C Hirst

Cardiff University, Cardiff, WLS, United Kingdom

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Publications (22)104.1 Total impact

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    ABSTRACT: BACKGROUND: Age of onset of multiple sclerosis (MS) peaks in the 3rd and 4th decades and is rarely less than 18. Robust longitudinal studies in paediatric-onset MS (POMS) are limited, and a clearer understanding of outcome could optimise management strategies. METHODS: Patients with disease onset <18 years were identified from a prospective population-based register. Clinical features including presenting symptoms, time to Expanded Disability Status Scale (EDSS) 4.0, 6.0 and 8.0 and onset of secondary progression were compared with patients with adult-onset MS (AOMS). RESULTS: 111 POMS patients were identified from a cohort of 2068. No significant differences in sex ratio, familial recurrence, relapse rate, ethnicity or clinical symptoms at presentation were identified between POMS and AOMS. However, interval to second relapse was longer (5 vs 2.6 years, p=0.04) and primary progressive disease was less common (0.9% vs 8.5%, p=0.003) in POMS than in AOMS. POMS patients also took longer to develop secondary progressive disease (32 vs 18 years, p=0.0001) and to reach disability milestones (EDSS 4.0, 23.8 vs 15.5 years, p<0.0001; EDSS 6.0, 30.8 vs 20.4 years, p<0.0001; EDSS 8.0, 44.7 vs 39 years, p=0.02), but did so between 7.0 and 12 years younger than in AOMS. CONCLUSIONS: 5.4% of patients with MS have POMS (2.7% <16 years; 0.3% <10 years) and have distinct phenotypic characteristics in early disease. Furthermore, while patients with POMS take longer to reach disability milestones, they do so at a younger age than their adult counterparts and could be considered to have a poorer prognosis. Management strategies for these patients should take account of these data.
    Journal of neurology, neurosurgery, and psychiatry 11/2012; · 4.87 Impact Factor
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    ABSTRACT: The expression of clinically significant depression symptoms during and post multiple sclerosis (MS) relapse was investigated. The point prevalence of possible depression during a confirmed MS relapse and at 2 and 6months post-relapse was examined and the influence of disability on the time course of depression symptoms post-relapse determined. 132 sequential patients were recruited from an open access relapse clinic. Clinical data including disability (Expanded Disability Status Scale: EDSS) and depression symptoms (Hospital Anxiety and Depression Scale depression subscale: HADS-D) were recorded at 0, 2 and 6months post-relapse. Prevalence of possible depression (HADS-D score of≥8) was 44.5% during relapse, reducing to 29.2% at 2months and 34.4% at 6months post-relapse. HADS-D scores were significantly lower at follow-up than during relapse. Possible depression at relapse was significantly related to a higher likelihood of possible depression at 2month follow-up (OR 12.12) and improvement in EDSS was related to a lower likelihood (OR 0.51). EDSS at relapse (OR 1.47) and possible depression at relapse (OR 11.87) were significantly associated with possible depression 6months post-relapse. High rates of possible depression were observed during relapse. Although depression scores reduced significantly post-relapse, rates of possible depression at follow-ups remained high. The results suggest that although improvements in disability may influence depression symptoms over the short-term, once depression symptoms are elevated at relapse then depression symptoms become persistent. Further studies are required on the relationship between relapses and depression and whether targeted psychological interventions are beneficial.
    Journal of psychosomatic research 10/2012; 73(4):272-6. · 2.91 Impact Factor
  • Claire L Hirst, Neil P Robertson
    Multiple Sclerosis 07/2012; 18(7):925-6. · 4.47 Impact Factor
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    ABSTRACT: Recent advances in MS genetics have led to the successful identification of a number of novel disease associated non-HLA genes. It is now becoming possible to begin to analyse the possible effects of these genes on aspects of disease phenotype where longitudinal clinical data is available. We examined phenotypic impact of 10 non-HLA disease associated single nucleotide polymorphisms (SNPs) in 1003 patients with MS followed for an average of 14.1 years. Association of SNPs with time to established disability milestones (Expanded Disability Status Scale (EDSS) 4.0, 6.0, 8.0), onset of secondary progression and cross-sectional aspects of early phenotype were tested using survival analysis. No SNP was associated with systematic deflection in time to disability milestones, age at onset or time to secondary progression. Genotypic information from non-HLA associated SNPs is unlikely to inform individual patient prognosis in the clinical setting although minor phenotypic effects operative at specific phases of disease cannot be excluded. This preliminary study provides a framework for future genotype-phenotype analysis in MS and will need to be replicated in independent patient cohorts.
