The Association of Health Locus of Control with Clinical and Psychosocial Aspects of Living with Multiple Sclerosis.

Health Locus of control (LOC) refers to one's beliefs regarding control over one's health. This study aimed to determine the relationship between LOC on clinical and psychosocial aspects associated with multiple sclerosis (MS). 5059 participants with MS completed a questionnaire pack including the Multidimensional Health Locus of Control Scale. Associations between LOC and sociodemographic (age, gender, educational level) and clinical variables (duration, disability, depression, anxiety, self-efficacy, QoL) were explored. LOC was found to be significantly associated with all of the clinical variables and age, but not gender or educational level. When controlling for level of disability, Chance (CLOC) was associated with higher self-efficacy, lower anxiety and higher QoL than Powerful Others (PLOC), while Internal (ILOC) had no association. The proportion with ILOC preference was lower in increased disability. In MS, believing that health is controlled mainly by chance confers the most benefit with regard to quality of life. There is prima-facie evidence that LOC preference changes with MS progression, in a pattern that is protective against psychological distress.

The WHOQOL-BREF: a modern psychometric evaluation of its internal construct validity in people with multiple sclerosis.

PURPOSE: Symptoms of Multiple Sclerosis (MS) differentially impact upon quality of life (QoL) and a comprehensive measure is required for use in observational and interventional studies. This study examines the abbreviated World Health Organisation Quality of Life tool (WHOQOL-BREF) which was designed to be used as a broad measure of QoL across different cultures and diseases. METHODS: Data were collected from 3186 subjects as part of the TONiC study in MS and was examined with a systematic, iterative approach using Rasch analysis to investigate the internal construct validity of the WHOQOL-BREF. RESULTS: Mean age was 49.8 years (SD 11.8), disease duration was 11.2 years (SD 9.6) and 73.2% were female. Subjects represented all stages of MS with EDSS scores of 0-4, 4.5-6.5, 7-7.5 and ≥ 8 seen in 49.8%, 38.5%, 6.8% and 4.9% of patients, respectively. Using a super-item approach, it was possible to demonstrate fit to the assumptions of the Rasch model for 3 of the 4 domains of the WHOQOL-BREF (physical, psychological and environment) as well as a broad 24-item total score. In addition, item subsets derived from the stem of each question were shown to function as novel scales measuring impact and life satisfaction. We have provided transformation tables from ordinal raw scores to interval scales where data are complete. CONCLUSIONS: The validation of multiple conceptual frameworks validates the WHOQOL-BREF as a powerful and flexible end-point for use in clinical trials and in testing conceptual models of factors influencing QoL in MS.

Development and validation of Spasticity Index-Amyotrophic Lateral Sclerosis.

OBJECTIVES: Spasticity is a common and disabling feature of amyotrophic lateral sclerosis (ALS). There are currently no validated ALS-specific measures of spasticity. The aim of this study was to develop and use a self-report outcome measure for spasticity in ALS. METHODS: Following semi-structured interviews with 11 ALS patients, a draft scale was administered across ALS clinics in the UK. Internal validity of the scale was examined using the Rasch model. The numerical rating scale (NRS) for spasticity and Leeds Spasticity scale (LSS) were co-administered. The final scale was used in a path model of spasticity and quality of life. RESULTS: A total of 465 patients (mean age 64.7 years (SD 10), 59% male) with ALS participated. Spasticity was reported by 80% of subjects. A pool of 71 items representing main themes of physical symptoms, negative impact and modifying factors was subject to an iterative process of item reduction by Rasch analysis resulting in a 20-item scale-the Spasticity Index for ALS (SI-ALS)-which was unidimensional and free from differential item functioning. Moderate correlations were found with LSS and NRS-spasticity. Incorporating the latent estimate of spasticity into a path model, greater spasticity reduced quality of life and motor function; higher motor function was associated with better quality of life. CONCLUSIONS: The SI-ALS is a disease-specific self-report scale, which provides a robust interval-level measure of spasticity in ALS. Spasticity has a substantial impact on quality of life in ALS.

Stratification and monitoring of natalizumab-associated progressive multifocal leukoencephalopathy risk: recommendations from an expert group.

