Mutations in SACS cause atypical and late-onset forms of ARSACS.

BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a complex neurodegenerative disorder caused by mutations in SACS. The phenotype consists of a childhood-onset triad of cerebellar ataxia, peripheral neuropathy, and pyramidal tract signs. OBJECTIVE: To provide more insight into the prevalence of SACS mutations and the variability of the associated phenotype. METHODS: Mutation screening of SACS by direct sequencing and multiplex amplicon quantification for detection of intragenic copy number variations in a cohort of 85 index patients with phenotypes suggestive for ARSACS. Additional short tandem repeat (STR) marker analysis was performed for haplotype sharing. RESULTS: In 11 families,18 new SACS mutations were found (12.9% of total cohort). Five patients displayed onset ages in adulthood, a feature not known to be associated with ARSACS. The remaining index patients displayed a classic early onset phenotype. Initial phenotypic presentation was atypical in several patients, obscuring the clinical diagnosis. A founder mutation in SACS was identified in 3 Belgian families. In one isolated patient, an intragenic SACS deletion of exons 3-5 was detected. Partial SACS deletions were not previously described. CONCLUSIONS: In this study, we enlarge the ARSACS phenotype and the underlying genetic spectrum of SACS mutations. Patients with ARSACS are more common than previously known and risk underdiagnosis due to late onset age and unusual presentation.

Diagnostic significance of antinuclear antibodies in neurologic patients.

In a combined retrospective and prospective study, we tried to define the prevalence of antinuclear antibodies (ANA) and its clinical relevance in neurological patients. Three hundred twenty-seven neurological patients who had ANA determined because of suspicion of connective tissue disease (CTD), were retrospectively studied. Thirty (9.2%) were ANA positive, 20 (66%) of whom had CTD. Of 327 consecutively admitted patients, prospectively studied, 18 (5.5%) were ANA positive, 5 (28%) of whom had evidence of CTD. Systemic lupus erythematosus (SLE) was the most frequently diagnosed CTD. In a prospective study of 48 multiple sclerosis (MS) patients, only 1 had detectable ANA at a dilution of 1:40. Lupus anticoagulant (LA) was prospectively detected in 2 patients but was not associated with a vascular or autoimmune systemic disease.

Bilateral faciobrachial paresis as a consequence of symmetrical capsular infarcts.

A 32-year old man presented with a bilateral faciobrachial paresis, pyramidal signs in the upper limbs and dysarthria. Computer tomographic (CT-)scans showed bilateral cortical zones of contrast enhancement and strikingly symmetrical capsular hypodensities. Angiography revealed a stenosis of the left internal carotid artery and an occlusion of the right internal carotid artery. Essential thrombocythemia was diagnosed as the underlying disorder. Since there are no indications of pontine lesions, we assume that the signs and symptoms in this patient could mainly be attributed to the bilateral capsular lesions, that resemble lacunar infarcts.

Serial magnetic resonance imaging studies with paramagnetic contrast medium: assessment of disease activity in patients with multiple sclerosis before and after influenza vaccination.

Eleven patients with a relapsing-remitting form of multiple sclerosis (MS) were examined clinically and with magnetic resonance imaging scans 3 weeks before, at the day of vaccination with killed influenza virus and 3 weeks afterwards. No exacerbations were noted in the pre- or postvaccination period. Eight contrast-enhanced or active lesions were present at the onset of the study. Three new active lesions appeared at the end of the prevaccination period while only 1 new active lesion was found at the end of the postvaccination period. We conclude that vaccination with killed influenza virus has no clinical or subclinical short-term effect on the activity of MS.