International Cooperative Ataxia Rating Scale Scores Research Articles

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.

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.

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.

Altered cerebral blood flow in patients with spinocerebellar degeneration.

ObjectivesSpinocerebellar degeneration (SCD) comprises a multitude of disorders with sporadic and hereditary forms, including spinocerebellar ataxia (SCA). Except for progressive cerebellar ataxia and structural atrophy, hemodynamic changes have also been observed in SCD. This study aimed to explore the whole-brain patterns of altered cerebral blood flow (CBF) and its correlations with disease severity and psychological abnormalities in SCD via arterial spin labeling (ASL).MethodsThirty SCD patients and 30 age- and sex-matched healthy controls (HC) were prospectively recruited and underwent ASL examination on a 3.0T MR scanner. The Scale for Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS) scores were used to evaluate the disease severity in SCD patients. Additionally, the status of anxiety, depression and sleep among all patients were, respectively, evaluated by the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Self-Rating Scale of Sleep (SRSS). We compared the whole-brain CBF value between SCD group and HC group at the voxel level. Then, the correlation analyses between CBF and disease severity, and psychological abnormalities were performed on SCD group.ResultsCompared with HC, SCD patients demonstrated decreased CBF value in two clusters (FWE corrected P < 0.05), covering bilateral dentate and fastigial nuclei, bilateral cerebellar lobules I-IV, V and IX, left lobule VI, right lobule VIIIb, lobules IX and X of the vermis in the cerebellar Cluster 1 and the dorsal part of raphe nucleus in the midbrain Cluster 2. The CBF of cerebellar Cluster 1 was negatively correlated with SARA scores (Spearman’s rho = –0.374, P = 0.042) and SDS standard scores (Spearman’s rho = –0.388, P = 0.034), respectively. And, the CBF of midbrain Cluster 2 also had negative correlations with SARA scores (Spearman’s rho = –0.370, P = 0.044) and ICARS scores (Pearson r = –0.464, P = 0.010).ConclusionThe SCD-related whole-brain CBF changes mainly involved in the cerebellum and the midbrain of brainstem, which are partially overlapped with the related function cerebellar areas of hand, foot and tongue movement. Decreased CBF was related to disease severity and depression status in SCD. Therefore, CBF may be a promising neuroimaging biomarker to reflect the severity of SCD and suggest mental changes.

The progression rate of spinocerebellar ataxia type 3 varies with disease stage

BackgroundIn polyglutamine (polyQ) diseases, the identification of modifiers and the construction of prediction model for progression facilitate genetic counseling, clinical management and therapeutic interventions.MethodsData were derived from the longest longitudinal study, with 642 examinations by International Cooperative Ataxia Rating Scale (ICARS) from 82 SCA3 participants. Using different time scales of disease duration, we performed multiple different linear, quadratic and piece-wise linear growth models to fit the relationship between ICARS scores and duration. Models comparison was employed to determine the best-fitting model according to goodness-of-fit tests, and the analysis of variance among nested models.ResultsAn acceleration was detected after 13 years of duration: ICARS scores progressed 2.445 (SE: 0.185) points/year before and 3.547 (SE: 0.312) points/year after this deadline. Piece-wise growth model fitted better to studied data than other two types of models. The length of expanded CAG repeat (CAGexp) in ATXN3 gene significantly influenced progression. Age at onset of gait ataxia (AOga), a proxy for aging process, was not an independent modifier but affected the correlation between CAGexp and progression. Additionally, gender had no significant effect on progression rate of ICARS. The piece-wise growth models were determined as the predictive models, and ICARS predictions from related models were available.ConclusionsWe first confirmed that ICARS progressed as a nonlinear pattern and varied according to different stages in SCA3. In addition to ATXN3 CAGexp, AOga or aging process regulated the progression by interacting with CAGexp.

