Acute Flaccid Myelitis (AFM): What Health Care Providers Need to Know

Moderator: Ibad Khan

Presenters: Adriana Lopez, MPH; Janell Routh, MD, MHS; Manisha Patel, MD, MS; Sarah E. Hopkins, MD, MSPH

Date/Time: November 13, 2018, 2:00 – 3:00 pm ET


Ibad Khan:
Good afternoon. I’m Commander Ibad Khan and I’m representing the Clinician Outreach and Communication Activity, COCA, with the Emergency Risk Communication Branch at the Centers for Disease Control and Prevention. Today I would like you to welcome to the COCA Call, Acute Flaccid Myelitis (AFM): What Healthcare Providers Need to Know. You may participate in today’s presentation via webinar or you may download the slides if you’re unable to access the webinar. The PowerPoint slides and the webinar link can be found on our COCA webpage at emergency.cdc.gov/coca. Again the web address is emergency.cdc.gov/coca.

Free continuing education is offered for this webinar. Instructions on how to earn continuing education will be provided at the end of the call. In compliance with continuing education requirements CDC, our planners, our presenters and their spouses/ partners wish to disclose they have no financial interest or other relationships with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters. Planners have reviewed content to ensure there is no bias. Content will not include any discussion of the unlabeled use of product or a product under investigational use, except Dr. Sarah Hopkins would like to disclose that she receives financial support from CDC for activities related to AFM surveillance. Dr. Hopkins would also like to disclose that she’s the site principal investigator for clinical trial of SA237 in neuromyelitis optica spectrum disorder. Additionally, the unapproved use of IVIG, steroids, and plasma exchange in certain situations may be discussed during this webinar. CDC did not accept commercial support for this continuing education activity.

After the speakers have presented, you will have the opportunity to ask questions. You may submit questions at any time through the webinar system by clicking the Q&A button at the bottom of your screen and then typing your questions. For those who have media questions, please contact CDC media relations at 404-639-3286 or send an email to media@cdc.gov. If you are a patient, please refer your questions to the healthcare provider.

At the conclusion of the session, participants will be able to accomplish the following; identify symptoms of AFM to look for in patients, explain the process for reporting suspected cases of AFM that meet the clinical criteria, list the types of specimens to collect from suspected cases of AFM and where to send them for testing, and discuss the activity CDC is conducting as part of its investigation into AFM.

We’d like to welcome our four presenters, Dr. Sarah Hopkins, Dr. Janell Routh, Dr. Adriana Lopez, and Dr. Manisha Patel. Dr. Sarah Hopkins is an assistant professor of clinical neurology and section head for multiple sclerosis and neuro-inflammatory disorders in the division of neurology at Children’s Hospital of Philadelphia. Today, Dr. Hopkins will be speaking about the clinical presentation and initial evaluation of AFM. Dr. Janell Routh is a medical officer on the acute flaccid myelitis team at the Centers for Disease Control and Prevention. Dr. Routh’s presentation will concentrate on treatment considerations for AFM. Adriana Lopez is an epidemiologist on the acute flaccid myelitis team at the Centers for Disease Control and Prevention. Her presentation will focus on current AFM epidemiology and case reporting. Finally, Dr. Manisha Patel is the acute flaccid myelitis team lead at the Centers for Disease Control and Prevention. Dr. Patel’s presentation will be ongoing about ongoing and planned activities for AFM at CDC. Thank you all for joining us today. I will now like to turn it over to Dr. Sarah Hopkins. Dr. Hopkins, you may proceed.

Sarah Hopkins:
AFM is an illness that’s characterized by the sudden onset of flaccid weakness in one or more extremities and also by distinct longitudinal gray matter lesions in the spinal cord. CDC and external partners have been investigating AFM since 2014, when we saw a sharp increase in cases that were noted both in the United States and globally. We know that AFM can be caused by different viral pathogens including non-polio enteroviruses, flaviviruses, herpes viruses, and adenoviruses. At this point, there has not been a definitive cause identified for most of the AFM cases that have been reported to CDC. Next slide.

Today’s presentation is intended to give an overview of AFM and its clinical presentation and characteristics, discuss initial clinical considerations for a child with acute limb weakness and treatment options, to summarize CDC’s surveillance data from 2018 and to emphasize the importance of identifying and reporting cases of AFM moving forward. And finally, to present ongoing and planned activities for AFM at CDC. Next slide. Of patients who have AFM. Oops, I’m sorry could we please go back to the previous slide.

