OBJECTIVE: To investigate progressive, severe neuromuscular weakness associated with lactic acidosis in some HIV-infected patients after exposure to nucleoside reverse transcriptase inhibitors (NRTI). METHODS: HIV-associated neuromuscular weakness syndrome (HANWS) was retrospectively identified and classified based on the level of diagnostic certainty: possible (progressive weakness owing to neuromuscular disease), probable (progressive neuromuscular weakness with documented exclusion of confounding causes), or definite (progressive weakness and electrophysiological or pathological evidence of neuromuscular pathology). RESULTS: Of 69 patients identified with HANWS, 27 had definite HANWS, 19 probable, and 23 possible. In 44 patients with documented follow-up, 16 required intubation and nine died. There was a marginal association between death and hyperlactatemia (P = 0.061). At onset of neurological symptoms, 68 were receiving antiretroviral therapy, including stavudine for 61 (89.7%). Serum lactate level was elevated (> 2.2 mmol/l) in 30/37 (81%), with a trend towards an association between hyperlactatemia and stavudine usage (P = 0.087). In 25, neurological symptoms occurred after antiretroviral therapy discontinuation (median, 14 days). Electrophysiological studies (n = 24) indicated sensorimotor neuropathy in 20 patients and myopathy in three. Nerve biopsy (n = 9) revealed axonal degeneration and inflammation in three, mixed axonal and demyelinating lesions in three, and primary axonal neuropathy in three. Of 15 muscle biopsies, three revealed inflammation and four mitochondrial abnormalities. CONCLUSIONS: A severe neuromuscular weakness syndrome may occur in HIV-infected individuals. The association with hyperlactatemia and NRTI exposure supports mitochondrial toxicity as a pathogenesis. In some, the onset of neurological symptoms lagged significantly after discontinuation of antiretroviral therapy, suggesting that different etiological mechanisms may underlie these cases.
OBJECTIVE: To investigate progressive, severe neuromuscular weakness associated with lactic acidosis in some HIV-infectedpatients after exposure to nucleoside reverse transcriptase inhibitors (NRTI). METHODS: HIV-associated neuromuscular weakness syndrome (HANWS) was retrospectively identified and classified based on the level of diagnostic certainty: possible (progressive weakness owing to neuromuscular disease), probable (progressive neuromuscular weakness with documented exclusion of confounding causes), or definite (progressive weakness and electrophysiological or pathological evidence of neuromuscular pathology). RESULTS: Of 69 patients identified with HANWS, 27 had definite HANWS, 19 probable, and 23 possible. In 44 patients with documented follow-up, 16 required intubation and nine died. There was a marginal association between death and hyperlactatemia (P = 0.061). At onset of neurological symptoms, 68 were receiving antiretroviral therapy, including stavudine for 61 (89.7%). Serum lactate level was elevated (> 2.2 mmol/l) in 30/37 (81%), with a trend towards an association between hyperlactatemia and stavudine usage (P = 0.087). In 25, neurological symptoms occurred after antiretroviral therapy discontinuation (median, 14 days). Electrophysiological studies (n = 24) indicated sensorimotor neuropathy in 20 patients and myopathy in three. Nerve biopsy (n = 9) revealed axonal degeneration and inflammation in three, mixed axonal and demyelinating lesions in three, and primary axonal neuropathy in three. Of 15 muscle biopsies, three revealed inflammation and four mitochondrial abnormalities. CONCLUSIONS: A severe neuromuscular weakness syndrome may occur in HIV-infected individuals. The association with hyperlactatemia and NRTI exposure supports mitochondrial toxicity as a pathogenesis. In some, the onset of neurological symptoms lagged significantly after discontinuation of antiretroviral therapy, suggesting that different etiological mechanisms may underlie these cases.
Authors: I W Husstedt; D Reichelt; E Neuen-Jakob; K Hahn; F Kästner; R von Einsiedel; B Vielhaber; G Arendt; S Evers Journal: Nervenarzt Date: 2009-10 Impact factor: 1.214
Authors: Lucieny da Silva Pontes; Bianca Callegari; Lizandra Magno; Anderson Moraes; Bruno Giovanni Silva; Kaio Manso; Brenison Barros; Ana Paula Araújo; Maria Clara Silva; George Alberto Dias; Beatriz Helena Vasconcelos; Anselmo Costa E Silva; Rosana Maria Libonati; Givago Silva Souza Journal: Sci Rep Date: 2019-03-13 Impact factor: 4.379
Authors: Newton Chagoma; Jane Mallewa; Symon Kaunda; Yasin Njalale; Elizabeth Kampira; Mavuto Mukaka; Robert S Heyderman; Joep J van Oosterhout Journal: Trans R Soc Trop Med Hyg Date: 2013-08-07 Impact factor: 2.184