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Combined central and peripheral demyelination in two siblings, immune mediated or genetic?

Abstract:
We report unusual cases of combined central and peripheral demyelination in two siblings related to pregnancy, each presenting with progressive tetraparesis and cranial nerve palsies. The elder sister had a relapsing-remitting course with optic nerve dysfunction and died during a relapse from respiratory insufficiency. The younger sister presented with disorientation and acute-onset limb and facial weakness. She responded well to corticosteroid therapy. Their clinical presentation, response to immunomodulatory therapy, nerve conduction studies, cerebrospinal fluid and histology supported an acquired demyelinating cause. Whole-exome sequencing identified variants in two genes not previously linked to this clinical phenotype. Serological tests for antibody-mediated demyelination were negative. Despite the undefined pathogenesis, these cases provide a platform to explore the confluence of genetic, immune and environmental factors in the context of acquired demyelination. We discuss the differential diagnosis and a diagnostic approach to such cases from the perspectives of neuroimmunology and neurogenetics.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1136/pn-2024-004114

Authors

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Role:
Author
ORCID:
0000-0001-5072-0522
More by this author
Role:
Author
ORCID:
0000-0003-4900-9877
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Role:
Author
ORCID:
0000-0002-2866-7777


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Funder identifier:
https://ror.org/029chgv08
Grant:
MR/S01165X/1


Publisher:
BMJ Publishing Group
Journal:
Practical Neurology More from this journal
Volume:
24
Issue:
5
Pages:
422-427
Place of publication:
England
Publication date:
2024-07-03
Acceptance date:
2024-05-01
DOI:
EISSN:
1474-7766
ISSN:
1474-7758
Pmid:
38960597


Language:
English
Pubs id:
2015325
Local pid:
pubs:2015325
Deposit date:
2025-02-14
ARK identifier:

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