MRI suggests hippocampal sclerosis in some patients after febrile status epilepticus

MRI T2 hyperintensities in the hippocampi of children after febrile status epilepticus often evolved to visual appearance of hippocampal sclerosis after a median follow-up of 1 year in a prospective, observational cohort study of 226 children.

Even children who had a normal MRI after an episode of febrile status epilepticus (FSE) had smaller mean size of hippocampi and abnormal, decreased right/left hippocampal volume ratios, compared with a control group of 38 children who had a simple febrile seizure and normal MRIs. The visually normal hippocampi in children with FSE also grew more slowly than in children with a simple febrile seizure, suggesting "a subtle acute hippocampal injury," according to lead investigator Darrell V. Lewis of the department of pediatrics at Duke University, Durham, N.C., and his associates.

Most of the cohort was derived from patients in the ongoing FEBSTAT study, which along with other previous studies have shown that FSE can result in acute hippocampal injury visible on MRI. This injury is suspected to cause hippocampal sclerosis, which is a common feature of temporal lobe epilepsy. Dr. Lewis and his colleagues’ study aimed to determine whether radiologically defined hippocampal sclerosis (as noted by an increased hippocampal signal and visual confirmation of atrophy) can be first detected on MRI in the days after an initial FSE episode and evolve further on later follow-up MRI.

Ultimately, the goal of this research is to find biomarkers for temporal lobe epilepsy following FSE that would allow clinicians to identify patients who could undergo an as yet unknown antiepileptogenic intervention, but until further follow-up is available from FEBSTAT and other studies, researchers can only look for biomarkers for hippocampal sclerosis because temporal lobe epilepsy may arise 10 or more years after FSE, according to Dr. Lewis and his associates.

The study involved 226 children with FSE aged 1 month to 6 years, including subjects from the FEBSTAT study, the Duke FEBSTAT pilot study, and the Columbia first FS study. In this cohort, 67% underwent an initial MRI within 3 days of FSE and 88% within 7 days (Ann. Neurol. 2013 Dec. 7 [doi:10.1002/ana.24081]).

At baseline, 22 of the 226 (9.7%) children with FSE had an abnormal hippocampal signal, most of which (15) were right-sided except for 6 on the left side and 1 that was bilateral. The side in which 21 patients had unilateral T2 hyperintensities was larger than the contralateral side in 13 patients (62%). Hyperintense hippocampi also had significantly larger mean volume than did contralateral hippocampi in these patients, excluding three children with preexisting small hippocampi.

Two children had visually small hippocampi that also measured small in volume and hyperintense at baseline and at follow-up. This finding was "unexpected and supports the suggestion that [hippocampal sclerosis] might occasionally precede FSE made by others," the investigators said. The other child with a preexisting small, hyperintense hippocampus also had a small, schizencephalic hemisphere on the same side.

On follow-up MRIs conducted a median of 1 year later (range, 1 month to 2.5 years) in 14 of the 22 patients with hippocampal abnormalities, 10 met visual criteria for hippocampal sclerosis (including 1 patient with hippocampal sclerosis on the initial MRI). Volume loss also occurred in 13 of 15 hyperintense hippocampi (including the one patient with bilateral hyperintense hippocampi).

During follow-up, 5 of the 22 (23%) patients with hippocampal hyperintensity developed epilepsy early, mostly not temporal lobe epilepsy, and all returned for follow-up. Of the 14 with follow-up MRIs, 3 (23%) developed epilepsy. Only one of the eight (12.5%) patients without follow-up MRIs is known to have epilepsy. Another 11 FSE patients with normal baseline MRIs later developed epilepsy.

Patients who had normal baseline MRIs later appeared to have small changes potentially indicating hippocampal injury. In 116 patients with both initial and follow-up MRIs, only 1 developed abnormal signal on follow-up after a second episode of FSE; none had radiologic evidence of hippocampal sclerosis.

However, hippocampi in FSE patients that were normal at baseline appeared to show subtle signs of injury on follow-up MRIs at 6-24 months. Follow-up MRIs in 59 (26%) FSE patients with completely normal MRIs at baseline showed a significantly lower right/left volume ratio estimate than 38 control patients with a simple febrile seizure who had completely normal baseline MRIs, after controlling for age and gender. Similarly, right and left hippocampal volumes were significantly lower among the FSE patients on follow-up MRIs, and their hippocampi appeared to grow more slowly.

"The combined decreased right hippocampal volume of the FSE hippocampi and the predominance of hyperintensity on the right suggest volume asymmetry may signify hippocampal vulnerability present before FSE, as has been suggested previously," the investigators wrote.

Differences in follow-up did not appear to bias the results. Among the patients with hippocampal abnormalities at baseline, there were no significant differences between patients with or without MRI follow-up for status epilepticus duration, T2 scores, presence of developmental delay, focal status, and abnormal acute EEG. However, in both patients with hippocampal abnormalities at baseline and in the FSE cohort overall, patients with multiple conditions that affect well-being, such as developmental delay, epilepsy, or recurrent status epilepticus, seemed to be more likely to undergo follow-up MRI.

