This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on ISI (9)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurogenetics  • Radiologic Imaging  • Magnetic Resonance Imaging  • Genetic Counseling/ Testing/ Therapy  • Alert me on articles by topic

Phenotypic Analysis, Magnetic Resonance Imaging Findings, and Review of the Literature

Roongroj Bhidayasiri, MD, MRCP(UK); Susan L. Perlman, MD; Stefan-M. Pulst, MD, DrMed; Daniel H. Geschwind, MD, PhD

Arch Neurol. 2005;62:1865-1869.

Background  Friedreich ataxia (FA), the most common hereditary ataxia, is caused by pathological expansion of GAA repeats in the first intron of the X25 gene on chromosome 9. Since the discovery of the gene, atypical features are increasingly recognized in individuals with FA, and up to 25% of patients with recessive or sporadic ataxia do not fulfill the Harding or Quebec Cooperative Study on Friedreich’s Ataxia criteria for FA. Late-onset FA (LOFA) is defined as onset after age 25 years.

Objectives  To describe and further delineate the clinical and magnetic resonance imaging findings in patients with LOFA and to review the literature.

Design  Clinical evaluation and comparison of clinical data and investigations.

Setting  Ataxia clinics at UCLA and Cedars-Sinai Medical Center.

Patients  Thirteen patients with LOFA with 13 sex-matched and Inherited Ataxia Progression Scale–matched patients with typical FA.

Results  Gait and limb ataxias were seen in all the participants. Dysarthria, loss of vibration sense, and abnormal eye movements were also common in both groups. Patients with LOFA more often had lower limb spasticity (40% vs 0%; ² = 4.0; P = .04) and retained reflexes (46.1% vs 7.7%; ² = 3.46; P = .05). They had no complaint of sphincter disturbances, and there was no evidence of cardiomyopathy on echocardiograms (² = 4.0; P = .04). Five of 9 patients with LOFA had cerebellar atrophy on neuroimaging.

Conclusions  Patients with gait and limb ataxias, dysarthria, loss of vibration sense, and fixational instability after age 25 years should be considered for molecular testing for GAA expansion in the FA gene. In contrast to previous studies, cerebellar vermian atrophy is not an uncommon finding.

Author Affiliations: Department of Neurology, UCLA Medical Center (Drs Bhidayasiri, Perlman, and Geschwind), and Departments of Medicine and Neurobiology (Dr Pulst), The David Geffen School of Medicine at UCLA, Los Angeles, Calif; Division of Neurology, Chulalongkorn University Hospital, Bangkok, Thailand (Dr Bhidayasiri); and Division of Neurology, Cedars-Sinai Medical Center, Los Angeles (Dr Pulst).