CEREBROVASCULAR ACCIDENT (STROKE)
Dr Vernon Nsofwa
INTRODUCTION
Stroke is a syndrome characterized by the acute onset of a neurologic deficit that persists for at least 24 hours, reflects focal involvement of the central nervous system, and is the result of a disturbance of the cerebral circulation. Stroke causes 9% of all deaths around the world and is the second most common cause of death after ischemic heart disease. There are three main types of stroke: ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage (about 80%, 15% and 5% of all strokes, respectively).
ISCHEMIC STROKE
Etiology
A variety of disorders of the blood vessels, heart and blood can lead to focal cerebral ischemia.
A. Atherosclerosis. In most cases, atherosclerosis of the large extra cranial arteries in the neck and at the base of the brain is the underlying cause of focal cerebral ischemia. The sites of predilection are the origin of the common carotid artery, the internal carotid artery just above the common carotid bifurcation and within the cavernous sinus, the origin of the middle cerebral artery, the vertebral artery at its origin and just above where it enters the skull, and the basilar artery. The pathogenesis of atherosclerosis is incompletely understood, but injury to vascular endothelial cells is thought to be an early step. Endothelial cells may be injured by the accumulation of cholesterol esters derived from circulating low- density lipoproteins or by other mechanical, biochemical, or inflammatory mechanisms. Blood monocytes, macrophages, and T lymphocytes adhere to the sites of endothelial injury or denudation and subsequently migrate sub-endothelially, where they are transformed into lipid-laden foam cells. The resulting lesion is called a fatty streak. The release of growth and chemotactic factors from endothelial cells and monocytic macrophages stimulates the proliferation and migration of intimal smooth muscle cells, and leads to formation of a fibrous plaque. Further endothelial injury or denudation ensues, promoting the adherence of platelets, which also release growth and chemotactic factors. The resulting atheromatous lesion may enlarge to occlude the vessel lumen, or it may pro- vide a source of atheromatous or platelet emboli. Ulcerated atheromas may be especially likely sources of emboli. The most important risk factor for atherosclerosis leading to stroke is systolic or diastolic hypertension. Atherosclerosis can also occur in the absence of hypertension. In such cases, other factors such as diabetes, elevated serum cholesterol and triglycerides, hyperhomocysteinemia, cigarette smoking, hereditary predisposition, and the use of oral contraceptives may be implicated.
B. Other vascular disorders. Dissection of the carotid or vertebral artery is associated with hemorrhage into the vessel wall, which can occlude the vessel or predispose to thrombus formation and embolization. Post Traumatic carotid dis sections present little difficulty in diagnosis. Certain patients, however – usually young men suffer cerebral infarction after apparently spontaneous carotid artery dissection. Internal carotid artery dissections usually originate near the carotid bifurcation and can extend to the base of the skull. Prodromal transient hemispheric ischemia or monocular blindness sometimes precedes a devastating stroke. Carotid dissection may be accompanied by pain in the jaw or neck, visual abnormalities akin to those that occur in migraine, or Horner's syndrome. Dissection of the vertebral or basilar artery is less common. The clinical features of this disorder include headache, posterior neck pain, and the sudden onset of signs of brainstem dysfunction.
Inflammatory vascular disorders. Polyarteritis nodosa is a segmental vasculitis of small and medium sized arteries that affects multiple organs. Systemic lupus erythematosus is associated with a vasculopathy that involves small cerebral vessels and leads to multiple microinfarctions. There is no correlation be- tween cerebral microinfarcts and verrucous (Libman-Sacks) endocarditis. Syphilitic arteritis is uncommon but is being seen with increasing frequency at present. Medium-sized penetrating vessels are typically involved, producing punctate areas of infarction in the deep white matter of the cerebral hemisphere. Giant cell arteritis, also called temporal arteritis or cranial arteritis, sometimes produces signs of cerebral ischemia. Inflammatory changes affect the branches of the external carotid, cervical internal carotid, posterior ciliary, extracranial vertebral, and intracranial arteries.
Fibromuscular dysplasia is a segmental nonatherosclerotic condition of large arteries characterized by segmental thinning of the media and fragmentation of the elastic lamina, alternating with rings of fibrous and muscular hyperplasia within the media. Extra cranial vessels are involved more often than intracranial ones, and the cervical portion of the internal carotid is involved more than is the vertebral artery.
Multiple progressive intracranial arterial occlusions (moya-moya). This syndrome has two essential features: bilateral narrowing or occlusion of the distal internal carotid arteries and the adjacent anterior and middle cerebral artery trunks; and the presence of a fine network of collateral channels at the base of the brain. The term moya-moya derives from a Japanese word meaning smoke or haze, which characterizes the angiographic appearance of these fine collaterals.
C. Lacunar infarction of the brain results from the occlusion of small penetrating branches of the major cerebral arteries, especially those that supply the basal ganglia, thalamus, internal capsule, and pons. Lacunar infarcts are believed to be caused by degenerative changes in arterial walls (including lipohyalinosis
and fibrinoid necrosis) Both hypertension and diabetes appear to predispose to this type of stroke.
D. Cardiac disorders. Mural thrombus complicating myocardial infarction or cardiomyopathy is a recognized source of cerebral embolism. The incidence of focal cerebral ischemia is increased in patients with rheumatic heart disease – particularly those with mitral stenosis and atrial fibrillation – presumably as a result of embolization. Patients with prosthetic heart valves are also at particular risk for cerebral emboli. Atrial fibrillation and the bradycardia-tachycardia (sicksinus) syndrome are well-recognized causes of embolic stroke. Other cardiac arrhythmias are more likely to produce pan cerebral hypoperfusion with diffuse rather than focal symptoms (eg, syncope, dimming of vision, nonspecific lightheadedness, generalized seizures) unless severe carotid artery stenosis is also present.
Infective (bacterial or fungal) endocarditis is a cause of transient cerebral ischemia and embolic cerebral infarction during the active phase of infection and during the first few months following antibiotic cure. Intracerebral or sub- arachnoid hemorrhage can also occur as a result of bleeding into an infarct or rupture of a mycotic aneurysm. Nonbacterial (marantic) endocarditis is most frequent in patients with cancer and is responsible for the vast majority of ischemic strokes in this population.
Buckling of the mitral valve due to stretching of the mitral annulus (mitral valve prolapse) is common, occurring in 4-8% of young adults, and usually pro- duces no symptoms. However, in some cases it is associated with significant mitral regurgitation, infective endocarditis, cardiac arrhythmias, or cerebral ischemic events. Congenital cardiac anomalies associated with a pathologic communication between the right and left sides of the heart, such as atrial septal defect or patent foramen ovale, permit the passage of embolic material from the systemic venous circulation to the brain. Under these circumstances, venous thrombi can give rise to embolic stroke.
E. Hematological disorders. Polycythemia. In addition to nonspecific signs such as headache, dizziness, and blurred vision, patients may have focal neurological symptoms that often respond to venesection. Sickle cell (hemoglobin S) disease results from a single amino acid substitution (Glu-6-Val) in the hemoglobin beta locus on chromosome 11 (11p15.5) that results in an abnormal beta hemoglobin chain. The most frequent neurological complication is stroke, which characteristically affects the intracranial internal carotid or proximal mid- dle or anterior cerebral artery. Transient cerebral ischemia has been reported in association with leukocytosis, usually in patients with leukemia and white blood cell counts in excess of 150,000/µL.
Hypercoagulable states. Hyperviscosity of the serum from paraproteine- mia (especially macroglobulinemia) is an infrequent cause of focal cerebral ischemia. Stasis of blood in these conditions can lead to cerebral infarction or diffuse encephalopathy. Many conditions, such as estrogen therapy or the use of
oral contraceptives, postpartum and postoperative states, and cancer, are accom- panied by coagulation abnormalities. Patients with such coagulopathies may ex- hibit symptoms of cerebral thrombosis or embolism. Antiphospholipid antibo- dies, including lupus anticoagulants and anticardiolipin antibodies, may be asso- ciated with an increased incidence of ischemic stroke. Stroke has also been re- ported in patients with hereditary coagulopathies, including heparin cofactor II deficiency, protein C or S deficiency, antithrombin III deficiency, defective re- lease of plasminogen activator, and factor XII deficiency.
A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST) (Adams H.P. et al., 1993). The TOAST classification de- notes five subtypes of ischemic stroke: 1) large-artery atherosclerosis, 2) car- dioembolism, 3) small-vessel occlusion, 4) stroke of other determined etiology, and 5) stroke of undetermined etiology.
Pathogenesis
Normal cerebral perfusion is about 58 mL per 100 g brain tissue per minute. Signs and symptoms of ischemia begin to appear when perfusion falls below 22 mL per 100 g per min. In this stage of relative ischemia, the functional metabolism of the affected brain tissue is impaired, but the infarction threshold has not yet been reached and the tissue can regain its normal function as soon as the perfusion renormalizes. The longer relative ischemia lasts, however, the less likely it is that normal function will be regained. Total ischemia causes irrevers- ible structural damage of the affected region of the brain. The zone of tissue in which the local cerebral perfusion lies between the functional threshold and the infarction threshold is called the ischemic penumbra (“partial shadow”).
Interruption of blood flow to the brain deprives neurons and other cells of substrate glucose and oxygen and, unless blood flow is promptly restored, leads ultimately to cell death. The pattern of cell death depends on the severity of ischemia. With mild ischemia, as may occur in cardiac arrest with reperfusion, selective vulnerability of certain neuronal populations results in their preferen- tial loss. More severe ischemia produces selective neuronal necrosis, in which all neurons die but glia and endothelial cells are preserved. Complete, permanent ischemia causes pannecrosis, affecting all cell types, and results in the chronic cavitary brain lesions seen after clinical stroke.
