acute flaccid myelitis - mcaap.org
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Acute Flaccid Myelitis –
A needle in the haystackLeslie Benson, MD
Pediatric MS and Neuro-Immunology ProgramBoston Children’s Hospital
12/3/2020
Presenter Disclosure Information
• I, Leslie Benson, have been asked to disclose any significant relationships with commercial entities that are either providing financial support for this program or whose products or services are mentioned during our presentations.
• I will discuss the use of medications in a manner not approved by the U.S. Food and Drug Administration.
2
Disclosures• Department of Public Health - AFM Consultant • CDC AFM Task Force member
• Unrelated financial disclosures:o Site PI on an Alexion clinical trial in the past year (product not
related to AFM)o Vaccine injury compensation program
• All patient pictures are used with consent
Objectives• The participants will be able to recognize common
presentations and exam findings to help identify this diagnosis.
• The participants will be able to recognize clinical and radiographic features differentiating acute flaccid myelitis from Guillain Barre syndrome and inflammatory transverse myelitis.
• The participants will understand the current data supporting an association between enterovirus D68 and acute flaccid myelitis.
Luca
Case (2014)• 3 year-old healthy boy
• Right deltoid vaccinations 2 weeks prior
• 5 days febrile URI with wheeze requiring albuterol
• Day 1o Right arm &
bilateral neck weakness
o Headache, neck pain, right arm and leg pain
• Examo Fevero Confirmed
weako Hyporeflexico Hypotonic
neck and limbs
Presentation
Messacar K. 2016.
Presentation
Messacar K. 2016.
Spectrum of Disease
Respiratory failure &
death
Clear weaknessMinor limp
Mimics
Neurological Differential Diagnosis
• Guillain Barre Syndrome (peripheral demyelinating)• Acute Transverse Myelitis
o Clinically isolated syndrome (CIS), idiopathico Multiple sclerosis (MS)o Neuromyelitis Optica (NMO)
• Ischemia/strokeo Anterior or posterior spinal artery infarcto AV fistulao AV malformationo Fibrocartilaginous embolus
• Infection o bacterial, fungal, parasitic, viral
Work Up• No diagnostic biomarker• Imaging – MRI with and without
contrast o MRI cervical, thoracic and lumbar spine
• *Include lumbar spine if AFM or Guillain Barre are on the differential!
• Axial imaging
• MRI Braino *Early imaging may be normal, consider repeat
• Labs
Case
Anterior horn/gray matter predominant lesions
Radiculitis – anterior predominant
Characteristic MRI findings of AFM
*From Maloney JA et al. Am J Neuroradiol 2015;36(2):245-50 16
Anterior horn cell predominant injury
Weakness predominates
Level(s) and side affect localization
Secondary inflammation may contribute to sensory and other deficits
Diagnostic Findings
Messacar K. 2016.
Work Up• Labs – AS EARLY AS POSSIBLE• State Lab - NP swab (PCR), serum, stool, CSF • NP/OP – EV PCR vs panel w/ EV• Serum -
o EV PCRo MOG Abo Consider Coxsackie, Echovirus, West Nile serology, HSV, EBVo Lyme o Aquaporin 4 Ab (NMO)
• CSFo Cell count, protein, glucose, Gram stain, cultureo oligoclonal bandso Consider EV PCR, broad panel testing
• Stool – EV PCR
• Others guided by differential diagnosis, season
Specimens to collect and send to CDC for testing of cases of suspected AFM
20https://www.cdc.gov/acute-flaccid-myelitis/hcp/specimen-collection.html
Case – Lab evaluation • CSF:
o 102 WBC (20% neutrophils, 64% lymphocytes and 16% monocytes )
o 21 red blood cells, o glucose 63 o protein of 32.8.
History• Fall 2012 – CA surveillance and publications• Fall 2014 – recognized as following enterovirus D68
(EV D68) respiratory illness outbreak, starting in COo Acute flaccid myelitis (AFM) =
• A type of acute flaccid paralysis• “Polio-like myelitis”
• Fall 2016 • Fall 2018
CDC Monitoring
https://www.cdc.gov/acute-flaccid-myelitis/cases-in-us.html
Social distancing and enhanced infection precautions
Definitions• CDC definitions are for reporting and epidemiologic
studyo https://www.cdc.gov/acute-flaccid-myelitis/hcp/case-definitions.html
• Clinical and research criteria are needed
AFM Pathophysiology
Post-infectious autoimmune vs
Direct viral invasion
Pathophysiology
• Epidemiology• Mice• Viral Genes• Neurons• Humans
Hixon, et al. Viruses. 2019
AFM paralleled Enterovirus D68
• AFM
• EV D68
Sejvar J, et al. 2016
*Larger proportion of AFM cases +EVD68 than controls getting NP swabs
Lab Findings
Messacar K. 2016.
