sensation in body
abducting eye. This syndrome, called an inter- thalamic tract
nuclear ophthalmoplegia, can be bilateral. Lesions
of the paramedian pontine tegmentum may also Nucleus ambiguus Horner syndrome,
affect the paramedian pontine reticular formation Autonomic fibers miosis, eyelid ptosis
(PPRF), the so-called pontine lateral gaze center
that mediates gaze to the same side. A lesion of Anterior spino- Medial Pyramid Anterior Vertebral Shaded area shows
this region causes an ipsilateral conjugate-gaze thalamic tract lemniscus spinal artery artery zone of infarction
paresis. A unilateral lesion can affect both the obstructed
PPRF and the MLF on the same side, resulting Posterior inferior
in the one-and-a-half syndrome because only one cerebellar artery
half of gaze (scoring 1 for gaze to each side) is
preserved. Nystagmus: the vestibular nuclei and Posterior
their connections are also often affected, causing cerebral
vertical and horizontal nystagmus. Other eye signs: artery
ptosis, small pupils, and ocular skewing are also
often found. SCA
4. Coma. When the reticular formation is affected
bilaterally in the medial pontine tegmentum, Basilar Intracranial obstruction of
coma results. Sensory and cerebellar abnormali- artery vertebral artery proximal to
ties are absent or slight because the infarct usually origin of posterior inferior
affects the midline and paramedian structures in Pons cerebellar artery (PICA)
the basis pontis, sparing the spinothalamic tracts AICA may be compensated by
and the cerebellum. Collateral circulation is Vertebral preserved flow from contra-
mainly through the circumferential vessels, which artery lateral vertebral artery. If
course around the lateral portions of the brain- Medulla PICA origin is blocked, lateral
stem to nourish the lateral base, tegmentum, PICA medullary syndrome (shown
and cerebellum. The cerebellar hemispheres are Dura above) may result. Clot also
mostly nourished by the posterior inferior cere- Anterior may extend to block anterior
bellar artery that originates before the basilar spinal spinal artery branch, causing
artery, and the superior cerebellar artery (SCA), artery hemiplegia, or embolization
which is preserved when the basilar artery clot to basilar bifurcation may
does not extend to the distal basilar artery. cause “top of basilar”
syndrome.
â•…

TOP-OF-THE-BASILAR ARTERY EMBOLISM midbrain and diencephalon through small vessels that
Occlusion of the distal basilar artery is most often pierce the posterior perforated substance. The findings
caused by embolism from the heart or the proximal in patients with top-of-the-basilar embolism include
vertebral artery system. Emboli small enough to pass
through the vertebral arteries seldom lodge in the prox- 1. Pupillary abnormalities. The lesion often inter-
imal basilar artery, a vessel larger than each intracranial rupts the afferent reflex arc by interfering with
vertebral artery, but reach the distal basilar artery or its fibers going toward the Edinger-Westphal
terminal branches. The distal basilar artery supplies the nucleus. The third-nerve nucleus can also be
involved, as well as the rostral descending sympa-
thetic system. The pupils are usually abnormal

220 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 9-22 Cerebrovascular Circulation and Stroke

