Roughly one out of every two patients with drug-resistant temporal lobe epilepsy will not become completely seizure-free after temporal lobe surgery. The reasons for this remain unclear and are most likely due to multiple factors. Preoperative automated fiber quantification (AFQ), however, may predict postoperative seizure outcome in patients with temporal lobe epilepsy, according to a study published online ahead of print November 15, 2016, in Brain.
“We have identified three important factors that contribute to persistent postoperative seizures: diffusion abnormalities of the ipsilateral dorsal fornix outside the future margins of resection, diffusion abnormalities of the contralateral parahippocampal white matter bundle, and insufficient resection of the uncinate fasciculus,” said lead author Simon S. Keller, MSc, PhD, and colleagues. Dr. Keller is a Lecturer in Molecular and Clinical Pharmacology at the University of Liverpool in the United Kingdom. “These results may have the potential to be developed into imaging prognostic markers of postoperative outcome and provide new insights for why some patients with temporal lobe epilepsy continue to experience postoperative seizures.”
Simon S. Keller, MSc, PhD
Sensitive Imaging Technology
MRI techniques such as quantitative volumetric imaging have provided limited insight into what causes recurrent seizures after temporal lobe surgery. AFQ is a diffusion tensor imaging (DTI) tractography technique that permits a comprehensive analysis of tissue characteristics along the length of white matter tract bundles. This technique may allow for a more sensitive measure of neuroanatomic white matter alterations in patients with neurologic disorders than whole-tract approaches.
Dr. Keller and colleagues conducted a comprehensive DTI study to evaluate the local tissue physical characteristics of preoperative temporal lobe white matter tracts by applying DTI and AFQ in patients with temporal lobe epilepsy who underwent surgical treatment and postoperative follow-up. The primary goal of their research was to identify preoperative diffusion markers of postoperative seizure outcome. Their secondary goal was to determine whether the extent of resection of the temporal lobe tract bundles was associated with seizure outcome.
Forty-three patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis and 44 healthy controls were included in the study. Patients underwent preoperative imaging, amygdalohippocampectomy, and postoperative assessment using the International League Against Epilepsy seizure outcome scale. The fimbria-fornix, parahippocampal, white matter bundle, and uncinate fasciculus were reconstructed from preoperative imaging. In addition, scalar diffusion metrics were calculated along the length of each tract.
Reliable Biomarkers
Results revealed that 51.2% of patients had a completely seizure-free outcome, and 48.8% of patients had persistent postoperative seizures. More men were rendered seizure-free, relative to women. Compared to controls, both patient groups showed strong and significant diffusion abnormalities along the length of the uncinate bilaterally, the ipsilateral parahippocampal white matter bundle, and the ipsilateral fimbria-fornix in regions located within the medial temporal lobe.
However, only patients with persistent postoperative seizures showed evidence of significant pathology of tract sections located in the ipsilateral dorsal fornix and in the contralateral parahippocampal white matter bundle. Using receiver operating characteristic curves, diffusion characteristics of these regions could project individual patient outcomes with 84% sensitivity and 89% specificity.
Pathologic changes in the dorsal fornix were observed beyond the margins of resection. In addition, contralateral parahippocampal changes may suggest a bitemporal disorder in some patients. Diffusion characteristics of the ipsilateral uncinate could potentially classify patients from controls with a sensitivity of 98%.
By coregistering the preoperative fiber maps to postoperative surgical lacuna maps, Dr. Keller and colleagues observed that the extent of the surgical uncinate resection was significantly greater in patients who were rendered seizure-free, suggesting that a smaller surgical resection of the uncinate may represent insufficient disconnection of an anterior temporal epileptogenic network.
“An important future step will be to perform a pragmatic prospective study of consecutive patients with consideration of these new findings,” said Dr. Keller and colleagues.
—Erica Tricarico
Suggested Reading
Keller SS, Glenn RG, Weber B, et al. Preoperative automated fibre quantification predicts postoperative seizure outcome in temporal lobe epilepsy. Brain. 2016 Nov 15 [Epub ahead of print].