Spinocerebellar Ataxia Patients Research Articles

Factors Influencing Health-Related Quality of Life of Patients with Spinocerebellar Ataxia.

Little is known about the progression of health-related quality of life (HRQoL) and predicting factors in spinocerebellar ataxia (SCA). Such knowledge is crucial to identify modifiable factors promoting everyday life with SCA and attenuating HRQoL decline. This study is to assess HRQoL progression and identify factors affecting SCA patients' HRQoL. Longitudinal data (three-year follow-up) of 310 SCA patients of the European SCA3/Machado-Joseph-Disease Initiative (ESMI) (2016-2022) and 525 SCA patients (SCA1, SCA2, SCA3 or SCA6) of the EUROSCA natural history study cohort (2006-2015) were assessed. Both large cohort studies share standardized assessments of clinical measures, SARA, INAS, PHQ-9, and HRQoL (EQ-5D-3L). The association between HRQoL and clinical measures was assessed by Spearman Correlation (rs). Multivariable panel regression models were performed to evaluate the impact of patients' socio-demographics, age of onset, SCA type and body mass index (BMI), and clinical measures on HRQoL progression. HRQoL significantly decreased over one (- 0.014, p = 0.095), two (- 0.028, p = 0.003), and three years (- 0.032, p = 0.002). Ataxia severity and mental health strongly correlated with HRQoL (rsSARA = - 0.589; rsPHQ-9 = - 0.507). HRQoL more intensively declined in male (ß = - 0.024, p = 0.038) patients with an earlier age of onset (ß = 0.002, p = 0.058). Higher progression of ataxia severity (ß = - 0.010, p ≤ 0.001), mental health problems (ß = - 0.012, p < 0.001), and higher BMI (ß = - 0.003, p = 0.029) caused more severe decline of patients' HRQoL over time. In absence of curative treatments, stronger focus on mental health and weight influence could help clinical evaluation and accompany treatment improving SCA patients' HRQoL, especially in male patients with early disease onset.

The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale in Spinocerebellar Ataxias.

The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls. We compared total raw scores, domain scores, and total fail scores between Symptomatic, Pre-symptomatic, and Control cohorts, and between SCA types. We calculated scale sensitivity and selectivity based on CCAS category designation among Symptomatic individuals and Controls, and correlated CCAS-S performance against age and education, and in Symptomatic patients, against genetic repeat length, onset age, disease duration, motor ataxia, depression, and fatigue. Definite CCAS was identified in 46% of the Symptomatic group. False positive rate among Controls was 5.4%. Symptomatic individuals had poorer global CCAS-S performance than Controls, accounting for age and education. The domains of semantic fluency, phonemic fluency, and category switching that tap executive function and linguistic processing consistently separated Symptomatic individuals from Controls. CCAS-S scores correlated most closely with motor ataxia. Controls were similar to Pre-symptomatic individuals whose nearness to symptom onset was unknown. The use of the CCAS-S identifies a high CCAS prevalence in a large cohort of SCA patients, underscoring the utility of the scale and the notion that the CCAS is the third cornerstone of clinical ataxiology.

Health-Related Quality of Life in Patients with Spinocerebellar Ataxia: a Validation Study of the EQ-5D-3L

Although health-related quality of life (HRQoL) has developed into a crucial outcome parameter in clinical research, evidence of the EQ-5D-3L validation performance is lacking in patients with spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. The objective of this study is to assess the acceptability, validity, reliability, and responsiveness of the EQ-5D-3L. For n = 842 predominantly European SCA patients of two longitudinal cohort studies, the EQ-5D-3L, PHQ-9 (Patient Health Questionnaire), and ataxia-specific clinical assessments (SARA: Scale for Assessment and Rating of Ataxia; ADL: activities of daily living as part of Friedreich’s Ataxia Rating Scale; INAS: Inventory of Non-Ataxia Signs) were assessed at baseline and multiple annual follow-ups. The EQ-5D-3L was evaluated regarding acceptability, distribution properties, convergent and known-groups validity, test-retest reliability, and effect size measures to analyze health changes. The non-item response was low (EQ-5D-3L index: 0.8%; EQ-VAS: 3.4%). Ceiling effects occurred in 9.9% (EQ-5D-3L) and 3.0% (EQ-VAS) with a mean EQ-5D-3L index of 0.65 ± 0.21. In total, convergent validity showed moderate to strong Spearman’s rho (rs > 0.3) coefficients comparing EQ-5D-3L and EQ-VAS with PHQ-9, SARA, ADL, and INAS. EQ-5D-3L could discriminate between groups of age, SARA, ADL, and INAS. Intra-class correlation coefficients (EQ-5D-3LICC: 0.95/EQ-VASICC: 0.88) and Kappa statistics (range 0.44 to 0.93 for EQ-5D-3L items) indicated tolerable reliability. EQ-5D-3L shows small (effect size < 0.3) to moderate (effect size 0.3–0.59) health changes regarding ataxia severity. The analysis confirms an acceptable, reliable, valid, and responsive recommended EQ-5D-3L in SCA patients, measuring the HRQoL adequately, besides well-established clinical instruments.

