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Etiology and course of cerebellar ataxia: A study from eastern India

 Department of Neurology, Bangur Institute of Neurosciences, IPGMER, Kolkata, West Bengal, India

Date of Submission01-May-2021
Date of Decision25-Jul-2021
Date of Acceptance30-Jul-2021

Correspondence Address:
Adreesh Mukherjee,
2-B, Surja Kumar Chatterjee Street, Kolkata - 700 025, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_314_21


Objective: The course of various cerebellar ataxia disorders in our population is relatively unexplored, especially beyond the hereditary spinocerebellar ataxias (SCA). This study was conducted to objectively assess the severity and progression of various disorders causing the cerebellar ataxia. Materials and Methods: This longitudinal prospective study evaluated the etiologies and the corresponding severity and progression of the cerebellar ataxia. Clinical examination and the relevant investigations were performed. The severity of ataxia was assessed using the Scale for Assessment and Rating of Ataxia (SARA) - at initial presentation and another at 6 months of follow-up, and the change in SARA scores were calculated to find the disease progression. Results: Out of 145 patients studied, SCA predominated followed by Autoimmune/paraneoplastic disorders, Multiple System Atrophy-Cerebellar (MSA-C), Wilson's disease, and Multiple sclerosis. On follow-up, human immunodeficiency virus (HIV) associated progressive multifocal leukoencephalopathy was the most rapidly advancing disease, followed by MSA-C, Friedreich's ataxia, and Huntington's disease, all of which progressed faster than SCA. SCA 3 emerged as the most progressive SCA followed by SCA 1, SCA 6, SCA 2, and SCA 12. The autoimmune etiologies showed favorable response to treatment, although with some variability across the different disorders. In the paraneoplastic category, anti Tr associated ataxia improved better than other disorders. Multiple sclerosis and other treatable disorders also responded to treatment. Conclusion: Cerebellar ataxia is the predominant clinical feature in a wide variety of disorders. While some are progressive, others are responsive to treatment, the extent of which differed according to the etiology.

Keywords: Ataxia, cerebellum, scale for assessment and rating of ataxia, spinocerebellar ataxia

How to cite this URL:
Bhuin S, Biswas S, Roy A, Mukherjee A, Pandit A, Gangopadhyay G. Etiology and course of cerebellar ataxia: A study from eastern India. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2023 Mar 20]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=337071

  Introduction Top

Ataxia refers to incoordination of voluntary movement and it is most commonly due to cerebellar dysfunction. There is an extensive differential diagnosis of disorders causing cerebellar ataxia, and while some are relentlessly progressive, others are treatable and show an improving course. To monitor the progress of such diseases and to evaluate the efficacy of the treatment (existent as well as potential new therapies), clinicians require an appropriate clinical rating scale to assess these various disorders. The International Cooperative Ataxia Rating Scale (ICARS) is widely used as a scale for assessing the severity of cerebellar ataxia and therapeutic effects, however, the application of this scale in daily examinations of ataxic patients is limited due to the large number of items to be evaluated.[1] Another relatively simpler scale named the Scale for Assessment and Rating of Ataxia (SARA) was devised, which is based on a semi-quantitative assessment of cerebellar ataxia on an impairment level.[2] SARA scoring tool has fewer assessment items than the ICARS and is less time-consuming. It does not require special training or technical equipment and has good reliability and internal consistency compared to ICARS.[3],[4] Although previous studies utilizing this scale were mostly on spinocerebellar ataxia (SCA), yet, it was also found useful in other disorders such as Multiple System Atrophy-Cerebellar (MSA-C) and Multiple sclerosis.[5],[6],[7]

A detailed study to evaluate the disease course of ataxia patients in our population with the help of such scales is a relatively uncharted field, and it may enhance our understanding of the progression of these diseases. Hence, this study was taken up in our institute to explore this aspect of cerebellar ataxia-etiology and respective disease course (based on SARA score).

