Reduced sensitivity to future consequences underlies gambling decision in cerebellar ataxia.

INTRODUCTION: Previous research has identified that people with cerebellar ataxia (CA) showed impaired reward-related decision-making in the Iowa Gambling Task (IGT). To investigate the mechanisms underlying this impairment, we examined CA participants' combination of performance in the IGT, which predominantly tests reward seeking, and the modified IGT (mIGT), which mainly assesses punishment avoidance. METHODS: Fifty participants with CA and one hundred controls completed the IGT and mIGT. Task performance in each of the five twenty-trial blocks was compared between groups and the learning rates were assessed with simple linear regressions. Each participant's IGT score and mIGT score were compared. RESULTS: CA participants performed worse than controls in both the IGT and the mIGT, especially in the last block (IGT: -0.24 ± 10.05 vs. 3.88 ± 10.31, p = 0.041; mIGT: 2.72 ± 7.62 vs. 8.65 ± 8.64, p < 0.001). In contrast to the controls, those with CA did not significantly improve their scores over time in either task. Controls performed better in the mIGT than the IGT, while CA participants' scores in the two tasks showed no significant difference. IGT and mIGT performance did not correlate with ataxia severity or depressive symptoms. CONCLUSION: Individuals with CA showed impaired performance in both the IGT and mIGT, which indicates disruption in both short-term reward seeking and short-term punishment avoidance. Therefore, these results suggest that reduced sensitivity to long-term consequences drives the risky decision-making in CA.

Impacts of the COVID-19 Pandemic on the Mental Health and Motor Deficits in Cuban Patients with Cerebellar Ataxias.

Although there are no convincing evidences of detrimental effect of SARS-CoV2 infection on the cerebellum, the COVID-19 pandemic could impact the life quality of patients with cerebellar ataxias, but few studies have addressed this concern. To assess the motor and mental health changes caused by the COVID-19 pandemics in Cuban patients with cerebellar ataxias, three hundred four patients with cerebellar ataxias and 167 healthy controls were interviewed for risks of exposure to COVID-19, and the self-perception of the pandemics' impact on the disease progression and on the mental health. All subjects underwent the Hospital Anxiety and Depression Scale. The patients reported low exposition to SARS-CoV2 infection, but one case was confirmed with a mild COVID-19. Overall, depressive and anxiety symptoms were significantly and marginally increased in patients, respectively, with higher scores in cases with severe and moderate ataxia. Positive patient's impression of psychopathological changes was associated to increased age, age at onset, and anxiety. Sixty-seven patients had a positive self-perception of ataxia progression, which was mainly influenced by higher anxiety scores but not by the adherence to at-home exercise programs. However, the practice of physical exercise was related with lower depression and anxiety scores, but this therapeutical effect was not significantly influenced by the disease stage. We demonstrated the negative effect of the COVID-19 pandemic on the mental and motor deficits in Cuban patients with cerebellar ataxias and the positive effect of the at-home physical exercise programs on their mental well-being. These findings give rationales to develop tele-medicine approaches to minimize these health impacts and to study the long-term effects of such sequelae and accordingly define their treatments.

Variants in the SK2 channel gene (KCNN2) lead to dominant neurodevelopmental movement disorders.

KCNN2 encodes the small conductance calcium-activated potassium channel 2 (SK2). Rodent models with spontaneous Kcnn2 mutations show abnormal gait and locomotor activity, tremor and memory deficits, but human disorders related to KCNN2 variants are largely unknown. Using exome sequencing, we identified a de novo KCNN2 frameshift deletion in a patient with learning disabilities, cerebellar ataxia and white matter abnormalities on brain MRI. This discovery prompted us to collect data from nine additional patients with de novo KCNN2 variants (one nonsense, one splice site, six missense variants and one in-frame deletion) and one family with a missense variant inherited from the affected mother. We investigated the functional impact of six selected variants on SK2 channel function using the patch-clamp technique. All variants tested but one, which was reclassified to uncertain significance, led to a loss-of-function of SK2 channels. Patients with KCNN2 variants had motor and language developmental delay, intellectual disability often associated with early-onset movement disorders comprising cerebellar ataxia and/or extrapyramidal symptoms. Altogether, our findings provide evidence that heterozygous variants, likely causing a haploinsufficiency of the KCNN2 gene, lead to novel autosomal dominant neurodevelopmental movement disorders mirroring phenotypes previously described in rodents.

