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

SHANMUGARAJAH, Priya D., HOGGARD, Nigel, CURRIE, Stuart, AESCHLIMANN, Daniel P, AESCHLIMANN, Pascale C, GLEESON, Dermot C, KARAJEH, Mohammed, WOODROOFE, Nicola, GRÜNEWALD, Richard A and HADJIVASSILIOU, Marios (2016). Alcohol-related cerebellar degeneration: not all down to toxicity? Cerebellum & Ataxias.

[img]
Preview
PDF
Woodroofe Alcohol-related cerebellar degeneration.pdf - Published Version
Available under License Creative Commons Attribution.

Download (405kB) | Preview
Official URL: https://cerebellumandataxias.biomedcentral.com/art...
Link to published version:: 10.1186/s40673-016-0055-1

Abstract

Background: Alcohol-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. Methods: Patients 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. Results: Thirty-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. Conclusions: Alcohol induced tissue injury to the CNS leading to cerebellar degeneration may also involve immune mediated mechanisms, including sensitisation to gluten.

Item Type: Article
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Identification Number: 10.1186/s40673-016-0055-1
SWORD Depositor: Ann Betterton
Depositing User: Ann Betterton
Date Deposited: 07 Nov 2016 16:50
Last Modified: 14 Jun 2017 20:55
URI: http://shura.shu.ac.uk/id/eprint/13873

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics