Search

Your search keyword '"Harrower, T."' showing total 100 results
Start Over Author "Harrower, T."
100 results on '"Harrower, T."'

2. Validating the portal population of the United Kingdom Multiple Sclerosis Register

Author

Middleton, R.M., Rodgers, W.J., Chataway, J., Schmierer, K., Rog, D., Galea, I., Akbari, A., Tuite-Dalton, K., Lockhart-Jones, H., Griffiths, D., Noble, D.G., Jones, K.H., Al-Din, A., Craner, M., Evangelou, N., Harman, P., Harrower, T., Hobart, J., Husseyin, H., Kasti, M., Kipps, C., McDonnell, G., Owen, C., Pearson, O., Rashid, W., Wilson, H., and Ford, D.V.

Published
2018
Full Text
View/download PDF

3. Cost-effectiveness analysis of abobotulinumtoxinA for the treatment of cervical dystonia in the United Kingdom

Author

Muthukumar M, Desai K, Abogunrin S, Harrower T, Gabriel S, and Dinet J

Subjects
cost-effectiveness analysis, cervical dystonia, botulinum neurotoxin type A, abobotulinumtoxinA, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Madhusubramanian Muthukumar,1 Kamal Desai,1 Seye Abogunrin,2 Timothy Harrower,3 Sylvie Gabriel,4 Jerome Dinet5 1Modelling and Simulation, 2Meta Research, Evidera, London, 3Royal Devon and Exeter NHS Foundation Trust, Exeter, UK; 4Global Market Access and Pricing, 5Health Economics and Outcomes Research (Global), Ipsen Pharma, Boulogne-Billancourt, France Background: Cervical dystonia (CD) involves painful involuntary contraction of the neck and shoulder muscles and abnormal posture in middle-aged adults. Botulinum neurotoxin type A (BoNT-A) is effective in treating CD but little is known about its associated cost-effectiveness.Objective: To evaluate the cost-effectiveness of abobotulinumtoxinA for treating CD from the UK payer perspective.Methods: A Markov model was developed to evaluate the cost-effectiveness of abobotulinumtoxinA versus best supportive care (BSC) in CD, with a lifetime horizon and health states for response, nonresponse, secondary nonresponse, and BSC in patients with CD (mean age: 53 years; 37% male). Clinical improvement measured using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was mapped to utility using data from a randomized trial of abobotulinumtoxinA. Health care resource use, costs, and other inputs were from the British National Formulary, Personal Social Services Research Unit, published literature, or expert opinion. Costs and outcomes were discounted at 3.5% per annum.Results: In the base case, the incremental lifetime quality-adjusted life-years (QALYs) gained from abobotulinumtoxinA arm versus BSC was 0.253 per patient, whereas the incremental cost was £7,160, leading to an incremental cost-effectiveness ratio (ICER) of £30,468 per QALY. One-way sensitivity analyses showed that these results were sensitive to the proportion of responders to abobotulinumtoxinA at first injection, duration between injections, the number of reinjections allowed among primary nonresponders, and any difference in baseline TWSTRS value between the BSC and abobotulinumtoxinA arms. Probabilistic sensitivity analysis showed that abobotulinumtoxinA was cost-effective 46% and 49% of times at thresholds of £20,000 and £30,000 per QALY, respectively. Scenarios are considered including vial-sharing, productivity losses, secondary response/nonresponse at subsequent injections, 5-year time horizon, and alternative reinjection intervals for BoNT-As produced ICERs ranging from cost-saving to £40,777 per QALY, versus BSC.Conclusion: AbobotulinumtoxinA was found to be cost-effective in treating adults with CD, at acceptable willingness-to-pay thresholds in the UK. Keywords: cost-effectiveness analysis, cervical dystonia, botulinum neurotoxin type A, abobotulinumtoxinA

Published
2017

4. AbobotulinumtoxinA in the management of cervical dystonia in the United Kingdom: a budget impact analysis

Author

Abogunrin S, Br, S, Desai K, Dinet J, Gabriel S, and Harrower T

Subjects
Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Seye Abogunrin,1 Sarah Brand,2 Kamal Desai,3 Jerome Dinet,4 Sylvie Gabriel,5 Timothy Harrower61Meta Research, Evidera, London, UK; 2Health Economics, Evidera, Bethesda, MD, USA; 3Health Economics, Evidera, London, UK; 4Health Economics and Outcomes Research (Global), 5Global Market Access and Pricing, Ipsen Pharma, Boulogne-Billancourt, France; 6Royal Devon and Exeter NHS Foundation Trust, Exeter, UKBackground: Cervical dystonia (CD) can be effectively managed by a combination of botulinum neurotoxin A (BoNT-A) and conventional therapy (skeletal muscle relaxants and rehabilitative therapy), but the costs of different interventions in the UK vary.Methods: A budget impact model was developed from the UK payer perspective with a 5-year time horizon to evaluate the effects of changing market shares of abobotulinumtoxinA, nabotulinumtoxinA, and incobotulinumtoxinA, and best supportive care from the UK payer perspective. Epidemiological and resource use data were retrieved from the published literature and clinical expert opinion. Deterministic sensitivity analyses were performed to determine the parameters most influential on the budgetary findings under base case assumptions.Results: Under base case assumptions, an increased uptake of abobotulinumtoxinA showed an accumulated savings of £2,250,992 by year 5. Treatment per patient per year with onabotulinumtoxinA and incobotulinumtoxinA costs more when compared to treatment with abobotulinumtoxinA. One-way sensitivity analyses showed that the prevalence of CD, dose per injection of each of the BoNT-As, and time to reinjection of incobotulinumtoxinA and abobotulinumtoxinA influenced the base case findings most.Conclusion: There is potential for cost savings associated with the greater use of abobotulinumtoxinA rather than other BoNT-A treatments, permitting more patients to benefit more from effective BoNT-A treatment with a fixed budget. Keywords: cervical dystonia, torticollis, botulinum toxin A, budget impact analysis

Published
2015

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

Author

Young, C. A., Ealing, J., McDermott, C. J., Williams, T. L., Al-Chalabi, A., Majeed, T., Talbot, K., Harrower, T., Faull, C., Malaspina, A., Annadale, J., Mills, R. J., and Tennant, A.

Subjects
MOTOR neuron diseases, AMYOTROPHIC lateral sclerosis, ANTIDEPRESSANTS, MENTAL depression, NEUROLOGICAL disorders
Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

7. INTEREST IN CD2, a global patient-centred study of long-term cervical dystonia treatment with botulinum toxin

Author

Misra, Vijay P., Colosimo, Carlo, Charles, David, Chung, Tae Mo, Maisonobe, Pascal, Om, Savary, Abdulnayef, A., Adatepe, N. U., Araujo Leite, M. A., Badarny, S., Bajenaru, O., Bares, M., Bejjani, P., Bergmans, B., Bhidayasiri, R., Bozic, H., Cardoso Costa, F. E., Carlstrom, C., Castelnovo, G., Chang, M. H., Chang, Y. Y., Coletti-Moja, M., Delvaux, V., Dioszhegy, P., Dogu, O., Duzynski, W., Ehler, E., Espinosa Sierra, L., Fabbrini, G., Ferreira, J., Ferreira Valadas, A., Foresti, C., Girlanda, P., Goh, K. J., Graca Velon, A., Grill, S., Gurevitch, T., Hadidi, M., Hamimed, M. A., Hamri, A., Harrower, T., Hassin, S., Hedera, P., Hernandez, J. F. J. G., Hernandez Franco, J., Ho, B., Ho, S. L., Hughes, A., Ilic, T., Inshasi, J. S., Ip, C. W., Jamieson, S., Jamora, R. D. G., Jech, R., Jeon, B. S., Kaminska, A., Karpova, M., Khasanova, D., Kim, J. M., Kim, J. W., Kok, C. Y., Korenko, A., Korv, J., Koussa, S., Kovacs, T., Kreisler, A., Krystkowiak, P., Kumthornthip, W., Lin, C. H., Lundin, F., Lus, G., Magalhaes, M., Masmoudi, A. N., Mercelis, R., Misbahuddin, A., Moebius, C., Mohammadi, B., Nazem, B., Ng, K., Nurlu, G., Nyberg, J., Nyholm, D., Ochudlo, S., Otruba, P., Pfister, R., Pirtosek, Z., Pokhabov, D., Quinones Aguilar, S., Quinones Canales, G., Raghev, S., Rickmann, H., Romano, M., Rosales, R. L., Rubanovits, I., Santilli, V., Schoels, L., Simonetta-Moreau, M., Simu, M. A., Sohn, Y. H., Soulayrol, S., Supe, I., Svetel, M., Sycha, T., Tan, E. K., Timerbaeva, S., Tokcaer, A. B., Trosch, R., Tugnoli, V., Tumas, V., van der Linden, C., Vetra, A., Vial, C., Vidry, E., Williams, D., Wimalaratna, S., Yiannikas, C., Misra, Vijay P., Colosimo, Carlo, Charles, David, Chung, Tae Mo, Maisonobe, Pascal, Om, Savary, Abdulnayef, A., Adatepe, N. U., Araujo Leite, M. A., Badarny, S., Bajenaru, O., Bares, M., Bejjani, P., Bergmans, B., Bhidayasiri, R., Bozic, H., Cardoso Costa, F. E., Carlstrom, C., Castelnovo, G., Chang, M. H., Chang, Y. Y., Coletti-Moja, M., Delvaux, V., Dioszhegy, P., Dogu, O., Duzynski, W., Ehler, E., Espinosa Sierra, L., Fabbrini, G., Ferreira, J., Ferreira Valadas, A., Foresti, C., Girlanda, P., Goh, K. J., Graca Velon, A., Grill, S., Gurevitch, T., Hadidi, M., Hamimed, M. A., Hamri, A., Harrower, T., Hassin, S., Hedera, P., Hernandez, J. F. J. G., Hernandez Franco, J., Ho, B., Ho, S. L., Hughes, A., Ilic, T., Inshasi, J. S., Ip, C. W., Jamieson, S., Jamora, R. D. G., Jech, R., Jeon, B. S., Kaminska, A., Karpova, M., Khasanova, D., Kim, J. M., Kim, J. W., Kok, C. Y., Korenko, A., Korv, J., Koussa, S., Kovacs, T., Kreisler, A., Krystkowiak, P., Kumthornthip, W., Lin, C. H., Lundin, F., Lus, G., Magalhaes, M., Masmoudi, A. N., Mercelis, R., Misbahuddin, A., Moebius, C., Mohammadi, B., Nazem, B., Ng, K., Nurlu, G., Nyberg, J., Nyholm, D., Ochudlo, S., Otruba, P., Pfister, R., Pirtosek, Z., Pokhabov, D., Quinones Aguilar, S., Quinones Canales, G., Raghev, S., Rickmann, H., Romano, M., Rosales, R. L., Rubanovits, I., Santilli, V., Schoels, L., Simonetta-Moreau, M., Simu, M. A., Sohn, Y. H., Soulayrol, S., Supe, I., Svetel, M., Sycha, T., Tan, E. K., Timerbaeva, S., Tokcaer, A. B., Trosch, R., Tugnoli, V., Tumas, V., van der Linden, C., Vetra, A., Vial, C., Vidry, E., Williams, D., Wimalaratna, S., and Yiannikas, C.

Subjects
Male, Neurology, SATISFACTION, International Cooperation, Cohort Studies, 0302 clinical medicine, QUALITY-OF-LIFE, Botulinum toxin, Observational study, Tremor, Epidemiology, 030212 general & internal medicine, Cervical dystonia, Botulinum Toxins, Type A, Torticollis, Neuroradiology, BLEPHAROSPASM, education.field_of_study, Original Communication, INTEREST IN CD2 study group, Middle Aged, Treatment Outcome, Neuromuscular Agents, Female, Life Sciences & Biomedicine, medicine.drug, Adult, medicine.medical_specialty, Population, Clinical Neurology, DIAGNOSIS, 03 medical and health sciences, Patient satisfaction, Neurology (clinical), Internal medicine, medicine, Humans, education, Aged, Science & Technology, Neurology & Neurosurgery, Electromyography, GUIDANCE, business.industry, 1103 Clinical Sciences, medicine.disease, NEUROTOXIN, REGISTRY, UPDATE, Neurosciences & Neurology, 1109 Neurosciences, business, 030217 neurology & neurosurgery
Abstract

Background Longitudinal cohort studies provide important information about the clinical effectiveness of an intervention in the routine clinical setting, and are an opportunity to understand how a population presents for treatment and is managed. Methods INTEREST IN CD2 (NCT01753349) is a prospective, international, 3-year, longitudinal, observational study following the course of adult idiopathic cervical dystonia (CD) treated with botulinum neurotoxin type A (BoNT-A). The primary objective is to document long-term patient satisfaction with BoNT-A treatment. Here we report baseline data. Results This analysis includes 1036 subjects (67.4% of subjects were female; mean age was 54.7 years old; mean TWSTRS Total score was 31.7). BoNT-A injections were usually given in line with BoNT-A prescribing information. The most commonly injected muscles were splenius capitis (87.3%), sternocleidomastoid (82.6%), trapezius (64.3%), levator scapulae (40.9%) and semispinalis capitis (26.9%); 35.5% of subjects were injected using a guidance technique. Most subjects (87.8%) had been previously treated with BoNT-A (median interval between last pre-study injection and study baseline was 4 months); of these 84.8% reported satisfaction with BoNT-A treatment at peak effect during their previous treatment cycle and 51.5% remained satisfied at the end of the treatment. Analyses by geographical region revealed heterogeneity in the clinical characteristics and BoNT-A injection practice of CD subjects presenting for routine treatment. Conclusions These baseline analyses provide sizeable data regarding the epidemiology and clinical presentation of CD, and demonstrate an international heterogeneity of clinical practice. Future longitudinal analyses of the full 3-year study will explore how these factors impact treatment satisfaction. Electronic supplementary material The online version of this article (10.1007/s00415-017-8698-2) contains supplementary material, which is available to authorized users.

Published
2017

9. Unilateral transplantation of human primary fetal tissue in four patients with huntington's disease: NEST-UK safety report ISRCTN no 36485475. (Paper)

Author

Rosser, A.E., Barker, R.A., Harrower, T., Watts, C., Farrington, M., Ho, A.K., Burnstein, R.M., Menon, D.K., Gillard, J.H., Pickard, J., and Dunnett, S.B.

Subjects
Fetal tissue transplantation -- Physiological aspects -- Research, Huntington's chorea -- Research -- Development and progression, Therapeutics, Experimental -- Research -- Physiological aspects, Health, Psychology and mental health, Physiological aspects, Development and progression, Research
Abstract

Objectives: Huntington's disease (HD) is an inherited autosomal dominant condition in which there is a CAG repeat expansion in the huntingtin gene of 36 or more. Patients display progressive motor, [...]