Hericium erinaceus potentially rescues behavioural motor deficits through ERK-CREB-PSD95 neuroprotective mechanisms in rat model of 3-acetylpyridine-induced cerebellar ataxia.

Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although several studies have demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), its mechanisms in cerebellar ataxia remain largely unknown. Here, we investigated the neuroprotective effects of H.E. treatment in an animal model of 3-acetylpyridine (3-AP)-induced cerebellar ataxia. Animals administered 3-AP injection exhibited remarkable impairments in motor coordination and balance. There were no significant effects of 25 mg/kg H.E. on the 3-AP treatment group compared to the 3-AP saline group. Interestingly, there was also no significant difference in the 3-AP treatment group compared to the non-3-AP control, indicating a potential rescue of motor deficits. Our results revealed that 25 mg/kg H.E. normalised the neuroplasticity-related gene expression to the level of non-3-AP control. These findings were further supported by increased protein expressions of pERK1/2-pCREB-PSD95 as well as neuroprotective effects on cerebellar Purkinje cells in the 3-AP treatment group compared to the 3-AP saline group. In conclusion, our findings suggest that H.E. potentially rescued behavioural motor deficits through the neuroprotective mechanisms of ERK-CREB-PSD95 in an animal model of 3-AP-induced cerebellar ataxia.

Dysphagia Affecting Quality of Life in Cerebellar Ataxia-a Large Survey.

Dysphagia is a common symptom in neurodegenerative disorders and is generally associated with increased mortality. In the clinical care setting of ataxia patients, no systematical and standardized assessment of dysphagia is employed. Its impact on patients' health-related quality of life is not well understood. To assess the impact of dysphagia in ataxia patients on diet, body weight, and health-related quality of life. We conducted a large survey using self-reported questionnaires for swallowing-related quality of life (Swal-QOL) and a food frequency list in combination with retrospective clinical data of 119 patients with cerebellar ataxia treated in the neurological outpatient clinic of a large German university hospital. Seventeen percent of ataxia patients suffered from dysphagia based on the Swal-QOL score. Less than 1% of all patients reported dysphagia as one of their most disabling symptoms. Dysphagia was associated with unintentional weight loss (p = 0.02) and reduced health-related quality of life (p = 0.01) but did not affect individual nutritional habits (p > 0.05; Chi-squared test). Dysphagia is a relevant symptom in cerebellar ataxia. A systematic screening for dysphagia in patients with cerebellar ataxia would be desirable to enable early diagnosis and treatment.

The Working Life of People with Degenerative Cerebellar Ataxia.

The aim of the present study was to characterize and analyze the most important individual and organizational variables associated with job accommodation in subjects with degenerative cerebellar ataxia by administering a series of international and validated work activity-related scales. Twenty-four workers (W) and 58 non-workers (NW) were recruited: 34 with autosomal dominant ataxia and 48 with autosomal recessive ataxia (27 with Friedreich ataxia and 21 with sporadic adult-onset ataxia of unknown etiology). The severity of ataxia was rated using the Scale for the Assessment and Rating of Ataxia. Our results showed that the ataxic W were predominantly middle-aged (41-50 years), high school graduate, and married men with a permanent work contract, who had been working for more than 7 years. The W with ataxia exhibited a good level of residual working capacity, irrespective of gender, age range, and duration of the disease, and they were observed to have a low or average-to-low job stress-related risk. Supporting patients with ataxia to find an appropriate job is an important priority because about 78% of NW search for a job and W and NW have the same potential work abilities (no relevant differences were found in terms of disease characteristics, gender, and work resilience). In this view, introducing NW to work-life may have a potential rehabilitative aspect. Findings of this study highlight that equal job opportunities for subjects affected by cerebellar ataxia are recommended.

Cognitive and Psychiatric Evaluation in SYNE1 Ataxia.

