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Physical Medicine and Rehabilitation for Charcot-Marie-Tooth Disease Medication

  • Author: Divakara Kedlaya, MBBS; Chief Editor: Robert H Meier, III, MD  more...
Updated: Jan 07, 2016

Medication Summary

Avoid drugs and medications known to cause nerve damage (eg, vincristine,[73, 74] isoniazid, nitrofurantoin). Identify the cause of any pain as accurately as possible. Musculoskeletal pain may respond to acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). Neuropathic pain may respond to tricyclic antidepressants or antiepileptic drugs, such as carbamazepine or gabapentin.

Dyck and colleagues[75] and Ginsberg and coauthors[76] described a few individuals with Charcot-Marie-Tooth disease type 1 (CMT-1) and sudden deterioration in whom treatment with steroids (prednisone) or intravenous immunoglobulin produced variable levels of improvement.

Sahenk and colleagues had studied the effects of neurotrophin-3 (NT3), a neurotrophic factor, on individuals with CMT-1A. It was known to promote axonal growth and was tested with favorable results in 2 animal models and in a pilot study involving 8 CMT-1A patients.[77, 78]

Passage and coauthors[79] reported therapeutic benefits from the administration of ascorbic acid (vitamin C) in a mouse model of CMT-1. Based on these results, clinical trials were undertaken at different centers worldwide, and 4 of them have been completed; unfortunately, however, none of them resulted in significant clinical improvements.[80, 81, 82, 83]

The progesterone antagonist onapristone proved to be effective in a rat model of CMT-1A; unfortunately, currently available progesterone antagonists are too toxic to be safely used in humans.[84, 85, 86]


Nonsteroidal Anti-inflammatory Drugs

Class Summary

Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase (COX) activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.

Ibuprofen (Motrin, Ibuprin)


DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Naprelan, Naprosyn, Anaprox)


For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease in prostaglandin synthesis.


Cyclooxygenase-2 Inhibitors

Class Summary

Although increased cost can be a negative factor, the incidence of costly and potentially fatal GI bleeds is clearly less with COX-2 inhibitors than with traditional NSAIDs. Ongoing analysis of cost avoidance of GI bleeds will further define the populations that will find COX-2 inhibitors the most beneficial.

Celecoxib (Celebrex)


Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, GI toxicity may be decreased. Seek lowest dose of celecoxib for each patient.



Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort and have sedating properties, which are beneficial for patients who experience pain.

Acetaminophen (Tylenol)


DOC for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI disease, or who are taking oral anticoagulants.


Tricyclic Antidepressants

Class Summary

A complex group of drugs that has central and peripheral anticholinergic effects, as well as sedative effects. They have central effects on pain transmission, blocking the active reuptake of norepinephrine and serotonin.

Amitriptyline (Elavil)


Analgesic for certain chronic and neuropathic pain. Inhibits membrane pump responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neuron.

Nortriptyline (Pamelor)


Has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the central nervous system.

Pharmacodynamic effects, such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors, also appear to play a role in its mechanisms of action.

Doxepin (Sinequan)


Inhibits histamine and acetylcholine activity and has proven useful in treatment of various forms of depression associated with chronic and neuropathic pain.

Desipramine (Norpramin)


May increase synaptic concentration of norepinephrine in CNS by inhibiting reuptake by presynaptic neuronal membrane. May have effects in the desensitization of adenyl cyclase, down-regulation of beta-adrenergic receptors, and down-regulation or serotonin receptors.



Class Summary

Used to manage pain and provide sedation in neuropathic pain.

Gabapentin (Neurontin)


Membrane stabilizer, a structural analogue of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors. Appears to exert action via the alpha(2)delta1 and alpha(2)delta2 subunit of the calcium channel.

Contributor Information and Disclosures

Divakara Kedlaya, MBBS Clinical Associate Professor, Department of Physical Medicine and Rehabilitation, Loma Linda University School of Medicine; Medical Director, Physical Medicine and Rehabilitation and Pain Management, St Mary Corwin Medical Center

Divakara Kedlaya, MBBS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Colorado Medical Society, American Association of Neuromuscular and Electrodiagnostic Medicine

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.

Michael T Andary, MD, MS Professor, Residency Program Director, Department of Physical Medicine and Rehabilitation, Michigan State University College of Osteopathic Medicine

Michael T Andary, MD, MS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, Association of Academic Physiatrists

Disclosure: Received honoraria from Allergan for speaking and teaching.

Chief Editor

Robert H Meier, III, MD Director, Amputee Services of America; Active Medical Staff, Presbyterian/St Luke’s Hospital, Spalding Rehabilitation Hospital, Select Specialty Hospital; Consulting Staff, Kindred Hospital

Robert H Meier, III, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists

Disclosure: Nothing to disclose.

