RSS-Feed abonnieren
Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.
https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000071.xml
PDF herunterladen
Semin Neurol 2008; 28(2): 212-227
DOI: 10.1055/s-2008-1062260
DOI: 10.1055/s-2008-1062260
Autoimmune Disorders of Neuromuscular Transmission
Weitere Informationen
Publikationsverlauf
Publikationsdatum:
19. März 2008 (online)
ABSTRACT
Myasthenia gravis and Lambert-Eaton syndrome are autoimmune disorders of the neuromuscular junction. The most common form of myasthenia gravis is associated with antibodies directed against the acetylcholine receptor on the postsynaptic membrane. In Lambert-Eaton syndrome, antibodies are directed against P/Q-type voltage-gated calcium channels on presynaptic cholinergic nerve terminals at the neuromuscular junction and in the autonomic nervous system. Lambert-Eaton syndrome may represent a paraneoplastic disease that is most commonly associated with small-cell lung carcinoma or an autoimmune disorder. In both myasthenia gravis and Lambert-Eaton syndrome, the approach to treatment includes symptomatic and immune therapy. Symptomatic therapy in both disorders includes acetylcholinesterase inhibitors. In Lambert-Eaton syndrome, agents that augment the quantal release of acetylcholine are also effective. Immune therapy includes immune suppression with various medications, short-term immune modulation with plasma exchange and intravenous immunoglobulin, and thymectomy in myasthenia gravis. When Lambert-Eaton syndrome is associated with cancer, the disease may improve or remit with effective treatment of the underlying malignancy. Current treatment options will be summarized for both disorders.
KEYWORDS
Myasthenia gravis - Lambert-Eaton myasthenic syndrome - autoimmune - immune suppression
REFERENCES
- 1 Hughes T. The early history of myasthenia gravis. Neuromuscul Disord. 2005; 15 878-886
- 2 Keesey J. Myasthenia Gravis: An Illustrated History. Roseville, CA; Publishers Design Group 2002
MissingFormLabel
- 3 Jolly F. Ueber Myasthenia gravis pseudoparalytica. Berlin Klin Wochenschr. 1895; 32 1-7
- 4 Phillips L H. The epidemiology of myasthenia gravis. Semin Neurol. 2004; 24 17-20
- 5 Isbister C M, Makenzie P J, Anderson D et al.. Co-occurrence of multiple sclerosis and myasthenia gravis in British Columbia: a population-based study. Neurology. 2002; 58(suppl 3) A185-A186
- 6 Phillips L H. The epidemiology of myasthenia gravis. Ann N Y Acad Sci. 2003; 998 407-412
- 7 Phillips L H, Torner J C. Epidemiologic evidence for a changing natural history of myasthenia gravis. Neurology. 1996; 47 1233-1238
- 8 Kalb B, Matell G, Pirskanen R, Lambe M. Epidemiology of myasthenia gravis: a population-based study in Stockholm, Sweden. Neuroepidemiology. 2002; 21 221-225
- 9 Phillips L H, Torner J C, Anderson M S et al.. The epidemiology of myasthenia gravis in central and western Virginia. Neurology. 1992; 42 1888-1893
- 10 Sanders D B, Howard Jr J F.
Disorders of neuromuscular transmission . In: Bradley WG, Daroff RB, Fenichel GM, et al Neurology in Clinical Practice, The Neurological Disorders. Philadelphia; Butterworth Heinemann 2004: 2441-2461MissingFormLabel - 11 Bhatt J R, Pascuzzi R M. Neuromuscular disorders in clinical practice: case studies. Neurol Clin. 2006; 24 233-265
- 12 Daroff R B.
Ocular myasthenia . In: Kaminski HJ Myasthenia Gravis and Related Disorders. Totowa, NJ; Humana Press 2003: 115-128MissingFormLabel - 13 Penn A S, Rowland L P.
