New AFM Information Sheet

The term Acute Flaccid Myelitis (AFM) was coined in 2014, but it is likely that many individuals with initial presentation of flaccid limb weakness and/or paralysis were diagnosed as having transverse myelitis or Guillain Barre Syndrome in previous years. As scientists and clinicians learn more about this disorder, the TMA strives to keep our community updated on their findings and to provide timely and accurate information and resources. As a part of this effort, we have recently updated our AFM disease information sheet so that information on AFM is easily accessible in a concise and helpful manner. The AFM information sheet has sections on Epidemiology, Signs and Symptoms, Diagnosis, Acute Treatments, Prognosis, and Rehabilitation and Symptom Management. You can find the AFM information sheet here.

Acute Flaccid Myelitis

Acute Flaccid Myelitis (AFM) is a type of inflammation in the spinal cord that has specific clinical and MRI features. AFM abnormalities noted on MRI are predominantly found in the gray matter (lower motor neuron) of the spinal cord. In 2012, an outbreak of AFM occurred in California and more cases were reported in the summer and fall of 2014, 2016, and 2018 across the United States. Non-polio enteroviruses have been implicated as potential causal factors in the development of AFM. The enterovirus D68 and enterovirus A71 have been suspect in many of these cases, although others such as coxsackie viruses have been implicated as well. Enterovirus D68 most often causes a respiratory illness and has been circulating in the United States during the summer and fall every two years since 2014, which coincides with the increase of cases of AFM seen every other year. It has not been definitively proven that these particular viruses have directly caused cases of AFM but the temporal onset of neurological symptoms with infections produced by those viruses implicate them as direct or indirect triggers of the neurological problem.

Epidemiology

There are no conclusive studies that identify the actual numbers of individuals specifically affected by AFM, but from 2014 to 2018, the CDC confirmed over 500 reports of those affected by AFM. Not all cases are reported to the CDC nor confirmed by the CDC, so this number is likely an underestimation. There have been reports of AFM in both children and adults, but AFM cases primarily affect children under the age of 18.

Until the recent characterization of AFM in 2014, it is likely that many individuals with initial presentation of flaccid limb weakness and/or paralysis have been diagnosed as having transverse myelitis or Guillain Barre Syndrome in previous years.

Signs & Symptoms

Most of those diagnosed with AFM report having a respiratory or gastrointestinal illness before the onset of weakness. The predominant presentation is a rapid onset of weakness that may affect the limbs, face, oropharyngeal muscles, or the muscles that control breathing. Those with AFM may not be able to breathe, swallow, or move their eyes normally. Weakness varies greatly ranging from mild to very severe. AFM may result in weakness, partial paralysis, or total paralysis of just one limb or all limbs. The pattern of paralysis and how individuals present are widely variable. Weakness most often occurs in proximal muscles, meaning the muscles closest to the center of the body. Pain in the neck, back, or limb may be an early symptom. Autonomic instability, such as issues with heart rate, may occur as well. Since it is mainly the gray matter of the spinal cord that is damaged in individuals with AFM, they may not have bladder or bowel dysfunction or issues with sensation. However, some individuals may have inflammation in both the white and gray matter of the spinal cord (upper and lower motor neuron), so some of those with AFM may experience impaired sensation, bladder, and/or bowel dysfunction.

Diagnosis

Acute flaccid myelitis is diagnosed based upon clinical exam, magnetic resonance imaging (MRI) of the spinal cord, and analysis of cerebrospinal fluid (CSF) (usually with increased white blood cells or pleocytosis). On MRI of the spinal cord, AFM lesions are longitudinal throughout the grey matter (the anterior horn cells). Sometimes imaging may appear normal early in the disease, but repeat imaging shows the lesions. In some situations, electrophysiological studies of the nerves and muscle (called nerve conduction and electromyogram [NCS/EMG]) may help to determine if there is injury to the lower motor neuron. Testing may also include blood draws, respiratory tract samples or collection of other bodily fluids to determine if a viral or infectious cause is present.

Acute Treatments

Specific treatments and intervention for AFM have not yet been identified, but some of the treatments available for transverse myelitis have been used (high dose intravenous (IV) steroids, intravenous immunoglobulin (IVIG), and plasma exchange (PLEX)). The purpose of the treatments is to attempt to reduce inflammation in the spinal cord and further prevent the individual’s immune system from causing damage. IVIG has antibodies that may have effect on limiting inflammation or neutralization or replication of enteroviruses and is widely used in treating AFM. The data on use of steroids or PLEX are mixed. Fluoxetine was used in several centers in the US in 2016 and was well tolerated but was not associated with improved outcomes among treated children. As is usual with treatment of rare neuroimmune disorders, in which placebo-controlled trials are difficult to perform, treatment must be individualized. Physical and occupational therapy are also believed to be significant for recovery in AFM.

Prognosis

Recovery varies among individuals with AFM. Most do not recover fully, but patients do regain strength and motor function over time to varying degrees. The most affected muscle may be the least likely to recover. Again, physical and occupational therapy are also believed to be critical for recovery in AFM.

Rehabilitation and Symptom Management

After the acute phase, rehabilitative care to improve functional skills and prevent secondary complications of immobility involves both psychological and physical accommodations. Rehabilitation may begin in the intensive care unit with the goal to transition individuals to an inpatient or outpatient rehabilitation program. There is very limited information in the medical literature specifically dealing with rehabilitation after AFM. However, much has been written regarding recovery from spinal cord injury (SCI), in general, and this literature applies. The physical issues include speech and oral motor skills training, bowel and bladder management, maintenance of skin integrity, spasticity, activities of daily living (i.e., dressing), mobility, sexual dysfunction (for adults), and pain.

The long-term management of AFM requires attention to a number of issues. These are the residual effects of any spinal cord injury, including AFM. In addition to chronic medical problems, there are the ongoing issues of ordering the appropriate equipment, reentry into school, re-socialization into the community, and coping with the psychological effects of this condition by the patients and their families. During the early recovery period, family education is essential to develop a strategic plan for dealing with the challenges to independence following return to the community.

