Clinical Characteristics and Management of 50 Patients with Anti-GAD Ataxia: Gluten-Free Diet Has a Major Impact.

The objective of this study is to report the clinical characteristics and treatment of patients with progressive cerebellar ataxia associated with anti-GAD antibodies. We performed a retrospective review of all patients with anti-GAD ataxia managed at the Sheffield Ataxia Centre over the last 25 years. We identified 50 patients (62% females) with anti-GAD ataxia. The prevalence was 2.5% amongst 2000 patients with progressive ataxia of various causes. Mean age at onset was 55 and mean duration 8 years. Gaze-evoked nystagmus was present in 26%, cerebellar dysarthria in 26%, limb ataxia in 44% and gait ataxia in 100%. Nine patients (18%) had severe, 12 (24%) moderate and 29 (58%) mild ataxia. Ninety percent of patients had a history of additional autoimmune diseases. Family history of autoimmune diseases was seen in 52%. Baseline MR spectroscopy of the vermis was abnormal at presentation in 72%. Thirty-five patients (70%) had serological evidence of gluten sensitivity. All 35 went on gluten-free diet (GFD). Eighteen (51%) improved, 13 (37%) stabilised, 3 have started the GFD too recently to draw conclusions and one deteriorated. Mycophenolate was used in 16 patients, 7 (44%) improved, 2 stabilised, 6 have started the medication too recently to draw conclusions and one did not tolerate the drug. There is considerable overlap between anti-GAD ataxia and gluten ataxia. For those patients with both, strict GFD alone can be an effective treatment. Patients with anti-GAD ataxia and no gluten sensitivity respond well to immunosuppression.

Treatment of Primary Autoimmune Cerebellar Ataxia with Mycophenolate.

Immune-mediated ataxias account for a substantial number of sporadic otherwise idiopathic ataxias. Despite some well-characterised entities such as paraneoplastic cerebellar degeneration where diagnostic markers exist, the majority of immune ataxias remained undiagnosed and untreated. We present here our experience in the treatment of suspected primary autoimmune cerebellar ataxia (PACA) using mycophenolate. All patients reported attend the Sheffield Ataxia Centre on a regular basis and had undergone extensive investigations, including genetic testing using next-generation sequencing, with other causes of ataxia excluded. The diagnosis of PACA was strongly suspected based on investigations, pattern of disease progression, and cerebellar involvement. Patients were treated with mycophenolate and monitored using MR spectroscopy of the cerebellar vermis. Thirty patients with PACA are reported here. Of these, 22 received mycophenolate (group 1). The remaining 8 were not on treatment (group 2-control group). Out of the 22 treated patients, 4 underwent serial MR spectroscopy prior to starting treatment and thus were used as controls making the total number of patients in the control group 12. The mean change of the MRS within the vermis (NAA/Cr area ratio) in the treatment group was + 0.144 ± 0.09 (improved) and in the untreated group - 0.155 ± 0.06 (deteriorated). The difference was significant. We also demonstrated a strong correlation between the spectroscopy and the SARA score. We have demonstrated the effectiveness of mycophenolate in the treatment of PACA. The results suggest that immune-mediated ataxias are potentially treatable, and that there is a need for early diagnosis to prevent permanent neurological deficit. The recently published diagnostic criteria for PACA would hopefully aid the diagnosis and treatment of this entity.

Causes of progressive cerebellar ataxia: prospective evaluation of 1500 patients.

BACKGROUND: Cerebellar ataxias are the result of diverse disease processes that can be genetic or acquired. Establishing a diagnosis requires a methodical approach with expert clinical evaluation and investigations. We describe the causes of ataxia in 1500 patients with cerebellar ataxia. METHODS: All patients were referred to the Sheffield Ataxia Centre, UK, and underwent extensive investigations, including, where appropriate genetic testing using next-generation sequencing (NGS). Patients were followed up on a 6-monthly basis for reassessment and further investigations if indicated. RESULTS: A total of 1500 patients were assessed over 20 years. Twenty per cent had a family history, the remaining having sporadic ataxia. The commonest cause of sporadic ataxia was gluten ataxia (25%). A genetic cause was identified in 156 (13%) of sporadic cases with other causes being alcohol excess (12%) and cerebellar variant of multiple system atrophy (11%). Using NGS, positive results were obtained in 32% of 146 patients tested. The commonest ataxia identified was EA2. A genetic diagnosis was achieved in 57% of all familial ataxias. The commonest genetic ataxias were Friedreich's ataxia (22%), SCA6 (14%), EA2 (13%), SPG7 (10%) and mitochondrial disease (10%). The diagnostic yield following attendance at the Sheffield Ataxia Centre was 63%. CONCLUSIONS: Immune-mediated ataxias are common. Advances in genetic testing have significantly improved the diagnostic yield of patients suspected of having a genetic ataxia. Making a diagnosis of the cause of ataxia is essential due to potential therapeutic interventions for immune and some genetic ataxias.