User login
The updated guidance on managing acute flaccid myelitis is unlikely to relieve the frustrations of physicians struggling to treat the condition.
After reviewing the extant data on the baffling disorder, the Centers for Disease Control and Prevention found no evidence that corticosteroids, interferon, antivirals, or any other immunologic or biologic therapy is an effective treatment.
All of the treatments mentioned in the guidance have been used anecdotally, and often for cases proven to be associated with enterovirus-related cases. However, there are no well validated studies confirming benefit for any of these approaches, the agency said in its clinical management document.
Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the CDC. The number of confirmed cases is triple that seen in 2017. Whether the disease is an infectious or autoimmune process, or something else entirely, remains unknown.
In response to the outbreak – the largest since 2014 – an expert panel of 4 CDC staff physicians reviewed the literature to find what, if any, treatments were effective; another 14 external experts provided input on the recommendations. At this point, nothing can be officially recommended, the agency said.
Corticosteroids
Corticosteroids should not be administered to most patients with AFM. In addition to “a theoretical concern” about the potential adverse effects of these drugs in acute infections, there is some hard evidence that they are associated with worse outcomes in enteroviral neuroinvasive diseases, particularly those caused by EV-71.
This observation, following a 2012 outbreak in Cambodia, led a World Health Organization commission to conclude that corticosteroids were contraindicated in the management of EV-71–associated neuroinvasive disease. This year, there has been an uptick in EV-A71-associated neurologic disease.
The CDC did hedge its advice on corticosteroids a bit in the setting of AFM, however. “There may be theoretical benefit for steroids in the setting of severe cord swelling or long tract signs suggesting white matter involvement, where steroids may salvage tissue that may be harmed due to an ongoing immune/inflammatory response. While AFM is clinically and radiographically defined by the predominance of gray matter damage in the spinal cord, some patients may have some white matter involvement. It is not clear if these different patterns are important relative to therapeutic considerations.”
Nevertheless, the agency does not recommend corticosteroid use for these patients. “The possible benefits of the use of corticosteroids to manage spinal cord edema or white matter involvement in AFM should be balanced with the possible harm due to immunosuppression in the setting of possible viral infection.”
IVIG
While IVIG holds some theoretical benefit for AFM, there are no high-level human data, the guidelines state. The treatment is generally safe and well tolerated, but the few reports of its use in AFM did not show clear benefit. These include two case series. One suggested an acute improvement of neurologic status, but no long-term resolution of deficits. The other indicated neither significant improvement nor deterioration.
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
The updated guidance on managing acute flaccid myelitis is unlikely to relieve the frustrations of physicians struggling to treat the condition.
After reviewing the extant data on the baffling disorder, the Centers for Disease Control and Prevention found no evidence that corticosteroids, interferon, antivirals, or any other immunologic or biologic therapy is an effective treatment.
All of the treatments mentioned in the guidance have been used anecdotally, and often for cases proven to be associated with enterovirus-related cases. However, there are no well validated studies confirming benefit for any of these approaches, the agency said in its clinical management document.
Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the CDC. The number of confirmed cases is triple that seen in 2017. Whether the disease is an infectious or autoimmune process, or something else entirely, remains unknown.
In response to the outbreak – the largest since 2014 – an expert panel of 4 CDC staff physicians reviewed the literature to find what, if any, treatments were effective; another 14 external experts provided input on the recommendations. At this point, nothing can be officially recommended, the agency said.
Corticosteroids
Corticosteroids should not be administered to most patients with AFM. In addition to “a theoretical concern” about the potential adverse effects of these drugs in acute infections, there is some hard evidence that they are associated with worse outcomes in enteroviral neuroinvasive diseases, particularly those caused by EV-71.
This observation, following a 2012 outbreak in Cambodia, led a World Health Organization commission to conclude that corticosteroids were contraindicated in the management of EV-71–associated neuroinvasive disease. This year, there has been an uptick in EV-A71-associated neurologic disease.
The CDC did hedge its advice on corticosteroids a bit in the setting of AFM, however. “There may be theoretical benefit for steroids in the setting of severe cord swelling or long tract signs suggesting white matter involvement, where steroids may salvage tissue that may be harmed due to an ongoing immune/inflammatory response. While AFM is clinically and radiographically defined by the predominance of gray matter damage in the spinal cord, some patients may have some white matter involvement. It is not clear if these different patterns are important relative to therapeutic considerations.”
Nevertheless, the agency does not recommend corticosteroid use for these patients. “The possible benefits of the use of corticosteroids to manage spinal cord edema or white matter involvement in AFM should be balanced with the possible harm due to immunosuppression in the setting of possible viral infection.”
IVIG
While IVIG holds some theoretical benefit for AFM, there are no high-level human data, the guidelines state. The treatment is generally safe and well tolerated, but the few reports of its use in AFM did not show clear benefit. These include two case series. One suggested an acute improvement of neurologic status, but no long-term resolution of deficits. The other indicated neither significant improvement nor deterioration.
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
The updated guidance on managing acute flaccid myelitis is unlikely to relieve the frustrations of physicians struggling to treat the condition.
After reviewing the extant data on the baffling disorder, the Centers for Disease Control and Prevention found no evidence that corticosteroids, interferon, antivirals, or any other immunologic or biologic therapy is an effective treatment.
All of the treatments mentioned in the guidance have been used anecdotally, and often for cases proven to be associated with enterovirus-related cases. However, there are no well validated studies confirming benefit for any of these approaches, the agency said in its clinical management document.
Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the CDC. The number of confirmed cases is triple that seen in 2017. Whether the disease is an infectious or autoimmune process, or something else entirely, remains unknown.
In response to the outbreak – the largest since 2014 – an expert panel of 4 CDC staff physicians reviewed the literature to find what, if any, treatments were effective; another 14 external experts provided input on the recommendations. At this point, nothing can be officially recommended, the agency said.
Corticosteroids
Corticosteroids should not be administered to most patients with AFM. In addition to “a theoretical concern” about the potential adverse effects of these drugs in acute infections, there is some hard evidence that they are associated with worse outcomes in enteroviral neuroinvasive diseases, particularly those caused by EV-71.
This observation, following a 2012 outbreak in Cambodia, led a World Health Organization commission to conclude that corticosteroids were contraindicated in the management of EV-71–associated neuroinvasive disease. This year, there has been an uptick in EV-A71-associated neurologic disease.
The CDC did hedge its advice on corticosteroids a bit in the setting of AFM, however. “There may be theoretical benefit for steroids in the setting of severe cord swelling or long tract signs suggesting white matter involvement, where steroids may salvage tissue that may be harmed due to an ongoing immune/inflammatory response. While AFM is clinically and radiographically defined by the predominance of gray matter damage in the spinal cord, some patients may have some white matter involvement. It is not clear if these different patterns are important relative to therapeutic considerations.”
Nevertheless, the agency does not recommend corticosteroid use for these patients. “The possible benefits of the use of corticosteroids to manage spinal cord edema or white matter involvement in AFM should be balanced with the possible harm due to immunosuppression in the setting of possible viral infection.”
IVIG
While IVIG holds some theoretical benefit for AFM, there are no high-level human data, the guidelines state. The treatment is generally safe and well tolerated, but the few reports of its use in AFM did not show clear benefit. These include two case series. One suggested an acute improvement of neurologic status, but no long-term resolution of deficits. The other indicated neither significant improvement nor deterioration.
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