Spinocerebellar ataxia type 2 presenting as complex hyperkinetic movement disorder with a dramatic response to anticholinergic therapy

Dear Sir,Spinocerebellar ataxia type 2 (SCA 2) is a progressive, degenerative autosomal dominant cerebellar ataxia (ADCA), characterized by extrapyramidal and pyramidal degeneration. Patients can have ataxia with early saccadic hypometria, hyporeflexia, ophthalmoparesis, tremors, and myoclonus.[1] However, SCA 2 has a vast phenotypic spectrum and can present without ataxia. Hence, a high clinical suspicion and a low threshold for sending SCA genetics in patients with complex hyperkinetic disorders with a positive family history is required. It occurs due to an expanded CAG trinucleotide repeat in the gene encoding ataxin-2. As a neurodegenerative disorder, no disease-modifying treatment is available, and patients are treated with symptomatic and palliative therapy. A 24-year-old male third born of non-consanguinity presented clinically with a new onset of dystonic posturing and involuntary movement of his left upper limb. In addition, his mother had dystonia with chorea that started at the age of 56 years. His grandfather had ataxia starting at the age of 81 years [Figure 1]. On examination [Video 1], he had mild cervical dystonia with mild anterior shift, left laterocollis with left upper limb mobile dystonia with left shoulder elevation, and wrist flexion and associated mild choreiform movement. Neurological examination revealed normal saccades and pursuit, finger–nose test for motor coordination, with lower limb hyperreflexia. His hemogram, routine biochemistry, electrolytes, ammonia, and lactate were normal. His serum copper level and ceruloplasmin activity were normal; slit-lamp examination did not show any evidence of Keyser–Fleischer ring. Peripheral smear and saline dilution tests for acanthocytes were negative. Magnetic resonance imaging (MRI) brain revealed mild cerebellar atrophy. Targeted ataxia gene panel for SCA 1,2,3,6,7,10,12, and DRPLA was positive for Ataxin 2 gene with a triplet repeat length of 41(Normal- 14-31). Home video of his mother (who could not be physically examined) revealed generalized chorea with perioral chorea and bilateral blepharospasm. She was later tested positive for SCA2 [Video 1]. He was started on trihexyphenidyl, following which he had a remarkable sustained response within 5 days with significant reduction of the left upper limb involuntary movement.Figure 1: The pedigree chart of the proband patient {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video 1","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_dqc9sj8z"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} Discussion SCA 2 is the most common SCA in India and the second most common worldwide, next only to SCA 3. It can present with different hypokinetic and hyperkinetic movement disorders even before the onset of ataxia, depending on the repeat length. The clinical hallmark is slow saccades. A European cohort reported rest tremor being the most common (14.9%) movement disorder, followed by dystonia (14.2%), myoclonus (13.7%), rigidity (7.4%), and chorea/dyskinesia (6.8%).[2] Complex phenotypic variations are common in SCAs as they depend largely on triplet repeat length. In another cohort, dystonia was present in both SCA 2 (17.9%) and SCA3 (17.6%), and chorea was present in SCA2 (7.1%).[3] Dystonia is usually an early feature with predominant cervical and lower cranial dystonia.[4] However, our patient had limb dystonia, which is rare. Although chorea is a common feature of SCA 17 and DRPLA, other SCA 1, 2, and 3 rarely present with chorea. All these disorders are polyglutamine disorders with similar neuropathological autopsy findings of widespread atrophy of the extrapyramidal system.[5] The search for definitive treatment is going on with several agents, including riluzole, memantine, and dantrolene, showing variable results in trials.[6] Symptomatic therapy with botulinum toxin for dystonia demonstrated promise for focal dystonia. Trihexyphenidyl is a centrally acting muscarinic receptor antagonist. It reduces dystonia by altering corticostriatal plasticity deficits by antagonizing M1 receptors in the striatum.[7] However, anticholinergic drugs may often aggravate the chorea. To our surprise, the mild choreiform movement also subsided in our patient.[8] Previously, one case was reported where lower limb choreiform movements were treated with trihexyphenidyl.[9] Our case highlights the importance of SCA 2 testing in patients presenting with complex phenotypic movement disorders with or without ataxia. Moreover, it addresses the importance of anticholinergics in the therapeutic armamentarium of degenerative causes of dystonia. Acknowledgment The authors thank the patient and the family members for their active contribution to this study. The authors also thank reviewers for their comments and suggestions. Author contributions Research project: Conception: Debayan Dutta, Ravi Yadav Organization: Debayan Dutta, Ravi Yadav, Sandeep Gurram Execution: Sandeep Gurram Statistical analysis: Design: Debayan Dutta, Sandeep Gurram Execution: Ravi Yadav Review and Critique: Manuscript preparation: Writing of the first draft: Review and Critique:. Ethical compliance statement The authors confirm that the approval of an institutional review board/patient consent was not required for this work. The patient has given informed written consent for the publication of his videos. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Data availability statement Additional data will be made available if requested.