Rehabilitation

It is important to begin occupational and physical therapies early during the course of recovery to prevent the inactivity related problems of skin breakdown and soft tissue contractures that lead to a decreased range of motion. Assessment and fitting for splints designed to passively maintain an optimal position for limbs that cannot be actively moved is an important part of the management at this stage.

Activity-based rehabilitation includes weight-bearing exercise, functional electrical stimulation (FES), locomotor training, task-specific practice, and massed practice. Individuals with AFM may not respond to FES, but therapists can adjust FES parameters to try to get a better muscle contraction. FES even without obvious muscle contraction may have benefits. Weight-bearing exercise has been shown to improve bone mineral density, range of motion, muscle tone, and bowel function. Vibration during weight bearing may also activate denervated muscles. Weight-bearing exercises can progress to locomotor training on the treadmill with appropriate orthotics. Aqua therapy can be helpful for stretching tight muscles. Task specific practice involves relearning functions that were lost due to AFM such as bed mobility and coming to a seated position, feeding, dressing, and personal hygiene. Some children who were younger when AFM onset occurred will have to learn these for the first time. Massed practice involves repetition and increased level of activity. It has been shown that children can tolerate up to 5 hours of therapy a day. It is important to keep in mind that spinal cord injuries in children result in risks of skeletal subluxations and decreased bone mineral density which can result in fractures.

Other rehabilitation factors to consider are pulmonary management for those with ventilator dependence, and speech and language pathologists for those children with difficulty swallowing (dysphagia) and talking (dysphonia).

Individuals with AFM may find ordinary tasks such as dressing, bathing, grooming, and eating very difficult. Many of these obstacles can be mastered with training and specialized equipment. For example, long handled sponges can make bathing easier as can grab bars, portable bath seats and hand-held shower heads. For dressing, elastic shoe-laces can eliminate the need to tie shoes while other devices can aid in donning socks. Occupational therapists are specialists in assessing equipment needs and helping people with limited function perform activities of daily living. A home assessment by an experienced professional is often helpful. Physical therapists assist with mobility. Besides teaching people to walk and transfer more easily, they can recommend mobility aids. This includes everything from canes (single point vs. small quad cane vs. large quad cane) to walkers (static vs. rolling vs. rollator) and braces. For a custom-fabricated orthotic (brace), an orthotist is necessary. Careful thought should go into deciding whether the brace should be an ankle-foot orthosis, whether it should be flexible or stiff, and what angle the foot portion should be in relationship to the calf portion. Some will benefit by a knee-ankle foot orthosis. Each person should be evaluated individually. The best results occur when a physician coordinates the team so that the therapists and orthotists are united on what is to be achieved. The physician best trained to take this role is the physiatrist.

Nerve Transfers

Some individuals may benefit from nerve transfer procedures, which is when nerves are taken from one area of the body and are transferred to a denervated nerve. The previous experience derived from obstetric brachial plexus injury has guided some of the approaches in patients with AFM. The value in recovery of selected upper extremity muscle groups in AFM patients appears promising although there is still need for a well-documented and validated approach to prove their beneficial outcomes. There are some cases reported in the literature of successful nerve transfers, but additional studies are needed to learn the correct timing for when nerve transfers should occur after onset.

Bladder Function

Bladder dysfunction may not occur in all individuals with AFM. Immediately after the onset of AFM, there is frequently a period of transient loss or depression of neural activity below the involved spinal cord lesion, referred to as “spinal shock,” which lasts about 3 weeks. Following this period, two general problems can affect the bladder. The bladder can become overly sensitive, and empty after only a small amount of urine has collected, or relatively insensitive, causing the bladder to become over extended and overflow. An overly distended bladder increases the likelihood of urinary tract infections and, in time, may threaten the health of the kidneys. Depending on the dysfunction, treatment options include timed voiding, medicines, external catheters for males (a catheter connected to a condom), padding for females, intermittent internal self-catheterization, an indwelling catheter, or electrical stimulation. Surgical options may be appropriate for some people.

Bowel Function

Another major area of concern is effective management of bowel function. A common problem in spinal cord injury is difficulty with evacuation of stool, although fecal incontinence can also occur. The neurologic pathways for defecation are similar to those of the bladder. Many lacking voluntary control of the bowel may still be able to achieve continence by diet, strategic use of stool softeners and fiber, and the technique of rectal stimulation. Other aids include suppositories, mini-enemas, anal irrigation, and oral medications. A high-fiber diet, adequate and timely fluid intake, and medications to regulate bowel evacuations are the basic components of success. Regular evaluations by medical specialists for adjustment of the bowel program are recommended to prevent potentially serious complications. There are some surgical options, although this is rarely necessary.

Sexual Dysfunction

Sexual dysfunction involves similar innervation and analogous syndromes as those found in bladder dysfunction. Treatment of sexual dysfunction in adults diagnosed with AFM should take into account baseline function before the onset of AFM. Until we learn more about this issue in AFM, individuals experiencing sexual dysfunction may want to refer to the strategies used in individuals with other rare neuroimmune disorders or spinal cord injuries.

Skin Breakdown

Skin breakdown occurs if the skin is exposed to pressure for a significant amount of time, without sensation or the strength to shift position as necessary. Sitting position should be changed at least every 15 minutes. This can be accomplished by standing, by lifting the body up while pushing down on armrests, or by just leaning and weight shifting. Wheelchairs can be supplied with either power mechanisms of recline or tilt-in-space to redistribute weight bearing.

A variety of wheelchair cushions are available to minimize sitting pressure. Redness that does not blanch when finger pressure is applied may signal the beginning of a pressure ulcer. Good nutrition, vitamin C, and avoidance of moisture all contribute to healthy skin. Pressure ulcers are much easier to prevent than to heal.

