MYASTHENIA GRAVIS AND ALLIED DISORDERS

MYASTHENIA GRAVIS AND ALLIED DISORDERS

DEFINITION

MYASTHENIA GRAVIS AND ALLIED DISORDERS is a disease of unknown aetiology characterised by fluctuating weakness of skeletal muscles particularly ocular and other muscles innervated by cranial nerves with improvement by cholinergic drugs without any evidence of neural lesion associated with acetyl choline receptor antibodies circulating in the blood.

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AETIOLOGY

The exact cause of this disease is unknown. Now-a-days it is thought to be due to presence of circulating antibodies (IgG) to acetyl choline receptors (Arc-R). In about 15 % of cases a thymic tumour is present, but thymic hyperplasia is found in 70% of cases. Sometimes this condition may be associated with Thyrotoxicosis, Hashimoto’s disease, Rheumatoid arthritis, Carcinoma, Pernicious anemia, SLE. Myasthenic syndromes are seen sometimes after therapy with D-penicillamine, Lithium, Propranolol, Aminoglycoside antibiotics like Neomycin, Kanamycin, Streptomycin etc. These are called secondary myasthenia gravis.

CLINICAL FEATURES

Age: Common in 2nd and 3rd decades but may occur even in new borns. When it occurs in old age, usually Thymoma is associated.

Sex: Both sexes are affected but in 2nd and 3rd decades, females are more often affected with HLA-DR3.

The characteristic symptom is abnormal fatiguability of skeletal muscles which become rapidly tired. This tiredness is prominent at the end of the day. Muscles most often affected are extraocular, bulbar, neck and shoulder girdle muscles.

Rarely the respiratory muscles and pelvic girdle muscles are affected. The earliest symptom is ptosis and diplopia which may be intermittent and asymmetric. There may be tiredness during chewing, swallowing, speaking and in movement of limbs. The pupils are never involved. Facial and pharyngeal muscles are affected in 75% of cases. The tongue is very week and sometimes furrowed on either side and is called trident tongue. Pharyngeal, laryngeal and palatal palsies may also develop. Due to weakness of masseter muscle mouth may not be closed and the jaw gradually hangs down. This is called “hanging jaw sign.”

All these symptoms may wax and wane from time to time. Relapses are seen during emotional upsets, severe muscular exercise, pregnancy, premenstrual period or during generalized infection. Paralysis of muscles of respiration may lead to asphyxia and death.

In long-standing cases there may be atrophy of the involved muscles. Sensory, reflex and sphincteric changes are always absent.

Bedsides, diagnosis is made by asking the patient to look upwards continuously when gradually the upper eyelids will droop down or by asking the patient to count the digits (1-100) gradually when the voice will become husky. Normal individuals can count clearly and distinctly upto 62 digits but here patient will not be able to do it.

Edrophonium Test (Tensilon test): Edrophonium hydrochloride 10 mg IV (2 mg initially and if there is no reaction then remaining 8 mg IV30 seconds later) will give quick relief to motor weakness.

Alternately Inj. Neostigmin 1.5 mg can be given IM which will give similar improvement and will be long lasting This test should be done in the hospital because it may result in bronchoconstriction and syncope. So Inj. Atropin musst e available at hand.

INVESTIGATIONS OF MYASTHENIA GRAVIS AND ALLIED DISORDERS

1. Acetyl choline receptor antibodies may be present in 90% of cases. Antiskeletal muscle antibody indicates thymoma.

2. Stimulation of the motor nerve will result in a characteristic dimension of evoked action potential. Gradually decrease in muscle response to repetitive 2 or 3 Hz stimulation of motor nerves indicates a neuromuscular transmission disturbance. This can be seen even in strong muscles. Needle EMG of the affected muscles will show variation in configuration and size of the individual motor unit potential. Single fibre EMG reveals an increased jilter and variability from the same motor unit.

3. Chest X-ray (PA) may show a mediastinal mass which may be due to Thymoma (15%) to be confirmed by Tomography and CT scan. Absence of Thymoma does not rule out the diagnosis.

4. Muscle biopsy may show lymphorrhages.

TREATMENT OF MYASTHENIA GRAVIS AND ALLIED DISORDERS

General

Avoid fatigue, exercises, infection, aminoglycoside drugs etc.

Drugs

Prostigmine 15-45 mg orally 4 times daily can be given. In several cases Prostigmine 2.5 mg IM may be required. To minimize the side effects of this drug, Atropine 0.6 mg may be injected 15-20 mins before or Propantheline bromide 15 mg twice may also be given. Long-acting drugs like Pyridostigmine (Mestinon) 30-180 mg may be given; 60 mg of this drug is equivalent to 15 mg of Prostigmine. Very large doses of Prostigmine may lead to “Cholonergic crisis” characterised by sweating, pallor, fasciculation, small pupil and salivation. Should these occur Atropine injection must be given at once. If there is evidence of repiratory distress artificial respiration may be started. Thymectomy may give rise to permanent cure in many cases, particularly in young females where the duration of the disease is not more than six years. 10 % of thymoma cases and 80% of non-thymoma cases will show improvement after operation.

In patients with thymoma X-ray irradiation may be given before operation. Steroids may be given when there is inadequate response with Anticholinestarase. An initial high dose, e.g, Prednisolone 60-100 mg and gradually tapering the dose to a maintenance level can be done. Azathioprine (2-3 mg daily) and plasmapheresis may also be done.

MYASTHENIA GRAVIS AND ALLIED DISORDERS