Clinical value of vestibulo-ocular reflex in the differentiation of spinocerebellar ataxias

The diagnosis of spinocerebellar ataxia (SCA) currently depends upon genetic testing. Although genetic testing for SCA is highly specific, clinical parameters for the differentiation of SCAs are still insufficient. We aimed to assess the vestibulo-ocular reflex (VOR) parameters of various SCA subtypes to determine whether they have substantial value in differential diagnosis. We consecutively enrolled 33 genetically confirmed SCA patients (SCA2 = 8, SCA3 = 6, SCA6 = 10, SCA7 = 9). Normative data were obtained from 36 age- and gender-matched healthy controls. Quantitative indicators of VOR were measured using video head impulse test (HIT) and combined ocular motor dysfunctions were investigated using video-oculography. Compared with the control group, the VOR gains in SCA2 were relatively spared, but were markedly decreased for all six canals in SCA3. The VOR gains for the posterior canals (PCs) were significantly decreased in SCA6, and for both vertical canals were decreased in SCA7. The VOR gains for the horizontal canals in SCA3 were negatively correlated with disease severity (R = -0.900, p = 0.037). Abnormal catch-up saccades were common in SCA3 and SCA6, rare in SCA7 and absent in SCA2. Spontaneous, headshaking-induced, and positional nystagmus were only documented in SCA6. SCA3 and SCA6 commonly showed horizontal gaze-evoked nystagmus, but SCA2 and SCA7 had characteristic saccadic slowing without gaze-evoked nystagmus. VOR impairments are common in SCAs, but their patterns vary depending on subtype. In addition to ocular motor characteristics, distinctive VOR performance for each subtype using video HIT may aid the differential diagnosis of the SCA genotypes.

Three Hertz postural leg tremor impairs posture maintenance in multiple system atrophy-cerebellar type.

Three-Hz postural leg tremor has recently been identified as highly prevalent in patients with the cerebellar type of multiple system atrophy, but its impact on posture maintenance remains poorly understood. Thirty-seven patients with spinocerebellar ataxia and 58 others with cerebellar type of multiple system atrophy were given Synapsys posturography examinations. Fifty-three healthy controls were also tested. Low, medium, and high-frequency sway were recorded to compute energy values. Frequency shift and postural strategy predominance were evaluated from the postural sway distributions, mainly from the proportions of higher frequency values among the total values. The trajectories of postural sway components were evaluated with the generalized additive mixed model. Distributions of the components and their relationships with falls and tremors were assessed through repeated measures correlation analysis. As the test difficulty increased, the standard controls showed slight increases in the energy values at every frequency. Distributions of the higher frequency (>0.5 Hz) values increased escalatingly with test difficulty, illustrating frequency shifts and hip strategy predominance. Medium and high-frequency values were strongly and positively inter-correlated in normal stances, but this was not observed among the spinocerebellar ataxia or multiple system atrophy patients. Unlike normal stances, the proportion of medium frequency values was negatively related to the total value among the spinocerebellar ataxia and multiple system atrophy patients, implying a failure of frequency shift in response to perturbation. Medium frequency proportions were also inversely correlated with tremors among the multiple system atrophy patients. The observed synchronized changes in medium and high-frequency postural sway indicate that they constitute a complete hip strategy for posture control. The strategy was rigid in those with spinocerebellar ataxia but completely disrupted in those with multiple system atrophy. Three Hertz postural leg tremors destabilize the ankle joints and interfere with postural adjustment among those with multiple system atrophy.

