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LANDMARKS IN THE HISTORY OF MYOTONIA

LANDMARKS IN THE HISTORY OF MYOTONIA. International Conference on the Nondystrophic Myotonias, June 3-4, 2007 Robert Layzer University of California, San Francisco. CLINICAL DESCRIPTIONS. Myotonia congenita Dr. JuliusThomsen, 1876

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LANDMARKS IN THE HISTORY OF MYOTONIA

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  1. LANDMARKS IN THE HISTORY OF MYOTONIA International Conference on the Nondystrophic Myotonias, June 3-4, 2007 Robert Layzer University of California, San Francisco

  2. 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

  3. 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

  4. CLINICAL DESCRIPTIONS • Paramyotonia congenita • Episodes of myotonia and weakness induced by exposure to cold: Eulenberg 1888; Rich 1894 • Myotonia typically paradoxical: Magee 1963

  5. CLINICAL DESCRIPTIONS • Hyperkalemic periodic paralysiswithout myotonia: Helweg-Larsen et al 1955, Gamstorp 1956 • Paramyotonia with attacks of generalized weakness induced by oral potassium: French & Kilpatrick, 1957

  6. CLINICAL DESCRIPTIONS • Hyperkalemic periodic paralysis with myotonia: Drager et al 1958; Van der Meulen et al 1961; Van’t Hoff 1962; McArdle 1962; Layzer et al 1967 • Myotonia aggravated by cold and potassium (without weakness): Heine et al 1993

  7. TREATMENT OF MYOTONIA • “Quinine: An Effective Form of Treatment for Myotonia.” Arch Neurol Psychiat 1936;36:382-3. “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)

  8. TREATMENT OF MYOTONIA • Procaine amide: Geschwind & Simpson, 1955 • Diphenylhydantoin: Munsat, 1967

  9. 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

  10. 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.”

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

  12. 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 endingsingoats (Brown & Harvey 1939)

  13. 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

  14. 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

  15. 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

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

  17. MOLECULAR PATHOLOGY • Sodium channel mutations: Ptacek et al 1971 • Hyperkalemic periodic paralysis • Paramyotonia congenita • Potassium-aggravated myotonia

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