Guillain-Barre Syndrome

Florentina Eller8/26/2014

Case

• CC: Lower extremities numbness and paralysis• HPI: MW is 34 yo female who is admitted to the hospital on 8/5 due to

numbness and paralysis in her right leg, weakness in her left leg, and inability to walk. She also complains of daily, non-bloody diarrhea for the last 2 months and some urinary incontinence. Patient lost 40 lbs in the last month. The burning she feels in both legs started 2 days ago. MW has thoracic, lumbar and sacroiliac pain as well. She denies any trauma, MVA or recent labor. She has not had any recent URI.

• PMH: HTN, anxiety, s/p cholecystectomy, T2DM, RA, fibromyalgia, asthma, hypothyroidism, hx of DVT.

• FH: Significant for CAD and MI• SH: Chronic smoker (1 pack/day for 18 years); denies alcohol or illicit

drug use

Case (cont.)• Home Medications: Synthroid 25 mcg PO QD; Metformin 1000 mg PO

QD; Prilosec PRN; Arava 20 mg PO QD; Hydroxychloroquine 200 mg PO BID; Endocet 10/325 PO Q 6H PRN pain; Valium 0.5 mg PO BID; Benicar 20 mg QD

• Allergies: codeine; penicillin• PE:

– Vital signs: T 97.6F; P 57bpm; BP 127/79 mmHg; RR 16 bpm; O2 sat 95%; – HEENT: PERRL; EOMI; no JVD; no lymphadenopathy; no meningism;– Cardiovascular: RRR; no murmurs, gallops, rubs; no LE edema; no calf

tenderness– Respiratory: CTA– GI: soft, nontender, nondistended– Psychiatric: Cooperative, but tearful– Integumentary: lower extremity cyst consistent with RA– Neurologic: Cranial nerves 2-12 intact; intact upper motor; lacking tendon

reflexes in LE

Problems

1. Bilateral LE paraplegia with paresthesias (neurology consult): Suspect AIDP; spine imaging and lumbar puncture is needed to rule out other causes; discuss IVIg tx with patient and if OK start Privigen 10% 35 g/350 ml IVPB every 24 H for 5 days (0.4 g/Kg max 2g/kg for 5 days); rule out infections or structural causes; cardiac telemetry to evaluate for arrhythmia; pain and anxiety rx.

2. Diarrhea: 3. Hypothyroidism, RA, HTN- continue home medications,

T2DM4. DVT prophylaxis

Guillain-Barre Syndrome (GBS) Introduction

• Definition: heterogeneous group of immune-mediated peripheral neuropathies– Common to all variants: rapidly evolving polyradiculoneuropathy

preceded by a triggering event– Cytomegalovirus or Campylobacter jejuni infection

• Prevalence: – GBS affects between 1 and 4 per 100,000 of the world’s population

annually.

• Prognosis: – 67% - persistent fatigue– 25% - respiratory failure requiring ventilation – 20% - persistent disability – 4% to 15% - death

Hughes RAC, Wijdicks EFM, Barohn R, et al. Practice parameter: immunotherapy for Guillain-Barré syndrome—report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2003; 61: 736–40.

Date of download: 8/24/2014 Copyright © 2014 McGraw-Hill Education. All rights reserved.

From: Section I. Cellular and Molecular Basis for Medical PhysiologyGanong's Review of Medical Physiology, 24e, 2012

From: Section I. Cellular and Molecular Basis for Medical PhysiologyGanong's Review of Medical Physiology, 24e, 2012

Subtypes of GBS

Harrison's Principles of Internal Medicine, 18ed. Chapter 385. Guillain-Barré Syndrome and Other Immune-Mediated Neuropathies. Access Pharmacy. Accessed 8/24/2014

.

GBS Pathophysiology AIDP

Ang CW, Jacobs BC, Laman JD. The Guillain-Barre Syndrome: a true case of molecular mimicry. Trends in Immunology. 2004. 25(2):61-66.

Signs and Symptoms

• Weakness• Tingling dysesthesias in the extremities

– legs more often affected than arms• Paresthesias

– seldom extends past the wrists and ankles• Loss of deep tendon reflexes

– within the first few days of symptom onset• Progressive phase lasts few days to 4 weeks• Plateau phase: persistent, unchanging symptoms• Improvement begins within days of the plateau

– The time to resolution of symptoms varies

Newswanger DL, Warren CR. Guillain-Barre Syndrome. Am Fam Physician. 2004 May 15;69(10):2405-10.

Diagnosis

Newswanger DL, Warren CR. Guillain-Barre Syndrome. Am Fam Physician. 2004 May 15;69(10):2405-10

• Required Factors:– Progressive weakness in both arms and legs– Areflexia (e.g. loss of knee jerk reflex)

• Strongly Supporting Diagnosis:– Progression of symptoms over days, up to 4 weeks– Relative symmetry of symptoms– Mild sensory symptoms or signs– Cranial nerve involvement ( bilateral weakness of facial muscles)– Recovery beginning 2-4 weeks after progression ceases– Absence of fever at onset– High concentration of protein in CSF

2003 American Academy of Neurology (AAN) Treatment Guidelines

Hughes RA, Wijdicks EF, Barohn R, et al. Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2003 Sep 23;61(6):736-40.

AAN Guidelines

• Treatment with PE or IVIg hastens recovery from GBS.• PE and IVIg are equally effective in patients with advance GBS symptoms.• PE may carry a greater risk of side effects and is more difficult to

administer.• Combining the two treatments is not recommended.• Steroid treatment is not beneficial. • High-dose IVIg (400 mg per kg daily for 5 days) or plasmapheresis (5

exchanges over 5-8 days) can be initiated. • Supportive care and monitoring for autonomic dysfunction

• Hughes RA, Wijdicks EF, Barohn R, et al. Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2003 Sep 23;61(6):736-40

• Newswanger DL, Warren CR. Guillain-Barre Syndrome. Am Fam Physician. 2004 May 15;69(10):2405-10

IVIg, PE or Combination RCT

• International, multicenter, randomized trial of 383 adult patients with Guillain-Barré syndrome.

