Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.

From spinal shock to spasticity: neuronal adaptations to a spinal cord injury.

OBJECTIVE: To investigate the adaptational changes in excitability of spinal neuronal circuits below the level of lesion from spinal shock to spasticity in patients with spinal cord injury (SCI). METHODS: More than 6 months after an acute SCI, clinical follow-up examinations were paralleled by electrophysiologic recordings with tibial nerve stimulation (M-wave, F-wave, H-reflex, and flexor reflex). RESULTS: During spinal shock, the loss of tendon tap reflexes and flaccid muscle tone were associated with low persistence of F-waves and loss of flexor reflexes, whereas H-reflexes were already elicitable. During the transition to spasticity, the reappearance of tendon tap reflexes and muscle tone and the occurrence of spasms was associated with the recovery of F-waves and flexor reflex excitability, whereas the H-to-M ratio remained about stable over months. At later stages (2 to 6 months after SCI) when clinical signs of spasticity became established, the electrophysiologic measures showed little change. In paraplegic patients, in contrast to tetraplegic patients, M-wave and flexor reflex amplitudes even decreased. CONCLUSIONS: The late decrease in M-wave and flexor reflex amplitude in paraplegic patients suggests a secondary impairment/degeneration of premotoneuronal circuits and of motoneurons. The divergent course of clinical signs of spasticity and their probable neuronal correlates indicates the occurrence of non-neuronal changes contributing to spasticity.

[Descending paralysis caused by wound botulism. A case report]. / Deszendierende Lähmung durch Wundbotulismus. Eine Falldarstellung.

We report on the history and clinical findings of an injecting drug abuser in the Canton of Zurich who presented with multiple deep abscesses in the arms and legs. A diagnosis of wound botulism was made based on his clinical presentation with a rapidly progressing descending paralysis starting at the cranial nerves, a neuromuscular junction disorder on neurophysiologic testing, and normal findings on lumbar puncture. Several cases of wound botulism have occurred in i.v. drug abuse in Switzerland since 1997. We suspect subcutaneous injections of contaminated heroin containing Clostridium spores as sites of entry. Wound botulism caused by Clostridium botulinum is a rare cause of rapidly progressing, generalized, flaccid paralysis and should be considered in patients with a history of i.v. drug abuse presenting with descending paralysis.

Progressive hemiparesis in frontal lobe degeneration.

Hemiparesis has rarely been observed in frontal lobe degeneration (FLD). We describe the clinical, neuropsychological and neuroimaging findings of a patient in whom a slowly evolving hemiparesis was the principal symptom of FLD, and of 2 demented patients in whom hemiparesis was an early and prominent symptom. The occurrence of central motor deficits in FLD is reviewed, and a synopsis of the differential diagnosis of hemiparesis in neurodegenerative diseases is given.

[Choreoacanthocytosis. A neurologic-hematologic syndrome]. / Die Choreoakanthozytose. Ein neurologisch-hämatologisches Syndrom.

A 43 year old male patient is reported who presented at the age of 33 years with a hyperkinetic movement disorder. At the time of presentation orofacial dyskinesias, tic-like hyperkinesias with vocalisation and behavioural disturbance dominated the clinical picture. In the course of his illness he developed a marked truncal choreoathetosis and a symmetrical, distal, predominantly motor polyneuropathy with wasting of lower leg muscles. Serum creatinine kinase levels were markedly elevated. Serum lipids and lipoproteins were within normal limits. These clinical features in combination with an increased number of acanthocytes, clearly visible after dilution of whole blood with normal saline (1:1), led to the diagnosis of choreoacanthocytosis (CA). Both parents were neurologically and behaviourally normal, but were found to have acanthocytes in saline diluted whole blood. The literature concerning CA is reviewed.