Guillain-Barré Syndrome By: Brittany Wyger, MD (PGY-1)

Definition Group of neuropathic conditions characterized by progressive weakness & dimished or absent reflexes. Inflammatory neuropathy due to cross reactivity between neural antigens & antibodies induced by specific infections Campylobacter (most common) but also reported following: Mycoplasma Pneumoniae, Hemophilus Influenza, CMV, EBV

Epidemiology Estimated annual incidence in the United States is 1.65 to 1.79 per 100,000 persons Incidence increases from 0.62 per 100,000 in those <9 years old to 2.66 per 100,000 in those 80-89 years old Male-to-female ratio is 3:2

Preceding illness Most common symptoms reported before onset of Guillain-Barré Syndrome are: fever, cough, sore throat and other upper respiratory symptoms Infection with Epstein-Barr virus has been linked to milder forms of Guillain-Barré Syndrome GI symptoms may be more likely to precede Guillain- Barré subtypes that are related to slower recovery and higher risk of residual disability

Guillain-Barré Syndrome Subtypes Acute inflammatory demyelinating polyradiculopathy Multifocal peripheral demyelination, slow remyelination, both humoral and cellular immune mechanisms Most common subtype (90% of Guillain-Barré Syndrome in the US) Acute motor axonal neuropathy Antibodies against gangliosides GM1, GD1a, GalNAc-GD1a and GD1b in peripheral motor nerve axons 5-10% of GBS cases Only motor symptoms Acute motor-sensory axonal neuropathy Similar to acute motor axonal neuropathy but with sensory axonal degeneration, predominantly sensory involvement

Guillain-Barré Syndrome Subtypes Miller Fisher syndrome Demyelination, immunoglobulin G antibodies against gangliosides GQ1b, GD3 and GT1a Rare, 3% of GBS cases in US Bilateral opthalmoplegia, ataxia, areflexia, facial & bulbar weakness in 50% of cases Trunk, extremity weakness occurs in 50% of cases Acute autonomic neuropathy Mechanism is unclear Autonomic symptoms, sensory loss Recovery is slow and may be incomplete

Presentation Presentation: Symmetrical weakness (ascending) Decreased or absent reflexes Also commonly seen: Weakness, numbness, tingling & pain in the limbs 25% of patients will have advancing weakness that compromise the respiratory muscles- will require mechanical ventilation

Presentation Respiratory failure is more common in patients with rapid progression of symptoms, upper limb weakness, autonomic dysfunction or bulbar palsy Facial, oropharyngeal & oculomotor muscles may be affected because of cranial neuropathy Autonomic symptoms include arrythmias, orthostasis, BP instability, urinary retention, decreased GI motility Pain is reported in 50-89% of Guillain-Barré Syndrome patients Pain is severe, deep, aching or cramping in muscles or back Difficult to control because pain is nociceptive and/or neuropathic

Disease progression Symptoms typically peak within 4 weeks, then plateau before resolving

Diagnosis Clinical criteria for diagnosis include: Lumbar puncture: Symmetric motor weakness (bilateral symptoms) Absent or decreased reflexes Lumbar puncture: Elevated protein in CSF, normal WBC count Protein level may be normal in the 1st week of symptoms, protein will be elevated in 90% of cases by then end of the 2nd week Nerve conduction studies: Slowed conduction (<60% normal velocity) or blockage of nerve conduction will be seen Must test at least 3 motor nerves & 3 sensory nerves, must avoid sural nerve (often normal in GBS) Can be used to track progression of the illnes

Differential Diagnosis Brainstem: Infection, stroke Spinal cord: compression, myelopathy, poliomyelitis, transverse myelitis Rhabdomyolysis Myasthenia gravis Toxicity: industrial chemicals and other toxins Infectious, inflammatory or toxic myopathy Lyme disease

Complications Neuropathic pain Autonomic dysfunction Hypotension, hypertension, arrythmias, bladder and bowel dysfuntion Increased risk of VTE Bulbar dysfunction & swallow difficulty, risk of aspiration

Complications Respiratory failure Close respiratory monitoring with frequent measurement of negative inspiratory force (NIF) should be instituted initially on all all Guillain-Barré Syndrome patients NIF is a noninvasive method to measure respiratory muscle strength Acceptable NIF range in Guillain-Barré Syndrome is - 20 to -40 at least Normal NIF is more negative than -60