Posterior OCCLUSION OF BASILAR ARTERY AND BRANCHES
cerebral
Vertebral Basilar System arteries Collateral circulation via
Disorders (Continued) SCA superior cerebellar (SCA),
Pons anterior inferior cerebel-
and can be small, midposition, or dilated, depend- Paramedian lar (AICA), and posterior
ing on the level and extent of the lesion. Decreased and short inferior cerebellar (PICA)
pupillary reactivity and eccentricity or an oval circumferential arteries may partially
shape of the pupil is also found. penetrating compensate for basilar
2. Eye movement abnormalities. Paralysis of upward branches occlusion. Basilar artery
or downward gaze is common. The eyes may also Basilar artery has paramedian, short
be skewed and deviated at rest, most often down- (occluded) circumferential and long
ward and inward. Hyperconvergence, retractory circumferential (AICA)
nystagmus, and pseudo–VI-nerve paresis are AICA and (SCA) penetrating
other oculomotor abnormalities noted. Reduced Medulla branches. Occlusion of
ocular abduction in patients with pseudo-VI Vertebral arteries any or several of these
paresis is explained by hyperadduction of the eye. branches may cause
The adduction vector neutralizes the abduction PICA pontine infarction.
motion, and so abduction is incomplete. The Occlusion of AICA or
lesion is far rostral to the sixth nerve nucleus or PICA may also cause
fibers. cerebellar infarction.
3. Decreased alertness. Hypersomnolence or frank
coma can result from bilateral paramedian rostral Anterior spinal artery Vestibular nuclei
brainstem dysfunction. After the acute phase, the
patient may remain relatively inert and apathetic. Cerebellar peduncles
Some patients sleep many hours a day unless
stimulated or coaxed into activities. Abducens (VI) nerve and nucleus
4. Memory loss. Patients are unable to form new
memories and may not be able to recall events just Tegmentum Descending spinal tract and
preceding their stroke. There often are other of pons nucleus of trigeminal (V) nerve
behavioral abnormalities, including agitation, hal- Descending sympathetic fibers
lucinations, and abnormalities that mimic lesions
of the frontal lobe. Facial (VII) nerve and nucleus

Spinothalamic tract

Reticular substance

Medial lemniscus

Base of pons Corticospinal (pyramidal) tract
Long circumferential artery

Short circumferential penetrating artery

Paramedian penetrating artery

Basilar artery

THALAMIC INFARCTS Large pontine infarction, resulting in pupillary Small infarct in the left base of the pons causing
The thalamus is supplied by arteries that arise at or and other ocular abnormalities, facial weakness, a right hemiparesis
near the basilar artery bifurcation and from the proxi- quadriplegia, and coma â•…
mal posterior cerebral arteries. The tuberothalamic with bilateral lesions. The amnesia often improves nuclei (ventral posterior lateral and ventral posterior
(polar) artery arises on each side from the middle third within 6 months in patients with unilateral infarcts. medial) and the ventral lateral and ventral anterior
of the posterior communicating artery and supplies Bilateral butterfly-shaped paramedian posterior tha- nuclei. The findings in patients with lateral thalamic
the anteromedial and anterolateral thalamic nuclei. lamic infarction can result from a branch occlusion of infarcts are contralateral hemisensory symptoms
Unilateral anterolateral thalamic infarction in the dis- a single supplying artery or pedicle and cause hyper- accompanied by contralateral limb ataxia. At times,
tribution of the polar artery on either side usually somnolence and bilateral third-nerve palsies. hemichoreic movements of the contralateral arm
causes abulia, facial asymmetry, transient minor contra- The thalamogeniculate group of arteries arises from the develop, and the hand may assume a fisted posture.
lateral motor abnormalities and, at times, aphasia (left posterior cerebral arteries to supply the ventrolateral Some patients have a transient hemiparesis at onset that
lesions) or visual neglect (right lesions). Abulia, with thalamus, an area that includes the somatosensory improves quickly.
slowness, decreased amount of activity and speech, and
long delays in responding to queries or conversation, is
the predominant abnormality. Memory may also be
affected.

The thalamic-subthalamic arteries (also called thal-
amoperforating) originate from the proximal posterior
cerebral arteries and supply the most posteromedial
portion of the thalamus near the posterior commissure.
The right- and left-sided arteries usually arise sepa-
rately but can originate from a single unilateral artery
or a common pedicle. Unilateral lesions are usually
characterized by paresis of vertical gaze (upward or
both upward and downward) and by amnesia. Motor
and sensory signs and symptoms are absent. Memory
loss may be severe, with profound difficulty in forming
new memories and encoding recent events, particularly

