| Key points |
Does injury-related epilepsy map to a brain network? Findings In this case-control study of lesion locations in patients who did or did not develop epilepsy, lesions associated with epilepsy occurred in multiple heterogeneous brain locations. However, these same lesion locations were part of a specific brain network defined by functional connectivity with the basal ganglia and cerebellum, and deep brain stimulation sites associated with seizure control were connected to this same network. Meaning The findings indicate that injury-related epilepsy mapped to a brain network that could help identify patients at risk for epilepsy after brain injury and guide brain stimulation therapies. |
Focal epilepsy affects more than 30 million patients worldwide and is usually caused by brain injuries, such as stroke. However, it is unclear why some lesion sites cause epilepsy and others do not.
Identifying the locations of lesions with greater or lesser risk of epilepsy is important for 3 reasons.
1. First, it can help refine models designed to predict epilepsy risk, allowing for better prognosis or early intervention.
2. Second, it may provide mechanistic insight into why some lesion locations, but not others, lead to epilepsy.
3. Third, brain lesions can help identify or refine therapeutic targets for brain stimulation and played a role in the identification of the thalamus as a therapeutic target for epilepsy.
Since the outcomes of brain stimulation in epilepsy remain heterogeneous, mapping lesions that do or do not cause epilepsy may help identify regions or networks that could be targeted for seizure control.
Lesion mapping methods have improved in recent years. Voxel-based lesion symptom mapping can assess whether lesions causing a specific symptom intersect with specific brain regions.
Lesion network mapping can test whether lesions causing a specific symptom intersect with specific brain networks and can therefore detect associations that go beyond individual brain regions. This latter technique uses a wiring diagram of the human brain called the human connectome to identify common network connections across different lesion locations.
It has proven to be particularly useful when lesions in different locations cause a similar symptom and has identified effective therapeutic targets for brain stimulation. Here, we use these lesion mapping techniques to evaluate whether the locations of epilepsy-associated lesions map to specific brain regions and networks.
| Importance |
It is not clear why lesions in some places cause epilepsy while others do not. Identifying brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions.
| Aim |
To evaluate whether the locations of lesions associated with epilepsy map to specific brain regions and networks.
| Design, environment and participants |
This case-control study used lesion location and lesion network mapping to identify brain regions and networks associated with epilepsy in a discovery data set of post-stroke epilepsy patients and stroke patients. control with stroke.
Patients with stroke injuries and epilepsy (n = 76) or without epilepsy (n = 625) were included. Generalization to other injury types was assessed using 4 independent cohorts as validation data sets. The total number of patients in all data sets (both discovery and validation data sets) was 347 with epilepsy and 1126 without epilepsy.
Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data was analyzed from September 2018 to December 2022. All shared patient data was analyzed and included; no patient was excluded.
| Main results and measures |
Epilepsy or not epilepsy.
| Results |
Lesion locations of 76 patients with post-stroke epilepsy (39 [51%] men; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2, 0] years) and 625 control stroke patients (366 [59%] men; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the set. discovery data.
Lesions associated with epilepsy occurred in multiple heterogeneous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity with the basal ganglia and cerebellum.
Findings were validated in 4 independent cohorts that included 772 brain-injured patients (271 [35%] with epilepsy; 515 [67%] men; median [IQR] age, 60 [50-70] years; follow-up range, 3- 35 years). P < 0.001) and in different types of injuries (OR, 2.85; 95% CI, 2.23-3.69; P < 0.001).
Deep brain stimulation site connectivity to this same network was associated with better seizure control (r, 0.63; p < 0.001) in 30 patients with drug-resistant epilepsy (21 [70%] men; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months).
| Conclusions and relevance |
The findings of this study indicate that injury-related epilepsy was mapped to a human brain network, which could help identify patients at risk for epilepsy after brain injury and guide brain stimulation therapies.
