A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores

Vera Fridman; Stefan Sillau; Gyula Acsadi; Chelsea Bacon; Kimberly Dooley; Joshua Burns; John Day; Shawna Feely; Richard S. Finkel; Tiffany Grider; Laurie Gutmann; David N. Herrmann; Callyn A. Kirk; Sarrah A. Knause; Matilde Laurá; Richard A. Lewis; Jun Li; Thomas E. Lloyd; Isabella Moroni; Francesco Muntoni; Emanuela Pagliano; Chiara Pisciotta; Giuseppe Piscosquito; Sindhu Ramchandren; Mario Saporta; Reza Sadjadi; Rosemary R. Shy; Carly E. Siskind; Charlotte J. Sumner; David Walk; Janel Wilcox; Sabrina W. Yum; Stephan Züchner; Steven S. Scherer; Davide Pareyson; Mary M. Reilly; Michael E. Shy

doi:10.1212/WNL.0000000000009035

A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores

Vera Fridman, Stefan Sillau, Gyula Acsadi, Chelsea Bacon, Kimberly Dooley, Joshua Burns, John Day, Shawna Feely, Richard S. Finkel, Tiffany Grider, Laurie Gutmann, David N. Herrmann, Callyn A. Kirk, Sarrah A. Knause, Matilde Laurá, Richard A. Lewis, Jun Li, Thomas E. Lloyd, Isabella Moroni, Francesco MuntoniEmanuela Pagliano, Chiara Pisciotta, Giuseppe Piscosquito, Sindhu Ramchandren, Mario Saporta, Reza Sadjadi, Rosemary R. Shy, Carly E. Siskind, Charlotte J. Sumner, David Walk, Janel Wilcox, Sabrina W. Yum, Stephan Züchner, Steven S. Scherer, Davide Pareyson, Mary M. Reilly, Michael E. Shy

Neurology

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

OBJECTIVE: To evaluate the sensitivity of Rasch analysis-based, weighted Charcot-Marie-Tooth Neuropathy and Examination Scores (CMTNS-R and CMTES-R) to clinical progression in patients with Charcot-Marie-Tooth disease type 1A (CMT1A).

METHODS: Patients with CMT1A from 18 sites of the Inherited Neuropathies Consortium were evaluated between 2009 and 2018. Weighted CMTNS and CMTES modified category responses were developed with Rasch analysis of the standard scores. Change from baseline for CMTNS-R and CMTES-R was estimated with longitudinal regression models.

RESULTS: Baseline CMTNS-R and CMTES-R scores were available for 517 and 1,177 participants, respectively. Mean ± SD age of participants with available CMTES-R scores was 41 ± 18 (range 4-87) years, and 56% were female. Follow-up CMTES-R assessments at 1, 2, and 3 years were available for 377, 321, and 244 patients. A mixed regression model showed significant change in CMTES-R score at years 2 through 6 compared to baseline (mean change from baseline 0.59 points at 2 years, p = 0.0004, n = 321). Compared to the original CMTES, the CMTES-R revealed a 55% improvement in the standardized response mean (mean change/SD change) at 2 years (0.17 vs 0.11). Change in CMTES-R at 2 years was greatest in mildly to moderately affected patients (1.48-point mean change, 95% confidence interval 0.99-1.97, p < 0.0001, for baseline CMTES-R score 0-9).

CONCLUSION: The CMTES-R demonstrates change over time in patients with CMT1A and is more sensitive than the original CMTES. The CMTES-R was most sensitive to change in patients with mild to moderate baseline disease severity and failed to capture progression in patients with severe CMT1A.

CLINICALTRIALSGOV IDENTIFIER: NCT01193075.

