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Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

ABSTRACT: Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brain, with a threshold of 0.2-0.3 pH units for seizure induction. Suppressing alkalosis with 5% ambient CO2 abolished seizures within 20 s. CO2 also prevented two long-term effects of hyperthermic seizures in the hippocampus: the upregulation of the I(h) current and the upregulation of CB1 receptor expression. The effects of hyperthermia were closely mimicked by intraperitoneal injection of bicarbonate. Our work indicates a mechanism for triggering hyperthermic seizures and suggests new strategies in the research and therapy of fever-related epileptic syndromes.

SUBMITTER: Schuchmann S

PROVIDER: S-EPMC1698875 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

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Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

Schuchmann Sebastian S Schmitz Dietmar D Rivera Claudio C Vanhatalo Sampsa S Salmen Benedikt B Mackie Ken K Sipilä Sampsa T ST Voipio Juha J Kaila Kai K

Nature medicine 20060702 7

Febrile seizures are frequent during early childhood, and prolonged (complex) febrile seizures are associated with an increased susceptibility to temporal lobe epilepsy. The pathophysiological consequences of febrile seizures have been extensively studied in rat pups exposed to hyperthermia. The mechanisms that trigger these seizures are unknown, however. A rise in brain pH is known to enhance neuronal excitability. Here we show that hyperthermia causes respiratory alkalosis in the immature brai ...[more]

PMID: 16819552

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Project description:BackgroundFebrile seizures are the commonest type of seizure in occurring in the first few years of life, mostly affecting children aged six months to five years old. While largely benign, the incidence of each febrile seizure increases the risk of recurrence, afebrile seizures and epilepsy. Viruses are the most frequent cause of febrile illnesses in which a febrile seizure occurs. Febrile seizure presentation patterns appear to follow a seasonal trend.AimsTo identify patterns of febrile seizure incidence across different seasons with specific viral activity, and to establish a framework for analysing virus circulation data with common illnesses within a shared region and population.SettingOur study was a study of febrile seizure presentations in Victoria, Australia and respiratory virus detection.ParticipantsWe obtained independent datasets of emergency department febrile seizure presentations at Monash Health and all respiratory multiplex PCR tests performed at Monash Health from January 2010-December 2019 to observe common trends in virus circulation and febrile seizure incidence.Study designTrends were studied temporally through mixed effects Poisson regression analysis of the monthly incidence of febrile seizures and the rate of positive PCR tests. Peak viral seasons (95th centile incidence) were compared to median viral circulation (50th centile incidence) to calculate peak season risk ratios.ResultsWe found a 1.75-2.06 annual risk ratio of febrile seizure incidence in June-September. Temporal analysis of our data showed this peak in febrile seizures was attributable to circulating viruses in this season, and virus modelling showed correlation with increased rates of positive Influenza A (1.48 peak season risk ratio), Influenza B (1.31 peak season risk ratio), Human metapneumovirus (1.19 peak season risk ratio) and Respiratory Syncytial Virus (1.53 peak season risk ratio) on PCR testing.ConclusionOur ecological study statistically demonstrates the recognised winter peak in febrile seizure incidence and ascribes the seasonal relationship to several viral infections which affect the community, including a novel association with Human metapneumovirus.

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Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

Publications

Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis.

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