Acute flaccid myelitis

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Acute flaccid myelitis
Other namesAcute flaccid paralysis with anterior myelitis, polio-like syndrome [1]
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Magnetic resonance imaging of the spinal cord in a case of AFM showing cord swelling in (d) which has resolved three weeks later in (e). [2]
Specialty Neurology [3]
Symptoms Weakness, decreased reflexes, trouble swallowing or speaking [3]
Complications Trouble breathing, urinary retention [3]
Usual onsetRapid [3]
CausesGenerally unknown; thought to be caused by viral infection [4]
Diagnostic method Medical imaging, nerve conduction studies, cerebral spinal fluid testing [3] [5]
Differential diagnosis Transverse myelitis, Guillain–Barré syndrome, acute disseminated encephalomyelitis [3] [5]
Treatment Supportive care, physical therapy, mechanical ventilation [3] [5]
Prognosis Variable [5]
FrequencyRare [4]

Acute flaccid myelitis (AFM) is a serious condition of the spinal cord. [3] [5] Symptoms include rapid onset of arm or leg weakness and decreased reflexes. [3] Difficulty moving the eyes, speaking, or swallowing may also occur. [3] Occasionally, numbness or pain may be present. [3] Complications can include trouble breathing. [3]

Contents

The cause of most cases is unclear as of 2018. [4] More than 90% of recent cases have followed a mild viral infection such as from enteroviruses. [4] While polio can cause AFM, since 2014, it has not been involved in cases in the United States. [3] [6] The underlying mechanism involves damage to the spinal cord's grey matter. [3] Diagnosis may be supported by medical imaging of the spine, nerve conduction studies, and cerebrospinal fluid testing. [3] [5]

Treatment involves supportive care. [5] [3] Physical therapy may be recommended. [3] Occasionally, mechanical ventilation is required to support breathing. [3] Outcomes are variable. [5] The condition is rare and occurs most commonly in children. [4] Fewer than one in 500,000 children is affected per year in the United States. [3] Although the illness is not new, an increase in cases has been seen since 2014 in the United States. [3] In 2018, 233 cases were confirmed in the United States. [7]

Signs and symptoms

Symptoms include:

A summary of the condition by the Centers for Disease Control and Prevention (CDC) in 2014: [9]

Common features included acute focal limb weakness and specific findings on magnetic resonance imaging (MRI) of the spinal cord consisting of nonenhancing lesions largely restricted to the grey matter. In most cases, these lesions spanned more than one level of the spinal cord. Some also had acute cranial nerve dysfunction with correlating nonenhancing brainstem lesions on MRI. None of the children experienced altered mental status or seizures. None had any cortical, subcortical, basal ganglial, or thalamic lesions on MRI. Most children reported a febrile respiratory illness in the two weeks preceding development of neurologic symptoms. In most cases, cerebrospinal fluid (CSF) analyses demonstrated mild-moderate pleocytosis (increased cell count in the CSF) consistent with an inflammatory or infectious process.

Causes

Maximum likelihood phylogenetic trees of enterovirus species A, B, C, D and rhinovirus A, B, or C isolates from Latin America: The 5'UTR region is much more affected by recombination events than the VP4/VP2 coding sequence. Polio is in the enterovirus C species; enterovirus 71, a strain of enterovirus A, has been reported to cause rare neurological complications; the suspected cause of the 2014 cases is a strain of enterovirus D. Most enteroviruses and rhinoviruses cause only common cold symptoms. Phylogenetic analyses of HRV and HEV.jpg
Maximum likelihood phylogenetic trees of enterovirus species A, B, C, D and rhinovirus A, B, or C isolates from Latin America: The 5'UTR region is much more affected by recombination events than the VP4/VP2 coding sequence. Polio is in the enterovirus C species; enterovirus 71, a strain of enterovirus A, has been reported to cause rare neurological complications; the suspected cause of the 2014 cases is a strain of enterovirus D. Most enteroviruses and rhinoviruses cause only common cold symptoms.