Spasticity

Spasticity may be an issue in AFM, particularly when a cervical spine lesion involved both the gray matter and the white matter. Damage to the white matter in the neck leads to a spastic weakness in the legs and can be seen in some AFM patients. The goal is to maintain flexibility with a stretching routine using exercises for active stretching and a bracing program with splints for a prolonged stretch. These splints are commonly used at the ankles, wrists, or elbows. Also recommended are appropriate strengthening programs for the weaker of the spastic muscles acting on a joint and an aerobic conditioning regimen. These interventions are supported by adjunctive measures that include antispasticity drugs (e.g., diazepam, baclofen, dantrolene, tizanidine), therapeutic botulinum toxin injections, and serial casting. The therapeutic goal is to improve the function of the individual in performing specific activities of daily living (i.e., feeding, dressing, bathing, hygiene, mobility) by improving the available joint range of motion, teaching effective compensatory strategies, and relieving pain.

Pain

Pain is common following AFM. The first step in treating pain effectively is obtaining an accurate diagnosis. Unfortunately, this can be very difficult. Causes of pain include muscle strain from using the body in an unaccustomed manner, nerve compression (i.e., compression of the ulnar nerve at the elbow due to excessive pressure from resting the elbow on an armrest continuously) or dysfunction of the spinal cord from the damage caused by the inflammatory attack. Muscle pain might be treated with analgesics, such as acetaminophen (Tylenol), non-steroidal, anti-inflammatory drugs such as naproxen or ibuprofen (Naprosyn, Aleve, Motrin), or modalities such as heat or cold. Nerve compression might be treated with repositioning and padding (i.e., an elbow pad for an ulnar nerve compression).

Nerve pain can be a significant challenge to find effective treatment. Nerve messages traveling through the damaged portion of the spinal cord may become scrambled and misinterpreted by the brain as pain. Besides the treatments listed above, certain antidepressants such as amitriptyline (Elavil), or anticonvulsants, such as carbamazepine, phenytoin, or gabapentin (Tegretol, Dilantin, Neurontin) may be helpful. Stress and depression should also be addressed since these conditions make pain harder to tolerate.

Depression

Individuals with AFM should be educated about the effect of AFM on mood regulation and routinely screened for the development of symptoms consistent with clinical depression. Warning signs that should prompt a complete evaluation for depression include failure to progress with rehabilitation and self-care, worsening fixed low mood, pervasive decreased interest, and/or social and professional withdrawal. A preoccupation with death or suicidal thoughts constitutes a true psychiatric emergency and should lead to prompt evaluation and treatment. Depression in AFM is similar to the other neurologic symptoms patients endure, which are mediated by the effects of the immune system on the brain. While the prevalence of depression among individuals with AFM is not known, depression is remarkably prevalent in TM, occurring in up to 25% of those diagnosed at any given time, and is largely independent of the patient’s degree of physical disability. Depression is not due to personal weakness or the inability to “cope.” It can have devastating consequences; not only can depression worsen physical disability (such as fatigue, pain, and decreased concentration) but it can have lethal consequences. Despite the severity of the clinical presentation of depression in AFM, there is a very robust response to combined aggressive psychopharmacologic and psychotherapeutic interventions.

Autonomic Dysreflexia

Autonomic dysreflexia can occur when a spinal cord is damaged above the T6 level. Symptoms can include nausea, sweating, fast heart rate and/or profound blood pressure changes (up or down). Episodes can be triggered by urinary tract infections, catheterizations, constipation or painful events in the lower extremities. Care should be given to minimize triggers and manage any blood pressure variations during an event.

Respiratory Dysfunction

A subset of patients with aggressive forms of AFM may experience marked respiratory and diaphragmatic dysfunction. It may occur when the neurons that control diaphragm movement innervated by the phrenic nerve, or intercostal muscles that partially control the mechanics of breathing, fail due to damage of motor neurons in the spinal cord. Thus, patients can have difficulty breathing and require long term ventilatory support. Over months or years patients can be weaned from the ventilator as motor control of the diaphragm comes back, but in some patients it has not yet returned. Strategies such as a diaphragm pacer are being used now although there is still need for a validated demonstration of its efficacy. Those with respiratory issues may also experiences issues with heart rate, like tachycardia (high heart rate) and bradycardia (low heart rate).

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CDC Case Confirmation for Acute Flaccid Myelitis

For children and adults diagnosed with Acute Flaccid Myelitis (AFM) in the United States, the process of confirming their case with Centers for Disease Control and Prevention (CDC) can be overwhelming. The Transverse Myelitis Association (TMA) and the Acute Flaccid Myelitis Association (AFMA) recently teamed up to create the following information sheet to explain the process of reporting a case of AFM to CDC.

You can find the CDC Case Confirmation for Acute Flaccid Myelitis information sheet in the TMA’s Resource Library here.

What is Acute Flaccid Myelitis?

In recent years we’ve seen an uptick in reports of children and adults being diagnosed with Acute Flaccid Myelitis (AFM). Cases have peaked every 2 years since 2012, and there have been over 500 cases confirmed by the Centers for Disease Control and Prevention (CDC) since 2014. Most individuals diagnosed with AFM are children, although there have also been cases in adults. Symptoms usually include a febrile respiratory illness followed by sudden onset of limb weakness/paralysis and the loss of muscle tone and reflexes. Some individuals have cranial nerve involvement and have a facial droop/weakness, difficulty moving the eyes, drooping eyelids, or difficulty swallowing or slurred speech. Some individuals may also experience respiratory failure where breathing assistance is necessary.

Although a definitive cause for AFM has not yet been established, many experts think it is due to infection from a non-polio enterovirus (EV), such as EV-D68 or EV-71. To better understand the potential causes, optimal treatment, and outcomes of AFM, health departments across the United States are conducting enhanced surveillance for AFM cases.

When children or adults are diagnosed with AFM, cases are reported to CDC, who then publish the data. The process for getting cases to CDC is clunky and, in many cases, parents or patients never hear back if their case was confirmed. The AFM community’s long held fear is that cases are underreported to CDC, and as a result, AFM is not getting the attention it deserves. It’s critical that CDC has an accurate count of cases so that research for AFM can be properly funded. Better treatment protocols and outcomes should follow research–and it all hinges on CDC having all the information it needs. The details for the case confirmation process are as follows:

How do cases get reported to CDC?

