Focal epilepsy caused by single cerebral cavernous malformation (CCM) is associated with regional and global resting state functional connectivity (FC) disruption

• Published in: NeuroImage clinical Vol. 24; p. 102072
• Main Authors: D'Cruz, Jason, Hefner, Matthew, Ledbetter, Christina, Frilot, Clifton, Howard, Brady, Zhu, Peimin, Riel-Romero, Rosario, Notarianni, Christina, Toledo, Eduardo Gonzalez, Nanda, Anil, Sun, Hai
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2019; Elsevier
• Subjects: Adolescent; Adult; Aged; Brain - diagnostic imaging; Brain - physiopathology; Brain - surgery; Brain connectomics; Case-Control Studies; Central Nervous System Neoplasms - complications; Central Nervous System Neoplasms - diagnostic imaging; Central Nervous System Neoplasms - physiopathology; Central Nervous System Neoplasms - surgery; Cerebral cavernous malformation; Default mode network; Drug Resistant Epilepsy - diagnostic imaging; Drug Resistant Epilepsy - etiology; Drug Resistant Epilepsy - physiopathology; Drug Resistant Epilepsy - surgery; Epilepsies, Partial - diagnostic imaging; Epilepsies, Partial - etiology; Epilepsies, Partial - physiopathology; Epilepsies, Partial - surgery; Epileptogenic zone; Female; Focal epilepsy; Functional connectivity; Functional Neuroimaging; Hemangioma, Cavernous, Central Nervous System - complications; Hemangioma, Cavernous, Central Nervous System - diagnostic imaging; Hemangioma, Cavernous, Central Nervous System - physiopathology; Hemangioma, Cavernous, Central Nervous System - surgery; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neural Pathways - diagnostic imaging; Neural Pathways - physiopathology; Neurosurgical Procedures; Radiology; Regular; Resting state functional MRI; Young Adult; Functional connectivity; Default mode network; Focal epilepsy; Resting state functional MRI; Cerebral cavernous malformation; Epileptogenic zone; Brain connectomics
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2019.102072

•To our knowledge, this is the first study to report resting state functional connectivity (FC) abnormalities associated with focal epilepsy caused by a single cerebral cavernous malformation (CCM).•We show, by comparing to the data acquired from the age and gender matched control group, that this type of focal epilepsy is associated with the disruption of the normal regional and global FC. The disruption includes a decrease in the coactivation between the region surrounding the CCM lesion, i.e., the lesional region, and its homotopic counterpart, a reduction in FC between the lesional region and the rest of the brain, and decreased FC among the default mode network (DMN).•These changes may be alleviated or reversed after the surgical resection of the CCM and the epileptogenic zone has successfully stopped recurrent seizures.•Finally, the severity of the FC disruption in the brain tissue adjacent to the CCM may be used to delineate the epileptogenic zone and to aid the surgical resection. Epilepsy, including the type with focal onset, is increasingly viewed as a disorder of the brain network. Here we employed the functional connectivity (FC) metrics estimated from the resting state functional MRI (rsfMRI) to investigate the changes of brain network associated with focal epilepsy caused by single cerebral cavernous malformation (CCM). Eight CCM subjects and 21 age and gender matched controls were enrolled in the study. Seven of 8 CCM subjects underwent surgical resection of the CCM and became seizure free and 4 of the surgical subjects underwent a repeat rsfMRI study. We showed that there was both regional and global disruption of the FC values among the CCM subjects including decreased in homotopic FC (HFC) and global FC (GFC) in the regions of interest (ROIs) where the CCMs were located. There was also the disruption of the default mode network (DMN) especially the FC between the middle prefrontal cortex (MPFC) and the right lateral parietal cortex (LPR) among these individuals. We observed the trend of alleviation of these disruptions after the individual has become seizure free from the surgical resection of the CCM. Using a voxel-based approach, we found the disruption of the HFC and GFC in the brain tissue immediately adjacent to the CCM and the severity of the disruption appeared inversely proportional to the distance of the brain tissue to the lesion. Our findings confirm the disruption of normal brain networks from focal epilepsy, a process that may be reversible with successful surgical treatments rendering patients seizure free. Some voxel-based metrics may help identify the epileptogenic zone and guide the surgical resection.