Journal article
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
Neuromuscular disorders : NMD, Vol.24(11), pp.1003-1017
11/2014
DOI: 10.1016/j.nmd.2014.06.431
PMID: 25085517
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 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.
Details
- Title: Subtitle
- 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
- Creators
- Manoj Mannil - Research Group “Molecular and Translational Neurology”, Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, GermanyAlessandra Solari - Unit of Neuroepidemiology, IRCCS Foundation, C. Besta Neurological Institute, Milan, ItalyAndreas Leha - Department of Medical Statistics, University Medical Center Göttingen, Göttingen, GermanyAna L Pelayo-Negro - Service of Neurology, University Hospital “Marqués de Valdecilla (IDIVAL)”, UC and CIBERNED, Santander, SpainJosé Berciano - Service of Neurology, University Hospital “Marqués de Valdecilla (IDIVAL)”, UC and CIBERNED, Santander, SpainBeate Schlotter-Weigel - Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-Universität, Munich, GermanyMaggie C Walter - Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-Universität, Munich, GermanyBernd Rautenstrauss - Medizinisch Genetisches Zentrum, Munich, GermanyTuuli J Schnizer - Research Group “Molecular and Translational Neurology”, Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, GermanyAngelo Schenone - Department of Neurology, Ophthalmology and Genetics, University of Genoa, and IRRCS San Martino-IST, Genoa, ItalyPavel Seeman - Charles University in Prague, 2nd Medical School and University Hospital Motol, Prague, Czech RepublicChandini Kadian - Department of Biochemistry, University of Zurich, Zurich, SwitzerlandOlivia Schreiber - Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-Universität, Munich, GermanyNatalia G Angarita - Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-Universität, Munich, GermanyGian Maria Fabrizi - Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Verona, ItalyFranco Gemignani - Department of Neurosciences, University of Parma, Parma, ItalyLuca Padua - Catholic University, Department of Neurosciences and Don Gnocchi Foundation, Rome, ItalyLucio Santoro - Department of Neurological Sciences, Naples, ItalyAldo Quattrone - Magna Graecia University, Neurology Clinic, and Neuroimaging Research Unit, National Research Council, Catanzaro, ItalyGiuseppe Vita - Department of Neurosciences, University of Messina, and Clinical Centre NEMO SUD, Fondazione Aurora Onlus, Messina, ItalyDaniela Calabrese - Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences, IRCCS Foundation, C. Besta Neurological Institute, Milan, ItalyPeter Young - Department of Sleep Medicine and Neuromuscular Disorders, University of Münster, Münster, GermanyMatilde Laurà - MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, National Hospital for Neurology, Queen Square, London WC1N 3BG, UKJana Haberlová - Charles University in Prague, 2nd Medical School and University Hospital Motol, Prague, Czech RepublicRadim Mazanec - Charles University in Prague, 2nd Medical School and University Hospital Motol, Prague, Czech RepublicWalter Paulus - Department of Clinical Neurophysiology, University Medical Center Göttingen, Göttingen, GermanyTim Beissbarth - Department of Medical Statistics, University Medical Center Göttingen, Göttingen, GermanyMichael E Shy - Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, USAMary M Reilly - MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, National Hospital for Neurology, Queen Square, London WC1N 3BG, UKDavide Pareyson - Clinic of Central and Peripheral Degenerative Neuropathies Unit, Department of Clinical Neurosciences, IRCCS Foundation, C. Besta Neurological Institute, Milan, ItalyMichael W Sereda - Department of Clinical Neurophysiology, University Medical Center Göttingen, Göttingen, Germany
- Resource Type
- Journal article
- Publication Details
- Neuromuscular disorders : NMD, Vol.24(11), pp.1003-1017
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.nmd.2014.06.431
- PMID
- 25085517
- ISSN
- 0960-8966
- eISSN
- 1873-2364
- Language
- English
- Date published
- 11/2014
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984020748502771
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