Evidence of a large current of transcranial alternating current stimulation directly to deep brain regions.

Deep brain regions such as hippocampus, insula, and amygdala are involved in neuropsychiatric disorders, including chronic insomnia and depression. Our recent reports showed that transcranial alternating current stimulation (tACS) with a current of 15 mA and a frequency of 77.5 Hz, delivered through a montage of the forehead and both mastoids was safe and effective in intervening chronic insomnia and depression over 8 weeks. However, there is no physical evidence to support whether a large alternating current of 15 mA in tACS can send electrical currents to deep brain tissue in awake humans. Here, we directly recorded local field potentials (LFPs) in the hippocampus, insula and amygdala at different current strengths (1 to 15 mA) in 11 adult patients with drug-resistant epilepsy implanted with stereoelectroencephalography (SEEG) electrodes who received tACS at 77.5 Hz from 1 mA to 15 mA at 77.5 Hz for five minutes at each current for a total of 40 min. For the current of 15 mA at 77.5 Hz, additional 55 min were applied to add up a total of 60 min. Linear regression analysis revealed that the average LFPs for the remaining contacts on both sides of the hippocampus, insula, and amygdala of each patient were statistically associated with the given currents in each patient (p < 0.05-0.01), except for the left insula of one subject (p = 0.053). Alternating currents greater than 7 mA were required to produce significant differences in LFPs in the three brain regions compared to LFPs at 0 mA (p < 0.05). The differences remained significant after adjusting for multiple comparisons (p < 0.05). Our study provides direct evidence that the specific tACS procedures are capable of delivering electrical currents to deep brain tissues, opening a realistic avenue for modulating or treating neuropsychiatric disorders associated with hippocampus, insula, and amygdala.

Integrative roles of human amygdala subdivisions: Insight from direct intracerebral stimulations via stereotactic EEG.

Substantial studies of human amygdala function have revealed its importance in processing emotional experience, autonomic regulation, and sensory information; however, the neural substrates and circuitry subserving functions have not been directly mapped at the level of the subnuclei in humans. We provide a useful overview of amygdala functional characterization by using direct electrical stimulation to various amygdala regions in 48 patients with drug-resistant epilepsy undergoing stereoelectroencephalography recordings. This stimulation extends beyond the anticipated emotional, neurovegetative, olfactory, and somatosensory responses to include visual, auditory, and vestibular sensations, which may be explained by the functional connectivity with cortical and subcortical regions due to evoked amygdala-cortical potentials. Among the physiological symptom categories for each subnucleus, the most frequently evoked neurovegetative symptoms were distributed in almost every subnucleus. Laterobasal subnuclei are mainly associated with emotional responses, somatosensory responses, and vestibular sensations. Superficial subnuclei are mainly associated with emotional responses and olfactory and visual hallucinations. Our findings contribute to a better understanding of the functional architecture of the human amygdala at the subnuclei level and as a mechanistic basis for the clinical practice of amygdala stimulation in treating patients with neuropsychiatric disorders.

The role of the orbitofrontal cortex and insula for prognosis of mesial temporal lobe epilepsy.

OBJECTIVE: We investigated the network between the medial temporal lobe (MTL) and extratemporal structures in patients with mesial temporal lobe epilepsy (MTLE) in order to explain the recurrence of MTLE after surgery. This study contributes to our current understanding of MTLE with stereotactic electroencephalography (SEEG). METHODS: We conducted a retrospective study of SEEG in 20 patients with MTLE in order to observe and analyze the intensity of interictal high-frequency oscillations (HFOs), as well as the dynamic course of coherence connectivity values of the MTL and extratemporal structures during the initial phase of the seizure. The results correlated with the patient prognosis. RESULTS: First, the presence of HFOs was observed during the interictal period in all 20 patients; these were localized to the MTL in 17 patients and the orbitofrontal cortex in seven patients and the insula in six patients. The better the prognosis, the greater the localization of the HFOs concentration in the MTL structures (p < 0.05). Second, significantly enhanced connectivity of MTL structures with the orbitofrontal cortex and insula was observed in most patients with MTLE, before and after the seizure onset (p < 0.05). Finally, the connectivity between extratemporal structures, such as the orbitofrontal cortex and insula, and MTL structures was significantly stronger in patients who had a worse prognosis than in other patients, before and after seizure onset (p < 0.05). INTERPRETATION: The epileptogenic network in recurrent MTLE is not limited to MTL structures but is also associated with the orbitofrontal cortex and insula. This can be used as a potential indicator for predicting the prognosis of patients after surgery, providing an important avenue for future clinical evaluation.

