International Cooperative Ataxia Rating Scale Research Articles

Testing of symmetric biphasic stimulation in Vim-DBS ET patients: a randomized-controlled pilot study.

Symmetric biphasic pulses have been shown to increase the therapeutic window compared to standard cathodic pulses in ET Vim-DBS patients. Furthermore, three hours of stimulation with biphasic pulses caused less stimulation-induced ataxia compared to cathodic pulses. Therefore, an investigation of the longer-term safety of biphasic pulses is warranted. Seven ET patients were included in a randomized double-blind, cross-over design of one week home-use of symmetric biphasic stimulation (anodic phase first) versus cathodic stimulation. Amplitude was set in a double-blinded way, at the tremor arrest threshold. The primary outcome was safety assessed by documenting the adverse events. Secondary outcome parameters were stimulation amplitude, tremor (Fahn-Tolosa-Marin Tremor Rating Scale) and ataxia (International Cooperative Ataxia Rating Scale) severity, quality of life (Quality of Life in Essential Tremor Questionnaire) and cognition (Montreal Cognitive Assessment). Three patients continued in the open-label extension phase for 3 months, during which biphasic stimulation-only was further assessed by the same outcome parameters. During the 1 week testing, no adverse effects were reported. To obtain equivalent tremor control, the amplitude of the biphasic pulse was significantly higher compared to that of the cathodic pulse (p = 0.003). The other outcome parameters were not significantly different. During the open-label study, one patient used the remote control to increase the amplitude, leading to two falls caused by stimulation-induced ataxia. No other adverse effects occurred. In a small cohort, when tested for one week, symmetric biphasic pulses suggest to be safe, but require higher stimulation amplitudes. Further follow-up studies are needed to investigate long-term effects and safety.

Visual Prediction of the Progression of Spinocerebellar Ataxia Type 3 Based on Machine Learning

Background: Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a clinically heterogeneous and progressive condition. Evaluation of its progression will contribute to clinical management and genetic counseling. Objective: The objective of this study was to provide a visualized interpretable prediction of the progression of SCA3/MJD based on machine learning (ML) methods. Methods: A total of 716 patients with SCA3/MJD were included in this study. The International Cooperative Ataxia Rating Scale (ICARS) and Scale for the Assessment and Rating of Ataxia (SARA) scores were used to quantitatively assess disease progression in the patients. Clinical and genotype information were collected as factors for predicting progression. Prediction models were constructed with ML algorithms, and the prediction results were then visualized to facilitate personalizing of clinical consultation. Results: The CAG repeat length of ATXN3 and its product with age, the duration of disease, and age were identified as the 4 most important factors for predicting the severity and progression of SCA3/MJD. The SVM-based model achieved the best performance in predicting the total ICARS and SARA scores, with accuracy (10%) values of 0.7619 for the SARA and 0.7042 for the ICARS. To visualize the predictions, line charts were used to show the expected progression over the next decade, and radar charts were used to show the scores of each part of the ICARS and SARA separately. Conclusion: We are the first group to apply ML algorithms to predict progression in SCA3/MJD and achieved desirable results. Visualization provided personalized predictions for each sample and can aid in developing clinical counseling regimens in the future.

Efficacy and Safety of Repetitive Transcranial Magnetic Stimulation in Spinocerebellar Ataxia Type 3: a Systematic Review and Meta‑analysis of Randomized Controlled Trials.

Therapeutic alternatives for spinocerebellar ataxia type 3 (SCA3) are limited. Repetitive transcranial magnetic stimulation (rTMS) as a potential intervention has drawn heightened interest because of its ease of implementation, cost-effectiveness, and safety profile. We conducted a systematic review and meta-analysis to evaluate the efficacy of rTMS in the treatment of SCA3. We systematically searched databases-PubMed, Embase, the Cochrane Library, and Springer-for randomized controlled trials (RCTs) investigating the use of rTMS in the treatment of SCA3. Major efficacy outcomes were assessed, including International Cooperative Ataxia Rating Scale (ICARS) scores, Scale for the Assessment and Rating of Ataxia (SARA) scores, and ICARS subscale scores. Six randomized controlled trials involving 175 patients were included in the analysis. The meta-analysis results indicated statistically significant increases in ICARS (mean difference (MD) = - 3.88, 95% confidence interval (CI) = - 7.46 to - 0.30; p = 0.03) and SARA (MD of - 1.59, 95% CI - 2.99 to - 0.19; p = 0.03) scores. No significant heterogeneity was observed across all outcomes (I2 = 0%). Dynamic function within the ICARS scale markedly improved with rTMS (MD = - 2.19, 95% CI = - 3.82 to - 0.55; p = 0.009). The majority of the included studies exhibited a low risk of bias, and no severe adverse reactions were noted. Our meta-analysis, consisting of six randomized controlled trials with 175 participants, suggests that rTMS exhibits efficacy in alleviating both ataxic symptoms and certain aspects of motor function in SCA3.

