chapter 37: disorders of brain function

Define seizure.

A seizure represents an abrupt and transient occurrence of signs and/or symptoms resulting from an abnormal, excessive discharge from an aggregate of neurons in the brain. [A SUDDEN, UNCONTROLLED ELECTRICAL DISTURBANCE IN THE BRAIN.]

Describe the etiology, pathophysiology, and clinical manifestations of infectious diseases affecting the brain: 1. acute bacterial meningitis 2. viral meningitis 3. encephalitis

ACUTE BACTERIAL MENINGITIS Acute bacterial meningitis, which has a high potential for morbidity and mortality, is an inflammatory process of the leptomeninges and CSF within the subarachnoid space. Most cases of bacterial meningitis are caused by Streptococcus pneumoniae (pneumococcus) or Neisseria meningitidis (meningococcus), except in neonates, who are more commonly infected by group B streptococci. The development of effective vaccines against Haemophilus influenzae and S. pneumoniae has resulted in a profound decline in bacterial meningitis among children in the United States.Among adults, however, the incidence of meningitis has not changed. Epidemics of meningococcal meningitis occur in settings such as colleges and the military, where young people reside in close contact with each other. Other pathogens in adults are gram-negative bacilli and Listeria monocytogenes. The very young and the very old are at highest risk for pneumococcal meningitis. Risk factors associated with contracting meningitis include head trauma with basilar skull fractures, otitis media, sinusitis or mastoiditis, neurosurgery, dermal sinus tracts, systemic sepsis, or immunocompromise. In the pathophysiologic process of bacterial meningitis, the microorganisms replicate and undergo lysis in the CSF, releasing endotoxins and cell wall fragments that cause inflammation, characterized by a cloudy, purulent exudate. Thrombophlebitis of the bridging veins and dural sinuses or obliteration of arterioles by inflammation may develop, causing vascular congestion and infarction in the surrounding tissues. Ultimately, the meninges thicken and adhesions form. These adhesions may impinge on the cranial nerves, giving rise to cranial nerve palsies, or may impair the outflow of CSF, causing hydrocephalus. The most common symptoms of acute bacterial meningitis are sudden onset of headache, fever, and stiffness of the neck (nuchal rigidity), sometimes accompanied by nausea, vomiting, photophobia, and altered mental status. Other signs include seizures, cranial nerve palsies, and focal cerebral signs. Meningococcal meningitis is characterized by a petechial (petite hemorrhagic spots) rash with palpable purpura (bleeding into the skin) in most people. These petechiae vary in size from pinhead to large ecchymoses or even areas of skin gangrene, often associated with rapid onset of hypotension, acute adrenal hemorrhage (Waterhouse-Friderichsen syndrome), and multiple organ failure. Persons infected with H. influenzae or S. pneumoniae may present with difficulty in arousal and seizures, whereas those with N. meningitidis infection may present with delirium or coma. Cranial nerve damage (especially CN VIII, with resulting deafness) and hydrocephalus may occur as complications of pyogenic meningitis. [A RAPIDLY PROGRESSIVE BACTERIAL INFECTION OF THE MENINGES AND SUBARACHNOID SPACE.] VIRAL MENINGITIS Viral meningitis can be caused by many different viruses, most often enteroviruses, including coxsackievirus, poliovirus, and echovirus. Others include Epstein-Barr virus, mumps virus, herpes simplex virus (HSV), and West Nile virus. Often the virus cannot be identified. Viral meningitis manifests in much the same way as bacterial meningitis, but the course is less severe and the CSF findings are markedly different. There are lymphocytes in the CSF rather than polymorphonuclear cells, the protein content is only moderately elevated, and the sugar content usually is normal. The acute viral meningitides are self-limited and usually require only symptomatic treatment, except for herpes simplex virus (HSV) type 2, which responds to intravenous acyclovir. [INFECTION OF THE MENINGES BY A VIRUS.] ENCEPHALITIS Encephalitis represents a generalized infection of the parenchyma of the brain or spinal cord. It usually is caused by a virus, but it also may be caused by bacteria, fungi, and other organisms. The nervous system is subject to invasion by many viruses, such as arbovirus, poliovirus, and rabies virus. The mode of transmission may be the bite of a mosquito (arbovirus), a rabid animal (rabies virus), or ingestion (poliovirus). Common causes of encephalitis in the United States are herpes simplex virus (HSV) and West Nile virus. Less-frequent causes of encephalitis are toxic substances such as ingested lead and vaccines for measles and mumps. The pathologic picture of encephalitis includes local necrotizing hemorrhage, which ultimately becomes generalized, with prominent edema. There is progressive degeneration of nerve cell bodies. The histologic picture, although rather general, may demonstrate some specific characteristics. For example, the poliovirus selectively destroys the cells of the anterior horn of the spinal cord. Like meningitis, encephalitis is characterized by fever, headache, and nuchal rigidity, but more often patients also experience neurologic disturbances, such as lethargy, disorientation, seizures, focal paralysis, delirium, and coma. [INFLAMMATION OF THE BRAIN, OFTEN DUE TO INFECTION.]

