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1. Effect of Disease Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years

Author

Kalincik, Tomas, Diouf, Ibrahima, Sharmin, Sifat, Malpas, Charles, Spelman, Tim, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Jokubaitis, Vilija, van der Walt, Anneke, GrandʼMaison, Francois, Sola, Patrizia, Ferraro, Diana, Shaygannejad, Vahid, Alroughani, Raed, Hupperts, Raymond, Terzi, Murat, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Van Pesch, Vincent, Granella, Franco, Bergamaschi, Roberto, Spitaleri, Daniele, Slee, Mark, Vucic, Steve, Ampapa, Radek, McCombe, Pamela, Ramo-Tello, Cristina, Prevost, Julie, Olascoaga, Javier, Cristiano, Edgardo, Barnett, Michael, Saladino, Maria Laura, Sanchez-Menoyo, Jose Luis, Hodgkinson, Suzanne, Rozsa, Csilla, Hughes, Stella, Moore, Fraser, Shaw, Cameron, Butler, Ernest, Skibina, Olga, Gray, Orla, Kermode, Allan, Csepany, Tunde, Singhal, Bhim, Shuey, Neil, Piroska, Imre, Taylor, Bruce, Simo, Magdolna, Sirbu, Carmen-Adella, Sas, Attila, and Butzkueven, Helmut

Published
2020
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6. Variability of the Response to Immunotherapy Among Sub-groups of Patients With Multiple Sclerosis (4107)

Author

Diouf, Ibrahima, primary, Malpas, Charles, additional, Horakova, Dana, additional, Havrdova, Eva, additional, Patti, Francesco, additional, Shaygannejad, Vahid, additional, Ozakbas, Serkan, additional, Ayuso, Guillermo Izquierdo, additional, Madueño, Sara Eichau, additional, Zakaria, Magd, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Alroughani, Raed, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Terzi, Murat, additional, Boz, Cavit, additional, Grand’Maison, Francois, additional, Hamdy, Sherif, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Grammond, Pierre, additional, Turkoglu, Recai, additional, Butzkueven, Helmut, additional, Yamout, Bassem, additional, Altintas, Ayse, additional, Van Pesch, Vincent, additional, Maimone, Davide, additional, Lechner-Scott, Jeannette, additional, Bergamaschi, Roberto, additional, Karabudak, Rana, additional, Iuliano, Gerardo, additional, McGuigan, Christopher, additional, Cartechini, Elisabetta, additional, Barnett, Michael, additional, Hughes, Stella, additional, Sa, Maria Jose, additional, Kappos, Ludwig, additional, Ramo-Tello, Cristina, additional, Cristiano, Edgardo, additional, Hodgkinson, Suzanne, additional, Spitaleri, Daniele Litterio A., additional, Soysal, Aysun, additional, Petersen, Thor, additional, Slee, Mark, additional, Butler, Ernest, additional, Granella, Franco, additional, Verheul, Freek, additional, McCombe, Pamela, additional, Ampapa, Radek, additional, Skibina, Olga, additional, Prevost, Julie, additional, Sinnige, L, additional, Sanchez-Menoyo, Jose Luis, additional, Vucic, Steve, additional, Laureys, Guy, additional, Van Hijfte, Liesbeth, additional, Khurana, Dheeraj, additional, Macdonell, Richard, additional, Castillo-Triviño, Tamara, additional, Gray, Orla, additional, Aguera-Morales, Eduardo, additional, Kister, Ilya, additional, Shaw, Cameron, additional, Deri, Norma, additional, Al-Harbi, Talal, additional, Fragoso, Yara, additional, Csepany, Tunde, additional, Sempere, Angel, additional, and Kalincik, Tomas, additional

Published
2021
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7. Disability Accrual in Primary Progressive & Secondary Progressive Multiple Sclerosis (2901)