Complications

Complications Predicts the need for mechanical ventilation Bulbar symptoms Inability to raise the head or flex the arms Inadequate cough Maximum expiratory pressure: < 40 cm H2O Maximum inspiratory pressure: < 30 cm H2O Vital capacity: < 60 percent of predicted or < 20 mL per kg Vital capacity, maximum inspiratory pressure, or maximum expiratory pressure reduced by at least 30 percent

Treatment Disease modifying therapy: IVIg- 400mg/kg/day x 5days OR 2g/kg/day x 2days Plasma exchange (Plasmapheresis) – optimal response if performed within 7 days onset Both IVIg and plasma exchange are equally effective according to the literature but combining them is not beneficial Mild Guillain-Barré syndrome cases benefit from 2 sessions of plasma exchange Severe disease often requires 4 sessions Corticosteroids are not recommended and may in fact delay long term recovery Plasma exchange- removes circulating antibodies, compliment, may require 4-6 exchanges over 8-10 days

Treatment Initial response to IVIg does not predict the outcome because patients may stabilize or continue to decline after therapy

Treatment Supportive care SQ anticoagulation & SCD’s to reduce risk of VTE Swallow eval in patients with facial or oropharyngeal weakness- risk of aspiration ICU monitoring- ANS dysfunction and risk of respiratory failure, patient can become very unstable very quickly

Treatment Bladder & bowel care ANS dysfunction Arrythmias Foley catheter, enemas & laxatives, erythromycin for treatment of ileus ANS dysfunction Paroxysmal HTN (24%), Orthostatic hypotension (19%), sustained HTN (3%) Severe HTN- use PRN Labetalol, Esmolol, Nitroprusside Hypotension- IV fluid boluses 1st, then low dose phenylephrine Arrythmias Sustained sinus tachycardia (37%)- requires no treatment Bradycardia & asystole (4%) Paroxysmal HTN (24%), Orthostatic hypotension (19%), sustained HTN (3%) Bradycardia & asystole (4%)- Atropine

Treatment Patients with limited mobility should be closely monitored for skin breakdown and treated appropriately Pain control- neuropathic pain in 40-50% of patients Gabapentin (Neurontin) Carbamazepine (Tegretol) NSAIDs TCA’s Tramadol Epidural morphine

Treatment Physical therapy and rehabilitation is recommended to decrease residual deficits and increase speed of recovery A supervised exercise program is also recommended to improve fatigue as well as functional abilities

Prognosis Even with appropriate treatment, 3% of patients with Guillain-Barré Syndrome will die 25% of patients will require mechanical ventilation which increases mortality risk Prognosis is worse in patients with rapid onset of symptoms, severe symptoms and in elderly patients Neurological deficits persist in 20% of patients, half of these remain severely disabled Up to 80% of patients experience persistent, severe fatigue after resolution of other symptoms

Prognosis Predicts long-term disability Absence of motor response Diarrheal illness Axonal involvement Campylobacter jejuni or cytomegalovirus infection Inability to walk at 14 days Older age Rapid progression of symptoms Severity of symptoms at their peak

CME Questions Q: A patient presents with leg pain. Which one of the following accompanying findings most consistently suggests Guillain-Barré syndrome? (check one) A. Prominent bowel or bladder symptoms. B. Cerebrospinal fluid leukocytosis. C. Relatively symmetrical weakness of the limbs. D. Normal results on nerve conduction studies.

CME Questions Answer: C. Relatively symmetrical weakness of the limbs

CME Questions Q: Which one of the following statements about disease- modifying therapy for Guillain-Barre syndrome is correct? (check one) A. Plasma exchange should be witheld for the first 30 days after symptom onset. B. Intravenous immune globulin therapy should be started within two weeks of symptom onset, and should be considered for patients who are nonambulatory. C. Most patients require six sessions of plasma exchange. D. Corticosteroids are first-line treatment.

CME Questions Answer: B. Intravenous immune globulin therapy should be started within two weeks of symptom onset, and should be considered for patients who are nonambulatory.

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