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Update on Acute Flaccid Myelitis: Recognition, Reporting, Aetiology and Outcomes Duriel Hardy, Sarah Hopkins

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Update on Acute Flaccid Myelitis: Recognition, Reporting, Aetiology and Outcomes Duriel Hardy, Sarah Hopkins Review Arch Dis Child: first published as 10.1136/archdischild-2019-316817 on 10 February 2020. Downloaded from Update on acute flaccid myelitis: recognition, reporting, aetiology and outcomes Duriel Hardy, Sarah Hopkins Division of Neurology, Children’s ABStract What is already known? Hospital of Philadelphia, Acute flaccid myelitis, defined by acute flaccid limb Philadelphia, Pennsylvania, USA weakness in the setting of grey matter lesions of Acute flaccid myelitis (AFM) presents with the spinal cord, became increasingly recognised in ► Correspondence to sudden paralysis and grey matter abnormality 2014 following outbreaks in Colorado and California, Dr Sarah Hopkins, Neurology, of the spinal cord, related to enteroviruses. Children’s Hospital of temporally associated with an outbreak of enterovirus Philadelphia, Philadelphia, PA Patients have residual disability, and optimal D68 respiratory disease. Since then, there have been management is unclear. 19104, USA; biennial increases in late summer/early fall. A viral hopkinss1@ email. chop. edu infectious aetiology, most likely enteroviral, is strongly Received 8 October 2019 suspected, but a definitive connection has yet to be Revised 8 January 2020 established. Patients typically present with asymmetric What this study adds? Accepted 17 January 2020 weakness, maximal proximally, in the setting of a febrile Published Online First illness. MRI demonstrates T2/FLAIR abnormalities in the 10 February 2020 ► Concise review of current knowledge, including Seguridad Social - BINASSS. Protected by copyright. central grey matter of the spinal cord, and cerebrospinal defining clinical characteristics, need for close fluid typically shows a lymphocytic pleocytosis with monitoring in the acute period, outcomes and variable elevation in protein. The weakness may be questions for further study. progressive over several days and involve respiratory muscles, making early recognition and close monitoring essential. Other complications in the acute period may include autonomic instability and bowel/bladder The initial AFM outbreaks in California and involvement. There is no clear recommended treatment Colorado prompted the Centers for Disease Control at this time, although intravenous immunoglobulin, and Prevention (CDC) to establish a case definition (boxes 1 and 2) in effort to enhance nationwide steroids and plasma exchange have been used. Intensive 7 8 therapies and rehab services have shown benefit in surveillance of AFM. There have been bien- nial increases in AFM since that time. Despite the maximising function, and surgical interventions may increasing recognition of children affected by this be considered in cases without optimal response illness, much remains to be discovered in regards to to therapies. Close attention should also be paid to predisposing factors, most appropriate diagnostic psychosocial factors. Prognosis is generally guarded, testing and optimal management of AFM. This http://adc.bmj.com/ and additional factors that predict final outcome, review discusses our current knowledge of AFM including host factors and treatment effects, have yet to and its association with EV-D68 and enterovirus be elucidated. Multicentre collaborative efforts will be A71 (EV-A71), including epidemiology and updates required to provide answers about this rare but serious on surveillance, aetiology, common diagnostic disorder. approaches and management strategies. EPIDEMIOLOGY AND REPORTING OF AFM on September 16, 2020 at Biblioteca Nacional de Salud y The first recognition of polio- like acute flaccid INTRODUCTION paralysis in the USA was in 2012 in California after Acute flaccid myelitis (AFM) came to national three cases of unexplained flaccid paralysis were attention in 2014 after reports from Colorado and reported to the California Department of Public California of an increase in children presenting Health.1 2 This was followed by identification of 1 3 with acute onset of flaccid paralysis with MRI find- a cluster of similar cases in Colorado in 2014. 