Comparison of Two Therapeutic Approaches of Cerebellar Transcranial Direct Current Stimulation in a Sardinian Family Affected by Spinocerebellar Ataxia 38: a Clinical and Computerized 3D Gait Analysis Study.

Spinocerebellar ataxia 38 (SCA 38) is a very rare autosomal dominant inherited disorder caused by a mutation in ELOV5 gene, specifically expressed in cerebellar Purkinje cells, encoding an enzyme involved in the synthesis of fatty acids. Seven symptomatic SCA 38 patients of a Sardinian family were administered 15 sessions of cerebellar anodal transcranial direct current stimulation (tDCS) in a cross-over study, employing deltoid cerebellar-only (C-tDCS) and cerebello-spinal (CS-tDCS) cathodal montage. Clinical evaluation was performed at baseline (T0), after 15 sessions of tDCS (T1) and after 1 month of follow-up (T2). Modified International Cooperative Ataxia Rating Scale (MICARS) and the Robertson dysarthria profile were used to rate ataxic and dysarthric symptoms, respectively. Alertness and split attention tests from Zimmermann test battery for attentional performance were employed to rate attentive functions. Moreover, 3D computerized gait analysis was employed to obtain a quantitative measure of efficacy of tDCS on motor symptoms. While clinical data showed that both CS and C-tDCS improved motor, dysarthric, and cognitive scores, the quantitative analysis of gait revealed significant improvement in spatio-temporal parameters only for C-tDCS treatment. Present findings, yet preliminary and limited by the small size of the tested sample, confirm the therapeutic potential of cerebellar tDCS in improving motor and cognitive symptoms in spinocerebellar ataxias and underline the need to obtain quantitative and objective measures to monitor the efficacy of a therapeutic treatment and to design tailored rehabilitative interventions. ClinicalTrials.gov identifier: NCT05951010.

Abnormal saccade profiles in hereditary spinocerebellar degeneration reveal cerebellar contribution to visually guided saccades

ObjectiveTo study how the pathophysiology underlying hereditary spinocerebellar degeneration (spinocerebellar ataxia; SCA) with pure cerebellar manifestation evolves with disease progression using saccade recordings. MethodsWe recorded visually- (VGS) and memory-guided saccade (MGS) task performance in a homogeneous population of 20 genetically proven SCA patients (12 SCA6 and eight SCA31 patients) and 19 normal controls. ResultsFor VGS but not MGS, saccade latency and amplitude were increased and more variable than those in normal subjects, which correlated with cerebellar symptom severity assessed using the International Cooperative Ataxia Rating Scale (ICARS). Parameters with significant correlations with cerebellar symptoms showed an aggravation after disease stage progression (ICARS > 50). The saccade velocity profile exhibited shortened acceleration and prolonged deceleration, which also correlated with disease progression. The main sequence relationship between saccade amplitude and peak velocity as well as saccade inhibitory control were preserved. ConclusionsThe cerebellum may be involved in initiating VGS, which was aggravated acutely during disease stage progression. Dysfunction associated with disease progression occurs mainly in the cerebellum and brainstem interaction but may also eventually involve cortical saccade processing. SignificanceSaccade recording can reveal cerebellar pathophysiology underlying SCA with disease progression.

Efficacy and safety of noninvasive brain stimulation for patients with cerebellar ataxia: a systematic review and meta-analysis of randomized controlled trials.

