CHAPTER 2

Overview of the Nervous System

The nervous system consists of the central nervous system (CNS) and the peripheral nervous system (PNS). The nerve roots of the spinal cord connect the CNS to the PNS. The CNS is made up of the brain (encephalon), which lies rostral to the foramen magnum, and the spinal cord (myelon), which lies caudal. The brain is made up of the cerebrum, diencephalon, brainstem, and cerebellum (Figure 2.1). The cerebrum (telencephalon) is the largest component of the CNS. It consists of two cerebral hemispheres connected by the corpus callosum. The diencephalon (L. “between brain,” “interbrain”) lies between the telencephalon and the midbrain. The brainstem connects the diencephalon with the spinal cord. It consists, from rostral to caudal, of the midbrain, pons, and medulla oblongata. The cerebellum (Latin diminutive of cerebrum) is a large, fissured structure that lies posterior to the brainstem. It is composed of a narrow midline strip (vermis) and paired lateral hemispheres and is connected to the brainstem by the superior, middle, and inferior cerebellar peduncles. The spinal cord extends from the cervicomedullary junction to the conus medullaris.

FIGURE 2.1 A. Gross brain. B. T1-weighted MR image. Approximately matched midline sagittal sections. Sagittal T1-weighted MRI of the brain and upper cervical spinal cord. Labels: 1, septum pellucidum; 2, corpus callosum (a, genu; b, body; c, splenium; d, rostrum); 3, cingulate gyrus; 4, central sulcus; 5, column of fornix; 6, quadrigeminal plate; 7, quadrigeminal cistern; 8, thalamus; 9, cerebellum; 10, aqueduct of Sylvius; 11, fourth ventricle; 12, medulla; 13, pons; 14, mammillary body; 15, optic tract; 16, olfactory area; 17, gyrus rectus; 20, parietal-occipital fissure; 21, calcarine fissure; 49, midbrain; 51, pineal gland. (Reprinted with permission from Barboriak DP, Taveras JM. Normal cerebral anatomy with magnetic resonance imaging. In: Ferrucci JT, ed. Taveras and Ferrucci’s Radiology on CD-ROM. Philadelphia: Lippincott Williams & Wilkins, 2003.)

Neuroembryology

In the embryo, development of the nervous system begins when ectodermal cells start to form the neural tube. The sonic hedgehog gene is vital for normal CNS development. It mediates a number of processes in development, including differentiation of the neuroectoderm. The neural tube begins to form in the 3rd week and is completed by the 4th week of embryonic life. The first stage in neural tube development is a thickening of ectoderm, forming the neural plate. A longitudinal fissure develops in the neural plate and progressively enlarges to form the neural groove. Differentiation of the cephalic from the caudal end of the neural groove is controlled by a signaling molecule called noggin. As the groove deepens, its edges become more prominent and become the neural folds. The folds eventually meet, fuse, and complete the transformation into a tubular structure. The neural tube lies between the ectoderm on the surface and the notochord below. The cranial part of the neural tube evolves into the brain, and the caudal part becomes the spinal cord. With closure of the neural tube, the neural crest—neuroectoderm not incorporated into the neural tube—lies between the neural tube and the surface. Neural crest cells give rise to the PNS. Cells that lie ventral in the neural tube develop into motor cells, and those that lie dorsal develop into sensory cells. Sonic hedgehog is involved in this differentiation. Retinoic acid is also important at this stage, and the use of retinoic acid derivatives for acne treatment in early pregnancy may have catastrophic effects on the developing nervous system.

Neuroepithelial cells in the wall of the neural tube form neuroblasts, which develop into neurons, and glioblasts, which develop into macroglial and ependymal cells. With further maturation, the neural tube wall develops three layers: an innermost ventricular layer composed of ependymal cells, a mantle (intermediate) layer consisting of neurons and macroglia, and an outer marginal layer, which contains the nerve fibers of the neuroblasts in the mantle layer. The ventricular layer eventually forms the lining of the ventricles and central canal of the spinal cord, the mantle layer becomes the central gray matter, and the marginal layer becomes the white matter. Closure of the tube (neurulation) separates the developing nervous system from the surface ectoderm, forming the neurula (the embryo at 19 to 26 days after fertilization). Neurulation begins near the midpoint of the neural tube and advances toward the anterior (cephalic) and posterior (caudal) neuropores at either end; the anterior and posterior neuropores are the last sites to close. Neurulation is complete by 4 weeks; afterward, the CNS is a long, fluid-filled, tubular structure, and this basic configuration is maintained throughout life. Defective neurulation is common. Neural tube defects (NTDs) are common congenital malformations that result from failure of normal neural tube closure during early embryogenesis (Box 2.1). Neural tube closure is complete by the end of the first month; NTDs happen before a mother knows she is pregnant.

