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The myasthenic patient in crisis: an update of the management in

Neurointensive Care Unit

Article  in  Arquivos de Neuro-psiquiatria · September 2013

DOI: 10.1590/0004-282X20130108 · Source: PubMed

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The myasthenic patient in crisis: an update of

the management in Neurointensive Care Unit
Pacientes miastênicos em crise: uma melhora de conduta na unidade de terapia intensiva
Daniel Agustin Godoy1,2, Leonardo Jardim Vaz de Mello3,4, Luca Masotti5, Mario Di Napoli6,7

ABSTRACT
Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission leading to generalized or localized muscle weak-
ness due most frequently to the presence of autoantibodies against acetylcholine receptors in the postsynaptic motor end-plate. Myasthe-
nic crisis (MC) is a complication of MG characterized by worsening muscle weakness, resulting in respiratory failure that requires intubation
and mechanical ventilation. It also includes postsurgical patients, in whom exacerbation of muscle weakness from MG causes a delay in
extubation. MC is a very important, serious, and reversible neurological emergency that affects 20–30% of the myasthenic patients, usually
within the first year of illness and maybe the debut form of the disease. Most patients have a predisposing factor that triggers the crisis,
generally an infection of the respiratory tract. Immunoglobulins, plasma exchange, and steroids are the cornerstones of immunotherapy.
Today with the modern neurocritical care, mortality rate of MC is less than 5%.
Key words: myasthenic crisis, myasthenia gravis, respiratory failure, immunosupressive therapy, thymectomy.

RESUMO
Miastenia grave (MG) é um distúbio autoimune que afeta principalmente a transmissão neuromuscular, levando a fraqueza muscu-
lar generalizada ou localizada. É devida mais frequentemente à presença de auto-anticorpos anti-receptores de acetilcolina na fenda
pós-sináptica da placa motora. A crise miastênica (CM) é uma complicação da MG caracterizada por piora da fraqueza muscular, resultando
en falência respiratória, o que requer entubação endotraqueal e ventilação mecânica.Isto ocorre também em pacientes pós-cirúrgicos, em
que há piora da fraqueza muscular devido à MG, causando um atraso na extubação. MC é uma emergência neurológica importante, séria e
reversível que afeta 20–30% dos pacientes miastênicos, usualmente duranteo primeiro ano de enfermidade, podendo a crise miastênica
ser a manifestação inicial da MG. A maioria dos pacientes tem fatores predisponentes que desencadeiam a crise, geralmente uma infecção
do trato respiratório. Imunoglobulina, plasmaférese e esteróides são a pedra angular da imunoterapia. Hoje, dentro da terapia neurocrítica,
a taxa de mortalidade na CM é menor que 5%.
Palavras-Chave: crise miatênica, miastenia gravis, falência respiratória, terapia imunosupressiva, timectomia.

Myasthenic crisis (MC) is an uncommon life-threatening (ICU) — preferably a neuroscience ICU — close observation,
neurological emergency1-3. It may occur in patients who have and, when necessary, intubation for ventilatory and feed-
previously diagnosed myasthenia gravis (MG) or may be the ing support2,8-13. In addition, acute care should be focused on
onset of the disease, generally during the first year after diag- reducing circulating antibody titers with immunologic ther-
nosis4-6. The hallmark of MC is the bulbar or respiratory fail- apy such as plasmapheresis (PE), immunoglobulin (IVIg), and
ure1,2,5,7-12. The management of these patients is challenging corticosteroids2,8-13. Despite the growing interest and newer
due to the fluctuating nature of the disease4,5,8-12. Prevention treatment modalities, deficiencies in management still persist.
and treatment of MC requires admission to intensive care unit Not all ICU physicians have experience in neurological aspects

1
Intensive Care Unit, Hospital San Juan Bautista, Catamarca, Argentina;
2
Neurointensive Care Unit, Sanatorio Pasteur, Catamarca, Argentina;
3
Neurology Service, Santa Casa de São João del Rei, São João del Rei MG, Brazil;
4
Hospital Nossa Senhora das Merces, São João del Rei MG, Brazil;
5
Internal Medicine, Cecina Hospital, Cecina, Italy;
6
Neurological Service, San Camillo de’ Lellis General Hospital, Rieti, Italy;
7
Neurological Section, SMDN – Center for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Sulmona, L’Aquila, Italy.
Correspondence: Daniel Agustín Godoy; Unidad de Cuidados Neurointensivos Sanatorio Pasteur; Chacabuco 675; 4700 Catamarca - Argentina;
E-mail: [email protected]
Conflict of Interest: There is no conflict of interest to declare.
Received 1 March 2013; Received in final form 3 April 2013; Accepted 10 April 2013.

 627
 of MG. This paper reviews the available evidence in the detec- should be considered in MC2,4-12,18. Although there is no uni-
tion and treatment of the MC from a multidisciplinary per- versally accepted definition, MC should be considered a true
spective, with the intention to help to correct management. neurological emergency characterized by “Severe weak-
ness of the bulbar (innervated by cranial nerves) and/or
respiratory muscles, enough to cause inability to maintain
EPIDEMIOLOGICAL DATA adequate ventilation and/or permeability of upper airways,
causing respiratory failure that requires artificial airway or
The annual incidence of MG is 1–2/100,00014, with an ventilatory support”2,6. Postoperative myasthenic patients
estimated prevalence of 5–15/100,0003,14; 21% of patients had in whom extubation has been delayed more than 24 hours
onset after 60 years15 and 30% of them will develop some also should be considered crisis7. Generally, patients with
degree of bulbar or respiratory muscle weakness15. About MC correspond to class 3 or 4 in Osserman and Genkins
15–20% of MG patients will develop MC, usually within the classification14 or class V according to Myasthenia Gravis
first year of illness4,6-11. MC may be the initial presentation Foundation14 (Table 1).
of MG in about 20% of patients and one-third of surviving
may experience another crisis4,6-11. Overall, women are twice
as likely as men to be affected3,14,. The average age of admis- PREDISPOSING FACTORS
sion with crisis is 59 years16. The occurrence of MG shows a
bimodal distribution, with the following male:female ratios: Patients who develop MC in their great majority have
3:7 if aged <40 years, 1:1 if aged 40–49 years, 3:2 if aged a precipitating factor, although, in 30–40% of cases, none
>50  years14,17. The outcome has improved significantly, and is found2,5-7,9-12,19,21. Respiratory infection (40%), emotional
today the reported mortality rate is around 5%2,7,9,10,16. stresses, microaspirations (10%), changes in medication regi-
men (8%), surgery, or trauma are among the most common
predisposing factors2,5-7,9-12,16,18. Many drugs exacerbate MG
HOW WE DEFINED MYASTHENIC CRISIS? and may determine MC19. They should be avoided or used
with caution. Some examples have been listed in Table  2.
By definition, all MG patients with acquired (neona- It is important to note that telithromycin, a macrolide, is
tal) or autoimmune form showing a respiratory failure due absolutely contraindicated in MG14,19-21. Initial treatment
to muscle weakness and requiring ventilatory assistance with prednisone led to exacerbation of MG in almost half of

Table 1. Clinical classifications (with modifications) of the severity of myasthenia gravis.