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 221

Plate 9-23 Brain: PART I

OCCLUSION OF “TOP-OF-BASILAR” AND POSTERIOR CEREBRAL ARTERIES

Internal carotid artery

Middle cerebral artery

Posterior communicating artery

Vertebral Basilar System Thalamoperforating arteries
Disorders (Continued) to medial thalamus
Thalamoperforating arteries
to lateral thalamus

Occlusion of branches of the thalamogeniculate hemisensory loss and hemianopia without paralysis is Posterior cerebral artery
arteries supplying the somatosensory nuclei is respon- virtually diagnostic of infarction in the posterior cere- Superior cerebellar artery
sible for most patients with pure sensory stroke (hemisen- bral artery territory. Rarely, occlusion of the proximal Basilar artery and obstruction
sory symptoms or signs without other abnormalities). portion of the artery can cause a hemiplegia. Penetrat- Anterior inferior cerebellar artery
The infarcts are usually smaller than those found in ing branches from the proximal posterior cerebral Vertebral artery
patients with the lateral thalamic syndrome. Occlusion artery penetrate into the midbrain to supply the cere-
of thalamogeniculate branches occasionally causes a bral peduncle. Areas supplied by posterior
syndrome referred to as sensory motor stroke character- cerebral arteries (blue)
ized by the sensory symptoms and signs of pure sensory Cognitive and behavioral abnormalities are also and clinical manifestations
stroke accompanied by paresis and pyramidal signs common. When the left posterior cerebral artery of infarction
involving the same limbs. Medial thalamus and midbrain
Hypersomnolence
The posterior choroidal arteries originate from the Small, nonreactive pupils
posterior cerebral arteries and course forward from Bilateral third cranial
caudal to rostral in the thalamus. The lateral posterior
choroidal arteries supply mostly the pulvinar, a portion nerve palsy
of the lateral geniculate body, and then loop around Behavioral alterations
the superior portion of the thalamus to supply the Hallucinosis
anterior nucleus. The medial arteries supply the Lateral thalamus and posterior
habenula, anterior pulvinar, parts of the center median limb of internal capsule
nucleus, and the paramedial nuclei. Hemianopia, hemi-
sensory symptoms, and behavioral abnormalities may Hemisensory loss
occur in patients with posterior choroidal artery terri- Hippocampus and medial
tory infarcts. temporal lobes

POSTERIOR CEREBRAL ARTERIES Memory loss
The posterior cerebral arteries are the main terminal Splenium of corpus callosum
branches of the basilar artery. Intrinsic atheromatous Alexia without agraphia
disease of the PCA most often affects the origin of the Calcarine area
vessel. Most often, infarcts in the PCA territory are Hemianopsia (or bilateral
caused by emboli to the posterior circulation.
blindness if both posterior
After giving off penetrating branches to the midbrain cerebral arteries occluded)
and thalamus, the posterior cerebral arteries supply
branches to the occipital lobes and the medial and infe- â•…
rior portions of the temporal lobes. Infarction in the
cerebral territories of the arteries most often affects territory is infracted, patients may lose the ability to
vision and somatic sensation but seldom causes paraly- read, although they retain the ability to write and spell.
sis. The most common finding is a hemianopia caused by Anomic aphasia and memory loss are also common.
infarction of the striate visual cortex on the banks of the When the right posterior cerebral artery territory is
calcarine fissure or by interruption of the geniculocal- involved, disorientation to place may develop.
carine tract as it nears the visual cortex. If just the lower
bank of the calcarine fissure is involved, the lingual When the posterior cerebral artery territory is
gyrus, a superior quadrant-field defect, results. An infe- infarcted bilaterally, as may occur with emboli, the most
rior quadrantanopia results if the lesion affects the common findings are cortical blindness, amnesia, and
cuneus on the upper bank of the calcarine fissure. When agitated delirium.
infarction is restricted to the striate cortex and does not
extend into the adjacent parietal cortex, the patient is
fully aware of the visual field loss.