Author

Harding-Forrester, Sam, primary, Roos, Izanne, additional, Sharmin, Sifat, additional, Diouf, Ibrahima, additional, Malpas, Charles, additional, Nguyen, Ai-Lan, additional, Moradi, Nahid, additional, Horáková, Dana, additional, Havrdová, Eva Kubala, additional, Patti, Francesco, additional, Ayuso, Guillermo Izquierdo, additional, Madueño, Sara Eichau, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Grand’Maison, Francois, additional, Weinstock-Guttman, Bianca, additional, Amato, Maria Pia, additional, Grammond, Pierre, additional, Gerlach, Oliver, additional, Ozakbas, Serkan, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Butzkueven, Helmut, additional, Lechner-Scott, Jeannette, additional, Boz, Cavit, additional, Alroughani, Raed, additional, Van Pesch, Vincent, additional, Cartechini, Elisabetta, additional, Terzi, Murat, additional, Maimone, Davide, additional, Ramo-Tello, Cristina, additional, Spitaleri, Daniele Litterio A., additional, Kappos, Ludwig, additional, Yamout, Bassem, additional, Sá, Maria José, additional, Slee, Mark, additional, Morgado, Yolanda Blanco, additional, Bergamaschi, Roberto, additional, Butler, Ernest, additional, Iuliano, Gerardo, additional, Granella, Franco, additional, Sidhom, Youssef, additional, Gouider, Riadh, additional, Ampapa, Radek, additional, Van Wijmeersch, Bart, additional, Karabudak, Rana, additional, Prevost, Julie, additional, Sánchez-Menoyo, José Luis, additional, De Gans, Koen, additional, McCombe, Pamela, additional, Castillo-Triviño, Tamara, additional, Macdonell, Richard, additional, Altintas, Ayse, additional, Laureys, Guy, additional, Van Hijfte, Liesbeth, additional, Van Der Walt, Anneke, additional, Vucic, Steve, additional, Türkoǧlu, Recai, additional, Barnett, Michael, additional, Cristiano, Edgardo, additional, Zakaria, Magd, additional, Shaygannejad, Vahid, additional, Hodgkinson, Suzanne, additional, Soysal, Aysun, additional, Buzzard, Katherine, additional, Skibina, Olga, additional, and Kalincik, Tomas, additional

Published
2021
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8. Association of Latitude and Exposure to Ultraviolet B Radiation with Severity of Multiple Sclerosis (2554)

Author

Vitkova, Marianna, primary, Diouf, Ibrahima, additional, Malpas, Charles, additional, Horakova, Dana, additional, Havrdova, Eva Kubala, additional, Patti, Francesco, additional, Ozakbas, Serkan, additional, Ayuso, Guillermo Izquierdo, additional, Madueño, Sara Eichau, additional, Shaygannejad, Vahid, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Alroughani, Raed, additional, Prat, Alexandre, additional, Larochelle, Catherine, additional, Girard, Marc, additional, Duquette, Pierre, additional, Terzi, Murat, additional, Boz, Cavit, additional, Grand’Maison, Francois, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Grammond, Pierre, additional, Butzkueven, Helmut, additional, Buzzard, Katherine, additional, Skibina, Olga, additional, Yamout, Bassem, additional, Karabudak, Rana, additional, Gerlach, Oliver H.H, additional, Lechner-Scott, Jeannette, additional, Maimone, Davide, additional, Bergamaschi, Roberto, additional, Van Pesch, Vincent, additional, Iuliano, Gerardo, additional, Cartechini, Elisabetta, additional, Sá, Maria José, additional, Ampapa, Radek, additional, Barnett, Michael, additional, Hughes, Stella, additional, Ramo-Tello, Cristina, additional, Hodgkinson, Suzanne, additional, Spitareli, Daniele, additional, Petersen, Thor, additional, Butler, Ernest, additional, Slee, Mark, additional, McGuigan, Christopher, additional, McCombe, Pamela, additional, Granella, Franco, additional, Cristiano, Edgardo, additional, Prevost, Julie, additional, Taylor, Bruce, additional, Sanchez-Menoyo, Jose Luis, additional, Laureys, Guy, additional, Van Hijfte, Liesbeth, additional, Vucic, Steve, additional, Macdonell, Richard, additional, Gray, Orla, additional, Urtaza, Francisco Javier Olascoaga, additional, Deri, Norma, additional, Fragoso, Yara, additional, Shaw, Cameron, additional, and Kalincik, Tomas, additional

