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Background Objective Methods Results Conclusions Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative disorder for which there are currently no disease‐modifying treatments. Recent trials of potential therapies had durations of 12 months, which may be insufficient because of nonrandom missingness due to death. Longer durations, incorporating PSP Rating Scale and survival, can reduce the potential for type II error. Selecting efficacy measures more sensitive to disease modification may facilitate identification of treatment effect.The objective of this study was to evaluate the simulated phase 3 PSP trial assessing the effect of disease‐modifying intervention on a novel combined primary endpoint comprising function (PSP Rating Scale) and survival, the Combined Assessment of Function and Survival (CAFS), and to determine operating characteristics of the CAFS.To simulate PSP progression in the trial population, we developed models of PSP Rating Scale and survival using data from published clinical studies. These models were used to define operating characteristics of the CAFS for use in a phase 3 trial.The sample size determined (N = 384; 1:1 randomization) would provide >80% power to detect significant treatment effects on the CAFS compared with placebo. The CAFS provides good operating characteristics and increased power to detect moderate treatment effects on the PSP Rating Scale. We propose a trial design allowing potential detection of treatment effects at a preplanned interim analysis after participants complete 12 months of treatment, with assessment of effects of treatment (≤24 months) on survival.Use of the CAFS could provide a comprehensive and robust estimate of the clinical benefit of future therapies. © 2024 UCB. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

In the last two decades, much neuroscientific research has been done on the pathomechanisms of catatonia. However, catatonic symptoms have mainly been assessed with clinical rating scales based on observer ratings. Although catatonia is often associated with strong affective reactions, the subjective domain of catatonia has simply been neglected in scientific research. The main objective of this study was to modify, extend and translate the original German version of the Northoff Scale for Subjective Experience in Catatonia (NSSC) and to examine its preliminary validity and reliability. Data were collected from 28 patients diagnosed with catatonia associated with another mental disorder (6A40) according to ICD-11. Descriptive statistics, correlation coefficients, internal consistency and principal component analysis were employed to address preliminary validity and reliability of the NSSC. NSSC showed high internal consistency (Cronbach's alpha = 0.92). NSSC total scores were significantly associated with Northoff Catatonia Rating Scale (r = 0.50, p <.01) and Bush Francis Catatonia Rating Scale (r = 0.41, p <.05) thus supporting its concurrent validity. There was no significant association between NSSC total score and Positive and Negative Symptoms Scale total (r = 0.26, p =.09), Brief Psychiatric Rating Scale (r = 0.29, p =.07) and GAF (r = 0.03, p =.43) scores. The extended version of the NSSC consists of 26 items and was developed to assess the subjective experience of catatonia patients. Preliminary validation of the NSSC revealed good psychometric properties. NSSC is a useful tool for everyday clinical work to assess the subjective experience of catatonia patients. [ABSTRACT FROM AUTHOR]

A comprehensive assessment of catatonic symptoms is decisive for diagnosis, neuronal correlates, and evaluation of treatment response and prognosis of catatonia. Studies conducted so far used different cut-off criteria and clinical rating scales to assess catatonia. Therefore, the main aim of this study was to examine the frequency and distribution of diagnostic criteria and clinical rating scales for assessing catatonia that were used in scientific studies so far. We conducted a systematic review using PubMed searching for articles using catatonia rating scales/criteria published from January 1st 1952 (introduction of catatonic schizophrenia to first edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM]) up to December 5th, 2022. 1928 articles were considered for analysis. 1762 (91,39 %) studies used one and 166 (8,61 %) used ≥2 definitions of catatonia. However, 979 (50,7 %) articles did not report any systematic assessment of catatonia. As for clinical criteria, DSM criteria were used by the majority of studies (n = 290; 14.0 %), followed by International Classification of Diseases (ICD) criteria (n = 61; 2.9 %). The Bush-Francis Catatonia Rating Scale (BFCRS) was found to be by far the most frequently utilized scale (n = 464; 22.4 % in the respective years), followed by Northoff Catatonia Rating Scale (NCRS) (n = 31; 1.5 % in the respective years). DSM and ICD criteria as well as BFCRS and NCRS were most frequently utilized and can therefore be recommended as valid instruments for the assessment of catatonia symptomatology. [ABSTRACT FROM AUTHOR]

