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Acute Flaccid Myelitis: Case Report

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Medical Surveillance Monthly Report

ABSTRACT

In August 2018, the U.S. Centers for Disease Control and Prevention (CDC) noted an increased number of reports of patients in the U.S. having symptoms clinically compatible with acute flaccid myelitis (AFM). AFM is characterized by rapid onset of flaccid weakness in one or more limbs and distinct abnormalities of the spinal cord gray matter on magnetic resonance imaging (MRI). Clinical and laboratory data suggest that AFM is associated with an antecedent viral infection. AFM may be difficult to differentiate from other causes of paralysis and, given that it is rare, has the potential to be overlooked. This case highlights important clinical characteristics of AFM and emphasizes the importance of including AFM in the differential diagnosis when evaluating active duty service members and Military Health System (MHS) beneficiaries presenting with paralysis.

 

CASE REPORT

On 23 September 2018, the previously healthy 9-year-old daughter of an active duty service member presented to the Fort Belvoir Community Hospital (FBCH) emergency department with sore throat, left earache, headache, neck pain, and history of fever to 101.0°F.

Symptoms of cough and congestion started approximately two weeks prior, on 10 September 2018. Unlike her younger brother, who had similar symptoms and improved, the patient’s symptoms worsened such that she missed school on Friday, 14 September 2018 and Monday, 17 September 2018. The patient attempted to resume normal activities but nearly fainted on 19 September 2018 while testing for her Purple Belt in Tae Kwon Do. On 20 September 2018, the patient developed nausea, anorexia, malaise, dizziness, and fever to 100.5°F. By 23 September 2018, her temperature had increased to 101.0°F and her symptoms progressed to include symptoms that led to her emergency room visit.

When the patient presented to the emergency department on 23 September 2018, her temperature was 98.8°F. Her left tympanic membrane appeared erythematous. Her neck was tender and lymphadenopathy was noted; Kernig and Brudzinski signs could not be elicited. The patient was diagnosed with left otitis media and neck strain. She was treated with ibuprofen 400 mg and dexamethasone 10 mg by mouth. She was discharged home on amoxicillin and ibuprofen.

By 25 September 2018, day 16 of illness, the patient had difficulty turning on the bathroom light due to weakness in her upper extremities. She also had weakness in her neck and imbalance such that she had difficulty ambulating. The patient presented to the pediatric clinic in a wheelchair with headache, neck pain, imbalance, and generalized weakness. Her examination was remarkable for left facial weakness and neck pain radiating to the lower back with neck flexion. She was directed to the emergency department for further evaluation and treatment.

On examination in the emergency department,  the patient’s vital signs were stable; her temperature was 99.6°F. Examination of her head, eyes, ears, nose and throat revealed dull tympanic membranes, pharyngeal erythema, and left facial weakness consistent with Bell’s palsy. Upper extremity weakness and nuchal rigidity were also noted. The patient’s chest x-ray was clear and computed tomography (CT) of the head was normal. Her rapid strep test was negative. A monospot was ordered (results not reported). Her white blood cell count (WBC) was 6,600 cells/µL with neutrophilic predominance (81.6%); hematocrit and platelets were normal. Her basic metabolic panel was also normal. A lumbar puncture was performed revealing clear, colorless cerebrospinal fluid (CSF) with a white blood count of 77 cells/µL (normal 0-5 cells/ µL) (neutrophils 19%; lymphocytes 64%; monocytes 17%), red blood count 0 cells/ µL; protein 49 mg/dl (normal 15-45 mg/ dl); glucose 64 mg/dl (normal 60-80 mg/dl). Gram stain of the CSF was negative. A rapid multiplex CSF PCR panel was negative for Escherichia coli Ag; Hemophilus influenzae rRNA; Listeria Monocytogenes rRNA; Neisseria meningitidis rRNA; Streptococcus agalactiae Ag; Streptococcus pneumoniae rRNA; Cytomegalovirus DNA; Herpes Simplex Virus 1 DNA; Herpes Simplex Virus DNA; Human Herpesvirus 6 DNA; Parechovirus RNA; Varicella Zoster Virus DNA; Enterovirus RNA; and Cryptococcus neoformans rRNA. Blood and CSF cultures were sent.

