Thalamostriatal disconnection underpins long-term seizure freedom in frontal lobe epilepsy surgery

Abstract

Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom.

Structural networking of the developing brain: from maturation to neurosurgical implications

“…More recently, Giampiccolo et al (2023) performed a retrospective analysis of the patterns of disconnection associated with long-term seizure outcome in a series of 47 patients who underwent surgery for frontal lobe epilepsy. The Authors found a significant correlation between seizure freedom and disconnection of the anterior thalamic radiation and the cortico-striatal tract, indicating the role of these pathways in the development of novel epileptic networks at the base of seizure recurrence.…”

Epilepsy Networks and Their Surgical Relevance

“…Similar to temporal lobe epilepsy, such concepts may be applied to other regions. Giampiccolo et al used tractography in 47 patients undergoing frontal lobectomy to identify the "disconnectome" and predict late seizure recurrence [33]. They found that long-term seizure freedom as durable as five years was associated with the disconnection of anterior thalamic and corticostriatal fibers.…”

A review of cell-type specific circuit mechanisms underlying epilepsy

“…Modulating these nodes may potentially modify epilepsy transmission [17]. Epileptic patients have a network of connections in the brain associated with seizures, and by selectively interrupting specific pathways (such as the thalamus or striatum to the frontal lobe), may enable patients to achieve long-term freedom from seizures [18]. One of the principles of epilepsy surgery or deep brain stimulation (DBS) for epilepsy is to desynchronize the epileptogenic neural network by influencing the activity of key nodes in the epilepsy network [19].…”