Preventing ischemic stroke. Current approaches to primary and secondary prevention.

Preventing stroke is the most important strategy for reducing the cost of this disease. Management of modifiable risk factors, especially hypertension and Oral anticoagulation with warfarin for selected high-risk patients with nonvalvular atrial fibrillation. Carotid endarterectomy for selected patients with carotid artery stenosis greater than 60%. Regular physical exercise. Treatment with statin medications for patients who have coronary artery disease with or without hyperlipidemia. Routine use of antiplatelet medication has no proven role in primary stroke prevention, although aspirin is often prescribed for patients with vascular risk factors who have not yet had symptoms of either stroke or ischemic heart disease. The major strategies for secondary stroke prevention are: Appropriate evaluation to identify the mechanism of the initial stroke. Carotid endarterectomy for patients with symptomatic carotid artery stenosis of 50% or more. Oral anticoagulation with warfarin for patients with nonvalvular atrial fibrillation. Use of various antiplatelet agents, including aspirin, ticlopidine, clopidogrel, and the combination of aspirin and slow-release dipyridamole. Whether treatment of risk factors reduces the risk of secondary stroke is currently being evaluated in clinical trials.

Carotid endarterectomy. Which patients can benefit?

Carotid endarterectomy for carotid artery stenosis is valuable for some patients, but not all. Results of clinical trials in symptomatic and asymptomatic patients provide guidance on use of this common vascular procedure. The authors of this article describe the controversies and concerns with the procedure and give their recommendations based on study results.

Autonomic function in hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease)

Autonomic tests of heart rate and blood pressure control using both invasive and noninvasive techniques were performed on 11 patients with hereditary motor and sensory neuropathy (HMSN) types 1, and 4 patients with HMSN type 2. The results were compared with those of 76 control subjects. No significant difference was found between the patient and control groups. Impairment of sweating on the extremities was found in patients with HMSN types 1 and 2, consistent with distal degeneration of sympathetic fibers in peripheral nerves, but there were no abnormalities of cardiovascular reflex control mechanisms.

Predictors of intracranial carotid artery atherosclerosis. Duration of cigarette smoking and hypertension are more powerful than serum lipid levels.

The effect of cigarette smoking on intracranial internal carotid artery atherosclerosis (ICAS) was studied by obtaining cigarette smoking histories and data on other potential predictors, including serum lipid estimations, for consecutive patients undergoing carotid arteriography. The duration of cigarette smoking was the most significant independent predictor of the presence of ICAS. Other independently significant predictors of ICAS were hypertension, diabetes mellitus, and current systolic blood pressure. The interaction of diabetes and duration of smoking was a significant negative predictor. In patients for whom serum lipid values were available, lower levels of apolipoprotein A-I were associated with a higher risk of having ICAS. However, the effect of apolipoprotein A-I as a predictor of the presence of ICAS was far outweighted by the effects of duration of smoking and hypertension.

Serum lipids and lipoproteins are less powerful predictors of extracranial carotid artery atherosclerosis than are cigarette smoking and hypertension.

The effect of serum lipids and lipoproteins on extracranial carotid artery atherosclerosis (CAS) was studied in patients who underwent carotid arteriography. Serum lipid and lipoprotein values along with data on other potential predictors of extracranial CAS were determined in 240 patients who had at least one extracranial carotid artery visualized. In a multiple logistic regression analysis, the independently significant predictors of the presence of extracranial CAS were, in decreasing order of significance, duration of smoking of cigarettes, hypertension, age, and low-density lipoprotein cholesterol. Serum cholesterol, triglycerides, high-density lipoprotein cholesterol, and apolipoprotein A-I did not show an independent effect. Although low-density lipoprotein cholesterol was an independent predictor of the presence of extracranial CAS, its effect as a predictor was far outweighed by the effects of the duration of smoking of cigarettes and a history of hypertension.

Autonomic function in Friedreich's ataxia.

Autonomic function studies were performed on 15 patients with Friedreich's ataxia, and the results compared with those of 76 healthy subjects. There was an increase in resting supine heart rate, attributed to cardiac abnormalities. Other tests of sympathetic and parasympathetic function were normal. The normal autonomic function studies are consistent with the pathological findings of degeneration predominantly of large diameter myelinated fibres with sparing of small myelinated and unmyelinated fibres.

The effect of ageing on autonomic nervous system function.

We studied 76 healthy subjects (five-85 years) with a number of invasive and non-invasive tests of autonomic function. Age related effects were found with the tests of predominantly vagal cardiovascular function. However, there were no age related effects found with the tests of predominantly sympathetic cardiovascular function. The age of the subject should be taken into consideration when evaluating tests of autonomic function and each laboratory should establish its own control values.

Duration of cigarette smoking is the strongest predictor of severe extracranial carotid artery atherosclerosis.