Osserman and Genkins14
Ocular myasthenia, localized nonprogressive
Generalizated disease of gradual onset involving more than one muscle group (bulbar or skeletal)
Acute fulminant disease
Late severe disease (>2 years after symptoms onset)
Muscle atrophy related to duration and clinical severity of the disease
Myasthenia Gravis Foundation†
Class I: Ocular myasthenia (may have weakness of eye closure all other muscles have normal strength)
Class II*: Mild weakness (affecting muscles besides ocular muscles; may also have ocular muscle weakness of any degree)
   Class IIa: mostly affecting extremities, axial muscles, or both; may also have involvement of oropharyngeal muscles to lesser degree
  Class IIb: mostly involving oropharyngeal, respiratory muscles, or both; may also have involvement of extremities, axial muscles, or
both to lesser or equal degree
Class III*: Moderate weakness (in muscles besides ocular muscles; may also have weakness of any degree of ocular muscles)
  Class IIIa: involvement is mostly of extremities, axial muscles, or both; may also have involvement of oropharyngeal muscles to lesser
degree
  Class IIIb: mostly involving oropharyngeal, respiratory muscles, or both; may also have involvement of extremities, axial muscles, or
both to lesser or equal degree
Class IV*: Severe weakness (in muscles besides ocular muscles; may also have weakness of any degree of ocular muscles)
  Class IVa: involvement is mostly of extremities, axial muscles, or both; may also have involvement of oropharyngeal muscles to lesser
degree
  Class IVb: mostly involving oropharyngeal, respiratory muscles, or both; may also have involvement of extremities, axial muscles, or
both to lesser or equal degree
Class V: Myasthenic crisis [intubation, with or without mechanical ventilation (except when intubated for routine postoperative manage-
ment), quantitative myastheniagravis scoring system developed for determination of disease severity]
*Class II–IV are divided into subgroups according to predominance of muscle weakness: (a) limb and trunk; (b) bulbar.
†
Myasthenia Gravis Foundation of America (MGFA) clinical classification based on neurologic examination limitations of clinical classification fluctuating
weakness examiner’s subjective classification of mild, moderate, severe classification should be based on most severely affected muscles.

628 Arq Neuropsiquiatr 2013;71(9-A):627-639

Table 2. Medication and drugs that may provoke myasthenia MG patients receiving ­ immunosuppression2,7,19. Contrast
crisis. agents and electrolyte alterations (hypokalemia, hypophos-
20

Drug Class Medication phatemia) may exacerbate muscle weakness2,7. Thyroid dis-
Antipsychotics Phenothiazines, sulpiride, atypicals ease, which can coexist with MG, can exacerbate or unmask
(clozapine)
MG weakness when untreated, while over-replacement with
Neuromuscular-blocking Succinylcholine, Vecuronium
drugs levothyroxine may also cause MC2,7,19. If a MG patient requires
Anticholinergic drugs Including ocular proparacaine general anaesthesia, neuromuscular-blocking agents should
Cardiovascular Cibenzoline be used cautiously since they are particularly sensitive to non-
­medications Lidocaine (systemic dosing) depolarizing agents and the response to depolarizing drugs
Procainamide
is variable2,7,21. The association of MG with thymic pathol-
Propranolol (and other beta blockers)
Quinidine ogy is well known. MC is almost as twice more frequent in
Verapamil patients with thymoma2,7,14,23-25. Pregnancy aggravates MG in
Bretylium 33% of the cases, and MC in pregnancy carries high p ­ erinatal
Statins
Neurologic and Chlorpromazine
­mortality .
2,7,26

­psychoactive Lithium
­medications Phenytoin
Carbamazepin
PATHOPHYSIOLOGY OF MYASTHENIC
Trihexyphenidyl
Trimethadione GRAVIS AND MYASTHENIC CRISIS
Antibiotics All aminoglycosides
Ciprofloxacin MG is an autoimmune disorder resulting from antibody-
Colistin
complement-mediated and T-cell-dependent immunologic
Lincomycins (includes clindamycin)
Macrolides attack on the postsynaptic membrane of the neuromuscular
Erythromycin junction, mainly against acetylcholine receptor (AchR)14,27,28
Clarithromycin (Fig 1). The antibodies that bind to epitopes of the skeletal
Telithromycin (has risk of
­exacerbation of MG, including muscle end-plate region result in abnormal neuromuscular
rapid onset of life-threatening acute transmission and clinical weakness14,27,28. There are differ-
­aespiratory failure ent antibodies directed at the neuromuscular junction and
Penicillins (include ampicillin and
imipenem-cilastatin)
detectable in the plasma (Table 4)14,27,28. AChR antibodies bind
Polymyxins to the main immunogenic region of alpha subunit of AChR of
Tetracyclines postsynaptic membrane resulting in decreased numbers and
Other antimicrobial drugs Emetine density of AChR14,27,28. They are present in 70–90% of patients
Imiquimod
Ritonavir
with generalized MG and between 30 and 70% of patients with
Antirheumatologic and Chloroquine ocular form14,27,28.
immunosuppressive Penicillamine About 10% of patients show antibodies to muscle-specific
medications Prednisone (and other tyrosine kinase (Anti MuSK)14,27,28. Patients with MuSK typi-
­glucocorticosteroids)
Interferons cally are female and have characteristical weakness pattern
Other medication Aprotinin involving principally bulbar, neck, shoulder, and respiratory
Iodinated-contrast agents muscles14,27,28. MuSK is a protein located at the postsynaptic
Levonorgestrel membrane, which is responsible for clustering the AChR at
Magnesium (including magnesium
sulfate) the muscle membrane surface during development, but the
Methoxyflurane function in mature skeletal muscle and its role in pathophysi-
Pyrantel pamoate ology of MG is unknown14,27,28. Other muscle autoantibodies
Propafenone
Dextro carnitine-levocarnitine but
reacting with striated muscle titin and ryanodin receptor
not levocarnitine alone (RyR) antigens are found in up to 95% of MG patients with
Interferon alfa thymoma and in 50% of late-onset MG patients29 (>50 years).
Methocarbamol
Thymomas are present in <2% of patients without antistri-
Transdermal nicotine
Acetazolamide ated antibodies30. Following thymectomy, rise in antistriated
muscle antibody titer may be a sign of recurrent tumor30.
patients, whereas 9–18% of them develop MC19,22. Therefore, These antibodies are usually associated with more severe
initiation of corticosteroids should always occur in a hospi- MG30. Titin is a protein, providing a direct link between
tal setting, where respiratory function can be monitored19,22. mechanical muscle strain and muscle gene activation14,28,28.
Predictors of exacerbation from prednisone include older Antititin antibodies may also be detected in 50% of patients
age, lower score on Myasthenia Severity Scale (Table 3), with late-onset generalized MG without thymoma28,29. The
and bulbar symptoms22. Live vaccines should be avoided in RyR is the calcium channel of the sarcoplasmic reticulum

