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Etiologies of Neurogenic Injury

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1 Etiologies of Neurogenic Injury
General Orientation

2 Cerebrovascular Accident (CVA)

3 CVA aka “Stroke” Cerebrovascular accident (CVA) is the medical term applied to a neurological event that has a vascular or circulatory origin. Stroke is lay term for describing a sudden diminution or loss of consciousness, sensation, and voluntary motion usually thought to be caused by the rupture or obstruction (as by a clot) of an artery of the brain. The most common cause of stroke-like illness is vascular disease. Loss of blood circulation to the brain results in rapid disruption of the ability of brain neurons to perform properly. If loss of circulation is severe and persistent, neuronal tissue dies.

4 CVA aka “Stroke” Strokes are twice as likely to occur between 6:00 a.m. and noon than at any other time of day. Strokes are typically divided into two types: ischemic and hemorrhagic. More than half, especially hemorrhagic strokes, occur on Mondays.

5 Ischemia Ischemia is a cerebrovascular disorder caused by insufficient blood flow in an area of the brain due to complete or partial occlusion of an arterial vessel. Ischemia accounts for about 80% of strokes. Risk factors include hypertension, heart disease, arrhythmias (e.g., atrial fibrillation), hyperlipidemia, and the effects of age on the cerebral vessels. Brain tissue malfunctions rapidly when deprived of adequate blood flow.

6 Ischemia Temporary disruption of blood flow may result in ischemia without infarction and thus produce only temporary symptoms. However, if blood flow to a brain region falls below a critical level needed to maintain cellular function and to remove accumulating toxic waste, cells begin to die. When ischemia is prolonged, infarction occurs and localized brain function is irrevocably lost. However, brain function is plastic, and other, nearby areas may eventually take over the lost function.

7 Ischemia An infarct develops subsequent to tissue death, or necrosis, as the dead neurons soften and tissue bulk is lost. When circulation return to the region, the dead tissue will be removed, leaving a residual cystic cavity. The size of the infarct will depend on the size of the occluded vessel and the ability of collateral arteries to maintain blood supply to endangered brain cells. As ischemia is caused by an impediment to blood flow, almost always due to a narrowed or occluded artery supplying a local brain region, arterial occlusion triggers a chain of events.

8 Ischemia Typically, in ischemic regions, there will be an inner zone of infarction with a surrounding zone of ischemia. In the ischemic zone, nerve cell function is limited by slow blood flow, edema, and compression by the expanding infarct. There may be a worsening of the neurologic deficit. However, compensatory body reactions, such as collateral circulation, may limit the ischemia and the subsequent deficit. For this reason, about 1/4 to 1/2 of ischemic strokes are generally presaged by at least one TIA and a stroke may occur days or months after a TIA.

9 Ischemia Ischemic strokes are classified on the basis of their site and causes. Atherosclerosis is a major cause of ischemic stroke in large vessels. It is a common arterial disorder characterized by yellowish plaques of cholesterol, lipids, and cellular debris in the inner layers of the walls of large and medium-sized arteries. The formation of plaque damages the arterial vessel, causing the vessels to become thick, fibrotic, and calcified.

10 Ischemia Among whites, atherosclerosis is most common at the origins of the internal carotid and the vertebral arteries in the neck (extracranial) and in the intracranial vertebral and basilar arteries. The large intracranial arteries (middle, anterior, and posterior cerebral arteries) and their superficial branches are affected much less often. Atherosclerosis of the extracranial internal carotid and vertebral arteries is twice as common among white men as among white women. It correlates highly with coronary and peripheral vascular occlusive disease and hyperlipidemia.

11 Ischemia Atherosclerosis of the extracranial internal carotid and vertebral arteries is less common among blacks and Asians than among whites, but atherosclerosis of the major intracranial arteries is more common. Among blacks and Asians, intracranial atherosclerosis does not have a strong male preponderance, does not correlate epidemiologically with coronary or peripheral vascular disease or with hyperlipidemia, and occurs at a younger age than does extracranial atherosclerosis. Among persons with diabetes or hypertension, prevalence of intracranial atherosclerosis is also high.

12 Ischemia The small arteries that penetrate deeper brain structures (e.g., basal nuclei, internal capsule, thalamus, pons) are especially susceptible to degenerative changes caused by hypertension. The vessels lumens gradually narrow, impeding blood flow. When a penetrating artery becomes occluded, a small, deep infarct (lacune) results. Lacunes are < 2 cm at their greatest diameter and affect only deeper structures; they are relatively more common in the posterior circulation. Prevalence increases with age but does not appear to be correlated with race or sex.