Describe the following mechanisms of brain injury: 1. hypoxic and ischemic injury 2. excitatory amino acid injury 3. cerebral edema

HYPOXIC AND ISCHEMIC INJURY Hypoxia interferes with the delivery of oxygen, whereas ischemia interferes with the delivery of oxygen and glucose as well as the removal of metabolic wastes. Hypoxia usually is seen in conditions such as exposure to reduced atmospheric pressure, carbon monoxide poisoning, severe anemia, and failure of the lungs to oxygenate the blood. Contrary to popular belief, hypoxia is fairly well tolerated, particularly in situations of chronic hypoxia. Neurons are capable of substantial anaerobic metabolism and are fairly tolerant of pure hypoxia, in which case it produces listlessness, drowsiness, and impaired problem solving. Unconsciousness and convulsions may occur when hypoxia is sudden and severe. However, the effects of severe hypoxia on brain function seldom are seen because the condition rapidly leads to cardiac arrest and ischemia. Ischemia is seen in conditions of low blood flow. Cerebral ischemia can be focal, as in a stroke due to cerebral artery occlusion, or global, as in cardiac arrest. Cerebral artery occlusion leads to focal ischemia, and if sustained, to infarction (death) of brain tissue in the distribution of the affected vessel. The location of the infarct and extent of tissue damage that results is determined by modifying variables, of which collateral blood flow is the most important. The collateral circulation may even provide sufficient blood flow to the borders of the focal ischemic region to maintain a low level of metabolic activity, thereby preserving tissue integrity. EXCITATORY AMINO ACID INJURY In many neurologic disorders, injury to neurons may be caused by inappropriate release of excitatory amino acid neurotransmitters such as glutamate. The neurologic conditions involved in excitotoxic injury range from acute events such as stroke, hypoglycemic injury, and trauma to chronic degenerative disorders such as Huntington disease and possibly Alzheimer dementia. During prolonged ischemia, metabolic depletion of adenosine triphosphate (ATP) results in the inappropriate release of glutamate. This initiates cell damage by allowing excessive influx of calcium ions (Ca++) through glutamate-N-methyl-d-aspartate (NMDA) glutamate channels. Excess intracellular Ca++ leads to a series of calcium-mediated processes called the calcium cascade, which results in the release of intracellular enzymes that cause protein breakdown, free radical formation, lipid peroxidation, deoxyribonucleic acid (DNA) fragmentation, mitochondrial injury, nuclear breakdown, and eventually cell death. The effects of acute glutamate toxicity may be reversible if the excess glutamate can be removed or if its effects can be blocked before the full cascade progresses. Various strategies that would protect viable brain cells from irreversible damage in the setting of excitotoxicity are currently under investigation. Pharmacologic strategies being explored include those that inhibit the synthesis or release of excitatory transmitters; block the NMDA receptors; prevent initiation of the calcium cascade; or block release of intracellular enzymes. CEREBRAL EDEMA Cerebral edema, or brain swelling, is an increase in tissue volume secondary to abnormal fluid accumulation. There are two types of brain edema: vasogenic and cytotoxic. Vasogenic edema occurs with conditions that impair the function of the blood-brain barrier and allow transfer of water and proteins from the vascular into the interstitial space. It occurs in conditions such as hemorrhage, brain injury, and infectious processes (e.g., meningitis). Vasogenic edema occurs primarily in the white matter of the brain, possibly because the white matter is more compliant than the gray matter. Vasogenic edema can result in displacement of a cerebral hemisphere and various types of brain herniation. The functional manifestations of vasogenic edema include focal neurologic deficits, disturbances in consciousness, and severe intracranial hypertension. Cytotoxic edema involves an increase in intracellular fluid. It can result from hypoosmotic states such as water intoxication or severe ischemia that impair the function of the sodium-potassium membrane pump. Ischemia also results in the inadequate removal of anaerobic metabolic end products such as lactic acid, producing extracellular acidosis. If blood flow is reduced to low levels for extended periods or to extremely low levels for a few minutes, cellular edema can cause the cell membrane to rupture, allowing the escape of intracellular contents into the surrounding extracellular fluid. This leads to damage of neighboring cells. Major changes in cerebral function, such as stupor and coma, occur with cytotoxic edema. The edema associated with ischemia may be severe enough to produce cerebral infarction with necrosis of brain tissue.

Compare the etiologies, pathophysiology, and clinical manifestations of: 1. ischemic stroke 2. transient ischemic attacks 3. thrombotic stroke 4. embolic stroke 5. hemorrhagic stroke