Effects of Repetitive Transcranial Magnetic Stimulation on Cerebellar Metabolism in Patients With Spinocerebellar Ataxia Type 3

BackgroundSpinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant hereditary ataxia, and, thus far, effective treatment remains low. Repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of spinal cerebellar ataxia, but the mechanism is unclear; in addition, whether any improvement in the symptoms is related to cerebellar metabolism has not yet been investigated. Therefore, the purpose of this study was to investigate the effects of low-frequency rTMS on local cerebellar metabolism in patients with SCA3 and the relationship between the improvement in the symptoms and cerebellar metabolism.MethodsA double-blind, prospective, randomized, sham-controlled trial was carried out among 18 SCA3 patients. The participants were randomly assigned to the real stimulation group (n = 9) or sham stimulation group (n = 9). Each participant in both the groups underwent 30 min of 1 Hz rTMS stimulation (a total of 900 pulses), differing only in terms of stimulator placement, for 15 consecutive days. To separately compare pre- and post-stimulation data (magnetic resonance spectroscopy (MRS) data and the International Cooperative Ataxia Rating Scale (ICARS) score) in the real and sham groups, paired-sample t-tests and Wilcoxon’s signed-rank tests were used in the analyses. The differences in the ICARS and MRS data between the two groups were analyzed with independent t-tests and covariance. To explore the association between the changes in the concentration of cerebellar metabolism and ICARS, we applied Pearson’s correlation analysis.ResultsAfter 15 days of treatment, the ICARS scores significantly decreased in both the groups, while the decrease was more significant in the real stimulation group compared to the sham stimulation group (p < 0.001). The analysis of covariance further confirmed that the total ICARS scores decreased more dramatically in the real stimulation group after treatment compared to the sham stimulation group (F = 31.239, p < 0.001). The values of NAA/Cr and Cho/Cr in the cerebellar vermis, bilateral dentate nucleus, and bilateral cerebellar hemisphere increased significantly in the real stimulation group (p < 0.05), but no significant differences were found in the sham stimulation group (p > 0.05). The analysis of covariance also confirmed the greater change in the real stimulation group. This study also demonstrated that there was a negative correlation between NAA/Cr in the right cerebellar hemisphere and ICARS in the real stimulation group (r = − 0.831, p = 0.02).ConclusionThe treatment with rTMS over the cerebellum was found to induce changes in the cerebellar local metabolism and microenvironment in the SCA3 patients. The alterations may contribute to the improvement of the symptoms of ataxia in SCA3 patients.

Evaluation of upper extremity ataxia through image processing in individuals with multiple sclerosis.

Impaired dexterity is a frequently reported disability among people with ataxic multiple sclerosis (MS). To quantify and standardize the evaluation of upper extremity coordination disorder among patients with multiple sclerosis (MS), using the Tablet Ataxia Assessment Program (TAAP). The X and Y axis movements of 50 MS patients and 30 healthy individuals who were evaluated using the International Cooperative Ataxia Rating Scale (ICARS) were also assessed using TAAP. The functional times of the participants' right and left hands were recorded using the nine-hole peg test (NHPT). The upper extremity coordination of individuals with MS was evaluated using the upper extremity kinetic functions section of ICARS. The deviations for the X and Y axis movements of the MS group were greater than those of the control group (p<0.05). Significant correlations were shown between TAAP scores and NHPT and ICARS scores. The strongest correlation was found between NHPT and ICARS in the dominant hand (rnhpt=0.356, pnhpt=0.001; ricars=0.439, picars=0.000). In correlating the Y axis with ICARS, the deviations in the Y axis were found to be greater in the non-dominant hand than those in the X axis (ryright=0.402, pyright=0.004; ryleft=0.691, pyleft=0.000). Measurement using TAAP is more sensitive than other classical and current methods for evaluating ataxia. We think that TAAP is an objective tool that will allow neurorehabilitation professionals and clinicians to evaluate upper extremity coordination.

Characterization of Retinal Architecture in Spinocerebellar Ataxia Type 3 and Correlation with Disease Severity.