SYNE1 gene mutations were identified as a cause of late-onset pure cerebellar syndrome. Non-cerebellar symptoms, including cognitive impairment, were already described in this condition. The aim of this study was to perform a detailed cognitive and psychiatric description of patients with SYNE1 gene mutations. We performed neuropsychological and psychiatric evaluations of six patients with SYNE1 ataxia and compared their performance with 18 normal controls paired for age and education level. SYNE1 ataxia patients present cognitive dysfunction, characterized by impairment in attention and processing speed domains. Otherwise, the psychiatric assessment reported low levels of overall behavioral symptoms with only some minor anxiety-related complaints. Although this is a small sample of patients, these results suggest that SYNE1 ataxia patients may represent a model to investigate effects of cerebellar degeneration in higher hierarchical cognitive functions. For further studies, abstract thinking impairment in schizophrenia may be related to dysfunction in cerebellum pathways.

15-White Dots APP-Coo-Test: a reliable touch-screen application for assessing upper limb movement impairment in patients with cerebellar ataxias.

BACKGROUND: The use of objective measurements is essential to assess disease progression and to evaluate the effectiveness of rehabilitation protocols and clinical treatments. AIM: The purpose of this study was to develop a touch-screen application, that we named 15-White Dots APP-Coo-Test (15-WDACT), able to carry out quantitative and objective measurements of the rapid and coordinated upper limb movements, typically impaired in patients with cerebellar ataxias (CA). METHODS: A total of 87 CA patients and 170 healthy subjects participated in this study. The subject was asked to touch with their index finger a white dot, appearing consecutively and randomly on the screen at different positions, for a total of 15 dots per session. The score is the execution time of a single session. RESULTS: 15-WDACT measurements have highly correlated with the scores obtained with the Scale for the Assessment and Rating of Ataxia (SARA), with the Composite Cerebellar Functional Severity (CCFS) and with the measurements obtained using two validated evaluating systems, i.e., the Nine Hole Pegboard test (9HPT) and the Click Test. We also observed high internal consistency and an excellent intra-rater and test-retest reliability. We found a small Standard Error of Measurement (SEM) and an excellent Minimal Detectable Change (MDC), indicating that even small variations in the 15-WDACT measurements are to be associated with real changes in performance. CONCLUSIONS: We have concluded that 15-WDACT is an easy, fast and reliable tool to assess the severity of the upper limb ataxia in patients with CA.

Effects of dance-based movement therapy on balance, gait, and psychological functions in severe cerebellar ataxia: A case study.

Purpose: Individuals in the later stages of cerebellar ataxia usually experience serious balance and immobility problems. Currently, there is a lack of adequate rehabilitative programs for individuals with severe cerebellar ataxia that can help improve ataxia-related motor impairment. The purpose of the present study was to explore the potential physiotherapeutic benefits of partnered dance on balance, motor functions, and psychological well-being in an individual demonstrating severe cerebellar ataxia symptoms. Methods: The individual was a 39-year-old male diagnosed with cerebellar atrophy. He had the disease for more than 15 years prior to the study. The individual attended 24 intervention sessions over an 8-week period of dance-based movement training that aimed to improve his balance and postural stability by facilitating the perception and control of static and dynamic balance movements and body alignment. Results: The individual demonstrated improvements in independent standing balance, gait characteristics, and functional mobility. In addition, improvements in self-reported depression and quality of life scores were observed after completion of the intervention. Conclusion: Although interpreting the findings of this study is limited to a single participant, partnered dance could be a suitable alternative physiotherapeutic intervention method for people with severely impaired mobility due to cerebellar dysfunction.

Visuospatial Organization and Recall in Cerebellar Ataxia.

