Acute flaccid myelitis (AFM) refers to a polio-like neurologic disease first reported in 2012 in California in a child with evidence of enterovirus D68 in the respiratory tract specimens.1 It affects the nervous system, specifically the area of the spinal cord called gray matter, which causes the muscles and reflexes in the body to weaken.2,3 This condition is not new. However, an increase in reported cases was observed in the late summer and fall of subsequent years, including 2014 when surveillance first started, 2016, and 2018.4,5
The risk of getting AFM varies by age and year. It mainly occurs in children and very rarely in adults. AFM cases have increased every two years since 2014 mostly in young children. Still, the Centers for Disease Control and Prevention (CDC) estimates that less than one to two in a million children in the United States will get AFM every year. AFM is not contagious person to person but may spread to humans from mosquitoes.
After completing this course, the participant will be able to meet the following objectives:
AFM is rare, with an estimated incidence of less than one case per one million population in the United States.6 During the late summer and fall of 2014, 120 confirmed cases of AFM were reported to the CDC in the United States, and standardized surveillance was established in 2015. Since 2014, nearly 400 cases have been reported in the United States.4,7 Similar cases have been reported from Europe, Canada, and Japan.8-14 The condition predominantly affects children and young adults.1,15
The following graph shows the seasonal nature of the occurrence of AFM. Note the increases that occurred in the late summers of 2014, 2016, and 2018.
The graph shows the number of AFM cases confirmed by the CDC as of February 1, 2019, with onset of the condition through January 31, 2019. The case counts are subject to change.
The data shown from August 2014 to July 2015 are based on the AFM investigation case definition: onset of acute limb weakness on or after August 1, 2014, and a magnetic resonance image (MRI) showing a spinal cord lesion largely restricted to gray matter in a patient age ≤ 21 years.
The data shown from August 2015 to present are based on the AFM case definition adopted by the Council of State and Territorial Epidemiologists (CSTE): acute onset of focal limb weakness and an MRI showing spinal cord lesion largely restricted to gray matter and spanning one or more spinal segments, regardless of age.
The CDC had confirmed 538 cases of Enterovirus 68 (also known as EV68, EVD68, EV-D68, HEV68) infection in 43 states. The CDC has determined and submitted to GenBank complete or nearly complete genomic sequences for three known strains of the virus, which are "genetically related to strains of Enterovirus 68 that were detected in previous years in the United States, Europe, and Asia."16,17
While rates of paralytic symptoms appear to be correlated with the number of respiratory infections, in initial anecdotal reports, the cases are not clustered within a family or school, suggesting that the paralysis per se is not directly contagious, but arises as a very rare complication of the common respiratory infection.18
Acute flaccid myelitis is not a new condition, but the incidence has spiked in recent years.
In 2013 a group in Texas reported having observed a pattern of one to four cases per year with similar polio-like characteristics.18
In 2014 the CDC Morbidity and Mortality Weekly Report19 and a CDC Clinician Outreach and Communication Activity (COCA) conference call,20 noted that many cases had neck, back, or extremity pain, but otherwise those affected generally had normal sensation in their limbs.21 A few participants in the conference call discussed whether pain, later abating, might precede the onset of paralysis.20,22
The CDC requested that physicians provide information about cases meeting the following criteria:23,26
In November 2018, the CDC reported that they were investigating 286 cases, with at least 116 confirmed cases in 31 states.27 The CDC is setting up a task force to investigate the causes and to find treatments.28
It is important to remember the following:
Until AFM is confirmed, often similar neurologic conditions are termed acute flaccid paralysis which can have multiple causations.
As of October 2018, the CDC regarded the cause of AFM or similar neurologic conditions (Table 1 below) as having "a variety of possible causes” such as:2
|Herpes zoster: r/o*|
|West Nile virus (WNV) and other family members:|
|SPINAL CORD DISORDERS|
|Acute disseminated encephalomyelitis: r/o|
|Transverse myelitis: r/o|
|Cord infarction: r/o|
|Cord compression: r/o|
|Guillain-Barré syndrome: r/o|
|Mononeuritis multiplex: r/o|
|Acute intermittent porphyria: r/o|
|DISORDERS OF NEUROMUSCULAR TRANSMISSION|
|Myasthenia gravis: r/o|
|Tick paralysis: r/o|
|DISORDERS OF MUSCLE|
|Inflammatory myopathy: r/o|
*Rule out (r/o)
Much research has focused on the non-polio enteroviruses 68 and 71, members of the enterovirus D and enterovirus A species respectively, as suspected causes. As of 2018, the exact cause of AFM is not widely agreed upon.26,29-31
Since 2014, most patients with AFM (more than 90%) had a mild respiratory illness or fever consistent with a viral infection before AFM developed. All the stool specimens received from AFM patients tested negative for poliovirus. Most patients had the onset of AFM between August and October, with increases in AFM cases every two years since 2014. At this same time of year, many viruses commonly circulate, including enteroviruses, and will be temporally associated with AFM.