4
AFM Pathophysiology• Mouse models suggests direct viral invasion
AFM Pathophysiology• 4/5 strains from 2014 →
paralyzed neonatal mice• Age dependent paralysis• Loss of motor neurons• Infectious virus, viron particles
and viral genome in spinal cords
• Immune sera protective against paralysis
Hixon, et al. PLOS Pathogens. 2017
EV68 Neuronal Transport• Like polio, EV-D68 can be transported from distal to
proximal nerveo Mouseo In vitro motor neurons
• Newer EV D68 strains (but not older) are neuro-invasive in vitro
• BUT Mice aren’t humans
Hixon et al. J Virology. 2019; Hixon, et al. PLOS Pathogens. 2017
CSF Anti-EV Antibodies
CSF Anti-EV Antibodies
Polio-like myelitis• Similar mechanism• Different virus an presentation:
o Arm predominant vs lego Case numbers
EVD68 is NOT the only culprit
Kincaid O, Lipton H. 2006.
CDC Monitoring
https://www.cdc.gov/acute-flaccid-myelitis/cases-in-us.html
?
Case – Hospital Course• 2-3 week hospitalization• Remained febrile• IVIG 2g/kg days 2 and 3• Progressive weakness – 4 limbs, neck• Respiratory decompensation day 3 requiring BiPAP,
intermediate care unit transfer• Plasma exchange with IVIG dosed after
Case – Hospital Course• Day 4
o Steroids + Pocapavir (anti-viral under a compassionate use emergency IND)
• Day 5 – started to improve
• Symptomatic/supportive managemento Gabapentin for paino NGTo Hypertension management
Treatment Approach• Acute & Chronic Rehab• Acute & Chronic supportive care• Acute anti-viral?• Acute anti-inflammatory?• IVIG?• Surgery?• New?
Treatment Approach
Messacar K. 2016.
Acute Treatment• Preliminary Mouse Data
o IVIG – GOOD o Steroids - BADo Fluoxetine – EQUIVOCALo More on the horizon
Tyler K. AAN 2017.
Acute Treatment• Preliminary Mouse Data
o IVIG – GOOD o Steroids – BAD - lethalo Fluoxetine – EQUIVOCALo More on the horizon?
Tyler K. AAN 2017.
as much and as early as possible?
Monoclonal antibody therapy
• BUT Mice aren’t humans
Case - Rehabilitation• 1 month rehabilitation
o Non-ambulatory, breathing unassisted -> walked out
• Years of outpatient therapy• Ongoing right shoulder weakness• Neck weakness requiring brace
Rehabilitation and Chronic Treatment
• Symptomatic• Supportive• Respiratory• Physical Therapy• Occupational Therapy• Speech therapy• Feeding therapy• Pool therapy• Bladder/Bowel• E-stim
Rehabiliation
E-Stim• Theory: Electrical stimulation
of the motor nerves to “exercise” the muscle while the nerves branch and reinnervate
Nerve Transfer Surgeries• Take fascicles from a strong nerve (donor) and
move to a weak nerve• Increasing publications• Promise with lots of uncertainty
Prognosis
Messacar K. 2016.
Prognosis• Joint
subluxations/dislocations• Limb length
discrepancies• Scoliosis• Contractures• Reduced protective
reflexes• Osteopenia• Fractures• Chest wall deformities• Ventilator dependence• Dysphagia• Constipation• Psychological struggles• Cosmetic concerns
Restorative surgeries• Muscle transfer• Tendon transfer• Scoliosis interventions
Prognosis- further theories
• Post Polio Syndrome?
• Early degenerative joint disease?
• Restrictive lung disease?
• Sleep disordered breathing/ hypoventilation?
What can you do?• Diagnose ->Refer• Hospitalize• Provide acute support• Report and send specimens• Be aware of acute treatment
options as evolves• Refer to centers doing research
https://www.cdc.gov/acute-flaccid-myelitis/hcp/clinicians-health-departments.html
TipsFindings Check
Fever History
Limb, back, neck pain History
Bulbar dysfunction Listen to speechHistory- swallow/cough
Cranial neuropathy Smile/cryEye tracking toy
Weakness (often proximal)
Jump, leg raise forward and backward, march, get up from floorLift arms over head
Gait/limp
Hyporeflexia CHECK REFLEXES
Flaccid tone Feel limb, resting posture
Why is Diagnosis Urgent• Avoid complications
o Unsupported respiratory decompensationo Aspiration
• Sample collection → understanding etiology• Optimize treatment response• Virus may prognosticate
Dominguez C et al. Canadian
Future Directions
• CDC AFM Task Force• National AFM Working Group• NIH “Natural History Study”• Biomarker, therapeutic and
vaccine discovery research• CSF EV-D68 Ab test• Long term follow up studies
• Collaboration!
Summary• AFM is caused by viral injury of the motor neurons
of the spinal cord similar to polio and linked to EV-D68
• A viral prodrome followed by neck or back pain, progressive weakness
• NP/OP, blood, stool and CSF labs along with MRI are indicated
• Early work up for higher yield• Cases should be reported to CDC
o https://www.cdc.gov/acute-flaccid-myelitis/hcp/index.html
• Early IVIG may help
Summary (cont)• Phone a friend –
• Page me• Visit www.cdc.gov/afm• Contact CDC AFM program at
[email protected]• Contact other AFM specialists
via the AFM Physician Consult and Support Portal: https://wearesrna.org/living-with-myelitis/resources/afm-physician-support-portal/