F.Ahmadabadi MD Child Neurologist July 2015 ARUMS Guillain-Barre syndrome & Myasthenia Gravis

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

Guillain-Barre Part 1 Guillain-Barre

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

Clinical Manifestations  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

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

o Miller Fisher variant: Ataxia,Ophthalmoplegia,Areflexia o Chronic relapsing polyradiculoneuropathy Recur intermittently or do not improve for a period of months or years o Congenital Guillain-Barre syndrom o 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

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

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

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.

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

Myasthenia Gravis Part 2

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

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

Diagnostic Studies 1. IV edrophonium chloride (Tensilon) transiently improves strength and decreases fatigability. 2. Antiacetylcholine receptor antibodies often can be detected in the serum. 3. Repetitive nerve stimulation shows a decremental response at 1 to 3 Hz. Repetitive nerve stimulation shows a decremental response at 1 to 3 Hz.

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

Neonatal Transitory Myasthenia Gravis o 10-20% of myasthenic mothers o 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. o Diagnosis is made by showing clinical improvement lasting approximately 45 minutes after IM administration of neostigmine methyl-sulfate, 0.04 mg/kg. o Treatment with oral pyridostigmine or neostigmine 30 minutes before feeding is continued until spontaneous resolution occurs.

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)