Hello, and welcome to the Pediatric Focused Review on Acute Flaccid Myelitis. This lecture was developed by Dr. Deike in 2020, and she has no financial or academic disclosures. By the end of this presentation, the participant should be able to explain the definition and differential diagnosis for acute flaccid myelitis, understand the epidemiology, surveillance, and prevention of AFM, and explore current treatment, rehabilitation, and surgical recommendations for AFM. Let's start with what is the definition of acute flaccid myelitis, or AFM. This is a disease that causes rapid onset of flaccid acute weakness or paralysis in one or more extremities that affects primarily young children. The weakness is caused by inflammation in the spinal cord and correlates to an MRI with enhancement of the gray matter, indicating anterior horn cell involvement. The range in presentation is from mild monoplegia to a tetraplegia requiring vent support. This was first taken notice in an initial rise in baseline cases of acute flaccid paralysis, or AFP, was noted in 2012 at the California Department of Health Affecting Children. In 2014, a concern for a new epidemic was raised when up to 120 cases were seen over multiple geographic areas. Since that time, a national surveillance was started to monitor the disease. These outbreaks have been noted in many other countries and continents, including Europe, Asia, South America, and throughout the world. In the U.S., there's continued to be biannual spikes in the late summer and fall months, with the last outbreak in 2018 containing 238 cases. Approximately all of these cases required hospitalization, and over half were admitted to the intensive care unit. Acute flaccid myelitis is a type of acute flaccid paralysis. The term AFP is a generalized umbrella term and includes multiple clinical entities, including paralytic poliomyelitis, AFM, Guillain-Barre syndrome, acute transverse myelitis, toxic neuropathy, muscle disorders, and others. The annual rate of acute flaccid paralysis among children under 15 years of age is approximately 1 per 100,000 children. The estimated annual rate of AFM in children is 1 per 1,000, even in years with increased case outbreaks. It remains a rare disease with a heterogeneous outcome. Let's look at a clinical diagnosis for acute flaccid myelitis. Clinical criteria for a diagnosis of AFM includes the presence of weakness or paralysis of one or more limbs. If MRI imaging is available, the image has a characteristic spinal cord lesion predominantly in the gray matter spanning one or more vertebral segments. Laboratory findings including blood, sputum, or stool may have an infectious cause, but this is found in less than half of the cases. The CSF may show a pleocytosis, but this is no longer necessary for a diagnosis of AFM. The most recent consensus at the time of this recording for a case definition was established by the CDC and the CST Epidemiologist, or the Council of State and Territorial Epidemiologists, in 2019. They have determined definitions for confirmed, probable, and suspected cases. Importantly, if AFM is suspected, treatment should not wait until classification by the CDC. T2 hyperintensity of the gray matter in the spinal cord is the hallmark of AFM. You can see the MRI T2 sagittal view of the cervical and thoracic spine show enhancement of an intramedullary signal between the blue lines indicated there. On MRI T2 transverse views, you can see the signal enhancement is restricted to the gray matter of the spinal cord in the high cervical and thoracic region bilaterally in between the blue arrows. Let's look at a review question. A six-year-old boy presents to the ED with paralysis of his right arm that started several hours ago. Parents report that he and his brother had a URI about one week prior. You have a high clinical suspicion for acute flaccid myelitis. What diagnostic test would best help make this diagnosis? A, a CBC with DIF, B, a lumbar puncture, C, a CT head, or D, an MRI of the spine. D, MRI of the spine, AFM is characterized by the acute onset limb weakness and characteristic MRI T2 hyperintensities in the gray matter of the spinal cord. The classic disease progression of AFM occurs in three stages. The initial stage is marked with a prodromal infection, usually URI and a fever. This commonly resolves before the onset of the weakness, but does not always. The second stage is the onset of rapidly progressive weakness or paralysis. This can last anywhere from a few hours to one week, the nadir of symptoms being about four days. This is when parents will seek treatment for their child or when they notice that they're not moving a limb, refusing to walk, are more fussier, have difficulty feeding, or are not acting like themselves. Some children also complain of pain, and some are too young to recognize their symptoms. Lastly, the recovery from the acute neurologic insult. This is a chronic disease that has a long-lasting recovery. The recovery is variable as a presentation of AFM. It appears that it's less severe. The initial acute injury has a better recovery can be made. Nearly all of the AFM cases that occurred in the peak years of outbreak were associated with a presumed viral illness. Unfortunately, lab sampling has not been able to capture an identifiable cause at this time. This is likely related to the illness can be one to seven days prior to the flaccid weakness. Samples taken at the time frame may not represent a true picture if there was a previous illness. Most of the infections were related to upper respiratory infection symptoms, and most have had a related fever. 