Optimized SEEG-guided three-dimensional radiofrequency thermocoagulation for insular epilepsy.

PURPOSE: The high risk of resection surgery for drug-resistant insular epilepsy has driven interest in new treatment techniques. Stereo-electroencephalography-guided three-dimensional radiofrequency thermocoagulation (SEEG-3D RFTC) offers an alternative option. Herein, we present the detailed protocol and investigation of the efficacy and safety of a preliminary observational study. METHODS: From February 2017 to April 2021, ten patients diagnosed with insular epilepsy were enrolled in the study. They underwent implantation of a combination of SEEG electrodes to form a high-density focal stereo-array in insula, including oblique electrodes through the long axis of insula and orthogonal electrodes to widely cover the medial and lateral insula. SEEG-3D RFTC was performed between two contiguous contacts of the same electrode, or between two adjacent contacts of different electrodes. RESULTS: Surgical procedures were well tolerated, with no related long-term complications. Seizure-free outcome was achieved in seven patients (70%), including ILAE I in four and ILAE II in three. Two other (20%) patients had rare seizures (ILAE III). One (10%) patient experienced an ILAE IV outcome (follow-up = 12--63 months). The responder rate (including ILAE I-IV) was 100%. CONCLUSION: The optimized SEEG-3D RFTC is an effective and safe option for the treatment of drug-resistant insular epilepsy.

Delineating the Decussating Dentato-rubro-thalamic Tract and Its Connections in Humans Using Diffusion Spectrum Imaging Techniques.

The objective of this study was to identify the decussating dentato-rubro-thalamic tract (d-DRTT) and its afferent and efferent connections in healthy humans using diffusion spectrum imaging (DSI) techniques. In the present study, the trajectory and lateralization of the d-DRTT was explored using data from subjects in the Massachusetts General Hospital-Human Connectome Project adult diffusion dataset. The afferent and efferent networks that compose the cerebello-thalamo-cerebral pathways were also reconstructed. Correlation analysis was performed to identify interrelationships between subdivisions of the cerebello-dentato-rubro-thalamic and thalamo-cerebral connections. The d-DRTT was visualized bilaterally in 28 subjects. According to a normalized quantitative anisotropy and lateralization index evaluation, the left and right d-DRTT were relatively symmetric. Afferent regions were found mainly in the posterior cerebellum, especially the entire lobule VII (crus I, II and VIIb). Efferent fibers mainly are projected to the contralateral frontal cortex, including the motor and nonmotor regions. Correlations between cerebello-thalamic connections and thalamo-cerebral connections were positive, including the lobule VIIa (crus I and II) to the medial prefrontal cortex (MPFC) and the dorsolateral prefrontal cortex and lobules VI, VIIb, VIII, and IX, to the MPFC and motor and premotor areas. These results provide DSI-based tratographic evidence showing segregated and parallel cerebellar outputs to cerebral regions. The posterior cerebellum may play an important role in supporting and handling cognitive activities through d-DRTT. Future studies will allow for a more comprehensive understanding of cerebello-cerebral connections.

Combined [18F]FDG-PET with MRI structural patterns in predicting post-surgical seizure outcomes in temporal lobe epilepsy patients.

