Chapter 21: The Nervous System

What is amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor weakness and progressive wasting of muscles, leading to death. ALS is rare, affecting 1 in 100,000 people.

Compare glioblastoma multiforme with other gliomas.

Astrocytic tumors include astrocytomas and glioblastoma multiforme. Glioblastoma multiforme is a highly malignant tumor that is invariably fatal. It is the most common CNS tumor, with a peak incidence at 65 years of age. The tumor often spreads through the corpus callosum from one cerebral hemisphere to the other. Other glial cell tumors include oligodendrogliomas and ependymomas. Oligodendrogliomas may contain astrocytes (mixed tumors), and some progress to glioblastoma multiforme. Ependymomas are derived ependymal cells.

What are the main pathologic findings following brain injury?

Brain injuries are classified as concussions (transient loss of consciousness), contusions (bruise), or lacerations (open trauma). Contusions and lacerations are associated with considerable mortality

Describe the pathology of cerebral infarcts.

Cerebral infarcts undergo liquefactive necrosis. This localized softening of the brain is referred to as encephalomalacia. The cerebral infarct may be pale or red, depending on its location. The margins of the cerebral infarct are swollen with edema fluid.

Describe the circulation of the cerebrospinal fluid.

Cerebrospinal fluid (CSF) protects the brain from injury. It is produced by the choroid plexus in the third ventricle. CSF flows through the third ventricle to the fourth ventricle. From there it may enter the central canal of the spinal cord or exit into the subarachnoid space. CSF is finally resorbed from the meninges into the venous system. This circulation depends on constant production (500 mL/day).

What is stroke?

Cerebrovascular disease (CVD) is the third most common cause of death behind ischemic heart disease and respiratory infections. The most important clinical manifestation of CVD is stroke. Stroke denotes local injury to the brain (infarction) caused by disorders of perfusion (e.g., atherosclerosis, thrombosis, embolism, and hemorrhage).

What are the most important diseases of the nervous system?

Diseases of the nervous system are common. The most important diseases of the nervous system are classified as (1) developmental/genetic; (2) traumatic; (3) circulatory; (4) infectious; (5) autoimmune, metabolic/nutritional; (6) neurodegenerative; and (7) neoplastic.

Compare the pathology of encephalitis and meningitis.

Encephalitis is a diffuse infection of the brain parenchyma typically caused by viruses that invade glial or neural cells. Meningitis is an inflammation of the meninges that is most commonly caused by viruses (e.g., common flu).

List the most common brain tumors and their predominant location.

Glioblastomas are highly malignant tumors that occur in the lateral hemispheres. Meningiomas are benign tumors that arise from the meninges. Oligodendrogliomas are rare tumors that occur in the cerebral hemispheres. Ependymomas are derived from ependymal cells that line the ventricles and central canal. Astrocytomas are glial cell tumors that occur as solid cerebral tumors in adults and cystic cerebellar tumors in children.

What is global cerebral ischemia, and what are its consequences?

Global cerebral ischemia develops in patients with widespread atherosclerosis, cardiac failure, or hypotensive shock. Hypoperfusion infarcts of the brain frequently develop in specific anatomic locations that are referred to as lacunar infarcts, watershed infarcts, and laminar necrosis.

How does alcohol affect the brain?

In small amounts, alcohol stimulates the brain, causing euphoria and lack of inhibition. However, in large amounts, alcohol depresses brain functions and may even act as a neurotoxin. Chronic alcoholism is often accompanied by serious metabolic changes and nutritional deficiencies (e.g., Wernicke-Korsakoff syndrome). It may also lead to cerebellar atrophy, atrophy of gyri, and pontine myelinolysis.

What is Alzheimer's disease, and how is it diagnosed?

In small amounts, alcohol stimulates the brain, causing euphoria and lack of inhibition. However, in large amounts, alcohol depresses brain functions and may even act as a neurotoxin. Chronic alcoholism is often accompanied by serious metabolic changes and nutritional deficiencies (e.g., Wernicke-Korsakoff syndrome). It may also lead to cerebellar atrophy, atrophy of gyri, and pontine myelinolysis.

Compare bacterial and viral infections of the central nervous system.

Infections of the CNS are common. Bacterial infections develop from hematogenous spread (sepsis or emboli). The most important bacterial pathogens are Neisseria meningitidis and Streptococcus pneumoniae. Viral infections are also spread to the brain by the hematogenous route. Herpesvirus or cytomegalovirus may infect the brain of children or adults. Herpesvirus is the most common viral cause of encephalitis in the United States. Neurotropic viruses include rabies and JC virus.

Compare hyperextension and hyperflexion injuries of the cervical spine.