The patient was treated presumptively for meningitis with intravenous ceftriaxone in the emergency room and she was admitted to the hospital. Additional history revealed that the patient had a bull’s-eye rash while living in Utah 16 months prior, and that she was treated presumptively for Lyme disease at the time. Her history also revealed that she had complained of knee and ankle pain since August 2018. Although the patient lived and vacationed in wooded areas where Lyme disease is prevalent, she had no history of a tick bite.

The patient developed a rash after her first dose of ceftriaxone and was switched to meropenem. She was also treated with doxycycline for presumed Lyme disease. CSF and blood cultures were negative at 48-hours and meropenem was discontinued. Lyme serology and Lyme CSF PCR were negative on 28 September 2018. Doxycycline was continued due to high suspicion for Lyme disease.

On 29 September 2018, magnetic resonance imaging (MRI) of the brain (without contrast) was normal. MRI of the cervical spine revealed abnormal central T2 signal within the spinal cord with expansion extending from the level of cervical vertebrae C2–C3 to C6–C7 consistent with myelitis. Given the clinical presentation, MRI findings, and CSF pleocytosis, the patient was diagnosed with acute flaccid myelitis (AFM). She was treated with methylprednisolone 1 gram IV daily for 3 days.

Repeat MRI of the brain (with contrast) and MRI of the internal auditory canals were performed on 1 October 2018 and were normal. MRI of the thoracic spine was normal on 2 October 2018. Additional testing included a respiratory virus culture which was negative for influenza A/B, parainfluenza, adenovirus, and respiratory syncytial virus. Tests for Mycoplasma pneumoniae IgM, Bartonella, West Nile Virus, and Ehrlichia were negative. Myelin-associated Glycoprotein-Sulfated Glucuronic Paragloboside IgM was less than 1:10 (negative) and Neuromyelitis Optica Antibody IgG was less than 1.5 U/ml (negative).

The patient’s weakness worsened during the first 2 days following admission then improved over the course of her hospitalization. Weakness was limited to the face, neck, and upper extremities. Her facial weakness was associated with transient left facial numbness and arm weakness was associated with reduced tendon reflexes. The patient did not experience lower extremity weakness, dysphagia, or respiratory compromise. Joint pain involving the knees, ankles, wrists and elbows was noted. Gabapentin provided partial relief.

The patient was discharged home in stable condition on 3 October 2018. In spite of her diagnosis, doxycycline was continued for the unlikely possibility of Lyme disease. Follow-up with primary care, pediatric neurology, pediatric infectious disease, and occupational and physical therapy was scheduled.

 

EDITORIAL COMMENT

The incidence of acute flaccid paralysis (AFP) in the U.S. decreased dramatically following the introduction of inactivated polio vaccine (IPV) in 1955 and oral polio vaccine (OPV) in 1961. However, cases of AFP attributable to oral trivalent attenuated polio vaccine1 and other viruses (including enterovirus [EV-A71],2 enterovirus D68 [EV-D68],3 Epstein-Barr virus,4 and West Nile virus5) continue to occur. The estimated incidence of AFP in the U.S. among those under 15 years of age is 1.4 per 100,000 person-years.6

In August 2012, the California Department of Public Health (CDPH) was notified of 3 cases of AFP associated with anterior myelitis. In spite of laboratory testing, a causative agent could not be found. Following these reports, CDPH posted alerts requesting early reporting of cases and collection of clinical samples. A case was defined as flaccid paralysis in at least one limb consistent with anterior myelitis as indicated by neuroimaging of the spine or electrodiagnostic studies (e.g., nerve conduction studies and electromyography) and with no known alternative etiology. Between June 2012 and June 2014, 23 cases of AFP with anterior myelitis were identified. Common features included an upper respiratory or gastrointestinal prodrome less than 10 days before AFP onset and CSF pleocytosis. The median age of patients was 10 years (range=1–73 years). The etiology of AFP among reported cases was unclear; poliovirus was determined to be an unlikely cause.7

