LETTERS/REPLIES
Hippocampal Sclerosis and Other Forms of Status Epilepticus Michael Yoong, MRCPCH, PhD,1 Marina M. Martinos, PhD,2 Suresh Pujar, MRCPCH PhD,3 Rodney C. Scott, MRCPCH PhD,3,4 and Richard F. Chin, PhD1 We note with interest the FEBSTAT 1-year follow-up study,1 in which they found significantly decreased right hippocampal volumes in children with febrile status epilepticus (FSE) compared to children with simple febrile seizures on initial and follow-up magnetic resonance imaging. However, in a longitudinal study [Status Epilepticus Imaging and Neurocognitive study (STEPIN)] of British children with all forms of convulsive status epilepticus (CSE; 26 with FSE),2 we found that 19% (95% confidence interval [CI] 5 4–35%) of children with FSE and 30% (95% CI 5 15–45%) of the non-FSE group showed significant hippocampal volume loss over the year following CSE. Thus, hippocampal injury is not only an FSE phenomenon, but occurs in all forms of CSE. Further follow-up is needed to determine how persistent this impact is and what the longer-term implications might be. Although we found no child who developed hippocampal sclerosis (HS) following FSE, our findings are consistent with the FEBSTAT findings of 7%, because the 95% CIs overlap (95% CI 5 0–13% and 4–13%, respectively). Taken together, however, a small proportion of children will develop HS within 1 year following FSE. In STEPIN, hippocampal volume loss was associated with a history of previous febrile seizures and recurrent CSE. It would be interesting to see whether similar findings emerge in FEBSTAT.
Acknowledgment Supported by grants from the NIH (R.C.S.), Great Ormond Street Hospital Children’s Charity (R.C.S.), Academy of Medical Sciences (S.P.), BUPA Foundation (S.P.), Wellcome Trust (S.P.), National Institute for Health Research (S.P.), and Medical Research Council (S.P.). S.P. received salary for clinical work from Young Epilepsy.
Potential Conflicts of Interest R.F.C.: grants, Wellcome Trust, Academy of Medical Sciences, BUPA Foundation; personal fees, Viropharma, Special Products Limited, Eisai, UCB. 1 Muir Maxwell Epilepsy Centre, University of Edinburgh, Edinburgh, United Kingdom 2 Developmental Cognitive Neurosciences Unit, UCL Institute of Child Health, London, United Kingdom
C 2014 American Neurological Association 316 V
3
Neurosciences Unit, UCL Institute of Child Health, London, United Kingdom 4 Department of Neurological Sciences, University of Vermont, Burlington, VT
References 1.
Lewis DV, Shinnar S, Hesdorffer DC, et al. Hippocampal sclerosis after febrile status epilepticus: the FEBSTAT study. Ann Neurol 2014;75:178–185.
2.
Yoong M, Martinos M, Chin R. Hippocampal volume loss following childhood convulsive status epilepticus is not limited to prolonged febrile seizures. Epilepsia 2013;54:2108–2015.
DOI: 10.1002/ana.24207
Reply Darrell Lewis, MD,1 Dale Hesdorffer, PhD,2 Solomon L. Moshe, MD,3 and Shlomo Shinnar, MD, PhD3 for the FEBSTAT Study Team Yoong et al make several comparisons between their Status Epilepticus Imaging and Neurocognitive Study (STEPIN) study and Consequences of Prolonged Febrile Seizures in Childhood Study (FEBSTAT). As they point out, hippocampal volume loss may well occur after afebrile status epilepticus. FEBSTAT was not designed to address afebrile status epilepticus. Instead, the large FEBSTAT prospective study addresses the relationship between prolonged febrile seizures and subsequent hippocampal sclerosis and temporal lobe epilepsy. This is one of the major controversies in neurology. The effect of afebrile status epilepticus on volume loss is an important question but a different study. Yoong et al describe differences between the studies. The STEPIN study had a relatively small number of febrile status epilepticus cases, and no cases of hippocampi with frankly abnormal hippocampal T2 signal were observed. Thus, it is not surprising that hippocampal sclerosis was absent in STEPIN, as this was only seen in FEBSTAT when the initial magnetic resonance imaging (MRI) showed abnormal hippocampal T2 signal; these were also the cases with dramatic volume loss. By extension, the less dramatic volume loss in the STEPIN study reflects the less dramatic volume loss seen in the FEBSTAT study without baseline T2 signal. The timing of the baseline MRI was also different in STEPIN and FEBSTAT. In STEPIN, the baseline MRI was performed up to 30 days after the episode of febrile status epilepticus, by which time some of the volume loss may have already occurred. Finally, Yoong et al note that there was an association between hippocampal volume loss and prior febrile seizures and prior episodes of status epilepticus in STEPIN. The FEBSTAT study focused on first episodes of status epilepticus, so we cannot provide data on which to comment, but it is certainly