BOX 2.1

Neural Tube Defects

Neural tube defects (NTDs) are very common. They may be divided into an upper type (anencephaly, encephalocele) and a lower type (spinal dysraphism). Anencephaly is a lethal malformation that results from failure of closure of the anterior neuropore. The brain fails to develop. The face develops, but the cranial vault does not, and the brain may consist of only a tangled knot of primordial central nervous system tissue. Anencephaly is a common cause of stillbirth. There may be enough brainstem present to support vegetative life for a brief period. Failure of the posterior neuropore to close normally causes congenital malformations affecting the lumbosacral region. The most severe of these is myelomeningocele, essentially the posterior neuropore equivalent of anencephaly. The posterior elements of the lumbosacral vertebra fail to develop, the spinal canal is open posteriorly, and the spinal cord and cauda equina are herniated dorsally into a sac that lies over the surface of the lower back. The patients have severe neurologic deficits involving the lower extremities, bowel, and bladder. When the defect is less severe, the sac contains only meninges (meningocele). A mild defect of posterior neuropore closure results only in failure of normal fusion of the posterior arches of the lumbosacral vertebra. Patients are neurologically normal, and the defect is seen only on imaging studies (spina bifida occulta). Spina bifida occulta is quite common, affecting up to 10% of the population. Incomplete defects of anterior neuropore closure cause similar defects affecting the head and neck. An encephalocele is herniation of brain tissue through a bony defect in the skull. Encephaloceles most commonly occur in the occipitocervical region and are clinically obvious. When they involve the base of the skull (basal encephalocele), they may not be obvious. Cranium bifidum is dysraphism limited to the bony elements of the skull, most often the occipital bone; it is the cephalic analogue of spina bifida occulta. Arnold-Chiari malformations may involve defects in closure of both the anterior and posterior neuropore; these complex anomalies are discussed further in Chapter 21.

The pathogenesis of NTDs is multifactorial; both genetic and environmental factors are important, and the pattern of occurrence suggests a multifactorial polygenic or oligogenic etiology. Overactivation of sonic hedgehog signaling has been implicated. There are significant geographic differences, for example, NTDs are very common in Ireland. Folic acid plays a pivotal role in neuroembryogenesis. Genetic defects of the folate and homocysteine pathways have been implicated in the etiology of NTDs; periconceptional folate supplementation reduces the risk, and mothers of affected children may have elevated plasma homocysteine levels. A group at particular risk for having children with NTDs is women receiving certain antiepileptic medications during pregnancy.

The brain develops from the region of the anterior neuropore, forming three and then five vesicles. First, there is segmentation into three parts: forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon) (Table 2.1). The forebrain then divides into the telencephalon, which becomes the cerebrum, and the diencephalon. The hindbrain divides into the metencephalon, which becomes the pons and cerebellum, and the myelencephalon, which becomes the medulla. The five-vesicle stage is complete by 6 weeks of embryonic life. The telencephalon then undergoes midline cleavage into a pair of side-by-side vesicles—primordial hemispheres. Regions of the telencephalon expand (evaginate) to form the cerebral hemispheres. The neural tube lumen continues into the evaginations, forming the ventricular system.

TABLE 2.1 The Derivatives of the Anterior Neuropore

Failure of normal cleavage into two hemispheres results in distinctive anomalies. Milder forms include arrhinencephaly, in which there is absence of the olfactory bulbs and tracts, and agenesis of the corpus callosum. Severe cleavage failure results in holoprosencephaly, in which there is only a single “hemisphere” (alobar prosencephaly), or a partial attempt at division (lobar and semilobar prosencephaly). Prenatal diagnosis is possible using sonography. The genes that control segmentation are also important in development of the face, and some anomalies involve both the face and the brain, particularly holoprosencephaly. Certain patterns of midline facial abnormality predict a severe brain malformation.