On 3 October 2014, CDC posted a Morbidity and Mortality Weekly Report (MMWR) Early Release describing a cluster of 9 children evaluated at Children’s Hospital Colorado for acute neurologic illness characterized by extremity weakness or cranial nerve dysfunction (or both) following a febrile illness. Among the 8 children who had magnetic resonance imaging of the spinal cord, 7 had lesions of the gray matter spanning multiple levels, and 8 had mild to moderate CSF pleocytosis. Based on reported clinical and anatomic characteristics, the illness was referred to as acute flaccid myelitis (AFM), to distinguish it from other forms of AFP.8 Given that the cases occurred during a national outbreak of EV-D68 and laboratory testing among some cases suggested recent EV-D68 infection, EV-D68 was identified as a potential cause.9 However, a definitive cause of the illness cluster could not be determined.10

From August through December 2014, 120 AFM cases from 34 states were reported to CDC. A case was defined as any person aged 21 years of age or younger, with acute onset of limb weakness and a spinal MRI revealing lesions predominantly of the gray matter. During the 5-month period, the crude nationwide AFM incidence among persons 21 years of age or younger was 0.32 cases/100,000 population/year. The most common site of involvement on MRI was the cervical spinal cord. CSF pleocytosis was present in 81% of cases. The median age was 7.1 years (range=0.4–20.8 years). Most affected individuals experienced a respiratory or febrile illness prior to the onset of limb weakness.11

In 2015, the Council of State and Territorial Epidemiologists (CSTE) and CDC updated the case definition for AFM to include CSF-based criteria. The current case definition for AFM is a person with onset of acute flaccid limb weakness, AND a magnetic resonance image showing a spinal cord lesion largely restricted to gray matter, and spanning one or more vertebral segments (confirmatory  evidence), OR cerebrospinal fluid (CSF) with pleocytosis (CSF white blood cell count >5 cells/ µL); CSF protein may or may not be elevated (supportive evidence).12 In spite of the broadened case definition, the number of cases reported to CDC dropped to 22 confirmed cases in in 2015. The count increased again in 2016 to 149 confirmed cases, then dropped in 2017 to 33 confirmed cases.

In August 2018, CDC noted an increase in the number of reports of patients with potential AFM.13 On 23 August 2018, CDC issued a notice via the Epidemic Information Exchange (Epi-X) to increase clinician awareness and provide guidance for case reporting. An MMWR Early Release dated 13 November 2018 reported 106 confirmed cases of AFM. This number increased to 165 confirmed cases among 320 reported cases on 14 December 2018.14

The case described in this report meets the CSTE and CDC case defini tion for AFM. Similar to other confirmed cases, limb weakness was accompanied by decreased deep tendon reflexes and preceded by a febrile illness. Of note, in the case reported here, the interval between onset of respiratory symptoms and onset of neurological symptoms (16 days) was longer than the median interval of 7 days (range=1–12 days) reported by CDC in 2017.15 The patient’s history of a bull’s eye rash and residence in a wooded area where Lyme is prevalent introduced a distracting clue into diagnostic deliberations. It also highlights the ambiguity and challenges clinicians face when they encounter rare conditions that have significant clinical overlap, an undefined etiology, and an evolving case definition.

Rapid identification of potential cases and early reporting have the potential to expedite identification of the etiologic agent or agents responsible for AFM, progressive characterization of clinical features, detection of risk factors, and identification of preventive measures.

Clinicians caring for patients with limb weakness should maintain a wide differential diagnosis, inquire about recent fever, respiratory and gastrointestinal symptoms, and perform MRI promptly. While AFM is not a reportable disease, potential cases of AFM should be referred to military Preventive Medicine departments and reported in the Disease Reporting System Internet (DRSi) under “Any Other Unusual Condition, Not Otherwise Specified.” Clinicians should also report potential cases of AFM to their state or local health departments, and to the CDC. In addition, specimens (i.e., cerebrospinal fluid, serum, stool, and respiratory samples) should be sent to CDC for standardized testing and expanded testing protocols. Information related to specimen collection and shipping is available at https://www.cdc.gov/acute-flaccid-myelitis/hcp/instructions.html.