Original language	English (US)
Pages (from-to)	e884-e896
Journal	Neurology
Volume	94
Issue number	9
DOIs	https://doi.org/10.1212/WNL.0000000000009035
State	Published - Mar 3 2020

Bibliographical note

Funding Information:
The INC is a part of the NIH RDCRN. The authors thank all the patients who participated in the INC and their families, without whom this study would not be possible. The authors also thank the people working at INC sites who contributed to this study, especially Julian Blake, Betsy Burgos, Daniela Calabrese, Vinay Chaudhry, David Corn-blath, Katy Eichinger, Tim Estilow, Claudia Gandioli, Audra Hamilton, Allan M. Glanzman, Ahmet Hoke, Andrea Kelley, Livija Medne, Manoj Menezes, Joan Mountain, Sinead Murphy, Jillian Olsen, Alex Rossor, Oranee Sanmaneechai, Paola Saveri, Anna Sorey, Mariola Skorupinska, Janet Sowden, and Andrea Swenson. This research was also supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

Funding Information:
The INC (2U54NS065712-07) is a part of the RDCRN, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences. The INC is funded through a collaboration between the National Center for Advancing Translational Sciences and the National Institute of Neurological Disorders and Stroke. The INC also receives support from the Muscular Dystrophy Association and Charcot-Marie-Tooth Association.

Funding Information:
V. Fridman, S. Sillau, G. Acsadi, C. Bacon, and K. Dooley report no disclosures relevant to the manuscript. J. Burns reports research and clinical activities funded by the Australian Department of Health (Medical Research Future Fund), US NIH, Charcot-Marie-Tooth Australia, Charcot-Marie-Tooth Association (USA), Diabetes Australia, Elizabeth Lottie May Rosenthal Bone Bequest, Perpetual Limited, and Humpty Dumpty Foundation. Dr Burns serves as a consultant for Acceleron Pharma. J. Day, S. Feely, R. Finkel, T. Grider, and L. Gutmann report no disclosures relevant to the manuscript. D. Herrmann reports grant support through U54 NS065712-09, 1R01DK115687-01A1, Muscular Dystrophy Association, Friedreich’s Ataxia Research Alliance and Voyager Pharmaceuticals, Acceleron Pharma, and Flex Pharma. Dr. Herrmann also reports consulting fees from Regenacy Pharmaceuticals, Acceleron Pharma, Alnylam, Neurogene, Flex Pharma, Narrow River Management, Guidepoint Global, GLG, Slingshot Insights, LAM Therapeutics, Inc, Voyager Therapeutics, ClearView Health Partners, MedPace, DDB Health NY, Cydan, Trinity Partners, Schlesinger, and Human First Therapeutics. C. Kirk, S. Knause, and M. Laurá report no disclosures relevant to the manuscript. R. Lewis reports providing consulting services for CSL Behring, Pharnext, Shire, Pharnext, Biotest, Annexon, Alexion, Akcea, and Alnylam. Pharnext has performed clinical trials in CMT1A. He is medical director of Premier Pharmacy Services, a home infusion company. J. Li, T. Lloyd, I. Moroni, F. Muntoni, E. Pagliano, C. Pisciotta, and G. Piscosquito report no disclosures relevant to the manuscript. S. Ramchandren is currently employed by a contract research organization (PRA Health Sciences) that works with pharmaceutical companies. M. Saporta, R. Sadjadi, R. Shy, and C. Siskind report no disclosures relevant to the manuscript. C. Sumner reports providing consulting services regarding spinal muscular atrophy to Biogen, Roche/ Genetech, Avexis, Cytokinetics, Pfizer, Ionis, and PTC Therapeutics. She serves on advisory committees to Cure SMA, SMA Foundation, Muscular Dystrophy Association, and CMT Research Foundation. D. Walk reports serving as a consultant for Acceleron Pharma. J. Wilcox, S. Yum, and S. Züchner report no disclosures relevant to the manuscript. S. Scherer reports serving as a consultant for Biogen and Disarm. D. Pareyson reports grant support from Telethon-UILDM, AFM-Telethon, the Charcot-Marie-Tooth Association; serves on clinical advisory boards for Inflectis, Alnylam, and Akcea; and has received travel grants from Kedrion Spa and Pfizer. Te Istituto Neurologico Carlo Besta receives donations for research from Pfizer, LAM Therapeutics, Acceleron Pharma Inc. M. Reilly reports grant support from U54 NS0657, the Muscular Dystrophy Association, and the Medical Research Council and consulting for Inflectis, Alnylam, and Akcea. M. Shy reports grant support from U54 NS0657, the Muscular Dystrophy Association, and the Charcot-Marie-Tooth Association. Go to Neurology.org/N for full disclosures.

