A 76-year-old woman presented with progressive left-sided motor incoordination, dystonia, and instability, clinically concerning for atypical parkinsonism. MRI showed Fazekas grade 1 chronic microvascular changes. ¹⁸F-FDG brain PET revealed asymmetric right cerebral hemisphere, sensorimotor cortex, and basal ganglia hypometabolism, suggestive of corticobasal degeneration. ¹⁸F-Florbetapir PET was negative. ¹⁸F-Flortaucipir PET demonstrated asymmetric right basal ganglia uptake, corresponding to hypometabolic regions and contralateral to left-sided symptoms. Although ¹⁸F-Flortaucipir demonstrates limited affinity for pure 4R tau and known off-target subcortical binding, the pronounced asymmetry in this Aβ-negative case of atypical parkinsonism supports a 4R tauopathy phenotype, illustrating potential utility beyond the current FDA-approved indication.

Hereditary ataxias are rare cerebellar disorders. Population level mortality patterns in the United States in the previous decades remain insufficiently described. We quantified national mortality trends associated with hereditary ataxias and described stratified trends by sex, race, census region, and urbanization. We analyzed U.S. Multiple Cause of Death data from CDC WONDER for 2000 to 2020. Decedents were identified using ICD-10 code G11 for hereditary ataxias. Age-adjusted mortality rates (AAMRs) per 100,000 were computed using the 2000 U.S. standard population, with 95% confidence intervals. Temporal trends were evaluated using joinpoint regression to estimate annual percent change (APC). Forecasts through 2050 were generated using ARIMA, with sensitivity analysis using linear regression. National AAMR increased significantly from 2000 to 2020. Rising rates were observed in both sexes, with consistently higher mortality among males. The largest relative increases occurred among Black or African American individuals and in the West census region. Trends were directionally consistent across urbanization categories, and the forecast analyses also indicated increasing overall mortality. Sensitivity analyses produced qualitatively similar patterns, with wider uncertainty within strata. Mortality associated with hereditary ataxias increased in the United States between 2000 and 2020, highlighting growing clinical and public health needs related to cerebellar disease. Improved phenotyping and coding, earlier diagnosis, and registry-linked surveillance may refine estimates and support service planning.

Hereditary ataxia is a neurodegenerative disorder notable for its early onset, with symptoms appearing in patients as young as two years old. Although affected individuals exhibit severe motor deficits and early mortality rates, the timeline of Purkinje cell loss remains unclear. To address this gap, we used the spastic Han-Wistar rat model, which harbors an unknown homozygous recessive variant that causes Purkinje cell loss. Here, we determined the onset and temporal progression of Purkinje neuronal loss in the spastic Han-Wistar model. To achieve this, we employed immunohistochemistry, Hematoxylin and Eosin histology, and neuronal density quantification. Behavioral testing demonstrated early-onset, progressive motor impairment in mutant rats, with motor deficits emerging around P45, following Purkinje cell loss detectable as early as P15. Additionally, guided by pedigree analysis indicating autosomal recessive inheritance for this ataxia, we performed whole-genome shotgun sequencing of a parent-offspring trio to identify amino acid-changing mutations consistent with this pattern. Sanger sequencing excluded Sbf2 as a causal variant, and whole-genome sequencing identified 273 candidate genes consistent with autosomal recessive inheritance. Together, our findings provide new insights into the onset and genetic complexity of ataxia, refining the value of the spastic Han-Wistar rat as a model for investigating mechanisms underlying hereditary ataxia.

