Myoclonus ataxia and refractory coeliac disease

Abstract

BackgroundCortical myoclonus with ataxia has only rarely been reported in association with Coeliac Disease (CD). Such reports also suggested that it is unresponsive to gluten-free diet. We present detailed electro-clinical characteristics of a new syndrome of progressive cortical hyperexcitability with ataxia and refractory CD. At our gluten/neurology clinic we have assessed and regularly follow up over 600 patients with neurological manifestations due to gluten sensitivity. We have identified 9 patients with this syndrome.ResultsAll 9 patients (6 male, 3 female) experienced asymmetrical irregular myoclonus involving one or more limbs and sometimes face. This was often stimulus sensitive and became more widespread over time. Three patients had a history of Jacksonian march and five had at least one secondarily generalised seizure. Electrophysiology showed evidence of cortical myoclonus. Three had a phenotype of epilepsia partialis continua at onset. There was clinical, imaging and/or pathological evidence of cerebellar involvement in all cases. All patients adhered to a strict gluten-free diet with elimination of gluten-related antibodies in most. However, there was still evidence of enteropathy in all, suggestive of refractory celiac disease. Two died from enteropathy-associated lymphoma and one from status epilepticus. Five patients were treated with mycophenolate and one in addition with rituximab and IV immunoglobulins. Their ataxia and enteropathy improved but myoclonus remained the most disabling feature of their illness.ConclusionsThis syndrome may well be the commonest neurological manifestation of refractory CD. The clinical involvement, apart from ataxia, covers the whole clinical spectrum of cortical myoclonus.Electronic supplementary materialThe online version of this article (doi:10.1186/2053-8871-1-11) contains supplementary material, which is available to authorized users.

Gluten-Related Disorders: Gluten Ataxia

“…A recent publication of a series of 9 patients with this phenotype described asymmetrical irregular myoclonus involving one or more limbs and sometimes the face [14]. The myoclonus was often stimulus sensitive and became widespread over time.…”

“…GA usually presents with pure cerebellar ataxia or rarely ataxia in combination with myoclonus, palatal tremor, opsoclonus-myoclonus [14,15,16]. GA is usually of insidious onset with a mean age at onset of 53 years.…”

Stimulus Sensitive Foot Myoclonus: A Clue to Coeliac Disease

“…Cortical lesions can cause epilepsia partialis continua (EPC), a simple focal motor status epileptics resulting in spontaneous and repetitive jerks restricted to a specific body region, which may be aggravated by action, or be stimulus‐sensitive. CD patients can display focal, continuous, and spontaneous myoclonus of cortical origin, fulfilling the definition of EPC . Indeed, patient two presented with spontaneous jerks that persisted during sleep, a feature frequently seen in EPC.…”

“…Cerebellar ataxia, sometimes associated with progressive myoclonus, is the most frequent movement disorder presentation . While there is a link between cerebellar pathology and cortical myoclonus in CD, and antibodies against a brain expressed transglutaminase, TG6, have been found in patients with cerebellar ataxia, the pathophysiological link between CD and the neurological presentation is not fully understood . It has been suggested that tissue transglutaminase antibodies may cross‐react with neuronal antigens, but it remains unclear how the antibodies should access their intracellular targets in vivo.…”

“…The fact that GFD seems not to consistently improve CD‐related neurological symptoms, and the concept of extraintestinal manifestations without enteropathy, suggests that the autoimmunity to the gut and the neurological manifestations may not be closely linked, especially in cases with myoclonus. Indeed, refractory CD can be severely disabling, despite GFD and poly‐immunotherapy and the normalization of gut mucosa under this regime …”