OBJECTIVES: To integrate the glucose metabolism measured using [18F]FDG PET/CT and anatomical features measured using MRI to forecast the post-surgical seizure outcomes of intractable temporal lobe epilepsy. METHODS: This retrospective study enrolled 63 patients with drug-resistant temporal lobe epilepsy. Z-transform of the patients' PET images based on comparison with a database of healthy controls, cortical thickness, and quantitative anisotropy (QA) of the diffusion spectrum imaging concordant/non-concordant with cortical resection was adopted to quantify their predictive values for the post-surgical seizure outcomes. RESULTS: The PET hypometabolism region was concordant with the surgical field in 47 of the 63 patients. Forty-two patients were seizure-free post-surgery. The sensitivity and specificity of PET in predicting seizure freedom were 89.4% and 68.8%, respectively. Complete resection of foci with overlapped PET, cortical thickness, and QA abnormalities resulted in Engel I in 27 patients, which was a good predictor of seizure freedom with an odds ratio (OR) of 19.57 (95% CI 2.38-161.25, p = 0.006). Hypometabolism involved in multiple lobes (OR = 7.18, 95% CI 1.02-50.75, p = 0.048) and foci of hypometabolism with QA/cortical thickness abnormalities outside surgical field (OR = 14.72, 95% CI 2.13-101.56, p = 0.006) were two major predictors of Engel III/IV outcomes. ORs of QA to predict Engel I and seizure recurrence were 14.64 (95% CI 2.90-73.80, p = 0.001) and 12.01 (95% CI 2.91-49.65, p = 0.001), respectively. CONCLUSION: Combined PET and structural pattern is helpful to predict the post-surgical seizure outcomes and worse outcomes of Engel III/IV. This might decrease unnecessary surgical injuries to patients who are potentially not amenable to surgery. KEY POINTS: • A combined metabolic and structural pattern is helpful to predict the post-surgical seizure outcomes. • Favorable post-surgical seizure outcome was most likely reached in patients whose hypometabolism overlapped with the structural changes. • Hypometabolism in multiple lobes and QA or cortical thickness abnormalities outside the surgical field were predictors of worse seizure outcomes of Engel III/IV.

Somatic MAP3K3 and PIK3CA mutations in sporadic cerebral and spinal cord cavernous malformations.

Cavernous malformations affecting the CNS occur in ∼0.16-0.4% of the general population. The majority (85%) of cavernous malformations are in a sporadic form, but the genetic background of sporadic cavernous malformations remains enigmatic. Of the 81 patients, 73 (90.1%) patients were detected carrying somatic missense variants in two genes: MAP3K3 and PIK3CA by whole-exome sequencing. The mutation spectrum correlated with lesion size (P = 0.001), anatomical distribution (P < 0.001), MRI appearance (P = 0.004) and haemorrhage events (P = 0.006). PIK3CA mutation was a significant predictor of overt haemorrhage events (P = 0.003, odds ratio = 11.252, 95% confidence interval = 2.275-55.648). Enrichment of endothelial cell population was associated with a higher fractional abundance of the somatic mutations. Overexpression of the MAP3K3 mutation perturbed angiogenesis of endothelial cell models in vitro and zebrafish embryos in vivo. Distinct transcriptional signatures between different genetic subgroups of sporadic cavernous malformations were identified by single cell RNA sequencing and verified by pathological staining. Significant apoptosis in MAP3K3 mutation carriers and overexpression of GDF15 and SERPINA5 in PIK3CA mutation carriers contributed to their phenotype. We identified activating MAP3K3 and PIK3CA somatic mutations in the majority (90.1%) of sporadic cavernous malformations and PIK3CA mutations could confer a higher risk for overt haemorrhage. Our data provide insights into genomic landscapes, propose a mechanistic explanation and underscore the possibility of a molecular classification for sporadic cavernous malformations.

Static 18F-FET PET and DSC-PWI based on hybrid PET/MR for the prediction of gliomas defined by IDH and 1p/19q status.

OBJECTIVES: To investigate the predictive value of static O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography (18F-FET PET) and cerebral blood volume (CBV) for glioma grading and determining isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status. METHODS: Fifty-two patients with newly diagnosed gliomas who underwent simultaneous 18F-FET PET and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) examinations on hybrid PET/MR were retrospectively enrolled. The mean and max tumor-to-brain ratio (TBR) and normalized CBV (nCBV) were calculated based on whole tumor volume segmentations with reference to PET/MR images. The predictive efficacy of FET PET and CBV in glioma according to the 2016 World Health Organization (WHO) classification was evaluated by receiver operating characteristic curve analyses with the area under the curve (AUC). RESULTS: TBRmean, TBRmax, nCBVmean, and nCBVmax differed between low- and high-grade gliomas, with the highest AUC of nCBVmean (0.920). TBRmax and nCBVmean showed significant differences between gliomas with and without IDH mutation (p = 0.032 and 0.010, respectively). Furthermore, TBRmean, TBRmax, and nCBVmean discriminated between IDH-wildtype glioblastomas and IDH-mutated astrocytomas (p = 0.049, 0.034 and 0.029, respectively). The combination of TBRmax and nCBVmean showed the best predictive performance (AUC, 0.903). Only nCBVmean differentiated IDH-mutated with 1p/19q codeletion oligodendrogliomas from IDH-wildtype glioblastomas (p < 0.001) (AUC, 0.829), but none of the parameters discriminated between oligodendrogliomas and astrocytomas. CONCLUSIONS: Both FET PET and DSC-PWI might be non-invasive predictors for glioma grades and IDH mutation status. FET PET combined with CBV could improve the differentiation of IDH-mutated astrocytomas and IDH-wildtype glioblastomas. However, FET PET and CBV might be limited for identifying oligodendrogliomas. KEY POINTS: • Static 18F-FET PET and DSC-PWI parameters differed between low- and high-grade gliomas, with the highest AUC of the mean value of normalized CBV. • Static 18F-FET PET and DSC-PWI parameters based on hybrid PET/MR showed predictive value in identifying glioma IDH mutation subtypes, which have gained importance for both determining the diagnosis and prognosis of gliomas according to the 2016 WHO classification. • Static 18F-FET PET and DSC-PWI parameters have limited potential in differentiating IDH-mutated with 1p/19q codeletion oligodendrogliomas from IDH-wildtype glioblastomas or IDH-mutated astrocytomas.