Injuries of the cervical spine are classified as either hyperextension injury or hyperflexion injury. In hyperextension injury an impact causes rupture of anterior spinal ligaments, resulting in compression of the posterior side of the spinal cord. In hyperflexion injury, impact causes extensive anterior flexion and compression of the anterior side of the spinal cord. Both injuries may cause complete transection of the spinal cord.

List the most important intracranial hemorrhages and describe their causes.

Intracranial hemorrhages are classified as epidural, subdural, subarachnoid, and intracerebral. Epidural hemorrhages are caused by trauma and rupture of the middle meningeal arteries. Subdural hemorrhages are caused by traumatic rupture of bridging veins (e.g., rapid rotation of the head). Subarachnoid hemorrhages are located between the arachnoid and the pia. They are usually caused by a traumatic contusion of the brain, with rupture of cerebral blood vessels at the base of the brain. Intracerebral hemorrhages are a common complication of trauma.

What are the sites of brain herniation caused by intracranial hypertension?

Intracranial hypertension is a life-threatening condition. A gradual increase in intracranial pressure will present as a severe headache accompanied by vomiting and loss of consciousness. Death usually results from compression of vital centers in the brainstem. Sites of brain herniation include (1) subfalcine herniation of the cingulate gyrus beneath the falx cerebri, (2) transtentorial herniation of the uncus below the tentorium cerebelli, and (3) tonsillar herniation of the cerebellar tonsils into the foramen magnum.

Correlate the pathologic features of multiple sclerosis with the clinical signs and symptoms of this disease.

MS is a demyelinating disease that primarily affects the white matter of the brain, optic nerves, and spinal cord. These lesions cause both sensory and motor abnormalities (e.g., loss of sensation of touch with tingling and blurred vision). Motor symptoms include unsteady gait, muscle weakness, and urinary incontinence.

Why do medulloblastomas metastasize?

Medulloblastomas have a poor prognosis because they can enter the cerebrospinal fluid and travel through the central canal to implant in the spinal cord.

How do inborn errors of metabolism affect the central nervous system?

Metabolic injury to the brain occurs in many inborn errors of metabolism. Tay-Sachs disease is a genetic deficiency of a glycosyl hydrolase (hexosaminidase A) that causes ganglioside accumulation and mental/motor deterioration. Niemann-Pick disease is a genetic deficiency of sphingomyelinase that causes sphingomyelin accumulation in the brain and profound brain atrophy.

What are meningiomas?

Most meningiomas are benign. They originate from the meninges and gradually impinge on the cerebral hemispheres. Compression of the brain may cause epileptic seizures or motor deficits. Localized tumors can be removed surgically and have an excellent prognosis.

What is multiple sclerosis?

Multiple sclerosis (MS) is a demyelinating disease that is thought to be of autoimmune origin. It has a prevalence of 1 in 1000. MS is the leading neurologic disease in young adults.

Describe the features of neurosyphilis.

Neurosyphilis usually presents as chronic meningitis. Fibrosis of the meninges in the healing stage may compress the dorsal roots of the spinal cord, resulting in loss of afferent sensory neurons (tabes dorsalis). Neurosyphilis may also causes ischemic necrosis of the cerebral cortex (syphilitic general paresis of the insane).

What is Parkinson's disease?

Parkinson's disease is a subcortical neurodegenerative disorder characterized by movement disorders and pathologic changes of the involuntary motor system. The cause is not known.

Correlate the pathology of Parkinson's disease with the clinical features of this disease.

Parkinson's disease is characterized pathologically by loss of dopaminergic neurons in the substantia nigra. This correlates with retarded transmission of neural impulses between the striatum and the substantia nigra. Patients present with tremor, postural instability, and bradykinesia, which are exacerbated by emotional stress. The treatment is symptomatic, and there is no cure.

What are prions?

Prions are small proteinaceous particles that cause spongiform encephalopathy (e.g., Creutzfeldt-Jakob disease and kuru). These infectious particles are mutant forms of normal brain proteins. The disease is transmitted by direct exposure (e.g., brain tissue of infected patients).

Describe the macroscopic and microscopic pathologic findings in Alzheimer's disease.

The brain in patients with Alzheimer's disease shows marked atrophy (thinning of gyri). Histopathologic changes include neuritic (senile) plaques, neurofibrillary tangles, granulovacuolar degeneration, and amyloid deposition.

List the main components of the central and peripheral nervous systems.

The central nervous system (CNS) consists of the brain and spinal cord. The brain is composed of the cerebrum, cerebellum, and brainstem (midbrain, pons, and medulla oblongata). The cerebrum is divided into two hemispheres, which are connected through commissures (e.g., corpus callosum). The peripheral nervous system consists of nerves emanating from the CNS and the autonomic nervous system.

