eMedicine Specialties > Neurology > Neuromuscular Diseases

Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies: Treatment & Medication

Author: Timothy C Parsons, MD, Fellow in EMG and Neuromuscular Disease, Department of Neurology, Columbia University Medical Center, New York
Coauthor(s): Thomas H Brannagan III, MD, Associate Professor of Clinical Neurology and Director, Peripheral Neuropathy Center, Columbia University, College of Physicians and Surgeons; Co-Director, EMG Laboratory, New York-Presbyterian Hospital, Columbia Campus, New York
Contributor Information and Disclosures

Updated: Nov 5, 2009

Treatment

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. 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.87,88 These may be patients with superimposed CIDP.89 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.90,91

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.92 Clinical tools have been developed to follow progression of the disease in preparation for therapeutic trials.93

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.

Consultations

  • 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.

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Nonsteroidal anti-inflammatory drugs (NSAIDS)

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase 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.
Supplied OTC in 200-mg dosing or prescribed as 400-, 600-, and 800-mg tabs.

Adult

400-800 mg PO tid with food

Pediatric

Not recommended

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy


Naproxen (Aleve, Naprelan, Naprosyn, Anaprox)

For relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which results in a decrease of prostaglandin synthesis.

Adult

500 mg PO bid with food

Pediatric

Not established

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug

Antidepressants

These drugs increase the synaptic concentration of serotonin and/or norepinephrine in CNS by inhibiting their reuptake at the presynaptic neuronal membrane. These mechanisms may play a role in the analgesic effects of these medications.


Nortriptyline (Pamelor, Aventyl HCl)

Has demonstrated effectiveness in treatment of pain.

Adult

25-100 mg PO hs; not to exceed 200 mg/d

Pediatric

Children: 0.1 mg/kg PO hs; increase as tolerated; not to exceed 0.5-2 mg/d hs
Adolescents: 25-50 mg/d PO; increase gradually to 100 mg/d

Cimetidine may increase nortriptyline levels; may increase effects of warfarin (monitor INR)

Documented hypersensitivity; narrow-angle glaucoma; MAOIs within 14 d

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Patients with cardiac conduction disturbances and a history of hyperthyroidism; those with renal or hepatic impairment; avoid using in elderly patients


Amitriptyline (Elavil)

Has demonstrated effectiveness in treatment of pain.

Adult

25-100 mg PO hs; not to exceed 150 mg/d

Pediatric

Children: 0.1 mg/kg PO hs; increase as tolerated; not to exceed 0.5-2 mg/d qhs
Adolescents: 25-50 mg/d PO; increase gradually to 100 mg/d

Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase amitriptyline levels; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram

Documented hypersensitivity; narrow-angle glaucoma; MAOIs within 14 d

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in cardiac conduction disturbances, history of hyperthyroidism, and renal or hepatic impairment; avoid using in elderly patients

Serotonin reuptake inhibitors

Serotoninergic antidepressants have had mixed reviews in the literature. Some of them have been reported to relieve painful sensory symptoms.


Paroxetine (Paxil)

Considered an alternative to TCAs, with fewer adverse anticholinergic and cardiovascular effects.

Adult

10 mg/d PO initially; titrate to maximum 50 mg/d

Pediatric

Not established

Phenobarbital and phenytoin decrease effects of paroxetine; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity of paroxetine; serotonin syndrome (ie, myoclonus, rigidity, confusion, nausea, hyperthermia, autonomic instability, coma, eventual death) occurs with simultaneous use of other serotonergic agents (eg, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan), discontinue other serotonergic agents at least 2 wk prior to using other SSRIs

Documented hypersensitivity; pregnancy and lactation; severe renal or hepatic disease

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Anxiety, insomnia or drowsiness, tremor, anorexia, anorgasmia, and other sexual dysfunctions have been reported; nausea, flu-like symptoms, and agitation that resolve within 1-2 wk also noted

Anticonvulsants

These medications reduce neuronal excitability and prevent neuronal discharges associated with pain sensation.