Be a voice! Please urge your clinician to report you or your child’s AFM diagnosis to the local health department. Below you can find the steps for cases to be reported to CDC.

1. Clinicians submit the Patient Summary Form, Medical Records and MRI to State/Local Health Departments.

2. State Health Departments pass this information along to CDC.

3. CDC evaluates the case (confirmed, probable) and updates the State Health Department.

4. The State Health Department updates the clinician.

5. The clinician updates the parent or patient.

How do I find out if my case was confirmed by CDC?

If you have not heard back about your case, these are the steps you can take to make sure it was reported.

1. Call your state health department. Find the contact for Infectious Disease or Epidemiology (if that fails, find the press person!)

2. Say, “My child/I was/were diagnosed with AFM in (Month/Year) in (County) and I would like to know my case’s status (confirmed, probable, pending) with CDC.”

  • If they say your case was confirmed, ask if it was reported back to the clinician.
  • If it wasn’t confirmed, determine where the breakdown occurred. Did they get the information from the clinician? Was it passed along to CDC? Are they waiting to hear back from CDC?
    • If the clinician never submitted information, contact your clinician.
    • If the State Health Department sent the information to CDC and are still waiting to hear back from CDC, it is likely the case has not yet been classified. CDC alerts health departments as soon as cases are classified. However, if the health department is unsure of the status, they can contact CDC with the patient’s case ID number for an update.

3. If all else fails, email AFMquestions@CDC.gov and they can try to contact State Health Departments. Please be sure to let them know which county/state you live in. CDC will still not be able to verify if your or your child’s case was confirmed because their data are anonymous, but they can help connect you with someone at the state department who will follow up with you and provide you that information. But call your state first —that helps raise awareness of AFM!

For your Clinician: AFM Classification Information

  • An illness with acute limb weakness and:
    • Confirmed: A magnetic resonance image (MRI) showing spinal cord lesion largely restricted to gray matter** and spanning one or more spinal segments.

    • Probable: Cerebrospinal fluid (CSF) showing pleocytosis (white blood cell count>5 cells/mm3, may adjust for presence of red blood cells by subtracting 1 white blood cell for every 500 red blood cells present).

** Normal or negative MRI images within the first 72 hours of symptoms does NOT rule out AFM. Terms used in the spinal cord MRI report such as “affecting mostly gray matter”, “affecting the anterior horn or anterior horn cells”, affecting the central cord”, “anterior myelitis” or “poliomyelitis” would all be consistent with this terminology. If you are unsure if this criterion is met, consider consulting the neurologist or radiologist directly.

Specimen Collection and Submittal

Urge clinicians to collect specimens on suspect cases as early as possible, preferably on the day of onset of limb weakness/paralysis, to increase the chance of virus detection.

The following is a check list of specimens and tests the clinician should submit to the health department.

1. MRI (performed within 72 hours) √
2. Nose and mouth swabs for viral detection √
3. Antibody levels (serum) collected prior to any treatments √
4. Lumbar Puncture √
5. Stool and urine samples √.

Additional Resources

The Transverse Myelitis Association
www.myelitis.org

Acute Flaccid Myelitis Association
www.afmanow.org

Centers for Disease Control and Prevention
https://www.cdc.gov/acute-flaccid-myelitis

*Some sections were adapted from the California Department of Public Health – November 2018 Acute Flaccid Myelitis (AFM) Quicksheet: ow.ly/GnpX30nHhh1

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Facts About Rare Neuroimmune Disorders: The 5 W’s

The TMA currently advocates for individuals with six rare neuroimmune disorders: acute disseminated encephalomyelitis (ADEM), acute flaccid myelitis (AFM), MOG antibody-associated disease (MOG-Ab disease), neuromyelitis optica spectrum disorder (NMOSD), optic neuritis (ON), and transverse myelitis (TM). While these conditions are similar in some ways, each disorder has a distinct criteria for diagnosis. In order to help our community understand the connections between the disorders as well as the differences, Dr. Cynthia Wang compiled the following information on the 5 W’s: who, where, what, which, and why.

You can find the Facts about rare neuroimmune disorders: The 5 W’s information sheet in the TMA’s Resource Library here.



Neuroimmune disorders, such as acute disseminated encephalomyelitis (ADEM), acute flaccid myelitis (AFM), MOG antibody-associated disease (MOG-Ab disease), neuromyelitis optica spectrum disorder (NMOSD), optic neuritis (ON), and transverse myelitis (TM) are conditions in which a person’s immune system mistakenly attacks parts of the central nervous system (CNS) – brain, spinal cord, optic nerve. 

Who gets these illnesses? 

  • ADEM tends to affect young children, typically ages 4-8, without a significant bias for specific gender or ethnic background.
  • AFM tends to affect children as well, and increases in cases have occurred every other year since 2012.
  • We are still learning about who is more likely to get MOG-Ab disease. Some studies have shown that those with MOG Antibody-Associated Disease are on average younger and are likely to be male compared to those with aquaporin-4 (AQP-4) positive NMOSD. Those with MOG-Ab disease may be more likely to have bilateral involvement of the optic nerves.
  • NMOSD associated with AQP-4 antibodies tends to disproportionately affect non-Caucasian women in their 30-40s.
  • TM can affect individuals of all ages, ethnicities, and either gender.
  • ON is more common in women and develops in most patients between the ages of 20 and 45. Additionally, ON typically occurs more frequently in Caucasians than African Americans.

Where in the nervous system do these disorders affect?

  • inflammation in optic nerves = optic neuritis (ON)
  • inflammation of spinal cord, primarily the white matter of the spinal cord = transverse myelitis (TM)
  • inflammation of spinal cord, primarily the grey matter of the spinal cord = acute flaccid myelitis (AFM)
  • inflammation of brain = encephalitis
  • inflammation of brain and spinal cord (and sometimes optic nerve) = encephalomyelitis (acute disseminated encephalomyelitis (ADEM) is a subtype that may or may not include spinal cord involvement)
  • inflammation of brain, optic nerves, and/or spinal cord = neuromyelitis optica spectrum disorder (NMOSD) or MOG antibody-associated disease (MOG-Ab disease)

What does monophasic or relapsing mean?