Published
2002

10. How satisfied are cervical dystonia patients after 3 years of botulinum toxin type A treatment? Results from a prospective, long-term observational study

Author

Colosimo, C, Charles, D, Misra, VP, Maisonobe, P, Om, S, Abdulnayef, A, Adatepe, NU, Leite, AMA, Badarny, S, Bajenaru, O, Bares, M, Bejjani, P, Bergmans, B, Bhidayasiri, R, Bozic, H, Costa, CFE, Carlstrom, C, Castelnovo, G, Chang, MH, Chang, YY, Chung, TM, Coletti-Moja, M, Delvaux, V, Dioszhegy, P, Dogu, O, Duzynski, W, Ehler, E, Sierra, EL, Fabbrini, G, Ferreira, J, Valadas, FA, Foresti, C, Girlanda, P, Goh, KJ, Velon, GA, Grill, S, Gurevitch, T, Hadidi, M, Hamimed, MA, Hamri, A, Harrower, T, Hassin, S, Hedera, P, Hernandez, JFJG, Franco, HJ, Ho, B, Ho, SL, Hughes, A, Ilic, T, Inshasi, JS, Ip, CW, Jamieson, S, Jamora, RDG, Jech, R, Jeon, BS, Kaminska, A, Karpova, M, Khasanova, D, Kim, JM, Kim, JW, Kok, CY, Korenko, A, Korv, J, Koussa, S, Kovacs, T, Kreisler, A, Krystkowiak, P, Kumthornthip, W, Lin, CH, Lundin, F, Lus, G, Magalhaes, M, Masmoudi, AN, Mercelis, R, Misbahuddin, A, Moebius, C, Mohammadi, B, Nazem, B, Ng, K, Nurlu, G, Nyberg, J, Nyholm, D, Ochudlo, S, Otruba, P, Pfister, R, Pirtosek, Z, Pokhabov, D, Aguilar, QS, Canales, QG, Raghev, S, Rickmann, H, Romano, M, Rosales, RL, Rubanovits, I, Santilli, V, Schoels, L, Simonetta-Moreau, M, Ma, S, Sohn, YH, Soulayrol, S, Supe, I, Svetel, M, Sycha, T, Tan, EK, Timerbaeva, S, Tokcaer, AB, Trosch, R, Tugnoli, V, Tumas, V, Van der Linden, C, Vetra, A, Vial, C, Vidry, E, Williams, D, Wimalaratna, S, and Yiannikas, C

Subjects
0301 basic medicine, Male, Pediatrics, Neurology, SATISFACTION, Botulinum toxin, Cervical dystonia, Observational study, Satisfaction, Treatment, 0302 clinical medicine, QUALITY-OF-LIFE, Outcome Assessment, Health Care, Prospective Studies, Botulinum Toxins, Type A, Torticollis, Neuroradiology, BLEPHAROSPASM, INTEREST IN CD2 study group, Middle Aged, Neuromuscular Agents, Patient Satisfaction, SAFETY, Female, Life Sciences & Biomedicine, medicine.drug, Adult, medicine.medical_specialty, Adolescent, MEDLINE, Clinical Neurology, Treatment results, DIAGNOSIS, 03 medical and health sciences, Young Adult, medicine, Humans, Aged, Science & Technology, Neurology & Neurosurgery, business.industry, Correction, 1103 Clinical Sciences, medicine.disease, EFFICACY, 030104 developmental biology, Neurology (clinical), Neurosciences & Neurology, business, FOLLOW-UP, 1109 Neurosciences, 030217 neurology & neurosurgery, Botulinum toxin type
Abstract

Background Patients with cervical dystonia (CD) typically require regular injections of botulinum toxin to maintain symptomatic control. We aimed to document long-term patient satisfaction with CD symptom control in a large cohort of patients treated in routine practice. Methods This was a prospective, international, observational study (NCT01753349) following the course of adult CD treated with botulinum neurotoxin type A (BoNT-A) over 3 years. A comprehensive clinical assessment status was performed at each injection visit and subjects reported satisfaction in two ways: satisfaction with symptom control at peak effect and at the end of treatment cycle. Results Subject satisfaction remained relatively stable from the first to the last injection visit. At 3 years, 89.9% of subjects reported satisfaction with symptom control at peak effect and 55.6% reported satisfaction with symptom control at end of treatment cycle. By contrast, objective ratings of CD severity showed an overall reduction over 3 years. Mean ± SD Toronto Western Spasmodic Rating Scale (TWSTRS) Total scores (clinician assessed at end of treatment cycle) decreased from 31.59 ± 13.04 at baseline to 24.49 ± 12.43 at 3 years (mean ± SD reduction from baseline of − 6.97 ± 11.56 points). Tsui scale scores also showed gradual improvement; the percent of subjects with a tremor component score of 4 reduced from 12.4% at baseline to 8.1% at 3 years. Conclusions Despite objective clinical improvements over 3 years, subject satisfaction with symptom control remained relatively constant, indicating that factors other than symptom control also play a role in patient satisfaction.

Published
2019

11. Identification of symbol digit modality test score extremes in Huntington's disease

Author

Braisch, U, Muche, R, Rothenbacher, D, Landwehrmeyer, GB, Long, JD, Bentivoglio, AR, Biunno, I, Bonelli, RM, Dunnett, SB, Illmann, T, Levey, J, Ramos-Arroyo, M, Nielsen, JE, Paivarinta, M, Sebastian, AR, Tabrizi, SJ, Vandenberghe, W, Uhrova, T, Come, A, Garde, MB, Betz, S, Capodarca, S, Wildson, SC, da Silva, V, Di Renzo, M, Finisterra, M, Genoves, C, Gilling, M, Handley, OJ, Hvalstedt, C, Koppers, K, Lamanna, C, Laura, M, Descals, AM, Monza, D, Mutze, L, Oehmen, M, Padieu, H, Paterski, L, Koivisto, SP, Rindal, B, Roren, N, Sasinkova, P, Seliverstov, Y, Timewell, E, Cubillo, PT, van Walsem, MR, Witjes-Ane, MN, Yudina, E, Zielonka, E, Zinzi, P, Braunwarth, EM, Brugger, F, Buratti, L, Hametner, EM, Hepperger, C, Holas, C, Hotter, A, Hussl, A, Larcher, B, Mahlknecht, P, Muller, C, Pinter, B, Poewe, W, Seppi, K, Sprenger, F, Wenning, G, Dupuis, M, Minet, C, Ribai, P, Van Paemel, D, Verellen-Dumoulin, C, Klempir, J, Majerova, V, Roth, J, Babiloni, B, Debruxelles, S, Duche, C, Goizet, C, Jameau, L, Lafoucriere, D, Spampinato, U, Bachoud-Levi, AC, Boisse, MF, de Langavant, LC, Lemoine, L, Morgado, G, Youssov, K, Annic, A, Barthelemy, R, De Bruycker, C, Cabaret, M, Carette, AS, Carriere, N, Decorte, E, Defebvre, L, Delliaux, M, Delval, A, Depelchin, A, Destee, A, Dewulf-Pasz, N, Dondaine, T, Dugauquier, F, Dujardin, K, Lemaire, MH, Manouvrier, S, Peter, M, Plomhause, L, Sablonniere, B, Simonin, C, Tard, C, Thibault-Tanchou, S, Vuillaume, I, Bellonet, M, Benoit, A, Blin, S, Courtin, F, Duru, C, Fasquel, V, Godefroy, O, Krystkowiak, P, Mantaux, B, Roussel, M, Tir, M, Schuler, B, Wannepain, S, Azulay, JP, Chabot, C, Delfini, M, Eusebio, A, Fluchere, F, Grosjean, H, Mundler, L, Nowak, M, Bioux, S, Bliaux, E, Girard, C, Guyant-Marechal, L, Hannequin, D, Hannier, V, Jourdain, S, Maltete, D, Pouliquen, D, Blondeau, L, Calvas, F, Cheriet, S, Delabaere, H, Demonet, JF, Pariente, J, Pierre, M, Beuth, M, Gelderblom, H, Priller, J, Pruss, H, Spruth, E, Thiel, S, Ellrichmannberlin, G, Herrmann, L, Hoffmann, R, Kaminski, B, Saft, C, Bosredon, C, Hunger, U, Lohle, M, Maass, A, Ossig, C, Schmidt, S, Storch, A, Wolz, A, Wolz, M, Kohl, Z, Kozay, C, Ullah, J, Winkler, J, Bergmann, U, Boringer, R, Capetian, P, Kammel, G, Lambeck, J, Meier, S, Rijntjes, M, Zucker, B, Boelmans, K, Ganos, C, Goerendt, I, Heinicke, W, Hidding, U, Munchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Diercks, G, Dressler, D, Francis, F, Gayde-Stephan, S, Gorzolla, H, Kramer, B, Minschke, R, Schrader, C, Tacik, P, Longinus, B, Lusebrink, A, Muhlau, M, Peinemann, A, Stadtler, M, Weindl, A, Winkelmann, J, Ziegler, C, Bechtel, N, Beckmann, H, Bohlen, S, Gopfert, N, Holzner, E, Lange, H, Reilmann, R, Rohm, S, Rumpf, S, Sass, C, Schepers, S, Weber, N, Barth, K, Buck, A, Connemann, J, Ecker, D, Geitner, C, Held, C, Kesse, A, Landwehrmeyer, B, Lezius, F, Lewerenz, J, Nepper, S, Niess, A, Orth, M, Schneider, A, Schwenk, D, Sussmuth, S, Trautmann, S, Weydt, P, Klebe, S, Musacchio, T, Leypold, C, Noth, K, Cormio, C, de Tommaso, M, Franco, G, Sciruicchio, V, Serpino, C, Calandra-Buonaura, G, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Sambati, L, Scaglione, C, Maserati, MS, Agosti, C, Barlati, S, Compostella, S, Marchina, E, Padovani, A, Bertini, E, Ghelli, E, Ginestroni, A, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, AM, Sorbi, S, Abbruzzese, G, di Poggio, MB, Ferrandes, G, Mandich, P, Marchese, R, Tamburini, T, Baake, V, van den Bogaard, SJA, Bos, R, Dumas, EM, t'Hart, EP, Kampstra, A, Roos, RAC, Schoonderbeek, A, Aaserud, O, Bjorgo, K, Borgeod, N, Dramstad, E, Fannemel, M, Frich, JC, Gorvell, PF, Heiberg, A, Lorentzen, E, Retterstol, L, Rosby, O, Sikiric, A, Stokke, B, van Walsem, M, Wehus, R, Bjornevoll, I, Sando, SB, Haug, MG, Storseth, HH, Arntsen, V, Dziadkiewicz, A, Konkel, A, Narozanska, E, Robowski, P, Sitek, E, Slawek, J, Soltan, W, Szinwelski, M, Arkuszewski, M, Blaszczyk, M, Boczarska-Jedynak, M, Ciach-Wysocka, E, Gorzkowska, A, Nska-Myga, BJ, Kaczmarczyk, A, Klodowska-Duda, G, Opala, G, Stompel, D, Banaszkiewicz, K, Bocwinska, D, Bojakowska-Jaremek, K, Dec, M, Grabska, N, Krawczyk, GM, Kubowicz, E, Malec-Litwinowicz, M, Rudzinska, M, Stenwak, A, Szczudlik, A, Szczygiel, E, Wojcik, M, Wasielewska, A, Bryl, JAA, Ciesielska, A, Klimberg, A, Marcinkowski, J, Samara, H, Sempolowicz, J, Sniewski, BW, Zielonka, D, Gogol, A, Janik, P, Jamrozik, Z, Kaminska, A, Kwiecinski, H, Antczak, J, Jachinska, K, Krysa, W, Rakowicz, M, Richter, P, Rola, R, Ryglewicz, D, Sienkiewicz-Jarosz, H, Stepniak, I, Sulek, A, Witkowski, G, Zaremba, J, Zdzienicka, E, Ziora-Jakutowicz, K, Januario, C, Julio, F, Guedes, LC, Coelho, M, Finisterra, AM, Ferreira, JJ, Mestre, T, Mendes, T, Rosa, MM, Valadas, A, Kopishinskaya, S, Korotysh, M, Herrera, CD, Moreno, PG, Bas, J, Busquets, N, Calopa, M, Classen, SJ, Dedicha, NR, Buongiorno, MT, Maria, ADS, Munoz, E, Santacruz, P, Barbera, MA, Pardo, SA, Guia, DB, Calzado, N, Hernanz, LC, Diaz-Zorita, JPT, Catena, JL, Ferrer, PQ, Carruesco, GT, Robert, MF, Viladrich, CM, Roca, E, Idiago, JMR, Riballo, AV, Campolongo, A, de Bobadilla, RF, Bojarsky, JK, Martinez-Horta, S, Pagonabarraga, J, Perez, JP, Ribosa, R, Villa, C, Gil, MAA, Corrales, KB, Esteban, JCG, Gonzalez, A, Merino, BT, Cubo, E, Polo, CG, Mariscal, N, Romero, SG, Arbelo, JM, de Molina, RM, Martin, I, Perianez, JM, Udaeta, B, Alonso-Frech, F, Frades, B, Villanueva, MA, Sevilla, MAZ, Frech, FA, Fenollar, MD, Garcia, RGR, Villanueva, C, Bascunana, M, Ventura, MF, Ribas, GG, de Yebenes, JG, Moreno, JLLS, Barral, VM, Ruiz, PJG, Garcia, A, Lopez, RG, Barcenas, AH, Martinez-Descals, A, Martin, VP, Martinez, NR, Artiga, MJS, Sanchez, V, Pueyo, A, Gonzalez, S, Guisasola, LM, Ribacoba, MPPR, Salvador, C, Lozano, PS, Caldentey, JG, Ramirez, IL, Arques, PN, Lopera, MR, Pastor, BV, Gaston, I, Garcia-Amigot, F, Martinez-Jaurrieta, MD, Ramos-Arroyo, MA, Carrillo, F, Redondo, MTC, Mir, P, Gonzalez, LV, Moreno, JMG, Lucena, CM, Pena, JC, Redondo, L, Sanchez, VS, Fernandez, CM, Mata, MP, Lemos, MDR, Bosca, M, Burguera, JA, Vilaplana, FCBCP, Solis, P, Figuerola, BJ, Palanca, PM, Berglund, P, Constantinescu, R, Fredlund, G, Hosterey-Ugander, U, Linnsand, P, Neleborn-Lingefjard, L, Wahlstrom, J, Palhagen, S, Svenningsson, P, Paucar, M, Wallden, T, Ekwall, C, Goller, ML, Sundblom, J, Stebler, Y, Kaelin, A, Romero, I, Schupbach, M, Zaugg, SW, Jung, H, Petersen, J, Auer, M, Mihaylova, V, Vernon, N, Akhtar, S, Crooks, J, Curtis, A, de Souza, J, Piedad, J, Rickards, H, Wright, J, Pallett, A, Coulthard, E, Gethin, L, Hayward, B, Sieradzan, K, Wright, A, Busse, M, Butcher, C, Dunnett, S, Clenaghan, C, Hunt, S, Jones, L, Jones, U, Khalil, H, Minster, S, Owen, M, Price, K, Townhill, J, Rosser, A, Edwards, M, Ho, C, McGill, M, Porteous, M, Pearson, P, Harrower, T, Irvine, S, Brockie, P, Foster, J, Johns, N, McKenzie, S, Rothery, J, Thomas, G, Yates, S, Deith, C, Ireland, J, Ritchie, S, Andrew, A, Frost, J, Noad, R, Cosgrove, J, Gallantree, D, Hamer, S, Hobson, E, Jamieson, S, Kraus, A, Longthorpe, M, Markova, I, Musgrave, H, Peacy, C, Raman, A, Rowett, L, Toscano, J, Wild, S, Yardumian, P, Clayton, C, Dipple, H, Freire-Patino, D, Hallam, C, Middleton, J, Alusi, S, Davies, R, Foy, K, Gerrans, E, Leggett, H, Pate, L, Anjum, U, Coebergh, J, Eddy, C, McEntagart, M, Patton, M, Peterson, M, Rose, S, Andrews, T, Brown, S, Bruno, S, Doherty, K, Golding, C, Haider, S, Hensman, D, Lahiri, N, Lewis, M, Novak, M, Patel, A, Robertson, N, Rosser, E, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Arran, N, Bek, J, Callaghan, J, Craufurd, D, Fullam, R, Howard, L, Huson, S, Johnson, L, Jones, M, Krishnamoorthy, A, Murphy, H, Oughton, E, Partington-Jones, L, Rogers, D, Sollom, A, Snowden, J, Stopford, C, Thompson, J, Tinkler, P, Trender-Gerhard, I, Verstraelen, N, Westmoreland, L, Cass, G, Davidson, L, Davison, J, Fullerton, N, Holmes, K, Komati, S, McDonnell, S, Mohammed, Z, Morgan, K, Savage, L, Singh, B, Wood, J, Chu, E, Knight, C, O'Neill, M, Das Purkayastha, D, Nemeth, AH, Siuda, G, Valentine, R, Dixon, K, Armstrong, R, Harrison, D, Hughes, M, Large, S, Donovan, JO, Palmer, A, Parkinson, A, Soltysiak, B, Timings, L, Williams, J, Burn, J, Weekes, R, Craven, J, Bailey, W, Coleman, C, Haig-Brown, D, Simpson, S, Hare, M, Majeed, T, Bandmann, O, Bradbury, A, Fairtlough, H, Fillingham, K, Foustanos, I, Gill, P, Kazoka, M, Nevitt, L, Peppa, N, Quarrell, O, Taylor, C, Tidswell, K, O'Donovan, K, Agarwal, V, Anderson, M, Gunner, K, Harris, K, Hayward, E, Heywood, M, Keys, L, Kipps, C, MacKinnon, L, Smalley, S, Gowers, L, Powell, K, Bethwaite, P, Edwards, R, Fuller, K, Phillips, M, Tan, L, Burgunder, JM, Lau, PN, Pica, E, Shoulson, I, Gusella, JG, Antonijevic, I, vankammen, D, Foroud, T, Warner, J, Giuliano, J, Vetter, L, Marshall, F, Marder, K, Frucht, S, Moskowitz, C, Clouse, R, Wasserman, P, Shannon, K, Jaglin, J, Jankovic, J, Palao, A, Harrison, M, Singer, C, Quesada, M, Hersch, S, Rosas, D, Tanev, K, Malarick, K, Colcher, A, Sanchez-Ramos, J, Kostyk, S, Paulsen, J, Perlmutter, J, Tabbal, S, Ross, C, Dorsey, R, Nucifora, F, Dubinsky, R, Dubinsky, H, Suchowersky, O, Klimek, ML, Jones, R, Morgan, J, Mohlo, E, Kang, U, Agarwal, P, Factor, S, Jennings, D, Higgins, D, Adams, J, Frank, S, Saint-Hilaire, M, Diggin, M, Furtado, S, Walker, F, O'Neill, C, Quaid, K, LeDoux, M, Raymond, L, Leavitt, B, Decolongon, J, Perlman, S, Peavy, G, Goldstein, J, Kumar, R, McCusker, E, Griffith, J, Loy, C, Wheelock, V, Tempkin, T, Martin, A, Nance, M, Mallonee, W, Suter, G, Revilla, F, Gartner, M, Drazinic, C, Fitzpatrick, MJ, Panisset, M, Duff, K, Scott, B, Weiner, W, Robottom, B, Chiu, E, Yastrubetskaya, O, Churchyard, A, Greenamyre, TJ, Oakes, D, Beck, C, Robertson, S, Eaton, K, Lindsay, P, Deuel, L, MacDonald, M, Hickey, C, Muratori, L, Leserman, A, Doucette, N, Uc, E, Rodnitzky, R, Vik, S, Davis, R, Dietrich, S, Segro, V, Erickson, D, Hunt, V, Lucarelli, N, Broyles, J, Delarosa, J, Louis, E, Panegyres, P, Schmidt, A, Barton, S, Sperin, E, Testa, C, Thiede, F, Zauber, SE, McInnis, R, Welsh, C, Wesson, M, Coleman, A, and European Commission