Ischemic neuronal injury is an active biochemical process that evolves over time. Lack of glucose and oxygen depletes the cellular energy stores re- quired to maintain membrane potentials and transmembrane ion gradients. Po- tassium leaks out of cells, causing depolarization-induced calcium entry, and al- so stimulates the release of glutamate through glial glutamate transporters. Syn- aptic glutamate activates excitatory amino acid receptors coupled to calcium- and sodium-preferring ion channels. The resulting influx of sodium into postsy- naptic neuronal cell bodies and dendrites causes depolarization and acute swe l-
ling. Calcium influx that exceeds the ability of the cell to extrude, sequester, or buffer calcium activates calcium-dependent enzymes (proteases, lipases, and nucleases). These enzymes and their metabolic products, such as eicosanoids and oxygen free radicals, cause the breakdown of plasma membranes and cy- toskeletal elements, leading to cell death. This sequence of events has been termed excitotoxicity because of the pivotal role of excitatory amino acids such as glutamate.
Where ischemia is incomplete and therefore permits more prolonged cell survival – as in the border zone or penumbra surrounding the core of an ischem- ic brain region – other biochemical processes that regulate cell death may be set into motion. These include the expression of proteins involved in programmed cell death. The action of these proteins leads to apoptosis, a form of cell death that is distinct from necrosis, and is characterized by margination of nuclear chromatin, cleavage of DNA into fragments of defined length (nucleosomes), relative preservation of cell membrane integrity, blebbing of the plasma mem- brane to form apoptotic bodies, and phagocytosis without inflammation.
If the blood flow to ischemic brain tissue is restored before neurons are ir- reversibly injured, the clinical symptoms and signs are transient. Prolonged in- terruption of blood flow, however, leads to irreversible ischemic injury (infarc- tion) and persistent neurologic deficits. By definition, stroke produces neurolog- ic deficits that persist for at least 24 hours. When symptoms and signs resolve completely after briefer periods (usually within 30 minutes), the term transient ischemic attack (TIA) is used. Although TIAs do not themselves produce lasting neurologic dysfunction, they are important to recognize because about one third of patients with TIAs will go on to have a stroke within 5 years – and because this risk may be reduced with treatment. In some cases, deficits last for longer than 24 hours but resolve completely or almost completely within a few days; the term reversible ischemic neurological deficit (RIND) or minor stroke is sometimes used to describe these events. As their names imply, TIAs and RINDs are uniquely associated with cerebral ischemia, as opposed to hemorr- hage.
Two pathogenetic mechanisms can produce ischemic stroke – thrombosis and embolism. While about two – thirds of ischemic strokes are attributed to thrombosis and about one third to embolism, the distinction is often difficult or impossible to make on clinical grounds.
Thrombosis produces stroke by occluding large cerebral arteries (especial- ly the internal carotid, middle cerebral, or basilar), small penetrating arteries (as in lacunar stroke), cerebral veins, or venous sinuses. Symptoms typically evolve over minutes to hours. Thrombotic strokes are often preceded by TIAs, which tend to produce similar symptoms because they affect the same territory recur- rently.
Embolism produces stroke when cerebral arteries are occluded by the dis- tal passage of thrombus from the heart, aortic arch, or large cerebral arteries.
Emboli in the anterior cerebral circulation most often occlude the middle cere- bral artery or its branches, since about 85% of the hemispheric blood flow is car- ried by this vessel. .Emboli in the posterior cerebral circulation usually lodge at the apex of the basilar artery or in the posterior cerebral arteries. Embolic strokes characteristically produce neurologic deficits that are maximal at onset. When TIAs precede embolic strokes, especially those arising from a cardiac source, symptoms typically vary between attacks since different vascular territo- ries are affected.
Pathology
A. Infarction in Major-Cerebral-Artery Distribution. On gross inspection at autopsy, a recent infarct is a swollen, softened area of brain that usually af- fects both gray and white matter. Microscopy shows acute ischemic changes in neurons (shrinkage, microvacuolization, dark staining), destruction of glial cells, necrosis of small blood vessels, disruption of nerve axons and myelin, and ac- cumulation of interstitial fluid from vasogenic edema. In some cases, perivascu- lar hemorrhages are observed in the infarcted area.
Cerebral infarcts are typically associated with cerebral edema, which is maximal during the first 4 or 5 days after onset. Most deaths that occur within 1 week after massive cerebral infarction are attributable to cerebral edema, with swelling of the affected hemisphere causing herniation of the ipsilateral cingu- late gyrus across the midline beneath the free edge of the dural falx, followed by downward displacement of the brain through the tentorial incisure.
B. Lacunar Infarction. In contrast to infarcts associated with major cere- bral blood vessels, smaller lacunar infarcts result from lipohyalinosis of small resistance vessels, usually in patients with chronic hypertension. Lacunar in- farcts – often multiple – are found in about 10% of brains at autopsy. The patho- logic appearance is of small cavities ranging in size from 0.5 to 15 mm in di-
ameter.
Signs and symptoms of ischemic stroke
The neurological deficits produced by ischemic stroke depend on the area of the brain that is ischemic or infracted. The clinical manifestations of the ma- jor cerebrovascular syndromes and the typical deficits produced by ischemia in circumscribed areas of the brain are described below.
A. Anterior Cerebral Artery. The anterior cerebral artery supplies the pa- rasagittal cerebral cortex, which includes portions of motor and sensory cortex related to the contralateral leg and the so-called bladder inhibitory or micturition center. Anterior cerebral artery strokes are uncommon, perhaps because emboli from the extracranial vessels or the heart are more apt to enter the larger-caliber middle cerebral artery, which receives the bulk of cerebral blood flow. There is a contralateral paralysis and sensory loss affecting the leg. Voluntary control of
micturition may be impaired because of failure to inhibit reflex bladder contrac- tions, resulting in precipitate micturition.
B. Middle Cerebral Artery (MCA). The middle cerebral artery supplies most of the remainder of the cerebral hemisphere and deep subcortical struc- tures. The cortical branches of the middle cerebral artery include the superior division, which supplies the entire motor and sensory cortical representation of the face, hand, and arm; and the expressive language (Broca's) area of the left hemisphere. The inferior division supplies the visual radiations, the region of visual cortex related to macular vision, and the receptive language (Wernicke's) area of the left hemisphere. Lenticulostriate branches of the most proximal por- tion (stem) of the middle cerebral artery supply the basal ganglia as well as mo- tor fibers related to the face, hand, arm, and leg as they descend in the genu and the posterior limb of the internal capsule.
Depending on the site of involvement, several clinical syndromes can oc- cur. 1) Superior division stroke results in contralateral hemiparesis that affects the face, hand, and arm but spares the leg; contralateral hemisensory deficit in the same distribution; but no homonymous hemianopia. If the dominant hemis- phere is involved, these features are combined with Broca's (expressive) aphasia, which is characterized by impairment of language expression with intact com- prehension. 2) Inferior division stroke is less common in isolation and results in contralateral homonymous hemianopia that may be denser inferiorly; marked impairment of cortical sensory functions, such as graphesthesia and stereognosis on the contralateral side of the body; and disorders of spatial thought, including a lack of awareness that a deficit exists (anosognosia), neglect of and failure to recognize the contralateral limbs, neglect of the contralateral side of external space, dressing apraxia, and constructional apraxia. If the left hemisphere is in- volved, Wernicke's (receptive) aphasia occurs and is manifested by impaired comprehension and fluent but often nonsensical speech. With involvement of the right hemisphere, an acute confusional state may occur. 3) Occlusion at the bifurcation or trifurcation of MCA involves a lesion situated at the point where the artery splits into two (superior and inferior) or three (superior, middle, and inferior) major divisions. This severe stroke syndrome combines the features of superior and inferior division stroke. Its clinical features include contralateral hemiparesis and hemisensory deficit involving the face and arm far more than the leg; homonymous hemianopia; and, if the dominant hemisphere is affected, global (combined expressive and receptive) aphasia. 4) Occlusion of the stem of the middle cerebral artery occurs proximal to the origin of the lenticulostriate branches. Since the entire territory of the artery is affected, this is the most de- vastating of middle cerebral artery strokes. The resulting clinical syndrome is similar to that seen following occlusion at the trifurcation except that, in addi- tion, infarction of motor fibers in the internal capsule causes paralysis of the contralateral leg. The result is a contralateral hemiplegia and sensory loss affect- ing the face, hand, arm, and leg.
C. Internal Carotid Artery. The internal carotid artery arises where the common carotid artery divides into internal and external carotid branches in the neck. In addition to its anterior cerebral and middle cerebral branches discussed above, the internal carotid artery also gives rise to the ophthalmic artery, which supplies the retina. The severity of internal carotid artery strokes is highly varia- ble, depending on the adequacy of collateral circulation, which tends to develop in compensation for a slowly evolving occlusion. Intra- or extracranial internal carotid artery occlusion is responsible for about one-fifth of ischemic strokes. In approximately 15% of cases, progressive atherosclerotic occlusion of the inter- nal carotid artery is preceded by premonitory TIAs or by transient monocular blindness caused by ipsilateral retinal artery ischemia. Carotid artery occlusion may be asymptomatic. Symptomatic occlusion results in a syndrome similar to that of middle cerebral artery stroke (contralateral hemiplegia, hemisensory def- icit, and homonymous hemianopia; aphasia is also present with the left hemis- phere involvement).
