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

2. 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

3. Epidemiology
Estimated annual incidence in the United States is 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 years old
Male-to-female ratio is 3:2

4. 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

5. 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

6. 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

7. 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

8. 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

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

10. 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

11. 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

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

13. 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 to -40 at least
Normal NIF is more negative than -60

14. Complications

15. 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

16. 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

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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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.

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

26. 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.

27. 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.

28. THANK YOU!!