With the development of noninvasive brain stimulation (NIBS) techniques, many researchers have turned their attention to NIBS as a promising treatment for cerebellar ataxia. Therefore, we conducted a systematic review and meta-analysis to investigate the efficacy and safety of NIBS in treating patients with cerebellar ataxia. Databases, including PubMed, Embase, Web of Science, Medline, and Cochrane Library, were retrieved for relevant randomized controlled trials (RCTs). Two researchers conducted literature screening, data extraction, literature quality assessment, and heterogeneity analysis between RCTs. According to the magnitude of heterogeneity I2, an appropriate data analysis model was selected for meta-analysis. A total of 14 RCTs including 406 patients with cerebellar ataxia met the inclusion criteria. The included RCTs had an overall low-risk bias and an intermediate level of evidence recommendation for key outcome indicators, such as the scale for the assessment and rating of ataxia (SARA) and international cooperative ataxia rating scale (ICARS). The results of meta-analysis showed that cerebellar NIBS, including transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), was effective in reducing the SARA scores (MD = -3.45, 95%CI = [-4.85, -2.50], P < 0.05) and ICARS scores (MD = -10.87, 95%CI = [-14.46, -7.28], P < 0.05) in patients with cerebellar ataxia compared to controls. Subgroup analysis showed that the efficacy of tDCS and rTMS was statistically different in patients with cerebellar ataxia as assessed by the SARA scores, but not by the ICARS scores. There was statistically significant difference in the efficacy of NIBS for the treatment of cerebellar ataxia caused by different etiologies. As for safety, 8 of 14 included studies documented the adverse effects of NIBS, and only two studies reported the mild adverse events of NIBS. Cerebellar NIBS was safe and effective in improving the motor coordination of patients with cerebellar ataxia, and tDCS was better than rTMS in the treatment of cerebellar ataxia. In addition, the efficacy of NIBS was different in the treatment of different types of cerebellar ataxia.

Efficacy of cerebellar transcranial magnetic stimulation in spinocerebellar ataxia type 3: a randomized, single-blinded, controlled trial.

Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA without effective treatment. This study aimed to evaluate the comparative efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) and intermittent Theta Burst Stimulation (iTBS) in a larger cohort of SCA3 patients. One hundred and twenty patients with SCA3 were randomly assigned to the 3 groups: 40 patients in the 1Hz rTMS, 40 in the iTBS and 40 in the sham group. Patients underwent 10 sessions of rTMS targeting the cerebellum delivering for 5 consecutive days per week for 2weeks (a total of 1200 pulses per session). Primary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Secondary outcomes included 10-m walking test (10MWT), nine-hole peg test (9-HPT), and PATA Rate Test (PRT). Outcome assessments were performed at baseline and on the last day of rTMS intervention. This study revealed that active rTMS outperformed sham in reducing the SARA and ICARS scores in SCA3 patients, but with no difference between the 1Hz rTMS and iTBS protocol. Moreover, no significant differences were observed in SARA and ICARS scores between the mild and moderate to severe groups after the 1Hz rTMS/iTBS therapy. Additionally, no severe adverse events were recorded in this study. The study concluded that both 1Hz rTMS and iTBS interventions targeting the cerebellum are effective to improve the symptoms of ataxia in patients with SCA3.

Effects of non-invasive brain stimulation for degenerative cerebellar ataxia: a protocol for a systematic review and meta-analysis

IntroductionTo date, the medical and rehabilitation needs of people with degenerative cerebellar ataxia (DCA) are not fully met because no curative treatment has yet been established. Movement disorders such as...

P300 Wave Alterations and Cognitive Impairment in Cerebellum Lesions.

Patients with cognitive deficits have a prolonged latency and reduced amplitude of the P300 wave. However, no study has correlated P300 wave alterations with the cognitive performance of patients with cerebellar lesions. We aimed to determine if the cognitive status of these patients was associated with P300 wave alterations. We recruited 30 patients with cerebellar lesions from the wards of the N.R.S. Medical College, Kolkata, in West Bengal (India). The Kolkata Cognitive Screening Battery tasks and the Frontal Assessment Battery (FAB)were used to assess the cognitive status and the International Cooperative Ataxia Rating Scale (ICARS)for cerebellar signs. We compared the results with the normative data of the Indian population. Patients had P300 wave alterations with a significant increase in latency and a non-significant trend in amplitude. In a multivariate model, P300 wave latency was positively associated with the ICARS kinetic subscale (p = 0.005) and age (p = 0.009), regardless of sex and years of education. In the model that included cognitive variables, P300 wave latency was negatively associated with performance in phonemic fluency (p = 0.035) and construction (p = 0.009). Furthermore, P300 wave amplitude was positively associated with the FAB total score (p < 0.001). In closing,patients with cerebellar lesions had an increase in latency and a decrease in the amplitude of the P300 wave. These P300 wave alterations were also associated with worse cognitive performance and some of the subscales of theICARS, reinforcing that the cerebellum has motor, cognitive, and affective functions.