Myasthenia gravis . In: Rowland LP Merritt's Neurology. Philadelphia; Lippincott Williams and Wilkins 2005: 877-884MissingFormLabel - 14 Sommer N, Melms A, Weller M, Dichgans J. Ocular myasthenia gravis: a critical review of clinical and pathophysiological aspects. Doc Ophthalmol. 1993; 84 309-333
- 15 Weinberg D H, Rizzo J F, Hayes M T, Kneeland M D, Kelly J J. Ocular myasthenia gravis: predictive value of single-fiber electromyography. Muscle Nerve. 1999; 22 1222-1227
- 16 Levin K.
Disorders of neuromuscular junction transmission . In: Levin K, Luders HO Comprehensive Clinical Neurophysiology. Philadelphia; WB Saunders Company 2000: 251-267MissingFormLabel - 17 Hughes B W, Moro de Casillas M L, Kaminski H J. Pathophysiology of myasthenia gravis. Semin Neurol. 2004; 24 21-30
- 18 Rowland L P. General discussion on the therapy in myasthenia gravis. Ann N Y Acad Sci. 1987; 505 607-609
- 19 Drachman D B. Myasthenia Gravis. N Engl J Med. 1994; 330 1797-1810
- 20 Olanow C W, Wechsler A S, Sirotkin-Roses M et al.. Thymectomy as primary therapy in myasthenia gravis. Ann N Y Acad Sci. 1987; 505 595-606
- 21 Perlo V P, Arnason B, Castleman B. The thymus gland in elderly patients with myasthenia gravis. Neurology. 1975; 25 294-295
- 22 Lindstrom J M, Seybold M E, Lennon V A et al.. Antibody to acetylcholine receptor in myasthenia gravis: prevalence, clinical correlates, and diagnostic value. Neurology. 1976; 26 1054-1059
- 23 Vincent A, Newsom-Davis J. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry. 1985; 48 1246-1252
- 24 Toyka K V, Drachman D B, Griffin D E et al.. Myasthenia gravis: study of humoral immune mechanisms by passive transfer to mice. N Engl J Med. 1977; 296 125-131
- 25 Engel A G, Sahashi K, Lambert E H, Howard F M.
The ultrastructural localization of the acetylcholine receptor, IgG and the third and ninth complement components at the motor end-plate and their implications for the pathogenesis of myasthenia gravis . In: Aguayo AJ, Karpati G Current Topics in Nerve and Muscle Research. Amsterdam; Excerpta Medica 1979: 111-122MissingFormLabel - 26 Patrick J, Lindstrom J. Autoimmune response to acetylcholine receptor. Science. 1973; 180 871-872
- 27 Hohlfeld R, Wekerle H. The thymus in myasthenia gravis. Neurol Clin. 1994; 12 331-342
- 28 Marx A, Muller-Hermelink H K, Strobel P. The role of thymomas in the development of myasthenia gravis. Ann N Y Acad Sci. 2003; 998 223-236
- 29 Hohlfeld R, Wekerle H. The role of the thymus in myasthenia gravis. Adv Neuroimmunol. 1994; 4 373-386
- 30 Wekerle H, Ketelson U. Intrathymic pathogenesis and dual genetic control of myasthenia gravis. Lancet. 1977; 1 678-680
- 31 Wekerle H, Hohlfeld R, Ketelson U P et al.. Thymic myogenesis, T lymphocytes and the pathogenesis of myasthenia gravis. Ann N Y Acad Sci. 1981; 377 455-475
- 32 Meriggioli M N, Sanders D B. Myasthenia gravis: diagnosis. Semin Neurol. 2004; 24 31-39
- 33 Vincent A, McConville J, Farrugia E et al.. Antibodies in myasthenia gravis and related disorders. Ann N Y Acad Sci. 2003; 998 324-335
- 34 Howard F M, Lennon V, Finley J et al.. Clinical correlations of antibodies that bind, block or modulate human acetylcholine receptors in myasthenia gravis. Ann N Y Acad Sci. 1987; 505 526-538