Intermuscular Coherence in Spinocerebellar Ataxias 3 and 6: a Preliminary Study

Spinocerebellar ataxias (SCAs) are familial neurodegenerative diseases involving the cerebellum and spinocerebellar tracts. While there is variable involvement of corticospinal tracts (CST), dorsal root ganglia, and motor neurons in SCA3, SCA6 is characterized by a pure, late-onset ataxia. Abnormal intermuscular coherence in the beta-gamma frequency range (IMCβγ) implies a lack of integrity of CST or the afferent input from the acting muscles. We test the hypothesis that IMCβγ has the potential to be a biomarker of disease activity in SCA3 but not SCA6. Intermuscular coherence between biceps brachii and brachioradialis muscles was measured from surface EMG waveforms in SCA3 (N = 16) and SCA6 (N = 20) patients and in neurotypical subjects (N = 23). IMC peak frequencies were present in the β range in SCA patients and in the γ range in neurotypical subjects. The difference between IMC amplitudes in the γ and β ranges was significant when comparing neurotypical control subjects to SCA3 (p < 0.01) and SCA6 (p = 0.01) patients. IMCβγ amplitude was smaller in SCA3 patients compared to neurotypical subjects (p < 0.05), but not different between SCA3 and SCA6 patients or between SCA6 and neurotypical subjects. IMC metrics can differentiate SCA patients from normal controls.

Gene therapy for selected neuromuscular and trinucleotide repeat disorders - An insight to subsume South Asia for multicenter clinical trials.

In this article, the authors discuss how they utilized the genetic mutation data in Sri Lankan Duchenne muscular dystrophy (DMD), Spinal muscular atrophy (SMA), Spinocerebellar ataxia (SCA) and Huntington's disease (HD) patients and compare the available literature from South Asian countries to identifying potential candidates for available gene therapy for DMD, SMA, SCA and HD patients. Rare disease patients (n=623) with the characteristic clinical findings suspected of HD, SCA, SMA and Muscular Dystrophy were genetically confirmed using Multiplex Ligation Dependent Probe Amplification (MLPA), and single plex PCR. A survey was conducted in the "Wiley database on Gene Therapy Trials Worldwide" to identify DMD, SMA, SCA, and HD gene therapy clinical trials performed worldwide up to April 2021. In order to identify candidates for gene therapy in other neighboring countries we compared our findings with available literature from India and Pakistan which has utilized the same molecular diagnostic protocol to our study. From the overall cohort of 623 rare disease patients with the characteristic clinical findings suspected of HD, SCA, SMA and Muscular Dystrophy, n=343 (55%) [Muscular Dystrophy- 65%; (DMD-139, Becker Muscular Dystrophy -BMD-11), SCA type 1-3-53% (SCA1-61,SCA2- 23, SCA3- 39), HD- 52% (45) and SMA- 34% (22)] patients were positive for molecular diagnostics by MLPA and single plex PCR. A total of 147 patients in Sri Lanka amenable to available gene therapy; [DMD-83, SMA-15 and HD-49] were identified. A comparison of Sri Lankan finding with available literature from India and Pakistan identified a total of 1257 patients [DMD-1076, SMA- 57, and HD-124] from these three South Asian Countries as amenable for existing gene therapy trials. DMD, SMA, and HD gene therapy clinical trials (113 studies) performed worldwide up to April 2021 were concentrated mostly (99%) in High Income Countries (HIC) and Upper Middle-Income Countries (UMIC). However, studies on the potential use of anti-sense oligonucleotides (ASO) for treatment of SCAs have yet to reach clinical trials. Most genetic therapies for neurodegenerative and neuromuscular disorders have been evaluated for efficacy primarily in Western populations. No multicenter gene therapy clinical trial sites for DMD, SMA and HD in the South Asian region, leading to lack of knowledge on the safety and efficacy of such personalized therapies in other populations, including South Asians. By fostering collaboration between researchers, clinicians, patient advocacy groups, government and industry in gene therapy initiatives for the inherited-diseases community in the developing world would link the Global North and Global South and breathe life into the motto "Together we can make a difference".

