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Aj Thompson - One of the best experts on this subject based on the ideXlab platform.
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Problems in designing and recruiting to therapeutic trials in primary progressive multiple sclerosis.
Journal of neurology, 1999Co-Authors: S M Leary, V. L. Stevenson, David H. Miller, Aj ThompsonAbstract:Patients with primary progressive multiple sclerosis have atypical clinical and magnetic resonance imaging (MRI) characteristics which present unique problems in designing and recruiting to therapeutic trials. The first randomised controlled therapeutic trial specifically for primary progressive multiple sclerosis is now underway. Although only an exploratory phase II study, it has provided further insight into difficulties in diagnosis, classification and choice of clinical and MRI outcome measures. Patients with primary progressive multiple sclerosis have a wide differential diagnosis and do not readily conform to the Poser Criteria. They may therefore present diagnostic uncertainty, particularly as their classification often relies on a retrospective history. This was highlighted during the recruitment to this study of interferon-β1a. Of the 138 patients referred with a definite diagnosis of primary progressive multiple sclerosis only 50 were enrolled in the study. Of the 88 patients not included, 50% either did not have primary progressive multiple sclerosis, or the diagnosis was not secure. Outcome measures pose particular problems. Clinically the focus must be on progression, and the measure should be both responsive and reliable. In relation to MRI, the currently recommended measures for therapeutic trials in relapsing/remitting and secondary progressive multiple sclerosis show little change in primary progressive multiple sclerosis, and therefore more pathologically specific MRI measures are required. Strict clinical guidelines and further developments in clinical and MRI measures are required to facilitate future therapeutic trials in primary progressive multiple sclerosis.
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Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI
Brain, 1996Co-Authors: J. W. Thorpe, D. Kidd, I. F. Moseley, Aj Thompson, D. G. Macmanus, D. A. S. Compston, W. I. Mcdonald, Dh MillerAbstract:Summary Although MRI detects the white matter lesions of multiple sclerosis within the brain with high sensitivity, a minority of patients have normal brain MRI. We describe 20 patients, selected from over 170 who had undergone brain imaging with minimal (n = 12) or no (n = 8) abnormalities (median number of lesions = 1, range, 0-3) but in whom spinal MRI was abnormal. Twelve had clinically definite or laboratory supported definite multiple sclerosis according to the Poser Criteria; one had clinically probable disease and seven, not fulfilling the Poser Criteria, were classified as possible
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Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI.
Brain : a journal of neurology, 1996Co-Authors: J. W. Thorpe, D. Kidd, I. F. Moseley, Aj Thompson, D. G. Macmanus, D. A. S. Compston, W. I. Mcdonald, Dh MillerAbstract:Although MRI detects the white matter lesions of multiple sclerosis within the brain with high sensitivity, a minority of patients have normal brain MRI. We describe 20 patients, selected from over 170 who had undergone brain imaging with minimal (n = 12) or no (n = 8) abnormalities (median number of lesions = I, range, 0-3) but in whom spinal MRI was abnormal. Twelve had clinically definite or laboratory supported definite multiple sclerosis according to the Poser Criteria; one had clinically probable disease and seven, not fulfilling the Poser Criteria, were classified as possible multiple sclerosis. All had presented with symptoms and signs referable to the spinal cord or optic nerves. Eleven had a primary progressive course, eight relapsing-remitting and only one secondary progressive. Moderate or severe disability was the rule in the primary progressive cases; all the relapsing-remitting patients had minimal disability. All had at least one lesion visible in the spinal cord (median 2; range 1-6). In patients in whom the diagnosis of multiple sclerosis is not supported by abnormalities on brain MRI, imaging of the spinal cord can be of considerable value.
Gilles Edan - One of the best experts on this subject based on the ideXlab platform.
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Register-based incidence of multiple sclerosis in Brittany (north-western France), 2000-2001.