Purpose: Despite the availability of the Unified Multiple System Atrophy (MSA) Rating Scale (UMSARS) for almost two decades, studies still use scales developed for Parkinson's disease (PD) or ataxia (ATX). Our aim was to evaluate the use of UMSARS (part II, motor) compared to other motor rating scales in patients with MSA. Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant literature search was conducted concerning studies of patients with MSA, reporting motor assessment with clinical rating scales, and focusing on the frequency of UMSARS use. Results: We included 261 articles, of which 42.9% did not use UMSARS, but rather scales for PD (59.8%), ATX (24.1%), or both (14.3%). Although UMSARS use increased with time, misuse of PD and ATX scales persists, with no evidence of a decremental trend. Conclusions: Although higher in observational studies, the misuse of PD and ATX-related scales in MSA patients persists in prospective (planned) trials. Reasons for that must be addressed. [ABSTRACT FROM AUTHOR]

Background: Ordinal scales based on qualitative observation are the mainstay in the clinical assessment of tremor, but are limited by inter-rater reliability, measurement precision, range, and ceiling effects. Quantitative tremor evaluation is well-developed in research, but clinical application has lagged, in part due to cumbersome mathematical application and lack of established standards. Objectives: To develop a novel method for evaluating tremor that integrates a standardized clinical exam, wrist-watch accelerometers, and a software framework for data analysis that does not require advanced mathematical or computing skills. The utility of the method was tested in a sequential cohort of patients with predominant postural and action tremor presenting to a specialized surgical clinic with the presumptive diagnosis of Essential Tremor (ET). Methods: Wristwatch accelerometry was integrated with a standardized clinical exam. A MATLAB application was developed for automated data analysis and graphical representation of tremor. Measures from the power spectrum of acceleration of tremor in different upper limb postures were derived in 25 consecutive patients. The linear results from accelerometry were correlated with the commonly used non-linear Clinical Rating Scale for Tremor (CRST). Results: The acceleration power spectrum was reliably produced in all consecutive patients. Tremor frequency was stable in different postures and across patients. Both total and peak power of acceleration during postural conditions correlated well with the CRST. The standardized clinical examination with integrated accelerometry measures was therefore effective at characterizing tremor in a population with predominant postural and action tremor. The protocol is also illustrated on repeated measures in an ET patient who underwent Magnetic Resonance-Guided Focused Ultrasound thalamotomy. Conclusion: Quantitative assessment of tremor as a continuous variable using wristwatch accelerometry is readily applicable as a clinical tool when integrated with a standardized clinical exam and a user-friendly software framework for analysis. The method is validated for patients with predominant postural and action tremor, and can be adopted for characterizing tremor of different etiologies with dissemination in a wide variety of clinical and research contexts in ageing populations. [ABSTRACT FROM AUTHOR]

BackgroundOrdinal scales based on qualitative observation are the mainstay in the clinical assessment of tremor, but are limited by inter-rater reliability, measurement precision, range, and ceiling effects. Quantitative tremor evaluation is well-developed in research, but clinical application has lagged, in part due to cumbersome mathematical application and lack of established standards.ObjectivesTo develop a novel method for evaluating tremor that integrates a standardized clinical exam, wrist-watch accelerometers, and a software framework for data analysis that does not require advanced mathematical or computing skills. The utility of the method was tested in a sequential cohort of patients with predominant postural and action tremor presenting to a specialized surgical clinic with the presumptive diagnosis of Essential Tremor (ET).MethodsWristwatch accelerometry was integrated with a standardized clinical exam. A MATLAB application was developed for automated data analysis and graphical representation of tremor. Measures from the power spectrum of acceleration of tremor in different upper limb postures were derived in 25 consecutive patients. The linear results from accelerometry were correlated with the commonly used non-linear Clinical Rating Scale for Tremor (CRST).ResultsThe acceleration power spectrum was reliably produced in all consecutive patients. Tremor frequency was stable in different postures and across patients. Both total and peak power of acceleration during postural conditions correlated well with the CRST. The standardized clinical examination with integrated accelerometry measures was therefore effective at characterizing tremor in a population with predominant postural and action tremor. The protocol is also illustrated on repeated measures in an ET patient who underwent Magnetic Resonance-Guided Focused Ultrasound thalamotomy.ConclusionQuantitative assessment of tremor as a continuous variable using wristwatch accelerometry is readily applicable as a clinical tool when integrated with a standardized clinical exam and a user-friendly software framework for analysis. The method is validated for patients with predominant postural and action tremor, and can be adopted for characterizing tremor of different etiologies with dissemination in a wide variety of clinical and research contexts in ageing populations.