ISCHEMIC STROKE Ischemic strokes result from a diverse set of causes of cerebrovascular obstruction by thrombosis or emboli. Among the major risk factors for ischemic stroke are family history of ischemic stroke, hypertension, cigarette smoking, overweight and obesity, high blood cholesterol and other lipids, diabetes mellitus, disorders of cardiac rhythm (e.g., atrial fibrillation), and chronic kidney disease. The incidence of stroke increases with age, and varies by sex and ethnicity. Men have higher rates in the younger age groups, though women catch up after menopause and live longer, resulting in higher rates of death among women. African Americans have almost twice the risk of first-ever strokes as whites. Blood pressure is a powerful determinant of stroke risk. Individuals with a blood pressure less than 120/80 mm Hg have about half the lifetime risk of stroke compared with persons with hypertension. Heart disease, particularly atrial fibrillation and other conditions that predispose to clot formation on the wall of the heart or valve leaflets, or to paradoxical embolism through right-to-left shunting, predisposes to cardioembolic stroke. Polycythemia, sickle cell disease (during sickle cell crisis), and blood disorders predispose to clot formation in the cerebral vessels. Other, less well-documented risk factors include obesity, physical inactivity, alcohol and drug abuse, hypercoagulability disorders, hormone replacement therapy, and oral contraceptive use. Heavy alcohol consumption can lead to hypertension, hypercoagulability of blood, reduction of cerebral blood flow, and greater likelihood of atrial fibrillation. Cocaine use causes both ischemic and hemorrhagic strokes by inducing vasospasm, enhanced platelet activity, and increased blood pressure, heart rate, body temperature, and metabolic rate.Various methods have been used to classify ischemic cerebrovascular disease. A common classification system identifies the five main mechanisms of stroke as stroke subtypes and their frequency: 20% large artery atherosclerotic disease (both thrombosis and arterial emboli); 25% small vessel or penetrating artery disease (so-called lacunar stroke); 20% cardiogenic embolism; 30% cryptogenic stroke (undetermined cause); and 5% other causes (i.e., migraine, vessel dissection, coagulopathy). [ARTERIES TO YOUR BRAIN BECOME NARROWED OR BLOCKED = REDUCED BLOOD FLOW.] TRANSIENT ISCHEMIC ATTACKS Transient ischemic attacks (TIAs) are brief episodes of neurologic dysfunction resulting from focal cerebral ischemia not associated with infarction. A TIA or "ministroke" is equivalent to "brain angina" and reflects a temporary disturbance in cerebral blood flow, which reverses before infarction occurs, analogous to angina in relation to heart attack. The traditional definition of TIAs as a neurologic deficit resolving within 24 hours was developed before the mechanisms of ischemic cell damage and the penumbra were known and before the newer, more advanced methods of neuroimaging became available. A more accurate definition now is a transient deficit without time limits, best described as a zone of penumbra without central infarction. The causes of TIAs are the same as those of ischemic stroke and include atherosclerotic disease of cerebral vessels and emboli. Transient ischemic attacks are important because they may provide warning of impending stroke. In fact, the risk for stroke is 15% in the 3 months following a TIA. [A BRIEF, STROKE-LIKE ATTACK THAT, DESPITE RESOLVING WITHIN MINUTES TO HOURS, STILL REQUIRES IMMEDIATE MEDICAL ATTENTION TO DISTINGUISH FROM AN ACTUAL STROKE.] THROMBOTIC STROKE Thrombi are the most common cause of ischemic strokes, usually occurring in atherosclerotic blood vessels. In the cerebral circulation, atherosclerotic plaques are most commonly found at arterial bifurcations of large arteries. Common sites of plaque formation include the origins of the internal carotid and vertebral arteries, and junctions of the basilar and vertebral arteries. Cerebral infarction can result from an acute local thrombosis and occlusion at the site of chronic atherosclerosis, with or without embolization of the plaque material distally, or from critical perfusion failure distal to a stenosis (watershed). These infarcts often affect the cortex, causing aphasia or hemineglect, visual field defects, or transient monocular blindness (amaurosis fugax). In most cases of stroke, a single cerebral artery and its territories are affected. Usually, thrombotic strokes are seen in older persons and frequently are accompanied by evidence of atherosclerotic heart or peripheral arterial disease. The thrombotic stroke is not associated with activity and may occur in a person at rest. [OCCRUS WHEN A BLOOD CLOT (THROMBUS) FORMS IN ONE OF THE ARTERIES THAT SUPPLY BLOOD TO YOUR BRAIN.] EMBOLIC STROKE An embolic stroke is caused by a moving blood clot that travels from its origin to the brain. It usually affects the larger proximal cerebral vessels, with emboli often lodging at bifurcations. The most frequent site of embolic strokes is the middle cerebral artery, reflecting the large territory of this vessel and its position at the terminus of the carotid artery. Although most cerebral emboli originate from a thrombus in the left heart, they also may originate in an atherosclerotic plaque in the carotid arteries. The embolus travels quickly to the brain and becomes lodged in a smaller artery through which it cannot pass. Embolic stroke usually has a sudden onset with immediate maximum deficit. Various cardiac conditions predispose to formation of emboli that produce embolic stroke, including rheumatic heart disease, atrial fibrillation, recent myocardial infarction, ventricular aneurysm, and bacterial endocarditis. [BLOOD CLOT OR DEBRIS (EMBOLUS) TRAVELS FROM ONE PART OF THE BODY = LODGES IN A NARROWER BRAIN ARTERY = BLOCKS BLOOD FLOW TO BRAIN.] HEMHORRAGIC STROKE The most frequently fatal stroke is caused by the spontaneous rupture of an intracerebral vessel. With rupture of a blood vessel, hemorrhage into the brain tissue occurs, resulting in a focal hematoma and sometimes intraventricular hemorrhage, edema, compression of the brain contents, or spasm of the adjacent blood vessels. The most common predisposing factors are advancing age and hypertension. Other causes of hemorrhage are aneurysm, trauma, erosion of the vessels by tumors, arteriovenous malformations, blood coagulation disorders, vasculitis, and drugs. A cerebral hemorrhage occurs suddenly, usually when the person is active. Vomiting commonly occurs at the onset, and headache is common. Focal symptoms depend on which vessel is involved. In the most common situation, hemorrhage into the basal ganglia results in contralateral hemiplegia, with initial flaccidity progressing to spasticity. The hemorrhage and resultant edema exert great pressure on the brain substance, and the clinical course progresses rapidly to coma and frequently to death. [RUPTURED BLOOD VESSEL IN BRAIN = BLEEDING.]

