Vanita Shukla1 Virendra RS Singh2 Maritza Fernandes2 Arvita Mahabir1 Nelicia Cooke1
1 Paediatric Department, Eric Williams Medical Sciences Complex, NCRHA, Trinidad & Tobago
2 The University of the West Indies, St Augustine, Trinidad & Tobago
No funding, conflicts of interest
Copyright: This is an open-access article under the terms of the Creative Commons Attribution License which permits use, distribution, and reproduction in any medium, provided the original work is properly cited.
©2022 The Authors. Caribbean Medical Journal published by Trinidad & Tobago Medical Association.
Guillain Barré Syndrome (GBS) is a clinical entity that may prove to be difficult to diagnose in children. With the emergence of the COVID-19 pandemic, it is especially important to not just recognize the classic form, but the variants and mimics as well.
Four cases are described, aiming to outline the differences in presentations and the importance of appropriate diagnosis.
Keywords – Paediatric education, Guillain Barré Syndrome, CNS leukaemia, Brainstem encephalitis
ADEM – Acute Disseminated Encephalomyelitis
ALL – Acute Lymphoblastic Leukaemia
ANA – Antinuclear Antibody
CNS – Central Nervous System
COVID-19 – Coronavirus disease of 2019
CSF – Cerebrospinal Fluid
DKA – Diabetic Ketoacidosis
ENA – Extractable Nuclear Antigen Antibody
ESR – Erythrocyte Sedimentation Rate
GBS – Guillain Barré Syndrome
GQ1b – Ganglioside Q1b
GlyR – Glycine receptor
Ig (G,M) – Immunoglobulin (G,M)
IVIG – Intravenous Immunoglobulin
LMN – Lower Motor Neurone
MOG – myelin oligodendrocyte glycoprotein
MRI – Magnetic Resonance Imaging
NCS/EMG – Nerve Conduction Studies/Electromyography
NMDAR – N-methyl-D-aspartate receptor
PCR – Polymerase Chain Reaction
SARS-CoV-2 – Severe Acute Respiratory Syndrome associated Coronavirus – 2
As medical practitioners, the diagnosis of rare clinical conditions is difficult at times. With the COVID-19 pandemic, as well as the seasonal viruses endemic to Trinidad & Tobago, there has been an upsurge in various neuroinflammatory conditions, including variations in classical presentations.
This is a description of cases encountered during a six (6) month period in a tertiary-care paediatric hospital setting. The case summaries do pose a question to the reader: “Is this a classic Guillain-Barré Syndrome (GBS), variant GBS or a GBS mimic?”
A 7-year-old female presented to the hospital with a 2-week history of frequent falling that was progressively worsening. There was no clear antecedent history of viral illness. Her clinical examination findings revealed that the weakness progressed over the subsequent 48 hours – with an inability to elicit reflexes in the lower limbs and diminished reflexes in the upper limbs.
- MRI head/Spine – Normal
- CSF studies – Cell count: 0 white cells, CSF protein 102 mg/dL
- Electrophysiology (NCS/EMG) – Could not be done because consumables were not available to perform in public hospital setting
A 15-year-old female was managed for newly diagnosed Diabetic Ketoacidosis (DKA). She presented 1 week later with abnormal taste and noticeable bilateral facial weakness. She was initially diagnosed as Bell’s palsy at the Emergency Department.
However, on examination on the ward the day after, cranial nerves VII (Lower Motor Neurone- LMN), IX, X, XI and XII were found to be affected. She subsequently developed diminished reflexes in her lower limbs over the next 2-3 days.
- MRI head/spine – Normal
- Inflammatory markers (ESR and Antinuclear antibodies – ANA) were elevated
- CSF studies – 0 white cells, CSF protein 89 mg/dL
A 15-year-old female presented with a 3-week history of vomiting, and a 2-day history of decreased responsiveness and difficulty walking. She was previously managed at San Fernando Teaching Hospital (SFTH) for appendicitis but vomiting persisted and she progressively worsened. There was a history of antecedent illness as 2 days prior to vomiting, she developed a 1-day history of fever, diarrhoea, cough and coryza when she was in contact with classmates for a face-to-face class.
- Amylase/lipase elevated (Lipase 3923; amylase 324); ANA 400 ENA 192.7; ESR elevated.
She was managed as acute pancreatitis/bacterial meningitis.
Five days after presenting, she suddenly deteriorated (urinary incontinence, unresponsive, worsening respiratory distress needing mechanical ventilation), with autonomic dysfunction (elevated blood pressure, tachycardic). She subsequently had progressive, ascending areflexia of her lower limbs, then upper limbs, eventually losing head and trunk control with Grade 1/5 power of her upper and lower limbs.
- CSF studies protein 77 mg/dL (glucose normal); white cells 80, RBC1141
- SARS-CoV2 PCR negative; COVID-19 IgG+ IgM (4-fold increase from initial result)
A 12-year-old female, with a background history of ALL (B-cell) on maintenance phase treatment, presented with difficulty walking, early morning nausea and headache, ascending weakness, facial muscle weakness and slurred speech
On examination, she had a convergent squint of her right eye, right cranial nerve VII (LMN) weakness, and developed areflexia of lower limbs and upper limbs over the next few days.
- CSF studies <1 lymphocytes <1 RBC 100 neutrophils; CSF protein 100mg/dL, glucose low
- MRI brain/spine Normal
The aforementioned case descriptions did not fit into the classic criteria for diagnosing GBS and hence the clinicians indeed queried if these cases were GBS.