1 2 3 ings of grey matter lesions of the spinal cord. The CDC subsequently made a national request for The outbreak of AFM in Colorado occurred during information about patients with acute onset of focal an outbreak of enterovirus D68 (EV- D68) respi- limb paralysis with longitudinal grey matter lesions ratory disease; however, it has taken some time of the spine on MRI, which led to increased aware- to conclude a more definitive causal relationship ness and surveillance of cases concerning for AFM. with this virus.4–6 The classic presentation of AFM © Author(s) (or their The evolution of the surveillance case definition is employer(s)) 2020. No is acute onset of flaccid paralysis in the setting of documented in boxes 1 and 2, which includes recent commercial re- use. See rights a febrile illness. There may be marked asymmetry, changes by the US Council of State and Territorial and permissions. Published even monoparesis. The diagnosis of AFM must be Epidemiologists to be implemented in 2020.7 Key by BMJ. considered in children with any flaccid paralysis changes are the elimination of age criteria in 2015, To cite: Hardy D, Hopkins S. given that worsening paralysis can develop quickly the inclusion of flaccid in the 2017 case definition Arch Dis Child in patients with AFM resulting in life-threatening and now the requirement of MRI abnormalities for 2020;105:842–847. respiratory compromise. both confirmed and probable cases, and exclusion 842 Hardy D, Hopkins S. Arch Dis Child 2020;105:842–847. doi:10.1136/archdischild-2019-316817 Review Arch Dis Child: first published as 10.1136/archdischild-2019-316817 on 10 February 2020. Downloaded from B ox 1 Past case definitions for acute flaccid myelitis Box 2 Current (2020 update) case definitions for as defined by the Council ofS tate and Territorial confirmed, probable and suspect acute flaccid myelitis Epidemiologists as defined by the Council ofS tate and Territorial Epidemiologists 2014–2015 AFM case definition Onset of acute limb weakness on or after 1 August 2014, and an Clinical criteria MRI showing a spinal cord lesion largely restricted to grey matter A person with onset of acute flaccid limb weakness. in a patient age ≤21 years. Laboratory Criteria An MRI showing a spinal cord lesion in at least some grey 2015–2017 AFM case definition matter and spanning one or more vertebral segments. Acute onset of focal limb weakness and an MRI showing spinal Excluding persons with grey matter lesions in the spinal cord cord lesion largely restricted to grey matter and spanning one or resulting from physician diagnosed malignancy, vascular disease more spinal segments, regardless of age. or anatomic abnormalities. 2017: Confirmed 2019 Case classification ► Acute onset of flaccid paralysis. Confirmed ► Confirmatory laboratory evidence: MRI showing spinal cord ► Clinically compatible case with confirmatory laboratory/ lesion largely restricted to grey matter and spanning one or imaging evidence (MRI showing spinal cord lesion with more spinal segments. predominant grey matter involvement and spanning one or Probable more vertebral segments) and absence of a clear alternative ► Acute onset of flaccid paralysis. diagnosis attributable to a nationally notifiable condition. ► Supportive laboratory evidence: cerebrospinal fluid showing Probable Seguridad Social - BINASSS. Protected by copyright. 3 pleocytosis (white cell count >5 cells/mm ). ► Clinically compatible case with presumptive laboratory/ Source: CDC AFM case definition (https://www.cdc.gov/acute-flaccid- imaging evidence (MRI showing spinal cord lesion where myelitis/hcp/case-definition.html). grey matter involvement is present but predominance cannot be determined) and absence of a clear alternative diagnosis attributable to a nationally notifiable condition. Suspect of cases with a clear diagnosis of malignancy, vascular disease or ► Clinically compatible case and available information is anatomic abnormalities. insufficient to classify case as probable or confirmed. Cases have thus far followed a biennial pattern of late summer/ early fall spikes with increases in 2016 and 2018.8 9 A total of 120 Source: https://cdn.ymaws.com/www.cste.org/resource/resmgr/2019ps/ cases of AFM were confirmed in 2014, 153 cases in 2016, with final/19-ID-05_AFM_final_7.31.19.pdf, and https://wwwn.cdc.gov/ the incidence reaching 237 cases confirmed across 41 states in nndss/conditions/acute-flaccid-myelitis/case-definition/2020/ 20188 (figure 1). Geographic involvement in the USA has varied each year. Cases have also been seen in other parts of the world, including Europe, Canada, Asia and South America.4 5 10 11 There between EV- D68 and AFM. Both found that the Bradford Hill 1 8 criteria supports a causal relationship between EV-D68 and is a slight male predominance in AFM cases with a recent, http://adc.bmj.com/ although small case series of 28 patients with AFM suggesting AFM by fulfilling the strength, consistency, temporality, plausi- 4 5 a predisposition in patients with a history of asthma, atopic bility, coherence, experiment and analogy criteria. dermatitis or head trauma.12 A possible increased risk in children A major challenge with determining a definitive aetiology in of Asian descent in this small sample has not been confirmed in cases of AFM has been that no infectious agents of clear signif- other datasets.12 13 The median age of patients affected is about icance have been identified in the CSF of cases reported to the 6 years.9 13 CDC.
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