Febrile Seizures Linked to Alkalosis

Pauline Anderson

September 22, 2011

September 22, 2011 — A new study has shed more light on the link between febrile seizures and fever-induced respiratory alkalosis.

The study shows that children with febrile seizures have a relatively high pH level, possibly because they hyperventilate and lose carbon dioxide (CO2), whereas children with gastroenteritis have acidosis and no seizures at similar levels of fever.

Coupled with earlier animal research, these results support the hypothesis that alkalosis could be a trigger that sets off febrile seizures in susceptible children, and that acidosis related to an infection might suppress seizures, said lead author Sebastian Schuchmann, MD, PhD, consultant in internal medicine at the Neuroscience Research Center, Charite-University Medicine, Berlin, Germany.

In the future, children who are prone to febrile seizures could simply breathe in a mixture of oxygen and 5% CO2 (standard carbogen) to enhance the seizure-inhibiting activity of acidosis, said Dr. Schuchmann. Research shows that a carbogen delivery system suppresses seizure activity in less than 2 minutes in adults, and because immature brains are relatively sensitive to pH changes, the therapy might be even more effective in young children.

The current study was published online September 12 in Epilepsia.

"Striking" Finding

Febrile seizures are generalized tonic-clonic seizures with a peak incidence at 16 to 18 months of age and a cumulative incidence of between 2% and 8%. These seizures likely result from a combination of genetic and environmental factors, the researchers note.

In this study, they looked at acidotic children, with patients with gastroenteritis matched for age and fever level, to look at the relationship between systemic pH changes and febrile seizures.

Specifically, the authors write, they examined whether age-matched children with identical levels of fever on admission to hospital for febrile seizures or gastroenteritis show differences in pH, PCO2 (partial pressure of carbon dioxide), and standard base excess, as measured from capillary blood. "Our data point to a tight association between fever-induced respiratory alkalosis and induction of [febrile seizures], not only at the level of overall statistics, but also at the level of individual patients with a clinical history of [febrile seizures]," the authors write.

The study included 433 children aged 6 months to 60 months with fever (>37.8°C) taken to a children's hospital in Berlin with either a simple or complex febrile seizure (n = 213) or gastroenteritis accompanied by diarrhea and/or vomiting and signs of dehydration (n = 220).

Simple febrile seizure was defined as a primary generalized convulsion lasting less than 15 minutes and not recurring within 24 hours; complex seizures included a focal or prolonged (>15 minutes) convulsion and/or more than 1 convulsion in 24 hours.

In the febrile seizure group, blood gas analyses indicated a respiratory alkalosis, with increased pH (mean, 7.46) and reduced PCO2 (mean, 29.5 mm Hg). Researchers noted a progressive fall in alkaline pH, which reached standard levels 2 hours or more after seizure onset.

There was no significant difference in body temperature or pH level between children with simple and complex febrile seizures, suggesting that the magnitude of respiratory alkalosis does not contribute to seizure complexity, according to the authors.

The gastroenteritis group showed a partially compensated metabolic acidosis with reduced pH (mean, 7.31) and normal PCO2 (mean, 37.7 mm Hg): parameters that differed significantly from the febrile seizure group (P < .001). Despite fever levels identical to the seizure group, none of the patients with gastroenteritis had febrile seizures.

The study included 8 patients who were taken to the hospital with febrile seizures and gastroenteritis at separate times during the study period. When admitted because of seizures, they had an alkalosis blood pH, but when admitted for gastroenteritis, they had an acidotic pH and no seizures. It was "striking" that patients with a susceptibility to febrile seizures did not have fever-induced seizures when admitted to the hospital with gastroenteritis and an associated acidosis, said Dr. Schuchmann.

The current study adds to previous animal and basic research showing a link between febrile seizures and alkalosis. Until now, it has been impossible to develop therapies directly targeting the disease mechanism involved in febrile seizures, the authors note. The disorder is difficult to study, as it appears mainly at home and not under hospital supervision.

Mask Therapy?

That may be changing. In an experimental rat model of febrile seizures previously published in Epilepsia, exposure to 5% ambient CO2, which blocked the hyperventilation-induced brain alkalosis, also blocked the experimental febrile seizure. Research that investigated the use of a mask with a valve regulating pressure and flow, and a replaceable container containing CO2, showed the benefits of this therapy in curbing seizures in humans. According to Dr. Schuchmann, emergency department personnel could eventually administer this portable mask, and paramedics and even parents may be able to administer it at home.

However, although the state of alkalosis may be a trigger for febrile seizures, Dr. Schuchmann said he is convinced it is not the only one.

Asked to comment, Eli M. Mizrahi, MD, professor of neurology and pediatrics, Baylor College of Medicine, Houston, Texas, and a member of the American Epilepsy Society, said the study addresses the complex interaction between genetic predisposition, specific risk factors, and the consequences of illness associated with febrile seizures.

"This relationship between respiratory alkalosis and febrile seizures can suggest new avenues of clinical research and consideration of novel therapies," said Dr. Mizrahi to Medscape Medical News in an email.

The authors have disclosed no relevant financial relationships.

Epilepsia. Published online September 12, 2011. Abstract


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