Disorders of the Neuromuscular Junction,Yijun Song May 2008,Outline,Review in normal anatomy and physiology of neuromuscular junctionMyasthenia GravisLamber-Eaton syndrome,Normal Anatomy and Physiology,Normal Anatomy and Physiology,Normal Anatomy and Physiology,Normal Anatomy and Physiology,Normal Anatomy and Physiology,Normal Anatomy and Physiology,Two of these disorders are well known clinically, which are manifested as weakness without sensory loss. Myasthenia Gravis: partial receptor blockade resulting in weakness that increases after exercise. Lamber-Eaton myasthenic syndrome: an impairment of release of acetylcholine from the nerve terminal, also resulting in weakness.,Myasthenia Gravis,Myasthenia gravis (MG) is an acquired autoimmune disorder characterized clinically by weakness of skeletal muscles and fatigability on exertion. MG affects the transmission of nerve impulses at the neuromuscular junction, causing the fluctuating weakness in voluntary muscle groups.,Etiology and Pathogenesis The primary cause is unknown. Immunological factors are clearly important. The pathogenesis is related with auto-antibodies destructive effects on Ach Receptor. Thymic hyperplasia is found in at least 70% of MG cases. In 10-15% of patients, a thymic tumor is found.,Pathophysiology The concentration of acetylcholine receptor on the muscle endplate decrease; Distortion and simplification of the postsynaptic muscle membrane; The blockade of the AChR by antibodies attached to the muscle membrane. Ach is normally released from the nerve,Symptoms of myasthenia gravis,1. The fluctuating nature of myasthenia weakness. The weakness varies during a single day. Patients usually show weakness after exercise or at afternoon.,2. The distribution of weakness: Ocular muscles could be affected in 40% of cases and ultimately involved in 95%. Ptosis and diplopia are the most common symptoms.,Symptoms of myasthenia gravis,3. The myasthenic weakness could be improved immediately after injection of cholinergic drugs, such as tensilon.,Symptoms of myasthenia gravis,Physical Examination Examination of patients with known or suspected MG must be performed in a way to detect fluctuating weakness in specific muscle groups. Ocular muscles are the best choice. Strength should be assessed repeatedly during maximum effort and after brief rest periods. Weakness can be present in a variety of different muscles and is usually proximal and symmetric.Sensory examination and deep tendon reflexes are normal.,Lab Studies 1. Anti-acetylcholine receptor antibody: The result of the test for the anti-AChR antibody is positive in 80-85% of patients. 2. Thyroid function tests should be done to evaluate for coexistent thyroid disease. 3. repetitive nerve stimulation of a muscle at 2-3Hz, the compound muscle action potentials amplitude decrease over 10%.,Pharmacological studies,Neostigmine test (Tensilon test ) : 0.5 or 1 mg of the drug with 0.5 mg atropine are given I.M. Muscular power improvement is appeared since 20 minutes up to 2 hours after drug injection. A positive response is a strong support for the diagnosis of MG. Sinus bradycardia is a serious complication of the Neostigmine test. An ampule of atropine should be available at the bedside or in the clinic room while performing the test.,Diagnosis Three characteristic symptoms Positive physical examination; sensory and tendon reflexes examination is normal. High titers of Anti-acetylcholine receptor antibody. EMG showed progressive decrement in compound muscle action potentials amplitude evoked by 2-3 Hz repetitive nerve stimulation. The results for neostigmine test is positive. Chest CT scan could identify thymoma, especially in older patients.,The modified osserman clinical classification of myasthenia gravis,1. Anticholinestrase drug therapy; 2. Plasma exchange or Plasmpheresis; 3. Thymectomy; 4. Steroids; 5. Other immunosuppressive drugs may be helpful.,Treatment,Anticholinesterase Drugs 1. Pyridostigmine, 30-180mg (average, 60mg) before three meals in a day. 2. Dosage individually determined. 3. Only provides symptomatic benefits without influencing the course of MG. 4. Small doses of atropine may attenuate side effects of Pyridostigmine such as bowel hypermotility or hypersalivation.,Plasma exchange (PE) is an effective treatment for MG, especially in preparation for surgery or as short-term management of an exacerbation. Improvement in strength may help to achieve rapid postoperative recovery and to shorten the period of assisted ventilation. Weakness improves within days, but the improvement effect only lasts 6-8 weeks.,Plasma exchange,PE usually is used as an assistance method to other immunomodulatory therapies and as a tool for crisis management.Long-term regular PE on a weekly or monthly basis can be used if other treatments cannot control the disease.,Plasma exchange,Crisis in myasthenia gravis The crisis is defined as deterioration of respiratory failure that require mechanical ventilation.,