Acute Flaccid Myelitis

Author(s): Rajashree Srinivasan, MD, MBBS, Kelli Chaviano, DO

Originally published:10/08/2019

Last updated:10/08/2019

1. DISEASE/DISORDER

Definition

Acute Flaccid Myelitis (AFM) is a rapidly progressive immune and infectious mediated disease process that causes flaccid weakness of one or more limbs1,2. It is further characterized by specific gray-matter abnormalities on MRI and probable pleocytosis (WBC >5 cells/mm3) in CSF3

Etiology

No exact cause has been specifically identified; however, it has temporally and geographically been noted to be associated with Enterovirus 68 (EVD68) and, to a lesser extent, Enterovirus A71 and coxsackie A161,2,4,5. AFM is not caused by polio.

Epidemiology including risk factors and primary prevention

  • AFM outbreaks occur every 2 years (since 2014) and primarily between the months of August and October4. There were 120 cases reported in 2014, 149 cases in 2016, and 223 cases in 20182.
  • Children represent over 90% of the reported AFM cases2.
  • There are no specific actions that have been identified to prevent AFM apart from decreasing risk of acquiring and spreading viral infections4,6.
  • There are no cases reported of recurrence after initial diagnosis2.

Patho-anatomy/physiology

  • While exact cause and pathology has yet to be identified, pathogenesis is likely initially infectious and immune-mediated1,2.
  • A possible viral cause is enterovirus which is a respiratory virus closely related to rhinovirus infrequently occurring in US until late 2000s1. Hixon et al. inoculated mice with a strain of EVD68 from 2014 that caused similar clinical picture of paralysis1,7.
  • A majority of insult appears to be in spinal column. There is a predilection for involvement of the anterior horn cells1,2,5,8.
  • Three general phases of pathogenic process have been proposed1:
  • Inflammatory: largely reversible
  • Demyelination: moderately reversible
  • Axon transection: marginally reversible
  • Two pathophysiological subtypes have been identified on imaging including gray-matter restricted and mixed gray-white matter1. It has been proposed that the initial inflammation that occurs in the anterior horn cells may “spill” into adjacent white matter. This may explain presentation of mixed upper motor neuron and lower motor neuron signs1.
  • Some patients may present with MRI brain abnormalities such as dorsal pons, medulla, cerebellum, or varied supratentorial lesions9,10,11.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

New onset/acute: Home to Acute Hospital Setting

  • Prodromal illness of fever, respiratory, or gastrointestinal symptoms lasting a median of 7 days in one study12.
  • Clinical presentation includes rapidly progressive flaccid limb weakness which is preceded by symptoms of viral illness1,2,4,6,8. Weakness often occurs over a few hours to a few days13. Upper extremities are involved more often than lower extremities, and weakness is usually asymmetric12. There is variable cranial nerve involvement resulting in dysphagia, dysarthria, facial weakness, dysphonia, and ophthalmoplegia.  There can be absent deep tendon reflexes.  Bowel and bladder dysfunction may be present. A mix of upper motor neuron signs and lower motor neuron signs may be present1.
  • Evidence of CSF pleocytosis and diffuse spinal cord gray matter lesions.
  • CSF pleocytosis resolution occurs at 2 weeks12.

Subacute: Inpatient rehabilitation

  • Functional and respiratory optimization (details discussed in section C).

Chronic/stable: Outpatient setting

  • Improvement and resolution of spinal cord changes in weeks to months
  • Persistent motor weakness common 1 year out from diagnosis14.
  • Functional improvement with intermittent plateaus anecdotally common
  • Slower motor gains, especially when compared to transverse myelitis2.
  • Muscle atrophy will occur10
  • Weakness may present with head tilt

Specific secondary or associated conditions and complications

  • Some studies have indicated that 25-40% require ventilation2.
  • A preceding viral illness is reported in 90% of patients4.
  • Autonomic dysfunction is often present8.

