Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia: A MELD study

Abstract

Objective: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome.

Methods: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom.

Results: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%.

Significance: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counseling in epilepsy.

Keywords: MRI; drug-resistant epilepsy; focal cortical dysplasia; lesions; neurosurgery.

FIGURE 1

Distribution of focal cortical dysplasia (FCD) lesions across the cerebral cortex. (A) All FCD lesion masks mapped to the left hemisphere of the template cortical surface. The distribution of FCDs across the cerebral cortex is nonuniform, with higher concentrations in the superior frontal sulcus, frontal pole, temporal pole, and superior temporal gyrus. (B) Three‐dimensional lesion likelihood atlas. Aggregated surface‐based lesion map values were normalized to between 0 and 1 and mapped back to the template magnetic resonance imaging volume. (C) Sample size required for consistent FCD lesion map. Rank correlation (y axis) was calculated by comparing the lesion map from a smaller cohort to a larger withheld cohort (n = 250). r_rank increased with sample size. Predictive learning curve (red line) estimated that a stable map of lesion distribution requires a sample size of n = 400. (D) Distribution of FCD lesions according to histopathological subtype. (E) Distributions of lesions across cortical lobes within each FCD histopathological subtype. The width of bars indicates the relative numbers of patients. Temporal lobe lesions made up larger proportions of FCD Types I and III, whereas frontal lobe lesions were more likely to be FCD Types IIA and IIB

FIGURE 2

Presurgical factors associated with lesion location. Surface‐based maps show distribution of demographic variables according to lesion location. The color at each vertex represents the average variable value for patients with overlapping lesions. Vertices where the presence of a focal lesion was significantly associated with that variable are delineated in red. Factors significantly (p < .01) associated with lesion location were (Ai) age at epilepsy onset, (Bi) duration of epilepsy, and (Bii) lesion size. (Aiii) Correlation between the sensorimotor‐association axis of cortical organization (Aii) and the age at epilepsy onset (Ai) maps in comparison to spatially permuted maps. Lesions in primary areas were associated with a younger age at onset, whereas association areas had older ages of onset (r_rank  = 0.39, p_spin  < .01). (Biii) Correlation between the duration of epilepsy (Bi) and lesion size (Bii) maps in comparison to spatially permuted maps. Mean duration was significantly negatively correlated with the size of epilepsy lesion, where cortical areas with smaller lesions, for example, precentral and frontal areas, were associated with a longer duration of epilepsy, whereas areas with larger lesions, for example, occipital cortex, had shorter durations of epilepsy (r_rank  = −0.42, p_spin  < .05)

FIGURE 3

Effect of lesion location, duration of epilepsy, and histopathological subtype on seizure freedom. (Ai) Percentage of patients seizure‐free (%) according to lesion location across the cerebral cortex. Visual, motor, and premotor areas had a low percentage of seizure‐free patients (30%–40%). (Aii) Mask of eloquent cortex. (B) Impact of overlap of lesion with eloquent cortex and magnetic resonance imaging scanner field strength on likelihood of seizure freedom. (C) Impact of duration and histopathology on predicted percentage likelihood of seizure freedom. FCD, focal cortical dysplasia; NA, not available

FIGURE 4

Interrelationships between features. (A) Pairwise comparison of demographic and clinical features. Significant relationships after correction for multiple comparisons are shown in yellow. (B) Statistical test used for each pairwise comparison. (C) Distributions of age at epilepsy onset, age at magnetic resonance imaging (MRI) scan, and duration of epilepsy. (D) Duration of epilepsy is significantly associated with seizure freedom (t = −3.0, p < .001). Patients with longer durations of epilepsy are less likely to be seizure‐free. (E) Age at epilepsy onset, lesion size (as a percentage of the total hemisphere size), and seizure freedom are significantly associated. Larger lesions are associated with younger age at epilepsy onset (r = −0.24, p < .001) and are more likely to be operated on (t = 3.69, p < .001). Similarly, patients with a younger age at epilepsy onset are more likely to be operated on (t = −3.76, p < .001). Anova, analysis of variance; Na, not applicable