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sidered to be unfavorable largely because of a high rate of cerebral hemorrhage In a second trial (ECASS II) in 800 patients, using the same dose as in the NINCDS-sponsored trial but giving the thrombolytic drug up to 6 h after the stroke, no bene t could be con rmed and the rate of symptomatic hemorrhage was 88 percent (compared with 34 percent in untreated patients) Yet a subgroup of patients with carotid middle cerebral artery strokes of moderate severity speci cally those with moderate-sized infarcts from occlusion of vessels distal to the carotid artery and adequate collateral circulation through surface vessels did appear to bene t In some patients with basilar artery occlusion with coma of only brief duration and those without extensive thrombosis, prompt t-PA treatment also resulted in an overall improvement in neurologic function, but there were numerous exceptions In all these trials, patients with large cerebral infarctions had poor outcomes and suffered a high incidence of cerebral hemorrhage It has been concluded, therefore, that the presence of blood in the rst CT scan and evidence of extensive infarction, occupying most of the MCA territory, precludes this mode of therapy In two similar trials conducted by the European MAST-I groups (see the Multicentre Acute Stroke Trial in References), using streptokinase within 6 h of stroke, there was actually an adverse outcome the treated group having an excess of early deaths; this trial had a 21 percent incidence of symptomatic cerebral hemorrhage and an 18 percent incidence of hemorrhagic infarctions At the present time the use of intravenous t-PA therapy can be advocated only in patients who arrive in the emergency department and can be fully evaluated within 3 h of the onset of a stroke, preferably even earlier (thus excluding those who awaken from a night s sleep with the symptoms) and have no hemorrhage on the CT scan Generally also excluded are those in whom the de cit is either very small (eg, hand affected only, dysarthria alone, minor aphasia) or, more importantly, so large as to implicate the entire territory of the middle cerebral artery Although seemingly a promising approach to acute stroke, the use of acute thrombolytic therapy depends on the very early identi cation of a restricted group of patients; therefore this therapy is applicable to only a limited proportion of stroke patients who present to the emergency department (approximately 5 percent) or those who have strokes while under observation in the hospital It is noteworthy that attempts to reproduce the bene cial effects of t-PA in a community setting have been disappointing largely because of deviations from treatment guidelines and an excess number of hemorrhages (Katzan et al) Nonetheless, acute intravenous thrombolysis that is managed closely by experienced individuals using validated protocols is a compelling treatment at the moment for acute ischemic stroke Public health education should increase the numbers of stroke patients who seek early attention and thus raise the proportion who are eligible for t-PA treatment Thrombolytics injected intra-arterially can in some instances dissolve occlusions of the middle cerebral and basilar arteries and, if administered within hours, reduce the neurologic de cit However, the routine intra-arterial injection of thrombolytics into infarcted tissue has produced a high incidence of cerebral hemorrhage, approaching 20 percent in some studies and leaving the overall morbidity about the same in treated and untreated patients There is also a high incidence of reocclusion of the treated vessel The exception, in our limited experience, has been basilar artery thrombosis without cerebellar infarctions, where large neurologic de cits are at times reversed with fewer complications Treatment even several hours after the rst symptoms may stop progression,
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but the lack of a systematic study of this approach makes it dif cult to endorse without reservation Mechanical lysis of an intra-arterial clot may be as effective Acute Surgical Revascularization Rarely is the patient who has had a stroke brought to medical attention within a few minutes of onset, although this may happen when a patient is in the hospital for another reason If it can be established that the common or internal carotid artery has just become thrombosed, intravenous or preferably intra-arterial t-PA or mechanical lysis of the clot may be effective We have had some experience with immediate surgical removal of the clot or the performance of a bypass to restore function Ojemann and colleagues operated on 55 such patients as an emergency procedure; 26 of these had stenotic vessels and 29 acutely thrombosed vessels Of the latter, circulation was restored in 21, with an excellent or good clinical result in 16 In 26 patients with stenotic carotid arteries, an excellent or good result was obtained in 19 Usually several hours will have elapsed before the diagnosis is established If the interval is longer than 12 h, opening the occluded vessel is usually of little value and may present additional dangers Reoperation after carotid endarterectomy is a special circumstance in which rapid removal of a clot is performed more or less routinely Treatment of Infarctive Cerebral Edema and Raised Intracranial Pressure In the rst few days following massive cerebral infarction, brain edema of the necrotic tissue may threaten life Most often this occurs with a complete infarction in the territory of the middle cerebral artery; some degree of mass effect is evident on a CT scan in the rst 24 h Additional infarction in the territory of the anterior cerebral artery (total carotid occlusion) worsens the situation Clinical deterioration occurs within several days of the stroke (usually worst on the third day, sometimes later) but may evolve as quickly as several hours after the onset (Fig 34-18) The clinical signs of worsening drowsiness, a xed (but not necessarily enlarged) pupil, and a Babinski sign on the side of the infarction are all due to secondary tissue shifts, as described in Chaps 17 and 30 In such instances, controlled hyperventilation may be useful as a temporizing maneuver Frank has shown that clinical deterioration is not always associated with an initial elevation of intracranial pressure It may therefore be advisable, in selected cases, to measure the ICP directly before embarking on an aggressive medical regimen to lower the pressure Intravenous mannitol in doses of 1 g/kg, then 50 g every 2 or 3 h, may forestall further deterioration, but most of these patients, once comatose, are likely to die unless drastic measures are taken Corticosteroids are probably of little value; several trials have failed to demonstrate their ef cacy In the past several years there has been renewed interest in hemicraniectomy as a means of reducing the mass effect and intracranial pressure in these extreme circumstances Our success in salvaging several patients even after a period of coma similar to reported series by Schwab, Carter, Delshaw, and Rengarchary and coworkers indicates that hemicraniectomy combined with an overlying duraplasty may be undertaken if the patient is progressing from a stuporous state to coma and imaging studies show increasing mass effect Of the 63 patients with severe brain swelling and coma in the series of Schwab et al, 46 survived and none remained severely disabled (But there is no question that a number of such patients will remain with hemiplegia) An anterior temporal lobectomy was performed in addition to the craniotomy in some
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