D. Posterior Cerebral Artery. The paired posterior cerebral arteries arise from the tip of the basilar artery and supply the occipital cerebral cortex, medial temporal lobes, thalamus, and rostral midbrain. Emboli carried up the basilar ar- tery tend to lodge at its apex, where they can occlude one or both posterior cere- bral arteries. These emboli can subsequently break up and produce signs of asymmetric or patchy posterior cerebral artery infarction. Occlusion of a post- erior cerebral artery produces homonymous hemianopia affecting the contrala- teral visual field. Macular vision may be spared, however, because of the dual (middle and posterior cerebral artery) blood supply to the portion of the visual cortex representing the macula. In contrast to visual field defects from infarction in the middle cerebral artery territory, those caused by posterior cerebral artery occlusion may be denser superiorly. With occlusions near the origin of the post- erior cerebral artery at the level of the midbrain, ocular abnormalities can in- clude vertical gaze palsy, oculomotor (III) nerve palsy, internuclear ophthalmop- legia, and vertical skew deviation of the eyes. When posterior cerebral artery oc- clusion affects the occipital lobe of the dominant (usually left) hemisphere, pa- tients may exhibit anomic aphasia (difficulty in naming objects), alexia without agraphia (inability to read, with no impairment of writing), or visual agnosia. The last is a failure to identify objects presented in the left side of the visual field, caused by a lesion of the corpus callosum that disconnects the right visual cortex from language areas of the left hemisphere. Bilateral posterior cerebral artery infarction may result in cortical blindness, memory impairment (from temporal lobe involvement), or the inability to recognize familiar faces (proso- pagnosia), as well as a variety of exotic visual and behavioral syndromes.
E. Basilar Artery. The basilar artery usually arises from the junction of the paired vertebral arteries, though in some cases only a single vertebral artery is present. The basilar artery courses over the ventral surface of the brainstem to terminate at the level of the midbrain, where it bifurcates to form the posterior
cerebral arteries (see above). Branches of the basilar artery supply the occipital and medial temporal lobes, the medial thalamus, the posterior limb of the inter- nal capsule, and the entire brainstem and cerebellum.
Thrombotic occlusion of the basilar artery – a serious event that is often incompatible with survival – produces bilateral neurologic signs referable to in- volvement of multiple branch arteries. Occlusion of both vertebral arteries or of alone unpaired vertebral artery produces a similar syndrome. Basilar thrombosis usually affects the proximal portion of the basilar artery, which supplies the pons. Involvement of the dorsal portion (tegmentum) of the pons produces unila- teral or bilateral abducens (VI) nerve palsy; horizontal eye movements are im- paired, but vertical nystagmus and ocular bobbing may be present. The pupils are constricted as a result of the involvement of descending sympathetic pupil- lodilator fibers in the pons, but they may remain reactive. Hemiplegia or qua- driplegia is usually present, and coma is common. Although the syndrome of ba- silar occlusion in unconscious patients may be confused with pontine hemorr- hage, a CT or MRI brain scan will differentiate the two. In some patients with basilar occlusion, the ventral portion of the pons (basis pontis) is infarcted and the tegmentum is spared. Such patients remain conscious but quadriplegic. The term locked-in syndrome has been applied to this state. Locked-in patients may be able to signify that they are conscious by opening their eyes or moving their eyes vertically on command. In other cases, a conventional EEG with stimula- tion may be needed to distinguish the locked-in state (in which the EEG is nor- mal) from coma.
Emboli small enough to pass through the vertebral arteries into the larger basilar artery are usually arrested at the top of the basilar artery, where it bifur- cates into the posterior cerebral arteries. The resulting reduction in blood flow to the ascending reticular formation of the midbrain and thalamus produces imme- diate loss or impairment of consciousness. Unilateral or bilateral oculomotor (III) nerve palsies are characteristic. Hemiplegia or quadriplegia with decere- brate or decorticate posturing occurs because of the involvement of the cerebral peduncles in the midbrain. Thus, the top of the basilar syndrome may be con- fused with midbrain failure caused by transtentorial uncal herniation. Less commonly, an embolus may lodge more proximally in an atheromatous nar- rowed portion of the basilar artery, producing a syndrome indistinguishable from basilar thrombosis. Smaller emboli may occlude the rostral basilar artery transiently before fragmenting and passing into one or both posterior cerebral arteries. In such cases, portions of the midbrain, thalamus, and temporal and oc- cipital lobes can be infarcted. If conscious, these patients display a variety of visual (homonymous hemianopia, cortical blindness), visuomotor (impaired convergence, paralysis of upward or downward gaze, diplopia), and behavioral (especially confusion) abnormalities without prominent motor dysfunction. Sluggish pupillary responses are a helpful sign of midbrain involvement.
F. Long circumferential vertebrobasilar branches: the posterior inferior cerebellar, the anterior inferior cerebellar, and the superior cerebellar arteries. These vessels supply the dorsolateral brainstem, including dorsolaterally si- tuated cranial nerve nuclei (V, VII, VIII) and pathways entering and leaving the cerebellum in the cerebellar peduncles. 1) Posterior inferior cerebellar artery oc- clusion results in the lateral medullary (Wallenberg's) syndrome. This syndrome varies in its presentation with the extent of infarction, but it can include ipsila- teral cerebellar ataxia, Homer's syndrome, and facial sensory deficit; contrala- teral impaired pain and temperature sensation; and nystagmus, vertigo, nausea, vomiting, dysphagia, dysarthria, and hiccup. The motor system is characteristi- cally spared because of its ventral location in the brain stem. 2) Anterior inferior cerebellar artery occlusion leads to infarction of the lateral portion of the caudal pons and produces a syndrome with many of the same features. Homer's syn- drome, dysphagia, dysarthria, and hiccup do not occur, however, but ipsilateral facial weakness, gaze palsy, deafness, and tinnitus are common findings. 3) The syndrome of lateral rostral pontine infarction from superior cerebellar artery oc- clusion resembles that associated with anterior inferior cerebellar artery lesions, but impaired optokinetic nystagmus or skew deviation of the eyes may occur. Auditory function is unaffected, and the contralateral sensory disturbance may involve touch, vibration, and position sense as well as pain and temperature
sense.
G. Long Penetrating Paramedian Vertebrobasilar Branches supply the medial brainstem from its ventral surface to the floor of the fourth ventricle. Structures located in this region include the medial portion of the cerebral pe- duncle, sensory pathways, the red nucleus, the reticular formation, and the mid- line cranial nerve nuclei (III, IV, VI, XII). Occlusion of a long penetrating artery causes paramedian infarction of the brainstem and results in contralateral hemi- paresis if the cerebral peduncle is affected. Associated cranial nerve involve- ment depends on the level of the brainstem at which occlusion occurs. Occlusion in the midbrain results in ipsilateral third nerve palsy, which may be associated with contralateral tremor or ataxia from involvement of pathways connecting the red nucleus and cerebellum (Benedikt syndrome). Ipsilateral 6th and 7th nerve palsies are seen in the pons, and 12th nerve involvement can occur in the medul- la. If the lesion appears patchy or involves both sides of the brainstem (as mani- fested by coma or quadriparesis), the differential diagnosis includes occlusion of a main trunk vessel (both vertebral arteries or the basilar artery); intramedullary lesions such as hemorrhage, pontine glioma, or multiple sclerosis; and compres- sion of the brainstem by a cerebellar mass (hemorrhage, infarct, or tumor).
H. Short Basal Vertebrobasilar Branches. Short branches arising from the long circumferential arteries (discussed above) penetrate the ventral brainstem to supply the brainstem motor pathways. Clinical syndrome of basal brainstem in- farction. The most striking finding is contralateral hemiparesis caused by corti- cospinal tract involvement in the cerebral peduncle or basis pontis. Cranial
nerves (eg, III, VI, VII) that emerge from the ventral surface of the brainstem may be affected as well, giving rise to ipsilateral cranial nerve palsies.
Lacunar Infarctions
Small penetrating arteries located deep in the brain may become occluded as a result of changes in the vessel wall induced by chronic hypertension. The resulting lacunar infarcts are most common in deep nuclei of the brain (putamen, 37%; thalamus, 14%; caudate nucleus, 10%), the pons (16%), and the posterior limb of the internal capsule (10%). They occur in lesser numbers in the deep ce- rebral white matter, the anterior limb of the internal capsule, and the cerebellum. Because of their small size and their frequent location in relatively silent areas of the brain, many lacunar infarctions are not recognized clinically. In as many as three-fourths of autopsy-proved cases, there is no history of stroke or clear evidence of neurologic deficit on antemortem examinations.
In many cases, the isolated nature of the neurologic deficit makes the clin- ical picture of lacunar infarction distinctive. The onset of lacunar stroke may be gradual, developing over several hours or days. Headache is absent or minor, and the level of consciousness is unchanged.
Recognition of lacunar stroke syndromes is important because the progno- sis for complete or nearly complete recovery is good. In addition, the likelihood of future lacunar strokes can be reduced by treating the hypertension that is usually associated with and causally related to them. Because the arteries in- volved are small, angiography is normal (for that reason, it is not required). The CSF is also normal, and it is possible that a CT brain scan or MRI will not dis- close the lesion. CT scanning or MRI should be performed to exclude other causes of stroke, however. Anticoagulation is not indicated since there is no evi- dence that it confers any benefit in this context. Aspirin is also of uncertain ben- efit, but it is often given because of the low risk of serious complications. Al- though a wide variety of deficits can be produced, there are four classic and dis- tinctive lacunar syndromes.
1. Pure motor hemiparesis. This consists of hemiparesis affecting the face, arm, and leg to a roughly equal extent, without an associated disturbance of sen- sation, vision, or language. When lacunar in origin, it is usually due to a lesion in the contralateral internal capsule or pons. Pure motor hemiparesis may also be caused by internal carotid or middle cerebral artery occlusion, subdural hema- toma, or intracerebral mass lesions.
