Distinguishing Features of Guillain-Barre Syndrome

Created on Tue, 06/30/2015 - 23:35
Last updated on Wed, 06/29/2016 - 18:42

The college perpetually want the candidates to compare various "weakening" disease states to Guillain-Barre Syndrome. In Question 10 from the first paper of 2013, the examiners had asked the candidates to compare its features with those of critical illness polyneuropathy. In Question 20 from the first paper of 2016, GBS was compared to myasthenia gravis.  GBS is discussed in greater detail elsewhere. It also receives a thorough LITFL treatment; so does critical illness polyneuropathy.

Guillain-Barre vs CIPN

In brief:

  • CIPN is associated with a severe illness, whereas GBS is associated with a mild one.
  • CIPN does not have autonomic dysfunction, whereas GBS does.
  • CIPN will not have any specific CSF findings, whereas GBS will have raised CSF protein and perhaps even a monocytosis
  • CIPN nerve conduction studies will not show any decrease in conduction velocity, whereas in GBS the cardinal feature is decreased conduction velocity.

The college answer is presented as a table.

A much better table is presented in the 2006 article by Upinder Dhand (Table 3, pp. 1034).

If one were to cut and paste this table into one's SAQ answer, the college examiners would have been very pleased. So impressive is it, that I have taken the liberty of reproducing it here with minimal modification, without any permission but with the best of intentions.

Differences between GBS and CIP

 GBS CIP History and Examination

Recent GI or resp illness. Progressive bilateral symmetric paralysis. Subtypes can be more localized e.g. MF opthalmoplegia and ataxia. Sensory involvement is common. Areflexic. Autonomic involvement may be present

Always occurs in association with a critical illness in particular severe sepsis. May have an association encephalopathy in early stages. It is a symmetrical weakness. May have muscle tenderness, hyporeflexic, diminished distal sensation Not associated with autonomic involvement

Investigations

Albuminocytologic dissociation in CSF. Identification of infection with campylobacter, mycoplasma, EBV,Varicella, CMV. Elevated csf IGG levels and possible serum antiganglioside antibodies

Elevated CK which may be transient.

Nerve conduction studies and EMG

When demyelinating form is present, you get a reduction in conduction velocity as well as reduction in CMAP. In axonal forms however it is only the distribution of the findings that helps determine the diagnosis.

A axonal neuropathy resulting in a decreased CMAP without a reduction in conduction velocity

Clinical Features and Laboratory Findings
Critical-Illness Polyneuropathy, Guillain-Barre´ Syndrome, and Critical Illness Myopathy
 

Critical illness polyneuropathy

Guillain-Barre

Critical Illness Myopathy

Clinical setting
 

Sepsis
Multiorgan failure

Septic encephalopathy

Antecedent viral illness

Surgery

Campylobacter jejuni

HIV

Neuromuscular blocking drugs

Corticosteroids

Asthma

Organ transplant

Motor weakness

Generalised and distal

Generalised and ascending

Generalised and proximal

Reflexes

Diminished

Absent

Preserved but weak

Cranial nerve palsy

Rare

Common

Absent

Dysautonomia

Normal autonomic function

Frequent dysautonomia

Normal autonomic function

Sensory deficit

Distal

Normal sensation, or slightly altered

Normal sensation

CK level

Normal

Normal

Elevated

Nerve conduction

Reduced CMAP and SNAP amplitude

(compound muscle action potentials and sensory nerve action potentials)

Marked slowing, conduction block

Reduced CMAP amplitude
Normal SNAP amplitude

Needle EMG

Abnormal spontaneous activity

Reduced recruitment

Large polyphasic motor unit potentials (MUPs)

Abnormal spontaneous activity

Reduced recruitment

Normal MUPs (early in disease)

Minimal spontaneous activity

Early recruitment

Small polyphasic MUPs;

Direct muscle stimulation

Normal

Normal

Absent or reduced

Muscle biopsy

Neuropathic changes

Neuropathic changes

Myopathic changes

Thick myosin filament loss

Muscle fiber necrosis

Guillain-Barre vs. myasthenia gravis

It would be possible but pointless to replicate the table above with myasthenia gravis plugged into the CIPN slot. Instead, a more directed approach will be taken, where clinical features, investigations and treatment are discussed in  atabulated form, best suited to answer Question 20 from the first paper of 2016.