Subjects
Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, COHORT, Cox hazard model, quantile regression, REGISTRY, symbol digit modalities test, Genotype, Neuropsychological Tests, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cognition, 0302 clinical medicine, Huntington's disease, Rating scale, mental disorders, medicine, Humans, Verbal fluency test, Longitudinal Studies, Genetics (clinical), Proportional Hazards Models, 030304 developmental biology, 0303 health sciences, Proportional hazards model, business.industry, Reproducibility of Results, Middle Aged, medicine.disease, nervous system diseases, Psychiatry and Mental health, Huntington Disease, Phenotype, Test score, Cohort, Disease Progression, Female, Observational study, business, 030217 neurology & neurosurgery, Stroop effect, Clinical psychology
Abstract

REGISTRY Investigators of the European Huntington's Disease Network and COHORT Investigators of the Huntington Study Group., Studying individuals with extreme phenotypes could facilitate the understanding of disease modification by genetic or environmental factors. Our aim was to identify Huntington's disease (HD) patients with extreme symbol digit modality test (SDMT) scores. We first examined in HD the contribution of cognitive measures of the Unified Huntington's Disease Rating Scale (UHDRS) in predicting clinical endpoints. The language-independent SDMT was used to identify patients performing very well or very poorly relative to their CAG and age cohort. We used data from REGISTRY and COHORT observational study participants (5,603 HD participants with CAG repeats above 39 with 13,868 visits) and of 1,006 healthy volunteers (with 2,241 visits), included to identify natural aging and education effects on cognitive measures. Separate Cox proportional hazards models with CAG, age at study entry, education, sex, UHDRS total motor score and cognitive (SDMT, verbal fluency, Stroop tests) scores as covariates were used to predict clinical endpoints. Quantile regression for longitudinal language-independent SDMT data was used for boundary (2.5% and 97.5% quantiles) estimation and extreme score analyses stratified by age, education, and CAG repeat length. Ten percent of HD participants had an extreme SDMT phenotype for at least one visit. In contrast, only about 3% of participants were consistent SDMT extremes at two or more visits. The thresholds for the one-visit and two-visit extremes can be used to classify existing and new individuals. The identification of these phenotype extremes can be useful in the search for disease modifiers., This work was in part funded by a grant from the EuropeanCommission under the 7th framework programme (RD-Connect, grantagreement number 305444).

Published
2019

12. Outcome of cell suspension allografts in a patient with\ud Huntington’s disease

Author

Maxan, A., Mason, S., Saint-Pierre, M., Smith, E., Ho, Aileen, Harrower, T., Watts, C., Tai, Y., Pavese, N., Savage, J. C., Tremblay, M-E, Gould, P., Rosser, A. E., Dunnett, S. B., Piccini, P, Barker, R. A., and Cicchetti, F.

Subjects
surgical procedures, operative
Abstract

For patients with incurable neurodegenerative disorders\ud such as Huntington’s (HD) and Parkinson’s disease,\ud cell transplantation has been explored as a potential\ud treatment option. Here, we present the first clinicopathological study of a patient with HD in receipt of\ud cell-suspension striatal allografts who took part in the\ud NEST-UK multicenter clinical transplantation trial. Using\ud various immunohistochemical techniques, we found a\ud discrepancy in the survival of grafted projection neurons\ud with respect to grafted interneurons as well as\ud major ongoing inflammatory and immune responses to\ud the grafted tissue with evidence of mutant huntingtin\ud aggregates within the transplant area. Our results indicate\ud that grafts can survive more than a decade posttransplantation,\ud but show compromised survival with\ud inflammation and mutant protein being observed\ud within the transplant site.

Published
2018

18. Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY

Author

Orth, M, Handley, Oj, Schwenke, C, Dunnett, S, Wild, Ej, Tabrizi, Sj, Landwehrmeyer, Gb, Bachoud Lévi AC, Bentivoglio, Ar, Biunno, I, Bonelli, R, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Giuliano, J, Heiberg, A, Illmann, T, van Kammen, D, Landwehrmeye, Gb, Levey, J, Nielsen, Je, Päivärinta, M, Roos, Ra, Sebastián, Ar, Vandenberghe, W, Verellen Dumoulin, C, Zaremba, J, Uhrova, T, Wahlström, J, Wallner, M, Barth, K, Guedes, Lc, Finisterra, Am, Garde, Mb, Bos, R, Burg, S, Ecker, D, Held, C, Koppers, K, Laurà, M, Descals, Am, Mclean, T, Mestre, T, Minster, S, Monza, D, Townhill, J, Padieu, H, Paterski, L, Peppa, N, Koivisto, Sp, Rialland, A, Røren, N, Sasinková, P, Cubillo, Pt, Tritsch, C, van Walsem MR, Witjes Ané MN, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Bonelli, Rm, Herranhof, B, Holl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinger, K, Scheibl, M, Hecht, K, Lilek, S, Müller, N, Schöggl, H, Ullah, J, Brugger, F, Hepperger, C, Hotter, A, Mahlknecht, P, Nocker, M, Seppi, K, Wenning, G, Buratti, L, Hametner, Em, Holas, C, Hussl, A, Mair, K, Poewe, W, Wolf, E, Zangerl, A, Braunwarth, Em, Sinadinosa, D, Walleczek, Am, Ladurner, G, Staffen, W, Ribaï, P, Flamez, A, Morez, V, de Raedt, S, Boogaerts, A, van Reijen, D, Klempíř, J, Kucharík, M, Roth, J, Šenkárová, Z, Hasholt, L, Hjermind, Le, Jakobsen, O, Nørremølle, A, Sørensen, Sa, Stokholm, J, Nielsen, J, Hiivola, H, Martikainen, K, Tuuha, K, Peippo, M, Sipponen, M, Ignatius, J, Kärppä, M, Åman, J, Santala, M, Allain, P, Guérid, Ma, Gohier, B, Olivier, A, Prundean, A, Scherer Gagou, C, Verny, C, Babiloni, B, Debruxelles, S, Goizet, C, Lafoucrière, D, De Bruycker, C, Carette, As, Decorte, E, Delval, A, Delliaux, M, Dujardin, K, Peter, M, Plomhouse, L, Simonin, C, Thibault Tanchou, S, Bellonet, M, Duru, C, Krystkowiak, P, Roussel, M, Wannepain, S, Azulay, Jp, Chabot, C, Delphini, M, Eusebio, A, Grosjean, H, Mundler, L, Nowak, M, Rudolf, G, Steinmetz, G, Tranchant, C, Wagner, C, Zimmermann, Ma, Calvas, F, Cheriet, S, Démonet, Jf, Galitzky, M, Kosinski, Cm, Milkereit, E, Probst, D, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Gelderblom, H, Priller, J, Prüss, H, Spruth, Ej, Andrich, J, Hoffmann, R, Kraus, Ph, Muth, S, Prehn, C, Saft, C, Salmen, S, Stamm, C, Steiner, T, Strassburger, K, Lange, H, Friedrich, A, Hunger, U, Löhle, M, Schmidt, S, Storch, A, Wolz, A, Wolz, M, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Hidding, U, Lewerenz, J, Münchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Diercks, G, Gorzolla, H, Schrader, C, Heinicke, W, Ribbat, M, Longinus, B, Bürk, K, Möller, Jc, Rissling, I, Peinemann, A, Städtler, M, Weindl, A, Bechtel, N, Beckmann, H, Bohlen, S, Hölzner, E, Reilmann, R, Rohm, S, Rumpf, S, Schepers, S, Beister, A, Dose, M, Hammer, K, Kieni, J, Leythaeuser, G, Marquard, R, Raab, T, Richter, S, Selimbegovic Turkovic, A, Schrenk, C, Schuierer, M, Wiedemann, A, Buck, A, Connemann, J, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Süssmuth, S, Trautmann, S, Weydt, P, Cormio, C, Difruscolo, O, Sciruicchio, V, Serpino, C, de Tommaso, M, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Rizzo, G, Scaglione, C, Bertini, E, Ghelli, E, Ginestroni, A, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, di Poggio MB, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Albanese, A, Di Bella, D, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Paridi, D, Soliveri, P, Tomasello, C, De Michele, G, Di Maio, L, Rinaldi, C, Russo, Cv, Salvatore, E, Tucci, T, Cannella, M, Codella, V, De Gregorio, F, De Nicola, N, Martino, T, Simonelli, M, Squitieri, F, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Modoni, A, Piano, C, Chiara, P, Quaranta, D, Romano, Silvia, Soleti, F, Spadaro, M, van Hout MS, van Vugt JP, de Weert AM, Bolwijn, Jj, Dekker, M, Leenders, Kl, van Oostrom JC, Dumas, Em, Jurgens, Ck, van den Bogaard SJ, 't Hart EP, Kremer, B, Verstappen, Cc, Frich, J, Wehus, R, Aaserud, O, Borgerød, N, Bjørgo, K, Fannemel, M, Gørvell, P, Pro Koivisto, S, Retterstøl, L, Overland, T, Stokke, B, Bjørnevoll, I, Sando, Sb, Blinkenberg, Eø, Hauge, E, Tyvoll, H, Sitek, E, Slawek, J, Soltan, W, Boczarska Jedynak, M, Jasinska Myga, B, Opala, G, Kłodowska Duda, G, Banaszkiewicz, K, Szczudlik, A, Rudzińska, M, Wójcik, M, Dec, M, Krawczyk, M, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Sempołowicz, J, Samara, H, Janik, P, Kalbarczyk, A, Kwiecinski, H, Jamrozik, Z, Antczak, J, Jachinska, K, Rakowicz, M, Richter, P, Ryglewicz, D, Witkowski, G, Zdzienicka, E, Sułek, A, Krysa, W, Júlio, F, Januário, C, Guedes, L, Coelho, M, Mendes, T, Valadas, A, Timóteo, Â, Costa, C, Vale, J, Cavaco, S, Damásio, J, Magalhães, M, Gago, M, Garrett, C, Guerra, Mr, Solis, P, Herrera, Cd, Garcia, Pm, Barrero, F, Morales, B, Cubo, E, Mariscal, N, Alonso Frech, F, Perez, Mr, Fenollar, M, García, Rg, Quiroga, Pp, Rivera, Sv, Villanueva, C, Bascuñana, M, Ventura, Mf, Ribas, Gg, de Yébenes JG, Moreno, Jl, Ruíz, Pj, Martínez Descals, A, Artiga, Mj, Sánchez, V, Perea, Mf, Lorenza, F, Torres, Mm, Reinante, G, Moreau, Lv, Barbera, Ma, Guia, Db, Hernanz, Lc, Catena, Jl, Ferrer, Pq, Carruesco, Gt, Bas, J, Busquets, N, Calopa, M, Buongiorno, Mt, Muñoz, E, Elorza, Md, López, Cd, Terol, Sd, Robert, Mf, Ruíz, Bg, Casado, Ag, Martínez, Ih, Viladrich, Cm, Càrdenas R, Pons i., Roca, E, Llesoy, Jr, Idiago, Jm, Vergara, Mr, García, Ss, Villa Riballo, A, González, Sg, Guisasola, Lm, Salvador, C, San Martín ES, Gorospe, A, Legarda, I, Arques, Pn, Rodríguez, Mj, Vives, B, Gaston, I, Ramos Arroyo MA, Moreno, Jm, Peña, Jc, Avarvarei, Ld, Bastida, Am, Recio, Mf, Vergé, Lr, Sánchez, Vs, Carrillo, F, Cáceres, Mt, Mir, P, Suarez, Mj, Bosca, M, Burguera, Ja, Garcia, Ac, Martínez, Lm, del Val JL, Loutfi, G, Olofsson, C, Stattin, El, Westman, L, Wikström, B, Höglund, A, Pålhagen, Se, Paucar, M, Sandström, B, Soltani, R, Svenningsson, P, Reza Soltani TW, Constantinescu, R, Fredlund, G, Høsterey Ugander, U, Neleborn Lingefjärd, L, Esmaeilzadeh, M, Tedroff, J, Winnberg, E, Björn, Y, Ekwall, C, Gøller, Ml, Johansson, A, Wiklund, L, Petersen, Å, Reimer, J, Widner, H, Burgunder, Y, Stebler, Y, Kaelin, A, Romero, I, Schüpbach, M, Zaugg, Sw, Jack, R, Matheson, K, Miedzybrodzka, Z, Rae, D, Simpson, S, Summers, F, Ure, A, Crooks, J, Curtis, A, de Souza Keylock, J, Rickards, H, Wright, J, Hayward, B, Sieradzan, K, Wright, A, Barker, Ra, Di Pietro, A, Fisher, K, Goodman, A, Hill, S, Kershaw, A, Mason, S, Paterson, N, Raymond, L, Bisson, J, Busse, M, Clenaghan, C, Ellison Rose, L, Handley, O, Hunt, S, Price, K, Rosser, A, Edwards, M, Hughes, T, Mcgill, M, Pearson, P, Porteous, M, Smith, P, Zeman, A, Causley, A, Harrower, T, Howcroft, D, Lambord, N, Rankin, J, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Miller, J, Ritchie, S, Burrows, L, Fletcher, A, Harding, A, Laver, F, Silva, M, Thomson, A, Burns, P, Chu, C, Evans, C, Hamer, S, Markova, I, Raman, A, Barnes, K, Hobson, E, Jamieson, S, Thomson, J, Toscano, J, Wild, S, Yardumian, P, Bourne, C, Clayton, C, Dipple, H, Clapton, J, Grant, D, Hallam, C, Middleton, J, Murch, A, Patino, D, Bate, L, Pate, L, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Patton, M, Peterson, M, Rose, S, Bruno, S, Chu, E, Doherty, K, Henley, S, Lahiri, N, Novak, M, Patel, A, Read, J, Rosser, E, Say, M, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Arran, N, Callaghan, J, Craufurd, D, Fullam, R, Howard, L, Huson, S, Oughton, E, Partington Jones, L, Snowden, J, Sollom, A, Stopford, C, Thompson, J, Trender Gerhad, I, Verstraelen, N, Westmoreland, L, Nemeth, Ah, Siuda, G, Harrison, D, Hughes, M, Parkinson, A, Soltysiak, B, Burn, J, Coleman, C, Majeed, T, Verstraelen Ritchie, N, Bandmann, O, Bradbury, A, Gill, P, Fairtlough, H, Fillingham, K, Foustanos, I, O'Donovan, K, Tidswell, K, Quarrell, O., Orth, M, European Huntington's Disease, Network, Handley, Oj, Schwenke, C, Dunnett, S, Wild, Ej, Tabrizi, Sj, Bachoud Lévi AC, Landwehrmeyer G. B., Bentivoglio, Ar, Biunno, I, Bonelli, R, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Giuliano, J, Heiberg, A, Illmann, T, van Kammen, D, Landwehrmeye, Gb, Levey, J, Nielsen, Je, Päivärinta, M, Roos, Ra, Sebastián, Ar, Vandenberghe, W, Verellen Dumoulin, C, Zaremba, J, Uhrova, T, Wahlström, J, Wallner, M, Barth, K, Guedes, Lc, Finisterra, Am, Garde, Mb, Bos, R, Burg, S, Ecker, D, Held, C, Koppers, K, Laurà, M, Descals, Am, Mclean, T, Mestre, T, Minster, S, Monza, D, Townhill, J, Padieu, H, Paterski, L, Peppa, N, Koivisto, Sp, Rialland, A, Røren, N, Sasinková, P, Cubillo, Pt, Tritsch, C, van Walsem, Mr, Witjes Ané, Mn, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Bonelli, Rm, Herranhof, B, Holl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinger, K, Scheibl, M, Hecht, K, Lilek, S, Müller, N, Schöggl, H, Ullah, J, Brugger, F, Hepperger, C, Hotter, A, Mahlknecht, P, Nocker, M, Seppi, K, Wenning, G, Buratti, L, Hametner, Em, Holas, C, Hussl, A, Mair, K, Poewe, W, Wolf, E, Zangerl, A, Braunwarth, Em, Sinadinosa, D, Walleczek, Am, Ladurner, G, Staffen, W, Ribaï, P, Flamez, A, Morez, V, de Raedt, S, Boogaerts, A, van Reijen, D, Klempíř, J, Kucharík, M, Roth, J, Šenkárová, Z, Hasholt, L, Hjermind, Le, Jakobsen, O, Nørremølle, A, Sørensen, Sa, Stokholm, J, Nielsen, J, Hiivola, H, Martikainen, K, Tuuha, K, Peippo, M, Sipponen, M, Ignatius, J, Kärppä, M, Åman, J, Santala, M, Allain, P, Guérid, Ma, Gohier, B, Olivier, A, Prundean, A, Scherer Gagou, C, Verny, C, Babiloni, B, Debruxelles, S, Goizet, C, Lafoucrière, D, De Bruycker, C, Carette, A, Decorte, E, Delval, A, Delliaux, M, Dujardin, K, Peter, M, Plomhouse, L, Simonin, C, Thibault Tanchou, S, Bellonet, M, Duru, C, Krystkowiak, P, Roussel, M, Wannepain, S, Azulay, Jp, Chabot, C, Delphini, M, Eusebio, A, Grosjean, H, Mundler, L, Nowak, M, Rudolf, G, Steinmetz, G, Tranchant, C, Wagner, C, Zimmermann, Ma, Calvas, F, Cheriet, S, Démonet, Jf, Galitzky, M, Kosinski, Cm, Milkereit, E, Probst, D, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Gelderblom, H, Priller, J, Prüss, H, Spruth, Ej, Andrich, J, Hoffmann, R, Kraus, Ph, Muth, S, Prehn, C, Saft, C, Salmen, S, Stamm, C, Steiner, T, Strassburger, K, Lange, H, Friedrich, A, Hunger, U, Löhle, M, Schmidt, S, Storch, A, Wolz, A, Wolz, M, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Hidding, U, Lewerenz, J, Münchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Diercks, G, Gorzolla, H, Schrader, C, Heinicke, W, Ribbat, M, Longinus, B, Bürk, K, Möller, Jc, Rissling, I, Peinemann, A, Städtler, M, Weindl, A, Bechtel, N, Beckmann, H, Bohlen, S, Hölzner, E, Reilmann, R, Rohm, S, Rumpf, S, Schepers, S, Beister, A, Dose, M, Hammer, K, Kieni, J, Leythaeuser, G, Marquard, R, Raab, T, Richter, S, Selimbegovic Turkovic, A, Schrenk, C, Schuierer, M, Wiedemann, A, Buck, A, Connemann, J, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Süssmuth, S, Trautmann, S, Weydt, P, Cormio, C, Difruscolo, O, Sciruicchio, V, Serpino, C, de Tommaso, M, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Rizzo, G, Scaglione, C, Bertini, E, Ghelli, E, Ginestroni, A, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, di Poggio, Mb, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Albanese, A, Di Bella, D, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Paridi, D, Soliveri, P, Tomasello, C, DE MICHELE, Giuseppe, Di Maio, L, Rinaldi, Carlo, Russo, Cv, Salvatore, Elena, Tucci, T, Cannella, M, Codella, V, De Gregorio, F, De Nicola, N, Martino, T, Simonelli, M, Squitieri, F, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Modoni, A, Piano, C, Chiara, P, Quaranta, D, Romano, S, Soleti, F, Spadaro, M, van Hout, M, van Vugt, Jp, de Weert, Am, Bolwijn, Jj, Dekker, M, Leenders, Kl, van Oostrom, Jc, Dumas, Em, Jurgens, Ck, van den Bogaard, Sj, 't Hart, Ep, Kremer, B, Verstappen, Cc, Frich, J, Wehus, R, Aaserud, O, Borgerød, N, Bjørgo, K, Fannemel, M, Gørvell, P, Pro Koivisto, S, Retterstøl, L, Overland, T, Stokke, B, Bjørnevoll, I, Sando, Sb, Blinkenberg, Eø, Hauge, E, Tyvoll, H, Sitek, E, Slawek, J, Soltan, W, Boczarska Jedynak, M, Jasinska Myga, B, Opala, G, Kłodowska Duda, G, Banaszkiewicz, K, Szczudlik, A, Rudzińska, M, Wójcik, M, Dec, M, Krawczyk, M, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Sempołowicz, J, Samara, H, Janik, P, Kalbarczyk, A, Kwiecinski, H, Jamrozik, Z, Antczak, J, Jachinska, K, Rakowicz, M, Richter, P, Ryglewicz, D, Witkowski, G, Zdzienicka, E, Sułek, A, Krysa, W, Júlio, F, Januário, C, Guedes, L, Coelho, M, Mendes, T, Valadas, A, Timóteo, Â, Costa, C, Vale, J, Cavaco, S, Damásio, J, Magalhães, M, Gago, M, Garrett, C, Guerra, Mr, Solis, P, Herrera, Cd, Garcia, Pm, Barrero, F, Morales, B, Cubo, E, Mariscal, N, Alonso Frech, F, Perez, Mr, Fenollar, M, García, Rg, Quiroga, Pp, Rivera, Sv, Villanueva, C, Bascuñana, M, Ventura, Mf, Ribas, Gg, de Yébenes, Jg, Moreno, Jl, Ruíz, Pj, Martínez Descals, A, Artiga, Mj, Sánchez, V, Perea, Mf, Lorenza, F, Torres, Mm, Reinante, G, Moreau, Lv, Barbera, Ma, Guia, Db, Hernanz, Lc, Catena, Jl, Ferrer, Pq, Carruesco, Gt, Bas, J, Busquets, N, Calopa, M, Buongiorno, Mt, Muñoz, E, Elorza, Md, López, Cd, Terol, Sd, Robert, Mf, Ruíz, Bg, Casado, Ag, Martínez, Ih, Viladrich, Cm, Pons i., Càrdenas R, Roca, E, Llesoy, Jr, Idiago, Jm, Vergara, Mr, García, S, Villa Riballo, A, González, Sg, Guisasola, Lm, Salvador, C, San Martín, E, Gorospe, A, Legarda, I, Arques, Pn, Rodríguez, Mj, Vives, B, Gaston, I, Ramos Arroyo, Ma, Moreno, Jm, Peña, Jc, Avarvarei, Ld, Bastida, Am, Recio, Mf, Vergé, Lr, Carrillo, F, Cáceres, Mt, Mir, P, Suarez, Mj, Bosca, M, Burguera, Ja, Garcia, Ac, Martínez, Lm, del Val, Jl, Loutfi, G, Olofsson, C, Stattin, El, Westman, L, Wikström, B, Höglund, A, Pålhagen, Se, Paucar, M, Sandström, B, Soltani, R, Svenningsson, P, Reza Soltani, Tw, Constantinescu, R, Fredlund, G, Høsterey Ugander, U, Neleborn Lingefjärd, L, Esmaeilzadeh, M, Tedroff, J, Winnberg, E, Björn, Y, Ekwall, C, Gøller, Ml, Johansson, A, Wiklund, L, Petersen, Å, Reimer, J, Widner, H, Burgunder, Y, Stebler, Y, Kaelin, A, Romero, I, Schüpbach, M, Zaugg, Sw, Jack, R, Matheson, K, Miedzybrodzka, Z, Rae, D, Simpson, S, Summers, F, Ure, A, Crooks, J, Curtis, A, de Souza Keylock, J, Rickards, H, Wright, J, Hayward, B, Sieradzan, K, Wright, A, Barker, Ra, Di Pietro, A, Fisher, K, Goodman, A, Hill, S, Kershaw, A, Mason, S, Paterson, N, Raymond, L, Bisson, J, Busse, M, Clenaghan, C, Ellison Rose, L, Handley, O, Hunt, S, Price, K, Rosser, A, Edwards, M, Hughes, T, Mcgill, M, Pearson, P, Porteous, M, Smith, P, Zeman, A, Causley, A, Harrower, T, Howcroft, D, Lambord, N, Rankin, J, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Miller, J, Ritchie, S, Burrows, L, Fletcher, A, Harding, A, Laver, F, Silva, M, Thomson, A, Burns, P, Chu, C, Evans, C, Hamer, S, Markova, I, Raman, A, Barnes, K, Hobson, E, Jamieson, S, Thomson, J, Toscano, J, Wild, S, Yardumian, P, Bourne, C, Clayton, C, Dipple, H, Clapton, J, Grant, D, Hallam, C, Middleton, J, Murch, A, Patino, D, Bate, L, Pate, L, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Patton, M, Peterson, M, Rose, S, Bruno, S, Chu, E, Doherty, K, Henley, S, Lahiri, N, Novak, M, Patel, A, Read, J, Rosser, E, Say, M, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Arran, N, Callaghan, J, Craufurd, D, Fullam, R, Howard, L, Huson, S, Oughton, E, Partington Jones, L, Snowden, J, Sollom, A, Stopford, C, Thompson, J, Trender Gerhad, I, Verstraelen, N, Westmoreland, L, Nemeth, Ah, Siuda, G, Harrison, D, Hughes, M, Parkinson, A, Soltysiak, B, Burn, J, Coleman, C, Majeed, T, Verstraelen Ritchie, N, Bandmann, O, Bradbury, A, Gill, P, Fairtlough, H, Fillingham, K, Foustanos, I, O'Donovan, K, Tidswell, K, Quarrell, O., Faculty of Economic and Social Sciences and Solvay Business School, Neurology, Clinical sciences, Neuroprotection & Neuromodulation, Orth M., European Huntington's Disease Network, Handley O.J., Schwenke C., Dunnet S., Wild E.J., Tabrizi S.J., Landwehrmeyer G.B., Capellari S., Cortelli P., Gallassi R., Poda R., Rizzo G., and Scaglione C.

