Brain problems from swine flu

The Center for Disease Control in the US has published the first report on brain complications from swine flu in children, based on case studies from Texas. Although these complications have been previously described in association with infections from seasonal flu, they have not yet been described in relation to the influenza A (H1N1) virus, swine flu.

This case series of four Dallas patients aged 7-17 years gives details of the symptoms and testing of the individuals who had neurological complications such as brain inflammation and seizures. All four patients were treated with antiviral therapies and recovered fully without any long-term brain damage.

The information shared through such reports is valuable for clinicians across the globe, helping build a profile of the behaviour of this new disease.

Key points

• The neurological complications known to occur with seasonal flu include seizures, encephalitis (inflammation of the brain), Reye’s syndrome (a rare syndrome also associated with aspirin use) and other neurologic disorders. These types of complications are uncommon.
• These complications have been previously described in association with seasonal influenza A and B viruses.
• These case reports are from four children and adolescents aged 7-17 years who were admitted to hospitals in Dallas County, Texas during 18-28 May 2009, with signs of influenza-like illness and seizures or altered mental status.
• Some of the children experienced drowsiness, weakness and disorientation and were slow to respond to questions. Two of the four had seizures.
• Three of the four patients had abnormal readings seen in electroencephalograms (EEGs). In all four patients, the presence of the novel influenza A (H1N1) virus was detected in the upper airways (nose and pharynx) but not in the fluid that surrounds the brain and spinal cord (cerebrospinal fluid, CSF). Antiviral therapy included oseltamivir (all four patients) and also rimantadine (in three patients).
• All four patients recovered fully and had no brain damage at discharge.

Where was the article published?

This research was published in the Morbidity and Mortality Weekly report of the Centers for Disease Control and Protection in the US (CDC). The authors of the reports are not identified, but the contributions of the clinicians involved at the medical centres reporting the cases in Dallas are acknowledged.

What kind of study was this?

This case series resulted from a request made by the Dallas County Department of Health and Human Services (DCHHS), asking hospitals to report details concerning patients admitted with influenza A (H1N1) virus infection (swine flu). This reporting period began 22 April 2009 and ended on July 20 2009. During this time, there were 405 cases of laboratory-confirmed swine flu and 44 patients were hospitalised. There were no deaths.

The study describes the characteristics of four of the 145 children with laboratory-confirmed swine flu seen at the Children's Medical Center of Dallas. Of the children seen, 26 were hospitalised due to swine flu. Three additional children with neurological symptoms were not covered as case reports because the cause of their problem was considered to be something other than swine flu.

The researchers were interested in recording those children who had neurological complications associated with H1N1 virus. They defined the complications as seizures or encephalopathy (altered mental status lasting 24 hours or more). They also recorded children with encephalitis, which was defined as altered mental state associated with two or more of the following: fever over 38.0°C, signs that specific areas of the brain were affected, abnormalities in the fluid surrounding the brain (CSF pleocytosis) or abnormal brain activity seen through either a scan (EEG) or imaging (MRI scan) .

The symptoms the researchers looked for to confirm altered mental state were tiredness, drowsiness or confusion. The children were also tested for swine flu using nose swab samples subjected to a range of rapid tests plus using CDC-approved testing kits for viral genetic material (RNA). They also tested cerebrospinal fluid samples.

What does the research say?

The researchers say that influenza infections account for about 5% of cases of acute childhood encephalitis, a severe infection and inflammation of the brain that can cause brain damage and death in some cases. Neurological complications were reported in 6% of flu-related deaths among children during the 2003-2004 flu season in the US.

The authors say that during most flu outbreaks children of varying ages are most at risk of being infected but that the current pandemic H1N1 virus appears to strike young adults and healthy older children.

The cases are described in some detail in the full report. In summary, all four were male and had fevers over 100 °F (from 38.2 to 40 °C ). One experienced just seizures, two had just encephalopathy and both encephalopathy and seizures. The symptoms came on soon after the first signs of a respiratory illness (under four days) and all children were discharged within six days.

The researchers were careful to exclude other causes for encephalopathy. Three patients received treatment with the two antiviral drugs oseltamivir and rimantadine, while one other patient received oseltamivir (Tamiflu) alone.

What is the implication and importance of this?

The researchers say their findings show that neurologic complications can occur after respiratory tract infection with the novel influenza A (H1N1) virus. They recommend that for children who have influenza-like illnesses accompanied by unexplained seizures or mental status changes, clinicians should consider acute influenza infection in their differential diagnosis and send respiratory specimens for appropriate diagnostic testing.

They say that while awaiting the results of these tests consideration should be given to this ‘empirical’ use of antiviral treatment (starting treatment based on a suspected cause), particularly in hospitalised patients.

What does the NHS Knowledge Service make of this research?

The researchers have concluded that "these findings indicate that, as with seasonal influenza, neurologic complications can occur after respiratory tract infection with novel influenza A (H1N1) virus".

It is important to note that this was a selected group of children and the overall rate for this complication may not be representative of what could be at present in the US or even in the UK. However, the rate of this complication seems high. Four children developing these neurological complications among 26 hospitalised over about 12 weeks suggests that the rate of these complications may be as high as 3% in children with swine flu, and 15% in those hospitalised.

The short length of stay and quick response to treatment without long-term effects is reassuring. Compiling similar reports and monitoring this sort of data in the UK will allow more accurate estimates of the neurological complication rates in children who catch this virus.