Published
2021
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9. MRI Patterns Distinguish Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis (4128)

Author

Clarke, Laura, primary, Arnett, Simon, additional, Bukhari, Wajih, additional, Khalilidehkordi, Elham, additional, Sanchez, Sofia Jimenez, additional, O’Gorman, Cullen, additional, Prain, Kerri, additional, Woodhall, Mark, additional, Silvestrini, Roger, additional, Bundell, Christine, additional, Abernethy, David, additional, Bhuta, Sandeep, additional, Blum, Stefan, additional, Boggild, Mike, additional, Boundy, Karyn, additional, Brew, Bruce, additional, Brownlee, Wallace, additional, Butzkueven, Helmut, additional, Carroll, William, additional, Chen, Celia, additional, Coulthard, Alan, additional, Dale, Russell, additional, Das, Chandi, additional, Fabis-Pedrini, Marzena, additional, Fulcher, David, additional, Gillis, David, additional, Hawke, Simon, additional, Heard, Robert, additional, Henderson, Andrew, additional, Heshmat, Saman, additional, Hodgkinson, Suzanne, additional, Kilpatrick, Trevor, additional, King, John, additional, Kneebone, Christopher, additional, Kornberg, Andrew, additional, Lechner-Scott, Jeannette, additional, Lin, Ming-Wei, additional, Lynch, Christopher, additional, Macdonell, Richard, additional, Mason, Deborah, additional, McCombe, Pamela, additional, Pereira, Jennifer, additional, Pollard, John, additional, Ramanathan, Sudarshini, additional, Reddel, Stephen, additional, Shaw, Cameron, additional, Spies, Judith, additional, Stankovich, James, additional, Sutton, Ian, additional, Vucic, Steve, additional, Walsh, Michael, additional, Wong, Richard, additional, Yiu, Eppie, additional, Barnett, Michael, additional, Kermode, Allan, additional, Marriott, Mark, additional, Parratt, John, additional, Slee, Mark, additional, Taylor, Bruce, additional, Willoughby, Ernest, additional, Brilot, Fabienne, additional, Vincent, Angela, additional, Waters, Patrick, additional, and Broadley, Simon, additional

Published
2021
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11. Clinical determinants and therapeutic modifiers of relapse and disability outcomes in neuromyelitis optica spectrum disorder (P1.2-072)

Author

Kunchok, Amy, primary, Malpas, Charles, additional, Nytrova, Petra, additional, Havrdova, Eva, additional, Alroughani, Raed, additional, Terzi, Murat, additional, Yamout, Bassem, additional, Hor, Jyh Yung, additional, Karabudak, Rana, additional, Boz, Cavit, additional, Ozakbas, Serkan, additional, Urtaza, Francisco Javier Olascoaga, additional, Simo, Magdolna, additional, Granella, Franco, additional, Patti, Francesco, additional, McCombe, Pamela, additional, Csepany, Tunde, additional, Singhal, Bhim, additional, Bergamaschi, Roberto, additional, Fragoso, Yara, additional, Al-Harbi, Talal, additional, Turkoglu, Recai, additional, Lechner-Scott, Jeannette, additional, Laureys, Guy, additional, Oreja-Guevara, Celia, additional, Pucci, Eugenio, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Altintas, Ayse, additional, Soysal, Aysun, additional, Vucic, Steve, additional, Grand-Maison, Francois, additional, Madueno, Sara Eichau, additional, Ayuso, Guillermo Izquierdo, additional, Lugaresi, Alessandra, additional, Onofrj, Marco, additional, Trojano, Maria, additional, Marriott, Mark, additional, Butzkueven, Helmut, additional, Kister, Ilya, additional, and Kalincik, Tomas, additional