Resective epilepsy surgery in tuberous sclerosis complex: a nationwide multicentre retrospective study from China.

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.

Detecting small conflicting drainages with contrast-enhanced magnetic resonance venography for surgical planning: a technical description and quantified analysis.

BACKGROUND: Recent studies have shown the challenges involved in detecting small conflicting vessels (1.0-1.5 mm) on contrast-enhanced (CE) T1 images during stereoelectroencephalography (SEEG) planning. Improving the resolution of non-invasive approaches to identify these vessels is possible and important. We present a superior sagittal sinus mapping-based CE-magnetic resonance venography (CE-MRV) protocol calibrated by craniotomies. METHOD: Seven patients with epileptic symptoms who received craniotomy were enrolled. CE-MRV was acquired with a bolus mapping of the superior sagittal sinus. Together with the T1 image, 3D veins and the brain surface were visualized. The resolution of the CE-MRV was quantified by measuring the diameter of superficial drainages after exposure of the brain surface during craniotomy. RESULTS: A total of 37 superficial drainages were exposed in the bone windows. CE-MRV visualized all these drainages. On average, one superficial drainage could be found in every 13.2 mm diameter of the bone window. The boundary resolution of the CE-MRV was 0.58-0.8 mm in vessel diameter, while drainages larger than 0.8 mm were visualized consistently. CONCLUSIONS: The resolution of the CE-MRV in the present study met the requirement for detection of small conflicting vessels during SEEG planning. The visualized venous landmarks could be used for visual guidance to the surgical zone. As a non-invasive approach, CE-MRV is practical to use in the clinical setting.

A Distributed Radio Beacon/IMU/Altimeter Integrated Localization Scheme with Uncertain Initial Beacon Locations for Lunar Pinpoint Landing.

As a growing number of exploration missions have successfully landed on the Moon in recent decades, ground infrastructures, such as radio beacons, have attracted a great deal of attention in the design of navigation systems. None of the available studies regarding integrating beacon measurements for pinpoint landing have considered uncertain initial beacon locations, which are quite common in practice. In this paper, we propose a radio beacon/inertial measurement unit (IMU)/altimeter localization scheme that is sufficiently robust regarding uncertain initial beacon locations. This scheme was designed based on the sparse extended information filter (SEIF) to locate the lander and update the beacon configuration at the same time. Then, an adaptive iterated sparse extended hybrid filter (AISEHF) was devised by modifying the prediction and update stage of SEIF with a hybrid-form propagation and a damping iteration algorithm, respectively. The simulation results indicated that the proposed method effectively reduced the error in the position estimations caused by uncertain beacon locations and made an effective trade-off between the estimation accuracy and the computational efficiency. Thus, this method is a potential candidate for future lunar exploration activities.

Automatic labeling of the fanning and curving shape of Meyer's loop for epilepsy surgery: an atlas extracted from high-definition fiber tractography.

