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Acute Flaccid Myelitis
Description
- polio-like disorder characterized by acute onset of flaccid paralysis associated with longitudinal lesion in gray matter of spinal cord(1,2,3)
- a distinct acute flaccid paralysis syndrome associated with anterior myelitis that is noted to be increasing in incidence in United States beginning in 2014(2,3)
Also Called
- AFM
- acute flaccid paralysis with anterior myelitis
Definitions
- acute flaccid myelitis (AFM) case definitions have evolved in recent years
- Council of State and Territorial Epidemiologists (CSTE) definitions for confirmed and probable AFM
- 2015 case definition – illness with onset of acute focal limb weakness plus
- for confirmed AFM – magnetic resonance imaging (MRI) showing spinal cord lesion largely restricted to gray matter and spanning ≥ 1 spinal segment
- for probable AFM – cerebrospinal fluid (CSF) analysis showing pleocytosis, defined as > 5 white blood cells (WBCs)/mm3(may adjust WBC count for presence of red blood cells)
- Reference – CSTE 2015 Standardized Case Definition for Acute Flaccid Myelitis PDF
- current definition updated in June 2017 changed “acute focal limb weakness” to “acute flaccid limb weakness” as clinical criterion, and added some clarifications/revisions to test criteria
- for confirmed AFM
- MRI showing spinal cord lesion largely restricted to gray matter and spanning ≥ 1 spinal segment (unchanged from 2015 definition)
- clarification added that negative findings ≤ 72 hours after onset of limb weakness does not exclude AFM
- for probable AFM
- CSF pleocytosis (defined as > 5 WBC/mm3, unchanged from 2015 definition)
- adjustment of WBC count for presence of red blood cells deleted from definition
- Reference – CSTE 2017 Revision to the Standardized Surveillance and Case Definition for Acute Flaccid Myelitis PDF
- for confirmed AFM
- 2015 case definition – illness with onset of acute focal limb weakness plus
- Centers for Disease Control and Prevention (CDC) definitions
- from August 2014 to July 2015, confirmed AFM defined as onset of acute limb weakness on or after August 1, 2014, plus MRI showing spinal cord lesion largely restricted to gray matter in a person ≤ 21 years old
- after July 2015, age restriction was eliminated, and CDC has used CSTE definitions to classify persons under investigation for AFM as confirmed or probable cases, or not a case
- Reference – CDC 2023 Feb 7
- Council of State and Territorial Epidemiologists (CSTE) definitions for confirmed and probable AFM
Epidemiology
Who Is Most Affected
- reported most commonly in children, although some previous case definitions excluded persons > 21 years old(3)
- most affected in review of cases reported by California Department of Public Health (CDPH), Children’s Hospital Colorado (CHCO), Primary Children’s Hospital (PCH) in Utah, and/or Centers for Disease Control and Prevention (CDC) from 2012 to 2015(3)
- older children (median age 7.1 years, range 5 months to 73 years)
- males (range 56%-91%)
- no racial or ethnic predisposition reported(3)
Incidence/Prevalence
- 491 cases of Centers for Disease Control and Prevention (CDC)-confirmed acute flaccid myelitis (AFM) reported in United States in 2014-2018, with biennial spikes in incidence
- based on suspected AFM reported to CDC with symptom onset from August 2014 through November 30, 2018 and confirmed by December 14, 2018
- case definition changed after July 2015 (including by eliminating age restriction)
- confirmed cases by year
- 2014 – 120 cases across 34 states
- 2015 – 22 cases across 17 states
- 2016 – 149 cases across 39 states and District of Columbia
- 2017 – 35 cases across 16 states
- 2018 – 215 cases across 40 states
- Reference – CDC 2023 Feb 7
Risk Factors
- no common environmental or travel exposure identified in review of acute flaccid myelitis cases reported by California Department of Public Health (59 cases), Children’s Hospital Colorado (12 cases), Primary Children’s Hospital in Utah (11 cases), and/or Centers for Disease Control and Prevention (CDC) (120 cases, including 77 cases not reported by already-cited sources) in 2012-2015(3)
Etiology and Pathogenesis
Causes
- clinical features and temporal association with certain viral outbreaks suggest viral etiology, but no single specific viral pathogen has been identified as causative(2)
- viral infections associated with acute flaccid myelitis (AFM)
- enteroviruses (EV) such as EV-D68, EV-A71, and coxsackievirus have been reported in recent AFM cases in United States (Centers for Disease Control and Prevention (CDC) 2019 Jan 14)
- non-EV pathogens reported include
- West Nile virus(1)
- adenovirus(2)
- herpesviruses including Epstein-Barr virus (EBV), human herpesvirus (HHV) 6a/b, and HHV 7 (Clin Infect Dis 2016 Sep 15;63(6):737full-text)
- viruses identified in retrospective cohort study of 120 children ≤ 21 years old (median age 7.1 years) diagnosed with AFM in August-December 2014 in United States who had cerebrospinal fluid (CSF), serum, respiratory samples, and/or stool submitted to CDC for viral testing
- 55 children (46%) had CSF samples tested
- 1 was positive for EV-D68 and Epstein-Barr virus
- of 35 specimens tested by metagenomic sequencing, 14 specimens (40%) were positive for viruses unlikely to be clinically significant (GB virus C in 8, human rhinovirus in 4, transfusion transmitted virus [TTV] in 1, TTV-like mini virus in 1)
- 56 children (47%) had respiratory samples tested, of which 11 children (20%) were positive for EV-D68 and 12 children (21%) were positive for other enteroviruses/rhinoviruses
- 54 children (45%) had stool samples tested, all of which were negative for poliovirus
- 43 children (36%) had serum samples tested, all of which were negative for enteroviruses
- viruses not detected in any sample included herpes simplex viruses, cytomegalovirus, and arboviruses
- Reference – Clin Infect Dis 2016 Sep 15;63(6):737full-text
- 55 children (46%) had CSF samples tested
- evidence for EV-D68 infection as causative
- respiratory infection due to EV-D68 may be associated with AFM in children (level 2 [mid-level] evidence)
- based on case-control study in Colorado, United States
- 11 children aged 1-18 years with confirmed AFM and nasopharyngeal (NP) specimen collected in August-October 2014 were compared with 337 controls
- NP specimens from 105 controls with acute respiratory infection were assessed by respiratory pathogen panel (RPP) for adenovirus, coronaviruses, influenza viruses, metapneumovirus, parainfluenza viruses, respiratory syncytial virus, enterovirus/rhinovirus, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae (RPP-tested controls)
- NP specimens from 232 controls with suspected B. pertussis were assessed by polymerase chain reaction (PCR) for B. pertussis (BP-tested controls)
- enterovirus/rhinovirus (EV/RV)-positive case specimens, EV/RV-positive RPP-tested control specimens, and all BP-tested control specimens had further enteroviral testing by CDC
- EV/RV identified in 64% of cases vs. 19% of RPP-tested controls vs. 29% of BP-tested controls (p values not reported)
- 36% of cases were positive for EV-D68 vs.