The use of natalizumab for highly active relapsing-remitting multiple sclerosis (MS) is influenced by the occurrence of progressive multifocal leukoencephalopathy (PML). Through measurement of the anti-JCV antibody index, and in combination with the presence or absence of other known risk factors, it may be possible to stratify patients with MS according to their risk of developing PML during treatment with natalizumab and detect early suspected PML using MRI including a diffusion-weighted imaging sequence. This paper describes a practical consensus guideline for treating neurologists, based on current evidence, for the introduction into routine clinical practice of anti-JCV antibody index testing of immunosuppressant-naïve patients with MS, either currently being treated with, or initiating, natalizumab, based on their anti-JCV antibody status. Recommendations for the frequency and type of MRI screening in patients with varying index-associated PML risks are also discussed. This consensus paper presents a simple and pragmatic algorithm to support the introduction of anti-JCV antibody index testing and MRI monitoring into standard PML safety protocols, in order to allow some JCV positive patients who wish to begin or continue natalizumab treatment to be managed with a more individualised analysis of their PML risk.

Highly Sensitive End-Point PCR and SYBR Green qPCR Detection of Phymatotrichopsis omnivora, Causal Fungus of Cotton Root Rot.

Phymatotrichopsis omnivora, the causal pathogen of cotton root rot, is a devastating ascomycete that affects numerous important dicotyledonous plants grown in the southwestern United States and northern Mexico. P. omnivora is notoriously difficult to isolate from infected plants; therefore methods for accurate and sensitive detection directly from symptomatic and asymptomatic plant samples are needed for disease diagnostics and pathogen identification. Primers were designed for P. omnivora based on consensus sequences of the nuclear ribosomal internal transcribed spacer (ITS) region of geographically representative isolates. Primers were compared against published P. omnivora sequences and validated against DNA from P. omnivora isolates and infected plant samples. The primer combinations amplified products from a range of P. omnivora isolates representative of known ITS haplotypes using standard end-point polymerase chain reaction (PCR) methodology. The assays detected P. omnivora from infected root samples of cotton (Gossypium hirsutum) and alfalfa (Medicago sativa). Healthy plants and other relevant root pathogens did not produce PCR products with the P. omnivora-specific primers. Primer pair PO2F/PO2R was the most sensitive in end-point PCR assays and is recommended for use for pathogen identification from mycelial tissue and infected plant materials when quantitative PCR (qPCR) is not available. Primer pair PO3F/PO2R was highly sensitive (1 fg) when used in SYBR Green qPCR assays and is recommended for screening of plant materials potentially infected by P. omnivora or samples with suboptimal DNA quality. The described PCR-based detection methods will be useful for rapid and sensitive screening of infected plants in diagnostic laboratories, plant health inspections, and plant breeding programs.

Perceived changes and minimum clinically important difference of the Neurological Fatigue Index for multiple sclerosis (NFI-MS).

The determination of the minimum clinically important difference (MCID) is an important aspect of scale development. The Neurological Fatigue Index for multiple sclerosis (NFI-MS) was administered before and after expected change or stability in fatigue in 208 multiple sclerosis (MS) patients. The overall change scores of the NFI-MS accorded with perceived direction of change; importantly, no change was seen when none was perceived. Using the interval level NFI-MS scores, the largest MCID equated to 2.49 points on the Summary scale, 2.36 points on the Physical scale, 0.84 points on the Cognitive scale, 0.97 on the Diurnal Sleep scale and 1.95 on the Nocturnal Sleep scale. Our conclusion is that the NFI-MS responds as expected to changes in fatigue and has desirably small MCID scores.

Poststroke fatigue: the patient perspective.

