Extension of the Clinicoradiologic Spectrum of Newly Described End-Truncating LAMB1 Variations.

Objectives: To refine the clinical spectrum of a very recently identified phenotype associated with LAMB1 end-truncating pathogenic variations. Methods: Detailed clinical, neuropsychological, and MRI investigation of 6 patients from 2 unrelated families segregating end-truncating LAMB1 variations. Results: All patients harbored a LAMB1 end-truncating pathogenic variation. The specific association of a hippocampal type episodic memory dysfunction and a diffuse leukoencephalopathy was observed in all 4 patients aged older than 50 years, slightly worsening over time in 2 patients with several years of follow-up. Additional unspecific neurologic symptoms are reported, such as episodes of numbness, language troubles, or faintness in these 4 patients and the 2 younger ones. Discussion: The association of an extensive leukoencephalopathy with an episodic memory dysfunction of the hippocampal type is strongly suggestive of a LAMB1 end-truncating variation in adults older than 50 years. Early cognitive complaints and imaging abnormalities might exist decades before. Additional transient manifestations can be observed, and this association should lead to LAMB1 screening to avoid unnecessary invasive investigations.

Phenotypic variability of episodic ataxia type 2 mutations: a family study.

BACKGROUND: Episodic ataxia type 2 (EA2) is characterized by paroxysmal bouts of ataxia and progressive cerebellar dysfunction. Other manifestations may also be associated, such as migraine attacks with or without aura, absence epilepsy and mental retardation. METHODS: To describe the intrafamilial variability of clinical manifestations of 3 patients harboring a novel CACNA1A point mutation in exon 7 (nucleotide insertion c.1063dupG) typical of EA2 mutation. RESULTS: All 3 patients presented paroxysmal bouts of ataxia, but age of onset, associated symptoms and symptoms at clinical onset were clearly distinct with hemiplegic migraine attacks in the father, absence epilepsy in one child and mental retardation in the other child. CONCLUSION: Typical manifestations of EA2 may be associated and temporally preceded by rare manifestations such as hemiplegic migraine attacks, epilepsy and mental retardation. Moreover, patients sharing a given CACNA1A mutation may present very different phenotypes even within the same family.

Insular involvement in brain infarction increases risk for cardiac arrhythmia and death.

OBJECTIVE: Brain injuries may induce cardiac dysrhythmias and sudden cardiac death. METHODS: We analyzed 12-lead electrocardiograms of 493 consecutive patients with brain infarction (BI) proved by an magnetic resonance imaging and 493 control subjects matched for age, sex, and center. Insular involvement (insula (+/-)) was assessed by two independent readings of the magnetic resonance imaging scans. Cases were followed for 5 years. RESULTS: Acute BI was independently associated with heart rate (< or = 64 beats/min), abnormal repolarization, atrial fibrillation, and ventricular and supraventricular ectopic beats. Lower heart rate in BI patients was due to an interaction with smoking (p for interaction = 0.004). Insula(+) group was significantly associated with abnormal repolarization with no interaction with infarct side. Atrial fibrillation by history was also more frequent in the insula(+) than in the insula(-) group (p = 0.07). After adjustment for age, sex, cardiovascular history, and handicap at admission, right insula(+) BI was significantly associated with 2-year all-cause death (hazard ratio, 2.11; 95% confidence interval, 1.27-3.52) and with vascular death (hazard ratio, 2.00; 95% confidence interval, 1.00-3.93). In multivariate analysis including age, sex, cardiovascular history, handicap at admission, and lesion side, increased QTc interval and left bundle branch block were independent predictors of all-cause and vascular mortality at 2 years in right insula(+) patients. INTERPRETATION: These findings support the notion that right insular involvement may lead to electrocardiographic abnormalities with potential prognostic implications. This could be important for optimal care in patients with right insular infarct.

Cerebral sinus venous thrombosis in two patients with spontaneous intracranial hypotension.

We report 2 patients who had clinical and neuroimaging signs of spontaneous intracranial hypotension and who developed cerebral sinus venous thrombosis. This sequence of events -- known after dural puncture but not in spontaneous intracranial hypotension -- was suggested by the change in the pattern of headache, from a postural to a permanent and increasing one. The diagnostic and therapeutic difficulties that this complication raises are discussed.