- 6% of RPP-tested controls (adjusted odds ratio [OR] 10.3, 95% CI 1.8-64.8)
- 13% of BP-tested controls (adjusted OR 4.5, 95% CI 1-21.2)
- no significant differences in frequency of EV/RV-positivity due to non-EV-D68 strains comparing cases vs. either control group
- Reference – Emerg Infect Dis 2016 Aug;22(8):1387full-text
- EV-D68 detected in respiratory secretions from 12 of 25 children (48%) with confirmed AFM in California and Colorado, United States in 2012-2014 in retrospective cohort study (Lancet Infect Dis 2015 Jun;15(6):671full-text)
- 29 cases of EV-D68-associated AFM reported in 12 different European countries in 2016 based on questionnaire sent to 66 members of 2016 EV-D68 AFM Working Group composed of virologists and clinicians (Pediatr Infect Dis J 2019 Jan;38(1):16full-text)
- EV-D68 detected in 4 of 11 children (36%) with AFM in Buenos Aires, Argentina in 2016 in retrospective cohort study (Eur J Paediatr Neurol 2017 Nov;21(6):884)
- similar findings supportive of causal relationship between EV-D68 and AFM in literature review of 20 studies (Euro Surveill 2018 Jan;23(3):doi:10.2807/1560-7917full-text)
- respiratory infection due to EV-D68 may be associated with AFM in children (level 2 [mid-level] evidence)
Pathogenesis
- weakness is due to damage to spinal motor neurons (anterior horn cells)(3)
- damage to anterior horn cells likely due to active infection or postinfectious inflammatory process, but exact pathogenesis unclear(3)
- although no single pathogen has been identified, lack of response to immunotherapy favors active infection over inflammation as underlying pathophysiology(2)
History and Physical
Clinical Presentation
- typical presentation is onset of weakness (flaccid paralysis) in ≥ 1 limb preceded by febrile prodrome(1,2,3)
- neurologic features(1,2,3)
- limb involvement
- often asymmetric
- weakness can range from mild-to-severe, with proximal muscles most affected
- symptoms and signs in affected limbs may include
- pain
- hyporeflexia
- sensory deficits
- other findings may include
- headache
- neck or back pain
- cranial nerve deficits
- bowel and/or bladder dysfunction
- autonomic instability
- rapidly progressive weakness leading to respiratory compromise
- limb involvement
- prodrome features
- clinical presentation reported in 4 cohorts of patients with acute flaccid myelitis (AFM) identified by California Department of Public Health (59 cases), Children’s Hospital Colorado (12 cases), Primary Children’s Hospital in Utah (11 cases), and/or Centers for Disease Control and Prevention (CDC) (120 cases, including 43 cases from first 3 cohorts) in 2012-2015(3)
- Children’s Hospital Colorado and Primary Children’s Hospital in Utah defined AFM as acute onset focal limb weakness and/or cranial nerve dysfunction associated with magnetic resonance imaging findings of predominantly gray matter lesions in spinal cord and/or brainstem, so patients not meeting current case definition requirements for limb and spinal cord involvement were included
- median age 7.1-11.5 years (range 0.4-73 years)
- 56%-91% male
- neurologic features
- limb weakness in 83%-100%
- asymmetric in 47%-70%
- upper extremity weakness in 64%-77%
- lower extremity weakness in 36%-66%
- hyporeflexia in 80%-81%
- cranial nerve dysfunction in 18%-83%
- bowel or bladder dysfunction in 0%-51%
- pain/temperature and/or fine touch/vibration deficits in 0%-44%
- headache in 49%-58%
- stiff neck in 34%-83%
- pain in 51%-69%
- altered mental status in 0%-22%
- limb weakness in 83%-100%
- prodromal illness in 64%-100%
- fever in 45%-100%
- respiratory symptoms in 71%-92%
- gastrointestinal symptoms in 0%-64%
- preexisting conditions included asthma in 0%-25%, and immunocompromise in 0%-8%
Table
Table 1: Similar Findings in Additional Retrospective Cohort Studies
| 16 Children Evaluated at Transverse Myelitis Center in Baltimore, Maryland and Diagnosed with AFM in 2014 or 2016 | 8 Children Aged 3 Months to 8 Years Diagnosed with AFM in Australia Between 2001 and 2014 | 29 Patients Aged 1.6-55 Years with EV-D68-associated AFM Identified in 12 Different European Countries in 2016 | ||
|---|---|---|---|---|
| Median age | 4 years | 5 years | 4 years | |
| % male | 69% | 25% | 52% | |
| Neurologic features | Limb weakness | 100% | 100% | 100% (4 limbs in 55%) |
| Hyporeflexia | 63% | 100% | 87% | |
| Cranial nerve involvement | Bulbar weakness in 50%Facial palsy in 6% (1 child) | 25% | 60%Bulbar symptoms in 32% (dysphagic in 14%)Facial nerve in 29%Eye movement abnormality in 18% | |
| Limb pain | NR | 87.5% | 14% | |
| Paresthesia | 6% | NR | 7% | |
| Autonomic dysfunction | NR | 0% | 10% | |
| Other findings reported | Neck or back pain in 50%Altered mental status in 0% | Sensory dysfunction in 0% | Ataxia in 3% (1 patient)Bladder dysfunction in 3%Generalized seizures in 3% | |
| Prodromal illness | 100% | 100% | NR | |
| Upper respiratory symptoms | 100% | 63% | 90% | |
| Fever | 94% | ≥38% | 92% | |
| Gastrointestinal symptoms | 13% | 25% | 24% | |
| Median time from onset of prodromal symptoms to onset of neurologic symptoms 3 days | 6 days | 3 days | 2 days | |
| Other findings report | Household sick contact in 44% | Fever without focal symptoms in 13% (1 child) | NR | |
| Preexisting conditions | Asthma | 13% | 25% | NR |
| Abbreviations: AFM, acute flaccid myelitis; NR, not reported.References – Dev Med Child Neurol 2019 Mar;61(3);366, Eur J Neurol 2017 Aug;24(8):1077, Pediatr Infect Dis J 2019 Jan;38(1):16 | ||||
History
Chief Concern (CC)
acute limb weakness(1,2,3)
History of Present Illness (HPI)
ask aboutlimb weakness, including onset, duration, progression, and limbs affected4
other neurologic symptoms including(1,2,3,4)limb pain
neck or back pain
headache
changes in bladder or bowel function
paresthesias or other sensory abnormalities
findings suggestive of cranial nerve dysfunction such as dysphagia or vision changes
change in mental status
less commonly reported neurologic symptoms such as ataxia or seizures (Pediatr Infect Dis J 2019 Jan;38(1):16full-text)
recent illness, including presence, onset, and duration of(1,4)fever
respiratory symptoms
gastrointestinal symptoms
skin or mucosal lesions – maculopapular/vesicular rash on hands/feet with painful oral lesions may suggest acute flaccid myelitis associated with enterovirus 71 infection
Past Medical History (PMH)
ask about underlying conditions such as asthma or immunocompromise(3)
Social History (SH)
ask about recent illness in family members or other contacts(4)
Physical
General Physical
assess vital signs – fever common, autonomic instability possible(1)
assess for respiratory distress (most common in patients with bulbar dysfunction and upper extremity weakness)(1)
Skin
maculopapular/vesicular rash on hands/feet may suggest acute flaccid myelitis associated with enterovirus 71 infection(1)
HEENT
assess for signs of upper respiratory infection such as rhinorrhea or pharyngeal erythema(3)
erythematous papulovesicular lesions on hard palate, gums, tongue, buccal mucosa, and/or posterior pharynx may suggest acute flaccid myelitis associated with enterovirus 71 infection(1)