BACKGROUND: Visual field defects caused by injury to Meyer's loop (ML) are common in patients undergoing anterior temporal lobectomy during epilepsy surgery. Evaluation of the anatomical shapes of the curving, fanning and sharp angles of ML to guide surgeries is important but still challenging for diffusion tensor imaging. We present an advanced diffusion data-based ML atlas and labeling protocol to reproduce anatomical features in individuals within a short time. METHODS: Thirty Massachusetts General Hospital-Human Connectome Project (MGH-HCP) diffusion datasets (ultra-high magnetic gradient & 512 directions) were warped to standard space. The resulting fibers were projected together to create an atlas. The anatomical features and the tractography correspondence rates were evaluated in 30 MGH-HCP individuals and local diffusion spectrum imaging data (eight healthy subjects and six hippocampal sclerosis patients). RESULTS: In the atlas, features of curves, sharp angles and fanning shapes were adequately reproduced. The distances from the anterior tip of the temporal lobe to the anterior ridge of Meyer's loop were 23.1 mm and 26.41 mm on the left and right sides, respectively. The upper and lower divisions of the ML were revealed to be twisting. Eighty-eight labeled sides were achieved, and the correspondence rates were 87.44% ± 6.92, 80.81 ± 10.62 and 72.83% ± 14.03% for MGH-HCP individuals, DSI-healthy individuals and DSI-patients, respectively. CONCLUSION: Atlas-labeled ML is comparable to high angular resolution tractography in healthy or hippocampal sclerosis patients. Therefore, rapid identification of the ML location with a single modality of T1 is practical. This protocol would facilitate functional studies and visual field protection during neurosurgery.

Ictal swearing network confirmed by stereoencephalography: a case report.

Ictal swearing, characterized by episodic utterance of deistic, visceral and other taboo words and phrases, is a rare manifestation of epilepsy. Limited manifestation of that elucidate neural network about manifestation of. Here we report a 43-year-old right-handed man who has suffered from refractory epilepsy manifestation of ictal swearing. The stereoencephalography(SEEG) investigation located the seizure onset zone in left orbito-frontal cortex and the involvement of left orbito-frontal and right hippocampus in the propagation of epileptic activities. Surgical resection has made the patient seizure-free. The present case gives us better understanding of these ictal phenomena and helps to optimize the placement of SEEG electrodes in refractory epilepsy patient with ictal swearing.

Distinctive Structural and Effective Connectivity Changes of Semantic Cognition Network across Left and Right Mesial Temporal Lobe Epilepsy Patients.

Occurrence of language impairment in mesial temporal lobe epilepsy (mTLE) patients is common and left mTLE patients always exhibit a primary problem with access to names. To explore different neuropsychological profiles between left and right mTLE patients, the study investigated both structural and effective functional connectivity changes within the semantic cognition network between these two groups and those from normal controls. We found that gray matter atrophy of left mTLE patients was more severe than that of right mTLE patients in the whole brain and especially within the semantic cognition network in their contralateral hemisphere. It suggested that seizure attacks were rather targeted than random for patients with hippocampal sclerosis (HS) in the dominant hemisphere. Functional connectivity analysis during resting state fMRI revealed that subregions of the anterior temporal lobe (ATL) in the left HS patients were no longer effectively connected. Further, we found that, unlike in right HS patients, increased causal linking between ipsilateral regions in the left HS epilepsy patients cannot make up for their decreased contralateral interaction. It suggested that weakened contralateral connection and disrupted effective interaction between subregions of the unitary, transmodal hub of the ATL may be the primary cause of anomia in the left HS patients.

The comparison of DBS and RNS for adult drug-resistant epilepsy: a systematic review and meta-analysis.

Objective: Neuromodulation has been proven to be a promising alternative treatment for adult patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) and responsive neurostimulation (RNS) were approved by many countries for the treatment of DRE. However, there is a lack of systematic studies illustrating the differences between them. This meta-analysis is performed to assess the efficacy and clinical characteristics of DBS and RNS in adult patients with DRE. Methods: PubMed, Web of Science, and Embase were retrieved to obtain related studies including adult DRE patients who accepted DBS or RNS. The clinical characteristics of these patients were compiled for the following statistical analysis. Results: A total of 55 studies (32 of DBS and 23 of RNS) involving 1,568 adult patients with DRE were included in this meta-analysis. There was no significant difference in seizure reduction and responder rate between DBS and RNS for DRE. The seizure reduction of DBS and RNS were 56% (95% CI 50-62%, p > 0.05) and 61% (95% CI 54-68%, p > 0.05). The responder rate of DBS and RNS were 67% (95% CI 58-76%, p > 0.05) and 71% (95% CI 64-78%, p > 0.05). Different targets of DBS did not show significant effect on seizure reduction (p > 0.05). Patients with DRE who accepted DBS were younger than those of RNS (32.9 years old vs. 37.8 years old, p < 0.01). The mean follow-up time was 47.3 months for DBS and 39.5 months for RNS (p > 0.05). Conclusion: Both DBS and RNS are beneficial and alternative therapies for adult DRE patients who are not eligible to accept resection surgery. Further and larger studies are needed to clarify the characteristics of different targets and provide tailored treatment for patients with DRE.

