Zusammenfassung
Die Behandlung der Myasthenia gravis (MG) und des
Lambert-Eaton-Syndroms (LEMS) entsprechend den Leitlinien der DGN ist in der
Regel sehr wirksam. Aufgrund des sehr individuellen Verlaufs beider
Erkrankungen, medikamentöser Unverträglichkeiten oder schwerwiegender
Begleiterkrankungen ist es allerdings nicht selten erforderlich, von den
„klassischen” Immuntherapeutika (Kortikosteroide, Azathioprin)
abzuweichen und andere Medikamente im Off-label-use einzusetzen, für die
zwar zumeist eine schwächere Studienlage besteht, aber doch eine
tragfähige klinische Evidenz gegeben ist. Der Ärztliche Beirat der
Deutschen Myasthenie-Gesellschaft hat daher die verfügbaren
wissenschaftlichen Daten zu diesen „Reservemedikamenten”
(Methotrexat, Cyclophosphamid, Cyclosporin A, Mycophenolat Mofetil, Tacrolimus,
Rituximab) hinsichtlich Indikationen und Zulassung, Studienergebnissen,
praktischer Anwendung einschließlich Therapiemonitoring,
unerwünschter Wirkungen und Komplikationsmöglichkeiten aktualisiert.
Für jedes Medikament werden darüber hinaus Erfahrungswissen und
Hinweise zur Anwendung in Schwangerschaft und Stillzeit gegeben. Diese Synopsis
will therapeutische Möglichkeiten aufzeigen und Hinweise liefern, wie auch
bei einem schweren Verlauf von MG oder LEMS Nutzen-Risiko-Abwägungen
vorgenommen werden können. Sie können den zielgerechten Umgang mit
dem unvermeidlichen Off-label-use der genannten Substanzen fördern. In
einem 2. Teil wird dann auf die Therapie mit intravenösen Immunglobulinen,
Plasmaaustausch und Immunadsorption eingegangen.
Abstract
The treatment of myasthenia gravis (MG) and Lambert-Eaton myasthenic
syndrome (LEMS) is – according to the guidelines of the German
Neurological Society – very effective in most patients. Nevertheless due
to the individual course of both diseases, adverse drug effects or severe
comorbidities, it is often necessary to stop the treatment with the
„classical” immunotherapeutics such as corticosteroids and
azathioprine and to change to other drugs in spite of the fact that experience
using them is much more scarce and that the drugs can only be given off-label.
The Medical Advisory Board of the German Myasthenia Society (DMG) has therefore
updated the available scientific data concerning these drugs (methotrexate,
cyclophosphamide, cyclosporine, mycophenolate mofetil, tacrolimus, rituximab)
with respect to indications and approval, study results, practical application
and monitoring of therapy as well as adverse events and complications.
Moreover, for each of these drugs, some practical information concerning
pregnancy and breast-feeding is given. This publication is intended to
demonstrate additional treatment modalities even in severe cases of MG or LEMS.
Moreover, it may offer some arguments for the off-label-use of these drugs. In
a second part of this publication, the treatment with high-dose
immunoglobulins, plasma exchange and immunoadsorption will be discussed.
Schlüsselwörter
Myasthenia gravis - Lambert-Eaton myasthenes Syndrom - Immuntherapie - medikamentöse Immunsuppression
Keywords
myasthenia gravis - Lambert-Eaton myasthenic syndrome - immunotherapy - drug-induced immunosuppression
Literatur
1 Fuhr P, Gold R, Toyka K V* et al. Myasthenia gravis.. In: Diener H C, Putzki N, Elger C, et al, Hrsg Leitlinien für Diagnostik und Therapie in der
Neurologie.. 4. Aufl. Stuttgart: Thieme; 2008: 686-704 (*federführend)
2
Schneider-Gold C, Gajdos P, Toyka K V et al.
Corticosteroids for myasthenia gravis.
Cochrane Database Syst Rev.
2005;
(2)
CD002828
3
Skeie G, Apostolski S, Evoli A et al.
