Semin Neurol 2004; 24(1): 5-16
DOI: 10.1055/s-2004-829584
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

A History of Treatments for Myasthenia Gravis

John Carl Keesey1
  • 1Department of Neurology, School of Medicine, University of California, Los Angeles, California
Further Information

Publication History

Publication Date:
01 July 2004 (online)

Much of the improvement in the treatment of myasthenia gravis (MG) over the past 125 years can be attributed to the effectiveness of general medical measures such as advances in respiratory care and the discovery of antibiotics. Although MG became the model of an antibody-mediated autoimmune disease in the 1970s (the most documented antigen being the muscle acetylcholine receptor at the neuromuscular junction), the pathogenesis of MG has not been the rationale for most treatments found to be useful for this disease. The serendipitous benefit of anticholinesterases for MG in the 1930s subsequently focused attention on the neuromuscular junction. The beginnings of the controversy over thymectomy for MG in the 1940s and 1950s preceded the discovery in 1960 of the function of the thymus. Before the autoimmune pathogenesis of MG was known, adrenocorticotropic hormone (ACTH) and steroids for MG were tried for reasons that turned out to be incorrect. Further immunosuppressive treatments for MG were largely empirical, following their use in organ transplantation and other autoimmune diseases. More specific treatments, based on our knowledge of pathogenesis, are still experimental but hopefully will be the history of the future.

REFERENCES

  • 1 Keesey J. Myasthenia Gravis, An Illustrated History. Roseville, CA; Publishers Design Group 2002
  • 2 Erb W H. Handbook of Electrotherapeutics. Pützel L, trans. New York; William Woods 1883
  • 3 Viets H R. A historical review of myasthenia gravis from 1672 to 1900.  JAMA. 1953;  153 1273-1280
  • 4 Goldflam S. Ueber einen scheinbar heilbaren bulbärparalytischen symptomencomplex mit betheiligung der extremitäten.  Deutsche Z Nervenheilkunde. 1893;  4 312-352
  • 5 Goldflam S. Weiteres uber die asthenische lahmung nebst einem obductionsbefund. Neurologishes Zentralblatt 1902 21 97-107 490-496
  • 6 Oppenheim H. Die Myasthenische Paralyse (Bulbärparalyse ohne anatomischen Befund. Berlin; S. Karger 1901
  • 7 Campbell H, Bramwell E. Myasthenia gravis.  Brain. 1900;  23 277-336
  • 8 Starr M A. Myasthenia gravis.  J Nerv Ment Dis. 1912;  39 721-731
  • 9 Oppenheim H. Weitere beitrag sur lehre von den acuten, night-eitrigen encephalitis und der poliencephalomyelitis.  Deutsche Z Nervenheilkunde. 1899;  15 1-21
  • 10 Weigert C. Pathologisch-anatomischer Beitrag zur Erb'schen Krankheit (Myasthenia gravis).  Neurologisches Zentralblatt. 1901;  20 596-601
  • 11 Schumacher C H, Roth P. Thymektomie bei einem Fall von Murbus Basedowi mit Myasthenia.  Mitteilungen Grensgebeiten Medizin Chirurgie. 1913;  25 746-765
  • 12 Keschner M, Strauss I. Myasthenia gravis.  AMA Arch Neurol Psychiatry. 1927;  17 337-376
  • 13 Kennedy F S, Moersch F P. Myasthenia gravis: a clinical review of eighty-seven cases observed between 1915 and early part of 1932.  Can Med Assoc J. 1935;  37 216-223
  • 14 Shaw L E. A case of bulbar paralysis without structural changes in the medulla.  Brain. 1890;  13 96-99