13 Thrombosis A thrombus is an aggregation of platelets, fibrin, clotting factors, and the cellular elements of the blood attached to the interior wall of a vein or artery. It contributes to progressive narrowing or stenosis of the artery and to further blood clot formation. Thromboses may arise also from inflammation of the arterial wall, mechanical damage following injury, or excessive clotting factor in the blood itself. Thrombotic strokes caused by atherosclerosis account for approximately 60% of all CVAs.

14 Thrombosis The most common presenting symptom with thrombotic events is at least one prior TIA, which is often brief. If untreated, TIAs may recur for weeks or months. With a thrombotic event, the individual usually awakens in the morning with a new onset of a deficit, or symptoms may develop progressively over a few minutes to several hours.

15 Embolus An embolus is a foreign object, such as a quantity of air or gas, a bit of tissue, or a fragment of a blood clot, which travels through the bloodstream until it becomes lodged in a blood vessel. Emboli of blood clot fragments are common in patients with disturbances in cardiac rhythm, heart valve disease, and significant damage by myocardial infarction. Cerebral embolism accounts for approximately 10% of all strokes, especially in the younger population.

16 Embolus Neurologic symptoms usually begin abruptly, often while the patient is awake and active. Most often, the deficit is maximal at or near onset, because the sudden blockage of a distal artery does not allow adequate time for collateral circulation to become established. When emboli cause a large infarct, headache and decreased alertness are common.

17 Hemorrhage A hemorrhage is defined as bleeding into brain tissue or meningeal spaces. A hemorrhagic strokes results from the rupture of a blood vessel within the intercranium and accounts for approximately 30% of all CVAs. It is most often caused by aneurysms, vascular malformations, bleeding disorders, hypertension, and use of illicit drugs. This type of CVA is more common in blacks than whites, possible because of the higher prevalence of untreated hypertension.

18 Intracerebral Hemorrhage
The hemorrhage can occur in three different spaces: the parenchyma (tissue) of the brain; the subarachnoid space; or the subdural space. The intraparenchymal or intracerebral hemorrhage occurs when there is bleeding directly into the brain. Bleeding destroys brain tissue because of effects of local pressure. Usually, intracerebral hemorrhage arises from small arteries or arterioles. Aneurysms and vascular malformations are uncommon causes.

19 Intracerebral Hemorrhage
Intracerebral hemorrhage accounts for about 10% of all strokes but for a much higher percentage of deaths due to stroke. After age 60, intracerebral hemorrhage is more common than subarachnoid hemorrhage. Hypertension and coexisting degenerative changes due to aging increase susceptibility to intracerebral hemorrhage in the elderly. Bleeding disorders and use of anticoagulants pose additional risk and more often result in death than does intracerebral hemorrhage due to other conditions.

20 Intracerebral Hemorrhage
Location of hemorrhage varies. Warfarin-induced (Coumadin) hemorrhages tend to occur in the lobes of the cerebrum and the cerebellum. They begin more insidiously and progress more gradually than hemorrhages due to other conditions. Occasionally, bleeding occurs into a previously unsuspected brain tumor, especially if it is metastatic. The earliest symptoms of hemorrhage result from loss of function subserved by the brain region in which the hemorrhage occurs.

21 Intracerebral Hemorrhage
For example, hemorrhage in the right occipital lobe causes a left visual field defect and cerebellar hemorrhage causes an inability to walk. The hemorrhage may expand within minutes, or at most a few hours, and act as a mass, increasing intracranial contents and pressure and causing headache, vomiting, and decreased alertness. However, these symptoms may not occur if the hemorrhage remains small.

22 Intracerebral Hemorrhage
Nearly 50% of elderly patients with small to moderate intracerebral hemorrhages do not have headache and remain alert because previous atrophy in the brain provides additional space to accommodate the extra contents. If intracerebral hemorrhage progresses, consciousness usually decreases and focal neurologic signs increase. Patients with large hemorrhages usually die before treatment can be initiated. Those with small hemorrhages, which are self-contained and self-limited, require little treatment except preventive measures (e.g., controlling hypertension).

23 Intracerebral Hemorrhage
Traumatically-induced hemorrhages leading to hematomas are usually multiple. They are located on the surface of the brain, commonly on the orbital frontal lobes and tips of the temporal lobes, which are close to the rough bony ridges at the base of the skull.

