F.Ahmadabadi MD Child Neurologist July 2015 ARUMS

1. F.Ahmadabadi MDChild NeurologistJuly 2015ARUMS Guillain-Barresyndrome & Myasthenia Gravis

2. Lower Motor Neuron Disease Neuronopathyas SMA Neuropathy as Guillain- barre Neuromuscular Junction as Myasthenia gravis Myopathy as dystrophies

3. Part 1 Guillain-Barre

4. Etiology • Post infectious autoimmune peripheral neuropathy • Mainly motor but sometimes sensory and autonomic nerves • Most patients have a Demyelinating neuropathy • Often occurs after a respiratory or gastrointestinal infection by about 10 days. • Infection with Campylobacter jejuniis associated with a severe form of the illness. • Following vaccines against Rabies, Influenza, Poliomyelitis (oral)and Possibly Conjugated Meningococcal vaccine.

6. ClinicalManifestations • Areflexia, flaccidity, and ascending symmetric weakness • Tenderness on palpation and pain (initial) Deep tendon reflexes are absent even when strength is relatively preserved. • Sensory signs are usually minor compared with the dramatic weakness • Bulbar involvement occurs in about half of cases • Dysphagia and facial weakness are often impending signs of respiratory failure Gag is very Important

7. Clinical Man… • Dysfunction of autonomic nerves can lead to: BP Changes, Tachycardia, and other arrhythmias Urinary or stool incontinance or retention; or episodes of abnormal sweating, flushing, or peripheral vasoconstriction • Preservation of bowel and bladder function, loss of arm reflexes, absence of a sensory level, and lack of spinal tenderness would point more toward Guillain-Barré syndrome

8. Miller Fisher variant: Ataxia,Ophthalmoplegia,Areflexia • Chronic relapsing polyradiculoneuropathy Recur intermittently or do not improve for a period of months or years • Congenital Guillain-Barresyndrom • Rare Generalized hypotonia, weakness, and areflexia in an affected neonate in the absence of maternal neuromuscular disease. Prognosis &Outcome 75% Cure (1-12 mo) 20% mild Sequels 5% Mortality 7% acute recurrence

9. Differential diagnosis • Porphyria • vasculitis, • Nutritional deficiency (vitamins B1, B12, and E) • Endocrine disorders • Infections (diphtheria, Lyme disease) • Toxins (organophosphate, lead)

10. Laboratory and Diagnostic Studies • Albuminocytologic Dissociation (2nd week) • NCV and EMG also may be normal early in the disease • Electromyography shows evidence of acute denervation of muscle • (CK) level may be mildly elevated or normal

11. Treatment • Moderate or severe weakness or rapidly progressive weakness should be cared for in a pediatric ICU. • Endotracheal intubation should be performed electively in patients who exhibit early signs of hypoventilation accumulation of bronchial secretions, or obtunded pharyngeal or laryngeal reflexes. • IV immunoglobulin is beneficial in rapidly progressive disease. • Plasmapheresis, and/or immunosuppressive drugs are alternatives, if IVIG is ineffective. Steroids are not effective .

12. Prognosis &Outcome 75% Cure (1-12 mo) 20% mild Sequels 5% Mortality 7% acute recurrence • Direction of cure GagExtremitiesDTRs • Poor outcome • Cranial nerve involvement • Intubation, and • Maximum disability at the time of presentation Conduction block is predictive of good outcome

13. Myasthenia Gravis Part 2

14. Etiology & Epidemiology • Autoimmune (complement-mediated ) • antibodies to the acetylcholine receptors at the neuromuscular junction

15. Clinical Manifestations • Classic myasthenia gravis may begin in the teenage years • onset of ptosis, diplopia, ophthalmoplegia, and weakness of extremities, neck, face, and jaw • Gradually worsen as the day progresses or with exercise • Two Subtypes • Ophthalmic Myasthenia • Systemic Myasthenia

16. Diagnostic Studies • IV edrophonium chloride (Tensilon) transiently improves strength and decreases fatigability. • Antiacetylcholine receptor antibodies often can be detected in the serum. • Repetitive nerve stimulation shows a decremental response at 1 to 3 Hz.

18. Treatment • Acetylcholine esterase inhibitors (pyridostigmine [Mestinon]) • Thymectomy • Prednisone • Plasmapheresis • Immunosuppressive agents. When respiration is compromised, immediate intubation and admission to an ICU

19. Neonatal Transitory Myasthenia Gravis • 10-20% of myasthenic mothers • Symptoms persist for 1 to 10 weeks (mean 3 weeks) Almost all infants born to mothers with myasthenia have antiacetylcholine receptor antibody, but neither antibody titer nor extent of disease in the mother predicts which neonates have clinical disease. • Diagnosis is made by showing clinical improvement lasting approximately 45 minutes after IM administration of neostigmine methyl-sulfate, 0.04 mg/kg. • Treatment with oral pyridostigmine or neostigmine 30 minutes before feeding is continued until spontaneous resolution occurs.

20. Congenital myasthenia • Its not an immune mediated. • Manifest as hypotonic infants with feeding disorders and variable degrees of weakness It has Three types: • Presynaptic(familial infantile myasthenia) • Synaptic(congenital end plate acetylcholinesterase deficiency) • Post Synaptic(slow channel myasthenic syndrome)