• Manoj Mannil, Alessandra Solari, Andreas Leha, Ana L Pelayo-Negro, José Berciano, Beate Schlotter-Weigel, Maggie C Walter, Bernd Rautenstrauss, Tuuli J Schnizer, Angelo Schenone, Pavel Seeman, Chandini Kadian, Olivia Schreiber, Natalia G Angarita, Gian Maria Fabrizi, Franco Gemignani, Luca Padua, Lucio Santoro, Aldo Quattrone, Giuseppe Vita, Daniela Calabrese, CMT-TRIAAL/CMT-TRAUK Group, Peter Young, Matilde Laurà, Jana Haberlová, Radim Mazanec, Walter Paulus, Tim Beissbarth, Michael E Shy, Mary M Reilly, Davide Pareyson, and Michael W Sereda.
• Research Group "Molecular and Translational Neurology", Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
• Neuromuscul. Disord. 2014 Nov 1; 24 (11): 1003-17.

AbstractThis 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 10m-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. Copyright © 2014 Elsevier B.V. All rights reserved.

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