2. Pure sensory stroke. This is characterized by hemisensory loss, which may be associated with paresthesia, and results from lacunar infarction in the contralateral thalamus. It may be mimicked by occlusion of the posterior cere- bral artery or by a small hemorrhage in the thalamus or midbrain.
3. Ataxic hemiparesis. In this syndrome (sometimes called ipsilateral atax- ia and crural (leg) paresis), pure motor hemiparesis is combined with ataxia of the hemiparetic side and usually predominantly affects the leg. Symptoms result
from a lesion in the contralateral pons, internal capsule, or subcortical white
matter.
4. Dysarthria – clumsy hand syndrome. This consists of dysarthria, facial weakness, dysphagia, and mild weakness and clumsiness of the hand on the side of facial involvement. When the syndrome is caused by a lacunar infarct, the le- sion is in the contralateral pons or internal capsule. Infarcts or small intracere- bral hemorrhages at a variety of locations can produce a similar syndrome, how- ever. In contrast to the lacunar syndromes described above, premonitory TIAs are unusual.
Clinical Findings
A. History. In patients with cerebrovascular disorders, possible risk fac- tors such as TIAs, hypertension, and diabetes should be sought. In women, the use of oral contraceptives has been associated with cerebral arterial and venous occlusive disease, especially in the presence of hypertension and cigarette smok- ing. The presence of such medical conditions as ischemic or valvular heart dis- ease or cardiac arrhythmias must also be ascertained. A variety of systemic dis- orders involving the blood or blood vessels also increase the risk of stroke. An- tihypertensive drugs can precipitate cerebrovascular symptoms if the blood pres- sure is lowered excessively in patients with nearly total cerebrovascular occlu- sion and poor collateral circulation.
B. General physical examination. The general physical examination of a patient with a cerebrovascular disorder should focus on searching for an under- lying systemic cause, especially a treatable one. 1) The blood pressure should be measured to ascertain whether hypertension – a known risk factor for stroke – is present. 2) Comparison of blood pressure and pulse on the two sides can reveal differences related to atherosclerotic disease of the aortic arch or coarctation of the aorta. 3) Ophthalmoscopic examination of the retina can provide evidence of embolization in the anterior circulation in the form of visible embolic material in retinal blood vessels. 4) Examination of the neck may reveal the absence of ca- rotid pulses or the presence of carotid bruits. Reduced carotid artery pulsation in the neck is a poor indicator of internal carotid artery disease, however. Although carotid bruits have been associated with cerebrovascular disease, significant ca- rotid stenosis can occur without an audible bruit; conversely, a loud bruit can occur without stenosis. 5) A careful cardiac examination is essential in order to detect arrhythmias or murmurs related to valvular disease, either of which may predispose to embolization from heart to brain. 6) Palpation of the temporal arte- ries is useful in the diagnosis of giant cell arteritis, in which these vessels may be tender, nodular, or pulseless.
C. Neurologic examination. Patients with cerebrovascular disorders mayor may not have abnormal neurologic findings on examination. A normal examination is expected, for example, after a TIA has resolved. Where deficits are found, the goal of the neurologic examination is to define the anatomic site
of the lesion, which may suggest the cause or optimal management of the stroke. Thus, clear evidence that the anterior circulation is involved may lead to angio- graphic evaluation in contemplation of possible surgical correction of an internal carotid lesion. Establishing that the symptoms are referable to the vertebrobasi- lar circulation or to a lacunar infarction is likely to dictate a different course of action. 1) Cognitive deficits that indicate cortical lesions in the anterior circula- tion should be sought. For example, if aphasia is present, the underlying disorder cannot be in the posterior circulation and is unlikely to represent lacunar infarc- tion. The same is true for the right hemisphere lesions producing parietal lobe syndromes such as unilateral neglect or constructional apraxia (see discussion of inferior division middle cerebral artery stroke, above). 2) The presence of visual field abnormalities similarly excludes lacunar infarction. Hemianopia may oc- cur, however, with involvement of either the anterior or posterior cerebral arte- ries. Isolated hemianopia suggests posterior cerebral artery infarction. 3) Ocular palsies, nystagmus, or internuclear ophthalmoplegia assign the underlying lesion to the brainstem and thus to the posterior circulation. 4) Hemiparesis can be due to lesions in cerebral cortical regions supplied by the anterior circulation, des- cending motor pathways in the brainstem supplied by the vertebrobasilar sys- tem, or lacunae at subcortical (corona radiata, internal capsule) or brainstem sites. However, hemiparesis affecting the face, hand, and arm more than the leg is characteristic of lesions within the distribution of the middle cerebral artery. Hemiparesis that is nonselective with respect to the face, arm, and leg is consis- tent with occlusion of the internal carotid artery or the stem of the middle cere- bral artery, lacunar infarction in the internal capsule or basal ganglia, or brains- tem disease. A crossed hemiparesis – ie, one that involves the face on one side and the rest of the body on the other – means that the abnormality must lie be- tween the level of the facial nerve nucleus in the pons and the decussation of the pyramids in the medulla. 5) Cortical sensory deficits such as astereognosis and agraphesthesia with preserved primary sensory modalities imply a cerebral cor- tical deficit within the territory of the middle cerebral artery. Isolated hemisen- sory deficits without associated motor involvement are usually lacunar in origin. Crossed sensory deficits result from brainstem lesions in the medulla, as seen in the lateral medullary plate syndrome. 6) Hemiataxia usually points to a lesion in the ipsilateral brainstem or cerebellum but can also be produced by lacunae in the internal capsule.
Investigative Studies
A. Blood Tests. These should be obtained routinely to detect treatable causes of stroke and to exclude conditions that can mimic stroke. 1) Complete blood count to investigate such possible causes of stroke as thrombocytosis, thrombocytopenia, polycythemia, anemia (including sickle cell disease), and leukocytosis (eg, leukemia). 2) Erythrocyte sedimentation rate to detect eleva- tions indicative of giant cell arteritis or other vasculitides. 3) Serologic assay for
syphilis – treponemal assay in blood, such as the FTA-ABS or MHA-TP, or the CSF VDRL test. 4) Serum glucose to document hypoglycemia or hyperosmolar nonketotic hyperglycemia, which can present with focal neurologic signs and thereby masquerade as stroke. 5) Serum cholesterol and lipids to detect eleva- tions that can represent risk factors for stroke.
B. ECG. An ECG should be obtained routinely to detect unrecognized myocardial infarction or cardiac arrythmias, such as atrial fibrillation, which predispose to embolic stroke.
C. CT Scan or MRI. A CT scan or MRI should be obtained routinely to distinguish between infarction and hemorrhage as the cause of stroke, to exclude other lesions (eg, tumor, abscess) that can mimic stroke, and to localize the le- sion. CT is usually preferred for initial diagnosis because it is widely available and rapid and can readily make the critical distinction between ischemia and hemorrhage. MRI may be superior to CT scan for demonstrating early ischemic infarcts (DW imaging), showing ischemic strokes in the brainstem or cerebel- lum, and detecting thrombotic occlusion of venous sinuses.
D. Lumbar Puncture. This should be performed in selected cases to ex- clude subarachnoid hemorrhage (manifested by xanthochromia and red blood cells) or to document meningovascular syphilis (reactive VDRL) as the cause of stroke.
E. Cerebral Angiography. Inta-arterial angiography is used to identify operable extracranial carotid lesions in patients with anterior circulation TIAs who are good surgical candidates. It is also useful in the diagnosis of certain vascular disorders associated with stroke, including vasculitis, fibromuscular dysplasia, and carotid or vertebral artery dissection. Transfemoral arch aortogra- phy (digital subtraction angiography) with selective catheterization of the caro- tid (and,if indicated, vertebral) arteries is the procedure of choice. MR- or CT- angiography may detect stenosis of large cerebral arteries, aneurysms, and other vascular lesions, but their sensitivity is generally inferior to that of conventional angiography.
F. Ultrasonography. Doppler ultrasonography can detect stenosis or oc- clusion of the internal carotid artery, but it lacks the sensitivity of angiography. In cases where the likelihood of finding operable symptomatic carotid stenosis is insufficient to justify the risk of angiography or where the risk is especially high because of coexisting illness or the lack of angiographic expertise, the finding of normal carotid blood flow or complete occlusion by Doppler studies can obviate the need for angiography. Transcranial doppler ultrasonography is sometimes used in the evaluation of suspected stenosis of the intracranial internal carotid artery, middle cerebral artery, or basilar artery and for detecting and following the course of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
G. Echocardiography. Echocardiography may be useful for demonstrating the cardiac lesions responsible for embolic stroke in patients' with clinically evi- dent cardiac disease, such as atrial fibrillation.
H. EEG. The EEG is rarely useful in evaluating stroke. It may, however, help differentiate between a seizure disorder and TIAs or between lacunar and cortical infarcts in the occasional patient in whom these possibilities cannot oth- erwise be distinguished.
Differential Diagnosis
In patients presenting with focal central nervous system dysfunction of sudden onset, ischemic stroke must be distinguished from structural and meta- bolic processes that can mimic it. An underlying process other than focal cere- bral ischemia should be suspected when the resulting neurologic deficit does not conform to the distribution of any single cerebral artery. In addition, strokes do not typically impair consciousness in the absence of profound focal deficits, while other cerebral disorders may do so.
Vascular disorders mistaken for ischemic stroke include intracerebral he- morrhage, subdural or epidural hematoma, and subarachnoid hemorrhage from rupture of an aneurysm or vascular malformation. These conditions can often be distinguished by a history of trauma or of excruciating headache at onset, a more marked depression of consciousness, or by the presence of neck stiffness on ex- amination. They can be excluded by CT scan or MRI.