Following the segmentation and cleavage stages of neuroembryogenesis, the developing nervous system enters a stage of cellular proliferation and migration that is not complete until after birth. Neurons in the germinal matrix proliferate intensely and then migrate to different parts of the nervous system. Cells destined to populate a specific brain region arise from a specific part of the germinal matrix. Processes that interfere with normal proliferation and migration cause another set of congenital malformations that includes microcephaly, megalencephaly, cortical heterotopia (band heterotopia, double cortex), agenesis of the corpus callosum, and schizencephaly. Three major callosal abnormalities have been identified: hypoplasia, hypoplasia with dysplasia, and complete agenesis. Finally, the brain develops its pattern of gyri and sulci. Defects at this stage of neocortical formation produce lissencephaly, in which the sulci and gyri fail to develop (smooth brain); pachygyria, in which the gyri are thicker than normal; and polymicrogyria, in which there are an excessive number of small gyri. These abnormalities may affect all or only part of the brain. Typically, children with these malformations have developmental delay and seizures. Other systems may be involved in these neuronal migration disorders, including eye and muscle (muscle-eye-brain disease, Walker-Warburg syndrome, and Fukuyama congenital muscular dystrophy). Modern imaging, including prenatal magnetic resonance imaging (MRI), may identify some of these disorders.

Even after normal formation, the nervous system may be affected by intrauterine processes. In hydranencephaly, the hemispheres are destroyed and the remnants lie in a sac of meninges. This is to be distinguished from hydrocephalus, where the ventricles are markedly expanded. In hydranencephaly, the skull is normal but devoid of meaningful contents, in contrast to anencephaly, in which the skull is malformed along with the brain. In porencephaly, a cyst forms in a region where developing brain has been destroyed or has developed abnormally. Transillumination of the skull with a strong light may help detect these disorders early. The diagnosis may be confirmed by computed tomography, MRI, or sonography, and the diagnosis can be made with sonography in the prenatal period. Numerous conditions may affect the neonatal brain, including germinal matrix hemorrhage, hypoxic-ischemic encephalopathy, cerebral infarction, and infection. Many of these disorders produce “cerebral palsy,” an umbrella term with little neurologic meaning.

Bony Anatomy

The skull is fashioned of several large bones and myriad complexly articulated smaller bones. The major bones are the frontal, temporal, parietal, occipital, and sphenoid; all are joined by suture lines. The major sutures are the sagittal and coronal, but there are numerous others. Sometimes sutures close prematurely (craniostenosis, craniosynostosis), before the skull has completed growth, producing malformed and misshapen skulls (Box 2.2; Figure 2.2). Noggin plays a role in the regulation of cranial suture fusion, and craniosynostosis may be the result of inappropriate down-regulation of noggin expression.

BOX 2.2

Craniosynostosis

The primary clinical manifestation of craniosynostosis is an abnormally shaped skull; the configuration depends on which suture(s) have fused prematurely. The skull is unable to expand in a direction perpendicular to the fused suture line. With synostosis of a major suture, the skull compensates by expanding in a direction perpendicular to the uninvolved sutures. Premature closure of the sagittal suture, the most common form of craniosynostosis, produces a skull that is abnormally elongated (scaphocephaly, dolichocephaly). Synostosis of both coronal sutures causes a skull that is abnormally wide (brachycephaly). When the coronal and lambdoid sutures are involved, the skull is tall and narrow (turricephaly, tower skull). Synostosis of the sagittal and both coronal sutures causes oxycephaly (acrocephaly), a pointed, conical skull. Plagiocephaly refers to a flattened spot on one side of the head; it is due to premature unilateral fusion of one coronal or lambdoid suture. Synostosis involving the metopic suture causes trigonocephaly, a narrow, triangular forehead with lateral constriction of the temples. Synostosis of the posterior sagittal and both lambdoidal sutures produces the “Mercedes Benz pattern.” Severe craniosynostosis involving multiple sutures may cause increased intracranial pressure. Craniosynostosis usually occurs as an isolated condition, but there are numerous syndromes in which craniosynostosis occurs in conjunction with other anomalies, particularly malformations of the face and the digits, for example, Crouzon’s, Apert’s, and Carpenter’s syndromes. Several genetic mutations may cause craniosynostosis. There are many potential causes of nonsyndromic craniosynostosis, including environmental, hormonal, and biomechanical factors.

FIGURE 2.2 Craniosynostosis involving the cranial sutures: (A) sagittal, (B) coronal, and (C) both sagittal and coronal. (With author’s permission from Reeves AG, Swenson RS. Disorders of the Nervous System: A Primer. New Haven: Dartmouth Medical School. Retrieved on August 28 from http://www.dartmouth.edu/~dons/figures/chapt_1/Fig_1_2.htm. Copyright © 2008 Reeves.)

The interior of the skull is divided into compartments, or fossae. The anterior fossa contains the frontal lobes, which rest on the orbital plates. The cribriform plate lies far anteriorly, between the orbital roofs; when fractured during head injury, cerebrospinal fluid (CSF) rhinorrhea may ensue. The middle fossa primarily contains the temporal lobes, and several major cranial nerves (CNs) run through the area. The posterior fossa contains the brainstem, cerebellum, and vertebrobasilar vessels. Except for CNs I and II, all the CNs run through or exit from the posterior fossa.

