Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study.

BACKGROUND: Despite recent progress in the field of genetics, sporadic late-onset (> 40 years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations. METHODS: We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations. RESULTS: We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich's ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p < 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p < 0.01). CONCLUSION: Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA.

Clonidine GH stimulation test to differentiate MSA from idiopathic late onset cerebellar ataxia: a prospective, controlled study.

INTRODUCTION: Despite the consensus criteria for multiple system atrophy (MSA), the diagnosis of MSA of cerebellar type (MSA-C) may be difficult in the early stage of the disease. There are several differential diagnoses including idiopathic late-onset cerebellar ataxias (ILOCA) and it is often necessary to wait for clinical worsening so that the criteria can be met. Our aim was to assess the efficacy of clonidine growth hormone test (CGH test) to distinguish MSA-C from ILOCA in the early stage of the disease. METHODS: Within our cohort of late-onset sporadic, progressive cerebellar ataxia, the group of patients meeting the criteria for possible or probable MSA was compared to the ILOCA group. Clinical and paraclinical examination including CGH test were repeated during the prospective follow-up. RESULTS: Eighty-six patients were recruited, including 42 patients in the MSA group and 44 ILOCA patients with a mean follow-up of 33 months. At the inclusion visit, CHG test was pathological for 31% MSA of patients and 18.2% of ILOCA patients (p = 0.35). During the follow-up, 52.4% of MSA-C had a pathological CGH test, while only 20.5% of ILOCA (p < 0.01). CGH test had a sensitivity of 69.1% and a specificity of 68.2%, (p < 0.001) for MSA-C patients; CGH test allows in three quarters of cases, if negative, to rule out a probable MSA-C (negative predictive value of 75%, p = 0.0014). CONCLUSION: This prospective, controlled study showed that CGH test could be helpful in clinical practice to differentiate MSA-C from ILOCA in the early stage of the disease.