Of patients who have AFM, over three quarters describe an illness that starts two weeks before weakness onset. And often these patients, mostly children, may still be ill at the time that they present with weakness. The symptoms of the associated illness typically include fever, runny nose, cough, and sometimes vomiting or diarrhea. In some cases hand, foot, and mouth disease is the associated illness. The onset of weakness can be rapid with onset of weakness occurring within hours but in some patients we see the weakness progress and in those cases it may progress over up to four or five days.

The weakness occurs in one or more extremities and maybe accompanied by a stiff neck, headache, or pain in the affected extremity. The pattern of limb involvement is highly variable and one of the very interesting things about AFM, it may be one or both arms or legs. It may be an arm and leg on the same side or some patients even have one arm and then the leg on the opposite side involved. Or three out of four or all four extremities. Patients do typically complain of neck, shoulder, back pain prior to onset of the weakness. And the pain in the affected limb can be severe and even lead to an initial diagnosis of an injury in that extremity. Cranial nerve abnormalities can be present and these can include a facial or eyelid droop. Difficulty swallowing or speaking and a hoarse or weak cry. There may also be accessory nerve involvement that can lead to difficulty holding the head up. Next slide.

Of course, based on the presenting symptoms, the differential here is broad and involves most of the neuroaxis. When any of these diagnoses are under consideration, particularly in the late summer and fall, and especially with preceding viral symptoms, AFM should be in the differential as well. Synovitis neuritis and injury are often considered when just one limb is involved. GBS and transverse myelitis typically have more symmetric presentation and more sensory involvement than AFM. And stroke, tumor, and cord compression will typically, particularly with tumor and cord compression, present with upper motor neuron signs as opposed to the lower motor neuron signs that we see with AFM. Acute cord injury may be associated with spinal shock and a flaccid paralysis temporarily but then those patients typically then become more spastic. This is different than AFM when the patients typically remain flaccid. We also have seen several patients discharged from an acute care setting with an initial diagnosis of conversion disorder. Next slide.

Many patients initially present to urgent care or the emergency room for limb weakness. Few actually wait to see their primary provider. In an urgent care emergency setting it’s important to ask the following questions about medical history in order to narrow the differential diagnosis. Details about preceding illness in the past four weeks should be collected, including respiratory symptoms and gastrointestinal symptoms and fever. We suggest asking about hand, foot, and mouth lesions, as we know the virus is associated with hand, foot, and mouth disease are also associated with AFM, such as enterovirus A71. This was noted in the outbreak this year in Colorado of enterovirus A71 associated neurologic disease.

Other symptoms to ask about that may indicate a diagnosis of AFM include: decreased appetite or difficulty swallowing; increased sleepiness or inactivity; neck, shoulder or back pain, or headache; pain in the extremities; bowel or bladder changes, particularly constipation; or difficulty holding the head up. Next slide.

On examination, it’s important to note muscle tone and reflexes in each extremity and to look for asymmetry in muscle strength and gait. Parents often report that their child appears clumsy when trying to pick up objects or they notice that a foot is dragging or the child is limping or refusing to walk entirely. On exam, it’s important to remember that weakness is most often proximal. The child may have normal fine finger movements but be unable to lift that arm above the head. Having the child sit on the floor and stand or squat and recover are easy ways to assess proximal lower extremity strength. We suggest conducting a thorough cranial nerve assessment to look for any facial, palatal or shoulder strength asymmetry and assess hoarseness or hypophonia.

Sensory exam is often normal but is important as it contributes to the differential. It is also important to assess the ability of the child to protect his or her airway if you have a high suspicion of AFM and to document respiratory sufficiency. Negative inspiratory force can be used if the child’s old enough and able to cooperate as can force vital capacity. In addition, if you’re seeing a patient in the acute care setting and suspecting AFM, we would also suggest getting a respiratory swab for respiratory PCRs and enterovirus PCR because we’re finding that the closer to onset of paralysis, we’re able to get those samples, the more likely they are to be positive for an associated virus or indicate what the child’s upper respiratory symptoms are from and that may help us to figure out ultimately the cause of AFM. Next slide.

Rapid specimen collection is essential to increase the chance of pathogen detection. In their 2016 publication about AFM, CDC noted that pathogens were more likely to be detected in respiratory samples if collected within seven days of limb weakness onset. But our experience here has been that typically if their collected within the first couple of days, they’re much more likely to be positive. It is important to note that in addition to hospital-based testing, certain specimens should be routed through the state health department to CDC for further testing and typing. We will go through a description of those specimens later in the call.

