Message from Dr. Furie: Dr. Seidman and I have revised these notes as of 3/15/02 to include all the new information from her lecture that she thought it was important for you to know. The notes contain a number of topics that Dr. Seidman did not present; you will NOT be tested on those topics.

THE NERVOUS SYSTEM

I. STRUCTURE AND FUNCTION OF THE CNS

The brain is composed of the relatively symmetrical cerebral hemispheres, the brainstem, and the cerebellum. The surface of the cerebral hemispheres has narrow infoldings, called sulci, that separate broad ridges of tissue, called gyri. All spaces are fairly small and tight. As we age, the brain gets smaller; the sulci increase in size and the gyri decrease. Damage to the brain is usually irreversible; no significant regeneration of neurons is possible at this time.

The brain is covered by the meninges. The outermost layer, which lines the bones of the skull, is the dura. It is composed of dense fibrous connective tissue. In elderly people, the dura adheres very tightly to the skull, and it is difficult to separate the two (for example, during an autopsy). The middle layer is the arachnoid, which is thin, transparent, and delicate. The innermost layer, which forms part of the surface of the brain, is the pia. Together, the arachnoid and pia form the leptomeninges. There really are not physical spaces between these layers in healthy individuals, but there are potential spaces between them. The interface between the dura and skull is nonetheless called the epidural space. The interface between the dura and arachnoid is called the subdural space, and that between the arachnoid and pia is called the subarachnoid space. The subarachnoid space contains superficial arteries and veins, which feed to and drain from the brain. It is also where the cerebrospinal fluid (CSF) circulates. The CSF cushions the brain and also serves metabolic functions. There is free communication throughout the subarachnoid space, extending into the spinal canal. This is why infections of the meninges and other conditions that affect the CSF can usually be detected by lumbar puncture (spinal tap).

The cranial cavity can expand in babies, but it is rigid in older children and adults. If part of the brain swells in adults, it necessarily compresses other parts and may result in herniation, which is discussed below. The ventricles are spaces in the brain that are filled with CSF. The term hydrocephalus refers to enlargement of the ventricles. Causes include blockage of the flow of CSF (e.g., due to tumors or developmental abnormalities), impaired resorption of CSF into the venous system, and passive dilatation of the ventricles due to loss of brain tissue. This is called hydrocephalus ex vacuo, because it results from the passive expansion of the ventricles to fill the “vacuum” left by the missing brain tissue. The first two causes of hydrocephalus can interfere with brain function, as the enlarged ventricles compress the surrounding structures. Passive expansion, on the other hand, does not itself interfere with brain function, although whatever caused the loss of brain tissue in the first place may result in problems.

It is important to recognize that specific anatomical areas of the central nervous system (CNS) control specific functions in the body. Therefore, the area of the brain that is damaged by a particular disorder will determine the clinical signs of the disorder. Furthermore, knowledge about the part of the brain that is malfunctioning may aid in diagnosis, since certain illnesses (e.g., polio) tend to affect specific parts of the CNS.

Coma is caused by bilateral dysfunction of the cerebral hemispheres, which can result from many causes, including metabolic problems. It may also result from a localized lesion in a particular part of the brainstem. Brain death is a condition from which patients cannot recover! Brain death refers to the complete, irreversible loss of brain function and blood flow. The brain will decompose and liquefy. Hospitals have very rigid criteria for determining whether a patient is brain dead.

Cells of the CNS include neurons, glia, and microglia. Neurons have many ribosomes, since they synthesize proteins and other substances very actively. Generally, neurons do not divide, although recent research indicates that there may be some limited capacity for division in post-natal life. The neurons are composed of a cell body, dendrites, which receive signals, and an axon. The axon may be very long and culminates in synaptic processes that release neurotransmitters. The axon is surrounded by a sheath of myelin, which insulates the axon and makes transmission of nerve impulses much more efficient. The axon also contains neurofilaments and microtubules, both of which serve an essential role in transport of substances through the neuron. Glia include astrocytes and oligodendroglia. Astrocytes are so named because they look like stars. They may react to disease processes by forming scar tissue. They have a metabolic relationship with neurons, and they contribute to the “blood-brain barrier,” which makes it more difficult for blood-borne substances to enter the brain than other bodily tissues. The oligodendroglia form myelin in the white matter. In the gray matter, they are “satellite cells” that “hug” the neurons. The gray matter of the CNS consists of cells bodies; the white matter contains many axons, which are white due to the insulating myelin. Microglia are macrophages that reside in the nervous system. They are usually not very apparent in a healthy brain.