Poor visuospatial skills can disrupt activities of daily living. The cerebellum has been implicated in visuospatial processing, and patients with cerebellar injury often exhibit poor visuospatial skills, as measured by impaired memory for the figure within the Rey-Osterrieth complex figure task (ROCF). Visuospatial skills are an inherent aspect of the ROCF; however, figure organization (i.e., the order in which the figure is reconstructed by the participant) can influence recall ability. The objective of this study was to examine and compare visuospatial and organization skills in people with cerebellar ataxia. We administered the ROCF to patients diagnosed with cerebellar ataxia and healthy controls. The cerebellar ataxia group included patients that carried a diagnosis of spinocerebellar ataxia (any subtype), autosomal dominant cerebellar ataxia, or cerebellar ataxia with unknown etiology. Primary outcome measures were organization and recall performance on the ROCF, with supplemental information derived from cognitive tests of visuospatial perception, working memory, processing speed, and motor function. Cerebellar ataxia patients revealed impaired figure organization relative to that of controls. Figure copy was impaired in the patients, but their subsequent recall performance was normal, suggesting compensation from initial organization and copying strategies. In controls, figure organization predicted recall performance, but this relationship was not observed in the patients. Instead, processing speed predicted patients' recall accuracy. Supplemental tasks indicated that visual perception was intact in the cerebellar ataxia group and that performance deficits were more closely tied to organization strategies than with visuospatial skills.

Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) associated with progressive cognitive and behavioral deterioration.

OBJECTIVE: Autosomal dominant cerebellar ataxia with deafness and narcolepsy (ADCA-DN) is an emerging syndrome caused by mutations in the C-terminus end of the TS domain of the DNMT1 gene. ADCA-DN is also associated with sensorimotor polyneuropathy, extrapyramidal, and dysautonomic signs, as well as dementia. Little has been reported about the progressive cognitive impairment associated with ADCA-DN. Our objective is to provide a detailed characterization of the cognitive profile of ADCA-DN. METHOD: Three members of a kindred with ADCA-DN underwent comprehensive neuropsychological testing and neuroimaging. RESULTS: At baseline, 2 individuals demonstrated cognitive profiles with executive difficulties in some areas consistent with frontal-system dysfunction behaviorally and on standardized testing. The third individual was further in the disease course and exhibited more globally impaired cognition consistent with a diagnosis of dementia. CONCLUSIONS: This family demonstrated progressive neurodegeneration beginning with isolated areas of executive dysfunction and leading to globally impaired cognition and dementia. Cognitive decline occurred in parallel with neurological deterioration. The cognitive profile is similar to case reports of other individuals with an allelic neurological phenotype, Hereditary Sensory Autonomic Neuropathy 1E, also caused by DNMT1 mutations. (PsycINFO Database Record

Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke.

Cerebellar lesions can cause motor deficits and/or the cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome). We used voxel-based lesion-symptom mapping to test the hypothesis that the cerebellar motor syndrome results from anterior lobe damage whereas lesions in the posterolateral cerebellum produce the CCAS. Eighteen patients with isolated cerebellar stroke (13 males, 5 females; 20-66 years old) were evaluated using measures of ataxia and neurocognitive ability. Patients showed a wide range of motor and cognitive performance, from normal to severely impaired; individual deficits varied according to lesion location within the cerebellum. Patients with damage to cerebellar lobules III-VI had worse ataxia scores: as predicted, the cerebellar motor syndrome resulted from lesions involving the anterior cerebellum. Poorer performance on fine motor tasks was associated primarily with strokes affecting the anterior lobe extending into lobule VI, with right-handed finger tapping and peg-placement associated with damage to the right cerebellum, and left-handed finger tapping associated with left cerebellar damage. Patients with the CCAS in the absence of cerebellar motor syndrome had damage to posterior lobe regions, with lesions leading to significantly poorer scores on language (e.g. right Crus I and II extending through IX), spatial (bilateral Crus I, Crus II, and right lobule VIII), and executive function measures (lobules VII-VIII). These data reveal clinically significant functional regions underpinning movement and cognition in the cerebellum, with a broad anterior-posterior distinction. Motor and cognitive outcomes following cerebellar damage appear to reflect the disruption of different cerebro-cerebellar motor and cognitive loops.

Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity.

The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions. Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans. Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates, functions that are likely conserved across all domains of life. Collectively, our results lend insight into the molecular activities of the ancient UbiB family and elucidate the biochemical underpinnings of a human disease.

Rehabilitation of ataxic gait following cerebellar lesions: Applying theory to practice.