Discuss the manifestations of deteriorating brain function: 1. level of consciousness 2. pupillary reflexes and eye movements 3. decorticate and decerebrate posturing 4. respiratory responses

LEVEL OF CONSCIOUSNESS Levels of consciousness reflect awareness and response to the environment. A fully conscious person is totally aware of his or her surroundings and able to react to stimuli in the environment. Levels of consciousness exist on a continuum that includes consciousness, confusion, delirium, obtundation, stupor, and coma. The earliest signs of diminution in level of consciousness are inattention, mild confusion, disorientation, and blunted responsiveness. With further deterioration, the delirious person becomes markedly inattentive and variably lethargic or agitated. The person may progress to become obtunded and may respond only to vigorous or noxious stimuli. Because of its simplicity of application, the Glasgow Coma Scale has gained almost universal acceptance as a method for assessing the level of consciousness in persons with brain injury. PUPILLARY REFLEXES AND EYE MOVEMENTSAlthough the pupils may initially respond briskly to light, they become unreactive and dilated as brain function deteriorates. A bilateral loss of the pupillary light response is indicative of lesions of the brain stem. A unilateral loss of the pupillary light response may be due to a lesion of the optic or oculomotor pathways. The oculocephalic reflex (doll's-head eye movement) can be used to determine whether the brain stem centers for eye movement are intact. If the oculocephalic reflex is inconclusive, and if there are no contraindications, the oculovestibular test (i.e., cold caloric test, in which cold water is instilled into the ear canal) may be used to elicit nystagmus. DECORTICATE AND DECEREBRATE POSTURING With the early onset of unconsciousness, there is some combative and purposeful movement in response to pain. As coma progresses, noxious stimuli can initiate rigidity and abnormal postures if the motor tracts are interrupted at specific levels. These abnormal postures are classified as decorticate and decerebrate. Both are poor prognostic signs. Decorticate (flexion) posturing is characterized by the arms being held tightly to the sides, with flexion of the arms, wrists, and fingers; and extension and internal rotation of the legs with plantar flexion of the feet. Decorticate posturing results from lesions of the cerebral hemisphere or internal capsule. Decerebrate (extensor) posturing results from increased muscle excitability. It is characterized by rigidity of the arms with the wrists and fingers flexed and turned away from the body and with stiffly extended legs and plantar flexion of the feet. This response occurs with rostral-to-caudal deterioration, when lesions of the diencephalon extend to involve the midbrain and upper brain stem. RESPIRATORY RESPONSES Early respiratory changes include yawning and sighing, with progression to Cheyne-Stokes breathing, in which there is waxing and waning of respirations with variable periods of apnea. When the progression of injury continues to the midbrain, respirations change to neurogenic hyperventilation, in which the frequency of respirations may exceed 40 breaths per minute because of uninhibited stimulation of inspiratory and expiratory centers. With medullary involvement, respirations become ataxic (i.e., totally uncoordinated and irregular). Apnea may occur because of a lack of responsiveness to carbon dioxide stimulation. Complete ventilatory assistance is often required at this point.

Compare the following post-stroke deficits between a left-hemispheric stroke and right-hemispheric stroke 1. motor deficits 2. dysarthria and aphasia 3. cognitive and other deficits

MOTOR DEFICITS Poststroke motor deficits are most common, followed by deficits of language, sensation, and cognition. After a stroke affecting the corticospinal tract such as the motor cortex, posterior limb of the internal capsule, basis pontis, or medullary pyramids, there is profound weakness on the contralateral side. Involvement at the level of the motor cortex is most often in the territory of the middle cerebral artery, usually with a sparing of the leg, which is supplied by the anterior cerebral artery. Subcortical lesions of the corticospinal tracts cause equal weakness of the face, arm, and leg. Within 6 to 8 weeks, the initial weakness and flaccidity are replaced by hyperreflexia and spasticity. Spasticity involves an increase in the tone of affected muscles and usually an element of weakness. The flexor muscles usually are more strongly affected in the upper extremities and the extensor muscles more strongly affected in the lower extremities. There is a tendency toward foot drop; outward rotation and circumduction of the leg with gait; flexion at the wrist, elbow, and fingers; lower facial paresis; slurred speech; an upgoing toe to plantar stimulation (Babinski sign); and dependent edema in the affected extremities. A slight corticospinal lesion may be indicated only by clumsiness in carrying out fine coordinated movements rather than obvious weakness. Passive range-of-motion exercises help to maintain joint function and to prevent edema, shoulder subluxation (i.e., incomplete dislocation), and muscle atrophy, and may help to reestablish motor patterns. If no voluntary movement or movement on command appears within a few months, significant function usually will not return to that extremity. DYSARTHRIA APHASIA Two key aspects of verbal communication are speech and language. Speech involves the mechanical act of articulating verbal sounds, the "motor act" of verbal expression, whereas language involves the written or spoken use of symbolic formulations, such as words or numbers. Dysarthria is a disorder of speech, which manifests as the imperfect articulation of speech sounds or changes in voice pitch or quality. It results from a stroke affecting the muscles of the pharynx, palate, tongue, lips, or mouth and does not relate to the content of speech. A person with dysarthria may demonstrate slurred speech while still retaining language ability, or may have a concurrent language problem as well. Aphasia is a general term that encompasses varying degrees of inability to comprehend, integrate, and express language. Aphasia may be localized to the dominant cerebral cortex or thalamus—on the left side in 95% of people who are right handed and 70% of people who are left handed. In children, language dominance can readily shift to the unaffected hemisphere, resulting in more transient language deficits after stroke. A stroke in the territory of the middle cerebral artery is the most common aphasia-producing stroke. Aphasia can be categorized as receptive or expressive, or as fluent or nonfluent. Receptive or fluent speech requires little or no effort, is intelligible, and is of increased quantity. The term fluent refers only to the ease and rate of verbal output, and does not relate to the content of speech or the ability of the person to comprehend what is being said. Verbal utterances are often paraphasic, meaning that letters, syllables, or whole words are substituted for the target words. There are three categories of fluent aphasia: Wernicke, anomic, and conduction aphasia. Wernicke aphasia is characterized by an inability to comprehend the speech of others or to comprehend written material. Lesions of the posterior superior temporal or lower parietal lobe are associated with receptive or fluent aphasia. Anomic aphasia is speech that is nearly normal except for difficulty with finding singular words. Conduction aphasia is manifest as impaired repetition and speech riddled with letter substitutions, despite good comprehension and fluency. Conduction aphasia (i.e., disconnection syndrome) results from destruction of the fiber system under the insula that connects the Wernicke and Broca areas. Expressive or nonfluent aphasia is characterized by an inability to easily communicate spontaneously or translate thoughts or ideas into meaningful speech or writing. Speech production is limited, effortful, and halting and often may be poorly articulated because of a concurrent dysarthria. The person may be able, with difficulty, to utter or write two or three words, especially those with an emotional overlay. Comprehension is normal, and the person seems to be fully aware of his or her deficits but is unable to correct them. This often leads to frustration, anger, and depression. Expressive, nonfluent aphasia is associated with lesions of the Broca area at the dominant inferior frontal lobe cortex. [DYSARTHRIA = WEAKNESS IN THE MUSCLES USED FOR SPEECH. APHASIA = LOSS OF ABILITY TO UNDERSTAND OR EXPRESS SPEECH.] COGNITIVE AND OTHER DEFICITS Stroke can also cause cognitive, sensory, visual, and behavioral deficits. One distinct cognitive syndrome is that of hemineglect or hemi-inattention. Usually caused by strokes affecting the nondominant (right) hemisphere, hemineglect is the inability to attend to and react to stimuli coming from the contralateral (left) side of space. Affected persons may not visually track, orient, or reach to the neglected side. They may neglect to use the limbs on that side, despite normal motor function, and may not shave, wash, or comb that side. Such persons are unaware of this deficit, which is another form of their neglect (anosognosia). Other cognitive deficits include impaired ability to carry out previously learned motor activities despite normal sensory and motor function (apraxia), impaired recognition with normal sensory function (agnosia), memory loss, behavioral syndromes, and depression. Sensory deficits affect the body contralateral to the lesion and can manifest as numbness, tingling paresthesias, or distorted sensations such as dysesthesia and neuropathic pain. Visual disturbances from stroke are diverse, but most common are hemianopia from a lesion of the optic radiations between the lateral geniculate body and the temporal or occipital lobes, and monocular blindness from occlusion of the ipsilateral central retinal artery, a branch of the internal carotid artery.