Somatosensory abnormalities are also common. The
lateral thalamus is the site of the major somatosensory
relay nuclei, the ventral posteromedial and lateral
nuclei. Ischemia to these nuclei or white matter tracts
carrying fibers from the thalamus to somatosensory
cortex produces sensory symptoms and signs, usually
without paralysis. Patients report paresthesias or numb-
ness in the face, limbs, and trunk. The combination of

222 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

P late 9-24 Cerebrovascular Circulation and Stroke
CARDIAC SOURCES OF BRAIN EMBOLI

Brain Emboli

There are three main participants in the process of Subacute bacterial
brain embolism: the recipient artery that catches and endocarditis, vegetations
receives the embolic material even temporarily, the
embolic material itself—the matter that makes up the
emboli, and the donor source from which embolic mate-
rial originates.

THE RECIPIENT ARTERIES Mitral stenosis, mural
The recipient artery is the main determinant of the clinical and valvular thrombi
symptoms and signs. When a recipient neck or intracra-
nial artery is blocked, blood flow to the area of brain Valve replacement with
supplied by the blocked artery suddenly becomes insuf- thrombus formation
ficient and normal function stops. The neurologic
symptoms that result from the arterial blockage depend Myocardial infarction with mural thrombus Arteriosclerotic
on the area of brain that is underperfused. If an embolus heart disease
blocks a posterior cerebral artery supplying the visual Ventricular aneurysm with
cortex, loss of vision in the opposite visual field might intraluminal clot formation
result. If an embolus blocks the left middle cerebral
artery, the right limbs might become weak and numb, Congestive heart failure, atrial fibrillation
and the patient might become aphasic. An embolus to
an intracranial vertebral artery might cause loss of cer- â•…
ebellar function and ataxia. The symptoms do not
depend on the nature of the embolic material. The DONOR SOURCES AND THEIR within ventricular aneurysms. The most common
recipient artery cannot tell what is blocking it or where EMBOLIC MATERIALS sources of embolism from the heart are arrhythmias,
the material came from. especially atrial fibrillation. Red thrombi form in the
The nature of the embolic material determines the inefficiently contracting, dilated left atrium and left
Whether the symptoms are transient or persist most likely prophylaxis and treatment. atrial appendage; valvular diseases are also common
depends on the size and fate of the embolus. Emboli sources. White platelet-fibrin thrombi form along irregu-
very often move through recipient arteries so quickly Cardiac Sources. Emboli that arise from the heart lar valvular surfaces and prosthetic valves. Many times,
that no or very transient obstruction occurs. These often consist of red erythrocyte-fibrin thrombi that form white thrombi form the nidus for a superimposed red
passing emboli can be identified as so-called HITS in the atria or on the surface of myocardial infarcts or
(high-intensity transient signals) that pass quickly under
an ultrasound probe monitoring an intracranial artery.
Emboli can cause no symptoms, TIAs, or persistent
infarction.

Most emboli that go into an internal carotid artery
from the heart or aorta, or arise from the carotid artery,
travel into the ipsilateral middle cerebral artery. The
embolus might rest first within the carotid artery in the
neck or head and then pass into the proximal middle
cerebral artery or its superior or inferior divisions, or
into one of the smaller cortical branches. Occasionally,
the embolus might go into other branches of the intra-
cranial carotid artery, the anterior cerebral artery, or the
anterior choroidal artery.