Published
2019
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12. Diagnostic criteria in amyotrophic lateral sclerosis

Author

Geevasinga, Nimeshan, primary, Menon, Parvathi, additional, Scherman, Daniel B., additional, Simon, Neil, additional, Yiannikas, Con, additional, Henderson, Robert D., additional, Kiernan, Matthew C., additional, and Vucic, Steve, additional

Published
2016
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13. Motor cortical function determines prognosis in sporadic ALS

Author

Shibuya, Kazumoto, primary, Park, Susanna B., additional, Geevasinga, Nimeshan, additional, Menon, Parvathi, additional, Howells, James, additional, Simon, Neil G., additional, Huynh, William, additional, Noto, Yu-ichi, additional, Götz, Jürgen, additional, Kril, Jillian J., additional, Ittner, Lars M., additional, Hodges, John, additional, Halliday, Glenda, additional, Vucic, Steve, additional, and Kiernan, Matthew C., additional

Published
2016
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14. Prospectively tracking disease course and treatment changes in Neuromyelitis Optica using NMOBase, a global online registry. (P5.307)

Author

Kister, Ilya, primary, Bacon, Tamar, additional, Shaygannejad, Vahid, additional, Hor, Jyh Yung, additional, Alroughani, Raed, additional, Haas, Shannon, additional, Terzi, Murat, additional, Boz, Cavit, additional, Olascoaga, Javier, additional, McCombe, Pamela, additional, Fragoso, Yara, additional, Lugaresi, Alessandra, additional, Sola, Patrizia, additional, Vucic, Steve, additional, Pucci, Eugenio, additional, Al-Harbi, Talal, additional, Sajedi, Seyed Aidin, additional, Rojas, Juan Ignacio, additional, Patrucco, Liliana, additional, Cristiano, Edgardo, additional, Suarez, Jose Alberto, additional, Tsolaki, Magdalini, additional, Taylor, Bruce, additional, Iuliano, Gerardo, additional, Devranis, Paschalis, additional, Marriott, Mark, additional, and Butzkueven, Helmut, additional

Published
2016
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20. FOSMN syndrome

Author

Vucic, Steve, primary, Stein, Thor D., additional, Hedley-Whyte, E. Tessa, additional, Reddel, Stephen R., additional, Tisch, Stephen, additional, Kotschet, Katya, additional, Cros, Didier, additional, and Kiernan, Matthew C., additional

Published
2012
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23. Teaching NeuroImages: Kearns-Sayre syndrome.

Author

Geevasinga, Nimeshan, Howells, James, Menon, Parvathi, van den Bos, Mehdi, Shibuya, Kazumoto, Matamala, José Manuel, Park, Susanna B, Byth, Karen, Kiernan, Matthew C, Vucic, Steve, Nguyen, Michael T B, Micieli, Jonathan, and Margolin, Edward

Published
2019
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24. Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis.

