Neuromuscular disorders Myasthenia gravis Eaton Lambert syndrome Botulism

MYASTHENIA GRAVIS • AUTOIMMUNE DISORDER • ANTIBODIES DIRECTED TOWRDS THE ACETYLCHOLINE RECPTORS AT POST SYNAPTIC MEMBRANE • AFFECTS ANY AGE • BUT MAINLY AGE 20 -30 YEARS • 2 FEMALE >1 MALE • ROLE OF THYMUS

Role of the thymus • Abnormalities of the thymus in 80 % • Production of T-cell lymphocytes which participate in the immune responses

Pathophysiology • Neuromuscular junction is composed of • I-Presynaptic nerve ending which contains the synaptic vesicles(Ach) • II. Synaptic cleft • III-postsynpatic membrane: Ach receptors • Reuptake of the Ach by choline-estetrase

Clinical features I • Fatigability

DEFINITION FAILURE TO SUSTAIN A MAINTAINED • OR REPEATED CONTRACTION OF STRIATED MUSCLES

Clinical features II • • Onset usually insidious Fluctuating weakness Weakness at the end of the day Extraocular muscles (ptosis) Bulbar muscles Limbs generalized

Clinical features III • • • Onset can be fulminant With involvement of respiratory muscles Weakness may be provoked by : Infection, hypo k. , hypocalcemia Drugs : Quinine. betablockers, phenytoin Sedatives (diazepam) Antibiotics Surgery, pregnancy

Clinical exam I • Look for fatigability • Examine motor power : first movement is normal • Repeat movements; weakness will appear • All muscles should be examined • Induce fatigue (no change of power in normal individual)

Clinical exam II • • • Every thing else is normal Reflexes unaffected No wasting No deformity Tone is normal No sensory change

Clinical exam III • May be associated with diseases • Malignancy • Autoimmune disorders. • Then look for associated features

Test to be used in the clinic : Tensilon test • • Technique: Inject edrophonium (10 mg in 1 cc) First 2 mg (0. 2 cc) If no hypotension or hypersensitivity Inject the rest (8 mg) Result: Weakness improves within 1 -2 minutes

CRISi. S I- Myasthenic crisis • II-Cholinergic crisis •

I. Myasthenic Crisis Precipitating factors Infections Changes of drugs Pregnancy Surgery • • •

II-cholinergic crisis Excessive use of • anticholinergic medication Myosis, diarrhea, • increased salivation • Abdominal cramps • bradycardia •

Investigations I • Logical (immune disorder) • Look for antibodies in serum EMG • Repetetive stimulation test • Technique : • Exert repetetive stimulation o nerve (ulnar) at 3, 10, 30 -50 (tetanization) and look for response > decremential response • Single fiber EMG : increased jitter. =delayed NMJ transmision

Investigations II • • Biopsy of the neuromuscular joint And electron microscope study Severe Loss of receptors Look for the thymus by CXR, CT, MRI

Neonatal MG • 12 -16 % of infant born to myasthenic mother have myasthenic features (ptosis, weakness, poor cry and suck) • Last up to 6 weeks • Due to transplacental transfer of maternal circulating anti-Ach receptor antibodies • Temporary administration of anti choline esterase agents may be needed

Treatment I • • • 1 -Anticholine esterase agents A-Short acting : neostigmine (Prostigmine) B-Long acting : pyridostigmine (Mestinon) 20. 60 and 180 mg 2 -4 times a day SE : increased bronchial secretions bronchspasm, miosis, diarrhea, abdominal cramps, bradycardia

Treatment II • Reduce circulating antibodies • Plasmpheresis

Treatment III : immunemodulation • Steroids • Immunosupressants • IVIG

Treatment VI Thymus • Thymectomy • Thymic hyperplasia ? More common : 70%

EATON LAMBERT SYNDROME I • Male > female • Later onset • Associated with oat cell carcinoma of the lung in 70% • Affects mainly lower extremities • Clinically initial fatigability-weakness which improves on continuing the effort • Due to impairment of the Ach release in the presynaptic part

E-L syndrome II • Neurophysilogy: incremental response • Treat the underlying cause

Botulism • Bacterial : clostridium botilinum an anaerobic spore forming bacteria -> very strong toxin • May be present in improperly canned food • In raw meat • Toxin impairs pre-synaptic Ach release • Leads to severe weakness and autonomic features

Botulism • • Supportive treatment Tracheostomy Death in about 15 % Botulinum toxin (Botox) is used in dystonia, spasticity and for cosmetic purposes