    Neuroscience Letters 06/2012; 526(1):15-9. · 2.03 Impact Factor
  • Journal of neurology, neurosurgery, and psychiatry 05/2012; 83(e1). · 4.87 Impact Factor
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    ABSTRACT: Relapse is a characteristic clinical feature of multiple sclerosis (MS) and is commonly employed as a measure of efficacy following therapeutic intervention. However, less is known about the temporal evolution of subsequent disability or factors predicting recovery. The objective of this study was to assess the pattern of recovery following relapse and identify factors which predict recovery and residual disability following relapse. A total of 226 relapses were studied prospectively in a cohort of 144 patients with standardised clinical assessments of physical disability including Expanded Disability Status Scale (EDSS), 10-m timed walk, 9-hole peg test and Multiple Sclerosis Impact Scale (MSIS-29) at 0, 2, 6 and 12 months. A total of 82 patients completed 12 months of follow up without further relapse. Thirty per cent of relapses were severe (change in EDSS >2.0) of which 11% failed to recover. All measures showed significant improvement at 2 months but additional improvement was also observed in 9-hole peg test and MSIS-29 up to 12 months following initial assessment. Mean time to second relapse was 382 days. The only predictor of relapse severity in the model tested was younger age; however, increasing age and initial relapse severity were also predictors of poor outcome. This study shows that the majority of improvement in physical disability following relapse occurs by 2 months but that more subtle recovery can take place over 12 months in a small sub-group of patients. These data will aid in patient counselling and will also inform the timing of therapeutic intervention and physical support.
    Multiple Sclerosis 01/2012; 18(8):1152-8. · 4.47 Impact Factor
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    ABSTRACT: Age at onset modifies prognosis in multiple sclerosis (MS) and may also exert an effect on the characteristics of disease ignition. Understanding how age influences presentation informs disease management and may allow differentiation of distinct clinical sub-groups. To determine the nature of age-specific presentations of relapsing-remitting MS (RRMS) with respect to onset symptoms, gender ratios and index event outcomes. In a prospective, population-based sample of 1424 patients in South-East Wales we examined associations between age at onset, clinical features and outcome of the onset event, making specific comparisons between paediatric, adolescent and late-onset MS. Age at onset varied significantly between sexes (Male 31.2, Female 29.3, p = 0.002), 0.7% had paediatric onset, 2.7% adolescent onset and 2.8% late-onset MS (>50 years). Optic neuritis was common in younger patients and declined after age 30. Lower limb motor, facial sensory, sexual and sphincteric symptoms rose with age independent of sex and disease course. F:M ratios were highest <16 years of age and declined with increasing age, with a male excess in those over 50. Probability of complete recovery from index event declined with age from 87.4% in the youngest group to 68% in the eldest (p = 0.009). Age at disease onset in RRMS exerts a significant effect on gender ratios and presenting phenotype, and allows identification of specific clinical sub-groups. In addition, ability to recover from initial relapse declines with age, suggesting accumulation of disability in MS is an age-dependent response to relapse.
    Multiple Sclerosis 08/2011; 18(1):45-54. · 4.47 Impact Factor
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    ABSTRACT: To define the rate, timing, and clinical risk factors for the development of autoimmune disease (AID) after alemtuzumab treatment for multiple sclerosis (MS). We analyzed prospective clinical and serologic data from 248 patients with MS treated with alemtuzumab, with median follow-up of 34.3 months (range 6.7-107.3). Novel AID developed in 22.2%. Thyroid AID was most frequent (15.7%). A range of hematologic, renal, and dermatologic AID were also observed as was asymptomatic development of novel autoantibodies. AID was seen from 2 weeks after initial treatment and was most frequent 12-18 months after first treatment. No new cases of AID were identified 60 months or more after initial treatment and risk of AID was independent of total alemtuzumab dose or interval of dosage. While established risk factors for AID including sex and age had no impact on AID frequency, both family history (odds ratio = 7.31, 95% confidence interval 3.02-17.68) of AID and a personal smoking history (odds ratio = 3.05, 95% confidence interval 1.50-6.19) were predictive of AID expression. Cumulative risk for AID in MS following alemtuzumab is 22.2%, most frequent between 12 and 18 months following first dose and evident for up to 5 years. Individual risk is modified by smoking and family history, which should be incorporated within the counseling process prior to treatment. This study provides Class IV evidence that the risk of AID after alemtuzumab treatment for MS is time-limited and modified by external factors.