Neck
assess for nuchal rigidity (meningeal signs possible)(3,4)
Neuro
assess foraltered mental status (check for signs such as decreased alertness, irritability, disorientation)(4)
motor deficits in ≥ 1 limb(1,3)typical findings in affected limbsstrength – mild-to-severe decrease
tone – flaccid
deep tendon reflexes – decreased or absent
distribution – deficits are frequently asymmetric, and often affect upper limbs more than lower limbs
sensory deficits in affected limb – possible, but sensation often normal(1,3)
signs of cranial nerve involvement such as diplopia, facial weakness, or bulbar palsy(3)
Diagnosis
Making the Diagnosis
Council of State and Territorial Epidemiologists (CSTE) 2017 criteria for acute flaccid myelitis (AFM) requires onset of acute flaccid limb weakness plusfor confirmed AFM – magnetic resonance imaging (MRI) showing spinal cord lesion largely restricted to gray matter and spanning ≥ 1 vertebral segment (spinal cord lesions may be absent on initial MRI; negative MRI ≤ 72 hours after onset of limb weakness does not exclude AFM)
for probable AFM – cerebrospinal fluid pleocytosis (> 5 white blood cells/mm3)
Reference – CSTE 2017 Revision to the Standardized Surveillance and Case Definition for Acute Flaccid Myelitis PDF
Differential Diagnosis
other causes of acute limb weaknesstransverse myelitis(1,2,3,4)
Guillain-Barre syndrome (also called acute inflammatory demyelinating polyneuropathy [AIDP])(1,2,3,4)
chronic inflammatory demyelinating polyneuropathy (may have more rapid onset in children than in adults)(4)
acute disseminated encephalomyelitis (ADEM)(1,2,3,4)
spinal shock(2)
spinal cord infarction(1,4)
neuromyelitis optica spectrum disorders (NMOSD)(1)
poliomyelitis(1,2,3,4)
acute viral myositis(4)
myasthenia gravis(4)
stroke(4)
syndromes associated with episodic weakness, including(4)alternating hemiplegia of childhood
hyperkalemic periodic paralysis
hypokalemic periodic paralysis
Testing Overview
suspect acute flaccid myelitis (AFM) and perform diagnostic testing in patients with onset of acute flaccid limb weakness(1,2,3)
monitor closely for respiratory depression throughout evaluation, ensure airway is protected, and provide support as needed(2)
evaluations should includemagnetic resonance imaging (MRI) of spinal cord – spinal cord lesion largely restricted to gray matter and spanning ≥ 1 vertebral segment confirms diagnosis, however lesion absence ≤ 72 hours after onset of limb weakness does not exclude AFM
lumbar puncture – cerebrospinal fluid (CSF) pleocytosis supports diagnosis, and identifies probable AFM if MRI not feasible or MRI normal within 72 hours after onset of limb weakness
testing of blood, urine, stool, respiratory specimens, and CSF to identify pathogens and help exclude alternative diagnoses
Centers for Disease Control and Prevention (CDC) advises for patients under investigation (PUIs) for AFMspecimen collection as early possible in disease course
pathogen-specific testing at hospital or state public health laboratory
submission of additional CSF, serum, stool, and respiratory samples to CDC
electrodiagnostic testing (electromyography [EMG], nerve conduction studies) may be considered if diagnosis unclear after MRI and lumbar puncture
Centers for Disease Control and Prevention Guidelines
Centers for Disease Control and Prevention (CDC) instructions regarding specimen collection and testing in patients under investigation (PUIs) for acute flaccid myelitiscollect specimens as early as possible in disease course, preferably on day that limb weakness first occurs
pathogen-specific testing should be performed at hospital or state public health laboratory
additional aliquots of cerebrospinal fluid (CSF), serum, stool, and respiratory samples should be sent to CDC to be tested for both infectious and noninfectious causesspecimen-specific collection instructions and resultsCSFcollect ≥ 1 mL, obtained at same time as or within 24 hours of serum sample if possible
used for special studies, results of enterovirus/rhinovirus (EV/RV) testing reported if sample size sufficient
serumcollect ≥ 0.4 mL, obtained at same time as or within 24 hours of CSF sample if possible
used for special studies, no individual results reported
if treated with intravenous immune globulin (IVIG), steroids, or plasmapheresis/plasma exchange before specimen collection, include type and date of treatment on Patient Summary Form
stoolcollect 2 samples (≥ 1 g each) obtained ≥ 24 hours apart as early in illness as possible, preferably within 14 days of onset
obtain whole stool, do not send rectal swab
results of EV/RV and poliovirus testing reported within 14 days
respiratory specimenscollect ≥ 1 mL by nasopharyngeal or oropharyngeal swab
results of EV/RV testing and typing reported within 10 days
storage and submissionsamples should be frozen and shipped on dry iceserum and CSF should be stored at -70 degrees C (-94 degrees F)
stool and respiratory specimens can be stored at – 20 degrees C (-4 degrees F), or can be frozen to -70 degrees C to facilitate shipping together with serum and CSF samples
include a Patient Summary Form for each patient, and a Specimen Submission Form for each specimen
if death occurs, submit fresh-frozen and formalin-fixed tissue samples if possibleif feasible, obtain representative sections from brain/spinal cord (include gray and white matter), heart, lung, liver, kidney, and other organs
fresh-frozen tissue should be stored at -70 degrees C (-94 degrees F) and shipped on dry ice
formalin-fixed or formalin-fixed, paraffin-embedded tissue should be stored and shipped at room temperature
full instructions for specimen collection, handling, and shipping can be found at CDC 2018 Nov 8
Reference – CDC 2018 Nov 8
Blood Tests
perform blood tests to identify possible infectious etiology and help exclude alternative diagnoses(1,2)inflammatory and metabolic markers to consider includecomplete blood count
comprehensive metabolic panel
vitamin B12
vitamin D 25-OH
neuromyelitis optica IgG (NMO-IgG)/aquaporin-4 antibody (AQP4-Ab)
myelin oligodendrocyte glycoprotein (MOG) antibodies
antinuclear antibodies
IgA
oligoclonal bands (to compare with cerebrospinal fluid)
pathogen-specific testing should take into consideration factors such as clinical features, and seasonal and geographic exposure; consider especiallyenterovirus polymerase chain reaction
antibodies forEpstein-Barr Virus (EBV) Infection
Lyme disease
West Nile virus
before starting intravenous immunoglobulin (IVIG), consider obtaining additional serum sample and reserving for possible further testing
Centers for Disease Control and Prevention (CDC) instructions for blood testing in patients under investigation (PUIs) for acute flaccid myelitiscollect specimens as early as possible in disease course, preferably on day that limb weakness first occurs
if possible, obtain blood sample at same time as or within 24 hours of collecting cerebrospinal fluid sample
