Influenza on the brain

A study of children infected by H1N1 influenza, also known as swine flu, and highlighted by the US Center for Disease Control (CDC), used MRI and other scanning techniques to determine what brain complications may have occurred during the progression of the disease.

On the basis of the results, the CDC is now recommending that US parents should they observe unexplained seizures and flu-like symptoms in their children should have them tested for infection with the H1N1 swine flu virus and be treated with antiviral drugs as early as possible.

The warning came after a team at the University of Texas Southwestern Medical Center pointed out that seasonal influenza can cause such symptoms as seizures, encephalitis, encephalopathy, Reye syndrome, and other neurologic disorders, but little is known about this new type of flu and its effects on neurology. In the CDC's Morbidity and Mortality Weekly Report (MMWR), it said that little was known about whether or not H1N1 would have any effect on the brain until four children aged 7 to 17 years were admitted to hospital in Dallas County with swine flu and had presented with seizures or changes in mental status, characterised by confusion and other problems.

The MMWR reports that details of the four children's cases was presented by the Dallas County Department of Health and Human Services suggesting they each had neurological complications associated with novel influenza A (H1N1) virus. However, viral RNA was detected in nasopharyngeal specimens but not in their cerebrospinal fluid.

The CDC points out that this is the first detailed report of H1N1 patients with neurological complications. Fortunately, the severity of symptoms was less than that observed in seasonal flu patients where severe static encephalopathy and death have been reported previously.

In the present pandemic, The Dallas County reporting period began 22 April 2009 and ended on July 20 2009, during which there were 405 cases of laboratory-confirmed H1N1 infection, with 44 patients were hospitalised and no deaths. Children with indicators of an altered mental state - tiredness, drowsiness or confusion - caused by the virus were considered for brain scanning. Neurological problems were present in other patients but these were discounted as being due to other underlying causes and simply coincidental with the presence of an H1N1 infection.

"Only two of the four patients described in this report had seizures," the MMWR reports, "and none died or had neurologic sequelae at discharge." Sequelae are pathological conditions resulting from a disease that remain with the patient after the disease has been otherwise successfully treated.

Indeed, all the children were given antiviral therapy, including oseltamivir (Tamiflu) (four patients) and rimantadine (three patients) and all recovered fully with no neurological problems on discharge from hospital as assessed by MRI, CT, and EEG.

Clusters of influenza-associated encephalopathy in children are common during widespread outbreaks of seasonal influenza, the CDC says. Neurological complications were seen in more than one in twenty cases (6%) of seasonal flu deaths among children during the 2003-2004 US influenza season. Given that children are currently being infected more frequently than adults with H1N1 virus, it is likely that additional neurological complications in children will emerge as the swine flu pandemic continues.

In a follow-up report by the UK's National Health Service in its online patient site Choices, it is noted that this was a selected group of children. The overall rate for neurological complications may not be representative of what could be present in the US or elsewhere. Nevertheless, the site says, the rate of complications seems high given that four children developed such symptoms among 26 hospitalised cases over a period of just three months. This, "suggests that the rate of these complications may be as high as 3% in children with swine flu, and 15% in those hospitalised," NHS Choices says.

The NHS site adds that the, "short length of stay and quick response to treatment without long-term effects is reassuring." It will be important to compile similar reports and monitor neurological problems associated with flu-like symptoms in children as the pandemic progresses. Brain scanning technology will be important in assessing such cases in this and other outbreaks of novel influenza viruses. 

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.