The κ-opioid receptor (KOR) is recognized as a promising therapeutic target for the development of nonaddictive analgesics. However, the clinical utility of typical KOR agonists is limited by central adverse effects. SLL-022CCP is a novel KOR-selective ligand derived from a northebaine-based 4,5-epoxymorphinan scaffold, and we have previously demonstrated its high binding affinity for KOR. In this study, we performed a systematic evaluation of SLL-022CCP through in vitro and in vivo assays. In vitro, SLL-022CCP acted as an extremely potent full agonist at the KOR, inhibiting cAMP production with an EC50 of 0.002 nM, and exhibited high receptor subtype selectivity over the μ-opioid receptor (MOR, EC50 = 1.6 nM) and δ-opioid receptor (DOR, EC50 = 30.0 nM). SLL-022CCP recruited β-arrestin at the KOR with an EC50 of 15.5 nM and at the MOR with an EC50 of 668.0 nM. Molecular docking data for SLL-022CCP revealed that it maintains canonical interactions with the KOR orthosteric site while extending its terminal phenyl moiety into a hydrophobic subpocket. In vivo, SLL-022CCP produced potent antinociception in the hot plate test (ED50 = 1.816 mg/kg), acetic acid-induced writhing test (ED50 = 0.113 mg/kg), and significant antipruritic effects in the histamine-induced itch test (ED50 = 0.079 mg/kg) and CFA-induced itch test (ED50 = 0.105 mg/kg). The antinociceptive effects of SLL-022CCP were antagonized by the KOR-selective antagonist Nor-BNI, but not by the MOR antagonist CTAP (1 mg/kg, i.p.), supporting primarily KOR-mediated activity. Importantly, at the antinociceptive dose, SLL-022CCP did not elicit significant motor incoordination or conditioned place aversion (CPA) under current experimental conditions, while eliciting transient sedation, distinguishing it from the typical arylacetamide derivatives, like U50,488H. Collectively, these results identify SLL-022CCP as a highly potent and selective KOR agonist with a unique pharmacological profile that exhibits robust antinociceptive and antipruritic effects with low central side effects.

Spinocerebellar ataxia 1 (SCA1) is a fatal hereditary neurodegenerative disorder with no approved therapies, and gene-targeting strategies have thus far failed in clinical trials. Exercise remains the only intervention shown to provide clinical benefit in patients with spinocerebellar ataxias (SCAs), yet the underlying mechanisms remain poorly understood. Using the Atxn1154Q/2Q knock-in mouse model, we implemented a prolonged voluntary wheel-running paradigm from 4 to 16 weeks of age. Mice were then phenotyped using motor and cognitive behavioral assays. Following euthanasia, cerebellar tissue was harvested for histological analysis and unbiased transcriptomics. Unrestricted exercise rescued motor ataxia but not degeneration in this SCA1 mouse model at the ages in this study. Transcriptional profiling of cerebellar tissue separated wild-type (WT) sedentary and exercise mice by differential gene expression, but in SCA1 mice the most pronounced changes occurred at the level of RNA splicing, particularly in ion channel modules. Exercise led to a significant rescue of splicing events in SCA1 mice, with minimal impact on gene expression changes. Further, both exercised SCA1 and WT mice exhibited splicing patterns more similar to each other than their sedentary counterparts. Together with emerging evidence in other SCAs, our findings confirm aberrant splicing as a central driver of SCA pathophysiology and identify splicing-regulated networks as actionable therapeutic targets. The observed benefits in SCA1 mice suggest that correcting mis-spliced ion channels may be a viable strategy for disease modification across SCAs and related neurodegenerative disorders. ANN NEUROL 2026.

BackgroundFriedreich's ataxia (FRDA), a common hereditary ataxia with multisystem involvement, is caused by a biallelic GAA trinucleotide repeat expansion in the FXN gene, leading to reduced frataxin, mitochondrial dysfunction, and oxidative stress. This study evaluates cough effectiveness through voluntary peak cough flow (PCF).ObjectivesThe objective was to assess airway clearance dysfunction in individuals with FRDA by examining PCF and its relationship with pulmonary and oral strength, disease severity, and genetic factors.MethodsThis cross-sectional study, part of the Biomarkers in Friedreich's Ataxia observational study, involved 51 participants with molecularly proven FRDA undergoing respiratory testing, including spirometry, PCF, maximal respiratory pressures, sniff nasal inspiratory pressure, and lingual strength. Neurological impairment was assessed using the Modified Friedreich's Ataxia Rating Scale (mFARS) and Functional Staging for Ataxia.ResultsForty-seven participants completed PCF tests (31 female; mean age 22.60 years). Twenty-nine (61.7%) remained ambulant (mean mFARS 49.91). Seventeen (36.17%) had reduced PCF (<270 L/min). Lower PCF correlated with younger age, earlier disease onset, and decreased respiratory muscle strength. PCF showed strong associations with maximal inspiratory pressure (MIP), forced vital capacity (FVCpp), and maximal expiratory pressure (MEP). Multiple regression identified MIP and age of symptom onset as primary predictors.ConclusionsThe study demonstrates respiratory dysfunction in patients with FRDA, and shows that disease severity and muscle weakness affect airway clearance. PCF is a more direct and clinically meaningful indicator of cough effectiveness than FVCpp. Comprehensive respiratory evaluations, including muscle-strength testing, can identify individuals who may benefit from targeted interventions to prevent complications.