Neurodegeneration affects the brain and peripheral nervous system in spinocerebellar ataxia type 3 (SCA3). As the retina is also involved, studying the retinal architecture in a cohort of patients could reveal clinically relevant biomarkers. The aim is to investigate retinal architecture in SCA3 to identify potential biomarkers. We evaluated 38 patients with SCA3 and 25 healthy age-matched controls, who underwent visual acuity assessment, intraocular pressure measurement, and fundoscopy and macular and peripapillary spectral domain optical coherence tomography (SD-OCT). We measured the peripapillary retinal nerve fiber layer (pRNFL) thickness in each quadrant of the temporal-superior-nasal-inferior-temporal chart and the macular layer thicknesses in each sector of the inner circle of the Early Treatment Diabetic Retinopathy Study (IC-ETDRS) grid. Linear regression analysis was employed to test the associations between retinal parameters and age, disease duration, CAG repeats, and SARA (Scale of the Assessment and Rating of Ataxia) and ICARS (International Cooperative Ataxia Rating Scale) scores in SCA3. In all sectors, except for the temporal quadrant, pRNFL was significantly thinner in SCA3 patients than in controls. Average total macular, ganglion cell layer (GCL), and inner plexiform layer (IPL) thicknesses were significantly decreased in SCA3 patients in comparison to controls. The average total macular thickness and the average thicknesses of RNFL, GCL, and IPL negatively correlated with ICARS scores, whereas average GCL and IPL thicknesses negatively correlated with SARA scores. The retinal ganglion cells, their dendrites, and axons are selectively affected in SCA3 patients. The RNFL, GCL, and IPL thicknesses in SD-OCT correlate with the clinical phenotype and represent potential biomarkers for future clinical trials and natural history studies. © 2021 International Parkinson and Movement Disorder Society.

Pattern of cerebellar grey matter loss associated with ataxia severity in spinocerebellar ataxias type 3: a multi-voxel pattern analysis.

Spinocerebellar ataxias type 3 (SCA3) patients are clinically characterized by progressive cerebellar ataxia combined with degeneration of the cerebellum. Previous neuroimaging studies have indicated ataxia severity associated with cerebellar atrophy using univariate methods. However, whether cerebellar atrophy patterns can be used to quantitatively predict ataxia severity in SCA3 patients at the individual level remains largely unexplored. In this study, a group of 66 SCA3 patients and 58 healthy controls were included. Disease duration and ataxia assessment, including theScale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS), were collected for SCA3 patients. The high-resolution T1-weighted MRI was obtained, and cerebellar grey matter (GM) was extracted using a spatially unbiased infratentorial template toolbox for all participants. We investigated the association between the pattern of cerebellar grey matter (GM) loss and ataxia assessment in SCA3 by using a multivariate machine learning technique. We found that the application of RVR allowed quantitative prediction of both SARA scores (leave-one-subject-out cross-validation: correlation = 0.56, p-value = 0.001; mean squared error (MSE) = 20.51, p-value = 0.001; ten-fold cross-validation: correlation = 0.52, p-value = 0.001; MSE = 21.00, p-value = 0.001) and ICARS score (leave-one-subject-out cross-validation: correlation = 0.59, p-value = 0.001; MSE = 139.69, p-value = 0.001; ten-fold cross-validation: correlation = 0.57, p-value = 0.001; MSE = 145.371, p-value = 0.001) with statistically significant accuracy. These results provide proof-of-concept that ataxia severity in SCA3 patients can be predicted by the alteration pattern of cerebellar GM using multi-voxel pattern analysis.

A Proposal for Classification of Retinal Degeneration in Spinocerebellar Ataxia Type 7.