The frontal bone contains the frontal sinuses. The temporal bone has two parts: the thin squamous portion forms the temple; the thick petrous part forms the floor of the middle fossa. The squamous part contains the groove of the middle meningeal artery and may be easily fractured, sometimes producing epidural hematoma. The petrous pyramids have their apices pointed medially and their thick bases pointed laterally; deep within are the middle and inner ear structures, the internal auditory meatus, the facial canal with its genu, and the air cells of the mastoid sinus. Fractures through the petrous bone may cause hemotympanum (blood in the middle ear cavity), hearing loss, or facial nerve palsy.

The sphenoid bone has greater and lesser wings and contains the sella turcica. The greater wings form the anterior wall of the middle fossa; the lesser wings form part of the floor of the anterior fossa. The greater and lesser wings attach to the body of the sphenoid, buried within which is the sphenoid sinus cavity. The best way to appreciate the anatomy of the sphenoid bone is to look at it in disarticulated isolation, when the “wings” become obvious. The sella turcica makes up a saddle-shaped depression in the body of the sphenoid; alongside the sella lie the cavernous sinuses. The pituitary gland lies within the sella, and neoplasms of the pituitary may enlarge the sella and push upward out of the sella onto the optic chiasm. Enlargement of the sella is a nonspecific finding in increased intracranial pressure.

The occipital bone makes up the posterior fossa. The clivus forms the anterior wall of the posterior fossa; it ends superiorly in the dorsum sellae and posterior clinoid processes. The basilar artery and brainstem lie along the clivus. Tumors, most often chordomas, may erode the clivus and produce multiple CN palsies. Various structures pass into or out of the skull through the numerous foramina that pierce its base (Table 2.2). Pathologic processes may involve different foramina; the resultant combination of CN abnormalities permits localization (see Chapter 21).

TABLE 2.2 Major Skull Base Foramina and Their Contents

Roman numerals refer to cranial nerves III through XII.

Meninges

The meninges are composed of the dura mater, pia mater, and arachnoid (Figure 2.2). The pia is thin, filmy, and closely adherent to the brain and its blood vessels, extending down into the sulci and perivascular spaces. The dura mater is thick and tough (the pachymeninges; Gr. pachys “thick”) and provides the substantive protective covering for the CNS. The dura has an inner, meningeal layer and an outer periosteal layer that is continuous with the periosteum of the inner calvarium. The two leaves of dura separate to enclose the cerebral venous sinuses. The dura closely adheres to the bone at the suture lines and around the foramen magnum. Sheaths of dura cover the cranial and spinal nerves as they exit and then fuse with the epineurium. The vaginal sheath of the optic nerve is a layer of meninges that follows the optic nerve; ultimately the dura fuses with the sclera of the eyeball. Folds of dura separate the two hemispheres (the falx cerebri) and the middle fossa from the posterior fossa structures (the tentorium cerebelli). A diminutive fold (the falx cerebelli) separates the cerebellar hemispheres. The cranial dura is, for the most part, a single layer, distinguishable as two sheets only at the venous sinuses and in the orbit. In contrast, the layers of the spinal dura are separate. The outer, periosteal layer forms the periosteum of the vertebral canal, and the meningeal layer closely covers the spinal cord. This separation creates a wide epidural space in the spinal canal that is not present in the head. The spinal epidural space is a frequent site for metastatic disease. The cranial and spinal dura fuse at the foramen magnum.

The arachnoid abuts the inner surface of the dura, and a web of fine, diaphanous trabeculae crosses the subarachnoid space to connect the arachnoid to the pia (Figure 2.3). Over the surface of the brain and spinal cord, the pia and the arachnoid are closely adherent and virtually inseparable, forming essentially one membrane: the pia-arachnoid, or leptomeninges (Gr. leptos “slender”). The subdural space is the space between the dura and the arachnoid. Normally, the space is more potential than real, but under some circumstances, fluid may accumulate in the subdural space. The subarachnoid space lies beneath the arachnoid membrane. Bleeding into the subarachnoid space is a common complication of craniocerebral trauma and the rupture of aneurysms or vascular malformations. The CSF flows through the subarachnoid space. Focal enlargements of the subarachnoid space (cisterns) develop in areas where the dura and arachnoid do not closely follow the contour of the brain, creating a wide space between the arachnoid and the pia. The cisterna magna (cerebellomedullary cistern) is a CSF reservoir posterior to the medulla and beneath the inferior part of the cerebellum (Figure 2.4). Other important cisterns include the perimesencephalic (ambient), interpeduncular (basal), prepontine, and chiasmatic. The term basal cisterns is sometimes used to include all the subarachnoid cisterns at the base of the brain. Focal enlargements of the subarachnoid space produce arachnoid cysts, which may rarely compress the brain or spinal cord.