Subjects
Gerontology, medicine.medical_specialty, Neurology, International Cooperation, Disease, Irritability, Data Collection/methods, Huntington's disease, medicine, Humans, Registries, Psychiatry, Suicidal ideation, Disease burden, business.industry, Data Collection, medicine.disease, Europe, Huntington Disease, Psychiatry and Mental health, European Huntington's Disease Network, Surgery, Observational study, Neurology (clinical), medicine.symptom, business
Abstract

BACKGROUND: Huntington's disease (HD) is a rare triplet repeat (CAG) disorder. Advanced, multi-centre, multi-national research frameworks are needed to study simultaneously multiple complementary aspects of HD. This includes the natural history of HD, its management and the collection of clinical information and biosamples for research. METHODS: We report on cross-sectional data of the first 1766 participants in REGISTRY, the European Huntington's Disease Network's (EHDN), multi-lingual, multi-national prospective observational study of HD in Europe. Data collection (demographics, phenotype, genotype, medication, co-morbidities, biosamples) followed a standard protocol. RESULTS: Phenotype, and the HD genotype, of manifest HD participants across different European regions was similar. Motor onset was most common (48%) with a non-motor onset in more than a third of participants. Motor signs increased, and cognitive abilities and functional capacity declined as the disease burden (CAGn-35.5) X age) increased. A life-time history of behavioural symptoms was common, but the behavioural score was not related to disease burden. One fifth of participants had severe psychiatric problems, e.g. suicidal ideation and attempts, and/or irritability/aggression, with psychosis being less common. Participants on anti-dyskinetic medication had a higher motor and lower cognitive score, were older, and more prone to physical trauma. A higher motor and a lower cognitive score predicted more advanced disease. CONCLUSIONS: The unparalleled collection of clinical data and biomaterials within the EHDN's REGISTRY can expedite the search for disease modifiers (genetic and environmental) of age at onset and disease progression that could be harnessed for the development of novel treatments.

Published
2011

19. Development and validation of Spasticity Index—Amyotrophic Lateral Sclerosis.

Author

Milinis, K., Tennant, A., Mills, R. J., Al‐Chalabi, A., Burke, G., Dick, D. J., Ealing, J., Hanemann, C. O., Harrower, T., McDermott, C. J., Majeed, T., Pinto, A., Talbot, K., Williams, T., Young, C. A., and the TONiC study group

Subjects
AMYOTROPHIC lateral sclerosis, SPASTICITY, QUALITY of life, RASCH models, NUMERICAL analysis
Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

21. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

Author

Quarrell, Ow, Handley, O, O'Donovan, K, Dumoulin, C, Ramos Arroyo, M, Biunno, I, Bauer, P, Kline, M, Landwehrmeyer, Gb, Barth, K, Correia Guedes, L, Maria Finisterra, A, Bascuñana Garde, M, Bos, R, Ecker, D, Held, C, Koppers, K, Laurà, M, Martínez Descals, A, Mclean, T, Mestre, T, Minster, S, Monza, D, Townhill, J, Orth, M, Padieu, H, Paterski, L, Peppa, N, Koivisto, Sp, Rialland, A, Røren, N, Šašinková, P, Cubillo, Pt, van Walsem MR, Witjes Ané MN, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Bachoud Lévi AC, Bentivoglio, Ar, Bonelli, R, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Handley, Oj, Heiberg, A, Illmann, T, Levey, J, Nielsen, Je, Päivärinta, M, Roos, Ra, Rojo Sebastián, A, Tabrizi, Sj, Vandenberghe, W, Verellen Dumoulin, C, Zaremba, J, Uhrova, T, Wahlström, J, Bonelli, Rm, Herranhof, B, Holl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinger, K, Scheibl, M, Hecht, K, Lilek, S, Müller, N, Schöggl, H, Ullah, J, Brugger, F, Hepperger, C, Hotter, A, Mahlknecht, P, Nocker, M, Seppi, K, Wenning, G, Buratti, L, Hametner, Em, Holas, C, Hussl, A, Mair, K, Poewe, W, Wolf, E, Zangerl, A, Braunwarth, Em, Ribaï, P, Flamez, A, Morez, V, de Raedt, S, Boogaerts, A, van Reijen, D, Klempíř, J, Kucharík, M, Roth, J, Hjermind, Le, Jakobsen, O, Stokholm, J, Hasholt, L, Nørremølle, A, Sørensen, Sa, Hiivola, H, Martikainen, K, Tuuha, K, Peippo, M, Sipponen, M, Kosinski, Cm, Milkereit, E, Probst, D, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Gelderblom, H, Priller, J, Prüss, H, Spruth, Ej, Andrich, J, Hoffmann, R, Kraus, Ph, Muth, S, Prehn, C, Saft, C, Salmen, S, Stamm, C, Steiner, T, Strassburger, K, Lange, H, Friedrich, A, Hunger, U, Löhle, M, Schmidt, S, Storch, A, Wolz, A, Wolz, M, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Hidding, U, Lewerenz, J, Münchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Heinicke, W, Longinus, B, Uni, M, Bürk, K, Möller, Jc, Rissling, I, Peinemann, A, Städtler, M, Weindl, A, Bechtel, N, Beckmann, H, Bohlen, S, Hölzner, E, Reilmann, R, Rohm, S, Rumpf, S, Schepers, S, Beister, A, Dose, M, Hammer, K, Kieni, J, Leythaeuser, G, Marquard, R, Raab, T, Richter, S, Selimbegovic Turkovic, A, Schrenk, C, Schuierer, M, Wiedemann, A, Buck, A, Connemann, J, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Süssmuth, S, Trautmann, S, Weydt, P, Cormio, C, Difruscolo, O, Sciruicchio, V, Serpino, C, de Tommaso, M, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Rizzo, G, Scaglione, C, Bertini, E, Ghelli, E, Ginestroni, A, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, Bandettini di Poggio, M, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Albanese, A, Di Bella, D, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Paridi, D, Soliveri, P, Tomasello, C, De Michele, G, Di Maio, L, Rinaldi, C, Valeria Russo, C, Salvatore, E, Tucci, T, Cannella, M, Codella, V, De Gregorio, F, De Nicola, N, Martino, T, Simonelli, M, Squitieri, F, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Modoni, A, Piano, C, Piccininni, C, Quaranta, D, Romano, Silvia, Soleti, F, Spadaro, M, van Hout MS, van Vugt JP, Marit de Weert, A, Bolwijn, Jj, Dekker, M, Leenders, Kl, van Oostrom JC, Dumas, Em, Jurgens, Ck, van den Bogaard SJ, 't Hart EP, Kremer, B, Verstappen, Cc, Aaserud, O, Wehus, R, Bjørgo, K, Fannemel, M, Gørvell, P, Retterstøl, L, Overland, T, Stokke, B, Bjørnevoll, I, Sando, Sb, Sitek, E, Slawek, J, Soltan, W, Boczarska Jedynak, M, Jasinska Myga, B, Opala, G, Kodowska Duda, G, Banaszkiewicz, K, Szczudlik, A, Rudziñska, M, Wójcik, M, Dec, M, Krawczyk, M, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Sempoowicz, J, Samara, H, Janik, P, Kalbarczyk, A, Kwiecinski, H, Jamrozik, Z, Antczak, J, Jachinska, K, Rakowicz, M, Richter, P, Ryglewicz, D, Witkowski, G, Zdzienicka, E, Suek, A, Krysa, W, Guedes, L, Coelho, M, Mendes, T, Valadas, A, Cavaco, S, Damásio, J, Magalhães, M, Gago, M, Garrett, C, Guerra, Mr, Barrero, F, Morales, B, Cubo, E, Mariscal, N, Sánchez, J, Alonso Frech, F, Rabasa Perez, M, Fenollar, M, García, R, Quiroga, Pp, Vázquez Rivera, S, Villanueva, C, Bascuñana, M, Fatás Ventura, M, García Ribas, G, García de Yébenes, J, López Sendón Moreno JL, García Ruíz PJ, José Saiz Artiga, M, Sánchez, V, Noguera Perea, F, Lorenza, F, Torres, Mm, Reinante, G, Vivancos Moreau, L, Barbera, Ma, Badenes Guia, D, Hernanz, Lc, Catena, Jl, Ferrer, Pq, Tome Carruesco, G, Bas, J, Busquets, N, Calopa, M, Dalmau Elorza, M, Díez, C, López, A, Durán, S, Terol, S, Floriach Robert, M, Garzón Ruíz, B, González Casado, A, Haro Martínez, I, Viladrich, Cm, Càrdenas R, Pons i., Roca, E, Llesoy, Jr, Ruiz Idiago JM, Ruíz Vergara, M, Soriano García, S, Villa Riballo, A, Gorospe, A, Legarda, I, Arques, Pn, Torres Rodríguez MJ, Vives, B, Gaston, I, Bosca, M, Burguera, Ja, Garcia, Ac, Pålhagen, Se, Paucar, M, Svenningsson, P, Walldén Reza Soltani, T, Höglund, A, Sandström, B, Høsterey Ugander, U, Fredlund, G, Constantinescu, R, Neleborn Lingefjärd, L, Tedroff, J, Esmaeilzadeh, M, Winnberg, E, Burgunder, Y, Stebler, Y, Kaelin, A, Romero, I, Schüpbach, M, Zaugg, Sw, Jack, R, Matheson, K, Miedzybrodzka, Z, Rae, D, Simpson, S, Summers, F, Ure, A, Crooks, J, Curtis, A, de Souza, J, Rickards, H, Wright, J, Barker, Ra, Di Pietro, A, Fisher, K, Goodman, A, Hill, S, Kershaw, A, Mason, S, Paterson, N, Raymond, L, Bisson, J, Busse, M, Clenaghan, C, Ellison Rose, L, Hunt, S, Price, K, Rosser, A, Edwards, M, Hughes, T, Mcgill, M, Pearson, P, Porteous, M, Smith, P, Zeman, A, Causley, A, Harrower, T, Howcroft, D, Lambord, N, Rankin, J, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Miller, J, Ritchie, S, Burrows, L, Fletcher, A, Harding, A, Laver, F, Silva, M, Thomson, A, Barnes, K, Chu, C, Hobson, E, Jamieson, S, Markova, I, Thomson, J, Toscano, J, Wild, S, Yardumian, P, Bourne, C, Clayton, C, Dipple, H, Clapton, J, Grant, J, Gross, D, Hallam, C, Middleton, J, Murch, A, Patino, D, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Patton, M, Peterson, M, Rose, S, Bruno, S, Chu, E, Doherty, K, Henley, S, Lahiri, N, Novak, M, Patel, A, Read, J, Rosser, E, Say, M, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Arran, N, Callaghan, J, Craufurd, D, Fullam, R, Howard, L, Huson, S, Oughton, E, Partington Jones, L, Snowden, J, Sollom, A, Stopford, C, Thompson, J, Trender Gerhad, I, Verstraelen, N, Westmoreland, L, Nemeth, Ah, Suida, G, Harrison, D, Hughes, M, Parkinson, A, Soltysiak, B, Bandmann, O, Bradbury, A, Gill, P, Fairtlough, H, Fillingham, K, Foustanos, I, Tidswell, K., Kaelin, André, Quarrel O.W., Handley O., O'Donovan K., Dumoulin C., Ramos-Arroyo M., Biunno I., Bauer P., Kline M., Capellari S., Cortelli P., Gallassi R., Landwehrmeyer G.B., European Huntington's Disease Network., Neurology, Clinical sciences, Neuroprotection & Neuromodulation, Quarrell, Ow, Handley, O, O'Donovan, K, Dumoulin, C, Ramos Arroyo, M, Biunno, I, Bauer, P, Kline, M, Landwehrmeyer, Gb, European Huntington's Disease, Network, European Huntington's Disease, N. e. t. w. o. r. k., Rinaldi, Carlo, Salvatore, Elena, and DE MICHELE, Giuseppe

Subjects
medicine.medical_specialty, Concordance, International Cooperation, Diagnostic Errors/statistics & numerical data, Nerve Tissue Proteins, Guidelines as Topic, Bioinformatics, Sensitivity and Specificity, Article, Huntingtin Gene, Huntington's disease, Trinucleotide Repeats, Internal medicine, External quality assessment, Genetics, medicine, Humans, Nerve Tissue Proteins/genetics, Diagnostic laboratory, Genetic Testing, Genetic Testing/methods/standards, Allele, Diagnostic Errors, standard reference material, Genetics (clinical), Alleles, Huntingtin Protein, ddc:618, business.industry, international cooperation, Nuclear Proteins, Reproducibility of Results, Reference Standards, medicine.disease, CAG repeat length, Nuclear Proteins/genetics, Huntington Disease, Huntington Disease/diagnosis, Mutation, Medical genetics, reproducibility of results, mutation, business, Trinucleotide repeat expansion, Huntington Disease/diagnosis/genetics, Genetic Testing/methods
Abstract

Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original results from 121 laboratories across 15 countries. We report on 1326 duplicate results; a discrepancy in reporting the upper allele occurred in 51% of cases, this reduced to 13.3% and 9.7% when we applied acceptable measurement errors proposed by the American College of Medical Genetics and the Draft European Best Practice Guidelines, respectively. Duplicate results were available for 1250 lower alleles; discrepancies occurred in 40% of cases. Clinically significant discrepancies occurred in 4.0% of cases with a potential unexplained misdiagnosis rate of 0.3%. There was considerable variation in the discrepancy rate among 10 of the countries participating in this study. Out of 1326 samples, 348 were re-analysed by an accredited diagnostic laboratory, based in Germany, with concordance rates of 93% and 94% for the upper and lower alleles, respectively. This became 100% if the acceptable measurement errors were applied. The central laboratory correctly reported allele sizes for six standard reference samples, blind to the known result. Our study differs from external quality assessment (EQA) schemes in that these are duplicate results obtained from a large sample of patients across the whole diagnostic range. We strongly recommend that laboratories state an error rate for their measurement on the report, participate in EQA schemes and use reference materials regularly to adjust their own internal standards.

Published
2012

23. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Author

Beecham, A.H., Patsopoulos, N.A., Xifara, D.K., Davis, M.F., Kemppinen, A., Cotsapas, C., Shah, T.S., Spencer, C., Booth, D., Goris, A., Oturai, A., Saarela, J., Fontaine, B., Hemmer, B., Martin, C., Zipp, F., D'Alfonso, S., Martinelli-Boneschi, F., Taylor, B., Harbo, H.F., Kockum, I., Hillert, J., Olsson, T., Ban, M., Oksenberg, J.R., Hintzen, R., Barcellos, L.F., Agliardi, C., Alfredsson, L., Alizadeh, M., Anderson, C., Andrews, R., Søndergaard, H.B., Baker, A., Band, G., Baranzini, S.E., Barizzone, N., Barrett, J., Bellenguez, C., Bergamaschi, L., Bernardinelli, L., Berthele, A., Biberacher, V., Binder, T.M.C., Blackburn, H., Bomfim, I.L., Brambilla, P., Broadley, S., Brochet, B., Brundin, L., Buck, D., Butzkueven, H., Caillier, S.J., Camu, W., Carpentier, W., Cavalla, P., Celius, E.G., Coman, I., Comi, G., Corrado, L., Cosemans, L., Cournu-Rebeix, I., Cree, B.A.C., Cusi, D., Damotte, V., Defer, G., Delgado, S.R., Deloukas, P., di Sapio, A., Dilthey, A.T., Donnelly, P., Dubois, B., Duddy, M., Edkins, S., Elovaara, I., Esposito, F., Evangelou, N., Fiddes, B., Field, J., Franke, A., Freeman, C., Frohlich, I.Y., Galimberti, D., Gieger, C., Gourraud, P-A, Graetz, C., Graham, A., Grummel, V., Guaschino, C., Hadjixenofontos, A., Hakonarson, H., Halfpenny, C., Hall, G., Hall, P., Hamsten, A., Harley, J., Harrower, T., Hawkins, C., Hellenthal, G., Hillier, C., Hobart, J., Hoshi, M., Hunt, S.E., Jagodic, M., Jelčić, I., Jochim, A., Kendall, B., Kermode, A., Kilpatrick, T., Koivisto, K., Konidari, I., Korn, T., Kronsbein, H., Langford, C., Larsson, M., Lathrop, M., Lebrun-Frenay, C., Lechner-Scott, J., Lee, M.H., Leone, M.A., Leppä, V., Liberatore, G., Lie, B.A., Lill, C.M., Linden, M., Link, J., Luessi, F., Lycke, J., Macciardi, F., Männistö, S., Manrique, C.P., Martin, R., Martinelli, V., Mason, D., Mazibrada, G., McCabe, C., Mero, I-L, Mescheriakova, J., Moutsianas, L., Myhr, K-M, Nagels, G., Nicholas, R., Nilsson, P., Piehl, F., Pirinen, M., Price, S.E., Quach, H., Reunanen, M., Robberecht, W., Robertson, N.P., Rodegher, M., Rog, D., Salvetti, M., Schnetz-Boutaud, N.C., Sellebjerg, F., Selter, R.C., Schaefer, C., Shaunak, S., Shen, L., Shields, S., Siffrin, V., Slee, M., Sorensen, P.S., Sorosina, M., Sospedra, M., Spurkland, A., Strange, A., Sundqvist, E., Thijs, V., Thorpe, J., Ticca, A., Tienari, P., van Duijn, C., Visser, E.M., Vucic, S., Westerlind, H., Wiley, J.S., Wilkins, A., Wilson, J.F., Winkelmann, J., Zajicek, J., Zindler, E., Haines, J.L., Pericak-Vance, M.A., Ivinson, A.J., Stewart, G., Hafler, D., Hauser, S.L., Compston, A., McVean, G., De Jager, P., Sawcer, S.J., McCauley, J.L., Beecham, A.H., Patsopoulos, N.A., Xifara, D.K., Davis, M.F., Kemppinen, A., Cotsapas, C., Shah, T.S., Spencer, C., Booth, D., Goris, A., Oturai, A., Saarela, J., Fontaine, B., Hemmer, B., Martin, C., Zipp, F., D'Alfonso, S., Martinelli-Boneschi, F., Taylor, B., Harbo, H.F., Kockum, I., Hillert, J., Olsson, T., Ban, M., Oksenberg, J.R., Hintzen, R., Barcellos, L.F., Agliardi, C., Alfredsson, L., Alizadeh, M., Anderson, C., Andrews, R., Søndergaard, H.B., Baker, A., Band, G., Baranzini, S.E., Barizzone, N., Barrett, J., Bellenguez, C., Bergamaschi, L., Bernardinelli, L., Berthele, A., Biberacher, V., Binder, T.M.C., Blackburn, H., Bomfim, I.L., Brambilla, P., Broadley, S., Brochet, B., Brundin, L., Buck, D., Butzkueven, H., Caillier, S.J., Camu, W., Carpentier, W., Cavalla, P., Celius, E.G., Coman, I., Comi, G., Corrado, L., Cosemans, L., Cournu-Rebeix, I., Cree, B.A.C., Cusi, D., Damotte, V., Defer, G., Delgado, S.R., Deloukas, P., di Sapio, A., Dilthey, A.T., Donnelly, P., Dubois, B., Duddy, M., Edkins, S., Elovaara, I., Esposito, F., Evangelou, N., Fiddes, B., Field, J., Franke, A., Freeman, C., Frohlich, I.Y., Galimberti, D., Gieger, C., Gourraud, P-A, Graetz, C., Graham, A., Grummel, V., Guaschino, C., Hadjixenofontos, A., Hakonarson, H., Halfpenny, C., Hall, G., Hall, P., Hamsten, A., Harley, J., Harrower, T., Hawkins, C., Hellenthal, G., Hillier, C., Hobart, J., Hoshi, M., Hunt, S.E., Jagodic, M., Jelčić, I., Jochim, A., Kendall, B., Kermode, A., Kilpatrick, T., Koivisto, K., Konidari, I., Korn, T., Kronsbein, H., Langford, C., Larsson, M., Lathrop, M., Lebrun-Frenay, C., Lechner-Scott, J., Lee, M.H., Leone, M.A., Leppä, V., Liberatore, G., Lie, B.A., Lill, C.M., Linden, M., Link, J., Luessi, F., Lycke, J., Macciardi, F., Männistö, S., Manrique, C.P., Martin, R., Martinelli, V., Mason, D., Mazibrada, G., McCabe, C., Mero, I-L, Mescheriakova, J., Moutsianas, L., Myhr, K-M, Nagels, G., Nicholas, R., Nilsson, P., Piehl, F., Pirinen, M., Price, S.E., Quach, H., Reunanen, M., Robberecht, W., Robertson, N.P., Rodegher, M., Rog, D., Salvetti, M., Schnetz-Boutaud, N.C., Sellebjerg, F., Selter, R.C., Schaefer, C., Shaunak, S., Shen, L., Shields, S., Siffrin, V., Slee, M., Sorensen, P.S., Sorosina, M., Sospedra, M., Spurkland, A., Strange, A., Sundqvist, E., Thijs, V., Thorpe, J., Ticca, A., Tienari, P., van Duijn, C., Visser, E.M., Vucic, S., Westerlind, H., Wiley, J.S., Wilkins, A., Wilson, J.F., Winkelmann, J., Zajicek, J., Zindler, E., Haines, J.L., Pericak-Vance, M.A., Ivinson, A.J., Stewart, G., Hafler, D., Hauser, S.L., Compston, A., McVean, G., De Jager, P., Sawcer, S.J., and McCauley, J.L.

Abstract

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.