In diagnosing diseases of the CNS, knowing the age of the patient and the circumstances of the illness are often quite helpful. Knowing the time course of the disease is also frequently useful. For example, disease with sudden onset often has a vascular cause. Subacute illness is often due to infections or metabolic disorders. Slowly progressive disease is most likely due to neoplasms or degenerative diseases. However, there are always exceptions. For instance, tumors sometimes cause sudden onset of symptoms.

II. NEURODEGENERATIVE DISEASES

Dementia is defined as “an acquired mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning.” The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other “executive functions,” i.e., planning, organizing, sequencing, and abstracting. The intellectual decline is usually progressive and, at least initially, spares the level of consciousness. Some causes of dementia are potentially reversible, including intoxications, infections, metabolic disorders, brain tumors, head injuries, depression, etc. Others are presently irreversible, including Alzheimer’s disease, vascular dementia, Parkinson’s disease, Creutzfeldt-Jakob disease, and Huntington’s disease.

A. Alzheimer’s disease

Alzheimer’s disease (AD) is the most prevalent of neurodegenerative diseases. It is the eighth leading cause of death in the US. The number of patients affected by AD doubles every 5 years past the age of 65. In people over 85, almost half suffer from AD. The duration of the illness is generally 8 to 10 years.

AD can develop over the course of many years. Loss of memory, both recent and long-term, usually occurs as an early sign. There may also be a loss of spatial orientation, e.g., the patient can no longer find his or her way home. There may be problems with language, such as difficulty in recalling specific words. The personality may unravel, with the patient displaying loss of enthusiasm, paranoia, and fear. Depression may or may not ensue. The patient’s motor skills usually remain intact. The ten warning signs of AD are:

Memory loss that affects job skills
Difficulty performing familiar tasks
Problems with language
Disorientation to time and place
Poor or decreased judgment
Problems with abstract thinking
Misplacing things
Changes in mood or behavior
Changes in personality
Loss of initiative

Often, neurodegenerative diseases are focal, affecting only specific parts of the brain. In AD, the frontal, temporal, and parietal lobes of the brain are most affected. AD patients have atrophy of the cerebral cortex, which is responsible for thinking, processing, and emotions - in short, for making you who you are. The ventricles in an AD patient appear expanded, due to loss of mass in the cortex. The sulci are widened, and the gyri are thinned. All people lose some brain mass as they age, but the loss is much more marked in AD.

In AD, the prime target of the disease process is the neuron and the synaptic processes at the end of its axons. Once destroyed, neurons cannot be replaced; they are generally non-dividing cells. In AD, neurons in the cortex and their synaptic endings are damaged. The neurons become filled with neurofibrillary tangles. This accumulation of fibrillar protein within neurons is seen to some extent with normal aging, but to a much greater degree in AD. The fibrils are composed of so-called tau protein, which in AD becomes abnormally phosphorylated. Normally, tau protein stabilizes microtubules, which help transport substances in the neuron. In AD, the tangles formed by the abnormal tau proteins disrupt the microtubules, which interferes with axonal transport. The affected cell may die, leaving the tangles behind.

Another change that is seen somewhat in normal aging but much more markedly in AD is formation of senile plaques. These plaques are seen not within the neurons, but rather outside of them in the cortical neuropil, where neuronal connections take place. These plaques are round structures, with a core composed of b-amyloid. b-amyloid is formed from a normal cell membrane protein called APP (amyloid precursor protein). In AD, APP is abnormally processed to form b-amyloid, which is insoluble and deposits in the tissue to form the senile plaques. Inflammatory changes may occur around the plaque, including accumulation of astrocytes and microglia. These changes may explain why use of anti-inflammatory drugs, such as ibuprofen, has recently been associated with a decreased risk of developing AD. Moreover, a vaccine against b-amyloid prevents the protein from depositing in the brains of mice and even removes it from brains that already have it. Perhaps a similar approach may someday be used to combat AD in humans.