Autosomal recessive cerebellar ataxias (ARCA) are clinically and genetically heterogeneous, often presenting as sporadic cases that pose a significant diagnostic challenge. The aim was to characterize the clinical and mutational landscape of ARCA in the largest Chinese cohort using whole-genome sequencing (WGS). We performed WGS on a cohort of 187 patients with suspected hereditary ataxia. Clinical severity was assessed using the Scale for the Assessment and Rating of Ataxia and the International Cooperative Ataxia Rating Scale. Pathogenicity was determined according to American College of Medical Genetics and Genomics guidelines, and variants were validated via Sanger sequencing and co-segregation analysis. We identified 109 variants across 56 genes, with a rate of 79.8% (87/109) being novel. Definitive molecular diagnoses were achieved in 21 cases across 11 distinct subtypes. SYNE1 and SETX were the most frequent genetic contributors, with SETX truncating mutations (c.22_23insTA) associated with higher clinical burden. Multisystemic features were identified, including conjunctival telangiectasia in ATM, progressive action myoclonus in SCARB2, and spastic paraplegia in CAPN1. In this study with, to date the largest Chinese cohort of ARCA, 87 novel variants were classified, which significantly expanded the genomic and phenotype landscape of ARCA in the Chinese population. © 2026 International Parkinson and Movement Disorder Society.

Disease-modifying therapies for degenerative ataxias, including emerging gene therapies, are in the clinical trial pipeline. Sensitive outcome measures are urgently needed for treatment monitoring and participant selection to improve trial feasibility in these rare diseases. In hereditary ataxias, the ability to identify people who carry disease-causing mutations before symptom onset also raises the possibility of enrolment into trials before symptom manifestation, but biomarker data are key for participant selection and outcome monitoring in such preventive trials. Quantitative neuroimaging readouts have emerged as viable candidate biomarkers of ataxia pathology and progression that could supplement traditional clinical outcome assessments as clinical trial end-points. In this Consensus Statement, the Ataxia Global Initiative MRI Biomarkers Working Group critically reviews candidate MRI end-points for trials in the most common spinocerebellar ataxias (SCA1, SCA2 and SCA3) and Friedreich ataxia and provides evidence-based, disease-specific recommendations for the selection of MRI end-points for trials in these diseases. Recommendations are also provided for further research to address remaining knowledge gaps.

Cerebral small vessel disease is a leading cause of cognitive decline and stroke in the elderly, with cerebral microbleeds (CMBs) serving as a key imaging biomarker. Despite their clinical significance, the pathophysiological mechanisms underlying cerebral small vessel disease remain poorly understood owing to a lack of appropriate animal models. We performed targeted deletion of Col4a1 in brain microvessels of adult mice using brain endothelium-specific adeno-associated virus (AAV)-BR1 vectors with clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). Eight-week-old Cas9 transgenic mice received retro-orbital injections of AAV-BR1 containing single guide RNA (sgRNA) targeting Col4a1 or control Rosa26 sequences. Animals underwent longitudinal behavioural testing, including novel object recognition, Y-maze and rotarod tests, over 6 months. Brain pathology was assessed using T2*-weighted MRI, histological analysis and electron microscopy. For human studies, we analysed MRI and genomic data from 836 participants from the BICWALZS biobank, examining associations between genetic variants and CMB burden using linear regression and χ2 analyses. T2*-weighted MRI revealed numerous CMBs with distributions remarkably similar to human CMBs, appearing within 3 months post-injection. CMB burden increased progressively over 6 months in a dose-dependent manner. Behaviourally, mice exhibited progressive cognitive decline and motor incoordination. Histological examinations revealed haemosiderin deposits corresponding to MRI-detected CMBs, without macroscopic intracerebral haemorrhage or white matter changes. Ultrastructural analysis demonstrated significant basement membrane thinning in Col4a1-depleted microvessels. CMB accumulation was associated with widespread astrocytic reactivity extending beyond microbleed sites, whereas microglial activation remained localized. In human subjects, we identified significant associations between four genetic variants of TIMP2, an endogenous inhibitor of the matrix-degrading enzyme MMP2 and CMB burden, with odds ratios of 1.50-1.96 for increased microbleed susceptibility. This work provides the first animal model demonstrating that selective disruption of collagen IV in adult brain microvessels is sufficient to generate CMBs with high penetrance and dose-dependent tunability. Our findings establish that basement membrane integrity is critical for preventing microbleed formation and suggest that dysregulated collagen IV homeostasis underlies sporadic human CMB development.

