jurnal iii miastenia gravis

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S H O R T C O M M U N I C A T I O N

Myasthenia gravis treatment of acute severe exacerbations in

the intensive care unit results in a favourable long-term prognosis

J. Spillanea, N. P. Hirschb, D. M. Kullmanna,b, C. Taylorb and R. S. Howardb

aUCL, Institute of Neurology, London; and bICU, National Hospital for Neurology and Neurosurgery, London, UK

Keywords:

intensive care,

myasthenic crisis,

myasthenia gravis

Received 26 November 2012

Accepted 3 January 2013

Background and purpose: Acute severe exacerbations of myasthenia gravis (MG)

are common in both early and late onset MG. We wished to examine the current

management in the intensive care unit (ICU) of severe exacerbations of MG and to

study the long-term prognosis of MG following discharge from the ICU.

Methods: We retrospectively reviewed the medical records of all patients admitted

to a specialist neuro-ICU with acute exacerbations of MG over a 12-year period.

Results: We identified 38 patients. Over 60% were over the age of 50 years, and

MG was newly diagnosed in over 40%. Intubation was required in 63%, and over

90% of patients were treated with prednisolone and/or intravenous immunoglobu-

lin. Four patients died in hospital. The remainder of patients were followed up for

a mean of 4 years, and the majority were either asymptomatic or had mild symp-toms of MG at clinical review.

Conclusions: Despite the significant morbidity and mortality associated with severe

exacerbations of MG, specialized neurointensive care can result in a good long-term

prognosis in both early- and late-onset MG.

Introduction

Myasthenic crisis (MC) is one of the most serious

complications of myasthenia gravis (MG), and occurs

in 1520% of patients during the course of their dis-

ease [1]. The definition of MC is acute respiratory fail-ure due to worsening MG, requiring mechanical

ventilation [2]. Fifty years ago, estimates of mortality

of MC ranged from 50% to 80%, but mortality is

now reported to be


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patients (21%) were new presentations. The average

duration of MG prior to admission in those with an

established diagnosis was 3.8 years (0.511 years;

Table 1).

A factor that precipitated the acute exacerbation

was identified in 22 patients (58%). Sepsis, namely,

lower respiratory tract infection, was present in 20patients (53%). One patient developed MC post-

thymectomy, while another patient deteriorated

during high-dose steroid treatment. No precipitant

was identified in the remainder (42%).

The mean ICU admission duration for the group

was 18.7 days (1111 days, SD 21.7, median 11.5), and

mean total hospital stay was 38.9 days (4157 days,

SD 31.1, median 30.5). Those with a new diagnosis of

MG had a trend towards a longer stay than those with

an established diagnosis, 25 days vs. 15 days, although

this did not reach statistical significance (P = 0.1733;

Table 1).

Intubation and mechanical ventilation wererequired in 24 patients (63%). Seventeen (71%) of

those requiring intubation had a preceding lower

respiratory tract infection, compared with 14% (2/14)

of those that were not intubated (P < 0.01). Four

additional patients (10.5%) required non-invasive ven-

tilation (Bilevel positive airway pressure).

Ninety-seven percent (37/38) of patients were trea-

ted with oral prednisolone, and 87% (33/38) received

intravenous immunoglobulin (IVIG). Seven patients

(18%) underwent plasma exchange. Additional oral

immunosuppression was initiated in 45% of patients

(17/38; Table 1).

Fourteen patients underwent thymectomy, eight

(21%) prior to admission and six (16%) after ICU

discharge. Eight (21%) had a thymoma.

Three patients died in the ICU (8%). Two died of

sepsis and respiratory failure. The third died of severe

autonomic instability. A fourth patient died after dis-

charge from the ICU of a pulmonary embolism.

There were no significant differences between older

and younger patients in terms of ICU admission dura-

tion or treatment in ICU. The majority of the patients

(29/38; 76%) had mild to moderate symptoms of MG

(MGFA Grades I, II, III) at ICU discharge, although

one patient had a tracheostomy in situ (MGFA V).There was a continued improvement in MGFA status

during follow-up in both age groups At the last clini-

cal review, a mean of 4 years after ICU discharge,

19% (6/31) of the patients for whom follow-up was

available were asymptomatic, and 48% (15/31) had

either purely ocular symptoms or mild generalized

Table 1 Clinical characteristics

Under 50 years 50 years or older

Number 14 24

Male 5 10

Female 9 14

New diagnosis 3 (21%) 11 (46%)

Established diagnosis 11 (29%) 13 (54%)

Average disease

duration

3.5 years

(0.514 years)

