Correspondence Address: Dr. Sahil Mehta Department of Neurology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh. India
Source of Support: None, Conflict of Interest: None
A variety of manifestations are known to occur in spinocerebellar ataxias (SCAs) other than ataxia. Dystonia may be the presenting or dominant manifestation of certain types of SCAs, commonly in SCA 3, SCA 17, and SCA 2. In this paper, we present a case of genetically proven SCA 1 with dystonia as a dominant manifestation. She additionally manifested dysphagia early in the course of her illness which led to her death due to choking within 3 years of onset. Through this case we attempt to highlight the occurrence of dystonia as well as dysphagia in SCA 1 which usually lends a more aggressive course and poorer prognosis to the condition compared to other SCAs.
How to cite this article: Mehta S, Ray S, Aleti S, Lal V. Dystonia and dysphagia in spinocerebellar ataxia 1 portends a severe phenotype. Ann Mov Disord 2020;3:185-7
How to cite this URL: Mehta S, Ray S, Aleti S, Lal V. Dystonia and dysphagia in spinocerebellar ataxia 1 portends a severe phenotype. Ann Mov Disord [serial online] 2020 [cited 2022 Aug 13];3:185-7. Available from: https://www.aomd.in/text.asp?2020/3/3/185/300261
Spinocerebellar ataxias (SCA) are clinically, pathologically, and genetically heterogeneous disorders that are characterized by predominant gait and appendicular ataxia. However, a variety of nonataxic manifestations can occur in SCA ranging from corticospinal tract signs, oculomotor disturbances, peripheral neuropathy, and movement disorders., Movement disorders can be the presenting or predominant feature of SCAs. We present a case of genetically proven SCA 1 who had segmental dystonia as a dominant manifestation apart from ataxia. She also manifested dysphagia early in the course of her disease and displayed rapid progression which led to her death within 3 years. The presence of early dysphagia and rapid clinical deterioration can be uncommonly seen in SCA1 which we attempt to highlight through this case.
A 38-year-old right-handed female belonging to the Khatri community of India without any prior history of illness presented with a history of imbalance and abnormal involuntary movements for two years. She started having imbalance while walking and slurred speech at the age of 36 years. At the onset, she noticed imbalance while getting up from sitting position. Gradually, she started swaying to either side while walking. She was unable to walk in a straight line and started walking like a drunkard. She used to walk while keeping her feet wide apart. She also had difficulty negotiating her feet into slippers but never smeared her face while eating. Her gait dysfunction gradually progressed in the coming months so that she started falling and acquiring injuries on multiple occasions. The frequency of falls was 1–2 in a month. Falls were predominantly in the backward direction. She denied any history of seizures, loss of consciousness, vertigo, double vision or dizziness, and tinnitus. One year into the illness, she developed abnormal posturing and twisting movements of her neck towards the left associated with teeth clenching and intermittent contractions of lower face and eyes. She also had abnormal posturing of upper limbs whenever she tried to reach the mouth while eating. These abnormal involuntary movements would aggravate on action and subside during sleep. There was no history of exposure to dopamine receptor blocking agents. She also reported dysphagia which caused multiple choking spells intermittently. The dysphagia was more to semisolid foods compared to solids. She felt as if food is stuck in the throat while eating and would often vomit. However, there was no history of nasal regurgitation of food. She also developed speech difficulty in the form of undue pauses while speaking. There was no history of cognitive impairment, delusions, hallucinations or depressive symptoms, limb weakness, sensory disturbances or bladder, and bowel dysfunction. There was no history of slowness of activities or stiffness. There was a significant history of loss of weight and appetite. Her father, paternal uncle, and one sister had positive family history of ataxia. Both father and paternal uncle became symptomatic at around 45 years of age and succumbed to their illness by 50 years of age. Her younger sister developed ataxia at the age of 25 years and died at the age of 30 years. However, apart from this, further details about the family history could not be elicited. General physical examination revealed generalized wasting and systemic examination was normal. She scored 29/30 on Montreal Cognitive Assessment (MOCA). Frontal lobe functions were normal. Cranial nerve examination revealed impaired pursuits horizontal more than vertical and slow saccades with use of compensatory head movements. Extraocular movements were full. Uvula was central and gag reflex was hypoactive. Rest of the cranial nerves including 11th and 12th were normal. Jaw jerk was present but not brisk. Motor system examination revealed generalized wasting with preserved power in all muscle groups. Rigidity was present in the upper limbs on activation (Froment’s sign). All the reflexes were 2+ except absent bilateral ankle reflexes and extensor plantars. Joint position and vibratory sense were impaired in the lower limbs. Cerebellar examination revealed scanning speech with gross appendicular ataxia with impaired finger nose test, dysdiadochokinesia, and impaired heel-shin test. Gait was wide based and ataxic. She demonstrated progressive reduction in speed and amplitude during finger tapping suggestive of bradykinesia. Examination of the hyperkinetic movement disorder revealed cervical dystonia in the form of predominant torticollis to the left side. In addition, right-sided laterocollis with intermittent retrocollis and opisthotonic posturing was also present. There were mild choreiform movements observed in the upper limbs. She could suppress these abnormal movements by touching her chin [Video]. Apart from cervical dystonia, she also had facial dystonia in the form of contractions of lower face, platysma, and oromandibular dystonia (jaw closing). Dystonic posturing was also evident in the upper limbs with spread to lower limbs in the form of extension at the ankle and left metatarsophalangeal joint.
