GBS MG crisis NMS and Serotonin syndrome GuillainBarre

GBS, MG crisis, NMS and Serotonin syndrome 雙和醫院神經科 洪千岱醫師

Guillain-Barre syndrome • Acute immune polyradiculoneuropathy predominantly characterized by flaccid weakness with areflexia, which in its most severe form can cause neuromuscular respiratory failure. • The syndrome is most often caused by demyelination (acute inflammatory demyelinating polyradiculoneuropathy [AIDP]), but an axonal type of greater severity exists (acute motor axonal neuropathy [AMAN]). • This section will focus on the diagnosis and management of patients with severe GBS associated with neuromuscular respiratory failure and requiring ICU care

Clinical features • The hallmark of the syndrome is the rapid development of ascending weakness associated with loss of deep tendon reflexes. • Cranial nerve deficits are present in approximately half of patients with GBS. • Dysautonomia is a major feature of severe GBS. Involvement of autonomic fibers can lead to cardiac arrhythmias, hemodynamic instability, gastroparesis, paralytic ileus, and urinary retention.

Respiratory Failure in GBS • Approximately 25% of patients with classic GBS. • Diaphragmatic failure can develop very suddenly and force emergency intubation. • Checking for the presence of a paradoxical breathing pattern. • A shorter interval between the onset of symptoms and hospitalization, more severe appendicular weakness and presence of bulbar or facial weakness are associated with a higher risk of respiratory insufficiency. • Patients with axonal GBS are also at increased risk of requiring mechanical ventilation.

Diagnostic work-up • A diagnosis of Guillain-Barre syndrome can be confirmed by electrophysiology and supported by the presence of elevated protein without increased nucleated cell count in the CSF. • Prolonged F-wave latency is usually the earliest sign of Guillain. Barre syndrome in nerve conduction studies. • Protein elevation in the CSF may be delayed and is not present in all cases.

Management • The first management priority when evaluating a patient with Guillain-Barre syndrome is to determine whether the patient needs admission to an intensive care unit. • Patients with Guillain-Barre syndrome with severe and rapidly progressive weakness should always be admitted to the intensive care unit for close monitoring. • Intubation and initiation of mechanical ventilation should not be delayed in patients with Guillain-Barre syndrome who develop early signs of ventilatory insufficiency or have substantial bulbar weakness.

Management • Immune therapy with plasma exchange or IV immunoglobulin (IVIg) is effective in patients with. GBS. • A full course of plasma exchange usually consists of five sessions (plasma exchange volume 250 m. L/kg each) over alternating days. • The full dose of IVIg is 2 g/kg (administered either as 0. 4 g/kg/d for 5 consecutive days or 1 g/kg/d for 2 days). • Plasma exchange and IVIg are comparably effective • The combination of plasma exchange followed by IVIg is not more effective than either treatment alone. • Corticosteroids are not beneficial in GBS.

Myasthenic Crisis • The presence of respiratory failure and the need for invasive or noninvasive mechanical ventilation. • About one-fifth of patients with MG will have at least one crisis during their disease course. • Common triggers include infections, surgery, and medication changes

Clinical Features • Ptosis, inability to sustain upgaze, bilateral facial weakness, jaw weakness, flaccid dysarthria, and very weak and fatigable limb muscles. • Cough is often weak. Poor vital capacity can be surmised when the patient cannot complete sentences and cannot count aloud from 1 to 20 in a single breath. • A paradoxical breathing pattern is a reliable marker of diaphragmatic weakness. • Cholinergic overactivity: increased miosis, salivation, and bronchial secretions, sweating, bradycardia, diarrhea, and, rarely, fasciculations

Diagnostic Evaluation • Serology, electrophysiology, or a therapeutic trial with a cholinesterase inhibitor. • In the ICU, these tests are only necessary when the patient does not have a previously established diagnosis of MG or the diagnosis is in question. • The value of pulmonary function tests in MG is much less well established than in GBS. • The fluctuating nature of weakness in patients with MG may result in variable and unpredictable measurements with serial spirometry.

Pharmacological Treatment • Plasma exchange and IVIg accelerate recovery in patients with MG exacerbation. • All patients with myasthenic crisis should receive corticosteroids. However, the ideal form of administration (eg, oral versus IV, optimal dose) in myasthenic crisis is not well established. • Pyridostigmine can be transiently discontinued after intubation to reduce respiratory secretions. Yet, pyridostigmine should never be stopped when the patient is receiving noninvasive ventilation and should always be restarted in adequate doses before initiating weaning from invasive ventilation

Neuroleptic malignant syndrome (NMS) • Idiosyncratic abrupt reaction to antidopaminergic drug treatment • Causative agents: – – “classic” neuroleptics, however the “atypical” agents have also been implicated other dopamine blocking drugs abrupt withdrawal of dopaminergic agents • Risk of NMS – male, young age, concomitant use of lithium SSRIs, high ambient temperatures, hyponatremia, dehydration, physical exhaustion, mental retardation, extrapyramidal syndromes, psychomotor agitation and a previous episode of NMS.

Clinical Phenomenon • Classic tetrad: hyperthermia, rigidity, altered mental status and dysautonomia • Can be associated with other signs: action and/or rest tremor, dystonia, chorea, myoclonus, seizures, ataxia, hyporeflexia and extensor plantar reflexes • May be associated with laboratory changes : High CK (>1000 IU/L), impaired liver, renal and coagulation status tests, leukocytosis, electrolyte disturbances, proteinuria and rhabdomyolysis with myoglobinuria

Management • Early recognition and offending medication withdrawal • Supportive care includes correction of volume and electrolyte imbalance, prevention of infection, thrombosis and pressure ulcers, and body cooling. • Patients with severe symptoms often require management in an intensive care facility • Pharmacological interventions – benzodiazepines or dantrolene: reducing muscle rigidity – reversing dopaminergic blockade: bromocriptine, levodopa or amantadine

Management • Finally, patients should be withdrawn of neuroleptics for, at least, two weeks after the termination of management of the acute phase of NMS. • Restart the background neuroleptic agent: low doses, slow titration, avoiding concomitant use of lithium, and close observation to prevent dehydration and the initial symptoms of NMS.

Serotonin syndrome (SS) • Combined use of two or more agents that enhance serotonin activity or concentration in the central nervous system • Acute development of agitation, mental status changes, myoclonus, incoordination, postural instability, hyperreflexia, rigidity and dysautonomic features (diaphoresis, fever, diarrhea, tachycardia and hemodynamic instability) after a change in serotonergic drug regimen • SS is not an idiosyncratic reaction, but a predictable one.

Offending drugs • Inhibitors of serotonin reuptake (SSRIs, tricyclic antidepressants, dextromethorphan, amphetamine and cocaine) • Inhibitors of serotonin metabolism (monoamine oxidase inhibitors [MAOIs]) • Serotonin precursors (L-tryptophan) • Enhancers of serotonin release (amphetamines, cocaine, fenfluramine) • Serotonin agonists (risperidone, sumatriptan, ergotamines) • Nonspecific enhancers of serotonin activity, as lithium and electroconvulsive therapy

Management • Withdrawal of the offending agents • Nonspecific 5 -HT receptor blockers, such as cyproheptadine and methysergide have been credited with shortening the syndrome’s duration • Others: benzodiazepines, chlorpromazine and propranolol • Supportive measures include treatment of seizures, cardiac arrhythmias, disseminated intravascular coagulation, muscle rigidity and hyperthermia.

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