Other structural brain lesions such as tumor or abscess can also produce focal cerebral symptoms of acute onset. Brain abscess is suggested by concur- rent fever, and both abscess and tumor can usually be diagnosed by CT scan or MRI. Metabolic disturbances, particularly hypoglycemia and hyperosmolar nonketotic hyperglycemia, may present in strokelike fashion. The serum glucose level should therefore be determined in all patients with apparent stroke.
Treatment
A. General stroke treatment. All acute stroke patients require specialist multidisciplinary care delivered in a stroke unit, and selected patients will re- quire additional high-technology interventions. There is consensus that the man- agement of general medical problems is the basis for stroke treatment. General treatment includes respiratory and cardiac care, fluid and metabolic manage- ment, BP control, the prevention and treatment of conditions such as seizures, venous thromboembolism, dysphagia, aspiration pneumonia, other infections, or pressure ulceration, and occasionally management of elevated intracranial pres- sure. Although hypertension contributes to the pathogenesis of stroke and many patients with acute stroke have elevated blood pressures, attempts to reduce the blood pressure in stroke patients can have disastrous results, since the blood supply to ischemic but as yet uninfarcted brain tissue may be further compro- mised. Therefore, such attempts should not be made. In the usual course of events, the blood pressure declines spontaneously over a period of hours to a few days. However, many aspects of general stroke treatment have not been adequately assessed in randomized clinical trials (RCTs).
B. Specific stroke treatment.
1) Thrombolysis. Tissue plasminogen activator (t-PA) is a serine protease that maps to chromosome 8 (8p12) in humans and catalyzes the conversion of plasminogen to plasmin. This accounts for its ability to lyse fibrin-containing clots such as those found in cerebrovascular thrombotic lesions. Some but not all controlled clinical data suggest that the intravenous administration of recombi- nant t-PA (rt-PA) within 3 hours of the onset of symptoms reduces disability and mortality from ischemic stroke. The drug is administered at a dose of 0.9 mg/kg, up to a maximum total dose of 90 mg; 10% of the dose is given as an intraven- ous bolus and the remainder as a continuous intravenous infusion over 60 mi-
nutes.
The major complication of rt-PA treatment is hemorrhage, which may af- fect the brain or other tissues. It is important that the time of onset of symptoms can be established with confidence. The CT scan should not already show evi- dence of a large ischemic stroke or of hemorrhage. Patients whose coagulation function has been compromised by the administration of warfarin or heparin or by thrombocytopenia (platelet count <100,000/mm3) should not receive rt-PA, nor should those who are at increased risk of hemorrhage because of seizures at the onset of symptoms, prior intracranial hemorrhage, another intracranial dis- order (including stroke or trauma) within 3 months, a major surgical procedure within 14 days, bleeding from the gastrointestinal or urinary tract within 21 days, or marked hypertension (systolic blood pressure >185 mm Hg or diastolic blood pressure >110 mm Hg). To avoid treating TIAs that are already resolving or other conditions unlikely to respond to rt-PA, or for which the risk exceeds likely benefit, patients whose deficits are improving rapidly and spontaneously, patients with mild and isolated deficits, and those with blood glucose concentra- tions consistent with a hypo- or hypergycemic origin of symptoms <50 mg/dl or >400 mg/dl) should be excluded. Patients receiving rt-PA for stroke should be managed in facilities where the capacity exists to diagnose stroke with a high degree of certainty and to manage bleeding complications. Within the first 24 hours after administration of rt-PA, anticoagulants and antiplatelet agents should not be given, blood pressure should be carefully monitored, and arterial puncture and placement of central venous lines, bladder catheters, and nasogastric tubes should be avoided.
2) Antiplatelet agents interfere with platelet function by irreversibly inhi- biting the enzyme cyclooxygenase, which catalyzes the synthesis of thrombox- ane A2 an eicosanoid with procoagulant and platelet-aggregating properties. Some but not all studies have shown a decrease in the incidence of subsequent stroke when aspirin is administered chronically following a stroke. It is recom- mended that aspirin (160–325 mg loading dose) be given within 48 h after ischemic stroke. The use of other antiplatelet agents (single or combined) is not recommended in the setting of acute ischemic stroke.
3) Anticoagulation. Anticoagulation has not been shown to be useful in most cases of completed stroke. Improvements in outcome or reductions in stroke recurrence rates were mostly counterbalanced by an increased number of hemorrhagic complications. Early administration of unfractionated heparin, low molecular weightheparin or heparinoids is not recommended for the treatment of patients with acute ischemic stroke. Despite this lack of evidence, some ex- perts recommend full-dose heparin in selected patients, such as those with car- diac sources of embolism with high risk of re-embolism, arterial dissection or high-grade arterial stenosis prior to surgery. Contraindications for heparin treat- ment include large infarcts (e.g. more than 50% of MCA territory), uncontrolla- ble arterial hypertension and advanced microvascular changes in the brain.
4) Surgery. The indications for surgical treatment of completed stroke are extremely limited. When patients deteriorate as a consequence of brainstem compression following cerebellar infarction, however, posterior fossa decom- pression with evacuation of infarcted cerebellar tissue can be lifesaving. In pa- tients up to 60 years of age with evolving malignant MCA infarcts is recom- mended surgical decompressive therapy within 48 h after symptom onset.
5) Antiedema agents. Antiedema agents such as mannitol and corticoste- roids have not been shown to be of benefit for cytotoxic edema (cellular swel- ling) associated with cerebral infarction.
6) Neuroprotective agents. A variety of drugs with diverse pharmacologic actions have been proposed as neuroprotective agents that might reduce ischem- ic brain injury by decreasing cerebral metabolism or interfering with the cyto- toxic mechanisms triggered by ischemia. These include barbiturates and the opioid antagonist naloxone, neither of which appears to be beneficial in stroke. Drugs that block voltage-gated or excitatory amino acid receptor-gated calcium channels have potential value in the treatment of stroke because cellular calcium overload may be an important mediator of irreversible ischemic neuronal injury. Clinical trials with these and related agents have yielded disappointing results thus far, however. Currently, there is no recommendation to treat ischemic stroke patients with neuroprotective substances.
Prognosis
Outcome following stroke is influenced by a number of factors, the most important being the nature and severity of the resulting neurologic deficit. The patient's age, the cause of stroke, and coexisting medical disorders also affect prognosis. Overall, somewhat less than 80% of patients with stroke survive for at least 1 month, and 10-year survival rates in the neighborhood of 35% have been cited. The latter figure is not surprising, considering the advanced age at which stroke commonly occurs. Of patients who survive the acute period, about one-half to two-thirds regain independent function, while approximately 15% require institutional care.
INTRACEREBRAL HEMORRHAGE
Nontraumatic intracerebral hemorrhage is bleeding into the parenchyma of the brain that may extend into the ventricles and, in rare cases, the subarach- noid space. Depending on the underlying cause of bleeding, intracerebral he- morrhage (ICH) is classified as either primary or secondary. Primary intracere- bral hemorrhage, accounting for 78 to 88 percent of cases, originates from the spontaneous rupture of small vessels damaged by chronic hypertension or amy- loid angiopathy. Secondary ICH occurs in a minority of patients in association with vascular abnormalities (such as arteriovenous malformations and aneu- rysms), tumors, or impaired coagulation.
Pathogenesis
Autoregulation of cerebral blood flow, which is achieved by changes in the caliber of small resistance cerebral arteries, maintains constant cerebral blood flow as systemic blood pressure rises and falls. The range of autoregulated blood pressures is variable. In normotensive individuals, the lowest mean blood pressure at which autoregulation is effective is approximately 60 mm Hg. Below this level, changes in the caliber of cerebral arteries cannot compensate for de- creased perfusion pressure; cerebral blood flow therefore declines, producing symptoms of hypoxia, such as lightheadedness, confusion, and dimming of vi- sion. These symptoms are followed by somnolence and loss of consciousness if the mean blood pressure falls below 35-40 mm Hg. In contrast, at blood pres- sures above the upper limit of the range of autoregulation (150-200 mm Hg), ce- rebral blood flow is increased, which can produce hypertensive encephalopathy.
In chronically hypertensive individuals, the lower limit of the autoregula- tory range is higher, which may be due to damage to small arterial walls. As a result, cerebral blood flow declines when the mean arterial blood pressure falls below about 120 mm Hg. The clinical relevance of this observation is that blood pressure should be reduced rarely, if ever – and never to hypotensive levels – in patients with stroke.
Chronic hypertension appears to promote structural changes in the walls of penetrating arteries, predisposing them to ICH. In 1888, Charcot and Bou- chard found minute aneurysms on the small intraparenchymal arteries of hyper- tensive patients (Fig. 16a1) and postulated that aneurysmal rupture led to intra- cerebral hemorrhage. Subsequently, Ross Russell showed micro aneurysms of small resistance arteries in cerebral sites at which hypertensive hemorrhages oc- cur most commonly. Some aneurysms were surrounded by small areas of he- morrhage, and the aneurysmal walls often showed changes of lipohyalinosis or fibrinoid necrosis. These processes are characterized by destruction of the vessel wall with deposition of fibrinoid material, focal aneurysmal expansion of the in- volved vessel, thrombotic occlusion, and extravasation of red cells. There is now
general agreement that massive cerebral hemorrhage often follows the rupture of either a microaneurysmal or lipohyalinotic segment of a small resistance artery and that the underlying lesion is caused by chronic hypertension. Acute eleva- tion of blood pressure may also be the immediate precipitating cause of intrace- rebral hemorrhage in chronically hypertensive patients with Charcot-Bouchard aneurysms.
