James L. Leach, Reem Awwad, Hansel M. Greiner, Jennifer J. Vannest, Lili Miles and Francesco T. Mangano
Diagnostic criteria for hippocampal malrotation (HIMAL) on brain MRI typically include a rounded hippocampus, vertical collateral sulcus, and architectural blurring. Relationship to epileptogenesis remains speculative, and usefulness for surgical guidance is unknown. The study was performed to determine the prevalence of hippocampal rotational anomalies in a cohort of pediatric patients with intractable epilepsy undergoing evaluation for surgery and to determine the significance of this finding in the context of surgical planning.
Forty-eight surgically treated children with intractable epilepsy were compared with matched healthy subjects; reviewers were blinded to surgical side. Each temporal lobe was evaluated for rounded hippocampus, blurring, vertical collateral sulcus, wide choroidal fissure, enlarged temporal horn, low fornix, hippocampal signal, and findings of hippocampal sclerosis. A mesial temporal lobe (MTL) score was calculated by summing the number of features, and the collateral sulcus angle (CSA) was measured in each temporal lobe. Surgical side, pathological diagnosis, and imaging findings elsewhere in the brain were tabulated. Presence of HIMAL, associated imaging features, and MTL score were compared between sides, between epilepsy and control groups, in relationship to side of surgery, and in relationship to postoperative outcome.
Only 3 epilepsy patients (6.2%) and no controls exhibited all 3 features of HIMAL (p = 0.12). Eight of 48 (16.7%) epilepsy versus 2 of 48 (4.6%) control subjects had both a rounded hippocampus and vertical collateral sulcus (suggesting HIMAL) (p = 0.045). In control and epilepsy subjects, most findings were more prevalent on the left, and the left CSA was more vertical (p < 0.0001). Epilepsy subjects had higher MTL scores (z = −2.95, p = 0.002) and more acute CSAs (p = 0.04) than controls. Only lateralizing raw MTL score had a significant association with surgical side (p = 0.03, OR 7.33); however, this was not significant when hippocampal sclerosis cases were excluded. HIMAL findings were more prevalent and MTL scores were higher in patients with resections involving the temporal lobes. On group analysis, HIMAL findings did not predict eventual surgical side and did not predict outcome, although the numbers are small. In 4 patients the abnormally rotated hippocampus was resected and showed hippocampal sclerosis and/or dysplastic changes on histopathology. All of these patients had a good outcome after surgery.
While increased in prevalence in children with intractable epilepsy, imaging findings of HIMAL did not have preoperative lateralizing utility in this group. Findings of HIMAL (including round hippocampus, architectural blurring, and vertical collateral sulcus) did not predict outcome after surgery, although the small number of patients with these findings limits evaluation. In the small number of patients in which the malrotated hippocampus was removed, outcome was good. Further research is needed to continue to define this association in children with intractable epilepsy, focusing on a temporal lobe cohort.
James L. Leach, Lili Miles, David M. Henkel, Hansel M. Greiner, Marcia K. Kukreja, Katherine D. Holland, Douglas F. Rose, Bin Zhang and Francesco T. Mangano
The authors conducted a study to correlate histopathological features, MRI findings, and postsurgical outcomes in children with cortical dysplasia (CD) by performing a novel resection site–specific evaluation.
The study cohort comprised 43 children with intractable epilepsy and CD. The MR image review was blinded to pathology but with knowledge of the resection location. An MRI score (range 0–7) was calculated for each resection region based on the number of imaging features of CD and was classified as “lesional” or “nonlesional” according to all imaging features. Outcome was determined using the International League Against Epilepsy (ILAE) scale. The determination of pathological CD type was based on the ILAE 2011 consensus classification system, and the cortical gliosis pattern was assessed on GFAP staining.
There were 89 resection regions (50 ILAE Type I, 29 Type IIa, and 10 Type IIb). Eleven (25.6%) of 43 children had more than one type of CD. The authors observed MRI abnormalities in 63% of patients, characteristic enough to direct resection (lesional) in 42%. Most MRI features, MRI score ≥ 3, and lesional abnormalities were more common in patients with Type II CD. Increased cortical signal was more common in those with Type IIb (70%) rather than Type IIa (17.2%) CD (p = 0.004). A good outcome was demonstrated in 39% of children with Type I CD and 72% of those with Type II CD (61% in Type IIa and 100% in Type IIb) (p = 0.03). A lesional MRI abnormality and an MRI score greater than 3 correlated with good outcome in 78% and 90% of patients, respectively (p < 0.03). Diffuse cortical gliosis was more prevalent in Type II CD and in resection regions exhibiting MRI abnormalities. Complete surgical exclusion of the MRI abnormality was associated with a better postoperative outcome.