PURPOSE: Fatigue is reported as a prevalent symptom post stroke. The purpose of this study is to explore the patent perspective of this symptom, how it is experienced, and its subjective impact on the patient. METHOD: The qualitative procedure of interpretative phenomenological analysis (IPA) was used to analyze the narratives of 10 subjects with previous stroke, who each undertook a single, semi-structured interview. RESULTS: Fatigue was a salient symptom for all the patients. Six main themes were identified. Tiredness/sleep was recognized in all the narratives, and themes of restriction, frustration, and determination/coping reflected varying degrees of physical, cognitive, and psychological dimensions to fatigue. Depression/motivation was also identified, reflecting low mood and helplessness. The remaining theme support indicated a social dimension, with patients recognizing the need for professional and familial support. Further subthemes were identified, and the thematic descriptions of the physical and psychosocial aspects indicated the complexity of fatigue and unique patient profiles. A holistic overview of each narrative furthered an understanding of the dynamic interrelationships between these aspects and their impact on the patient. There were prevalent patterns, but these were different for each patient. CONCLUSION: A better understanding of the varied dimensions or themes elaborated for poststroke fatigue, and their interrelationships, should help in mitigating its impact. The analysis cautions against giving any simplistic and unitary advice to patients about dealing with fatigue.

Is the Epworth sleepiness scale suitable for use in stroke?

BACKGROUND: The Epworth Sleepiness Scale (ESS-8) is frequently used in stroke but has never been validated for this condition. There is concern regarding the suitability of the driving item (item 8). A summed raw score of 10 or more (from a maximum of 24) signifies pathological sleepiness. OBJECTIVE: To determine the construct validity of the ESS-8 by Rasch analysis and in particular to determine whether omission of item 8 confounds the scale. METHOD: A pack containing the ESS-8 and questions regarding sleep and demographics was sent to 999 patients who had experienced a stroke within the past 4 years. Data were assessed for fit to the Rasch model. RESULTS: Analysis of 269 records revealed a unidimensional scale that was free from differential item functioning by age and sex with good overall fit to the Rasch model. Item 4 had disordered thresholds. Analysis of the ESS without item 8 (ESS-7) also revealed a valid scale. Equating person locations between the ESS-8 and ESS-7 showed no differences below a summed raw score of 18. CONCLUSION: The ESS-8 has good construct validity for use in stroke and is reliable at the cutpoint of 10. Summed raw scores below 18 will be unaffected if nondrivers either score as zero or simply omit item 8. The scale is therefore robust for detecting cases of pathological sleepiness in stroke but may not be suitable for measuring high levels of sleepiness in a sample containing both drivers and nondrivers. Instead, the ESS-7 could be used for this purpose.

Prevalence of depression in amyotrophic lateral sclerosis/motor neuron disease: multi-attribute ascertainment and trajectories over 30 months.

Objective: Evidence is equivocal about the prevalence of depression in amyotrophic lateral sclerosis (ALS). This study uses a multi-attribute ascertainment of the prevalence of depression and examines this prevalence over time. Methods: Patients with ALS were recruited into the Trajectories of Outcome in Neurological Conditions (TONiC-ALS) study. Caseness was identified by the Modified-Hospital Anxiety and Depression Scale (M-HADS). In addition, participants provided data on co-morbidities and medication use. A combination of the three was used to derive the estimate for the prevalence of depression, treated or untreated. Longitudinal data were analyzed by trajectory analysis of interval level M-HADS-Depression data. Results: Among 1120 participants, the mean age was 65.0 years (SD 10.7), 60.4% male, and the median duration since diagnosis was 9 months (IQR 4-24). Caseness of probable depression at baseline, defined by M-HADS-Depression, was 6.45% (95%CI: 5.1-8.0). Taken together with antidepressant medication and co-morbidity data, the prevalence of depression was 23.1% (95%CI: 20.7-25.6). Of those with depression, 17.8% were untreated. Trajectory analysis identified three groups, one of which contained the most cases; the level of depression for each group remained almost constant over time. Conclusion: Depression affects almost a quarter of those with ALS, largely confined to a single trajectory group. Prevalence estimates based on screening for current depressive symptoms substantially under-estimate the population experiencing depression. Future prevalence studies should differentiate data based on current symptoms from those including treated patients. Both have their place in assessing depression and the response by the health care system, including medication, depending upon the hypothesis under test.

The unidimensional self-efficacy scale for MS (USE-MS): developing a patient based and patient reported outcome.