pathogen-specific testing should be performed at hospital or state public health laboratory
0.4 mL of serum should be frozen at -70 degrees C (-94 degrees F) and shipped on dry ice to CDC for additional testingsample used for special studies, no individual results reported
if treated with IVIG, steroids, or plasmapheresis/plasma exchange before specimen collection, include type and date of treatment on Patient Summary Form
full instructions for specimen collection, handling, and shipping can be found at CDC 2018 Nov 8
Reference – CDC 2018 Nov 8
Urine Studies
consider enterovirus polymerase chain reaction(2)
Stool Studies
obtain stool sample or rectal swab for enterovirus polymerase chain reaction(1,2)
send stool samples to Centers for Disease Control and Prevention (CDC) for additional testing, including testing for poliovirus
CDC instructions for stool testing in patients under investigation for acute flaccid myelitiscollect specimen as early as possible in disease course, preferably on day that limb weakness first occurs
pathogen-specific stool testing should be performed at hospital or state public health laboratory
collect 2 stool samples and submit to CDC for additional testingcollect ≥ 1 g of whole stool for each sample
obtain samples ≥ 24 hours apart and as early in illness as possible, preferably within 14 days of onset
do not send rectal swab because negative predictive value is low (due to limited amount of fecal material collected)
specimens should be frozen and shipped on dry ice; stool can be stored at -20 degrees C (-4 degrees F), or can be frozen to -70 degrees C (-94 degrees F) to facilitate shipping together with serum and cerebrospinal fluid (CSF) samples
results of enterovirus, rhinovirus, and poliovirus testing reported within 14 days
full instructions for specimen collection, handling, and shipping can be found at CDC 2018 Nov 8
Reference – CDC 2018 Nov 8
Imaging Studies
magnetic resonance imaging (MRI)perform spinal MRIspinal cord lesion largely restricted to gray matter and spanning ≥ 1 vertebral segment in patient with onset of acute flaccid limb weakness meets Council of State and Territorial Epidemiologists (CSTE) 2017 criteria for confirmed acute flaccid myelitis (AFM) (CSTE 2017 Revision to the Standardized Surveillance and Case Definition for Acute Flaccid Myelitis PDF)
typical findingsbutterfly-shaped longitudinal lesion characterized by central gray matter T2 and fluid attenuated inversion recovery hyperintensities, predominantly affecting anterior horn(1,2)
lesion spanning ≥ 1 vertebral segment meets diagnostic criteria, but lesions are usually longer, and may extend full length of spinal cord(2)
location variable, cervical spine frequently involved(2)
nerve root enhancement possible(1,2)
early findingsnegative MRI ≤ 72 hours after onset of limb weakness does not exclude AFM (CSTE 2017 Revision to the Standardized Surveillance and Case Definition for Acute Flaccid Myelitis PDF)
spinal MRI may be normal early in disease course, or edema may obscure abnormalities(2)
consider repeat imaging if AFM suspected but spinal cord lesion not apparent on MRI performed early in disease course
early lesions may involve entire central gray matter, then localize to anterior horn cells over first week or longer(2)
associated brain abnormalities possible, with changes reported in brainstem, cerebellum, thalamus, and other locations(1,2)
imaging findings reported in 4 cohorts of patients with AFM identified by California Department of Public Health (59 cases), Children’s Hospital Colorado (12 cases), Primary Children’s Hospital in Utah (11 cases), and/or Centers for Disease Control and Prevention (CDC) (120 cases, including 43 cases from first 3 cohorts) in 2012-2015(3)Children’s Hospital Colorado and Primary Children’s Hospital in Utah defined AFM as acute onset focal limb weakness and/or cranial nerve dysfunction associated with MRI findings of predominantly gray matter lesions in spinal cord and/or brainstem, so patients not meeting current case definition requirements for limb and spinal cord involvement were included
median age 7.1-11.5 years (range 0.4-73 years)
findings on spinal cord MRIT2 gray matter lesions spanning multiple vertebral levels in 90%-100%
nerve root enhancement in 20%-40%
findings on brain MRIbrainstem lesions in 35%-75%
supratentorial lesions in 11%-31%
Cerebrospinal Fluid (CSF) Analysis
perform CSF analysis to identify possible infectious etiology and help exclude alternative diagnoses(1,2)
testing should includecell countlymphocytic pleocytosis supports diagnosis(1)
> 5 white blood cells/mm3 in patient with onset of acute flaccid limb weakness meets Council of State and Territorial Epidemiologists (CSTE) 2017 criteria for probable acute flaccid myelitis (AFM) (CSTE 2017 Revision to the Standardized Surveillance and Case Definition for Acute Flaccid Myelitis PDF)
mild pleocytosis is typical, persists for about 2 weeks after onset of weakness, then resolves within next 2 weeks(3)
protein – typically normal or mildly elevated early in disease course, may be increased in weeks following acute phase(1,3)
oligoclonal bands(1,2)
polymerase chain reaction for enterovirus, herpes simplex virus , varicella-zoster virus, Epstein-Barr Virus (EBV) Infection(1,2)
also considerneuromyelitis optica IgG (NMO-IgG)/aquaporin-4 antibody (AQP4-Ab)(2)
West Nile virus IgM if infection possible based on clinical features and seasonal and geographic exposure(1)
Centers for Disease Control and Prevention (CDC) instructions for CSF collection and testing in patients under investigation for AFMcollect specimen as early as possible in disease course, preferably on day that limb weakness first occurs
if possible, obtain sample at same time as or within 24 hours of collecting serum sample
pathogen-specific testing should be performed at hospital or state public health laboratory
≥ 1 mL of CSF should be frozen at -70 degrees C (-94 degrees F) and shipped on dry ice to CDC for additional testingused for special studies
results of enterovirus/rhinovirus testing reported if sample size sufficient
full instructions for specimen collection, handling, and shipping can be found at CDC 2018 Nov 8
Reference – CDC 2018 Nov 8
CSF findings reported in 4 cohorts of patients with AFM identified by California Department of Public Health (59 cases), Children’s Hospital Colorado (12 cases), Primary Children’s Hospital in Utah (11 cases), and/or CDC (120 cases, including 43 cases from first 3 cohorts) in 2012-2015(3)Children’s Hospital Colorado and Primary Children’s Hospital in Utah defined AFM as acute onset focal limb weakness and/or cranial nerve dysfunction associated with MRI findings of predominantly gray matter lesions in spinal cord and/or brainstem, so patients not meeting current case definition requirements for limb and spinal cord involvement were included
median age 7.1-11.5 years (range 0.4-73 years)
pleocytosis in 64%-91%
protein > 45 mg/dL in 45%-48%
virus detected in 0%-2%
Biopsy and Pathology