Background: Niemann-Pick disease, type C1 (NPC1) is a rare neurodegenerative genetic disorder characterized by impaired intracellular transport of cholesterol and other lipids. The Niemann-Pick Disease, type C1 Severity Scale (NPC-SS) was developed to quantify neurological progression of NPC; it is used to monitor the natural history of disease progression and assess response to treatment. The objective of the study was to examine the interrater reliability of the NPC-SS in a phase 2/3 trial.Methods: Study data were from a multicenter, prospective, randomized, double-blind trial of adrabetadex in 56 subjects with NPC1. Clinical data recorded at each study site were distributed to two independent blinded central raters to generate a severity score. A composite four-item score was utilized as the primary clinical study end point, whereas a five-item focused score has been utilized in other NPC1 trials. Interrater reliability was assessed using two-way mixed models for instrument stability, Cohen kappa, weighted kappa, and percent agreement for the four- and five-item scores.Results: The frequency distribution and mean (S.D.) of the NPC-SS domain assessments by the raters were almost identical. Evaluation at the patient visit level showed wide variability between visits; however, weighted kappa calculation provided a lower variability between visits. The average kappa coefficients ranged between 0.69 and 0.89, indicating good to very good agreement between raters.Conclusions: These results support the NPC-SS, including derived four- and five-item composite scores, as reliable measures for use in a clinical trial setting. [ABSTRACT FROM AUTHOR]

Background: This review highlights the recent scientific advances that have enabled rational design of novel clinical trials for pantothenate kinase‐associated neurodegeneration (PKAN), a rare autosomal recessive neurogenetic disorder associated with progressive neurodegenerative changes and functional impairment. PKAN is caused by genetic variants in the PANK2 gene that result in dysfunction in pantothenate kinase 2 (PANK2) enzyme activity, with consequent disruption of coenzyme A (CoA) synthesis, and subsequent accumulation of brain iron. The clinical phenotype is varied and may include dystonia, rigidity, bradykinesia, postural instability, spasticity, loss of ambulation and ability to communicate, feeding difficulties, psychiatric issues, and cognitive and visual impairment. There are several symptom‐targeted treatments, but these do not provide sustained benefit as the disorder progresses. Objectives: A detailed understanding of the molecular and biochemical pathogenesis of PKAN has opened the door for the design of novel rationally designed therapeutics that target the underlying mechanisms. Methods: Two large double‐blind phase 3 clinical trials have been completed for deferiprone (an iron chelation treatment) and fosmetpantotenate (precursor replacement therapy). A pilot open‐label trial of pantethine as a potential precursor replacement strategy has also been completed, and a trial of 4‐phosphopantetheine has begun enrollment. Several other compounds have been evaluated in pre‐clinical studies, and additional clinical trials may be anticipated. Conclusions: Experience with these trials has encouraged a critical evaluation of optimal trial designs, as well as the development of PKAN‐specific measures to monitor outcomes. PKAN provides a valuable example for understanding targeted drug development and clinical trial design for rare disorders. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration.Methods: In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol. The motor examination was filmed, allowing 3 independent specialists in movement disorders to analyze 28 patients for interrater reliability assessment. The scale included 34 items (maximal score, 135) encompassing 6 subscales for cognition, behavior, disability, parkinsonism, dystonia, and other neurological signs.Results: Forty-seven genetically confirmed patients (30 ± 17 years; range, 6-77 years) were examined with the scale (mean score, 62 ± 21; range, 20-106). Dystonia with prominent cranial involvement and atypical parkinsonian features were present in all patients. Other common signs were cognitive impairment, psychiatric features, and slow and hypometric saccades. Dystonia, parkinsonism, and other neurological features had a moderate to strong correlation with disability. The scale showed good internal consistency for the total scale (Cronbach's α = 0.87). On interrater analysis, weighted kappa values (0.30-0.93) showed substantial or excellent agreement in 85% of the items. The scale also discriminated a subgroup of homozygous c.1583C>T patients with lower scores, supporting construct validity for the scale.Conclusions: The proposed scale seems to be a reliable and valid instrument for the assessment of pediatric and adult patients with pantothenate kinase-associated neurodegeneration. Additional validation studies with a larger sample size will be required to confirm the present results and to complete the scale validation testing. © 2017 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Patients with Alzheimer's disease (AD) manifest various impairments in eating behavior. However, few previous studies have directly investigated the gustatory function of AD patients, and results have been inconsistent.Methods: Thirty-two AD patients (Clinical Dementia Rating (CDR) 0.5/1/2, respectively 11/15/6 patients) and 22 normal control participants were examined to measure detection and recognition thresholds of the four elemental tastes (sweet, salty, sour, and bitter), and their ability to discriminate between tastes. Effects of demographic and clinical factors (age, sex, histories of alcohol and tobacco consumption, and CDR grade) on gustatory threshold were examined using ordinal logistic regression analysis. Performance was compared between AD and control groups.Results: Total threshold values (the sum of threshold grades for the four tastes) for detection and recognition of tastes were significantly higher in the AD group. Detection thresholds for sweet, salty, and bitter, and recognition thresholds for sweet and sour, were also significantly higher in the AD group. Ordinal logistic regression analysis revealed that CDR grade was the only factor that significantly affected both total threshold values. Regarding taste discrimination, there were no significant differences between the AD group and control group.Conclusions: These findings suggest that progression of dementia severity accompanies gustatory decline. Although it seemingly paradoxical, weight loss and preference for sweet tastes are frequently, often simultaneously, observed in AD. Gustatory dysfunction may be partially involved in these symptoms. Thus, the nutritional care of patients with AD could be improved by making the taste of meals stronger, while controlling calorie and mineral intake. [ABSTRACT FROM AUTHOR]