FIGURE 2.3 Schematic diagram of a coronal section of the meninges and cerebral cortex, showing the relationship of the arachnoid villus to the subarachnoid space and superior sagittal sinus. (Modified from Weed LH. The absorption of cerebrospinal fluid into the venous system. Am J Anat 1923;31:191–207.)

FIGURE 2.4 Schematic diagram of the leptomeninges and nervous tissue, showing the relationship of the subarachnoid space, perivascular channels, and nerve cells. (Modified from Weed LH. The absorption of cerebrospinal fluid into the venous system. Am J Anat 1923;31:191–207.)

The lateral ventricles are made up of a body and an atrium (common space), from which extend the horns (Figure 2.4). The temporal horn extends forward into the temporal lobe; the occipital horn extends backward into the occipital lobe. Within the atrium of each ventricle lies CSF-forming choroid plexus. The two lateral ventricles come together in the midline, where they join the third ventricle. The foramen of Monro is the passageway between the lateral and third ventricles. The third ventricle is a thin slit lying in the midline between and just below the lateral ventricles. Anteriorly it forms spaces, or recesses, above and below the pituitary; posteriorly it creates a recess above the pineal gland. The third ventricle ends at the cerebral aqueduct (of Sylvius), which conveys CSF down to the fourth ventricle. The fourth ventricle is also a midline structure that has superior, inferior, and lateral extensions like narrow cul-de-sacs. The inferior extension of the fourth ventricle ends at the cervicomedullary junction; at the obex, it becomes continuous with the central canal of the spinal cord. The lateral recesses of the fourth ventricle contain small apertures—the foramina of Luschka—through which CSF empties into the subarachnoid space surrounding the brainstem. A midline aperture in the roof of the fourth ventricle—the foramen of Magendie—joins the fourth ventricle with the cisterna magna. Choroid plexus lies in the roof of the fourth ventricle. Obstruction to the flow of CSF through this system may cause hydrocephalus (see Chapter 50).

The Cerebral Hemispheres

The cerebrum is composed of two hemispheres that are covered by a layer of gray matter, the cerebral cortex. Underneath the cortex is the white matter, which consists of projection, commissural, and association fibers. Deep in the midline of each hemisphere are masses of gray matter: the basal ganglia and the diencephalon. The diencephalon is made up of the thalamus, metathalamus, epithalamus, subthalamus, and hypothalamus.

The cerebral cortex along with its underlying white matter is the pallium, or cerebral mantle. The pallium consists of the phylogenetically recent neopallium, which makes up the majority of the hemispheres, and the paleopallium and archipallium, more primitive areas that are small in humans. The paleopallium is the piriform lobe, and the archipallium is the hippocampal formation. The paleopallium and archipallium constitute the rhinencephalon, which is connected structurally and functionally with the limbic lobe.

The cerebral mantle is intricately folded and traversed by fissures and sulci (Figures 6.1 and 6.2). The cortex is arranged in layers of cells and fibers. Differences in the anatomy of the layers form the basis for cytoarchitectonic maps of the brain. The best-known and most widely used map is that of Brodmann, which divides the brain into 52 identifiable areas (Figures 6.3, 25.1, and 25.2). In primates, especially humans, a huge number of neurons are able to occupy the relatively small intracranial space because of layering of the cortex and the folding that vastly increases the surface area of the brain. The more important fissures divide the hemispheres into lobes, and these in turn are subdivided by the sulci into gyri, or convolutions. A fissure and a sulcus are different, but the terms are not used consistently. Lissencephaly is a congenital malformation in which the normal pattern of sulci fails to develop. A normally sulcated brain is gyrencephalic. Separation of the parts of the brain by surface landmarks is practical anatomically, but the divisions are morphologic; the individual lobes are not necessarily functional units.