in event of death of patient under investigation for acute flaccid myelitis, Centers for Disease Control and Prevention (CDC) requests tissue specimensif feasible, obtain representative sections from brain/spinal cord (include gray and white matter), heart, lung, liver, kidney, and other organsfresh-frozen tissue should be stored at -70 degrees C (-94 degrees F) and shipped on dry ice
formalin-fixed or formalin-fixed, paraffin-embedded tissue should be stored and shipped at room temperature
full instructions for specimen collection, handling, and shipping can be found at CDC 2018 Nov 8
Reference – CDC 2018 Nov 8
Other Diagnostic Testing
Respiratory Specimens
obtain nasopharyngeal and/or oropharyngeal swab for polymerase chain reaction (PCR) to identify viral pathogens(1,2)include enterovirus PCR
if available, consider respiratory viral PCR panel
Centers for Disease Control and Prevention (CDC) instructions for collection and testing of respiratory specimens in patients under investigation for acute flaccid myelitisobtain nasopharyngeal or oropharyngeal swab as early as possible in disease course, preferably on day that limb weakness first occurs
pathogen-specific testing should be performed at hospital or state public health laboratory
respiratory specimen ≥ 1 mL should be stored in viral transport medium, frozen at – 20 degrees C (-4 degrees F), and shipped on dry ice to CDC for additional testing (can be frozen to -70 degrees C [-94 degrees F] to facilitate shipping together with serum and cerebrospinal fluid [CSF] samples)
results of enterovirus and rhinovirus testing and typing reported within 10 days
full instructions for specimen collection, handling, and shipping can be found at CDC 2018 Nov 8
Reference – CDC 2018 Nov 8
Electrodiagnostic Testing
electromyography (EMG) and nerve conduction studies may be considered if diagnostic uncertainty persists after initial and follow-up magnetic resonance imaging (MRI) and cerebrospinal fluid analysis(1,2,3)
may help differentiate between anterior horn cell disease (such as acute flaccid myelitis [AFM]) and Guillain-Barre syndrome(1)
findings in AFM generally include(3)low response amplitude of compound muscle action potentials (CMAPs)
reduced recruitment of motor unit potentials (MUPs)
fibrillation potentials
no sensory abnormalities
results may be normal at onset of neurologic symptoms, and progress over time(3)reduced recruitment of MUPs typically present by 1-3 weeks after symptom onset
low response amplitude of CMAPs and fibrillations may be present in early weeks, or may develop later in convalescent phase (months to year after symptom onset)
electrophysiologic findings reported in 4 cohorts of patients with AFM identified by California Department of Public Health (CDPH, 59 cases), Children’s Hospital Colorado (CHC, 12 cases), Primary Children’s Hospital in Utah (PCH, 11 cases), and/or Centers for Disease Control and Prevention (CDC) (120 cases, including 43 cases from first 3 cohorts) in 2012-2015(3)CHC and PCH defined AFM as acute onset focal limb weakness and/or cranial nerve dysfunction associated with MRI findings of predominantly gray matter lesions in spinal cord and/or brainstem, so patients not meeting current case definition requirements for limb and spinal cord involvement were included
median age 7.1-11.5 years (range 0.4-73 years)
electrodiagnostic test results were reported for 12 patients (20%) from CDHP cohort, and 5 patients (42%) from CHC cohortmotor abnormalities in affected limb reported in 100% of both cohorts
sensory abnormalities in affected limb reported in 0% of CHC cohort, not reported in CDPH cohort
Management
Management Overview
confirmed or suspected acute flaccid myelitis (AFM) requires close monitoring because rapid clinical deterioration is possibleadmission usually indicated, and admission to intensive care unit should be considered
provide supportive care as needed for complications of neurologic dysfunction such as respiratory compromise and autonomic instability
no specific intervention has clear evidence for benefit in AFMempiric treatments are based on presumed infectious or inflammatory etiology
in the absence of evidence to guide treatment, Centers for Disease Control and Prevention (CDC) has provided interim considerations for clinical management of AFM
medications to considerintravenous immunoglobulin (IVIG) is often used based on potential boost to humoral immunity in setting of possible viral infection and low likelihood of serious adverse events
corticosteroids may be indicated for management of associated spinal cord edema or white matter involvement, but consider potential harm due to immunosuppression in setting of possible viral infection
biologic modifiers and other immunosuppressive medications generally not indicated due to potential for harm in setting of active infection
antiviral medication generally not indicated unless herpesvirus suspected
fluoxetine does not appear to improve long-term limb weakness in children with AFM (level 2 [mid-level] evidence)
plasma exchange lacks evidence for benefit but has low likelihood of serious adverse events, however consider potential deleterious effects of removing innate antibodies in setting of acute infection
regular physical and occupational therapy should be initiated early
nerve transfer surgery may be considered in some patients with persistent extremity weakness
Recommendations
Centers for Disease Control and Prevention (CDC) updated interim considerations for clinical management of acute flaccid myelitis (AFM)(5)based on expert observations and opinions and literature review, not intended as consensus recommendations or official guidelines
no indication that the following should be preferred or avoided in treatment of AFMintravenous immunoglobulin (IVIG) – evidence for efficacy is limited to early treatment in animal models; no evidence that IVIG likely to cause harm
corticosteroids – possible benefits in management of spinal cord edema or white matter involvement should be balanced with potential for harm due to immunosuppression in setting of possible viral infection
plasma exchange (PLEX) – no evidence for efficacy in humans; aside from procedure-associated risks, no evidence that PLEX likely to cause harm
no indication that the following should be used for treatment of AFM due to lack of clear evidence for efficacy and/or potential for harmfluoxetine
antiviral medication (if herpesvirus infection suspected, administer appropriate antivirals such as acyclovir or ganciclovir until herpesvirus excluded)
interferon – concern for potential harm from immunomodulatory effects in setting of possible ongoing viral replication
biologic modifiers and other immunosuppressive medications – concern for potential harm in setting of possible infection
Treatment Setting
admission for monitoring and supportive care generally indicated for confirmed or suspected acute flaccid myelitis(1,2)monitor closely forneurologic deterioration
progression to respiratory compromise
autonomic instability
consider intensive care admission, especially in patients with cervical lesions, which increase risk of autonomic instability and respiratory deterioration
