Motor performance deterioration accelerates after 50 years of age in Charcot-Marie-Tooth type 1A patients
S. Tozza
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorD. Bruzzese
Department of Public Health, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorC. Pisciotta
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorR. Iodice
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorM. Esposito
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorR. Dubbioso
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorL. Ruggiero
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorA. Topa
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorE. Spina
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorL. Santoro
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorCorresponding Author
F. Manganelli
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Correspondence: F. Manganelli, Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Via Sergio Pansini 5, 80131 Naples, Italy (tel.: +39 081 7462664; fax: +39 081 7462667; e-mail: [email protected]).Search for more papers by this authorS. Tozza
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorD. Bruzzese
Department of Public Health, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorC. Pisciotta
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorR. Iodice
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorM. Esposito
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorR. Dubbioso
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorL. Ruggiero
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorA. Topa
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorE. Spina
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorL. Santoro
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Search for more papers by this authorCorresponding Author
F. Manganelli
Department of Neuroscience, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Naples, Italy
Correspondence: F. Manganelli, Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples ‘Federico II’, Via Sergio Pansini 5, 80131 Naples, Italy (tel.: +39 081 7462664; fax: +39 081 7462667; e-mail: [email protected]).Search for more papers by this authorAbstract
Background and purpose
The aim of our study was to describe, by a case-control and cross-sectional design, the correlation between clinical impairment and age in Charcot-Marie-Tooth type 1A (CMT1A) patients.
Methods
Seventy CMT1A patients and 70 sex- and age-matched healthy controls were enrolled. Motor performance was assessed through the 10-m walk test, the 6-min walk test and the 9-hole peg test of the dominant and non-dominant side, and muscle strength was measured by using the Medical Research Council score. In the CMT1A group, disability and quality of life were evaluated using the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and the Short Form 36 (SF-36) questionnaire. Cross-sectional relationships between age and all clinical measures were analyzed and differences in the slopes between cases and controls were calculated. The occurrence of a structural change in the age-related progression of clinical measures was explored.
Results
The deterioration of motor performance correlated with age in both groups with a greater slope in CMT1A patients than controls. The deterioration of CMTNS and SF-36 correlated with age in the CMT1A group. The deterioration of all clinical measures with the exception of the SF-36 questionnaire showed a structural change at the 50th year of age. The rate of deterioration was no different between patients and controls until 50 years of age, whereupon it became significantly greater in CMT1A patients.
Conclusion
Our study supports that the disease progression in CMT1A patients is an age-related process and the 50th year of age represents a critical moment after which the clinical decline becomes faster.
Supporting Information
| Filename | Description |
|---|---|
| ene13494-sup-0001-TableS1.docxWord document, 18.9 KB | Table S1. Descriptive and clinical data. |
| ene13494-sup-0002-TableS2.docxWord document, 19.3 KB | Table S2. Multiple linear regression model with age and disease duration. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Manganelli F, Tozza S, Pisciotta C, et al. Charcot−Marie−Tooth disease: frequency of genetic subtypes in a southern Italy population. J Peripher Nerv Syst 2014; 19: 292–298.
- 2Pareyson D, Marchesi C. Diagnosis, natural history, and management of Charcot−Marie−Tooth disease. Lancet Neurol 2009; 8: 654–667.
- 3Shy ME, Chen L, Swan ER, et al. Neuropathy progression in Charcot−Marie−Tooth disease type 1A. Neurology 2008; 70: 378–383.
- 4Krajewski KM, Lewis RA, Fuerst DR, et al. Neurological dysfunction and axonal degeneration in Charcot−Marie−Tooth disease type 1A. Brain 2000; 123: 1516–1527.
- 5Verhamme C, van Schaik IN, Koelman JH, de Haan RJ, Vermeulen M, de Visser M. Clinical disease severity and axonal dysfunction in hereditary motor and sensory neuropathy 1a. J Neurol 2004; 251: 1491–1497.
- 6Videler AJ, van Dijk JP, Beelen A, de Visser M, Nollet F, van Schaik IN. Motor axon loss is associated with hand dysfunction in Charcot−Marie−Tooth disease 1a. Neurology 2008; 71: 1254–1260.
- 7van Dijk JP, Verhamme C, van Schaik IN, et al. Age-related changes in motor unit number estimates in adult patients with Charcot−Marie−Tooth type 1A. Eur J Neurol 2010; Aug 17: 1098–1104.
- 8Manganelli F, Pisciotta C, Reilly MM, et al. Nerve conduction velocity in CMT1A: what else can we tell? Eur J Neurol 2016; 23: 1566–1571.
- 9Padua L, Pareyson D, Aprile I, et al. Natural history of CMT1A including QoL: a 2-year prospective study. Neuromuscul Disord 2008; 18: 199–203.
- 10Verhamme C, van Schaik IN, Koelman JH, de Haan RJ, de Visser M. The natural history of Charcot−Marie−Tooth type 1A in adults: a 5-year follow-up study. Brain 2009; 132: 3252–3262.
- 11Dyck PJ, Karnes JL, Lambert EH. Longitudinal study of neuropathic deficits and nerve conduction abnormalities in hereditary motor and sensory neuropathy type 1. Neurology 1989; 39: 1302–1308.
- 12Smith CD, Umberger GH, Manning EL, et al. Critical decline in fine motor hand movements in human aging. Neurology 1999; 53: 1458–1461.
- 13Leversen JSR, Haga M, Sigmundsson H. From children to adults: motor performance across the life-span. PLoS One 2012; 7: e38830.
- 14Ferrucci L, Cooper R, Shardell M, Simonsick EM, Schrack JA, Kuh D. Age-related change in mobility: perspectives from life course epidemiology and geroscience. J Gerontol A Biol Sci Med Sci 2016; 71: 1184–1194.