- 35 Baggi F, Andreetta F, Antozzi C et al.. Anti-titin and antiryanodine receptor antibodies in myasthenia gravis patients with thymoma. Ann N Y Acad Sci. 1998; 841 538-541
- 36 Skeie G O, Romi F, Aarli J A et al.. Pathogenesis of myositis and myasthenia associated with titin and ryanodine receptor antibodies. Ann N Y Acad Sci. 2003; 998 343-350
- 37 Somnier F E, Engel P J. The occurrence of anti-titin antibodies and thymomas: a population survey of MG 1970-1999. Neurology. 2002; 59 92-98
- 38 Vincent A, Bowen J, Newsom-Davis J et al.. Seronegative generalized myasthenia gravis: clinical features, antibodies, and their targets. Lancet Neurol. 2003; 2 99-106
- 39 Vincent A, McConville J, Farrugia M E et al.. Seronegative myasthenia gravis. Semin Neurol. 2004; 24 125-133
- 40 Sanders D B, El-Salem K, Massey J M, McConville J, Vincent A. Clinical aspects of MuSK antibody positive seronegative MG. Neurology. 2003; 60 1978-1980
- 41 Hoch W, McConville J, Helms S et al.. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med. 2001; 7 365-368
- 42 Evoli A, Tonali P A, Padua L et al.. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain. 2003; 126 2304-2311
- 43 Keesey J C. Clinical evaluation and management of myasthenia gravis. Muscle Nerve. 2004; 29 484-505
- 44 Keesey J C. AAEE mimeograph #33: electrodiagnostic approach to defects of neuromuscular transmission. Muscle Nerve. 1989; 12 613-626
- 45 Sanders D B, Stalberg E V. AAEM minimonograph #25: single-fiber electromyography. Muscle Nerve. 1996; 19 1069-1083
- 46 Mercelis R. Abnormal single-fiber electromyography in patients not having myasthenia. Ann N Y Acad Sci. 2003; 998 509-511
- 47 Pascuzzi R M. The edrophonium test. Semin Neurol. 2003; 23 83-88
- 48 Phillips II L H, Melnick P A. Diagnosis of myasthenia gravis in the 1990s. Semin Neurol. 1990; 10 62-69
- 49 Saperstein D S, Barohn R J. Management of myasthenia gravis. Semin Neurol. 2004; 24 41-48
- 50 Kaminski H J.
Treatment of myasthenia gravis . In: Kaminski HJ Myasthenia Gravis and Related Disorders. Totowa, NJ; Humana Press 2003: 197-221MissingFormLabel - 51 Seybold M E, Drachman D. Gradually increasing doses of prednisone in myasthenia gravis. N Engl J Med. 1974; 290 81-84
- 52 Meriggioli M N, Ciafaloni E, Al-Hayk K et al.. Mycophenolate mofetil for myasthenia gravis: an analysis of efficacy, safety and tolerability. Neurology. 2003; 61 1438-1440
- 53 Meriggioli M N, Rowin J, Richman J G, Leurgans S. Mycophenolate mofetil for myasthenia gravis: a double-blind, placebo-controlled pilot study. Ann N Y Acad Sci. 2003; 998 494-499
- 54 Mowzoon N, Sussman A, Bradley W G. Mycophenolate (CellCept) treatment of myasthenia gravis, chronic inflammatory polyneuropathy and inclusion body myositis. J Neurol Sci. 2001; 185 119-122
- 55 Schneider C, Gold R, Reiners K et al.. Mycophenolate mofetil in the therapy of severe myasthenia gravis. Eur Neurol. 2001; 46 79-82
- 56 Ciafaloni E, Massey J M, Tucker-Lipscomb B et al.. Mycophenolate mofetil for myasthenia gravis: an open-label pilot study. Neurology. 2001; 56 97-99