Describe the etiology and pathophysiology of arteriovenous malformations.

Arteriovenous malformations are a complex tangle of abnormal arteries and veins linked by one or more fistulas. These vascular networks lack a capillary bed, and the small arteries have a deficient muscularis layer. Arteriovenous malformations are thought to arise from failure in development of the capillary network in the embryonic brain. As the child's brain grows, the malformation acquires additional arterial contributions that enlarge to form a tangled collection of thin-walled vessels that shunt blood directly from the arterial to the venous circulation. Arteriovenous malformations typically present before 40 years of age and affect men and women equally. Rupture of vessels in the malformation causing hemorrhagic stroke accounts for approximately 2% of all strokes. The hemodynamic effects of arteriovenous malformations are twofold. First, blood is shunted from the high-pressure arterial system to the low-pressure venous system without the buffering advantage of the capillary network. The draining venous channels are exposed to high levels of pressure, predisposing them to rupture and hemorrhage. Second, the elevated arterial and venous pressures divert blood away from the surrounding tissue, impairing tissue perfusion. Clinically, this is evidenced by slowly progressive neurologic deficits. The major clinical manifestations of arteriovenous malformations are intracerebral and subarachnoid hemorrhage, seizures, headache, and progressive neurologic deficits. Headaches often are severe, and persons with the disorder may describe them as throbbing and synchronous with their heartbeat. Other, focal symptoms depend on the location of the lesion and include visual symptoms (i.e., diplopia and hemianopia), hemiparesis, mental deterioration, and speech deficits. [AN ABNORMAL CONNECTION BETWEEN ARTERIES AND VEINS.]

Discuss the etiologies, pathophysiology, and manifestations of increased intracranial pressure: 1. brain herniation 2. hydrocephalus