71% of the cases had both a URI and fever reported. Half of the cases reported neck or back pain, and about one-fifth reported GI infectious symptoms. Upon onset of weakness, there's almost always asymmetric involvement of the limbs, the most common involvement in the cervical spine, and so the upper extremities are more commonly affected than the lower extremities. It's also noted the proximal weakness is more severely affected than the distal muscles. Pain is a common complaint among the children, but sensory involvement with AFM is rare and should be caused to look for another diagnosis. It's consistent with the lower motor neuron injury, and there is a decrease or loss of reflexes as well as loss of muscle tone. Additionally, cranial nerve involvement is common, noting a facial droop, ptosis, dysphagia, and dysarthria can be associated with cranial nerve nuclei gray matter enhancement in the brainstem. Fortunately, the cranial nerve recovery is more common than the limb weakness. Depending on the spinal cord involvement, urine retention and constipation can happen acutely. This often resolves. It's estimated that one-third of the patients that require hospitalization will also require intubation and ventilation related to phrenic nerve or truncal involvement. There's also less commonly autonomic dysfunction in patients that are most significantly affected. This includes blood pressure and temperature instability, irregular heart rates, and breathing patterns. The subacute and long-term recovery. The recovery of AFM can be as variable as its presentation. While the MRI enhancement will improve or resolve, this does not indicate symptom resolution and the motor deficits more often persist. A minority of children with AFM have full recovery. It's estimated around 5% acutely will make a full recovery and 10% to 20% will have a full recovery within four months. The majority require long-term rehabilitation care and support. On the left side of the slide is acute imaging where the patient was two to three days out after the flaccid weakness with characteristics spinal cord gray matter enhancement. On the right side is a subacute imaging at 38 days out where you can see the spinal cord signal is greatly diminished or resolved. You can also see cranial nerve root enhancement after the initial acute presentation starts to resolve. The significance of this is unknown and does not correlate clinically. Looking at some of the long-term consequences of acute flaccid myelitis, generally there is significant muscle atrophy of all levels involved. This can lead to decreased weight bearing, joint instability, decreased bone density and joint subluxations. With decreased muscle tone in the neck and trunk, a scoliosis can develop rapidly. Over time with child growth, asymmetries in growth and development can be seen. This may be a limb size difference, leg length discrepancy or contracture that develops. The affected areas commonly need bracing such as shoulder, elbow, wrist, knee or ankle bracing. Children with lower extremity involvement often need long-term wheelchair use. It's recommended they are followed long-term by a pediatric physiatrist and neurologist. Depression and anxiety are not uncommon in children with AFM and were found to improve over time. This was several children whose outcomes were published from the 2014 outbreak. You can see the severe muscle atrophy surrounding the scapula in the top right corner picture and the range of motion asymmetry in the top right picture. The bottom right picture shows a two-year-old child that has difficulty with weight bearing and walking and attaining developmental milestones because of the involvement of his right lower extremity. Let's do another quick review question. Which of the following is not an expected finding in an acute flaccid myelitis patient? A. Reflexia, pain, spasticity or rapid onset of weakness. B. Spasticity. AFM affects the anterior horn cell which is a part of the peripheral nervous system although located within the spinal cord. Upper motor neuron findings like spasticity should not be present. Let's turn our focus now on who is affected, what we know about what causes this disease and further management. The incidence of acute flaccid myelitis is one in one million. More than 85% of those affected are children, the median age being 6 years