Hippocampal Sclerosis and Other Forms of Status Epilepticus Michael Yoong, MRCPCH, PhD,1 Marina M. Martinos, PhD,2 Suresh Pujar, MRCPCH PhD,3 Rodney C. Scott, MRCPCH PhD,3,4 and Richard F. Chin, PhD1 We note with interest the FEBSTAT 1-year follow-up study,1 in which they found significantly decreased right hippocampal volumes in children with febrile status epilepticus (FSE) compared to children with simple febrile seizures on initial and follow-up magnetic resonance imaging. However, in a longitudinal study [Status Epilepticus Imaging and Neurocognitive study (STEPIN)] of British children with all forms of convulsive status epilepticus (CSE; 26 with FSE),2 we found that 19% (95% confidence interval [CI] 5 4–35%) of children with FSE and 30% (95% CI 5 15–45%) of the non-FSE group showed significant hippocampal volume loss over the year following CSE. Thus, hippocampal injury is not only an FSE phenomenon, but occurs in all forms of CSE. Further follow-up is needed to determine how persistent this impact is and what the longer-term implications might be. Although we found no child who developed hippocampal sclerosis (HS) following FSE, our findings are consistent with the FEBSTAT findings of 7%, because the 95% CIs overlap (95% CI 5 0–13% and 4–13%, respectively). Taken together, however, a small proportion of children will develop HS within 1 year following FSE. In STEPIN, hippocampal volume loss was associated with a history of previous febrile seizures and recurrent CSE. It would be interesting to see whether similar findings emerge in FEBSTAT.
Acknowledgment Supported by grants from the NIH (R.C.S.), Great Ormond Street Hospital Children’s Charity (R.C.S.), Academy of Medical Sciences (S.P.), BUPA Foundation (S.P.), Wellcome Trust (S.P.), National Institute for Health Research (S.P.), and Medical Research Council (S.P.). S.P. received salary for clinical work from Young Epilepsy.
Potential Conflicts of Interest R.F.C.: grants, Wellcome Trust, Academy of Medical Sciences, BUPA Foundation; personal fees, Viropharma, Special Products Limited, Eisai, UCB. 1 Muir Maxwell Epilepsy Centre, University of Edinburgh, Edinburgh, United Kingdom 2 Developmental Cognitive Neurosciences Unit, UCL Institute of Child Health, London, United Kingdom
C 2014 American Neurological Association 316 V
3
Neurosciences Unit, UCL Institute of Child Health, London, United Kingdom 4 Department of Neurological Sciences, University of Vermont, Burlington, VT
References 1.
Lewis DV, Shinnar S, Hesdorffer DC, et al. Hippocampal sclerosis after febrile status epilepticus: the FEBSTAT study. Ann Neurol 2014;75:178–185.
2.
Yoong M, Martinos M, Chin R. Hippocampal volume loss following childhood convulsive status epilepticus is not limited to prolonged febrile seizures. Epilepsia 2013;54:2108–2015.
DOI: 10.1002/ana.24207
Reply Darrell Lewis, MD,1 Dale Hesdorffer, PhD,2 Solomon L. Moshe, MD,3 and Shlomo Shinnar, MD, PhD3 for the FEBSTAT Study Team Yoong et al make several comparisons between their Status Epilepticus Imaging and Neurocognitive Study (STEPIN) study and Consequences of Prolonged Febrile Seizures in Childhood Study (FEBSTAT). As they point out, hippocampal volume loss may well occur after afebrile status epilepticus. FEBSTAT was not designed to address afebrile status epilepticus. Instead, the large FEBSTAT prospective study addresses the relationship between prolonged febrile seizures and subsequent hippocampal sclerosis and temporal lobe epilepsy. This is one of the major controversies in neurology. The effect of afebrile status epilepticus on volume loss is an important question but a different study. Yoong et al describe differences between the studies. The STEPIN study had a relatively small number of febrile status epilepticus cases, and no cases of hippocampi with frankly abnormal hippocampal T2 signal were observed. Thus, it is not surprising that hippocampal sclerosis was absent in STEPIN, as this was only seen in FEBSTAT when the initial magnetic resonance imaging (MRI) showed abnormal hippocampal T2 signal; these were also the cases with dramatic volume loss. By extension, the less dramatic volume loss in the STEPIN study reflects the less dramatic volume loss seen in the FEBSTAT study without baseline T2 signal. The timing of the baseline MRI was also different in STEPIN and FEBSTAT. In STEPIN, the baseline MRI was performed up to 30 days after the episode of febrile status epilepticus, by which time some of the volume loss may have already occurred. Finally, Yoong et al note that there was an association between hippocampal volume loss and prior febrile seizures and prior episodes of status epilepticus in STEPIN. The FEBSTAT study focused on first episodes of status epilepticus, so we cannot provide data on which to comment, but it is certainly
