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Abstract
Management of myasthenic crisis (MC) requires admission of the patient into a neurological intensive care unit and timely institution of
an efficient and safe treatment. Despite the growing clinical experience with disease modifying immunotherapy there is no clinical consensus
regarding the use of plasma exchange or high dose immunoglobulin treatment in an ICU setting. The choice of treatment modalities seem to
rely mostly on institutional preferences primarily due to a lack of well-designed clinical trials comparing currently available therapeutic
options. In our experience and based on a review of recent literature we advocate the use of plasma exchange (PE) as a primary modality in
the acute care setting, supported by other immunomodulatory medications such as corticosteroids. Pharmacological management cannot
substitute for adequate intensive care management of the respiratory and bulbar insufficiency associated with MC. Every effort should be
done to prevent myasthenic exacerbation/crisis and to develop a maintenance management that leads to effective prevention.
2007 Elsevier B.V. All rights reserved.
Keywords: Myasthenic crisis; Plasma exchange; Corticosteroids
1. Introduction
Acquired myasthenia gravis is an autoimmune disorder of
neuromuscular junction transmission clinically manifesting as
variable and fluctuating weakness of certain muscles.
Symptoms are due to reduced binding of acetylcholine at the
neuromuscular junction (NMJ) due to either the presence of
acetylcholine receptor (AChR) antibodies reducing the
available postsynaptic acetylcholine receptors found on the
end plate of skeletal muscle or by the presence of autoantibodies directed towards other postsynaptic skeletal muscle
components, such as Muscle Specific Kinase (MuSK). Among
others systemic illness, surgery, fever, pregnancy, emotional
upset and certain drugs may exacerbate myasthenic symptoms.
This severe, at times fatal condition may lead to an acute
inability to breath and swallow. This status is defined as
myasthenic crisis [13]. Prevention and treatment of myasthenic crisis (MC) often requires admission to an intensive care
unit, preferably a neuroscience ICU, close observation and
when necessary, intubation of the patient for acute ventilatory
and feeding support. Delay in appropriate medical care may
Corresponding author.
E-mail address: rlisak@med.wayne.edu (R.P. Lisak).
0022-510X/$ - see front matter 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jns.2007.04.045
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apheretic techniques, double filtration PE and immunoadsorption [47] showed similar clinical effects for patients with
generalized myasthenia with only minor differences noted in
post PE serum immunoglobulin levels.
Dau [55] emphasized the importance of patient tailored
treatment regimens based on the clinical severity of the
exacerbation in MC. A series of early, non-randomized
studies [5458] quickly established the beneficial, primarily
short-term effect of PE and since then it has gained wide
application in acute care setting [33,35,59,60]. The 1986
NIH consensus statement supported the use of PE, and no
placebo controlled clinical trials have been conducted [61].
PE has shown benefit in MC, management of exacerbations
and has become a part in presurgical/prethymectomy preparation [62] as well.
One of the limitations of PE is the relatively short-lived
(2 to 3 weeks) improvement in strength that makes the coadministration of other longer acting immunosuppressive
or immunomodulatory agents generally necessary. In
addition, significant limitation of PE is its relatively high
cost, invasive features (need for venous access and cardiac
and hemodynamic instability) and the rare toxic reaction to
the anticoagulants such as citrates [13,17,63]. The report of
the largest PE database, the French plasma exchange registry
reports a decrease in the immediate complications since 1985
due to improved quality of the applied techniques and
plasma substitutes [64].
The only randomized early controlled trial by Gajdos
was limited by co-administration of prednisone and lack
of blinding [65]. Based on their data the Cochrane
Review's evidence based evaluation concludes that further
trials may need to address long-term effects of PE in MC.
The more recent clinical retrospective case series by
Mahalati et al. of 36 patients (32 in MC) over a 10 year
period reported predictable clinical improvement with
successful extubation. They reported no fatalities in the
acute phase by using an average of 7.8 exchanges [66]. The
retrospective case series of Berroushot did not find
however any significant difference between their patients
in MC treated with PE, pyridostigmine or pyridostigmine
and prednisone regarding effect on ventilation, clinical
outcome and fatality rate [33].
