Myasthenia gravis is a rare disease characterized clinically by an abnormal and
progressive muscular weakness, with recovery after a period of rest. It is one
of the best known autoimmune diseases and the antigens and mechanisms of the
disease have been precisely identified. Muscle weakness is caused by circulating
antibodies that block postsynaptic cholinergic receptors or the muscle-specific
tyrosine kinases (MuSK) proteins of the neuromuscular junction, inhibiting the
stimulating effect of the neurotransmitter acetylcholine. The cause is an
alteration of nerve impulse transmission at the neuromuscular junction. The
pathogenesis is autoimmune, from autoantibody reaction towards cholinergic
receptors located in the motor plate. Anticholinesterase drugs work by
inhibiting the cholinesterase enzyme, which degrades acetylcholine, increasing
its plaque concentration and temporarily restoring neuromuscular transmission.
Symptoms
The most frequent symptoms at the onset are eyelid ptosis and diplopia. The
muscles of chewing, swallowing (dysphagia) and phonation (dysphonia) can be
involved. The involvement of the facial muscles causes amimia, with a typical
smile with half-closed lips and a falling jaw. The head is kept hyperextended to
compensate for the vertical reduction of the visual field due to the palpebral
ptosis. Sometimes there may be ptosis of the head due to hyposthenia of the
nuchal muscles. The involvement of the muscles of the shoulder girdle is evident
in the difficulty in performing repetitive movements with the arms raised, such
as combing. Hypostenia of the muscles of the lower limbs can determine the onset
of an anserine gait. In more advanced or more severe cases respiratory muscles
are also affected. At the onset of the disease, the symptoms are mild and recede
after a short period of rest. Subsequently, the weakness is accentuated and the
period of rest necessary for the functional recovery gradually lengthens, until
the onset of an almost continuous functional paralysis.
Aggravation of symptoms
The symptoms are aggravated during pregnancy, during the menstrual cycle, during
a general anesthesia, for the administration of commonly used drugs (aminoglycoside
antibiotics, beta-blockers, curaria, quinidine: promazine, tranquilizers) and
following infections of the respiratory tract. they can trigger a mystical
crisis.
The myasthenic crisis
The myasthenic crisis is a medical emergency. The rapid worsening of symptoms
can lead the patient to respiratory failure and to tetraparesis within a few
hours. It can occur at any time: after the diagnosis of myasthenia, but in half
of the cases in the first two years. Dyspnea can be associated with swallowing
disorders, which can fade a serious state of anxiety that further worsens the
situation.
It is important to distinguish clinically the myasthenic crisis from the rarest
cholinergic aia, due to super-dosing of anticholinesterases. The cholinergic
crisis consists of a rapid increase in muscle weakness, associated with the
muscarinic effects of the drug (arterial hypotension, nausea, vomiting, pallor,
sweating, salivation, bronchial hypersecretion, diarrhea, pupillary miosis,
bradycardia). Recede with the slow administration of atropine sulfate (0.5-1
mg). With caution, edrophonium chloride (2 mg), m anticholinesterase with
immediate and short action (Tensilon test) can be injected, which provokes
aggravation in the event of a cholinergic crisis and a marked improvement in
symptoms in the event of a myasthenic crisis.
Therapy
Treatment of the myasthenic crisis involves the administration of neo-stigmin (Prostigmine
1.5 mg im or 0.5 mg iv), to be repeated in the absence of improvement. In the
meantime, the patient must be urgently hospitalized in an intensive care unit to
undergo intubated assisted breathing. Both plasmapheresis and immunoglobulins
are useful.
Outside of the acute crisis, the treatment of myasthenia gravis consists in the
use of an anticholinesterase, with a higher half-life than the previous ones,
pyridostigmine bromide (Mestinon 60 mg per os every 4-8 hours), associated, in
the most severe cases , to immunosuppressive therapies (cortisone, aza,
cyclophosphamide, plasmapheresis, immunoglobulin iv). The timecto-mia, for a
sure but not yet clarified role of the thymus, is indicated in all cases of
myasthenia gravis, with the exception of the forms with isolated ocular
localization, regardless of the presence or absence of thymoma.
neurology index