As of October 2018, the U.S. CDC regarded the cause of AFM as having "a variety of possible causes such as viruses, environmental toxins, and genetic disorders", listing poliovirus, nonpolio enteroviruses, West Nile virus, and adenoviruses among the potential causes. [3] [7] More than 90% of people with AFM reported having symptoms consistent with a mild viral infection before the onset of AFM. [11]

Much research has focused on the nonpolio enteroviruses 68 (EV-D68) and 71 (EV-A71), a common cause of hand, foot, and mouth disease in infants and young children, members of the enterovirus D and enterovirus A species, respectively, as suspected causes. [7] Some evidence supports a causal role of EV-D68. [12] Coxsackievirus A16 may also play a role in some cases. [13]

A 2014 Morbidity and Mortality Weekly Report report noted the difficulty of establishing causation by the virus. [14] Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke and president of the International Society for NeuroVirology, compared the situation to the prolonged investigations that led to confirmation of HIV as the cause of AIDS. In response to the suggestion that the enterovirus might be taking over the role of polio, Nath said that EV-D68 was far less virulent and spread much more slowly than polio, and that unlike in polio, only a few cases of paralysis were seen per thousand children infected. He also suggested that adults with respiratory diseases should also be evaluated for neurological deficits, and that infectious disease should be considered as a cause when patients presented with neurological symptoms. [15]

A subsequent report described 29 cases of EV-D68-associated AFM in Europe in 2016, noting, "these probably represent only the tip of the iceberg". [16]

CDC sees 2018 as a record year, annual documented cases of AFM reached a record 238 nationwide. The relatively lower circulation in 2020 may reflect the use of COVID-19 pandemic infection mitigation measures. [17]


Because of the EV-D68 surge in 2022 Health Alert Network (HAN) released a notice for Healthcare providers and hospitals. The CDC warned clinicians that EV-D68 detections have continued to be high. "Sentinel surveillance sites are reporting a higher proportion of EV-D68 positivity in children who are [rhinovirus and/or enterovirus] positive compared to previous years," the agency wrote. Clinicians should be aware of "the potential for an increase in AFM cases in the upcoming weeks." CDC urges healthcare providers to consider EV-D68 as a possible cause of acute, severe respiratory illness and a potential increase in AFM cases.

Diagnosis

AFM is diagnosed by examining a person's nervous system in combination with reviewing images of the spinal cord. [18] A doctor can examine a person's nervous system and the places on the body where he or she has weakness, poor muscle tone, and decreased reflexes. In addition, a doctor can do magnetic resonance imaging to look at a person's brain and spinal cord, do laboratory tests on the cerebrospinal fluid (CSF, the fluid around the brain and spinal cord), and may check nerve conduction (impulse sent along a nerve fiber) and response. [19]

Diagnosis of AFM requires acute onset limb paralysis and at least one gray-matter spinal-cord lesion. CSF should show pleocytosis. [20]

Prevention

The CDC recommends, "To prevent infections in general, persons should stay home if they are ill, wash their hands often with soap and water, avoid close contact (such as touching and shaking hands) with those who are ill, and clean and disinfect frequently touched surfaces." [14]

Treatment

Treatment involves supportive care. [5] [3] Physical therapy may be recommended. [3] Occasionally mechanical ventilation is required to support breathing. [3] [7]

If immunoglobulin, corticosteroids, plasma exchange, or antiviral medication are useful is unclear. [5] [7]

Outcomes

Studies from 2014 to 2017 indicated a poor outcome for many cases. Seven of 61 cases with EVD68 detected and eight long-term follow-ups had full recovery; two deaths were described in severely immunocompromised people (one with EVD68 and one with both EVD68 and coxsackie A16 detected). [21]

Six of 10 children in Denver were sent home for outpatient treatment. Some of the children with mild and moderate cases have recovered partially from temporary limb weakness but still have permanent weakness, whereas those with more severe cases have not recovered as much. Intensive physical therapy and occupational therapy may be beneficial for recovery. [22] [23] [24]

Epidemiology

Graph showing the seasonal nature of the occurrence of AFM: Notable increases occurred in the late summers of 2014, 2016, and 2018. Paralysie flasque aigue acute flaccid myelitis US CDC graph 2018 en.png
Graph showing the seasonal nature of the occurrence of AFM: Notable increases occurred in the late summers of 2014, 2016, and 2018.