GBS is a descriptive clinical entity. The hallmarks of diagnosis include:
- Distal weakness beginning in the legs, ascending weakness, symmetrical involvement
- ± sensory disturbance
- High CSF protein, Normal cell count (albumino-cytologic dissociation)
- ± neuropathic pain
There are 2 main subtypes – Acute Inflammatory Demyelinating Polyneuropathy (AIDP) and Acute Motor Axonal Neuropathy (AMAN). The AMAN subtype can be more difficult to diagnose as there is a more rapid progression of weakness with an earlier peak, but about 10% of patients have normal/hyperreflexia. This can be explained by the association with antiganglioside IgG antibodies (GM1, GD1a). The spinal nerve roots, where the blood-nerve barrier is anatomically deficient, are preferentially affected in GBS. Inflammation in the spinal roots may lead to local dysfunction of the blood-CNS barrier and allow anti-GM1 antibodies to bind with the neural structures in the spinal cord1. One theory underpins this to an increase in motor neuron excitability by the disruption of intramedullary interneurones.
Patient 1 was diagnosed with Classic GBS (probable AIDP) and treated with IVIG (2 grams/kg total over 5 days). She subsequently improved and reflexes returned.
GBS has several subtypes, which present in various ways and can be difficult to diagnose. The most common variants include Miller Fisher variant (MFv), pharyngeal-cervical-brachial variant, and Bickerstaff’s brainstem encephalitis variant (BBE). Pan-dysautonomia, pure sensory GBS, sixth nerve palsy with paresthesia, and facial diplegia with paresthesia (FDP) are the other rare variants of GBS2. Furthermore, there are reports of crossover where the MFv and BBE variants have been found to overlap3.
In GBS, unilateral facial palsy simulating unilateral Bell’s palsy is a rare presenting symptom, especially in children – with less than 10 cases reported4. Additionally, GBS with multiple cranial nerve involvement can rarely involve the XII nerve5. Due to our patient’s presentation, she was diagnosed with this rare GBS variant.
Patient 2 was treated with IVIG (2 grams/kg total over 5 days). Her gait improved, lower limb reflexes returned, and then gradually her facial muscles weakness resolved over 2 months as her inflammatory markers (including ANA) normalized.
Brainstem encephalitis is an uncommon condition, and little is known about the aetiologies. This patient was diagnosed with an extensive longitudinal transverse myelitis/ADEM (due to the concurrent spinal cord swelling) with brainstem involvement.
Several entities including infectious, autoinflammatory, and paraneoplastic syndromes have been reported. Brainstem encephalitis associated with antibody positivity, including CNS surface antibodies (GQ1b, GlyR, NMDAR, MOG, Aquaporin-4), does not comprise a new clinical phenotype, but rather a previously unrecognized one6. Early consideration of an autoimmune pathogenesis and aggressive immunotherapy offers better outcomes.
Notably, there have been case reports of a rare overlap between GBS and cervical transverse myelitis – considered a new GBS variant7. This was also a consideration in our patient due to progression of her condition to include LMN findings.
Patient 3 was treated with high-dose steroids, IVIG and rituximab. She was slow to recover and eventually needed tracheostomy and gastrostomy insertion. However, with her immunomodulation regime (IVIG every 6 weeks, Rituximab maintenance), there was progressive improvement in her motor skills. She was subsequently weaned off mechanical ventilation, she developed head and trunk control and was able to feed orally, and 6 months post hospitalization, was able to walk without needing assistance.
The leukemic cells found in the cerebrospinal fluid (CSF) are cytogenetically identical to those found in the bone marrow. Leukemic lymphocytes appear to metastasize to the CNS by hematogenous spread or through the CNS lymphatics near the dural sinuses8,9.
Symptoms present in half of patients with greater than or equal to 5 leukocytes/µL with blasts in the CSF or signs of CNS involvement on neurologic examination10. Although rare, neurologic symptoms associated with CNS leukaemia include headaches (17%), nausea and vomiting (14%), lethargy, and irritability. Cranial nerve involvement is less common but may include seventh, third, fourth, and sixth nerve impairment.
Unfortunately, this patient had CNS relapse, with confirmation of blasts via CSF cytological examination.
The diagnosis of Guillain–Barré syndrome (GBS) is largely based on clinical features, and supported by serological, electrodiagnostic, and immunological investigations. The manifestations of GBS are protean and include limited forms such as variants. Unless Bickerstaff encephalitis is in consideration, altered mental state should not be present in GBS. Albumino-cytologic dissociation in spinal fluid examined about 1 week after symptoms is useful in the diagnosis of GBS.
Autoimmunity should be sought when investigating children with these rare neuroinflammatory pathologies. It is important to consider GBS mimics, including brainstem encephalitis and CNS leukaemia, as the treatment course and prognosis differ in these conditions.
Acknowledgements – Paediatric department, EWMSC, NCRHA
Conflict of Interest statement – No conflicts of interest
Funding – No funding
Ethical Approval – Institutional and University ethical approval granted
Consent – Patient identifiers anonymised, consent to share approved by ethics committees
Corresponding author: Dr Vanita Shukla
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Figure 1: MRI head/C-spine showing bilateral symmetric high T2 signal in medulla; C-Spine expansion over long segment C2-7 with symmetrical high T2 signal involving central grey matter and dorsal columns.