Intraoperative changes in large-scale thalamic circuitry following laser ablation of hypothalamic hamartomas

Karim Mithani; Oliver L Richards; Mark Ebden; Noor Malik; Ladina Greuter; Hrishikesh Suresh; Farbod Niazi; Flavia Venetucci Gouveia; Elysa Widjaja; Shelly Weiss; Elizabeth Donner; Hiroshi Otsubo; Ayako Ochi; Puneet Jain; Ivanna Yau; Elizabeth N Kerr; James T Rutka; James M Drake; Alexander G Weil; George M Ibrahim

doi:10.1016/j.nicl.2024.103613

Intraoperative changes in large-scale thalamic circuitry following laser ablation of hypothalamic hamartomas

Neuroimage Clin. 2024 May 1:42:103613. doi: 10.1016/j.nicl.2024.103613. Online ahead of print.

Authors

Karim Mithani¹, Oliver L Richards², Mark Ebden³, Noor Malik², Ladina Greuter², Hrishikesh Suresh², Farbod Niazi⁴, Flavia Venetucci Gouveia³, Elysa Widjaja⁵, Shelly Weiss⁶, Elizabeth Donner⁶, Hiroshi Otsubo⁶, Ayako Ochi⁶, Puneet Jain⁶, Ivanna Yau⁶, Elizabeth N Kerr⁷, James T Rutka², James M Drake², Alexander G Weil⁸, George M Ibrahim⁹

Affiliations

¹ Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: karim.mithani@utoronto.ca.
² Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada.
³ Neurosciences & Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.
⁴ Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
⁵ Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada.
⁶ Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
⁷ Department of Psychology, Hospital for Sick Children, Toronto, Ontario, Canada.
⁸ Division of Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
⁹ Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada; Neurosciences & Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.

Abstract

Background and objectives: Gelastic seizures due to hypothalamic hamartomas (HH) are challenging to treat, in part due to an incomplete understanding of seizure propagation pathways. Although magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) is a promising intervention to disconnect HH from ictal propagation networks, the optimal site of ablation to achieve seizure freedom is not known. In this study, we investigated intraoperative post-ablation changes in resting-state functional connectivity to identify large-scale networks associated with successful disconnection of HH.

Methods: Children who underwent MRgLITT for HH at two institutions were consecutively recruited and followed for a minimum of one year. Seizure freedom was defined as Engel score of 1A at the last available follow-up. Immediate pre- and post- ablation resting-state functional MRI scans were acquired while maintaining a constant depth of general anesthetic. Multivariable generalized linear models were used to identify intraoperative changes in large-scale connectivity associated with seizure outcomes.

Results: Twelve patients underwent MRgLITT for HH, five of whom were seizure-free at their last follow-up. Intraprocedural changes in thalamocortical circuitry involving the anterior cingulate cortex were associated with seizure-freedom. Children who were seizure-free demonstrated an increase and decrease in connectivity to the pregenual and dorsal anterior cingulate cortices, respectively. In addition, children who became seizure-free demonstrated increased thalamic connectivity to the periaqueductal gray immediately following MRgLITT.

Discussion: Successful disconnection of HH is associated with intraoperative, large-scale changes in thalamocortical connectivity. These changes provide novel insights into the large-scale basis of gelastic seizures and may represent intraoperative biomarkers of treatment success.

Keywords: Connectomics; Epilepsy Surgery; Gelastic epilepsy; Hypothalamic hamartoma; Laser interstitial thermal therapy; Pathologic laughter.