Publisher Copyright:
© American Academy of Neurology.

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Charcot-Marie-Tooth Disease/diagnosis
Child
Child, Preschool
Disease Progression
Female
Humans
Longitudinal Studies
Male
Middle Aged
Models, Theoretical
Sensitivity and Specificity
Severity of Illness Index
Time Factors
Young Adult

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Multicenter Study
Journal Article
Research Support, N.I.H., Extramural

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10.1212/WNL.0000000000009035

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Fridman, V., Sillau, S., Acsadi, G., Bacon, C., Dooley, K., Burns, J., Day, J., Feely, S., Finkel, R. S., Grider, T., Gutmann, L., Herrmann, D. N., Kirk, C. A., Knause, S. A., Laurá, M., Lewis, R. A., Li, J., Lloyd, T. E., Moroni, I., ... Shy, M. E. (2020). A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores. Neurology, 94(9), e884-e896. https://doi.org/10.1212/WNL.0000000000009035

Fridman, V, Sillau, S, Acsadi, G, Bacon, C, Dooley, K, Burns, J, Day, J, Feely, S, Finkel, RS, Grider, T, Gutmann, L, Herrmann, DN, Kirk, CA, Knause, SA, Laurá, M, Lewis, RA, Li, J, Lloyd, TE, Moroni, I, Muntoni, F, Pagliano, E, Pisciotta, C, Piscosquito, G, Ramchandren, S, Saporta, M, Sadjadi, R, Shy, RR, Siskind, CE, Sumner, CJ, Walk, D, Wilcox, J, Yum, SW, Züchner, S, Scherer, SS, Pareyson, D, Reilly, MM & Shy, ME 2020, 'A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores', Neurology, vol. 94, no. 9, pp. e884-e896. https://doi.org/10.1212/WNL.0000000000009035

@article{493fb7020ff345cd840aa637b2f8057e,

title = "A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores",

abstract = "OBJECTIVE: To evaluate the sensitivity of Rasch analysis-based, weighted Charcot-Marie-Tooth Neuropathy and Examination Scores (CMTNS-R and CMTES-R) to clinical progression in patients with Charcot-Marie-Tooth disease type 1A (CMT1A).METHODS: Patients with CMT1A from 18 sites of the Inherited Neuropathies Consortium were evaluated between 2009 and 2018. Weighted CMTNS and CMTES modified category responses were developed with Rasch analysis of the standard scores. Change from baseline for CMTNS-R and CMTES-R was estimated with longitudinal regression models.RESULTS: Baseline CMTNS-R and CMTES-R scores were available for 517 and 1,177 participants, respectively. Mean ± SD age of participants with available CMTES-R scores was 41 ± 18 (range 4-87) years, and 56% were female. Follow-up CMTES-R assessments at 1, 2, and 3 years were available for 377, 321, and 244 patients. A mixed regression model showed significant change in CMTES-R score at years 2 through 6 compared to baseline (mean change from baseline 0.59 points at 2 years, p = 0.0004, n = 321). Compared to the original CMTES, the CMTES-R revealed a 55% improvement in the standardized response mean (mean change/SD change) at 2 years (0.17 vs 0.11). Change in CMTES-R at 2 years was greatest in mildly to moderately affected patients (1.48-point mean change, 95% confidence interval 0.99-1.97, p < 0.0001, for baseline CMTES-R score 0-9). CONCLUSION: The CMTES-R demonstrates change over time in patients with CMT1A and is more sensitive than the original CMTES. The CMTES-R was most sensitive to change in patients with mild to moderate baseline disease severity and failed to capture progression in patients with severe CMT1A.CLINICALTRIALSGOV IDENTIFIER: NCT01193075.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Charcot-Marie-Tooth Disease/diagnosis, Child, Child, Preschool, Disease Progression, Female, Humans, Longitudinal Studies, Male, Middle Aged, Models, Theoretical, Sensitivity and Specificity, Severity of Illness Index, Time Factors, Young Adult",