  Materials and Methods Top

This longitudinal prospective study recruited patients attending the Department of Neurology of our institute in Kolkata over duration of 2½ years. Patients with cerebellar ataxia as the principal clinical feature were included in the study. Patients with predominant sensory ataxia or vestibular disorder were excluded. Vascular and Neurosurgical causes (trauma, tumor, etc.,) of ataxia were also not included. Diseases with additional neurological dysfunction beyond cerebellar involvement (such as spasticity, extrapyramidal dysfunction, neuropathy, etc.,) were included in this study if cerebellar dysfunction was the foremost feature and the predominant cause of motor impairment. Patients in whom no etiology could be ascertained were not included. Total patients studied (with mentioned required investigations and diagnostic etiology ascertained) were 145. Three patients of Creutzfeldt-Jakob Disease (CJD) and 1 patient of Ataxia-telangiectasia could not be followed-up.

Written informed consent was taken from the patients/guardians, and the study was approved by our institutional ethics committee for human research.

These patients were evaluated by detailed history, clinical examination, and relevant investigations including neuroimaging (mostly 3T Magnetic resonance imaging) and genetic study. Genetic etiology was established with gene panel study and both familial and sporadic cases were found. Family members were screened in accordance with the inheritance pattern of the etiology. Regarding the patients with the abnormal paraneoplastic panel, malignancy was searched using positron emission tomography scan (whole body) in most of the patients, and computed tomography scan (contrast enhanced) of thorax/abdomen was done in some cases [Figure 1]. For MSA-C, we included patients who were diagnosed as probable MSA-C as per the second consensus statement.[8]
Figure 1: Approach to a patient of cerebellar ataxia

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Clinical severity of ataxia was assessed by SARA, and scores were obtained for each patient-first at initial presentation and another at 6 months follow-up. Change in SARA scores between the initial presentation and follow-up was calculated to find the individual disease course and its progression/improvement. It is a clinical scale which assesses a range of different impairments in cerebellar ataxia. The scale is made up of 8 items with accumulative score ranging from 0 (no ataxia) to 40 (most severe ataxia). Each category is assessed and scored accordingly. Scores for the eight items range as follows - gait (0–8), stance (0–6), sitting (0–4), speech disturbance (0–6), finger chase (0–4), nose-finger test (0–4), fast alternating hand movement (0–4), and heel-shin slide (0–4). For the last 4 items of motor activities of the extremities, assessments are performed bilaterally, and the mean values are used to obtain the total score.[2] Average time taken for each patient was 15–20 min. Scoring was done at initial presentation and at 6 months of follow-up (which was predefined in view of the duration of the study). In addition to 6 monthly SARA scoring, in between follow-up was done as per patients' requirement. Scoring was done by a single assessor (SB) initially and at follow-up.

The patients were treated according to the standard recommendations as applicable for the respective etiologies. For the autoimmune/paraneoplastic disorders, the initial treatment was done with intravenous methylprednisolone and intravenous immunoglobulin. In some patients, plasma exchange therapy was done, while some of the refractory cases received Rituximab. Treatment of any malignancy was carried out in accordance with other concerned departments. In addition to the specific treatments, the patients also received symptomatic management (such as baclofen for spasticity) as well as rehabilitation measures (with the help of physical medicine experts).

Statistical analysis

Categorical variables are expressed as number and percentage. Continuous variables are expressed as mean, median, and standard deviation and compared across the groups using Mann–Whitney U-test/Kruskal–Wallis test as appropriate. The statistical software SPSS version 20 IBM SPSS Statistics for Windows, version 20 (IBM Corp., Armonk, N.Y., USA) has been used for the analysis. An alpha level of 5% has been taken, any P < 0.05 was considered significant.

  Results Top

Epidemiology and etiology

Out of the total 145 patients studied, 81 were male and 64 female. The mean age of onset for ataxia was found to be 37.4 (±14.66) years. Most patients were found to be in the 30–50 years age category (50%) followed by 21% in >50 years age category, 16% in 15–30 years age category and least (13%) in <15 years age category.

The predominant etiology was SCA in which SCA2 was highest with 12 patients followed by SCA 3, SCA 1, SCA 6, and SCA 12 [Table 1]. Autoimmune/paraneoplastic disorders formed another major part of cerebellar ataxias (23 patients) which consisted of Anti-NMDAR (N-Methyl D-Aspartate Receptor) antibody, Anti- GAD (Glutamic acid decarboxylase) antibody, Anti-Yo antibody, Anti-Gliadin antibody, Anti-Hu antibody, Anti-Tr antibody, and anti-TPO (Thyroid Peroxidase) antibody positive steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) (Hashimoto). This group was followed by MSA-C, Wilson's disease, and Multiple sclerosis as the next major etiologies causing cerebellar ataxia.
Table 1: Scale for Assessment and Rating of Ataxia scores (at initial presentation and at 6 months follow-up) of individual diseases of cerebellar ataxia

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Regarding Wilson's disease, our institute being a tertiary referral center for this disease, we see a good number of such patients every year. We included only the ataxic patients in this study. Some of them also had dystonia (mostly in the upper limbs), while few had early signs of Parkinsonism. However, in all patients accepted for evaluation in this study, cerebellar ataxia was the predominant feature.

