Morvan Syndrome

A rare autoimmune disorder characterized by peripheral nerve hyperexcitability, autonomic dysfunction, and encephalopathy. First described by Augustin Morvan in 1890, also known as Morvan's fibrillary chorea or La Chorée Fibrillaire.

Key Points

• Ultra-rare condition with fewer than 100 reported cases
• Strong association with thymoma (>40% cases)
• Male predominance (2:1 ratio)
• Can be paraneoplastic or autoimmune
• Potentially fatal if untreated

Epidemiology

• Mean age of onset: 40-50 years
• Pediatric cases are extremely rare
• Higher prevalence in Asian populations
• Associated with HLA-DRB1*11 genotype

Cardinal Features

• Neuromuscular Hyperexcitability:
  • Neuromyotonia (continuous muscle fiber activity)
  • Muscle cramps and fasciculations
  • Myokymia (wave-like muscle contractions)
  • Pseudomyotonia (delayed muscle relaxation)
  • Muscle weakness and wasting
• Autonomic Dysfunction:
  • Hyperhidrosis (excessive sweating)
  • Tachycardia
  • Blood pressure fluctuations
  • Gastrointestinal dysmotility
  • Urinary symptoms
  • Temperature dysregulation
• CNS Manifestations:
  • Severe insomnia
  • Agitation and anxiety
  • Hallucinations
  • Memory impairment
  • Confusion
  • Behavioral changes

Associated Symptoms

• Weight loss
• Pruritus
• Pain syndromes
• Speech disturbances
• Visual disturbances
• Sleep disorders

Molecular Mechanisms

• Autoimmune Components:
  • Anti-CASPR2 antibodies (>70% cases)
  • Anti-LGI1 antibodies (occasional)
  • Anti-VGKC complex antibodies
  • Other neuronal autoantibodies
• Cellular Effects:
  • Ion channel dysfunction:
    • Potassium channel disruption
    • Sodium channel alterations
    • Calcium channel involvement
  • Neuronal hyperexcitability
  • Synaptic transmission changes
  • Blood-brain barrier disruption
• Associated Conditions:
  • Thymoma
  • Other autoimmune diseases
  • Genetic predisposition

Diagnostic Approach

• Laboratory Studies:
  • Autoantibody testing:
    • Anti-CASPR2 antibodies
    • Anti-LGI1 antibodies
    • Anti-VGKC complex antibodies
  • CSF analysis:
    • Protein levels
    • Cell count
    • Oligoclonal bands
    • Autoantibody testing
  • Complete metabolic panel
  • Thyroid function tests
  • Inflammatory markers
• Electrophysiological Studies:
  • EMG:
    • Neuromyotonic discharges
    • Fasciculations
    • Myokymic discharges
  • Nerve conduction studies
  • EEG monitoring
  • Sleep studies
• Imaging:
  • Chest CT/MRI (thymoma screening)
  • Brain MRI
  • PET scan if malignancy suspected

Differential Diagnosis

• Isaac's syndrome
• Limbic encephalitis
• Neuromyotonia
• Stiff-person syndrome
• Other autoimmune encephalitis
• Psychiatric disorders

Treatment Strategy

• First-line Treatments:
  • Immunotherapy:
    • IVIG (2g/kg divided over 5 days)
    • Plasmapheresis
    • High-dose corticosteroids
  • Thymoma treatment if present:
    • Thymectomy
    • Radiation therapy
    • Chemotherapy if malignant
• Second-line Treatments:
  • Rituximab
  • Cyclophosphamide
  • Mycophenolate mofetil
  • Azathioprine
• Symptomatic Treatment:
  • Anticonvulsants (carbamazepine, phenytoin)
  • Sleep medications
  • Antipsychotics if needed
  • Pain management

Potential Complications

• Acute Complications:
  • Status epilepticus
  • Autonomic crisis
  • Cardiac arrhythmias
  • Respiratory failure
  • Severe weight loss
• Chronic Complications:
  • Cognitive decline
  • Chronic pain
  • Depression
  • Sleep disorders
  • Quality of life impairment

Monitoring Requirements

• Regular neurological assessment
• Cardiac monitoring
• Sleep evaluation
• Psychological support
• Nutritional status
• Thymoma surveillance

Recent Advances

• Biomarker Discovery:
  • Novel autoantibodies
  • Genetic associations
  • Imaging markers
• Treatment Developments:
  • New immunotherapy protocols
  • Targeted therapies
  • Clinical trials
• Pathophysiology Understanding:
  • Ion channel mechanisms
  • Immune system involvement
  • Genetic factors