2. ESSENTIALS OF ASSESSMENT

History

  • Acute Flaccid Myelitis presents with history of a viral infection with either respiratory or gastrointestinal symptoms4.
  • After prodromal viral symptoms of 7 days, patients report sudden onset of arm or leg weakness and loss of muscle tone12,18.
  • Other symptoms reported include headaches, neck pain, facial droop, double vision, difficulty swallowing, pain in affected limbs, difficulty moving eyes, drooping eyelids, numbness and tingling, change in voice, and/or inability to urinate18.
  • In severe cases, patients can have respiratory failure needing ventilation or neurological complication leading to death18.

Physical examination

  • Examination of these patients reveal findings similarly seen in patients with spinal cord injury; this includes spinal shock19.
  • Weakness is evaluated as asymmetric paralysis in arms or legs.  Often, patients are weaker proximally and stronger distally.  Sometimes, this results in children “finger crawling” where their fingers will direct movement of the extremity across tables or their torso without elbow flexion to complete a functional task like scratching the nose.  In some patients with cervical involvement, they may present with flaccid upper extremities and hypertonic lower extremities with; however, this is not always the case.
  • Patients will also present with diplopia, ophthalmoplegia, dysphagia, dysphonia, dysarthria, impaired sensation (allodynia, dysesthesias, paresthesias), decreased tone, hyporeflexia, autonomic instability, facial weakness, and decreased trunk/cervical tone8,19.

Clinical functional assessment: mobility, self-care cognition/behavior/affective state

  • Mobility: inability to sit, stand, walk, or transfer
  • Self care: deficits in dressing, eating, drinking, bathing, toileting, bowel and bladder function affected
  • Cognition/Behavior/Affect: abnormal coping strategies.  With associated hypoxic events, there may be cognitive issues like memory, executive function being affected.
  • Respiratory status may be affected

Laboratory studies

Source 8 Test
Nasopharynx Respiratory PCR panel, enterovirus PCR
Serum- for differential diagnosis
Infectious West Nile IgG, IgM, EBV antibodies, Lyme serology, Enterovirus PCR
Inflammatory/metabolic  CBC, CMP, Vitamin B12, D-25-OH,IgA, NMO-IgG, ANA, Oligo clonal bands
CSF-
Infectious CSF HSV, EBV PCR, enterovirus PCR
Inflammatory Oligo clonal bands, ?NMO IgG
Urine Enterovirus PCR
Stool Enterovirus PCR (CDC per polio testing guidelines)

Imaging

  • MRI spinal cord may show increased T2 signal, non-enhancing, throughout central gray matter of spinal cord, mainly the anterior horn cells1,2,5,8.
  • By current definition, these spinal cord lesions span one or more spinal segment4.
  • Cord lesions have a predilection for the cervical area, but lesions can extend below this region20.
  • MRI brain may show prominent increased T2 changes in pons and medulla and occasional involvement of dentate nucleus of cerebellum, substantia nigra with enhancement of facial nerves, and supratentorial changes10. Lesions may be seen primarily affecting cortical and subcortical gray matter, including caudate nucleus and thalamus is seen11.

Supplemental assessment tools

  • Electrodiagnostic studies may be normal acutely12. Electromyography (EMG) changes are usually observed in C5 to C7 levels, but changes are also noted in muscle groups and limbs that were clinically unaffected12.
  • At 1-3 weeks following neurologic injury, EMG may variably show fibrillations and reduced recruitment of motor unit action potentials; nerve conductions studies (NCS) may show low amplitudes of compound unit action potentials (CMAPs)12,14.
  • After 3 weeks, most patients with AFM will definitively show fibrillations, reduced recruitment of MUAPs, and CMAPs with low amplitude12. Similar results can be seen at months to 1 year, or even over a year in some cases12.

Early prediction of outcomes

  • Highest frequency of residual abnormalities on neuroimaging seen in lumbar spinal cord, is associated with higher frequency of disability in lower extremities21.
  • Atlas-based measures of proportion of GM T2 signal abnormality measured on a single axial MR imaging section and across the full lesion segment correlate with motor impairment and outcome in patients with acute flaccid myelitis22.
  • Anecdotally, patients who present with mixed gray-white matter lesions may respond to treatment better than restricted gray-matter lesions.
  • There seems to be a better prognosis for vent weaning when chest and shoulder musculature returns, but this is speculative.