ObjectivesBiallelic variants in HSD17B4 cause D-bifunctional protein (DBP) deficiency, a disorder of peroxisomal fatty acid β-oxidation initially associated with a neonatal phenotype and early lethality. Recently, thanks to advances in genetic analyses, the clinical spectrum has expanded to include a slowly progressive adult-onset ataxic syndrome with additional features. Our aim was to describe 5 additional affected adults and to highlight the characteristic phenotype.MethodsFive affected individuals (4 from one family; 1 from a second family) were examined in our tertiary neurogenetics referral center. The core clinical manifestations consisted of a slowly progressive cerebellar ataxia, with subclinical evidence of sensorineural hearing loss and hypergonadotropic hypogonadism leading to premature ovarian failure in affected women. Genetic analysis was performed using a custom-targeted sequencing panel for genes associated with hereditary ataxias. Causative variants were confirmed by Sanger sequencing and segregated within the families. Peroxisomal investigations were performed on blood specimens.ResultsIn family A, the affected siblings born from consanguineous parents carried a novel homozygous HSD17B4 variant, c.557A>T (p.Asn186Ile), whereas in the proband from the other family, 2 novel compound heterozygous variants, c.652G>T (p.Val218Leu) and c.2116C>T (p.Gln706), were identified. The peroxisomal profiles were normal.DiscussionOur case series expand the phenotypic-genotypic spectrum of DBP deficiency and provide long-term follow-up data. While no disease-modifying treatments currently exist, diagnosis has implications for genetic counseling, particularly for reproductive planning in affected women.

Neurogenic stuttering caused by supplementary motor area and premotor cortex dysfunction due to acute encephalopathy: A case report

Parkinson's disease is a progressive and severe neurodegenerative disease with loss of dopaminergic neurons of substantia nigra. Sigma-1 receptor activation by ligand/agonist has shown neuroprotective effect in various diseases including Parkinson's disease. Present study aimed to investigate the neuroprotective potential of 1,3-di-o-tolylguanidine, a Sigma-1 receptor agonist in rat model of Parkinson's disease. Male Wistar rats underwent intraperitoneal administration of rotenone with simultaneous treatment of 1,3-di-o-tolylguanidine for 28 days. After 28 days, behavioural tests were conducted for assessing motor symptoms. Sigma 1 receptor, dopamine, alpha synuclein, IL-6, glutamate levels were measured in brain homogenate. Histopathological studies were performed for assessing neurodegeneration. Rotenone treated disease control group showed significant bradykinesia, impaired grip strength and motor incoordination compared to normal control group. Further, brain sigma 1 receptor, dopamine, alpha synuclein, IL-6, glutamate levels as well as histological features were significantly compromised. Treatment with 1,3-di-o-tolylguanidine significantly improved behavioural parameters, biochemical parameters and histological features in dose dependent manner. These findings suggest that 1,3-di-o-tolylguanidine has neuroprotective effects in rotenone-induced model of Parkinson's disease in rats.

BackgroundAtaxia comprises a heterogeneous group of disorders with multiple clinical and etiological presentations. The frontal subtype, in particular, is poorly defined and often misdiagnosed, reflecting both its complex historical evolution and lack of formal diagnostic criteria.ObjectiveTo evaluate clinical and epidemiological characteristics of a sample of patients with ataxia under follow-up in a private neurology clinic.MethodsWe evaluated 48 patients diagnosed with ataxia over a 4-month period and followed them for 1-year in a private neurology clinic in southern Brazil. Clinical, neuroimaging, and laboratory data were analyzed. Patients were classified according to clinical and etiological subtypes based on criteria defined by the authors.ResultsFrontal ataxia was the most frequent presentation (n = 15; 31.3%), predominantly affecting elderly patients with systemic arterial hypertension, diabetes mellitus, and MRI evidence of small vessel disease. These patients had a later disease onset (mean: 75.9 ± 8.8 years), lower SARA scores, and a nonprogressive course compared with degenerative cerebellar ataxias (p < 0.0001). No correlation was observed between the severity of small vessel disease (Fazekas scale) and gait ataxia (rs = -0.28,p = 0.31). Hereditary ataxias, particularly spinocerebellar ataxias (SCAs), were the second most frequent group, followed by atypical Parkinsonian syndromes.ConclusionFrontal ataxia emerged as a frequent and underrecognized subtype in routine neurological practice. These findings underscore the need for increased awareness and the development of evidence-based diagnostic criteria to better define and distinguish it within the spectrum of ataxic disorders.