The aim of this study is to propose a classification system for the spinocerebellar ataxia type 7 retinal degeneration (SCA7-RD). Twenty patients with molecularly confirmed SCA7 underwent slit lamp examination, fundus photography, and optical coherence tomography (Spectralis®). Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale (ICARS) were applied, and age, sex, age at symptom onset, and number of CAG expansions were recorded. After analyzing the ophthalmological findings in each participant, a panel of retinal disease experts created a qualitative classification system for SCA7-RD comprising four stages. We assessed the correlations of retinal degeneration severity with SARA and ICARS scores, number of CAG repeats in ATXN7 allele, and age at symptom onset. We graded retinal degeneration as stage 1 in nine participants, as stage 2 in five, and as stage 3 in six. No differences in age and visual symptoms duration were found between groups. SARA and ICARS scores correlated with the severity of SCA7-RD on the classification system (p = 0.024 and p = 0.014, respectively). After adjusting for disease duration, retinal disease stage association with SARA and ICARS scores remained significant (ANCOVA, p < 0.05). The classification system for SCA7-RD was able to characterize different disease stages representing the landmarks in the cone-rod dystrophy natural history. Neurodegeneration appears to occur in parallel in the cerebellum and in the visual pathway. We conclude that retinal degeneration in SCA7 is a potential biomarker of the neurological phenotype severity.

CAG Repeat Size Influences the Progression Rate of Spinocerebellar Ataxia Type 3.

In spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the expanded cytosine adenine guanine (CAG) repeat in ATXN3 is the causal mutation, and its length is the main factor in determining the age at onset (AO) of clinical symptoms. However, the contribution of the expanded CAG repeat length to the rate of disease progression after onset has remained a matter of debate, even though an understanding of this factor is crucial for experimental data on disease modifiers and their translation to clinical trials and their design. Eighty-two Dutch patients with SCA3/MJD were evaluated annually for 15 years using the International Cooperative Ataxia Rating Scale (ICARS). Using linear growth curve models, ICARS progression rates were calculated and tested for their relation to the length of the CAG repeat expansion and to the residual age at onset (RAO): The difference between the observed AO and the AO predicted on the basis of the CAG repeat length. On average, ICARS scores increased 2.57 points/year of disease. The length of the CAG repeat was positively correlated with a more rapid ICARS progression, explaining 30% of the differences between patients. Combining both the length of the CAG repeat and RAO as comodifiers explained up to 47% of the interpatient variation in ICARS progression. Our data imply that the length of the expanded CAG repeat in ATXN3 is a major determinant of clinical decline, which suggests that CAG-dependent molecular mechanisms similar to those responsible for disease onset also contribute to the rate of disease progression in SCA3/MJD. ANN NEUROL 2021;89:66-73.

Clinical observation of acupuncture plus Frenkel exercises for ataxia after cerebral stroke

To observe the clinical efficacy of mind-refreshing and balance-restoring needling method combined with Frenkel exercises in treating ataxia after cerebral stroke. The recruited 120 patients were randomized into an observation group and a control group, with 60 cases in each group. The control group was intervened by mind-refreshing and balance-restoring needling method, while the observation group was given additional lower-limb Frenkel exercises. Before and after treatment and at the follow-up, the ataxic lower-limb function was scored using Berg balance scale (BBS) and international cooperative ataxia rating scale (ICARS), and Barthel index (BI) was adopted to score the activities of daily living (ADL). After treatment, the markedly effective rate was 70.2% and the total effective rate was 96.5% in the observation group, versus 39.7% and 87.9% in the control group, and the differences in the markedly effective rate and the total effective rate were statistically significant (P 0.05), while the between-group differences in the ICARS and BI scores were statistically significant at the follow-up (both P<0.05). The interaction effects between the scoring time of BBS and BI and the group factor were statistically significant (P<0.01, P<0.05). Mind-refreshing and balance-restoring needling can effectively improve the lower-limb ataxic symptoms and ADL after stroke; when combined with Fenkel exercises, this needling method can produce more significant efficacy.

