A Prospective Magnetic Resonance Imaging Study of Brain Injury During Complex Febrile Convulsions

Darrell Lewis, M.D.

Duke University Medical Center , Durham, NC

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

December 1999, for 3 years

Funding Amount:

$71,259

Investigator Biographies

Darrell Lewis, M.D.

Professor of Pediatrics and Neurobiology, Duke University Medical Center

Hypothesis

Hypothesis:
1. Predictors of development of acute hippocampal edema following complex febrile seizures will be the duration of ictal activity and focality of ictal activity.
2. Whether or not medial temporal sclerosis develops after a febrile seizure will be accurately predicted by a postictal radiological prognostic index comprising the anatomical extent of hippocampal edema, severity of edema, and type of edema.

Goals:
1. To determine risk factors predicting acute hippocampal edema after complex febrile seizures. A multiple logistic regression model will be used to evaluate the following potential predictors of acute hippocampal edema: patient age, sex, body temperature, focality of seizures, number of seizures, number of anticonvulsants administered acutely, total seizure duration, and prior neurodevelopmental abnormalities.
2. To develop a MRI based prognostic index for predicting the development of medial temporal sclerosis following complex febrile seizures. Four standardized scores or measures from the acute postictal MRI will be used to develop the prognostic index; i) anatomical extent of hippocampal edema, ii) hippocampal T2 relaxation time constant (T2RT) iii) total hippocampal volume, and iv) hippocampal apparent diffusion constant for water (ADC) measured with diffusion weighted imaging (DWI). Presence and severity of medial temporal sclerosis seen on follow-up MRIs will be scored using the T2 relaxation time constant (T2RT) and total hippocampal volume as a measure of hippocampal atrophy.

Methods:
Children under 6 years with complex febrile seizures will have initial postictal MRIs within 24 to 72 hours of the seizure and follow-up MRIs 4 months after the ictus. Hippocampal volume, T2RT and ADC values will be measured. Total hippocampal volumes, ADCs and T2RTs will be expressed as a standardized score using normal control means and standard deviations. The presence and severity of medial temporal sclerosis in follow-up MRIs will be scored based on total hippocampal volume and T2RTs. Using the acute and follow-up measures, a multiple logistic regression model will be used to predict the development of medial temporal sclerosis after febrile seizures.

Follow-on Funding:
Consequences of Prolonged Febrile Seizures in Childhood. (PI) NIH NINDS.

Findings:
About 10 to 12% of the 150 enrolled children with febrile status epilepticus have MRI evidence of hippocampal injury due to the status.

This injury produces hippocampal growth failure and atrophy.

The degree of MRI abnormality, referred to as T2 signal intensity, is predictive of lasting hippocampal injury and atrophy. This cohort of children will be followed for 5 to 10 more years, provided funding is renewed, to determine who develops temporal lobe epilepsy.

Selected Publications

Vanlandingham K.E., Heinz J.E., Cavazos J.E., Lewis D.V. (1998). MRI evidence of hippocampal injury following prolonged, focal febrile convulsions. Annals of Neurology, 43:413-426.

Lewis D.V. (1999). Febrile convulsions and mesial temporal sclerosis. Current Opinion in Neurology, 12:197-201.

Mitchell, T.V., Lewis, D.V. (2001). Do prolonged febrile seizures injure the hippocampus: Human MRI studies. Febrile Seizures, Eds. T.Z. Baram and S. Shinnar.

Lewis, D.V., Barboriak D., MacFall, J.R., Provenzale, J.M., Mitchell, T.V., and VanLandingham, K.E. (2002) Do Prolonged Febrile Seizures Produce Medial Temporal Sclerosis? Hypotheses, MRI Evidence and Unanswered Questions. Prog in Brain Res, 135:263-278.