BACKGROUND: Self-efficacy concerns the individual's belief that he or she is capable of performing a certain task and producing a desired effect, i.e. it reflects the person's perceptions of their capability for specific tasks, as distinct from their actual ability. Self-efficacy has been shown to influence motivation, psychological well-being, adherence with treatment regimes and quality of life in multiple sclerosis and other conditions. OBJECTIVE: To develop a unidimensional scale of MS self-efficacy with robust psychometric properties, suitable for patient self report. METHODS: A questionnaire pack covering three MS self-efficacy scales, the Dispositional Resilience Scale and demographic data was posted to MS patients from two MS databases. Data underwent Rasch analysis. RESULTS: Response rate was 309/600 (51.5%). None of the existing MS self-efficacy scales were unidimensional. A new 12-item scale, created by combining items from our two scales, was shown to fit the Rasch model, was unidimensional, and invariant for gender, education and disease duration. CONCLUSION: The Unidimensional Self-Efficacy scale for MS (USE-MS) provides a simple summated scale for an ordinal estimate of a persons' self efficacy. A transformation to interval scaling is available for use in the calculation of change scores and effect sizes.

In vitro assessment of the DNA damage and senility of CD117+ stem cells collected from diabetic mice.

OBJECTIVE: Angiogenesis impairment is a common feature of diabetes mellitus (DM), whereas CD117+ bone marrow cells (BMCs) injury might be responsible for such complication. In this study, we studied the effect of hyperglycemia on the DNA damage and senility of CD117+ bone marrow cells. MATERIALS AND METHODS: We isolated CD117+ BMCs from the Streptozotocin (STZ) induced diabetes and healthy control mice. Oxidative stress was detected by flow cytometric analysis. γ-H2AX, which is the DNA damage mark, was detected by using Western blotting and immunofluorescence histochemistry. We also detected the expression of γ-H2AX and p16 by using Western blotting. RESULTS: Compared with the control mice, the level of reactive oxygen species (ROS) was increased significantly in the CD117+ BMCs collected from the diabetic mice (p<0.05), and the percentage of γ-H2AX positive cells was higher significantly (p<0.01). The expression of γ-H2AX and p16 was increased significantly in the CD117+ BMCs from the diabetic mice. CONCLUSIONS: Our experiments demonstrated the oxidative stress in CD117+ BMCs under DM conditions, while accelerating the DNA damage and senility in CD117+ BMCs as well.

Measuring coping in people with amyotrophic lateral sclerosis using the Coping Index-ALS: A patient derived, Rasch compliant scale.

OBJECTIVE: The progressively disabling and terminal nature of ALS/MND imposes major coping demands on patients. We wished to improve the psychometric properties of our previously published MND-Coping Scale, so that parametric analyses were valid, and to make it simpler for patients to complete and clinicians to score. METHODS: After a new qualitative analysis of 26 patients with ALS/MND, the draft Coping Index-ALS (CI-ALS) was administered to 465 additional patients, alongside COPE-60, General Perceived Self Efficacy scale, and WHOQOL-BREF. Validity of the CI-ALS was assessed using the Rasch model. External validity was checked against comparator measures. RESULTS: Thirteen centres contributed 465 patients, mean age 64.9 years (SD 10.8), mean disease duration 28.4 months (SD 37.5). The CI-ALS-Self and CI-ALS-Others both satisfied Rasch model expectations and showed invariance across age, gender, marital status and type of onset. Expected correlations were observed with comparator scales. A nomogram is available to convert the raw scores to interval level measures suitable for parametric analysis. CONCLUSIONS: Coping abilities in ALS/MND can now be measured using a simple 21 item self-report measure, offering two subscales with a focus of 'coping by self ' and 'coping with others'. This allows clinicians to identify individuals with poor coping and facilitates research on interventions that may improve coping skills.

Rasch analysis of the Modified Fatigue Impact Scale (MFIS) in multiple sclerosis.