A seasonal pattern is seen in outbreaks, with a marked increase in cases reported in the late summer and early fall. [25]

The CDC has determined and submitted to GenBank complete or nearly complete genomic sequences for three known strains of the virus, which are "genetically related to strains of EV-D68 virus that were detected in previous years in the United States, Europe, and Asia." [26]

While rates of paralytic symptoms appear to be correlated with the number of respiratory infections, in initial anecdotal reports, the cases are not clustered within a family or school, suggesting that the paralysis per se is not directly contagious, but arises as a very rare complication of the common respiratory infection. [22]

Cases of similar illnesses have been reported in Canada, Northern Europe, and Japan. [20] Over 90% of reported cases are in children. [27]

History

AFM has only been formally tracked since 2014, since the incidence has spiked in recent years.[ citation needed ]

A group in Texas reported having observed a pattern in 2013 of one to four cases per year with similar polio-like characteristics. [22]

In 2014, the CDC Morbidity and Mortality Weekly Report [14] and a CDC Clinician Outreach and Communication Activity (COCA) conference call, [28] noted that many cases had neck, back, or extremity pain, but otherwise those affected generally had normal sensation in their limbs. [29] A few participants in the conference call discussed whether pain, later abating, might precede the onset of paralysis. [28] [30]

An October 2014 report described outbreaks in California and Colorado, suggesting that the number of cases might be 100 or more nationwide. [31] Diagnosis included a detailed medical history, MRI imaging, and the elimination of transverse myelitis or Guillain–Barré syndrome as potential causes. Physicians were using an online mailing list to communicate about similar cases in Alabama and Kansas. The largest known cluster of cases was in Colorado, with 29 total, 12 of whom had been reported from August and onwards of that year. [31]

Three of four cases treated in Alabama involved a complete inability to move one arm, reminiscent of peripheral nerve injury:

The three cases since August really look like each other. They have severe arm flaccidity and no mental status changes. All of them have similar spine MRIs showing gray-matter involvement. You could lay all three MRIs on top of each other and they look almost the same. It's pretty striking. ... It you lift the arm up, it literally drops. Sensation is usually intact. There might be slightly decreased sensation in the other arm, but these are younger kids, so they're not always so cooperative in giving you a good sensory exam. [31]

Children's Mercy Hospital, which had three or four cases in 2014, reported that the MRI images and symptoms closely mimicked polio. They reported: "The sudden onset of flaccid paralysis in single or multiple limbs with absolutely no sensory findings, the MRIs all showing uniformly a signal increase in the ventral horns of the spinal cord — this is exactly the same region of the spinal cord affected in polio ... Almost all of the patients have an increase in their white blood cells in the cerebrospinal fluid. Some of the patients have brainstem findings and cranial-nerve findings." [31]

Of 64 patients meeting the CDC criteria before October 29, 2014, 80% had had a preceding respiratory illness and 75% reported fever in the days leading up to limb weakness, the onset of which was generally abrupt. [32] By November 20, the number of confirmed cases stood at 88 from 29 states. [33]

The CDC requested that physicians provide information about cases meeting these criteria: patients diagnosed after August 1, 2014, who are no older than 21 years of age, showing acute onset of focal limb weakness, with a spinal-cord lesion largely restricted to grey matter visualized by MRI. [9] [31]

In November 2018, the CDC reported that they were investigating 286 cases, with at least 116 confirmed cases in 31 states. [34] The CDC is setting up a task force to investigate the causes and to find treatments. [35]

Related Research Articles

<span class="mw-page-title-main">Foix–Alajouanine syndrome</span> Medical condition

Foix–Alajouanine syndrome, also called subacute ascending necrotizing myelitis, is a disease caused by an arteriovenous malformation of the spinal cord. In particular, most cases involve dural arteriovenous malformations that present in the lower thoracic or lumbar spinal cord. The condition is named after Charles Foix and Théophile Alajouanine who first described the condition in 1926.

<span class="mw-page-title-main">Polio</span> Infectious disease caused by poliovirus

Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 75% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe symptoms develop such as headache, neck stiffness, and paresthesia. These symptoms usually pass within one or two weeks. A less common symptom is permanent paralysis, and possible death in extreme cases. Years after recovery, post-polio syndrome may occur, with a slow development of muscle weakness similar to what the person had during the initial infection.

