A 59-year-old African American woman with a history of Hashimoto thyroiditis presented with nearly 1 year of progressively worsening ataxia, dysarthria, and illegible handwriting. She had been thoroughly worked up at an outside hospital and diagnosed with a rare, autoimmune ataxia related to Hashimoto thyroiditis.
She further endorsed dizziness upon standing, dysphagia, falls, and increasing difficulty working her retail job. History included hypothyroidism well controlled with levothyroxine after thyroid ablation for thyroiditis. She had no family history of similar disorders or of autoimmune disease, and she denied tobacco, alcohol, and illicit drug use.
Her physical examination revealed an alert and oriented woman with no cognitive problems. Neurologic examination was remarkable for dysmetria, dysdiadochokinesia, and wide-based, unsteady gait. Aside from orthostatic hypotension, the remaining examination was benign.
Outside records showed normal thyroid function tests, positive antithyroid peroxidase antibodies, and a magnetic resonance imaging (MRI) impression suggestive of isolated cerebellar degeneration. Her extensive work-up had also included autoimmune serologies, which returned negative, and nutrition studies that were normal.
The patient’s presentation and outside work-up suggested isolated, subacute, progressive, cerebellar pathology of autoimmune origin. Initially, we found no family history, no exposure history, and nothing else suggestive of an alternative etiology. Our initial work-up considered a paraneoplastic process, but a repeat brain MRI study revealed diagnostic findings, including: bilateral middle cerebellar peduncle hyperintensity, posterior putamen hypointensity, and hot cross bun sign on T2 imaging (Figure). Revisiting her history, we found newly discovered rapid eye movement (REM) sleep disorder; she had been acting out her nightmares, only noticed by her daughter who had been spending the previous nights by her bedside. With findings of REM sleep disorder, autonomic dysfunction evidenced by orthostatic hypotension, and the hot cross bun MRI sign, a diagnosis of multiple system atrophy–cerebellar type was made.
Discussion
Multiple system atrophy is a progressive, fatal, neurodegenerative disorder characterized by autonomic, pyramidal, parkinsonian, and cerebellar features in variable combinations, that can present as isolated ataxia. The disease is subdivided into parkinsonian and cerebellar subtypes; ataxia is the predominating symptom in the latter. Prevalence ranges from 1/50,000-1/20,000 with equal sex distribution, a mean age of onset in the sixth decade, and possible environmental and genetic contributions.1 The disease is neuropathologically defined as a primary oligodendroglial α-synucleinopathy, differentiated from Parkinson disease, which is a neuronal α-synucleinopathy. Autonomic dysfunction, vasomotor symptoms, and REM sleep disorder may also be present. Radiologic features include atrophy of the pons, middle cerebellar peduncle, and putamen, with the hot cross bun sign being highly specific, though not pathognomonic. Diagnosis is probable with autonomic dysfunction and parkinsonian/cerebellar signs, but definitive diagnosis can be made only with postmortem histopathology.2
Progressive, nonfamilial, adult-onset cerebellar degeneration associated with Hashimoto thyroiditis has been described in very few patients.3 Acquired ataxia due to hypothyroidism is a reversible complication, however; irreversible cerebellar degeneration in euthyroid patients with positive antithyroid peroxidase antibodies has been infrequently observed and may suggest thyroid and cerebellar immunogenicity.3
This case ultimately demonstrates the potential for oversight in identifying multiple system atrophy. A detailed history, thorough examination, and proper radiologic interpretation are crucial in identifying multiple system atrophy–cerebellar type, which should ultimately be considered in any patient with late-onset cerebellar ataxia with no other appreciable causes.
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-Sipan Mathevosian, MS, Sunny R.K. Singh, MD, Chan Yeu Pu, MD
This article originally appeared in the September 2016 issue of The American Journal of Medicine.