Some of these disorders are monophasic, meaning a one-time confused reaction of the immune system, without any further episodes of inflammation (TM, AFM, ADEM, ON).

Other disorders are known as relapsing, in which a persistently confused immune system can continue to cause inflammatory episodes (NMOSD and MOG-Ab disease, although ADEM, TM, and ON can be initial presentations of these relapsing diseases) 

For the disorders that can be relapsing, people are given long-term therapies to diminish the chance of future episodes or to lessen their impact should they occur.  

Testing for AQP-4 and MOG antibodies can help predict if someone will have a monophasic or relapsing course.  

If antibody testing is negative, the longer one goes without another attack, the more likely it is that the condition is monophasic.

Which of these conditions tend to be relapsing or recurring?

Multiple sclerosis and neuromyelitis optica spectrum disorder associated with aquaporin-4 (AQP-4) antibodies are the two most well recognized forms of relapsing CNS auto-immune disorders.

60-80% of individuals with optic neuritis and longitudinally extensive transverse myelitis (involvement of greater or equal to the length of 3 vertebrae) have antibodies to aquaporin-4 (AQP-4), a water channel in astrocytes, a type of support cell in the central nervous system.

A proportion of individuals who test negative for AQP-4 and some of those diagnosed with recurrent ON or ADEM are now known to have antibodies against another target, called myelin oligodendrocyte glycoprotein (MOG). MOG is a protein on myelin and oligodendrocytes, the myelin-producing cells of the central nervous system and are thought to have MOG-Ab disease. Individuals who continue to test positive for MOG antibodies 6-12 months after their initial attack are at risk for recurrent disease and should discuss with their provider if chronic immunosuppression is warranted.

Why do people get these disorders?

This is a central question in neuroimmunology and currently we still don’t know for sure. It is hypothesized that these disorders result from a specific set of circumstances, namely 1) a person whose immune system may be primed to overreact or get confused, or a genetic predisposition to auto-immunity and environmental triggers, and 2) a life event, perhaps a bodily stressor, such as an infection, to trigger the attack. We do not yet know the genetics or environmental factors that lead to these conditions.



Author

Dr. Cynthia Wang received her medical degree from University of Texas Southwestern Medical Center in Dallas, Texas and completed a pediatrics and pediatric neurology residency at Mott Children’s Hospital, University of Michigan Health System in Ann Arbor, Michigan. Dr. Cynthia Wang completed her James T. Lubin Fellowship under the mentorship of Dr. Benjamin Greenberg at The University of Texas Southwestern and Children’s Health. Her research study was a prospective, longitudinal study on acute disseminated encephalomyelitis (ADEM) to identify the clinical characteristics, treatment methods, and follow-up interventions that are associated with better and worse patient-centered outcomes.

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Q&A on Relapsing vs Monophasic Rare Neuroimmune Disorders with Dr. Cynthia Wang

Individuals who are diagnosed with a rare neuroimmune disorder sometimes experience new or worsening symptoms months or years after the initial onset of their inflammatory attack. Understandably, this causes concern that a relapse of their disorder has occurred. To help our community understand the difference between a relapse and worsening symptoms, we asked Dr. Cynthia Wang to answer some questions about relapsing versus monophasic rare neuroimmune disorders and what to do if you think you may be experiencing a relapse.

You can find the Relapsing vs Monophasic Rare Neuroimmune Disorders fact sheet in the TMA’s Resource Library here.



Are diseases such as transverse myelitis (TM), acute flaccid myelitis (AFM), optic neuritis (ON), acute disseminated encephalomyelitis (ADEM), MOG antibody-associated disease (MOG-Ab disease), or neuromyelitis optica spectrum disorder (NMOSD) one-time or relapsing diseases?

It depends. TM, ON, and syndromes resembling ADEM can occur in the setting of relapsing conditions, such as multiple sclerosis, neuromyelitis optica associated with aquaporin-4 antibodies (AQP-4), and some systemic/ rheumatologic diseases. Once an individual has undergone sufficient workup for these conditions and they have been ruled out, the likelihood he or she has idiopathic transverse myelitis or monophasic ADEM increases, which are considered one-time disorders. In the past year, clinicians have also been able to test for a new antibody called MOG (myelin oligodendrocyte glycoprotein). Like AQP-4, MOG antibodies can be assessed with good accuracy through a blood sample. Although the MOG story is still unfolding, many physicians following patients who continue to test positive for MOG antibodies 6-12 months after the initial episode have reported relapsing disease in this population and are thought to have MOG antibody-associated disease.

I had transverse myelitis (TM), optic neuritis (ON), or acute disseminated encephalomyelitis (ADEM) in the past and was told I don’t have multiple sclerosis or neuromyelitis optica spectrum disorder (NMOSD). I am now experiencing new or worsening neurological symptoms? What should I do?

It is very important for you and your provider to determine if the worsening symptoms are related to new inflammation (i.e., a relapse), or from some temporary disturbance in your body’s normal state unmasking symptoms from a prior injury, without new inflammation (pseudo-relapse).

For symptoms that last over 24 hours and do not improve with rest, hydration, being in a comfortable temperature, and/or recovery from an acute illness (e.g., respiratory or urinary tract infection), contact your neurology provider. He or she may order blood or urine tests to make sure you are not experiencing any acute infections or metabolic disturbances. If ruled out, additional tests may include an MRI of suspected area of new inflammation (i.e., brain, spine, and/or optic nerves).

Evidence of new inflammation on MRI and/or symptoms related to a part of the nervous system that was not affected in the past suggests a new acute inflammatory episode. This should be treated with immunotherapy such as corticosteroids to stop ongoing inflammation, and trigger a discussion with your clinician about whether ongoing immunotherapy to prevent another attack is needed.

If I am concerned I have a relapsing disorder, what should I do?  

Discuss this concern with your neurology provider, and ask if you would be an appropriate candidate to test for AQP-4 and MOG antibodies (available through Mayo Medical Laboratories as “CDS1” order).  

