Alcohol-related cerebellar degeneration: not all down to toxicity? View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10-03

AUTHORS

Priya D. Shanmugarajah, Nigel Hoggard, Stuart Currie, Daniel P. Aeschlimann, Pascale C. Aeschlimann, Dermot C. Gleeson, Mohammed Karajeh, Nicola Woodroofe, Richard A. Grünewald, Marios Hadjivassiliou

ABSTRACT

BackgroundAlcohol-related cerebellar degeneration is one of the commonest acquired forms of cerebellar ataxia. The exact pathogenic mechanisms by which alcohol leads to cerebellar damage remain unknown. Possible autoreactive immune mediated mechanisms have not been explored previously. In this study, we aim to investigate the potential role of alcohol-induced immune mediated cerebellar degeneration.MethodsPatients with ataxia and a history of alcohol misuse were recruited from the Ataxia and Hepatology tertiary clinics at Sheffield Teaching Hospitals NHS Trust. We determined the pattern of cerebellar involvement both on clinical (SARA score) and imaging (MRI volumetry and MR spectroscopy) parameters. In addition, HLA genotyping, serological markers for gluten-related disorders and serological reactivity on rat cerebellar tissue using indirect immunohistochemistry were assessed.ResultsThirty-eight patients were included in the study all of whom had ataxia. The gait (97 %), stance (89 %) and heel-shin slide (89 %) were the predominant SARA elements affected. MRI volumetric and spectroscopy techniques demonstrated significant structural, volumetric and functional deficits of the cerebellum with particular involvement of the cerebellar vermis. Circulating anti-gliadin antibodies were detected in 34 % patients vs. 12 % in healthy controls. Antibodies to transglutaminase 6 (TG6) were detected in 39 % of patients and 4 % of healthy control subjects. Using immunohistochemistry, Purkinje cell and/or granular layer reactivity was demonstrated in 71 % of patient sera.ConclusionsAlcohol induced tissue injury to the CNS leading to cerebellar degeneration may also involve immune mediated mechanisms, including sensitisation to gluten. More... »

PAGES

17

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40673-016-0055-1

DOI

http://dx.doi.org/10.1186/s40673-016-0055-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1007403324

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27729985


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