Until AFM is confirmed, often similar neurologic conditions are termed acute flaccid paralysis which can have multiple causations.
As of October 2018, the CDC regarded the cause of AFM or similar neurologic conditions (Table 1 below) as having "a variety of possible causes” such as:2
TABLE 1 Probable Causes of AFM are in bold text. Other causes of acute flaccid paralysis are in standard text.
|Herpes zoster: r/o*|
- EV-D68 (also known as EV68, EVD68, EV-D68, HEV68)
- EV-A71 (also known as EV71, EVA71)
|West Nile virus (WNV) and other family members:|
- Japanese encephalitis virus
- Saint Louis encephalitis virus
| SPINAL CORD DISORDERS |
|Acute disseminated encephalomyelitis: r/o|
|Transverse myelitis: r/o|
|Cord infarction: r/o|
|Cord compression: r/o|
| PERIPHERAL NEUROPATHY |
|Guillain-Barré syndrome: r/o|
|Mononeuritis multiplex: r/o|
|Acute intermittent porphyria: r/o|
| DISORDERS OF NEUROMUSCULAR TRANSMISSION |
|Myasthenia gravis: r/o|
|Tick paralysis: r/o|
| DISORDERS OF MUSCLE |
|Inflammatory myopathy: r/o|
*Rule out (r/o)
Much research has focused on the non-polio enteroviruses 68 and 71, members of the enterovirus D and enterovirus A species respectively, as suspected causes. As of 2018, the exact cause of AFM is not widely agreed upon.26,29-31
Since 2014, most patients with AFM (more than 90%) had a mild respiratory illness or fever consistent with a viral infection before AFM developed. All the stool specimens received from AFM patients tested negative for poliovirus. Most patients had the onset of AFM between August and October, with increases in AFM cases every two years since 2014. At this same time of year, many viruses commonly circulate, including enteroviruses, and will be temporally associated with AFM.
A 2014 MMWR report noted the difficulty of establishing causation by the virus.19 Avindra Nath, clinical director of the National Institute of Neurological Disorders and Stroke and president of the International Society for NeuroVirology, compared the situation to the prolonged investigations that led to the confirmation of HIV as the cause of AIDS. In response to the suggestion that the enterovirus might be taking over the role of polio, Nath said that enterovirus 68 was far less virulent and spread much more slowly than polio, and that, unlike in polio, only a few cases of paralysis were seen per thousand children infected. He also suggested that adults with respiratory diseases should also be evaluated for neurologic deficits and that infectious disease should be considered as a cause when patients presented with neurologic symptoms.32
A subsequent report described 29 cases of enterovirus D68-associated AFM in Europe in 2016, noting that "these probably represent only the tip of the iceberg."14
As of 2018, the cause of most cases of AFM remains unclear.33 More than 90% of recent cases have followed a mild viral infection such as from enteroviruses.33 While polio can cause AFM, since 2014, it has not been involved in cases in the United States.2,34 The underlying mechanism involves damage to the spinal cord’s grey matter.2 Diagnosis may be supported by medical imaging of the spine, nerve conduction studies, and cerebral spinal fluid testing.2,3
Coxsackievirus A16, EV-A71, and EV-D68 were detected in the spinal fluid of four of 537 confirmed cases of AFM since 2014, which points to the cause of their AFM. For all other patients, no pathogen has been detected in their spinal fluid to confirm a cause. When a pathogen is found in the spinal fluid, it is good evidence that it was the cause of a patient’s illness.
Oftentimes, however, despite extensive testing of AFM patients, no pathogens are found in the spinal fluid. Three reasons for this may be that:
- The pathogen has been cleared by the body.
- The pathogen is hiding in tissues that make it difficult to detect.
- The pathogen triggers an immune response in the body that causes damage to the spinal cord. What triggers AFM in some children who have had a fever and/or respiratory illness compared to most children who do not get AFM is currently being investigated.