Carbamazepine (Tegretol)

A sodium channel blocker that typically provides substantial or complete relief of pain in 80% of individuals with both idiopathic and MS-associated TN within 24-48 h. Adverse effect profile for older patients is more onerous than with newer anticonvulsants, thereby limiting usefulness in this group. As more published data on long-term efficacy of agents such as lamotrigine and gabapentin become available, these medications may soon become drugs of choice.

Adult

100 mg PO bid initially; may be increased qd by 200 mg until adequate relief is obtained
For maximum effect, dosage can be administered in divided doses 1 h before each meal
Maintenance dose: 100-600 mg PO bid; not to exceed 1200 mg; may continue for several wk depending on disease course
Patients may require maintenance dosage as low as 200 mg/d to prevent recurrences

Pediatric

Not established

Levels are increased by CYP3A4 inhibitors (eg, cimetidine, macrolides, diltiazem, fluoxetine, ketoconazole, verapamil, valproate); levels are decreased by CYP3A4 inducers (eg, cisplatin, doxorubicin, felbamate, phenobarbital, phenytoin, primidone, rifampin, theophylline); may increase levels of clomipramine, phenytoin, and primidone and lithium toxicity; may decrease levels of phenytoin, warfarin, PO contraceptives, doxycycline, theophylline, haloperidol, alprazolam, clozapine, ethosuximide, and valproate; may interfere with other anticonvulsants, thyroid function, and pregnancy and TFTs

Documented hypersensitivity; bone marrow depression; sensitivity to tricyclics; MAOIs within last 14 d

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with history of cardiac, hepatic, renal, or hematologic dysfunction, latent psychosis, glaucoma, or adverse hematologic reaction to other drugs; may be converted to ER formulation on a mg/mg basis; common adverse reactions include ataxia, nausea, vomiting, sedation, and vertigo; because of risk of persistent leukopenia and aplastic anemia, patients should undergo CBC before starting and at 1, 3, and 6 mo; non–dose-dependent and idiosyncratic suppression of bone marrow may occur mandating vigilance early in therapy


Gabapentin (Neurontin)

Uncontrolled studies have indicated possible effectiveness in patients whose pain has become refractory to carbamazepine. Often is tolerated better than carbamazepine by elderly patients. No placebo-controlled studies have been published.

Adult

900-2700 mg/d PO

Pediatric

Not established

Potentiates CNS depression due to acute alcohol ingestion or other CNS depressants; antacids may reduce absorption, so separate administration by at least 2 h; may interfere with Multistix-SC urine protein tests

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal dysfunction; dosage in renal insufficiency is as follows:
CrCl >60 mL/min: 400 mg tid
CrCl 30-60 mL/min: 300 mg bid
CrCl 15-30 mL/min: 300 mg qid
CrCl <15 mL/min: 300 mg qid
Hemodialysis: 200-300 mg after 4 h of each hemodialysis

More on Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies

Overview: Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies
Differential Diagnoses & Workup: Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies
Treatment & Medication: Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies
Follow-up: Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies
References
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Further Reading

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Keywords

Charcot-Marie-Tooth neuropathy, Charcot-Marie-Tooth disorder, Charcot-Marie-Tooth syndrome, CMT, Hereditary Motor and Sensory Neuropathy, HMSN, peroneal muscular atrophy, Dejerine-Sottas syndrome

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Contributor Information and Disclosures

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, College of Physicians and Surgeons; Co-Director, EMG Laboratory, New York-Presbyterian Hospital, Columbia Campus, New York
Thomas H Brannagan III, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Peripheral Nerve Society
Disclosure: Nothing to disclose.

Medical Editor

Dianna Quan, MD, Associate Professor of Neurology, Director, Electromyography Laboratory, University of Colorado Health Sciences Center
Dianna Quan, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa
Disclosure: e-medicine Honoraria Other

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Neil A Busis, MD, Chief, Division of Neurology, Department of Medicine, Head, Clinical Neurophysiology Laboratory, University of Pittsburgh Medical Center-Shadyside
Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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