No abstract

At least 50% of patients with tuberous sclerosis complex present with intractable epilepsy; for these patients, resective surgery is a treatment option. Here, we report a nationwide multicentre retrospective study and analyse the long-term seizure and neuropsychological outcomes of epilepsy surgery in patients with tuberous sclerosis complex. There were 364 patients who underwent epilepsy surgery in the study. Patients’ clinical data, postoperative seizure outcomes at 1-, 4-, and 10-year follow-ups, preoperative and postoperative intelligence quotients, and quality of life at 1-year follow-up were collected. The patients’ ages at surgery were 10.35 ± 7.70 years (range: 0.5–47). The percentage of postoperative seizure freedom was 71% (258/364) at 1-year, 60% (118/196) at 4-year, and 51% (36/71) at 10-year follow-up. Influence factors of postoperative seizure freedom were the total removal of epileptogenic tubers and the presence of outstanding tuber on MRI at 1- and 4-year follow-ups. Furthermore, monthly seizure (versus daily seizure) was also a positive influence factor for postoperative seizure freedom at 1-year follow-up. The presence of an outstanding tuber on MRI was the only factor influencing seizure freedom at 10-year follow-up. Postoperative quality of life and intelligence quotient improvements were found in 43% (112/262) and 28% (67/242) of patients, respectively. Influence factors of postoperative quality of life and intelligence quotient improvement were postoperative seizure freedom and preoperative low intelligence quotient. The percentage of seizure freedom in the tuberectomy group was significantly lower compared to the tuberectomy plus and lobectomy groups at 1- and 4-year follow-ups. In conclusion, this study, the largest nationwide multi-centre study on resective epilepsy surgery, resulted in improved seizure outcomes and quality of life and intelligence quotient improvements in patients with tuberous sclerosis complex. Seizure freedom was often achieved in patients with an outstanding tuber on MRI, total removal of epileptogenic tubers, and tuberectomy plus. Quality of life and intelligence quotient improvements were frequently observed in patients with postoperative seizure freedom and preoperative low intelligence quotient.

High frequency oscillations (HFOs) are considered as biomarker for epileptogenicity. Reliable automation of HFOs detection is necessary for rapid and objective analysis, and is determined by accurate computation of the baseline. Although most existing automated detectors measure baseline accurately in channels with rare HFOs, they lose accuracy in channels with frequent HFOs. Here, we proposed a novel algorithm using the maximum distributed peak points method to improve baseline determination accuracy in channels with wide HFOs activity ranges and calculate a dynamic baseline. Interictal ripples (80-200[Formula: see text]Hz), fast ripples (FRs, 200-500[Formula: see text]Hz) and baselines in intracerebral EEGs from seven patients with intractable epilepsy were identified by experienced reviewers and by our computer-automated program, and the results were compared. We also compared the performance of our detector to four well-known detectors integrated in RIPPLELAB. The sensitivity and specificity of our detector were, respectively, 71% and 75% for ripples and 66% and 84% for FRs. Spearman's rank correlation coefficient comparing automated and manual detection was [Formula: see text] for ripples and [Formula: see text] for FRs ([Formula: see text]). In comparison to other detectors, our detector had a relatively higher sensitivity and specificity. In conclusion, our automated detector is able to accurately calculate a dynamic iEEG baseline in different HFO activity channels using the maximum distributed peak points method, resulting in higher sensitivity and specificity than other available HFO detectors.

No abstract

During awake brain surgeries, electrocorticogram (ECoG) was recorded using a high density electrode grid from the motor cortex of two subjects while they were asked to execute spontaneous hand extension and flexion. Firstly, we characterized the spatio-spectral patterns of high-density ECoG during the hand movements. In both subjects, we observed event related desynchronization (ERD) in low frequency band (LFB: 8-32 Hz) and event related synchronization (ERS) in high frequency band (HFB: 60-200 Hz) where HFB-ERS was more spatially localized and movement specific compared to LFB-ERD. In particular, improved spatial resolution of high density ECoG revealed HFB-ERS patterns with distinct timing in different anatomical regions. A few channels located anterior to the central sulcus were associated with HFB-ERS which started several hundred milliseconds prior to the movement onset. Several channels were associated with HFB-ERS which started close to the movement onset. Most importantly, only a small number of channels in the motor cortex regions exhibited long duration ERS which lasted while the subjects maintained their hand posture. A common spatial pattern (CSP) algorithm fused with linear discriminant analysis (LDA) was used to distinguish between hand extension and flexion at different time points based on subband features. ECoG data recorded from the channels located either anterior or posterior to the central sulcus were tested separately in classification. For both subjects, using channels located in motor area, HFB yielded almost 100% classification accuracy within 150-250 ms after the movement onset. The classification accuracies obtained from sensory areas were poor compared to motor areas and lagged the movement onset. These results suggest that spatial patterns of motor cortex captured with high-density ECoG in HFB can effectively drive a neural prosthetic to perform hand flexion and extension.