old. There's a slight predilection for males. The outbreak peaks have been noted to occur from August to October of every other year, first noted in 2014. The most recent data from the CDC at the time of this recording is that it continues to show a cyclic distribution every other year in the late summer and fall since 2014. Each outbreak has shown a greater number of cases than the last. This may be attributed to better surveillance and recognition of the disease. There's a baseline amount of AFM that occurs every year. This can be caused by numerous etiologies including infections, neuroinflammatory diseases or other conditions. However, it's been difficult to assign one specific cause to the reason to the peak cases in every other year. There's an association with enterovirus circulation, specifically enterovirus D68 and enterovirus A71. The CDC and other centers are continuing surveillance of this disease, further cases and possible outbreaks for more definitive evidence. In most cases, the cause of AFM is unknown. Historically, polio was rampant in the 1950s causing childhood paralysis. This caused national surveillance and mandatory reporting. The vaccine for polio was developed in the 1960s and has since been eradicated from the Western Hemisphere. Currently, there have been no cases with positive polio virus during these outbreaks. Most experts believe that this is caused by a neuroinvasive viral infection. When looking at the 2014 and 2016 outbreak, there was also an increase of enterovirus D68 cases causing hospitalizations. This association has caused more poignant testing for some respiratory viruses, including enteroviruses. Currently, the consensus to follow the AFM trend, with close attention to sampling, collection and evaluation of enterovirus D68 and A71. Other viruses that are known to cause AFM include the flaviviruses, adenoviruses, and herpesviruses. The pathogenesis remains unclear. It's possible there's a direct neuronal damage from viral infection, similar to the pathogenesis of the polio virus. The symptoms could be elicited by a post-infectious immune response, with or without an inflammatory damage to gray matter. Commonly, acute paralysis is treated with IVIG, IV steroids, or plasmapheresis. These interventions and others, such as immunomodulators, antivirals, and SSRIs, have been studied and have not had statistically significant improvement in the overall outcome of AFM management. The CDC currently does not endorse or discourage any treatment for AFM at this time. The main agreed-upon treatment for AFM is early and aggressive rehabilitation. This may start in the acute setting, but many will need acute inpatient rehabilitation and will need long-term skilled therapies, such as PT, OT, and speech therapy. The current recommendations include early electrical stim to avoid muscle atrophy, weight bearing to prevent bone density loss and facilitate functional motor recovery with gait or locomotor training, as well as tailored rehabilitation strategies to the child's neurological and functional deficits. Nerve grafting and nerve transfers are being performed more commonly and have showed improved strength, range of motion, and function in published case series. The timing and selection of the patients is not certain, and so early referral to a specialized surgeon is recommended. Diaphragmatic pacing is being considered in children with at least partially intact phrenic nerves. This has been successful with published case series. Surveillance and prevention. The CDC continues to work on and expand research and preparedness for this disease. The goals of continued surveillance include to provide a standard case definition for AFM and to help surveillance and to facilitate interpretation of apparent increases in this condition, better define the etiology, pathogenesis, and improve tracking. General guidelines from the CDC for the prevention of acute flaccid paralysis include standard care for the virus prevention, including frequent hand washing, keeping children immunized while there is no current AFM vaccine, maintaining recommended vaccines will help prevent disease spread and has led to the eradication of polio from the Western Hemisphere. While uncommon, AFP can be spread through mosquito vectors, and avoiding mosquito bites can help prevent this disease. In conclusion, physician awareness, appropriate testing, and timely diagnosis will help to better treat, support, and understand the long-term consequences of our AFM children. Continued surveillance and screening will better understand the causes, etiology, and sequelae of the AFM epidemic. Rehabilitation focus on preserving motor function, strengthening affected muscles, and learning compensatory strategies will help functional outcomes. Here's a list of references used to prepare this focused review. Thank you all for your time, and best of luck with your educational endeavors.

Acute Flaccid Myelitis

Pediatric

Diagnosis

Management

CDC surveillance