William S. Fields

EFFICACY OF CAROTID ENDARTERECTOMY FOR ASYMPTOMATIC CAROTID STENOS IS. THE VETERANS AFFAIRS COOPERATIVE STUDY GROUP

BACKGROUND The efficacy of carotid endarterectomy in patients with asymptomatic carotid stenosis has not been confirmed in randomized clinical trials, despite the widespread use of operative intervention in such patients. METHODS We conducted a multicenter clinical trial at 11 Veterans Affairs medical centers to determine the effect of carotid endarterectomy on the combined incidence of transient ischemic attack, transient monocular blindness, and stroke. We studied 444 men with asymptomatic carotid stenosis shown arteriographically to reduce the diameter of the arterial lumen by 50 percent or more. The patients were randomly assigned to optimal medical treatment including antiplatelet medication (aspirin) plus carotid endarterectomy (the surgical group; 211 patients) or optimal medical treatment alone (the medical group; 233 patients). All the patients at each center were followed independently by a vascular surgeon and a neurologist for a mean of 47.9 months. RESULTS The combined incidence of ipsilateral neurologic events was 8.0 percent in the surgical group and 20.6 percent in the medical group (P < 0.001), giving a relative risk (for the surgical group vs. the medical group) of 0.38 (95 percent confidence interval, 0.22 to 0.67). The incidence of ipsilateral stroke alone was 4.7 percent in the surgical group and 9.4 percent in the medical group. An analysis of stroke and death combined within the first 30 postoperative days showed no significant differences. Nor were there significant differences between groups in an analysis of all strokes and deaths (surgical, 41.2 percent; medical, 44.2 percent; relative risk, 0.92; 95 percent confidence interval, 0.69 to 1.22). Overall mortality, including postoperative deaths, was primarily due to coronary atherosclerosis. CONCLUSIONS Carotid endarterectomy reduced the overall incidence of ipsilateral neurologic events in a selected group of male patients with asymptomatic carotid stenosis. We did not find a significant influence of carotid endarterectomy on the combined incidence of stroke and death, but because of the size of our sample, a modest effect could not be excluded.

Controlled trial of aspirin in cerebral ischemia. Part II: surgical group.

Patients (125) who had carotid transient ischemic attacks (TIAs) and one or more accessible carotid lesions visualized angiographically had reconstructive operations of the carotid artery and werethen randomly assigned to aspirin or placebo treatment. They were followed to determine the incidence of subsequent TIAs, death, cerebral infarction, or retinal infarction. Life table analysis (for 24 months follow up) that eliminated deathswhich were not stroke-related revealed a significant difference in favor of aspirin. Because of the small number of patients and the short period of follow up, these results should be interpreted only as consistent with those reported in the initial publication but not conclusive of an aspirin effect in preventing cerebral infarction.

Intracarotid infusion of cis‐diamminedichloroplatinum in the treatment of recurrent malignant brain tumors

Thirty‐five patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation chemotherapy received cisplatin, 60 to 120 mg/m2, into the internal carotid artery by a transfemoral approach. Courses of therapy were repeated every 4 weeks. Therapeutic evaluation was performed monthly using the CT scan of the brain and clinical neurologic examination. Thirty patients were evaluable for response. Of 20 evaluable patients with primary malignant brain tumors, 6 responded to therapy and 5 had stable disease. The median time to tumor progression for responding patients was 33 weeks, for stable patients 16 weeks, and 13 weeks for all patients. Five of 10 evaluable patients with brain metastases responded to intracarotid cisplatin, and 2 patients had stable disease. The estimated median time to progression for responding patients was 30+ weeks and 12+ weeks for patients with stable disease. Side effects included seizures in 5 courses, mental agitation and motor restlessness in 1, and transient hemiparesis in 7. One patient may have had a drug‐related death, and one patient appeared to develop encephalopathy after treatment. Five patients had clinical deterioration in vision; in two patients it was bilateral. Intracarotid cisplatin has definite activity in patients with malignant primary brain tumors and in patients with brain metastases. The recommended starting dose for intracarotid cisplatin is 60 to 75 mg/m2. At this dose level side effects are uncommon, but includes the risk of neurologic and retinal toxicity.

Current management of amaurosis fugax

We present a consensus on the pathophysiology, etiology, diagnosis, and treatment of amaurosis fugax. The phenomenon is defined and described, and the roles that extracranial and ocular vascular diseases play are discussed. Nonvascular ophthalmic and neurologic disorders that can be confused with amaurosis fugax are listed, and an algorithm for evaluation (which includes ophthalmic examination, laboratory studies, and noninvasive carotid artery studies) is given. Treatment of atherosclerosis, carotid artery disease, and other causes of amaurosis fugax are also discussed.

