A 2-year-old girl, Amy, attends the emergency department. Her father says that for the last 24 hours she has been refusing to walk. Prior to this, she was running amuck without difficulty. In the ED, you notice that she is now having difficulty crawling. She has no significant medical history but did have fever along with a runny nose and cough 2 weeks prior to her attendance which her parents managed with paracetamol at home.
What is Guillain-Barré Syndrome?
Guillain-Barré Syndrome (GBS) is a group of acute immune-mediated polyneuropathies. It most commonly presents as an acute monophasic, paralysing illness provoked by a preceding infection.
It is the most common cause of acute flaccid paralysis in children. The annual incidence is 0.34 to 1.34 cases per 100,000 in under 18s, making it less common in children than adults. It rarely occurs in children younger than two years, but it can be tricky to diagnose when it affects younger children because GBS is way off our radars. Boys are affected more often than girls.
What causes it?
It’s thought that an immune response cross-reacts with the myelin or axon of peripheral nerves due to molecular mimicry. Similar peptide sequences between the body’s own peptides and foreign peptides sometimes cause the immune system to get confused and attack its own tissues. You probably knew that myasthenia gravis is due to auto-antibodies against the acetylcholine receptor but did you know that the receptor shares a 7 amino acid sequence with HSV, the herpes simplex virus? It’s thought that exposure to HSV may be the precipitant for myasthenia gravis.
Approximately 2/3 of patients give a history of an antecedent respiratory tract or GI infection. Campylobacter infection is the most commonly identified precipitant and can be demonstrated in as many as 30% of cases. Other infectious precipitants include CMV, EBV, Mycoplasma pneumoniae, and influenza-like illnesses.
Other suggested triggers include immunisation; although there is no clear causal relationship, several cases suggest an association, as well as one with trauma and surgery.
What about Guillain Barre and COVID?
Several case studies have reported GBS associated with SARS-CoV-2 during the COVID-19 pandemic. Given the small number of cases, it is unclear whether severe neurological deficits are typical features of COVID-19-associated GBS. An answer to the diagnostic problem of whether the respiratory compromise in COVID19-associated-GBS is due to coronavirus or muscle weakness is yet to be answered.
How can I recognise it?
GBS classically begins with paraesthesia in the extremities – fingers and toes – followed by lower extremity symmetric, or modestly asymmetric, weakness that ascends up the body. In severe cases, the muscles of respiration are affected, in about 10-20% of children.
Cranial neuropathy can also occur, most commonly affecting facial nerves and causing bilateral facial weakness.
Autonomic dysfunction occurs in approximately half of children with GBS: cardiac dysrhythmias, orthostatic hypotension, hypertension, paralytic ileus, bladder dysfunction, and sweating.
Physical exam typically reveals:
- Symmetric weakness
- Diminished or absent reflexes
- Gait abnormalities
- Sensory symptoms include pain, paraesthesia (reflecting nerve irritability)
Generally, children have shorter clinical courses and more complete recoveries compared to adults. A child’s function typically deteriorates for 2-4 weeks, followed by a slow return of function over the coming weeks to months.
On examination, you find a quiet child who is otherwise acting appropriately. She is afebrile and the rest of her vitals are within normal limits. No bruises or rashes are observed on her skin and there is no evidence of trauma. Cardiovascular, respiratory, abdominal and ENT exams are unremarkable. Her extremities are warm and well perfused with normal pulses. There is no bony tenderness or deformities on palpation of her limbs. On neurological examination, she is moving all 4 limbs spontaneously. However, she will not bear weight or stand. Both her lower limbs are weak on exam. Her grip strength is reduced and when given a toy, it falls. Both upper and lower extremity reflexes are absent.
Subtypes
GBS most commonly presents in the classical way above: a mixed motor and sensory polyneuropathy with lower limb pain and ascending weakness. This is the classic Acute Inflammatory Demyelinating  Polyradiculopathy (AIDP), which accounts for 85 to 90% of cases in the developed world. But you should be aware of a few other subtypes of GBS.
Acute Motor Axonal Neuropathy (AMAN) is a purely motor form of GBS, occurring mainly in Asia and Central and South America and associated with a preceding Campylobacter infection. Its clinical features are similar to AIDP, but respiratory failure is more common.
Acute Motor-Sensory Axonal Neuropathy (AMSAN) is similar to AMAN but with more sensory symptoms. The course tends to be prolonged and severe but is uncommon in children.
Miller-Fisher syndrome is characterised by external ophthalmoplegia, ataxia and muscle weakness with areflexia. It affects adults more commonly than children but should be on your radar in a child presenting with cranial nerve and lower limb neurology.
How can you diagnose GBS?
The initial diagnosis of GBS is based on the history and clinical exam – be suspicious of a child with lower limb weakness, weak reflexes and a preceding illness. Use investigations to confirm your suspicion.
CSF
CSF protein above 45mg/dL with a normal WCC count is present in 50-66% of patients in the first week after symptoms onset and ≥75% in the third week. This disconnect between protein and white cells is called albuminocytologic dissociation.
Gadolinium-enhanced MRI of Spine
MRI will show contrast enhancement of the spinal nerve roots, cauda equina or cranial nerve roots. These changes aren’t specific to the GBS but can be helpful in the correct clinical setting.