    Neurology 08/2011; 77(6):573-9. · 8.25 Impact Factor
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    ABSTRACT: The aetiology of events initiating relapse in MS is unclear but it has been postulated that environmental factors linked to climatic change may act as triggers. We analyse month of relapse from data collected prospectively from a large population-based cohort of patients over a 5-year-period (2005-9) and examine associations with climatic variables. A total of 1473 relapses from 617 patients were modelled using Poisson regression. In order to minimise recall bias subgroup analyses were also performed on relapses from patients attending a self-referral relapse clinic (n=722), and surveyed by validated questionnaire (n=221). Compared to April (baseline) a trough in relapses was observed in September (relapse ratio 0.76, 95% CI 0.58 to 0.99, p=0.04) and January (relapse ratio 0.75, 95% CI 0.56 to 0.98, p=0.03). In addition there was a nonsignificant peak in relapses in June (relapse ratio 1.23, 95% CI 0.98 to 1.56, p=0.08). The pattern of relapses could be modelled by a sinusoidal curve p=0.0003. Furthermore the number of monthly sunshine hours predicted relapse frequency (relapse ratio 1.06, 95% CI 1.00 to 1.12, p=0.04 per standard deviation unit). The summer relapse frequency peak was replicated in clinic subgroup data but not in the questionnaire subgroup. This is the largest seasonal analysis of relapses and supports findings from prior small European studies of summer peaks and autumnal troughs. The causes for this seasonal variation remain unclear though sun exposure may be relevant.
    Journal of neurology, neurosurgery, and psychiatry 11/2010; 81(11):e26. · 4.87 Impact Factor
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    ABSTRACT: Alemtuzumab is a anti-CD52 humanised monoclonal antibody shown to be an effective treatment for relapsing multiple sclerosis (MS) in phase II studies but exhibits a unique adverse event profile. In limited follow-up studies development of autoimmune disease has been observed 20-30% of patients. Currently, the exact range and temporal evolution of autoimmune disease following treatment remains unclear but will have important implications for screening and safety monitoring. In this study we analyse prospective clinical and serological data from 225 patients treated with Alemtuzumab for a mean of 40.5 months (range 0.2-93.8). Novel autoimmune disease developed in 22.7%. Thyroid autoimmune disease was most common (17.8%) but a range of other autoimmune diseases including immune thrombocytopenic purpura, anti-GBM disease, neutropoenia, skin disorders and asymptomatic development of novel auto-antibodies was also observed. Risk of autoimmune disease was constant up to 55 months, following which there was a rapid decline, and independent of the number of treatments received or interval of dosage. Whilst established risk factors for autoimmune disease such as sex and age had no impact on autoimmune disease frequency, smoking was identified as a major risk factor with a relative risk of 4.95 for ever smokers. Risk of autoimmune disease in MS following alemtuzumab appears to be time limited and screening will need to continue for at least 5 years posttreatment. Individual risk for autoimmune disease is modified by external factors which should be incorporated within the counselling process prior to treatment.
    Journal of neurology, neurosurgery, and psychiatry 11/2010; 81(11):e26. · 4.87 Impact Factor
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    ABSTRACT: Clinical details of disease onset in multiple sclerosis (MS) are valuable, providing insight into disease outcome. Age is recognised as an important modifying factor for prognosis and may also exert an effect on characteristics of disease ignition. Understanding age-specific presentations improves interpretation of early disease, informing future management and may identify groups of patients with distinct clinical features. Using prospective data gathered over more than 20 years we have examined associations between age and clinical features at onset in 1207 patients from the UK, making specific comparisons between childhood and late-onset multiple sclerosis (LOMS). Age at onset varied significantly between sexes (M:32.2, F:29.8), 0.6% had paediatric, 2.9% adolescent and 4.0% LOMS. Only 6% had a progressive disease from onset (PPMS). F:M ratios were highest <16 years of age and reversed over the age of 50 (1:1.3). Ataxia at onset was common in the young but fell rapidly after age 30. Sphincteric, lower limb and facial motor symptoms rose with age independent of disease course. Probability of complete recovery from first event declined with age from 84% to 39.6% (p>0.001). Age at disease onset in MS exerts a significant effect on sex ratios, degree of recovery and symptoms. The rate of PPMS is only 6% when recall bias is eliminated. This, together with reducing odds of recovery with age provides little support for the aetiological separation of relapsing and progressive disease.