- 57 Mantegazza R, Antozzi C, Peluchitte D et al.. Azathioprine as a single drug or in combination with steroids in the treatment of myasthenia gravis. J Neurol. 1988; 235 449-453
- 58 Palace J, Newsom-Davis J, Lecky B. A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group. Neurology. 1998; 50 1778-1783
- 59 Herrlinger U, Weller M, Dichgans J, Melms A. Association of primary central nervous system lymphoma with long-term azathioprine therapy for myasthenia gravis. Ann Neurol. 2000; 47 682-683
- 60 Tindall R SA, Phillips J T, Jollins J A, Wells L, Hall K. A clinical therapeutic trial of cyclosporine in myasthenia gravis. Ann N Y Acad Sci. 1993; 681 539-551
- 61 De Feo L G, Schottlender J, Martelli N A, Molfino N A. Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia gravis. Muscle Nerve. 2002; 26 31-36
- 62 Qureshi A I, Choudhry M A, Akbar M S et al.. Plasma exchange versus intravenous immunoglobulin treatment in myasthenic crisis. Neurology. 1999; 52 629-632
- 63 Ronager J, Ravnborg M, Hermansen I, Vorstrup S. Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis. Artif Organs. 2001; 25 967-973
- 64 Blalock A, Mason M F, Morgan H J et al.. Myasthenia gravis and tumors of the thymic region: report of a case in which the tumor was removed. Ann Surg. 1939; 110 544-561
- 65 Gronseth G S, Barohn R J. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000; 55 7-15
- 66 Mulder D G, Graves M, Herrmann C. Thymectomy for myasthenia gravis: recent and comparisons with past experience. Ann Thorac Surg. 1989; 48 551-555
- 67 Verma P K, Oger J JF. Seronegative generalized myasthenia gravis: low frequency of thymic pathology. Neurology. 1992; 42 586-589
- 68 Lauriola L, Ranelletti F, Maggiano N et al.. Thymus changes in anti-MuSK-positive and -negative myasthenia gravis. Neurology. 2005; 64 536-538
- 69 Leite M I, Strobel P, Jones M et al.. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol. 2005; 57 444-448
- 70 Illa I, Diaz-Manera J A, Juarez C et al.. “Seronegative” myasthenia gravis and anti-MuSK antibodies: description of Spanish series. Med Clin (Barc). 2005; 125 100-102
- 71 Tellez-Zenteno J F, Remes-Troche J M, Garcia-Ramos G et al.. Prognostic factors of thymectomy in patients with myasthenia gravis: a cohort of 132 patients. Eur Neurol. 2001; 46 171-177
- 72 Romi F, Gilhus N E, Varhaug J E, Myking A, Aarli J A. Thymectomy in nonthymomatous early-onset myasthenia gravis in correlations with disease severity and muscle antibodies. Eur Neurol. 2003; 49 210-217
- 73 Jaretzki III A, Steinglass K M, Sonett J R. Thymectomy in the management of myasthenia gravis. Semin Neurol. 2004; 24 49-62
- 74 Schumm F, Wietholter H, Fateh-Mogbadan A, Dichgans J. Thymectomy in myasthenia with pure ocular symptoms. J Neurol Neurosurg Psychiatry. 1985; 48 332-337
- 75 Evoli A, Batocchi A P, Minisci C, DiShino C, Tonali P. Therapeutic options in ocular myasthenia gravis. Neuromuscul Disord. 2001; 11 208-216
- 76 Tim R W, Massey J M, Sanders D B. Lambert-Eaton myasthenic syndrome (LEMS): clinical and electrodiagnostic features and response to therapy in 59 patients. Ann N Y Acad Sci. 1998; 841 823-826
- 77 Wirtz P W, Wintzen A R, Verschuuren J J. The Lambert-Eaton myasthenic syndrome has a more progressive course in patients with lung cancer. Muscle Nerve. 2005; 32 226-229