BACKGROUND: The 21-item Modified Fatigue Impact Scale (MFIS) has been recommended as an outcome measure for use in multiple sclerosis and is commonly used to generate an overall score of fatigue. OBJECTIVE: To test if the MFIS total score is valid by application of the Rasch measurement model. METHOD: The MFIS was sent by post to patients with clinically definite multiple sclerosis in two centres in the UK. Data were fitted to the Rasch model. RESULTS: Analysis was based on 415 records (55% response). The 21-item scale did not fit the Rasch model mainly because of multidimensionality. The scale was found to contain a "physical" dimension and a "cognitive" dimension, consistent with the original subscale structure. Valid physical and cognitive subscales were derived after deletion of some items. CONCLUSION: The MFIS cannot be used to generate a single overall score of fatigue. The conceptual interaction between the two dimensions remains unclear, which poses problems when interpreting change scores in these individual scales. Studies in which a global MFIS score was used as either an outcome measure or selection tool may need to be re-evaluated.

Use of coping strategies in multiple sclerosis: Association with demographic and disease-related characteristics✰.

BACKGROUND: Coping positively and negatively influences psychosocial and other outcomes in multiple sclerosis (MS), but there is conflicting evidence about the use of different coping strategies and their associations with demographic and disease characteristics. Our aims were to examine which coping strategies are used by a large sample of people with MS, then to identify any associations between demographic and disease related factors with use of individual coping strategies. METHODS: Participants in the Trajectories of Outcomes in Neurological Conditions (TONiC) study completed the Coping Orientations to Problems Experienced (COPE60) questionnaire. Relationships between demographic and clinical characteristics and coping strategies were examined by multiple ordinal logistic regression to assess the effect of each potential predictor after adjustment for other possible covariates. RESULTS: From 722 patients, the most commonly used strategy was Acceptance, followed by Active Coping, Planning and Positive Reinterpretation and Growth. All but two strategies showed significant associations with demographic and clinical characteristics. The most marked effects were found for Restraint, with people in employment 2.1 times as likely to utilise this strategy compared to those unemployed, and Seeking of Emotional Social Support and Focus on and Venting of Emotions, which were utilised twice as much by women compared to men. Behavioural and Mental Disengagement were highly associated with greater disability and not being in employment. CONCLUSION: Clinicians should be aware of several disease and demographic characteristics that are associated with use of potentially maladaptive coping strategies.

Sporadic Creutzfeldt-Jakob disease in two adolescents.

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (CJD) is a condition predominantly affecting older age groups, with cases aged less than 45 years rare and an age at onset or death of less than 20 years exceptional. METHODS: Data from the systematic study of sporadic CJD in the UK are available from 1970 onwards. Clinical and pathological data are reviewed in order to identify atypical cases, including those at the extremes of the age range of sporadic CJD. Detailed analysis of atypical cases is undertaken, and in selected cases laboratory transmission studies are carried out in order to provide information on the characteristics of the infectious agent. RESULTS: In the UK, two cases of sporadic CJD in adolescents have been identified, dying at ages 16 and 20 years. The first case predated the epidemic of bovine spongiform encephalopathy and the characteristics of the second case, including laboratory transmission studies, are consistent with a diagnosis of sporadic rather than variant CJD. CONCLUSION: The cases in this report indicate that sporadic CJD can develop at a very young age, that variant CJD is not the only form of CJD occurring in this age group and that neuropathological examination is essential for accurate diagnosis of human prion disease.

A medical definition of fatigue in multiple sclerosis.

BACKGROUND: The symptom of fatigue has been described in a variety of ways but absence of a single taxonomy may be hindering research into this prevalent symptom. OBJECTIVE: To define the symptom of fatigue, as experienced by patients with multiple sclerosis (MS), in terms of a common framework, typical of a medical history. DESIGN: Qualitative phase followed by cross-sectional questionnaire survey. METHOD: Forty patients, with clinically definite MS, underwent semi-structured interviews which were analysed within a common framework of: experience (with derived themes of motor, cognitive, somatic/energy, sleep, other features) cadence (i.e. short-term variability), chronicity, precipitating and aggravating factors, relieving factors, severity and associated features. The prevalence of each feature of fatigue, emergent from the interviews, was subsequently determined by questionnaire survey of a further 635 MS patients. RESULTS: Despite variance across patients, fatigue could be described within the derived themes and framework. Nearly all themes were endorsed by the majority of questionnaire respondents. In summary, fatigue could be defined as reversible motor and cognitive impairment, with reduced motivation and desire to rest. It could appear spontaneously or may be brought on by mental or physical activity, humidity, acute infection and food ingestion. It was relieved by daytime sleep or rest without sleep. It could occur at any time but was usually worse in the afternoon. CONCLUSION: A framework, not only derived from patient experience but also meaningful in a medical context, was shown to be capable of describing fatigue in a large cross-section of MS patients. The definition may facilitate inter-disease comparison of fatigue as well as physiological enquiry.