Daniel Agustin Godoy et al. Myasthenic patients: crisis 629

 Table 3. Quantitative myasthenia gravis score for disease severity.
Test item None Mild Moderate Severe Score
Grade 0 1 2 3
Double vision on lateral gaze right or left (circle
61 11–60 1–10 Spontaneous
one), seconds
Ptosis (upward gaze), seconds 61 11–60 1–10 Spontaneous
Normal lid Complete, weak, Complete, without
Facial muscles Incomplete
closure some resistance resistance
Severe coughing/
Minimal coughing
Swallowing 4 oz water (1/2 cup) Normal choking or nasal Cannot swallow
or throat clearing
regurgitation
Speech after counting aloud from 1 to 50 (onset Dysarthria at Dysarthria at
None at 50 Dysarthria at 9
of dysarthria) 30–49 10–29
Right arm outstretched (90° sitting), 240 seconds 90–239 10–89 0–9
Left arm outstretched (90 degrees sitting), 240 seconds 90–239 10–89 0–9
Vital capacity, % predicted ≥80 65–79 50–64 <50
Right-hand grip, kgW
Men ≥45 15–44 5–14 0–4
Women ≥30 10–29 5–9 0–4
Light-hand grip, kgW
Men ≥35 15–34 5–14 0–4
Women ≥25 10–24 5–9 0–4
Head lifted (45° supine), seconds 120 30–119 1–29 0
Right leg outstretched (45° supine), seconds 100 31–99 1–30 0
Right leg outstretched (45° supine), seconds 100 31–99 1–30 0

Nerve terminal acetylcholine

agrin
acetylcholine in a
presynaptic vesicle

nicotinic acetylcholine
receptor
muscle specific
tyrosine kinase
rapsyn
voltage gated
sodium channel
acetylcholine
binding site
acetylcholinesterase
Muscle fibre

Fig 1. Normal neuromuscular junction and pathophysiology of myasthenia gravis. In the normal neuromuscular junction,
acetylcholine (Ach) released from the nerve terminal following a nerve action potential binds to the acetylcholine receptor
(AChRs) on the postsynaptic muscle, triggering a muscle action potential propagated by the voltage-gated sodium channel.
Acetylcholinesterase scavenges and breaks down unbound ACh. In a separate pathway, neural agrin binds muscle-specific
tyrosine kinase (MuSK) initiating clustering of phosphorylated rapsyn and AChRs, stabilizing the postsynaptic structure opposite
the nerve. MuSK initiates clustering of the cytoplasmic protein rapsyn and AChRs and is believed to maintain normal postsynaptic
architecture.
In myasthenia gravis caused by antibodies to the AChRs, there is blockade of the binding site for ACh, cross-linking of the AChR
with subsequent internalization and reduction in its surface expression, and initiation of complement and cellular inflammatory
cascades with damage to the post- and presynaptic structures. The molecular physiology of myasthenia gravis mediated by
antibodies to MuSK has not been established.

630 Arq Neuropsiquiatr 2013;71(9-A):627-639

Table 4. Clinical subtypes and the occurrence of the various muscle autoantibodies in the different subgroups of
myasthenia gravis.
Muscle autoantibodies
(percentage of patients)
MG subgroups Age of Thymic HLA AChR MuSK Titin RyR Clinical findings
onset histology ­associations
Early-onset <40 Hyperplasia DR3-B8 + (100%) – (100%) + (10%) – (100%) These patients are more often female.
non-MuSK DR9 (in In addition to anti-AChR antibodies,
nonthymoma Asians) other organ-specific autoantibodies
might be present, and patients might
be affected by other autoimmune dis-
eases, most commonly autoimmune
thyroid disease. Antibodies to non-
AChR muscle components are not
typically seen in early-onset MG
Late-onset >40 Normal/ DR2-B7 + (100%) – (100%) + (58%) + (14%) These patients are more often male
non-MuSK thymic and usually have normal thymic his-
non-thymoma atrophy tology or thymic atrophy. They can
present with ocular or generalized
weakness, but typically have a more
severe disease course compared
with early-onset MG, and spontane-
ous remissions are rare. The pres-
ence of anti-ryanodine receptor an-
tibodies has been associated with
more severe, generalized, or predom-
inantly oropharyngeal weakness,
and frequent myasthenic crises
MuSK positive <40 Normal DR14-DQ5 – (100%) + (100%) NA NA Whereas patients with anti-MuSK
(regardless of (most antibodies can have presentations
onset age) ­ atients)
p similar to anti-AChR-positive MG,
they commonly have atypical clini-
cal features, such as selective facial,
bulbar, neck, and respiratory mus-
cle weakness and marked muscle
atrophy, occasionally with relative
sparing of ocular muscles. Respira-
tory crises are more common than in
generalized anti-AChR–positive dis-
ease. Weakness can involve muscles
that are not usually symptomatic
in MG, such as paraspinal and up-
per esophageal muscles. Enhanced
sensitivity, nonresponsiveness, and
even clinical worsening in response
to anticholinesterase agents have
also been reported. Disease onset in
patients with anti-MuSK MG tends
to be earlier, and patients are pre-
dominantly female
Seronegative – (100%) – (100%) – (100%) – (100%) Patients with MG who lack both anti-
(regardless of AChR and anti-MuSK antibodies (so-
onset age) called seronegative MG) are clini-
cally heterogeneous and can have
purely ocular, mild generalized, or
severe generalized disease. The true
prevalence of seronegative MG might
be quite low, because some patients
might have low-affinity anti-AChR
antibodies that are not detected with
currently available assays. Not sur-
prisingly, these patients are essen-
tially indistinguishable from patients
with anti-AChR–positive MG in terms
of clinical features, pharmacological
treatment response, and even thym-
ic abnormalities in some cases
Continue...