Neurofilament light chain is a promising serum biomarker in spinocerebellar ataxia type 3

BackgroundSpinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression or therapeutic response. Neurofilament light chain (NfL) was recently proposed as a serum biomarker for many neurodegenerative disorders. The present study investigated whether NfL was a promising serum biomarker for SCA3.MethodsSeventeen SCA3 patients and 9 controls were enrolled in cohort A, and 116 SCA3 individuals (preclinical and patients) and 91 controls were recruited as cohort B. We assessed whether serum NfL correlated with cerebrospinal fluid (CSF) NfL in cohort A and correlations between serum NfL levels and clinical features and brain volumes were determined in cohort B. The single-molecule array method was used to measure serum NfL levels. Disease severity was determined using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). Cerebellar and brainstem volumes were assessed using MRI neuroimaging measurements.ResultsSerum/CSF NfL levels in cohort A were elevated in SCA3 patients, and serum and CSF NfL exhibited a significant positive correlation (r = 0.9179, p < 0.0001). Levels of serum NfL in cohort B were significantly higher in preclinical SCA3 (15.03 ± 7.49 vs 6.88 ± 2.72 pg/ mL, p < 0.0001) and manifest SCA3 subjects (37.56 ± 13.47 vs 9.07 ± 6.02 pg/ mL, p < 0.0001) compared to those in controls. Serum NfL concentrations increased from early disease stage to the next stage. Levels of serum NfL in ATXN3 mutation carriers were positively associated with SARA (r = 0.5458, p < 0.0001) and ICARS scores (r = 0.5522, p < 0.0001). Significant negative associations with cerebellar volumes (r = − 0.4217, p = 0.0003) and brainstem volumes (r = − 0.4263, p = 0.0003) were observed. All changes remained significant after adjustment for age and CAG repeat.ConclusionsLevels of serum NfL were significantly elevated in SCA3 individuals and correlated with disease severity. Serum NfL is a promising serum biomarker of disease onset and progression, and a potential candidate biomarker of treatment response in SCA3.

Clinical analysis of sequelae of acute trimethyltin oxide poisoning

Objective: Clinical analysis of sequelae of 16 patients with trimethyltin chloride (TMT) poisoning after 2 years. Methods: Sixteen patients with TMT poisoning from a waste recycling company in Ganzhou City in August 2016 were enrolled. They were investigated by questionnaires and assessed by various scales after two years. 6 cases of severe poisoning were examined by head MRI. The scale includes Hamilton Anxiety Scale (HAMA) , Depression Scale (HAMD) , Simple Mental State Examination Scale (MMSE) , Activity of Daily Living (ADL) , International Cooperative Ataxia Rating Scale (ICARS) . Results: 16 cases of TMT poisoning still have headache, dizziness and other symptoms. Instability of walking in 4 patients with severe poisoning, and the brain MRI manifestations included obvious atrophy of temporal lobe, hippocampus, insula lobe, cerebellum and ventricle enlargement. Two patients were rated as severe mixed anxiety and depression, one as moderate mixed anxiety and depression, and one as mild anxiety. 3 cases were diagnosed as dementia and 1 case as mild cognitive impairment. Two cases were totally dependent on living ability. ICARS scores were 66 points and 63 points respectively. Two cases were mildly dependent on living ability. ICARS scores were 28 points and 6 points respectively. There were 2 cases of mild mixed anxiety and depression in mild and moderate poisoning patients, and 1 case of mild cognitive impairment in each patient. They could live independently. ICARS scores were 0. Conclusion: After 2 years of TMT poisoning, some patients still have general clinical symptoms such as dizziness, headache and so on. There are also mental and intellectual symptoms such as anxiety, depression and cognitive impairment. Some of patients with severe poisoning presented with dementia and cerebellar ataxia, and even lost independent living ability.