BRAIN HERNIATION The brain is protected by the nonexpandable skull and two supporting septa, the falx cerebri and the tentorium cerebelli, which divide the intracranial cavity into compartments that normally protect against excessive movement. The falx cerebri is a sickle-shaped septum that divides the supratentorial space into right and left hemispheres. The tentorium cerebelli (so named because it is shaped like a tent) is a double fold of dura mater that forms a sloping partition between the cerebrum and cerebellum. In the center of the tentorium is a large semicircular opening called the incisura or tentorial notch. The brain stem, blood vessels (anterior cerebral, internal carotid, posterior communicating, and posterior and superior cerebellar arteries), and oculomotor nerve (cranial nerve [CN] III) pass through the inciscura. Brain herniation represents a displacement of brain tissue under the falx cerebri or through the tentorial notch of the tentorium cerebelli. It occurs when an elevated ICP in one brain compartment causes displacement of the cerebral tissue toward an area of lower pressure. The different types of herniation syndromes are based on the area of the brain that has herniated and the structure under which it has been pushed. They commonly are divided into two broad categories, supratentorial and infratentorial, based on whether they are located above or below the tentorium. [THE SHIFTING OF THE BRAIN TISSUE FROM ONE SPACE IN THE BRAIN TO ANOTHER AS A RESULT OF PRESSURE IN THE SKULL.] HYDROCEPHALUS Hydrocephalus represents a progressive enlargement of the ventricular system due to an abnormal increase in CSF volume. It can result because of overproduction of CSF, impaired reabsorption of CSF, or obstruction of CSF flow in the ventricular system. There are two types of hydrocephalus: communicating and noncommunicating. Communicating hydrocephalus is caused by impaired reabsorption of CSF from the arachnoid villi into the venous system. Decreased absorption can result from a block in the CSF pathway to the arachnoid villi or a failure of the villi to transfer the CSF to the venous system. It can occur if too few villi are formed, if postinfective (meningitis) scarring occludes them, or if the villi become obstructed with fragments of blood or infectious debris. Adenomas of the choroid plexus can cause an overproduction of CSF. This form of hydrocephalus is much less common than that resulting from decreased absorption of CSF. Noncommunicating or obstructive hydrocephalus occurs when obstruction in the ventricular system prevents the CSF from reaching the arachnoid villi. Cerebrospinal fluid flow can be obstructed due to congenital malformations, tumors encroaching on the ventricular system, or inflammation or hemorrhage. Similar pathologic patterns occur with noncommunicating and communicating types of hydrocephalus. The cerebral hemispheres become enlarged, and the ventricular system beyond the point of obstruction becomes dilated. The sulci on the surface of the brain become effaced and shallow, and the white matter reduced in volume.In adults and children in whom the cranial sutures have fused, head enlargement does not occur. Acute-onset hydrocephalus usually is marked by symptoms of increased ICP, including headache, vomiting, and papilledema or deviation in eye movements due to pressure on the cranial nerves. If the obstruction is not relieved, progression to herniation ensues. Signs and symptoms of hydrocephalus vary greatly, depending on age and rapidity of onset. When hydrocephalus develops in utero or before the cranial sutures of the skull have fused in infancy, the ventricles expand beyond the point of obstruction, the cranial sutures separate, the head expands, and there is bulging of the fontanels. Because the skull is able to expand, signs of increased ICP may be absent, and intelligence spared. However, seizures are not uncommon, and in severe cases, optic nerve atrophy leads to blindness. Weakness and uncoordinated movement are common. Surgical placement of a shunt allows for diversion of excess CSF fluid, preventing extreme enlargement of the head and neurologic deficits. [A CONDITION IN WHICH EXCESS CSF BUILDS UP WITHIN THE VENTRICLES OF THE BRAIN.]

Describe the etiology, pathophysiology, and manifestations of a traumatic brain injury: 1. contusions 2. hematomas -epidural -subdural -traumatic intracerebral hematoma 3. concussions 4. diffuse axonal injury

CONTUSIONS Contusions represent a bruising on the brain surface or a lacerations or tearing of brain tissue. Contusions can result from direct force, a depressed skull fracture, or a closed acceleration-deceleration injury. Closed injury contusions are often distributed along the rough, irregular inner surface of the brain and are more likely to occur in the frontal or temporal lobes, resulting in cognitive and motor deficits. The clinical effects of a contusion depend on its size and related cerebral edema. Small, unilateral, frontal lesions may be asymptomatic; whereas larger lesions may result in neurological defects. They can cause secondary mass effects from edema resulting in an increased ICF, and possible herniation syndromes. Persons suffering from cerebral contusions are usually managed medically with emphasis toward prevention of secondary injuries. [BLOOD OR BLEEDING UNDER THE SKIN (BRUISE)]. HEMATOMAS Hematomas result from vascular injury and bleeding. Depending on the anatomic position of the ruptured vessel, bleeding can occur in any of several compartments, including the epidural, subdural, and subarachnoid spaces, or into the brain itself (intracerebral hematoma). [BLEEDING OUTSIDE OF BLOOD VESSELS.] EPIDURAL HEMATOMA An epidural hematoma is one that develops between the inner side of the skull and the dura1. It usually results from a tear in an artery, most often the middle meningeal, usually in association with a head injury in which the skull is fractured. Because bleeding is arterial in origin, rapid expansion of the hematoma compresses the brain. Epidural hematoma is more common in a young person because the dura is less firmly attached to the skull surface than in an older person; as a consequence, the dura can be easily separated from the inner surface of the skull, allowing the hematoma to grow. Typically, a person with an epidural hematoma presents with a history of head injury and a brief period of unconsciousness followed by a lucid period in which consciousness is regained. There is then a rapid progression to unconsciousness. The lucid interval does not always occur, but when it does, it is of great diagnostic value. With rapidly developing unconsciousness, there are focal symptoms related to the area of the brain involved. These symptoms can include ipsilateral pupil dilation and contralateral (opposite side) hemiparesis from uncal herniation. If the hematoma is not removed, the condition progresses, with increased ICP, tentorial herniation, and death. The prognosis is excellent, however, if the hematoma is removed before loss of consciousness occurs. [BLEEDING BETWEEN THE DIRA MATER AND THE SKULL.] SUBDURAL HEMATOMA A subdural hematoma develops in the area between the dura and the arachnoid (subdural space) and usually is the result of a tear in the small bridging veins that connect veins on the surface of the cortex to dural sinuses. The bridging veins pass from the pial vessels through the CSF-filled subarachnoid space, penetrate the arachnoid and the dura, and empty into the intradural sinuses. These veins are readily snapped in head injury when the brain moves suddenly in relation to the cranium. Bleeding can occur between the dura and arachnoid (i.e., subdural hematoma) or into the CSF-filled subarachnoid space (i.e., subarachnoid hematoma). The venous source of bleeding in a subdural hematoma develops more slowly than the arterial bleeding in an epidural hematoma. Subdural hematomas are classified as acute, subacute, or chronic. This classification system is based on the approximate time before the appearance of symptoms. Symptoms of acute hematoma are seen within 24 hours of the injury, whereas subacute hematoma does not produce symptoms until 2 to 10 days after injury. Symptoms of chronic subdural hematoma may not arise until several weeks after the injury. Acute subdural hematomas progress rapidly and have a high mortality rate because of the severe secondary injuries related to edema and increased ICP. The high mortality rate has been associated with uncontrolled ICP increase, loss of consciousness, decerebrate posturing, and delay in surgical removal of the hematoma. The clinical picture is similar to that of epidural hematoma, except that there usually is no lucid interval. By contrast, in subacute subdural hematoma, there may be a period of improvement in the level of consciousness and neurologic symptoms, only to be followed by deterioration if the hematoma is not removed. Symptoms of chronic subdural hematoma develop weeks after a head injury, so much later that the person may not remember having had a head injury. Chronic subdural hematoma is more common in older persons because brain atrophy causes the brain to shrink away from the dura and stretch fragile bridging veins. When these veins rupture, there is slow seepage of blood into the subdural space. Fibroblastic activity causes the hematoma to become encapsulated. The sanguinous (blood fluid) in this encapsulated mass, with its high concentration of osmotically-active particles, draws fluid from the surrounding subarachnoid space, causing the hematoma to expand and exert pressure on the surrounding brain tissue. In some instances, the clinical picture is less defined, with the most prominent symptom being a decreasing level of consciousness, as manifested by drowsiness, confusion, headache, and apathy. [BLEEDING BETWEEN THE DURA MATER AND ARACHNOID MEMBRANE.] TRAUMATIC INTRACEREBRAL HEMATOMA Traumatic intracerebral hematomas may be single or multiple. They can occur in any lobe of the brain but are most common in the frontal or temporal lobes, related to the bony prominences on the inner skull surface. They may occur in association with the severe motion that the brain undergoes during head injury, or a contusion can coalesce into a hematoma. Intracerebral hematomas occur more frequently in older persons and alcoholics, whose cerebral vessels are more friable. The signs and symptoms produced by an intracerebral hematoma depend on its size and location in the brain. Signs of increased ICP can be manifested if the hematoma is large and encroaching on vital structures. A hematoma in the temporal lobe can be dangerous because of the potential for lateral herniation. CONCUSSIONS A cerebral concussion can be defined as a transient neurogenic dysfunction caused by mechanical force to the brain. Acceleration-deceleration is the mechanism of injury, usually due to a nonpenetrating force such as a sudden blow to the head. There may be a momentary loss of consciousness without demonstrable symptoms, except for residual amnesia. Microscopic changes can often be detected in neurons and neuroglia within hours of injury, but brain imaging is usually negative. Although recovery usually takes place within 24 hours, mild symptoms, such as headache, irritability, insomnia, and poor concentration and memory, may persist for months. This is known as the postconcussion syndrome. The amnesia or memory loss usually includes an interval of time preceding the injury (retrograde amnesia) and following the injury (anterograde amnesia). The duration of retrograde amnesia correlates with the severity of the brain injury. DIFFUSE AXONAL INJURY Diffuse axonal injury is caused by shearing of fragile axons by acceleration-deceleration forces at the time of trauma. The difference in acceleration-deceleration gradient on certain areas of the brain, permits generation of rotational forces that cause axonal shearing injury. It is characterized by distinct and microscopic findings, including axonal swelling, that are widely distributed in the cerebral hemispheric white matter, corpus callosum, and upper brain stem. Diffuse axonal injury is characterized clinically by functional cerebral impairment, which may range from confusion to coma and death.

