Mapping Lesion-Related Epilepsy to a Human Brain Network

Abstract

ImportanceIt remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions.ObjectiveTo assess whether lesion locations associated with epilepsy map to specific brain regions and networks.Design, Setting, and ParticipantsThis case-control study used lesion location and lesion network mapping to identify the brain regions and networks associated with epilepsy in a discovery data set of patients with poststroke epilepsy and control patients with stroke. Patients with stroke lesions and epilepsy (n = 76) or no epilepsy (n = 625) were included. Generalizability to other lesion types was assessed using 4 independent cohorts as validation data sets. The total numbers of patients across all datasets (both discovery and validation datasets) were 347 with epilepsy and 1126 without. Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data were analyzed from September 2018 through December 2022. All shared patient data were analyzed and included; no patients were excluded.Main Outcomes and MeasuresEpilepsy or no epilepsy.ResultsLesion locations from 76 patients with poststroke epilepsy (39 [51%] male; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2.0] years) and 625 control patients with stroke (366 [59%] male; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the discovery data set. Lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity to the basal ganglia and cerebellum. Findings were validated in 4 independent cohorts including 772 patients with brain lesions (271 [35%] with epilepsy; 515 [67%] male; median [IQR] age, 60 [50-70] years; follow-up range, 3-35 years). Lesion connectivity to this brain network was associated with increased risk of epilepsy after stroke (odds ratio [OR], 2.82; 95% CI, 2.02-4.10; P < .001) and across different lesion types (OR, 2.85; 95% CI, 2.23-3.69; P < .001). Deep brain stimulation site connectivity to this same network was associated with improved seizure control (r, 0.63; P < .001) in 30 patients with drug-resistant epilepsy (21 [70%] male; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months).Conclusions and RelevanceThe findings in this study indicate that lesion-related epilepsy mapped to a human brain network, which could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies.

Seizing the Brain Networks in Lesional Focal Epilepsies

“… 6 Similar to these, authors found that after stroke, bigger lesions and higher cortical damage were associated with a higher epilepsy risk, while subcortical damage was associated with a reduced epilepsy risk. 5 Contrary to previous literature, authors found no difference in epilepsy risk based on vascular territory or lobar location. 5 They controlled all further analyses for these potential risk factors for post-stroke epilepsy.…”

“…3 Over the past decade, the notion that epileptogenicity in both lesional and nonlesional focal epilepsies is distributed across an epileptic network has become more widely accepted. 4 In this case-control study, 5 Schaper et al build upon the existing understanding of epilepsy networks and attempt to answer an exciting question using advanced lesion location and lesion network mapping techniques: Does lesion-related epilepsy across various etiologies and locations map to specific brain networks? The authors compared patients with poststroke epilepsy in the discovery dataset to controls who had strokes but did not develop epilepsy.…”

“…External validation to assess the generalizability of results to other lesion types, including hematomas, trauma, tumors, and tubers, was examined in 4 independent datasets. 5 Lesion size, lobar location, vascular territory, and cortical involvement have often been identified as risk factors for poststroke epilepsy. 6 SeLECT score, an internationally validated multivariate prediction model, showed that severity of stroke based on higher NIHSS scores, larger lesions, cortical involvement, early seizures, large-artery atherosclerotic etiology, and middle cerebral artery territory involvement are factors predictive of post-stroke epilepsy.…”

“…External validation to assess the generalizability of results to other lesion types, including hematomas, trauma, tumors, and tubers, was examined in 4 independent datasets. 5 …”

Abolition of seizures following Forel‐H‐tomy for drug‐resistant epilepsy: A case report

“…This is due to its role as a convergent point of the pallidothalamic tract from the globus pallidus interna (GPi) to the thalamus in the basal ganglia‐thalamocortical circuit (BTCC) 5 . Recent studies have highlighted the involvement of the basal ganglia in the pathogenesis of FBTCS, seizure termination, and the network of poststroke epilepsy 6–9 . This has led to a growing understanding of the potential therapeutic effects of Forel‐H‐tomy on epilepsy.…”