Myasthenia gravis

Disorders of neuromuscular junction are relatively rare. Myasthenia gravis is the prevalent one and Eaton-Lambert syndrome is less common. Those disorders cause specific muscle dysfunction. Patients suffering myasthenia have muscle weakness but it is not always an ordinary complaint of them. Palpebral ptosis, diplopia and blurry vision are the main complaints and reason to visit a doctor if patient is suffering from ocular form of myasthenia. Bulbar form of myasthenia manifests with slurred speech, nasal voice, chewing difficulty and dysphagia. Usually, symptoms are variable and tend to resolve after a rest or exacerbate after physical strain. Generalized form of myasthenia causes ocular symptoms, swallowing difficulties and other bulbar signs, and weakness of extremities’ muscles.

Presentation

In 85% of cases, ocular symptoms occur at the beginning of the disease and approximately 50-80% of patients will progress to generalized form in 2 years. If ocular form of myasthenia stays stable in two year period it is 90% it will not progress to generalized form at all. Usually, palpebral ptosis is asymmetric without any papillary disorders. Patients complain about blurred vision and diplopia which are more severe in the evenings and improve after a rest. Commonly patient can’t squint due to ocular muscle weakness.

In the begging, 15% of patients can have bulbar form of myasthenia. Main complains are slurred speech, chewing difficulty, inability to swallow, liquids are flowing back through the nose (caused by paresis of soft palate). Patient can’t maintain normal head position due to neck muscle weakness and it’s falling on to his chest, it’s called dropped head sign.

Muscles of extremities, neck, and torso are affected symmetrically and muscle weakness isn’t equal when comparing musculature of different parts of patient’s body. Weakness of respiratory musculature in complex with severe bulbar syndrome can be life threatening and even lethal without ICU and mechanical lung ventilation.

Myasthenia gravis considered being a young people disease this is not right because parallel to young –onset form (before 50, late onset form exists (after 50 years). Incidence of late onset myasthenia increases worldwide due to ageing and growing of human population. Neurologists face more patients suffering myasthenia and diagnostic serologic methods are improving.

Pathophysiology

The cause of characteristic muscle weakness in case of myasthenia evolves due to lesion in neuromuscular junction’s postsynaptic membrane (it’s a place where nerve ending connects with muscle’s membrane and electric impulse conduction from nerve ending to muscle happens here, with a help of acetylcholine – a specific substance that binds to muscle cell’s specific receptors and causes a depolarization with subsequent muscle contraction). Specific antibodies to acetylcholine receptors are produces in case of myasthenia; they are blocking impulse conduction to muscle cells. Rudimentary thymus’ tissues have an important role in pathogenesis of myasthenia; those tissues are promoting autoimmune reactions. 65% of patients with myasthenia have thymus’ hyperplasia and 10-15% have thymus tumor – thymoma. If patient have thymoma without myasthenia it’s 50% risk to get myasthenia in a life time.

Diagnostics

In case of generalized myasthenia 85% of patients got circulating antibodies to acetylcholine receptors, antibodies are 97-98% specific to myasthenia gravis. But false positive result can be in patients suffering from thymoma or Eaton-Lambert syndrome, small cell lung cancer, rheumatoid arthritis and systemic lupus erythematosus, or lateral amyotrophic sclerosis and also, patients who take penicillamine.  Elderly population (>70) and first degree relatives of patients with myasthenia in 1-3% of cases may have circulating antibodies to acetylcholine receptors. Remaining 15% of patients have other antibodies (MuSK, anti-thytin, anti RyR) and 10-13% has no antibodies found at all.

Nerve conduction studies, especially neurography are useful diagnostic tool assessing sensory and motor nerve impulse conduction by performing myasthenic reaction. If after a repetitive stimulation of motor nerve, decreases amount of reacting motor units this is a positive myasthenic reaction.  It’s necessary to stop taking anticholinesterase inhibitors 12 h (optimal 48h) before the procedure.

Thoracic CT to exclude a thymoma should be performed in every patient with myasthenia. Extensive workup should be performed to exclude any other oncology because it can cause so called myasthenic syndrome – condition with symptoms similar to myasthenia gravis due to cross-reaction of antibodies produces to fight tumor but attacking normal neural tissues because of structural antigenic similarity with tumor’s cells.

Therapy

To alleviate symptoms of myasthenia anticholinesterase inhibitors (Kalymin) are used but they do not treat the disease, they just take the weakness off.

Thymectomy is a resection of thymoma aimed to fight the oncology, not myasthenia.  Thymectomy is indicated in patient aged from 10 to 60 years, because there is an involution of thymus expected at puberty but elderly patients will have no any benefits from operation and exacerbation of myasthenia is expected. Thymectomy lowers concentration of antibodies and myasthenic symptoms are getting better.

Corticosteroids – are potent immunosuppressive drugs which give positive therapeutic effects on 2-3 week of treatment are the first line therapy. Full recovery is expected after a 3 months long therapeutic course with corticosteroids. It’s necessary to control bone mineral density regularly because corticosteroids cause osteoporosis.

Patients suffering a severe muscle weakness, especially with bulbar form can benefit from plasmapheresis or IVIG.

Azathyoprine and Cyclosporine are the second line drugs and they usually are administered simultaneously with corticosteroids because therapeutic effect is expected much later then in case of steroids. If corticosteroid therapeutic course is stopped but second line treatment was not initiated relapse of myasthenia is expected.

Patients with myasthenia should be recommended to do vaccinations against influenza and pneumococcus because any infection can cause an exacerbation or even a myasthenic crisis. Patients with myasthenia should star antibiotic therapy even in case of mild infection to prevent myasthenic crisis.