LANDMARKS IN THE HISTORY OF MYOTONIA

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LANDMARKS IN THE HISTORY OF MYOTONIA

• International Conference on the Nondystrophic
  Myotonias, June 3-4, 2007
• Robert Layzer
• University of California, San Francisco

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CLINICAL DESCRIPTIONS

• Myotonia congenita
• Dr. JuliusThomsen, 1876
• Monograph described disease in himself and 20
  members of his family in 4 generations
• Symptoms static and benign
• Work extended by Erb, 1886

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CLINICAL DESCRIPTIONS

• Recessive myotonia congenita Becker, 1961
• Myotonia more severe, muscles larger (Infant
  Hercules) with distal thinning
• Transient weakness during initial contraction
  after rest
• Declining electrical response of muscle to nerve
  stimulation

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CLINICAL DESCRIPTIONS

• Paramyotonia congenita
• Episodes of myotonia and weakness induced by
  exposure to cold Eulenberg 1888 Rich 1894
• Myotonia typically paradoxical Magee 1963

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CLINICAL DESCRIPTIONS

• Hyperkalemic periodic paralysis without myotonia
  Helweg-Larsen et al 1955, Gamstorp 1956
• Paramyotonia with attacks of generalized weakness
  induced by oral potassium French Kilpatrick,
  1957

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CLINICAL DESCRIPTIONS

• Hyperkalemic periodic paralysis with myotonia
  Drager et al 1958 Van der Meulen et al 1961
  Vant Hoff 1962 McArdle 1962 Layzer et al 1967
• Myotonia aggravated by cold and potassium
  (without weakness) Heine et al 1993

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TREATMENT OF MYOTONIA

• Quinine An Effective Form of Treatment for
  Myotonia. Arch Neurol Psychiat 193636382-3.
• I shall give a brief report of the effectiveness
  of quinine in the treatment of myotonia, a
  condition hitherto almost entirely uninfluenced
  by any mode of therapy.--A. Wolf, M.D. Cornell
  1932 (Bellevue, Foster Kennedy)

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TREATMENT OF MYOTONIA

• Procaine amide Geschwind Simpson, 1955
• Diphenylhydantoin Munsat, 1967

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MYOTONIA IN GOATS

• Descended from a small flock imported from
  Syria? into Marshall County, Tennessee
• 1904 White Plaskett Nervous, stiff-legged or
  fainting goats
• 1932 Clark et al A form of congenital myotonia
  in goats
• 1938 L.C. Kolb (b. 1911) clinical and
  electrical features typical of myotonia relieved
  by quinine

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CLINICAL PHYSIOLOGY

• EMG Myotonia is associated with profuse
  electrical activity (Lindsley Curnen 1936),
  interpreted as neurogenic!
• After-discharge attributed to spinal reflex from
  hyperexcitable sensory end-organs in the muscle.

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CLINICAL PHYSIOLOGY

• Mechanically-induced myotonia persists
• after spinal anesthesia (Grund 1919 Kennedy
  Wolf 1938)
• after nerve block (Denny-Brown Nevin 1941
  Buchthal Clemmensen 1941)

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CLINICAL PHYSIOLOGY

• Mechanical myotonia persists
• after curare blockade
• in goats (Brown Harvey 1939)
• in man (Lanari 1946 Landau 1952)
• after nerve section and degeneration of motor
  nerve endings in goats (Brown Harvey 1939)

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CLINICAL PHYSIOLOGY

• It appears, then, that the myotonia is due to
  an abnormality of some part of the muscle fibre
  itself. . .The essential abnormality appears to
  be a tendency of the muscle fibres to respond
  repetitively to any form of stimulation.
• Brown Harvey, 1939

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MEMBRANE PHYSIOLOGY

• Rm 3-4 times normal in goat (Bryant et al
  1962-69) and man (Lipicky et al 1971)
• Chloride conductance markedly reduced in goat,
  accounting for increased Rm Bryant
  Morales-Aguilera 1971

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MEMBRANE PHYSIOLOGY

• Accumulation of potassium in T-tubules is
  responsible for repetitive activity Adrian
  Bryant 1974
• Computer modeling of membrane excitability with
  low chloride conductance explains why sodium
  channel blocking drugs control myotonia Barchi
  1975

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MOLECULAR PATHOLOGY

• Chloride channel gene mutations in myotonia
  congenita (George et al 1993)
• one abnormal copy autosomal dominant
• two abnormal copies autosomal recessive

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MOLECULAR PATHOLOGY

• Sodium channel mutations Ptacek et al 1971
• Hyperkalemic periodic paralysis
• Paramyotonia congenita
• Potassium-aggravated myotonia