What is the best approach to manage Charcot Marie Tooth disease?

Management of Charcot-Marie-Tooth Disease

The best approach to manage Charcot-Marie-Tooth disease is through a multidisciplinary team that includes neurologists, physical and occupational therapists, physiatrists, orthotists, and genetic counselors, with early implementation of rehabilitation therapy and orthotic support to preserve functionality and quality of life. 1, 2

Diagnosis and Assessment

Clinical Evaluation

• Look for classical phenotype: distal muscle weakness, atrophy, sensory loss, and skeletal deformities
• Assess for pes cavus (high-arched feet), hammer toes, and hand deformities
• Evaluate gait pattern and balance issues

Diagnostic Testing

1. Neurophysiological studies - Essential first step after clinical assessment 2

   • Nerve conduction studies to classify as demyelinating (CMT1) or axonal (CMT2)
   • Parameters should follow standardized protocols

2. Genetic testing - Sequential approach 2

   • First test for PMP22 duplication (most common cause of CMT1A)
   • If negative, proceed to next-generation sequencing panels

Treatment Algorithm

Physical Rehabilitation (First-line)

• Individualized exercise program focusing on:
  • Strength training for less affected muscle groups
  • Stretching to prevent contractures
  • Balance and proprioception exercises
  • Aerobic conditioning appropriate to patient's capabilities

Orthotic Management

• Ankle-foot orthoses (AFOs) for foot drop and stability
• Custom-fitted orthoses preferred over prefabricated ones
• Consider knee-high devices for more severe cases 3

Surgical Interventions

• Consider when conservative measures fail to provide stability or prevent deformity 4
• Surgical options include:
  • Tendon transfers to improve foot and hand function
  • Osteotomies to correct skeletal deformities
  • Joint arthrodesis for severe instability

Pain Management

• Address neuropathic pain with:
  • Gabapentin or pregabalin
  • Tricyclic antidepressants
  • Topical agents for localized pain

Monitoring and Follow-up

• Regular clinical assessments to track disease progression
• No routine imaging or electrophysiological testing needed during follow-up 2
• Adjust orthotic devices and rehabilitation program as needed

Emerging Therapies

• Currently no FDA-approved disease-modifying treatments 5
• Promising research directions include:
  • Gene therapy approaches (particularly for recessive forms)
  • PXT3003 (in phase III trials for CMT1A)
  • Ascorbic acid (vitamin C) supplementation 6, 7

Common Pitfalls and Caveats

• Delayed diagnosis - Early intervention is critical to prevent irreversible deformities
• Inadequate orthotic prescription - Must be customized to patient's specific deficits
• Overexertion - Excessive exercise can worsen symptoms; moderate activity is recommended
• Ignoring hand function - Focus often centers on lower limbs, but hand function is equally important
• Medication caution - Some medications (certain antibiotics, chemotherapeutics) may worsen neuropathy

Special Considerations

• For patients with diabetes and CMT with foot complications, be vigilant for Charcot neuro-osteoarthropathy
• If Charcot neuro-osteoarthropathy develops, use MRI for diagnosis and total contact casting for treatment 3
• Monitor for signs of active Charcot: red, hot, swollen foot 3

By implementing this comprehensive approach early in the disease course, patients with CMT can maintain better function, experience less pain, and enjoy improved quality of life despite this progressive condition.