Activity
physical and occupational therapy(1,2)initiate rehabilitation therapies early in disease course, including in inpatient setting
provide regular and ongoing treatment – although motor deficits usually persist, functional improvement may be possible with continued therapy
Medications
Overview
medications for acute flaccid myelitis (AFM) have insufficient evidence for benefit in AFM(1,2,3)
immunomodulatory therapies and antiviral medications are often used despite lack of clarity concerning AFM pathogenesis (active infection vs. inflammatory response)(1,2,3)
Centers for Disease Control and Prevention (CDC) updated interim considerations for medications in clinical management of AFM(5)no indication that intravenous immunoglobulin (IVIG) or corticosteroids should be preferred or avoided, however potential benefits of steroids in management of spinal cord edema or white matter involvement should be balanced with potential harm due to immunosuppression in setting of possible viral infection
no indication that fluoxetine, antiviral medications (unless herpesvirus suspected), or biologic modifiers or other immunosuppressive agents should be used
Intravenous Immunoglobulin (IVIG)
frequently used for acute treatment of AFM despite lack of evidence for clinical efficacy(1,2,3)
IVIG use proposed based on potential for boosting humoral immunity (presumes active infection as underlying cause of AFM)(1,2)
consider especially in immunocompromised patients with enterovirus-associated AFM (IVIG contains antibodies to multiple enterovirus strains)(3)
CDC updated interim considerations regarding IVIG for treatment of AFM(5)no indication that IVIG should be preferred or avoided
efficacyno clear evidence for efficacy in humans
early IVIG has shown evidence for benefit in animal trials, preventing progression to neuroinvasive disease in rodents infected with enterovirus D68 (EV-68) or West Nile virus
no evidence that IVIG likely to be harmful, however adverse effects possible
adverse effects5common intra-infusion adverse effects (usually related to infusion rate) may includefever
chills
headache
myalgia
nausea
vomiting
less common intra-infusion adverse effects may includeflushing
tachycardia
hypotension
postinfusion adverse effects may includeheadache
fatigue
arthralgias
aseptic meningitis
serious adverse effects (uncommon) may includeacute renal failure
thromboembolism
hemolytic anemia
neutropenia
Corticosteroids
may be indicated for acute management of severe spinal cord edema(,2,3)
use with caution due to concern to risk of immune suppression during active infection(,2,3)
CDC updated interim considerations regarding corticosteroids for treatment of AFM(5)no indication that corticosteroids should be preferred or avoided
no clear evidence for efficacy in humans
potential benefit in management of associated spinal cord edema or white matter involvement should be balanced with potential harm due to immunosuppression in setting of possible viral infectiondexamethasone has shown evidence for harm in mice infected with EV-D68, with greater mortality in treated mice than in controls
in patients with severe cord swelling or long tract signs suggestive of white matter involvement, steroid use may reduce potential tissue damage due to ongoing immune/inflammatory response
Biologic Modifiers and Other Immunosuppressive Agents
CDC updated interim considerations regarding biologic modifiers and other immunosuppressive agents for treatment of AFM(5)no indication that interferon or other biologic modifiers or immunosuppressive medications should be used
concern for use in setting of possible active infection
interferon has limited and conflicting anecdotal evidence for benefit in some viral infections (West Nile virus, Saint Louis encephalitis, Japanese encephalitis), but insufficient evidence to support use given potential for harm due immunomodulatory effects in setting of possible ongoing viral replication
Antiviral Medications
despite proposed viral etiology, antiviral agents have not been shown to improve clinical outcome(3, 5)
CDC updated interim considerations regarding antiviral medications for treatment of AFM(5)no indication that antiviral agents should be used unless herpesvirus infection suspected
suspect herpesvirus infection in patients with concomitant supra-tentorial disease or other clinical or radiologic features suggestive of herpesvirus infection
if herpesvirus infection suspected, start empiric treatment with appropriate antiviral medication (such as acyclovir or ganciclovir)
Fluoxetine
selective serotonin reuptake inhibitor with anti-enteroviral activity in vitro, including activity against EV-68(1,2,3, 5)
CDC updated interim considerations regarding fluoxetine for treatment of AFM(5)no indication that fluoxetine should be used
no clear evidence for efficacy in humans or in animal models
fluoxetine does not appear to improve long-term limb weakness in children with AFM (level 2 [mid-level] evidence) based on multicenter retrospective cohort study
56 children (median age 3.8 years) with proven or presumptive enterovirus D68–associated AFM were assessed for fluoxetine use, symptom improvement, and adverse eventsefficacy analysisfluoxetine-treated group included 28 children who received > 1 dose of fluoxetine; 2 children who received 1 dose each were included in untreated group
efficacy assessed based on change in summative limb strength score (SLSS) in all 4 limbs (range 0 for complete quadriparesis to 20 for normal strength) comparing initial exam to latest follow-up at median of 210 days from onset of neurologic symptoms
safety and tolerability analyses considered all 30 children who received ≥ 1 dose of fluoxetine to be fluoxetine-exposed
compared to untreated children, fluoxetine-treated children had higher rate of enterovirus-D68 identified (57% vs. 14%, p < 0.001)
mean change in SLSS comparing fluoxetine-treated vs. fluoxetine-untreated children- 0.4 (95% CI -2.5 to +1.8) vs. +2.1 (95% CI 0-4.3) (p = 0.1)
in analysis adjusted for age, sex, SLSS at initial exam, and use of corticosteroids, immunoglobulin, or plasmapheresis -0.2 (95% CI -1.8 to +1.4) vs. +2.5 (95% CI 0.7-4.4) (p = 0.02)
most common adverse effects were anxiety, agitation, and gastrointestinal symptoms, with no significant differences in fluoxetine-exposed vs. fluoxetine-unexposed children
no serious adverse events reported
Reference – Neurology 2019 Apr 30;92(18):e2118full-text
Plasma Exchange
plasma exchange (plasmapheresis) lacks evidence for benefit in acute flaccid myelitis (AFM)(2,5)
all reported use has been in combination with other therapies (intravenous immunoglobulin and/or corticosteroids), and no treatment regimen has been shown to be effective for treating AFM(2,3, 5)
presuming viral infection as underlying cause of AFM, potential for harm due to removal of circulating antibodies produced in response to acute infection is a concern(2,5)
