GUILLAIN BARRE SYNDROME (GBS)

Guillain Barre Syndrome (GBS)

Epidemiology

- Most common cause of acute flaccid paralysis in Western countries

- Overall incidence 1-2/100,000; up to 8.6/100,000 in elderly population

- All age groups can be affected, however, more common in elderly

- Bimodal peak, small peak in young adults and larger peak in elderly; rare in infancy

- 75% have an antecedent ‘event’ 1-4 weeks before onset of weakness:

respiratory (68%), GI (22%), resp and GI (10%), surgery (2%), vaccination or pregnancy

- Associated organisms: CMV, EBV, VZV, HIV, C. jejuni, M. pneumoniae, Shigella

Clinical course

- Initial paresthesias in fingers / toes followed by weakness

- Weakness rapidly worsens, sensory loss usually minimal

- Usually symmetric, though can be asymetric initially

- Classically distal weakness ascending up legs and arms, but proximal weakness not uncommon at onset

- Cranial nerve involvement (unilateral or bifacial weakness 50%, oculomotor paralysis 5%, characteristic in Miller Fisher Syndrome)

- 66% reach nadir in 2 weeks, 92% in 3 weeks; by definition MUST peak at 4 weeks

- Brief plateau phase then improvement and gradual resolution over weeks to months

Complications

Respiratory weakness / failure

20-30% will need intubation at some point during admission

Autonomic dysfunction (in up to 65%) including:

Arrythmias (sinus tachycardia, brady and tachy arrythmias)

Hypotension or hypertension, labile fluctuating BP

Ileus (beware of Ogilvy Syndrome)

Urinary retention

Pain (85%)

Typically back pain, radiculopathic and musculoskeletal (often ‘straight leg raise’ positive)

Papilledema (secondary to high CSF protein)

Compression neuropathies (particularly ulnar and peroneal)

DVT / PE

SIADH (26%)

Renal failure (secondary to IVIg treatment)

Hypercalcemia (secondary to immobility)

Hepatocellular dysfunction

30% early on, as high as 60% later in course

Diagnostic criteria for ‘typical’ GBS

Required features:

Progressive weakness in both arms and legs

Areflexia (or hyporeflexia)

Features supportive of diagnosis

Progression of symptoms over days to 4 weeks

Relatively symmetric

Mild sensory signs or symptoms

CN involvement, especially bilateral facial weakness

Recovery begins 2-4 weeks after progression ceases

Autonomic dysfunction

Absence of fever at onset

Typical CSF and EMG/NCS features

Pathophysiology:

- auto-immune

- develop autoantibodies / cell-mediated immune responses vs. myelin / gangliosides and consequently get segmental demyelination +/- axonal degeneration. In ~ 10% of cases immune response is directed against ganglioside epitopes in axonal membrane (molecular mimicry)

Types / Variants

Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)

Most common variant, 85% of cases

Primarily motor

Inflammatory demyelination +/- secondary axonal damage ('bystander effect')

Maximum of 4 weeks of progression

Acute Motor-Sensory Axonal Neuropathy (AMSAN)

Motor and sensory involvement with severe course

Respiratory and bulbar involvement

Primary axonal degeneration

Poorer prognosis

Acute Motor Axonal Neuropathy (AMAN)

Motor only with early and severe respiratory involvement

Primary axonal degeneration

Often children, young adults

Up to 75% positive C. jejuni serology, often also anti-GM1, anti-GD1a positive

Miller Fisher Variant

Triad: opthalmoplegia, sensory ataxia, areflexia

5% of all cases

96% positive for anti-GQ1b antibodies

Pharyngeal-Cervical-Brachial Variant

Often associated with IgG anti-GT1a

Presents with proximal descending weakness

Must distinguish from botulism and diphteria

Acute Pandysautonomia

Widespread sympathetic and parasympathetic failure

DDx

See Approach to Acute Flaccid Paralysis review

Management / Initial orders

- Admit for close observation until maximum progression reached and then as required

- ABCs!

