With respect to Guillain Barre Syndrome and Myasthenia Gravis, compare and contrast the respective:

a) Clinical features. (30% marks)

b) Investigations needed to make the diagnosis. (30% marks)

c) Specific treatment strategies with the relevant evidence/recommendations for the strategies listed (40% marks)

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College Answer

Condition

Clinical Features

Investigations

Treatment Strategies

Guillain-Barre

Syndrome

Diarrhoeal prodrome

Autonomic instability Symmetrical, progressive ascending weakness with associated areflexia. Ventilatory failure May be cranial nerve involvement. Sensory loss usually mild or absent. 

Nerve conduction studies show demyelination (reduction in conduction velocities)

CSF analysis: high   protein and normal WCC

IVIG

Plasmapheresis

The use of plasma exchange or IVIG depends on the institution or whether the patient has a contraindication to IG such as IgA deficiency. Both have been shown to be equally efficacious. One Cochrane review suggested that IVIG given within 2 weeks of the onset was as efficacious as plasma exchange, and more likely to be completed than plasma exchange. Their combination is not supported.

Myasthenia Gravis

Fluctuating, often fatiguable, weakness and possible progression to ventilator failure but reflexes intact.

Ptosis with associated diplopia. 

Auto-antibodies against nicotinic Ach receptors and MuSK Antibodies

EMG and NCS

studies

Anticholinesterases e.g. Pyridostigmine – symptomatic

treatment more effective in antiAChR than MuSK Rapid Immunotherapy (IVIG and PLEX) – recommended for

myasthenic crises Chronic Immunotherpay

(Steroids and immunosuppressants) – majority require this with

antiAChase Thymectomy – not recommended routinely for age>60 unless thymoma present

Discussion

a)

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

b)

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".

c)

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 answersuggests 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

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.

Hughes, Richard AC, Anthony V. Swan, and Pieter A. van Doorn. "Intravenous immunoglobulin for Guillain‐Barré syndrome." The Cochrane Library (2014).

Sussman, Jon, et al. "Myasthenia gravis: association of British Neurologists’ management guidelines." Practical neurology 15.3 (2015): 199-206.