Damage to the cerebellum can result in ataxic gait, which affects the ability to walk safely and independently. Physiotherapy is the main treatment for ataxic gait, but there is limited high-quality evidence for interventions used. This review explores the neural mechanisms of the symptoms of ataxic gait, by discussing the cerebellum's role in coordination, motor learning, anticipatory postural control, balance reactions and adapting gait to meet environmental demands. It discusses mechanisms that occur at cellular level throughout the whole cerebellum and then focuses on difficulties that arise from damage to specific lobes of the cerebellum. Physiotherapy-based interventions, such as balance training, developing postural control, specific gait training, and use of compensatory orthotics and aids, are discussed in relation to the theoretical understanding of cerebellar functioning. Consideration is given to difficulties of using trial-and-error-based learning, which will impact on teaching techniques and strategies used during gait rehabilitation. This theoretical understanding will aid physiotherapists to target their assessment, treatment, management, and goal setting with individuals who have difficulties with ataxic gait following a cerebellar lesion.

Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory.

Mutations in Amyloid ß Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers.

Modulation of error-sensitivity during a prism adaptation task in people with cerebellar degeneration.

Cerebellar damage can profoundly impair human motor adaptation. For example, if reaching movements are perturbed abruptly, cerebellar damage impairs the ability to learn from the perturbation-induced errors. Interestingly, if the perturbation is imposed gradually over many trials, people with cerebellar damage may exhibit improved adaptation. However, this result is controversial, since the differential effects of gradual vs. abrupt protocols have not been observed in all studies. To examine this question, we recruited patients with pure cerebellar ataxia due to cerebellar cortical atrophy (n = 13) and asked them to reach to a target while viewing the scene through wedge prisms. The prisms were computer controlled, making it possible to impose the full perturbation abruptly in one trial, or build up the perturbation gradually over many trials. To control visual feedback, we employed shutter glasses that removed visual feedback during the reach, allowing us to measure trial-by-trial learning from error (termed error-sensitivity), and trial-by-trial decay of motor memory (termed forgetting). We found that the patients benefited significantly from the gradual protocol, improving their performance with respect to the abrupt protocol by exhibiting smaller errors during the exposure block, and producing larger aftereffects during the postexposure block. Trial-by-trial analysis suggested that this improvement was due to increased error-sensitivity in the gradual protocol. Therefore, cerebellar patients exhibited an improved ability to learn from error if they experienced those errors gradually. This improvement coincided with increased error-sensitivity and was present in both groups of subjects, suggesting that control of error-sensitivity may be spared despite cerebellar damage.

Natural history of multiple system atrophy in the USA: a prospective cohort study.

BACKGROUND: Multiple system atrophy is a rare, fatal neurodegenerative disorder with symptoms of autonomic failure plus parkinsonism, cerebellar ataxia, or both. We report results of the first prospective natural history study of multiple system atrophy in the USA, and the effects of phenotype and autonomic failure on prognosis. METHODS: We recruited participants with probable multiple system atrophy-of either the parkinsonism subtype (MSA-P) or the cerebellar ataxia subtype (MSA-C)-at 12 neurology centres in the USA specialising in movement or autonomic disorders. We followed up patients every 6 months for 5 years and assessed them with the Unified Multiple System Atrophy Rating Scale part I (UMSARS I; a functional score of symptoms and ability to undertake activities of daily living), UMSARS II (neurological motor evaluation), and the Composite Autonomic Symptoms Scale (COMPASS)-select (a measure of autonomic symptoms and autonomic functional status). We assessed potential predictors of outcome. We used Cox proportional hazards models to calculate univariate hazard ratios for shorter survival using age at disease onset as a continuous variable and sex, clinical phenotype, and early development of neurological and autonomic manifestations as categorical variables. FINDINGS: We recruited 175 participants. Mean age at study entry was 63·4 years (SD 8·6). Median survival from symptom onset was 9·8 years (95% CI 8·8-10·7) and median survival from enrolment was 1·8 years (0·9-2·7). Participants with severe symptomatic autonomic failure (symptomatic orthostatic hypotension, urinary incontinence, or both) at diagnosis (n=62) had a worse prognosis than those without severe disease (n=113; median survival 8·0 years, 95% CI 6·5-9·5 vs 10·3 years, 9·3-11·4; p=0·021). At baseline, patients with MSA-P (n=126) and MSA-C (n=49) had much the same symptoms and functional status: mean UMSARS I 25·2 (SD 8·08) versus 24·6 (8·34; p=0·835); mean UMSARS II 26·4 (8·8) versus 25·4 (10·5; p=0·764); COMPASS-select 43·5 (18·7) versus 42·8 (19·6; p=0·835). Progression over 5 years, assessed by change in UMSARS I, UMSARS II, and COMPASS-select, was modest. INTERPRETATION: Probable multiple system atrophy is a late-stage disease with short survival. The natural histories of MSA-P and MSA-C are similar and severe symptomatic autonomic failure at diagnosis is associated with worse prognosis. FUNDING: US National Institutes of Health, Mayo Clinic, and Kathy Shih Memorial Foundation.