<span class="mw-page-title-main">Transverse myelitis</span> Inflammation of the entire cross-section of the spinal cord

Transverse myelitis (TM) is a rare neurological condition wherein the spinal cord is inflamed. The adjective transverse implies that the spinal inflammation (myelitis) extends horizontally throughout the cross section of the spinal cord; the terms partial transverse myelitis and partial myelitis are sometimes used to specify inflammation that affects only part of the width of the spinal cord. TM is characterized by weakness and numbness of the limbs, deficits in sensation and motor skills, dysfunctional urethral and anal sphincter activities, and dysfunction of the autonomic nervous system that can lead to episodes of high blood pressure. Signs and symptoms vary according to the affected level of the spinal cord. The underlying cause of TM is unknown. The spinal cord inflammation seen in TM has been associated with various infections, immune system disorders, or damage to nerve fibers, by loss of myelin. As opposed to leukomyelitis which affects only the white matter, it affects the entire cross-section of the spinal cord. Decreased electrical conductivity in the nervous system can result.

<span class="mw-page-title-main">Hand, foot, and mouth disease</span> Common human disease caused by a group of viruses

Hand, foot, and mouth disease (HFMD) is a common infection caused by a group of enteroviruses. It typically begins with a fever and feeling generally unwell. This is followed a day or two later by flat discolored spots or bumps that may blister, on the hands, feet and mouth and occasionally buttocks and groin. Signs and symptoms normally appear 3–6 days after exposure to the virus. The rash generally resolves on its own in about a week. Fingernail and toenail loss may occur a few weeks later, but they will regrow with time.

<span class="mw-page-title-main">Tetraplegia</span> Paralysis of all four limbs and torso

Tetraplegia, also known as quadriplegia, is defined as the dysfunction or loss of motor and/or sensory function in the cervical area of the spinal cord. A loss of motor function can present as either weakness or paralysis leading to partial or total loss of function in the arms, legs, trunk, and pelvis. The paralysis may be flaccid or spastic. A loss of sensory function can present as an impairment or complete inability to sense light touch, pressure, heat, pinprick/pain, and proprioception. In these types of spinal cord injury, it is common to have a loss of both sensation and motor control.

Myelitis is inflammation of the spinal cord which can disrupt the normal responses from the brain to the rest of the body, and from the rest of the body to the brain. Inflammation in the spinal cord can cause the myelin and axon to be damaged resulting in symptoms such as paralysis and sensory loss. Myelitis is classified to several categories depending on the area or the cause of the lesion; however, any inflammatory attack on the spinal cord is often referred to as transverse myelitis.

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Hopkins syndrome is a neurological disorder. Its cause has not been established, but its association with asthma exacerbations has led to suspicion that the initial viral insult that causes the respiratory infection is also implicated in the subsequent paralysis. Herpes simplex virus type I DNA has been found in the cerebrospinal fluid of at least one patient diagnosed with Hopkins syndrome. In several cases, anti-viral antibody titers for echovirus, enterovirus, coxsackievirus and poliovirus types 1, 2 and 3 were specifically sought; all were negative., There is one reported case in which Mycoplasma pneumoniae infection was found in the patient.

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Vascular myelopathy refers to an abnormality of the spinal cord in regard to its blood supply. The blood supply is complicated and supplied by two major vessel groups: the posterior spinal arteries and the anterior spinal arteries—of which the Artery of Adamkiewicz is the largest. Both the posterior and anterior spinal arteries run the entire length of the spinal cord and receive anastomotic (conjoined) vessels in many places. The anterior spinal artery has a less efficient supply of blood and is therefore more susceptible to vascular disease. Whilst atherosclerosis of spinal arteries is rare, necrosis in the anterior artery can be caused by disease in vessels originating from the segmental arteries such as atheroma or aortic dissection.

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Polio-like syndrome is a general description of a group of symptoms which mimic polio, including rarely permanent paralysis. Various triggers have been found, including some viruses from the same virus group as polio: enterovirus 68, enterovirus 71, and coxsackievirus A7. These are suspected in many cases of acute flaccid myelitis. Other non-virus causes of polio-like symptoms are observed, though rarely, from snake bite, spider bite, scorpion sting, tick bite, or chemicals such as arsenic and organophosphorus insecticides.