Environmental

As discussed previously, no exact cause has been specifically identified; but due to its possible association with EVD68, Enterovirus A71, and coxsackie A16, assessing recent illness or travel is warranted1,2,4,5.

Social role and social support system

Families face social isolation while caring for their loved ones. It is important to help families be connected with other families in similar situations. The patients and families may also require counseling for coping strategies.

Professional issues

  • Suspected cases should be reported to CDC
  • Difficulty in performing placebo controlled trials limits the ability to definitively identify treatment options.
  • Families should be encouraged to pursue options for recreation for their loved ones, thus enhancing their quality of life.
  • Families should be provided with appropriate equipment, splinting to maintain mobility, ROM. It is possible that some of the recommended equipment may not be covered by insurance.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

  • Acute treatment consists of intravenous immunoglobulin (IVIG), steroids, and/or plasmapheresis (PLEX). However, there is no evidence to suggest one over the other.
  • There is limited research that provides specific guidelines and recommendations for rehabilitation management of AFM.
  • Early initiation of therapies while in acute phases of illness is preferred to address functional needs8.

At different disease stages

  • New onset/acute: Hospital setting
    • Early initiation of therapies includes physical therapy, occupational therapy, and speech therapy
    • Orthotics for positioning, support, and function.
    • Pressure Relief Ankle Orthotics (PRAFO) to prevent ankle contractures and skin breakdown at the heel for leg weakness
    • Neuromuscular electrical stimulation
    • Monitor for spastic neurogenic bladder. There is no specific duration as to when a spastic bladder emerges from flaccidity. This is complicated in the setting of mixed gray-white matter involvement.
    • Monitor for constipation
    • Address sleep/wake cycle as indicated
    • May require turns every 2 hours to prevent skin breakdown with limited mobility and/or a specialized mattress
    • Pain management for neuropathic pain but not common
    • Neurology treatment plan during acute hospital stay
    • Monitoring medical stability for potential transfer to inpatient rehabilitation
    • Addressing role as PM&R physician in their child’s care
  • Subacute: Inpatient Rehabilitation
    • In addition to above, address the following:
    • Neuromuscular electrical stimulation has been shown to be one of the current best effective practices in treatment
    • Robotic-assisted technologies
    • Vent optimization
    • Shoulder subluxation prevention with sling and/or kinesiotaping
    • Addressing adjustment and mood disorders
    • Neck bracing for weak cervical musculature in the setting of tracheostomy status and ventilation
    • Dysphagia diet management as indicated
    • Assessing cervical and truncal stability
  • Chronic/stable: Outpatient Management
    • Continues outpatient therapies
    • Episodic inpatient rehabilitation admissions
    • Osteopenia management
    • Consideration for nerve transfer surgeries at 6 months after diagnosis
    • Consider pool therapy or hippotherapy.
    • Continues neuromuscular electrical stimulation home exercise program

Coordination of care

  • Throughout each setting, adequate handoff is crucial across the continuum of care. A multi-disciplinary team-based approach is optimal for management.
  • Medical teams may also include pulmonology (vent support or sleep study), ENT, primary pediatrician, endocrinology (osteopenia assessment), gastroenterology/surgery (possible gastrostomy tube placement)
  • Therapy teams include physical therapy, occupational therapy, or speech therapy. Other therapies to consider are pet therapy, music therapy, or art therapy.
  • Other team members include child life, social work, care coordinators, nursing, nutrition/dietician, psychology/counseling, and respiratory therapy.
  • Alternative treatments may include massage, osteopathic manipulation, and acupuncture.
  • After inpatient stay, follow up in an outpatient clinic may include pediatric physiatry, neurology, neuropsychology, physical therapy, social worker, and nursing coordinator.