In younger patients, development of AD has been linked to mutations in several genes; how all of these function is not known. The gene for APP is on chromosome 21. People with Down syndrome have an extra copy of chromosome 21 and develop AD at an early age. There are also some risk factors for the disease that can be inherited, and individuals possessing certain forms of genes for these risk factors have a greater likelihood of developing the disease as they age than those who do not have these forms of the genes.

B. Parkinson’s disease

Parkinson’s disease (PD) is also a progressive neurodegenerative disease, but different neurons are targeted than in AD. PD is usually seen in older people (mean age of onset is 61), and it is characterized by certain abnormalities of motor function. The classical signs are bradykinesia (slow movement), tremor, and rigidity. Patients also have lack of facial expression, stooped posture, postural instability, and difficulty starting and stopping movements. Some patients with PD develop dementia.

In PD, the darkly pigmented motor neurons in the substantia nigra of the midbrain are lost. These neurons are concerned with control of motion and produce dopamine. Note that the pigment is not missing from these cells in PD; rather, it is the cells themselves that die. Microscopically, the remaining neurons may contain inclusions called Lewy bodies. Within the cell, these may appear as one or more round, pink masses surrounded by a white halo.

The cause of Parkinson’s disease is not known; it has been suggested that toxins or other environmental agents might be responsible. There are also genetic factors, and damage by free radicals may also play a role. Some specific causes of Parkinson-like syndromes have been described. Transplants of fetal cells have been tried as a therapy.

III. DEMYELINATING DISEASES

Myelin is the insulating sheath, formed by oligodendroglial cells, that wraps around axons to allow rapid conduction of nerve impulses. Most myelin is located in the white matter. The main disease of demyelination is multiple sclerosis (MS), which usually affects young adults (20 to 40 years old). Whereas neurodegenerative diseases are relentlessly progressive, the course of MS is quite variable, and the disease is characterized by relapses and remissions. For some patients, remission may be permanent. For others, deficits accrue over time, leading to permanent losses of function. The time between relapses is unpredictable, as is the prognosis. The disease may or may not lead to a shortened life span. The disease can have a very long course, from 5 to 20 years or more.

MS mostly involves the white matter. Myelin in any part of the central nervous system (CNS) can be affected, meaning that the symptoms produced can be quite variable. Lesions can involve the cerebrum, the brainstem, the cerebellum, the spinal cord, and optic nerves. Lesions are never seen in the peripheral nerves. The axons themselves are usually intact, but conduction of nerve impulses is slowed or blocked completely. Visual disturbances, weakness and sensory problems commonly develop over the course of a few hours to a few days. Visual symptoms are especially common. Often, a flu-like malaise precedes the onset of disease. In the brain, loss of function, particularly in the frontal lobe, can often be tolerated comparatively well. Lesions in the brainstem and spinal cord, however, are bound to cause significant symptoms.

Pathologically, multiple tan areas, which represent regions of demyelination, often appear within the white matter, especially around the ventricles. These lesions are called plaques (although clearly they are different from senile plaques). The plaques can be seen by MRI or CAT scan. Certain immunological changes in the cerebrospinal fluid (CSF) also may aid in diagnosis. The lesions are sharply delimited, but why they stop spreading is not known. Often, astrocytes proliferate around the areas of damage.

The cause of MS is unknown, but it is thought to involve an autoimmune process in which there are abnormalities of both cell-mediated and humoral immunity. Lymphocytes and macrophages attack and remove the myelin. There is a genetic predisposition to develop the disease and marked variations in geographical distribution. It has been proposed that MS develops in response to an infection in early childhood, but this has not been proven. A number of new drugs are appearing for treatment.

IV. INFECTIONS

The brain has many barriers to prevent invasion by microorganisms, so infection is relatively rare. Fortunately, infections can often be treated successfully. Infections of the CNS may be carried in from the blood (sepsis, endocarditis), spread from adjacent tissues (sinusitis, otitis), be directly inoculated (trauma, iatrogenic causes), or be transported along peripheral nerves (herpes, rabies). Meningitis (leptomeningitis is most common) is infection that affects the coverings of the brain. Encephalitis, abscesses, and granulomas occur in within the brain itself. All sorts of organisms may cause infections in the CNS, including bacteria, viruses, fungi, protozoans, and parasites.