author = "Vera Fridman and Stefan Sillau and Gyula Acsadi and Chelsea Bacon and Kimberly Dooley and Joshua Burns and John Day and Shawna Feely and Finkel, {Richard S.} and Tiffany Grider and Laurie Gutmann and Herrmann, {David N.} and Kirk, {Callyn A.} and Knause, {Sarrah A.} and Matilde Laur{\'a} and Lewis, {Richard A.} and Jun Li and Lloyd, {Thomas E.} and Isabella Moroni and Francesco Muntoni and Emanuela Pagliano and Chiara Pisciotta and Giuseppe Piscosquito and Sindhu Ramchandren and Mario Saporta and Reza Sadjadi and Shy, {Rosemary R.} and Siskind, {Carly E.} and Sumner, {Charlotte J.} and David Walk and Janel Wilcox and Yum, {Sabrina W.} and Stephan Z{\"u}chner and Scherer, {Steven S.} and Davide Pareyson and Reilly, {Mary M.} and Shy, {Michael E.}",

note = "Funding Information: The INC is a part of the NIH RDCRN. The authors thank all the patients who participated in the INC and their families, without whom this study would not be possible. The authors also thank the people working at INC sites who contributed to this study, especially Julian Blake, Betsy Burgos, Daniela Calabrese, Vinay Chaudhry, David Corn-blath, Katy Eichinger, Tim Estilow, Claudia Gandioli, Audra Hamilton, Allan M. Glanzman, Ahmet Hoke, Andrea Kelley, Livija Medne, Manoj Menezes, Joan Mountain, Sinead Murphy, Jillian Olsen, Alex Rossor, Oranee Sanmaneechai, Paola Saveri, Anna Sorey, Mariola Skorupinska, Janet Sowden, and Andrea Swenson. This research was also supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Funding Information: The INC (2U54NS065712-07) is a part of the RDCRN, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences. The INC is funded through a collaboration between the National Center for Advancing Translational Sciences and the National Institute of Neurological Disorders and Stroke. The INC also receives support from the Muscular Dystrophy Association and Charcot-Marie-Tooth Association. Funding Information: V. Fridman, S. Sillau, G. Acsadi, C. Bacon, and K. Dooley report no disclosures relevant to the manuscript. J. Burns reports research and clinical activities funded by the Australian Department of Health (Medical Research Future Fund), US NIH, Charcot-Marie-Tooth Australia, Charcot-Marie-Tooth Association (USA), Diabetes Australia, Elizabeth Lottie May Rosenthal Bone Bequest, Perpetual Limited, and Humpty Dumpty Foundation. Dr Burns serves as a consultant for Acceleron Pharma. J. Day, S. Feely, R. Finkel, T. Grider, and L. Gutmann report no disclosures relevant to the manuscript. D. Herrmann reports grant support through U54 NS065712-09, 1R01DK115687-01A1, Muscular Dystrophy Association, Friedreich{\textquoteright}s Ataxia Research Alliance and Voyager Pharmaceuticals, Acceleron Pharma, and Flex Pharma. Dr. Herrmann also reports consulting fees from Regenacy Pharmaceuticals, Acceleron Pharma, Alnylam, Neurogene, Flex Pharma, Narrow River Management, Guidepoint Global, GLG, Slingshot Insights, LAM Therapeutics, Inc, Voyager Therapeutics, ClearView Health Partners, MedPace, DDB Health NY, Cydan, Trinity Partners, Schlesinger, and Human First Therapeutics. C. Kirk, S. Knause, and M. Laur{\'a} report no disclosures relevant to the manuscript. R. Lewis reports providing consulting services for CSL Behring, Pharnext, Shire, Pharnext, Biotest, Annexon, Alexion, Akcea, and Alnylam. Pharnext has performed clinical trials in CMT1A. He is medical director of Premier Pharmacy Services, a home infusion company. J. Li, T. Lloyd, I. Moroni, F. Muntoni, E. Pagliano, C. Pisciotta, and G. Piscosquito report no disclosures relevant to the manuscript. S. Ramchandren is currently employed by a contract research organization (PRA Health Sciences) that works with pharmaceutical companies. M. Saporta, R. Sadjadi, R. Shy, and C. Siskind report no disclosures relevant to the manuscript. C. Sumner reports providing consulting services regarding spinal muscular atrophy to Biogen, Roche/ Genetech, Avexis, Cytokinetics, Pfizer, Ionis, and PTC Therapeutics. She serves on advisory committees to Cure SMA, SMA Foundation, Muscular Dystrophy Association, and CMT Research Foundation. D. Walk reports serving as a consultant for Acceleron Pharma. J. Wilcox, S. Yum, and S. Z{\"u}chner report no disclosures relevant to the manuscript. S. Scherer reports serving as a consultant for Biogen and Disarm. D. Pareyson reports grant support from Telethon-UILDM, AFM-Telethon, the Charcot-Marie-Tooth Association; serves on clinical advisory boards for Inflectis, Alnylam, and Akcea; and has received travel grants from Kedrion Spa and Pfizer. Te Istituto Neurologico Carlo Besta receives donations for research from Pfizer, LAM Therapeutics, Acceleron Pharma Inc. M. Reilly reports grant support from U54 NS0657, the Muscular Dystrophy Association, and the Medical Research Council and consulting for Inflectis, Alnylam, and Akcea. M. Shy reports grant support from U54 NS0657, the Muscular Dystrophy Association, and the Charcot-Marie-Tooth Association. Go to Neurology.org/N for full disclosures. Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2020",