Systematic assessment of plasma biomarkers in spinocerebellar ataxia

Background and objectivesPlasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), phosphorylated-tau (p-tau), and β-amyloid (Aβ) have emerged as promising markers in several neurodegenerative disorders, but whether they can be used as biomarkers in spinocerebellar ataxias (SCA) is yet to be determined. This study aimed to identify sensitive plasma markers for SCA and investigate their effectiveness in tracking ataxia severity, cognition, non-motor symptoms, and brain atrophy. MethodsThis observational study recruited consecutive participants from Huashan Hospital and the CABLE study from November 2019. Patients with SCA were genetically diagnosed, grouped according to the ataxia severity, and compared with healthy older individuals and patients with multiple system atrophy type C (MSA-C). Plasma NfL, GFAP, p-tau, and Aβ levels were measured by Simoa in all participants. Analysis of covariance, Spearman correlation, and multivariable regression were used to explore candidate markers in SCA. ResultsA total of 190 participants (60 SCA, 56 MSA-C, and 74 healthy controls) were enrolled. Plasma NfL level increased early in the pre-ataxic stage of SCA (32.23 ± 3.07 vs. 11.41 ± 6.62 pg/mL in controls), was positively associated with the ataxia severity (r = 0.45, P = 0.005) and CAG repeat length (r = 0.51, P = 0.001), varied among the different SCA subtypes (39.57 ± 13.50 pg/mL in SCA3, which was higher than 28.17 ± 8.02 pg/mL in SCA2, 17.08 ± 6.78 pg/mL in SCA8, and 24.44 ± 18.97 pg/mL in rare SCAs; P < 0.05), and was associated with brainstem atrophy. NfL alone (area under the curve [AUC] 0.867) or combined with p-tau181 and Aβ (AUC 0.929), showed excellent performance in discriminating SCA patients from controls. Plasma GFAP distinguished SCA from MSA-C with moderate accuracy (AUC > 0.700) and correlated with cognitive performance and cortical atrophy. Changes in levels of p-tau181 and Aβ were observed in SCA patients compared to controls. They were both correlated with cognition, while Aβ was also associated with non-motor symptoms, such as anxiety and depression. DiscussionPlasma NfL may serve as a sensitive biomarker for SCA, and its level is elevated in the pre-ataxic stage. The different performance of NfL and GFAP indicates differences in the underlying neuropathology of SCA and MSA-C. Moreover, amyloid markers may be useful for detecting memory dysfunction and other non-motor symptoms in SCA.

Cerebellar presence of immune cells in patients with neuro-coeliac disease

Although various neurodegenerative disorders have been associated with coeliac disease (CD), the underlying neuropathological link between these brain and gut diseases remains unclear. We postulated that the neuronal damage sporadically observed in CD patients is immune-mediated. Our aim was to determine if the loss of neurons, especially Purkinje cells, coincides with microglia activation and T- and B-cell infiltration in the cerebellum of patients with CD and a concomitant idiopathic neurological disease affecting the cerebellum (NeuroCD). Post-mortem cerebellar tissue was collected of validated NeuroCD cases. Gender- and age-matched genetic spinocerebellar ataxia (SCA) controls and non-neurological controls (NNC) were selected based on clinical reports and pathological findings. Cerebellar tissue of seventeen patients was included (6 NeuroCD, 5 SCA, 6 NNC). In SCA cases we found that the Purkinje cell layer was 58.6% reduced in comparison with NNC. In NeuroCD cases this reduction was even more prominent with a median reduction of 81.3% compared to NNC. Marked increased numbers of both CD3+ and CD8+ cells were observed in the NeuroCD but not in SCA patients. This coincided with significantly more microglial reactivity in NeuroCD patients. These findings demonstrate that the massive loss of Purkinje cells in the cerebellum of neuro CD patients is accompanied by local innate and T-cell mediated immune responses.

Motor neuron involvement threatens survival in spinocerebellar ataxia type 1.

Motor neuron involvement threatens survival in spinocerebellar ataxia type 1.