A. Bacterial infections: In bacterial leptomeningitis, a purulent exudate (pus) can fill the spaces between the meninges. The patient presents with fever, headache, stiff neck and, often, altered mental status. The CSF may contain elevated levels of protein and neutrophils, low amounts of glucose, and the infecting organisms themselves, which can be detected by gram stain. Frequent culprits are Streptococcus, Meningococcus, and E. coli. Until the development of an effective vaccine, Hemophilus influenzae used to the most common cause of meningitis in young children. When epidemic bacterial meningitis occurs in setting where large groups of people are brought together in close contact, e.g., army barracks, it is usually due to Neisseria meningitidis (meningococcus). The brain itself is usually not attacked, but the infection can cause swelling and interfere with vascular function and the flow of cerebrospinal fluid. As you know from the lecture on inflammation, the neutrophils that accumulate in response to the infection can release a lot of damaging substances. Bacterial meningitis is a medical emergency; rapid diagnosis and therapy are essential. Death can sometimes occur within hours of the onset of symptoms. Treatment is with high doses of antibiotics.

Abscesses can form in the brain and are generally caused by different organisms than cause meningitis. Meningitis usually arises from blood-borne organisms that initially infect other parts of the body, e.g., an upper respiratory infection. Abscesses usually arise from a locally spreading infection, e.g., infections of the sinus, middle ear, or oral cavity. Abscesses may rupture or cause symptoms simply due to their mass. They are hard to treat, since fibrous layers that form around the abscess may hinder antibiotics from penetrating the lesion. Drainage of abscesses is often the only option for treatment, but is associated with high mortality.

C. Viral infections: can cause meningitis or more diffuse infection of the brain tissue itself, which is called encephalitis. Symptoms include fever, headache, stiff neck, and sometimes altered mental status. The CSF contains elevated levels of protein, normal amounts of glucose, and lymphocytes (rather than the neutrophils that appear in bacterial infections). Some of these infections can be relatively mild and self-limited. In many cases, viral meningitis is milder than bacterial meningitis, and patients recover without consequence.

Rabies encephalitis is a real risk on the East Coast of the US. The rabies virus is introduced by the bite of an infected animal. It then travels from the site of the bite to the brain along nerve axons. It travels slowly, so there is usually time to intervene by vaccination. A bite on the neck of a small child might be a problem, because the virus would not have very far to travel. Immunization is essential following a bite by an unknown animal that cannot be captured, since rabies is invariably fatal once symptoms appear. If the animal can be caught, it needs to be observed for two weeks to make sure that it is free of disease, or it can be sacrificed and examined for evidence of disease in the brain. Raccoons, skunks, and bats can all carry rabies.

Herpes encephalitis can arise from oral herpes (type 1). For unknown reasons, the virus sometimes spreads upward to the brain from the peripheral nerve ganglia where it usually lies sequestered, instead of traveling downward to the skin. It can infect both the meninges and the brain (meningoencephalitis). It often affects the temporal lobes, which control memory and behavior. It can be a very devastating disease, but luckily it is relatively uncommon. Prompt treatment with acyclovir may help to avoid severe, long-term deficits.

V. TRAUMA

Traumatic brain injury is a very serious problem: every 21 seconds, one person in the US sustains a brain injury, and 22% (>50,000) of these die. Motor vehicle accidents account for 50% of these injuries; falls are the second leading cause. Types of injuries include skull fractures, epidural and subdural hematomas, and brain parenchymal injuries, including contusions (bruises), lacerations (tears), hematomas, and diffuse injury to the axons. In addition to the damage caused directly by the trauma, secondary damage can develop due to brain swelling or hypoxic/ischemic injury. The role of the physician is to minimize the development of the secondary damage.