For hospital-based testing, please collect the following; nasopharyngeal and oropharyngeal swabs for respiratory multiplex testing and enterovirus PCR. A rectal swab for enterovirus PCR. In CSF, a cell count with differential protein and glucose, oligoclonal bands, and PCR for enterovirus, HZV, VZV, or a meningitis and encephalitis panel if your facility has one. In serum, we suggest obtaining enterovirus PCR and if the MRI is abnormal with a distinctive gray matter lesions that we’ll talk about, then anti-myelin oligodendrocyte glycoprotein and anti-aquaporin antibodies should be considered as anti-MOG disease and neuromyelitis optica can present with similar MRI findings and would be treated in a way that’s very different. Additional pathogen specific testing for example, West Nile Virus, Epstein-Barr Virus, Lyme Disease, should be considered based on seasonality, exposures, and geography. Next slide.

I wanted to talk next about some guidelines for imaging patients suspected of having AFM. Imaging should, of course, be guided by clinical presentation and we would suggest using a 3 Tesla magnet if one is available. We know that imaging within the first 72 hours after the onset of limb weakness may be normal and thus would suggest that the images should be repeated if there’s a high suspicion for acute flaccid myelitis and the initial images were normal. Axial and sagittal T2-weighted images are often the most helpful in identifying the lesions. If a patient is able to tolerate imaging of the entire spinal cord that would be a reasonable approach as often multiple levels of the cord are involved. Higher cuts of the brain stem or a complete brain MRI should be considered in a patient with cranial nerve deficits. Clearly full MRI of the brain would be indicated in patients with encephalopathy. For patients with AFM, lesions are predominately in the gray matter, although, some cases may present with some additional peripheral subtle white matter involvement. Next slide.

MRI abnormalities noted among cases of AFM include the following: spinal cord lesions that are largely restricted to gray matter and are typically longitudinal. The criteria is greater than one spinal segment but in reality for most of these patients we find that it’s actually several levels, often three or more levels involved. Spinal cord lesions are largely restricted to the gray matter and are mostly cervical. C3 to C5 or C6, which explains the pattern of proximal greater than distal weakness we see in these patients. Ventral anterior horn cells are most commonly involved, in some cases have entire central gray matter involvement producing a characteristic H pattern on axial images. Ventral and dorsal nerve roots may demonstrate a signal abnormality as well and are typically enhancing. The conus medullaris and cauda equina are frequently involved with enhancement as well. The spinal cord lesions are frequently characterized by hyperintensity on T2 and FLAIR weighted sequences and usually don’t enhance. Finally, we do see brain stem involvement. And that’s typically described as dorsal pons and medullary involvement.

Now to look a little bit at some characteristic MRI findings. Next slide please. These MRI images provide examples of the characteristic MRI findings among cases presenting with AFM. A and B demonstrate sagittal and axial images showing the central gray matter of the thoracic spinal cord. You can see this longitudinal abnormality in image A. And in image B, the axial images, you can see the characteristic H or butterfly shaped pattern that we typically see, especially early on, in acute flaccid myelitis. Panels D and E also show sagittal and axial T2 images demonstrating T2 hyper-intensity that in this case is more confined to the left anterior horn cells and we typically see patients coming in earlier in the course with axial images that look more like B and then evolve with over the course of about a week with abnormalities settling more into the anterior horn cells and beginning to look more like that in panel E. This is actually a good way, if there is some question about whether or not AFM is the correct diagnosis because the way that abnormality settles into the anterior horn is fairly distinct. Next slide.

This is actually an image from one of our patients at CHOP with upper extremity weakness, left greater than right. And you can see this patient’s early imaging had this distinct butterfly shaped abnormality, slightly more pronounced on the left side as well. Next slide.

When AFM is suspected, hospitalization is recommended. This is for several reasons. The most important one being that there is the potential for rapid deterioration of weakness as well as respiratory compromise. There is also an association with autonomic dysfunction in these patients. It is often easier to obtain early specimen collection for the possibility of pathogen detection and to get the appropriate MRI imaging to evaluate for confirmation of the diagnosis of acute flaccid myelitis. Just actually go back to the first point just for a second, the one thing about AFM is that we have had several patients who presented and were really doing quite fine and seemed to just have upper extremity weakness but then very rapidly progress to respiratory difficulties. So that is really something to keep in mind for these patients and really just underscores the need to monitor them closely. And, of course, finally, the other reason to admit the patient would be for consultation with neurology and infectious disease experts as needed to help to guide management of acute flaccid myelitis. Now going to hand off to Dr. Janell Routh at CDC for treatment considerations for AFM.