Thus:

Clinical Features of Guillain Barre Syndrome vs. Myasthenia Gravis
Features Guillain-Barre Myasthenia Gravis
Clinical setting
 
  • Antecedent viral illness;
    usually with diarrhoea
  • Surgery
  • Campylobacter jejuni
  • HIV
  • Autoimmune diseases, eg. SLE
  • Thyroid disease
  • Pregnancy
  • Thymoma
Motor weakness
  • Generalised and ascending
  • Symmetrical
  • Not fatiguable
  • Weakness of the limbs is mainly distal
  • Weakness is progressive
  • Eye muscles are the first to go
  • Ptosis and diplopia are early features
  • Fatiguability (weakness worse after sustained exercise)
  • Neck extensor and flexor muscles
  • Weakness of the limbs is mainly proximal
  • Weakness fluctuates
Sensory loss
  • Mild or absent
  • No sensory loss
Reflexes
  • Absent
  • Reflexes are usually normal
Cranial nerve involvement
  • Common
  • Earliest manifestations are cranial nerve signs (ptosis and diplopia)
  • Facial muscles become involved early; patients become expresisonless
Dysautonomia
  • Common
  • Uncommon

Investigations of Guillain Barre Syndrome vs. Myasthenia Gravis
Guillain Barre Syndrome
  • CSF protein is elevated
  • GQ1b antibodies (Miller Fischer variant)
  • Nerve conduction studies: Marked slowing, conduction block
  • Electromyography: Abnormal spontaneous activity, reduced recruitment, normal MUPs (early in disease).
Myasthenia Gravis
  • Ice pack test: neuromuscular transmission should improve with cold; ptosis should be reversed when the eyelid is cooled with an icepack.
  • Edrophonium challenge: 10mg of edrophonium is given to transiently antagonise acetylcholinesterase. The myasthenic patient should immediately regain their muscle strength.
  • Acetylcholine receptor antibodies: (AChr-Ab)
  • Muscle specific tyrosine kinase antibodies (MuSK-Ab)
  • Repetitive nerve stimulation: the characteristic finding is a progressive decline in the CMAP amplitude.
  • Electromyography: the characteristic finding is "abnormal jitter".

Management of Guillain Barre Syndrome vs. Myasthenia Gravis
Guillain Barre Syndrome
  • Intubation and ventilation
  • Corticosteroids are counterproductive.
  • Plasmapheresis works: 4 exchanges of 1-2 plasma volumes, over 1-2 weeks.
    Plasma exchange for Guillain-Barre syndrome aims to clear the aetiological autoantibody from the bloodstream. In essence, we say "we have no idea which antibody is causing the demyelination, so we will get rid of all of them". The evidence seems to support a 5-treatment regimen; it seems that six treatments are no better than four. Because there is no missing proteins to replace, the exchanged plasma can be FFP or albumin - it does not seem to matter to the resolution of disease. However, because FFP has a slightly higher risk of transfusion reactions, so in general albumin is the recommended replacement solution, unless there are specific reasons to replace blood proteins.
  • IV immunoglobulin is at least as effective as plasmapheresis. Dose is 2g/kg, over 5 days. The college answer mentions a Cochrane review, probably referring to Hughes et al (2014) who demonstrated that in severe disease IVIG within the first 2 weeks "hastens recovery as much as plasma exchange".
Myasthenia Gravis
  • Thymectomy
    • Clear-cut indication in thymoma
    • In absence of thymoma, likelihood of remission is still twice as high if you get your thymus removed (Gronseth et al, 2000)
    • The college answer suggests that thymectomy is "not recommended routinely for age>60", which probably refers to the recent British guidelines (Sussman et al, 2015). They recommend thymectomy for under-45s within 2 years of diagnosis.
  • Maintenance therapy:
    • Acetylcholinesterase inhibitors:  pyridostigmine is the mainstay
    • Immunosuppressants:
      • Corticosteroids
      • Azathioprine
      • Mycophenolate
      • Cyclosporine
  • Crisis therapy:
    • Intubation and ventilation
    • Escalate steroids: eg. prednisolone 1mg/kg/d
    • Acetylcholinesterase inhibitors:  pyridostigmine as IV preparation
    • Plasmapheresis
      • Only useful as a short-term treatment
      • Only applicable in myasthenic crisis
      • Useful as a bridge to slower-acting immunosuppressants
      • Useful preoperatively before thymectomy
      • No real difference in outcomes when compared to IVIG (Gajdos et al, 2002)
    • Intravenous immunoglobulin
      • Like plasmapheresis, only useful as a short-term treatment and only applicable in myasthenic crisis
      • Usually given as 2g/kg over 5 days (i.e. 0.4g/kg per day)
      • A single dose of 1g/kg is probably equally effective (Gajdos, 2005)