Compare the functions of the midbrain, pons, and medulla oblongata with that of the cerebellum.

The cerebellum is the major regulator of motor activities. It receives sensory input from the spinal cord, inner ear, and cerebral cortex. In contrast, the brainstem (midbrain, pons, and medulla oblongata) contains myelinated nerve bundles that regulate vital bodily functions, such as heartbeat and respiration.

Correlate the pathology of amyotrophic lateral sclerosis with the clinical features of this disease.

The diagnosis of ALS is made clinically. Electromyography shows denervation and muscular atrophy. Pathologically, ALS is characterized by loss of motor neurons in the spinal cord, midbrain, and (finally) cerebral cortex. Most prominent is loss of the lateral cerebrospinal pathways, which is related to loss of motor axons and muscle atrophy.

. Describe the functions of the four major lobes of the brain.

The four major lobes of the brain are known as the frontal, parietal, temporal, and occipital lobes. The frontal lobe primarily controls motor functions but also regulates behavior, emotions, and intellectual functions. The parietal lobe has primarily sensory functions. The occipital lobe is the visual center. The temporal lobe plays an important role in hearing and smelling.

List the main cells of the nervous system.

The main cells of the nervous system are neurons and support cells (neuroglia). Glial cells are classified as astrocytes, oligodendrocytes, microglia, and ependymal cells. Oligodendrocytes synthesize myelin.

List the main dysraphic disorders of the central nervous system and describe their pathogenesis.

The main dysraphic disorders of the CNS are anencephaly (calvaria and brain not formed) and milder malformations, including meningocele, myelomeningocele and spina bifida, which are characterized by lack of fusion of posterior bone coverings. In myelomeningocele, the herniated sac contains meninges, plus a portion of the spinal cord.

Which brain tumors occur most often in children?

The most common CNS tumors found in infants and children are medulloblastoma, ependymoma, and cystic astrocytoma. Medulloblastomas are composed of fetal-like neuroectodermal cells. These tumors are limited to the cerebellum and are found only in children. They grow quickly but are sensitive to radiation and chemotherapy.

Correlate the pathology of intracerebral hemorrhage with the clinical features of this disease.

The most common sites of intracerebral hemorrhage are the basal ganglia (two-thirds of cases), followed by cerebellar and pontine hemorrhages. Hemorrhage into the basal ganglia is accompanied by rapid onset of hemiplegia and hemiparesis. Cerebellar hemorrhage presents with severe headache, nausea, and vomiting. Pontine hemorrhages are almost invariably fatal.

What are the most important AIDS-related central nervous system lesions?

The most important AIDS-related CNS lesions include multiple bacterial, viral, parasitic, and fungal infections (e.g., Toxoplasma and Cryptococcus). In addition, HIV-infected cells in the brain are thought to release neurotoxins that cause so-called AIDS-related encephalopathy.

What are the most important neurodegenerative diseases?

The most important neurodegenerative diseases are Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS).

List the most important protozoal and fungal causes of opportunistic diseases of the central nervous system.

The most important protozoal cause of opportunistic infections is Toxoplasma gondii. The most important fungal causes of opportunistic infections are Candida albicans, Aspergillus flavus, and Cryptococcus neoformans.

Describe the function of the spinal cord.

The spinal cord consists of both gray matter and white matter. Neurons of the anterior horn (gray matter) give rise to peripheral nerves and carry motor impulses. The white matter of the spinal cord consists of myelinated nerve fibers representing descending motor tracts or ascending sensory tracts. Spinal ganglia are external to the spinal cord.

Classify brain tumors.

Tumors of the CNS are classified according to their derivation and include glial cells (75%), neural cell precursors (2%), meninges (15%), and cranial and spinal nerves (5%).

Which tumors originate from the peripheral nerves?

Tumors originating from peripheral nerves are referred to as neuromas. Those composed of Schwann cells are referred to as schwannomas. Multiple tumors of peripheral nerves are a feature of neurofibromatosis type I. Most neurofibromas are benign. Intracranial schwannomas most often arise from cranial nerve VIII.

What is the pathogenesis of "watershed infarcts" and laminar necrosis of the brain?

Watershed infarcts of the brain develop in areas representing the marginal zones of blood supply by branches of the carotid artery on one side and the basilar artery on the other. In cases of hypotension, this "border zone" becomes hypoxic. Laminar necrosis develops in deeper zones of the brain that receive blood from short penetrator arteries entering the cortex from the surface.

What is the cause and what are the signs of Wernicke-Korsakoff syndrome?

Wernicke-Korsakoff syndrome denotes disturbances in ocular function, gait, and mental function caused by thiamine deficiency. Many patients are alcoholics, some of whom lose memory and make up incredible stories. Degenerative neural changes are typically found in the hypothalamus.