- 78 Barr C W, Claussen G, Thomas D et al.. Primary respiratory failure as the presenting symptom in Lambert-Eaton myasthenic syndrome. Muscle Nerve. 1993; 16 712-715
- 79 Beydoun S R. Delayed diagnosis of Lambert-Eaton myasthenic syndrome in a patient presenting with recurrent refractory respiratory failure. Muscle Nerve. 1994; 17 689-690
- 80 Smith A G, Wald J. Acute ventilatory failure in Lambert-Eaton myasthenic syndrome and its response to 3,4-diaminopyridine. Neurology. 1996; 46 1143-1145
- 81 Anderson H J, Churchill-Davidson H C, Richardson A T. Bronchial neoplasm with myasthenia: prolonged apnea after administration of succinylcholine. Lancet. 1953; 265 1291-1293
- 82 Burns T M, Russell J A, LaChance D H, Jones H R. Oculobulbar involvement is typical with Lambert-Eaton myasthenic syndrome. Ann Neurol. 2003; 53 270-273
- 83 Oh S J, Kurokawa K, Claussen G C, Ryan H F. Electrophysiological diagnostic criteria of Lambert-Eaton syndrome. Muscle Nerve. 2005; 32 515-520
- 84 Nilsson O, Rosén I. The stretch reflex in the Eaton Lambert syndrome, myasthenia gravis and myotonic dystrophy. Acta Neurol Scand. 1978; 58 350-357
- 85 O'Neill J H, Murray N M, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome: a review of 50 cases. Brain. 1988; 111 577-596
- 86 Wirtz P W, de Keizer R J, de Visser M, Wintzen A R, Verschuuren J J. Tonic pupils in Lambert-Eaton myasthenic syndrome. Muscle Nerve. 2001; 24 444-445
- 87 Khurana R K.
Paraneoplastic autonomic dysfunction . In: Low PA Clinical Autonomic Disorders. Boston; Little Brown Co 1993: 506-511MissingFormLabel - 88 Lambert E H, Eaton L M, Rooke E D. Defect of neuromuscular conduction associated with malignant neoplasms. Am J Physiol. 1956; 187 612-613
- 89 Juel V C, Massey J M, Sanders D B. The Lambert-Eaton myasthenic syndrome: findings in 97 patients. Muscle Nerve. 2006; 34 543 , (Abstract)
- 90 Wirtz P W, Smallegange T M, Wintzen A R, Verschuuren J J. Differences in clinical features between the Lambert-Eaton myasthenic syndrome with and without cancer: an analysis of 227 published cases. Clin Neurol Neurosurg. 2002; 104 359-363
- 91 Sanders D B. Lambert-Eaton myasthenic syndrome: clinical diagnosis, immune-mediated mechanisms, and update on therapy. Ann Neurol. 1995; 37(suppl 1) S63-S73
- 92 Harper C M, Lennon V A.
The Lambert-Eaton myasthenic syndrome . In: Kaminski HJ Current Clinical Neurology: Myasthenia Gravis and Related Disorders. Totowa NJ; Humana Press 2003: 269-291MissingFormLabel - 93 Gutmann L, Crosby T W, Takamori M, Martin J D. The Eaton-Lambert syndrome and autoimmune disorders. Am J Med. 1972; 53 354-356
- 94 Lennon V A, Lambert E H, Whittingham S, Fairbanks V. Autoimmunity in the Lambert-Eaton syndrome. Muscle Nerve. 1982; 5 S21-S25
- 95 Wirtz P W, Bradshaw J, Wintzen A R, Verschuuren J J. Associated autoimmune diseases in patients with the Lambert-Eaton myasthenic syndrome and their families. J Neurol. 2004; 251 1255-1259
- 96 Tim R W, Massey J M, Sanders D B. Lambert-Eaton myasthenic syndrome: electrodiagnostic findings and response to treatment. Neurology. 2000; 54 2176-2178
- 97 Lennon V A.