The study was supported by grants from the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. No financial disclosures were reported.

jevans@frontlinemedcom.com

MRI T2 hyperintensities in the hippocampi of children after febrile status epilepticus often evolved to visual appearance of hippocampal sclerosis after a median follow-up of 1 year in a prospective, observational cohort study of 226 children.

Even children who had a normal MRI after an episode of febrile status epilepticus (FSE) had smaller mean size of hippocampi and abnormal, decreased right/left hippocampal volume ratios, compared with a control group of 38 children who had a simple febrile seizure and normal MRIs. The visually normal hippocampi in children with FSE also grew more slowly than in children with a simple febrile seizure, suggesting "a subtle acute hippocampal injury," according to lead investigator Darrell V. Lewis of the department of pediatrics at Duke University, Durham, N.C., and his associates.

Most of the cohort was derived from patients in the ongoing FEBSTAT study, which along with other previous studies have shown that FSE can result in acute hippocampal injury visible on MRI. This injury is suspected to cause hippocampal sclerosis, which is a common feature of temporal lobe epilepsy. Dr. Lewis and his colleagues’ study aimed to determine whether radiologically defined hippocampal sclerosis (as noted by an increased hippocampal signal and visual confirmation of atrophy) can be first detected on MRI in the days after an initial FSE episode and evolve further on later follow-up MRI.

Ultimately, the goal of this research is to find biomarkers for temporal lobe epilepsy following FSE that would allow clinicians to identify patients who could undergo an as yet unknown antiepileptogenic intervention, but until further follow-up is available from FEBSTAT and other studies, researchers can only look for biomarkers for hippocampal sclerosis because temporal lobe epilepsy may arise 10 or more years after FSE, according to Dr. Lewis and his associates.

The study involved 226 children with FSE aged 1 month to 6 years, including subjects from the FEBSTAT study, the Duke FEBSTAT pilot study, and the Columbia first FS study. In this cohort, 67% underwent an initial MRI within 3 days of FSE and 88% within 7 days (Ann. Neurol. 2013 Dec. 7 [doi:10.1002/ana.24081]).

At baseline, 22 of the 226 (9.7%) children with FSE had an abnormal hippocampal signal, most of which (15) were right-sided except for 6 on the left side and 1 that was bilateral. The side in which 21 patients had unilateral T2 hyperintensities was larger than the contralateral side in 13 patients (62%). Hyperintense hippocampi also had significantly larger mean volume than did contralateral hippocampi in these patients, excluding three children with preexisting small hippocampi.

Two children had visually small hippocampi that also measured small in volume and hyperintense at baseline and at follow-up. This finding was "unexpected and supports the suggestion that [hippocampal sclerosis] might occasionally precede FSE made by others," the investigators said. The other child with a preexisting small, hyperintense hippocampus also had a small, schizencephalic hemisphere on the same side.

On follow-up MRIs conducted a median of 1 year later (range, 1 month to 2.5 years) in 14 of the 22 patients with hippocampal abnormalities, 10 met visual criteria for hippocampal sclerosis (including 1 patient with hippocampal sclerosis on the initial MRI). Volume loss also occurred in 13 of 15 hyperintense hippocampi (including the one patient with bilateral hyperintense hippocampi).

During follow-up, 5 of the 22 (23%) patients with hippocampal hyperintensity developed epilepsy early, mostly not temporal lobe epilepsy, and all returned for follow-up. Of the 14 with follow-up MRIs, 3 (23%) developed epilepsy. Only one of the eight (12.5%) patients without follow-up MRIs is known to have epilepsy. Another 11 FSE patients with normal baseline MRIs later developed epilepsy.

Patients who had normal baseline MRIs later appeared to have small changes potentially indicating hippocampal injury. In 116 patients with both initial and follow-up MRIs, only 1 developed abnormal signal on follow-up after a second episode of FSE; none had radiologic evidence of hippocampal sclerosis.

However, hippocampi in FSE patients that were normal at baseline appeared to show subtle signs of injury on follow-up MRIs at 6-24 months. Follow-up MRIs in 59 (26%) FSE patients with completely normal MRIs at baseline showed a significantly lower right/left volume ratio estimate than 38 control patients with a simple febrile seizure who had completely normal baseline MRIs, after controlling for age and gender. Similarly, right and left hippocampal volumes were significantly lower among the FSE patients on follow-up MRIs, and their hippocampi appeared to grow more slowly.

"The combined decreased right hippocampal volume of the FSE hippocampi and the predominance of hyperintensity on the right suggest volume asymmetry may signify hippocampal vulnerability present before FSE, as has been suggested previously," the investigators wrote.

Differences in follow-up did not appear to bias the results. Among the patients with hippocampal abnormalities at baseline, there were no significant differences between patients with or without MRI follow-up for status epilepticus duration, T2 scores, presence of developmental delay, focal status, and abnormal acute EEG. However, in both patients with hippocampal abnormalities at baseline and in the FSE cohort overall, patients with multiple conditions that affect well-being, such as developmental delay, epilepsy, or recurrent status epilepticus, seemed to be more likely to undergo follow-up MRI.