 

References

Oh's Intensive Care manual:

Chapter   57   (pp. 617)  Neuromuscular  diseases  in  intensive  care by George  Skowronski  and  Manoj  K  Saxena

van den Berg, Bianca, et al. "Guillain-Barre syndrome: pathogenesis, diagnosis, treatment and prognosis." Nature Reviews Neurology 10.8 (2014): 469-482.

Yuki, Nobuhiro, and Hans-Peter Hartung. "Guillain–Barré syndrome." New England Journal of Medicine 366.24 (2012): 2294-2304.

Raphael, J. C., et al. "Plasma exchange for Guillain-Barré syndrome." Cochrane Database Syst Rev 2.2 (2002).

Venkata Umakant, K., B. Seshulakshmi, and B. Srinivasa Rao. "Miller Fisher Syndrome–An Atypical Clinical Presentation." Intern Med 3.119 (2013): 2.

Berlit, Peter, and Josef Rakicky. "The Miller Fisher syndrome: review of the literature." Journal of Neuro-Ophthalmology 12.1 (1992): 57-63.

Odaka, M., N. Yuki, and K. Hirata. "Anti-GQ1b IgG antibody syndrome: clinical and immunological range." Journal of Neurology, Neurosurgery & Psychiatry70.1 (2001): 50-55.

Alkan, Ozlem, et al. "Spinal MRI findings of guillain-barre syndrome." Journal of radiology case reports 3.3 (2009): 25.

Cabrera Serrano, M., and A. A. Rabinstein. "Usefulness of pulmonary function tests and blood gases in acute neuromuscular respiratory failure." European Journal of Neurology 19.3 (2012): 452-456.

Farrero, Eva, et al. "Guidelines for the Management of Respiratory Complications in Patients With Neuromuscular Disease." Archivos de Bronconeumología (English Edition) 49.7 (2013): 306-313.

Hughes, Richard AC, et al. "Supportive care for patients with Guillain-Barré syndrome." Archives of neurology 62.8 (2005): 1194-1198.

Massam, M., and R. S. Jones. "Ventilatory failure in the Guillain-Barré syndrome." Thorax 35.7 (1980): 557-558.

González-Suárez, Inés, et al. "Guillain-Barré Syndrome: Natural history and prognostic factors: a retrospective review of 106 cases." BMC neurology 13.1 (2013): 95.

Dhand, Upinder K. "Clinical approach to the weak patient in the intensive care unit." Respiratory care 51.9 (2006): 1024-1041.

Sanders, Donald B., and Janice M. Massey. "Clinical features of myasthenia gravis." Handbook of clinical neurology 91 (2008): 229-252.

Bird, Shawn J. "Clinical manifestations of myasthenia gravis." Up-to-date 16.1 (2008): 1-8.

Gronseth, Gary S., and Richard J. Barohn. "Practice parameter: Thymectomy for autoimmune myasthenia gravis (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology." Neurology 55.1 (2000): 7-15.

Gajdos, Philippe, Sylvie Chevret, and Klaus V. Toyka. "Plasma exchange for generalised myasthenia gravis." The Cochrane Library (2002).

Gajdos, Philippe, et al. "Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin: a randomized double-blind clinical trial." Archives of neurology 62.11 (2005): 1689-1693.