Serological diagnosis of myasthenia gravis and the Lambert-Eaton myasthenic syndrome . In: Lisak RP Handbook of Myasthenia Gravis and Myasthenic Syndromes. New York; Marcel Dekker 1994: 149-164MissingFormLabel - 98 Elmqvist D, Lambert E H. Detailed analysis of neuromuscular transmission in a patient with the myasthenic syndrome sometimes associated with bronchogenic carcinoma. Mayo Clin Proc. 1968; 43 689-713
- 99 Fukunaga H, Engel A G, Osame M, Lambert E H. Paucity and disorganization of presynaptic membrane active zones in the Lambert-Eaton myasthenic syndrome. Muscle Nerve. 1982; 5 686-697
- 100 Lang B, Newsom-Davis J, Wray D W, Vincent A, Murray N. Autoimmune aetiology for myasthenic (Lambert-Eaton) syndrome. Lancet. 1981; 2 224-226
- 101 Lang B, Johnston I, Leys K et al.. Autoantibody specificities in Lambert-Eaton myasthenic syndrome. Ann N Y Acad Sci. 1993; 681 382-393
- 102 Kim Y I. Passively transferred Lambert-Eaton syndrome in mice receiving purified IgG. Muscle Nerve. 1986; 9 523-530
- 103 Fukunaga H, Engel A G, Lang B, Newsom-Davis J, Vincent A. Passive transfer of Lambert-Eaton myasthenic syndrome with IgG from man to mouse depletes the presynaptic membrane active zones. Proc Natl Acad Sci U S A. 1983; 80 7636-7640
- 104 Fukuoka T, Engel A G, Lang B, Prior C, Wray D W. Lambert-Eaton myasthenic syndrome: I. Early morphological effects of IgG on the presynaptic membrane active zones. Ann Neurol. 1987; 22 193-199
- 105 Nagel A, Engel A G, Lang B, Fukuoka T. Lambert-Eaton myasthenic syndrome IgG depletes presynaptic membrane active zone particles by antigenic modulation. Ann Neurol. 1988; 24 552-558
- 106 Lennon V A, Kryzer T J, Griesmann G E et al.. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med. 1995; 332 1467-1474
- 107 Maddison P, Lang B, Mills K, Newsom-Davis J. Long term outcome in Lambert-Eaton myasthenic syndrome without lung cancer. J Neurol Neurosurg Psychiatry. 2001; 70 212-217
- 108 Wirtz P W, van Dijk J G, van Doorn P A et al.. The epidemiology of the Lambert-Eaton myasthenic syndrome in the Netherlands. Neurology. 2004; 63 397-398
- 109 Sanders D B, Juel V C.
The Lambert-Eaton myasthenic syndrome . In: Engel AG Handbook of Clinical Neurology, Third Series. New York; Elsevier 2007 In pressMissingFormLabel - 110 Eaton L M, Lambert E H. Electromyography and electric stimulation of nerves in diseases of the motor unit. JAMA. 1957; 163 1117-1124
- 111 Lambert E H. Defects of neuromuscular transmission in syndromes other than myasthenia gravis. Ann N Y Acad Sci. 1966; 135 367-384
- 112 AAEM Quality Assurance Committee, American Association of Electrodiagnostic Medicine. . Practice parameter for repetitive nerve stimulation and single fiber EMG evaluation of adults with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome: summary statement. Muscle Nerve. 2001; 24 1236-1238
- 113 Sanders D B. Lambert-Eaton myasthenic syndrome: diagnosis and treatment. Ann N Y Acad Sci. 2003; 998 500-508
- 114 Sanders D B. The effect of firing rate on neuromuscular jitter in Lambert-Eaton myasthenic syndrome. Muscle Nerve. 1992; 15 256-258
- 115 Trontelj J V, Stålberg E. Single motor end-plates in myasthenia gravis and LEMS at different firing rates. Muscle Nerve. 1991; 14 226-232
- 116 Trontelj J V, Stålberg E. The effect of firing rate on neuromuscular jitter in Lambert-Eaton myasthenic syndrome: a reply. Muscle Nerve. 1992; 15 258