If an embolus goes into a vertebral artery in the neck
or arises from an extracranial vertebral artery most
often it will travel rostrally into the ipsilateral intracra-
nial vertebral artery or go even further to reach the
basilar artery bifurcation or into one or both posterior
cerebral arteries or the superior cerebellar arteries
located at the top-of-the basilar artery. If the embolus
is large enough it could obstruct the basilar artery itself,
leading to severe brainstem ischemia or infarction. A
shower of emboli can block multiple arteries simultane-
ously or sequentially.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 223

P late 9-25 Brain: PART I

UNCOMMON CARDIAC MECHANISMS IN STROKE

Brain Emboli (Continued)

thrombus so that both are involved in the thromboem- Myocardiopathy with thrombi Mitral valve prolapse with clots
bolism. In patients with systemic lupus erythematosus,
antiphospholipid antibody syndrome, and cancer, a Atrial myxomatous tumor emboli
nonthrombotic fibrinoid valvulitis develops and serves
as a nidus for white clots. Calcium present in calcific aortic
valves and in mitral annulus calcifications can break loose
and embolize to the brain. Bacteria and fungi engrafted
upon valves in patients with infective endocarditis can
travel into the bloodstream and into the cranium,
causing meningitis, brain abscesses, and infarcts as well
as infecting arteries, causing mycotic aneurysms. Tumor
tissue present in cardiac myxomas and fibroelastomas can
form the matter of emboli.

In some patients, red thrombi originate in veins of
the limbs and pelvis and embolize to the right heart and
then pass through atrial septal defects or patent foramen
ovale into the left atrium. They then embolize to the
brain. This process is called paradoxic embolism. A
similar process of right-to-left shunting also occurs in
patients with arteriovenous fistulas in the lungs.

Similarly emboli arising from the aorta are composed
of different substances. White platelet-fibrin thrombi
form in crevices and irregular surfaces. These white
clots activate the coagulation cascade and promote red
thrombi to form on their surface. Red thrombi often
form within ulcers or regions of plaque rupture. Red
and white thrombi often break off and reach the brain.
Large protuberant and mobile plaques often contain
red thrombi. Cholesterol crystals within aortic plaques or
other complex plaque constituents themselves can travel to
the brain. Calcium may also be a component of aorto-
genic emboli.

Artery-to-artery emboli have the same basic compo-
nents as those that arise from the aorta: calcium,
cholesterol fragments, red and white clots, and so
forth. Occasionally air, fat, and foreign materials enter
the bloodstream and embolize to the brain and other
viscera.

TREATMENT Marantic emboli Probe–patent foramen ovale
Selection of treatment for acute embolic brain ischemia against embolism in patients with infective endocarditis transmitting venous clots
should consider the nature of the embolic material. are antibacterial and antifungal agents. â•…
Thrombolytic drugs, such as recombinant tissue plas-
minogen activator (rt-PA) can lyse red clots but are Secondary prevention also depends on the nature of the Abnormal valves can be repaired or replaced by pros-
ineffective against white clots. Glycoprotein IIB/IIIA donor sources. Atrial fibrillation might respond to antiar- thetic valves. Cardiac tumors can be removed. Surgeons
inhibitors that are active against platelet-fibrin bridges rhythmics or cardiac conduction pathway ablation pro- have operated on protruding aortic atheromas, and in
can potentially lyse white clots. These treatments are cedures. Intra-atrial septal abnormalities and defects the future these lesions might be attacked by endovas-
likely to be ineffective against calcium, cholesterol crys- can be repaired. Ventricular aneurysms can be resected. cular techniques. Arterial lesions are often repaired
tals, tumor fragments, infective agents, and foreign surgically or using endovascular technology in the form
matter. Mechanical methods of retrieving emboli can of angioplasty and/or stenting.
snare different materials.

Similarly, prophylaxis against re-embolization (sec-
ondary prevention) must consider the nature of the
embolic material. The most effective prophylaxes

224 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 9-26 Cerebrovascular Circulation and Stroke
LACUNAR INFARCTION

Small (100-µm) artery within brain parenchyma
showing typical pathologic changes secondary
to hypertension. Vessel lumen almost completely
obstructed by thickened media and enlarged to
about 3 times normal size. Pink-staining
fibrinoid material within walls.