  • 15 Goerig M, Filos K, Ayisi K W. George Edward Fell and the development of respiratory machines. In: Atkinson RS, Boulton TB The History of Anesthesia. Park Ridge, NJ; Parthenon Publishing Group 1987: 386-393
  • 16 Drinker P, McKhann C F. The use of a new apparatus for the prolonged administration of artificial respiration.  JAMA. 1929;  92 1658-1660
  • 17 Secher O. The polio epidemic in Copenhagen 1952. In: Atkinson RS, Boulton TB The History of Anesthesia. Park Ridge, NJ; Parthenon Publishing Group 1987: 425-432
  • 18 Remen L. Zur pathogenese und therapie der myasthenia gravis pseudoparalytica.  Deutsche Z Nervenheilkunde. 1932;  128 66-78
  • 19 Boothby W M, Adams M, Power M H et al.. Myasthenia gravis: second report on the effect of treatment with glycine.  Mayo Clin Proc. 1932;  7 737-756
  • 20 Walker M B. Treatment of myasthenia gravis with physostigmine.  Lancet. 1934;  1 1200-1201
  • 21 Keesey J C. Contemporary opinions about Mary Walker, a shy pioneer of therapeutic neurology.  Neurology. 1998;  51 1433-1439
  • 22 Everts W H. The treatment of myasthenia gravis by the oral administration of Prostigmin.  Bull Neurol Inst. 1935;  4 523-530
  • 23 Viets H R. Myasthenia gravis.  JAMA. 1945;  127 1089-1096
  • 24 Eaton L M. Care of the patient who has myasthenia gravis.  Med Clin North Am. 1947;  31 907-923
  • 25 Keesey J C. “Crisis” in myasthenia gravis: an historical perspective.  Muscle Nerve. 2002;  26 1-3
  • 26 Laurent L PE, Walther W W. The influence of large doses of potassium chloride on myasthenia gravis.  Lancet. 1935;  1 1434-1435
  • 27 Minot A S, Dodd K, Riven S S. Use of guanidine hydrochloride in treatment of myasthenia gravis.  JAMA. 1939;  113 553-559
  • 28 Blalock A, Mason M F, Morgan H J, Riven S S. Myasthenia gravis and tumors of the thymic region: report of a case in which the tumor was removed.  Ann Surg. 1939;  110 544-561
  • 29 Blalock A, Harvey A M, Ford F R, Lilienthal J L. The treatment of myasthenia gravis by removal of the thymus gland: preliminary report.  JAMA. 1941;  117 1529-1533
  • 32 Clagett O T, Eaton L M. Surgical treatment of myasthenia gravis.  J Thorac Surg. 1947;  16 62-80
  • 30 Kirschner P A. Alfred Blalock and thymectomy for myasthenia gravis.  Ann Thorac Surg. 1987;  43 348-349
  • 31 Keynes G. The results of thymectomy in myasthenia gravis.  BMJ. 1949;  1 611-616
  • 33 Eaton L M, Clagett O T. Thymectomy in the treatment of myasthenia gravis. Results in seventy-two cases compared to one hundred and forty-two control cases.  JAMA. 1950;  142 963-967
  • 34 Eaton L M, Clagett O T. Present status of thymectomy in treatment of myasthenia gravis.  Am J Med. 1955;  19 703-717
  • 35 Givel J C. Historical review. In: Givel JC Surgery of the Thymus. Berlin; Springer-Verlag 1990: 1-9
  • 36 Schwab R S, Leland C C. Sex and age in myasthenia gravis as critical factors in incidence and remission.  JAMA. 1953;  153 1270-1280
  • 37 Grob D. Myasthenia gravis, current status of pathogenesis, clinical manifestations, and management.  J Chronic Dis. 1958;  8 536-566
  • 38 Perlo V P, Poskanzer D C, Schwab R S, Viets H R, Osserman K E, Genkins G. Myasthenia gravis: evaluation of treatment in 1,355 patients.  Neurology. 1966;  16 431-439
