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Slowly Progressive Cerebellar Ataxia in a 55-Year-Old Female Patient

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 55-year-old female patient with a history of hypercholesterolemia and anxiety was referred for progressive imbalance while walking and intense fear of falling for the past 14 years. The patient had become progressively disabled and had been using a wheelchair for 4 years prior to presentation. Neurological examination showed gaze-evoked horizontal nystagmus in both directions along with slow saccades and gaze restriction in both vertical and horizontal planes. There was ataxic dysarthria. Tone was normal in all 4 limbs but stretch reflexes were absent and plantar fascia were mute. Limb power was normal. Ataxia was seen on finger-to-nose and heel-knee-shin tests. Chorea was present in both legs. Ankle inversion with bilateral hammertoes was noted. Electromyography revealed sensory neuronopathy. On brain magnetic resonance imaging (MRI), diffuse cerebellar atrophy was noted along with T2 hyperintensities in bilateral middle cerebellar peduncles, cerebellar white matter, pons, and bilateral thalamus (Figure). Psychiatric treatment was commenced for her severe anxiety but did not relieve the fear of falling.

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D. Mitochondrial ataxia

Friedreich ataxia (FRDA; choice A) is one of the most common autosomal recessive cerebellar ataxias, caused by GAA trinucleotide repeat expansions in the frataxin (FXN) gene, with onset typically occurring in the second decade of life. Associated peripheral neuropathy, dorsal root ganglionopathy, and dorsal column involvement lead to areflexia with early loss of distal vibration sense. Oculomotor findings include fixation instability and frequent square-wave jerks, while gaze-evoked nystagmus is less common.1 Common systemic manifestations include cardiomyopathy, diabetes, and musculoskeletal abnormalities like scoliosis, pes cavus, foot inversion, and hammertoes.2 Late-onset cases commonly present with spastic ataxia with preserved or even brisk reflexes, without systemic manifestations.2 Brain MRI in patients with FRDA shows spinal cord atrophy with preserved cerebellar volume.1 This patient had sensory neuronopathy and skeletal deformities in the feet. However, disease onset was in the fourth decade of life with absent reflexes, prominent gaze evoked nystagmus, slow saccades, gaze palsy, and diffuse cerebellar atrophy on MRI. Test results for FRDA genetics were negative.

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Article Information

Corresponding Author: Mandar Jog, MD, Movement Disorder Centre, London Health Sciences Centre, The University of Western Ontario, 339 Windermere Rd, London, ON N6A 5A5, Canada (mandar.jog@lhsc.on.ca).

Published Online: November 7, 2022. doi:10.1001/jamaneurol.2022.3791

Conflict of Interest Disclosures: Dr Tuesta Bernaola reported fellowship funding from the Parkinson Society of Southwestern Ontario. Dr Ganguly reported grants and fellowship funding from the Academic Medical Organization of Southwestern Ontario. No other disclosures were reported. Dr Jog reported speaker’s fees and research funding from Allergan, AbbVie, Merz Pharmaceuticals, Boston Scientific, Valeo Pharma, Sunovion, and Paladin Labs and grants from Parkinson Society of Canada, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Mathematics of Information Technology and Complex Systems, the Research Council of Norway, Parkinson Society of Southwestern Ontario, Dystonia Medical Research Foundation, and Academic Medical Organization of Southwestern Ontario. No other disclosures were reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

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