However, current practice at Children’s Hospital of Philadelphia is to initiate IVIG therapy at AFM diagnosis in hopes of boosting humoral immunity.
Nevertheless, the CDC said, “For IVIG to modify disease in an active viral infectious process, early administration is likely required, and possibly prior to exposure,” and the treatment cannot be recommended.
Plasma exchange
Plasma exchange in combination with IVIG and corticosteroids was ineffective in a case series of four Argentinian children, although a single case published last year found that the combination was associated with significant improvement. However, there are not enough data to recommend this approach.
Fluoxetine
Fluoxetine’s antiviral potential turned up in a high-throughput screening project to identify novel compounds with antiviral efficacy against enteroviruses. In 2012, researchers from the University of California, Los Angeles, tested more than 1,000 compounds and found that the SSRI is a potent inhibitor of coxsackievirus. A later project at the National Institutes of Health replicated this finding, and determined that fluoxetine inhibited several enteroviruses, including the AFM suspect, EV-D68.
Fluoxetine concentrates more highly in the central nervous system than it does in plasma, but its antiviral properties have nothing to do with neurotransmitter activity. Rather, it appears to inhibit protein 2C, a highly conserved nonstructural protein that’s crucial to the assembly of RNA into virion particles.
In early November, a retrospective study examined fluoxetine’s use in 30 AFM patients, compared with 26 who did not receive it. The primary outcome was change in summative limb strength score. The study did little to clarify any benefit, however. The authors concluded that fluoxetine was preferentially given to patients with EDV-68 infections. They had more severe impairment at nadir, and at the last follow-up of about 1 year, they had worse outcomes.
“There is no clear human evidence for efficacy of fluoxetine in the treatment of AFM based on a single retrospective evaluation conducted in patients with AFM, and data from a mouse model also did not support efficacy,” the CDC said.
Antiviral medications
The CDC is quite clear on its recommendation that these drugs are not indicated in AFM, since it is not yet proven to be an infectious process.
“Any guidance regarding antiviral medications should be interpreted with great caution, given the unknowns about the pathogenesis of this illness at present ... Testing has been conducted at CDC for antiviral activity of compounds pleconaril, pocapavir, and vapendavir and none have significant activity against currently circulating strains of EV-D68 at clinically relevant concentrations.”
Interferon
There is some anecdotal evidence that interferon alpha-2b was beneficial in treating a polio-like syndrome associated with West Nile virus and Saint Louis encephalitis. “Although there are limited in vitro, animal, and anecdotal human data suggesting activity of some interferons against viral infections, sufficient data are lacking in the setting of AFM,” the agency said. “There is no indication that interferon should be used for the treatment of AFM, and there is concern about the potential for harm from the use of interferon given the immunomodulatory effects in the setting of possible ongoing viral replication.”
SOURCE: CDC Acute Flaccid Myelitis: Interim Considerations for Clinical Management