Intracranial EEG (icEEG) monitoring is critical in epilepsy surgical planning, but it has limitations. The advances of neuroimaging have made it possible to reveal epileptic abnormalities that could not be identified previously and improve the localization of the seizure focus and the vital cortex. A frequently asked question in the field is whether non-invasive neuroimaging could replace invasive icEEG or reduce the need for icEEG in presurgical evaluation. This review considers promising neuroimaging techniques in epilepsy presurgical assessment in order to address this question. In addition, due to large variations in the accuracies of neuroimaging across epilepsy centers, multicenter neuroimaging studies are reviewed, and there is much need for randomized controlled trials (RCTs) to better reveal the utility of presurgical neuroimaging. The results of multiple studies indicate that non-invasive neuroimaging could not replace invasive icEEG in surgical planning especially in non-lesional or extratemporal lobe epilepsies, but it could reduce the need for icEEG in certain cases. With technical advances, multimodal neuroimaging may play a greater role in presurgical evaluation to reduce the costs and risks of epilepsy surgery, and provide surgical options for more patients with drug-resistant epilepsy.

Background and Purpose To characterize changes in DTI scalars in WM tracts of the remaining hemisphere in children after hemispherectomy, assess the associations between WM DTI scalars and age at surgery and time since surgery, and evaluate the changes in GM fractional anisotropy (FA) values in patients compared to controls. Materials and Methods Patients with congenital or acquired neurological diseases who required hemispherectomy and high-quality postsurgical DTI data were included into this study. Atlas- and voxel-based analysis of DTI raw data of the remaining hemisphere was performed. FA, mean (MD), axial (AD) and radial (RD) diffusivity values were calculated for WM and GM regions. A linear regression model was used for correlation between DTI scalars and age at and time since surgery. Results 19 patients after hemispherectomy and 21 controls were included. In patients, a decrease in FA and AD values and an increase in MD and RD values of WM regions were observed compared to controls (p<0.05, corrected for multiple comparisons). In patients with acquired pathologies, time since surgery had a significant positive correlation with white matter FA values. In all patients, an increase in cortical GM FA values was found compared to controls. (p<0.05) Conclusions Changes in DTI metrics likely reflect Wallerian and/or transneuronal degeneration of the WM tracts within the remaining hemisphere. In patients with acquired pathologies, postsurgical FA values correlated positively with elapsed time since surgery suggesting a higher ability to recovery compared to patients with congenital pathologies leading to hemispherectomy.

Nuclear receptor subfamily 4 group A member 1 (NR4A1), a downstream target of CREB that is a key regulator of epileptogenesis, has been implicated in a variety of biological processes and was previously identified as a seizure-associated molecule. However, the relationship between NR4A1 and epileptogenesis remains unclear. Here, we showed that NR4A1 protein was predominantly expressed in neurons and up-regulated in patients with epilepsy as well as pilocarpine-induced mouse epileptic models. NR4A1 knockdown by lentivirus transfection (lenti-shNR4A1) alleviated seizure severity and prolonged onset latency in mouse models. Moreover, reciprocal coimmunoprecipitation of NR4A1 and NR2B demonstrated their interaction. Furthermore, the expression of p-NR2B (Tyr1472) in epileptic mice and the expression of NR2B in the postsynaptic density (PSD) were significantly reduced in the lenti-shNR4A1 group, indicating that NR4A1 knockdown partly decreased surface NR2B by promoting NR2B internalization. These results are the first to indicate that the expression of NR4A1 in epileptic brain tissues may provide new insights into the molecular mechanisms underlying epilepsy.