month = mar,

day = "3",

doi = "10.1212/WNL.0000000000009035",

language = "English (US)",

volume = "94",

pages = "e884--e896",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "9",

}

TY - JOUR

T1 - A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores

AU - Fridman, Vera

AU - Sillau, Stefan

AU - Acsadi, Gyula

AU - Bacon, Chelsea

AU - Dooley, Kimberly

AU - Burns, Joshua

AU - Day, John

AU - Feely, Shawna

AU - Finkel, Richard S.

AU - Grider, Tiffany

AU - Gutmann, Laurie

AU - Herrmann, David N.

AU - Kirk, Callyn A.

AU - Knause, Sarrah A.

AU - Laurá, Matilde

AU - Lewis, Richard A.

AU - Li, Jun

AU - Lloyd, Thomas E.

AU - Moroni, Isabella

AU - Muntoni, Francesco

AU - Pagliano, Emanuela

AU - Pisciotta, Chiara

AU - Piscosquito, Giuseppe

AU - Ramchandren, Sindhu

AU - Saporta, Mario

AU - Sadjadi, Reza

AU - Shy, Rosemary R.

AU - Siskind, Carly E.

AU - Sumner, Charlotte J.

AU - Walk, David

AU - Wilcox, Janel

AU - Yum, Sabrina W.

AU - Züchner, Stephan

AU - Scherer, Steven S.

AU - Pareyson, Davide

AU - Reilly, Mary M.

AU - Shy, Michael E.

