ReviewAcute flaccid myelitis: cause, diagnosis, and management
Introduction
Unusual clusters of a disabling, polio-like illness, now termed acute flaccid myelitis (AFM), were recognised in California in 2012, and Colorado in 2014.1, 2 AFM is now recognised as a global disease, with hundreds of cases reported across Europe,3, 4 Asia,5, 6, 7 Australia,8 Africa,9 North America,10, 11 and South America.12, 13 Epidemic enteroviral infection is believed to be the main driver of AFM in recent years, particularly enterovirus D68 infection.14 Cases have usually occurred in geographical clusters, with a distinct seasonal biennial pattern in temperate regions.15 AFM most frequently affects young children, and is characterised by acute onset of flaccid weakness of one or more limbs, with MRI showing abnormalities of the spinal cord grey matter.5 Trunk, neck, respiratory, bulbar, facial, and extraocular muscles can also be affected. The clinical presentation of AFM may mimic other causes of acute weakness such as Guillain-Barré syndrome, demyelinating myelitis, and other infectious myelitis. The diagnosis of AFM can be informed by interpretation of the clinical features alongside findings of laboratory, neuroimaging, and electrophysiological tests.
Acute management of AFM is largely supportive because there is an absence of therapeutic agents proven to alter outcomes. A substantial proportion of patients with AFM will become critically ill during the acute illness, requiring intubation due to respiratory failure or severe bulbar weakness.16, 17 Neurological recovery after AFM is usually incomplete, with many patients having substantial residual weakness and muscle atrophy. Over the long term, patients can be affected by a range of neurological, musculoskeletal, and psychological sequelae.18, 19, 20 Appropriate rehabilitation can improve functional status and quality of life after AFM.19 Additionally, surgical approaches including tendon or nerve transfer surgery have been used in individual cases to manage residual impairments.21, 22 In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation.
Section snippets
Epidemiology and cause
Several features support a viral link to AFM cases. Most individuals affected by AFM report a febrile prodrome accompanied by respiratory symptoms in the days before the onset of weakness.15, 23 The primary sites of neurological involvement parallel poliomyelitis, with lesions targeting the anterior horn cells of the spinal cord and motor nuclei of the brainstem. To date, the virus suspected to be the predominant driver of the seasonal, biennial outbreaks of AFM observed in many global regions
Clinical presentation
AFM is predominantly a childhood disease (median age 6·3 years),16 with less than 15% of cases occurring in adults (more commonly in the immunocompromised), although AFM in adults could be under-recognised or under-reported.1, 3, 4, 5, 12, 23, 46 A slight predilection for males has been suggested.4, 5, 15, 23 Most patients with AFM have a prodromal illness manifesting with fever and respiratory symptoms (cough, rhinorrhea, pharyngitis, or asthma-like illness). Gastrointestinal symptoms such as
Diagnosis
MRI of the spinal cord is the most useful diagnostic test in AFM. T2 hyperintensity of the spinal cord grey matter is the hallmark of AFM (figure 1). Lesions in the early acute phase (hours to days) are typically confluent and ill defined, and affect the entire grey matter of the spinal cord when viewed axially,47, 62, 63 with a varying degree of surrounding white matter involvement and oedema.47 Spinal cord grey matter lesions are longitudinally extensive in most cases.62 The cervical cord is
Acute management
Patients with AFM progress from neurological onset to nadir of weakness within hours to days.23 In 2018, 96% of identified AFM cases in the USA were admitted to hospital, and 58% to an intensive-care unit.16 Supportive treatment with careful monitoring focused upon potential emerging vital complications is the mainstay of early management. Although there is no specific evidence for optimal management of AFM, acute supportive management is similar to other causes of acute neuromuscular weakness.
Recovery, rehabilitation, and long-term sequelae
AFM seems to be a monophasic disorder with high potential for residual impairment. Prognostication is challenging, but electromyography or nerve conduction studies and MRI could both have potential utility.20, 62, 65 Denervated muscles with severe neurogenic changes on electromyography or nerve conduction studies in the weeks to months after AFM onset are likely to experience residual weakness.5, 20, 72 Quantitative measures of grey matter MRI involvement during the acute phase of the illness
Implications of current evidence: diagnostic criteria and clinical care
Literature to date focused on AFM is limited by no uniform diagnostic criteria, which is a barrier to advances in knowledge about treatment and outcomes in patients with AFM. Additionally, management approaches have been variable and centre based. On the basis of best evidence from published knowledge from multiple cohorts, we provide pathogen-agnostic diagnostic criteria (figure 2), and an approach to the clinical assessment (panel 1), management (panel 2), and rehabilitation (panel 3) of
Conclusions and future directions
The increasing incidence, since 2012, of a likely enterovirus-driven severe paralytic disease with lifelong sequelae identifies AFM as a major global public health concern of high priority. Its relative rarity, widely disparate distribution, and resemblance to other causes of acute weakness argues for widespread education of clinicians and health-care providers on the characteristics necessary to appropriate diagnosis, acute management, and chronic rehabilitation. Whether the pattern of
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