    Journal of neurology, neurosurgery, and psychiatry 11/2010; 81(11):e31. · 4.87 Impact Factor
  • Gillian Ingram, Claire L Hirst, Neil P Robertson
    Neurology 08/2010; 75(9):837; author reply 837-8. · 8.25 Impact Factor
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    ABSTRACT: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an idiopathic immune mediated neuropathy causing demyelination and conduction block thought to occur as the result of an aberrant autoimmune response resulting in peripheral nerve inflammation mediated by T cells and humoral factors. Diagnosis commonly prompts initial treatment with steroids or intravenous immunoglobulin (IVIG) on which 5-35% subsequently become dependent to maintain function. Despite a number of small scale trials, the role for alternative long-term immunosuppression remains unclear. Alemtuzumab is a humanised monoclonal antibody targeting the CD52 antigen present on the surface of lymphocytes and monocytes. A single intravenous infusion results in rapid and profound lymphopoenia lasting >12 months. We report its use and clinical outcome in a small series of patients with severe IVIG-dependent CIDP. Seven patients (4 Males; 3 Females) who had failed to respond to conventional immunosuppression were treated in 5 centres receiving 9 courses of alemtuzumab (dose range 60-150 mg). Following treatment, mean monthly IVIG use fell 26% from 202 to 149 g and IVIG administration frequency from 22 to 136 days. Two patients had prolonged remission, two patients had a partial response and no clear benefit was observed in the remaining three patients (2 Males, 1 Females). Responding patients had a younger age at onset (19.5 years) and shorter disease duration than non-responders. Three patients developed autoimmune disease following treatment. Alemtuzumab may offer an alternative treatment for a subset of early onset IVIG dependent CIDP patients failing conventional immunosuppressive agents, but concerns about toxicity may limit its use.
    Journal of Neurology 06/2010; 257(6):913-9. · 3.58 Impact Factor
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    ABSTRACT: Multiple sclerosis has a variable phenotypic presentation and subsequent disease course that, although unpredictable at disease onset, is of crucial importance in guiding interventions. Effective and accessible biomarkers are required in order to stratify patients and inform treatment. We examined whether the complement regulator factor H and its Tyr402His polymorphism, recently implicated as biomarkers in other chronic inflammatory central nervous system conditions, might identify or predict specific pathological processes and outcomes in multiple sclerosis. Employing novel assays, we measured factor H and its His402 variant in serum from 350 patients with multiple sclerosis classified according to disease course and relapse status. Serum factor H levels were significantly higher in progressive disease (P < 0.001) compared to controls and relapsing patients, after controlling for variables including disease duration, age, gender, disability and treatment. Serum factor H levels were capable of distinguishing secondary progressive from relapsing remitting disease (excluding patients in clinical relapse) with a sensitivity of 89.41%, specificity of 69.47% and a positive predictive value of 72.38%. Acute relapse was also associated with transiently increased factor H levels (P = 0.009) compared to stable relapsing disease. In clinically stable patients, factor H levels remained constant over 1 year (coefficient of variation percentage = 6.8), however, in patients in transition from relapsing to progressive disease, factor H levels significantly increased over a period of 2 years (P = 0.007). Concentration of the His402 variant in heterozytgotes was significantly higher in secondary progressive (P < 0.01) and primary progressive (P < 0.05) disease, suggesting altered expression or consumption of variants when factor H is upregulated. Serum factor H may be an effective indicator of progression and a practical and accessible biomarker and stratifying tool in determining disease course, providing objective evidence to help guide therapeutic decisions.
    Brain 06/2010; 133(Pt 6):1602-11. · 10.23 Impact Factor
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    ABSTRACT: Patient-derived historical data are widely employed to make fundamental management decisions in multiple sclerosis, although the validity of the information provided is unclear. The objectives of this study were to determine validity of patient-derived historical data and to describe the utility of a locally relevant, patient-administered questionnaire designed to ascertain current disability and other important disease milestones. A well-described cohort of 99 patients was identified for whom comparable, detailed, prospective longitudinal clinician-derived data were available. Patient-derived data were collected by completion of a standardized questionnaire or telephone interview for comparison. Reliability analysis for current Expanded Disability Status Scale (EDSS) demonstrated an intraclass correlation coefficient of 0.79 between questionnaire and clinician-derived data in 79 patients, with complete agreement in 75.9%. Intraclass correlation coefficient for year of disease onset, diagnosis and onset of secondary progression was 0.86, 0.91 and 0.78, respectively. Time to EDSS >4.0, 6.0 and 8.0 all had an intraclass correlation coefficient of >0.9. Less robust agreement was observed for current disease course (Kappa coefficient 0.71), initial relapse rate (intraclass correlation coefficient 0.37) and clinical features at disease onset (Kappa 0.25). We conclude that self-reported questionnaires can provide reliable current and retrospective data on time-to-disability milestones with high levels of correlation observed for some additional elements, supporting the use of selected components of patient-derived data in clinical practice and for epidemiological studies.
