Medical Care

Management of orthopedic complications is paramount.

The common foot deformities of CMT can lead to discomfort, impaired ambulation, and disability and should be managed with physical therapy, which can be both preventive and therapeutic. Stretching, exercises, and adaptive maneuvers can all be helpful.
Ankle weakness and instability can be treated with boots or orthoses, and can ease ambulation, keep patients active, and prevent potentially disabling injuries such as sprains or ankle fractures.
While dysesthetic pain is not typical, it can occur, and responds to medications commonly used for neuropathic pain such as tricyclic antidepressants or anticonvulsants.
More commonly, patients experience local musculoskeletal pain resulting from abnormal posture or overuse of certain muscle groups brought on by weakness or joint deformity.^[92]Joint deformity itself may be painful. NSAIDs and acetaminophen are first-line therapies.

There are no definitive medical therapies for CMT. Steroid responsive forms of Charcot-Marie-Tooth disease were originally recognized by Dyck in 1982. This finding has also been reported several times in patients with MPZ mutations and atypical features such as elevated CSF protein.^{[93, 94]}These may be patients with superimposed CIDP.^[95]It is unlikely that immunomodulatory therapy will be effective in typical cases of CMT.

Ascorbic acid has been shown to repress PMP22 gene expression in a dose-dependent manner, and multicenter international trials of long-term ascorbic acid treatment for CMT1A are underway.^{[96, 97]}The CMT-TRIAAL and CMT-TRAUK trial was a multicenter, 2-year trial to test the efficacy and tolerability of ascorbic acid in patients with CMT1A.^[98]The results suggest that ascorbic acid supplementation had no significant effect on neuropathy compared with placebo after 2 years, suggesting that no evidence is available to support treatment with ascorbic acid in adults with CMT1A.

Studies in animal models have shown reduction in PMP22 mRNA levels and clinical improvement after treatment with progesterone antagonists. These findings may lead to a clinical trial.^[99]Clinical tools have been developed to follow progression of the disease in preparation for therapeutic trials.^[100]

Surgical Care

If foot deformities are disabling, patients may benefit from tendon transfers or lengthening (especially the Achilles tendon), hammer toe correction, and release of the plantar fascia. The ankle can be fused to provide stability. Ideally, conservative measures such as those mentioned above, if instituted early, can prevent surgery.^[101]

Consultations

See the list below:

Physiatrists
Physical therapists
Orthotics specialists
Podiatrists
Genetic counseling

Diet

A balanced diet is important to prevent obesity and diabetes, both of which can compound disability and pain and contribute to the development of certain entrapment neuropathies.

Activity

Activity as tolerated. Moderate activity is recommended. Overexertion should be avoided.

Prevention

Even if patients and carriers were to abstain from having children, CMT mutations occur de novo with some regularity and the disease would remain prevalent. Boerkoel and colleagues found that one third (6 of 16) of the point mutations detected in their series of 159 patients represent de novo events.^[42] As examined by Hoogendijk and colleagues, of 10 patients with CMT1 and no family history, 9 of them had PMP22 duplications.^[72]

Prevention should focus on avoiding conditions that can cause or worsen generalized or focal neuropathy, such as diabetes mellitus, vitamin deficiency, medication toxicity, and prolonged immobilization of limbs during surgery.

Medication

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Author

Timothy C Parsons, MD Fellow in EMG and Neuromuscular Disease, Department of Neurology, Columbia University Medical Center, New York

Timothy C Parsons, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Coauthor(s)

Thomas H Brannagan III, MD Associate Professor of Clinical Neurology and Director, Peripheral Neuropathy Center, Columbia University Vagelos College of Physicians and Surgeons; Co-Director, EMG Laboratory, New York-Presbyterian Hospital, Columbia Campus

Thomas H Brannagan III, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Peripheral Nerve Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Neil A Busis, MD Chief of Neurology and Director of Neurodiagnostic Laboratory, UPMC Shadyside; Clinical Professor of Neurology and Director of Community Neurology, Department of Neurology, University of Pittsburgh Physicians

Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Academy of Neurology<br/>Serve(d) as a speaker or a member of a speakers bureau for: American Academy of Neurology<br/>Received income in an amount equal to or greater than $250 from: American Academy of Neurology.

Chief Editor

Nicholas Lorenzo, MD, CPE, MHCM, FAAPL Co-Founder and Former Chief Publishing Officer, eMedicine and eMedicine Health, Founding Editor-in-Chief, eMedicine Neurology; Founder and Former Chairman and CEO, Pearlsreview; Founder and CEO/CMO, PHLT Consultants; Former Chief Medical Officer, MeMD Inc

Nicholas Lorenzo, MD, CPE, MHCM, FAAPL is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association for Physician Leadership

Disclosure: Nothing to disclose.

Additional Contributors

Dianna Quan, MD Professor of Neurology, Director of Electromyography Laboratory, University of Colorado School of Medicine

Dianna Quan, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Neurological Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Association of Neuromuscular and Electrodiagnostic Medicine<br/>Received research grant from: Alnylam; Pfizer; Ionis; Cytokinetics; Momenta; Viela Bio; .