The hemispheres are incompletely separated by the median longitudinal (interhemispheric) fissure, within which lies the falx cerebri (Figure 6.4). Deep in the fissure run branches of the anterior cerebral artery. Two major surface landmarks are visible on the lateral hemispheric surface: the lateral (sylvian) fissure and the central (rolandic) sulcus (Figure 6.1). The sylvian fissure begins at the vallecula on the basal surface between the frontal and temporal lobes and runs laterally, posteriorly, and superiorly. It divides the frontal and parietal lobes above from the temporal lobe below. In the depths of the sylvian fissure lies the insula (island of Reil), surrounded by the limiting, or circular, sulcus. The frontal, parietal, and temporal opercula are overhanging aprons of cerebrum that cover the insula. More superficially in the sylvian fissure run branches of the middle cerebral artery. The central sulcus runs obliquely from posterior to anterior, at an angle of about 70 degrees, from about the midpoint of the dorsal surface of the hemisphere nearly to the sylvian fissure, separating the frontal lobe from the parietal. The anatomy of the cerebral hemispheres is discussed further in Chapter 6.

Basal Ganglia

Basal ganglia terminology can be confusing, and usage is inconsistent. The caudate, putamen, and globus pallidus (GP) are all intimately related from an anatomical and functional standpoint. The term basal ganglia includes these plus other related structures such as the subthalamic nucleus and substantia nigra. The caudate and putamen are actually two parts of a single nucleus connected by gray matter strands and separated from each other by fibers of the anterior limb of the internal capsule. The heavily myelinated capsular fibers passing between and intermingling with the gray matter bridges cause the caudate-putamen junction to look striped, hence the term corpus striatum or striatum (L. “striped body”) to refer to the caudate and putamen. The term corpus striatum is sometimes used to include the GP as well. The caudate and putamen are the neostriatum; the GP is the archi- or paleostriatum. The putamen and GP together are shaped like a lens, hence the term lenticular or lentiform nuclei. The claustrum, amygdala, and substantia innominata are sometimes included as basal ganglia; they are indeed gray matter masses lying at the base of the hemispheres but bear little functional relationship to the other basal ganglia.

The caudate (L. “tail”) nucleus is composed of a head, body, and tail. The body and progressively thinner tail extend backward from the head and arch along just outside the wall of the lateral ventricle, ultimately following the curve of the temporal horn and ending in the medial temporal lobe in close approximation to the amygdala. The caudate is thus a long, C-shaped structure with bulbous ends. The putamen lies just lateral to the GP. The GP lies medial to the putamen and just lateral to the third ventricle, separated from the caudate by the anterior limb and from the thalamus by the posterior limb of the internal capsule. The GP (L. “pale body”) or pallidum is traversed by myelinated fibers, making it look lighter than the putamen, hence the name. The substantia nigra lies in the midbrain just posterior to the cerebral peduncle. It is divided into pars compacta and pars reticulata portions. In the pars compacta lie the prominent melanin-containing neurons that give the region its dark color and its name.

The basal ganglia are part of the extrapyramidal motor system. The caudate and putamen serve as the central receiving area of the basal ganglia; they send efferent fibers primarily to the GP. The GP is then responsible for most of the output of the basal ganglia. Fahr’s disease is a rare inherited disorder causing calcification and cell loss in the basal ganglia.

The basal ganglia generally serve to suppress activity in thalamocortical motor neurons. Hypokinetic movement disorders are characterized by reduced motor function because of higher than normal basal ganglia output, for example, Parkinson’s disease. Hyperkinetic movement disorders are characterized by excessive motor activity because of lower than normal basal ganglia output, for example, Huntington’s disease. Dysfunction of nonmotor circuits of the basal ganglia has been implicated in Tourette’s syndrome and obsessive-compulsive disorder. The basal ganglia are discussed further in Chapters 26 and 30.

Thalamus

The thalamus is a large, paired, ovoid structure that lies deep in the midline of each cerebral hemisphere, sitting atop the brainstem. The third ventricle lies between the two thalami, which are joined together by the massa intermedia. The dorsal aspect of the thalamus forms the floor of the lateral ventricle, and its medial aspect forms the wall of the third ventricle. It is bounded laterally by the internal capsule and basal ganglia; ventrally it is continuous with the subthalamus. The thalamus is connected with the cerebral cortex by the thalamic peduncles. The anterior thalamic peduncle consists of frontothalamic, thalamofrontal, striothalamic, and thalamostriatal fibers that run in the anterior limb of the internal capsule. The superior thalamic peduncle consists of thalamoparietal sensory fibers from the thalamus to the cortex; these fibers run in the posterior limb of the internal capsule. The posterior thalamic peduncle contains the optic radiations from the lateral geniculate body to the occipital cortex, and the inferior thalamic peduncle carries auditory radiations from the medial geniculate body to the temporal cortex. The thalamic syndrome (Dejerine-Roussy) is characterized by contralateral hemianesthesia and pain due to infarction of the thalamus. The thalamus is discussed further in Chapter 6.

