Claire L Hirst

University of Wales, Cardiff, Wales, United Kingdom

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Publications (18)86.02 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; 84(2). DOI:10.1136/jnnp-2012-303996 · 5.58 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. DOI:10.1016/j.jpsychores.2012.08.004 · 2.84 Impact Factor
  • Claire L Hirst, Neil P Robertson
    Multiple Sclerosis 07/2012; 18(7):925-6. DOI:10.1177/1352458512450089 · 4.86 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. DOI:10.1016/j.neulet.2012.06.040 · 2.06 Impact Factor
  • Journal of neurology, neurosurgery, and psychiatry 05/2012; 83(e1). DOI:10.1136/jnnp-2011-301993.185 · 5.58 Impact Factor
  • Journal of Neurology Neurosurgery & Psychiatry 02/2012; 83(3):e1-e1. DOI:10.1136/jnnp-2011-301993.168 · 5.58 Impact Factor
  • Journal of Neurology Neurosurgery & Psychiatry 02/2012; 83(3):e1-e1. DOI:10.1136/jnnp-2011-301993.33 · 5.58 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. DOI:10.1177/1352458511433919 · 4.86 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. DOI:10.1136/jnnp.2010.226340.55 · 5.58 Impact Factor
  • Gillian Ingram, Claire L Hirst, Neil P Robertson
    Neurology 08/2010; 75(9):837; author reply 837-8. DOI:10.1212/WNL.0b013e3181eeea87 · 8.30 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. DOI:10.1007/s00415-009-5437-3 · 3.84 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. DOI:10.1093/brain/awq085 · 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. DOI:10.1177/1352458509358902 · 4.86 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. DOI:10.1136/jnnp.2008.150896 · 5.58 Impact Factor
  • Molecular Immunology 10/2008; 45(16):4176-4177. DOI:10.1016/j.molimm.2008.08.244 · 3.00 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. DOI:10.1007/s00415-008-0743-8 · 3.84 Impact Factor
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    ABSTRACT: Campath 1-H (Alemtuzumab) is a humanised monoclonal antibody which targets the CD52 antigen, a low molecular weight glycoprotein present on the surface of most lymphocyte lineages, causing complement mediated lysis and rapid and prolonged T lymphocyte depletion. Following encouraging initial data from other centres we report our open label experience of using Campath 1-H as a treatment in aggressive relapsing multiple sclerosis in a consecutive series of 39 highly selected patients treated across three regional centres and followed for a mean of 1.89 years. The mean annualised relapse rate fell from 2.48 pre treatment to 0.19 post treatment with 29% of documented relapses observed in the 12 weeks following initial infusion. Mean change in EDSS was -0.36 overall and -0.15 in those patients completing > or =1 year of follow- up. Eighty-three per cent of patients had stable or improved disability following treatment. Infusion related side effects were common including rash, headache and pyrexia but were usually mild and self limiting. Transient worsening of pre-existing neurological deficits during infusion was observed in 3 patients. 12 patients developed biochemical evidence of autoimmune dysfunction, 2 patients developed thyroid disease and 1 patient autoimmune skin disease. We conclude that relapse rates fall following Campath 1-H. Whilst side effects were common these were normally self limiting or easily managed, suggesting Campath 1-H may be of use in the treatment of very active relapsing remitting multiple sclerosis.
    Journal of Neurology 02/2008; 255(2):231-8. DOI:10.1007/s00415-008-0696-y · 3.84 Impact Factor
  • Congress of the European Committee for Treatment and Research in Multiple Sclerosis; 01/2006