1. Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patients
- Author
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Mannil, M., Solari, A., Leha, A., Pelayo-Negro, A. L., Berciano, J., Schlotter-Weigel, B., Walter, M. C., Rautenstrauss, B., Schnizer, T. J., Schenone, A., Seeman, P., Kadian, C., Schreiber, O., Angarita, N. G., Fabrizi, G. M., Gemignani, F., Padua, L., Santoro, L., Quattrone, A., Vita, G., Calabrese, D., Marchesi, C., Salsano, E., Nanetti, L., Marelli, C., Scaioli, V., Ciano, C., Rimoldi, M., Lauria, G., Rizzetto, E., Camozzi, F., Narciso, E., Grandis, M., Monti-Bragadin, M., Nobbio, L., Cavallaro, T., Casano, A., Bertolasi, L., Cabrini, I., Corra, K., Manganelli, F., Pisciotta, C., Nolano, M., Mazzeo, A., Aguennouz, M., Di Leo, R., Majorana, G., Lanzano, N., Valenti, F., Valentino, P., Nistico, R., Pirritano, D., Lucisano, A., Canino, M., Pazzaglia, C., Granata, G., Foschini, M., Brindani, F., Vitetta, F., Allegri, I., Visioli, F., Bogani, P., Blake, J., Koltzenburg, M., Hutton, E., Lunn, M., Young, P., Laura, M., Haberlova, J., Mazanec, R., Paulus, W., Beissbarth, T., Shy, M. E., Reilly, M. M., Pareyson, D., Sereda, M. W., Manoj, Mannil, Alessandra, Solari, Andreas, Leha, Ana L., Pelayo Negro, Josè, Berciano, Beate Schlotter, Weigel, Maggie C., Walter, Bernd, Rautenstrau, Tuuli J., Schnizer, Angelo, Schenone, Pavel, Seeman, Chandini, Kadian, Olivia, Schreiber, Natalia G., Angarita, Gian Maria, Fabrizi, Franco, Gemignani, Luca, Padua, Santoro, Lucio, Aldo, Quattrone, Giuseppe, Vita, Daniela, Calabrese, Cmt, Trial, Manganelli, Fiore, CMT TRIAL Chiara, Pisciotta, CMT TRAUK, Group, Peter, Young, Matilde, Laurà, Jana, Haberlova, Radim, Mazanec, Walter, Paulu, Tim, Beissbarth, Michael E., Shy, Mary M., Reilly, Davide, Pareyson, and Michael W., Sereda
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Male ,Outcome Assessment ,CMTNS ,Disease ,Ascorbic Acid ,Walking ,Severity of Illness Index ,Antioxidants ,Cohort Studies ,Charcot-Marie-Tooth Disease ,Outcome Assessment, Health Care ,Charcot-Marie-Tooth ,CMT1A ,HMSN ,secondary clinical outcome measures ,score generation ,Cluster Analysis ,Age Factor ,Genetics (clinical) ,Score generation ,Secondary clinical outcome measures ,Adolescent ,Adult ,Age Factors ,Disease Progression ,Double-Blind Method ,Female ,Humans ,Middle Aged ,Muscle Strength ,Pain Measurement ,Psychomotor Performance ,Young Adult ,Snap ,Outcome measures ,Dorsal flexion ,Compound muscle action potential ,Settore MED/26 - NEUROLOGIA ,Secondary clinical outcome measure ,Neurology ,Antioxidant ,Human ,medicine.medical_specialty ,Outcome Assessment (Health Care) ,Physical medicine and rehabilitation ,Disease severity ,medicine ,Sensory symptoms ,Cluster Analysi ,business.industry ,Health Care ,Pediatrics, Perinatology and Child Health ,Sensory nerve action potential ,Neurology (clinical) ,Cohort Studie ,business - Abstract
This study evaluates primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy controls. Using hierarchical clustering, we identified four significant clusters of patients according to clinical severity. We then tested the impact of each of the CMTNS components and of the secondary clinical parameters with regard to their power to differentiate these four clusters. The CMTNS components ulnar sensory nerve action potential (SNAP), pin sensibility, vibration and strength of arms did not increase the discriminant value of the remaining five CMTNS components (Ulnar compound motor action potential [CMAP], leg motor symptoms, arm motor symptoms, leg strength and sensory symptoms). However, three of the six additional clinical outcome measures the 10 m-timed walking test (T10MW), 9 hole-peg test (9HPT), and foot dorsal flexion dynamometry further improved discrimination between severely and mildly affected patients. From these findings, we identified three different composite measures as score hypotheses and compared their discriminant power with that of the CMTNS. A composite of eight components CMAP, Motor symptoms legs, Motor symptoms arms, Strength of Legs, Sensory symptoms), displayed the strongest power to discriminate between the clusters. As a conclusion, five items from the CMTNS and three secondary clinical outcome measures improve the clinical assessment of patients with CMT1A significantly and are beneficial for upcoming clinical and therapeutic trials. (C) 2014 Elsevier B.V. All rights reserved.
- Published
- 2014
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