Although upper-limb movement impairments are common, the primary tools for assessing and tracking impairments in clinical settings are limited. Markerless motion capture (MMC) technology has the potential to provide a large amount of quantitative, objective movement data in routine clinical use. Many past studies have focused on whether MMC are sufficiently accurate. However, another necessary step is to create meaningful clinical tests that can be administered via MMC in a robust manner. Four conventional upper-limb motor tests common in clinical assessments (visually guided movement, finger tapping, postural tremor, and reaction time) were modified so they can be administered via a particular MMC sensor, the Leap Motion Controller (LMC). In this proof-of-concept study, we administered these modified tests to 100 healthy subjects and present here the successes and challenges we encountered. Subjects generally found the LMC and the graphical user interfaces of the tests easy to use. The LMC recorded movement with sufficiently high sampling rate (>106 samples/s), and the rate of LMC malfunctions (mainly jumps in time or space) was low, so only 1.9% of data was discarded. However, administration of the tests also revealed some significant weaknesses. The visually guided movement test was easily implemented with the LMC; the modified reaction time test worked reasonably well with the LMC but is likely more easily implemented with other existing technologies; and the modified tremor and finger tapping tests did not work well because of the limited bandwidth of the LMC. Our findings highlight the need to develop and evaluate motor tests specifically suited for MMC. The real strength of MMC may not be in replicating conventional tests but rather in administering new tests or testing conditions not possible with conventional clinical tests or other technologies., (© 2023 IOP Publishing Ltd.)

Abstract: Background: A scale for the Assessment and Rating of Ataxia (SARA) was developed for evaluation of autosomal dominant cerebellar ataxias (ADCA) and was also recommended for clinical trials of Friedreich's ataxia patients (FRDA). FRDA, unlike ADCA, is characterized as being a sensory type of ataxia for which the disease-specific Friedreich ataxia rating scale (FARS) was developed. The objective of this study was to determine whether SARA and FARS scores are associated with posturographic parameters in FRDA patients. Method: Adult patients with genetically confirmed FRDA (n =11) and ADCA (n =13) were evaluated by SARA, FARS and posturography. Results: FRDA patients' postural stability parameters, in stance with visual control, correlated with balance impairment in FARS (r =0.622; p <0.05) and SARA (r =0.735; p <0.05). Without visual control, only FARS correlated with balance impairment (r =0.732; p <0.05). Conclusion: The SARA, in FRDA patients, correlates with stance with visual control but not without visual control which emphasizes sensory ataxia. This suggests that application of the SARA in Friedreich's ataxia patients according to posturography is possible but presumably limited and FARS, although being a more time consuming scale, may have advantages over SARA in FRDA patients. [Copyright &y& Elsevier]