Centers for Disease Control and Prevention (CDC) updated interim considerations regarding plasma exchange for treatment of AFM(5)no indication that plasma exchange should be used or avoided
no clear evidence for efficacy in humans
no evidence that plasma exchange likely to be harmful, although there are inherent procedure-associated risks
Surgery and Procedures
nerve, muscle, and/or tendon transfer surgery may be considered for persistent extremity weakness, however evidence is lacking regarding which patients may benefit(1,2,3)
nerve transfer surgery(2)nerve from region less essential for normal function is transferred to denervated muscle causing significant functional impairment
consider especially for unilateral upper extremity weakness
additional considerationsacceptable donor nerve may not be available in patients with severe bilateral weakness
optimal timing for procedure unclear
procedure used for brachial plexus disorders and spinal cord injury but has very limited evidence in acute flaccid myelitis (AFM)
nerve transfer reported safe and effective for improving strength and function in children with persistent upper extremity weakness after AFM (level 3 [lacking direct] evidence) based on case series of 2 children treated with nerve transfer surgery for upper extremity weakness following enterovirus D68-associated AFM
12-year-old boy with right upper extremity weakness 8 months after symptom onsetpreoperative findings – grade 0/5 shoulder and elbow strength
postoperative findings at 35-month follow-up – strength 5-/5 at elbow and 3/5 at shoulder, no dysfunction in donor nerve distribution
14-year-old girl with bilateral upper extremity weakness 9 months after symptom onsetpreoperative findingsright subacromial subluxation, absent shoulder abduction, impaired elbow flexion
left triceps weakness, absent wrist and digit extension, absent pronation, and absent wrist, thumb, index, and middle finger flexion
postoperative findings at 32-month follow-upright extremity – 5-/5 brachialis strength, shoulder abduction to 45 degrees and full external rotation, full elbow range of motion
left extremity – full digit flexion, but weak pinch strength due to intrinsic muscle atrophy; follow-up surgery for muscle transfer and joint arthrodesis restored excellent function
no dysfunction in any donor nerve distribution
Reference – Pediatr Neurol 2018 Nov;88:25
Consultation and Referral
consultations should include(5)neurology
infectious disease
consider ophthalmology consultation if diagnosis unclear(2)
refer for(1,2)physical and occupational therapy
psychosocial support
Supportive Care
supportive care is mainstay of acute management(2)
specific measures depend on type and severity of disease manifestations(1,2,3)
supportive care often required includes(1,2,3)noninvasive or invasive ventilatory support forrespiratory compromise due to weak respiratory musculature
inability to protect airway due to bulbar weakness
see alsoNoninvasive Respiratory Support in Neonates or Noninvasive Positive Pressure Ventilation (NPPV) in Adults
Invasive Mechanical Ventilation
Airway management
feeding support for patients with bulbar weakness
treatment for neuropathic pain
treatment for constipation
Follow-up
long-term follow-up indicated to monitor recovery(3)
assess for(1,2,3)muscle strength
muscle atrophy
pain
function
psychological adjustment to persisting dysfunction
adherence to rehabilitation regimens
Complications
complications may include(1,2,3)respiratory compromise due to inability to protect airway or weak respiratory muscles
feeding difficulties
diplopia
significant muscle atrophy
bowel or bladder dysfunction, constipation
functional impairment
complications in 120 cases of acute flaccid myelitis (AFM) reported to Centers for Disease Control and Prevention in patients ≤ 21 years old with AFM onset in Aug-Dec 2014 in United Statesrespiratory compromise requiring mechanical ventilation in 20%
dysphagia in 12%
diplopia in 9%
dysarthria in 7%
seizures in 4%
Reference – Clin Infect Dis 2016 Sep 15;63(6):737
complications reported in retrospective cohort study of 11 children aged 13 months to 14 years with AFM in United States in 2014-2015 includedimpaired daily function in 4 children
neurogenic bladder in 2 children
ambulation assistance (walker) requirement for long distances in 2 children
persistent ventilator and gastrostomy dependence in 1 child
Reference – Pediatr Neurol 2016 Feb;55:17
Prognosis
mortality low, but morbidity may be significantmortality in retrospective cohort study of 59 patients with acute flaccid myelitis (AFM) reported to Department of Public Health in California, United States in 2012-20152 adults aged 55 and 73 years with underlying immunocompromise died within 60 days of symptom onset
no other deaths reported
Reference – JAMA 2015 Dec 22;314(24):2663
strength may improve over time, but most patients do not recover full function of affected extremities(2,3)in patients with > 1 limb affected, most affected limb is more likely to have persistent dysfunction
proximal muscles less likely to regain strength than distal muscle groups
improved function possible with rehabilitation therapies directed toward recruitment of surrounding muscle groups
cranial nerve deficits generally improve or resolve(3)
no recurrences reported(3)
among children with acute flaccid myelitis with symptom onset in 2018 in the United States, no or minor impairment reported in 44% at 6 months and 45% at 12 months based on retrospective cohort study
238 children with acute flaccid myelitis with symptom onset in 2018 in the United States were assessed
analysis included90 patients (median age 5 years, 58% male) who had follow-up data available at 6 months
80 patients (median age 5 years, 54% male) who had follow-up data available at 12 months
outcomes comparing follow-up at 6 months vs. 12 months (no p values reported)level of impairmentnone in 8% vs. 16%
minor impairment in 36% vs. 29%
significant impairment (≥ 2 extremities with major involvement) in 54% vs. 48%
severe impairment (≥ 3 extremities and respiratory involvement) in 1% vs. 8%
limb and sensory functionsage-appropriate independence without upper limb impairment in 30% vs. 40%
independence in mobility without lower limb impairment in 52% vs. 55%
age-appropriate independence in communication or vision with no impairment in 75% vs. 80%
minimal medical monitoring in 41% vs. 50%
ability to fulfill usual age-appropriate roles and perform tasks in 32% vs. 38%
complete voluntary control of bladder and bowel sphincters in 80% vs. 79%
no deaths were reported
Reference – J Pediatr Rehabil Med 2023;16(2):391
persistent motor and functional deficits appear common at 1-year follow-up in children with AFM based on prospective cohort study
12 children aged 1-18 years diagnosed with AFM in 2014 in Colorado, United States were recruited for follow-up every 3 months for 1 year or until complete resolution of neurologic deficits
8 children completed follow-up and were included in outcome analyses 6 children (75%) had persistent motor or functional deficits at 1 yearupper extremity outcomesof 7 children with upper extremity weakness on initial assessment, 6 children (86%) had persistent weakness and minimal or no improvement in strength