Acta neurologica Scandinavica, 2014Co-Authors: J. Yaouanq, Isabelle Tron, Anne Kerbrat, E. Leray, Stéphanie Hamonic, M. Merienne, P Hinault, Gilles EdanAbstract:Objectives – To report on multiple sclerosis (MS) incidence in Brittany, north-western France. Materials & Methods – From 2000, we set up a population-based register for patients presenting a putative incident MS (PIMS), that is first symptoms compatible with MS onset. We used 3 medical sources of case ascertainment (neurologists, CSF, regional MS-Clinic). Eligibility Criteria required both clinical onset and being permanent resident of Brittany in 2000 or 2001. From 2010, all medical records were tracked, the 10-year follow-up allowing previously reported data to be updated. Results – Of 313 eligible PIMS, there were 208 definite MS (both McDonald and Poser Criteria), 41 CIS-probable MS (Poser Criteria), 32 CIS-possible MS and 32 non-MS. Our incident cohort of 249 MS cases with definite/ probable MS (sex ratio 2.95) gave a crude annual incidence of 4.28 per 100,000 inhabitants (6.22 for women, 2.23 for men), and age-standardized rates (adjustment to the European population) of 4.41 [3.32–5.51], 6.68 [4.75–8.60], and 2.21 [1.12–3.31], respectively. Age-specific rates by gender and initial course showed that attack onset MS peaked at 25–29 years and progressive onset MS at 40–44 years in women (20–24 years and 45–49 years in men, respectively). Conclusions – Brittany is confirmed a high-risk region for MS. Our data show marked differences in sex-specific pattern of MS incidence by clinical course and point out 25-to 29-year-old women as having the highest MS risk. While temporal variations cannot be excluded, comparison with overall French data suggests that other factors rather than latitude may influence the MS risk in France.
Dh Miller - One of the best experts on this subject based on the ideXlab platform.
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Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI
Brain, 1996Co-Authors: J. W. Thorpe, D. Kidd, I. F. Moseley, Aj Thompson, D. G. Macmanus, D. A. S. Compston, W. I. Mcdonald, Dh MillerAbstract:Summary Although MRI detects the white matter lesions of multiple sclerosis within the brain with high sensitivity, a minority of patients have normal brain MRI. We describe 20 patients, selected from over 170 who had undergone brain imaging with minimal (n = 12) or no (n = 8) abnormalities (median number of lesions = 1, range, 0-3) but in whom spinal MRI was abnormal. Twelve had clinically definite or laboratory supported definite multiple sclerosis according to the Poser Criteria; one had clinically probable disease and seven, not fulfilling the Poser Criteria, were classified as possible
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Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI.
Brain : a journal of neurology, 1996Co-Authors: J. W. Thorpe, D. Kidd, I. F. Moseley, Aj Thompson, D. G. Macmanus, D. A. S. Compston, W. I. Mcdonald, Dh MillerAbstract:Although MRI detects the white matter lesions of multiple sclerosis within the brain with high sensitivity, a minority of patients have normal brain MRI. We describe 20 patients, selected from over 170 who had undergone brain imaging with minimal (n = 12) or no (n = 8) abnormalities (median number of lesions = I, range, 0-3) but in whom spinal MRI was abnormal. Twelve had clinically definite or laboratory supported definite multiple sclerosis according to the Poser Criteria; one had clinically probable disease and seven, not fulfilling the Poser Criteria, were classified as possible multiple sclerosis. All had presented with symptoms and signs referable to the spinal cord or optic nerves. Eleven had a primary progressive course, eight relapsing-remitting and only one secondary progressive. Moderate or severe disability was the rule in the primary progressive cases; all the relapsing-remitting patients had minimal disability. All had at least one lesion visible in the spinal cord (median 2; range 1-6). In patients in whom the diagnosis of multiple sclerosis is not supported by abnormalities on brain MRI, imaging of the spinal cord can be of considerable value.
Thomas Leist - One of the best experts on this subject based on the ideXlab platform.
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090 The effect of cladribine tablets on delaying the time to conversion to clinically definite multiple sclerosis (MS) or McDonald MS is consistent across subgroups in the ORACLE-MS study
Journal of Neurology Neurosurgery & Psychiatry, 2019Co-Authors: James D. Bowen, Alan Gillett, Doris Damian, Yann Hyvert, Fernando Dangond, Megan Grosso, Thomas LeistAbstract:Introduction In the Phase 3 ORACLE-MS trial in 616 subjects with a first demyelinating event at high risk of converting to multiple sclerosis (MS), treatment with cladribine tablets 10 mg (3.5 mg/kg or 5.25 mg/kg cumulative dose over 2 years [CT3.5 and CT5.25, respectively]) significantly delayed time to conversion to clinically definite multiple sclerosis (CDMS) according to Poser Criteria (67% or 62% risk reduction [RR], respectively) and time to conversion to 2005 McDonald MS (50% or 57% RR, respectively), versus placebo. The objective was to analyze the effect of cladribine tablets vs placebo on converstion to CDMS and McDonald MS across ORACLE-MS patient subgroups based on baseline characteristics. Methods In this post-hoc analysis, time-to-conversion to CDMS or McDonald MS over the double-blind period was analyzed for patients treated with CT5.25 (N=204), CT3.5 (N=206) or placebo (N=206) across different subgroups. Subgroups were defined by baseline characteristics which have been investigated as potential predictors of CDMS conversion (age [ Results Treatment with CT3.5 or CT5.25 was consistently efficacious across the subgroups examined on conversion to CDMS versus placebo for most comparisons (RR range: CT3.5, 39%–72%; CT5.25, 36%–79%). Similarly, treatment effect of both doses on conversion to 2005 McDonald MS was consistent across subgroups (CT3.5,40%–59%;CT5.25,42%–79%). Conclusions The effect of cladribine tablets on delaying the time-to-conversion to CDMS, or to McDonald MS, is consistent across subgroups.
