MRI as a Biomarker for Hippocampal Injury in Febrile Status Epilepticus
Abstract & Commentary
By Padmaja Kandula, MD
Assistant Professor of Neurology and Neuroscience, Comprehensive Epilepsy Center, Weill Cornell Medical College
Dr. Kandula reports no financial relationships relevant to this field of study.
Synopsis: In this prospective study, the authors use brain imaging criteria to determine whether acute febrile status results in acute hippocampal injury and potentially chronic hippocampal sclerosis.
Source: Lewis DV, et al, and the FEBSTAT study team. Hippocampal sclerosis after febrile status epilepticus: The FEBSTAT study. Ann Neurol 2014;75:178-185.
The interaction between prolonged febrile seizures in childhood and the development of hippocampal sclerosis has been hotly debated. In this prospective study, both the acute and long-term imaging characteristics of febrile status are compared to a cohort of controls with simple febrile seizures.
In total, 226 patients aged 1 month to 6 years, derived from three prospective studies, were included in the final analysis. Febrile status in this study was defined as status epilepticus lasting 30 minutes or longer or repetitive febrile seizures lasting at least 30 minutes without resumption of consciousness. All patients were imaged with 1.5 T MRI within one week of febrile status. Hippocampal T2 signal scores (0-normal,1-equivocal, 2-mildly abnormal) were assigned by two blinded experienced neuroradiologists. T2 scores ≥ 2 were considered a definite abnormality. Radiographic criteria for hippocampal sclerosis required hippocampal atrophy and T2 scores ≥ 2. In addition, hippocampal volumes and ADC maps were also incorporated in the study. Patients with normal MRI hyperintensity, volume, and ADC maps with either febrile status or simple febrile seizures served as controls.
Of 226 patients, 22 had acute T2 hyperintensity and increased hippocampal volume on MRI. ADC maps were available on 13 of 22 patients and showed that the mean ADC for the hyperintense hippocampi was lower than matched contralateral hippocampi. Follow-up MRI was performed 1 year later on 14 of the 22 patients with initial abnormal hippocampal signal. Ten of 14 patients met formal criteria for hippocampal sclerosis. Twelve of 14 patients showed reduced hippocampal volume. In contrast, follow-up MRI of 116 children without acute hyperintensity (initial normal MRI) showed abnormal T2 signal in only one patient (following another episode of febrile status). In addition, compared to controls with simple febrile seizures, febrile status epilepticus patients with initial normal acute MRI had abnormally low right to left hippocampal volume ratios, smaller hippocampi initially, and reduced hippocampal growth suggesting subtle hippocampal injury.
Commentary
The results of this study suggest that T2 hyperintensity after febrile status likely reflects acute injury, which then evolves to radiographic hippocampal sclerosis. Impaired hippocampal growth, 1 year after febrile status, in initially normal imaging suggests a possible biomarker of subtle injury. Although MRI may potentially identify those febrile status patients ultimately at risk for long-term hippocampal injury, this does not confirm definite pathologic injury. That is not to say that the initial results of this prospective study are not promising. However, further conclusions should be tempered until additional follow-up imaging can be performed to determine what proportion of these febrile status patients ultimately develop medically refractory temporal lobe epilepsy.
