During relapses in relapsing-remitting multiple sclerosis (RRMS), serum soluble HLA class I surface antigen (sHLA-I) levels are reported to either decrease or remain unchanged, whereas serum sHLA-II levels increase. Interferon-beta1b therapy was recently reported to increase serum sHLA-I in RRMS. In the present prospective study, solid-phase enzyme-linked immunosorbent assay was used to measure sHLA-I and sHLA-II in the sera of 21 RRMS patients during a clinical exacerbation, and then six weeks after treatment with high-dose interferon-beta1a (IFN-beta1a). Pretreatment serum sHLA-I was significantly lower in patients than in normal controls (P < 0.0005). Pretreatment sHLA-II was also significantly lower than in normal controls (P = .003) unless enhancing MRI lesions (objectified relapse) were present; then sHLA-II levels were similar to normal controls (relative increase). Six weeks after initiation of IFN-beta1a treatment, a significant increase in serum sHLA-I was observed in all 21 RRMS patients (P < .0005). Conversely, serum sHLA-II decreased significantly after treatment in the entire patient group (P < .0005). The acute effect of IFN-beta1a on serum sHLA-I and sHLA-II was observed to be the opposite of that occurring during RRMS relapses. Monitoring of both sHLA-I and sHLA-II appears necessary if these molecules are to be developed as RRMS activity markers.

Adult↗

PubMed2004

Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia.

The molecular basis of idiopathic generalized epilepsy remains poorly understood. Absence epilepsy with 3 Hz spike-wave EEG is one of the most common human epilepsies, and is associated with significant morbidity. Several spontaneously occurring genetic mouse models of absence epilepsy are caused by dysfunction of the P/Q-type voltage-gated calcium channel CaV2.1. Such mice exhibit a primary generalized spike-wave EEG, with frequencies in the range of 5-7 Hz, often associated with ataxia, evidence of cerebellar degeneration and abnormal posturing. Previously, we identified a single case of severe primary generalized epilepsy with ataxia associated with CaV2.1 dysfunction, suggesting a possible link between this channel and human absence epilepsy. We now report a family in which absence epilepsy segregates in an autosomal dominant fashion through three generations. Five members exhibit a combination of absence epilepsy (with 3 Hz spike-wave) and cerebellar ataxia. In patients with the absence epilepsy/ataxia phenotype, genetic marker analysis was consistent with linkage to the CACNA1A gene on chromosome 19, which encodes the main pore-forming alpha1A subunit of CaV2.1 channels (CaV2.1alpha1). DNA sequence analysis identified a novel point mutation resulting in a radical amino acid substitution (E147K) in CaV2.1alpha1, which segregated with the epilepsy/ataxia phenotype. Functional expression studies using human CACNA1A cDNA demonstrated that the E147K mutation results in impairment of calcium channel function. Impaired function of the brain calcium channel CaV2.1 may have a central role in the pathogenesis of certain cases of primary generalized epilepsy, particularly when associated with ataxia, which may be wrongly ascribed to anticonvulsant medication.

Adult↗

PubMed2003

Acute verbal dyspraxia, a rare presentation in multiple sclerosis: a case report with MRI localization.

Cortical speech disorders rarely occur in multiple sclerosis (MS). We report a patient with relapsing-remitting MS, who presented with acute verbal dyspraxia. Magnetic resonance imaging (MRI) demonstrated an acute T2/Flair hyperintense, primarily white matter lesion underlying the middle third of the inferior frontal gyrus. The verbal dyspraxia cleared beginning 48 hours after the initiation of iv dexamethasone. Follow-up MRI demonstrated qualitative and quantitative diminution of the hyperintensity. This is the first report of a clinically definite MS patient with acute verbal dyspraxia. Moreover, there was a suggestive localization of verbal praxis to Brodmann areas 44/45.

Acute Disease↗