My doctors say they can still see TM or an area of damage on my MRI. Does this mean I have a relapsing disorder?

During an inflammatory attack in the spinal cord, as occurs in TM, there may be evidence of inflammation on MRI (areas of contrast enhancement indicating compromise of the blood-brain-barrier) or an increase in inflammatory cells in cerebrospinal fluid. After this inflammation subsides, there may be evidence of where this attack occurred, or an area showing previous damage (T2/ FLAIR abnormalities), but not ongoing inflammation (e.g., continued contrast enhancement). Gliosis, essentially a scar in the brain, can be seen for months or years and does not indicate ongoing inflammation or relapsing disease. An MRI that shows new inflammation suggests a new acute inflammatory episode.

My doctor told me I am AQP-4 positive, now what?

An episode consistent with neuromyelitis optica spectrum disorder and a single positive test for AQP-4 in blood or spinal fluid are typically adequate to establish a diagnosis of NMOSD. These individuals should be placed on immunosuppressive therapy, which we currently advise be continued indefinitely. This is because NMOSD attacks can be severe, cause lasting visual or motor impairment, and are very likely to recur unless treated.

My doctor told me I am MOG positive, now what?

This depends on when MOG antibodies were tested in relation to your demyelinating event. If MOG antibodies were detected at the time of the attack or in the first 6 months following attack, we recommend retesting for MOG antibodies 6-12 months after your event. If you become MOG negative, you are unlikely to have future relapses.

If MOG antibodies are positive again, you are considered to have MOG antibody-associated disease, and may be at risk for future demyelinating episodes. You should speak to your neurologist about whether you should be placed on a therapy to prevent the likelihood of a relapse.

For individuals who undergo MOG testing for the first time 12 months or greater after their demyelinating event, one positive MOG test would be sufficient to diagnosis persistent MOG antibodies and then you should have a discussion with your physician as above about chronic immunotherapy.

I already have any existing diagnosis of multiple sclerosis or neuromyelitis optica spectrum disorder. Should I be tested for MOG?

It depends on your clinical history and if you have tested positive for AQP-4. MOG testing is reasonable in people who’ve been told their presentation is atypical for multiple sclerosis and neuromyelitis optica spectrum disorder and previously have been negative on AQP-4 testing. AQP-4 positive patients with symptoms consistent with NMOSD do not need MOG testing, as being double positive (MOG and AQP-4 positive) is exceedingly rare. In addition, this information ultimately would not change management as recurrent MOG and AQP-4 associated NMOSD are currently managed very similarly.

People with presumptive multiple sclerosis who do not respond as well as expected to MS drugs should have a discussion with their doctor about MOG testing as MOG syndromes can be misdiagnosed as MS. A positive MOG test may change medical management as some MS therapies might be ineffective or perhaps even exacerbate MOG antibody-associated disease.

People with MRI and spinal fluid studies consistent with multiple sclerosis should not be routinely screened for MOG antibodies, but decided on a case- by-case basis after discussion with a neurologist.

Glossary

Central Nervous System: Includes the brain, spinal cord, and optic nerve.

Monophasic rare neuroimmune disorder: A disorder that causes only one episode of inflammation in the central nervous system.

Recurrent or relapsing rare neuroimmune disorder:
A disorder that causes more than one episode of inflammation in the central nervous system.

Relapse: New inflammation in the central nervous system.

Pseudo-relapse: Temporary disturbance in the body’s normal state unmasking or worsening symptoms from a prior injury, without new inflammation in the central nervous system.

Attack: An event of inflammation in the central nervous system.

Onset: The first symptoms of a rare neuroimmune disorder. Typically, the first attack.

Inflammation: Part of the body’s immune system meant to eliminate noxious agents. In rare neuroimmune disorders, the immune system mistakenly attacks the brain, spinal cord, or optic nerve, causing inflammation in these areas.


DisorderAreas of CNS InvolvementSpecific Diagnostic TestsRelapsing or MonophasicOngoing Immuno-suppresion indicated?
ADEMBrain
Spinal Cord
Optic Nerve

None if monophasic

___________________________

MOG Antibody

If MOG negative 6-12 months after onset, typically monophasic

__________________________

If MOG positive 6-12 months after onset, might be recurrent (MOG-Ab disease)


No

_________________________

Yes

AFMSpinal Cord (primarily grey matter)Enterovirus PCR in CSF (though virus is very difficult to isolate), positive enterovirus/rhinovirus on respiratory specimen is supportiveMonophasicNo
Mog-Ab DiseaseBrain
Spinal Cord
Optic Nerve
MOG AntibodyUncertain, persistence of MOG antibodies are associated with relapsing diseaseYes, if relapses occur
MSBrain
Spinal Cord
Optic Nerve
None, though CSF oligoclonal bands are supportiveRelapsingYes
NMOSDBrain
Spinal Cord (typically lesions more than 3 vertebral segments in length)
Optic Nerve
Aquaporin-4 antibodyRelapsingYes
ONOptic NerveNoneDepends if ON is a part of MS, NMOSD, or MOG-Ab diseaseTypically yes if relapsing
TMSpinal Cord (primarily white matter)NoneMonophasic

_________________

In very rare cases can be recurrent

No

__________________

Case-by-case


Author

Dr. Cynthia Wang received her medical degree from University of Texas Southwestern Medical Center in Dallas, Texas and completed a pediatrics and pediatric neurology residency at Mott Children’s Hospital, University of Michigan Health System in Ann Arbor, Michigan. Dr. Cynthia Wang completed her James T. Lubin Fellowship under the mentorship of Dr. Benjamin Greenberg at The University of Texas Southwestern and Children’s Health. Her research study was a prospective, longitudinal study on acute disseminated encephalomyelitis (ADEM) to identify the clinical characteristics, treatment methods, and follow-up interventions that are associated with better and worse patient-centered outcomes.