Brainstem

The brainstem extends caudally from the diencephalon to the spinal cord. Rostrally, the midbrain is continuous with the subthalamus and thalamus; caudally, the medulla is continuous with the spinal cord. The rostral limit of the midbrain is an imaginary line between the posterior commissure and mammillary bodies; the caudal limit is defined by a line between the pontomesencephalic sulcus and the inferior colliculi. The pons extends from this point caudally to the pontomedullary sulcus and the medulla from that point to the cervicomedullary junction at the foramen magnum.

The dominant feature of the ventral midbrain is the paired crus cerebri, which contain the cerebral peduncles. Dorsally, the dominant feature is the quadrigeminal plate, made up of the superior and inferior colliculi. The superior colliculus is connected to the lateral geniculate body by the brachium of the superior colliculus; the inferior colliculus is connected to the medial geniculate body in similar fashion. The pulvinar, the most caudal portion of the thalamus, overlies the rostral midbrain laterally. The cerebral peduncles connect the midbrain to the cerebrum above. The superior cerebellar peduncle (brachium conjunctivum) connects the midbrain to the cerebellum behind. The ventral pons is a massive, bulging structure because of the underlying transverse pontocerebellar fibers. Of the brainstem segments, the pons lies closest to the clivus and dorsum sellae. The pons is connected to the cerebellum posteriorly by the middle cerebellar peduncle (brachium pontis). Posteriorly, the cerebellum overlies the pons, separated from it by the fourth ventricle. The cerebellopontine angle is the space formed by the junction of the pons, medulla, and overlying cerebellar hemisphere. Neoplasms may form in the cerebellopontine angle, most often acoustic neuromas. The dorsal aspect of the pons consists of the structures that make up the floor of the ventricular cavity.

The medulla oblongata is the most caudal segment of the brainstem, lying just above the foramen magnum, continuous with the pons above and spinal cord below. The transition to spinal cord is marked by three features: the foramen magnum, the decussation of the pyramids, and the appearance of the anterior rootlets of C1. The inferior olives form a prominent anterolateral bulge on the ventral medulla. Between the two olives lie the midline medullary pyramids. Posteriorly, the cerebellum overlies the medulla, connected to it by the inferior cerebellar peduncle (restiform body). The gracile and cuneate tubercles are prominences on the posterior aspect of the medulla at the cervicomedullary junction.

CNs III through XII emerge from the brainstem. The third nerve exits through the interpeduncular fossa, the fourth nerve through the tectal plate posteriorly. CN V enters the pons laterally, and CNs VI, VII, and VIII all emerge at the pontomedullary junction (VI anteriorly, VII and VIII laterally through the cerebellopontine angle). CNs IX, X, and XI emerge from the groove posterior to the inferior olive. CN XII exits anterolaterally in the sulcus between the inferior olive and the medullary pyramid.

The brainstem is a conduit for conduction of information. All signaling between the body and the cerebrum traverses the brainstem. Information to and from the cerebellum also traverses the brainstem. The brainstem is also the location of CN nuclei III through XII. In addition, the brainstem reticular formation controls vital visceral functions, such as cardiovascular and respiratory function and consciousness.

Many disorders may affect the brainstem. These characteristically produce CN abnormalities on the side of the lesion and long tract motor or sensory abnormalities contralaterally, that is, crossed syndromes. A mnemonic called the “rule of 4” helps recall the anatomy and the brainstem syndromes. The anatomy of the brainstem is discussed further in Chapter 11.

Cerebellum

The cerebellum is the largest portion of the rhombencephalon, about one-tenth as large as the cerebrum. The cerebellum is deeply fissured; its surface is broken into a number of folia. If unfolded, the surface area would be about half that of the cerebral cortex. The cerebellar cortex overlies a medullary core of white matter. The cortex is densely packed with neurons, primarily granule cells; in fact, the cerebellum contains more neurons than the cerebral cortex. The branching of the white matter into the cortical mantle and the structure of the folia lends a treelike appearance (arbor vitae). The cerebellum lies in the posterior part of the posterior fossa, behind the brainstem and connected to it by the three cerebellar peduncles (Figure 2.5). It forms the roof of the fourth ventricle and is separated from the occipital lobe above by the tentorium cerebelli. The cerebellar tonsils are small, rounded masses of tissue on the most inferior part of each cerebellar hemisphere, just above the foramen magnum. Increased intracranial pressure may cause tonsillar herniation: the tonsils move through the foramen magnum into the upper cervical spinal canal. In Arnold-Chiari malformation, the tonsils are also herniated below the foramen magnum, but this is a congenital anomaly and is not due to increased intracranial pressure.