Age-related differences of cerebellar cortex and nuclei: MRI findings in healthy controls and its application to spinocerebellar ataxia (SCA6) patients

Understanding cerebellar alterations due to healthy aging provides a reference point against which pathological findings in late-onset disease, for example spinocerebellar ataxia type 6 (SCA6), can be contrasted. In the present study, we investigated the impact of aging on the cerebellar nuclei and cerebellar cortex in 109 healthy controls (age range: 16 – 78 years) using 3 Tesla magnetic resonance imaging (MRI). Findings were compared with 25 SCA6 patients (age range: 38 – 78 years). A subset of 16 SCA6 (included: 14) patients and 50 controls (included: 45) received an additional MRI scan at 7 Tesla and were re-scanned after one year. MRI included T1-weighted, T2-weighted FLAIR, and multi-echo T2*-weighted imaging. The T2*-weighted phase images were converted to quantitative susceptibility maps (QSM). Since the cerebellar nuclei are characterized by elevated iron content with respect to their surroundings, two independent raters manually outlined them on the susceptibility maps. T1-weighted images acquired at 3T were utilized to automatically identify the cerebellar gray matter (GM) volume. Linear correlations revealed significant atrophy of the cerebellum due to tissue loss of cerebellar cortical GM in healthy controls with increasing age. Reduction of the cerebellar GM was substantially stronger in SCA6 patients. The volume of the dentate nuclei did not exhibit a significant relationship with age, at least in the age range between 18 and 78 years, whereas mean susceptibilities of the dentate nuclei increased with age. As previously shown, the dentate nuclei volumes were smaller and magnetic susceptibilities were lower in SCA6 patients compared to age- and sex-matched controls. The significant dentate volume loss in SCA6 patients could also be confirmed with 7T MRI. Linear mixed effects models and individual paired t-tests accounting for multiple comparisons revealed no statistical significant change in volume and susceptibility of the dentate nuclei after one year in neither patients nor controls. Importantly, dentate volumes were more sensitive to differentiate between SCA6 (Cohen's d = 3.02) and matched controls than the cerebellar cortex volume (d = 2.04). In addition to age-related decline of the cerebellar cortex and atrophy in SCA6 patients, age-related increase of susceptibility of the dentate nuclei was found in controls, whereas dentate volume and susceptibility was significantly decreased in SCA6 patients. Because no significant changes of any of these parameters was found at follow-up, these measures do not allow to monitor disease progression at short intervals.

Myelinating Glia: Potential Therapeutic Targets in Polyglutamine Spinocerebellar Ataxias.

Human studies, in combination with animal and cellular models, support glial cells as both major contributors to neurodegenerative diseases and promising therapeutic targets. Among glial cells, oligodendrocytes and Schwann cells are the myelinating glial cells of the central and peripheral nervous system, respectively. In this review, we discuss the contributions of these central and peripheral myelinating glia to the pathomechanisms of polyglutamine (polyQ) spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17. First, we highlight the function of oligodendrocytes in healthy conditions and how they are disrupted in polyQ SCA patients and diseased model systems. We then cover the role of Schwann cells in peripheral nerve function and repair as well as their possible role in peripheral neuropathy in polyQ SCAs. Finally, we discuss potential polyQ SCA therapeutic interventions in myelinating glial.

Scale for the assessment and rating of ataxia: Age-dependent performance of healthy adults.

The Scale for Assessment and Rating of Ataxia (SARA) is a widely used clinical scale. The objective was to study the age dependence of SARA in healthy adults and to define age-specific cut-off values to differentiate healthy from ataxic individuals. Data from 390 healthy individuals and 119 spinocerebellar ataxia patients were analyzed. SARA scores were mapped on functional SARA (fSARA). Age-adjusted cut-off values were determined by receiver operating characteristic curve analysis. The cut-off value was 3 for SARA and 1.5 for fSARA. Older patients had higher SARA cut-off values (4.5 for 60-69 years and 6.5 for 70-79 years). Age-adjusted cut-off values for fSARA are 1 for 18-29, 30-39 and 50-59 years, 2 for 40-49 and 60-69 years and 3 for 70-79 years. Sensitivity and specificity were higher for SARA than for fSARA. In this study, age-dependent cut-off values were defined for SARA and fSARA. The results may be relevant for the design of future preventive trials in spinocerebellar ataxias that use conversion to ataxia as an outcome.

