Autosomal dominant cerebellar ataxias: a systematic review on clinical features

MALCO ROSSI; SANTIAGO PEREZ LLORET; LEILA DOLDAN; DANIEL CERQUETTI; JORGE BALEJ; PATRICIO MILLAR VERNETTI; MAXIMILIANO HAWKES; ANGEL CAMMAROTA; MARCELO MERELLO

Sydney

Congreso; 17th International Congress of Parkinson’s Disease and Movement Disorders; 2013

Movement Disorders Society

Objective: To assess autosomal dominant cerebellar ataxias (ADCAs) distinctive clinical signs through a systematic review.To assess autosomal dominant cerebellar ataxias (ADCAs) distinctive clinical signs through a systematic review. Background: ADCAs are clinically heterogeneous disorders and are classified in several genetic subtypes known as spinocerebellar ataxias (SCAs). Precise frequency and distinction of diverse clinical features is lacking. spinocerebellar ataxias (SCAs). Precise frequency and distinction of diverse clinical features is lacking. ADCAs are clinically heterogeneous disorders and are classified in several genetic subtypes known as spinocerebellar ataxias (SCAs). Precise frequency and distinction of diverse clinical features is lacking. Methods: A structured search was conducted by two independent reviewers in electronic databases up to September 2012. All publications containing proportions or descriptions of ADCAs clinical features and written in several languages were included. Publications were selected initially by titles and abstracts screening and further by full-text reading of those potentially relevant. Clinical findings and demographic data from genetically confirmed patients were extracted. Data was analyzed by chi-square test controlling for a-error inflation by Holms step-down procedure.aaa All publications containing proportions or descriptions of ADCAs clinical features and written in several languages were included. Publications were selected initially by titles and abstracts screening and further by full-text reading of those potentially relevant. Clinical findings and demographic data from genetically confirmed patients were extracted. Data was analyzed by chi-square test controlling for a-error inflation by Holms step-down procedure.aaa A structured search was conducted by two independent reviewers in electronic databases up to September 2012. All publications containing proportions or descriptions of ADCAs clinical features and written in several languages were included. Publications were selected initially by titles and abstracts screening and further by full-text reading of those potentially relevant. Clinical findings and demographic data from genetically confirmed patients were extracted. Data was analyzed by chi-square test controlling for a-error inflation by Holms step-down procedure.aaa Results: 1062 publications were included, containing 12 141 patients (52% male) from 29 SCA subtypes. Mean age at onset was 35±11 years. Onset symptoms ascertained in 3945 patients revealed gait ataxia as the most frequent (67%) followed by dysarthria (13%), whereas overall non-ataxia symptoms frequency was 50%. Some SCA began more often with nonataxia symptoms, like SCA7 (visual disturbances), SCA12, SCA27 (cerebellar tremor), and SCA10 and DRPLA (seizures). During overall disease course, dysarthria (90%), saccadic eye movement alterations (69%), nystagmus (56%) and ophtalmoparesis (51%) were the most prevalent non-ataxia signs. Some genetic subtypes were clinically restricted to cerebellar dysfunction and others showed several non-cerebellar distinctions, allowing their categorization into two main groups: pure and mixed; the latter subgrouped according to varied clinical distinctions. Conclusions: ADCAs encompass a broad spectrum of clinical features with an elevated frequency of non-ataxia symptoms. Some clinical findings distinguished several genetic subtypes from each other. An updated Harding´s classification is proposed. Some clinical findings distinguished several genetic subtypes from each other. An updated Harding´s classification is proposed. ADCAs encompass a broad spectrum of clinical features with an elevated frequency of non-ataxia symptoms. Some clinical findings distinguished several genetic subtypes from each other. An updated Harding´s classification is proposed. was 35±11 years. Onset symptoms ascertained in 3945 patients revealed gait ataxia as the most frequent (67%) followed by dysarthria (13%), whereas overall non-ataxia symptoms frequency was 50%. Some SCA began more often with nonataxia symptoms, like SCA7 (visual disturbances), SCA12, SCA27 (cerebellar tremor), and SCA10 and DRPLA (seizures). During overall disease course, dysarthria (90%), saccadic eye movement alterations (69%), nystagmus (56%) and ophtalmoparesis (51%) were the most prevalent non-ataxia signs. Some genetic subtypes were clinically restricted to cerebellar dysfunction and others showed several non-cerebellar distinctions, allowing their categorization into two main groups: pure and mixed; the latter subgrouped according to varied clinical distinctions. Conclusions: ADCAs encompass a broad spectrum of clinical features with an elevated frequency of non-ataxia symptoms. Some clinical findings distinguished several genetic subtypes from each other. An updated Harding´s classification is proposed. Some clinical findings distinguished several genetic subtypes from each other. An updated Harding´s classification is proposed. ADCAs encompass a broad spectrum of clinical features with an elevated frequency of non-ataxia symptoms. Some clinical findings distinguished several genetic subtypes from each other. An updated Harding´s classification is proposed. 1062 publications were included, containing 12 141 patients (52% male) from 29 SCA subtypes. Mean age at onset was 35±11 years. Onset symptoms ascertained in 3945 patients revealed gait ataxia as the most frequent (67%) followed by dysarthria (13%), whereas overall non-ataxia symptoms frequency was 50%. Some SCA began more often with nonataxia symptoms, like SCA7 (visual disturbances), SCA12, SCA27 (cerebellar tremor), and SCA10 and DRPLA (seizures). During overall disease course, dysarthria (90%), saccadic eye movement alterations (69%), nystagmus (56%) and ophtalmoparesis (51%) were the most prevalent non-ataxia signs. Some genetic subtypes were clinically restricted to cerebellar dysfunction and others showed several non-cerebellar distinctions, allowing their categorization into two main groups: pure and mixed; the latter subgrouped according to varied clinical distinctions. Conclusions: ADCAs encompass a broad spectrum of clinical features with an elevated frequency of non-ataxia symptoms. Some clinical findings distinguished several genetic subtypes from each other. An updated Harding´s classification is proposed. Some clinical findings distinguished several genetic subtypes from each other. An updated Harding´s classification is proposed. ADCAs encompass a broad spectrum of clinical features with an elevated frequency of non-ataxia symptoms. Some clinical findings distinguished several genetic subtypes from each other. An updated Harding´s classification is proposed.