Epidural hematomas, located between the skull and the dura, occur in the setting of blunt cranial trauma in which there is a skull fracture. The hemorrhage typically arises from a ripped middle meningeal artery and accumulates rapidly and under high pressure, because it is an arterial hemorrhage. If the hematoma becomes large enough, it can compress the brain, leading to herniation, loss of consciousness, and even death. Epidural hematoma is a surgical emergency, requiring drainage of the hematoma.

A subdural hematoma forms between the dura and the arachnoid. This is often seen in the setting of trauma, but can also occur without a history of significant head injury. In subdural hematoma, the bleeding is venous in origin, and the hematoma can accumulate more slowly than with epidural hematoma. In the elderly, the development of some brain atrophy (shrinkage) causes traction on the superficial veins that drain into the venous sinuses. If the brain moves (even with relatively minor trauma that the patient might not notice), the veins may twist and tear, and bleeding ensues. In acute, severe head injury, a subdural hematoma is a surgical emergency. A subdural hematoma can cause focal neurological signs, herniation, and coma. In an elderly person, in which there is room to accommodate the hematoma around an atrophic brain, the neurological signs may be subtle and a subdural hematoma can present as dementia. Alcoholics are also at risk for developing subdural hematomas.

Herniation refers to the shifting of brain tissue from one compartment of the cranial cavity to another due to the presence of a mass lesion in the brain. Tumors, abscesses, edema, or hematomas can all act as mass lesions. Herniation is a medical or surgical emergency. Herniation of the cerebellar tonsils through the foramen magnum as the brain shifts downward leads to compression of the brain stem, which interferes with vital functions and causes death.

Contusions are bruises of the brain. Most are caused by the movement of the soft brain tissue over the irregular contours of the inner surfaces of the bones of the skull. There are characteristic locations for contusions. The location of the contusion depends upon the site of impact and whether the person is moving or stationary. If the person is moving (for example, a person falling backwards), the contusion is likely to occur on the side of the brain opposite to the impact (contra-coup injury). Most coup contusions, which are bruises that develop at the site of the impact, are actually due to fractured bone compressing the underlying brain.

VI. TUMORS OF THE NERVOUS SYSTEM

Brain tumors account for 10% of primary neoplasms. In children, they comprise 20% of all malignancies and are the most common solid tumors in children under the age of 15. The most common types and locations of brain tumors differ between adults and children. Primary tumors of the brain may arise in the brain itself or from its covering, the meninges. Tumors may also metastasize from other organs to the brain. It is interesting to note that primary brain tumors do not metastasize to other organs. The only exception is that metastasis to the lung is sometimes seen following neurosurgery to remove a primary tumor. In the brain, benign (slowly growing) tumors may kill just as readily as malignant (rapidly growing) ones, depending on their location. If a tumor cannot be reached surgically or is compressing a vital structure, it may not matter whether it is benign or malignant. However, the choice of treatment may depend on how rapidly the tumor is proliferating. Treatments include surgical resection of as much tumor as possible, chemotherapy, and radiotherapy. Radiation is generally not used for small children, since it can result in loss of intellectual function. Brain tumors can kill by 1) destroying vital structures; 2) compressing vital structures; and/or 3) raising intracranial pressure and causing herniation.

A. Primary brain tumors

Primary brain neoplasms tend to be very infiltrative and thus difficult to completely resect surgically. Sometimes tumors (especially those with necrotic centers) and abscesses can be mistaken for one another, since they appear radiologically similar. Since neurons for the most part do not divide, they rarely give rise to tumors (see the lecture on neoplasia). Tumors are much more likely to arise from glial cells, such as astrocytes. In fact, astrocytomas are the most common type of brain tumor. Astrocytomas can be of a very low grade that is considered benign, or they can be very anaplastic and thus considered malignant. Some types of astrocytomas are more commonly seen in adults, whereas other types are usually found in children. In adults, the majority of astrocytomas are malignant. Cerebellar juvenile astrocytoma is a slowly growing tumor that occurs most commonly in children and can often be cured. Usually, astrocytomas develop in different locations in adults vs. children (cerebral hemispheres for adults, cerebellum and pons for children). One type of highly malignant astrocytoma that is found in adults (usually over the age of 45 or 50) is glioblastoma multiforme. This is a rapidly growing tumor that can get necrotic and hemorrhagic. The tumor cells may be quite variable in their appearance. These tumors tend to cross from one side of the brain to the other via the corpus callosum. The prognosis is poor; most patients die within 6 months to a year. Another type of glial tumor is oligodendroglioma, which frequently hemorrhages due to a large content of very thin-walled vessels. Ependymoma is also a glial tumor; it arises from the cells that line the ventricles and is more common in children than adults.