Lacunar Stroke

Penetrating arteries are branches that supply the deeper Myelin-stained brain section
portions of the brain. They take origin at nearly 90 showing extensive demyelination
degrees from their parent arteries. The most prominent
of these vessels are: lenticulostriate branches of the
middle cerebral arteries, Huebner’s artery branches
of the anterior cerebral arteries, thalamogeniculate
branches of the posterior cerebral arteries, and parame-
dian basilar artery branches. These arteries bear much
of the brunt of hypertension. Occlusion of these pen-
etrating arteries causes lacunes—small deep infarcts.

LACUNAR INFARCTS Lacunar infarcts â•…
Lacunar infarcts are miniature, discrete lesions, ranging in base of pons
from 1 to 20╯mm in size. The most common locations interrupting some A hereditary angiopathic condition associated with
are the putamen and the pallidum, followed by the corticospinal mutations in a gene encoding procollagen type IV alpha
pons, thalamus, caudate nucleus, internal capsule, and (pyramidal) fibers. 1 (COL 4, A1) effects small brain arteries as well as
corona radiata. Rarer are lacunes in the cerebral pedun- Such lesions cause larger retinal and cerebral arteries. The clinical findings
cles, pyramids, and subcortical white matter. Lacunes mild hemiparesis. include perinatal hemorrhages and porencephaly, ten-
are not found in the cerebral or cerebellar cortices. dency to brain hemorrhage after trauma, retinal artery
Multiple bilateral lacunes and scars tortuosity, cerebral aneurysms, penetrating artery
The two most common pathologies that affect of healed lacunar infarcts in thalamus, related infarcts, white matter gliosis, and kidney disease.
penetrating arteries are lipohyalinosis and atheromatous putamen, globus pallidus, caudate
branch disease. Serial sections of penetrating arteries nucleus, and internal capsule. Such
that supply the territory of lacunar infarcts often have infarcts produce diverse symptoms.
focal enlargements and small hemorrhagic extravasa- COL 4, A1 mutations. In CADASIL, penetrating arter-
tions through the walls of the arteries. Subintimal foam ies contain a granular material in the media that extends
cells sometimes obliterate the lumens, and pink-staining into the adventitia. Smooth muscle cells in the media
fibrinoid material lies within vessel walls. Arterial seg- are swollen and often degenerated, and the endothe-
ments are often replaced by whorls, tangles, and wisps lium may be absent and replaced by collagen fibers.
of connective tissue that obliterate the usual vascular This hereditary condition causes lacunar infarcts in the
layers. This vascular pathology has been called segÂ

Plate 9-27 Brain: PART I

RISK FACTORS FOR CARDIOVASCULAR DISEASE

50 Coronary artery disease Stroke Peripheral artery disease Heart failure
45 45.4
Biennial age-adjusted rate/1000
40 27.7
35
Lacunar Stroke (Continued) 21.3
30
Diagnosis. Intracerebral branch atheromatous 25 12.4 13.9
disease can be imaged using high-resolution magnetic
resonance imaging (MRI). Plaques in the middle cere- 20 9.5 9.9 7.3
bral artery and basilar artery can be shown to impinge 15
upon or occlude penetrating branches by MRI tech- 3.3 6.2 5 3.5 6.3
niques that show axial sections of the origins of branches 10 2.4 2 2.1
from the parent arteries. 5 Men
Men Women Men Women Men Women Women
Differential. The major important condition to 0 4.0
separate from these “micropathologies” is occlusion 2.0 2.2 3.8 2.6 2.0 3.7 10.4 3.0
of parent arteries blocking flow in penetrating artery Risk ratio 22.7 11.8 9.1 3.8 4.9 5.3 4.2
branches. In patients of Asian origin, especially Japan, Excess risk
Korea, and China, small deep infarcts are often caused
by occlusive disease of the large intracranial parent Normal subjects Hypertensive subjects
arteries. When small deep infarcts are caused by severe
occlusive disease of the intracranial large parent arter- *According to hypertensive status in subjects 35–64 years of age from the Framingham at 36-year follow-up.
ies, the infarcts are slightly larger, the neurologic signs Adapted from Kannel WB. Blood pressure as a cardiovascular risk factor: prevention and treatment. JAMA 1996; 275:1571–1576.
are slightly worse, and recurrence is more common
than in infarcts caused by intrinsic disease of the pen- Level of blood pressure is associated with cardiovascular events
etrating arteries. in a continuous, graded, and apparently independent fashion**