Guidelines for the treatment of autoimmune neuromuscular
transmission disorders.
Eur J Neurol.
2010;
17
893-902
4
Jeffrey J A, Scala S, Royden Jones H.
Ocular myasthenia gravis in a senior population. Diagnosis,
therapy, and prognosis.
Muscle Nerve.
2010;
41
379-384
5 Schneider-Gold C, Melms A, Hohlfeld R. Myasthenia gravis und myasthene Syndrome.. In: Brandt T, Dichgans J, Diener H C, Hrsg Therapie und Verlauf neurologischer Erkrankungen.. 5. Aufl. Stuttgart: Kohlhammer; 2007: 1320-1342
6
Park-Wyllie L, Mazzotta P, Pastuszak A et al.
Birth defects after maternal exposure to corticosteroids:
prospective cohort study and meta-analysis of epidemiological studies.
Teratology.
2000;
62
385-392
7
Gur C, Diav-Citrin O, Shechtman S et al.
Pregnancy outcome after first trimester exposure to
corticosteroids: a prospective controlled study.
Reprod Toxicol.
2004;
18
93-101
8
Pradat P, Robert-Gnansia E, Di Tanna G L et al.
Contributors to the MADRE database. First trimester exposure
to corticosteroids and oral clefts.
Birth Defects Res A Clin Mol Teratol.
2003;
67
968-970
9
Mertens H G, Balzereit F, Leipert M.
The treatment of severe myasthenia gravis with
immunosuppressive agents.
Eur Neurol.
1969;
2
321-339
10
Witte A S, Cornblath D R, Parry G J et al.
Azathioprine in the treatment of myasthenia gravis.
Ann Neurol.
1984;
15
602-605
11
Mantegazza R, Antozzi C, Peluchetti D et al.
Azathioprine as a single drug or in combination with steroids
in the treatment of myasthenia gravis.
J Neurol.
1988;
237
339-344
12
Matell G, Bergstrom K, Franksson C et al.
Effects of some immunosuppressive procedures in myasthenia
gravis.
Ann N Y Acad Sci.
1976;
274
659-676
13
Mertens H G, Hertel G, Reuther P et al.
Effect of immunosuppressive drugs (azathioprine).
Ann N Y Acad Sci.
1981;
377
691-699
14
Kuks J BM, Djojoatmodjo S, Oosterhuis H JHG.
Azathioprine in myasthenia gravis: observations in 41
patients and a review of literature.
Neuromusc Disord.
1991;
1
423-431
15
Sommer N, Sigg B, Melms A et al.
Ocular myasthenia gravis: response to long-term
immunosuppressive treatment.
J Neurol Neurosurg Psychiatry.
1997;
62
156-162
16
Heckmann J M, LeePan E B, Eastman R W.
High-dose immunosuppressive therapy in generalised myasthenia
gravis – a 2-year follow-up study.
S Afr Med J.
2001;
91
765-770
17
Hohlfeld R, Toyka K V, Besinger U A et al.
Myasthenia gravis: Reactivation of clinical disease and of
autoimmune factors after discontinuation of long-term azathioprine.
Ann Neurol.
1985;
17
238-242
18
Michels M, Hohlfeld R, Hartung H P et al.
Myasthenia gravis: discontinuation of long-term
azathioprine.
Ann Neurol.
1988;
24
798
19
Myasthenia Gravis Clinical Study Group .
A randomised clinical trial comparing prednisolone and
azathioprine in myasthenia gravis. Results of a second interim analysis.
J Neurol Neurosurg Psychiatry.
1993;
56
1157-1163
20
Bromberg M B, Wald J J, Forshew D A et al.
Randomized trial of azathioprine or prednisolone for initial
immunosuppressive treatment of myasthenia gravis.
J Neurol Sci.
1997;
150
59-62
21
Palace J, Newsom-Davis J, Lecky B.
A randomized double-blind trial of prednisolone alone or with
azathioprine in myasthenia gravis.