  • 39 Bernatz PE in discussion following Buckingham JM . Howard F M, Bernatz P E, Payne W S, Harrison E G, O'Brien P C, Weiland L H. The value of thymectomy in myasthenia gravis: a computer-assisted matched study.  Ann Surg. 1976;  184 453-458
  • 40 Kirschner P A. The history of surgery of the thymus gland.  Chest Surg Clin N Am. 2000;  10 153-165
  • 41 Osserman K E, Teng P, Kaplan L I. Studies in myasthenia gravis. Preliminary report on therapy with Mestinon bromide.  JAMA. 1954;  155 961-965
  • 42 Comroe J H, Todd J, Gammon G D et al.. The effect of di-isopropyl-fluorophosphate (DFP) upon patients with myasthenia gravis.  Am J Med Sci. 1946;  212 641-651
  • 43 Westerberg M R, Luros J T. The clinical use of hexaethyl tetraphosphate in myasthenia gravis.  Med Bull (Ann Arbor). 1948;  14 15-17
  • 44 Burgen A SV, Keel C A, McAlpine D. Tetra-ethylpyrophosphate in myasthenia gravis.  Lancet. 1948;  1 519-521
  • 45 Rider J A, Schulman S, Richter R B, Moeller H C, DuBois K P. Treatment of myasthenia gravis with octamethyl phyrophosphoramide.  JAMA. 1951;  145 967-972
  • 46 Artusio J F, Riker W F, Wescoe W C. Studies on the inter-relationship of certain cholinergic compounds. IV. Anti-curare action in anesthetized man.  J Pharmacol Exp Ther. 1950;  100 227-237
  • 47 MacFarlane D W, Pelikan W e, Unna K R. Evaluation of curarizing drugs in man. V. Antagonism to curarizing effects of d-tubocurarine by neostigmine, m-hydroxy phenyltrimethylammonium and m-hydroxy phenylethyldimethylammonium.  J Pharmacol Exp Ther. 1950;  100 382-392
  • 48 Westerberg M R, Magee K R, Shideman F E. Effect of 3-hydroxy phenyldimethylethyl ammonium chloride (Tensilon) in myasthenia gravis.  Med Bull (Ann Arbor). 1951;  17 311-316
  • 49 Westerberg M R, Magee K R, Shideman F E. Effect of Tensilon in myasthenia gravis.  Neurology. 1953;  3 302-305
  • 50 Tether J E. Mestinon in myasthenia gravis (preliminary report).  Dis Nerv Syst. 1954;  15 227-231
  • 51 Schwab R S, Timberlake W H. Pyridostigmin (Mestinon) in the treatment of myasthenia gravis.  N Engl J Med. 1954;  251 271-272
  • 52 Westerberg M R, Magee K R. Mestinon in the treatment of myasthenia gravis.  Neurology. 1954;  4 762-771
  • 53 Schwab R S. WIN 8077 in the treatment of sixty myasthenia gravis patients, a twelve-month report.  Am J Med. 1955;  19 734-736
  • 54 Westerberg M R. Clinical evaluation of ambenonium (Mysuran) chloride.  AMA Arch Neurol Psychiatry. 1956;  75 91-94
  • 55 Kraupp O, Stumpf C, Herzfeld E, Pillat B. Pharmakologische Eigenschaften einiger langwirksamer Cholinesterase-Hemmkörper aus der Reihe der Polymethylen-bis-(Carbaminoyl-m-Trimethylammoniumphenole).  Arch Int Parmacodyn Ther. 1955;  102 281-303
  • 56 Pateisky K, Herzfeld E, Stumpf C. Der Effekt von Polymethylen-bis-(N-methyl-m- trimethylammonium-phenolen) BC40, BC47, BC58 auf Cholinesteraseaktivität und Muskeltätigkeit bei Myasthenia gravis pseudparalytica.  Wein KlinWochenschr. 1957;  69 2-7
  • 57 Hoefer P FA, Aronow H, Rowland L P. Long-acting compounds, especially BC 51, in the treatment of myasthenia gravis. In: Viets HR Myasthenia Gravis. The Second International Symposium Proceedings Springfield, IL; Charles C. Thomas 1961: 545-555
  • 58 Schwarz H. Urecholine in myasthenia gravis.  Can Med Assoc J. 1955;  72 346-351
  • 59 Gottlieb B, Laurent L PE. Spironolactone in the treatment of myasthenia gravis.  Lancet. 1961;  2 528-529
