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 III-postsynpatic membrane:Ach receptors 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 1cc) First 2 mg (0.2 cc) If no hypotension or hypersensitivity Inject the rest (8mg) Result: Weakness improves within 1-2 minutes

CRISiS 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