    Multiple Sclerosis 02/2010; 16(4):472-9. · 4.47 Impact Factor
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    ABSTRACT: Oligoclonal band (OCB) negative multiple sclerosis (MS) is well recognised but uncommon, studied in only a few usually small case series. These reached differing conclusions on whether its clinical features or course differ from OCB positive disease. The study hypothesis was that a definitive study would not only be of clinical and prognostic value but also potentially offer information about the possible role of CSF oligoclonal immunoglobulins in MS disease processes. A collaborative cohort of well documented patients in southwest England and south Wales was used to identify and analyse a large group of patients with OCB negative MS and make comparisons with age and sex matched OCB positive controls. An approximate minimum 3% of patients with MS were OCB negative. They were significantly more likely to exhibit neurological or systemic clinical features atypical of MS (headaches, neuropsychiatric features and skin changes). Non-specific MRI, blood and (other) CSF abnormalities were also more common, emphasising the need for continued diagnostic vigilance, although the incautious application of McDonald diagnostic criteria in OCB negative cases renders categorisation as "definite" MS more likely. Studying the uniformly assessed Cardiff group (69 patients), we found the prognosis for neurological disability was significantly better for OCB negative cases. The age adjusted hazard ratio for OCB negative and OCB positive subjects to reach Disability Scale Status (DSS) 4 and DSS 6 was, respectively, 0.60 (95% CI 0.39 to 0.93; p = 0.02) and 0.51 (95% CI 0.27 to 0.94; p = 0.03). There are clear clinical differences between OCB negative and OCB positive MS, in particular a better prognosis for disability. This is consistent with a secondary but nonetheless contributory role in disease process for intrathecally synthesised immunoglobulins.
    Journal of neurology, neurosurgery, and psychiatry 11/2008; 80(3):292-6. · 4.87 Impact Factor
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    ABSTRACT: Epidemiological studies of multiple sclerosis suggest a trend of increasing disease prevalence in susceptible populations. The reasons for this are unclear and may be the results of methodological differences between studies, incomplete ascertainment or advances in technologies that allow the increased identification of early or mild disease. In addition, direct comparison of cross sectional prevalence estimates performed in different epochs in ethnically and geographically distinct populations may be inappropriate. Using detailed phenotypic information and standardised methodology, a geographically defined Welsh population was resurveyed after a significant interval, establishing contemporary prevalence rates and examining demographic and clinical data to determine causes of changing disease frequency. Disease prevalence increased 45% from 101 to 146 per 100,000 population over 20 years. The greatest increase was observed in women between the ages of 45 and 54 years. No significant increase in disease frequency was observed in the male population overall, or within specific age groups. There was no demographic evidence for a pattern of earlier age at onset or diagnosis to explain increased disease frequency or decrease in mean age of the prevalent population. In addition, we failed to identify a pattern of recognition of patients with less severe disability. Although there was a modest 13% increase of 2.2 years in mean disease duration, and eight new previously prevalent patients were identified, the main cause of rising disease frequency was related to a 2.8-fold increase in disease incidence for women over 23 years from 2.65 to 7.30/100,000/year increasing the sex ratio of incident patients from 1.8 to 4.3 (women:men). Recent change in disease incidence and prevalence in this population is likely to be the result of environmental factors that have been operative in the past few decades in women alone and infers avoidable risk factors. Modelling of current overall incidence suggests a further increase in prevalence to 260 per 100 000 population within the next 20-40 years. Further studies are needed in order to identify recent changes in sex specific environment and lifestyle that confer susceptibility.