Although tumors of neuronal origin are rare, they do occur. They include ganglioneuroma, ganglioglioma, and neuroblastoma. These can range greatly in the degree of their aggressiveness. Medulloblastoma, the most common malignant brain tumor in children, is located in the cerebellum. It is a type of tumor that arises from primitive, undifferentiated stem cells in the brain and has a propensity to spread along the entire neuraxis, seeding the brain and spinal cord.

Tumors that arise from the meninges that cover the brain are called meningiomas. Meningiomas are usually benign. They can present with headache, focal neurological signs due to compression of underlying brain or, occasionally, seizures, due to irritation of the brain.

B. Neurofibromatosis: is a genetic disease that can vary a lot in terms of how it is expressed. Often, superficial tumors of the peripheral nerves cause multiple lumps under the skin, and affected people may have multiple pigmented areas on the skin called café au lait spots. Skeletal abnormalities are sometimes seen. Tumors may develop near the spinal cord; these can be a lot more troublesome than the more common skin tumors.

C. Metastatic tumors of the brain: When tumors from other organs metastasize to the brain, spread is usually through the blood. Often, multiple metastatic lesions are seen. Tumors that have a particular tendency to metastasize to the brain include cancers of the lung (by far the most common), breast, kidney, and GI tract, as well as melanomas. Breast, prostate, and kidney cancers tend to go to the dura, where they may be mistaken for a meningioma.

VII. CEREBROVASCULAR DISEASE (STROKE)

A stroke is defined as a sudden or rapidly developing focal neurological deficit with a vascular cause. Formally, stroke is described as “rapidly developing clinical signs of focal (at times global) disturbance of cerebral function, lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin.” Strokes are the third leading cause of death in the U.S. Risk factors include increasing age, male gender, African-American race, heredity, hypertension, diabetes mellitus, cigarette smoking, hypercholesterolemia, heart disease, and a history of transient ischemic attacks. Strokes can be due to global loss of blood flow to the brain (for example, drop in blood pressure), or due to focal vascular events, which are occlusion of a vessel (atherosclerosis, thrombosis, embolism) or hemorrhage (a vessel ruptures or leaks). The clinical presentation is sudden onset of neurological signs and symptoms that reflect the region of the brain that is affected. Later, secondary changes can occur, such as herniation due to swelling.

A. Infarction

Infarction is death of brain tissue due to interruption of blood flow to that area of brain. Infarction can result from inadequate functioning of the heart. If the heart does not perfuse the brain well, the most vulnerable parts of the brain can die. Brain tissue will begin to die after it has been deprived of blood for as little as four minutes. The patient may survive, but with significant loss of function. After a person has been without heart function for some time, he or she may be able to be revived with CPR, but the loss of brain function may be irreversible and unacceptable.

Infarction also can be caused by occlusion of vessels due to thrombi, emboli, or narrowing of the vascular lumen as a consequence of atherosclerosis. The location of the infarct in the brain allows one to determine the affected vessel, which often gives a clue as to the cause. For example, occlusion of the common or internal carotid arteries can be due to narrowing of the vessel lumen (stenosis) due to an atherosclerotic plaque in the wall, or thrombosis, often initiated by the presence of an atherosclerotic plaque. Occlusion of the superficial vessels of the brain is usually due to emboli. Pieces of debris or thrombus may break off from atherosclerotic lesions in larger vessels and clog smaller vessels downstream. Emboli may also be thrown off from vegetations on the heart valves (endocarditis), or thrombi formed during a myocardial infarction may break off and embolize. Thrombi formed on the left side of the circulation (for example, in the carotid artery) have the potential to lodge in vessels of the brain. Medical procedures (e.g., angioplasty) can break off pieces of atherosclerotic plaque, causing emboli. In contrast, the vessels that penetrate the brain are more likely to rupture or be occluded due to arteriosclerosis, which is caused by hypertension. Arteriosclerosis is a condition in which the walls of arteries become thickened due to fibrosis, but they are also weaker than normal. Infarcts in the brain may also occur if vessels are compressed due to herniation. Thrombolytic (clot-dissolving) agents are often very useful for treatment of occlusive strokes caused by thrombi or emboli.

