What is the management approach for Charcot-Marie-Tooth (CMT) disease?

Management of Charcot-Marie-Tooth Disease

The management of Charcot-Marie-Tooth (CMT) disease requires a comprehensive rehabilitation-focused approach with orthotic devices and supportive care, as there is currently no effective pharmacological treatment available for this genetic condition. 1

Diagnostic Evaluation

• Perform thorough clinical assessment for:

  • Distal muscle weakness and wasting
  • Sensory loss in "glove and stocking" distribution
  • Foot deformities and digit contractures 1

• Imaging studies:

  • Plain X-rays (standing/weight-bearing when possible) to assess foot deformities 2
  • MRI when X-rays appear normal but clinical suspicion remains high 2
  • Consider nuclear imaging, CT scan, or SPECT-CT when MRI is unavailable 2

Non-Pharmacological Management

Foot Care and Orthotics

• Use total contact cast (TCC) as first-line treatment for active Charcot neuro-osteoarthropathy 2
• Provide custom-molded shoes for severe deformities 1
• Consider knee-high customized devices for additional protection with deformity or joint instability 2
• Avoid below-ankle offloading devices as they provide inadequate immobilization 2

Physical Rehabilitation

• Implement structured exercise program including:

  • Strengthening exercises
  • Stretching
  • Core stability training
  • Balance and resistance training
  • Aerobic exercises 1

• Avoid high-impact activities that increase risk of foot trauma 1

• Consider low-impact alternatives:

  • Aquatic exercise
  • Cycle ergometry
  • Recumbent cycle ergometry 1

Monitoring and Prevention

• Regularly inspect feet for injuries, especially in areas with sensory loss 1
• Monitor skin temperature and restrict activity during periods of inflammation 1
• Assess muscle strength, balance, and functional capacity regularly 1
• Evaluate for development of foot deformities and pressure points 1

Surgical Interventions

• Consider surgical intervention when:
  • Foot/ankle joint instability is present
  • Deformity with high risk of developing ulcers exists
  • Pain cannot be adequately managed with conservative measures 1

Important Considerations

What to Avoid

• Do not use pharmacological agents including:
  • Bisphosphonates (alendronate, pamidronate, zoledronate)
  • Calcitonin
  • PTH
  • Methylprednisolone
  • Denosumab 2

Potential Complications

• Progression to foot deformities
• Development of ulcers at pressure points
• Potential for infection at sites of sensory loss
• Re-activation of the disease process 1

Emerging Treatments

While current management relies on rehabilitation therapy and surgery for skeletal deformities, several promising approaches are under investigation:

• Gene therapy approaches for specific CMT subtypes 3
• PXT3003 compound (currently in phase-III trials for CMT1A) 3
• Compounds targeting neuregulin pathway for both hypo-demyelinating and hypermyelinating neuropathies 3

Multidisciplinary Care

CMT management requires coordination among multiple specialists:

• Neurologists
• Physical and occupational therapists
• Physiatrists
• Orthotists
• Genetic counselors 4

Regular follow-up is essential for monitoring disease progression and adjusting management strategies accordingly, with assessment primarily based on clinical evaluation rather than ancillary testing 5.