Possible anticipation associated with a novel splice site mutation in episodic ataxia type 2.

Anticipation is a phenomenon characterized by decreasing age at onset and increasing severity of symptoms of a disease in successive generations within a pedigree. Anticipation mostly occurs in neurodegenerative diseases with expansion of unstable trinucleotide repeats. However, it has not been previously pointed out in episodic ataxia type 2 (EA2). Clinical and genetic analyses were performed in nine members from three consecutive generations of a Korean family with EA2. We performed a polymerase chain reaction (PCR)-based direct sequence analysis of all coding regions of CACNA1A using genomic DNA. The clinically affected family members showed recurrent vertigo, interictal nystagmus, and childhood epilepsy. There is a decrease in the age onset (possible genetic anticipation) in three succeeding generations of the family. Genetic analysis identified a splice site mutation (p.Val1465Glyfs13X) and normal trinucleotide repeats in CACNA1A in all clinically affected and one unaffected members. Recognizing anticipation would aid in genetic counseling in EA2.

A case of Lewis-Sumner syndrome showing dramatic improvement after plasma exchange.

We report a patient with Lewis-Sumner syndrome (LSS) who showed an improvement only with plasma exchange (PE). The patient, 32-yr old man, had progressive multifocal motor-sensory deficits with persistent, multiple conduction blocks and marked slowing of NCVs. Nerve pathology supported a diagnosis of demyelinating neuropathy by revealing marked loss of myelinated fibers with inter- and intrafascicular variation. Although the patient was refractory to treatment with corticosteroid and intravenous immunoglobulin, PE produced a dramatic improvement. Our experience strongly proposes that PE should be tried for refractory LSS.