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Title:
Motor neuron disease clinically limited to the lower motor neuron is a diffuse TDP-43 proteinopathy | Acta Neuropathologica
Description:
Motor neuron disease (MND) may present as an isolated lower motor neuron (LMN) disorder. Although the significance of pathological 43 kDa transactive responsive sequence DNA binding protein (TDP-43) for amyotrophic lateral sclerosis (ALS) was appreciated only recently, the topographical distribution of TDP-43 pathology in MND clinically isolated to the LMN versus normal controls (COs) is only incompletely described. Therefore, we performed longitudinal clinical evaluation and retrospective chart review of autopsied patients diagnosed with isolated LMN disease. Cases with a disease duration over 4 years were designated as progressive muscular atrophy (PMA), and those with a more rapid course as MND/LMN. Immunohistochemistry was employed to identify neuronal and glial TDP-43 pathology in the central nervous system (CNS) in patients and COs. We examined 19 subjects including six patients (i.e., four with MND/LMN and two with PMA) and 13 COs. All patients showed significant TDP-43 linked degeneration of LMNs, and five cases showed a lesser degree of motor cortex degeneration. Additional brain areas were affected in varying degrees, ranging from predominantly brainstem pathology to significant involvement of the whole CNS including neocortical and limbic areas. Pathological TDP-43 was present only rarely in the CO group. We conclude that MND limited to the LMN and PMA is part of a disease continuum that includes ALS and FTLD-TDP, all of which are characterized by widespread TDP-43 pathology. Hence, we suggest that the next revision of the El Escorial criteria for the diagnosis of ALS include MND patients with disease clinically limited to the LMN and PMA as variants of ALS, which like classical ALS, are TDP-43 proteinopathies.
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article, google, scholar, pubmed, tdp, disease, cas, motor, trojanowski, lateral, sclerosis, neuron, acta, lee, pathology, amyotrophic, neuropathol, kwong, degeneration, neurol, neurology, frontotemporal, van, medicine, geser, mccluskey, patients, lobar, research, lower, pathological, clinical, sporadic, grossman, arch, neumann, department, elman, deerlin, progressive, access, miller, clark, usa, privacy, cookies, content, clinically, limited, xie,

Topics {✒️}

month download article/chapter disease clinically limited motor neuron disease neurodegenerative disease research lower motor neuron motor neuron disorders long-term prospective study progressive muscular atrophy primary lateral sclerosis ubiquitin-positive inclusions delineated amyotrophic lateral sclerosis amyotrophic lateral sclerosis anti-phosphorylated tdp-43 antibody neuromuscular diseases mnd clinically isolated lower motor neurons full article pdf motor cortex degeneration tdp-43 pathologic lesions diffuse tdp-43 proteinopathy machado-joseph disease lewy body disease privacy choices/manage cookies isolated lmn disease amyotroph lateral scler disease core center progressive supranuclear palsy ubiquitin-positive inclusions related subjects el escorial revisited frontotemporal lobar degeneration disease duration article geser tdp-43-immunoreactive inclusions severe mental illness mnd limited corticospinal tract degeneration temporal lobar predominance el escorial criteria van swieten jc european economic area retrospective chart review central nervous system dendritic spine abnormalities mackenzie ir additional autopsy case albert einstein college maloney 3rd floor glial tdp-43 pathology widespread tdp-43 pathology

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         description:Motor neuron disease (MND) may present as an isolated lower motor neuron (LMN) disorder. Although the significance of pathological 43 kDa transactive responsive sequence DNA binding protein (TDP-43) for amyotrophic lateral sclerosis (ALS) was appreciated only recently, the topographical distribution of TDP-43 pathology in MND clinically isolated to the LMN versus normal controls (COs) is only incompletely described. Therefore, we performed longitudinal clinical evaluation and retrospective chart review of autopsied patients diagnosed with isolated LMN disease. Cases with a disease duration over 4 years were designated as progressive muscular atrophy (PMA), and those with a more rapid course as MND/LMN. Immunohistochemistry was employed to identify neuronal and glial TDP-43 pathology in the central nervous system (CNS) in patients and COs. We examined 19 subjects including six patients (i.e., four with MND/LMN and two with PMA) and 13 COs. All patients showed significant TDP-43 linked degeneration of LMNs, and five cases showed a lesser degree of motor cortex degeneration. Additional brain areas were affected in varying degrees, ranging from predominantly brainstem pathology to significant involvement of the whole CNS including neocortical and limbic areas. Pathological TDP-43 was present only rarely in the CO group. We conclude that MND limited to the LMN and PMA is part of a disease continuum that includes ALS and FTLD-TDP, all of which are characterized by widespread TDP-43 pathology. Hence, we suggest that the next revision of the El Escorial criteria for the diagnosis of ALS include MND patients with disease clinically limited to the LMN and PMA as variants of ALS, which like classical ALS, are TDP-43 proteinopathies.
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