Transcript Overview of myesthenic crisis

Overview of myasthenic
crises
Dr. Sonal Dodhiya
Physiology of neuromuscular
junction
 The nerve terminates at
the ‘pre-synaptic
membrane’,which is
separated by a
‘junctional/synaptic cleft’
from the ‘post synaptic
membrane’ of the
muscle.
 The pre-synaptic
membrane has Ach
filled vesicles.
 The post synaptic
membrane has Ach
nicotinic receptors.
Physiology of muscle contraction
Discharge of motor neuron.
Release of Ach at motor end plate.
Binding of Ach to nicotinic Ach receptors.
Generation of EPP.
Generation of action potential in muscle fiber.
Contraction of the muscle.
Myasthenia Gravis
 Myas-Greek for muscle
 Asthenia-Greek for weak
 Gravis-latin for very severe
 Neuromuscular disease leading to fluctuating
muscle weakness and fatiguability.
 Autoimmune disorder where in antibodies are
directed against nicotinic Ach receptors.
 Patient becomes symptomatic when
receptors have reduced to <30% of normal.
Pathophysiology of MG
 Myasthenia gravis occurs
when the immune system
makes antibodies that
damage or block many of the
muscle's acetylcholine (ACh)
receptors on the surface of
muscle cells.
 This prohibits ACh from
binding to the damaged
receptors and acting on the
muscle, which reduces
muscle contractions, leading
to weakness and fatigue.
Classification after Ossreman & Genkins
 Adult MG
Group I: Ocular (20%)
Group IIA: Mild generalized (30%)
Group III: Acute fulminating (11%), rapid onset, early
respiratory involvement, high mortality.
Group IV: Late Severe (9%), > 2 years after onset.
 Transient Neonatal MG: 1/6 born to MG mother. Last
a few weeks.
 Congenital Myasthenic Syndrome.
The Myasthenia Gravis Foundation of
America Clinical Classification
 Class I: Any eye muscle weakness, possible ptosis, no
other evidence of muscle weakness elsewhere .
 Class II: Eye muscle weakness of any severity, mild
weakness of other muscles .
 Class IIa: Predominantly limb or axial muscles
 Class IIb: Predominantly bulbar and/or respiratory
muscles
 Class III: Eye muscle weakness of any severity
Moderate weakness of other muscles
 Class IIIa: Predominantly limb or axial muscles
 Class IIIb: Predominantly bulbar and/or respiratory
muscles
The Myasthenia Gravis Foundation of
America Clinical Classification
 Class IV: Eye muscle weakness of any severity,
severe weakness of other muscles.
 Class IVa: Predominantly limb or axial muscles
 Class IVb: Predominantly bulbar and/or respiratory
muscles (Can also include feeding tube without
intubation)
 Class V: Intubation to maintain airway
Myasthenic crisis
 Definition: Life-threatening condition , defined as
weakness from acquired myasthenia gravis that is
severe enough to necessitate intubation or delayed
extubation following surgery.
 Severe bulbar weakness that produces dysphagia
and aspiration often complicates the respiratory
failure.
 American classification stage V
Patient presentation
 Slack facial muscles,expressionless face.
 Unable to support his head.
 Nasal voice quality
 Limp body
 Absent gag-risk of aspiration.
Respiratory distress
 Pt. unable to generate adequate ventilation &clear
bronchial secretions-UTMOST CONCERN
 Inability to cough leads to accumulation-
rales.ronchi&wheez may be auscultated
 Patient may have evidence of
pneumonia(fever,cough,dyspnea,consolidation)
Predisposing factors
 Non compliance with the medications
 Infections
 Physiologic stress
 Emotional stress
 Drugs
Drugs predisposing to myasthenic
crisis
 Macrolides, fluoroquinolones, aminoglycosides,
tetracycline, and chloroquine.
 Beta-blockers, calcium channel blockers, quinidine,
lidocaine, procainamide, and trimethaphan.
 Miscellaneous - Diphenylhydantoin, lithium,
chlorpromazine, muscle relaxants, levothyroxine,
adrenocorticotropic hormone (ACTH), and,
paradoxically, corticosteroids oral contraceptives.
Assessment of patient in crises
 Confirmation of the diagnosis of myasthenia gravis
 A search for potentially treatable triggers
 Withdrawal of any offending drugs
 Determination of whether the patient needs
intubation or swallowing restrictions.
Differential diagnosis

Other NMJ disorders-cholinergic crisis,eatonlambert syndrome,botulism,OP poisoning.

