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.Electronic supplementary materialThe online version of this article (doi:10.1186/s40673-016-0055-1) contains supplementary material, which is available to authorized users.
Highlights
Alcohol-related cerebellar degeneration is one of the commonest acquired forms of cerebellar ataxia
A further group of 8/38 (21 %) patients recruited from the Hepatology clinics, were selected on the basis of having alcohol-related chronic liver disease, but were found to have ataxia, categorised as ‘chronic liver disease and ataxia’ (CLDA)
We show that 71 % of patients with alcohol ataxia have circulating antibodies that react with neural tissue
Summary
Alcohol-related cerebellar degeneration is one of the commonest acquired forms of cerebellar ataxia. We aim to investigate the potential role of alcohol-induced immune mediated cerebellar degeneration. Alcohol-related cerebellar degeneration is one of the commonest causes of acquired cerebellar ataxia. Some argue that the direct toxic effects of alcohol on cerebellar cells is responsible, whilst others. The anterior superior cerebellar vermis is predominantly affected [3, 4] with the Purkinje cell, granular and white matter layers being most susceptible [2]. This has been confirmed in large autopsy studies [5, 6]. MRI findings of vermian atrophy, with preferential involvement of the lingula [7], are in keeping with the neuropathological findings
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