24 Intracranial Hemorrhage
Subarachnoid and subdural hemorrhages constitute intracranial bleeds. Intracranial bleeds account for about 10% of all strokes but for a much higher percentage of deaths due to stroke.

25 Subarachnoid Hemorrhage
A subarachnoid hemorrhage involves bleeding into the subarachnoid space. Subarachnoid hemorrhage increases the pressure within the cranium, impairs the drainage of cerebrospinal fluid (CSF), and irritates the arteries at the base of the brain. The blood is usually released quickly into the subarachnoid space at arterial pressure and becomes widely dispersed around the brain and spinal cord. It is common for vasoconstriction of the cerebral arteries to be delayed for at least 48 hours after hemorrhage and possibly continuing for up to1 week.

26 Subarachnoid Hemorrhage
Vasoconstriction with delayed brain ischemia is likely when the hemorrhage is large or produces thick focal collections of blood. The most common causes of subarachnoid hemorrhage are vascular malformations, cerebral aneurysms, bleeding disorders (most often due to use of anticoagulants), and head trauma. Vascular malformations, also known as arteriovenous malfromations (AVM) are abnormalities in the vascular distribution of arteries and veins.

27 Subarachnoid Hemorrhage
In normal vascular distribution, arteries and veins are interfaced by capillaries which can adjust to the pressure differentials between arteries and veins. With an AVM, arteries and veins interface directly, and the vein is often unable to handle the pressure differential of the artery, resulting in a hemorrhage into the subarachnoid space.

28 Subarachnoid Hemorrhage
In elderly patients, AVMs and saccular aneuryms rarely cause subarachnoid hemorrhage. They are less likely to be life threatening in persons > 60 because dangerous ones have usually ruptured before that age.

29 Subarachnoid Hemorrhage
Head trauma, common among the elderly because of their tendency to fall, is often an undiagnosed cause of hemorrhage. After a fall, patients are often confused or amnesic and cannot clearly describe the event. Symptoms and signs of subarachnoid hemorrhage are no different in the elderly than in younger patients. Patients invariably have headache, often beginning suddenly and during physical activity, and becoming severe almost immediately. The pain is usually diffuse, but at times it is most severe at the back of the head and neck and may radiate down the back or down the lower limbs in a sciatic pattern.

30 Subarachnoid Hemorrhage
Nausea and vomiting, due to the sudden increase in intracranial pressure, are common. Patients have difficulty performing any activity and often become restless, agitated, and confused. At presentation, they are usually not paralyzed and often do not have important focal neurologic signs (e.g., hemiparesis). During physical examination, the most apparent abnormality is the change in the level of consciousness, resulting in restlessness, delirium, sleepiness, stupor, or coma. Stiff neck, difficulty concentrating, impaired short-term memory, and impaired extensor plantar reflexes are also common.

31 Subdural Hemorrhage A subdural hematoma results from an accumulation of blood between the dura mater and the arachnoid mater, usually from bleeding of the bridging veins. Subdural hematomas develop when blunt head trauma causes brain motion within the skull, shearing off the bridging veins between the brain's surface and adjacent dural venous sinuses. The blood leaks and accumulates slowly. The resulting subdural hematoma may be absorbed spontaneously or after about 2 weeks, or may become encapsulated with a liquefied center, called a hematoma.

32 Subdural Hemorrhage The vascular outer membrane of the hematoma may continue to bleed, causing the center to enlarge. Subdural hematomas may be acute (due to severe head trauma) or chronic (usually due to minor trauma). Chronic subdural hematomas typically occur in elderly persons taking anticoagulants or in alcoholics who have some degree of brain atrophy. Other causes include falls and bleeding disorders. Some patients forget a fall or other trauma or consider it too inconsequential to mention. The most common findings are headache, decreased alertness, and abnormalities of hemispheric function.

33 Subdural Hemorrhage Headache, usually ipsilateral to the hematoma, may worsen at night. Drowsiness and decreased alertness are due to increased intracranial pressure. Slight weakness, hyperreflexia, and Babinski's sign in the contralateral limbs are common. Patients with a left-sided hematoma may have slight aphasia, and patients with a right-sided hematoma may have right-sided spatial neglect. Usually, neurologic abnormalities are mild. Seizures may occur, probably indicating contusion of underlying brain tissue.

34 Traumatic Brain Injury

35 Traumatic Brain Injury
The term traumatic brain injury (TBI) refers to an acquired injury to the brain caused by an external force, resulting in total or partial functional disability, psychosocial impairment, or both. Closed head injury (CHI) is frequently used to denote an injury in which the primary mechanism of damage is blunt impact to the head. Open head injury denotes an injury in which the skull is penetrated by some sort of sharp instrument or explosively propelled missiles.

36 Closed Head Injuries The majority of CH injuries occur as a consequence of motor vehicle crashes (MVC), followed by motorcycle, and bicycle crashes. The accident rate among motorcyclists is estimated to be 4 times higher than that for other motor vehicle operators. Motorcyclists are both more likely to be head injured and more likely to die as a result of their injuries than are drivers of other vehicles. Head injuries also result from falls, pedestrian injuries, and assaults.

37 Open Head Injuries Penetrating head injuries are frequently sustained as a result of accidental, self-inflicted, or premeditated violence involving firearms. Penetrating head injuries are most often fatal. Head injury resulting from violence is reportedly higher for lower SES groups from multicultural communities. Head injury from violence is higher among African- American (AA) males than Hispanic males, and higher for both of these groups than for Euro-Americans (EA) males of similar SES status.

38 Traumatic Brain Injury
Head injury rates are comparative among suburban AA and EA individuals with MVC being the most common cause of injury in year old age bracket and fall for the older group (44+years). In children under 5 years of age, falls constitute the major source of CH injury, followed by sports-related/recreational injuries in the 5-14 year old range, and MVCs in the 15+ age group. Skull fractures occur in about 40% of infants who fall, possible due to the flexibility of the skull and open sutures.

39 Traumatic Brain Injury
Head injury resulting from falls, with or without skull fracture, may develop delayed intracranial hematomas. MVCs are more likely to cause concussion in school-aged children and adolescents, although hematomas and contusions are common as well.

40 Dementia Syndromes

41 Dementia Syndromes Dementia refers to a syndrome, or constellation of signs and symptoms, associated with a morbid process. It is not a consequence of normal aging, but a condition of chronic progressive deterioration of intellect, personality, and communicative functioning. It can be associated with numerous causes, including infection, anoxia, tumor, trauma, toxicity, nutritional disturbances, and progressive degenerative diseases, such as Alzheimer’s disease. Not all dementias are irreversible.

42 Dementia Syndromes Deteriorating intellectual capacity may be caused by a variety of diseases and disorders. The National Institute on Aging states that some100 conditions which mimic serious disorders are actually reversible. These are often times called “pseudodementias” and are often treatable.

43 Reversible Causes of Dementia
Reactions to Medications: Confusion is a common reaction to prescription medications, such as sedatives, neuroleptics, antihypertensives, and antiarthritic medications. Metabolic Disturbances: Confusional state, changes in sleep, appetite, and emotions can be provoked by metabolic disturbances, including renal failure, liver failure, electrolyte imbalances, hypoglycemia, hypercalcermia, hepatic diseases, or pancreatic disorders.

44 Reversible Causes of Dementia
Nutritional Deficiencies: Deficiencies of folate, niacin, riboflavin, and thiamine can produce cognitive impairment. Lost of taste and smell, loss of appetite, poorly fitting dentures, or even difficulty shopping or preparing food may lead to nutritional deficiencies. Vision and Hearing: Undetected problems of vision or hearing may result in inappropriate responses. This could be misinterpreted as dementia, because the individual is unable to perceive surroundings or understand conversations.

45 Reversible Causes of Dementia
Endocrine Abnormalities: Hypothyroidism, hyperthyroidism, parathyroid disturbances, or adrenal abnormalities can cause confusion which mimics dementia. Infections: Older persons can develop infections which produce a sudden onset of confusional state. Emotional Distress: Depression or major life changes such as retirement, divorce, or loss of a loved one can affect one’s physical and mental health. Several treatable neurological disorders, such as subdural hematoma, normal pressure hydrocephalus, and brain tumor can also produce dementia like symptoms.

46 Irreversible Causes of Dementia
Dementia caused by a degenerative disease produces progressive cognitive deterioration that cannot be reversed. The most common irreversible dementia is Alzheimer’s disease. Other degenerative diseases which can also cause dementia include Parkinson’s disease, Huntington’s disease, Pick’s disease, and Lewy body disease. Other causes of dementia include multi-infarct dementia , anoxia, Creutzfeld-Jakob disease, Binswanger disease, AIDS, and multiple sclerosis.

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