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Myasthenia Gravis
Essentials
- Myasthenia gravis is arare autoimmune disease, in which the function of the myoneural junction of the voluntary muscles is impaired
- Symptoms include variable degrees of fatigue and weakness in voluntary musculature, which is aggravated by strain - often towards evening - and relieved by rest.
- Two main types:
- Ocular, limited to the eye muscles (ca. 15% of the cases)
- Generalised; the symptoms are usually most prominent in nuchal muscles and in the proximal muscles of the shoulder and pelvic region.
- Treatment is the domain of neurology units.
- Patients with myasthenia are very sensitive to drugs: check always the compatibility with myasthenia when starting a new drug for a myasthenic patient!
Epidemiology and aetiology
- The incidence of myasthenia gravis is about 4.1-30 cases per 1 million person-years and prevalence about 150-200 cases per million http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196750/ http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=589.
- In myasthenia gravis, antibodies are formed, most typically, against the acetylcholine receptors (AChR) of the postsynaptic membrane in the neuromuscular junction, whereby the number of receptors is reduced and impulse transmission is impaired in the synaptic cleft.
- In the generalised disease there are often AChR antibodies (in 80% of the patients), in the ocular form only in about one half of the patients.
- Anti-MuSK (muscle specific kinase) antibodies are found in about 4-5% of the patients.
- Thymic hyperplasia is found in ca. 70% of patients; ca. 10% have a benign thymoma. The onset of the disease may not occur until several years after the discovery of the thymoma.
Symptoms
- Double vision, uni- or bilateral ptosis
- Bulbar symptoms: nasal tone of speech and tiredness when speaking, difficulty in swallowing
- Facial muscle weakness: hypomimia, grimacing/whistling are not possible
- Muscle fatigue in neck muscles and proximal muscles of the limbs and pelvis
- Clinical symptoms vary.
- The patient may be asymptomatic in the morning or after rest; symtoms are often more prominent towards evening.
Accompanying disorders
- About 15% of the patients have also another autoimmune disease.
- Autoimmune thyreoiditis, arthritis, SLE, pernicious anaemia, coeliac disease, Sjögren's syndrome
- Clinical demonstration of muscle fatigability in muscle stimulation tests
- Serum anti-AChR antibodies and, if needed, anti-MuSK antibodies
- Neurophysiological tests: myasthenia EMG, or jitter EMG, includes single-fibre EMG and repetitive nerve stimulation (RNS) tests.
Differential diagnostics
- Myopathies, myositis, myasthenic syndrome, congenital myasthenia, Guillain-Barré syndrome, polyneuritides, tumours in the brainstem (when ocular and bulbar symptoms are present), MS, ALS, hypokalaemia, hypocalcaemia, hypomagnesaemia, hypothyroidism, burn-out, depression, congenital strabismus/heterophoria
- None of the currently available pharmacotherapies for myasthenia have been studied with modern, controlled research methods, but they have been found effective and safe in decades' use.
- Treatment is symptomatic. The primary medication is pyridostigmine Acetylcholinesterase Inhibitor Treatment for Myasthenia Gravis
- Overdose may cause a cholinergic crisis, whose differential diagnosis from a myasthenic crisis is difficult based on symptoms.
- Symptoms of overdose: diarrhoea, muscle twitches, increased salivation and muscle weakness, which is aggravated after taking the medication
- During follow-up visits, ask the patient about overdose symptoms, since they can be helpful in adjusting the dosage of medication.
- Thymectomy is considered in generalised myasthenia if the patient is below 70 years old.
- Immunosuppressive medications if the effect of pyridostigmine is not sufficient
- Glucocorticoid either orally or intravenously as pulse therapy Corticosteroids for Myasthenia Gravis
- methylprednisolone pulse therapy may initially, paradoxically, worsen muscle fatique
- Azathioprineis used as a so-called cortisone-sparing treatment; the effect is shown within 6 months
- It is used in an attempt to be able to get rid of continuous glucocorticoid therapy.
- Plasmapheresis (primarily in myasthenic crisis).
Myasthenic crisis
- Some ordinary infection is the most common triggering factor.
- The symptom is pronounced muscle weakness, most importantly weakness of the respiratory muscles and bulbar symptoms.
- Treatment
- Respiratory therapy, do not rely on arterial acid-base balance values
- Intravenous anticholinesterase medication
- Plasmaphaeresis or intravenous immunoglobulin as needed
- After the crisis, a permanent immunosuppressive medication is started (see above)
Prognosis
- Following thymectomy, the disease is relieved in ca. 70% of all patients, but a complete remission is rare.
Special problems
- Infections
- These often aggravate the disease symptoms
- Influenza vaccination and other vaccinations belonging to a national immunization programme are indicated, irrespective of pharmacotherapy for myasthenia.
- Vaccinations containing live attenuated viruses should not be used during immunosuppressive medication.
- Do not use expectorants or respiratory centre-depressing antitussives. Teophylline or ephedrine (special permit may be required) often relieves bulbar and respiratory muscle weakness during infections.
- Limitations concerning most common medicines
- Absolutely contraindicated: botulinum toxin, intravenous magnesium, macrolides and fluoroquinolones
- To be used with caution (because they may aggravate symptoms): beta blockers, calcium blockers, macrolides, sertraline, citalopram, lithium, amisulpiride, gabapentin, contrast media containing iodine and chloroquine, aminoglycosides, statins
- Glucocorticoids in different forms (oral, as an infusion) can temporarily worsen symptoms, but they are used for acute and long-term treatment of myasthenia.
- Pregnancy and parturition require monitoring by a specialist. Breastfeeding can be undertaken in the normal manner.
- The newborn may develop a transient neonatal myasthenia gravis (the anti-acetylcholine receptor antibodies are transferred from the mother to the foetus through the placenta). The symptoms appear in 3 to 6 days after birth and disappear in about 3 weeks. A mother with myasthenia gravis should stay in hospital about 6 days after delivery.
- When anaesthesia is planned, the staff must absolutely be informed if the patient has myasthenia gravis. Slow recovery from anaesthesia may actually be the first symptom of myasthenia.
Dental care
- Pyridostigmine medication should be taken one hour before a dental procedure.
- Local anasthesia (lidocaine + adrenaline) suits most patients.
- If there are severe myasthenia symptoms despite medication, the patient should receive dental care in hospital.
References
- Narayanaswami P, Sanders DB, Wolfe G ym. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology 2021;96(3):114-122. [PubMed]
- Gronseth GS, Barohn R, Narayanaswami P. Practice advisory: Thymectomy for myasthenia gravis (practice parameter update): Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 2020;94(16):705-709. [PubMed]
- Wolfe GI, Kaminski HJ, Aban IB ym. Randomized Trial of Thymectomy in Myasthenia Gravis. N Engl J Med 2016;375(6):511-22. [PubMed]