Acute stimulation with symmetric biphasic pulses induces less ataxia compared to cathodic pulses in DBS for essential tremor

BackgroundSymmetric biphasic pulses have been shown to acutely increase the therapeutic window of ventralis intermedius deep brain stimulation (Vim-DBS) for essential tremor (ET) compared to cathodic pulses. Acute supratherapeutic stimulation can induce ataxic side effects in Vim-DBS. ObjectiveTo investigate the effect on tremor, ataxia and dysarthria of 3 h of biphasic stimulation in patients with DBS for ET. MethodsA randomized, doubled-blind, cross-over design was used to compare standard cathodic pulses with symmetric biphasic pulses (anode-first) during a 3-h period per pulse shape. During each 3-h period, all stimulation parameters were identical, except for the pulse shape. Tremor (Fahn-Tolosa-Marin Tremor Rating Scale), ataxia (International Cooperative Ataxia Rating Scale) and speech (acoustic and perceptual measures) were assessed hourly during the 3-h periods. ResultsTwelve ET patients were included. During the 3-h stimulation period, tremor control was equivalent between the two pulse shapes. Biphasic pulses elicited significantly less ataxia than cathodic pulses (p = 0.006). Diadochokinesis rate of speech was better for the biphasic pulse (p = 0.048), but other measures for dysarthria were not significantly different between the pulses. ConclusionSymmetric biphasic pulses induce less ataxia than conventional pulses after 3 h of stimulation DBS in ET patients.

Synaptic Loss in Spinocerebellar Ataxia Type 3 Revealed by SV2A Positron Emission Tomography.

Severe reduced synaptic density was observed in spinocerebellar ataxia (SCA) in postmortem neuropathology, but in vivo assessment of synaptic loss remains challenging. OBJECTIVE SPINOCEREBELLAR ATAXIA TYPE 3: The objective of this study was to assess in vivo synaptic loss and its clinical correlates in spinocerebellar ataxia type 3 (SCA3) patients by synaptic vesicle glycoprotein 2A (SV2A)-positron emission tomography (PET) imaging. We recruited 74 SCA3 individuals including preataxic and ataxic stages and divided into two cohorts. All participants received SV2A-PET imaging using 18 F-SynVesT-1 for synaptic density assessment. Specifically, cohort 1 received standard PET procedure and quantified neurofilament light chain (NfL), and cohort 2 received simplified PET procedure for exploratory purpose. Bivariate correlation was performed between synaptic loss and clinical as well as genetic assessments. In cohort 1, significant reductions of synaptic density were observed in cerebellum and brainstem in SCA3 ataxia stage compared to preataxic stage and controls. Vermis was found significantly involved in preataxic stage compared to controls. Receiver operating characteristic (ROC) curves highlighted SV2A of vermis, pons, and medulla differentiating preataxic stage from ataxic stage, and SV2A combined with NfL improved the performance. Synaptic density was significantly negatively correlated with disease severity in cerebellum and brainstem (International Co-operative Ataxia Rating Scale: ρ ranging from -0.467 to -0.667, P ≤ 0.002; Scale of Assessment and Rating of Ataxia: ρ ranging from -0.465 to -0.586, P ≤ 0.002). SV2A reduction tendency of cerebellum and brainstem identified in cohort 1 was observed in cohort 2 with simplified PET procedure. We first identified in vivo synaptic loss was related to disease severity of SCA3, suggesting SV2A PET could be a promising clinical biomarker for disease progression of SCA3. © 2023 International Parkinson and Movement Disorder Society.

Oculomotor Impairments in Children After Posterior Fossa Tumors Treatment.