Janell Routh:
Thank you very much, Sarah. Next slide. Providing treatment considerations for AFM is challenging for many reasons. First, there is uncertainty about the pathogenesis of AFM. We know that most cases have a preceding respiratory or gastrointestinal symptom but many people have these symptoms. We’re continuing to investigate why AFM develops only in rare instances. Second, diagnosis and treatment may be delayed. Mildly affected people may not seek care immediately and as we have heard already, the differential diagnosis for limb weakness is broad, making alternative diagnoses possible. And third, systematic trials regarding many of the treatment modalities used for AFM have not been performed. Treatments are usually given in combination, either together or sequentially. So it’s difficult to tease apart if a single agent shows efficacy. Overall the published evidence for treatment of AFM is limited to either case reports or patient case series. Consultation with experts treating AFM remains essential. Next slide.

Since the large number of AFM cases in 2014, CDC has received numerous requests from clinicians and public health officials for guidance on how to manage and treat patients with this condition. In November 2014, CDC consulted subject matter experts from an array of disciplines to assist CDC in developing considerations for management of children with this neurologic illness. These experts were from fields of infectious diseases, neurology, pediatrics, critical care medicine, virology, and public health epidemiology. The opinions from these individual consultations formed the basis of the Interim Consideration for Clinical Management of AFM, which is a document drafted in 2014. In 2016 and 17, CDC continued to reach out to clinical experts for input on this document as experience in treating AFM patients grew nationally. In 2018, this year, CDC updated this information following a review of the peer reviewed published literature and consultation with national experts. The clinical considerations discussed today reflect the observations and input from these individual experts. They do not represent consensus recommendations or official guidelines, rather they summarize these experts’ approaches to clinical treatments of AFM. The 2018 update will be available as a link on the CDC AFM website. Next slide.

The next two slides summarize treatment considerations based on this 2018 update. For the three main treatments used for AFM, intravenous immunoglobulin or IVIG, corticosteroids, and plasmapheresis, there’s not enough evidence to indicate a preference or an avoidance for their use at this time. Treatment decisions should be made in conjunction with neurology and infectious diseases experts. The possible benefits of using corticosteroids for spinal cord edema or white matter involvement must be balanced by the possible harm due to immunosuppression and the setting of a possible viral infection. There is no indication for the use of other immunosuppressive agents in the management of AFM. Next slide.

Fluoxetine is a selective serotonin reuptake inhibitor that demonstrates activity against enteroviruses. Both in a mouse model and a retrospective case comparison of AFM patients, neither showed improvement of neurologic outcomes when given fluoxetine. At this time, there is no indication that fluoxetine should be used for the treatment of AFM. And for other antiviral medications or interferons, there is no data to indicate their use at this time. Next slide.

To summarize the clinical and treatment considerations, discussed at the first part of this call, most AFM patients have a preceding illness one to two weeks before limb weakness and are often febrile at the time of presentation. Clinicians should consider AFM on the differential diagnosis of the patients, in particular pediatric patients who present with acute flaccid limb weakness. A workup including laboratory testing and MR imaging should be begin and consultation with neurology and infectious diseases experts is important. There’s currently no indication that any specific targeted therapy or intervention should be either preferred or voided in the treatment of AFM. Next slide.

And now I’d like to introduce Adriana Lopez, our surveillance lead who will share our current AFM epidemiology and talk about case reporting.

Adriana Lopez:
Thank you Janell. Next slide please.

After the emergence of AFM in 2014, we started standardized surveillance in 2015 to help monitor this condition. The AFM case definition includes clinical criteria, which is an illness with acute onset of flaccid limb weakness. A confirmed case of AFM is defined as a patient that meets the clinical criteria who also has an MRI showing spinal cord lesions largely restricted to gray matter. A probable case is defined as a patient that meets the clinical criteria and has cerebral spinal fluid or CSF showing pleocytosis or white blood cell count of greater than five cells. To help us track AFM and monitor the epidemiology, we ask the clinicians report all patients meeting the clinical criteria for AFM to the health department regardless of laboratory test results or MRI findings. Of note, the purpose of our classification process is for surveillance only and is not meant to supersede the patient diagnosis or delay treatment and management of decision. Next slide.