Author

Roos I, Malpas C, Leray E, Casey R, Horakova D, Havrdova EK, Debouverie M, Patti F, De Seze J, Izquierdo G, Eichau S, Edan G, Prat A, Girard M, Ozakbas S, Grammond P, Zephir H, Ciron J, Maillart E, Moreau T, Amato MP, Labauge P, Alroughani R, Buzzard K, Skibina O, Terzi M, Laplaud DA, Berger E, Grand'Maison F, Lebrun-Frenay C, Cartechini E, Boz C, Lechner-Scott J, Clavelou P, Stankoff B, Prevost J, Kappos L, Pelletier J, Shaygannejad V, Yamout BI, Khoury SJ, Gerlach O, Spitaleri DLA, Van Pesch V, Gout O, Turkoglu R, Heinzlef O, Thouvenot E, McCombe PA, Soysal A, Bourre B, Slee M, Castillo-Trivino T, Bakchine S, Ampapa R, Butler EG, Wahab A, Macdonell RA, Aguera-Morales E, Cabre P, Ben NH, Van der Walt A, Laureys G, Van Hijfte L, Ramo-Tello CM, Maubeuge N, Hodgkinson S, Sánchez-Menoyo JL, Barnett MH, Labeyrie C, Vucic S, Sidhom Y, Gouider R, Csepany T, Sotoca J, de Gans K, Al-Asmi A, Fragoso YD, Vukusic S, Butzkueven H, and Kalincik T

Subjects
Humans, Female, Natalizumab therapeutic use, Fingolimod Hydrochloride therapeutic use, Retrospective Studies, Recurrence, Immunosuppressive Agents adverse effects, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology, Multiple Sclerosis chemically induced
Abstract

Background and Objectives: To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy., Methods: This was a retrospective cohort study from 2 large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12 months were included in the analysis. The primary study outcome was annualized relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation., Results: A total of 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for 7 therapies. Annualized rates of relapse (ARRs) started to increase 2 months after natalizumab cessation (month 2-4 ARR 0.47, 95% CI 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89) and stabilized faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01 to 0.29). The magnitude of disease reactivation for other therapies was low but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were a higher relapse rate in the year before cessation, female sex, younger age, and higher EDSS score. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95% CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80)., Discussion: The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued different therapies. These results suggest that untreated intervals should be minimized after stopping antitrafficking therapies (natalizumab and fingolimod)., Classification of Evidence: This study provides Class III that disease reactivation occurs within months of discontinuation of MS disease-modifying therapies. The risk of disease activity is reduced by commencement of a subsequent therapy., (© 2022 American Academy of Neurology.)

Published
2022
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25. Association of Latitude and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study.

Author

Vitkova M, Diouf I, Malpas C, Horakova D, Kubala Havrdova E, Patti F, Ozakbas S, Izquierdo G, Eichau S, Shaygannejad V, Onofrj M, Lugaresi A, Alroughani R, Prat A, Larochelle C, Girard M, Duquette P, Terzi M, Boz C, Grand'Maison F, Sola P, Ferraro D, Grammond P, Butzkueven H, Buzzard K, Skibina O, Yamout BI, Karabudak R, Gerlach O, Lechner-Scott J, Maimone D, Bergamaschi R, Van Pesch V, Iuliano G, Cartechini E, José Sà M, Ampapa R, Barnett M, Hughes SE, Ramo-Tello CM, Hodgkinson S, Spitaleri DLA, Petersen T, Butler EG, Slee M, McGuigan C, McCombe PA, Granella F, Cristiano E, Prevost J, Taylor BV, Sãnchez-Menoyo JL, Laureys G, Van Hijfte L, Vucic S, Macdonell RA, Gray O, Olascoaga J, Deri N, Fragoso YD, Shaw C, and Kalincik T

Subjects
Disability Evaluation, Female, Humans, Male, Registries, Severity of Illness Index, Ultraviolet Rays adverse effects, Multiple Sclerosis diagnosis, Multiple Sclerosis epidemiology
Abstract

Background and Objectives: The severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, UV B radiation (UVB) exposure, and the severity of MS., Methods: This observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and ≥1 Expanded Disability Status Scale score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from National Aeronautics and Space Administration's Total Ozone Mapping Spectrometer) at ages 6 and 18 years and the year of disability assessment were calculated. Disease severity was quantified with Multiple Sclerosis Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB, and MSSS., Results: The 46,128 patients who contributed 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2 ± 12 years, resident between latitudes 19°35' and 56°16') were included in this study. Latitude showed a nonlinear association with MS severity. In latitudes <40°, more severe disease was associated with higher latitudes (β = 0.08, 95% CI 0.04-0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes <40° (β = -0.02, 95% CI -0.06 to 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 years (β = - 0.5, 95% CI -0.6 to 0.4) and 18 years (β = - 0.6, 95% CI -0.7 to 0.4), as well as with lower lifetime UVB exposure at the time of disability assessment (β = -1.0, 95% CI -1.1 to 0.9)., Discussion: In temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure contributing to both MS susceptibility and severity., (© 2022 American Academy of Neurology.)

