Phenotype of Paramyotonia congenita

1
Phenotype of Paramyotonia congenita

• Dr Doreen Fialho, MRCP
• Clinical Research Fellow
• MRC centre for Neuromuscular Disease, Institute
  of Neurology, Queen Square, London UK

2
Original Description

• Eulenburg 1886
• German family, 6 generations
• Mothers diagnosis

3
Classical Features

• Paradoxical exercise and cold induced myotonia
• Episodes of paralysis
• Autosomal dominant with high penetrance

4
Distribution

• Cranial musculature
• myotonia
• Upper and lower limbs
• short lasting myotonia
• Longer lasting paralysis
• In LL often followed by fatigue
• Most affected face, eyes, pharynx, hands

5
Other Features

• Reduced electrical muscle excitability during
  attacks
• No significant change with age
• Occupational restriction

6
Spectrum vs distinct categories
7
Triggers

• Exercise (rest)
• Cold
• Potassium
• Fasting

8
Exercise and Myotonia

• Worsening during exercise vs warm-up
• Absence of warm-up
• Worsening after exercise and short period of rest

9
Pain

• Probably underestimated
• Usually associated with muscle stiffness and
  weakness

10
Diagnosis

• Clinical
• Neurophysiology (EMG, SET/Cooling)
• Genetic analysis
• (Potassium challenge , muscle biopsy used
  historically)

11
Neurophysiology

• Protocol Fournier et al. (Ann Neurol 2004 and
  2006)
• EMG
• Repeated SET and cooling - stability of CMAP (PMC
  vs PAM)

12
Differential Diagnosis

• Myotonic Dystrophy I/II
• SJS
• Stiff person syndrome
• Acquired peripheral nerve hyperexcitability
• EA1 with prominent neuromyotonia

13
Treatment/ Management

• Mexiletine (myotonia)
• As required
• ECG monitoring, side effects
• Acetazolamide (paralysis)
• Lifestyle advice
• Genetic counselling
• Anaesthesia advice

14
Anaesthesia

• Problems
• MH like reaction - myotonic crisis
• Post-op respiratory depression/paralysis
• Avoidance of triggers
• Drugs - depolarising agents (suxamethonium),
  anticholinesterases, opiods
• Temperature
• Immobility (general vs local anaesthetic, post-op
  mobilisation, length of procedure)
• Potassium levels

15
Classification

• PMC - paralytic/non-paralytic vs Sodium channel
  myotonias
• Potassium aggravated myotonias
• Myotonia Fluctuans
• Myotonia permanens
• Acetazolamide responsive myotonia

16
PAM vs PMC

• PAM range between clinically similar to Myotonia
  congenita to paradoxical myotonia similar to PMC
• Defining difference presence of exercise/cold
  induced decrease in muscle excitability
• Episodes of weakness
• Progressive CMAP decrement after SET (cooling)

17
PAM

• Distinction to MC
• Fluctuation
• Absence or less pronounced warm-up
• Absence transient weakness
• (potassium sensitivity)
• (dominant inheritance)
• Distinction to PMC
• Absence of weakness

18
Acknowledgement

• MRC Centre - Prof M.G.Hanna
• Clinical Research Fellows - Dr E.Matthews
• Clinical Neurophysiologist - Dr V.Tan
• Funding
• NSCAG
• MRC, Wellcome, CINCH