Among the other etiologies, there were Post Viral cerebellitis, Kearns-Sayre syndrome (KSS), Huntington's disease (with cerebellar dysfunction as a prominent feature), Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS), HIV associated progressive multifocal leukoencephalopathy (PML), Metronidazole toxicity, Sporadic CJD, vitamin E deficiency, Idiopathic hypertrophic pachymeningitis, Friedreich's ataxia, and Wernicke's Encephalopathy. The rest of the patients consisted of 1 each of Pelizaeus-Merzbacher disease (PMD), Superficial siderosis, and Ataxia-Telangiectasia.

The onset varied according to the etiologies. While Post viral cerebellitis was acute in onset, others also showed acute-to-subacute onset. These included Multiple sclerosis, Autoimmune/paraneoplastic disorders, CJD, Vitamin E deficiency, Wernicke's Encephalopathy, MELAS, Metronidazole toxicity, HIV-PML, and Idiopathic hypertrophic pachymeningitis. Chronicity in onset consisted of SCA, MSA-C, Superficial siderosis, and rest of the hereditary disorders.

Scale for Assessment and Rating of Ataxia scores

SARA scores were applied to each patient at initial presentation and at 6 months of follow-up.

Scale for Assessment and Rating of Ataxia scores (Initial)

[Table 1] shows the mean individual diseases SARA scores at initial presentation. CJD had the highest initial score (19.67) followed by autoimmune/paraneoplastic etiologies-(Score 19-Anti-GAD, Anti-gliadin, Anti-Tr, and 18.75-anti-Yo), Multiple sclerosis (18.67), Anti-Hu-associated ataxia and MELAS (both at 18), Vitamin E deficiency (17.67), Ataxia Telangiectasia and PMD (both at 17), Wilson's disease (15.94), SCA 3 (15.88), Huntington's disease (with predominant cerebellar dysfunction) (15.75), HIV PML (15.67), and Friedreich's ataxia (15.5). In Vitamin E deficiency and Multiple sclerosis, patients presenting with predominant cerebellar dysfunction were included, and SARA score was applied to them, whereas patients with mainly sensory ataxia were excluded from the study. MSA-C had initial SARA score of 15 equivalents to SCA 2 along with SREAT and Wernicke's Encephalopathy followed by SCA6 (14.75) and SCA 1 (14.57). Another mitochondrial disease, KSS was next with a score of 14.5 followed by postviral cerebellitis (14.25) and Metronidazole toxicity (13.67). Anti NMDAR had a lower SARA score (13.5) than others in the autoimmune/paraneoplastic category. Idiopathic hypertrophic pachymeningitis (13.33) and superficial siderosis (13) were next followed by SCA 12 (12) which had the least initial score among all diseases studied.

Change in Scale for Assessment and Rating of Ataxia scores (over the course of follow up)

The change in SARA score was divided into two parts-diseases with increase in SARA score and diseases with decrease in SARA score. CJD and Ataxia telangiectasia patients could not be followed up, hence no follow-up SARA score for them was found.

Diseases with increase in Scale for Assessment and Rating of Ataxia score

[Table 2] shows diseases with increase in SARA score denoting progressive course of disease. HIV-associated PML (+7.81) had the highest positive change followed by MSA-C (+5.44), Friedreich's ataxia (+4.83), Huntington's disease (+4.53), KSS (+4.22), and SCA 3 (+3.98). Among the SCAs, SCA 3 had the highest change of score (+3.98) followed by SCA1 (+3.68), SCA 6 (+3.52), SCA 2 (+3.24) and SCA 12 (+2.04), and this difference was statistically significant (P = 0.002) [Table 3]. The duration of disease at presentation for the SCAs was longest for SCA 2 (mean-4.75 years), while the rest of the SCAs had average duration of 2.4–3.1 years. Compared to SCA 3, which was the most progressive SCA, MSA-C (P = 0.01), Friedreich's ataxia (P = 0.028), and Huntington's disease (P = 0.034) progressed significantly faster. KSS also showed a higher mean change of SARA score than SCA 3, although it was not statistically significant (P = 0.087). PMD showed a change of +3 and the least positive change in SARA score was noticed in superficial siderosis (+2).
Table 2: Diseases with increase in Scale for Assessment and Rating of Ataxia scores (follow-up - initial) - progressive course