Daniel Agustin Godoy et al. Myasthenic patients: crisis 631

 Table 4. Continuation
Thymoma + (100%) May + (95%) + (70%) About 10–15% of patients with MG
(regardless of occur have a thymic epithelial tumor – a
onset age) in some thymoma. Thymoma-associated MG
patients is equally common in men and wom-
en and can occur at any age, with
peak onset at the age of 50 years23,24.
Clinical presentations tend to be
more severe than in nonthymoma-
tous patients with early-onset MG,
commonly with progressive general-
ized and oropharyngeal weakness.
However, long-term prognosis is
similar to that of late onset, non-
thymomatous MG. With rare excep-
tions, MG patients with thymoma
have high titers of anti-AChR anti-
bodies, and they usually also have
antibodies against titin. Additional
paraneoplasia-associated antibod-
ies (and their related syndromes)
might occur in thymomatous MG,
including anti-voltage-gated K+ and
Ca2+ channel, anti-Hu (antineuronal
nuclear autoantibody 1), antidihy-
dropyrimidinase-related protein 5
(formerly anticollapsin response
mediator protein 5), and antiglutam-
ic acid decarboxylase antibodies.
The presence of autoantibodies to
a voltage-gated K+ channel, KCNA4
(formerly Kv1.4), has been recently
reported in Japanese patients with
severe MG, thymoma, and concomi-
tant myocarditis and/or myositis.
In patients with thymoma, surgery
(thymothymectomy) often com-
pletely and permanently removes
the tumor, but symptoms of MG usu-
ally persist and require chronic im-
munotherapy
HLA: histocompatibility antigen; AChR: acetylcholine receptor; MuSK: muscle-specific tyrosine kinase; RyR: ryanodin receptor.

involved in excitation-contraction coupling of striated mus- are considered seronegative14,27. Clinically they are similar to
cle14,28-30. It is found in 50% of patients with MG and thy- patients with AChR antibodies.
moma14,28-30. Higher RyR antibody levels are associated with During MC, the respiratory failure can be hypoxemic,
severity14,28-30. Patients with RyR antibodies are character- hypercapnic, or both and result from poor airway protection,
ized by frequent involvement of bulbar, respiratory, and neck inadequate secretions clearance, and hypoventilation. Bulbar
muscles14,28-30. Neck weakness at onset is a distinctive feature (oropharyngeal) muscle dysfunction may be the predominant
of patients with RyR antibodies, while respiratory symptoms feature in some patients31. In MuSK-MG, bulbar weakness
are found in patients with titin antibodies with and without always precedes respiratory failure7. The dysfunction of bul-
RyR antibodies14,28-30. Limb involvement with few or no bulbar bar muscles alters cough, swallowing reflexes, as well as sigh
signs is typical in RyR-antibody-negative MG28-30. Since many mechanisms2,5,7,9-11,31,32. Signs of bulbar weakness include dys-
thymoma patients have RyR antibodies, neck weakness and phagia, nasal regurgitation, nasal and staccato speech, jaw and
nonlimb bulbar distribution of symptoms are initial char- tongue weakness, and bifacial paresis32. It is difficult to handle
acteristic features. Such symptom distribution should raise secretions that accumulate in the oropharynx. Upper airway
the suspicion of thymoma28-30. Thymoma and late-onset MG patent is lost2,5,7,9-11,31,32. These alterations increase the likeli-
share similar serological profile with high prevalence of titin hood of microaspiration, atelectasis, upper airway resistance,
and RyR antibodies and lower AChR antibody concentra- dead space, and work of breathing2,5,7,9-11,31,32. Muscle weakness
tions compared with early-onset MG29,30. in AchR-MG tends to initially affect intercostals and accessory
Finally, there is a remaining group of patients who do muscles and then the diaphragm7. The recruitment of acces-
not have either AChR or MuSK antibodies and they actually sory muscles indicates significant inspiratory weakness32. Weak

632 Arq Neuropsiquiatr 2013;71(9-A):627-639

cough or difficulty in counting notes weakness of expiratory deterioration of bulbar and respiratory muscles. For these
muscles32. Anxiety, accompanied by tachycardia and tachyp- reasons, a strict monitoring of respiratory status with regular
nea, may be the first sign of air hunger32. Respiratory muscles bedside pulmonary function testing is appropriate2,5,7,9-11,31-33.
are unable to maintain adequate tidal volume. Ventilation
becomes rapid and shallow, decreasing pulmonary functional Patients with previous
residual capacity, resulting in atelectasis, closing a vicious circle diagnosed Myasthenia gravis
that increases work of breathing with exacerbation of muscle The presence or worsening of clinical features, such as
weakness that culminates altering the ventilation/perfusion progressive muscle weakness (arms, limbs), palpebral pto-
relationship causing hypoxia and hypercapnia2,5,7,9-11,31,32 (Fig 2). sis, bulbar muscle envolvement, and disphagia together with
The signs of MC should be sought in all patients with MG, the presence of respiratory distress (dyspnea, shortness of
even when they do not complain weakness because central breath, tachypnea, use of accessory muscles) may help to
ventilatory drive usually remains intact during crisis; so, even identify patients at risk for MC2,5,7,9-11,31-33.
when minute ventilation response to CO2 is poor, the gener-
alized weakness can mask the usual signs of respiratory dis- Patients without a previous
tress. Respiratory muscles may suddenly fatigue, producing diagnosis of Myasthenia gravis
precipitous respiratory collapse32. In addition, some patients If MC is the first presentation of the disease, the specific clin-
may present with respiratory insufficiency out of proportion ical features of the myasthenic state cannot be evident. These
to limb or bulbar weakness2,5,7,9-11,31-33. In rare cases of MC, ven- patients quite suddenly show a severe respiratory distress, facial
tilatory failure is the only clinically overt manifestation34,35. weakness, airway collapse, and muscle failure. Initially, oxygena-
tion is preserved32. A suspected clinical diagnosis should be con-
firmed using electrophysiological, pharmacological, and labora-
HOw TO Make a CORReCT diaGnOSiS? tory testing2,7,14,17,36, usually not available on an emergent basis36.