Unveiling the hidden connection: the blood-brain barrier's role in epilepsy.

Epilepsy is characterized by abnormal synchronous electrical activity of neurons in the brain. The blood-brain barrier, which is mainly composed of endothelial cells, pericytes, astrocytes and other cell types and is formed by connections between a variety of cells, is the key physiological structure connecting the blood and brain tissue and is critical for maintaining the microenvironment in the brain. Physiologically, the blood-brain barrier controls the microenvironment in the brain mainly by regulating the passage of various substances. Disruption of the blood-brain barrier and increased leakage of specific substances, which ultimately leading to weakened cell junctions and abnormal regulation of ion concentrations, have been observed during the development and progression of epilepsy in both clinical studies and animal models. In addition, disruption of the blood-brain barrier increases drug resistance through interference with drug trafficking mechanisms. The changes in the blood-brain barrier in epilepsy mainly affect molecular pathways associated with angiogenesis, inflammation, and oxidative stress. Further research on biomarkers is a promising direction for the development of new therapeutic strategies.

Wearable sensor devices can automatically identify the ON-OFF status of patients with Parkinson's disease through an interpretable machine learning model.

Introduction: Accurately and objectively quantifying the clinical features of Parkinson's disease (PD) is crucial for assisting in diagnosis and guiding the formulation of treatment plans. Therefore, based on the data on multi-site motor features, this study aimed to develop an interpretable machine learning (ML) model for classifying the "OFF" and "ON" status of patients with PD, as well as to explore the motor features that are most associated with changes in clinical symptoms. Methods: We employed a support vector machine with a recursive feature elimination (SVM-RFE) algorithm to select promising motion features. Subsequently, 12 ML models were constructed based on these features, and we identified the model with the best classification performance. Then, we used the SHapley Additive exPlanations (SHAP) and the Local Interpretable Model agnostic Explanations (LIME) methods to explain the model and rank the importance of those motor features. Results: A total of 96 patients were finally included in this study. The naive Bayes (NB) model had the highest classification performance (AUC = 0.956; sensitivity = 0.8947, 95% CI 0.6686-0.9870; accuracy = 0.8421, 95% CI 0.6875-0.9398). Based on the NB model, we analyzed the importance of eight motor features toward the classification results using the SHAP algorithm. The Gait: range of motion (RoM) Shank left (L) (degrees) [Mean] might be the most important motor feature for all classification horizons. Conclusion: The symptoms of PD could be objectively quantified. By utilizing suitable motor features to construct ML models, it became possible to intelligently identify whether patients with PD were in the "ON" or "OFF" status. The variations in these motor features were significantly correlated with improvement rates in patients' quality of life. In the future, they might act as objective digital biomarkers to elucidate the changes in symptoms observed in patients with PD and might be used to assist in the diagnosis and treatment of patients with PD.

Comparative Efficacy of Neuromodulatory Strategies for Drug-Resistant Epilepsy: A Systematic Review and Meta-Analysis.