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Table 3: Comparison of change in Scale for Assessment and Rating of Ataxia scores in Spinocerebellar ataxia 3

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Diseases with decrease in Scale for Assessment and Rating of Ataxia score

[Table 4] shows diseases with decrease in SARA score denoting improving course of disease. In diseases with negative change in SARA score on follow-up, Anti-GAD was highest (-10.12), followed by Anti Gliadin (-9.84), SREAT (-9.51), postviral cerebellitis (-9.38), Wernicke's encephalopathy (-8.92), Metronidazole toxicity (-8.54), and Vitamin E deficiency (-7.93). Multiple sclerosis followed them at score change of-6.84 and then the other autoimmune/paraneoplastic etiologies-Anti-Tr associated ataxia (-6.12), Anti- NMDAR (-5.33), Anti-Hu (-3.84), Anti-Yo (-3.42). MELAS showed a change of-3.21 followed by Wilson's disease (-1.48) and Idiopathic hypertrophic pachymeningitis (-1.22). Of the autoimmune disorders, Anti-NMDAR showed less improvement with the treatment compared to Anti-GAD, Anti-Gliadin, and SREAT (P = 0.004). In the paraneoplastic group, Anti-Tr improved much better after the treatment than Anti-Hu and Anti-Yo (P = 0.04).
Table 4: Diseases with decrease in Scale for Assessment and Rating of Ataxia scores (follow-up - initial)-improving course

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Assessment of Wilson's disease patients using SARA was interesting. The presence of other movement disorders sometimes creates difficulty in implementing SARA. However, our patients had predominant ataxic symptoms with co-existent dystonia/Parkinsonism in some cases. Hence, SARA could be used adequately in them. Moreover, on follow-up, improvement with the treatment was observed, predominantly in gait, stance, and speech components of SARA. Dystonia and Parkinsonism also did not increase much in the 6 months of follow-up, to cause any significant hindrance in applying SARA.

  Discussion Top


Out of 145 patients of cerebellar ataxia, male patients were predominant (55.86%), and most patients were int30–50 years age category (50%). Etiology wise, in the present study conducted from eastern India, cerebellar ataxia was predominated by SCA in which SCA2 was most common followed by SCA3, SCA1, SCA6, and SCA12. This finding differs from that of an Iranian study by Nafissi et al., which showed multiple sclerosis to be the most common cause of cerebellar ataxia with much lower proportion of hereditary ataxias.[9] Overall, the global prevalence of SCA is 0.3–2/100,000 population.[10],[11] SCA3 is the most common variety worldwide accounting for 20%–50% of all cases, though it is comparatively less common in India.[10],[12] In India, SCA2 is the most common form of ataxia in studies from northern and Western India.[13] Although Chakravarty and Mukherjee[14] reported SCA3 to be the most common variety in ethnic Bengali population (eastern India), in another study from eastern India, SCA2 was the most common followed by SCA1, SCA3, SCA6, and SCA12.[13] A south Indian study documented high frequency of SCA-1.[15]

Following this, autoimmune/paraneoplastic category (Anti-GAD antibody, Anti-Gliadin antibody, Anti-NMDAR antibody, Anti-Yo antibody, Anti-Hu antibody, Anti-Tr antibody, and Anti-TPO antibody positive SREAT), MSA-C, Wilson's disease and Multiple sclerosis formed a major part of cerebellar ataxias. There were miscellaneous other etiologies such as genetic (including mitochondrial), infective/post-infective, inflammatory, toxic, and metabolic. Epidemiological study of cerebellar ataxia by Kim et al. in the Korean population showed the most common cause of nonfamilial ataxia as MSA-C, followed by sporadic ataxia of unknown etiology, postinfectious, alcoholic degeneration, superficial siderosis, and toxic causes, and the least was paraneoplastic etiologies (<1%).[16] In the study by Gebus et al. of cerebellar ataxia, MSA-C was found to be the most frequent etiology followed by inherited diseases, immune mediated, and other acquired causes.[17]

Disease severity and course on follow-up

The SARA scores of individual diseases at initial presentation are depicted in [Table 1] which indicates the presenting severity of the diseases in terms of cerebellar dysfunction before any treatment. Increase in SARA score (positive change) denotes progression of severity, while decrease (negative change) indicates improvement. In most of the cases showing improvement in SARA scores, there was clinically meaningful gain in function for the patient.