MC is an acute respiratory failure due to worsening MG, electrophysiological testing

characterized by forced vital capacity (FVC) below 1 L, nega- In MG, repetitive nerve stimulation (RNS) shows a sig-
tive inspiratory force (NIF) of 20 cm H2O or less, and the need nificant decremental response (>9%) between the first and
for ventilatory support2,5,7,9-11,31-33. Arterial blood gas analysis fourth or fifth compound muscle action potential (CMAP) at
commonly shows hypercarbia before hypoxia. There should low rates (2–5 Hz)14,17,36. RNS depletes Ach stores at neuromus-
be a low threshold for endotracheal intubation due to rapid cular junction, reducing the safety factor and the probability
of successful neuromuscular transmission CMAP becomes
reduced in amplitude and area14,17,36. In patients with respira-
tory involvement, phrenic and long thoracic nerves should
Myasthenic also be tested37. The results of repetitive long thoracic nerve
crisis
and phrenic stimulation show a good correlation with res-
Ventilatory
piratory symptoms and management requirements37. Single-
Bulbar
muscles fiber electromyography (SFEMG)38 is the most sensitive test
weakness
weakness for abnormal neuromuscular transmission detection; how-
Accumulation of Alteration sign ever, it is time consuming and requires special expertise38.
secretions mechanism and
Orofaringeal “lake” cough and Tidal volumen
swallowing reflexes Functional residual Pharmacologic testing: edrophonium (Tensilon)
capacity The Tensilon (edrophonium) test is useful in diagnosing
Atelectasis, Microaspirations
Increase upper airways MG and in distinguishing MC from cholinergic crisis2,7,14,17.
resistance and WOB Edrophonium is a acetylcholinesterase inhibitor with rapid
onset (30 seconds), and effects lasting 5 minutes reported
Hypoventilation
Pneumonia
Dead space a sensitivity of 86% for ocular MG and 95% for generalized
V/Q alterations MG14,17. Edrophonium temporarily improves the safety factor
of neuromuscular transmission and may elicit improved mus-
Hypoxemia-Hypercapnia cle strength2,7,14,17. Once airway and ventilation are secured,
give an initial dose of 1–2 mg and watch for 1 minute, then give
3 mg, and another 3 mg if neccesary14,17. Typical side effects
Respiratory failure
of sweating, tearing, fasciculations, and abdominal cramping
may indicate peak edrophonium effect. Observe for possible
WOB indicates work of breathing; V/Q: ventilation/perfusion relationship. serious adverse effects such as hypotension or arrhythmias
Fig 2. Pathophysiology of myasthenic crisis. and have always atropine available as antidote14,17.

Daniel Agustin Godoy et al. Myasthenic patients: crisis 633

 If muscle strength improves within 1 minute of any dose A number of disorders that cause respiratory failure due
increment, test is positive and no further edrophonium to muscle weakness should be considered in the differential
needs to be administered14,17. Edrophonium test is not rec- diagnosis (Table 5).
ommended in patient in crisis because of likelihood of false-­
positive or false-negative results, and the risk of worsening
­muscle weakness above all in patients with anticholinest- ACUTE MANAGEMENT
erase overdose2,7,14,17. Patients with a cholinergic crisis may
respond to edrophonium challenge by increasing salivation
and bronchopulmonary secretions, diaphoresis, and gastric General evaluation
motility2,5,7,14,17. These changes should be managed expectantly, The management of MC should follow a step by step,
as the half-life of edrophonium is short (10 min). In addition, sequential, and multidisciplinary protocol (Fig 3), based on
worsening of bulbar and respiratory symptoms in MuSK-MG guidelines of the European Federation of Neurological Socie-
after anticholinesterase administration is known and could ties40. Prompt recognition of impending respiratory paralysis
confound the clinical diagnosis17. If the patient requires ven- is the key to successful management31-33. The evolution of res-
tilatory support there is no need to distinguish the two crisis piratory muscle weakness in AChR-MG often follows a pat-
entities17. False-positives have been also reported in lower tern where the intercostals and accessory muscles weaken
motor neuron diseases and brainstem tumors17. first, followed by the diaphragm31-33. In MuSK-MG, bulbar
weakness always precedes respiratory failure7.
Serological testing
If MG is suspected, the patients should be tested for Trigger detection and assessment
AChR antibodies14,17,39. If these are negative, MuSK antibod- of the respiratory and bulbar functions
ies should also be tested14,17,39. Antibodies should be sent for It is essential to evaluate bulbar and respiratory func-
analysis before the institution of any immunotherapy. Anti- tions together with ensure life support and detecting trigger
AChR antibodies are elevated in 85–90% of patients with gen- conditions (precipiting factors)1,2,5,7-13,16,33. Habitually, bulbar
eralized MG14,17,28,39. MuSK-related autoimmune-acquired MG and respiratory dysfunction occurs simultaneously with
presents with slightly different phenotype 14,17,28,39.
Table 5. Neurologic and systemic causes of muscle/respiratory
Other testing weakness/failure.
Chest computerized tomography (CT) should be per- Central nervous system (CNS)
formed in patients with MG to exclude thymoma14,17. Chest Head trauma
Spinal cord Injury (traumatica, vascular, compressive, inflamma-
CT is more sensitive than plain chest radiographs for delin- tory)
eating anterior mediastinal masses. MRI does not improve Infections (tetanus, rabies)
diagnostic sensitivity. Iodinated contrast agents may pre- Brainstem stroke (hemorrhagic, isquemic)
Drugs (barbiturates, alcohol)
cipitate worsening of myasthenic weakness20. Although
Motor neuronopathy
this is an uncommon phenomenon, we do not routinely Amyotrophic lateral sclerosis
use iodinated contrast agents during chest CT to assess for Poliomielytis
thymoma. These examination should be made in a stable Infections (West Nile virus)
patient. Since MG often coexists with other autoimmune Peripheral nerve disorders
Guillain Barrè syndrome
disorders, particularly thyroid disease, patients should Acute intermittent porphyria
undergo thyroid and other autoimmune testing when clini- Vasculitis neuropathy
cally appropriate14,17,39. Diphtheric polyneurophaty
Neuromuscular junction disorders
Lambert-Eaton myasthenic syndrome
Cholinergic crisis
DIFFERENTIAL DIAGNOSIS Botulism
Organophosphate overdose
Poisons (spider, snake)
Differential diagnosis includes other disorders of the neu-
Primary muscle disease
romuscular junction including Lambert–Eaton syndrome, Acid maltase defficiency
botulism, congenital myasthenic syndromes, and tick paraly- Rhabdomyolysis
sis2,5,7,9-11,14,17. In addition, acute inflammatory demyelinating Polymyositis
Dystrophic muscle disease (Duchenne’s)
polyradiculoneuropathy (AIDP) and variants, particularly
Systemic diseases
those featuring external ophthalmoplegia and ptosis, may Hypothyroidism
simulate MG,2,5,7,9-11,14,17. Motor neuron disease and brainstem Hyphophosphaemic myopathy
ischemia involving oropharyngeal weakness may appear Hyper/hypokalemic periodic paralysis
Electrolyte disturbances
in MG14,17.