A 2014 MMWR report noted the difficulty of establishing causation by the virus.19 Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke and president of the International Society for NeuroVirology, compared the situation to the prolonged investigations that led to the confirmation of HIV as the cause of AIDS. In response to the suggestion that the enterovirus might be taking over the role of polio, Nath said that enterovirus 68 was far less virulent and spread much more slowly than polio, and that, unlike in polio, only a few cases of paralysis were seen per thousand children infected. He also suggested that adults with respiratory diseases should also be evaluated for neurologic deficits and that infectious disease should be considered as a cause when patients presented with neurologic symptoms.32
A subsequent report described 29 cases of enterovirus D68-associated AFM in Europe in 2016, noting that "these probably represent only the tip of the iceberg."14
As of 2018, the cause of most cases of AFM remains unclear.33 More than 90% of recent cases have followed a mild viral infection such as from enteroviruses.33 While polio can cause AFM, since 2014, it has not been involved in cases in the United States.2,34 The underlying mechanism involves damage to the spinal cord’s grey matter.2 Diagnosis may be supported by medical imaging of the spine, nerve conduction studies, and cerebral spinal fluid testing.2,3
Coxsackievirus A16, EV-A71, and EV-D68 were detected in the spinal fluid of four of 537 confirmed cases of AFM since 2014, which points to the cause of their AFM. For all other patients, no pathogen has been detected in their spinal fluid to confirm a cause. When a pathogen is found in the spinal fluid, it is good evidence that it was the cause of a patient’s illness.
Oftentimes, however, despite extensive testing of AFM patients, no pathogens are found in the spinal fluid. Three reasons for this may be that:
Many of the AFM cases reported in 2014 were temporally associated with outbreaks of respiratory illness attributed to enterovirus D68. Testing has not identified enterovirus D68 or other viral pathogens in the cerebrospinal fluid in the vast majority of cases.35 Several factors suggest a possible association of AFM with enterovirus D68 infections:36,37
Characteristic clinical features of AFM are:
The nature of AFM in the United States is illustrated by the following observations:
Criteria for a probable case of AFM (in patients without MRI) require:
Clinical criteria for a confirmed case of AFM require:
Such cases should be reported to state and local health departments in the United States using the patient summary form available online. The CDC also requests that healthcare professionals collect and submit specimens to the CDC for testing as early as possible in the course of the illness, to include cerebrospinal fluid, blood, and stool. The CDC requests submission of nasopharyngeal or nasal (mid-turbinate) plus oropharyngeal swab specimens only if the patient tests positive for enterovirus or rhinovirus at an external lab. Specimens submitted to the CDC are not intended for clinical diagnosis. Pathogen-specific testing should be performed at a hospital or state public health laboratories.
Important factors to be taken in the health history include:47,48
A comprehensive neurological examination should be performed preferably by a neurologist to assess focal limb weakness, poor muscle tone, and decreased reflexes. None of the children experienced altered mental status or seizures.
|Mental Status Examination||"A&O x 3, short and long-term memory intact"|
|Cranial Nerve Examination||"CNI-XII grossly intact"|
|Motor System||"Strength 5/5 throughout, tone WNL"|
|Deep Tendon Reflexes||"2+ symmetric, downgoing plantar reflex"|
|Sensation||"Intact to sharp and dull throughout"|
|Cerebellum||"Intact finger-to-nose, gait WNL"|
The results of the neurologic examination are taken together to anatomically identify the lesion. This may be diffuse (e.g., neuromuscular diseases, encephalopathy) or highly specific (e.g., abnormal sensation in one dermatome due to compression of a specific spinal nerve by a tumor deposit).
General principles include:50
A differential diagnosis may then be constructed that takes into account the patient's past health history and present findings to include the most likely causes. Examinations are aimed at ruling out the most clinically significant causes.
It is important that the tests are done as soon as possible after the patient develops symptoms.
Blood testing may include:
Other laboratory tests may include:
Diagnostic tests may include:
Magnetic resonance imaging of the spinal cord in a case of AFM showing cord swelling in (d) which has resolved three weeks later in (e).
