Annals of neurology
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Pathological limb pain patients show decreased attention to some stimuli on the painful limb and increased attention to others, a paradox that has dogged the field for over a decade. We hypothesized that pathological pain involves a spatial inattention confined to bodily representations. Patients showed inattention to the painful side for visual processing of body parts but not letters, tactile processing but not auditory, and body-part bisection tasks but not line bisection tasks. We propose the new term "somatospatial inattention" to describe bodily-specific spatial inattention associated with pathological limb pain.
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Annals of neurology · Apr 2016
Multicenter StudyMetabolic crisis occurs with seizures and periodic discharges after brain trauma.
Traumatic brain injury (TBI) results in persistent disruption of brain metabolism that has yet to be mechanistically defined. Early post-traumatic seizures are one potential mechanism for metabolic crisis and hence could be a therapeutic target. We hypothesized that seizures and pseudoperiodic discharges (PDs) may be mechanistically linked to metabolic crisis as measured by cerebral microdialysis. ⋯ In TBI patients, seizures and periodic discharges are one mechanism for metabolic crisis, and hence represent a therapeutic target for future study.
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Annals of neurology · Apr 2016
Adeno-associated virus-delivered artificial microRNA extends survival and delays paralysis in an amyotrophic lateral sclerosis mouse model.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of motor neurons, resulting in progressive muscle weakness, paralysis, and death within 5 years of diagnosis. About 10% of cases are inherited, of which 20% are due to mutations in the superoxide dismutase 1 (SOD1) gene. Riluzole, the only US Food and Drug Administration-approved ALS drug, prolongs survival by only a few months. Experiments in transgenic ALS mouse models have shown decreasing levels of mutant SOD1 protein as a potential therapeutic approach. We sought to develop an efficient adeno-associated virus (AAV)-mediated RNAi gene therapy for ALS. ⋯ These studies clearly demonstrate that an AAV9-delivered SOD1-specific artificial microRNA is an effective and translatable therapeutic approach for ALS.
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Annals of neurology · Feb 2016
Cerebellar neuronal loss in amyotrophic lateral sclerosis cases with ATXN2 intermediate repeat expansions.
Despite evidence suggesting that the cerebellum may be targeted in amyotrophic lateral sclerosis (ALS), particularly in cases with repeat expansions in the ATXN2 and C9ORF72 genes, the integrity of cerebellar neurons has yet to be examined. The present study undertakes a histopathological analysis to assess the impact of these repeat expansions on cerebellar neurons and determine whether similar cerebellar pathology occurs in sporadic disease. ⋯ The present study has established a selective loss of Purkinje cells in the cerebellar vermis of ALS cases with intermediate repeat expansions in the ATXN2 gene, suggesting a divergent pathogenic mechanism independent of upper and lower motor neuron degeneration in ALS. We discuss these findings in the context of large repeat expansions in ATXN2 and spinocerebellar ataxia type 2, providing evidence that intermediate repeats in ATXN2 cause significant, albeit less substantial, spinocerebellar damage compared with longer repeats in ATXN2.