Patient & family education

  • Centers for Disease Control and Protection (CDC) and AFM Task Force website has resources for clinicians and family members4.
  • Some families find social media outlets helpful such as the Facebook group for AFM families.
  • Podcasts about AFM are available23.

Measurement of Treatment Outcomes including those that are impairment-based, activity participation-based and environmentally-based

  • Functional Independent Measures for Children (WeeFIM).
  • AFM Task Force Rehab Subgroup is currently discussing a variety of possible functional measures for research

Translation into Practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  • Incorporate neuromuscular electrical stimulation as early as possible in the course of their disease process. Encourage family to obtain NMES units for home use with guidance from PM&R or therapist for use. Settings and frequency should be based on what the child can tolerate with guidance from therapists. It is common to initiate at lower amplitudes, but enough to generate a motor response. The range for use can be 30-90 minutes daily, but psychosocial factors must be taken into consideration such as timing for therapies, school, etc.
  • Patients often require multiple stays at an inpatient rehabilitation facility to address new goals towards function. If possible, consider increasing daily therapy time from 3 hours up to 6 hours; this patient population can generally tolerate this intensity of therapy and functionally benefit from this intense “burst” of therapies. These can include therapy co-treatments.
  • There have been functional gains noted in patients post-nerve transplants and could be considered for inpatient rehabilitation9,16.
  • There is a likely risk of osteopenia in this patient population; be aware of risk with aggressive ROM and electrical stimulation as this could cause fracture.
  • Consider use of fluoxetine for depression/anxiety due to its anti-viral properties, however, this is not officially recommended by the CDC2,17.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

  • Early mobility programs that include activity based rehabilitative therapies including weight bearing activities, bed mobility, NMES, and transfers may be advantageous.
  • NMES and functional electrical stimulation (FES) with and without muscle contraction is beneficial.
  • Utilization of aquatic therapy
  • Massed practice with repetition and increased level of activity is tolerated by children up to 5 hours per day.
  • Vibration therapy may help activate denervated muscles.
  • Nerve transfers need validated studies to guide timing for maximum benefit.
  • Use of robotic therapies may be useful to obtain functional goals.

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

  • There is no specific definite cause of AFM.
  • It is also unclear why some patients are affected more than others.
  • Though it is considered a condition affecting the gray matter, there is some extension to white matter as well.
  • Recovery is also variable.
  • Difficulty in performing placebo controlled trials.