Describe the etiology, pathophysiology, and clinical manifestations of Alzheimer Disease.

Dementia of the Alzheimer type is the most common type of dementia. Alzheimer disease most often presents with a subtle onset of memory loss followed by slowly progressive dementia that has a course of several years. Evidence from familial forms of AD indicates that the accumulation of a peptide (amyloid beta or Aβ) in the brain initiates a chain of events that result in the morphologic changes of AD and dementia. This peptide is derived from a larger membrane-spanning protein known as amyloid precursor protein (APP), which can be processed in either of two ways. It can be cleaved by the enzymes, α-secretase and γ-secretase, in a proteolytic pathway that prevents the formation of Aβ, or it can be cleaved by β-secretase and γ-secretase in a pathway that generates Aβ. It is likely that AD is caused by several factors that interact differently in different persons. Progress in the genetics of inherited early-onset AD shows that mutations in at least three genes—the APP gene on chromosome 21; presenilin-1 (PS1), a gene on chromosome 14; and presenilin-2 (PS2), a gene on chromosome 1—can cause AD in certain families. The APP gene is associated with an autosomal dominant form of early-onset AD and can be tested clinically. Virtually all persons with Down syndrome (trisomy 21) exhibit the pathologic features of AD as they age. Presenilin-1 and presenilin-2, both intracellular proteins, are components of γ-secretase and possibly part of a multiprotein complex containing the proteolytic site for breakdown of Aβ. A fourth gene, the apolipoprotein E (ApoE) gene, has been found to increase the risk of AD and lowers the age of onset of the disease. Alzheimer-type dementia follows an insidious and progressive course. The hallmark symptoms are loss of short-term memory and denial of such memory loss, with eventual disorientation, impaired abstract thinking, apraxias, and changes in personality and affect. Various stages of the disease have been recognized; all are characterized by progressive degenerative changes. The initial changes are often subtle, characterized by a short-term memory loss that often is difficult to differentiate from the normal memory loss that often occurs in the elderly, and usually is reported by caregivers and denied by the person. Although most elderly persons have trouble retrieving from memory incidental information and proper names, persons with AD randomly forget important and unimportant details. They forget where things are placed, get lost easily, and have trouble remembering appointments and performing novel tasks. Mild changes in personality, such as lack of spontaneity, social withdrawal, and loss of a previous sense of humor, occur during this stage. As the disease progresses, the person with AD enters the moderate stage. This stage may last several years and is marked by a more global impairment of cognitive functioning. During this stage, there are changes in higher cortical functioning needed for language, spatial relationships, and problem solving. Depression may occur in persons who are aware of their deficits. There is extreme confusion, disorientation, lack of insight, and inability to carry out the activities of daily living. Personal hygiene is neglected, and language becomes impaired because of difficulty in remembering and retrieving words. Behavioral changes can include agitation, sleep problems, restlessness and wandering, aggression, and suspiciousness. Some persons may become hostile and abusive toward family members. Persons who enter this stage become unable to live alone and should be assisted in making decisions about supervised placement with family members or friends or in a community-based facility. Severe AD is the last stage of the disease. It is characterized by a loss of ability to respond to the environment. Individuals in this stage require total care and spend most of their time bedridden. Death can occur as a result of complications related to chronic debilitation. [A PROGRESSIVE DISEASE THAT DESTROYS MEMORY, THINKING SKILLS, AND OTHER IMPORTANT MENTAL FUNCTIONS.]

