Machado-Joseph disease in a Nigerian family: mutational origin and review of the literature.

Machado-Joseph disease (MJD) has been described in Africans, but no cases have been reported from Nigeria. Current MJD global distribution results from both the ancestral populations-of-origin and the founder effects of mutations, some as a consequence of the Portuguese sea travels in the 15th to 16th century. Two main ancestral haplotypes have been identified: the Machado lineage, which is more recent, predominant in families of Portuguese extraction, and the Joseph lineage, which is much older and worldwide spread, postulated to have an Asian origin. We report a Nigerian family with MJD from Calabar, once settled by Portuguese slave traders, and assessed its mutational origin. The proband was a 33-year-old man with progressive unsteady gait, weakness of all limbs, dysphagia, dysarthria, urinary frequency and diaphoresis. He had end-of-gaze nystagmus, spastic quadriparesis and atrophic small muscles of the hand. He showed fibrillation potentials on EMG, and nerve conduction studies suggested a central axonopathy without demyelination. This family bears the Joseph haplotype, which has a founder effect in the island of Flores, in the Azores (and their descendants in North-America), but is also the most common in non-Portuguese populations worldwide, with an estimated mutation age of around 7000 years.

The neurological consequences of explosives.

Neurological injuries produced by explosive blasts are the result of a cascade of events that begin with the initial explosion and evolve from the secondary, tertiary, and quaternary effects that the explosion engenders [Lavonis EJ. Blast Injuries. EMedicine.htm]. Only the results of the primary blast are predictable, and subsequent actions ripple outward in an increasingly random and chance sequence. This article reviews and explains how the ensuing chain of circumstances injures the nervous system, and what examining physicians should anticipate when they treat these patients.

A comparison of two treatment regimens of ceftriaxone in late Lyme disease.

BACKGROUND: The optimal duration of treatment for patients with late Lyme disease is unresolved. METHODS: In a prospective, open label, randomized, multi-center study, a 14 day course of ceftriaxone was compared to 28 days of therapy. Entry criteria included objective abnormalities compatible with late Lyme disease and serologic reactivity to Borrelia burgdorferi. Randomization took place prior to obtaining serologic results. Clinical response was rated as cure; improvement; failure; or not assessable. RESULTS: Of the 201 patients randomized, 21 patients in the 14 day group and 37 in the 28-day group were excluded from the study for failure to meet serologic criteria. Of those who met serologic criteria, 80 patients received 14 days and 63 received 28 days of ceftriaxone. At time of last evaluation, there were 5 treatment failures in the 14 day group and none in the 28 day group (p = 0.07). Clinical cure rates were 76% for the 14 day group and 70% for the 28 day group (p = NS). Therapy was discontinued due to adverse events for a significantly greater proportion of patients in the 28-day group compared to the 14-day group (p < 0.02). CONCLUSIONS: Ceftriaxone for 14 days eradicated the signs and symptoms of late Lyme disease in the majority of evaluable patients. Although there were more failures in the 14-day group than in the 28-day group, this study did not have the power to determine if a clinical subset of patients may benefit from 28 days of therapy.