Most hypertensive hemorrhages originate in certain areas of predilection (Fig. 16b), corresponding to long, narrow, penetrating arterial branches along which Charcot-Bouchard aneurysms are found at autopsy. These include : A) some white matter branches of the cerebral arteries (10%), especially in the pa- rieto-occipital and temporal lobes; B) the caudate and putaminal branches of the middle cerebral arteries (42%); C) thalamic branches of the posterior cerebral arteries (15%); D) branches of the basilar artery supplying the pons (16%); E) branches of the superior cerebellar arteries supplying the dentate nuclei and the deep white matter of the cerebellum (12%).
Cerebral amyloid (congophilic) angiopathy is another cause of ICH. Amy- loid deposits are present in the walls of small cortical blood vessels and in the meninges (Fig. 16a2). The disorder is most common in elderly patients (a mean age of 70 years) and typically produces lobar hemorrhages at multiple sites. Some cases are familial.
Clinical Findings
Hypertensive hemorrhage occurs without warning, most commonly while the patient is awake. Headache is present in 50% of patients and may be severe; vomiting is common. Blood pressure is elevated after the hemorrhage has oc- curred. Thus, normal or low blood pressure in a patient with stroke makes the diagnosis of hypertensive hemorrhage unlikely. Following the hemorrhage, edema surrounding the area of hemorrhage produces clinical worsening over a period of minutes to days. The duration of active bleeding, however, is brief. Once the deficit stabilizes, improvement occurs slowly. Since the deficit is caused principally by hemorrhage and edema, which compress rather than de- stroy brain tissue, considerable return of neurologic function can occur. Massive hypertensive hemorrhages may rupture through brain tissue into the ventricles, producing bloody CSF; direct rupture through the cortical mantle is unusual. A fatal outcome is most often due to herniation caused by the combined mass ef- fect of the hematoma and the surrounding edema. Clinical features vary with the site of hemorrhage.
1. Deep cerebral hemorrhage. The two most common sites of hypertensive hemorrhage are the putamen and the thalamus, which are separated by the post- erior limb of the internal capsule. This segment of the internal capsule is tra- versed by descending motor fibers and ascending sensory fibers, including the optic radiations. Pressure on these fibers from an expanding lateral (putaminal) or medial (thalamic) hematoma produces a contralateral sensorimotor deficit. In
general, putaminal hemorrhage leads to a more severe motor deficit and thalam- ic hemorrhage to a more marked sensory disturbance. Homonymous hemianopia may occur as a transient phenomenon after thalamic hemorrhage and is often a persistent finding in putaminal hemorrhage. In large thalamic hemorrhages, the eyes may deviate downward, as in staring at the tip of the nose, because of im- pingement on the midbrain center for upward gaze. Aphasia may occur if he- morrhage at either site exerts pressure on the cortical language areas. A separate aphasic syndrome has been described with localized hemorrhage into the thala- mus; it carries an excellent prognosis for full recovery.
2. Lobar hemorrhage. Hypertensive hemorrhages also occur in subcortical white matter underlying the frontal, parietal, temporal, and occipital lobes. Symptoms and signs vary according to the location; they can include headache, vomiting, hemiparesis, hemisensory deficits, aphasia, and visual field abnor- malities. Seizures are more frequent than with hemorrhages in other locations, while coma is less so.
3. Pontine hemorrhage. With bleeding into the pons, coma occurs within seconds to minutes and usually leads to death within 48 hours. Ocular findings typically include pinpoint pupils. Horizontal eye movements are absent or im- paired, but vertical eye movements may be preserved. In some patients, there may be ocular bobbing, a bilateral downbeating excursion of the eyes at about 5- second intervals. Patients are commonly quadriparetic and exhibit decerebrate posturing. Hyperthermia is sometimes present. The hemorrhage usually ruptures into the fourth ventricle, and rostral extension of the hemorrhage into the mid- brain with resultant midposition fixed pupils is common. In contrast to the clas- sic presentation of pontine hemorrhage described above, small hemorrhages that spare the reticular activating system – and that are associated with less severe deficits and excellent recovery – also occur.
4. Cerebellar hemorrhage. The distinctive symptoms of cerebellar he- morrhage (headache, dizziness, vomiting, and the inability to stand or walk) be- gin suddenly, within minutes after onset of bleeding. While patients may initial- ly be alert or only mildly confused, large hemorrhages lead to coma within 12 hours in 75% of patients and within 24 hours in 90%. When coma is present at the onset, the clinical picture is indistinguishable from that of pontine hemorr- hage.
Common ocular findings include impairment of gaze to the side of the le- sion or forced deviation away from the lesion caused by pressure on the pontine lateral gaze center. Skew deviation may also occur, in which case the eye ipsila- teral to the lesion is depressed. The pupils are small and reactive. Ipsilateralfa- cial weakness of lower motor neuron type occurs in about 50% of cases, but strength in the limbs is normal. Limb ataxia is usually slight or absent. Plantar responses are flexor early in the course but become extensor as the brainstem becomes compromised and the patient deteriorates. Impairment of voluntary or reflex upward gaze indicates upward transtentorial herniation of the cerebellar
vermis and midbrain, leading to compression of the pretectum. It implies a poor prognosis.
Differential Diagnosis
Putaminal, thalamic, and lobar hypertensive hemorrhages may be difficult to distinguish from cerebral infarctions. To some extent, the presence of severe headache, nausea and vomiting, and impairment of consciousness are useful clues that a hemorrhage may have occurred; the CT scan identifies the underly- ing disorder definitively.
Brainstem stroke or cerebellar infarction can mimic cerebellar hemorr- hage. When cerebellar hemorrhage is a possibility, CT scan or MRI is the most useful diagnostic procedure, since hematomas can be quickly and accurately lo- calized. If neither CT nor MRI is available, vertebral angiography should be per- formed. The angiogram shows a cerebellar mass effect in about 85% of cases, but the procedure is time-consuming. Bloody CSF will confirm the diagnosis of hemorrhage, but a clear tap does not exclude the possibility of an intracerebellar hematoma, and lumbar puncture may hasten the process of herniation. Lumbar puncture is therefore not advocated if a cerebellar hemorrhage is suspected.
Like cerebellar hemorrhage, acute peripheral vestibulopathy also produces nausea, vomiting, and gait ataxia. Severe headache, impaired consciousness, elevated blood pressure, or later age at onset, however, strongly favors cerebel- lar hemorrhage.
Treatment
There are 5 main areas in the treatment of acute ICH (European Stroke In- itiative recommendations, 2006) : 1) General treatment does not substantially dif- fer from the treatment of ischemic stroke. The neurological status and vital func- tions (blood pressure, pulse rate, oxygenation and temperature) should be conti- nuously or regularly monitored. 2) Prevention and treatment of complications, which may be either neurological or medical. 3) Early secondary prevention to reduce the incidence of early recurrence of ICH. 4) Early rehabilitation is also essential for ICH patients. 5) Specific therapy directed against the growth of the haematoma that is currently the subject of surgery and ongoing RCTs.
Cerebellar decompression. The most important therapeutic intervention in hypertensive hemorrhage is surgical decompression for cerebellar hematomas. Unless this step is taken promptly, there may be a fatal outcome or unexpected deterioration. Note that this procedure may also reverse the neurologic deficit. Since surgical results are much better for responsive than unresponsive patients, surgery should be performed early in the course when the patient is still con- scious.
Cerebral decompression. Surgery can be useful when a superficial he- morrhage in the cerebral white matter is large enough to cause a mass effect with shift of midline structures and incipient herniation. The prognosis is direct-
ly related to the level of consciousness before the operation, and surgery is usually fruitless in an already comatose patient. Surgery is not indicated for pon- tine or deep cerebral hypertensive hemorrhages, since in most cases spontaneous decompression occurs with rupture into the ventricles and the areas in question are accessible only at the expense of normal overlying brain.
Medical measures. The use of antihypertensive agents in acute intracere- bral hemorrhage is controversial. Attempts to lower systemic blood pressure may compromise cerebral blood flow and lead to infarction, but continued hypertension may exacerbate cerebral edema. On this basis, it seems reasonable to lower blood pressure to diastolic levels of approximately 100 mm Hg follow- ing intracerebral hemorrhage, but this must be done with great care because the cerebral vasculature may be unusually sensitive to antihypertensive agents. There is no other effective medical treatment for intracerebral hemorrhage. The use of haemostatic agents to control bleeding has been tried in ICH or subarach- noid hemorrhage with various agents (tranexamic acid, ε-aminocaproic acid, aprotinin). These trials could not demonstrate safety or efficacy. Corticosteroids are commonly prescribed to reduce vasogenic edema in patients withintracere- bral hemorrhage, but the evidence of their benefit is poor. Antiedema agents provide only temporary benefit.
Secondary intracerebral hemorrhage
Vascular Malformations. Bleeding from cerebral angiomas and aneurysms can lead to both intracerebral and subarachnoid hemorrhage. Angiomas may come to medical attention because of seizures, in which case anticonvulsants are the treatment of choice, or because of bleeding. In the latter instance, surgical removal is indicated to prevent rebleeding – provided the malformation is surgi- cally accessible. Aneurysms usually present with intracranial hemorrhage but occasionally with compressive focal deficits such as third-nerve palsy.
Coagulopathies and anticoagulation. Intracerebral hemorrhage is a com- plication of disorders of both clotting factors and platelets, such as hemophilia (factor VIII deficiency) and idiopathic thrombocytopenic purpura. Acute myelo- genous leukemia with white blood cell counts greater than 150,000/µL may also predispose to intracerebral hemorrhage. Patients receiving heparin or warfarin are at increased risk for developing spontaneous or traumatic intracerebral he- morrhage.
Hemorrhage into Tumors. Bleeding into primary or metastatic brain tu- mors is an occasional cause of intracerebral hemorrhage. Tumors associated with hemorrhage include glioblastoma multiforme, melanoma, choriocarcinoma, renal cell carcinoma, and bronchogenic carcinoma. Bleeding into a tumor should be considered when a patient with known cancer experiences acute neurologic deterioration; it may also be the presenting manifestation of cancer.