Improving course

The initial presenting severity of most of the autoimmune/paraneoplastic conditions along with multiple sclerosis and MELAS was high. However, most of the autoimmune disorders showed remarkable improvement with the treatment as documented by the decrease in follow-up SARA scores. The paraneoplastic disorders also improved, although to a lesser extent, and Anti-Tr associated paraneoplastic cerebellar ataxia showed greater improvement with treatment than Anti-Hu and Anti-Yo-associated disorders. This finding was concurrent with other studies, where the functional outcome and survival from time of diagnosis was found to be worse in anti-Hu and anti-Yo patients compared to anti-Tr antibody-associated paraneoplastic disorder.[18],[19]

Anti-NMDAR antibody-associated cerebellar ataxia took a slightly different course than other autoimmune conditions (Anti-GAD, Anti-Gliadin, and SREAT), displaying less decrease of SARA score, although its SARA score remained lower than Anti-GAD and Anti- Gliadin. A longer follow-up is required to know whether this lower rate of change of SARA score ultimately leads to a higher disability in Anti-NMDAR antibody-associated cerebellar ataxia. A larger cohort with longer follow-up might also elaborate whether cerebellar dysfunction predominant form of Anti-NMDAR is comparatively more resistant to the treatment. Several studies have shown variable treatment responses in anti-Gliadin and anti-GAD-associated ataxias.[20],[21] A previous study also demonstrated favorable treatment response of ataxia in SREAT,[22] and in our patients, we could document the improvement objectively using SARA scores. A favorable response in Anti-NMDAR-associated diseases is seen in other studies, although with chances of relapse later.[23],[24] However, studies comparing the treatment response to immunomodulators in ataxia associated with these autoimmune disorders is scarce.

Other disorders which showed notable improvement (with treatment) were Post-viral cerebellitis, Wernicke's encephalopathy, Metronidazole toxicity, Vitamin E Deficiency, and Multiple sclerosis. The significant improvement in Multiple Sclerosis patients indicates good short-term recovery in this disorder, although longer follow-up would better delineate the effect of relapse and long-term disability. A contrasting pattern was seen in the course and progression of the two mitochondrial disorders with cerebellar predominant dysfunction in our study-MELAS had an improvement of the disease course, whereas KSS had a progression of illness and further deterioration during follow-up. This highlights the importance of a specific diagnosis within the mitochondrial disorders group, as different diseases have different clinical courses. Wilson's disease and Idiopathic hypertrophic pachymeningitis showed improving course, although at much slower pace. Wilson's disease patients at presentation were drug-naive and were given chelation therapy with Penicillamine along with symptomatic medications (trihexyphenidyl, clonazepam, baclofen), with regular urinary copper monitoring. These patients of Wilson's disease showed no treatment-related worsening on follow-up.

Hence, although the treatable causes may present with initial higher SARA scores, an adequate treatment leads to the improvement, the extent of which varies according to the etiology. Wernicke's encephalopathy, SREAT, Metronidazole toxicity, and Post viral cerebellitis were among the least severe cerebellar ataxias after the treatment and follow-up.

Progressive course

HIV-associated PML was the most disabling and rapidly progressive among all the disorders that could be followed up. Also noteworthy was MSA-C which was the next most disabling condition on follow-up and outpaced all the genetic causes of ataxia in terms of rate of disease progression. Despite having a lower initial severity than SCA 3, Friedreich's ataxia and Huntington's disease, MSA-C surpassed all these disorders on follow-up. In another follow-up study utilizing SARA scores by Lee et al.,[5] MSA-C patients showed faster progression than SCA. Klockgether et al.[25] also documented quicker progression in MSA compared to Friedreich's ataxia and SCA. Of the genetic disorders manifesting ataxia, Friedreich's ataxia, Huntington's disease, and KSS showed faster progression than SCA. SCA 3 initially showed a higher severity than Friedreich's ataxia and Huntington's disease, however, on follow-up, both diseases overtook SCA 3 in terms of their SARA scores.