This is the epidemic curve by month of weakness onset for confirmed cases of AFM from August 2014 through October 2018, as updated on our website today. The 2018 cases are highlighted in yellow. The curve highlights the every other year occurrence of an increase in AFM. And the Summer/Fall predominance of cases. As of today, from January through October of this year, 90 cases of AFM have been confirmed at CDC. This figure is updated weekly on the CDC website. Next slide.

Earlier today, we released an MMWR summarizing cases reported to CDC from January 1st through November 2nd, 2018. I will present some of the key clinical findings here and some of the key laboratory findings in the next slide. Through November 2nd, there have been 80 confirmed cases of AFM in 25 states. 59% of those are among males and the median age of cases is four years with a range of seven months to 32 years. However, 94% of confirmed cases are less than 18 years of age.

Seventy eight percent of the cases reported of preceding respiratory illness but almost all reported either a fever and or respiratory illness. The median time between onset of preceding illness to onset of limb weakness was four and a half days, ranging from zero to 66 days.

Forty eight percent of cases have upper limb weakness only, while 9% had lower limb weakness only. All confirmed cases were hospitalized and of those, 59% were admitted to pediatric ICUs. Pleocytosis was common among confirmed cases with a median of 103 white blood cells and a lymphocyte predominance. Next slide.

Because some enteroviruses can cause acute flaccid limb weakness and because of the temporal association with AFM and a nationwide severe respiratory outbreak of EV-D68, noted in 2014, CDC performs enterovirus and rhinovirus testing for all patients meeting the clinical criteria for AFM but are sent to CDC for testing in an effort to identify etiologies for AFM cases. As recorded in the MMWR, from January 1st through November 2nd, testing was performed on 125 clinical specimens from 71 patients with confirmed AFM. 38 of the patients with confirmed AFM had specimens positive for enteroviruses. Two patients had a CSF specimen that was positive, one for EV-A71 and one for EV-D68. 31 patients had respiratory specimens positive with the following; EV-A71 in ten patients, EV-D68 in 14 patients, and other enteroviruses in seven patients. All of the stool specimens tested to date have been negative for polio virus. Next slide.

Now, I would like to talk about the reporting process. When a patient meeting the clinical criteria for AFM presents and while the patient workup is ongoing with MRI and specimen collection, we ask that the clinician call their state or local health department to report the patient. The health department then gets in touch with our team at CDC. We would like CSF, serum, stool, and respiratory specimens to be collected for both diagnostic and research purposes. Specimens should undergo pathogen specific testing at the local hospital or lab and we request that some be sent to CDC as well. Both for systematic diagnostic testing and for use in assay development for AFM etiologies. Next slide.

This table illustrates which samples to collect from patients meeting the clinical criteria for AFM and to send to CDC for AFM testing. Please be sure to coordinate with your health department when planning to send specimens to CDC for testing. CSF, respiratory, and stool specimens are now all being tested for enteroviruses and results provided within seven to ten days of receipt at CDC. Stool specimens are also tested for polio virus. Remaining CSF and serum specimens are being used for exploring immune mediated responses and mechanisms for AFM. So individual results from that testing will not be provided. However, any information learned from that testing that provides clues to AFM will be disseminated rapidly. Next slide.

Once the health department is made aware of a patient meeting the criteria for AFM, they help collect medical information on the patient and coordinate the specimen shipment to CDC. Next slide. Next slide, please. Thank you.

CDC receives the information from the health department and passes it to the expert neurology panel for case classification, which is done based on medical information, MRI reports, and a review of images. Starting in 2017, two medical experts have been reviewing each case and if their determinations are discordant, a third is brought in for adjudication. Next slide.

Once classification is completed, the information is sent back to the health department who then communicates the classification to the clinician along with test results from the respiratory, stool, and CSF specimen, all of which undergo pan antivirus testing. As mentioned earlier, this case classification does not take the place of the medical diagnosis for the patient. It is used for surveillance purposes and is not meant to supersede the physician’s final diagnosis in their patient. Next slide.

Now I’d like to introduce Manisha Patel, the AFM team lead, who will discuss CDC’s activities.

Manisha Patel:
Thank you Adriana. We know providers have a lot of questions on what can be causing AFM. We do know that AFM, as a condition, is not new. And some of you on this call may have even diagnosed patients with AFM in the past. What seems to be new is the epidemiology of AFM in the past few years. And for those of us who work on AFM at CDC as well as our collaborators and health departments and academic centers, understanding why this is happening is an area of active investigation. Next slide.