Trauma. Intracerebral hemorrhage is a frequent consequence of closed- head trauma. Such hemorrhages may occur under the skull at the site of impact
or directly opposite the site of impact (contrecoup injury). The most common locations are the frontal and temporal poles. The appearance of traumatic he- morrhages on CT scans may be delayed for as much as 24 hours after injury; MRI permits earlier detection.
Amphetamine or cocaine abuse. Intravenous, intranasal, and oral amphe- tamine or cocaine use can result in intracerebral hemorrhage, which typically occurs within minutes to hours after the drug is administered. Most such he- morrhages are located in subcortical white matter and may be related to either acute elevation of blood pressure, leading to spontaneous hemorrhage or rupture of a vascular anomaly, or drug-induced arteritis.
SUBARACHNOID HEMORRHAGE
Spontaneous (nontraumatic) subarachnoid hemorrhage (bleeding into the subarachnoid space) is usually the result of a ruptured cerebral arterial aneurysm or an arteriovenous malformation (AVM). Rupture of a berry aneurysm ac- counts for about 75% of cases and occurs most often during the fifth and sixth decades, with an approximately equal sex distribution. Hypertension has not been conclusively demonstrated to predispose to the formation of aneurysms, but acute elevation of blood pressure may be responsible for their rupture. Intra- cranial AVMs, a less frequent cause of subarachnoid hemorrhage (10%), occur twice as often in men and usually bleed in the second to fourth decades, al- though a significant incidence extends into the 60s. Blood in the subarachnoid space can also result from intracerebral hemorrhage, embolic stroke, and trauma.
Pathogenesis
Cerebral artery aneurysms are most commonly congenital "berry" aneu- rysms, which result from developmental weakness of the vessel wall, especially at sites of branching. These aneurysmal dilatations arise from intracranial arte- ries about the circle of Willis at the base of the brain and are multiple in about 20% of cases. Other congenital abnormalities, including polycystic kidney dis- ease and coarctation of the aorta, may be associated with berry aneurysms. Oc- casionally, systemic infections such as infective endocarditis disseminate to a cerebral artery and cause aneurysm formation; such "mycotic" aneurysms ac- count for 2-3% of aneurysmal ruptures. Mycotic aneurysms are usually more distal (along the course of cerebral arteries) than are berry aneurysms.
AVMs consist of abnormal vascular communications that permit arterial blood to enter the venous system without passing through a capillary bed. They are most common in the middle cerebral artery distribution.
Rupture of an intracranial artery elevates intracranial pressure and distorts pain-sensitive structures, producing headache. Intracranial pressure may reach systemic perfusion pressure and acutely decrease cerebral blood flow; together
with the concussive effect of the rupture, this is thought to cause the loss of con- sciousness that occurs at the onset in about 50% of patients. Rapid elevation of intracranial pressure can also produce subhyaloid retinal hemorrhages. Because aneurysmal hemorrhage is usually confined to the subarachnoid space, it does not produce a focal cerebral lesion. Prominent focal findings on neurologic ex- amination are accordingly uncommon except with middle cerebral artery aneu- rysms. Ruptured AVMs, however, produce focal abnormalities that correspond to their parenchymallocation.
Clinical Findings
A. Symptoms and Signs. The classic (but not invariable) presentation of subarachnoid hemorrhage is the sudden onset of an unusually severe generalized headache ("the worst headache I ever had in my life"). The absence of headache essentially precludes the diagnosis. Loss of consciousness is frequent, as are vomiting and neck stiffness. Symptoms may begin at any time of day and during either rest or exertion.
The most significant feature of the headache is that it is new. Milder but otherwise similar headaches may have occurred in the weeks prior to the acute event. These earlier headaches are probably the result of small prodromal he- morrhages (sentinel, or warning, hemorrhages) or aneurysmal stretch. The head- ache is not always severe, however, especially if the subarachnoid hemorrhage is from a ruptured AVM rather than an aneurysm. Although the duration of the hemorrhage is brief, the intensity of the headache may remain unchanged for several days and subside only slowly over the next 2 weeks. A recrudescent headache usually signifies recurrent bleeding.
Blood pressure frequently rises precipitously as a result of the hemorr- hage. Meningeal irritation may induce temperature elevations to as high as 39°C during the first 2 weeks. There is frequently confusion, stupor, or coma. Nuchal rigidity and other evidence of meningeal irritation are common, but these signs may not occur for several hours after the onset of the headache. Preretinal globu- lar subhyaloid hemorrhages (found in 20% of cases) are most suggestive of the diagnosis. Because bleeding occurs mainly in the subarachnoid space in patients with aneurysmal rupture, prominent focal signs are uncommon on neurologic examination. When present, they may bear no relationship to the site of the aneurysm. An exception is oculomotor nerve palsy occurring ipsilateral to a posterior communicating artery aneurysm. Bilateral extensor plantar responses and VI nerve palsies are frequent in such cases. Ruptured AVMs may produce focal signs, such as hemiparesis, aphasia, or a defect of the visual fields, which help to localize the intracranial lesion.
B. Laboratory Findings. Patients presenting with subarachnoid hemorr- hage are generally investigated first by CT scan, which will usually confirm that hemorrhage has occurred and may help to identify a focal source. CT brain scanning will detect subarachnoid blood in more than 90% of patients with
aneurysmal rupture. The test is highly sensitive on the day bleeding occurs; it is most sensitive in patients with altered consciousness. Intracerebral or intraven- tricular blood, associated hydrocephalus, and infarction can also be identified. Aneurysms may not be evident on the CT scan, but most AVMs can be seen with contrast. MRI is especially useful in detecting small AVMs localized to the brain stem (an area poorly seen on CT scan). If the CT scan fails to confirm the clinical diagnosis of subarachnoid hemorrhage, lumbar puncture is performed.
The CSF examination usually reveals markedly elevated pressure, often above the maximum recordable value (600 mm H20) using the standard CSF manometer; the fluid is grossly bloody and contains from 100,000 to more than 1 million red cells/ μL. As a result of the breakdown of hemoglobin from red cells, the supematant of the centrifuged CSF becomes yellow (xanthochromic) within several hours (certainly by 12 hours) following the hemorrhage. White cells are initially present in the spinal fluid in the same proportion to red cells as in the peripheral blood. The chemical meningitis caused by blood in the sub- arachnoid space, however, may produce a pleocytosis of several thousand white blood cells during the first 48 hours and a reduction in CSF glucose between the fourth and eighth days after the hemorrhage. In the absence of pleocytosis, CSF glucose following subarachnoid hemorrhage is normal. The peripheral blood white count is often modestly elevated but rarely exceeds 15,000 cells/ μL. The ECG may reveal a host of abnormalities: peaked or deeply inverted T waves, short PR interval, or tall U waves.
Cerebral angiography of both the carotid and vertebral arteries should be performed to visualize the entire cerebral vascular anatomy, since multiple aneu- rysms occur in 20% of patients and AVMs are frequently supplied from multiple sources. Angiography can be performed at the earliest time convenient for radi- ology department personnel; emergency studies in the middle of the night are rarely indicated. Recent advances in three-dimensional CT angiography may obviate the need for invasive cerebral angiography and its inherent risks. Angio- graphy is a prerequisite to the rational planning of surgical treatment and is therefore not necessary for patients who are not surgical candidates, eg, those who are deeply comatose.
Differential Diagnosis
The history of a sudden severe headache with confusion or obtundation, nuchal rigidity, a nonfocal neurologic examination, and bloody spinal fluid is highly specific for subarachnoid hemorrhage.
Hypertensive intracerebral hemorrhage is also manifested by obtundation and hemorrhagic spinal fluid, but there are prominent focal findings. Bacterial meningitis is excluded by the CSF examination. Ruptured mycotic aneurysm is suggested by other signs of endocarditis. Traumatic spinal puncture can be ex- cluded as the cause of bloody CSF by examination of the centrifuged CSF spe- cimen. Since blood that results from traumatic lumbar puncture has not yet un-
dergone enzymatic breakdown to bilirubin, centrifugation of the spinal fluid specimen reveals a colorless supernatant.
Complications
A. Recurrence of hemorrhage. Recurrence of aneurysmal hemorrhage (20% over 10- 14 days) is the major acute complication and roughly doubles the mortality rate. Recurrence of hemorrhage from AVM is less common in the acute period.
B. Intraparenchymal extension of hemorrhage. While it is common for hemorrhages from an AVM to involve the cerebral parenchyma, this is far less common with aneurysm. Nevertheless, rupture of an aneurysm of the anterior cerebral or middle cerebral artery may direct a jet of blood into brain parenchy- ma, producing hemiparesis, aphasia, and sometimes transtentorial herniation.
C. Arterial vasospasm. Delayed arterial narrowing, termed vasospasm, occurs in vessels surrounded by subarachnoid blood and can lead to parenchym- al ischemia in more than one-third of cases. Clinical ischemia typically does not appear before day 4 after the hemorrhage, peaks at day 10- 14, and then sponta- neously resolves. The diagnosis can be confirmed by transcranial Doppler or ce- rebral angiography. The severity of spasm is related to the amount of subarach- noid blood, and therefore is less common where less blood is usually seen, such as in traumatic subarachnoid hemorrhage or AVM.
D. Acute or subacute hydrocephalus. Acute or subacute hydrocephalus may develop during the first day – or after several weeks – as a result of im- paired CSF absorption in the subarachnoid space. Progressive somnolence, non- focal findings, and impaired upgaze should suggest the diagnosis.
E. Seizures. Seizures occur in fewer than 10% of cases and only following damage to the cerebral hemisphere. Decorticate or decerebrate posturing is common, however, and may be mistaken for seizures.