634 Arq Neuropsiquiatr 2013;71(9-A):627-639

 Myasthenic crisis
Myasthenic crisis

Withoutprevious
Without previous diagnosis
diagnosis
(15–20%)
(15–20%) MGMG previously diagnosed
previously diagnosed

Stop
Stop Continue
Continue
Confirm
Confirmdiagnosis
diagnosis ICU
ICU anticholinesterase immunosupressors
immunosupressors
anticholinesterase
drugs

General critical care Avoid

Avoidand treat
and treat Evaluate bulbar
Evaluate bulbar and
and Search
Searchprecipitating
precipitating Specific
Specific
General critical care Immunotherapy
systemiccomplications
systemic complications respiratory functions
respiratory functions factors
factors Immunotherapy
Plasmapheresis
Plasmapheresis
IV IV Immunoglobulin
Immunoglobulin
Corticosteroids
Corticosteroids
Ventilatory support
Ventilatory support

ICU: intensive care unit; IV: intravenous; MG: myasthenia gravis.

Fig 3. Algorithm for myasthenic crisis management.

generalized muscle weakness characteristic of myasthenic Table 6. Ventilatory test in patients with myasthenic crisis.
patients. Typical clinical features include shortness of breath, Intubation Weaning Extubation
Normal
tachypnea, orthopnea, discomfort, tachycardia, sweating, criteria criteria criteria
use of accessory muscles of respiration, or paradoxical ven- FVC
>60 <20 >15 >25
(mL/kg)
tilation31-33. The collapse of the airway is marked by coughing
NIP
and swallowing disability, leading to accumulation of secre- (cmH2O)
>-70 <-30 >20 >40
tions in the pharynx31-33. Patients are unable to swallow 5 cc PEP
>100 <40 >40 >50
of water or count until 20 in a single respiratory cycle7,31-33. (cmH2O)
FVC: indicates forced vital capacity; NIP: negative inspiratory pressure;
Intubation and mechanical ventilation PEP: positive expiratory pressures.

The decision of the mode of ventilatory support should

be based on clinical judgement. Careful observation and tuates, and patients can develop apnea suddenly, or may
bedside measurements (vital capacity, peak flow measure- precipitously fatigue with the rapid development of respira-
ment, pulse rate, and blood pressure) are more important tory failure before a downward trend in these parameters is
than repeated monitoring of blood gases1,2,5,7-13,16,33. Never- noted1,2,5,7-13,16,31-33. Moreover, none of them have been shown to
theless, certain ventilatory tests can be performed, includ- be reliable predictors of the need for mechanical ventilation.
ing forced vital capacity (FVC), negative inspiratory pres- Life-threatening hypoxemia (PaO2<60 mmHg) occurs late in
sure (NIP), positive expiratory pressure (PEP), and arterial neuromuscular respiratory failure and generally improves
blood gases1,2,5,7-13,16,33. The 20/30/40 rule (FCV<20 mL/kg; with supplemental oxygen1,2,5,7-13,16,31-33. In this situation,
NIP<30 cmH2O; and PEP<40 cmH2O) is probably the most we can attempt the use of bilevel positive airway pressure
helpful guide to decide intubation (Table 6). FVC<30 mL/kg (BiPAP), since the application of positive pressure helps to
is associated with ineffective cough, poor handling of endure increased resistance of the upper airways in addition
secretions, atelectasis, and hypoxemia. NIP<20 cmH2O sig- to preventing alveolar collapse and atelectasis2,5,7,31-33. Severe
nals marked weakness of the inspiratory muscles and dia- hypercapnia (PaCO2>50 mmHg) predicts BiPAP failure and
phragm, while PEP<40 cmH2O indicates involvement of indicates that muscle fatigue is imminent36. The absolute
expiratory muscle function closely linked with the ability indications for intubation may include cardiac or respira-
to cough and clear secretions1,2,5,7-13,16,33. These determina- tory arrest, impaired consciousness, shock, life-threatening
tions require training, depending on the patients’ effort, arrhythmias, severe blood–gas alterations, and bulbar dys-
and require proper closure of the mouth — all conditions function with confirmed aspiration1,2,5,7-13,16,50. Much more
are difficult to obtain during the crisis. Furthermore, these difficult is the decision to intubate when such strict criteria
threshold values have not been established through pro- are not met. If doubt exists, it is recommended to intubate
spective studies. In addition, muscle weakness often fluc- and ventilate inmediately2,7-13,33. Endotracheal intubation