Systematic review of the psychometric properties of balance measures for cerebellar ataxia.

OBJECTIVE: To review systematically the psychometric properties of balance measures for use in people with cerebellar ataxia. DATA SOURCES: Medline, AMED, CINAHL, Web of Science and EMBASE were searched between 1946 and April 2014. REVIEW METHODS: Two reviewers independently searched data sources. Cerebellar-specific and generic measures of balance were considered. Included studies tested psychometric properties of balance measures in people with cerebellar ataxia of any cause. Quality of reported studies was rated using the Consensus Based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. RESULTS: Twenty-one articles across which 16 measures had been tested were included for review. Using the COSMIN, quality of methodology in studies investigating psychometric properties of generic balance measures (n=10) was rated predominantly as 'poor'. Furthermore, responsiveness has not been tested for any generic measures in this population. The quality of studies investigating psychometric properties of balance sub-components of the cerebellar-specific measures (n=6) ranged from 'poor' to 'excellent'; however, Minimally Clinically Important Difference has not been determined for these cerebellar-specific measures. CONCLUSION: The Posture and Gait (PG) sub-component of the International Cooperative Ataxia Rating Scale (ICARS) demonstrates the most robust psychometric properties with acceptable clinical utility.

Monitoring mood states in everyday life: a new device for patients with cerebellar ataxia.

Thirty patients with cerebellar ataxia and 40 healthy volunteers underwent 7 days of mood monitoring using a new device requiring a low motor load. Its convergent validity and compliance were tested. The measurements resulted consistent with validated scale scores. Patients׳ motor impairment did not affect the compliance.

The effects of sleep dysfunction on cognition, affect, and quality of life in individuals with cerebellar ataxia.

STUDY OBJECTIVE: Cerebellar ataxia comprises a group of debilitating diseases that are the result of progressive cerebellar degeneration. Recent studies suggest that, like other neurodegenerative diseases, sleep impairments are common in cerebellar ataxia. In light of the role of sleep in mood regulation and cognition, we sought to assess interactions between sleep, cognition, and affect in individuals with cerebellar ataxia. METHODS: A survey of 176 individuals with cerebellar ataxia was conducted. The battery of instruments included a modified International Cooperative Ataxia Rating Scale, Pittsburgh Sleep Quality Index, Restless Leg Syndrome Questionnaire, REM Behavior Disorder Questionnaire, Beck Depression Inventory, Epworth Sleepiness Scale, and a Composite Cognitive Questionnaire. RESULTS: Fifty-one percent of individuals indicated significant sleep disturbances on the Pittsburgh Sleep Quality Index, 73% of participants had two or more symptoms of restless leg syndrome, and 88% had two or more symptoms of REM behavior disorder. Ataxia severity, based on the modified International Cooperative Ataxia Rating Scale, predicted scores on the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale and REM Behavior Disorder Questionnaire. Median split analyses revealed that cognitive function appeared to be reduced and depressive symptoms were greater for those individuals with poor subjective sleep quality and severe RLS. Importantly, sleep appears to play a mediatory role between disease severity and depressive symptoms. CONCLUSIONS: These results suggest that disturbed sleep may have detrimental effects on cognition and affect in individuals with cerebellar ataxia. While objective measures are needed, such results suggest that treating sleep deficits in these individuals may improve cognitive and mental health as well as overall quality of life.