Myopathies secondary to electrolyte abnormalties or
acid maltase deficiency

Neuropathies –Guillain-barre syndrome and motor
neuron disease

Central lesions including cervical cord or brain stem
compression by an expanding mass.
Diagnosis of myasthenic crisis
ANTIBODY TITRE:
 Anti-Ach receptor Ab
 MuSK Ab(antibodies to muscle-specific receptor
tyrosine kinase)
 Antibodies to striated muscle(StrAb)
Diagnosis contd.
 Tensilon test(edrophonium):
give in incremental doses.start with
2mg,observe for 45 to 60 sec,followed by dose of 3 &
5mg obs for 1 to 2 mins following each dose
patients are given Atropine sulphate 0.6mg
im/iv to counter act the nicotinic side-effects of
edroohonium
postive means unequivocally improvement of
weakness
mild to moderate improvement has been seen
in patients with-brain stem lession,occulomotor palsy
due to cerebral artery aneurysm,diabetic abducens
paresis & normal contral subjects.
Diagnosis contd.
 Electro physiology:repetitive stimulation at 3 hertz
 Single fiber EMG
 HRCT Chest to rule out thymoma
Cholinergic crisis
 Most confusing differential diagnosis
 Due to excess cholinesterase
inhibitors(pyridostigmine,neostigmine,physostigmine)
 Resembles organophosphate poisoning
 Excessive stimulation of Ach causes flaccid muscle
paralysis - clinically indistinguishable from
myasthenic crisis
Cholinergic crisis
 Bronchospasm with wheezing,respiratory
failure,diaphoresis,and cyanosis.
 Miosis and SLUDGE
syndrome(salivation,lacrimation,urinary
incontinence,diarrhea,GI upset and hyper
motility,emesis)may mark cholinergic crisis
 Deep tendon reflexes are preserved.
Treatment of myasthenic crisis
 Admit to intensive care unit
 Measure FVC frequently,as often as every two hours
if respiratory status is deteriorating
 Electively intubate if:
- FVC <15ml/kg body weight
- declines in serial measurements of FVC
approaches 15ml/kg
- declines in serial measurements of NIF
approaches 25cm of water
- clinical signs of respiratory distress
- difficulty handling oral secretions,swallowing,or
speaking
Treatment contd.
 Withdraw anticholinesterase medications to reduce
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airway secretions in patients who are intubated.
Begin rapid therapy with plasmapheresis or IVIG to
treat myasthenic crises.
Begin immunomodulating therapy with high dose
corticosteroids(eg,prednisolone 60 to 80 mg per day).
Consider azathioprine,mycophenolate
mofetil,orcyclosporine if steroids are
contraintraindicated or previously ineffective.
Initiate weaning from ventilation when respiratory
muscle strength improving with plasmapharesis or
IVIG,as quantified by a FVC>15ml/kg&NIF>30cm of
water.
Contraindications of PE
 Related to extracorporeal line and
anticoagulation
 - precarious hemodynamics (cardiogenic shocks)
 - unstabilized angina pectoris
 - pericardial effusion (heparin)
 Related to immunosuppression
 - non controlled infectious diseases (septicemia)
Immediate Side effects of PE
 Related to extracorporeal line and anticoagulation
- vagus nerve syndrome, low or high blood
pressure.
 - venous puncture hazards, air embolism.
 - excessive bleeding, allergy or thrombocytopenia
induced by heparin, citrate poisoning with
hypocalcaemia manifestations (headache-crampsswarming-tetanus rarely cardiac arrhythmia).
 Related to replacement fluids :
 - chills-fever
 - nausea-vomiting, diarrhea (albumin)
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Delayed complications of PE
 Impaired hemostasis :
- hypocoaguable state 8-12 hours after session
 - hypercoaguable state 24-72 hours by rebound
effect (antithrombin 3 synthesis delayed)
 -> THROMBOSIS RISK increased especially
when other promoting conditions (inflammation,
confinement to bed)
 Preventive heparin treatment with normal
coagulation tests objective is the rule in these
conditions.
 Immunosuppression :
 Particular sensitivity to bacterial infections
(humoral immunity deficiency)
