Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency.

BACKGROUND: Although hyperhomocyst(e)inemia (Hyper-Hcy) may predispose to atherosclerosis and venous thrombosis, the mechanisms of stroke associated with Hyper-Hcy are not defined. METHODS: Clinical and biochemical phenotypes and genetic features of three unrelated patients with premature stroke and severe Hyper-Hcy due to cystathionine beta-synthase (CBS) deficiency are described. Plasma Hcy and amino acids were measured by fluorescence polarization immune assay and ion exchange chromatography. Analysis of the CBS and methylenetetrahydrofolate reductase genes was performed by restriction enzyme digestion and sequence analysis. RESULTS: Two of the three index cases had no known diagnosis of homocystinuria and initially presented with embolic cerebral and retinal infarction in mid-adulthood. Mechanisms of cerebrovascular disease were carotid intraluminal thrombosis, arterial dissection, and possible cardiac embolism. Family screening revealed additional members with clinically silent homocystinuria and severe Hyper-Hcy. Excluding tall stature in two individuals, all had mild phenotypes, without classic findings of CBS deficiency. Plasma total and free Hcy, methionine, and urine Hcy were elevated. Genotyping revealed heterozygous CBS mutations (I278T, D444N, G307S) in affected individuals. CONCLUSION: Artery-to-artery embolism and dissection may cause stroke in young adults with homocystinuria. The results also support a rationale for screening for Hyper-Hcy in young adults with stroke without a phenotype suggestive of classic homocystinuria.

Stroke following coronary-artery bypass surgery. A case-control estimate of the risk from carotid bruits.

The causes of stroke following coronary-artery bypass surgery are largely unknown. To determine whether carotid bruits increase the risk of these events, we compared 54 patients with postoperative stroke or transient ischemic attacks with 54 randomly selected control patients. Both groups were drawn from 5915 consecutive patients who had coronary bypass surgery at our hospital from 1970 to 1984. Carotid bruits were noted preoperatively in 13 patients with postoperative stroke and in 4 control patients. Case-control analysis showed that the presence of carotid bruits increased the risk of stroke or transient ischemic attacks by 3.9-fold (95 percent confidence interval, 1.2 to 12.8; P less than 0.05). This increased risk remained essentially unchanged after adjustment for potentially confounding variables in a multiple logistic regression analysis. Other factors associated with a significantly increased risk (P less than 0.05) of these neurologic deficits were a history of stroke or transient ischemic attack (odds ratio, 6.0; 95 percent confidence interval, 1.6 to 22.1), a history of congestive heart failure (odds ratio, 5.3; confidence interval, 1.6 to 17.0), mitral regurgitation (odds ratio, 4.3; confidence interval, 1.4 to 12.9), postoperative atrial fibrillation (odds ratio, 3.0; confidence interval, 1.4 to 6.7), a cardiopulmonary-bypass pump time of more than two hours (odds ratio, 2.7; confidence interval, 1.1 to 6.7), and a previous myocardial infarction (odds ratio, 2.3; confidence interval, 1.1 to 5.1). We conclude that the presence of carotid bruits increases the risk of stroke after coronary-artery bypass surgery. However, the absolute magnitude of this risk, 2.9 percent, is small and comparable to the reported risk of stroke from carotid endarterectomy.

Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D.

A group of young patients having multiple sclerosis was treated with dietary supplements containing calcium, magnesium and vitamin D for a period of one to two years. The experimental design employed self-pairing: the response of each patient was compared with his/her own case history as control. The number of exacerbations observed during the program was less than one half the number expected from case histories. No side effects were apparent. The dietary regimen may offer a new means of controlling the exacerbation rate in MS, at least for younger patients. The results tend to support a theory of MS which states that calcium and magnesium are important in the development, structure and stability of myelin.

Asymmetrical hydrocephalus following ventriculitis from rupture of a thalamic abscess.

Ventriculitis developed suddenly in a patient with an undiagnosed abscess and was accompanied by obtundation, fever, meningismus, and hemiplegia. Aspiration of a streptococcal thalamic abscess and high doses of intravenous penicillin produced marked improvement. Increasing dysphasia 5 weeks later was accompanied by ventricular dilatation, most marked on the left, with no evidence of recurrent abscess. The left foramen of Monro was demonstrably patent. Shunting relieved the symptoms of aphasia; they recurred with one episode of malfunction of the shunt. This case lends support to the belief that parenchymal characteristics are important in hydrocephalus and demonstrates how asymmetrical ventricular dilatation can produce focal symptoms.