Published
2013

24. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Author

Beecham, AH, Patsopoulos, NA, Xifara, DK, Davis, MF, Kemppinen, A, Cotsapas, C, Shah, TS, Spencer, C, Booth, D, Goris, A, Oturai, A, Saarela, J, Fontaine, B, Hemmer, B, Martin, C, Zipp, F, D'Alfonso, S, Martinelli-Boneschi, F, Taylor, B, Harbo, HF, Kockum, I, Hillert, J, Olsson, T, Ban, M, Oksenberg, JR, Hintzen, R, Barcellos, LF, Agliardi, C, Alfredsson, L, Alizadeh, M, Anderson, C, Andrews, R, Sondergaard, HB, Baker, A, Band, G, Baranzini, SE, Barizzone, N, Barrett, J, Bellenguez, C, Bergamaschi, L, Bernardinelli, L, Berthele, A, Biberacher, V, Binder, TMC, Blackburn, H, Bomfim, IL, Brambilla, P, Broadley, S, Brochet, B, Brundin, L, Buck, D, Butzkueven, H, Caillier, SJ, Camu, W, Carpentier, W, Cavalla, P, Celius, EG, Coman, I, Comi, G, Corrado, L, Cosemans, L, Cournu-Rebeix, I, Cree, BAC, Cusi, D, Damotte, V, Defer, G, Delgado, SR, Deloukas, P, di Sapio, A, Dilthey, AT, Donnelly, P, Dubois, B, Duddy, M, Edkins, S, Elovaara, I, Esposito, F, Evangelou, N, Fiddes, B, Field, J, Franke, A, Freeman, C, Frohlich, IY, Galimberti, D, Gieger, C, Gourraud, P-A, Graetz, C, Graham, A, Grummel, V, Guaschino, C, Hadjixenofontos, A, Hakonarson, H, Halfpenny, C, Hall, G, Hall, P, Hamsten, A, Harley, J, Harrower, T, Hawkins, C, Hellenthal, G, Hillier, C, Hobart, J, Hoshi, M, Hunt, SE, Jagodic, M, Jelcic, I, Jochim, A, Kendall, B, Kermode, A, Kilpatrick, T, Koivisto, K, Konidari, I, Korn, T, Kronsbein, H, Langford, C, Larsson, M, Lathrop, M, Lebrun-Frenay, C, Lechner-Scott, J, Lee, MH, Leone, MA, Leppa, V, Liberatore, G, Lie, BA, Lill, CM, Linden, M, Link, J, Luessi, F, Lycke, J, Macciardi, F, Mannisto, S, Manrique, CP, Martin, R, Martinelli, V, Mason, D, Mazibrada, G, McCabe, C, Mero, I-L, Mescheriakova, J, Moutsianas, L, Myhr, K-M, Nagels, G, Nicholas, R, Nilsson, P, Piehl, F, Pirinen, M, Price, SE, Quach, H, Reunanen, M, Robberecht, W, Robertson, NP, Rodegher, M, Rog, D, Salvetti, M, Schnetz-Boutaud, NC, Sellebjerg, F, Selter, RC, Schaefer, C, Shaunak, S, Shen, L, Shields, S, Siffrin, V, Slee, M, Sorensen, PS, Sorosina, M, Sospedra, M, Spurkland, A, Strange, A, Sundqvist, E, Thijs, V, Thorpe, J, Ticca, A, Tienari, P, van Duijn, C, Visser, EM, Vucic, S, Westerlind, H, Wiley, JS, Wilkins, A, Wilson, JF, Winkelmann, J, Zajicek, J, Zindler, E, Haines, JL, Pericak-Vance, MA, Ivinson, AJ, Stewart, G, Hafler, D, Hauser, SL, Compston, A, McVean, G, De Jager, P, Sawcer, SJ, McCauley, JL, Beecham, AH, Patsopoulos, NA, Xifara, DK, Davis, MF, Kemppinen, A, Cotsapas, C, Shah, TS, Spencer, C, Booth, D, Goris, A, Oturai, A, Saarela, J, Fontaine, B, Hemmer, B, Martin, C, Zipp, F, D'Alfonso, S, Martinelli-Boneschi, F, Taylor, B, Harbo, HF, Kockum, I, Hillert, J, Olsson, T, Ban, M, Oksenberg, JR, Hintzen, R, Barcellos, LF, Agliardi, C, Alfredsson, L, Alizadeh, M, Anderson, C, Andrews, R, Sondergaard, HB, Baker, A, Band, G, Baranzini, SE, Barizzone, N, Barrett, J, Bellenguez, C, Bergamaschi, L, Bernardinelli, L, Berthele, A, Biberacher, V, Binder, TMC, Blackburn, H, Bomfim, IL, Brambilla, P, Broadley, S, Brochet, B, Brundin, L, Buck, D, Butzkueven, H, Caillier, SJ, Camu, W, Carpentier, W, Cavalla, P, Celius, EG, Coman, I, Comi, G, Corrado, L, Cosemans, L, Cournu-Rebeix, I, Cree, BAC, Cusi, D, Damotte, V, Defer, G, Delgado, SR, Deloukas, P, di Sapio, A, Dilthey, AT, Donnelly, P, Dubois, B, Duddy, M, Edkins, S, Elovaara, I, Esposito, F, Evangelou, N, Fiddes, B, Field, J, Franke, A, Freeman, C, Frohlich, IY, Galimberti, D, Gieger, C, Gourraud, P-A, Graetz, C, Graham, A, Grummel, V, Guaschino, C, Hadjixenofontos, A, Hakonarson, H, Halfpenny, C, Hall, G, Hall, P, Hamsten, A, Harley, J, Harrower, T, Hawkins, C, Hellenthal, G, Hillier, C, Hobart, J, Hoshi, M, Hunt, SE, Jagodic, M, Jelcic, I, Jochim, A, Kendall, B, Kermode, A, Kilpatrick, T, Koivisto, K, Konidari, I, Korn, T, Kronsbein, H, Langford, C, Larsson, M, Lathrop, M, Lebrun-Frenay, C, Lechner-Scott, J, Lee, MH, Leone, MA, Leppa, V, Liberatore, G, Lie, BA, Lill, CM, Linden, M, Link, J, Luessi, F, Lycke, J, Macciardi, F, Mannisto, S, Manrique, CP, Martin, R, Martinelli, V, Mason, D, Mazibrada, G, McCabe, C, Mero, I-L, Mescheriakova, J, Moutsianas, L, Myhr, K-M, Nagels, G, Nicholas, R, Nilsson, P, Piehl, F, Pirinen, M, Price, SE, Quach, H, Reunanen, M, Robberecht, W, Robertson, NP, Rodegher, M, Rog, D, Salvetti, M, Schnetz-Boutaud, NC, Sellebjerg, F, Selter, RC, Schaefer, C, Shaunak, S, Shen, L, Shields, S, Siffrin, V, Slee, M, Sorensen, PS, Sorosina, M, Sospedra, M, Spurkland, A, Strange, A, Sundqvist, E, Thijs, V, Thorpe, J, Ticca, A, Tienari, P, van Duijn, C, Visser, EM, Vucic, S, Westerlind, H, Wiley, JS, Wilkins, A, Wilson, JF, Winkelmann, J, Zajicek, J, Zindler, E, Haines, JL, Pericak-Vance, MA, Ivinson, AJ, Stewart, G, Hafler, D, Hauser, SL, Compston, A, McVean, G, De Jager, P, Sawcer, SJ, and McCauley, JL

Abstract

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.

Published
2013

25. Long term survival of porcine expanded neural precursors in the rat model of Parkinson's disease. (ABN Abstracts)

Author

Harrower, T., Ratcliffe, E., Richards, A., Dunnett, S., and Barker, R.

Subjects
Graft versus host reaction -- Research, Parkinson's disease -- Physiological aspects -- Research, Stem cells -- Transplantation, Health, Psychology and mental health, Physiological aspects, Research
Abstract

Background: Porcine embryonic tissue has been considered as an alternative source of cells for neural transplantation. However, such tissue is readily rejected as a result of the host immune system. [...]

Published
2002

30. Gal is widely expressed in embryonic porcine stem cells and neural tissue

Author

Harrower, T. P., Richards, A., Cruz, G., Copeman, L., Dunnett, S. B., and Barker, R. A.

Abstract

Fetal porcine neural xenografts are an alternative to human fetal tissue for cell based treatments of a number of neurodegenerative conditions but are currently limited by host immunological rejection. The expression of a major immunological epitope, Gal1-3Gal1-4GlcNAc-R (Gal) was determined on stem cells and primary cells derived from E26 porcine fetal brains. Gal was detected on the majority of neural stem cells and cells from primary cell suspensions. The expression of this epitope paralleled the binding of human IgG and IgM to the cells, a binding that was significantly reduced with anti-Gal depleted human serum. This study demonstrates that Gal expression is extensive in embryonic porcine neural cells and will be of relevance to any clinical trials using this tissue.

Published
2002

35. PWE-066 Clinical features of demyelination during anti-tnf therapy: preliminary outcomes of the pred4 study

Author

Hendy, P, Heerasing, N, Walker, G, Heap, G, Bewshea, C, Kennedy, N, Goodhand, J, Harrower, T, Hobart, J, Spiers, A, Coles, A, Martin, R, and Ahmad, T

Abstract

IntroductionAnti-TNFα therapy has been associated with demyelination since early trials in Multiple Sclerosis (MS) demonstrated disease worsening.Subsequent small case series have reported plausible clinical associations although epidemiological studies have produced conflicting data.The specific clinical features of demyelination following anti-TNF therapy have not been described.This study uses a systematic independent assessment of causality to describe the clinical characteristics and outcomes of anti-TNFα associated demyelination.MethodPatients were recruited from 28 hospitals.Inclusion criteria included i)no history of neurological symptoms prior to anti-TNFα exposure,ii)MRI brain and/or spinal cord or electrophysiological tests consistent with PNS or CNS demyelination,iii)demyelination illness confirmed by neurologist and drug withdrawn.An adjudication panel comprising at least 3 neurologists and a neuro-radiologist identified definite and probable cases from case report forms.Probable cases required a consistent history and signs and objective radiological±electrophysiological evidence of demyelination.Definite cases had a recurrence of demyelination on drug rechallenge.Results54 cases were recruited, of whom 35 (24 female) were adjudicated as definite or probable cases. Adalimumab,Infliximab,Etanercept and Certolizumab were implicated in 17/35 (49%), 15/35 (43%), 5/35 (14%), and 1/35 (3%) of cases respectively.Average age of symptom onset was 40 (95%CI 37–44) years. The mean duration of anti-TNFα exposure was 27 (95%CI 18–36) months prior to symptom onset onset of demyelination. 22 cases (63%) presented with brain ± spinal lesions, 8 (23%) spine only demyelination, and 5 (14%) peripheral demyelination.On drug withdrawal patients were followed for a mean of 42 (95%CI 32–52) months.Of those with CNS lesions, 11/30 (37%) developed a relapsing demyelinating syndrome or MS and only 5/30 (17%) had complete resolution of their symptoms with a mean time to resolution of 419 days (95% CI 36–802).ConclusionThis large case series adds comprehensive clinical information to the existing reports of demyelinating events associated with anti-TNFα therapy for inflammatory disorders.Consistent with known risk factors for MS, young females appear to be over represented.Over one third of patients appear to develop a relapsing illness/MS and complete neurological recovery is uncommon.We aim to build this cohort further so that we might explore clinically useful genetic markers that identify at-risk patients.Disclosure of InterestNone Declared

Published
2017
Full Text
View/download PDF

38. Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2)

Author

Sally-Anne Vincent, Michael S. Zandi, Camilla Buckley, Giuliano Tomei, Belinda R Lennox, Ly-Mee Yu, Ksenija Yeeles, Mio Shimazaki, Francis Dowling, Eileen M. Joyce, Anne Lingford Hughes, Alasdair Coles, Peter B. Jones, Thomas Kabir, Thomas R. E. Barnes, Iona Cairns, Timothy Harrower, Rebecca Pollard, Akram A. Hosseini, Lennox B., Yeeles K., Jones P.B., Zandi M., Joyce E., Yu L.-M., Tomei G., Pollard R., Vincent S.-A., Shimazaki M., Cairns I., Dowling F., Kabir T., Barnes T.R.E., Lingford Hughes A., Hosseini A.A., Harrower T., Buckley C., Coles A., Zandi, Michael [0000-0002-9612-9401], Coles, Alasdair [0000-0003-4738-0760], and Apollo - University of Cambridge Repository

Subjects
Male, Time Factors, Placebo-controlled study, Medicine (miscellaneous), Research & Experimental Medicine, DISEASE, law.invention, Study Protocol, PROGNOSTIC-FACTORS, 0302 clinical medicine, Randomized controlled trial, Risk Factors, law, SCHIZOPHRENIA, Multicenter Studies as Topic, Pharmacology (medical), Infusions, Intravenou, 030212 general & internal medicine, Infusions, Intravenous, 1102 Cardiorespiratory Medicine and Haematology, Randomized Controlled Trials as Topic, lcsh:R5-920, Positive and Negative Syndrome Scale, Hazard ratio, Immunoglobulins, Intravenous, RECEPTOR ENCEPHALITIS, Middle Aged, 3. Good health, Treatment Outcome, Medicine, Research & Experimental, Female, Rituximab, lcsh:Medicine (General), Life Sciences & Biomedicine, Human, Antipsychotic Agents, medicine.drug, Adult, Psychosis, medicine.medical_specialty, Time Factor, Adolescent, Psychotic Disorder, Placebo, MECHANISMS, Young Adult, 03 medical and health sciences, Clinical Trials, Phase II as Topic, Double-Blind Method, General & Internal Medicine, Internal medicine, medicine, Humans, Aged, Science & Technology, business.industry, Risk Factor, 1103 Clinical Sciences, medicine.disease, United Kingdom, Clinical trial, Antipsychotic Agent, Psychotic Disorders, Cardiovascular System & Hematology, Immunoglobulins, Intravenou, business, 030217 neurology & neurosurgery
Abstract

Background Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis. The SINAPPS2 phase IIa double-blinded randomised controlled trial will test the efficacy and safety of immunoglobulin and rituximab treatment versus placebo for patients with acute psychosis symptoms as added to psychiatric standard of care. Methods We will screen approximately 2500 adult patients with acute psychosis to identify 160 with antibody-positive psychosis without co-existing neurological disease and recruit about 80 eligible participants to the trial in the period from September 2017 to September 2021 across the UK. Eligible patients will be randomised 1:1 either to intravenous immunoglobulin (IVIG) followed by rituximab or to placebo infusions of 1% albumin followed by 0.9% sodium chloride, respectively. To detect a time-to-symptomatic-recovery hazard ratio of 0.322 with a power of 80%, 56 participants are needed to complete the trial, allowing for up to 12 participants to drop out of each group. Eligible patients will be randomised and assessed at baseline within 4 weeks of their eligibility confirmation. The treatment will start with IVIG or 1% albumin placebo infusions over 2–4 consecutive days no later than 7 days from baseline. It will continue 4–5 weeks later with a rituximab or sodium chloride placebo infusion and will end 2–3 weeks after this with another rituximab or placebo infusion. The primary outcome is the time to symptomatic recovery defined as symptomatic remission sustained for at least 6 months on the following Positive and Negative Syndrome Scale items: P1, P2, P3, N1, N4, N6, G5 and G9. Participants will be followed for 12 months from the first day of treatment or, where sustained remission begins after the first 6 months, for an additional minimum of 6 months to assess later response. Discussion The SINAPPS2 trial aims to test whether immunotherapy is efficacious and safe in psychosis associated with anti-neuronal membrane antibodies. Trial registration ISRCTN, 11177045. Registered on 2 May 2017. EudraCT, 2016-000118-31. Registered on 22 November 2016. ClinicalTrials.gov, NCT03194815. Registered on 21 June 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3336-1) contains supplementary material, which is available to authorized users.