Sydenham chorea is a post-streptococcal, autoimmune, neuropsychiatric, movement disorder. There is no effective treatment. In a randomized study, comparison was made of the outcomes of 10 children treated with standard management alone compared to 10 who received additional intravenous immunoglobulin. The outcomes were assessed using a clinical rating scale, brain single-photon emission computed tomography, and the duration of symptomatic treatment. All three outcome measurement tools found improved outcomes in the group that received intravenous immunoglobulin. [ABSTRACT FROM AUTHOR]

Objective To examine the reliability and validity of the mCDR, a modified version of the clinical dementia rating (CDR) scale. Methods The mCDR is an informant-based, technician-administered, structured interview with multiple choice responses, which does not include objective cognitive testing. Subjects (n = 556) with no cognitive impairment (NCI), amnestic mild cognitive impairment (aMCI), and dementia were assessed with mCDR, CDR, and neuropsychological evaluation, while medial temporal atrophy (MTA) was measured on MRI scans. The mCDR and CDR were compared with respect to inter-rater reliability, validity, and ability to predict progression in cognitive diagnosis at 12 month follow-up. Results The mCDR can be administered in less than one third of the time required to administer the CDR (30 min). Inter-rater reliability (Cohen's weighted κ) was 0.86 for the mCDR and 0.56 for the CDR. Ability to distinguish between NCI, aMCI, and Dementia subjects, and correlations to memory and non-memory measures were marginally better for the CDR, in comparison to the mCDR. Correlations of mCDR and CDR scores to MTA scores did not differ. Baseline mCDR scores predicted transition from NCI to aMCI, whereas baseline CDR scores predicted transition from aMCI to Dementia. Conclusions The mCDR, as compared to the CDR, is briefer and more reliable, and is a valid measure of functional ability among subjects with normal cognition, mild cognitive impairment, and mild dementia. The mCDR should be particularly useful as a reliable and economical instrument for assessing change in functional abilities, especially in multi-center clinical trials and population studies of MCI and mild dementia. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: With the aid of assistive technology, some patients with amyotrophic lateral sclerosis (ALS) are able to live for several years past the lowest measurable level of function on the Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS-R), a widely used end-point in ALS assessment. There is a research need to monitor patient function at the end of life, particularly in the face of severe impairment or ‘locked in syndrome’. Methods: We used an online community for people with ALS (PALS) (PatientsLikeMe) to construct and pilot a number of new items to add to the ALSFRS-R scale to improve its sensitivity at lower levels of physical function in patients with advanced ALS. Results: Ten new scale items were generated by a survey of PALS with advanced disease. These were added to the existing ALSFRS-R and data was received from 326 PALS as baseline with 271 PALS (83%) completing a 1-week test-retest and 218 PALS (67%), completing a 3-month retest. Conclusions: Three new items were selected which conformed to the existing factor structure of the ALFRS-R. These relate to the ability to use fingers to manipulate devices, ability to show emotional expression in the face, and ability to get around inside the home. Real-world validation is the next step to assess the utility of the ALFRS-EX. [ABSTRACT FROM AUTHOR]

Objective – In this study, the validity of a motor task, i.e., the Global Mobility Task (GMT), was assessed in a group of Parkinson’s disease (PD) patients. Patients and Methods – Fifty-eight PD patients (mean age: 68.7 years) and 18 healthy subjects (mean age: 65.8 years) were enrolled in the study. The GMT measures the ability of an adult to roll over on the floor and stand up in five steps using two parameters: ‘Time’ and ‘Score’, i.e., the time needed and the ability to perform each step of the task. As the GMT has never been evaluated before, internal consistency and concurrent and discriminative validity were considered in assessing its characteristics in a group of PD patients at the beginning and at the end of a motor rehabilitation program. To determine whether the GMT could also quantify the extrapyramidal impairment, we compared data collected using this task with data obtained using clinical scales such as the Unified Parkinson’s Disease Rating Scale III (UPDRS part III) and Hoehn & Yahr’s score. Results – Results showed that the GMT had good consistency and inter-rater reproducibility, was closely related to clinical scales and was able to detect the amelioration of extrapyramidal symptoms at the end of the motor rehabilitation program. Conclusion – we propose the GMT as a tool for measuring impaired mobility in PD patients and for evaluating the objective effects of motor rehabilitation programs. [ABSTRACT FROM AUTHOR]

