Original Article
Myasthenic crisis: A retrospective study
S. Panda, V. Goyal, M. Behari, S. Singh, T. Srivastava
Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
Background and Objective: Myasthenic crisis (MC) is one of
the important and common complications in the natural history
of myasthenia gravis (MG). MC can be precipitated by multiple
factors including deficiency or excess of the ace-
tylcholinesterase inhibitors (AChEI). Any episode of MC is an
emergency requiring aggressive therapy. We studied the
demographic, clinical and treatment-related characteristics of
patients who developed MC. Materials and Methods: A
retrospective study was conducted in patients with MC ad-
mitted during a 31-month period from February 1999 to Au-
gust 2001, at a tertiary care center in India. Results: Eleven
patients (9.69% of the total 114 patients with MG) were ad-
mitted with 12 episodes of MC. Mean age at presentation was
39.83 + 13.18 years with male predominance. Seven patients
had undergone thymectomy previously; of which 2 had
postoperative MC. Six patients had thymoma. Steroid or
cholinesterase inhibitor withdrawal and infections were the
commonest precipitating factors for MC. Patients required
ventilatory support for median 14 days. They responded to low
volume of plasma exchange (PE) (mean 854 ml / day with
mean 6.5 cycles per patient). Conclusions: This re-port
highlights that the subset of Indian patients with MG who are at
rd th
risk to develop MC belong to the 3 and 4 dec-ade, have
bulbar symptoms at presentation and are associ-ated with
thymoma. Patients with MC should have judicious drug
adjustments under supervision and should be treated
aggressively during impending MC.
Key Words: Myasthenia gravis, myasthenic crisis, thymoma.
Introduction
Myasthenia gravis (MG), an acquired disorder of neuromus-
cular transmission, has a prevalence of 0.5-12.5 per 100,000
and an incidence of 0.4 per 100,000 in the general popula-tion 1,2
with a male to female ratio of 2:3. 3 The exact preva-lence of
MG in India is not known. Myasthenic crisis (MC) is a life-
threatening situation, where the weakness arising from
Vinay Goyal
Assistant Professor, Department of Neurology, AIIMS, New Delhi - 110029, India. E-mail: drvinaygoyal@hotmail.com
Neurology India December 2004 Vol 52 Issue 4
MG is severe enough to cause respiratory failure, necessitat-ing
intubation with or without mechanical ventilation. It has been
reported in 15-25% of patients of MG.4,5 With the ad-vances in
critical care neurology, the mortality due to MC has
significantly reduced from 30-40% in the 1960s and 1970s to 5-
10% at present.5,6 This has largely been achieved by im-proved
intensive care facilities, early mechanical ventilation,
management of precipitating factors, use of acetylcholinestrase
inhibitors (AChEI), steroids, antibiotics, plasmapheresis (PP)
and intravenous immunoglobulins (IVIG). There have been no
systematic epidemiological studies on the prevalence and
demographic characteristics of MC in India. However, it may
be speculated that with a higher incidence of infections and
delayed access to health care in developing countries, more
number of patients with MG develop MC which respond well to
aggressive respiratory and immunomodulatory care.7
This retrospective study reviews the demographic profile,
clinical features, outcome and mortality in patients of MC
admitted at a tertiary care center in India.
Materials and Methods
The case records of patients admitted to the neurology ward and
ICU with the diagnosis of MG from February 1999 to August 2001
were screened and cases of MC identified. The diagnosis of MG
was based on evidence of muscle weakness, fatigability and diurnal
fluc-tuation of symptoms, and clinical examination, supplemented
by positive decrement response on repetitive nerve stimulation test
and improvement with edrophonium or neostigmine testing.
MC was defined as an episode of severe myasthenia requiring intu-
bation with or without ventilatory support. As a treatment protocol of
the department, patients were intubated if clinical assessment suggested
compromised respiratory effort documented by decreased patient
comfort with either respiratory rate more than 30 per minute,
paradoxical diaphragmatic movements, decreased chest expansion,
single breath count less than 10 or arterial blood gases showing drop in
oxygen saturation.8 Patients were weaned off the ventilator once the
patient’s respiratory effort was sufficient to maintain adequate
oxygenation. The decline in vital capacity below 15 ml/kg and above
25 ml/kg has generally been considered as indication for intubation and
extubation, respectively.9 However, the retrospective nature of
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this study provided limited information. Case records were scruti-
nized to identify the cause of MC, antecedent events, therapeutic
interventions, duration of ventilatory support, hospital stay and any
complications during hospital stay.
Results
Eleven patients with MG (9.64% of the total 114 patients with
MG) had 12 episodes of MC. The mean age at presenta-tion
was 39.83 + 13.18 (range, 22-66) years with male pre-
dominance (M:F=3:1). The median duration of disease be-fore
presentation as MC was 20.02 + 22.93 months (median of 8
months and ranged from 7 days to 5 years). The demo-graphic
and clinical features of the patients are given in Table
1. Seven patients underwent thymectomy prior to the MC. Two
patients had MC immediately after thymectomy in the
postoperative period. Histologically, six patients had thymoma,
and one patient had thymic hyperplasia. At the time of ad-
mission, 75% of the patients were on pyridostigmine while 33%
were on neostigmine. Sixty per cent of the patients were on
steroids and 42% patients were on azathioprine. The fac-tors
which could have potentially precipitated MC were
cholinesterase inhibitor and steroid withdrawal (3, 25%), res-
piratory tract infection (3, 25%), thymectomy (2, 16.6%),
gastrointestinal tract infection (1, 8.3%), steroid initiation (1,
8.3%) and radiotherapy (1, 8.3%). Among infections, res-
piratory tract infections predominated. No definite
precipitants could be identified in 3 cases.
The clinical features during MC, treatment and response to
therapy in these cases are detailed in Table 2. Eight (66.66%)
episodes of MC were treated with PP and 3 (25%) episodes
with IVIG. One case required PP followed by IVIG due to
worsening even after PP. Two cases did not receive any therapy
(one patient could be weaned off the ventilator by the third post
thymectomy day and the other expired on the second day of
admission). As a protocol, PP was done on alternate days by
small volume PP involving exchange of 10-20 ml/kg of plasma.
The average volume of plasma exchange per cycle was 854 ml
(range, 600-980 ml) per day and 6.5 cycles (mean) were given
per case (range, 5-11 cycles, 11 cycles in one pa-tient).
Perceptible improvement (defined as the point of wean-ing off
the ventilator) was observed after an average of 4.2 cycles. The
only side-effect observed during PP was hypoten-sion in one
patient. IVIG was given in the dose of 0.4 g/kg/ day for 5 days
in 3 episodes.
Drug holiday of AChEI was given throughout the period of
ventilation in all the patients. Azathioprine was continued in the
same doses as prior to MC while steroids were optimized to 1
mg/kg in 72.72% (8 patients). The duration of ventilatory
support varied from 2-32 days (median 14 days) with median
stay in intensive care unit of 17 days (range, 2-44). At the