Neurology.
1998;
50
1778-1783
22
Tumani H, George A, Nau R.
Myasthene Krise durch Azathioprin-induziertes Fieber.
Nervenarzt.
1997;
68
336-338
23
Ford L T, Berg J D.
Thiopurine S-methyltransferase (TPMT) assessment prior to
starting thiopurine drug treatment; a pharmacogenomic test whose time has
come.
J Clin Pathol.
2010;
63
288-295
24
Jabin D, Kumar S, Gow P J.
Outcome of patients on azathioprine: a need for a better
pre-treatment assessment and dosing guideline.
N Z Med J.
2010;
123
67-73
25
Confavreux C, Saddier P, Grimaud J et al.
Risk of cancer from azathioprine therapy in multiple
sclerosis: A case control study.
Neurology.
1996;
46
1607-1612
26
Rawoot A, Little F, Heckmann J M.
Risk of malignancy in myasthenia gravis patients exposed to
azathioprine therapy for a median period of 3 years.
S Afr Med J.
2006;
96
1249-1251
27
O'Donovan P, Perrett C M, Zhang X et al.
Azathioprine and UVA light generate mutagenic oxidative DNA
damage.
Science.
2005;
309
1871-1874
28
Polifka J E, Friedman J M.
Teratogen update: azathioprine and 6-mercaptopurine.
Teratology.
2002;
65
240-261
29
Goldstein L H, Dolinsky G, Greenberg R et al.
Pregnancy outcome of women exposed to azathioprine during
pregnancy.
Birth Defects Res A Clin Mol Teratol.
2007;
79
696-701
30
Cleary B J, Källén B.
Early pregnancy azathioprine use and pregnancy outcomes.
Birth Defects Res A Clin Mol Teratol.
2009;
85
647-654
31
Hoeltzenbein M, Weber-Schoendorfer C, Padberg S et al.
Paternal exposure to
azathioprine / 6-mercaptopurine – Experience of Berlin
TIS.
Reprod Toxicol.
2010;
238-239
(abstract)
32
Francella A, Dyan A, Bodian C et al.
The safety of 6-mercaptopurine for childbearing patients with
inflammatory bowel disease: a retrospective cohort study.
Gastroenterology.
2003;
124
9-17
33
Zelinkova Z, De Boer I P, Van Dijke M J et al.
Azathioprine treatment during lactation.
Aliment Pharmacol Ther.
2009;
30
90-91 author reply 91
34
Christensen L A, Dahlerup J F, Nielsen M J et al.
Azathioprine treatment during lactation.
Aliment Pharmacol Ther.
2008;
28
1209-1213
35
Hart I K, Sathasivam S, Sharshar T.
Immunosuppressive agents for myasthenia gravis.
Cochrane Database Syst Rev.
2007;
(4)
CD005224
36
Hilton-Jones D.
When the patient fails to respond to treatment: Myasthenia
gravis.
Pract Neurol.
2007;
7
405-411
37
Tarner H J, Manger B, Fleck M et al.
Evidenzbasierte Empfehlungen einer nationalen Expertenrunde
zum Einsatz von Methotrexat bei entzündlich-rheumatischen
Erkrankungen.
Akt Rheumatol.
2009;
34
59-66
38
Pagnoux C, Mahr A, Hamidou M A et al.
Azathioprine or methotrexate maintenance for ANCA-associated
vasculitis.
N Engl J Med.
2008;
359
790-803
39
Goodkin D E, Rudick R A, van der Brug-Medendorp S et al.
Low dose (7,5 mg) oral methotrexate reduces the rate
of progression in chronic progressive multiple sclerosis.
Ann Neurol.
1995;
37
30-40
40
Schneider-Gold C.
Aktuelle Therapie der Myasthenia gravis und der autoimmunen
Myositiden.
Akt Neurol.
2009;
36
266-269
41
Raja F M, Wimachkie M, McVey A L et al.
Clin Neuromusc Dis.