4 years

(0.59 years)

Treatment prior to ICU admission

Prednisolone 7 (64%) 8 (62%)

Azathioprine 4 (36%) 1 (8%)

IVIG 2 (18%) 1 (8%)

Plasma exchan ge 2 (18 %)

Antibody status

AChR 11 (79%) 20 (83%)

MuSK 3 (21%) 1 (4%)

Seronegative 3 (13%)

Mean duration of

ICU admission

(days) (SD)

(median)

22.4 (19.8) (14.5) 16.7 (SD 22.9) (9)

Mean total stay

(days) (SD)

(median)

42.1 (28.7) (42.5) 37.1 (32.9) (26.5)

Intubation 9 (64%) 15 (63%)

Thymectomy

Before ICU

admission

4 (29%) 3 (13%)

After ICU admission 5 (36%) 1 (4%)

No thymectomy 5 (36%) 20 (83%)

Thymoma 4 (29%) 4 (17%)

Treatment in ICUIntubation 9 (64%) 15 (63%)

Prednisolone 14 (100%) 23 (96%)

IVIG 13 (93%) 20 (83%)

Plasma exchange 3 (4%) 4 (17%)

Other immunosuppressant agent

Azathioprine 6 (43%) 8 (33%)

Mycophenolate 2 (14%) 2 (8%)

Rituximab 1

Cyclophosphamide 1 0

AChR, acetylcholine receptor; ICU, intensive care unit; IVIG, intra-

venous immunoglobulin; MuSK, muscle specific tyrosine kinase

Table 2 MG severity at ICU discharge and last clinical review

Clinical severity

(MGFA)

Number of patients

ICU discharge

Number of patients

Last clinical review

(mean time from

ICU discharge)

Age (years) 50

(n = 24)

50 (n = 24)

2.7 years

Asymptomatic 2 4

I 1 2 1 1

II 2 14 5 8

III 6 4 1 4

IV 3 2

V 1

Died 2 1 4 1

Lost to follow-up 1 6

2013 The Author(s)European Journal of Neurology 2013 EFNS

172 J. Spillaneet al.


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weakness (Table 2). Sixty-five percent (20/31)

remained on oral prednisolone (average dose of

12.5 mg). Forty-eight per cent took additional oral

immunosuppression (8/31 on azathioprine, 6/31 on

mycophenolate and 1/31 on methotrexate). Three

patients (10%) required IVIG. There were no signifi-

cant differences in outcome between the older andyounger age groups. One patient, a 23-year-old female

with MuSK MG, had a sudden respiratory arrest and

died 2 years after discharge.

Discussion

Although our study is limited by its small size and ret-

rospective nature, we have demonstrated that acute

exacerbations of MG continue to carry a significant

morbidity and mortality [1]. Our centre is a specialist

referral centre, and 60% of our admissions were trans-

ferred from other hospitals. It is possible that our

ICU is biased towards admission of more severe cases

of MG, which may explain the high mortality rate in

our group.

Our study has highlighted the need to be vigilant

for MG in the differential diagnosis of acute respira-

tory failure particularly in older adults. MG is

increasingly recognized in the older population; 60%

of our cohort was over the age of 50 years, and over

40% of these patients were newly diagnosed with MG

in the ICU. Even in those with an established diagno-

sis of MG, predicting the occurrence of an acute exac-

erbation can be difficult; 42% of patients had no

obvious precipitant.The management of acute exacerbations of MG has

changed in recent years. The vast majority (87%) of

our cohort received IVIG. Ten years ago, only 11.4%

of a similar cohort received IVIG, whereas 60%

underwent plasma exchange [5]. IVIG and plasma

exchange have recently been found to be equally

effective for exacerbations of MG, but the former is

better tolerated and is used increasingly [6].

Little is known about the long-term outcome of

patients with acute severe exacerbations of MG

following hospital discharge. We have follow-up data

for 82% of our patients for a mean of 4 years, and

found that the vast majority of patients were

asymptomatic or had mild manifestations of MG at

final review. There was no significant difference in

long-term outcome between older and younger

patients.

We suggest that, despite the acute risk of mortalityassociated with severe exacerbations of MG, the long-

term prognosis is favourable. The appropriate man-

agement of these patients requires the easy availability

of specialized neurointensive care facilities.

Disclosure of conflicts of interest

The authors declare no financial or other conflicts of

interest.

Acknowledgement

J.S. is funded by a grant from the Myasthenia Gravis

Association UK.

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2013 The Author(s)European Journal of Neurology 2013 EFNS

Myasthenia gravistreatment of acute severe exacerbations in ICU 173

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