Differentiate between a focal and a generalized seizure.

FOCAL SEIZURE Focal seizures, which are the most common type of seizures among newly diagnosed cases of epilepsy, can be viewed as those with neural networks limited to one hemisphere or the other. They may originate in subcortical structures, and may be discretely localized or widely distributed. For each seizure type, the site of onset is consistent from one seizure to another, with preferential propagation patterns that can involve the contralateral hemisphere. Focal seizures are described according to their manifestations; that is, they may occur without or with impairment of consciousness or awareness. [WHEN THE ABNORMAL ELECTRICAL DISTURBANCES REMAIN IN A LIMITED AREA OF THE BRAIN.] GENERALIZED SEIZURE Generalized-onset seizures are the most common type in young children. The seizures are classified as primary or generalized when clinical signs, symptoms, and supporting EEG changes indicate involvement of both hemispheres at onset. The clinical symptoms include unconsciousness and involve varying bilateral degrees of symmetric motor responses without evidence of localization to one hemisphere. These seizures are divided into six broad categories: tonic-clonic, absence seizures (typical, atypical, myoclonic absence, absence of eyelid myoclonia), myoclonic seizures (myoclonic, myoclonic atonic, myotonic clonic), clonic seizures, tonic seizures, and atonic seizures. [WHEN BOTH HEMISPHERES ARE AFFECTED SINCE THE BEGINNING OF THE SEIZURE.]

Discuss modifiable and nonmodifiable factors for stroke.

MODIFIABLE FACTORS -Hypertension -Hyperlipidemia -Smoking -Diabetes -Heart disease -Atrial fibrillation -Wall motion defects -Carotid artery disease -Coagulation disorders -Obesity/inactivity -Heavy alcohol use -Cocaine use NONMODIFIABLE FACTORS -Age -Gender -Race -Heredity

Differentiate between provoked and non-provoked seizures.

PROVOKED SEIZURES Provoked seizures include febrile seizures (which occur in children), seizures precipitated by systemic metabolic conditions, and those that follow a primary insult to the CNS. Transient systemic metabolic disturbances may precipitate seizures. Examples include electrolyte imbalances, hypoglycemia, hypoxia, hypocalcemia, uremia, alkalosis, and rapid withdrawal of sedative drugs. Specific CNS injuries such as toxemia of pregnancy, water intoxication, meningitis, trauma, cerebral hemorrhage and stroke, and brain tumors may precipitate a seizure. In most cases of provoked seizures, treatment of the immediate underlying cause often results in their resolution. [SINGLE SEIZURES THAT MAY OCCUR AS A RESULT OF TRAUMA, LOW BLOOD SUGAR, LOW BLOOD SODIUM, HIGH FEVER, OR ALCOHOL OR DRUG ABUSE.] UNPROVOKED SEIZURES The International League Against Epilepsy (ILAE) Commission on Classification and Terminology determines seizure type by clinical symptoms and EEG activity. It divides epileptic seizures into two broad categories: focal and generalized. Focal seizures are those in which the seizure begins in a specific or focal area of one cerebral hemisphere. Generalized seizures are those which begin simultaneously in both hemispheres. The system also has a category of unknown origin, such as epileptic spasms. [SEIZURES THAT OCCUR IN THE ABSENCE OF PRECIPITATING FACTORS.]

Discuss tonic-clonic seizure activity in terms of generalize convulsive status epilepticus.

Tonic-clonic seizures, formerly called grand mal seizures, are the most common major motor seizures. Frequently, a person has a vague warning (probably a simple focal seizure) and experiences a sharp tonic contraction of the muscles with extension of the extremities and immediate loss of consciousness. Incontinence of bladder and bowel is common. Cyanosis may occur from contraction of airway and respiratory muscles. The tonic phase is followed by the clonic phase, which involves rhythmic bilateral contraction and relaxation of the extremities. At the end of the clonic phase, the person remains unconscious until the RAS begins to function again. This is called the postictal phase. The tonic-clonic phases last approximately 60 to 90 seconds. Seizures that do not stop spontaneously or occur in succession without recovery are called status epilepticus. There are as many types of status epilepticus as there are types of seizures. Tonic-clonic status epilepticus is a medical emergency and, if not promptly treated, may lead to respiratory failure and death. The disorder occurs most frequently in the young and old. Morbidity and mortality rates are highest in elderly persons and persons with acute symptomatic seizures, such as those related to anoxia or cerebral infarction. If status epilepticus is caused by neurologic or systemic disease, the cause needs to be identified and treated immediately because the seizures probably will not respond until the underlying cause has been corrected. [A TYPE OF SEIZURE THAT INVOLVES A LOSS OF CONSCIOUSNESS AND VIOLENT MUSCLE CONTRACTIONS.]