Nerve conduction studies
This is the most specific and sensitive test available for GBS, abnormal in up to 90% of cases. The test can be technically tricky in small children.
Antibodies
Antibodies against GQ1b (the ganglioside component of a nerve) are present in most patients with Miller-Fisher syndrome.
In the emergency department, you send baseline bloods (FBC, U&E, LFTs and CRP) which are all normal and organize a CT head under sedation which is unremarkable. After getting consent from her parents you perform a lumbar puncture. The CSF appears clear. It has no red blood cells, 2 white blood cells and CSF glucose is within the normal limits but her protein is mildly elevated. No organisms were seen on gram stain and cultures had no growth after 5-days. You refer her to the neurology team for further investigation.
What else could it be?
The differential diagnosis of GBS is long.
Brain
- Bilateral strokes
- Acute disseminated encephalomyelitis
- Acute cerebellar ataxia syndrome
- Psychogenic symptoms
Spine
- Anterior spinal artery syndrome
- Compressive myelopathy
- Transverse myelitis
- Poliomyelitis
- Infectious causes of acute myelitis
Peripheral nervous system
- Chronic inflammatory demyelinating polyneuropathy
- Critical illness polyneuropathy
- Infection-related radiculitis (e.g. HIV, CMV, Lyme disease)
- Thiamine deficiency
- Toxins: biologic toxins (diphtheria), heavy metals (arsenic)
- Vasculitis
- Metabolic and electrolyte disorders (e.g. hypoglycaemia, hypophosphatemia)
Neuromuscular junction
- Botulism
- Myasthenia gravis
- Neuromuscular blocking agents
Muscle
- Acute inflammatory myopathies (e.g. dermatomyositis, polymyositis)
- Acute viral myositis
- Acute rhabdomyolysis
- Critical illness myopathy
- Metabolic myopathies (e.g. hypokalaemia, hyperkalaemia)
- Mitochondrial myopathies
What is the treatment?
The mainstay of treatment is supportive management, including close monitoring of motor, autonomic and respiratory function, pain management and prevention of immobility complications, such as pressure ulcers. ICU admission for mechanical ventilation will be required in 10-20% of kids. This is more likely to be needed in children with:
- rapidly increasing weakness,
- bulbar dysfunction,
- bilateral facial weakness or
In addition, IV immunoglobulin (IVIG) and plasmapheresis (plasma exchange) can be used in children with severe, progressive GBS (i.e. worsening respiratory status or need for mechanical ventilation, rapidly progressing weakness, inability to walk unaided or significant bulbar weakness).
IVIG is typically preferred to plasmapheresis in children due to its better safety record and ease of administration
Plasmapheresis can be helpful in bigger children where technically, it is more feasible to perform. However, no reliable studies suggest one has better efficacy than the other in children.
During her admission, Amy has a Gadolinium-enhanced MRI of the spine and nerve conduction studies which are consistent with the acute inflammatory demyelinating polyradiculopathy (ADIP) subtype of GBS. She is given IVIG. She does not develop any respiratory complications. On discharge after three weeks, her weakness is greatly improved and completely resolves over the next two months.
Bottom line
Clinical examination is key – do not forget to examine reflexes!
Always ask about recent viral illnesses.
GBS is the most common cause of acute flaccid paralysis in children and 10-20% will require mechanical ventilation.
Selected references
Bloch SA, Akhavan M, Avarello J. Weakness and the Inability to Ambulate in a 14-Month-Old Female: A Case Report and Concise Review of Guillain-Barre Syndrome. Case Rep Emerg Med [Internet]. 2013 [cited 2020 Apr 11];2013. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572648/
Yuki N, Hartung H-P. Guillain–Barré Syndrome. New England Journal of Medicine [Internet]. 2012 Jun 14 [cited 2020 Apr 5];366(24):2294–304. Available from: https://doi.org/10.1056/NEJMra1114525
Rudant J, Dupont A, Mikaeloff Y, Bolgert F, Coste J, Weill A. Surgery and risk of Guillain-Barré syndrome: A French nationwide epidemiologic study. Neurology. 2018 25;91(13):e1220–7.
Hicks CW, Kay B, Worley SE, Moodley M. A clinical picture of Guillain-Barré syndrome in children in the United States. J Child Neurol. 2010 Dec;25(12):1504–10.
Dimachkie MM, Barohn RJ. Guillain-Barré Syndrome and Variants. Neurol Clin [Internet]. 2013 May [cited 2020 Apr 5];31(2):491–510. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939842/
Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. The Lancet [Internet]. 2016 Aug 13 [cited 2020 Apr 5];388(10045):717–27. Available from: https://www.sciencedirect.com/science/article/pii/S0140673616003391
Ryan MM. Pediatric Guillain-Barré syndrome. Curr Opin Pediatr. 2013 Dec;25(6):689–93.
Hughes RAC, Wijdicks EFM, Barohn R, Benson E, Cornblath DR, Hahn AF, et al. Practice parameter: Immunotherapy for Guillain–Barré syndrome. Neurology. 2003 Sep 23;61(6):736.