Treatment
A. Medical Treatment. Medical treatment is traditionally directed toward preventing elevation of arterial or intracranial pressure that might re-rupture the aneurysm or AVM. Typical measures include absolute bed rest with the head of the bed elevated 15-20 degrees, mild sedation, and analgesics for headache. Drugs impairing platelet function (eg, aspirin) should be avoided. Since patients who are hypertensive on admission have an increased mortality risk, reducing the blood pressure (to approximately 160/100 mm Hg) is prudent. Bed rest and mild sedation are often adequate in this regard. Hypotension should be pre- vented, however, to ensure adequate cerebral perfusion. Intravenous fluids should be administered with care, since overhydration can exacerbate cerebral swelling. Intravenous fluids should be iso-osmotic to minimize free water ex- acerbating brain edema. Normal saline can be given in amounts to ensure nor-
movolemia. Hyponatremia is frequently seen, and usually represents, at least in part, cerebral salt-wasting; it should be managed with sodium replacement such as NaCl orally or 3% normal saline intravenously rather than fluid restriction. Prophylactic use of the calcium channel antagonist drug nimodipine, 60 mg oral- ly (or by nasogastric tube) every 4 hours for 21 days, may reduce the ischemic sequelae of cerebral vasospasm in patients with a ruptured aneurysm. Vasos- pasm is treated by induced hypertension with phenylephrine or dopamine; this intervention is more safely performed after definitive surgical treatment of the aneurysm. Although seizures are uncommon after aneurysmal rupture, the hypertension accompanying a seizure increases the risk of rerupture; a prophy- lactic anticonvulsant (eg, valproic acid 15–45 mg/kg/day) is therefore recom- mended routinely.
B. Surgical Treatment. 1) Aneurysm. Definitive surgical therapy consists of clipping the neck of the aneurysm or the endovascular placement of a coil to induce clotting. The neurologic examination is used to grade the patient's clini- cal state relative to surgical candidacy. In patients who are fully alert (grades I and II) or only mildly confused (grade III), surgery has been shown to improve the clinical outcome. Stuporous (grade IV) or comatose (grade V) patients do not appear to benefit from the procedures. Although there is some controversy about the optimal timing of surgery, current evidence supports early interven- tion, within about 2 days following the hemorrhage.
This approach reduces the period at risk for rebleeding and permits ag- gressive treatment of vasospasm with volume expansion and pharmacologic ele- vation of blood pressure. 2) AVMs. Surgically accessible AVMs may be re- moved by en bloc resection or obliterated by ligation of feeding vessels or em- bolization via local intra-arterial catheter. Because the risk of an early second hemorrhage is much less with AVMs than with aneurysms, surgical treatment can be undertaken electively at a convenient time after the bleeding episode.
Prognosis
The mortality rate from aneurysmal subarachnoid hemorrhage is high. About 20% of patients die before reaching a hospital, 25% die subsequently from the initial hemorrhage or its complications, and 20% die from rebleeding if the aneurysm is not surgically corrected. Most deaths occur in the first few days after the hemorrhage. The probability of survival following aneurysmal rupture is related to the patient's state of consciousness and the elapsed time since the hemorrhage. On day 1, the prognosis for survival for symptom-free and somno- lent patients is, respectively, 60% and 30%; such patients still alive at 1 month have survival probabilities of 90% and 60%, respectively. Recovery from sub- arachnoid hemorrhage resulting from rupture of intracerebral AVMs occurs in nearly 90% of patients, and although recurrent hemorrhage remains a danger, conservative management compares favorably with surgical therapy.
VASCULAR DEMENTIA
Impairment of blood supply to the brain used to be considered to be the main cause of dementia in the elderly, until it was recognized that such a me- chanism is rarely, if ever, implicated. Multiple small strokes, referred to as mul- ti-infarct dementia, were subsequently identified as the principal mechanism, both clinically and at autopsy. In most neuropathological and clinical series, vascular dementia is the most common cause after Alzheimer's disease, account- ing for some 10-20 percent of dementia cases alone, and an important concomi- tant of Alzheimer's disease or other degenerative dementias. The incidence of vascular dementia may be falling with better management of vascular risk fac- tors. It is also believed that many cases of dementia with Lewy bodies were pre- viously diagnosed clinically as vascular dementia. If cases of dementia where there is a vascular component are considered, then there is no doubt that vascu- lar disease is a major cause or contributor to cognitive. The term 'vascular de- mentia' is preferable to 'multiinfarct dementia' as it reflects the considerable he- terogeneity of the condition and includes cases due to haemorrhage, small lacu- nar infarcts, large cortical infarcts, and vasculitis. In comparison to Alzheimer's disease, there is a paucity of epidemiological data on vascular dementia. In part, this is due to the fact that patients with major strokes are often excluded, and yet, in one study, up to 25 per cent of patients 3 months after a stroke were con- sidered to have dementia using DSM-IV criteria, and up to 60 per cent had cog- nitive impairment.
Clinical criteria for the diagnosis of vascular dementia have been domi- nated by the development of criteria for Alzheimer's disease. Thus, memory re- mains as a key component and yet may be relatively less important in vascular dementia. Early criteria assumed that stepwise deterioration and motor abnor- malities would be characteristic, and from this was developed the Hachinski score. Patients with a score of 4 or less were considered likely to bedegenera- tive by contrast to those with a score of 7 or more, who were thought to have a multi-infarct dementia. This remains a useful guide, and series have been veri- fied pathologically. More recently, the NINCDS-AIREN criteria have been de- veloped, which require the appearance of cognitive impairment within 3 months of a stroke, or sudden onset and fluctuation of cognitive impairment. In view of the potential contribution of focal neuropsychological deficits from a discrete stroke, the cognitive criteria for dementia are that there should be memory im- pairment plus at least two other domains. There should also be relevant vascular changes on imaging which are thought to be directly related. However, very dif- ferent proportions of cases are diagnosed as vascular dementia, depending upon the use of NINCDS-AIREN, DSM-IV, or ICD- 10 criteria.
Three main vascular pathologies are believed to be associated with vascu- lar dementia; namely, single discrete cortical infarcts, multiple infarcts (multi-
infarct dementia), and subcortical arteriosclerotic encephalopathy (Binswanger's disease). In reality, these may overlap.
Single discrete infarcts, for example, in right middle cerebral and post- erior cerebral artery territories and thalamic infarcts, can present with a picture suggestive of dementia. Much more common, however, is the accumulation of deficits from multiple single cortical and/or subcortical infarcts. Men are more commonly affected than women, and there is usually a vascular history, particu- larly of hypertension. There is a gradual accumulation of cognitive deficits with episodes of confusion or focal neurology. If there are mainly subcortical in- farcts, patients tend to have a subcortical pattern of cognitive deficit with cogni- tive slowing and additional motor features. Some may develop an extrapyramid- al syndrome, and in others a pseudobulbar palsy can be prominent with path o- logical laughing and crying. Neuropathologically, multiple small subcortical in- farcts appear to be more important in vascular dementia than single large in- farcts.
Subcortical arteriosclerotic encephalopathy (Binswanger's disease)
Binswanger originally described eight cases of periventricular demyelina- tion and dementia. This was considered a rarity until the advent of neuroimag- ing, and many patients with white matter changes on scanning acquired this di- agnosis. Clinically, the features are very similar to those seen in patients with multiple subcortical infarcts, namely frontal and subcortical cognitive features, dysarthria, and pseudobulbar palsy. Gait impairment may occur early and is cha- racterized by a wide-based shuffling gait, in contrast to the narrower base seen in Parkinson's disease. Criteria have been suggested for the diagnosis of Bins- wanger's disease.
Much confusion has arisen from attempts to diagnose Binswanger's dis- ease from neuroimaging. Non-specific periventricular white matter abnormali- ties are common both in patients with dementia and in the non-demented elder- ly, and the term leuko-araiosis has been proposed. Leuko-araiosis appears as low attenuation on CT scan, particularly around the frontal and occipital horns, and as increased signal on T2-weighted MRI. Neuropathologically, there is demyeli- nation, gliosis, and hyalinosis, with fibrinoid necrosis of small blood vessels, similar to that seen in hypertension. Minor degrees of white matter disease are also seen in pure Alzheimer's disease.
Treatment is primarily that of management of vascular disease risk factors such as hypertension, smoking, diabetes, carotid stenosis, and heart disease. There have been few control trials of management of risk factors and its affect on cognition, but treatment of isolated systolic hypertension in the elderly may reduce the incidence of dementia.
Other causes of vascular dementia
Significant cognitive impairment, sufficient to justify the criteria of de- mentia, can occur after subarachnoid haemorrhage, subdural haematomas, and global ischaemia following cardiac arrest with laminar necrosis and hippocam- pal cell loss. A variety of vasculitides can also be associated with the early de- velopment of cognitive impairment and even present as a dementia; these in- clude systemic lupus erythematosus (SLE) and primary cerebral angiitis, which is usually accompanied by headaches. Sneddon's syndrome is the association of livedo reticularis with cerebrovascular disease, and can present with cognitive impairment. A number, but not all, are associated with anticardiolipin antibo- dies.
The rare cases of hereditary cerebral amyloidosis, both of the Icelandic and the Dutch and the Flemish type, can be associated with cognitive impair- ment, although the salient clinical feature is that of recurrent cerebral haemorr- hage. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is characterized by recurrent subcortical ischaemic events with the subsequent development of a pseudobulbar palsy and cognitive impairment. Early symptoms include migraine-like headache and psy- chiatric disturbance. The MRI scan shows a striking leucoencephalopathy in ad- dition to multiple small infarcts. This condition, which is increasingly recognized, is linked to mutations in the Notch 3 gene.
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