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Frequently Asked Questions about AFM

The recent increase in cases of Acute Flaccid Myelitis (AFM) is causing concern across the United States. The TMA has received many questions from the community about AFM, so at the 2018 Regional Rare Neuroimmune Disorders Symposium in Boston, we asked Dr. Benjamin Greenberg of the University of Texas Southwestern Medical Center to respond to the most commonly asked questions we have received. You can view his responses below. You can also view the rest of the videos from the symposium on our YouTube page here. You can find more resources on AFM in our Resource Library, including our 2018 Podcast on Acute Flaccid Myelitis and Dr. Greenberg’s presentation on AFM at the 2018 Regional RNDS.


What is acute flaccid myelitis?




What causes acute flaccid myelitis?




Is acute flaccid myelitis contagious?



Will someone who already has TM or another neuroimmune disorder be susceptible to AFM?



What are the symptoms of acute flaccid myelitis?



What should a parent do when they suspect symptoms of acute flaccid myelitis?



Where should treatment be sought?



How do you diagnose acute flaccid myelitis?



What are the treatments for acute flaccid myelitis?



Is there a relation between vaccinations and acute flaccid myelitis?



Can acute flaccid myelitis be prevented?



Is there a cure for acute flaccid myelitis?



What is the relationship between EVD68 and acute flaccid myelitis?


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Does my child need an IEP or 504?

By Beth Schwartz

Beth is the mother of a child with NMOSD and has attended the TMA Quality of Life Family Camp. You can find Beth’s blog at http://thesurpriseturn.blogspot.com/.

Your child is out of the hospital, hopefully has a diagnosis and now is ready to go back to school. Now what?

Depending on your child’s needs, you can talk to your child’s school about different levels of support.

My daughter had a seizure, so the first thing the school needed was a seizure action plan. This is a plan the doctor created with directions on what to do if she had another seizure. I needed to provide the school with the seizure action plan (signed by her doctor) and a medical form (also signed by her doctor) for her prescription rescue medication before she could go back to school.

A similar protocol is often used for children diagnosed with diabetes. Schools may require a diabetes action plan that is signed by the doctor and includes information on how to manage the child’s diabetic needs.

If your child is doing well in school and able to do things like he or she did before? That is awesome. Do a little happy dance!

Some children, though, need more. For our daughter, we saw that her school success was being hindered by the visual and memory problems that resulted from her NMO. She didn’t need special instruction or therapies, but she did need some accommodations. We met with the school staff and determined that she was eligible for a 504 plan. 504 plans are based on the individual needs of the child and can allow for things such as extra time and preferential seating.

Some children require specialized instruction or therapies. In these situations, students may need to be evaluated to see if the qualify for an IEP (Individualized Education Plan). This requires an evaluation process in which the school district often does both cognitive and academic testing.

What’s the difference between a 504 and an IEP? They are both individualized plans. A 504 provides accommodations to the general education instruction, where as an IEP is providing specialized instruction. IEPs include specific goals for areas of need. These goals can be related to specific areas such as academics, behavior, speech, occupational therapy and physical therapy. 504 plans do not include goals. Information from the doctor, your child’s teacher and school evaluations can help you determine if your child is eligible for one of these plans.

Not sure what to do? Call your child’s school. They can meet with you to talk about your concerns and determine what the next steps should be for your child’s success.

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Recent Spike in Cases of Acute Flaccid Myelitis

Reports have been circulating across the United States concerning the recent spike in cases of Acute Flaccid Myelitis (AFM), a subtype of Transverse Myelitis. AFM is inflammation of the spinal cord, and it predominantly affects children. From August 2014 through August 2018, the Centers for Disease Control and Prevention (CDC) has received information on a total of 362 cases of AFM across the U.S.1 The exact cause of AFM has not yet been determined, but it usually follows a respiratory infection and is believed to be caused by a common virus. However, most children who are infected by the virus do not contract AFM.

The most common symptom of AFM is weakness in the limbs and can result in partial or full paralysis in some cases. AFM is diagnosed based upon clinical exam, MRI findings, lumbar puncture, and may also include a nerve conduction study (EMG) to determine if there is injury to the lower motor neuron. Testing may also include blood draws, respiratory tract samples, or collection of other bodily fluids to determine if a viral or infectious component is present. A diagnosis of AFM differs from classically described Transverse Myelitis in that abnormalities on an MRI are predominantly found in the gray matter of the spinal cord in cases of AFM.

To date, there have not been any conclusive studies that prove a viable treatment for AFM; however, treatments available for Transverse Myelitis have been used. These treatments include high dose IV steroids, IVIG, and plasma exchange (PLEX). The CDC does not recommend the use of steroids, IVIG, or plasma exchange in AFM because of a lack of controlled data, but individuals with AFM or caregivers of children with AFM should discuss treatment recommendations with their physician. Multiple centers have used these therapies with variable results. Physical therapy is believed to be critical for recovery in AFM.

If you or someone you know has a child experiencing symptoms consistent with AFM, it is important to seek emergency care immediately. The TMA will be hosting a special podcast on AFM next week with Dr. Benjamin Greenberg of UT Southwestern Medical Center. We will announce the podcast once all details are finalized. Information and support for those affected by AFM can be found using the following resources:

Membership Form: https://myelitis.org/join/

Information Sheet on AFM: https://tma.ong/2y9Ie5v

AFM Resources: https://tma.ong/AFM-resources

Management of AFM: https://www.youtube.com/watch?v=mpe-TkQhrD4&feature=youtu.be&list=PLXi60bECkjnXxzgkf2bk3J12iwVU1Q4ML

Q&A and Podcast: https://myelitis.org/acute-flaccid-myelitis-understanding-recent-outbreak/

2017 Collaborative Meeting on AFM: https://myelitis.org/collaborative-meeting-acute-flaccid-myelitis/

Parents of Children with AFM Share Stories: https://myelitis.org/resources/power-sharing-stories/2/

AFM – What Is It?: https://archive.myelitis.org/resources/Newsletter_Articles/2015_04_15_afm.pdf

[1] AFM Investigation. (2018, October 5). Retrieved October 11, 2018, from https://www.cdc.gov/acute-flaccid-myelitis/afm-surveillance.html

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Proposed Legislation to Improve Air Travel for People with Disabilities

The House of Representatives of the United States Congress passed a bill that renews authorization and funding to the Federal Aviation Administration (FFA) for five years and proposes updates to the Air Carrier Access Act (ACAA). The ACAA was originally enacted in 1986 to protect individuals with disabilities from discrimination in air travel. Although the ACAA has led to progress in this endeavor, individuals with disabilities still experience issues such as damage to their assistive devices, a lack of seating accommodations, inaccessible bathrooms, mishandling of service animals, and lack of training by the airline staff to provide adequate assistance. The proposed amendments to the ACAA aim to rectify some of these issues by ensuring streamlined boarding, deplaning, and connections between flights, accessible accommodations, and accessible communication, including both visual and audible announcements.