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References

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  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 "About Acute Flaccid Myelitis". Centers for Disease Control and Prevention (CDC). Archived from the original on 2018-10-11. Retrieved 2018-10-11.PD-icon.svg This article incorporates text from this source, which is in the public domain .
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  19. ↑ "About Acute Flaccid Myelitis". Centers for Disease Control and Prevention (CDC). Archived from the original on 10 October 2018. Retrieved 10 October 2018.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  20. 1 2 "UpToDate". www.uptodate.com. Archived from the original on 1 November 2018. Retrieved 31 October 2018.
  21. ↑ Suresh S, Forgie S, Robinson J (January 2018). "Non-polio Enterovirus detection with acute flaccid paralysis: A systematic review". J Med Virol. 90 (1): 3–7. doi:10.1002/jmv.24933. PMID   28857219. S2CID   33163720.
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  23. ↑ Enterovirus D68 and Paralysis (2014-10-03). "Enterovirus D68 and Paralysis". The Disease Daily/Outbreak News/Healthmap. Archived from the original on 2014-10-25. Retrieved 2014-10-25.{{cite web}}: CS1 maint: numeric names: authors list (link)
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  25. ↑ "AFM Cases in the US". Centers for Disease Control and Prevention (CDC) Centers for Disease Control and Prevention (CDC). 1 March 2019. Archived from the original on 29 March 2019. Retrieved 29 March 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  26. ↑ "CDC continues investigation of neurologic illness; will issue guidelines". AAP News: E141003-1. 2014-10-03. doi:10.1542/aapnews.20141003-1 (inactive 2024-09-19). Archived from the original on 2014-10-26. Retrieved 2014-10-26.{{cite journal}}: CS1 maint: DOI inactive as of September 2024 (link)
  27. ↑ "Acute Flaccid Myelitis". Centers for Disease Control and Prevention (CDC). 1 March 2019. Archived from the original on 29 March 2019. Retrieved 29 March 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  28. 1 2 "Neurologic Illness with Limb Weakness in Children". Centers for Disease Control and Prevention (CDC). 2014-10-03. Archived from the original on 2014-10-25. Retrieved 2014-10-25.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  29. ↑ "Neurologic Deficits in Children Preceded by Febrile Illness". American Academy of Family Physicians. 2014-10-13. Archived from the original on 2014-10-25. Retrieved 2014-10-25.
  30. ↑ Robert Roos (2014-10-03). "Role of EV-D68 in polio-like illnesses still unclear". Center for Infectious Disease Research and Policy. Archived from the original on 2014-10-25. Retrieved 2014-10-25.
  31. 1 2 3 4 5 Dan Hurley (2014-10-21). "Cases of acute flaccid myelitis in children suspected in multiple states, prompting comparisons to polio". Neurology News. Archived from the original on 2014-10-24. Retrieved 2014-10-24.
  32. ↑ "CDC releases guidance on acute flaccid myelitis". AAP News. AAP News (American Academy of Pediatrics): E141112-1. 2014-11-12. doi:10.1542/aapnews.20141112-1 (inactive 2024-09-19).{{cite journal}}: CS1 maint: DOI inactive as of September 2024 (link)
  33. ↑ "Investigation of Acute Neurologic Illness with Focal Limb Weakness of Unknown Etiology in Children, Fall 2014". Centers for Disease Control and Prevention (CDC). Archived from the original on 2014-11-18. Retrieved 2014-11-21.PD-icon.svg This article incorporates text from this source, which is in the public domain . Note: despite the URL, this Web document is regularly updated, including the text: "As of November 20, CDC has verified reports of 88 cases in 32 states. We are working with healthcare professionals and state and local officials to investigate all of these cases. We are also in the process of verifying less than half a dozen additional reports."
  34. ↑ Fox M (November 26, 2018). "More cases of this paralyzing condition have been reported to CDC". NBC News. Archived from the original on November 27, 2018. Retrieved 2018-11-27.
  35. ↑ "CDC confirms 116 cases of rare polio-like illness, acute flaccid myelitis". www.msn.com. Archived from the original on 2018-11-27. Retrieved 2018-11-27.
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