Abstracts

Rationale: Up to one-third of people with epilepsy worldwide are drug-resistant. For focal epilepsy, resective or ablative surgery confers the best chance of cure for appropriately selected candidates, but many people are not eligible. For the remainder, neuromodulation provides palliative alternatives. Despite good evidence for efficacy of deep brain stimulation of the anterior nucleus of the thalamus, relatively little is known about the details of the role of the thalamus in focal epilepsies, and what the optimal stimulation parameters might be. Hence there is an urgent need for better understanding of the role of the thalamus in focal epilepsy.

Methods: We investigated thalamic ictal neurophysiology and anatomy using invasive (stereo) EEG recordings and MRI, which were obtained during evaluation for drug-resistant focal epilepsy at our institution. Stereo EEG electrodes sampled hypothesized seizure onset zones as well as sparsely spatial sampling thalamic structures based on clinical judgement. The presence or absence of a corresponding thalamic ictal discharge with cortical discharge was characterized using time domain and spectral features. Brain MRI was co-registered with post-operative CT for electrode localization.

Results: Seven subjects were studied in total, with 2 to 13 seizures analyzed from each patient, for a total of 46 seizures. Stereo EEG electrodes sampled both temporal and extra-temporal SOZ. The sampled thalamic nuclei included mediodorsal (5/7), centrolateral (5/7), ventral lateral (5/7), anterior (2/7), pulvinar (2/7), ventral anterior (1/7), and lateral posterior (1/7).

A distinct spectral seizure discharge signature was noted in the thalamus in all patients for at least one seizure type. In patients with multifocal seizure onset zones, distinct thalamic activation patterns – spectral and anatomical - were seen corresponding to distinct cortical SOZ. Across different patients, SOZ from the same cortical lobe appeared to preferentially activate different thalamic nuclei. Finally, different clinical semiology – subclinical vs focal vs evolution to bilateral tonic-clonic – were associated with distinct thalamic activation patterns in five of the seven cases.

Figure: Top - 3D rendering of sEEG lead with the thalamus, Bottom - EEG and spectral plots of seizure discharge in cortex and thalamus.
Table: Thalamic and cotical seizure discharge patterns.

Conclusions: A wide range of thalamic nuclei are consistently recruited in focal temporal and extratemporal lobe seizures. The degree and pattern of thalamic involvement varies between patients, and between different seizure types within individual patients. These findings represent a wider spectrum of thalamocortical network involvement in focal seizures than may generally be assumed, and is relevant both for future potential targets for neuromodulation, as well as for invasive monitoring of drug-resistant focal epilepsy patients in routine clinical care.

Funding: Please list any funding that was received in support of this abstract.: The support of NIH UH3-NS095495 “Neurophysiologically Based Brain State Tracking & Modulation in Focal Epilepsy” is acknowledged.