Microsurgery in Cavernoma-Related Epilepsy in Children: Do Results in Children Differ from Adults?^[*]

Surgical Treatment and Long-Term Outcome of Cerebral Cavernous Malformations-Related Epilepsy in Pediatric Patients

Cavernous malformation (CM) of the brain is a rare disease (incidence, 0.4–0.9%). Prospective data (including few children) reveal the annual risk for new seizure onset in patients with a CM as 2.4% (5.5% for recurrent seizure).[1] Risk factors for seizures are cortical and archicortical location of CM, larger CM size (> 10 mm including the hemosiderin rim), and left hemisphere, but again in a cohort with only 3.6% children included.[2] In adults, surgical resection of CM including the hemosiderin rim[3] [4] seems effective in terms of control of epilepsy in patients with short-term history of epilepsy (< 1–2 years) or a very low number of seizures (< 2) and simple focal epilepsy. Seizure outcome in patients with long-term epilepsy or complex epilepsy pattern as well as restrictions for complete or extensive surgical resections of the irritative or epileptogenic zone, along with the CM, fare worse and recommendations have been published by the International League Against Epilepsy (ILAE).[5]

In the pediatric population, data are sparse. In this issue of Neuropediatrics, Lin et al[6] from China report the effectiveness of surgical resection on seizure outcome in 27 pediatric patients. All received interviews for seizure semiology, long-term video electroencephalogram (EEG), and magnetic resonance (MR) imaging, and some were additionally studied with invasive EEG and/or positron emission tomography-computed tomography (PET-CT). There was only one child with multiple CMs, so this cohort was quite homogenous for the number of CM per patient (i.e., 1). Duration of epilepsy prior to resection (lesionectomy or extensive resection) varied (2.3 years mean) and all resections were supported by electrocorticography (ECoG), which lead to a more extensive resection (extended resection in 78% of patients) compared with pure lesionectomy just based on imaging or intraoperative impression of the neurosurgeon (hemosiderin rim).[7] Despite this, the authors could not demonstrate a statistical significant benefit from early resection of CM in children with epilepsy, which has been reported by von der Brelie et al (with one-third of their patients being 18 years old).[8] Lin et al did, however, demonstrate a low surgical risk (no mortality; unexpected transient new neurological deficit in 7% of patients) as did Hugelshofer et al[9] and Gross et al.[10] Where to go from here in counseling and clinical research? As in adults, distinction of two gross scenarios might help: (1) A “simple constellation” with a noneloquent location of CM, sporadic seizures or focal epilepsy, and as short as possible history of epilepsy with only one (or none) antiepileptic medication trial: low surgical risk, over 85%–near 100% Engel I outcome.[11] This might include patients with multiple CMs (not unlikely to be associated with focal cortical dysplasia[12]) when the presurgical workup clearly defines one CM-area as causative for the epilepsy. (2) A “complex constellation” with long-term epilepsy, near-to-eloquent CM, involvement of temporo-mesial structures, etc.: enhanced risk of (calculated) new neurological deficit, and more limited chance of Class I results. This distinction might help to speed up the decision for surgical treatment of children with CM and one CM-related seizure. Initial surgery in CM-related sporadic seizures has been recently shown to be superior over conservative treatment in outcome (88% vs. 32%, Engel Class I at 2 years) and the chance of relief from antiepileptic medication (78% vs. 8%) with identical percentage of morbidity (3%) in a multicenter retrospective cohort.[11] For counseling, data for safety of surgical resection with the “simple scenario” seem robust and valid. For effectiveness and clinical research, more reports of cohorts, but with a very detailed workup, using comparable catalogs of items,[5] [13] might help to substantiate the hypotheses drawn from adult data by meta-analyses of cohort studies in children. Beyond that, questions remain, e.g., why do seizures occur with a single cortico-subcortical CM in some patients at childhood and not later in life? Do we miss CM-associated focal cortical malformations? Do we have to improve on preoperative high-resolution MR imaging in CM-associated seizures and neuropathological workup of the surgical specimen? For the “simple scenario,” randomized controlled trials in children seem problematic because the surgical effect seems quite positive, but a standardized workup and reporting is needed. For the “complex scenario,” randomization might fall short due to complexity and—very low case numbers. This is why larger cohort studies like that from Lin et al add valid information to the field of pediatric neurology and epileptology.

^* This article is an editorial comment on “Surgical Treatment and Long-Term Outcome of Cerebral Cavernous Malformations-Related Epilepsy in Pediatric Patients” by Qiao Lin et al (Neuropediatrics 2018; doi: 10.1055/s-0038-1645871).

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