Posterior fossa tumors (PFT) are the most common pediatric brain tumors, and the study of the somatic and cognitive status of PFT survivors still remains a critical problem. Since cerebellar damage can affect eye movement centers located in the vermis and hemispheres, such patients suffer from disturbances in visual perception, visual-spatial functions, reading, etc. Our investigation aimed at describing oculomotor impairments in PFT survivors linked to core oculomotor functions assessed through eye tracking method: gaze holding, reflexive saccades, and organization of voluntary saccades and their dependency on age at tumor diagnosis. Also, we investigated the relationship between oculomotor functions and ataxia measured with International Cooperative Ataxia Rating Scale (ICARS). A total of 110 children (patients and age-matched healthy controls, aged 9-17 years old) participated in the study. We found that the earlier the child had a tumor, the more impaired gaze holding (p = 0.0031) and fewer isometric saccades (p = 0.035) were observed at the time of examination. The above-mentioned functions in healthy controls improved with age. Visual scanning was also impaired compared to controls but was not related to age at diagnosis. A positive correlation between ICARS scores and number of hypermetric saccades (r = 0.309, p = 0.039), but no correlation with the number of hypometric saccades (r = - 0.008, p = 0.956). Furthermore, number of hypometric saccades did not differ between patients and controls (p = 0.238). Thus, primarily hypermetric saccades can be considered a prominent oculomotor symptom of cerebellar tumors. Our study provides basis for new methods of PFT diagnosis and rehabilitation procedure evaluation, both playing essential roles in modern pediatric neurooncology.

Efficacy and Safety of Repetitive Transcranial Magnetic Stimulation in Cerebellar Ataxia: a Systematic Review and Meta-analysis.

Cerebellar ataxia(CA) is defined as a degenerative disease of the nervous system. Repetitive transcranial magnetic stimulation (rTMS) has been a promising treatment for neurological and psychiatric diseases. Hence, to find out whether cerebellar rTMS impacts CA as a potential therapy, we performed a systematic review and meta-analysis. Qualified studies through a systematic search were retrieved for randomized controlled trials (RCTs) using acknowledged databases. Review Manager 5.4 software was employed to synthesize the data. A total of seven studies were identified as eligible and included in the quantitative review. Comparing real and sham-rTMS interventions, the utilization of rTMS on cerebellum improved the scale for the assessment and rating of ataxia (SARA) (SMD - 0.87, 95% CI - 1.41 to - 0.34; P = 0.001; I2 = 62%), the International Cooperative Ataxia Rating Scale (ICARS) (SMD - 1.06, 95% CI - 1.47 to - 0.64; P < 0.00001; I2 = 0%) and Berg balance Scale (BBS) (SMD 0.76, 95% CI 0.33 to 1.19; P = 0.0005; I2 = 39%). The subgroup analysis demonstrated high-frequency of rTMS had a positive effect (SMD - 1.28, 95% CI - 1.82 to - 0.74; P < 0.00001; I2 = 0%). For the safety, the incidence of adverse events between the two groups was not significantly different (OR 1.73, 95% CI 0.55 to 5.46; P = 0.35; I2 = 0%). In conclusion, this meta-analysis provided limited evidence, suggesting a possible strategy that rTMS over the cerebellum could be a viable therapy for symptoms associated with CA. Besides, rTMS intervention was well-attended and did not result in unanticipated negative effects.

Association Between Serum Neurofilament Light Chain and Neurochemistry Deficits in Patients with Spinocerebellar Ataxia Type 3.

Extensive evidence supports the claim that the serum neurofilament light chain (sNfL) can be used as a biomarker to monitor disease severity in patients with spinocerebellar ataxia type 3 (SCA3). However, little is known about the associations between sNfL levels and neurochemical alterations in SCA3 patients. In this study, we performed a cross-sectional study to analyze the association between sNfL and brain metabolic changes in SCA3 patients. The severity of ataxia was assessed by using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). The sNfL levels and brain metabolic changes, represented by N-acetyl aspartate (NAA)/creatine (Cr) and choline complex (Cho)/Cr ratios, were measured by a single-molecule array and proton magnetic resonance spectroscopy, respectively. In this cohort, we observed consistently elevated sNfL levels and reduced brain metabolites in the cerebellar hemispheres, dentate nucleus, and cerebellar vermis. However, this correlation was further validated in the cerebellar cortex after analysis using pairwise comparisons and a Bonferroni correction. Taken together, our results further confirmed that sNfL levels were increased in SCA3 patients and were negatively correlated with metabolic changes in the cerebellar cortex. Our data also support the idea that sNfL levels are a promising potential complementary biomarker for patients with SCA3.