- 117 Lennon V A, Lambert E H. Autoantibodies bind solubilized calcium channel-omega-conotoxin complexes from small cell lung carcinoma: a diagnostic aid for Lambert-Eaton myasthenic syndrome. Mayo Clin Proc. 1989; 64 1498-1504
- 118 Sher E, Gotti C, Clementi F. A new assay for the detection of anti-voltage operated channel antibodies in Lambert-Eaton myasthenic syndrome. Neurology. 1989; 39 S267
- 119 Nakao Y K, Motomura M, Fukudome T et al.. Seronegative Lambert-Eaton myasthenic syndrome: study of 110 Japanese patients. Neurology. 2002; 59 1773-1775
- 120 Lang B, Johnston I, Leys K et al.. Autoantibody specificities in Lambert-Eaton myasthenic syndrome. Ann N Y Acad Sci. 1993; 681 382-393
- 121 Leys K, Lang B, Johnston I, Newsom-Davis J. Calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. Ann Neurol. 1991; 29 307-314
- 122 Kanzato N, Motomura M, Suehara M, Arimura K. Lambert-Eaton myasthenic syndrome with ophthalmoparesis and pseudoblepharospasm. Muscle Nerve. 1999; 22 1727-1730
- 123 Katz J S, Wolfe G I, Bryan W W, Tintner R, Barohn R J. Acetylcholine receptor antibodies in the Lambert-Eaton myasthenic syndrome. Neurology. 1998; 50 470-475
- 124 Newsom-Davis J, Leys K, Vincent A, Ferguson I, Modi G, Mills K. Immunological evidence for the co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis in two patients. J Neurol Neurosurg Psychiatry. 1991; 54 452-453
- 125 Oh S J, Sher E. MG and LEMS overlap syndrome: case report with electrophysiological and immunological evidence. Clin Neurophysiol. 2005; 116 1167-1171
- 126 Chalk C H, Murray N M, Newsom-Davis J, O'Neill J H, Spiro S G. Response of the Lambert-Eaton myasthenic syndrome to treatment of associated small-cell lung carcinoma. Neurology. 1990; 40 1552-1556
- 127 Jenkyn L R, Brooks P L, Forcier R J, Maurer L H, Ochoa J. Remission of the Lambert-Eaton syndrome and small cell anaplastic carcinoma of the lung induced by chemotherapy and radiotherapy. Cancer. 1980; 46 1123-1127
- 128 Maddison P, Newsom-Davis J, Mills K R, Souhami R L. Favourable prognosis in Lambert-Eaton myasthenic syndrome and small-cell lung carcinoma. Lancet. 1999; 353 117-118
- 129 Oh S J, Kim D S, Head T C, Claussen G C. Low dose guanidine and pyridostigmine: relatively safe and effective long-term symptomatic therapy in Lambert-Eaton myasthenic syndrome. Muscle Nerve. 1997; 20 1146-1152
- 130 Silbert P L, Hankey G J, Barr A L. Successful alternate day guanidine therapy following guanidine-induced neutropenia in the Lambert-Eaton myasthenic syndrome. Muscle Nerve. 1990; 13 360-361
- 131 Yeh J Z, Oxford C H, Wu C H, Narahashi T. Interactions of aminopyridines with potassium channels of squid axon membranes. Biophys J. 1976; 16 77-81
- 132 Sanders D B, Massey J M, Sanders L L, Edwards L J. A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology. 2000; 54 603-607
- 133 McEvoy K M, Windebank A J, Daube J R, Low P A. 3,4-Diaminopyridine in the treatment of Lambert-Eaton myasthenic syndrome. N Engl J Med. 1989; 321 1567-1571
- 134 Maddison P, Newsom-Davis J. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst Rev. 2003; (2) CD003279
- 135 Rich M M, Teener J W, Bird S J. Treatment of Lambert-Eaton syndrome with intravenous immunoglobulin. Muscle Nerve. 1997; 20 614-615
- 136 NIH Consensus Conference Statement. The utility of therapeutic plasmapheresis for neurological disorders. JAMA. 1986; 256 1333-1337
Lawrence H PhillipsII M.D.
Department of Neurology, University of Virginia
Box 800394, Charlottesville, VA 22908
eMail: lhp3n@virginia.edu