N1 - Funding Information: The INC is a part of the NIH RDCRN. The authors thank all the patients who participated in the INC and their families, without whom this study would not be possible. The authors also thank the people working at INC sites who contributed to this study, especially Julian Blake, Betsy Burgos, Daniela Calabrese, Vinay Chaudhry, David Corn-blath, Katy Eichinger, Tim Estilow, Claudia Gandioli, Audra Hamilton, Allan M. Glanzman, Ahmet Hoke, Andrea Kelley, Livija Medne, Manoj Menezes, Joan Mountain, Sinead Murphy, Jillian Olsen, Alex Rossor, Oranee Sanmaneechai, Paola Saveri, Anna Sorey, Mariola Skorupinska, Janet Sowden, and Andrea Swenson. This research was also supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Funding Information: The INC (2U54NS065712-07) is a part of the RDCRN, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences. The INC is funded through a collaboration between the National Center for Advancing Translational Sciences and the National Institute of Neurological Disorders and Stroke. The INC also receives support from the Muscular Dystrophy Association and Charcot-Marie-Tooth Association. Funding Information: V. Fridman, S. Sillau, G. Acsadi, C. Bacon, and K. Dooley report no disclosures relevant to the manuscript. J. Burns reports research and clinical activities funded by the Australian Department of Health (Medical Research Future Fund), US NIH, Charcot-Marie-Tooth Australia, Charcot-Marie-Tooth Association (USA), Diabetes Australia, Elizabeth Lottie May Rosenthal Bone Bequest, Perpetual Limited, and Humpty Dumpty Foundation. Dr Burns serves as a consultant for Acceleron Pharma. J. Day, S. Feely, R. Finkel, T. Grider, and L. Gutmann report no disclosures relevant to the manuscript. D. Herrmann reports grant support through U54 NS065712-09, 1R01DK115687-01A1, Muscular Dystrophy Association, Friedreich’s Ataxia Research Alliance and Voyager Pharmaceuticals, Acceleron Pharma, and Flex Pharma. Dr. Herrmann also reports consulting fees from Regenacy Pharmaceuticals, Acceleron Pharma, Alnylam, Neurogene, Flex Pharma, Narrow River Management, Guidepoint Global, GLG, Slingshot Insights, LAM Therapeutics, Inc, Voyager Therapeutics, ClearView Health Partners, MedPace, DDB Health NY, Cydan, Trinity Partners, Schlesinger, and Human First Therapeutics. C. Kirk, S. Knause, and M. Laurá report no disclosures relevant to the manuscript. R. Lewis reports providing consulting services for CSL Behring, Pharnext, Shire, Pharnext, Biotest, Annexon, Alexion, Akcea, and Alnylam. Pharnext has performed clinical trials in CMT1A. He is medical director of Premier Pharmacy Services, a home infusion company. J. Li, T. Lloyd, I. Moroni, F. Muntoni, E. Pagliano, C. Pisciotta, and G. Piscosquito report no disclosures relevant to the manuscript. S. Ramchandren is currently employed by a contract research organization (PRA Health Sciences) that works with pharmaceutical companies. M. Saporta, R. Sadjadi, R. Shy, and C. Siskind report no disclosures relevant to the manuscript. C. Sumner reports providing consulting services regarding spinal muscular atrophy to Biogen, Roche/ Genetech, Avexis, Cytokinetics, Pfizer, Ionis, and PTC Therapeutics. She serves on advisory committees to Cure SMA, SMA Foundation, Muscular Dystrophy Association, and CMT Research Foundation. D. Walk reports serving as a consultant for Acceleron Pharma. J. Wilcox, S. Yum, and S. Züchner report no disclosures relevant to the manuscript. S. Scherer reports serving as a consultant for Biogen and Disarm. D. Pareyson reports grant support from Telethon-UILDM, AFM-Telethon, the Charcot-Marie-Tooth Association; serves on clinical advisory boards for Inflectis, Alnylam, and Akcea; and has received travel grants from Kedrion Spa and Pfizer. Te Istituto Neurologico Carlo Besta receives donations for research from Pfizer, LAM Therapeutics, Acceleron Pharma Inc. M. Reilly reports grant support from U54 NS0657, the Muscular Dystrophy Association, and the Medical Research Council and consulting for Inflectis, Alnylam, and Akcea. M. Shy reports grant support from U54 NS0657, the Muscular Dystrophy Association, and the Charcot-Marie-Tooth Association. Go to Neurology.org/N for full disclosures. Publisher Copyright: © American Academy of Neurology.