10. Intravenous immunoglobulin
The use of high dose intravenous immunoglobulin (IVIg)
has gained wide application in the treatment of autoimmune
and immunopathologically mediated neuromuscular diseases. This was noticeable in the growing number of
publications dealing with its application both in acquired
adult and juvenile MG and other antibody-mediated
neuromuscular diseases such as GuillainBarre syndrome
(GBS), CIDP, Multifocal Motor Neuropathy (MMN) and
dermatomyositis [17,21,29,30,33,6771,74]. The increased
interest can be explained by a number of different factors
such as the relative ease of administration compared to PE,
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[26] Bedlock RS, Sanders DB. How to handle myasthenic crisis. Essential
steps in patient care. Postgrad Med 2000;107:2114.
[27] Graves M, Katz JS. Myasthenia gravis. Curr Treat Options Neurol
2004;6(2):16371.
[28] Gajdos P, Chevret S, Clair B, Tranchant C, Chastang C, for the
Myasthenia Gravis Clinical Study Group. Clinical trial of plasma
exchange and high-dose intravenous immunoglobulin in myasthenia
gravis. Ann Neurol 1997;41:78996.
[29] Qureshi AI, Choudhry MA, Akbar MS, Mohammad Y, Chua HC,
Yahia AM, et al. Plasma exchange versus intravenous immunoglobulin
treatment in myasthenic crisis. Neurology 1999;52:629.
[30] Gajdos P, Chevret S, Toyka K. Intravenous immunoglobulin for
myasthenia gravis. Cochrane Database Syst Rev 2003(2):CD002277.
[31] Mayer SA, Thomas CE. Therapy of myasthenic crisis. Crit Care Med
1998;26:11367.
[32] Tripathy M, Kaushik S, Dubey P. The effect of use of pyridostigmine
and requirement of vercuronium in patients with myasthenia gravis.
J Postgrad Med 2003;49:3114 Discussion 314315.
[33] Berroushot J, Baumann I, Kalishewski P, Sterker M, Schneider D.
Therapy of myasthenic crisis. Crit Care Med 1997;25(7):122835.
[34] O'Riordan JI, Miller DH, Mottershead JP, Hirsch NP, Howard RS. The
management and outcome of patients with myasthenia gravis treated
acutely in a neurological intensive care unit. Eur J Neurol 1998;5:
13742.
[35] Kawaguchi N, et al, for The Study Group for Maysthenia Gravis in
Japan. J Neurol Sci 2004;224:437.
[36] Panda S, Goyal V, Behari M, Singh S, Srivastava T. Myasthenic crisis:
a retrospective study. Neurol India 2004;52(4):4536.
[37] Seybold ME. Treatment of myasthenia gravis. In: Engle Andrew G,
editor. Myasthenia gravis and myasthenic disorders, vol. 8. New York:
Oxford University Press; 1999. p. 167201.
[38] Pascuzzi RM, Coslett HB, Johns TR. Long-term corticosteroid
treatment of myasthenia gravis: report of 116 patients. Ann Neurol
1984;15:2918.
[39] Schneider-Gold C, Gajdos P, Toyka KV, Hohlfeld RR. Corticosteroids for
myasthenia gravis. Cochrane Database Syst Rev 2005;2:CD002828.
[40] Bromberg MB, Carter O. Corticosteroid use in the treatment of
neuromuscular disorders: empirical and evidence-based data. Muscle
Nerve 2004;30:2037.
[41] Marsh DO. Adrenal therapy for neuromuscular disease including
myasthenia gravis from 1896. N Y State J Med Oct 1974;74(11):
19746.
[42] Shy GM, Rabinovitch R, McEachern D. Effects of cortisone on certain
neuromuscular disorders. JAMA 1950;144:13538.
[43] Engel WK. Myasthenia gravis, corticosteroids, anticholinesterases.
Ann NY Acad Sci 1976;274:62330.
[44] Axelrod L. Glucocorticoid therapy. Medicine 1976;55:3965.
[45] Sanders DB. Myasthenia gravis and Lambert-Eaton myasthenic
syndrome. In: Pourmand R, editor. Neuromuscular diseases. Expert
clinicians' views, vol. 13. Boston: Butterworth-Heinemann; 2001.
p. 43957.
[46] Panegyres PK, Squier M, Mills KR, Newsom-Davis J. Acute
myopathy associated with large parenteral dose of corticosteroid in
myasthenia gravis. J Neurol Neurosurg Psychiatry 1993;56(6):7024.
[47] Yeh JH, Chiu HC. Comparison between double-filtration plasmapheresis and immunoadsorption plasmapheresis in the treatment of
patients with myasthenia gravis. J Neurol 2000;247(7):5103.