OBJECTIVE: The study aims to evaluate the efficacy of neuromodulatory strategies for people who have drug-resistant epilepsy (DRE). METHODS: We searched electronic repositories, including PubMed, Web of Science, Embase, and the Cochrane Library, for randomized controlled trials, their ensuing open-label extension studies, and prospective studies focusing on surgical or neuromodulation interventions for people with DRE. We used seizure frequency reduction as the primary outcome. A single-arm meta-analysis synthesized data across all studies to assess treatment effectiveness at multiple time points. A network meta-analysis evaluated the efficacy of diverse therapies in randomized controlled trials. Grading of Recommendations, Assessment, Development, and Evaluations was applied to evaluate the overall quality of the evidence. RESULTS: Twenty-eight studies representing 2936 individuals underwent 10 treatments were included. Based on the cumulative ranking in the network meta-analysis, the top 3 neuromodulatory options were deep brain stimulation (DBS) with 27% probability, responsive neurostimulation (RNS) with 22.91%, and transcranial direct current stimulation with 24.31%. In the single-arm meta-analysis, in the short-to-medium term, seizure control is more effective with RNS than with invasive vagus nerve stimulation (inVNS), which in turn is slightly more effective than DBS, though the differences are minimal. However, in the long term, inVNS appears to be less effective than both DBS and RNS. Trigeminal nerve stimulation, transcranial magnetic stimulation, and transcranial alternating current stimulation did not demonstrate significant seizure frequency reduction. CONCLUSIONS: Regarding long-term efficacy, RNS and DBS outperformed inVNS. While transcranial direct current stimulation and transcutaneous auricular VNS showed promise for treating DRE, further studies are needed to confirm their long-term efficacy.

Aberrant individual structure covariance network in patients with mesial temporal lobe epilepsy.

Objective: Mesial temporal lobe epilepsy (mTLE) is a complex neurological disorder that has been recognized as a widespread global network disorder. The group-level structural covariance network (SCN) could reveal the structural connectivity disruption of the mTLE but could not reflect the heterogeneity at the individual level. Methods: This study adopted a recently proposed individual structural covariance network (IDSCN) method to clarify the alternated structural covariance connection mode in mTLE and to associate IDSCN features with the clinical manifestations and regional brain atrophy. Results: We found significant IDSCN abnormalities in the ipsilesional hippocampus, ipsilesional precentral gyrus, bilateral caudate, and putamen in mTLE patients than in healthy controls. Moreover, the IDSCNs of these areas were positively correlated with the gray matter atrophy rate. Finally, we identified several connectivities with weak associations with disease duration, frequency, and surgery outcome. Significance: Our research highlights the role of hippo-thalamic-basal-cortical circuits in the pathophysiologic process of disrupted whole-brain morphological covariance networks in mTLE, and builds a bridge between brain-wide covariance network changes and regional brain atrophy.

A disease warranting attention from neurosurgeons: primary central nervous system post-transplant lymphoproliferative disorder.

Background: Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare condition, posing diagnostic and treatment challenges, with histological biopsy essential for diagnosis. Standardized treatment protocols are lacking. This disease requires urgent attention due to the increasing number of organ transplant surgeries and the use of immunosuppressive agents. Methods: From 2020 to 2023, our center diagnosed five patients with PCNS-PTLD. We reviewed their clinical records and conducted a comprehensive analysis of 22 literatures on PCNS-PTLD cases following renal transplantation or allogeneic hematopoietic stem cell transplantation (HSCT). Results: Four patients had previously received a kidney transplant, one had undergone allogeneic HSCT. The median time from the last transplant surgery to the diagnosis of PCNS-PTLD differs between kidney transplant (21.5 years) and allogeneic HSCT (9 months). Common symptoms included motor weakness (n = 4), headache (n = 2), confusion (n = 2), and nausea (n = 2), with ring-enhancing (n = 5), typically solitary (n = 3) and supratentorial (n = 3) lesions on imaging. Diagnosis involved robot-assisted stereotactic brain biopsy (n = 4) or craniotomy (n = 1), all showing Epstein-Barr virus and CD20 positivity. Most cases (n = 4) were monomorphic diffuse large B-cell lymphoma. Treatment included rituximab (n = 3), surgical resection (n = 2), zanubrutinib (n = 1), whole-brain radiation (n = 1), and methotrexate (n = 1). At the last follow-up, the median duration of follow-up for all patients was 19 months. During this time, 3 patients had died and 2 patients were still alive. Conclusion: In patients with a history of kidney transplantation or allogeneic HSCT who are on long-term immunosuppressive therapy, any neurological symptoms, particularly the presence of supratentorial ring-enhancing masses in the brain on imaging, whether solitary or multiple, should raise high suspicion for this disease, warranting a timely brain biopsy. Additionally, we found that besides reducing immunosuppressants, zanubrutinib may be a potential, safe, and effective treatment for this condition. Moreover, post-surgical administration of rituximab in conjunction with whole-brain radiotherapy also appears to be a potentially safe and effective approach.