Daniel Agustin Godoy et al. Myasthenic patients: crisis 635

 can often be ­performed electively rather than as an emer- such as a satisfactory oxygenation, PaO2/FIO2≥200 mmHg,
gent response32,33. The initial ventilatory support should be PEEP ≤5 cmH2O; hemodynamic stability, and a good con-
directed to improve muscle fatigue and to mantain lung sciousness status able to cough effectively2,5,7-13,16,33. Patients
expansion1,2,5,7-13,16,33. We suggest as initial mode assist-control should be transitioned to a spontaneous mode of ventilation
ventilation, with low tidal volumes (6–8 mL/kg), respiratory (e.g., pressure support ventilation) previous to T-tube trial.
rate 12–16/min, and positive end-expiratory pressure (PEEP) Pressure support can then gradually be decreased to minimal
of 5 cmH2O. FiO2 should be adjusted to achieve a SaO2 >92% settings33,43. If the patient does not tolerate weaning, assisted
or PaO2 >70 mmHg7-13,16,33. Pressure support ventilation ventilation should be reinstituted.
between 5 and 15 cmH2O is another option7-13,16,33. In case of It remains unclear when to attempt extubation after MC.
atelectasis, we consider recruitment manoeuvres or the uti- Prolonged intubation in myasthenic patients may lead to several
lization of sighs (1.5 × tidal v­ olume) 3 to 4 times per hour10. complications such as atelectasis, anemia, urinary tract infec-
The degree of support is patient dependent and should be tion, congestive heart failure, and ventilator-associated pneu-
adjusted and based on arterial blood analysis. In patients monia11,45. To prevent atelectasis, aggressive chest physiotherapy
with chronic hypercarbia, PaO2 should be kept above 45 mm and frequent suctioning should be implemented together with
Hg to avoid alkalosis and bicarbonate wasting, which make continuous positive airway pressure (CPAP). Age>50 years, peak
weaning more d ­ ifficult2,5,7-13,16,33. VC<25 mL/kg on postintubation days 1 to 6, and a serum bicar-
Bronchodilators may be useful in maintaining airway bonate ≥30 mmol/L are independent risk factors for prolonged
patency and overcoming bronchospasm. Inhaled ipratro- intubation (>14 days)7. Extubation failure is most commonly
pium bromide may be of choice because it is safe and can associated with a weak cough and inadequate airway clear-
decrease bronchial secretions41. Terbutaline, a β2 adrenergic ance33,45-47. Tracheostomy is generally not needed in MC because
agonist, may be an effective adjunct therapy in these patients, the duration of intubation is often less than 2 weeks2,5,7-13,16,33,46.
although confirmation with larger trials will be required42. One rare condition that often requires tracheostomy is
Meticulous attention to pulmonary toilet is required due to severe upper airway obstruction due to bilateral vocal cord
ineffective cough. Aggressive chest physiotherapy (percus- paralysis. Furthermore, patients with a prolonged intubation
sion, vibration, and postural drainage) and airway clearance are usually hospitalized three times longer and are less likely
(regular suctioning and therapeutic fiberoptic bronchoscopy to be functionally independent upon discharge7.
in severe cases) should be implemented43. Inspired gas humid- A maximal expiratory pressure has been demonstrated
ity should be around 80% at 37°C. Patients with a peak cough to independently predict extubation success. However, there
flow <180 L/min can augment cough response with manual are no good clinical criteria for when and how to extubate
physiotherapy and with insufflation-exsufflation devices. safely. Fluctuating weakness and pulmonary complications
Cough response increases and is associated with improved often confound the decision to extubate47. Patients are typi-
prognosis independent of FVC or breathing pattern44 . cally extubated if VC, PImax, and PEmax are ≥15 mL/kg,
Adequate nutrition is important to avoid negative energy ≤-20 cmH2O, and >40 cmH2O respectively, and tidal volume
balance and worsening of muscle strength12. All patients should ≥5 mL/kg2,5,12,45,48. If the patient complains of fatigue or short-
receive adequate nutritional support (25–35 calories/kg) ness of breath, extubation should not be performed even if the
via enteral route whenever possible. In patients with hyper- criteria of these indices are met and blood gases are normal.
carbia and difficulty weaning, low carbohydrate feeds are the
preferred solution43. Potassium, magnesium, and phosphate Noninvasive positive pressure ventilation
depletion can exacerbate MC and should be repleted. Anemia Noninvasive ventilation may be used to prevent intuba-
can also increase weakness, and several experts recommend tion or reintubation in MC49-52. With BiPAP, positive pressure
transfusions when hematocrit values are under 30%12. Addi- is applied during both phases of respiratory cycle, enhancing
tionally, deep-vein thrombosis prophylaxis, hemodynamic sta- airflow, alleviating the work of breathing during inspiration,
bility, and glycemia control are strongly ­recommended2,7-13,16. and preventing airway collapse and atelectasis during expi-
Weaning from ventilation should start when the patient ration49-52. There are studies of Noninvasive positive pressure
regains muscular strength; is hemodynamically stable with- ventilation (NIPPV) during MC49-52. In 2002, Rabinstein and
out electrolite disturbances, fever, infections, or systemic Wijdicks first reported their experience49. All patients have had
complications; and the reason for mechanical ventila- bulbar compromise. NIPPV was well tolerated and the length
tion has been resolved or is in the process of frank resolu- of hospital stay was significantly reduced compared with
tion2,5,7-13,16,33. Improvement in the strength of neck flexors and those who were intubated (mean 7±5 days versus 23±16 days;
other adjunct muscles usually is associated with improve- p=0.03). paCO2>50 mmHg portends BiPAP inefficiency49.
ment in bulbar and respiratory muscle strength and can be Subsequent reports suggest that NIPPV may be useful in
a useful tool for assessing clinical improvement7-13,16,33. Cur- preventing intubation or reintubation in these patients47-51.
rent recommendations about managing the weaning pro- A recent prospective study suggests that NIPPV, combined
cess emphasize the daily determination of simple criteria with assisted coughing after extubation, avoids the need for

636 Arq Neuropsiquiatr 2013;71(9-A):627-639

reintubation or tracheostomy in patients with neuromuscu- e­ fficacy, so they can be chosen by availability, adverse effects,
lar diseases, besides shortening their stay in the ICU50,51. Early costs, experience, and patients’ profile2,5,7-13,16,18,40.
application of NIPPV after extubation can reduce the risk IVIg is a IgG-purified blood derivate.The mechanism of
of respiratory failure and lowered mortality in hypercapnic action is unknown. It needs about 5 days to exert maximun
patients with chronic respiratory disorders51. Use of NIPPV to therapeutic effects. The usual regimen is 0.4 g/kg/day for
avoid reintubation in MC is well established but is a relatively 3–5 days2,5,7-13,16,18,40. One study did not find a difference
uncommon practice51. Some studies reported that NIPPV between 1 or 2 g as total dose52. Patients should be screened
prevented reintubation in 70% of patients49,50. It should be for IgA deficiency to avoid anaphylaxis2,5,7-13,16. More prevalent
included in the routine approach to these patients at high side effects are fever, overload of fluids, nausea, and headache.
risk for postextubation respiratory failure. Less frequent and more serious complications are aseptic
meningitis, pulmonar edema, anafilaxia, renal dysfunction,
cardiac arrhythmia, thrombocytopenia, stroke, myocardial
COMPLICATIONS IN THE infarction, and pulmonary embolism2,7-13,14,16.
MANAGEMENT OF MYASTHENIC CRISIS PE and IA are most effective when we need a fast response,
particulary in patients who do not improve, are worsening, or
Fever is the most common complication associated are having severe complications2,5,7-13,16,18,40,53. Response to treat-
with MC2,5,7-13,16. Infectious complications include pneu- ment generally occurs after 2 days. The optimal response of PE
monia, bronchitis, urinary tract infections, Clostridium and IA occurs in both AChR-Ac- and MuSK-positive patients.
difficile colitis, bacteremia, and sepsis2,5,7-13,16.When compared The proposed mechanism of action is rapid depletion of path-
with patients admitted for noncrisis, patients admitted with ogenic antibodies from plasma, which causes an osmotic equi-
MC are more likely to experience sepsis, deep-vein throm- libration between extra- and intravascular spaces leading to
bosis, and cardiac complications including congestive heart reduction of antibodies in neuromuscular junction2,5,7-13,16,18,40.
failure, acute myocardial infarction, arrhythmias, and cardiac Both apheresis procedures, PE and IA, must be performed at
arrest. These complications, however, are not independent low-dose regimen; it is 1.5 L of plasma (20–25 mL/kg), per ses-
predictors of mortality2,5,7-13,16. sion, with an exchange rate of 10–20 mL/min. The procedure
needs central venous access and anticoagulation. PE should
be made in a course of five exchanges every other day over
STOP ANTICHOLINESTERASE DRUGS 10 days. Replacement fluid is generally normal saline/5% albu-
min2,5,7-13,16,18,40. A series of nonrandomized studies have dem-
Anticholinesterase therapy should be temporarily with- ostrated benefical short-term efficacy of this therapy in acute
drawn immediately after establishing mechanical ventilatory setting and during preparation for thymectomy2,5,7-13,16,18,40.
support because they are unnecessary in this situation and
may complicate pulmonary management2,5,7-13,16. In addition,
the continued use of these medications may promote cho- plasmapheresis OR immunoglobulin?
linergic crisis by overdose11. Although cholinergic crisis is
an important consideration in the evaluation of the patient This question does not have a response. IVIg may be bet-
in MC, it is uncommon2,5,7-13,16. Cholinergic crisis may cause ter tolerated than PE; however PE showed similar short-term
increase of pulmonary secretions (muscarinic effects) and effects in comparison with IVIg in one RCT54 but was more
fasciculations (nicotinic effects), both of which contribute effective than IVIg in a retrospective study55. PE may probably
to exacerbate muscle weakness and respiratory failure2,5,7-13,16. have a more predictable response than IVIg during crisis. IVIg
Furthermore, acetylcholinesterase inhibitors may promote and PE are equally effective in preparation for surgery56. In
cardiac arrythmias and myocardial infarction2,5,7-13,16. The conclusion, until now there is not enough evidence of high
time to start cholinergic agents (pyridostigmine) preferably quality to support one therapy over another during MC. If
orally or by nasogastric tube is not well established, but is there is insufficient or no response to treatment, PE can be
recommended when the patient shows clinical improvement given after IVIg, and IVIg can be administered after PE.
before weaning of mechanical ventilation2,5,7-13,16,18.