- 15Solari A, Laurà M, Salsano E, Radice D, Pareyson D; CMT-TRIAAL study group. Reliability of clinical outcome measures in Charcot−Marie−Tooth disease. Neuromuscul Disord 2008; 18: 19–26.
- 16Padua L, Pazzaglia C, Pareyson D, et al. Novel outcome measures for Charcot−Marie−Tooth disease: validation and reliability of the 6-min walk test and StepWatch™ Activity Monitor and identification of the walking features related to higher quality of life. Eur J Neurol 2016; 23: 1343–1350.
- 17Pareyson D, Schenone A, Fabrizi GM, et al. A multicenter, randomized, double-blind, placebo-controlled trial of long-term ascorbic acid treatment in Charcot−Marie−Tooth disease type 1A (CMT-TRIAAL): the study protocol [EudraCT no.:2006-000032-27]. Pharmacol Res 2006; 54: 436–441.
- 18Piscosquito G, Reilly MM, Schenone A, et al. Is overwork weakness relevant in Charcot−Marie−Tooth disease? J Neurol Neurosurg Psychiatry 2014; 85: 1354–1358.
- 19Murphy SM, Herrmann DN, McDermott MP, et al. Reliability of the CMT neuropathy score (second version) in Charcot−Marie−Tooth disease. J Peripher Nerv Syst 2011; 16: 191–198.
- 20Padua L, Shy ME, Aprile I, et al. Correlation between clinical/neurophysiological findings and quality of life in Charcot−Marie−Tooth type 1A. J Peripher Nerv Syst 2008; 13: 64–70.
- 21Muggeo VM. Estimating regression models with unknown break-points. Stat Med 2003; 22: 3055–3071.
- 22Shy ME, Rose MR. Charcot−Marie−Tooth disease impairs quality of life: why? And how do we improve it? Neurology 2005; 65: 790–791.
- 23Vinci P, Serrao M, Millul A, et al. Quality of life in patients with Charcot−Marie−Tooth disease. Neurology 2005; 65: 922–924.
- 24Bennett RL, Knowlton GC. Overwork weakness in partially denervated skeletal muscle. Clin Orthop 1958; 12: 22–29.
- 25Borg K, Borg J, Edstrom L, Grimby L. Effects of excessive use of remaining muscle fibers in prior polio and LV lesion. Muscle Nerve 1988; 11: 1211–1218.
- 26Peach FE. Overwork weakness with evidence of muscle damage in a patient with residual paralysis from polio. Arch Phys Med Rehabil 1990; 71: 348–350.
- 27Bonsett RW. Pseudohypertrophic muscular dystrophy: distribution of degenerative feature as revealed by anatomical study. Neurology 1963; 13: 728–738.
- 28Johnson EW, Braddom R. Overwork weakness in facioscapulohumeral muscular dystrophy. Arch Phys Med Rehabil 1971; 52: 333–336.
- 29Janiszewski DW, Caroscio JT, Wisham LH. Amyotrophic lateral sclerosis: a comprehensive rehabilitation approach. Arch Phys Med Rehabil 1983; 64: 304–307.
- 30Vinci P, Esposito C, Perelli SL, Antenor JA, Thomas FP. Overwork weakness in Charcot−Marie−Tooth disease. Arch Phys Med Rehabil 2003; 84: 825–827.
- 31Videler AJ, Beelen A, Nollet F. Verifying the hypothesis of overwork weakness in Charcot−Marie−Tooth. J Rehabil Med 2010; 42: 380.
- 32van Pomeren M, Selles RW, van Ginneken BT, Schreuders TA, Janssen WG, Stam HJ. The hypothesis of overwork weakness in Charcot−Marie−Tooth: a critical evaluation. J Rehabil Med 2009; 41: 32–34.
- 33Arthur-Farraj PJ, Murphy SM, Laura M, et al. Hand weakness in Charcot−Marie−Tooth disease 1X. Neuromuscul Disord 2012; 22: 622–626.
- 34Vita G, La Foresta S, Russo M, et al. Sport activity in Charcot−Marie−Tooth disease: a case study of a paralympic swimmer. Neuromuscul Disord 2016; 26: 614–618.
- 35Verdú E, Ceballos D, Vilches JJ, Navarro X. Influence of aging on peripheral nerve function and regeneration. J Peripher Nerv Syst 2000; 5: 191–208.
- 36Gabreëls-Festen AA, Joosten EM, Gabreëls FJ, Jennekens FG, Janssen-van Kempen TW. Early morphological features in dominantly inherited demyelinating motor and sensory neuropathy (HMSN type I). J Neurol Sci 1992; 107: 145–154.
- 37Berciano J, García A, Calleja J, Combarros O. Clinico-electrophysiological correlation of extensor digitorum brevis muscle atrophy in children with Charcot−Marie−Tooth disease 1A duplication. Neuromuscul Disord 2000; 10: 419–424.
- 38Lewis RA, Li J, Fuerst DR, Shy ME, Krajewski K. Motor unit number estimate of distal and proximal muscles in Charcot−Marie−Tooth disease. Muscle Nerve 2003; 28: 161–167.
- 39Fabrizi GM, Simonati A, Morbin M, et al. Clinical and pathological correlations in Charcot−Marie−Tooth neuropathy type 1A with the 17p11.2p12 duplication: a cross-sectional morphometric and immunohistochemical study in twenty cases. Muscle Nerve 1998; 21: 869–877.
10.1002/(SICI)1097-4598(199807)21:7<869::AID-MUS4>3.0.CO;2-4 CAS PubMed Web of Science® Google Scholar