Published
2019

39. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Author

Bénédicte Dubois, Lucia Corrado, Deborah F. Mason, Allan G. Kermode, Pentti J. Tienari, Annette Bang Oturai, Charles Hillier, Adrian J. Ivinson, Stephen L. Hauser, Ashley Beecham, Jeannette Lechner-Scott, Vincent Thijs, Jonathan L. Haines, Sarah Edkins, Alexander T. Dilthey, Daniele Cusi, Guy Nagels, David A. Hafler, Mark Slee, Petra Nilsson, James S. Wiley, Lou Brundin, Amy Strange, Elizabeth Visser, Mireia Sospedra, Athena Hadjixenofontos, Sergio E. Baranzini, Jenny Link, Robert Andrews, Viola Biberacher, Helle Bach Søndergaard, Vittorio Martinelli, Tomas Olsson, Gillian L Hall, Stephen Sawcer, Stacy J. Caillier, Per Soelberg Sørensen, Céline Bellenguez, Cornelia M. van Duijn, Frauke Zipp, Nikolaos A. Patsopoulos, Cristin McCabe, Colin Freeman, Simon Broadley, Luisa Bernardinelli, Margaret A. Pericak-Vance, Jan Hillert, Wassila Carpentier, Sandip Shaunak, Anne Spurkland, Barnaby Fiddes, Judith Field, Jan Lycke, Christina M. Lill, Federica Esposito, Ioanna Konidari, Elisabeth Gulowsen Celius, Christian Gieger, Helmut Butzkueven, Ling Shen, James F. Wilson, Magdalena Lindén, Tejas S. Shah, Amie Baker, Dionysia K. Xifara, Hong Quach, Laura Bergamaschi, Rogier Q. Hintzen, Jacob L. McCauley, Janna Saarela, J W Thorpe, Christine Lebrun-Frenay, Felix Luessi, Sandra D'Alfonso, B. E. Kendall, Helga Westerlind, Giancarlo Comi, Nathalie Schnetz-Boutaud, Paola Brambilla, Chris Cotsapas, Anders Hamsten, William Camu, Achim Berthele, Kjell-Morten Myhr, Clive Hawkins, Richard Nicholas, James Harley, Carl A. Anderson, Keijo Koivisto, Irene Coman, Neil Robertson, Hakon Hakonarson, Finn Sellebjerg, Fredrik Piehl, Alessia Di Sapio, Loukas Moutsianas, Mehdi Alizadeh, Lars Alfredsson, Catherine Schaefer, David Rog, Virpi Leppa, C. Martin, Bruce A.C. Cree, Christopher Halfpenny, Irina Elovaara, Filippo Martinelli-Boneschi, Cordelia Langford, Hanne F. Harbo, Wim Robberecht, Isabelle Cournu-Rebeix, Steve Vucic, Izaura Lima Bomfim, Irene Y. Frohlich, Michelle Lee, Bertrand Fontaine, Bernhard Hemmer, Eva Zindler, Chris C. A. Spencer, Malin Larsson, Simon Shields, Ilijas Jelcic, Juliane Winkelmann, Jorge R. Oksenberg, Alastair Wilkins, Silvia Delgado, Volker Siffrin, Helena C. Kronsbein, Bruno Brochet, Panos Deloukas, Daniela Galimberti, Nikos Evangelou, Rebecca C. Selter, Maja Jagodic, Martin Duddy, Timothy Harrower, Per Hall, Nadia Barizzone, Siân Price, Matti Pirinen, Pierre-Antoine Gourraud, Thomas M.C. Binder, Giuseppe Liberatore, Mark Lathrop, M.-M. Hoshi, Garrett Hellenthal, Melissa Sorosina, Thomas Korn, Clara Guaschino, Roland Martin, Jeremy Hobart, Marco Salvetti, Peter Donnelly, Ingrid Kockum, An Goris, Alastair Compston, Mariaemma Rodegher, Dorothea Buck, Clara P. Manrique, Christiane Graetz, Benedicte A. Lie, Trevor J. Kilpatrick, Andrew Graham, Anu Kemppinen, Maria Ban, Gil McVean, John Zajicek, Hannah Blackburn, Mary F. Davis, Emilie Sundqvist, Bruce V. Taylor, Maurizio Leone, Lisa F. Barcellos, Fabio Macciardi, Gilles Defer, Vincent Damotte, Satu Männistö, Graeme J. Stewart, Gordon Mazibrada, Inger Lise Mero, Andre Franke, Philip L. De Jager, Verena Grummel, Mauri Reunanen, David R. Booth, Anna Ticca, Angela Jochim, Leentje Cosemans, Julia Y Mescheriakova, Cristina Agliardi, Paola Cavalla, Jeffrey C. Barrett, Sarah E. Hunt, Gavin Band, School of Life Sciences, University of Technology Sydney (UTS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Profium Oy [Helsinki], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Michigan Technological University (MTU), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], The Wellcome Trust Sanger Institute [Cambridge], Génétique épidémiologique et structures des populations humaines (Inserm U535), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Karolinska Institutet [Stockholm], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Plateforme Post-génomique de la Pitié-Salpêtrière (P3S), UMS omique (OMIQUE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Statistics [Oxford], Centro Dino Ferrari [Milano], Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Epidémiologie et Analyses en Santé Publique : risques, maladies chroniques et handicap (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical Epidemiology and Biostatistics (MEB), University College of London [London] (UCL), Fondation Jean Dausset CEPH, Centre Hospitalier Universitaire de Nice (CHU Nice), Dublin Institute of Technology (DIT), University of California [Irvine] (UCI), University of California, Géosciences Environnement Toulouse (GET), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Kaiser Permanente, Universität Zürich [Zürich] = University of Zurich (UZH), University Hospitals Leuven [Leuven], Department Biostatistics University of North Carolina, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Institute of Bioinformatics and Systems Biology [München], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Yale University School of Medicine, Big Data Institute, Department of Clinical Neurosciences [Cambridge], University of Cambridge [UK] (CAM), Faculty of Engineering, Neuroprotection & Neuromodulation, Internal Medicine Specializations, Neurology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Yale School of Medicine [New Haven, Connecticut] (YSM), University of Oxford, Università degli Studi di Milano = University of Milan (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of California [Irvine] (UC Irvine), University of California (UC), Cardiology, Epidemiology, Oral and Maxillofacial Surgery, International Multiple Sclerosis Genetics, Consortium, Beecham, Ah, Patsopoulos, Na, Xifara, Dk, Davis, Mf, Kemppinen, A, Cotsapas, C, Shah, T, Spencer, C, Booth, D, Goris, A, Oturai, A, Saarela, J, Fontaine, B, Hemmer, B, Martin, C, Zipp, F, D'Alfonso, S, Martinelli Boneschi, F, Taylor, B, Harbo, Hf, Kockum, I, Hillert, J, Olsson, T, Ban, M, Oksenberg, Jr, Hintzen, R, Barcellos, Lf, Wellcome Trust Case Control Consortium, 2, International IBD Genetics, Consortium, Agliardi, C, Alfredsson, L, Alizadeh, M, Anderson, C, Andrews, R, Søndergaard, Hb, Baker, A, Band, G, Baranzini, Se, Barizzone, N, Barrett, J, Bellenguez, C, Bergamaschi, L, Bernardinelli, L, Berthele, A, Biberacher, V, Binder, Tm, Blackburn, H, Bomfim, Il, Brambilla, P, Broadley, S, Brochet, B, Brundin, L, Buck, D, Butzkueven, H, Caillier, Sj, Camu, W, Carpentier, W, Cavalla, P, Celius, Eg, Coman, I, Comi, Giancarlo, Corrado, L, Cosemans, L, Cournu Rebeix, I, Cree, Ba, Cusi, D, Damotte, V, Defer, G, Delgado, Sr, Deloukas, P, di Sapio, A, Dilthey, At, Donnelly, P, Dubois, B, Duddy, M, Edkins, S, Elovaara, I, Esposito, F, Evangelou, N, Fiddes, B, Field, J, Franke, A, Freeman, C, Frohlich, Iy, Galimberti, D, Gieger, C, Gourraud, Pa, Graetz, C, Graham, A, Grummel, V, Guaschino, C, Hadjixenofontos, A, Hakonarson, H, Halfpenny, C, Hall, G, Hall, P, Hamsten, A, Harley, J, Harrower, T, Hawkins, C, Hellenthal, G, Hillier, C, Hobart, J, Hoshi, M, Hunt, Se, Jagodic, M, Jelčić, I, Jochim, A, Kendall, B, Kermode, A, Kilpatrick, T, Koivisto, K, Konidari, I, Korn, T, Kronsbein, H, Langford, C, Larsson, M, Lathrop, M, Lebrun Frenay, C, Lechner Scott, J, Lee, Mh, Leone, Ma, Leppä, V, Liberatore, G, Lie, Ba, Lill, Cm, Lindén, M, Link, J, Luessi, F, Lycke, J, Macciardi, F, Männistö, S, Manrique, Cp, Martin, R, Martinelli, V, Mason, D, Mazibrada, G, Mccabe, C, Mero, Il, Mescheriakova, J, Moutsianas, L, Myhr, Km, Nagels, G, Nicholas, R, Nilsson, P, Piehl, F, Pirinen, M, Price, Se, Quach, H, Reunanen, M, Robberecht, W, Robertson, Np, Rodegher, M, Rog, D, Salvetti, M, Schnetz Boutaud, Nc, Sellebjerg, F, Selter, Rc, Schaefer, C, Shaunak, S, Shen, L, Shields, S, Siffrin, V, Slee, M, Sorensen, P, Sorosina, M, Sospedra, M, Spurkland, A, Strange, A, Sundqvist, E, Thijs, V, Thorpe, J, Ticca, A, Tienari, P, van Duijn, C, Visser, Em, Vucic, S, Westerlind, H, Wiley, J, Wilkins, A, Wilson, Jf, Winkelmann, J, Zajicek, J, Zindler, E, Haines, Jl, Pericak Vance, Ma, Ivinson, Aj, Stewart, G, Hafler, D, Hauser, Sl, Compston, A, Mcvean, G, De Jager, P, Sawcer, Sj, and Mccauley, J. L.

Subjects
Multiple Sclerosis, Genotype, [SDV]Life Sciences [q-bio], European Continental Ancestry Group, Genome-wide association study, CLEC16A, Biology, multiple sclerosis, Major histocompatibility complex, Polymorphism, Single Nucleotide, Article, White People, 03 medical and health sciences, 0302 clinical medicine, Research Support, N.I.H., Extramural, Gene Frequency, Polymorphism (computer science), Journal Article, Genetics, medicine, Humans, Genetic Predisposition to Disease, Allele, Genotyping, Allele frequency, 030304 developmental biology, 0303 health sciences, Research Support, Non-U.S. Gov't, Multiple sclerosis, Chromosome Mapping, Genetic Variation, medicine.disease, 3. Good health, Genetic Loci, biology.protein, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract

International audience; Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.

Published
2016

40. Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK.

Author

Blackstone J, Williams T, Nicholas JM, Bordea E, De Angelis F, Bianchi A, Calvi A, Doshi A, John N, Apap Mangion S, Wade C, Merry R, Barton G, Lyle D, Jarman E, Mahad D, Shehu A, Arun T, McDonnell G, Geraldes R, Craner M, Hillier C, Ganesalingam J, Fisniku L, Hobart J, Spilker C, Robertson N, Kalra S, Pluchino S, Harikrishnan S, Mattoscio M, Harrower T, Young C, Lee M, Chhetri S, Ahmed F, Rog D, Silber E, Gallagher P, Duddy M, Straukiene A, Nicholas R, Rice C, Nixon SJ, Beveridge J, Hawton A, Tebbs S, Braisher M, Giovannoni G, Ciccarelli O, Greenwood J, Thompson AJ, Hunter R, Pavitt S, Pearson O, Evangelou N, Sharrack B, Galea I, Chandran S, Ford HL, Frost C, and Chataway J

Subjects
Humans, Double-Blind Method, United Kingdom, Middle Aged, Adult, Multicenter Studies as Topic, Clinical Trials, Phase III as Topic, Cost-Benefit Analysis, Male, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Randomized Controlled Trials as Topic, Disability Evaluation, Aged, Treatment Outcome, Simvastatin therapeutic use, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Chronic Progressive physiopathology, Disease Progression
Abstract

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS., Methods and Analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0-6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years.Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate.The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression.Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur., Ethics and Dissemination: The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations., Trial Registration Numbers: NCT03387670; ISRCTN82598726., Competing Interests: Competing interests: JC has received support in the last 3 years from the Health Technology Assessment (HTA) Programme (National Institute for Health Research, NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by MS Canada. A local principal investigator for commercial trials funded by Ionis and Roche; and has taken part in advisory boards/consultancy for Biogen, Janssen, Lucid, Merck, NervGen, Novartis and Roche. OC declares being NIHR Research Professor (RP-2017-08-ST2-004); over the last 2 years, member of independent DSMB for Novartis; she gave a teaching talk in a Merck local symposium and contributed to an Advisory Board for Biogen; she is Deputy Editor of Neurology, for which she receives an honorarium; has received research grant support from the UK MS Society, the NIHR UCLH Biomedical Research Centre, the Rosetree Trust, the US National MS Society and the NIHR-HTA. HLF has received honoraria for advisory boards and/or educational activities from Biogen, Merck, Novartis and Roche. HLF has research grant support from the NIHR Health Technology Assessment Programme and EME, UK MS Society and the Horne Family Charitable Trust. LF has received honoraria for speaking or as an advisory board member from Biogen, Novartis, Merck, Sanofi Genzyme and Roche, and received support for attending educational meetings from Biogen, Novartis, Merck, Sanofi Genzyme and Teva. GG declares that in the last 2 years he has received compensation for serving as a consultant or speaker or research support from Astoria Biologica, Aurinia Pharmaceuticals, Biogen, BMS-Celgene, GlaxoSmithKline, Janssens/J&J, Japanese Tobacco, Merck KGaA/EMD Serono, Moderna, Novartis, Sandoz, Sanofi, Roche/Genentech, Vir Biotechnology and Viracta. NJ is a principal investigator on commercial MS trials sponsored by Roche, Novartis and Biogen. He has received speakers honoraria from Merck and travel congress sponsorship from Novartis. MM has received travel support, speaker honoraria and consultation fees from Genzyme, Merck-Sereno, Novartis, Roche, the MS Academy and the Italian Multiple Sclerosis Foundation (FISM). RN attended paid advisory board for Novartis and Roche. SPavitt was MRC/National Institute for Health Research (NIHR)—Efficacy & Mechanism Evaluation Board Member from 2012–2018. SPluchino is founder, CSO and shareholder (>5%) of CITC and Chair of the Scientific Advisory Board at ReNeuron plc. CR declares research funding from Sanofi. DR declares consulting and/or speaker fees received from Biogen, Celgene, Janssen, MedDay, Merck, Novartis, Roche, Sanofi Genzyme and Teva. Additionally, research support paid to an institutional fund from Actelion, Biogen, GW Pharmaceuticals, Merck Serono, Mitsubishi, Novartis, Sanofi Genzyme, Teva and TG Therapeutics. AJT receives a fee from being Co-Chair, UCL-Eisai Steering Committee drug discovery collaboration; Member, National MS Society (USA) Research Programs Advisory Committee; Clinical Trials Committee, Progressive MS Alliance; Board member, European Charcot Foundation; Editor in Chief, Multiple Sclerosis Journal; Editorial Board Member, The Lancet Neurology. He receives no fee from being: Chair (Scientific Ambassadors), ‘Stop MS’ Appeal Board, UK MS Society; Research & academic counsellor, Fundació Privada Cemcat; Ambassador, European Brain Council. AJT additionally holds a patent for the MSIS-29 Impact Scale., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Published
2024
Full Text
View/download PDF

41. Dyspnea (breathlessness) in amyotrophic lateral sclerosis/motor neuron disease: prevalence, progression, severity, and correlates.

Author

Young CA, Chaouch A, Mcdermott CJ, Al-Chalabi A, Chhetri SK, Talbot K, Harrower T, Orrell RW, Annadale J, Hanemann CO, Scalfari A, Tennant A, and Mills R

Subjects
Humans, Male, Female, Middle Aged, Aged, Prevalence, Motor Neuron Disease epidemiology, Motor Neuron Disease physiopathology, Motor Neuron Disease diagnosis, Motor Neuron Disease complications, Quality of Life, Adult, Dyspnea physiopathology, Dyspnea diagnosis, Dyspnea epidemiology, Dyspnea etiology, Amyotrophic Lateral Sclerosis epidemiology, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis physiopathology, Amyotrophic Lateral Sclerosis complications, Disease Progression, Severity of Illness Index
Abstract

Objective: Dyspnea, or breathlessness, is an important symptom in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). We examined the measurement properties of the Dyspnea-12., Methods: Rasch analysis enabled conversion of raw Dyspnea-12 scores to interval level metric equivalents. Converted data were used to perform trajectory modeling; those following different trajectories were compared for demographic, clinical, symptom, and functioning characteristics. Logistic regression examined differences between distinct trajectories., Results: In 1022 people, at baseline, mean metric Dyspnea-12 was 7.6 (SD 9.3). 49.8% had dyspnea, severe in 12.6%. Trajectory analysis over 28 months revealed three breathlessness trajectories: group 1 reported none at baseline/follow-up (42.7%); group 2 significantly increased over time (9.4%); group 3 had a much higher level at baseline which rose over follow-up (47.9%). Group 3 had worse outcomes on all symptoms, functioning and quality of life; compared to group 1, their odds of: respiratory onset sixfold greater; King's stage ≥3 2.9 greater; increased odds of being bothered by choking, head drop, fasciculations, and muscle cramps; fatigue and anxiety also elevated ( p  < .01)., Conclusion: Dyspnea is a cardinal symptom in ALS/MND and can be quickly measured using the Dyspnea-12. Raw scores can easily be converted to interval level measurement, for valid change scores and trajectory modeling. Dyspnea trajectories reveal different patterns, showing that clinical services must provide monitoring which is customized to individual patient need. Almost half of this large population had worsening dyspnea, confirming the importance of respiratory monitoring and interventions being integrated into routine ALS care.

