Myasthenic Crisis: An Intensive Care Emergency

Abstract

Myasthenia Gravis (MG) is an autoimmune disorder affecting neuromuscular transmission leading to generalized or localized muscle weakness. This occurs most frequently dueto the presence of auto-antibodies against acetylcholine receptors (AChR) in the postsynaptic motor end-plate, the so called AChR- MG. MG patients with auto-antibodies to muscle-specific tyrosine kinase (MuSK) represent a distinct subset of those with this disease. Patients who are negative for both AChR and MuSK antibodies are now classified as “seronegative” MG. Thymic hyperplasia is present in 65 % of cases and thymoma is present in 10 % of cases. Based on the clinical manifestations, the disease is usually classified into ocular MG and generalized MG. Ocular MG affects only the extra-ocular mus¬cles, whereas generalized MG affects other muscles beyond the ocular muscles, and may include limb, bulbar, facial and respi¬ratory muscles. Diagnosis of MG depends on clinical features, serological, pharmacological and electrophysiological tests. TheevolutionofrespiratorymuscleweaknessinAChR-MGoftenfollowsapatternwheretheintercostalsandaccessorymuscles of respirationweakenfirst,followedbythediaphragm.InMuSK-MG,bulbarweaknessalwaysprecedesrespiratoryfailure.AsystematicreviewexaminingtheutilityofdiagnostictestsinMGconcludedthatonly theanti-AChRantibodytestingandsingle-fibreelectromyography(SFEMG)wereadequatelyvalidated. Acetylcholinesterase inhibitorsareusedinitially in the treatment of the disease.DefinitiveMGtreatmentstargettheautoimmuneresponsebysuppressingtheproductionofpathogenicantibodiesorthedamageinducedbytheantibodies.Theaimofimmunotherapyistoinduceandthenmaintainremission.Immunotherapy includes plasma exchange, immunoadsorption andintravenousimmunoglobulin for short-term therapy and other drugs for long-term management. These includecorticosteroids, azathioprine,cyclosporine A,methotrexate andmycophenolate. All of these drugs have demonstrated similar efficacy, so they can be chosen by availability, adverse effects, costs, experience and patient's profile. Thymectomy is the indicated surgical treatment. Getting pregnant in the presence of MG has some considerations. Pregnancy is one of the known causes of exacerbation of MG.Worseningsymptomsoccurinonethirdofpregnantwomen, theyaremorelikelytooccurduringthefirsttrimesterorthefirstmonthpostpartum.TheeffectofMGonpregnancyisrelativelysmall.Thereisnoincreaseintherateofspontaneousabortionorlowbirthweightchildren.MG is associated with a slightly increased rate of complications during birth and more frequent need of operative interventions.Acetylcholinesterase inhibitors and immunosuppressive drugs should be continued during pregnancy when necessary for the MG, except for methotrexate which is damaging to ova and sperm and should be stopped at least 3 months before attempting conception. Inpediatricpatients,MGisclassifiedastransientneonatal,neonatalpersistent,orjuvenile. Myasthenic crisis (MC) should be considered a true neurological emergency. It is characterized by severe weakness of the bulbar (innervated by cranial nerves) and/or respiratory muscles, enough to cause inability to maintain adequate ventilation causing respiratory failure that requires ventilatory support. Postoperative myasthenic patients in whom extubation has been delayed more than 24 hours should be also considered in myasthenic crisis. PatientspresentingwithMCarenormallyadmittedtoanintensivecareunitbecauseoftheacuterespiratoryfailure.ItisimportantfortheexaminertohaveahighindexofsuspicionforMCastheinitialmanifestationsmaybesubtle.Insomepatients,MCoccursastheirinitialpresentationofMG.Becauseofthis,MCshouldbestronglyconsideredinanypatientwithunexplainedrespiratoryfailure,particularlyinthoserequiringprolonged mechanical ventilation. Evidence of respiratoryfailure may be noted through ABG determination, pulmonary function tests or pulse oximetry according to the emergency of the case. The management of MC should follow a step by step, sequential, and multidisciplinary protocol. Prompt recognition of impending respiratory paralysis is the key to successful management. Patients with myasthenia gravis who are in respiratory distress may be experiencing a myasthenic crisis or a cholinergic crisis that results from overdose of anticholinesterase drugs. Before these possibilities can be differentiated, ensuring adequate ventilation and oxygenation is important. Respiratory management of patients with myasthenic crisis; however, is very challenging due to the fluctuating nature of the disease. These patients can develop apnea very suddenly, and they must be observed closely. Preliminary studies suggest that noninvasive bilevel positive airway pressure (BiPAP) can prevent intubation in patients with myasthenic crisis without overt hypercapnia and should be considered in the patient who can be closely monitored. Hypercapnia present at the time of BiPAP initiation can predict failure and the need to proceed to endotracheal intubation. The decision of the mode of ventilatory support should be based on clinical judgement. Meticulous attention to pulmonary toilet is required due to ineffective cough which may causepulmonary aspiration. Aggressive chest physiotherapy (percussion, vibrationand postural drainage) and airway clearance (regular suctioning and therapeutic fiberoptic bronchoscopy in severe cases) should be implemented to avoid complications such as atelectasis and infection. Searching for precipitating factors starts immediately after securing the airway and properly ventilating the patient. Treatment of such precipitating cause improves the condition of the patient. Management of complications that may arise while the patient is mechanically ventilated is of utmost importance such as deep venous thrombosis, stress ulcers and gastrointestinal bleeding. Acute therapy of MC usually includes either plasma exchange therapy, immunoadsorption or IV immunoglobulins (IVIg). The resulting improvement with these therapies is usually transient and needs to be followed by long-term immunosuppression with either corticosteroids or another agent such as azathioprine, cyclosporine or mycophenolate.