This study provides a detailed correlation of MRI findings, neuropathological features, and outcomes in children with intractable epilepsy by using a novel resection site–specific evaluation. Because 25% of the patients had multiple CD subtypes, a regional analysis approach was mandated. Those children with lesional MRI abnormalities, Type II CD, and surgical exclusion of the MRI abnormality had better outcomes. Type II CD is more detectable by MRI than other types, partly because of the greater extent of associated gliosis in Type II. Although MRI findings were correlated with the pathological CD type and outcome in this study, the majority of patients (58%) did not have MRI findings that could direct surgical therapy, underscoring the need for improved MRI techniques for detection and for the continued use of multimodal evaluation methods in patient selection.
Ravindra Arya, Jeffrey R. Tenney, Paul S. Horn, Hansel M. Greiner, Katherine D. Holland, James L. Leach, Michael J. Gelfand, Leonid Rozhkov, Hisako Fujiwara, Douglas F. Rose, David N. Franz and Francesco T. Mangano
Tuberous sclerosis complex (TSC) with medically refractory epilepsy is characterized by multifocal brain abnormalities, traditionally indicating poor surgical candidacy. This single-center, retrospective study appraised seizurerelated, neuropsychological, and other outcomes of resective surgery in TSC patients with medically refractory epilepsy, and analyzed predictors for these outcomes.
Patients with multilesional TSC who underwent epilepsy surgery between 2007 and 2012 were identified from an electronic database. All patients underwent multimodality noninvasive and subsequent invasive evaluation. Seizure outcomes were classified using the International League Against Epilepsy (ILAE) scale. The primary outcome measure was complete seizure remission (ILAE Class 1). Secondary outcome measures included 50% responder rate, change in full-scale IQ, electroencephalography improvement, and reduction in antiepileptic drug (AED) burden.
A total of 37 patients with TSC underwent resective surgery during the study period. After a mean follow-up of 5.68 ± 3.67 years, 56.8% achieved complete seizure freedom (ILAE Class 1) and 86.5% had ILAE Class 4 outcomes or better. The full-scale IQ on follow-up was significantly higher in patients with ILAE Class 1 outcome (66.70 ± 12.36) compared with those with ILAE Class 2 or worse outcomes (56.00 ± 1.41, p = 0.025). In 62.5% of the patients with ILAE Class 2 or worse outcomes, the number of AEDs were found to be significantly reduced (p = 0.004).
This study substantiates the evidence for efficacy of resective epilepsy surgery in patients with bilateral multilesional TSC. More than half of the patients were completely seizure free. Additionally, a high proportion achieved clinically meaningful reduction in seizure burden and the number of AEDs.
Ravindra Arya, Francesco T. Mangano, Paul S. Horn, Sabrina K. Kaul, Serena K. Kaul, Celie Roth, James L. Leach, Michele Turner, Katherine D. Holland and Hansel M. Greiner
There is emerging data that adults with temporal lobe epilepsy (TLE) without a discrete lesion on brain MRI have surgical outcomes comparable to those with hippocampal sclerosis (HS). However, pediatric TLE is different from its adult counterpart. In this study, the authors investigated if the presence of a potentially epileptogenic lesion on presurgical brain MRI influences the long-term seizure outcomes after pediatric temporal lobectomy.
Children who underwent temporal lobectomy between 2007 and 2015 and had at least 1 year of seizure outcomes data were identified. These were classified into lesional and MRI-negative groups based on whether an epilepsy-protocol brain MRI showed a lesion sufficiently specific to guide surgical decisions. These patients were also categorized into pure TLE and temporal plus epilepsies based on the neurophysiological localization of the seizure-onset zone. Seizure outcomes at each follow-up visit were incorporated into a repeated-measures generalized linear mixed model (GLMM) with MRI status as a grouping variable. Clinical variables were incorporated into GLMM as covariates.
One hundred nine patients (44 females) were included, aged 5 to 21 years, and were classified as lesional (73%), MRI negative (27%), pure TLE (56%), and temporal plus (44%). After a mean follow-up of 3.2 years (range 1.2–8.8 years), 66% of the patients were seizure free for ≥ 1 year at last follow-up. GLMM analysis revealed that lesional patients were more likely to be seizure free over the long term compared to MRI-negative patients for the overall cohort (OR 2.58, p < 0.0001) and for temporal plus epilepsies (OR 1.85, p = 0.0052). The effect of MRI lesion was not significant for pure TLE (OR 2.64, p = 0.0635). Concordance of ictal electroencephalography (OR 3.46, p < 0.0001), magnetoencephalography (OR 4.26, p < 0.0001), and later age of seizure onset (OR 1.05, p = 0.0091) were associated with a higher likelihood of seizure freedom. The most common histological findings included cortical dysplasia types 1B and 2A, HS (40% with dual pathology), and tuberous sclerosis.
A lesion on presurgical brain MRI is an important determinant of long-term seizure freedom after pediatric temporal lobectomy. Pediatric TLE is heterogeneous regarding etiologies and organization of seizure-onset zones with many patients qualifying for temporal plus nosology. The presence of an MRI lesion determined seizure outcomes in patients with temporal plus epilepsies. However, pure TLE had comparable surgical seizure outcomes for lesional and MRI-negative groups.