Tremor of unknown origin is detected in 10–30% of early–treated and in more than 30% late–treated phenylketonuric patients. With the aim of characterizing tremor in phenylketonuria, we carried out a systematic study in 54 patients aged 6 to 37 years. Tremor examination was done by applying the WHIGET Tremor Rating Scale and by accelerometer recording (BYOPAC System MP100WSW). Age at diet onset, IQ test results, concomitant plasma phenylalanine levels and index of dietary control were also studied. Tremor was not observed at rest in any case, but was apparent in 22 patients (40.7%) when carrying out a kinetic task. In 15 patients tremor was also evident during maintenance of a postural task at a frequency ranging between 7.5 and 12.7 Hz. Frequency of tremor was not significantly modified by loading the arms or by increasing muscle contraction. Patients with tremor had a later age at onset of phenylalanine restricted diet (p < 0.001). Other treatment–related variables did not differ between patients with and without tremor. Our results of the neurophysiological examination suggest that tremor in phenylketonuric patients is dependent on a dysfunction of central nervous system networks and may be an index of cerebral damage. [ABSTRACT FROM AUTHOR]

The article presents a clinical study in the U.S. on Progressive Supranuclear Palsy Rating Scale (PSPRS). The objective of the study is to validate the PSPRS as a quantitive measure of disability and as a clinical prognostic guide. It is concluded that the PSPRS score is a useful indicator of progressive supranuclear palsy (PSP) prognosis in clinical practice.

BACKGROUND In 2004, a group of neurologists participating in the European integrated project on spinocerebellar ataxias (EUROSCA) developed the Scale for the Assessment and Rating of Ataxia (SARA). In its final form, SARA comprised eight items: evaluation of gait (score 0-8), stance (score 0-6), sitting (score 0-4) and speech (score 0-6), and four tests assessing limb kinetic function (finger chase [score 0-4], fast alternating hand movements [score 0-4], finger-nose-finger test [score 0-4] and heel-shin test [score 0-4]). OBJECTIVE To validate the new clinical scale for the evaluation of spinocerebellar ataxia (SCA). DESIGN AND INTERVENTION SARA was validated in 119 patients (mean age 50.3±13.2 years, mean disease duration 13.3±8.3 years) with genetically confirmed progressive SCA, and a control group of 110 healthy people (mean age 47.1 ± 15.0 years). Two or three investigators independently evaluated the correlations between SARA and disease indices, such as the disease stage, by calculating Pearson's correlation coefficient r. In addition, 11 representative video recordings of patient assessments were available. Two examiners who had not been involved in the clinical assessments assigned SARA ratings on the basis of these recordings, whereas 14 examiners used a visual analogue scale (range 0-100) to assess the severity of ataxia in these 11 cases. OUTCOME MEASURES The main outcome measures were the correlations of SARA with the ataxia disease stage (extent of gait difficulty), the Barthel Index of activities of daily living and the functional assessment component of the Unified Huntington's Disease Rating Scale (UHDRS-lV). RESULTS The mean SARA score was 15.9±8.5 (range 1.5-40.0) in patients with SCA and 0.4± 1.1 (range 0-7.5) in controls; 79% of controls had a score of 0. The mean time to administer SARA was 14.2 ±7.5 minutes in patients and 7.2 ± 2.6 minutes in controls. Results obtained for 95 patients who were examined by two investigators indicated that the SARA total score had a high inter-rater reliability, with an intraclass coefficient of 0.98. Test-retest reliability (intraclass coefficient 0.90) and internal consistency (Cronbach's a 0.94) were also high. Factorial analysis showed that the concept of a single underlying factor (cerebellar ataxia) can explain all rating results. Regression analysis revealed a linear relationship between SARA ratings and global assessments using the visual analogue scale. The SARA score increased with progressing disease (P <0.001), and it was strongly correlated with scores on the Barthel Index (r= -0.80, P <0.0001) and the UHDRS-lV (r=-0.89, P<0.0001). The correlation with disease duration was weak (r=0.34, P<0.0002), but was improved in patients with one of two common genotypes, SCA1 and SCA3 (r=0.74, P<0.003 and r=0.59, P<0.002, respectively). CONCLUSION SARA is a reliable and valid measure for the severity of ataxia, and is simple to administer in clinical practice. [ABSTRACT FROM AUTHOR]