Isoniazid exposure and pyridoxine levels in human immunodeficiency virus associated distal sensory neuropathy.

SETTING: Distal sensory polyneuropathy (DSP) may manifest in human immunodeficiency virus (HIV) infected individuals before or after antiretroviral therapy (ART). DSP can also occur in response to isoniazid (INH); this can be prevented by pyridoxine supplementation. N-acetyltransferase 2 (NAT2) polymorphisms influence drug acetylation and possibly the risk for INH-associated DSP. OBJECTIVE: To investigate the relationship between previous/current TB, pyridoxine deficiency and DSP in HIV-infected individuals enrolled in a government-sponsored HIV programme. DESIGN: Neuropathy assessments were performed among 159 adults pre-ART and 12 and 24 weeks thereafter. DSP was defined as ⩾1 neuropathic symptom and sign. NAT2 genotypes predicted acetylation phenotype. Serum pyridoxine levels (PLP) were quantified at baseline and week 12. RESULTS: DSP was present in 16% of individuals pre-ART and was associated with previous/current TB (P = 0.020). Over 50% were pyridoxine deficient (PLP < 25 nmol/l), despite supplementation with vitamin B complex supplements (2-4 mg/day pyridoxine). Those with a history of TB and pre-ART DSP were more likely to be pyridoxine deficient (P = 0.029), and slow/intermediate NAT2 phenotypes impacted on their PLP levels. Incident/worsening DSP after ART developed in 21% of the participants. PLP levels remained low after ART, particularly among those with prior TB, but without an association between DSP or NAT2 phenotypes. CONCLUSION: Adequate pyridoxine supplementation before ART initiation should be prioritised, particularly in those with a history of TB or current TB.

Antiepileptic drug-induced visual hallucinations in a child.

The neurologic signs and symptoms of carbamazepine and phenytoin toxicity, such as ataxia, dysarthria, and nystagmus, are well known. The psychiatric manifestations of toxicity, such as psychosis and hallucinations, however, are less widely recognized. This study reports the case of a 9-year-old male with seizures who developed intermittent complex visual hallucinations after therapy with antiepileptic drugs was begun. This study considered seizures, migraine, underlying psychiatric diathesis, and drug toxicity as possible etiologies but after extensive investigation concluded that his symptoms were most likely a drug side effect.

Human immunodeficiency virus-associated pure motor lumbosacral polyradiculopathy.

BACKGROUND: Neuromuscular disease is a common manifestation of human immunodeficiency virus infection and acquired immunodeficiency syndrome, but isolated and severe pathology confined to the motor roots or anterior horn cells are not a recognized clinical entity. OBJECTIVE: To describe the novel clinical presentation of human immunodeficiency virus-related polyradiculopathy manifesting as isolated severe motor symptoms confined to the legs. DESIGN: A case series comprising 4 patients identified prospectively during a 6-month period. SETTING: Patients were seen in the Department of Neurology, Groote Schuur Hospital, Cape Town, South Africa. This is an 800-bed teaching hospital, with approximately 5000 patients seen annually in the Department of Neurology. PATIENTS: Patients were identified by their unique presentation with a severe isolated motor neuropathy in the lower limbs. All were Xhosa-speaking African women. RESULT: Early human immunodeficiency virus infection may be associated with pure motor lumbosacral polyradiculopathy. CONCLUSION: It remains unclear whether this clinical syndrome should be regarded as a variant of the Guillain-Barre syndrome or whether it represents a unique disorder associated with early human immunodeficiency virus infection.

Lack of effect of Miller Fisher sera/plasmas on transmitter release from PC12 cells.

IgG antibodies to GQ1b ganglioside are found in > 90% of patients with the Miller Fisher Syndrome (MFS). MFS sera or IgG preparations have marked effects on neurotransmitter release at the neuromuscular junction, but their mode(s) of action remain unclear. To establish a cell-based system for investigating the mechanism of action of MFS serum preparations, we looked at neurotransmitter release from three cell lines. We failed to demonstrate substantial 14C-acetylcholine release from two motor-neuronal cell lines, VSC4.1 and NSC19, and therefore studied 3H-noradrenaline release from NGF-differentiated PC12 cells, a neural-crest derived catecholaminergic cell line. K(+)-induced release was inhibited by botulinum toxin and basal release was enhanced by alpha-latrotoxin, resembling that at the neuromuscular junction, although K(+)-induced release was dependent on L-type rather than P/Q-type calcium channels. The cells expressed polysialylated gangliosides on the cell surface. Incubation in heat-inactivated or untreated MFS preparations did not, however, affect basal or K(+)-induced release. Thus the PC12 cells do not appear to be sensitive to the effects of serum antibodies from MFS patients.