The severity of motor dysfunctions and urinary dysfunction is not correlated in multiple system atrophy

ObjectiveAlthough it is well known that patients with multiple system atrophy (MSA) cerebellar dominant type (MSA-C) show severe autonomic dysfunction, the relationship between autonomic and motor dysfunction remains uncertain. Previously we reported that severe urinary voiding dysfunction is useful in differential diagnosis of MSA and other diseases. Herein, we aimed to clarify the relationship between the severity of motor dysfunctions and urinary dysfunction. MethodThis study is a retrospective review of 46 patients with MSA-C diagnosed according to Gilman's second consensus criteria. The severity of motor dysfunctions was evaluated using International Cooperative Ataxia Rating Scale (ICARS). Urinary voiding dysfunction was evaluated by measuring post-void residual (PVR). The mean duration of motor unit potentials in external anal sphincter muscles on electromyography, which represents the severity of neurodegeneration in Onuf's nucleus, was also examined. ResultsThe mean age of patients was 63.8 ± 8.2 years and mean disease duration was 3.0 ± 1.9 years. The mean ICARS score was 40.1 ± 14.7. The mean PVR was 119.1 ± 102 ml and the mean duration of motor unit potentials (MUPs) in anal sphincter electromyography was 9.2 ± 2.2 ms. The correlation coefficient between ICARS and PVR was 0.093 (p = .539), and between ICARS and mean duration of MUPs was 0.105 (p = .811). A significant positive correlation (r = 0.296, p = .005) was noted between PVR and the mean duration of MUP. ConclusionMotor and urinary dysfunctions were not correlated in MSA-C.

Targeted ballet program mitigates ataxia and improves balance in females with mild-to-moderate multiple sclerosis.

BackgroundMultiple sclerosis (MS) is a disease of the central nervous system that causes ataxia and deficits in balance. Exercise-based therapies have been identified as integral to the recovery of motor function in MS, but few studies have investigated non-traditional movement interventions. We examined a targeted ballet program (TBP) designed to mitigate ataxia and improve balance in females with mild-to-moderate relapsing-remitting MS.Methods and findingsTwelve females with mild-to-moderate disability due to MS were assessed for study eligibility for the study. Ten participants met the inclusion criteria. Two were lost to unrelated health complications. Eight participants completed the TBP. The TBP met twice a week for 60 minutes for 16 weeks. Assessments included (a) the International Cooperative Ataxia Rating Scale (ICARS), (b) the Mini-Balance Evaluations Systems Test (Mini-BESTest), (c) smoothness of movement during a five-meter walk, and (d) balance in a step to stand task before and after the TBP. There were no TBP-related adverse events. Single-tailed paired samples t-tests and Wilcoxon tests were conducted. Improvements were observed in ICARS (p = 7.11E-05), Mini-BESTest (p = 0.001), smoothness of movement in the left (p = 0.027) and right (p = 0.028) sides of the body, and balance in a step-to-stand task in the back (p = 0.025) direction. Results yielded 42% and 58% improvements in the mean Mini-BESTest and ICARS scores, respectively.ConclusionsThis study adds to current research by providing support for a TBP intervention targeting ataxia and balance in MS. The TBP was well tolerated, improved balance, and mitigated ataxia. Clinical improvements were larger than those of previous studies on physical rehabilitation in MS with similar outcome measures.Trial registrationISRCTN ISRCTN67916624.

Clinical Assessment of Dysarthria in Children with Cerebellar Syndrome Associated with PMM2-CDG.