PY - 2020/3/3

Y1 - 2020/3/3

N2 - OBJECTIVE: To evaluate the sensitivity of Rasch analysis-based, weighted Charcot-Marie-Tooth Neuropathy and Examination Scores (CMTNS-R and CMTES-R) to clinical progression in patients with Charcot-Marie-Tooth disease type 1A (CMT1A).METHODS: Patients with CMT1A from 18 sites of the Inherited Neuropathies Consortium were evaluated between 2009 and 2018. Weighted CMTNS and CMTES modified category responses were developed with Rasch analysis of the standard scores. Change from baseline for CMTNS-R and CMTES-R was estimated with longitudinal regression models.RESULTS: Baseline CMTNS-R and CMTES-R scores were available for 517 and 1,177 participants, respectively. Mean ± SD age of participants with available CMTES-R scores was 41 ± 18 (range 4-87) years, and 56% were female. Follow-up CMTES-R assessments at 1, 2, and 3 years were available for 377, 321, and 244 patients. A mixed regression model showed significant change in CMTES-R score at years 2 through 6 compared to baseline (mean change from baseline 0.59 points at 2 years, p = 0.0004, n = 321). Compared to the original CMTES, the CMTES-R revealed a 55% improvement in the standardized response mean (mean change/SD change) at 2 years (0.17 vs 0.11). Change in CMTES-R at 2 years was greatest in mildly to moderately affected patients (1.48-point mean change, 95% confidence interval 0.99-1.97, p < 0.0001, for baseline CMTES-R score 0-9). CONCLUSION: The CMTES-R demonstrates change over time in patients with CMT1A and is more sensitive than the original CMTES. The CMTES-R was most sensitive to change in patients with mild to moderate baseline disease severity and failed to capture progression in patients with severe CMT1A.CLINICALTRIALSGOV IDENTIFIER: NCT01193075.

AB - OBJECTIVE: To evaluate the sensitivity of Rasch analysis-based, weighted Charcot-Marie-Tooth Neuropathy and Examination Scores (CMTNS-R and CMTES-R) to clinical progression in patients with Charcot-Marie-Tooth disease type 1A (CMT1A).METHODS: Patients with CMT1A from 18 sites of the Inherited Neuropathies Consortium were evaluated between 2009 and 2018. Weighted CMTNS and CMTES modified category responses were developed with Rasch analysis of the standard scores. Change from baseline for CMTNS-R and CMTES-R was estimated with longitudinal regression models.RESULTS: Baseline CMTNS-R and CMTES-R scores were available for 517 and 1,177 participants, respectively. Mean ± SD age of participants with available CMTES-R scores was 41 ± 18 (range 4-87) years, and 56% were female. Follow-up CMTES-R assessments at 1, 2, and 3 years were available for 377, 321, and 244 patients. A mixed regression model showed significant change in CMTES-R score at years 2 through 6 compared to baseline (mean change from baseline 0.59 points at 2 years, p = 0.0004, n = 321). Compared to the original CMTES, the CMTES-R revealed a 55% improvement in the standardized response mean (mean change/SD change) at 2 years (0.17 vs 0.11). Change in CMTES-R at 2 years was greatest in mildly to moderately affected patients (1.48-point mean change, 95% confidence interval 0.99-1.97, p < 0.0001, for baseline CMTES-R score 0-9). CONCLUSION: The CMTES-R demonstrates change over time in patients with CMT1A and is more sensitive than the original CMTES. The CMTES-R was most sensitive to change in patients with mild to moderate baseline disease severity and failed to capture progression in patients with severe CMT1A.CLINICALTRIALSGOV IDENTIFIER: NCT01193075.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Charcot-Marie-Tooth Disease/diagnosis

KW - Child

KW - Child, Preschool

KW - Disease Progression

KW - Female

KW - Humans

KW - Longitudinal Studies

KW - Male

KW - Middle Aged

KW - Models, Theoretical

KW - Sensitivity and Specificity

KW - Severity of Illness Index

KW - Time Factors

KW - Young Adult

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UR - http://www.scopus.com/inward/citedby.url?scp=85081131083&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000009035

DO - 10.1212/WNL.0000000000009035

M3 - Article

C2 - 32047073

AN - SCOPUS:85081131083

SN - 0028-3878

VL - 94

SP - e884-e896

JO - Neurology

JF - Neurology

IS - 9

ER -

A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores

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