Home-Based Telerehabilitation for Core Stability in Hereditary Ataxia: Feasibility and Preliminary Effects of a Pilot RCT.

Communication depends on precise coordination between motor execution and cognition. Here we reveal that the cerebellum exerts real-time control over social vocalizations in adult mice. Optogenetic activation of excitatory cerebellar output in the superior cerebellar peduncle suppressed ultrasonic vocalizations with frequency-dependent potency while inducing distinct motor phenotypes. Systematic, functional mapping across cerebellar regions and cell types revealed that vocal suppression can occur in the absence of overt motor impairment, suggesting selective control of vocal output beyond gross movement disruption. We identified the periaqueductal gray (PAG), a conserved midbrain vocal control center, as a key downstream mediator of this effect. Deep brain stimulation of the PAG rescued vocal deficits in a model of cerebellar dysfunction without rescuing motor incoordination. These findings define a cerebellar–midbrain pathway that gates vocal behavior and demonstrate that targeted therapeutic neuromodulation can selectively restore communication-related output even in the presence of persistent cerebellar-driven motor deficits.

Hereditary ataxias are genetically heterogeneous; however, despite major advances in next-generation sequencing technologies, 20%-54% of childhood-onset cases remain genetically undiagnosed. To elucidate the genetic etiology of childhood-onset hereditary ataxia. Oxford Nanopore long-read genome sequencing (LRS) was performed in two unrelated Chinese patients with clinically suspected childhood-onset hereditary ataxia. Both patients presented with childhood-onset, slowly progressive ataxia, accompanied by mild cognitive impairment. Brain magnetic resonance imaging demonstrated cerebellar atrophy, and electromyography showed neurogenic damage. Muscle biopsy revealed fiber-type grouping, indicative of neurogenic changes, with no evidence of primary myopathy. LRS detected pathogenic-length CGG repeat expansions (>100 repeats) in GIPC1, which were validated by repeat-primed polymerase chain reaction. These findings expand the phenotypic spectrum associated with GIPC1 CGG repeat expansion and define a novel subtype of childhood-onset hereditary ataxia accompanied by mild cognitive impairment and neurogenic involvement. © 2026 International Parkinson and Movement Disorder Society.

BackgroundChristianson syndrome is an x-linked recessive neurodevelopmental and neurodegenerative condition caused by mutations to the SLC9A6 gene encoding NHE6, a sodium-hydrogen exchanger critical for regulating endosomal pH. Using an adeno-associated viral (AAV) vector targeting Purkinje cells (PHP.eB-L7-Slc9a6-GFP), we recently performed functional complementation studies to demonstrate that mutation to the rat Slc9a6 gene causes a Christianson syndrome-relevant cerebellar phenotype in the shaker rat.MethodsWe carried out a longitudinal study evaluating the impact of gene replacement targeting Purkinje cells on ataxia and tremor in the shaker rat. Further, in a smaller follow-up study, we tested administration of AAV9-CAG-hSLC9A6 to determine whether key molecular and motor findings could be replicated with a more clinically relevant viral construct. In both experimental cohorts, we performed molecular studies to evaluate expression of NHE6 and key cerebellar markers.ResultsAdministration of either of PHP.eB-L7-Slc9a6-GFP or AAV9-CAG-hSLC9A6 AAV vectors led to significant improvement in both the molecular and motor phenotypes. The abundance of each disease-relevant cerebellar proteins was strongly correlated to motor ataxia, but less so to tremor. Further, while ataxia and tremor were initially strongly correlated early in the disease progression, this relationship weakened over time.ConclusionsThese findings impact future SLC9A6-targeted gene therapy efforts for Christianson syndrome and support gene replacement as a potentially viable therapeutic strategy. Common markers associated with cerebellar degeneration are much more strongly tied to ataxia than to tremor, indicating that ataxia may be more tied related to degenerative processes than tremor.