  • 60 Satoyoshi E, Murakami K, Okazaki T. Triamterene in the treatment of myasthenia gravis.  Lancet. 1964;  15 741-742
  • 61 Somers J E, Irwin R L, Shy G M. The use of lycoramine derivatives in myasthenia gravis.  Neurology. 1963;  13 543-553
  • 62 Foldes F F, Foldes V M, McNall P G. The use of echothiophate in myasthenia gravis.  Clin Pharmacol Ther. 1966;  7 620-630
  • 63 Hofmann W W. Action of veratrine on human skeletal muscle with special reference to myasthenia gravis.  Neurology. 1958;  8 417-432
  • 64 Flacke W, Caviness V S, Samaha F G. Treatment of myasthenia gravis with germine diacetate.  N Engl J Med. 1966;  275 1207-1214
  • 65 Marsh D O. Adrenal therapy for neuromuscular disease including myasthenia gravis from 1896.  N Y State J Med. 1974;  74 1974-1976
  • 66 Simon H E. Myasthenia gravis, effect of treatment with anterior pituitary extract: preliminary report.  JAMA. 1935;  104 2065-2066
  • 67 Schlezinger N S. Evaluation of therapy in myasthenia gravis.  Arch Intern Med. 1940;  65 60-77
  • 68 Torda C, Wolff H G. Effects of adrenocorticotrophic hormone on neuro-muscular function in patients with myasthenia gravis.  Proc Soc Exp Biol Med. 1949;  71 432-435
  • 69 Millikan C H, Eaton L M. Clinical evaluation of ACTH and cortisone in myasthenia gravis.  Neurology. 1951;  1 145-152
  • 70 Grob D, Harvey A M. Effect of adrenocorticotropic hormone (ACTH) and cortisone administration in patients with myasthenia gravis, and report on onset of myasthenia gravis during prolonged cortisone administration.  Bull Johns Hopkins Hosp. 1952;  91 124-136
  • 71 Freydberg L D. The place of corticotrophin in the treatment of myasthenia gravis.  Ann Intern Med. 1960;  52 806-818
  • 72 Schlezinger N S. Present status of therapy in myasthenia gravis.  JAMA. 1952;  148 508-513
  • 73 Osserman K E. Myasthenia Gravis. New York; Grune & Stratton 1958: 159
  • 74 von Reis G, Liljestrand Å, Matell G. Results with ACTH and spironolactone in severe cases of myasthenia gravis.  Acta Neurol Scand Suppl. 1965;  13 463-471
  • 75 Simpson J. Myasthenia gravis: a new hypothesis.  Scott Med J. 1960;  5 419-436
  • 76 Osserman K E, Genkins G. Studies in myasthenia gravis. Short-term massive corticotrophin therapy.  JAMA. 1966;  198 699-702
  • 77 Grob D, Namba T. Corticotrophin in generalized myasthenia gravis. Effect of short, intensive courses.  JAMA. 1966;  198 703-707
  • 78 Thevènard A. Carotid sinus denervation in myasthenia gravis. In: Viets HR Myasthenia Gravis. The Second International Symposium Proceedings Springfield, IL; Charles C Thomas 1961: 624-633
  • 79 Kjaer M. Myasthenia gravis and myasthenic syndromes treated with prednisone.  Acta Neurol Scand. 1971;  47 464-474
  • 80 Warmolts J R, Engel W K. Benefit from alternate-day prednisone in myasthenia gravis.  N Engl J Med. 1972;  286 17-20
  • 81 Jenkins R B. Treatment of myasthenia gravis with prednisone.  Lancet. 1972;  1 765-767
  • 82 Shy G M, Brendler S, Rabinovitch R, McEachern D. Effects of cortisone in certain neuromuscular disorders.  JAMA. 1950;  144 1353-1358
  • 83 Strauss A JL, Seegal B C, Hsu K C, Burkholder P M, Nastuk W L, Osserman K E. Immunofluorescence demonstration of a muscle binding, complement fixing serum globulin fraction in myasthenia gravis.  Proc Soc Exp Biol Med. 1960;  105 184-191