Tremor, Gait, and Balance Disorders in Essential Tremor and the Efficacy of Atenolol

ABSTRACT Background: To assess gait and balance in patients with essential tremor (ET), which is the most common tremor disorder characterized by bilateral action tremor of the hands with possible involvement of further tremor locations and to test the efficacy of atenolol on tremor and gait and balance. Methods: In this prospective study, gait and balance were evaluated by static posturography in addition to International Cooperative Ataxia Rating Scale (ICARS) in 22 ET patients without any additional neurologic signs on examination. Tremor severity was assessed by The Essential Tremor Rating Assessment Scale (TETRAS). The efficacy of atenolol 100 mg/day both on tremor and gait and balance was investigated. Posturographic recordings were performed in gender, age-, and height-matched healthy volunteers who constituted the control group. Results: The mean center of gravity sway velocity of the ET patients recorded on firm and foam surfaces with eyes open and closed was not significantly different from the healthy controls but sway velocity on tandem stance was significantly increased (P = 0.032). Gait speed (P = 0.015) was decreased and step width was increased (P = 0.001). An improvement in TETRAS scores was recorded with atenolol treatment (P = 0.046). An improvement not reaching statistical significance was present in ICARS scores (P = 0.059). However, posturographic parameters did not change significantly (P &gt; 0.05). Conclusion: Increased sway velocity on tandem stance, decreased gait speed and increased step width are consistent with midline cerebellar dysfunction in ET patients with no obvious gait and balance deficits on clinical examination. Atenolol seems to be effective on tremor but does not cause a significant improvement in gait and balance deficits.

Validity and Reliability of the Korean-Translated Version of the International Cooperative Ataxia Rating Scale in Cerebellar Ataxia.

The International Cooperative Ataxia Rating Scale (ICARS) is a semiquantitative clinical scale for ataxia that is widely used in numerous countries. The purpose of this study was to investigate the validity and reliability of the Korean-translated version of the ICARS. Eighty-eight patients who presented with cerebellar ataxia were enrolled. We investigated the construct validity using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). We also investigated the internal consistency using Cronbach's α and intrarater and interrater reliability using intraclass correlation coefficients. The Korean-translated ICARS showed satisfactory construct validity using EFA and CFA. It also revealed good interrater and intrarater reliability and showed acceptable internal consistency. However, subscale 4 for assessing oculomotor disorder showed moderate internal consistency. This is the first report to investigate the validity and reliability of the Korean-translated ICARS. Our results showed excellent construct and convergent validity. The reliability is also acceptable.

Short-term efficacy of repetitive transcranial magnetic stimulation in SCA3: A prospective, randomized, double-blind, sham-controlled study

ObjectiveSpinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia globally. No effective treatment is currently available for SCA3. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive form of brain stimulation, demonstrated to improve symptoms in patients with neurodegenerative cerebellar ataxias. The present study investigated whether treatment with rTMS over the cerebellum for 15 consecutive days improved measures of ataxia in SCA3 patients. MethodsA double-blind, prospective, randomized, sham-controlled trial was carried out on 44 SCA3 patients. Participants were randomly assigned to two groups: real or sham stimulation. Each participant underwent 30 minutes of 1Hz rTMS stimulation (a total of 900 pulses) for 15 consecutive days. The primary outcome measure was the score on the International Cooperative Ataxia Rating Scale (ICARS), and secondary outcomes were from the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). ResultsNausea was the only adverse effect reported by 2 participants from the sham and real group. After 15 days of treatment, there was a significant improvement in all performance scores in both real and sham stimulation groups. However, compared to the sham group, the improvements were significantly larger in the real group for the ICARS (P = 0.002), SARA (P = 0.001), and BBS (P = 0.001). InterpretationA 15 days treatment with rTMS over the cerebellum improves the symptoms of ataxia in SCA3 patients. Our results suggest that rTMS is a promising tool for future rehabilitative approaches in SCA3.

Harmonizing results of ataxia rating scales: mFARS, SARA, and ICARS.