Phosphomannomutase deficiency (PMM2-CDG) causes a cerebellar syndrome that has been evaluated using the International Cooperative Ataxia Rating Scale (ICARS). However, no particular dysarthria tests have been used. Speech ICARS subscore subjectively assesses fluency and clarity of speech with two items. Repetition of syllables, traditionally used for characterization of ataxic speech, was validated in early-onset ataxia conditions. We assess the validity of the PATA test (SCA Functional Index [SCAFI]) in PMM2-CDG patients.PATA rates from 20 patients were compared with a control population were and correlated with ICARS and neuroimaging.There was a difference between the PATA rate in patients and controls. PATA rate increased with age in controls. In patients, the improvement of PATA rate with age was not significant. In patients, the PATA rate was negatively correlated with the total ICARS score and the Speech ICARS subscore. Regarding neuroimaging, midsaggital vermis relative diameter was positively correlated with PATA results. These last differences were also significant when the results are corrected by age.PATA rate provides an easy measure for a quantitative assessment of dysarthria that may help clinicians to monitor patients' evolution in a regular consultation. It could also be used in PMM2-CDG clinical trials implementing ICARS speech subscore information.

Microstructural Alterations in Asymptomatic and Symptomatic Patients with Spinocerebellar Ataxia Type 3: A Tract-Based Spatial Statistics Study.

Spinocerebellar ataxia type 3 (SCA3) is the most commonly occurring type of autosomal dominant spinocerebellar ataxia. The present study aims to investigate progressive changes in white matter (WM) fiber in asymptomatic and symptomatic patients with SCA3. A total of 62 participants were included in this study. Among them, 16 were asymptomatic mutation carriers (pre-SCA3), 22 were SCA3 patients with clinical symptoms, and 24 were normal controls (NC). Group comparison of tract-based spatial statistics was performed to identify microstructural abnormalities at different SCA3 disease stages. Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were found in the left inferior cerebellar peduncle and superior cerebellar peduncle (SCP) in the pre-SCA3 group compared with NC. The symptomatic SCA3 group showed brain-wide WM tracts impairment in both supratentorial and infratentorial networks, and the mean FA value of the WM skeleton showed a significantly negative correlation with the International Cooperative Ataxia Rating Scale (ICARS) scores. Specifically, FA of the bilateral posterior limb of the internal capsule negatively correlated with SCA3 disease duration. We also found that FA values in the right medial lemniscus and SCP negatively correlated with ICARS scores, whereas FA in the right posterior thalamic radiation positively correlated with Montreal Cognitive Assessment scores. In addition, MD in the middle cerebellar peduncle, left anterior limb of internal capsule, external capsule, and superior corona radiate positively correlated with ICARS scores in SCA3 patients. WM microstructural changes are present even in the asymptomatic stages of SCA3. In individuals in which the disease has progressed to the symptomatic stage, the integrity of WM fibers across the whole brain is affected. Furthermore, abnormalities in WM tracts are closely related to SCA3 disease severity, including movement disorder and cognitive dysfunction. These findings can deepen our understanding of the neural basis of SCA3 dysfunction.

Neurovisual Assessment in Children with Ataxia Telangiectasia.

Visual impairment is present in almost all patients with ataxia telangiectasia (AT) and, due to their early onset, constitute an important disabling aspect of the syndrome: the quality of vision is limited by dyspraxia and oculomotor abnormal movements. The purpose of this observational study was to describe visual disorders, notably oculomotor impairment, in a sample of children with AT. Fifteen AT patients (mean age 12 years and 4 months) underwent a neurovisual evaluation, particularly focused on oculomotor functions (fixation, smooth pursuit, saccades, and abnormal ocular movements). We compared the visual profile obtained with that described using the International Cooperative Ataxia Rating Scale (ICARS) subscale of oculomotor dysfunction. Refractive errors were seen in eight patients and strabismus in three. Major oculomotor findings were fixation abnormalities (6/15), saccadic impairment (15/15), and abnormal smooth pursuit (14/15). Abnormal ocular movements were seen in 13/15 (saccadic intrusion in 8 and nystagmus in 5). Using ICARS scale, 13/15 children presented gaze-evoked nystagmus, 4/15 a clearly saccadic pursuit, and 11/15 dysmetria of saccades. We propose a clinical neurovisual evaluation, which could be integrated with ICARS scores in the study of oculomotor involvement in AT pediatric patients. We strongly recommend the empowerment of visual functions to slow down progressive global disability of these patients.