Published
2022
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26. Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years.

Author

Kalincik T, Diouf I, Sharmin S, Malpas C, Spelman T, Horakova D, Havrdova EK, Trojano M, Izquierdo G, Lugaresi A, Prat A, Girard M, Duquette P, Grammond P, Jokubaitis V, van der Walt A, Grand'Maison F, Sola P, Ferraro D, Shaygannejad V, Alroughani R, Hupperts R, Terzi M, Boz C, Lechner-Scott J, Pucci E, Van Pesch V, Granella F, Bergamaschi R, Spitaleri D, Slee M, Vucic S, Ampapa R, McCombe P, Ramo-Tello C, Prevost J, Olascoaga J, Cristiano E, Barnett M, Saladino ML, Sanchez-Menoyo JL, Hodgkinson S, Rozsa C, Hughes S, Moore F, Shaw C, Butler E, Skibina O, Gray O, Kermode A, Csepany T, Singhal B, Shuey N, Piroska I, Taylor B, Simo M, Sirbu CA, Sas A, and Butzkueven H

Subjects
Adult, Disability Evaluation, Disease Progression, Female, Fingolimod Hydrochloride therapeutic use, Glatiramer Acetate therapeutic use, Humans, Immunosuppressive Agents therapeutic use, Interferon-beta therapeutic use, Longitudinal Studies, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting physiopathology, Natalizumab therapeutic use, Proportional Hazards Models, Immunologic Factors therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

Objective: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients., Methods: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity., Results: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, p = 0.0016), worsening of disability (0.56, 0.38-0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, p = 10 -9 ) and worsening of disability (0.81, 0.67-0.99, p = 0.043)., Conclusion: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term., Classification of Evidence: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability., (© 2020 American Academy of Neurology.)

Published
2021
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27. Pathophysiologic insights into motor axonal function in Kennedy disease.

Author

Vucic S and Kiernan MC

Subjects
Action Potentials genetics, Adult, Aged, Chromosomes, Human, X genetics, Electric Stimulation, Electrodiagnosis methods, Electromyography methods, Evoked Potentials, Motor genetics, Fasciculation diagnosis, Fasciculation genetics, Fasciculation physiopathology, Female, Genetic Diseases, X-Linked diagnosis, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked physiopathology, Humans, Male, Middle Aged, Motor Neuron Disease diagnosis, Motor Neuron Disease genetics, Muscle Strength genetics, Muscle Weakness diagnosis, Muscle Weakness genetics, Muscle Weakness physiopathology, Muscular Atrophy, Spinal diagnosis, Muscular Atrophy, Spinal genetics, Neural Conduction genetics, Peripheral Nervous System Diseases diagnosis, Peripheral Nervous System Diseases genetics, Receptors, Androgen genetics, Sensitivity and Specificity, Time Factors, Axons pathology, Motor Neuron Disease physiopathology, Motor Neurons pathology, Muscular Atrophy, Spinal physiopathology, Peripheral Nerves physiopathology, Peripheral Nervous System Diseases physiopathology
Abstract

