By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: Compared to children with Guillain-Barré syndrome, children with acute flaccid myelitis have a more rapid presentation to nadir of weakness, fewer sensory abnormalities, and an inflammatory spinal fluid early in the course.
SOURCE: Helfferich J, Roodbol J, de Wit MC, et al. Acute flaccid myelitis and Guillain-Barré syndrome in children: A comparative study with evaluation of diagnostic criteria. Eur J Neurol 2021;29:593-604.
Occurring more often in children and presenting with rapid onset weakness in one or more limbs, acute flaccid myelitis (AFM) may be confused with the flaccid weakness of Guillain-Barré syndrome (GBS). Cytoalbuminogenic dissociation and multifocal demyelination on electrodiagnostic testing can differentiate between these entities but may not be helpful early in the course of disease. How might early diagnostic accuracy be improved?
Two well-described cohorts of children, one diagnosed with AFM associated with enterovirus EV-D68 and the other diagnosed with GBS, were compared to provide recommendations for early and accurate diagnosis of AFM vs. GBS. AFM EV-D68 children (n = 26) were retrospectively identified through the European AFM Working Group, having experienced acute onset focal limb weakness associated with magnetic resonance imaging (MRI) abnormalities and a positive polymerase chain reaction (PCR) for EV-D68 in either respiratory, fecal, blood, or cerebrospinal fluid (CSF) specimens. When MRI was normal or not available, diagnosis was established by CSF pleocytosis, which, per the 2018 Centers for Disease Control and Prevention (CDC) case definition, was sufficient for a probable diagnosis of AFM.
Children with GBS (n = 156) came from nine Netherlands hospitals, and all fulfilled 1990 National Institute of Neurological Disorders and Stroke (NINDS) diagnostic criteria for GBS. Data gathered on these AFM and GBS cohorts included preceding prodrome, initial symptoms, neurological deficits at admission and nadir, results of CSF analysis, nerve conduction studies (NCS), brain and spinal cord MRI, and virology testing, as well as disease course and treatment type.
Comparison between cohorts included: presence, type, and timing of preceding prodromal illness; clinical features at admission and nadir; results of additional investigations, including CSF, NCS, and MRI; and clinical course and outcome. Lastly, Brighton Collaboration criteria, previously validated and used for GBS diagnosis, consisting of bilateral limb weakness, decreased or absent deep tendon reflexes in weak limbs, monophasic disease course, normal CSF cell count, increased CSF protein level, and NCS findings consistent with GBS, were applied to both cohorts. AFM diagnostic criteria, published by the CDC in 2018, also were applied to both groups, and comprised an acute flaccid limb weakness with MRI spinal cord gray matter abnormalities required for a definite diagnosis, and acute flaccid limb weakness with CSF pleocytosis required for a probable diagnosis. Criteria for a definite AFM diagnosis in 2019 comprised a combination of acute flaccid weakness and predominantly gray matter abnormalities on MRI spanning one or more segments, with exclusion of malignancy, vascular disease, or anatomic abnormalities as an explanation for the spinal cord lesion. Criteria for a probable diagnosis were like those for a definite diagnosis, except that spinal cord gray matter involvement needed to be present but not predominant. Statistical analysis comprised the t-test, the Mann-Whitney U test, the chi-squared or Fisher exact test, and the Bonferroni correction applied as appropriate, with P < 0.05 considered significant.
Compared to an eight-day interval from onset of weakness to nadir for children with GBS, those with AFM experienced a significantly shorter three-day interval, were more likely to have asymmetric limb weakness, and were less likely to have sensory deficits. CSF leukocyte counts were higher, and protein concentrations were lower in AFM, and only AFM patients had spinal cord lesions on MRI. No GBS case fulfilled CDC criteria for definite AFM, whereas 8% of AFM children fulfilled Brighton criteria for GBS. In children, AFM may be differentiated from GBS, but, in atypical GBS, AFM must be excluded early in the course of disease, since otherwise it may fulfill GBS diagnostic criteria.
COMMENTARY
Although optimal medical treatment remains unclear, it is recommended that all patients with possible AFM be admitted for close monitoring of respiratory function and testing. Intravenous immunoglobulin has shown efficacy in a mouse model when given early and often is used in the clinical setting. Potentially exacerbating an underlying viral infection gives one pause before administering steroids, which may be used after careful consideration on a case-by-case basis.
Anti-enterovirus D68 antibodies neutralize enterovirus D68 in a mouse model, limiting the course of disease, but its use remains at the preclinical level and there are no definitive clinical trials in humans.1
REFERENCE
- Hopkins SE, Desai J, Benson L. Acute flaccid myelitis: A call for vigilance and an update on management. Pediatr Neurol 2021;114:26-28.
