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Myasthenia gravis (Neuromuscular disorder)
- 1. Neuromuscular junction disorders Dr Mohamed Rizk Khodair Lecturer of neurology Faculty of medicine
- 2. Introduction Diseases of the neuromuscular junction can be classified as either presynaptic (e.g., Lambert-Eaton syndrome, botulism) or postsynaptic (e.g., myasthenia gravis) .
- 3. Disorders of Neuromuscular Junctions Myasthenia Gravis Lambert Eaton Syndrome Congenital Myasthenic Syndromes Botulism
- 4. Myasthenia gravis It is a disorder of neuromuscular junction (NMJ) causing easy fatigability of skeletal muscles. There is no weakness or atrophy .
- 5. Etiology Autoimmune production of antibodies against acetylcholine (nicotinic) receptors (AChR) in the NMJ. Antibodies are produced from B cells and helped by T cells in cultures of hyperplastic thymus. The production of these antibodies will lead to: a) Accelerating internalization of Acetyl choline receptor molecules. b) Destruction of junctional folds. c) Blocking binding of Acetyl choline to Acetyl choline receptor d) Reduction of postsynaptic Acetyl choline receptors e) Inefficient neuromuscular transmission. Patients become symptomatic when the number of AChRs is reduced to approximately 30% of normal.
- 6. Other autoimmune conditions associated with MG: Thyroiditis, Graves’ Disease, Rheumatoid Arthritis, SLE, Pernicious Anemia, Addison’s Disease, Vitiligo, NMO.
- 7. Clinical picture Age: at any age (20-40 years). Sex: females more than males = 3: 2 Easy fatigability on repetition of movement, but without weakness. Fluctuation of symptoms and diurnal variation; patient is better in the morning Temporary increase weakness occurs after: Vaccination, Menstruation, And Extremes of Temperature. The disease affects the skeletal muscle in a descending march: - Ocular muscles: Ptosis and diplopia (muscles affected are levator palpebrae superioris, (superior rectus, lateral rectus), usually asymmetric. - Facial muscles: Expressionless face, Myasthenic snarl on smiling (lip retractors are affected more than elevator's). - Bulbar muscles: Dysphagia, Nasal Intonation of Voice, And Nasal Regurgitation. - Upper limbs and Lower limbs weakness: (Proximal more than distal). In UL, deltoids, and extensors of the wrist' and fingers are affected most. Triceps > biceps. In LL, hip flexors, quadriceps, and hamstrings. - Respiratory muscles (more. with cholinergic crisis}. Recognize imminent respiratory failure. - Neck muscles and erector spinae muscles. o sensory, normal DTRs, no sphincteric manifestation .
- 8. Complications Myasthenic crisis (rapid respiratory deterioration and failure) Aspiration pneumonia.
- 9. Bedside tests Provoke weakness by repetitive or sustained use of muscles involved fatigue. Walker test: apply the sphygmomanometer, raise the pressure and the patient does repetitive movements with his hand ptosis appear. Ice pack test (i.e., placing ice over the lids) improvement in ptosis Counting test: it is a bed side test for follow up.
- 10. 1) Pharmacological Tests: • Prostigmine test: give atropine sulfate I.M. 9 (to guard against muscarinic side effects), plus prostigmine 2.5 mg IM (20 minutes later) à improvement of myasthenic symptoms after 20 minutes (improvement must be > 50%, sustained for 1 hour at least). • Tensilon {edrophonium) test: 1 mg test dose is given first then 8 mg Tensilon IV à improvement in one minute. 2) Neurophysiological Studies: • Repetitive Nerve Stimulation: low amplitude of action potentials with repetition. of movements, or decrement response; supramaximal, repetitive stimulation. Of the nerve (3 Hz) decreases in amplitude of the action potentials (compare 5th with 1st if > 10- 15% à MG) • Single Fiber EMG: more sensitive but difficult à increased jitter. • Routine NCS: normal. Click icon to add picture
- 11. 3) laboratory Tests: • Anti-acetylcholine receptor (AChR) antibody "most specific": positive in 90% with generalized MG, and 50-70% with pure ocular MG. • Anti-striated muscle antibody (in about 84% of with thymoma who< 40 years). • Anti-MuSK antibody (present in .1/2 of patients with negative results for antiAChR antibody}. MuSK plays a critical role in postsynaptic differentiation and clustering of AChRs. • Antistriational antibody (present in almost all patients with thymoma and MG, as well as in half of MG patients with. onset of MG at SO years or older). • Lab for associated thyrotoxicosis, thyroiditis, SLE, rheumatoid. 4) Muscle biopsy: • Widening of myoneural junction. • Normal presynaptic membrane. • Flattening of postsynaptic membrane. • Marked reduction of post synaptic proteins. • Increase lymphocytes. 5) Radiology: • X-ray (lateral view), CT chest to detect thymic enlargement (thymic hyperplasia in young, or malignant thymoma in old).
- 12. Treatment Initial Treatment Plan Choose inpatient care: For significant bulbar symptoms early on, low vital capacity, respiratory symptoms, or progressive deterioration. Choose outpatient care: For ocular symptoms, mild-to moderate limb weakness and mild bulbar symptoms. A. Pharmacological: 1) Acetylcholine esterase. (AChE) inhibitors: Pyridostigmine (mestinon): 60 mg tab 3-6 times/day long-acting effect, decrease by 4-6 hours Action: they inhibit the cholinesterase enzyme responsible for the destruction of Ach increase Ach in the MNJ. Side effects: a. Fasciculation, pupillary constriction. b. Increase secretions, lacrimation, salivation, bronchial, and diarrhea. c. Increase muscle contraction: bronchial asthma, incontinence to urine. d. Cardiac arrhythmias·; and cholinergic crisis.
- 13. 2) Prednisolone - Steroids indicated in patients who are not adequately controlled with cholinesterase inhibitors and are unsuitable for thymectomy. 3)Azathioprine - Azathioprine, with its actions predominantly on T cells. - It is prescribed for: - Those in whom corticosteroids are contraindicated. - Those with an insufficient response to corticosteroids as a steroid-sparing agent.
- 14. 4) Rituximab (anti-CD20 B-cell monoclonal antibody) 375 mg/m2 IV four times weekly reports of benefit in resistant cases. 5) Plasma exchange and IV immunoglobulin - Both may be used for patients in myasthenic crisis with severe bulbar and respiratory compromise. - Patients may also be pre-treated prior to thymectomy. - Patients with seronegative MG may also respond. The effects last 4–6 weeks. - Plasma exchange: five exchanges, 3–4 L per exchange over 2 weeks. - IV immunoglobulin: 0.4 g/kg/day for 5 days. 6) Thymectomy - Therapeutic benefit in MG (generalized and less often in ocular myasthenia): results in complete remission in some patients or a reduction in immunosuppressive medication in others.