Spinocerebellar ataxia type 3 with dopamine-responsive dystonia: A case report

Abstract

BACKGROUND Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease with high genetic heterogeneity. SCA3 mainly manifests as progressive cerebellar ataxia accompanied by paralysis of extraocular muscles, dysphagia, lingual fibrillation, pyramidal tract sign, and extrapyramidal system sign. However, it rarely has clinical manifestations similar to Parkinson-like symptoms, and is even rarer in patients sensitive to dopamine. We report a patient initially diagnosed with dopamine-responsive dystonia who was ultimately diagnosed with SCA3 by genetic testing, which was completely different from the initial diagnosis. CASE SUMMARY A 40-year-old Chinese woman was admitted to hospital due to severe inflexibility. At the beginning of the disease, she presented with anxiety and sleep disorder. At the later stage, she presented with gait disorder, which was similar to Parkinson's disease. Her medical history was unremarkable, but her mother, grandmother, and uncle all had similar illnesses and died due to inability to take care of themselves and related complications. Laboratory and imaging examinations showed no abnormalities, but electromyography and electroencephalography revealed delayed somatosensory evoked potentials and slow background rhythm, respectively. Her symptoms fluctuated during the daytime, and we initially diagnosed her with dopamine-responsive dystonia. After treatment with low-dose levodopa, the patient’s symptoms were significantly improved, but the final genetic diagnosis was SCA3. CONCLUSION SCA3 has various clinical phenotypes and needs to be differentiated from Parkinson's syndrome and dopamine-responsive dystonia.

Autophagic vacuolar myopathy involving the phenotype of spinocerebellar ataxia type 3

“…Our patient showed parkinsonism-related symptoms mildly in the morning and more severely in the afternoon and evening, which was consistent with the fluctuating diurnal characteristics in SCA3. 7 Some patients with SCA3-related parkinsonism have a poor response to dopamine, while the others are levodopa-responsive. 7,11 Our patients had a good response to dopamine, which might be mainly dependent on the progression of the pathological changes between the substantia nigra and dentate nucleus in the cerebellum.…”

“…7 Some patients with SCA3-related parkinsonism have a poor response to dopamine, while the others are levodopa-responsive. 7,11 Our patients had a good response to dopamine, which might be mainly dependent on the progression of the pathological changes between the substantia nigra and dentate nucleus in the cerebellum. 7 Therefore, parkinsonism can be the initial or main symptom of SCA3, while the clinical characteristics of SCA3-related parkinsonism show some heterogeneity.…”

“…[2][3][4][5][6] Gait ataxia is the most common initial symptom in SCA3 patients, while some patients also show atypical initial symptoms, such as dysarthria, dysphagia, diplopia, dizziness, tremor, parkinsonism, spastic paraplegia, limb numbness, and limb weakness, which frequently cause the misdiagnosis or diagnostic delay of SCA3. 7,8 In 2020, a few SCA3 patients have been noticed to be predisposed to the development of inclusion body myositis (IBM), which indicates that skeletal muscle may be primarily involved in the pathogenesis of SCA3. 9 In this study, we describe an autosomal dominant inherited family in which the index patient initially presented with parkinsonism, sensory ataxia, and distal myopathy but the absence of cerebellar and pyramidal symptoms.…”

Drug repurposing of dopaminergic drugs to inhibit Ataxin-3 aggregation

“…Although extrapyramidal signs such as dystonia and rigidity can be masked in patients with dominant spinocerebellar ataxia [10,57], subtypes I and III of MJD feature extrapyramidal signs and subtype IV features levodopa-responsive parkinsonism [9,10,60,61]. Finally, an interesting case report was documented in 2021 about a patient presenting signs indistinguishable from Parkinson’s disease who was later diagnosed with MJD; it was not until ten years of treatment with levodopa and other dopamine agonists the patient developed the classical MJD symptoms, cerebellar ataxia and pyramidal signs [11].…”

“…With currently no available disease-modifying therapies for MJD, several symptomatic therapies can be prescribed based on the knowledge of other related diseases and the patient's needs [8]. For example, dopaminergic drugs such as levodopa and dopamine agonists can be used to ameliorate the parkinsonian symptoms that characterize a MJD subtype associated with CAG expansions within the 60-70 repeat ranges [9][10][11].…”