The study was supported by grants from the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. No financial disclosures were reported.

jevans@frontlinemedcom.com

MRI T2 hyperintensities in the hippocampi of children after febrile status epilepticus often evolved to visual appearance of hippocampal sclerosis after a median follow-up of 1 year in a prospective, observational cohort study of 226 children.

Even children who had a normal MRI after an episode of febrile status epilepticus (FSE) had smaller mean size of hippocampi and abnormal, decreased right/left hippocampal volume ratios, compared with a control group of 38 children who had a simple febrile seizure and normal MRIs. The visually normal hippocampi in children with FSE also grew more slowly than in children with a simple febrile seizure, suggesting "a subtle acute hippocampal injury," according to lead investigator Darrell V. Lewis of the department of pediatrics at Duke University, Durham, N.C., and his associates.

Most of the cohort was derived from patients in the ongoing FEBSTAT study, which along with other previous studies have shown that FSE can result in acute hippocampal injury visible on MRI. This injury is suspected to cause hippocampal sclerosis, which is a common feature of temporal lobe epilepsy. Dr. Lewis and his colleagues’ study aimed to determine whether radiologically defined hippocampal sclerosis (as noted by an increased hippocampal signal and visual confirmation of atrophy) can be first detected on MRI in the days after an initial FSE episode and evolve further on later follow-up MRI.

Ultimately, the goal of this research is to find biomarkers for temporal lobe epilepsy following FSE that would allow clinicians to identify patients who could undergo an as yet unknown antiepileptogenic intervention, but until further follow-up is available from FEBSTAT and other studies, researchers can only look for biomarkers for hippocampal sclerosis because temporal lobe epilepsy may arise 10 or more years after FSE, according to Dr. Lewis and his associates.

The study involved 226 children with FSE aged 1 month to 6 years, including subjects from the FEBSTAT study, the Duke FEBSTAT pilot study, and the Columbia first FS study. In this cohort, 67% underwent an initial MRI within 3 days of FSE and 88% within 7 days (Ann. Neurol. 2013 Dec. 7 [doi:10.1002/ana.24081]).

At baseline, 22 of the 226 (9.7%) children with FSE had an abnormal hippocampal signal, most of which (15) were right-sided except for 6 on the left side and 1 that was bilateral. The side in which 21 patients had unilateral T2 hyperintensities was larger than the contralateral side in 13 patients (62%). Hyperintense hippocampi also had significantly larger mean volume than did contralateral hippocampi in these patients, excluding three children with preexisting small hippocampi.

Two children had visually small hippocampi that also measured small in volume and hyperintense at baseline and at follow-up. This finding was "unexpected and supports the suggestion that [hippocampal sclerosis] might occasionally precede FSE made by others," the investigators said. The other child with a preexisting small, hyperintense hippocampus also had a small, schizencephalic hemisphere on the same side.

On follow-up MRIs conducted a median of 1 year later (range, 1 month to 2.5 years) in 14 of the 22 patients with hippocampal abnormalities, 10 met visual criteria for hippocampal sclerosis (including 1 patient with hippocampal sclerosis on the initial MRI). Volume loss also occurred in 13 of 15 hyperintense hippocampi (including the one patient with bilateral hyperintense hippocampi).

During follow-up, 5 of the 22 (23%) patients with hippocampal hyperintensity developed epilepsy early, mostly not temporal lobe epilepsy, and all returned for follow-up. Of the 14 with follow-up MRIs, 3 (23%) developed epilepsy. Only one of the eight (12.5%) patients without follow-up MRIs is known to have epilepsy. Another 11 FSE patients with normal baseline MRIs later developed epilepsy.

Patients who had normal baseline MRIs later appeared to have small changes potentially indicating hippocampal injury. In 116 patients with both initial and follow-up MRIs, only 1 developed abnormal signal on follow-up after a second episode of FSE; none had radiologic evidence of hippocampal sclerosis.

However, hippocampi in FSE patients that were normal at baseline appeared to show subtle signs of injury on follow-up MRIs at 6-24 months. Follow-up MRIs in 59 (26%) FSE patients with completely normal MRIs at baseline showed a significantly lower right/left volume ratio estimate than 38 control patients with a simple febrile seizure who had completely normal baseline MRIs, after controlling for age and gender. Similarly, right and left hippocampal volumes were significantly lower among the FSE patients on follow-up MRIs, and their hippocampi appeared to grow more slowly.

"The combined decreased right hippocampal volume of the FSE hippocampi and the predominance of hyperintensity on the right suggest volume asymmetry may signify hippocampal vulnerability present before FSE, as has been suggested previously," the investigators wrote.

Differences in follow-up did not appear to bias the results. Among the patients with hippocampal abnormalities at baseline, there were no significant differences between patients with or without MRI follow-up for status epilepticus duration, T2 scores, presence of developmental delay, focal status, and abnormal acute EEG. However, in both patients with hippocampal abnormalities at baseline and in the FSE cohort overall, patients with multiple conditions that affect well-being, such as developmental delay, epilepsy, or recurrent status epilepticus, seemed to be more likely to undergo follow-up MRI.

The study was supported by grants from the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. No financial disclosures were reported.

jevans@frontlinemedcom.com