Diagnosis of AFM requires acute onset limb paralysis and at least one gray-matter spinal-cord lesion. CSF should show pleocytosis.51
Since the cause of most of these AFM cases or what triggers AFM is unknown, there is no specific action to take to prevent AFM. However, most children had a respiratory illness or fever consistent with a viral infection before developing AFM. Recommendations to decrease the risk of catching or spreading viral infections include:
To prevent infections in general, the CDC recommends that individuals:19
Poliovirus and West Nile virus may sometimes lead to AFM. Recommendations include:
There is no specific treatment for AFM, but a neurologist may recommend certain interventions on a case-by-case basis. Treatment primarily involves:2,3
Since the recognition of AFM in 2014, the CDC has received numerous requests from clinicians and public health officials for guidance on how to manage and treat patients with this condition. In October 2014, the CDC consulted subject matter experts from a range of disciplines to assist the CDC in developing considerations for management of children with AFM. These experts were from the fields of infectious diseases, neurology, pediatrics, critical care medicine, public health epidemiology, and virology. The opinions from these individual consultations formed the basis of the “Interim Considerations for Clinical Management of AFM” document drafted in 2014.52 The CDC updated this information following consultation with national experts and review of the peer-reviewed, published literature. There continues to remain a paucity of published evidence for treatment of AFM, limited to case reports and case-series of patients with AFM. Consultation with experts treating AFM patients remains essential. The clinical considerations below reflect the observations and input from individual experts and a review of available scientific literature. The clinical considerations do not represent consensus recommendations or official guidelines. Rather, they summarize these experts’ approaches to clinical treatment of AFM.
Based on the available evidence and input from individual experts:
Although evidence is limited to clinical experience, immunomodulatory therapies or interventions used to treat AFM have shown no evidence of effectiveness, including glucocorticoids, intravenous immune globulin, plasma exchange, interferon, antivirals, or other immunomodulatory agents.1,35,44 Thus, management is supportive.
The long-term prognosis for individuals with AFM is unknown.
Approximately 20 to 35% of patients have respiratory failure requiring ventilatory support due to respiratory muscle and/or bulbar muscle weakness, including some with prolonged ventilator dependence.15 Neurologic recovery is variable and often incomplete. Most children have persistent motor deficits and significant muscle atrophy in the affected limbs a year or more after disease onset.
Outcomes are variable.3 Studies from 2014 to 2017 indicated a poor outcome for many cases. In 7 of 61 cases with EVD68 detected and eight long-term follow-ups, few had a full recovery. Two deaths were described in severely immunocompromised people (one with EVD68 and one with both EVD68, and coxsackievirus A16 detected).78
Six of 10 children in Denver were sent home for outpatient treatment. Some children with mild symptoms have recovered from temporary limb weakness, while the fate of those more severely affected remains unclear. Intensive physical therapy and occupational therapy may be beneficial for recovery.18,79,80
Mr. Williams runs into the Emergency Room triage area on August 5, 2019, at 0700 carrying his 9-year-old daughter, Emily, in his arms. He states she is unable to speak clearly and cannot lift her right arm. The previous evening she had been playing with his other two children (2 and 5-year-olds) after finishing her homework. She had taken a shower, kissed everyone goodnight and went off to bed. Upon waking her up to go to school, he had difficulty understanding her and noticed that her right arm just hung down by her side.
Emily lives with her biologic parents and two younger siblings in a one-story house. Both parents and siblings are in good health. Emily is an elementary school student in third grade at Wilber elementary school and is right-handed. Past medical history is remarkable for only “colds” and “ear infections” when she was younger than five. She has no surgical history.
Emily had a “chest cold” with fever seven days ago but recovered after three days with children’s Tylenol given every 4-6 hours when her temperature went above 100o F. Otherwise, she is on no medications
The registered nurse immediately brought Emily and her father into the back of the Emergency Department and notified the emergency room physician of Emily’s symptoms. A cardiac monitor and O2 saturation monitor were attached to Emily. Emily’s vital signs were taken with initial readings of: 99.7, 110, 24. O2 sat obtained was 97%. IV access was obtained with blood drawn, and 0.9 Normal Saline hung at 40 cc/hr.
Emergency physician obtained an initial neurologic examination:
Emily was transferred by a children’s EMS team to a University Children’s Hospital for further evaluation by a pediatric neurologist. Report was called by both the physician and nurse to University Children’s Hospital with accompanying notes faxed. Results of the stat brain and spinal cord MRI are pending and will be faxed to the University Children’s Hospital upon receipt in the Emergency Department.
Childs health history and physical assessment performed quickly with appropriate orders written. Transfer to appropriate level of care at a University Children's Hospital arranged and accomplished safely.