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effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event oracle ms a phase 3 randomised trial
Lancet Neurology, 2014Co-Authors: Thomas Leist, Giancarlo Comi, Mark S Freedman, Florence Cassetsemanaz, Bruce A C Cree, Patricia K Coyle, Hanspeter Hartung, P Vermersch, Matthew ScaramozzaAbstract:Summary Background Patients who develop relapsing-remitting multiple sclerosis (MS) present with a first clinical demyelinating event. In this double-blind, multicentre, randomised, phase 3 study we investigated the effect of oral cladribine on conversion to clinically definite MS in patients with a first clinical demyelinating event, when given at the same doses shown to be effective in relapsing-remitting MS. Methods Between Oct 21, 2008, and Oct 11, 2010, we recruited patients aged 18–55 years, inclusive, from 160 hospitals, private clinics, or treatment centres in 34 countries. Eligible patients had a first clinical demyelinating event within 75 days before screening, at least two clinically silent lesions of at least 3 mm on a T2-weighted brain MRI scan, and an Expanded Disability Status Scale score of 5·0 or lower. Patients with a first clinical demyelinating event ≤75 days before screening were randomly assigned (1:1:1) to receive cladribine tablets at cumulative doses of 5·25 mg/kg or 3·5 mg/kg or placebo. Randomisation was done with a central web-based randomisation system and was stratified by geographic region. Masking was maintained using a two-physician model. The primary endpoint of this 96-week study was time to conversion to clinically definite MS according to the Poser Criteria. This study is registered with ClinicalTrials.gov, number NCT00725985. Findings Of 903 participants assessed for eligibility, 616 patients received cladribine 5·25 mg/kg (n=204), cladribine 3·5 mg/kg (n=206), or placebo (n=206). At trial termination on Oct 25, 2011, cladribine was associated with a risk reduction versus placebo for time to conversion to clinically definite MS (hazard ratio [HR] for 5·25 mg/kg=0·38, 95% CI 0·25–0·58, p Interpretation Both doses of cladribine significantly delayed MS diagnosis compared with placebo. The safety profile of cladribine was similar to that noted in a trial in patients with relapsing-remitting MS. Further research could clarify the potential effects of oral cladribine treatment in the early stages of MS. Funding Merck Serono SA Geneva, a subsidiary of Merck KGaA, Darmstadt, Germany.
S A Hawkins - One of the best experts on this subject based on the ideXlab platform.
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Clinical study of primary progressive multiple sclerosis in Northern Ireland, UK
Journal of neurology neurosurgery and psychiatry, 1998Co-Authors: G V Mcdonnell, S A HawkinsAbstract:Objective—To investigate the clinical and demographic characteristics of primary progressive multiple sclerosis (PPMS) in Northern Ireland and to establish a database of such patients for genetic and immunological studies and future therapeutic trials. Methods—Diagnosis and categorisation were performed by two neurologists, potential cases being identified from the following sources: neurology outpatient clinics; neurology inpatients; a review of hospital discharges; and an ongoing epidemiological study of multiple sclerosis in Northern Ireland. Only those with a progressive course from onset and a clear history of no prior relapses were accepted. Potential cases were invited for interview and assessment, the minimal record of disability (MRD) being established. Results—One hundred and eleven cases of PPMS have been identified,63 women and 48 men (ratio 1.3:1), with a mean age at onset of 39.5 (SD 11.0) (range 17‐66)years, and mean disease duration of 13.6 (SD 9.3)years. The mean interval between onset and diagnosis was 4.7 (SD 4.2) years. Nineteen patients (17.1%) did not satisfy the requirements for any category in the Poser Criteria. Motor disturbance was the commonest mode of onset (67.6%) with visual loss occurring only rarely at onset (3.6%). Kurtzke EDSS scores were concentrated at the upper end of the scale with a median of 6.0 and levels of unemployment and financial dependence were high. Conclusions—PPMS in Northern Ireland has a generally later age at onset, lower female preponderance, and predominantly motor onset compared with other subgroups of multiple sclerosis. The delay to diagnosis reflects the often insidious onset and the nature of the clinical course makes application of the Poser Criteria diYcult. Levels of neurological impairment, disability, and handicap as measured by the MRD are high. (J Neurol Neurosurg Psychiatry 1998;64:451‐454)