A randomized group intervention trial to enhance mood and self-efficacy in people with multiple sclerosis.

OBJECTIVES: To document mood, self-efficacy, and resiliency in people with multiple sclerosis (MS) following a brief group psychological intervention, and to examine whether benefits were greater than those derived from provision of education or group social interaction. DESIGN: A randomized controlled intervention trial assessing outcomes at five time points over a 1-year follow-up. METHODS: Participants with MS were assigned to one of three groups: one receiving brief group psychological intervention (PG) comprising three 90 minute cognitive behavioural sessions supported by an Information Booklet dealing with mental and emotional issues relating to MS; a group provided only with educational material - the information booklet group (IBG); and a group who not only received the booklet but also participated in non-structured social discussion (SDG) sessions similar in length and number to PG participants. Outcomes were documented using questionnaires. RESULTS: Outcomes were assessed using area under the curve (AUC) analysis: a summary measure that considers individual changes serially over time to provide a more meaningful picture than the one based on single time points. Ninety participants were followed up over the 12-month post-intervention, and their data are included in the analysis. Analyses indicated benefits in all outcome dimensions for the psychotherapeutic (PG) and social discussion groups (SDG) relative to the IBG group, but no differences between PG and SDG. CONCLUSION: The study indicates benefits from psychosocial intervention compared with bibliotherapy, with some additional benefit from psychological intervention compared with a social discussion group. Results suggest that much of the benefit may derive from non-specific therapeutic components. Without psychosocial intervention, the psychological status of people with MS worsened over time.

Detection of hearing impairment and handicap in Paget's disease of bone using a simple scoring system: a case control study.

Paget's disease of bone is known to be associated with hearing loss but there are limited data on the prevalence of hearing impairment and handicap in people with Paget's disease. Previous published population studies have used patient-completed questionnaires or review of GP records, none have included audiometry. 80 Paget's subjects were selected at random from a hospital database, 75 (94%) entered the study and were matched by age and gender with 76 controls. All participants completed a screening questionnaire for hearing handicap, the HHIE-S; a questionnaire on perception of hearing-related handicap, noise exposure, hearing aids and GP consultations regarding hearing; and audiometry. The results show significant problems from hearing loss in people with Paget's disease of bone. Paget's patients were significantly more likely to perceive hearing handicap (P=0.0001), 41% Paget's patients rated themselves moderate-severe compared to none of the controls. Paget's patients were significantly more likely to report difficulties such as hearing normal speech, watching TV or hearing over background noise (all P=0.0001). They were more likely to consult their GP due to hearing problems (P=0.004) or tinnitus (P=0.0001), or use a hearing aid (P=0.0001). Audiometry confirmed higher rates of deafness in Paget's patients. 41/75 Paget's patients compared to 19/76 controls had at least 40 decibels hearing loss (dBHL) (P=0.0001). The HHIE-S proved to be an effective screening tool. A score of greater than 8 increased the odds ratio of detecting moderate hearing impairment (>40 dBHL) in people with Paget's disease by 5.1. The specificity of HHIE-S >8 as a screening tool to select for audiometry appears good, 1/46 (2%) of Paget's patients would have proved to have normal hearing thresholds. The sensitivity is better with worse hearing loss, 7/16 Paget's patients with moderate loss (>40 dBHL) and 2/25 with severe-profound loss (>60 dBHL) would have been missed. In conclusion, 55% unselected Paget's patients have at least moderate levels of hearing loss, compared to 25% of age and gender matched controls. Paget's patients and controls under-reported hearing problems, many of which can be ameliorated. Screening for hearing problems in Paget's disease of bone can be done using the HHIE-S.

Treatment for ataxia in multiple sclerosis.