Table 1: Demographic and clinical features of patients

Patient No. Age/Gender Presentation of MG MGFA Class Duration of MG before MC Thymectomy Thymoma
1. 22/F Ocular II b 12 mths No No
2. 33/M Ocular I 5 yrs Yes Yes
3. 24/M Ocular III b 3 mths No No
4. 40/M Ocular + bulbar III b 1 mth No No
5. 32/F Ocular I 3 yrs Yes Yes
6. 53/M Ocular II b 2.5 yrs Yes Yes
7. 66/M Bulbar IV b 1 week No No
8. 55/F Limb II b 5 yrs Yes No
9. 33/M Limb III a 3 mths Yes Yes
10. 47/M Ocular II b 7 mths Yes Yes
11. 40/M Limb II a 8 mths Yes Yes
(Class = classification, F = female, M = male, MC = myasthenic crisis, MG = myasthenia gravis, MGFA 19 = Myasthenia gravis foundation of America of MG at time
of maximum severity prior to crisis)

Table 2: Clinical characteristics at onset of MC and response to treatment

Sr. Ppt Fc Duration from Involved Rx Duration of At discharge- At discharge- Death
No. Ppt. to MC sites ventilation Walking without Accepting
(days) support orally
1. ACI and Strdtapering 5 days O,B,L,R PP 16 Yes Yes No
2. ACI and Strdstopped+URI 10 days O,B,L,R PP 14 No No No
3. Diarrhea 2 days O,B,L,R Nil 2 - - Yes
4. Strd started+ URI 30 days O,B,L,R PP+IVIG 12 No No No
5. Nil - O,B,L,R PP 18 No Yes No
6. URI 15 days O,L,R PP 10 Yes Yes No
7. ACI tapered 6 mths O,B,R IVIG 8 Yes Yes No
8. Nil - B,R IVIG 9 No Yes No
9. Post TM 3 days O,B,L,R PP 15 No Yes No
10. Nil - O,B,L,R PP 14 Yes No
11. Post RT 18 days O,B,L,R PP 32 Yes No No
12. Post TM 1 day O,B,L,R Nil 5 Yes Yes No
(Strd- steroid; ACI- Acetylcholinestrase inhibitor; IVIG- intravenous immunoglobulin; B-bulbar; L- limb; O- ocular; R- respiratory; MC-Myasthenic crisis; PP-
Plasmapharesis, Ppt Fc- Precipitating factor; RT-Radiotherapy; Rx-Treatment; TM-Thymectomy; URI- upper respiratory infection)