[48] Yeh JH, Chen WH, Chiu HC. Double filtration plasmapheresis in the
treatment of myasthenic crisis-analysis of prognostic factors and
efficacy. Acta Neurol Scand 2001;104(2):7882.
[49] Natarajan N, Weinstein R. Therapeutic apheresis in neurology critical
care. J Intensive Care Med 2005;20:21225.
[50] Weinstein R. Therapeutic apheresis in neurological disorders. J Clin
Apher 2000;15(12):74128.
[51] Tesar V, Jelinkova E, Jirsa Jr M, Bakosova M, Pitha P, Chabova V.
Soluble adhesion molecules and cytokines in patients with myasthenia
gravis treated by plasma exchange. Blood Purif 2000;18(2):11520.
A. Jani-Acsadi, R.P. Lisak / Journal of the Neurological Sciences 261 (2007) 127133
[52] Psaridi-Linardaki L, Trakas N, Mamalaki A, Tzartos SJ. Specific
immunoadsorption of the autoantibodies from myasthenic patients
using the extracellular domain of the human muscle acetylcholine
receptor alpha-subunit. Development of an antigen-specific therapeutic
strategy. J Neuroimmunol 2005;159(12):18391.
[53] Flachenecker P, Taleghani BM, Gold R, Grossmann R, Wiebecke D,
Toyka KV. Treatment of severe myasthenia gravis with protein A
immunoadsorption and cyclophosphamide. Transfus Sci 1998;19:
436 [Suppl].
[54] Dau PC. Plasmapheresis therapy in myasthenia gravis. Muscle Nerve
1980;3(6):46882.
[55] Dau PC, Lindstrom JM, Cassel CK, Denys EH, Shev EE, Spitler LE.
Plasmapheresis and immunosuppressive drug therapy in myasthenia
gravis. N Engl J Med 1977;297(21):113440.
[56] Newsom-Davis J, Vincent A, Wilson SG, Ward CD, Pinching AJ,
Hawkey C. Plasmapheresis for myasthenia gravis. N Engl J Med
1978;298(8):4567.
[57] Pinching AJ, Peters DK. Remission of myasthenia gravis following
plasma-exchange. Lancet 1976;2(8008):13736.
[58] Lisak RP. Immunologic aspects of myasthenia gravis. Ann Clin Lab
Sci 1975;5(4):28893.
[59] Tireli H, Karlikaya G, Tutkavul K, Akpinar A, Okay T. Myasthenia
gravis: how to treat? Acta Myol 2004;23(3):1405.
[60] Carandina-Maffeis R, Nucci A, Marques Jr JF, Roveri EG, Pfeilsticker
BH, Garibaldi SG, et al. Plasmapheresis in the treatment of myasthenia
gravis: retrospective study of 26 patients. Arq Neuro-Psiquiatr 2004;62
(2B):3915.
[61] NIH Consensus. The utility of therapeutic plasmapheresis for neurological disorders. NIH Consensus Conference. JAMA 1986;256: 13337.
[62] Yeh JH, Chen WH, Huang KM, Chiu HC. Prethymectomy
plasmapheresis in myasthenia gravis. J Clin Apher Dec 2005;20(4):
21721.
[63] Graves M, Katz JS. Myasthenia Gravis. Current treatment options in
neurology 2004;6:163-171.
[64] Korach JM, Petitpas D, Paris B, Bourgeade F, Passerat V, Berger P,
et al. Plasma exchange in France: Epidemiology 2001. Transfus
Apheresis Sci 2003;29(2):1537.
[65] Gajdos P, Simon N, de Rohan-Chabot P, Raphael JC, Goulon M. Longterm effects of plasma exchange in myasthenia. Results of a
randomized study. Presse Med 1983;12(15):93942.
[66] Mahalati K, Dawson RB, Collins JO, Mayer RF. Predictable recovery
from myasthenia gravis crisis with plasma exchange: thirty-six cases
and review of current management. J Clin Apher 1999;14(1):18.
[67] Dalakas MC. The use of intravenous immunoglobulin in the treatment
of autoimmune neuromuscular diseases: evidence-based indications
and safety profile. Pharm Ther 2004;102:17793.
[68] Latov N, Chaudhry V, Koski CL, Lisak RP, Apatoff BR, Hahn AF,
et al. Use of intravenous gamma globulins in neuroimmunologic
diseases. J Allergy Clin Immunol 2001;108(4):S12632.
133