The ever-increasing body of ataxia research provides opportunities for large-scale meta-analyses, systematic reviews, and data aggregation. Because multiple standardized scales are used to quantify ataxia severity, harmonization of these measures is necessary for quantitative data pooling. We applied the modified Friedreich Ataxia Rating Scale (mFARS), the Scale for the Assessment and Rating of Ataxia (SARA), and the International Cooperative Ataxia Rating Scale (ICARS) to a large cohort of people with Friedreich's ataxia. We provide regression coefficients for scale interconversion and discuss the reliability of this approach, together with insights into the differential sensitivities of mFARS and SARA to disease progression.

Combined Short-Pulse and Directional Deep Brain Stimulation of the Thalamic Ventral Intermediate Area for Essential Tremor

ObjectiveNovel deep brain stimulation (DBS) systems allow directional and short-pulse stimulation to potentially improve symptoms and reduce side effects. The aim of this study was to investigate the effect of short-pulse and directional stimulation, in addition to a combination of both, in the ventral intermediate thalamus (VIM)/posterior subthalamic area (PSA) on tremor and stimulation-induced side effects in patients with essential tremor. Materials and MethodsWe recruited 11 patients with essential tremor and VIM/PSA-DBS. Tremor severity (Fahn-Tolosa-Marin), ataxia (International Cooperative Ataxia Rating Scale), and paresthesia (visual analog scale) were assessed with conventional omnidirectional and directional stimulation with pulse width of 60 μs and 30 μs. ResultsAll stimulation conditions reduced tremor. The best directional stimulation with 60 μs reduced more tremor than did most other stimulation settings. The best directional stimulation, regardless of pulse width, effectively reduced stimulation-induced ataxia compared with the conventional stimulation (ring 60 μs) or worst directional stimulation with 60 μs. All new stimulation modes reduced occurrence of paresthesia, but only the best directional stimulation with 30 μs attenuated paresthesia compared with the conventional stimulation (ring 60 μs) or worst directional stimulation with 60 μs. The best directional stimulation with 30 μs reduced tremor, ataxia, and paresthesia compared with conventional stimulation in most patients. Correlation analyses indicated that more anterior stimulation sites are associated with stronger ataxia reduction with directional 30 μs than with conventional 60 μs stimulation. ConclusionDirectional and short-pulse stimulation, and a combination of both, revealed beneficial effects on stimulation-induced adverse effects.

Neurological and cerebellar soft signs in bipolar disorder: The role of staging, type and history of psychotic symptoms

AimBipolar disorder (BD) patients show neurological abnormalities in form of neurological and cerebellar soft signs (NSS and CSS). NSS represents heterogeneous group of symptoms representing i.a. deficits of motor coordination, sequencing of complex motor acts and sensory integration. CSS were introduced as group of the neurological deficits of posture, gait, kinetic functions, eye movements and speech, associated more specifically to cerebellar abnormalities than NSS. Studies show significant effect size variability of those symptoms in BD group suggesting the existence of differing subpopulations. The aim of our study was to evaluate the effect of BD type, stage and the history of psychotic symptoms (HoPS) on the severity of CSS and NSS as none of the previous studies had verified the role of those categories. MethodsThis study involved 181 participants: 116 euthymic BD patients (66 BD I, 50 BD II) and 65 healthy controls (HC). CSS was assessed with the International Cooperative Ataxia Rating Scale and NSS with Neurological Evaluation Scale. Patients were divided into early and late stage of the disorder according to Kapczinski's criteria. Rater was blind to patients' stage, type and HoPS. ResultsStaging was related to vast majority of CSS and NSS scores. HoPS was related to oculomotor deficits. The effect of BD type was the least significant. Late stage BD showed more severe CSS and NSS than HC in every measure. There were no differences between early stage BD and HC, apart of posture and gait disturbances. Except of sensory integration scores, late stage BD showed higher CSS and NSS rates than early stage patients. ConclusionIn this hitherto the largest study of neurological abnormalities in BD we have shown significant role of staging in CSS and NSS severity. Progression criteria based on inter-episode psychosocial functioning may stand as unrecognised factor responsible for variability observed in previous studies evaluating neurological abnormalities in BD. Our study suggests that in clinical practice NSS and CSS may be potentially used as easy-to-assess biological marker of BD staging. Observed severity of neurological impairments of BD patients may more likely correspond to the disease progression than to BD type and HoPS.