Lancet neurology
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Multicenter Study Comparative Study Clinical Trial
Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study.
Many women of childbearing potential take antiepileptic drugs, but the cognitive effects of fetal exposure are uncertain. We aimed to assess effects of commonly used antiepileptic drugs on cognitive outcomes in children up to 6 years of age. ⋯ Fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains at 6 years of age. Reduced right-handedness and verbal (vs non-verbal) abilities might be attributable to changes in cerebral lateralisation induced by exposure to antiepileptic drugs. The positive association of periconceptional folate with IQ is consistent with other recent studies.
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Two decades after the discovery that 20% of familial amyotrophic lateral sclerosis (ALS) cases were linked to mutations in the superoxide dismutase-1 (SOD1) gene, a substantial proportion of the remainder of cases of familial ALS have now been traced to an expansion of the intronic hexanucleotide repeat sequence in C9orf72. This breakthrough provides an opportunity to re-evaluate longstanding concepts regarding the cause and natural history of ALS, coming soon after the pathological unification of ALS with frontotemporal dementia through a shared pathological signature of cytoplasmic inclusions of the ubiquitinated protein TDP-43. ⋯ Identification of C9orf72 repeat expansions in patients without a family history of ALS challenges the traditional division between familial and sporadic disease. By contrast, the 90% of apparently sporadic cases and incomplete penetrance of several genes linked to familial cases suggest that at least some forms of ALS arise from the interplay of multiple genes, poorly understood developmental, environmental, and age-related factors, as well as stochastic events.
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Peripheral nerve disorders are associated with all stages of HIV infection. Distal sensory polyneuropathy is characterised by often-disabling pain that is difficult to treat. It is prevalent in both high-income and low-income settings. ⋯ Sensorimotor polyneuropathies and polyradiculopathies are less frequent than distal sensory polyneuropathy, but still occur in low-income settings and have potentially devastating consequences. However, many of these diseases can be treated successfully with a combination of antiretroviral and immune-modulating therapies. To distinguish between peripheral nerve disorders that have diverse, overlapping, and frequently atypical presentations can be challenging; a framework based on a clinicoanatomical approach might assist in the diagnosis and management of such disorders.