Over the past few years, since we started surveillance under a standardized case definition, we have gotten more clues about what could be causing this condition. Both the seasonality and the presence of a preceding illness in most patients suggest an infectious etiology, including enteroviruses. And CDC as well as others have been looking closely at enteroviruses as a potential cause of AFM. One issue though is that enteroviruses are ubiquitous and even enteroviruses, such as EV-D68 have been circulating in the US, even before the large number of AFM cases were reported in 2014. In fact, based on some recent data looking at seroprevalence rates against EV-D68 using sera that was collected before 2014, most people actually already have antibodies to EV-D68 even young children. We need more data to understand the association between enteroviruses and AFM. In the meanwhile, CDC continues to look broadly to investigate the triggers and mechanisms that may lead certain patients to develop AFM and others to not.

Another issue is that since AFM remains a rare event and we have not seen any particular geographic clustering with cases being reported all over the country, we’ve had some challenges conducting evaluations like a case control study to look for risk factors. It is really critical that providers report patients that have acute flaccid limb weakness to their health department so that we can make sure we have the most accurate picture of what is occurring in these patients.

In terms of pathogenesis, the lack of rapid recovery in some patients and historical comparisons suggest direct viral invasion of neural tissue. We have limited pathology specimens to confirm this. When a pathogen is found in the spinal fluid, it is good evidence that it was the cause of the patient’s illness. However, despite extensive testing of our AFM cases, no pathogens have been consistently identified in the CSF of these AFM cases. Now, it is possible this may be because a pathogen has been cleared by the body or it is hiding in tissues that make it difficult to detect. Another possibility is that the pathogen triggers an immune response in the body that causes damage to the spinal cord. And CDC and others are also looking at a post-infectious process as a possible explanation for some of these AFM cases. Next slide.

So I wanted to share with the callers today some of the investigations CDC is doing to help address our knowledge gaps. We are working closely with health departments to collect in depth information on all AFM cases including the clinical spectrum, exposure history, and long-term outcomes. We know some patients with AFM have had full recoveries and others have not. And we are working hard to gather as much of a complete picture of these cases as possible.

One question that has come up is, is AFM actually new? I mentioned the condition is not new but it appears the epidemiology is. So CDC is working with academic centers as well as doing studies using administrative data bases to look at baseline rates of AFM before 2014. We are also conducting syndromic surveillance to assess national trends in both acute respiratory illness and AFM and see how these may track alongside each other. For example, in 2014 CDC noted large outbreaks of severe respiratory illness in addition to AFM. We did not see a similar temporal trend in 2016, which was a peak year of AFM. Using syndromic surveillance to look more closely at this trend will help us further characterize this potential association. Next slide.

CDC is also collaborating with seven pediatric hospitals to conduct active case finding and retrospective review to establish baseline rates and long term follow up of AFM cases. A key feature of this collaboration is that since 2017 all of these sites are doing year round perspective respiratory and gastrointestinal surveillance and collecting samples in patients that present with these symptoms. This is going to give us important information on what viruses, including enteroviruses, are circulating throughout the year. We’re also looking at a case control study to evaluate risk factors and as I mentioned because case counts are low within a specific area or state, this will require multi-jurisdictional approach to achieve the adequate sample sizes. Next slide.

So here are a couple of our selected CDC laboratory activities. Of course, we’re continuing to do diagnostic testing which would be providing pathogen specific testing for enteroviruses on clinical specimens including CSF, nasopharyngeal and stool samples. What is also critical is collating the external lab results. We know a lot of physicians are performing laboratory testing on site and so that information will also be important to gather and present a complete picture of the laboratory results. We’re also using metagenomic sequencing approaches to identify pathogens not currently considered in specifically targeted approaches. And I just want to mention this was also done in 2014 and we were not really able to identify a consistent pathogen.

There are a number of immunologic assays and work that is being done at the CDC laboratory, including developing assays to look for biomarkers associated with AFM and investigating post-infectious immune pathology as a mechanism for AFM. Next slide.

So on this slide we provide a couple of resources for you all. There’s a provider toolkit available through the health department. It’s available for providers to walk through, earlier what Adriana presented, on how you would report a case and the specimens that you would need to collect. It allows for rebranding by health departments, so that way you have their information if you need to contact them. There’s also a frequently asked questions document that health departments can share with you that was worked together with CDC and the health departments. And we’re currently developing a standardized slide deck so that there’s education for providers as well as providers that do work on AFM, for instance a neurologist that may want to provide some education to their emergency room physicians.