2009;
10
abstract 136
42
Sathasivam S.
Steroids and immunosuppressant drugs in Myasthenia gravis.
Nature clinical practice.
Neurology.
2008;
4
317-327
43
Gold R, Schneider-Gold C.
Current and future standards in treatment of myasthenia
gravis.
Neurotherapeutics.
2008;
5
535-541
44
Gold R, Schneider-Gold C, Toyka K V.
Fortschritte in Pathogenese und Therapie der Myasthenia
gravis und des Lambert-Eaton-Syndromes.
Akt Neurol.
2008;
35
192-203
45
Skeie G O, Apostolski S, Evoli A et al.
Guidelines for treatment of autoimmune transmission
disorders.
Eur J Neurol.
2006;
13
691-699
46
Hilton-Jones D, Palace J.
The management of myasthenia gravis.
Pract Neurol.
2005;
5
18-27
47
Tran H, Cheung C, Gill D et al.
Methotrexate – associated mantle-cell lymphoma in an
elderly man with myasthenia gravis.
Nat Clin Pract Oncol.
2008;
5
234-238
48
Buckley L M, Bullaboy C A, Leichtman L et al.
Multiple congenital anomalies associated with weekly low-dose
methotrexate treatment of the mother.
Arthritis Rheum.
1997;
40
971-973
49
Lewden B, Vial T, Elefant E et al.
French Network of Regional Pharmacovigilance Centers. Low
dose methotrexate in the first trimester of pregnancy: results of a French
collaborative study.
J Rheumatol.
2004;
31
2360-2365
50
Chakravarty E F, Sanchez-Yamamoto D, Bush T M.
The use of disease modifying antirheumatic drugs in women
with rheumatoid arthritis of childbearing age: a survey of practice patterns
and pregnancy outcomes.
J Rheumatol.
2003;
30
241-246
51
Hoeltzenbein M, Weber-Schoendorfer C, von Stackelberg L et al.
Paternal exposure to drugs – Is there an increased risk
for congenital abnormalities? Experience of the Berlin Institute for Clinical
Teratology and Drug Risk Assessment during Pregnancy.
Reprod Toxicol.
2008;
26
64
(abstract)
52
Tindall R SA, Rollins J A, Phillips J T et al.
Preliminary results of a double blind, randomized,
placebo-controlled trial of cyclosporine in myasthenia gravis.
N Engl J Med.
1987;
316
719-724
53
Tindall R SA, Phillips J T, Rollins J A et al.
A clinical therapeutic trial of ciclosporine in myasthenia
gravis.
Ann NY Acad Sci.
1993;
681
539-551
54
Evoli A, Bianchi M R, Riso R et al.
Response to therapy in myasthenia gravis with anti-MuSK
antibodies.
Ann NY Acad Sci.
2008;
1132
76-83
55
Armenti V T, Radomskir J S, Moritz M J et al.
Report from the National Transplantation Pregnancy Registry
(NTPR): Outcomes of pregnancy after transplantation.
Clinical Transplants.
2005;
69-83
56
Bar-Oz B, Hackman R, Einarson T et al.
Pregnancy outcome after cyclosporine therapy during
pregnancy: a meta-analysis.
Transplantation.
2001;
71
1051-1055
57
Moretti M E, Sgro M, Johnson D W et al.
Cyclosporine excretion into breast milk.
Transplantation.
2003;
75
2144-2146
58
Nouza K, Smat V.
The favourable effect of cyclophosphamide in myasthenia
gravis.
Rev Fr Etud Clin Biol.
1968;
13
161-163
59
Pestronk A, Drachman D B, Adams R N.
Treatment of ongoing experimental myasthenia gravis with
short-term high dose cyclophosphamide.
Muscle Nerve.
1982;
5
79-84
60
Perez M C, Buot W L, Mercado-Danguilan C et al.
Stable remission in myasthenia gravis.
Neurology.
1981;
31
32-37
61
Gladstone D E, Brannagan 3rd T H, Schwartzman R J et al.