Clinical Presentations. The most common clinical Stroke Stroke and usual diastolic blood pressure (DBP)
syndromes caused by lacunar infarction are pure motor 4.00 -
hemiparesis (weakness of face, arm, and leg on one side
of the body with no sensory, visual, or cognitive abnor- 2.00 -
malities; pure sensory stroke (hemisensory loss without Relative risk of CHD
other signs); dysarthria–clumsy hand syndrome; and - 1.00 -
ataxic hemiparesis. -
CHRONIC SUBCORTICAL VASCULAR DISEASE - 0.50 -
Multiple lacunes, white matter gliosis, and atrophy -
almost always occur together and are accompanied by - 0.25 -
widespread abnormalities of penetrating small arteries.
When severe and clinically evident, this chronic micro- Relative risk of stroke
vasculopathy is often called Binswanger disease. In this -
condition, the cerebral white matter has confluent areas -
of soft, puckered, and granular tissue. These areas are -
patchy and predominate in the occipital lobes and peri- -
ventricular white matter, especially anteriorly and near -
the ventricular surface. The cerebellar white matter is Stroke leading to intracerebral 76 84 91 98 105 mm Hg
also often involved. The ventricles are enlarged, and at hemorrhage into putamen Approximate mean usual DBP
times, the corpus callosum is small. The volume of and ventricle
white matter is reduced, but the cortex is generally Coronary heart disease
spared. There are nearly always some lacunes. Micro-
scopic study shows myelin pallor. Usually, the myelin Coronary heart disease and usual DBP Cardiac hypertrophy and anteroseptal
pallor is not homogeneous, but islands of decreased 4.00 - infact with coronary heart disease
myelination are surrounded by normal tissue. Gliosis is 2.00 -
prominent in zones of myelin pallor. The walls of pen-
etrating arteries are thickened and hyalinized, but 1.00 -
occlusion of the small arteries is rare. Occasional
patients with Binswanger white-matter changes have 0.50 -
had amyloid angiopathy and CADASIL as the underly-
ing vascular pathology. In these patients, arteries within 0.25 -
the cerebral cortex and leptomeninges are thickened
and contain a congophilic substance. 76 84 91 98 105 mmHg Angina
Approximate mean usual DBP
The clinical picture in patients with Binswanger
white matter abnormalities is variable. Most patients ** Relative risk of stroke and coronary heart disease as a function of usual diastolic pressure in 420,000 individuals 25 years or older with a mean
follow-up period of 10 years. Adapted from MacMahon S, Peto R, Cutter S, et al. Blood pressure, stroke, and coronary heart disease: part one.
Lancet 1990;335:765-767.

â•…

have abnormal cognitive function and behavior. Most are plateau periods with relative clinical stability. Many
become slow and abulic. Memory loss, aphasic abnor- patients also have acute lacunar strokes that present
malities, and visuospatial dysfunction are also found. clinically with hemiparesis. MRI defines the full extent
Pseudobulbar palsy, pyramidal signs, extensor plantar of white matter involvement and has spatial resolution
reflexes, and gait abnormalities are common. The clini- that allows detection of small lacunar lesions. Diffusion-
cal findings often progress gradually or stepwise, with weighted imaging can show even small acute and sub-
worsening during periods of days to weeks. Often, there acute infarcts with great accuracy.

