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Hyperbaric oxygen may reduce ischemic de cits temporarily but has no sustained effect Induced hypothermia limits the size of ischemic stroke, but it is technically dif cult to administer and often has serious side effects Calcium channel blockers of the types administered for cardiac disease have also been found to increase CBF and to reduce lactic acidosis in stroke patients However, several multicenter clinical trials that compared calcium channel blockers with placebo did not establish a difference in outcome in the two groups There has also been interest, as noted earlier in this chapter, in drugs that inhibit excitatory amino acid transmitters and free-radical scavengers such as dimethyl sulfoxide (DMSO) and growth factors, but so far none of these has been successfully applied to humans Despite some experimental evidence that certain vasodilators, such as CO2 and papaverine, increase CBF, none has proved bene cial in carefully studied human stroke cases at the stage of TIAs, thrombosis in evolution, or established stroke Vasodilators may actually be harmful, at least on theoretical grounds, since by lowering the systemic blood pressure or dilating vessels in normal brain tissue (the autoregulatory mechanisms are lost in vessels within the infarct), they may reduce the intracranial anastomotic ow Moreover, the vessels in the margin of the infarct (border zone) are already maximally dilated New discoveries regarding the role of nitric oxide in vascular control will probably give rise to new pharmacologic agents, which will have to be evaluated Surgery and Angioplasty for Symptomatic Carotid Stenosis Comments have already been made concerning the opening of an occluded carotid artery soon after a stroke Here we discuss the patient who has passed the acute period, when surgery is safer, or who has TIAs The region that most often lends itself to such therapy is the carotid sinus (the bulbous expansion of the internal carotid artery just above its origin from the common carotid) Other sites suitable for surgical management include the common carotid, innominate, and subclavian arteries Operation on the vertebral artery at its origin has proved successful only in exceptional circumstances In recent years balloon angioplasty and stenting of the carotid artery have become increasingly popular as an alternative to surgery (see below) Surgery and angioplasty, in our opinion, are as yet applicable mainly to the group of patients with symptomatic carotid artery stenosis (the asymptomatic ones are discussed below) who have substantial extracranial stenosis but not complete occlusion, and, in special instances, in those with nonstenotic ulcerated plaques Those with stenosis constitute less than 20 percent of all patients with TIAs (Marshall); but from the perspective of surgical therapy, the term symptomatic encompasses both TIAs and small strokes ipsilateral to the stenosis There is now convincing evidence that well-executed surgery in appropriately chosen cases arrests the TIAs and diminishes the risk of future strokes These views have received strong af rmation from two well-designed randomized studies the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) The conclusion, reached in each of these studies, was that carotid endarterectomy for symptomatic lesions causing severe degrees of stenosis ( 70 to 80 percent reduction in diameter) is effective in reducing the incidence of ipsilateral hemispheral strokes These two trials differed in the method of estimating the degree of stenosis, but when adjustments are made, the results are comparable (Donnan et al) Patients in the European study with mild or moderate stenosis (up to 70 percent) did not bene t from endar-
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terectomy In the North American study, however, they did so, but to a lesser extent than the group with severe stenosis Further analysis of the North American trial by Gasecki and colleagues has indicated that the risk of cerebral infarction on the side of the symptomatic stenosis is increased if there is a contralateral carotid stenosis but that operated patients (on the side of symptomatic stenosis) still had fewer strokes than those treated with medication alone In those with bilateral carotid disease, the risk of stroke after 2 years was 69 percent, and if operated, 22 percent In the nal analysis, the relative bene ts of surgery or medical treatment (anticoagulation or aspirin) depend mainly on the true surgical risk ie, on the record of an individual surgeon If the surgeon, by an independent audit of his procedures, has an established operative complication rate of no more than 4 to 5 percent and preferably lower, then surgery can be recommended in symptomatic patients with carotid stenosis greater than 70 percent This bene t extends to elderly patients and, indeed, it has been shown on a statistical basis to be most evident in patients over age 75 (see the reanalysis of NASCET data by Alomamowitch and colleagues) Before operation or angioplasty, the existence of the lesion and its extent must be determined Arteriography, the procedure that yields the best images and most accurate measurements of the residual lumen, carries a very small risk of worsening the stroke or producing new focal signs (this notion has never been documented systematically) Severe stenosis is re ected in conventional angiography by the lling of the distal branches of the external carotid artery before the branches of the middle cerebral artery are opaci ed a reversal of the usual lling pattern, indicating low ow in the distal carotid circulation Increasingly the diagnosis of carotid stenosis is being made by noninvasive methods, but with both ultrasound and magnetic resonance arteriography, there is dif culty in quantifying severe stenosis and separating it from complete carotid artery occlusion Perfusion CT imaging may provide a more accurate alternative at low risk (the volume of dye required may still be prohibitive in patients with renal failure) If the patient is in good medical condition, has normal vessels on the contralateral side, and has normal cardiac function (no heart failure, uncontrolled angina, or recent infarction), these lesions can usually be dealt with safely by endarterectomy The procedure is not, however, innocuous It may be followed by a new hemiplegia or aphasia that becomes evident immediately or soon after endarterectomy, usually by the time the patient arrives in the recovery room In general, surgeons prefer to return the patient to the operating room and open the artery, as discussed earlier on An intimal ap at the distal end of the endarterectomy and varying amounts of fresh clot proximal to it are usually encountered; but after removal and repair of the vessel, the effects of the stroke, if one has occurred, are not usually improved An uncommon but rather striking hyperperfusion syndrome develops several days to a week after carotid endarterectomy The features are headache, focal de cits, seizures, brain edema, or cerebral hemorrhage; these are thought to re ect an abrupt loss of autoregulatory ability of the cerebral vasculature in the face of hypertension and increased perfusion on the side of the recently opened artery Unilateral severe headache is the commonest symptom and may be the only manifestation On occasion the cerebral edema is so massive as to lead to death (Breen et al) Treatment is by control of hypertension; it is unclear whether anticonvulsant medications are required if there has been a single seizure, but they seem valuable to us We mention here that an identical syndrome of focal cerebral de cits and brain edema, perhaps with the excep-
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