 Transfusion related infection :
 Has not been reported since the exclusive use of
viro-inactivated, heat treated (Albumin) or artificial
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Undesirable effects from IVIG occur in less than 5% of patients. The most
common adverse effects occur soon after infusions and can include headache,
flushing, chills, myalgia, wheezing, tachycardia, lower back pain, nausea, and
hypotension. If this happens during an infusion, the infusion should be slowed or
stopped. If symptoms are anticipated, a patient can be premedicated with
antihistamines and intravenous hydrocortisone.
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IVIG can induce reactions in patients with IgA deficiency. This occurs in 1 in 5001000 patients. Serious anaphylactoid reactions occur soon after the
administration of IVIG. Anaphylaxis associated with sensitization to IgA in
patients with IgA deficiency can be prevented by using IgA-depleted immune
globulin. The presence of IgG anti-IgA antibodies is not always associated with
severe adverse reactions to IVIG.4
An uncommon but potentially irreversible adverse event is acute renal failure.
From June 1985 to November 1998, the US Food and Drug Administration
received 120 reports worldwide, 88 in the United States, of renal injury. Acute
renal failure with IVIG therapy occurs with the sucrose-stabilized formulation, but
not with the D-sorbitol–stabilized formulation.
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 IVIG is associated with rare cases of thrombosis. It has caused
disseminated intravascular coagulation, transient serum
sickness, and transient neutropenia.
 risk One study reported 7 patients who had thromboembolic
events while being treated with IVIG.22 Four patients had
strokes or transient ischemic attacks, 1 had an inferior wall
myocardial infarction, 1 developed deep venous thrombosis,
and 1 had a retinal artery infarct. The age range of the patients
was 57-81 years, and most had underlying risk factors such as
hypertension, hypercholesterolemia, atrial fibrillation, history of
vascular disease and stroke, and deep venous thrombosis.
Three patients received multiple IVIG infusions before
developing the thromboembolic complications. Therefore,
clinicians should be vigilant about the possibility of
thromboembolic complications with each IVIG infusion and
should be especially judicious with the use of IVIG in patients
with underlying factors.
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Life-threatening human parvovirus B19 infection and hepatitis C have been transmitted by
IVIG.
Severe cutaneous vasculitis has been reported following an intravenous infusion of
gammaglobulin in a patient with type II mixed cryoglobulinemia.
IVIG can precipitate acute myocardial infarction.
Aseptic meningitis is a rare but well-recognized complication of IVIG therapy. It manifests as
fever, neck stiffness, headache, confusion, nausea, and vomiting.
IVIG therapy can result in postinfusion hyperproteinemia, increased serum viscosity, and
pseudohyponatremia.
IVIG should not be given to patients with sensitivity to thimerosal.
IVIG has caused eczematous dermatitis and alopecia.
Complement consumption associated with an eczematous cutaneous reaction has been
noted during infusions of high doses of IVIG.
Orbach et al noted encouraging reports on the efficacy of IVIG in different types of
glomerulonephritis (mainly lupus nephritis) resistant to conventional therapy, but the exact
success rate and clinical indications remain undetermined. However, the issue of IVIG
treatment and renal function is a 2-edged sword because nephrotoxicity can be a serious
rare complication of IVIG therapy. Products containing sucrose as a stabilizer are mainly
associated with such injury through the mechanism of osmotic nephrosis. Preexisting renal
disease, volume depletion, and old age are risk factors for such toxicity