High dose cyclophosphamide for severe refractory myasthenia
gravis.
J Neurol Neurosurg Psychiatry.
2004;
75
789-791
62
De Assis J L, Marchiori P E, Scaff M et al.
Treatment of myasthenia gravis by immunosuppressive
non-steroidal drugs.
Arq Neuropsiquiatr.
1986;
44
109-116
63
Niakan E, Harati Y, Rolak L A.
Immunosuppressive drug therapy in myasthenia gravis.
Arch Neurol.
1986;
43
155-156
64
Hart I K, Sharshar T, Sathasivam S.
Immunosuppressant drugs for myasthenia gravis.
J Neurol Neurosurg Psychiatry.
2009;
80
discussion 6
65
García-Carrasco M, Escárcega R O, Fuentes-Alexandro S et al.
Therapeutic options in autoimmune myasthenia gravis.
Autoimmun Rev.
2007;
6
373-378
66
Spring P J, Spies J M.
Myasthenia gravis: options and timing of immunomodulatory
treatment.
BioDrugs.
2001;
15
173-183
67
Lisak R P.
Myasthenia gravis.
Curr Treat Options Neurol.
1999;
1
239-250
68
Drachman D B, Adams R N, Hu R et al.
Rebooting the immune system with high-dose cyclophosphamide
for treatment of refractory myasthenia gravis.
Ann N Y Acad Sci.
2008;
1132
305-314
69
Lin P T, Martin B A, Weinacker A B et al.
High-dose cyclophosphamide in refractory myasthenia gravis
with MuSK antibodies.
Muscle Nerve.
2006;
33
433-435
70
Schumm F, Brinkmann A, Fateh-Moghadam A.
Antibody-controlled cytostatic therapy of malignant thymoma
with concomitant myasthenia gravis.
Dtsch Med Wochenschr.
1984;
109
1244-1246
71
Kosmidis P A, Iliopoulos E, Pentea S.
Combination chemotherapy with cyclophosphamide, adriamycin,
and vincristine in malignant thymoma and myasthenia gravis.
Cancer.
1988;
61
1736-1740
72
Chorzelski T, Hashimoto T, Maciejewska B et al.
Paraneoplastic pemphigus associated with Castleman tumor,
myasthenia gravis and bronchiolitis obliterans.
J Am Acad Dermatol.
1999;
41
393-400
73
Tomida C, Yamagata K, Ishizu T et al.
A case of nephrotic syndrome associated with myasthenia
gravis and malignant thymoma.
Nippon Jinzo Gakkai Shi.
1999;
41
77-82
74
Denayer M A, Rao K R, Wirz D et al.
Hepatic metastatic thymoma and myasthenia gravis twenty-two
years after the apparent cure of an invasive thymoma. A case report and review
of the literature.
J Neurol Sci.
1986;
76
23-30
75
Flachenecker P, Taleghani B M, Gold R et al.
Treatment of severe myasthenia gravis with protein A
immunoadsorption and cyclophosphamide.
Trans Sci.
1998;
19
43-46
76
Zeitler H, Ulrich-Merzenich G, Hoffmann L et al.
Long-term effects of a multimodal approach including
immunoadsorption for the treatment of myasthenic crisis.
Artif Organs.
2006;
30
597-605
77
Haas M, Mayr N, Zeitlhofer J et al.
Long-term treatment of myasthenia gravis with
immunoadsorption.
J Clin Apher.
2002;
17
84-87
78
Nakashima I, Kikuchi A, Onodera J et al.
A juvenile case of Lambert-Eaton myasthenic syndrome with
severe emaciation.
Rinsho Shinkeigaku.
1997;
37
402-406
79
Maddison P, Newsom-Davis J.
Treatment for Lambert-Eaton myasthenic syndrome.
Cochrane Database Syst Rev.
2003;
(2)
CD003279
80
De Feo L G, Schottlender J, Martelli N A et al.