Pure cerebellar ataxia is a neurological disorder characterised by isolated cerebellar dysfunction, arising from either developmental anomalies or progressive degenerative processes. Precise genetic diagnosis remains challenging. The aim of this study was to use a whole-exome sequencing approach to study a large, highly consanguineous Italian family in order to identify a new gene correlated with pure cerebellar ataxia. Sequencing excluded the presence of mutations in known-related genes but revealed a homozygous missense variant in CLIC5; however invivo analysis of a CLIC5 KO mouse model showed vestibular dysfunction without cerebellar involvement, suggesting that CLIC5 is not directly involved in pure cerebellar ataxia onset. Further analysis identified two compound heterozygous variants in NEFM, and in silico analysis showed that they dysregulate NEFM phosphorylation. Phosphorylation of neurofilaments and subsequent formation of aggregates has already been linked to conditions such as ageffing and neurodegeneration. Moreover, invivo studies on mice transgenic for human NEFM have correlated NEFM phosphorylation and aggregation with neurodegeneration. Finally, neurofilaments have been proposed to be correlated to ataxia and autoimmune cerebellar ataxia. We therefore propose NEFM as a possible new candidate gene for hereditary cerebellar ataxia. These findings could be useful for advancing the genetic diagnosis of hereditary pure cerebellar ataxia, possibly enabling the screening of healthy carriers.

Cerebellar-type multiple system atrophy (MSA-C) presents significant challenges for early diagnosis due to the absence of specific biomarkers and its clinical similarity to other forms of ataxia. The presented clinical case highlights the importance of dynamic monitoring of magnetic resonance imaging (MRI) changes for confirming the diagnosis of MSA-C and demonstrates the characteristic temporal evolution of key neuroimaging markers.A clinical observation of a 47‑year-old patient with progressive cerebellar ataxia and autonomic failure (orthostatic hypotension, urinary incontinence) consistent with established diagnostic criteria for MSA-C is presented. Brain MRI findings obtained in follow-up with a 7‑month interval are of particular value. First detection of the highly specific “hot cross bun” sign for MSA-C – a cross-shaped area of hyperintense signal in the central pons. Progressive thinning of the middle cerebellar peduncles (by 3 mm), cerebellar vermis atrophy (by 2 mm), and enlargement of the fourth ventricle and pontine cisterns were also documented. These changes objectively correlated with the progression of cerebellar clinical symptoms in the patient.The findings of this clinical case indicate that dynamic MRI evaluation is an indispensable method in the diagnosis of MSA-C. The appearance of the pathognomonic “hot cross bun” sign and quantitatively measurable progression of atrophy in specific posterior fossa structures (the cerebellum, middle cerebellar peduncles, and pons) over a short time interval represent highly specific radiological criteria that allow reliable differentiation of MSA-C from hereditary ataxias even in the absence of definitive biomarkers. Early and sequential MRI with assessment of imaging changes over time significantly improves the accuracy of antemortem diagnosis of this severe neurodegenerative disease.

Ataxia is a coordination disorder that encompasses more than 300 neurological diseases and more than 200 types of hereditary ataxia. Depending on the pathology with which it is associated, the symptomatology present is different: balance and gait disturbance, dysdiadochokinesia, dysarthria, nystagmus, etc. Due to this heterogeneity, the assessment of ataxia is a complex task that is further hindered by the broad variety of existing tools, both specific to ataxia and related to a particular pathology, such as those that assess coordination and gait components. Analyse, organize and compare the structural and psychometric characteristics of the tools used for the assessment of different types of ataxia. A meta-review registered in PROSPERO was conducted following the PRISMA Checklist System. Six database were used and two blinded researchers selected the papers according the criteria. Five reviews were included in this study. The main psychometric properties of the 16 scales found to assess ataxia symptoms in different pathologies were analysed. Internal consistency and reliability obtained good-to-excellent values for the total score of the different scales and parameters studied. However, validity and sensitivity showed less homogeneous values. The scales that globally assess the severity of the disease stand out, with a great variety of scales, including the International Cooperative Ataxia Assessment Scale (ICARS) and the Scale for the Assessment and Rating of Ataxias (SARA) as the most widely used.