There appears to be a relationship between retroviruses such as HIV and the development of an ALS-like syndrome. Few cases have been reported; however, there exists evidence of a higher frequency of motor neuron disease in HIV-infected patients, as well as potential slowing and reversibility of disease course with combination antiretroviral therapy. We conducted a retrospective chart review of patients presenting to the George Washington University ALS Clinic from September 2006 to June 2018 to identify patients with HIV receiving HAART who were subsequently diagnosed with ALS or an ALS-like disorder. Our goals were to describe our patients' disease course and compare them to general characteristics of ALS. We report three cases of HIV-positive individuals, all male, who were subsequently diagnosed with ALS. Each presented with symptoms of limb onset ALS with involvement of upper and lower motor neurons and whose disease originated at the cervical level. All three had been diagnosed with HIV prior to presentation and were presumably compliant with antiretroviral therapy throughout. Our patients demonstrated effective control of their HIV infection. Each experienced relatively slow progression of motor impairment compared to general ALS characteristics. Our study offers a distinct profile of HIV-positive patients compliant with HAART subsequently diagnosed with an ALS-like disorder. Further study should aim to uncover pathophysiological similarities between motor neuron disease both in the presence and absence of retroviral infection and to develop effective medical therapy for each.
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http://dx.doi.org/10.1159/000511203 | DOI Listing |
Exp Neurol
February 2025
Department of Developmental Biology, Washington University School of Medicine, St. Louis 63110, United States; Needleman Center for Neurometabolism and Axonal Therapeutics, St. Louis 63110, United States. Electronic address:
Pathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. Stathmin2 (Stmn2) is a key target of TDP-43 regulation and aberrantly spliced Stmn2 mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion in vivo partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
January 2025
Department of Neuroscience, School of Life Sciences, University of Sussex, Brighton, United Kingdom. Electronic address:
Cytoplasmic dynein 1, a motor protein essential for retrograde axonal transport, is increasingly implicated in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). In this study, we developed a novel mouse model that combines the Legs at odd angles (Loa, F580Y) point mutation in the dynein heavy chain with a cholinergic neuron-specific knockout of the dynein heavy chain. This model, for the first time, allows us to investigate the impact of Loa allele exclusivity in these neurons into adulthood.
View Article and Find Full Text PDFSci Rep
October 2024
Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Amyotrophic lateral sclerosis (ALS) progressively impairs motor neurons, leading to muscle weakness and loss of voluntary muscle control. This study compared the effects of SOD1 mutation on masticatory and limb muscles from disease onset to death in ALS model mice. Notably, limb muscles begin to atrophy soon after ALS-like phenotype appear, whereas masticatory muscles maintain their volume and function in later stages.
View Article and Find Full Text PDFCNS Neurosci Ther
September 2024
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province, Department of Neurology, Institute of Neuroscience, Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Exp Neurol
December 2024
Department of Neurology and Neurosurgery, Montreal Neurological Institute, Faculty of Medicine, McGill University, Canada. Electronic address:
Mutations in the nuclear-encoded mitochondrial gene CHCHD10 have been observed in patients with a spectrum of diseases that include amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). To investigate the pathogenic nature of disease-associated variants of CHCHD10 we generated a zebrafish knock-in (KI) model expressing the orthologous ALS-associated CHCHD10 variant (zebrafish: Chchd10). Larval chchd10 fish displayed reduced Chchd10 protein expression levels, motor impairment, reduced survival and abnormal neuromuscular junctions (NMJ).
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