STEROIDS AND OTHER

IMMUNOTHERAPY IMMUNOSUPPRESSIVE AGENTS

Immunomodulatory treatment is considered standard Patients who are taking steroids should not stop
of care for patients with MC2,5,7-13,16,18,40. Specific immunother- them2,5,7-13,16,18,40. Possibly after crisis, the dose should be
apy consists in plasma exchange (PE), immunoadsorption increased. If we need to start steroids after PE or IVIg, oral pred-
(IA), and human IVIg. All of them have demostrated similar nisone is preferred at 1 mg/kg/day (60–100 mg daily)2,7-13,16,40.

Daniel Agustin Godoy et al. Myasthenic patients: crisis 637

 The timing of initiation is controversial, but usually it is IIA, IIB, and III according to clinical grade of ­Osserman
indicated when the patients cannot be extubated 2 weeks ­classification)57,58, a history of MC23, preoperative pres-
after specific immunotherapy2,7-13,16,40. It may be initiated ence of bulbar weakness23, serum AChR antibody levels
concurrently with IVIg or PE, since prednisone begins to >100 nmol/L, and intraoperative blood loss of >1 L. Other
work after 2 weeks. Enteral administration is preferred, predisposing factors are obesity (BMI >25.6), higher doses
and initiation of prednisone may be deferred until after of pyridostigmine (>270 mg) and immunosupressants,
extubation if the patient improves with IVIg or PE treat- FVC <2 L, and history of infection 1 month before surgery25.
ment2,5,7-13,16,18,40. The mean time to improvement with pred- Type and technique of surgery may affect the occurrence of
nisone is around 13 days. Worsening of symptoms with MC after thymectomy58-60. The presence of thymoma is the
the initiation of corticosteroids is not predictive of overall more important isolated postoperative factor to develop MC
response to corticosteroids22. Once the patient has begun together with radiation therapy, delayed ventilator weaning,
to show improvement, dose can be decreased and gradually and upper or lower pulmonary tract infections23-25,57. The risk
converted to alternate-day dosing. It is important to have of MC has decreased with less invasive surgical tecniques such
in mind that steroids can exacerbate muscle weakness or as cervicotomy, partial sternotomy, or video-assisted thoraco-
may increase the risk of critical illness myopathy2,7-13,18,22. In scopic57,59,60. In a study of 218 thymectomies with different tech-
septic patients, it is preferable to delay steroids until infec- niques and approachs, no significant differences were found in
tion is under control. Relative contraindications are dia- terms of incidence or severity of MC or in the final outcome25.
betes with poor metabolic control or severe osteoporosis.
Other immunosuppressive drugs, necessary to long-term
management of MG, such as cyclosporine, azathioprine, or CONCLUSIONS
mycophenolate, are not useful during MC principally due to
the delayed onset of action2,5,7-13,16,40. MC is a severe and life-threatening neurological condition
characterized by generalized muscle weakness with respira-
tory or bulbar compromise that require ventilatory s­ upport.
ROLE OF THYMUS: SURGICAL CONSIDERATIONS It can be the debut form of MG, so the diagnosis should be
confirmed following a standardized protocol. Evaluation
Thymectomy plays a central role in management of of bulbar and respiratory functions is imperative. The cor-
MG14,17,40. About 65% of the patients in seropositive group nerstones of the treatment are correct ventilatory manage-
have thymic hyperplasia and 15% thymoma14,17. Thymec- ment, search and correction of predisposing factors, specific
tomy is the only treatment in MG that offers possibilities of immunotherapy (PE, IVIg), avoiding systemic complications,
complete remission14,17. Indications for tymectomy include: and planification of long-term treatment (immunosupres-
(a) failure of long-term conservative therapy, (b) thymoma, sors). The majority of patients with MC require endotra-
and (c) new onset of generalizated MG14,17,40. Patients with cheal intubation and mechanical ventilation. Thymectomy
more benefits after thymectomy are those <60 years, sero- should be evaluated. With modern intensive care, the out-
positives, and with thymic hyperplasia14,17,40. The role of a comes are excellent with mortality near to 5% attribuited
thymectomy in MuSK patients is not clear. Chu et al.57 sug- principally to comorbidities, cardiac complications, or
gested that thymectomy seems to have a preventive effect pulmonary ­embolism.
in both incidence and severity of MC, but the frequency
of postoperative crisis varied from 6% to 21.9%23 defined
as respiratory failure or delayed postoperative extubation Aknowlegdments
(>24 hours)57. Postoperative crisis has been related to age
(onset of the disease more than 50 years)58, severity (type We thank Mrs. Vanessa Starling for her editorial assistance.

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