Authors :
Presenting Author: Elena Pasini, MD – IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center (full member of the European Reference Network EpiCARE), Bologna, Italy
Matteo Martinoni, MD – IRCCS Istituto delle Scienze Neurologiche di Bologna, Neurosurgical Unit, Bologna, Italy
Elena Cantoni, PhD – IRCCS Istituto delle Scienze Neurologiche di Bologna, Functional and Molecular Neuroimaging Program, Bologna, Italy
Gianfranco Vornetti, MD, PhD – IRCCS Istituto delle Scienze Neurologiche di Bologna, Functional and Molecular Neuroimaging Program, Bologna and Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Italy
Lorenzo Ferri, MD, PhD – IRCCS Istituto delle Scienze Neurologiche di Bologna, Epilepsy Center (full member of the European Reference Network EpiCARE), Bologna, Italy
Sofia Asioli, MD, PhD – Department of Biomedical and Neuromotor Sciences (DIBINEM)- Alma Mater Studiorum- University of Bologna. IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Diagnostica Neuropatologica dei Tumori Cerebrali
Francesca Bisulli, MD – Department of Biomedical and NeuroMotor Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
Caterina Tonon, MD, PhD – IRCCS Istituto delle Scienze Neurologiche di Bologna, Functional and Molecular Neuroimaging Program, Bologna and Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Italy
Rationale:
The limbic system is a group of different cerebral structures strictly involved in feelings reactions, behavioural responses and memory processing. Seizures involving this network can arise autonomic, psychic, as well as motor symptoms. Moreover, limbic epilepsies are known to generate chronic disruption of interictal emotional state with a higher prevalence of anxiety, fear and depression. Surgical treatment for epilepsy can alter the balance between different structures in both hemispheres giving rise to psychiatric symptoms, which maybe better understood thanks to structural connectivity studies.
Methods:
We report a right-handed woman affected since the age of 13 years by multi-daily gelastic seizures, subjectively correlated with terror and brief loss of consciousness. A misdiagnosis of anxiety disorder delayed the correct identification of epilepsy for over 30 years and when she finally was diagnosed epileptic, she was discovered to have a focal cortical dysplasia of the left anterior cingulate cortex. She subsequently underwent lesionectomy guided by intraoperative SEEG monitoring.
The patient-specific MRI study employs an advanced DTI-multishell sequence b=0,300,1000,2000s/mm2 to estimate whole-brain tractogram generating 10 million streamlines using MRtrix3 iFOD2 probabilistic algorithm acquired on a 3 Tesla MRI-scanner pre and post-surgery (PRE, POST). Twenty-two regions of interest involved in limbic system were extracted from FreeSurfer cortical and subcortical parcellation. Percentual difference of structural connectivity (SC) and Strength metric (Str) from graph theory were calculated between pre- and post-surgery acquisitions (15 months apart).
Results:
Following surgery the patient showed an optimum seizure outcome (ILAE score 1), but she developed major depression requiring medical therapy.
The comparison between PRE and POST limbic fiber connectivity using DTI techniques highlighted significant loss of post-surgical SC of the left lateral orbitofrontal cortex, and to a lesser extent, of the right amygdala (Fig. 1).
Marked percentage decrease in the left lateral orbitofrontal cortex Str was observed after surgery.
Additionally, the distribution of SC within the left limbic network was right-skewed in the PRE study, while the POST study showed comparable distributions in both hemispheres (Fig.2).
Conclusions:
Orbitofrontal cortex, as well as the anterior cingulate and the amygdala, are known to be involved in the depression’s network also if the exact mechanisms are far from being clarified. Changing the balance between node’s connection may explain the huge dichotomic symptomatology during seizure and subsequently the depression after the epileptic network disconnection. We infer that the last may explain the occurrence of psychiatric symptoms after epilepsy surgery, previously attributed to forced normalization.
Moreover, the pre-surgical left epileptic limbic network showed a higher number of nodes compared to the right one, suggesting that epileptogenic networks may have redundant pathways or connections that contribute to seizure propagation which tend to normalize after the removal of the lesion.
Funding: Italian Ministry of Health–Ricerca Corrente