%0 Journal Article %T Phenotypic variability in amyotrophic lateral sclerosis %+ Neuroépidémiologie Tropicale (NET) %+ Service de Neurologie [CHU Limoges] %+ Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST) %+ CHU Limoges %+ Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours] (SLA CHRU Tours) %+ Hôpital Bretonneau %A Couratier, Philippe %A Lautrette, Géraldine %A Luna, Jaime %A Corcia, Philippe %< avec comité de lecture %@ 0035-3787 %J Revue Neurologique %I Elsevier Masson %8 2021-04 %D 2021 %R 10.1016/j.neurol.2021.03.001 %M 33902945 %K Amyotrophic lateral sclerosis %K Lower motor neuron %K Phenotype %K Transactivation Response DNA %K Binding Protein %K Upper motor neuron %Z Life Sciences [q-bio]/Santé publique et épidémiologieJournal articles %X Clinically, ALS phenotypes depend on the areas of the body that are affected, the different degrees of involvement of upper and lower motor neurons, the degrees of involvement of other systems, particularly cognition and behavior, and rates of progression. Phenotypic variability of ALS is characteristic and can be declined on the distribution of motor manifestations but also on the presence of extra-motor signs present in a variable manner in ALS patients. Neuropathologically, ALS is defined by the loss of UMN and LMN and the presence of two representative motor neuronal cytoplasmic inclusions, Bunina bodies and 43kDa Transactivation Response DNA Binding Protein (TDP-43) - positive cytoplasmic inclusions. The distribution of cytopathology and neuronal loss in patients is variable and this variability is directly related to phenotypic variability. Key regulators of phenotypic variability in ALS have not been determined. The functional decrement of TDP-43, and region-specific neuronal susceptibility to ALS, may be involved. Due to the selective vulnerability among different neuronal systems, lesions are multicentric, region-oriented, and progress at different rates. They may vary from patient to patient, which may be linked to the clinicopathological variability across patients. %G English %2 https://unilim.hal.science/hal-03217164/document %2 https://unilim.hal.science/hal-03217164/file/S0035378721005051.pdf %L hal-03217164 %U https://unilim.hal.science/hal-03217164 %~ INSERM %~ UNILIM %~ NET %~ SANTE_PUB_INSERM %~ GEIST %~ ELSEVIER %~ EPIMACT %~ OMEGAHEALTH %~ LABCIS