By Pegah Afra, MD
Associate Professor of Neurology, Weill Cornell Medical College; Associate Attending Neurologist; NewYork-Presbyterian Hospital; Adjunct Associate Professor, University of Utah
SYNOPSIS: This comprehensive meta-analysis of the surgical outcomes for drug-resistant epilepsy caused by focal cortical dysplasia demonstrated an excellent result with post-surgical freedom from seizures in 70% of patients followed for more than 24 months.
SOURCE: Willard A, Antonic-Baker A, Chen Z, et al. Seizure outcome after surgery for MRI-diagnosed focal cortical dysplasia: A systematic review and meta-analysis. Neurology 2022;98:e236-e248.
Epilepsy surgery is one of the treatment modalities for intractable pharmacoresistant epilepsy. After hippocampal sclerosis and brain tumors, focal cortical dysplasia (FCD) is the third most common indication for epilepsy surgery.1,2 However, the postsurgical outcomes for FCD are reported to be poorer compared to other pathologies.3,4 This is mainly the result of histopathological-based prognostication, which ultimately includes both magnetic resonance imaging (MRI)-positive and MRI-negative FCDs, resulting in a wide range (8.3% to 86.4%) of seizure-free (Engel class I) outcomes. One meta-analysis of 37 studies with histopathological-based prognostication found an overall rate of Engel class I outcome of 55.8% ± 16.2%.5 In routine clinical practice, when a patient presents with intractable epilepsy secondary to FCD, they are MRI-positive. MRI-negative/non-lesional cases are identified only after postsurgical histopathological examination. There is a knowledge gap regarding the postsurgical outcome in a patient with drug-resistant epilepsy who has an MRI lesion consistent with FCD.
To address this gap, the authors performed a systematic review and meta-analysis of the existing literature on intractable pharmacoresistant epilepsy secondary to FCD. Their primary objective was to determine the overall rate of favorable seizure outcomes after surgery for drug-resistant epilepsy associated with MRI-positive or MRI-detected FCD. They also tried to identify predictors of favorable seizure outcomes and determine any effect of MRI quality on favorable seizure outcomes. Their study was done under PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and was registered in the PROSPERO international prospective register of systematic reviews.
The inclusion criteria included randomized controlled trials, cohort studies, or case series of more than 10 patients who underwent resective surgery for drug-resistant epilepsy with MRI-identified FCD and had ≥ 12 months of postsurgical follow-up and a specified study population. Unpublished data, letters, reviews, studies in languages other than English, and studies in patients with FCD and other concomitant epileptogenic lesions (dual pathology or FCD type III) were excluded. When multiple eligible publications reported on the same patients, only the latest publication was included.
From the 3,745 references identified, 3,710 were excluded. Thirty-five studies were included in the meta-analysis, all of good quality according to the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Case Series. These 35 articles consisted of observational case series from tertiary epilepsy centers around the world (11 in Europe, 12 in Asia, nine in North America, two in Australasia, and one in South America).
Data extracted from the 35 articles were publication details and study population characteristics (patient demographics, seizure types, location and extent of the FCD lesion on MRI), use of intracranial electrocencephalogram (EEG) (intraoperative electrocorticography, intracranial or stereo-EEG) before epilepsy surgery, surgical procedure, completeness of FCD resection, FCD histopathologic type, duration of postsurgical follow-up, and postsurgical seizure outcome. The articles were heterogenous: 14/35 focused on postsurgical seizure outcomes in patients with histologically confirmed FCD, 9/35 on utility of specific presurgical investigations, 6/35 on surgical outcomes in specific epilepsy types, 3/35 on effect of volume and completeness of resection on surgical outcomes, 2/35 on surgical outcomes in localized FCD, and 1/35 on neurodevelopmental outcomes of pediatric epilepsy surgery.
For their primary objective, the authors calculated the proportion of patients with drug-resistant epilepsy associated with an MRI-detected FCD who achieved a favorable outcome after epilepsy surgery. Random effects meta-analysis was used to calculate the proportion of patients attaining a favorable outcome. For favorable postsurgical outcome, three definitions were used: 1) seizure-free status; 2) Engel class I outcome; and 3) International League Against Epilepsy (ILAE) class 1 to 2 outcomes during the first ≥ 12 months after epilepsy surgery. Of the 35 studies, 26 used Engel classification, four used ILAE classification, and five reported seizure-free outcomes.
In the studies that used Engel classification, Engel class I generally was used as a synonym for seizure freedom, with only nine studies detailing the proportion of patients who became completely seizure-free after surgery (Engel class IA). The authors found that about 70% of MRI-positive, drug-resistant epilepsy patients had favorable outcomes.