Author affiliations: Walter Reed National Military Medical Center, Bethesda, MD (CPT Donahue); Armed Forces Health Surveillance Branch, Silver Spring, MD (CDR Clausen); Uniformed Services University of the Health Sciences, Bethesda, MD (Dr. Malloy); Defense Health Agency National Capital Region Medical Directorate (COL Dennison); Fort Belvoir Community Hospital, VA (CPT Falcon).

Disclaimer: The views expressed herein are those of the authors and do not necessarily reflect the official policy or position of the Army, the Department of Defense, or the United States Government.

Disclosure: The authors have no financial or non-financial interest to disclose.

 

REFERENCES

1. Platt LR, Estivariz CF, Sutler RW. Vaccine-associated paralytic poliomyelitis: a review of the epidemiology and estimation of the global burden. J of Inf Dis. 2014; 210(supp1):S380–S389.

2. Teoh HL, Mohammad SS, Britton PN, et al. Clinical Characteristics and Functional Motor  Outcomes of Enterovirus 71 Neurological Disease in Children. JAMA Neurol. 2016;73(3):300–307.

3. Greninger AL, Naccache SN, Messacar K, et al. A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): a retrospective cohort study. Lancet Infect Dis. 2015;15(6):671–682.

4. Wong M, Connolly AM, Noetzel MJ. Poliomyelitis-like syndrome associated with Epstein-Barr virus infection. Pediatr Neurol. 1999;20:235–237.

5. Sejvar JJ, Bode AV, Marfin AA, et al. West Nile virus-associated flaccid paralysis. Emerg Infect  Dis. 2005; 11(7):1021–1027.

6. Zangwill KM, Yeh SH, Wong EJ, et al. Paralytic syndromes in children: epidemiology and relationship to vaccination. Pediatr Neurol. 2010;42:206–212.

7. Ayscue P, Van Haren K, Sheriff H, et al. Acute Flaccid Paralysis with Anterior Myelitis — California, June 2012–June 2014. MMWR. 2014;63:903–905.

8. Centers for  Disease  Control  and  Prevention. Notes from  the  field:  acute  flaccid  myeli tis among persons aged =21 years—United  States, August 1-November 13, 2014. MMWR. 2015;63:1243–1244.

9. Sejvar JJ, Lopez AS, Cortese MM, et al. Acute flaccid myelitis in the United States, August-December 2014: results of nationwide surveillance. Clin Infect Dis. 2016;63(6):737–745.

10. Pastula DM, Aliabadi N, Haynes AK, et al. Acute neurologic illness of unknown etiology in children — Colorado, August–September 2014. MMWR. 2014;63(40):901–902.

11. Messacar K, Schreiner TL, Van  Haren  K, et al. Acute flaccid myelitis: a clinical review of U.S. cases 2012-2015. Ann Neurol. 2016;80:326–328.

12. Council of State and Territorial Epidemiologists. Standardized Case Definition of Acute Flaccid Myelitis. https://c.ymcdn.com/sites/www.cste.org/resource/resmgr/2017PS/2017PSFinal/17-ID-01.pdf. Accessed on 10 December 2018.

13. McKay SL, Lee AD, Lopez AS, et al. Increase in Acute Flaccid Myelitis — United States, 2018. MMWR Early Release. 2018;67:1–3.

14. Centers for Disease Control and Prevention. Acute Flaccid Myelitis. https://www.cdc.gov/acute-flaccid-myelitis/afm-surveillance.html. Accessed on 10 December 2018.

15. Bonwitt J, Poel A, DeBolt C, et al. Acute flaccid myelitis among children--Washington, September-November 2016. MMWR. 2017;66(31):826–829.















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