Abstract
Approximately one in every two patients with pharmacoresistant temporal lobe epilepsy will not be rendered completely seizure-free after temporal lobe surgery. The reasons for this are unknown and are likely to be multifactorial. Quantitative volumetric magnetic resonance imaging techniques have provided limited insight into the causes of persistent postoperative seizures in patients with temporal lobe epilepsy. The relationship between postoperative outcome and preoperative pathology of white matter tracts, which constitute crucial components of epileptogenic networks, is unknown. We investigated regional tissue characteristics of preoperative temporal lobe white matter tracts known to be important in the generation and propagation of temporal lobe seizures in temporal lobe epilepsy, using diffusion tensor imaging and automated fibre quantification. We studied 43 patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis and 44 healthy controls. Patients underwent preoperative imaging, amygdalohippocampectomy and postoperative assessment using the International League Against Epilepsy seizure outcome scale. From preoperative imaging, the fimbria-fornix, parahippocampal white matter bundle and uncinate fasciculus were reconstructed, and scalar diffusion metrics were calculated along the length of each tract. Altogether, 51.2% of patients were rendered completely seizure-free and 48.8% continued to experience postoperative seizure symptoms. Relative to controls, both patient groups exhibited 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 classify individual patients according to outcome with 84% sensitivity and 89% specificity. Pathological changes in the dorsal fornix were beyond the margins of resection, and contralateral parahippocampal changes may suggest a bitemporal disorder in some patients. Furthermore, diffusion characteristics of the ipsilateral uncinate could classify patients from controls with a sensitivity of 98%; importantly, by co-registering the preoperative fibre maps to postoperative surgical lacuna maps, we observed that the extent of uncinate resection was significantly greater in patients who were rendered seizure-free, suggesting that a smaller resection of the uncinate may represent insufficient disconnection of an anterior temporal epileptogenic network. 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.
Highlights
Epilepsy is the most common serious neurological disorder, affecting over 50 million people worldwide (Ngugi et al, 2010; Neligan et al, 2012)
In the only randomized controlled trial of surgery for refractory Temporal lobe epilepsy (TLE), it was reported that surgical intervention is significantly superior for the attainment of seizure freedom 1 year after surgery compared to continuing pharmacological treatment (Wiebe et al, 2001); at 1 year, 58% of patients receiving surgery were free from seizures impairing awareness and 38% were free from any seizure-related symptom, whereas only 8% were seizure-free in the nonsurgical control group
We focused on three temporal lobe tract bundles that are known to be important in the generation and propagation of temporal lobe seizures and susceptible to pathological alterations in refractory TLE: the fimbriafornix (Concha et al, 2005, 2009, 2010), parahippocampal white matter bundle (McDonald et al, 2008; Yogarajah et al, 2008; Ahmadi et al, 2009; Keller et al, 2012) and uncinate fasciculus (Diehl et al, 2008; Lin et al, 2008; Ahmadi et al, 2009)
Summary
Epilepsy is the most common serious neurological disorder, affecting over 50 million people worldwide (Ngugi et al, 2010; Neligan et al, 2012). Temporal lobe epilepsy (TLE) is the most common pharmacoresistant focal epilepsy disorder (Semah et al, 1998; Engel, 2001) and is potentially remediable by neurosurgical intervention. There are contrasting reports regarding the proportion of patients attaining seizure freedom after temporal lobe surgery for refractory seizures, which may range from 35 to 80% (Berkovic et al, 1995; Wiebe et al, 2001; McIntosh et al, 2004; de Tisi et al, 2011; Giulioni et al, 2013; Hemb et al, 2013). The development of predictive biomarkers for the future success of surgical intervention in epilepsy represents an important research endeavour, as a reliable prognostic marker could inform patient clinical management and surgical decision-making
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