Brain-heart Connections in Spinocerebellar Ataxia: Role of Central

More than a century ago, C. Bernard stated the connection between the brain and the heart. Here, we have emphasized on the central autonomic network (CAN) based on our previous pioneering work of structure-function connectivity in spinocerebellar ataxia (SCA) patients. In order to study the correlation, SCA was the suitable disease model as being neurodegenerative disorder with fequent autonomic manifestations. The prefrontal cortex, bilateral middle temporal, left cuneus, left lingual and left caudate were the key brain areas of CAN for top down regulation of autonomic function assessed as heart rate variability and severity scoring. We have evaluated CAN to know parasympathetic and sympathic autonomic brain areas vis-a-vis parasympathetic and sympathetic autonomic function in SCA which may shed light on putative pathophysiology.

Psychiatric-Like Impairments in Mouse Models of Spinocerebellar Ataxias.

Many patients with spinocerebellar ataxia (SCA) suffer from diverse neuropsychiatric issues, including memory impairments, apathy, depression, or anxiety. These neuropsychiatric aspects contribute per se to the reduced quality of life and worse prognosis. However, the extent to which SCA-related neuropathology directly contributes to these issues remains largely unclear. Behavioral profiling of various SCA mouse models can bring new insight into this question. This paper aims to synthesize recent findings from behavioral studies of SCA patients and mouse models. The role of SCA neuropathology for shaping psychiatric-like impairments may be exemplified in mouse models of SCA1. These mice evince robust cognitive impairments which are shaped by both the cerebellar as well as out-of-cerebellar pathology. Although emotional-related alternations are also present, they seem to be less robust and more affected by the specific distribution and character of the neuropathology. For example, cerebellar-specific pathology seems to provoke behavioral disinhibition, leading to seemingly decreased anxiety, whereas complex SCA1 neuropathology induces anxiety-like phenotype. In SCA1 mice with complex neuropathology, some of the psychiatric-like impairments are present even before marked cerebellar degeneration and ataxia and correlate with hippocampal atrophy. Similarly, complete or partial deletion of the implicated gene (Atxn1) leads to cognitive dysfunction and anxiety-like behavior, respectively, without apparent ataxia and cerebellar degeneration. Altogether, these findings collectively suggest that the neuropsychiatric issues have a biological basis partially independent of the cerebellum. As some neuropsychiatric issues may stem from weakening the function of the implicated gene, therapeutic reduction of its expression by molecular approaches may not necessarily mitigate the neuropsychiatric issues.

Comparison of Cardiac Autonomic Function in Type 2 Spinocerebellar Ataxia With Normal Control Using Heart Rate Variability as a Tool: A Cross-Sectional Study in Eastern India.

Background: Spinocerebellar ataxia (SCA) is a disease that refers to a category of inherited ataxias that are characterized by degenerative alterations in the cerebellum, pons, and spinocerebellar tracts. There are several different varieties of SCA and they are classified based on the mutant (altered) gene that causes the disease.Objective: To analyze the cardiovascular autonomic regulation in patients with type-2 spinocerebellar ataxia (SCA-2) from the heart rate variability (HRV) of 20 minutes resting electrocardiogram (ECG) and compare with the age and gender-matched controls.Materials and methods: HRV of 27 type-2 spinocerebellar ataxia patients was calculated offline from the resting ECG recording and compared with 23 age and gender-matched controls. The HRV was analyzed by HRV software module MLS 310. The frequency and time domain parameters were computed and compared.Result: Type-2 spinocerebellar ataxia patients have significantly low HRV and parasympathetic activity at rest compared to normal control. The total power in SCA-2 is 13491.63 ± 7660.77 ms2 and the normal control is 21784.76 ± 11008.67 ms2. High-frequency power (HF) which is a marker of parasympathetic activity in SCA-2 is 3823.1 ± 364 ms2 and in normal control is 9006.1 ± 920.64 ms2. The standard deviation of all NN intervals (SDNN), the square root of the mean-squared differences of successive intervals (RMSSD), spectral interval, and delta NN is significantly low in SCA-2.Conclusion: There is decreased parasympathetic tone and low HRV in SCA-2 as compared to normal controls.

Pharmacological and non-pharmacological management of spinocerebellar ataxia: A systematic review.

