C9ORF72 expansion in amyotrophic lateral sclerosis/frontotemporal dementia also causes parkinsonism

Spinocerebellar ataxia (SCA6) manifests a wide spectrum of noncerebellar symptoms including parkinsonism. However, cerebellar ataxia is the main clinical feature, even in patients with extracerebellar involvement. Here, we describe an SCA6 patient with the parkinsonian phenotype without cerebellar dysfunction. A 41-year-old man visited our clinic because of progressive slowness in the prior 3 months. The slowness was more severe on his right side. His walking had also slowed. There was no history of other medical disease or medications. His elder brother had died at age 40 from an unknown cause. However, his brother had been an alcoholic and had shown gait disturbance. The patient showed normal cognitive functions on the Mini–Mental State Examination and Frontal Assessment Battery. His speech was slow, monotonous, hypokinetic, and not cerebellar. His facial expressions and eye-blinking rate had both slowed. Ocular motility was normal. Motor power was intact, and sensory examination was normal. Knee jerks were brisk, and plantar responses were flexor. There was generalized bradykinesia, more severe on the right side. He had rigidity that was more prominent axially and on the right side. Mild terminal tremor was observed in the right hand. His gait was slow and his arm swing was decreased on the right side. There was no limb or truncal ataxia (see Video Segment 1). There was no improvement with levodopa at 800 mg/day. Laboratory tests were negative for Wilson’s disease, Park2, Huntington’s disease, SCA1, SCA2, SCA3, SCA7, and SCA17. The trinucleotide repeat number of SCA6 was increased to 20. Brain magnetic resonance imaging was normal, and there was no cerebellar atrophy (Fig. 1). Dopamine transporter (DAT) density was reduced, with a rostrocaudal gradient typical of Parkinson’s disease (PD) according to [I]-floropropyl 2-carbomethoxy-3-(4-iodophenyl) tropane positron emission tomography (FP-CIT PET). DAT binding was more decreased on the left side (Fig. 1). He did not complain of hyposmia; however, threshold-discrimination-identification was abnormal on an olfactory function test with a validated Korean version of the Sniffin’ stick test. During the follow-up exam, he complained of epigastric discomfort, and gastric cancer was found during an endoscopy. a-Synuclein immunohistochemistry in the resection margin from his stomach showed no a-synucleinpositive inclusions. On a follow-up visit after 2 years, his tremor, bradykinesia, and postural instability were aggravated. Heel-to-shin test was mildly impaired because of bradykinesia rather than ataxia. However, tandem gait was normal. He did not have gaze-evoked nystagmus, perverted head shaking, and positional down-beating nystagmus (see Video Segment 2). Parkinsonism was reported in SCA6 and was associated with a variable pattern of DAT imaging abnormalities. However, the main clinical feature in these parkinsonian patients is cerebellar dysfunction. This is the first clinical report of SCA6 presenting features at onset closely resembling pure parkinsonism. No a-synuclein-positive inclusions in the stomach tissue suggest that this case is not synucleinopathy. The current case expands the clinical spectrum of SCA6 compared with that previously reported.