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The H1N1 influenza pandemic that struck during 2009 was characterized by severe neurologic complications in a small group of hospitalized children, a retrospective study found.
Among 303 children admitted to the hospital for influenza between April and November of that year, 18 had neurologic complications, according to Jeffrey J. Ekstrand, MD, PhD, of the University of Utah in Salt Lake City, and colleagues.
The most common manifestations were seizures, which were seen in 12 patients (67%
, with seven of the children presenting in status epilepticus, the researchers reported online in Annals of Neurology.
Neurologic complications are known to occur in children with seasonal influenza, and although small case series have suggested that similar complications also occurred during the H1N1 pandemic, it has not been determined if the incidence and severity differed from what is seen with seasonal influenza.
To investigate this, Ekstrand and colleagues compared the records of children admitted to the neurology service during the H1N1 pandemic with the records of the 234 children hospitalized with seasonal influenza between 2004 and 2008, 16 of whom had neurologic manifestations.
Median length of hospitalization for patients in both groups was two days, but ten of the H1N1 children were admitted to the intensive care unit, and five required mechanical ventilation.
Fewer children in the seasonal influenza group required intensive care admission and mechanical ventilation (four and three, respectively), but this was not a statistically significant difference.
Children in the H1N1 group were older, with a mean age of 6.5 years, compared with a mean age of 2.4 years in the seasonal group.
More children in the H1N1 group had underlying medical conditions (83% versus 25%), and the underlying condition was neurologic in two-thirds of the H1N1 group.
Compared with the children who had none of these complications, those in the H1N1 cohort had the following manifestations:
* Encephalopathy in 50% (P=0.0011)
* Aphasia in 33% (P=0.020)
* Focal neurologic findings in 28% (P=0.047)
In addition, electroencephalogram abnormalities were detected in 44% of the H1N1 patients compared with 6% of the seasonal cohort (P=0.020).
These abnormalities included spike-and-wave discharges and diffuse slowing.
Among the seven H1N1 patients who had MRI studies of the brain, abnormalities such as multifocal subcortical white matter attenuation were seen in three.
No brain abnormalities were found on MRI among the seasonal cohort.
Ten of the H1N1 patients were given new or additional antiepileptic medications, and because of persistent encephalopathy one child was given intravenous steroids and another received intravenous immunoglobulin, without benefit.
In addition, 15 of the H1N1 patients were treated with oseltamivir (Tamiflu), while none of the seasonal influenza patients received antiviral treatment.
One child with H1N1 influenza and neurologic complications died of respiratory and cardiac arrest. None of the children in the seasonal cohort died.
The H1N1 pandemic began in April and new infections decreased during the summer, but a second wave struck in the fall.
This second wave was associated with a trend toward more severe neurologic complications. For instance, encephalopathy had been present in 22% of affected children during the first wave, but was seen in 78% of those in the second wave (P=0.057).
Focal neurologic findings were present in 11% in the first wave and in 44% of those in the second wave (P=0.29).
The reasons for neurologic complications in influenza are unclear, but some authors have suggested that these developments may result from an autoimmune response.
Ekstrand and colleagues noted that their finding of an absence of pleocytosis supported this autoimmune hypothesis.
They also highlighted the lack of response of two of the children with encephalopathy to treatment with steroids and immunoglobulin.
"The absence of proven treatments for influenza-related neurological complications underlines the importance of vaccination, although neurological complications can result from vaccination as well," they cautioned.
The study was limited by its small sample size and potential ascertainment bias relating to the use of direct fluorescent antibody staining for diagnosis.
Among 303 children admitted to the hospital for influenza between April and November of that year, 18 had neurologic complications, according to Jeffrey J. Ekstrand, MD, PhD, of the University of Utah in Salt Lake City, and colleagues.
