Gilbert J. Toffol

High-dose intravenous naloxone for the treatment of acute ischemic stroke.

To evaluate the safety and possible efficacy of high-dose naloxone for the treatment of acute cerebral ischemia, 38 patients received a loading dose of 160 mg/m2 over 15 minutes followed by a 24-hour infusion at the rate of 80 mg/m2/hr. Nausea and/or vomiting were common side effects. Naloxone was discontinued in seven patients (because of hypotension in one, bradycardia and hypotension in two, myoclonus in one, focal seizures in two, and hypertension in one); all seven patients responded to treatment and no permanent sequelae to naloxone were noted. Twelve of the 38 patients showed early neurologic improvement (by completion of the naloxone loading dose). However, there was no correlation between such a loading dose response and clinical outcome at 3 months. Our experience suggests that naloxone is safe at the dose used, but data for efficacy are inconclusive.

Echocardiographic evaluation of young adults with nonhemorrhagic cerebral infarction.

We reviewed echocardiographic findings in patients aged 15 to 45 years with acute nonhemorrhagic cerebral infarction (NHCI). Among 132 patients with NHCI, 96 (72.7%) had M-mode and two-dimensional echocardiography, including contrast echocardiography with intravenous saline injection when clinically indicated. Echocardiograms were abnormal in 33 patients. Of these, 7 had other conditions that could cause NHCI. Echocardiography corroborated the clinical diagnosis of a cardiogenic source for cerebral infarction in 17 others. The other 9 had no other clues for cardiovascular disease. Potential etiologies of NHCI diagnosed by echocardiography in these 9 cases included: paradoxical embolism, 5 patients; right atrial myxoma, 1; rheumatic mitral valve vegetation, 1; myxomatous mitral valve (marantic endocarditis at postmortem), 1; and left atrial enlargement associated with decreased left ventricular function, 1. Routine echocardiography frequently conveys useful information in patients under age 45 with NHCI. In young patients with cerebral embolism of unknown etiology if routine M-mode and two dimensional echocardiographic studies are normal, contrast echocardiographic studies should be performed to rule out intracardiac shunts and the possibility of paradoxical cerebral embolism.

The predicted value of arteriography in nontraumatic intracerebral hemorrhage.

We retrospectively assessed the diagnostic value of cerebral arteriography for the search of an etiology in 102 patients with nontraumatic intracerebral hemorrhages evaluated between 1980 and 1985. Arteriography was diagnostic in 22 of 50 non-hypertensive patients and in only 6 of 47 hypertensive patients. Five patients with a bleeding diathesis had normal arteriography. From the total group, we found 12 saccular aneurysms, 9 arteriovenous malformations, 3 cases of moya-moya and 3 instances of superior sagittal sinus thrombosis. One patient had metastatic choriocarcinoma. Sites of hemorrhage among all patients with diagnostic arteriograms were: lobar 19, intraventricular 5, thalamic 2, caudate 1, and corpus callosum 1. Lobar hemorrhages in the non-hypertensive group and intraventricular hemorrhages in hypertensive individuals had the highest yield of arteriographic abnormalities. We believe cerebral arteriography is indicated in non-hypertensive patients with lobar hemorrhages. Most hypertensive patients, in particular those with putaminal hemorrhages, do not require arteriography.

Paradoxical cerebral embolism: eight cases.

We evaluated eight patients with possible or probable paradoxical cerebral embolism. One patient had a hemispheric transient ischemic attack; the others had infarcts. Ischemic symptoms followed a Valsalvas maneuver in three cases. Others were linked to placement of a Swan-Ganz catheter, deep venous thrombosis and pulmonary embolism, right atrial myxoma, and use of oral contraceptives. Four had no known predisposing conditions. In six patients, contrast echocardiography showed right-to-left shunting. Cardiac catheterization showed a patent foramen ovale in three patients; one had an atrial septal defect. In the clinical setting of otherwise unexplained cerebral embolism in a young patient, paradoxical cerebral embolism should be considered. Contrast echocardiography is a useful screening test for this purpose.

A dose escalation study of ORG 10172 (low molecular weight heparinoid) in stroke

An intravenous infusion of a low molecular weight heparinoid, with a reduced risk of hemorrhage, may be an alternative to heparin in the management of acute ischemic stroke. To evaluate this hypothesis, we studied the safety of the heparinoid, ORG 10172, in a dose-escalation study in 26 patients. The drug was administered as a loading bolus followed by a 7-day infusion in five rates with target anti-factor Xa levels from 0.2 to 1.0 U/ml. The drug was well tolerated; no major bleeding complications or thrombocytopenia occurred. There were no deaths or hemorrhagic transformation of cerebral infarctions. The results indicate that ORG 10172 at doses to achieve a level of 1.0 U/ml or less may be used safely in management of acute cerebral infarction.

Spontaneous subarachnoid hemorrhage in young adults.

We evaluated 95 hospitalized patients (50 women and 45 men) aged 15 to 45 who had nontraumatic subarachnoid hemorrhage (SAH). Aneurysmal SAH was identified in 75 patients. Other causes for SAH were ruptured arteriovenous malformations (2 cases), amphetamine arteritis (1 case), and leptomeningeal melanoma (1 case). The cause of SAH was undetermined in 16 (17%) patients. Thirteen patients had histories of hypertension, 5 used oral contraceptives, and 4 had consumed large quantities of alcohol during the day before SAH. Only 1 patient had Type I diabetes mellitus. Diagnosis was delayed in 21 patients. Operation was performed in 71 patients, with only 3 (4.2%) deaths. The overall mortality was 8.4% (8 of 95), with all deaths due to neurological causes. Our data suggest that the overall management and surgical results of treatment of ruptured aneurysms in young adults are excellent, diabetes is rare among young adults with SAH, recent alcohol consumption does not seem to be a major factor predisposing to SAH in young adults, and misinterpretation of the early symptoms of SAH continues to be a serious problem.

Angiography of nonhemorrhagic cerebral infarction in young adults.

The radiographic examinations and hospital records of 93 young adult patients (15-45 years of age) with nonhemorrhagic cerebral infarction evaluated at our institution during the past 9 years were reviewed. The angiographic examinations were abnormal in 76% of patients. The most common abnormalities were embolic disease and atherothrombotic disease. Forty-seven patients underwent angiography within 7 days of their event. There were no major neurologic or systemic complications related to early angiography. We believe that angiography performed early in the course of the illness is a high-yield, safe procedure that may significantly alter the management of acute stroke in young adults.