Use of intravenous cyclophosphamide in severe, generalized
myasthenia gravis.
Muscle Nerve.
2002;
26
31-36
81
Badurska B, Ryniewicz B, Strugalska H.
Immunosuppressive treatment of juvenile myasthenia
gravis.
Eur J Pediatr.
1992;
151
215-217
82 Melms A, Hohlfeld R. Myasthenia gravis und myasthene Syndrome.. In: Brandt T, Dichgans J, Diener H-C, Hrsg Therapie und Verlauf neurologischer Erkrankungen.. Stuttgart, Berlin, Köln: Kohlhammer; 1998: 1097-1119
83
Diaz-Manera J, Rojas-Garcia R, Illa I.
Treatment strategies for myasthenia gravis.
Expert Opin Pharmacother.
2009;
10
1329-1342
84
Drachman D B, Jones R J, Brodsky R A.
Treatment of refractory myasthenia: „rebooting”
with high-dose cyclophosphamide.
Ann Neurol.
2003;
53
7-9
85
Enns G M, Roeder E, Chan R T et al.
Apparent cyclophosphamide (cytoxan) embryopathy: a distinct
phenotype?.
Am J Med Genet.
1999;
86
237-241
86
Hahn K M, Johnson P H, Gordon N et al.
Treatment of pregnant breast cancer patients and outcomes of
children exposed to chemotherapy in utero.
Cancer.
2006;
107
1219-1226
87
Ring A E, Smith I E, Jones A et al.
Chemotherapy for breast cancer during pregnancy: an 18-year
experience from five London teaching hospitals.
J Clin Oncol.
2005;
23
4192-4197
88
Bargman H B, Fefferman I.
Multiple dermatofibromas in a patient with myasthenia gravis
treated with prednisone and cyclophosphamide.
J Am Acad Dermatol.
1986;
14
351-352
89
Chaudhry V, Cornblath D R, Griffin J W et al.
Mycophenolate mofetil: A safe and promising immunosuppressant
in neuromuscular diseases.
Neurology.
2001;
56
94-96
90
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
91
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
92
Schneider C, Gold R, Reiners K et al.
Mycophenolate mofetil in the therapy of severe myasthenia
gravis.
Eur Neurol.
2001;
46
79-82
93
Meriggioli M N, Rowin J, Richman J G et al.
Mycophenolate mofetil for myasthenia gravis: a double-blind,
placebo-controlled pilot study.
Ann NY Acad Sci.
2003;
998
494-499
94
Sanders D B, Hart I K, Mantegazza R et al.
An international, phase III, randomized trial of
mycophenolate mofetil in myasthenia gravis.
Neurology.
2008;
71
400-406
95
The Muscle Study Group .
A trial of mycophenolate mofetil with prednisone as initial
immunotherapy in myasthenia gravis.
Neurology.
2008;
71
394-399
96
Benatar M, Rowland L P.
The muddle of mycophenolate mofetil in myasthenia.
Neurology.
2008;
71
390-391
97
Hehir M K, Burns T M, Alpers J et al.
Mycophenolate Mofetil in AChR-antibody-positive myasthenia
gravis: Outcomes in 102 patients.
Muscle Nerve.
2010;
41
593-598
98
Newsom-Davis J.
Therapy in myasthenia gravis and Lambert-Eaton myasthenic
syndrome.
Semin Neurol.
2003;
23
191-198
99
Anderka M T, Lin A E, Abuelo D N et al.
Reviewing the evidence for mycophenolate mofetil as a new
teratogen: case report and review of the literature.
Am J Med Genet A.
2009;
149A
1241-1248
100
Merlob P, Stahl B, Klinger G.
Tetrada of the possible mycophenolate mofetil embryopathy: a
review.
Reprod Toxicol.
2009;
28
105-108
101
Hoeltzenbein M, Elefant E, Garayt C et al.
Maternal exposure to mycophenolate mofetile in pregnancy
– Results of the ENTIS collaborative study.
Reprod Toxicol.