FIGURE 2.5 Diagram of the cerebrospinal fluid spaces, showing lateral, third, and fourth ventricles; foraminal connections with the subarachnoid space; and some of the major subarachnoid cisterns. I and II, lateral ventricles; III, third ventricle; IV, fourth ventricle. (Modified from Dandy WE. Bull Johns Hopkins Hosp 1921;32:67–123.)

The cerebellum can be divided into three lobes: anterior, posterior, and flocculonodular, each of which has a vermis and hemisphere portion. There are three major fissures: primary, horizontal, and posterolateral. The anterior lobe lies anterior to the primary fissure; the posterior lobe, by far the largest, lies between the primary fissure and the posterolateral fissure; and the flocculonodular lobe lies posterior to the posterolateral fissure. Anatomists have further divided the cerebellum into a number of lobules and given them arcane names that are not clinically useful. From a physiologic and clinical standpoint, the cerebellum can be viewed as having three components: the flocculonodular lobe, the vermis, and the hemispheres. The flocculonodular lobe is phylogenetically the oldest and is referred to as the archicerebellum. It has extensive connections with the vestibular nuclei and is concerned primarily with eye movement and gross balance. The vermis is the paleocerebellum, or spinocerebellum. It has extensive connections with spinal cord pathways and is concerned primarily with gait and locomotion. The most phylogenetically recent part of the cerebellum is the neocerebellum, or the cerebellar hemispheres, which make up the bulk of the cerebellum. These are concerned with coordinating movement and providing fine motor control and precise movement to the extremities (Figure 2.6). Numerous disorders may affect the cerebellum (see Chapter 43).

FIGURE 2.6 Midline sagittal section of the brainstem and cerebellum with the third ventricle retouched.

Spinal Cord

The spinal cord is elongated and nearly cylindrical, continuous with the medulla above and ending in a conical tip, the conus medullaris (Figures 2.7 and 2.8). The spinal cord occupies approximately the upper two-thirds of the vertebral canal, extending from the foramen magnum to a level that varies slightly from individual to individual but in adults lies between the lower border of L1 and the upper border of L2. The filum terminale is a delicate filament of connective tissue that descends from the apex of the conus medullaris to the periosteum of the posterior surface of the first segment of the coccyx (Figure 2.8). The dentate ligaments extend along the lateral surface of the spinal cord, between the anterior and posterior nerve roots, from the pia to the dura mater. They suspend the spinal cord in the vertebral canal. The general organization is the same throughout, but there is some variability in detail at different segmental levels. The cord and vertebral column are of different lengths because of different fetal growth rates, so there is not absolute concordance between cord levels and vertebral levels; this discrepancy grows more significant at more caudal levels. Each spinal cord segment has anterior and posterior roots. The anterior roots convey motor and autonomic fibers into the peripheral nerve. Posterior roots bear ganglia composed of unipolar neurons, and the roots are made up of the central processes of these neurons. The ganglion lies in the intervertebral foramen in close proximity to the anterior root. The anterior and posterior roots join just distal to the dorsal root ganglion to form the mixed spinal nerve. In the thoracolumbar region, white and gray rami connect the spinal nerve to the paravertebral sympathetic chain. The spinal cord ends in the conus medullaris. Roots from the lower cord segments descend to their exit foramina, forming the cauda equina (Figure 2.9).

FIGURE 2.7 Drawings of dissections of the left dentate nucleus with portions of the cerebellar cortex and vermis intact. A. Dissection of the posterior surface of the cerebellum exposing the dentate nucleus. B. Dissection of the superior surface of the cerebellum from above showing the left dentate nucleus in relationship to the isthmus of the pons. (From Mettler FA. Neuroanatomy. St. Louis: Mosby, 1948.)

FIGURE 2.8 The spinal cord. A. Section of the spinal cord with anterior and posterior nerve roots attached. B. Anterior view of the spinal cord. C. Posterior view of the spinal cord.

FIGURE 2.9 Sagittal section of the vertebral canal, showing the lower end of the spinal cord, filum terminale, and subarachnoid space. (Modified from Larsell O. Anatomy of the Nervous System. New York: D Appleton-Century, 1939.)

Central Nervous System Blood Supply

The brain receives its blood supply from the internal carotid arteries (anterior circulation) and the vertebrobasilar system (posterior circulation). The anterior circulation supplies the frontal, parietal, and most of the temporal lobes. The posterior circulation supplies the occipital lobes, brainstem, and cerebellum. Vascular anatomy is discussed in more detail in Chapter 49.

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