We are currently updating the website based on comments and questions from the general public, you all, and health departments. And that should be going live this week or updated this week. And then certainly the AFMInfo@CDC.gov is an email inquiry box that we monitor 24/7, so if there are additional questions, please feel free to send that to that email box. Next slide.

I also wanted to mention that CDC with other collaborators are developing an AFM task force, this is including national experts across multiple disciplines, those are listed there, with two main objectives. One is to develop the research agenda to further characterize the pathogenesis of AFM and develop hypotheses about potential etiologies. And second is to review and update the clinical guidance on the management of patients with AFM that Dr. Routh went over. And again, that should be up on the website but we will have this task force to be continually looking at the data to date to be able to share that with you. Next slide.

So in summary, despite the increase in cases this year, AFM is still rare. As of November 13th, CDC has confirmed 90 cases this year and 414 cases since August 2014. There has been limited detection of pathogens in the CSF of these AFM cases, which would be good evidence that of the cause for the patient’s condition. However, like I mentioned there are a number of reasons that we may not be able to detect pathogens in the CSF and therefore CDC is continuing to look broadly. CDC continues to investigate all potential causes of AFM including viral infections like enteroviruses. And CDC and partners are working to better characterize the risk factors for AFM and why some people develop this condition and others may not.

In my final slide, we first want to thank you all for your work on AFM. We know this is a serious disease and we very much appreciate your working with these patients and these families to help us understand what this condition is. I just want to mention that all conditions involving patient care may encounter a patient with acute flaccid limb weakness and understanding the next steps in the patient work up is critical like Dr. Hopkins highlighted. And then secondly, to be vigilant for AFM and report those patients with acute flaccid limb weakness to your local state health department. Thank you very much.

Ibad Khan:
Thank you so much Dr. Hopkins, Routh, Lopez, and Patel. We will now go to our Q&A session. If we did not get to your question, please send your question to COCA@CDC.gov. Again, that email address is COCA@CDC.GOV. Our first question is regarding the lab testing. Can you please elaborate on the types of lab testing that are being conducted in the labs?

Steve Oberste:
Thank you. This is Steve Oberste, I’m the Chief of the Polio and Picornavirus Laboratory here at CDC. So as you heard from the speakers, we’ve been conducting specific testing for enteroviruses, including polio, just to make sure that we have no polio introduced into the US. This is on CSF, respiratory, stool, and serum samples. We had also done some metagenomic sequencing that was published last year on, I think, 35 samples from patients. None of those yielded a real cause of their illness. We’re going back and doing some additional metagenomic sequencing on specimens from newer patients, so that’s currently in progress.

Given that there’s really been no clear detection of an agent in sterile site specimen, such as CSF, which you would expect, because even in the case of polio from polio virus, you can detect the virus in CSF by molecular tests at some frequency, maybe 15% of the time. So we’re a bit surprised we haven’t seen something higher than that and literally can count on one hand the number of specimens that we’ve detected a virus on out of several hundred. So we’re looking at other biomarkers, things like cytokines antibodies to host proteins that could be markers of either inflammation, post-infectious pathological processes, that sort of thing that may either point to a particular pathogen or group of pathogens or at the very least give a profile that we can use to classify AFM patients. Thank you.

Ibad Khan:
Thank you for that. Our next question is regarding recovery. Can children recover from AFM? And what is helpful in their recovery?

Sarah Hopkins:
Hi, so this is Sarah Hopkins from the Children’s Hospital Philadelphia. So I think this is a good question. It’s always difficult to know exactly what to tell a family when their child presents with AFM. And there really does seem to be a broad spectrum of recovery for these patients. We see a few patients who seem to improve pretty rapidly and that may be related to the underlying etiology or perhaps to that child’s immune response. The others and in fact most of these patients require long-term physical and occupational therapy, sometimes long in patient in rehab stays. And many of them have residual weakness, kind of a varying severity. We have found that our patients over the years have continued to improve with therapies, including the traditional physical and occupational therapy but aqua therapy, E-stim, and we feel that our patients really do better when these therapies are implemented as soon as the child’s stable enough to participate. And the other thing I would say is that even for our patients that might be four years out from diagnosis, we still see them making gains with therapies. So, I think it’s important to, even if the recovery seems slow, to not back off because we do occasionally see patients even regress when the therapies are removed. So really continuing therapy over time, we have seen those patients have some improvements.

Ibad Khan:
Thank you. Our next question is regarding the distribution of the disease. Is AFM being seen anywhere else besides the United States?