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time of discharge, AChEI drugs were increased in 9 patients and
azathioprine added in 7 patients. At the time of discharge, 40%
could walk unsupported and 70% could feed orally. One patient
(previously operated for thymoma and with history of MC) died
due to septicemia during the second episode of MC.
Discussion
Early recognition of MC and its precipitating factors with
prompt management of MC is life-saving. This study high-
lights the characteristics of MC and the treatment response
in the Indian context. This is a descriptive study of patients
with MC encountered in a tertiary care center in north India.
The relatively high proportion of patients with MG and MC
reported during this short period is a reflection of the referral
bias from a large catchment area.
The demographic profile reflects that younger patients in
the 3rd and 4th decades developed crisis. Though Werneck et
al10 found the mean age at MC to be 24 years, other studies
demonstrated bimodal distribution, with preponderance of
female patients in the less than 55 years age group and equal
gender predominance in patients more than 55 years of age
though an overall female predominance was noted. 5,6,11 A re-
versal of male to female ratio seen compared to previous
stud-ies, could be due to the small sample size.6,10,11
The median duration of myasthenic symptoms from onset
to first crisis was less than in earlier studies (12 months
against 21 months to 5-6 years. 5,12 However, this is
comparable to a study on 73 episodes of MC in which the
median interval was 8 months. 9 A lesser time to crisis could
be the result of more severe myasthenia due to varied
reasons. The majority of our patients had thymoma, which is
associated with more severe disease. In addition, respiratory
infections and different ge-netic susceptibility for MC in the
Indian population may be contributory.13
Fewer patients of MG developed MC compared to the re-
ported incidence of 15-25% in myasthenic patients. 5,6 A strong
association was found between severe bulbar symptoms and
development of MC in the presence of precipitating factors.
This was evident from the fact that at the time of presenta-tion
with MC, 9 cases (81.81%) had generalized symptoms and all
11 cases had bulbar symptoms. MC occurs more fre-quently in
patients with generalized weakness (75%) com-pared to
oropharyngeal (20%) and respiratory (up to 5%) weakness
alone.14 A higher incidence of bulbar symptoms com-pared to
Berrouschot et al14 is probably because more patients (6 out of
11 patients) had thymoma. Amongst patients who had
undergone thymectomy, 85% had histologically proven
thymoma. The natural history of patients of MG with thy-moma
is a short, stormy course. They develop more frequent episodes
of crisis, respond less adequately to immunosuppres-sion,
require aggressive therapy with lesser chances of achiev-ing
complete remission and have higher mortality. The asso-
Neurology India December 2004 Vol 52 Issue 4
Panda S, et al: Myasthenic crisis
ciation between thymoma and poor prognosis of MG has
been well documented.15,16 In series of patients with MC,
thymoma was present in 32% and 20%.9,10
The commonest precipitating factor for MC was drug with-
drawal and infections, (especially respiratory infections). This
observation is similar to prior series which reported infections
to be the major precipitant of crisis. 5,6,9,11,12 Drug withdrawal,
however, was frequent in this study. As most of the patients
belonged to poor socioeconomic status, drug non-affordability
is a common reason for poor drug compliance.
All cases of MC received early mechanical ventilation in ICU
settings. The exact ventilatory parameters could not be as-
sessed due to the retrospective nature of the study. However, a
combination of early, effective mechanical ventilation, ad-
equate antibiotic therapy and aggressive immunotherapy re-
duced the duration of MC. Aggressive respiratory interven-tion
comprising use of suction, intermittent positive pressure
ventilation, bronchodilator treatment and chest physiotherapy
helps shorten the course of MC.8,17
Despite of lack of Class I evidence in favor of a specific
therapy like PP and IVIG, these treatment modalities are the
treatment of choice in MC. Most of the cases received PP due to
easy accessibility and low cost (being subsidized at our in-
stitute) as compared to IVIG. Low volume (854 ml per cycle)
PP and less number of cycles (4.2 cycles/ patient) were suffi-
cient for improvement. Despite the small number of cases, this
suggests a trend for lower volume PP to be effective in MC.
This is further supported by the fact that the median duration of
ventilatory support (14 days) and ICU stay (17 days) in the
study was similar to the previously reported du-
ration of 13 and 15 days, respectively. 6,9 The longest duration of
crisis reported till date lasted 661 days. 18 These findings
contrast with studies recommending higher volume exchange
(1.5-2 liters per cycle).19
The disability at hospital discharge was considerably reduced
suggesting effectiveness of treatment during MC. However,
similar to other studies9,10 no significant difference was ob-
served in the outcome of MC between thymectomized and
non-thymectomized patients and between those with and
without thymoma.
Conclusion
In the present study relatively young patients with thymoma,
generalized myasthenia and oropharyngeal weakness were
predisposed to MC. It is prudent to exercise great care while
withdrawing cholinesterase inhibitors and steroids. Similar care
is also necessary while introducing steroids in patients with
MG. Respiratory infection being a common precipitat-ing factor
for MC, early institution of antibiotic therapy is recommended
in patients with MG. Though the patients showed a trend for a
good response to low volume plasma ex-changes, we cannot
recommend any treatment-oriented deci-
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sions due to the small size of this study. Larger systematic
studies should be conducted prospectively to answer these
questions.
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