- Diet: high protein, high caloric +/- NG tube and dietary consult as required

- Activity: bed rest, HOB <30 degrees

- Vitals q1h-q4h

- Spinal cord testing BID initially then OD

- CBC, electrolytes, urea, creatinine, glucose, liver enzmes, INR/PTT, bilirubin

- Serum protein electrophoresis and quantitative immunoglobulins (BEFORE starting IVIg)

- Anaphylaxis may occur more commonly in patients with IgA deficiency treated with IVIg

- Bedside spirometry (FVC/FEV1) BID-QID

- Cap gases daily and as required (see NOTE below)

- Pulse oximetry (see NOTE below)

- Telemetry / cardiac monitoring

- Initial ECG

NOTE:

- hypoxia, hypercarbia, acidosis are LATE manifestations of respiratory failure!

*** If FVC falls below 1L (15 cc/kg) or there is a rapid drop in volume, contact ICU, consider intubation

Specific investigations

Lumbar puncture / CSF analysis

- Do this PRIOR to treatment with IVIg (else will get falsely elevated protein)

- Send for cell count and differential, protein/glucose, oligoclonal banding, C/S, gram stain

- Typical profile: elevated protein (may take 1-2 wks. to develop) with normal to mild increase (<10) lymphocytes (albumino-cytologic dissociation)

- May be normal early on and 10% may have normal profile throughout course of disease

- In HIV associated GBS, get elevated protein AND lymphocytosis. This profile may also be seen in Lyme disease, sarcoidosis and lymphoproliferative disorders.

EMG/NCS (baseline and q1-2weeks)

- In typical AIDP, early on normal then develop loss of F waves and reduced conduction velocities (late slowing) with conduction block, can get reduced amplitude of CMAPs and signs of denervation on EMG, indicating axonal involvement

MRI

- Proximal nerve roots may be slightly hyperintense or enhance with gadolinium

Anti-ganglioside and campylobacter serology

- These are very expensive tests and should NOT be ordered routinely

- AMAN: C. jejuni, GM1, GD1a

- MFV: GQ1b

Stool cultures

Throat swab

Supportive treatments

- IV access with adequate hydration

- Foley catheter

- NG tube with feeds as required

- DVT prophylaxis: TED stockings and heparin 5000 units SC BID

- Nerve protectors to nerve pressure points to prevent sec. compression palsies

- OT / PT / swallowing consults

- Chest physiotherapy

- Pain control: NSAIDs or morphine, will usually require narcotics

- Aggressive bowel routine (lactulose or milk of magnesium PO 15-30 cc OD to BID, colace 100 mg PO BID, dulcolax supp OD prn, fleet prn)

- Psychological / social suport

Specific treatments

IVIg

- Improved 4 week and long term outcome

- 10% may have secondary worsening, which usually responds to repeated infusions

- Use as per protocol (fill out appropriate forms)

- Usual regimen 2 g/kg given over 2-5 days

- First 30 minutes at 25 cc/hour monitoring BP q5min

- If tolerated infuse remainder at 125 cc/h, monitoring BP q1h

- If allergic reaction, stop IVIg infusion, give 25 mg IV benadryl, MD to assess

- Potential complications: malaise, nausea, fever, rash, elevation in liver enzymes, renal failure, leukopenia, anaphylaxis, aseptic meningitis, sinus thrombosis

Plasma exchange

- Improves long term outcome if administered within first 2 weeks of disease

- Equally efficacious as compared to IVIg

- Give 2-5 cycles (50 cc/kg each) on alternating days depending on severity 10% may get secondary worsening, provide additional cycles

Steroids

Not effective

Prognosis:

- 20-30% require intubation

- 70% complete recovery at 1 year

- 25 -30% will have residual deficit

- Usually monophasic illness, 3% recur

- 3-5% mortality

Poor prognostic factors:

Age > 60, rapidly progression to quadriparesis over first week, intubation, mean distal motor amplitude less than 20% (axonal pattern)

References:

NICP. Bradley, Daroff, Fenichel, Marsden

Chalela. Seminars in Neurology 4:399-405, 2001

Hahn. Lancet 352: 635-641, 1998

Hahn. Bailliere's Clinical Neurology 5: 627-644, 1996

Last update: October 16, 2003

Reviewed by: Dr. A. Hahn

Neurological Medicine Pocketbook

http://www.uwo.ca/cns/resident

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