BACKGROUND: Disabling tremor or ataxia is common in multiple sclerosis (MS) and up to 80% of patients experience tremor or ataxia at some point during their disease. A variety of treatments are available, ranging from pharmacotherapy or stereotactic neurosurgery to neurorehabilitation. OBJECTIVES: To assess the efficacy and tolerability of both pharmacological and non-pharmacologic treatments of ataxia in patients with MS. SEARCH STRATEGY: The following electronic resources were searched: Cochrane MS Group trials register (June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2006), National Health Service National Research Register (NRR) including the Medical Research Council Clinical Trials Directory (Issue 2, 2006), MEDLINE (January 1996 to June 2006), and EMBASE (Jan 1988 to June 2006). Manual searches of bibliographies of relevant articles, pertinent medical and neurology journals and abstract books of major neurology and MS conferences (2001-2006) were also performed. Direct communication with experts and drug companies was sought. SELECTION CRITERIA: Blinded, randomised trials which were either placebo-controlled or which compared two or more treatments were included. Trials testing pharmacological agents must have had both participant and assessor blinding. Trials testing surgical interventions or effects of physiotherapy, where participants could not have been blinded to the treatment, must have had independent assessors who were blinded to the treatment. Cross-over trials were included. DATA COLLECTION AND ANALYSIS: Three independent reviewers extracted data and the findings of the trials were summarised. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed. MAIN RESULTS: Ten randomised controlled trials met the inclusion criteria. Six placebo-controlled studies (pharmacotherapy) and four comparative studies (one stereotactic neurosurgery and three neurorehabilitation) were reviewed. No standardised outcome measures were used across the studies. In general, pharmacotherapies were unrewarding and data on neurosurgery or rehabilitation is insufficient to lead to a change in practice. AUTHORS' CONCLUSIONS: The absolute and comparative efficacy and tolerability of pharmacotherapies to treat ataxia in MS are poorly documented and no recommendations can be made to guide prescribing. Although studies on neurosurgery and neurorehabilitation showed promising results, the absolute indications for treating with those methods cannot be developed. Standardised, well validated measures of ataxia and tremor need to be developed and employed in larger randomised controlled trials with careful blinding.

Systematic review of the influence of spasticity on quality of life in adults with chronic neurological conditions.

OBJECTIVE: To conduct a systematic review of the published evidence on the relationship between spasticity and quality of life (QOL) in chronic neurological conditions in adults. DATA SOURCES: MEDLINE, Embase, CINAHL and PsycINFO databases. METHODS: The databases were searched from inception to October 2014 using keywords 'spasticity' and 'quality of life' for publications in English language. Cross-sectional and longitudinal studies reporting quantitative analyses on the association between spasticity and QOL were included. Appraisal of the studies and data extraction were conducted in accordance with Strengthening the Reporting of Observational Studies in Epidemiology guidance. RESULTS: 17/652 studies (total of 27 827 patients) met inclusion criteria for review. These examined the relationship between spasticity and QOL in multiple sclerosis (MS), spinal cord injury (SCI) and stroke. Spasticity was found to be associated with significantly lower scores on health status measures, namely SF-12, SF-36 and EQ-5D, in MS and SCI, but less so in stroke. Spasticity was associated with considerably lower scores on physical components of the health status questionnaires, but with only marginally lower scores on mental components. The studies that employed global QOL measures, such as the World Health Organisation Quality of Life - BREF, found no significant relationship between spasticity and QOL. Spasticity was often associated with pain, sleep problems, fatigue and urinary dysfunction. CONCLUSIONS: Spasticity is associated with worse health status, however its relationship with overall QOL is not established. The relationship between spasticity and QOL is confounded by other impairments and requires multivariate analysis. Implications for Rehabilitation Effective management of spasticity may result in significant improvements in HRQOL. It is important to address multiple factors in the management of spasticity including pain, bladder problems, fatigue and sleep, as the interplay of these may have significant negative effects on HRQOL. Clinician-administered methods for measuring spasticity, such as the Ashworth scale, may not provide comprehensive assessment of spasticity. Incorporation of patient-reported measures for spasticity is pivotal in the assessment of therapeutic interventions.