MRI brain revealed cerebellar and brainstem atrophy [Figure 1]. Nerve conduction studies revealed axonal sensorimotor polyneuropathy. Genetic analysis revealed 51 CAG repeats in the mutated allele of ataxin-1 gene suggestive of SCA-1. She reported a modest benefit with a combination of levodopa, trihexyphenidyl, and botulinum toxin injections. Unfortunately, she succumbed to her condition due to choking while eating food at home.
Figure 1: MRI brain showing (A) normal basal ganglia on T2W images. (B) and (C) Brainstem and cerebellar atrophy of T1W axial and sagittal images
SCA 1 is caused by the expansion of CAG repeats in the ataxin-1 gene on chromosome 6p22. Both hypokinetic and hyperkinetic movement disorders have been described in various SCAs. These include Parkinsonism More Details, action tremors, dystonia, chorea, and myoclonus. Dystonia is most commonly reported in SCA 3,17 and 2 but can also occur in SCA 1,14 and 6.The prevalence of dystonia reported within different SCAs ranges from 5% to 30%. In a series of 85 patients with genetically confirmed SCA from India, dystonia was present in 15.3% patients. It was most commonly seen in SCA-2 (17.9%) followed by SCA-3 (17.6%). SCA-1 accounted for 12.5% patients in their series. Dystonia is usually focal or segmental in distribution but rarely can be generalized. It can be a prominent manifestation with mild cerebellar involvement or can even precede cerebellar symptoms. Wu Yih-Ru et al. described a case of genetically proven SCA-1 in whom blepharospasm, oromandibular dystonia, and retrocollis preceded the onset of ataxia. Presence of dystonia usually signify more severe ataxia but is not associated with a faster progression of ataxia. SCA 1 patients with extrapyramidal manifestations are usually younger and have an earlier age of onset as compared to the cohort who do not have extrapyramidal features. Earlier age of onset and larger CAG expanded alleles are associated with faster progression of ataxia as well as non-ataxia symptoms as evidenced by EUROSCA study. Our patient had 51 CAG repeats in the mutated allele which may be responsible for faster progression as well as development of non-ataxia manifestations. This number of CAG repeats may be an important point to consider in a patient suffering from the SCA-1 subtype showing signs of rapid progression.
Dystonia is now considered a network disorder where dysfunction can occur at the cortico-thalamic-basal ganglia level. However, recently the cerebellum is also being implicated in the genesis of dystonia based on imaging and neurophysiological studies. Neuropathological studies in SCA-1 have shown variable affection of the putamen, pallidum and the subthalamic nucleus apart from cerebellar cortex and brainstem nuclei which may explain the occurrence of dystonia in these patients.
The other prominent feature in our patient was presence of dysphagia. The prevalence of dysphagia in SCAs is reported to be around 60% and is a negative predictor of survival in SCAs. Amongst the other SCAs, SCA 1 has the highest prevalence of dysphagia (70%). Loss of motor neurons in the brainstem and cerebellar dysfunction can both contribute to dysphagia. The severity of ataxia, longer disease duration, and number of CAG repeats have been found to be significantly associated with the development of dysphagia and are genotype specific. SCA 1 has a more aggressive course compared to other SCAs. The early development of dysphagia and death within 3 years is suggestive of a severe phenotype and fast progression in our patient.
In conclusion, segmental dystonia may occur as a predominant non-ataxic manifestation in a genetically proven SCA-1 patient. Higher number of CAG repeats may portend a more severe phenotype with rapid progression of disease and early death. We highlight early recognition of dysphagia to enhance care of these patients.
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Dragasević NT, Culjković B, Klein C, Ristić A, Keckarević M, Topisirović I, et al. Frequency analysis and clinical characterization of different types of spinocerebellar ataxia in serbian patients. Mov Disord 2006;21:187-91.
Jacobi H, Bauer P, Giunti P, Labrum R, Sweeney MG, Charles P, et al. The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: A 2-year follow-up study. Neurology [Internet]. 2011;77:1035-41. Available from: http://www.neurology.org/cgi/doi/10.1212/WNL.0b013e31822e7ca0
Genis D, Matilla T, Volpini V, Rosell J, Dávalos A, Ferrer I, et al. Clinical, neuropathologic, and genetic studies of a large spinocerebellar ataxia type 1 (SCA1) kindred: (CAG)n expansion and early premonitory signs and symptoms. Neurology 1995;45:24-30.
Yang C-Y, Lai R-Y, Amokrane N, Lin C-Y, Figueroa KP, Pulst SM, et al. Dysphagia in spinocerebellar ataxias type 1, 2, 3 and 6. J Neurol Sci [Internet]. 2020;415:116878. Available from: https://doi.org/10.1016/j.jns.2020.116878.