  • 84 Miller J FAP. Immunological function of the thymus.  Lancet. 1961;  2 748-749
  • 85 Wolf S M, Rowland L P, Schotland D L, McKinney A S, Hoefer P FA, Aranow H. Myasthenia as an autoimmune disease. Clinical aspects.  Ann N Y Acad Sci. 1966;  135 517-535
  • 86 Rowland L P. Immunosuppressive drugs in treatment of myasthenia gravis.  Ann N Y Acad Sci. 1971;  183 351-357
  • 87 Delwaide P J, Salmon J, van Cauwenberger H. Premiers essais de traitement de la myasthenia par azathioprine.  Acta Neurol Psychiatr Belg. 1967;  67 701-712
  • 88 Guille-Minault C. Premiers essais de traitement de la myasthenia par azathioprine.  Gaz Med Fr. 1968;  75 6545
  • 89 Mertens H G, Balzereit F, Leipert M. The treatment of severe myasthenia gravis with immunosuppressive agents.  Eur Neurol. 1969;  2 321-339
  • 90 Hertel G, Mertens H G, Reuther P, Ricker K. The treatment of myasthenia gravis with azathioprine. In: Dau PC Plasmapheresis and the Immunobiology of Myasthenia Gravis. Boston, MA; Houghton Mifflin 1979: 315-328
  • 91 Matell G, Bergström K, Franksson C et al.. Effects of some immunosuppressive procedures on myasthenia gravis.  Ann N Y Acad Sci. 1976;  274 659-676
  • 92 Szobor A, Petrányi G. Immunosuppressive therapy of myasthenia gravis.  Acta Med Acad Sci Hung. 1970;  27 397-411
  • 93 Nouza K, Šmat V. The favourable effect of cyclophosphamide in myasthenia gravis.  Rev Fr Etud Clin Biol. 1968;  13 161-163
  • 94 Perez M C, Buot W L, Mercado-Danguilan C, Bababaldo Z G, Renales L D. Stable remission in myasthenia gravis.  Neurology. 1981;  31 32-37
  • 95 Goulon M, Elkharrat D, Gajdos P, Lokiec F, Morel E. Preliminary results in myasthenia gravis treated with cyclosporin.  Ann N Y Acad Sci. 1987;  505 857-860
  • 96 Tindall R SA, Rollins J A, Phillips J T, Greelee R G, Wells L, Belendiuk G. Preliminary results of a double-blind, randomized, placebo-controlled trial of cyclosporine in myasthenia gravis.  N Engl J Med. 1987;  316 719-724
  • 97 Nyberg-Hansen R, Gjerstad L. Myasthenia gravis treated with cyclosporin.  Acta Neurol Scand. 1988;  77 307-313
  • 98 Hauser R A, Malek A R, Rosen R. Successful treatment of a patient with severe refractory myasthenia gravis using mycophenolate mofetil.  Neurology. 1998;  51 912-913
  • 99 Chaudhry V, Cornblath D R, Griffin J W, O'Brien R, Drachman D B. Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases.  Neurology. 2001;  56 94-96
  • 100 Ciafaloni E, Massey J M, Tucker-Lipscomb B, Sanders D B. Mycophenolate mofetil for myasthenia gravis: an open-label pilot study.  Neurology. 2001;  56 97-99
  • 101 Riven S S, Mason M F. The treatment of myasthenia gravis.  South Med J. 1937;  30 181-190
  • 102 Aring C D. Treatment of myasthenia gravis with the Roentgen ray.  Ohio State Med J. 1943;  39 241-244
  • 103 Keynes G. Investigations into thymic disease and tumour formation.  Br J Surg. 1955;  42 449-462
  • 104 Grob D. Course and management of myasthenia gravis.  JAMA. 1953;  153 529-532
  • 105 Henson R A, Stern G A, Thompson V C. Thymectomy for myasthenia gravis.  Brain. 1965;  88 11-28
  • 106 Schwab R S. Evaluation of one hundred and thirty thymectomies. In: Viets HR Myasthenia Gravis. The Second International Symposium Proceedings Springfield, IL; Charles C Thomas 1961: 597-601