Janell Routh:
Thanks for that question, this is Janell Routh. The United States is definitely not the only country that sees cases of AFM. Beginning in 2014, which was the year that the United States reported a large number of cases, Canada, Australia, and countries within Europe also reported and published about their AFM case series. And since then we’ve continued to read reports about cases from Japan and Argentina. One thing to note is that because the emergence of AFM in 2014 coincided with the outbreak of severe respiratory illness caused by enterovirus D-68, some countries took a slightly different approach to finding cases of AFM. Within their surveillance systems for enteroviruses, they look for acute flaccid weakness rather than trying to capture all cases of acute flaccid weakness as our surveillance system does. This approach then takes into account laboratory values in addition to that flaccid limb weakness. Whereas our case definition is not dependent on a laboratory value.

And one thing I want to mention also is that as part of polio eradication efforts, we know that most countries conduct surveillance for acute flaccid paralysis in order to rule out polio virus. Because AFM is a type of acute flaccid paralysis, there are most likely cases of AFM in the surveillance system. But without MR imaging they’re hard to tease apart. We’re definitely continuing to collaborate with our international partners and work together to learn more about this condition and how often it occurs worldwide. Thank you.

Ibad Khan:
Thank you for that. A follow up question regarding distribution of cases is that, what is the distribution of confirmed and probable cases by state and if this information is available to be shared?

Adriana Lopez:
Thank you. This is Adriana Lopez. So we’re currently not releasing state level data, as many of the states voluntarily reporting cases have only had a few cases. CDC strives to strike a balance between providing information that is beneficial to the public’s health and protecting the privacy of patients and their families. Therefore, CDC is currently deferring to states to release information about cases as they choose. We’re also working with the states to ask about their willingness to let us share this information.

Ibad Khan:
Thank you. The next question asks, has a polio virus either wild or vaccine-type being associated with AFM?

Steve Oberste:
A polio virus can cause very similar illness and MRI findings can be similar. However in the United States, there is no polio virus detected in any AFM case and I’m not aware of polio being detected in the AFM cases in other countries.

Ibad Khan:
Thank you. The next question asks, once all the clinical information and MRI are sent to CDC, how long does it take to get a case classification?

Janell Routh:
This is Janell Routh. The process takes on average about two to four weeks. One thing to note is that it’s time intensive because it does require a review by two medical experts to confirm a case of AFM. And this is something that is done similar to the classification process for polio. We often have to go back to states to ask for additional information in order to help classify that case so that can add an extended period of time. One issue that we do have is getting MRI images here because we require for the case classification process those MRI images be reviewed. And one thing I’d like to ask for your help with is if you know you will be reporting a patient with limb weakness to the health department, one thing you can do to assist is to begin to gather those images together in order for us to review them. That would be of great help. Thank you.

Ibad Khan:
Thank you and we have time for one last question and this question is regarding patient presentation. What proportion of patients experience weakness in all four limbs?

Janell Routh:
This is Janell Routh again. That proportion definitely varies from year to year. I would say in our peak years, so 2014, ’16, and ’18, the proportion of patients who have all four extremities affected range from about 30 to 40%.

Ibad Khan:
Thank you very much. This concludes our Q&A session. On behalf of COCA I would like to thank everyone for joining us today with a special thank you to our presenters Drs. Routh, Patel, Hopkins, and Lopez. And if there is a question that we were not able to get to please note that you can send that to COCA@CDC.GOV, again that’s COCA@CDC.GOV. The recording of this call and the transcript will be posted within the next few days to the COCA website at emergency.cdc.gov/coca. Again, that web address is emergency.cdc.gov/coca. All continuing education for COCA Calls are issued online to TCE Online. The CDC’s training and continuing education online system at www.cdc.gov/tceonline. Those who participated in today’s live COCA Call and would like to receive continuing education should complete the online evaluation by December 17th, 2018 and use course code WC2922. Those who will review the call on demand and would like to receive continuing education should complete the online evaluation between December 18th, 2018 and December 18th, 2020 and use course code WD2922.

Please join us for our next COCA Call on Thursday November 29, at 2:00 PM Eastern, where the topic will be the multi-state hepatitis A outbreak. To receive information on upcoming COCA Calls, or other COCA products and services, join the COCA mailing list by visiting the COCA webpage at emergency.cdc.gov/coca and click on the join the COCA mailing list link. To stay connected to the latest news from COCA, be sure to like and follow us on Facebook at Facebook.com/cdcclinicianoutreachandcommunicationactivity. Again thank you for joining us for today’s COCA Call. Have a great day.

END

Page last reviewed: November 19, 2018