The bill also creates a Select Subcommittee for Aviation Consumers with Disabilities, which will advise the Secretary of Transportation on the air travel needs of individuals with disabilities. The bill also orders the U.S. Department of Transportation to conduct a study on the use of in-cabin wheelchair restraint systems and issue a report to Congress within 180 days of completing the study. Finally, the bill requires that the training provided to airport and airline staff be reviewed and updated.

Now that the bill has been passed by the House of Representatives, it has moved to the Senate. To contact your Senators to voice your support of the Bill, please visit this site: https://tma.ong/2PUs2ve. To view the proposed bill in its entirety, please visit https://www.congress.gov/bill/115th-congress/senate-bill/1318/text.

If you would like to learn more about using air travel as a person with a disability, the TMA recently hosted a podcast on this subject. You can listen to the podcast here: https://myelitis.org/resources/air-travel-with-a-disability-your-rights-best-practices-and-suggestions/.

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2017 Ask the Expert Podcast Recap

In 2017, the TMA hosted 11 podcasts as part of our Ask the Expert Podcast Series. In total, 362 people attended the live broadcast of these podcasts, and the recordings on YouTube have been played more than 2,300 times!

We started the year with a podcast on “Building a multidisciplinary team for complex care after a rare neuroimmune diagnosis” with Dr. Ben Greenberg and Dr. Sara Qureshi. We then learned about “Vaccinations and rare neuroimmune disorders” with Dr. Teri Schreiner and Dr. Augusto Miravalle, and how there is still much research to be done on this topic. In March, Katherine Treadaway and Paula Hardeman joined us for a podcast on “Managing your health after a rare neuroimmune diagnosis” where we learned about having a comprehensive approach to maintaining a healthy lifestyle.

Next, we were joined by registered dieticians Tad Campbell and Christopher Flores for a podcast on “The role of nutrition in managing your health”, and we learned about the importance of a balanced diet, hydration, and weight management. We then hosted a series of podcasts focusing on each of the rare neuroimmune disorders in an open forum: transverse myelitis (including acute flaccid myelitis), neuromyelitis optica spectrum disorder, and acute disseminated encephalomyelitis.

In August, we learned about “Gaining functional recovery through occupational therapy” from occupational therapists Rebecca Martin and Kathleen Zackowski. They explained how occupational therapy is used to teach individuals how to use “strength and endurance, but also cognition and coordination to engage in more meaningful activities” such as bathing and eating. We then learned “How to get the most out of your appointments: Physician and patient perspectives” with Dr. Ben Greenberg and Kristin Smith, an individual diagnosed with TM.

In November, we were joined by licensed social workers Sandra J. King and Katherine Treadaway for a podcast on “How to manage and cope with grief”, where we learned how grief takes many forms and can be caused by experiencing a life-changing disorder. Finally, we ended the year with a podcast on “Rheumatological conditions and ADEM, NMOSD, TM, and ON.” Dr. Julius Birnbaum and Dr. Tracey Cho spoke about how rheumatological conditions often coincide with rare neuroimmune disorders.

If you were unable to join any of the TMA Ask the Expert podcasts in 2017, they were recorded and can be found in our Resource Library here. Additionally, we have transcribed some of our podcasts, which can be found here.

We would love your feedback on how to improve the podcasts! Please click the button below to take a brief survey on your experience, and feel free to tell us what you would like to learn about in future podcasts!

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2017 Symposium Videos are Here!

The 2017 Rare Neuroimmune Disorders Symposium was held on October 20th-21st in Columbus, OH at the Hilton Columbus at Easton. We hope that the opportunity to meet the medical professionals, to connect with others in our community and learn more about TM, AFM, ADEM, ON, and NMOSD was a beneficial experience for those who attended. For those who couldn’t join us in person, symposium sessions were recorded and are available on the TMA’s YouTube Page and our Resource Library.

We strive to continue hosting educational events like these in order to fulfill the TMA mission of promoting awareness and empowering patients, families, clinicians and scientists through education programs and publications.

“The word rare doesn’t really apply in this room because for you it’s not rare, it’s real.” Dr. Brenda Banwell started the symposium with an overview about rare neuroimmune disorders.

Then there were disorder workshop sessions on Transverse Myelitis, Neuromyelitis Optica Spectrum Disorder and Optic Neuritis, Acute Disseminated Encephalomyelitis, and Acute Flaccid Myelitis. Speakers also gave talks on neuropathic pain, fatigue, bladder, bowel, and sexual dysfunction, neuropsychological issues, and rehabilitation.

We ended the 2017 RNDS with an afternoon on research updates where scientists and researchers shared exciting and promising information about the diagnosis, management, and treatment of these disorders. Below, you can find the video of Dr. Michael Levy’s talk on the Genetics of Familial Transverse Myelitis and his ongoing research to uncover a genetic link to TM. You can find all of the research talks on the 2017 RNDS page in our resource library.

If you would like to get involved, use your voice to connect with others and foster strong relationships in our community, or start a support group near you, please reach out to our Community Partnerships Manager, Jeremy Bennett at jbennett@myelitis.org to learn more.

We look forward to seeing more of our community next year at a regional symposium we are planning. Please check our website for more details in 2018.

Our work is made possible through the generous donations of individuals who believe in our mission. By choosing to donate to The Transverse Myelitis Association today, you are taking an active role in efforts to help advance research, education and awareness of rare neuroimmune disorders.

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