Additional Contributors

Milton J Klein, DO, MBA Consulting Physiatrist, Heritage Valley Health System-Sewickley Hospital and Ohio Valley General Hospital

Milton J Klein, DO, MBA is a member of the following medical societies: American Academy of Disability Evaluating Physicians, American Academy of Medical Acupuncture, American Academy of Osteopathy, American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Osteopathic Association, American Osteopathic College of Physical Medicine and Rehabilitation, American Pain Society, Pennsylvania Medical Society

Disclosure: Nothing to disclose.

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Foot deformities in a 16-year-old boy with Charcot-Marie-Tooth disease type 1A.
Charcot-Marie-Tooth disease type 1A DNA test showing duplication in the short arm of chromosome 17 (A) compared with normal (B).
Nerve conduction study showing decreased nerve conduction velocity in the median nerve in an 18-year-old woman with Charcot-Marie-Tooth disease type 1.
Foot of 29-year-old with advanced Charcot-Marie-Tooth disease type 1.
Hands of 29-year-old with advanced Charcot-Marie-Tooth disease type 1.
Right ulnar motor nerve conduction study in a 29-year-old patient with advanced Charcot-Marie-Tooth disease type 1.
Left ulnar motor nerve conduction study in 29-year-old patient with advanced Charcot-Marie-Tooth disease type 1.
Table. Charcot-Marie-Tooth Disorders: Genetic and Clinical Feature Comparison
CMT Type Chromosome; Inheritance Pattern Age of Onset Clinical Features Average NCVs§
CMT-1A (PMP-22 dupl.) 17p11.2; AD* First decade Distal weakness 15-20 m/s
CMT-1B (P0 -MPZ)** 1q23.3; AD First decade Distal weakness < 20 m/s
CMT-1C (non-A, non-B) (LITAF) 16p13.13;AD Second decade Distal weakness 26-42 m/s
CMT-1D (EGR-2)# 10q21.3; AD First decade Distal weakness 15-20 m/s
CMT-1E (PMP22) 17p11.2; AD First decade Distal weakness, deafness 15-20 m/s
CMT-1F (NEFL) 8p21.2; AD First decade Distal weakness 15-20 m/s
CMT-X (connexin-32)[31, 32, 33, 34] Xq13; XD Second decade Distal weakness 25-40 m/s
CMT-2A 1p36; AD 10 y Distal weakness >38 m/s
CMT-2B 3q21; AD Second decade Distal weakness,

sensory loss, skin ulcers

Axon loss; Normal
CMT-2C 12q23-q24, AD First decade Vocal cord, diaphragm, and

distal weakness

>50 m/s
CMT-2D 7p14; AD 16-30 y Distal weakness, upper limb predominantly Axon loss; N††
CMT-2E 8p21; AD 10-30 y Distal weakness, lower limb predominantly Axon loss; N
CMT-2F 7q11-q21; AD 15-25 y Distal weakness Axon loss; N
CMT-2G 12q12-q13; AD 9-76 y Distal weakness Axon loss; N
CMT-2H 8q21; AD 15-25 y Distal weakness, pyramidal features Axon loss; N
CMT-2I 1q23; AD 47-60 y Distal weakness Axon loss; N
CMT-2J 1q23; AD 40-50 y Distal weakness, hearing loss Axon loss; N
CMT-2K 8q13-q21; AD < 4 y Distal weakness Axon loss; N
CMT-2L 12q24; AD 15-25 y Distal weakness Axon loss; N
CMT–R-Ax (Ouvrier) AR First decade Distal weakness Axon loss; N
CMT–R-Ax (Moroccan) 1q21; AR Second decade Distal weakness Axon loss; N
Cowchock syndrome Xq24-q26 First decade Distal weakness, deafness, mental retardation Axon loss; N
HNPP|| (PMP-22 deletion)[35]

or tomaculous neuropathy

17p11; AD All ages Episodic weakness and numbness Conduction Blocks
Dejerine-Sottas-syndrome (DSS) or HMSN-3[36] P0; AR

PMP-22; AD

8q23; AD

2 y Severe weakness < 10 m/s

hypomyelination (CH)

P0, EGR-2 or PMP-22


Birth Severe weakness < 10 m/s
CMT-4A[37] 8q13; AR Childhood Distal weakness Slow

(myotubularin- related

protein 2)[38, 39]

11q23; AR 2-4 y Distal and proximal


CMT-4C 5q23; AR 5-15 y Delayed walking 14-32 m/s
CMT-4D (Lom)

(N-myc downstream-

regulated gene 1)

8q24; AR 1-10 y Distal muscle wasting, foot and hand deformities 10-20 m/s
CMT-4E (EGR-2) 10q21; AR Birth Infant hypotonia 9-20 m/s
CMT-4G 10q23.2; AR 8-16 years Distal weakness 9-20 m/s
CMT-4H 12p11.21-q13.11; AR 0-2 years Delayed walking 9-20 m/s
CMT-4F 19q13; AR 1-3 y Motor delay Absent
*Autosomal dominant

†Autosomal recessive

‡X-linked dominant

§Nerve conduction velocities

||Hereditary neuropathy with liability to pressure palsy

¶Peripheral myelin protein

#Early growth response

**Myelin protein zero


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