    Journal of neurology, neurosurgery, and psychiatry 11/2008; 80(4):386-91. · 4.87 Impact Factor
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    ABSTRACT: Detailed studies of mortality in multiple sclerosis (MS) are limited. Studying death certificates in a prospective cohort of patients known to have MS is of value in establishing mortality data and can also provide important information on the accuracy and use of death certificates for epidemiological studies. A population-based survey performed in South Wales in 1985 identified 441 patients. Cases were flagged with the Office of Population Censuses and Surveys and death certificates collected prospectively for more than 20 years. Median observed survival time was 38.0 years from symptom onset. Mean age at death was 65.3 for women and 65.2 years for men. Mean age at death in patients dying from MS-related causes was 62.5 and 69.3 years (p<0.001) for unrelated deaths. Those dying of MS-related causes had a younger age at disease onset (32.5) compared with those dying of unrelated causes (36.8 years) (p = 0.01). Cause of death was related to MS in 57.9% and unrelated in 42.1% of individuals. In 27% of patients, "MS" was absent from the death certificate. The most common cause of death was respiratory disease (47.5%). The standardised mortality ratio was 2.79 (95% CI 2.44 to 3.18) so that MS patients were almost three times more likely to die prematurely relative to the general population. These results confirm a continuing trend of premature death in patients with MS. Relying on data derived from death certificates will underestimate disease prevalence. Differences were identified between those dying from MS-related causes and those dying from other causes.
    Journal of neurology, neurosurgery, and psychiatry 03/2008; 79(9):1016-21. · 4.87 Impact Factor
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    ABSTRACT: In patients with multiple sclerosis (MS), the natural history of the disease is of considerable importance to predict and understand long-term outcome and inform choices made by patients and clinicians. This information should ideally be derived from data that reflects the entire disease course. In this study, morbidity data from a prevalent cohort established in 1985 have been re-examined after an interval of 20 years to assess factors that may be important in determining outcome. Of 379 patients who fulfilled criteria for definite or probable MS in the original population-based cohort, 221 (58.3%) had died, 149 (39.3%) were alive and 9 (2.4%) were untraceable. Mean Expanded Disability Status Scale (EDSS) score in 1985 was 5.15 (SD 2.7, range 0-9.5) and 8.01 (SD 2.6, range 0-10) in those alive in 2005. Mean worsening of EDSS scores in surviving patients was +3.02 EDSS points, but 14.0% had worsened by <1 EDSS point over 20 years. 61.4% of patients with EDSS 3.5-5.5 and 82.2% of those with an EDSS of <or=3 in 1985 had an EDSS of >or=6 after 20 years. Lower baseline EDSS scores (p<0.0001), higher pyramidal functional system score (p = 0.02) and a greater number of functional systems involved (p = 0.001) were significantly more likely to be associated with greater worsening of disability. Of those with benign disease in 1985, only 19% remained benign after 20 years of follow-up; however, 12.6% of patients had minimal disability after at least 20 years after their disease onset and 14% of patients failed to worsen by >or=1 EDSS point. This study emphasises the importance of long-term epidemiological studies and the development of clinically relevant measures that effectively predict outcome and can guide decisions on therapeutic management.
    Journal of neurology, neurosurgery, and psychiatry 03/2008; 79(10):1137-43. · 4.87 Impact Factor
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    ABSTRACT: The impact of relapses on long-term disability in multiple sclerosis remains unclear; however some evidence suggests that relapses play an important role in determining subsequent prognosis. We report on outcome, prognostic factors for recovery and the contribution of relapses to the accumulation of fixed disability in a large series of patients with documented relapses. Two hundred and seventy-nine relapses in 182 patients were assessed before, during and after relapse by expanded disability status scale and data analysed to assess degree of recovery. Factors affecting outcome were considered including sex, age and site of relapse. Mean EDSS prior to relapse was 3.73, during relapse 5.18 and post relapse 4.23. Mean interval to post relapse assessment was 127 days post relapse. Mean residual change in EDSS score (pre to post relapse) was 0.50 points. Overall 49.4 % of patients had a residual increase in disability post relapse of at least 0.5 EDSS points and 32.7 % had an increase of at least 1 point. No significant difference was observed in mean residual EDSS for sex, site of relapse or age at relapse or in the proportion of patients with a residual increase in disability of > or = 1 EDSS point post relapse. 14.4 % of patients had no increase in EDSS score during relapse compared to pre relapse. These results suggest that acute relapses are commonly associated with an objective worsening of disability in the majority of patients with MS and that recovery is incomplete in approximately half and not influenced by gender, age or site of lesion. Therapies which reduce relapse frequency and/or severity might therefore be expected to slow or prevent worsening of disability if initiated prior to the onset of more permanent damage.
    Journal of Neurology 03/2008; 255(2):280-7. · 3.58 Impact Factor