The authors subsequently stratified studies by population age group (adult, pediatric, or mixed ages) and performed meta-analyses of stratified studies. There were a total of 1,353 patients gathered from 35 articles (10 to 136 patients per article); 371 patients from 11/35 articles described postsurgical seizure outcomes in children only, 196 patients from 6/35 articles described postsurgical seizure outcomes in adults only, and 786 patients from 18/35 articles described postsurgical seizure outcomes in mixed adult and pediatric cohorts. Meta-analysis stratified by age group did not show any significant difference in the surgical outcome of FCD-positive cases in these three groups.
It was not possible to determine the effect of MRI quality on favorable seizure outcomes. This was mainly because of marked heterogeneity across the 35 articles regarding MRI techniques: different MRI field strengths, different MRI sequence protocols, and different MRI parameters. Twenty-six studies (26/35) ascertained completeness of FCD resection as determined by histologic examination of the surgical margins, intraoperative MRI, and postoperative MRI, either alone or in combination. In the subgroup analysis, the two factors of complete resection and temporal location of FCD lesion were strongly associated with increased chances of a favorable outcome.
The use and extent of invasive EEG studies in MRI-positive cases, as well as the surgical procedures, varied widely. The study did not find any meta-analytic evidence for prognostic value of invasive intracranial EEG (ICEEG) in MRI-positive FCD in the subgroup analysis. The surgical procedures ranged from 29/35 lesionectomy (with additional corticectomy, amygdalohippocampectomy, or multiple subpial transections in some patients); 12/35 multilobar resection, 10/35 lobectomy, 4/35, hemispherotomy, 2/35 corpus callosotomy, and 1/35 hemispherectomy.
Regarding surgical outcomes, 8/35 studies included data on postsurgical seizure outcome for patients with complete vs. incomplete resection of the MRI-detected FCD. Four studies reported surgical complications separately for MRI-positive cases. Of 118 patients with MRI-detected FCD included in these four studies, 31 (26%) experienced surgical complications; the most common complications were sensorimotor deficits (27 patients, six of whom had permanent deficits), followed by visual deficits (two patients, both with permanent deficits), psychiatric issues (one patient), and empyema (one patient). Postsurgical follow-up in 89% of studies was more than 24 months and more than 61 months in 8/35 articles (23%).
COMMENTARY
This is an important systematic review and meta-analysis that reported 70% of postsurgical patients with MRI-detected FCD had favorable outcomes. This puts the outcome of epilepsy surgery for MRI-positive FCD in line with the favorable outcome rates of well-accepted surgically remediable syndromes such as drug-resistant temporal lobe epilepsy associated with mesial temporal sclerosis, and it is higher than surgical series with histopathologically confirmed FCD (which include both MRI-positive and MRI-negative cases).
Additionally, there was no significant difference in surgical outcomes after stratification by population age groups (adult, pediatric, or mixed ages). The strength of this study is the sample size (> 1,300 patients from around the world) with the majority (89%) of studies having more than 24 months of follow-up. All studies were determined as good-quality studies by the NHLBI Quality Assessment Tool for Case Series. The limitation of the study is that only a few series qualified for subgroup analysis. Expected and in line with previous studies were complete resection and temporal location of FCD lesion being strongly associated with increased chances of a favorable outcome. In general, temporal FCDs can be better appreciated on MRI than those located outside the temporal lobe. Additionally, these findings reinforce the importance of identifying lesions suggestive of FCD on MRI to guide more effective surgical resections.
On the unexpected side, there was no prognostic value of invasive ICEEG in MRI-positive FCD. It is not possible to determine if this could be attributable to the limited number of studies for subgroup analysis. MRI does not always detect the entire extent of focal cortical dysplasia and, therefore, lesion positivity in MRI does not warrant complete resection.6 Further investigations are needed to determine the role of ICEEG in MRI-positive FCD.
REFERENCES
- Blumcke I, Spreafico R, Haaker G, et al. Histopathological findings in brain tissue obtained during epilepsy surgery. N Engl J Med 2017;377:1648-1656.
- Lamberink HJ, Boshuisen K, van Rijen PC, et al. Changing profiles of pediatric epilepsy surgery candidates over time: A nationwide single-center experience from 1990 to 2011. Epilepsia 2015;56:717-725.
- West S, Nolan SJ, Cotton J, et al. Surgery for epilepsy. Cochrane Database Syst Rev 2015; Jul 1:CD010541.
- Lamberink HJ, Otte WM, Blumcke I, Braun KPJ. Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: A retrospective multicentre cohort study. Lancet Neurol 2020;19:748-757.
- Rowland NC, Englot DJ, Cage TA, et al. A meta-analysis of predictors of seizure freedom in the surgical management of focal cortical dysplasia. J Neurosurg 2012;116:1035-1041.
- Yokota H, Uetani H, Tatekawa H, et al. Focal cortical dysplasia imaging discrepancies between MRI and FDG-PET: Unique association with temporal lobe location. Seizure 2020;81:180-185.