Cerebral infarcts can be silent or minimally symptomatic, or they may result in death. Death may result because the control centers for cardiovascular function have suffered from an infarct. Alternatively, the mechanism of death may be less direct. Immediately after the infarct occurs, there are no gross changes in the damaged area. Over the first three days, there is increasing edema, and, around one week after the infarct, the area of dead tissue separates from the normal brain. Due to the edema, the brain may herniate downward, pressing on the brainstem and destroying it. If a patient survives a stroke, eventually a fluid-filled cavity replaces the dead tissue. The patient will be left with a deficit related to the part of the brain that was destroyed. Usually, the functional loss is most severe right after the stroke occurs; some function may be regained as the swelling subsides.

B. Hemorrhage

Hemorrhage within the brain: Hemorrhagic strokes may have a number of causes. The most common cause is hypertension. Primary hypertensive hemorrhage occurs in the basal ganglia, pons, and cerebellum. In this condition, vessels (usually arterioles with weakened walls) can rupture in the setting of very high blood pressure. The resulting stroke can be catastrophic, often leading to death. The hemorrhage occurs under high pressure and can dissect through the brain and rupture into a ventricle. It can cause herniaton. It is a disease that strikes with little warning; good screening for elevated blood pressure (which can be treated medically) is key. Treatment for those who survive a primary hypertensive hemorrhage is difficult.

Arteriovenous malformation is a congenital condition in which there is an abnormal collection of arteries that connect directly to veins, without an intervening capillary bed. The veins are exposed to abnormally high pressures and thus may burst. Such a rupture may lead to massive hemorrhage and sudden death.

Hemorrhage outside the brain: Saccular aneurysms are berry-like outpouchings of vessels that form at arterial branch points in the circle of Willis at the base of the brain. At these points, one of the layers of the vessel (the media) may be thinned or missing, so there is an intrinsic weakness. Aneurysms are found in approximately 2% of adults, so they are very common. If these aneurysms rupture, they cause hemorrhage into the subarachnoid space. The patient presents with a complaint of sudden onset of the “worst headache of my life” and often has a stiff neck, resistance to full extension of the leg, and flexion of the neck when the knees are bent (similar to symptoms of meningitis, since the bleeding irritates the meninges). CT scan is the best first test to look for subarachnoid hemorrhage. If it is negative, but the suspicion of subarachnoid hemorrhage persists, lumbar puncture can be performed, and there will be blood in the spinal fluid. If it is known that an aneurysm is present, it can be clipped off surgically to prevent bleeding.

VIII. CONGENITAL DEFECTS

Spina bifida is a fairly common defect in which the spinal cord and/or overlying skin and bone do not close properly. It is caused by improper closure of the neural tube, the earliest form of the nervous system in the developing embryo. The neural tube closes by day 28 of gestation, so the presence of spina bifida is determined by that time very early in gestation. Either the meninges alone (meningocele) or the meninges and spinal cord itself (myelomeningocele) can protrude through the back of the baby. It can be treated surgically; the prognosis can vary greatly depending on how abnormal the spinal cord is, the level of the defect, and whether there are also abnormalities of the brain.

Failure of closure of the most rostral (top or forward) portion of the neural tube can result in anencephaly, in which the cerebral hemispheres of the brain fail to form.

In hydrocephalus, the ventricles enlarge due to obstruction of the flow of CSF. There are many different causes for such obstruction. Babies can be screened for this condition by periodically measuring the circumference of the head. A shunt can be surgically implanted to drain the fluid from the ventricle to the peritoneal cavity. Otherwise, the increased pressure in the ventricle will destroy the surrounding brain tissue.

Premature babies are susceptible to germinal mantle hemorrhages. These can be small and of no consequence, large and fatal, or anything in between. Infarctions may also occur in the developing brain in utero.