Published
2024
Full Text
View/download PDF

42. Correlates and trajectories of relapses in relapsing-remitting multiple sclerosis.

Author

Young CA, Rog DJ, Sharrack B, Tanasescu R, Kalra S, Harrower T, Tennant A, and Mills RJ

Subjects
Humans, Quality of Life, Recurrence, Health Status, Multiple Sclerosis, Relapsing-Remitting epidemiology, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis
Abstract

Background and Aims: In people with relapsing-remitting multiple sclerosis (pwRRMS), data from studies on non-pharmacological factors which may influence relapse risk, other than age, are inconsistent. There is a reduced risk of relapses with increasing age, but little is known about other trajectories in real-world MS care., Methods: We studied longitudinal questionnaire data from 3885 pwRRMS, covering smoking, comorbidities, disease-modifying therapy (DMT), and patient-reported outcome measures, as well as relapses during the past year. We undertook Rasch analysis, group-based trajectory modelling, and multilevel negative binomial regression., Results: The regression cohort of 6285 data sets from pwRRMS over time showed that being a current smoker was associated with 43.9% greater relapse risk; having 3 or more comorbidities increased risk and increasing age reduced risk. Those diagnosed within the last 2 years showed two distinct trajectories, both reducing in relapse frequency but 25.8% started with a higher rate and took 4 years to reduce to the rate of the second group. In the cohort with at least three data points completed, there were three groups: 73.7% followed a low stable relapse rate, 21.6% started from a higher rate and decreased, and 4.7% had an increasing then decreasing pattern. These different trajectory groups showed significant differences in fatigue, neuropathic pain, disability, health status, quality of life, self-efficacy, and DMT use., Conclusions: These results provide additional evidence for supporting pwRRMS to stop smoking and underline the importance of timely DMT decisions and treatment initiation soon after diagnosis with RRMS., (© 2023. The Author(s).)

Published
2024
Full Text
View/download PDF

43. Measuring disability in multiple sclerosis: the WHODAS 2.0.

Author

Young CA, Rog DJ, Sharrack B, Constantinescu C, Kalra S, Harrower T, Langdon D, Tennant A, and Mills RJ

Subjects
Humans, Reproducibility of Results, Quality of Life psychology, Disability Evaluation, Psychometrics, World Health Organization, Multiple Sclerosis, Disabled Persons rehabilitation
Abstract

Introduction: Reliable measurement of disability in multiple sclerosis (MS) using a comprehensive, patient self-reported scale, such as the World Health Organization Disability Assessment Schedule (WHODAS) 2.0, would be of clinical and research benefit., Methods: In the Trajectories of Outcome in Neurological Conditions-MS study, WHODAS 2.0 (WHODAS-36 items for working, WHODAS-32 items if not working, WHODAS-12 items short-form) was examined using Rasch analysis in 5809 people with MS., Results: The 36- and 32-item parallel forms, and the cognitive and physical domains, showed reliability consistent with individual or group use. The 12-item short-form is valid for group use only. Interval level measurement for parametric statistics can be derived from all three scales which showed medium to strong effect sizes for discrimination across characteristics such as age, subtype, and disease duration. Smallest detectable difference for each scale was < 6 on the standardised metric of 0-100 so < 6% of the total range. There was no substantial differential item functioning (DIF) by age, gender, education, working full/part-time, or disease duration; the finding of no DIF for time or sample supports the use of WHODAS 2.0 for longitudinal studies, with the 36- and 32-item versions and the physical and cognitive domains valid for individual patient follow-up., Conclusions: Disability in MS can be comprehensively measured at interval level by the WHODAS 2.0, and validly monitored over time. Routine use of this self-reported measure in clinical and research practice would give valuable information on the trajectories of disability of individuals and groups., (© 2023. The Author(s).)

Published
2023
Full Text
View/download PDF

44. Quality assurance programs for vitamin A and E in serum: are we doing enough to assess laboratory performance?

Author

Fitzpatrick M, Andersen T, Bush J, Greaves RF, Woollard G, Hoad K, Collie JTB, Browning S, Harrower T, Graham P, and Punyalack W

Subjects
Humans, gamma-Tocopherol, Laboratories, Vitamin E, Vitamins, Vitamin K, Vitamin A, alpha-Tocopherol
Abstract

Objectives: Monitoring serum vitamin A (retinol) and vitamin E (α-tocopherol) concentrations is common practice for assessing nutritional status. Measurement of these vitamins can be challenging due to several factors. Whilst the RCPAQAP Vitamins: Serum Program assists participating laboratories in harmonisation, the materials provided do not contain the analogues of retinol and α-tocopherol that may be present in real patient samples. We aimed to assess participants' capacity to accurately report retinol and α-tocopherol in the presence of the vitamin E analogues tocopherol acetate and γ-tocopherol., Methods: A supplementary series of a control sample and three matched spiked samples were distributed to each laboratory participating in the Program. Retinol and α-tocopherol results for each spiked sample were compared to the results of the control sample submitted by each participant. Acceptability of retinol and α-tocopherol results was determined based on the RCPAQAP allowable performance specifications (APS)., Results: Thirteen participants returned results for the supplementary sample series. Interference from α-tocopherol acetate was observed with results below the APS in 30 % (n=4) of laboratories for retinol quantification and in 23 % (n=3) for α-tocopherol quantification. One laboratory returned results above the APS for α-tocopherol when γ-tocopherol was present., Conclusions: This supplementary sample series has shown that the presence of vitamin E analogues can lead to the over or under estimation of nutritional status by some participants. Affected laboratories are encouraged to review their analytical procedures. To further assess laboratory competence, EQA providers should consider using patient samples or spiked challenge samples., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Published
2023
Full Text
View/download PDF

45. Measuring disability in amyotrophic lateral sclerosis/motor neuron disease: the WHODAS 2.0-36, WHODAS 2.0-32, and WHODAS 2.0-12.

Author

Young CA, Ealing J, McDermott CJ, Williams TL, Al-Chalabi A, Majeed T, Talbot K, Harrower T, Faull C, Malaspina A, Annadale J, Mills RJ, and Tennant A

Subjects
Humans, Disability Evaluation, Reproducibility of Results, Surveys and Questionnaires, Psychometrics, Amyotrophic Lateral Sclerosis, Disabled Persons
Abstract

Aim: To investigate whether the World Health Organization Disability Assessment Schedule 2.0 (WHODAS) can provide interval level measurement of disability in Amyotrophic Lateral Sclerosis (ALS), allowing parametric analyses. Methods : Data on the WHODAS 12, 32, and 36-item versions, from 1120 patients studied at one or more time points, were fit to the Rasch model and comparisons made against ALSFRS-R, King's staging, and mortality. Trajectory modeling was undertaken for a newly diagnosed (≤6 months) cohort of 454 individuals. Results : Total scores for WHODAS 32 and 36-item versions can be converted to interval level measurement suitable for individual clinical use, and the 12-item WHODAS total for group use. The 36-item version is shown to be equivalent to the 32-item version. Expected correlations were seen with King's staging, ALSFRS-R, and EQ-5D-5L. Trajectory analysis of disability (WHODAS 2.0) showed three clearly demarcated groups with differences in King's staging, depressive symptomatology and mortality, but not age. Conclusions : The WHODAS 2.0 is a brief patient reported outcome measure which can be used to measure disability in ALS. Provided the patient answers all 36 (32 if not working) items, the conversion table produces an interval level estimate for parametric analyses. The different trajectories demonstrated from diagnosis support the concept of a prodromal period, and suggest the WHODAS 2.0 could be used for surveillance of at risk populations, such as those with genetic predisposition.

Published
2023
Full Text
View/download PDF

46. Measuring coping in multiple sclerosis: The Coping Index-MS.

Author

Young CA, Mills RJ, Langdon D, Rog DJ, Sharrack B, Kalra S, Majeed T, Footit D, Harrower T, Nicholas RS, Ford HL, Woolmore J, Johnstone C, Thorpe J, Paling D, Ellis C, Hanneman CO, and Tennant A

Subjects
Humans, Adaptation, Psychological, Benchmarking, Drugs, Generic, Patient Reported Outcome Measures, Multiple Sclerosis
Abstract

Background: Coping in multiple sclerosis (MS) refers to cognitive and behavioural efforts to manage stresses imposed by the illness. Existing generic and disease-specific coping scales do not meet modern guidelines for scale development and cannot produce interval-level metrics to allow for change scores., Objective: The main aim of this study was to develop a brief patient-reported outcome measure for coping in MS, capable of interval-level measurement., Methods: Qualitative work in 43 people with MS leads to a draft scale which was administered to 5747 participants, with longitudinal collection in 2290. A calibration sample of 1000 subjects split into development and validation sets was used to generate three scales consistent with Rasch model expectations., Results: The total Coping Index-MS (CI-MS-T), CI-MS-Internal (CI-MS-I) and CI-MS-External (CI-MS-E) cover total, internal and externally focused coping. All three scales are capable of interval-level measurement. Trajectory analysis of 9000 questionnaires showed two trajectories in CI-MS-T: Group 1 showed a low level of coping with slight decline over 40 months, while Group 2 had a better and stable level of coping due to improving CI-MS-I which compensated for the deteriorating CI-MS-E over time. CI-MS-T < 30 identified group membership at baseline., Conclusion: The CI-MS-T, CI-MS-I and CI-MS-E, comprising 20 items, provide interval-level measurement and are free-for-use in not-for-profit settings.

Published
2022
Full Text
View/download PDF

47. The impact of smoking cessation on multiple sclerosis disease progression.

Author

Rodgers J, Friede T, Vonberg FW, Constantinescu CS, Coles A, Chataway J, Duddy M, Emsley H, Ford H, Fisniku L, Galea I, Harrower T, Hobart J, Huseyin H, Kipps CM, Marta M, McDonnell GV, McLean B, Pearson OR, Rog D, Schmierer K, Sharrack B, Straukiene A, Wilson HC, Ford DV, Middleton RM, and Nicholas R

Subjects
Adult, Disease Progression, Humans, Prospective Studies, Retrospective Studies, Disabled Persons, Motor Disorders, Multiple Sclerosis complications, Smoking Cessation
Abstract

The negative impact of smoking in multiple sclerosis is well established; however, there is much less evidence as to whether smoking cessation is beneficial to progression in multiple sclerosis. Adults with multiple sclerosis registered on the United Kingdom Multiple Sclerosis Register (2011-20) formed this retrospective and prospective cohort study. Primary outcomes were changes in three patient-reported outcomes: normalized Multiple Sclerosis Physical Impact Scale (MSIS-29-Phys), normalized Multiple Sclerosis Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS). Time to event outcomes were clinically significant increases in the patient-reported outcomes. The study included 7983 participants; 4130 (51.7%) of these had ever smoked, of whom 1315 (16.5%) were current smokers and 2815/4130 (68.2%) were former smokers. For all patient-reported outcomes, current smokers at the time of completing their first questionnaire had higher patient-reported outcomes scores indicating higher disability compared to those who had never smoked (∼10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 points for HADS-Anxiety and HADS-Depression). There was no improvement in patient-reported outcomes scores with increasing time since quitting in former smokers. Nine hundred and twenty-three participants formed the prospective parallel group, which demonstrated that MSIS-29-Phys [median (IQR) 5.03 (3.71, 6.34)], MSWS-12 [median (IQR) 5.28 (3.62, 6.94)] and HADS-Depression [median (IQR) 0.71 (0.47, 0.96)] scores worsened over a period of 4 years, whereas HADS-Anxiety remained stable. Smoking status was significant at Year 4; current smokers had higher MSIS-29-Phys and HADS-Anxiety scores [median (IQR) 3.05 (0.22, 5.88) and 1.14 (0.52, 1.76), respectively] while former smokers had a lower MSIS-29-Phys score of -2.91 (-5.03, -0.79). A total of 4642 participants comprised the time to event analysis. Still smoking was associated with a shorter time to worsening event in all patient-reported outcomes (MSIS-29-Phys: n = 4436, P = 0.0013; MSWS-12: n = 3902, P = 0.0061; HADS-Anxiety: n = 4511, P = 0.0017; HADS-Depression: n = 4511, P < 0.0001). Worsening in motor disability (MSIS-29-Phys and MSWS-12) was independent of baseline HADS-Anxiety and HADS-Depression scores. There was no statistically significant difference in the rate of worsening between never and former smokers. When smokers quit, there is a slowing in the rate of motor disability deterioration so that it matches the rate of motor decline in those who have never smoked. This suggests that smoking cessation is beneficial for people with multiple sclerosis., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2022
Full Text
View/download PDF

48. The four self-efficacy trajectories among people with multiple sclerosis: Clinical associations and implications.

Author

Young CA, Mills R, Langdon D, Sharrack B, Majeed T, Kalra S, Footitt D, Rog D, Harrower T, Nicholas R, Woolmore J, Thorpe J, Hanemann CO, Ford H, Paling D, Ellis C, Palace J, Constantinescu C, and Tennant A

Subjects
Female, Humans, Longitudinal Studies, Male, Middle Aged, Self Efficacy, Surveys and Questionnaires, Multiple Sclerosis complications, Multiple Sclerosis, Relapsing-Remitting complications
Abstract

Background: Longitudinal studies among people with Multiple Sclerosis (pwMS) have shown that self-efficacy is linked to physical, cognitive and psychological functioning., Objectives: To determine the distribution of self-efficacy in a large sample of pwMS, examining whether there are distinct groups which show different self-efficacy trajectories over time, and the health status characteristics of any groups identified., Methods: Participants completed serial questionnaire packs, including Unidimensional Self-efficacy-MS (USE-MS) scale, for the Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study over an average 46-month period. The resulting longitudinal data were analysed by a group-based trajectory model., Results: 5887 pwMS were studied: mean age 50.2 years (SD 12.0); 73.6% female; Relapsing Remitting MS (61.8%), Secondary Progressive (22.9%), Primary Progressive (11.1%), Rapidly Evolving Relapsing Remitting MS (4.2%). Four distinct self-efficacy trajectories emerged, with declining, slightly declining, stable or improving self-efficacy, each showing different patterns of health status indicators such as EQ-5D-5L, disability and depression. USE-MS ≤ 18 at baseline detected all participants in the two declining groups., Conclusion: Future trials on interventions for self-efficacy should assume a priori that those with low levels of self-efficacy (USE-MS ≤ 18 at baseline) are likely to be on a declining trajectory and may need different interventions from those with stable self-efficacy., (Copyright © 2022. Published by Elsevier B.V.)

Published
2022
Full Text
View/download PDF

49. Quality of life in multiple sclerosis is dominated by fatigue, disability and self-efficacy.

Author

Young CA, Mills R, Rog D, Sharrack B, Majeed T, Constantinescu CS, Kalra S, Harrower T, Santander H, Courtald G, Ford HL, Woolmore J, and Tennant A

Subjects
Cross-Sectional Studies, Disability Evaluation, Fatigue etiology, Humans, Self Efficacy, Multiple Sclerosis complications, Multiple Sclerosis therapy, Quality of Life
Abstract

Background and Objective: Quality of life in multiple sclerosis (MS) reflects complex relationships between symptoms (fatigue, spasticity pain, and bladder or vision dysfunction), disability, health perceptions, and self-efficacy., Methods: In this cross-sectional study, a self-report questionnaire pack of patient reported outcome measures was collected from 5695 people with MS (pwMS) alongside clinical data from their neurologists. Each patient reported outcome measure was converted to interval-scaled estimates following fit to the Rasch model. The patient reported outcome measures, as well as perceived health, age, disease subtype and gender, were then subject to path analysis to analyse their relationships with quality of life (QoL), guided by the Wilson and Clearly conceptual framework., Results: The final model explains 81.2% of the variance of QoL. Fatigue is clearly dominant, suggesting a means to intervene and improve QoL. The next most influential factors were disability and self-efficacy, which have similar effect levels. The model can be replicated for pwMS on disease modifying therapy and is largely invariant for gender and disease subtype. Age had an insignificant effect., Conclusions: In order to promote better QoL, MS care should include management of fatigue, interventions to ameliorate disability, and support to enhance self-efficacy. The range of skills needed for these treatments will require input from medical, nursing, therapy and psychology staff, so these findings provide evidence substantiating the need for pwMS to be provided with care by comprehensive multidisciplinary teams., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Published
2021
Full Text
View/download PDF

50. Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.

Author

Lin S, Green HD, Hendy P, Heerasing NM, Chanchlani N, Hamilton B, Walker GJ, Heap GA, Hobart J, Martin RJ, Coles AJ, Silverberg MS, Irving PM, Chung-Faye G, Silber E, Cummings JRF, Lytvyak E, Andersen V, Wood AR, Tyrrell J, Beaumont RN, Weedon MN, Kennedy NA, Spiers A, Harrower T, Goodhand JR, and Ahmad T

Subjects
Adult, Case-Control Studies, Demyelinating Diseases genetics, Female, Humans, Male, Middle Aged, Multiple Sclerosis etiology, Multiple Sclerosis genetics, Prospective Studies, Retrospective Studies, Risk Factors, State Medicine organization & administration, State Medicine statistics & numerical data, Tumor Necrosis Factor Inhibitors therapeutic use, Demyelinating Diseases etiology, Tumor Necrosis Factor Inhibitors adverse effects
Abstract

Background: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS]., Methods: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination., Results: Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7-63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1-28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10-4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10-3, SD 0.0042] [p = 0.23]., Conclusions: Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results