of 5 children with abnormal upper extremity function on initial assessment, 2 children (40%) had significant improvement and 3 children (60%) had minimal or no improvement
lower extremity outcomesof 3 children with lower extremity weakness on initial assessment, 1 recovered fully and 2 improved but had persistent weakness
of 2 children with abnormal lower extremity function on initial assessment, both had persistent dysfunction (wheelchair dependence in 1, gait impairment in 1)
cranial nerve outcomesof 6 children with cranial nerve involvement on initial assessment, 5 children (83%) had functional improvement but only 2 children (33%) had full recovery; 1 child with subjective dysphagia had no improvement
other persistent deficits included hypophonia, nasolabial fold flattening, and mild sternocleidomastoid weakness
3 children (37%) reported depressive symptoms at 3 months, of whom 1 reported persistent symptoms at 1 year
4 children did not consent to follow-up, of whom 2 reported complete resolution of deficits within 2 months of symptom onset and 2 were lost to follow-up
Reference – Neurology 2017 Jul 11;89(2):129full-text
prolonged hospital stay and long-term disability appears common in children with enterovirus D68-associated AFM based on small prospective cohort study of 5 children aged 2-6 years admitted with enterovirus D68-associated AFM in Scotland in 2016
hospital length of stay ranged from 62 to 376 days, and includedintensive care in 3 children
invasive ventilation in 2 children
intravenous immunoglobulin (IVIG) in 4 children, steroids in 2, and no treatment in 1
outcomes at 18-month follow-upbreathing – normal in 3 children, tracheostomy and ventilatory support during sleep in 2
mobility – limited to walking short distances in 3 children, almost normal in 2
speech and swallowing in 4 children with cranial nerve involvement on admission – normal in 3 children, almost normal in 1
limb weakness and other abnormalitiessignificant proximal upper limb weakness in 3 children, of whom 3 had shoulder dislocation and head tilt, and 2 had scoliosis
significant proximal lower limb weakness in 1 child, who also had scoliosis
mild distal lower limb weakness affecting gait in 1 child
Reference – Dev Med Child Neurol 2019 Mar;61(3):376
persistent limb weakness and prolonged functional impairment appear common after AFM based on cohort study of 120 patients ≤ 21 years old with AFM onset in August-December 2014 reported to Centers for Disease Control and Prevention
56 patients (47%) with outcome reported had follow-up at median of 4.2 months after onset of limb weakness (range 0.8-7.5 months)limb weakness since symptom onsetno change in 20%
some improvement in 73%
worsening in 2%
complete recovery in 5%
effect of limb weakness on activities of daily livingcomplete dependence on caretaker in 14%
function somewhat impaired in 68%
normal function in 18%
Reference – Clin Infect Dis 2016 Sep 15;63(6):737full-text
Prevention and Screening
Prevention
no specific interventions are known to prevent acute flaccid myelitis, however standard measures to avoid viral infection may potentially reduce risk (Centers for Disease Control and Prevention 2019 Jan 14)
see also prevention inUpper Respiratory Infection (URI) in Children or Viral Upper Respiratory Infection (URI) in Adults and Adolescents
Enterovirus D68 Infection
West Nile Virus Infection
Screening
not applicable
Guidelines and Resources
Guidelines
United States Guidelines
Centers for Disease Control and Prevention (CDC) interim considerations on clinical management of acute flaccid myelitis (AFM) can be found at CDC 2018 Nov 26; CDC AFM Task Force established Nov 19, 2018, recommendations pending (Lancet 2018 Dec 1;392(10162):2339)
CDC instructions on specimens to collect and send to CDC for testing for patients under investigation for AFM can be found at CDC 2018 Nov 8
CDC case definitions for AFM can be found at CDC 2019 Jan 3
Council of State and Territorial Epidemiologists (CSTE) 2017 revision to the standardized surveillance and case definition for AFM can be found at CSTE 2017 Jan PDF
United Kingdom Guidelines
UK Health Security Agency (UKHSA) guidance on clinical management of acute flaccid paralysis/acute flaccid myelitis can be found at UKHSA 2022 Nov 15
Review Articles
review can be found in Lancet 2021 Jan 23;397(10271):334
review can be found in JAMA Pediatr 2018 Nov 30:doi:10.1001/jamapediatrics.2018.4896
review of diagnosis of acute flaccid myelitis and management with nerve transfers can be found in Plast Reconstr Surg 2023 Jan 1;151(1):85e
review can be found in Curr Treat Options Neurol 2017 Nov 28;19(12):48
review can be found in Ann Neurol 2016 Sep;80(3):326full-text
review can be found in Lancet Child Adolesc Health 2018 Dec 20:doi:10.1016/S2352-4642(18)30406-1
review can be found at CDC 2018 Nov 23
review of assessment of acute motor deficit in pediatric emergency room can be found in J Pediatr (Rio J) 2017 Nov – Dec;93 Suppl 1:26
review of acute muscular weakness in children can be found in Arq Neuropsiquiatr 2017 Apr;75(4):248full-text
review of enterovirus D68 – the new polio? can be found in Front Microbiol 2018 Nov 13;9:2677full-text
review of non-polio enteroviruses associated with acute flaccid paralysis can be found in J Med Virol 2018 Jan;90(1):3, editorial can be found in J Med Virol 2018 Jan;90(1):1
editorial on outbreaks of acute flaccid myelitis in United States and role of enteroviruses, particularly D68 can be found in BMJ 2018 Dec 19;363:k5246
MEDLINE Search
to search MEDLINE for (Acute flaccid myelitis) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosis
Patient Information
handouts from Centers for Disease Control and Prevention onacute flaccid myelitis (AFM) or in Spanish
how to spot symptoms of AFM in your child PDF
AFM in children PDF
AFM in United States children or in Spanish
References
General References Used
The references listed below are used in this DynaMed topic primarily to support background information and for guidance where evidence summaries are not felt to be necessary. Most references are incorporated within the text along with the evidence summaries.
Hopkins SE, Elrick MJ, Messacar K. Acute Flaccid Myelitis-Keys to Diagnosis, Questions About Treatment, and Future Directions. JAMA Pediatr. 2018 Nov 30:doi:10.1001/jamapediatrics.2018.4896.
Hopkins SE. Acute Flaccid Myelitis: Etiologic Challenges, Diagnostic and Management Considerations. Curr Treat Options Neurol. 2017 Nov 28;19(12):48.
Messacar K, Schreiner TL, Van Haren K, et al. Acute flaccid myelitis: A clinical review of US cases 2012-2015. Ann Neurol. 2016 Sep;80(3):326-38full-text.
Vasconcelos MM, Vasconcelos LGA, Brito AR. Assessment of acute motor deficit in the pediatric emergency room. J Pediatr (Rio J). 2017 Nov – Dec;93 Suppl 1:26-35.
Centers for Disease Control and Prevention (CDC). Acute Flaccid Myelitis: Interim Considerations for Clinical Management. CDC 2018 Nov 26.