Spinocerebellar ataxias (SCA) comprise a rare, genetic subgroup within the degenerative ataxias and are dominantly inherited, with up to 48 recognized genetic subtypes. While an updated review on the management of degenerative ataxia is published recently, an evidence-based review focussed on the management of SCA is lacking. Here, we reviewed the pharmacological and non-pharmacological management of SCA by conducting a systematic review on Medline Ovid and Scopus. Of 29,284 studies identified, 47 studies (pharmacological: n = 25; non-pharmacological: n = 22) that predominantly involved SCA patients were included. Twenty studies had a high risk of bias based on the Cochrane's Collaboration risk of bias tool. As per the European Federation of Neurological Societies 2004 guideline for therapeutic intervention, the remaining 27 studies were of Class I (n = 4) and Class II (n = 23) evidence. Only two therapies had Level A recommendations for the management of ataxia symptoms: riluzole and immediate in-patient neurorehabilitation. Ten therapies had Level B recommendations for managing ataxia symptoms and require further investigations with better study design. These include high dose valproate acid, branched-chain amino acid, intravenous trehalose; restorative rehabilitation using cycling regimen and videogame; and cerebellar stimulations using transcranial direct current stimulation and transcranial magnetic stimulation. Lithium and coaching on psychological adjustment received Level B recommendation for depressive symptoms and quality of life, respectively. Heterogeneous study designs, different genotypes, and non-standardized clinical measures alongside short duration and small sample sizes may hamper meaningful clinical translation. Therefore, rating of recommendations only serve as points of reference.

Assessment of gait and balance impairment in people with spinocerebellar ataxia using wearable sensors.

To explore the use of wearable sensors for objective measurement of motor impairment in spinocerebellar ataxia (SCA) patients during clinical assessments of gait and balance. In total, 14 patients with genetically confirmed SCA (mean age 61.6 ± 8.6years) and 4 healthy controls (mean age 49.0 ± 16.4years) were recruited through the Massachusetts General Hospital (MGH) Ataxia Center. Participants donned seven inertial sensors while performing two independent trials of gait and balance assessments from the Scale for the Assessment and Rating of Ataxia (SARA) and Brief Ataxia Rating Scale (BARS2). Univariate analysis was used to identify sensor-derived metrics from wearable sensors that discriminate motor function between the SCA and control groups. Multivariate linear regression models were used to estimate the subjective in-person SARA/BARS2 ratings. Spearman correlation coefficients were used to evaluate the performance of the model. Stride length variability, stride duration, cadence, stance phase, pelvis sway, and turn duration were different between SCA and controls (p < 0.05). Similarly, sway and sway velocity of the ankle, hip, and center of mass differentiated SCA and controls (p < 0.05). Using these features, linear regression models showed moderate-to-strong correlation with clinical scores from the in-person rater during SARA assessments of gait (r = 0.73, p = 0.003) and stance (r = 0.90, p < 0.001) and the BARS2 gait assessment (r = 0.74, p = 0.003). This study demonstrates that sensor-derived metrics can potentially be used to estimate the level of motor impairment in patient with SCA quickly and objectively. Thus, digital biomarkers from wearable sensors have the potential to be an integral tool for SCA clinical trials and care.

Vestibulo-ocular reflex in spinocerebellar ataxia: Does it have a differentiating value?

The differential diagnosis of spinocerebellar ataxia (SCA) is often difficult and usually dependent upon genetic testing since the clinical phenotypes of SCAs considerably overlap. SCA may present VOR impairments, though the previous studies have shown inconsistent results. We aimed to assess VOR of SCA patients with various subtypes using video head impulse test (HIT) device, and to determine whether they have differentiating value.

Spinocerebellar ataxia (SCA) 38 with evidence of excessive brain iron accumulation: A neurodegeneration with brain iron accumulation (NBIA) look alike

Introduction Neuro-degeneration with brain iron accumulation(NBIA) is where early deposition of iron in the basal ganglia and the other deep grey matter is characteristically associate with movement disorders.Spinocerebellar ataxia(SCA) is characteristically a neurodegenerative disorder predominantly affecting the cerebellum and the cortico-spinal tracts.Rarely excess iron accumulation is reported in long standing SCA patients. We report a case of genetically proven SCA38 with evidence of excess iron deposition in the basal ganglia similar to a NBIA.