Journal of neurology · 2026
Progressive motor impairment from intracerebral critical demyelinating lesions.
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Chowdhury Purnashree, Flanagan Eoin P, Guo Yong, Tobin W Oliver, Coen Bianca Albites, Lucchinetti Claudia F, Weinshenker Brian G, Kantarci Orhun H, Keegan B Mark
Аннотация
BACKGROUND: Focal critical demyelinating lesions anatomically associated with progressive motor impairment are described in multiple sclerosis (MS) and restricted demyelinating diseases, typically within the spinal cord lateral column and ventral cervicomedullary junction (CMJ). This study describes such lesions within the intracerebral corticospinal tracts.
METHODS: We retrospectively reviewed people seen at Mayo MS Clinic (2002-2025) with progressive central nervous system demyelinating disease and progressive (≥ 1 year) upper motor neuron weakness anatomically associated with a presumed demyelinating lesion of the cerebral white matter, internal capsule, or upper brainstem, excluding alternative spinal cord or CMJ lesions. Demographics, disease course, Expanded Disability Status Scale (EDSS), MS disease-modifying therapy use, brain and spinal cord magnetic resonance imaging, cerebrospinal fluid studies and neuropathology findings were reviewed.
RESULTS: Seventeen people had an intracerebral critical demyelinating lesion: cerebral white matter in 12 (70%), internal capsule in 3 (18%) and upper brainstem in 2 (12%). Ten were female, and all were white. Progression from onset course was 13 (76%) and from relapse onset was 4 (24%). Median, interquartile range (IQR) for age at progressive motor impairment onset was 46 (IQR 38-52) years, and EDSS at last evaluation was 5.5 (IQR 4.0-5.5). Sixteen (94%) had progressive spastic hemiparesis and 1 (6%) monoparesis. Cognitive impairment occurred in 6/12 (50%) and seizures in 3/12 (25%) with cerebral white matter critical lesions. Abnormal intrathecal production of immunoglobulin G markers was consistent with MS in 10/15 (66%). Neuropathology confirmed demyelination in 4/6 biopsies.
CONCLUSIONS: Intracerebral critical demyelinating lesions associated with progressive motor impairment can rarely occur along the corticospinal tracts of the brain.
METHODS: We retrospectively reviewed people seen at Mayo MS Clinic (2002-2025) with progressive central nervous system demyelinating disease and progressive (≥ 1 year) upper motor neuron weakness anatomically associated with a presumed demyelinating lesion of the cerebral white matter, internal capsule, or upper brainstem, excluding alternative spinal cord or CMJ lesions. Demographics, disease course, Expanded Disability Status Scale (EDSS), MS disease-modifying therapy use, brain and spinal cord magnetic resonance imaging, cerebrospinal fluid studies and neuropathology findings were reviewed.
RESULTS: Seventeen people had an intracerebral critical demyelinating lesion: cerebral white matter in 12 (70%), internal capsule in 3 (18%) and upper brainstem in 2 (12%). Ten were female, and all were white. Progression from onset course was 13 (76%) and from relapse onset was 4 (24%). Median, interquartile range (IQR) for age at progressive motor impairment onset was 46 (IQR 38-52) years, and EDSS at last evaluation was 5.5 (IQR 4.0-5.5). Sixteen (94%) had progressive spastic hemiparesis and 1 (6%) monoparesis. Cognitive impairment occurred in 6/12 (50%) and seizures in 3/12 (25%) with cerebral white matter critical lesions. Abnormal intrathecal production of immunoglobulin G markers was consistent with MS in 10/15 (66%). Neuropathology confirmed demyelination in 4/6 biopsies.
CONCLUSIONS: Intracerebral critical demyelinating lesions associated with progressive motor impairment can rarely occur along the corticospinal tracts of the brain.