In the SCA group, SCA 3 had the highest severity on presentation, followed by SCA 2, SCA 6, SCA 1, and SCA 12. In fact, SCA 12 had the least severity among all cerebellar ataxias at presentation. At follow-up, SCA 3 remained highest in terms of severity scores and displayed the fastest progression (among SCA patients). SCA 1 had initially lower severity than SCA 2 and SCA 6, but on follow-up, SCA 1 progressed and showed higher severity than them. Next in terms of progression was SCA 6. Both SCA1 and SCA 6 had faster disease progression than SCA 2, despite SCA 2 having higher initial severity. This was particularly interesting for SCA 6. In a multicenter study from the United States by Ashizawa et al.,[7] out of 345 patients of SCA, the annual increase of SARA score was found to be greater in SCA1 patients (1.61 ± 0.41) than SCA6 (0.87 ± 0.28), SCA2 (0.71 ± 0.31), and SCA3 (0.65 ± 0.24) patients. In contrast to this, our study demonstrated SCA3 as having the fastest rate of progression. Jacobi et al.[26] from a European multicentric longitudinal cohort study, reported the annual increase of SARA score to be greatest in SCA1 (2.18 ± 0.17) followed by SCA3 (1.61 ± 0.12) and SCA2 (1.40 ± 0.11). Earlier age at onset and larger expanded alleles were associated with faster SARA progression and accelerated the annual SARA increase.[26] In this study, the progression of SCA6 was slowest in the 1st year (0.35 ± 0.34) but jumped to 1.44 (±0.34) in the 2nd year. Hence, SCA 6 should be followed up frequently to detect subsequent increases in progression. SCA 12 remained the slowest progressing SCA.

Regarding the application of SARA, it was interesting to employ it in patients of Wilson's disease and Huntington's disease. Although the use of SARA might be difficult in the presence of concomitant movement disorders, it probably depends on the predominant clinical feature in such patients. In Wilson's disease, we could apply the SARA score adequately because dystonia and Parkinsonism were only accompaniment to the predominant ataxic presentation. Patients of Huntington's disease included in this study were somewhat atypical, with ataxia as a prominent dysfunction associated with chorea (predominantly in the upper limbs). On follow-up also, ataxia remained prominent, and an increase in SARA score was observed with the progression of the disease. However, an increase in these other movement disorders (such as chorea, dystonia, etc.,) in such patients may also lead to an increase in the score of some of the SARA components. Moreover, it is sometimes difficult to properly assess cerebellar signs in the presence of significant chorea. Hence, it would be prudent to identify the predominant movement disorder phenomenology in these patients before applying SARA, as other specific scales are available for both these diseases. Nevertheless, SARA may also be useful as an additional tool in such cases when ataxia is prominent.

A limitation of the present study is that a larger study population is required for better delineation of the clinical and etiological spectrum of cerebellar ataxia. Furthermore, a longer follow- up period would be helpful to determine the severity and disease progression more accurately. Moreover, since we excluded patients with predominant nonataxic presentations, our study shows the progression of each disease only presenting as ataxia.

  Conclusion Top

This study explored the etiology, severity, and course of cerebellar ataxias-some improving while others progressive. The treatable ataxias showed improvement, the extent of which differed according to the etiology. The autoimmune disorders showed favorable response to treatment, although with some variability across the different etiologies. Among the paraneoplastic disorders, Anti-Tr associated ataxia showed greater improvement than Anti- Hu and Anti-Yo associated disorders. MELAS and KSS, the two mitochondrial disorders in our study followed opposite course with MELAS improving and KSS progressing. HIV-associated PML was the most rapidly progressive disorder. MSA-C showed a faster rate of progression than all the genetic causes of ataxia. Among the genetic disorders, Friedreich's ataxia, Huntington's disease, and KSS showed quicker progression than SCA. In the SCA group, in contrast to studies from Western countries, we found the fastest rate of progression in SCA3. Moreover, SCA6 progressed faster than SCA2.

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4]


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