226 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

P late 9-28 Cerebrovascular Circulation and Stroke

Hypertensive Encephalopathy

Hypertensive encephalopathy refers to the conse- Normal brain Hypertensive encephalopathy, with
quences for brain function associated with severe and generalized constriction of cerebral
acute rises in systemic blood pressure. The effects of
severe hypertension involve a variety of clinical fea- arteries and their small branches
tures, including generalized tonic-clonic seizures,
decreased level of consciousness, cortical blindness, and Diffusely increased signal in MRI (FLAIR sequence)
the funduscopic features of hypertensive retinopathy or in medulla and cerebellum in patient with posterior
“malignant” hypertension. This clinical picture has an reversible encephalopathy syndrome restricted to
imaging correlate in computed tomography (CT) scan the posterior fossa structures. Reprinted with per-
and, especially magnetic resonance imaging (MRI) in MRI (T2) showing bright signal predominantly in the mission from Karakis I, MacDonald JA, Stefanidou M,
the form of abnormal signal that especially involves the white matter of the posterior aspect of both cerebral Kase CS. Clinical and radiological features of brain-
white matter of the cerebral hemispheres, predomi- hemispheres in a patient with posterior reversible stem variant of hypertensive encephalopathy.
nantly posteriorly; because these changes tend to be encephalopathy syndrome J Vasc Interv Neurol 2009;2:172-176.
reversible after normalization of blood pressure, the
initial imaging correlate of hypertensive encephalopa- â•…
thy was initially labeled the posterior reversible leukoen-
cephalopathy syndrome. this highlights the fact that the imaging changes reflect formation of vasogenic edema. It is still unclear why
edema, not infarction. most instances predominantly involve the posterior
The MRI features of the syndrome are characterized aspects of the cerebral hemispheres. The prevailing
by vasogenic edema, which corresponds to bright signal The pathogenesis of the clinical-radiologic syndrome theory is that the posterior cerebral circulation has less
on diffusion-weighted imaging (DWI) sequences as of hypertensive encephalopathy is thought to reflect the sympathetic innervation than the anterior circulation,
well as on apparent diffusion coefficient (ADC) maps, effects of an acute increase in blood pressure, leading thus making it more prone to vasodilation with devel-
the latter differentiating vasogenic edema from infarc- to fibrinoid necrosis of the arterial wall with increase opment of cerebral edema in the event of a sudden
tion, because the latter is expected to show decreased in the permeability of the blood-brain barrier and loss increase in systemic arterial pressure.
signal to accompany the bright signal on DWI. These of cerebral autoregulation, with the end result of
features are generally reversible, the same as the clinical
manifestations, including cortical blindness. The fea-
tures of the posterior reversible leukoencephalopathy syn-
drome demonstrate substantial variability, because the
MRI changes can also have an anterior location, with
gray, as well as white matter involvement, and there
may be only partial reversibility.

An important aspect of this disorder that needs to be
emphasized is that hypertensive encephalopathy is not
a function of the absolute levels of systemic blood pres-
sure elevation but rather of the percentage increase
in blood pressure based on the individual patient’s
baseline blood pressure. Thus a normotensive person
can present with hypertensive encephalopathy after
a modest blood pressure elevation, whereas a chronic
hypertensive patient may require a severe blood pres-
sure elevation in order to develop the syndrome.
Although the majority of patients experience clinical
recovery with concomitant resolution of the imaging
changes after blood pressure control, there is the poten-
tial for persistent deficits to occur as a result of con-
comitant intracerebral bleeding into the areas of the
brain affected by the encephalopathy.

There are a number of clinical as well as imaging
variations in patients presenting with hypertensive
encephalopathy. One that is occasionally seen is a syn-
drome predominantly affecting the brainstem and cer-
ebellum, with presentation with headache, nausea, and
vomiting, as well as mild and nonspecific brainstem
signs, such as gait disturbance, in the setting of florid
vasogenic edema, at times involving the whole extent of
the brainstem. In some instances, the patient may actu-
ally not have any clinical signs of brainstem involve-
ment while having florid vasogenic edema in that area;

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 227