  • 107 Schulz M D, Schwab R S. Results of thymic (mediastinal) irradiation in patients with myasthenia gravis.  Ann N Y Acad Sci. 1971;  183 303-307
  • 108 Philllips T L, Buschke F. The role of radiation therapy in myasthenia gravis.  Calif Med. 1967;  106 282-289
  • 109 Currier R D, Routh A, Hickman B T, Douglas M A. Thymus irradiation for myasthenia gravis.  Radiology. 1983;  146 199-201
  • 110 Engel W K, Lichter A S, Dalakas M. Spenic and total-body irradiation treatment of myasthenia gravis.  Ann N Y Acad Sci. 1981;  377 744-754
  • 111 Durelli L, Ferrio M F, Urgesi A, Poccardi G, Ferrero B, Bergamini L. Total body irradiation for myasthenia gravis: a long-term follow-up.  Neurology. 1993;  43 2215-2221
  • 112 Stricker E, Thölen H, Massini M A, Stauf H. The effect of haemodialysis in myasthenia gravis.  J Neurol Neurosurg Psychiatry. 1960;  23 291-294
  • 113 Hedger R W, Davis F A, Schwartz F D, Ing T S. Improvement of myasthenia gravis by hemodialysis in a patient with chronic renal failure.  Ann Intern Med. 1971;  75 749-752
  • 114 Patten B M. A hypothesis to account for the Mary walker phenomenon.  Ann Intern Med. 1975;  82 411-415
  • 115 Lefvert A K, Matell G. Thoracic duct lymph drainage in myasthenia gravis: clinical effect and kinetic studies of the acetylcholine receptor antibody. In: Dau PC Plasmapheresis and the Immunobiology of Myasthenia Gravis. Boston, MA; Houghton Mifflin 1979: 151-160
  • 116 Tindall S C, Peters B H, Caverley J R, Sarles H E, Fish J C. Thoracic duct lymphocyte depletion in myasthenia gravis.  Arch Neurol. 1973;  29 202-203
  • 117 Bergstrom K, Franksson C, Matell G et al.. Drainage of thoracic duct lymph in twelve patients with myasthenia gravis.  Eur Neurol. 1975;  13 19-30
  • 118 Lindstrom J M, Seybold M E, Lennon V A, Whittingham S, Duane D D. Antibody to acetylcholine receptor in myasthenia gravis.  Neurology. 1976;  26 1054-1059
  • 119 Pinching A F, Peters D K, Newsom-Davis J. Remission of myasthenia gravis following plasma exchange.  Lancet. 1976;  2 1373-1376
  • 120 Dau P C, Lindstrom J M, Cassel C K, Denys E H, Shev E E, Spitler L E. Plasmapheresis and immunosuppressive drug therapy in myasthenia gravis.  N Engl J Med. 1977;  297 1134-1140
  • 121 Pirofsky B, Reid R H, Bardana E J, Baker R L. Antithymocyte antiserum therapy in myasthenia gravis.  Postgrad Med J. 1976;  52(suppl 5) 112-117
  • 122 Pirofsky B, Reid R H, Bardana E J, Baker R L. Myasthenia gravis treated with purified antithymocyte antiserum.  Neurology. 1979;  29 112-116
  • 123 Leövey A, Szobor A, Szegedi G, Szathmáry I, Petrányi G. Myasthenia gravis: ALG treatment of seriously ill patients.  Eur Neurol. 1975;  13 422-432
  • 124 Genkins G, Paptestas A E, Kornfeld P, Horowitz S H. Studies in myasthenia gravis: staging and gamma globulin. In: Dau PC Plasmapheresis and the Immunobiology of Myasthenia Gravis. Boston, MA; Houghton Mifflin 1979: 144-150
  • 125 Gajdos P, Outin H, Elkharrat D et al.. High-dose intravenous gammaglobulin for myasthenia gravis.  Lancet. 1984;  1 406-407
  • 126 Arsura E L, Bick A, Brunner N G, Namba T, Grob D. High-dose intravenous immunoglobulin in the management of myasthenia gravis.  Arch Intern Med. 1986;  146 1365-1368

John KeeseyM.D. 

1144 Iliff Street

Pacific Palisades, CA 90272