• Objectives: – Whether IVIg is equivalent/ superior to PE– PE followed by IVIg is superior to single treatment

• Methods:– Random assignment to:

• PE (five 50 mL/kg exchanges over 8–13 days)• IVIg (Sandoglobulin, 0·4 g/kg daily for 5 days)• PE course immediately followed by the IVIg course. • Retreatment with original treatment was permitted if relapse

Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Randomized trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome. Lancet 1997 Jan 25;349(9047):225-30.

Outcomes Measurements: Disability Assessment Grades

Grades Disability Assessment Arm Assessment

0 Healthy; no signs or symptoms of GBS

Normal

1 Minor symptoms; able to run Minor symptoms; able to put hand on top of head and able to oppose thumb to each finger

2 Able to walk 5 m without assistance

Able to do one or the other @ 1 not both

3 Able to walk 5 m with assistance Some movement ; unable to perform either tasks above

4 Chair - bound; unable to walk No movement

5 Require assisted ventilation ( part of the day)

Dead

6 Dead N/A

Plasma Exchange Group. Lancet 1997.

IVIg, PE or Combination RCT (cont.)

• Inclusion criteria: – GBS diagnosis by a qualified neurologist

• Clinical and • Cerebrospinal-fluid diagnostic criteria

– Severe disease (requiring aid to walk or worse)– Older than 16 years– Onset of neuropathic symptoms within the previous 14 days

• Statistics– Equivalence definition: If the true mean difference in the improvement of

the disability grade among the two groups <0.5 – Power: 122 patients were expected to give 90% power to detect a true

difference of ≥0.5 in the IVIg versus PE comparison and to exceed 0

Plasma Exchange Group. Lancet 1997.

Treatment Groups Features

Plasma Exchange Group. Lancet 1997.

Primary Outcome and Results

Mean disability-grade improvement after 4 weeks: No significant difference between the groups

– Difference of improvement between PE vs IVIg : 0.09 grade (95% CI 0.23 to 0.42)

– Proved equivalence between groups– Difference between the PE+IVIg and IVIg alone groups: 0.29 grade

(95% CI 0.04 to 0.63)– The difference between the PE+IVIg and PE alone groups: 0.20 grade

(0.14 to 0.54). – The combined treatment was not superior to either treatment

alone

Plasma Exchange Group. Lancet 1997.

Adverse Events

• 8 cases in PE group : hypotension in five, septicemia, pneumonia, malaise, abnormal clotting, and hypocalcaemia

• 6 cases in IVIg group: nausea or vomiting, meningism, exacerbation of chronic renal failure, possible myocardial infarction, and painful erythema at the infusion site

• Conclusion– IVIg may be preferable to PE (in severe GBS that requires aid to walk

and the disorder was diagnosed < 2 weeks of onset) based on :• equal therapeutic benefit• greater convenience

Plasma Exchange Group. Lancet 1997.

Treatment of the patient• Bilateral LE paraplegia with paresthesias (neurology consult): Suspect AIDP; spine

imaging and lumbar puncture is needed to rule out other causes; discuss IVIg tx with patient and if OK start Privigen 10% 35 g/350 ml IVPB every 24 H for 5 days (0.4 g/Kg max 2g/kg for 5 days); rule out infections or structural causes; cardiac telemetry to evaluate for arrhythmia; pain and anxiety rx.

• Workup– MRI of cervical and thoracic spine: soft tissue density in the epidural space

causing effacement of the right lateral thoracic cord at C7, T1 and T2– LP: 2WBC, 11RBC, protein 48

• Patient was treated with 5-day course of IVIg; – Weakness in leg improved, discharged home after 6 days of hospitalization

• MW came back to hospital less than 24 hours later for almost the same complaint: – Progressive weakness in her LE and UE – Was able to walk but with difficulty

• Patient treated successfully with PE @5

Assessment of the Treatment• Patient received Provigen 10% 35 g/350 ml IVPB every 24 hours for 5

days • MW weighs 119Kg ( IBM 75.4Kg, AdjBW 92.6 Kg)

– If dosed at 0.4g/Kg* 119Kg= 47.6 g/day– Patient received 35 g/day (dosed based on ~ Adj BW : 37 g/day)

• Patient came back less than 24 hours later– MRI was ordered to asses for possible worsening of abnormal tissue density at

level C7-T12

• PE was ordered, @ 5 exchanges patient improved

Assessment: Starting with a higher dose of IVIg could have been more effective (use ABW instead of Adj BW)

Future Possible Treatment

• Chinese herbal medicine Tripterygium polyglycoside ( Thunder God Vine) – Significantly better outcome after 8 weeks compared with

high-dose corticosteroids*• Very low quality of evidence RCT, found after• Meta analysis of 1271 references to possible RCT

• Other trials not large enough to find clinical significant benefits – Interferon beta-1a (IFNb-1a) vs placebo– Brain-derived neurotrophic factor (BDNF) vs placebo– CSF filtration vs regular PE

*Hughes RA, Pritchard J, Hadden RD. Pharmacological treatment other than corticosteroids, intravenous immunoglobulin and plasma exchange for GBS. Cochrane Database of Systematic Reviews, Feb 01, 2013, No. 2.

Tripterygium wilfordii (Thunder God Vine)

http://en.wikipedia.org/wiki/Tripterygium_wilfordii