REFERENCES

  1. Greenberg B. Acute Flaccid Myelitis: A Modern Day Polio? Presentation at New Frontiers in Pediatric Neurology. 31 May 2019.
  2. Wang C and B Greenberg. Clinical Approach to Pediatric Transverse Myelitis, Neuromyelitis Optica Spectrum Disorder, and Acute Flaccid Myelitis. Children (Basel). 2019 May; 6(5): 70.
  3. Standardized Case Definition for Acute Flaccid Myelitis. https://c.ymcdn.com/sites/www.cste.org/resource/resmgr/2017PS/2017PSFinal/17-ID-01.pdf
  4. Centers for Disease Control and Prevention AFM Investigation 2019. [(accessed on 15 May 2019)]; Available online:https://www.cdc.gov/acute-flaccid-myelitis/afm-surveillance.html.
  5. Fernandez-Garcia MD, Kebe O, Fall AD, Dia H, Diop OM, Delpeyroux F, Ndiaye K. Enterovirus A71 Genogroups C and E in Children with Acute Flaccid Paralysis, West Africa. Emerg Infect Dis. 2016 Apr; 22(4):753-5.
  6. Centers for Disease Control and Protection. Causes and Preventions of AFM. https://www.cdc.gov/acute-flaccid-myelitis/causes-prevention.html
  7. Hixon AM, Yu G, Leser JS, Yagi S, Clarke P, Chiu CY, et al. A mouse model of paralytic myelitis caused by enterovirus D68. PLoS Pathog. 2017:13.
  8. Hopkins S. Acute Flaccid Myelitis: Etiologic Challenges, Diagnostic and Management Considerations. Curr Treat Options Neurol (2017) 19: 48 DOI 10.1007/s11940-017-0480-3
  9. Maloney JA, Mirsky DM, Messacar K, Dominguez SR, Schreiner T, Stence NV. MRI findings in children with acute flaccid paralysis and cranial nerve dysfunction occurring during the 2014 enterovirus D68 outbreak. Am J Neuroradiol. 2015;36:245–50. (now 9)
  10. Sejvar JJ, Lopez AS, Cortese MM, Leshem E, Pastula DM, Miller L, et al. Acute flaccid myelitis in the United States, August-December 2014: results of nationwide surveillance. Clin Infect Dis. 2016;63:737–45. (now 10)
  11. Van Haren K, Ayscue P, Waubant E, Clayton A, Sheriff H, Yagi S, et al. Acute flaccid myelitis of unknown etiology in California, 2012-2015. JAMA. 2015;314:2663–71. (now 11)
  12. Messacar K, Schreiner TL, Van Haren K, Yang M, Glaser CA, Tyler KL, Dominguez SR. Acute flaccid myelitis: A clinical review of US cases 2012-2015.Ann Neurol. 2016;80(3):326. Epub 2016 Aug 4.
  13. Van Haren K, Ayscue P, Waubant E, Clayton A, Sheriff H, Yagi S, Glenn-Finer R, Padilla T, Strober JB, Aldrovandi G, Wadford DA, Chiu CY, Xia D, Harriman K, Watt JP, Glaser CA Acute Flaccid Myelitis of Unknown Etiology in California, 2012-2015. JAMA. 2015;314(24):2663.
  14. Martin JA, Messacar K, Yang ML, Maloney JA, Lindwall J, Carry T, Kenyon P, Sillau SH, Oleszek J, Tyler KL, Dominguez SR, Schreiner TL. Outcomes of Colorado children with acute flaccid myelitis at 1 year. Neurology. 2017 Jul 11; 89(2):129-137.
  15. Nath RK and C Somasundaram. Functional Improvement of Upper and Lower Extremity After Decompression and Neurolysis and Nerve Transfer in a Pediatric Patient with Acute Flaccid Myelitis.” Am J Case Rep. 2019; 20: 668–673.
  16. Hopkins SE, Elrick MJ, Messacar K.
    Acute Flaccid Myelitis-Keys to Diagnosis, Questions About Treatment, and Future Directions. JAMA Pediatr. 2018 Nov 30.
  17. Messacar K et al. 1901. Tolerability, and Efficacy of Fluoxetine as an Antiviral for Enterovirus D68 Associated Acute Flaccid Myelitis: A Retrospective Multicenter Cohort Study. Open Forum Infect Dis. 2018 Nov; 5(Suppl 1): S546.
  18. Centers for Disease Control. Symptoms of AFM. [Accessed 11 August 2019]; Available online: https://www.cdc.gov/acute-flaccid-myelitis/symptoms.html
  19. Transverse Myelitis Association. Acute Flaccid Myelitis. [10 August 2019]; Available online: https://myelitis.org/living-with-myelitis/disease-information/afm/
  20. Maloney JA et al. MRI findings in children with acute flaccid paralysis and cranial nerve dysfunction occurring during the 2014 entervorus D68 outbreak. Am J Neuroradiol. 2015;36:245-50.
  21. Gordon-Lipkin E et al. Comparative quantitative clinical, neuroimaging, and functional profiles in children with acute flaccid myelitis at acute and convalescent stages of disease. Dev Med Child Neurol. 2019 Mar;61(3):366-375.
  22. McCoy DB et al. MRI Atlas-Based Measurement of Spinal Cord Injury Predicts Outcome in Acute Flaccid Myelitis.  AJNR Am J Neuroradiol. 2017 Feb;38(2):410-417.
  23. Transverse Myelitis Association. Resource library.  [Accessed on 10 August 2019];  Available online: https://myelitis.org/living-with-myelitis/resources/resource-library/

Author Disclosure

Rajashree Srinivasan, MD, MBBS
Nothing to Disclose

Kelli Chaviano, DO
Nothing to Disclose

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