TORTUOSITY, COILING, AND KINKING OF THE INTERNAL CAROTID ARTERY. II. RELATIONSHIP OF MORPHOLOGICAL VARIATION TO CEREBROVASCULAR INSUFFICIENCY.

SEVERAL recent publications have suggested a relationship between cerebrovascular insufficiency and kinking and coiling of the internal carotid artery in its extracranial portion. Riser and associates1 reported a case of coiling and kinking associated with severe attacks of vertigo. After a surgical procedure in which the artery was straightened by attaching it to the sternocleidomastoid muscle, the episodes subsided. Two patients reported by Derrick and Smith2 had not only a loop in the left internal carotid artery but also kinking of the artery on the opposite side. Henly and associates3 reported 7 patients in whom cerebral manifestations were believed to be due to coiling of the internal carotid artery. A review of the symptoms reported in their patients reveals that the cerebral disturbance was on the side of the coiling in only one case and that even in this instance it would appear more likely that the symptoms were due to disease of the small intracranial vessels. There was no evidence of narrowing of the lumen in the coiled segment, nor was there any report that the size of the lumen was altered by the position of the head. In their other 6 patients the symptoms suggested insufficiency in the vertebrobasilar system rather than a disorder related to a unilateral carotid lesion. These patients were not followed over a long enough period of time, and the results are inconclusive.

Central nervous system toxicity with high-dose Ara-C

We evaluated the CNS complications in 118 adults with acute leukemia who received IV high-dose Ara-C therapy. Fourteen (12%) had cerebellar signs, encephalopathy, seizures, or leukoencephalopathy. Symptoms usually occurred within 24 hours after the last treatment. Patients receiving a cumulative dose in excess of 24 g/m2 had more severe or irreversible symptoms. After lower cumulative doses, symptoms often resolved even though treatment was continued. The incidence of CNS complications of high-dose Ara-C is acceptable and is potentially reversible if appropriate precautions are taken.

Does platelet antiaggregant therapy lessen the severity of stroke

Data from the Aspirin in Transient Ischemic Attack (AITIA) study, an ongoing study of two platelet antiaggregant drugs, and other published therapeutic trials were reviewed to determine whether the severity of stroke is reduced in patients taking platelet antiaggregants. Data from three of four studies suggest that strokes in treated patients are less severe than those in untreated patients. Further studies evaluating platelet antiaggregant therapy should include assessment of the severity as well as the incidence of stroke.

The significance of carotid stenosis or ulceration

Data from the medical treatment group of the Aspirin in TIA study were reviewed, and prospective analysis of patients with asymptomatic bruits was performed to see whether carotid stenosis (0 to 49% or 50 to 99%) or ulceration produced an increased risk of ipsilateral TIA or infarct. In symptomatic arteries, > 50% stenosis without ulceration implied a higher risk of subsequent symptoms. Ulceration was associated with an increased risk only in nonstenotic vessels. Lesion anatomy was not related to outcome in asymptomatic arteries, and the incidence of cerebral infarct was low. Factors other than anatomy must play a large role in determining subsequent risk.

Treatment-related Leukoencephalopathy: A Study Of Three Cases And Literature Review

The etiology and pathogenesis of treatment-related leukoencephalopathy remain obscure. The evidence is substantial, however, that radiation therapy in combination with higher cerebral concentrations of certain chemotherapeutic agents such as MTX increases the likelihood of permanent damage. There is no therapy of apparent benefit for treatment-related leukoencephalopathy, but reasonable alternatives include 1) withholding chemotherapy and/or radiation, 2) administering calcium leucovorin in high doses intravenously in methotrexate-induced leukoencephalopathy (26), or 3) perfusing the subarachnoid space (2) from above through an Ommaya reservoir and out from below through a lumbar puncture needle or lumbar subarachnoid catheter. Because CT scan abnormalities and subtle mental or intellectual changes are often noted before the full-blown clinical presentation, a prospective study involving periodic CT scanning as well as formal neuropsychologic testing appears worthwhile in all patients who are to receive cranial irradiation and/or chemotherapy in the prophylaxis or active treatment of CNS disease in order to detect and perhaps even to prevent this adverse side effect of cancer therapy.

Carotid endarterectomy: what is its current status?

The plethora of recent articles regarding carotid endarterectomy has tended to confuse rather than clarify its indications, efficacy, and acceptability. The National Institutes of Health has recently funded two large multicenter controlled clinical trials, one including asymptomatic persons with carotid stenoses, and the other, patients having transient ischemic episodes or minor strokes. Eight academic professors of neurology (four), neurosurgery (two), and vascular surgery (two) with a long and abiding interest in cerebrovascular disease prepared a statement delineating acceptable levels of mortality and morbidity from this procedure. These might serve as guidelines until the large trials have been completed.