The effect of cigarette smoking on extracranial carotid atherosclerosis was studies by obtaining cigarette smoking histories and information on other potential risk factors from consecutive patients undergoing carotid arteriography. At least on extracranial carotid artery was visualized in 752 patients in whom the extent of carotid atherosclerosis was assessed. The total years of cigarette smoking was the most significant independent predictor of the presence of severe carotid atherosclerosis. Other independent predictors, in order of significance, were age, hypertension, diabetes mellitus, male sex, and current systolic blood pressure. By age 60 years, the risk of having severe carotid atherosclerosis for a person who had smoked for 40 years was approximately 3.5 times that for a never smoker. The major benefit of smoking cessation is in limiting the accumulation of smoking years.

Autonomic function and unmyelinated fibers in chronic inflammatory demyelinating polyradiculoneuropathy.

Because autonomic function may be abnormal in some demyelinating peripheral neuropathies, it has been studied with a number of noninvasive and invasive tests in 14 patients with chronic inflammatory demyelinating polyradiculoneuropathy. There were abnormalities of the 30:15 ratio in 3 patients and an abnormal thermoregulatory sweat test in 5 patients. These findings are indicative of mild parasympathetic and sympathetic dysfunction. Minor pathological changes in unmyelinated fibers were demonstrated on morphometric examination of sural nerves of 10 patients.

Has there been a decline in subarachnoid hemorrhage mortality?

We studied subarachnoid hemorrhage in the population of Rochester, Minnesota, for the 40-year period from 1945 through 1984. The average annual incidence rate of subarachnoid hemorrhage in Rochester has remained constant at approximately 11 per 100,000 population. Age-specific incidence rates increased with age. However, the average annual mortality rate for subarachnoid hemorrhage in Rochester has shown a decreasing trend, from 6.8 per 100,000 population in 1955-1964 to 4.3 in 1975-1984. It is likely that this is due to a decrease in case-fatality rates from 57% in 1945-1974 to 42% in 1975-1984 (p = 0.10). This decreasing trend was also evident in annual mortality rates from subarachnoid hemorrhage for US white men and women. The reason for the improved case-fatality rate is unclear, but it may be related to changes in management. The interval from onset of subarachnoid hemorrhage to surgery decreased from a median of 12 days in 1975-1979 to 2 days in 1980-1984, and of those who survived to receive medical attention, more patients received some form of medical treatment in 1980-1984. Whether either or both of these changes have led to the decrease in the case-fatality rate is uncertain.

Predictive value of carotid bruit for carotid atherosclerosis.

To assess the predictive value of carotid bruit for moderate-to-severe carotid atherosclerosis, the results of carotid arteriograms performed on 1004 subjects were correlated with the findings of auscultation of the carotid arteries. Predictive values of carotid bruit for ipsilateral extracranial carotid atherosclerosis were 77% for localized bruits and 74% for diffuse bruits. The predictive values of extracranial carotid bruit for ipsilateral intracranial carotid atherosclerosis were 16% for localized bruits and 18% for diffuse bruits. Assessing both carotid arteries together, the predictive value of carotid bruit for moderate-to-severe atherosclerosis at any extracranial carotid site was 85%, there being no difference whether the bruits were diffuse, localized, bilateral, or unilateral. Diffuse or localized bruits, whether unilateral or bilateral, are equally predictive of moderate-to-severe atherosclerosis in the extracranial carotid artery, but both are poor predictors of intracranial carotid artery disease.

Peripheral sensorimotor and autonomic neuropathy associated with systemic lupus erythematosus. Clinical, pathological and immunological features.

The clinical features and pathological findings in the sural nerves are described of 7 patients with peripheral neuropathy; in 4 cases the criteria for diagnosis of systemic lupus erythematosus (SLE) were satisfied and in 3 other cases there was serological evidence of an undifferentiated connective tissue disease, most probably SLE. The peripheral neuropathy was of a chronic sensorimotor type with predominantly sensory features and gradual onset. In 2 cases the presentation was asymmetric. One patient had autonomic dysfunction. The pathological findings in the biopsied sural nerves were those of axonal degeneration and vasculitis. In 6 nerves there was increased expression of Class II (Ia) antigen within the nerve fascicle, perineurium and within endothelial cells.

Neuroleptic malignant syndrome.

The neuroleptic malignant syndrome is a relatively rare but potentially fatal complication of the use of major tranquillizers; mortality may be as high as 20%. The syndrome is manifest by the onset of hyperpyrexia, muscular rigidity and tremor, impaired consciousness and autonomic dysfunction. The pathophysiology is thought to be by way of dopamine receptor blockade. The syndrome is managed by cessation of the neuroleptic medication, by supportive measures and by instituting treatment with one or more of a number of specific drugs whose use is based on theoretical considerations rather than empirical evidence of efficacy; these drugs include anticholinergics, L-dopa, bromocriptine amantidine and dantrolene sodium. Although not proven, early recognition and treatment may reduce both the mortality and the longer term morbidity of this syndrome.