2010;
30
228
(abstract)
102
Yoshikawa H, Iwasa K, Satoh K et al.
FK506 prevents induction of rat experimental autoimmune
myasthenia gravis.
J Autoimmun.
1997;
10
11-16
103
Evoli A, Di Schino C, Marsili F et al.
Successful treatment of myasthenia gravis with
tacrolimus.
Muscle Nerve.
2002;
25
111-114
104
Ponseti J M, Azem J, Fort J M et al.
Long-term results of tacrolimus in cyclosporine- and
prednisone-dependent myasthenia gravis.
Neurology.
2005;
64
1641-1643
105
Ponseti J M, Gamez J, Azem J et al.
Tacrolimus for myasthenia gravis: a clinical study of 212
patients.
Ann NY Acad Sci.
2008;
1132
254-263
106
Christopher V, Al-Chalabi T, Richardson P D et al.
Pregnancy outcome after liver transplantation: a
single-center experience of 71 pregnancies in 45 recipients.
Liver Transpl.
2006;
12
1138-1143
107
Jain A B, Shapiro R, Scantlebury V P et al.
Pregnancy after kidney and kidney-pancreas transplantation
under tacrolimus: a single center's experience.
Transplantation.
2004;
77
897-902
108
Gardiner S J, Begg E J.
Breastfeeding during tacrolimus therapy.
Obstet Gynecol.
2006;
107
453-455
109
Zaja F, Russo D, Fuga G et al.
Rituximab for myasthenia gravis developing after bone marrow
transplant.
Neurology.
2000;
55
1062-1063
110
Wylam M E, Anderson P M, Kuntz N L et al.
Successful treatment of refractory myasthenia gravis using
rituximab: a pediatric case report.
J Pediatr.
2003;
143
674-677
111
Illa I, Diaz-Manera J, Rojas-Garcia R et al.
Sustained response to Rituximab in anti-AChR and anti-MuSK
positive Myasthenia Gravis patients.
J Neuroimmunol.
2008;
201–202
90-94
112
Nelson Jr R P, Pascuzzi R M, Kessler K et al.
Rituximab for the treatment of thymoma-associated and de novo
myasthenia gravis: 3 cases and review.
J Clin Neuromuscul Dis.
2009;
10
170-177
113
Hain B, Jordan K, Deschauer M et al.
Successful treatment of MuSK antibody-positive myasthenia
gravis with rituximab.
Muscle Nerve.
2006;
33
575-580
114
Baek W S, Bashey A, Sheean G L.
Complete remission induced by rituximab in refractory,
seronegative, muscle-specific, kinase-positive myasthenia gravis.
J Neurol Neurosurg Psychiatry.
2007;
78
771
115
Pellkofer H L, Voltz R, Kuempfel T.
Favorable response to rituximab in a patient with
anti-VGCC-positive Lambert-Eaton myasthenic syndrome and cerebellar
dysfunction.
Muscle Nerve.
2009;
40
305-308
116
Maddison P, McConville J, Farrugia M E et al.
The use of rituximab in myasthenia gravis and Lambert-Eaton
myasthenic syndrome.
J Neurol Neurosurg Psychiatry.
2010;
[Epub ahead of print] PubMed PMID:
20392977
117
Stieglbauer K, Topakian R, Schäffer V et al.
Rituximab for myasthenia gravis: three case reports and
review of the literature.
J Neurol Sci.
2009;
280
120-122
118
Zebardast N, Patwa H S, Novella S P et al.
Rituximab in the management of refractory myasthenia
gravis.
Muscle Nerve.
2010;
41
375-378
119
Klink D T, van Elburg R M, Schreurs M W et al.
Rituximab administration in third trimester of pregnancy
suppresses neonatal B-cell development.
Clin Dev Immunol.
2008;
2008
271-363
Prof. Dr. med. Thomas Henze
Reha-Zentrum Nittenau
Eichendorffstr. 21
93149 Nittenau
eMail: t.henze@rz-ni.de