Objective: Kennedy disease (KD), or spinobulbomuscular atrophy, is a slowly progressive inherited neurodegenerative disorder, marked by prominent fasciculations that typically precede the development of other symptoms. Although the genetic basis of KD relates to triplet (CAG) repeat expansion in the androgen receptor (AR) gene on the X chromosome, the mechanisms underlying the clinical presentation in KD have yet to be established. Consequently, the present study applied axonal excitability techniques to investigate the pathophysiologic mechanisms associated with KD., Methods: Peripheral nerve excitability studies were undertaken in 7 patients with KD with compound muscle action potentials (CMAP) recorded from the right abductor pollicis brevis., Results: Strength-duration time constant (KD 0.54 +/- 0.03 msec; controls, 0.41 +/- 0.02 msec, p < 0.01) and the hyperpolarizing current/threshold gradient (KD 0.42 +/- 0.01; controls, 0.37 +/- 0.01, p < 0.05) were significantly increased in KD. Strength-duration time constant correlated with the CMAP amplitude (R = 0.68) and the fasciculation frequency (R = 0.62). Threshold electrotonus revealed greater changes in response to subthreshold depolarizing (KD TEd [90 to 100 msec], 50.75 +/- 1.98%; controls TEd [90 to 100 msec], 45.67 +/- 0.67%, p < 0.01) and hyperpolarizing (KD TEh [90 to 100 msec], 128.5 +/- 6.9%; controls TEh [90 to 100 msec], 120.5 +/- 2.4%) conditioning pulses. Measurements of refractoriness, superexcitability, and late subexcitability changed appropriately for axonal hyperpolarization, perhaps reflecting the effects of increased ectopic activity., Conclusion: In total, the increase in the strength-duration time constant may be the primary event, occurring early in course of the disease, contributing to the development of axonal hyperexcitability in Kennedy disease, and thereby to the generation of fasciculations, a characteristic hallmark of the disease.

Published
2007
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28. Multifocal motor neuropathy: decrease in conduction blocks and reinnervation with long-term IVIg.

Author

Vucic S, Black KR, Chong PS, and Cros D

Subjects
Action Potentials drug effects, Adult, Axons drug effects, Axons physiology, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Immunoglobulins, Intravenous administration & dosage, Male, Middle Aged, Motor Neuron Disease physiopathology, Muscle Weakness physiopathology, Muscle Weakness therapy, Muscles drug effects, Muscles physiopathology, Nerve Degeneration physiopathology, Polyneuropathies physiopathology, Immunoglobulins, Intravenous therapeutic use, Motor Neuron Disease therapy, Neural Conduction drug effects, Polyneuropathies therapy
Abstract

Background: Multifocal motor neuropathy with conduction blocks (MMNCB) is an immune-mediated motor neuropathy. Previous long-term IV immunoglobulin (IVIg) treatment studies have documented improvement in muscle strength and functional disability but revealed a concomitant increase in acute axonal degeneration (AD) and conduction block (CB)., Objective: To determine the long-term effects of IVIg therapy on clinical and neurophysiologic outcome measures in MMNCB patients responsive to IVIg., Methods: The authors reviewed medical records of 10 patients with MMNCB for outcomes in muscle strength (Medical Research Council score), functional disability (Modified Rankin Disability score), CB, and AD. All patients had received IVIg (2g/kg in 5 days for 3 consecutive months), followed by monthly maintenance therapy., Results: Patients were followed for an average of 7.25 years (range, 3.5 to 12 years). There was significant and sustained improvement in muscle strength and functional disability while on IVIg therapy. Furthermore, the authors found significant improvement in CB, decrease in AD, and evidence of reinnervation by the end of the follow-up period., Conclusion: Long-term IV immunoglobulin therapy improves muscle strength and functional disability, decreases the number of conduction blocks and the extent of axonal degeneration, and promotes reinnervation. These findings differ from previous reports of deterioration in neurophysiologic outcome measures. Comparison of the IV immunoglobulin regimen in those reports and this study shows that the authors' patients were treated with significantly higher IV immunoglobulin maintenance doses. These findings have implications for the long-term treatment of patients with multifocal motor neuropathy with conduction blocks.

Published
2004
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