Structural and Functional Imaging ‘Phenotypes’ in Refractory Temporal Lobe Epilepsy Patients
By Kimberly Pargeon, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Pargeon reports no financial relationships relevant to this field of study.
SYNOPSIS: Using high-resolution 3-T magnetic resonance imaging, temporal lobe epilepsy-hippocampal sclerosis showed significant preoperative ipsilateral volume loss, T2 hyperintensity, and mean diffusivity increases across all subfields, with the greatest effects seen anteriorly. However, temporal lobe epilepsy-gliosis showed increased volume in the dentate gyrus bilaterally, and more focal and subtle increases in T2 intensity and mean diffusivity.
SOURCE: Bernhardt BC, Bernasconi A, Liu M, et al. The spectrum of structural and functional imaging abnormalities in temporal lobe epilepsy. Ann Neurol 2016;80:142-153.
Temporal lobe epilepsy (TLE) is the most common cause of refractory epilepsy in adults, with up to 20% of patients having continued seizures, despite adequate trials of antiepileptic medications.1 Many of these patients may be appropriate surgical candidates with either standard anterior temporal lobectomy or selective amygdalohippocampectomy, but the success of surgery is highly dependent on the presurgical evaluation, which is aimed at accurately identifying the epileptogenic zone and predicting postoperative complications. This process can include both structural and functional imaging.1
The most common pathological finding in refractory TLE is hippocampal sclerosis (TLE-HS), characterized radiographically by hippocampal atrophy, increased T2 signal, and increased tissue diffusivity. These imaging markers are notably absent in up to half of patients, sometimes leading to delays in surgery, and even when surgery is performed, postoperative seizure recurrence may be higher. For these patients, there may be no apparent cell loss, but instead there may be isolated gliosis (TLE-G). There also seems to be some mounting evidence that TLE is associated with abnormalities in functional network connections, particularly one called the default mode network (DMN), involving areas of the temporal, parietal, and frontal lobes, and appearing to play a role in internal thought processing.2
The goal of the present study was to identify unique structural and functional imaging “phenotypes” in patients with clearly defined TLE-HS and TLE-G. Thirty-nine consecutive medically refractory TLE patients treated from 2008 to 2014 were selected from a hospital database in Montreal. All patients underwent a research-dedicated high-resolution 3T brain MRI, had a selective amygdalohippocampectomy with a clear pathological diagnosis, and did not have an alternate etiology for their refractory TLE. Based on histopathology, 20 patients had hippocampal sclerosis (TLE-HS) and 19 patients had only gliosis (TLE-G). The groups were comparable in age, epilepsy duration, age at seizure onset, monthly seizure frequency, and seizure semiologies. However, TLE-HS had a tendency for a higher prevalence of febrile seizures, more male subjects, more generalized tonic-clonic seizures, and a higher, though nonsignificant, rate of postoperative seizure freedom.
The authors gave a detailed description of the MRI acquisition, preprocessing, subfield mapping, and final analyses. For all comparisons, the hippocampus was divided into three consistently identifiable subfields, specifically CA1-3, CA4-dentate gyrus (DG), and subicular complex. Each group was compared to a control group (sex- and age-matched) and then to one another. Relative to controls, the primary finding was that TLE-HS typically presented with significant and only ipsilateral hippocampal atrophy affecting all subfields, whereas TLE-G presented with increased volumes within the CA4-DG bilaterally. TLE-HS also showed marked bilateral increases in T2 intensity and mean diffusivity (MD) with the highest effects in the ipsilateral CA1-3 and CA4-DG, whereas TLE-G showed subtler ipsilateral increases. When comparing the groups, the TLE-HS still showed significant ipsilateral atrophy and MD increases across all fields, but the T2 increases were only seen in the anterior ipsilateral CA1-3 subfield.
When evaluating hippocampal functional connectivity, TLE-G showed only subtle disruptions, which were localized to the subiculum. However, TLE-HS demonstrated significant “reconfigurations” of hippocampal networks, typically with decreased connectivity between areas of the DMN, including connections to the ipsilateral anterior and dorsal medial prefrontal cortex. In addition, patients with higher hippocampal T2 signal and atrophy seemed more likely to have associated “functional disconnections” from key structures in this so-called DMN.
Per the authors, “best practice” radiological studies can fail to show a pathological lesion in up to 50% of patients. Thus, the primary goal of this study was to determine “phenotypes” associated with two of the more common pathological diagnoses in TLE from high-resolution imaging. As described above, the authors were able to delineate some clear structural and functional imaging characteristics associated with TLE-HS with subtler findings associated with TLE-G. Prior to surgery, this type of detailed analysis could be used to determine the potential histopathological diagnosis. This could be applied in imaging “negative” cases, which may represent early or subtle instances of TLE-HS. Findings could then be used to determine treatment options and to better predict postoperative prognosis. In addition, as the authors mention, in instances where histopathology may be unobtainable, such as with thermal ablation, these techniques could possibly be used instead.
However, there are some drawbacks. First, this type of “research-dedicated” imaging would not be readily available in all locations. In addition, the analysis, including the preprocessing and subfield mapping, would not be a service provided by all radiology departments and likely would be performed by the treating team. Although these analyses usually utilize freely available software, they often are complicated, multi-step processes and can lead to errors. Finally, insurance companies do not support some types of specialized imaging, including some functional imaging. Regardless of its present clinical applicability, this study sheds some interesting light on the idea of TLE as a heterogeneous disorder, likely representing a “spectrum.”
- Stylianou P, Hoffmann C, Blat, Harnof S. Neuroimaging for patient selection for medial temporal lobe epilepsy surgery: Part 1 structural neuroimaging. J Clin Neurosci 2016;23:14-22.
Using high-resolution 3-T magnetic resonance imaging, temporal lobe epilepsy-hippocampal sclerosis showed significant preoperative ipsilateral volume loss, T2 hyperintensity, and mean diffusivity increases across all subfields, with the greatest effects seen anteriorly. However, temporal lobe epilepsy-gliosis showed increased volume in the dentate gyrus bilaterally, and more focal and subtle increases in T2 intensity and mean diffusivity.
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