Question 20

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

• Antecedent viral illness;
  usually with diarrhoea
• Surgery
• Campylobacter jejuni
• HIV

• Autoimmune diseases, eg. SLE
• Thyroid disease
• Pregnancy
• Thymoma

• 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

• Mild or absent

• No sensory loss

• Absent

• Reflexes are usually normal

• Common

• Earliest manifestations are cranial nerve signs (ptosis and diplopia)
• Facial muscles become involved early; patients become expresisonless

• Common

• Uncommon

• 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).

• 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".

• 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".

• 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)