Reversible, predominantly posterior leukoencephalopathy may develop in patients who have renal insufficiency or hypertension or who are immunosuppressed. The findings on neuroimaging are characteristic of subcortical edema without infarction.

We describe and functionally characterize six mutations of the acetylcholine receptor (AChR) epsilon subunit gene in three congenital myasthenic syndrome patients. Endplate studies demonstrated severe endplate AChR deficiency, dispersed endplate regions and well preserved junctional folds in all three patients. Electrophysiologic studies were consistent with expression of the fetal gamma-AChR at the endplates in one patient, prolongation of some channel events in another and gamma-AChR expression as well as some shorter than normal channel events in still another. Genetic analysis revealed two recessive and heteroallelic epsilon subunit gene mutations in each patient. One mutation in each (epsilonC190T [epsilon R64X], epsilon 127ins5 and epsilon 553del 7) generates a nonsense codon that predicts truncation of the epsilon subunit in its N-terminal, extracellular domain; and one mutation in each generates a missense codon (epsilon R147L, epsilon P245L and epsilon R311W). None of the mutations was detected in 100 controls. Expression studies in HEK cells indicate that the three nonsense mutations are null mutations and that surface expression of AChRs harboring the missense mutations is significantly reduced. Kinetic analysis of AChRs harboring the missense mutations show that epsilon R147L is kinetically benign, epsilon P245L prolongs burst open duration 2-fold by slowing the rate of channel closing and epsilon R311W shortens burst duration 2-fold by slowing the rate of channel opening and speeding the rate of ACh dissociation. The modest changes in activation kinetics are probably overshadowed by reduced expression of the missense mutations. The consequences of the endplate AChR deficiency are mitigated by persistent expression of gamma-AChR, changes in the release of transmitter quanta and appearance of multiple endplate regions on the muscle fiber.

Background: Vertebrobasilar dolichoectasia is often found in patients with posterior circulation ischemia. Brain ischemia is caused by abnormal flow in the dilated artery and obstruction of paramedian arteries or intraluminal thrombus with artery-to-artery embolism. We report a patient with vertebrobasilar dolichoectasia and luminal thrombus treated with intravenous urokinase who did well but died 2 months later of subarachnoid hemorrhage. Case Description: A 60-year-old man developed right-hand clumsiness, dysarthria and ataxia. Computed tomography showed vertebrobasilar dolichoectasia and thrombus in the basilar artery. Symptoms quickly resolved on heparin but recurred on warfarin and again resolved on heparin. Two weeks later, while on warfarin and aspirin 325 mg, he developed hand numbness, oscillopsia and ataxia. Symptoms again resolved on heparin. Angiography showed severe dolichoectasia of the distal right vertebral artery and basilar artery. A large mural thrombus was detected in the ventral part of the distal basilar artery narrowing the lumen by 50%. He was treated with intravenous urokinase 4,400 units/kg as a bolus followed by 4,400 units/kg/h for 12 h. Repeat angiography showed almost complete recanalization and improved filling of basilar artery branches. He was maintained on warfarin and aspirin 81 mg and had no further ischemic episodes. He died 2 months later of rupture of the basilar artery and subarachnoid hemorrhage. Conclusion: Some patients with thrombosis of vertebrobasilar dolichoectactic arteries continue to have ischemic symptoms despite adequate anticoagulation. Intravenous thrombolysis may be effective in reducing the risk of stroke, but the risk/benefit ratio needs to be assessed in each patient.

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