The most common manifestations were seizures, which were seen in 12 patients (67%
, with seven of the children presenting in status epilepticus, the researchers reported online in Annals of Neurology.Neurologic complications are known to occur in children with seasonal influenza, and although small case series have suggested that similar complications also occurred during the H1N1 pandemic, it has not been determined if the incidence and severity differed from what is seen with seasonal influenza.
To investigate this, Ekstrand and colleagues compared the records of children admitted to the neurology service during the H1N1 pandemic with the records of the 234 children hospitalized with seasonal influenza between 2004 and 2008, 16 of whom had neurologic manifestations.
Median length of hospitalization for patients in both groups was two days, but ten of the H1N1 children were admitted to the intensive care unit, and five required mechanical ventilation.
Fewer children in the seasonal influenza group required intensive care admission and mechanical ventilation (four and three, respectively), but this was not a statistically significant difference.
Children in the H1N1 group were older, with a mean age of 6.5 years, compared with a mean age of 2.4 years in the seasonal group.
More children in the H1N1 group had underlying medical conditions (83% versus 25%), and the underlying condition was neurologic in two-thirds of the H1N1 group.
Compared with the children who had none of these complications, those in the H1N1 cohort had the following manifestations:
* Encephalopathy in 50% (P=0.0011)
* Aphasia in 33% (P=0.020)
* Focal neurologic findings in 28% (P=0.047)
In addition, electroencephalogram abnormalities were detected in 44% of the H1N1 patients compared with 6% of the seasonal cohort (P=0.020).
These abnormalities included spike-and-wave discharges and diffuse slowing.
Among the seven H1N1 patients who had MRI studies of the brain, abnormalities such as multifocal subcortical white matter attenuation were seen in three.
No brain abnormalities were found on MRI among the seasonal cohort.
Ten of the H1N1 patients were given new or additional antiepileptic medications, and because of persistent encephalopathy one child was given intravenous steroids and another received intravenous immunoglobulin, without benefit.
In addition, 15 of the H1N1 patients were treated with oseltamivir (Tamiflu), while none of the seasonal influenza patients received antiviral treatment.
One child with H1N1 influenza and neurologic complications died of respiratory and cardiac arrest. None of the children in the seasonal cohort died.
The H1N1 pandemic began in April and new infections decreased during the summer, but a second wave struck in the fall.
This second wave was associated with a trend toward more severe neurologic complications. For instance, encephalopathy had been present in 22% of affected children during the first wave, but was seen in 78% of those in the second wave (P=0.057).
Focal neurologic findings were present in 11% in the first wave and in 44% of those in the second wave (P=0.29).
The reasons for neurologic complications in influenza are unclear, but some authors have suggested that these developments may result from an autoimmune response.
Ekstrand and colleagues noted that their finding of an absence of pleocytosis supported this autoimmune hypothesis.
They also highlighted the lack of response of two of the children with encephalopathy to treatment with steroids and immunoglobulin.
"The absence of proven treatments for influenza-related neurological complications underlines the importance of vaccination, although neurological complications can result from vaccination as well," they cautioned.
The study was limited by its small sample size and potential ascertainment bias relating to the use of direct fluorescent antibody staining for diagnosis.
This study is published in Annals of Neurology. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.
Full citation: "Heightened Neurologic Complications in Children with Pandemic H1N1 Influenza." Jeffrey J. Ekstrand, Amy Herbener, Julia Rawlings, Beth Turney, Krow Ampofo, E. Kent Korgenski, Joshua L. Bonkowsky. Annals of Neurology; Published Online: September 20, 2010 (DOI:10.1002/ana.22184).
Full citation: "Heightened Neurologic Complications in Children with Pandemic H1N1 Influenza." Jeffrey J. Ekstrand, Amy Herbener, Julia Rawlings, Beth Turney, Krow Ampofo, E. Kent Korgenski, Joshua L. Bonkowsky. Annals of Neurology; Published Online: September 20, 2010 (DOI:10.1002/ana.22184).
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