High-frequency and brief-pulse stimulation pulses terminate cortical electrical stimulation-induced afterdischarges

Brief-pulse stimulation at 50 Hz has been shown to terminate afterdischarges observed in epilepsy patients. However, the optimal pulse stimulation parameters for terminating cortical electrical stimulation-induced afterdischarges remain unclear. In the present study, we examined the effects of different brief-pulse stimulation frequencies（5, 50 and 100 Hz） on cortical electrical stimulation-induced afterdischarges in 10 patients with refractory epilepsy. Results demonstrated that brief-pulse stimulation could terminate cortical electrical stimulation-induced afterdischarges in refractory epilepsy patients. In conclusion,（1） a brief-pulse stimulation was more effective when the afterdischarge did not extend to the surrounding brain area.（2） A higher brief-pulse stimulation frequency（especially 100 Hz） was more likely to terminate an afterdischarge.（3） A low current intensity of brief-pulse stimulation was more likely to terminate an afterdischarge.

Emerging personalized virtual brain models: next-generation resection neurosurgery for drug-resistant epilepsy?

Recently,a novel workflow known as the virtual epileptic patient(VEP)has been proposed by a research team from Aix Marseille Universitéin their papers published in Lancet Neurology,Science Translational Medicine and Epilepsia.This method involves creating an individualized virtual brain model based on computational modelling,which can facilitate clinical decision-making by estimating the epileptogenic zone and performing the virtual surgery.Here,we summarize brief workflow,strengths,and limitations of VEP,as well as its performance in a retrospective study of 53 patients with drug-resistant focal epilepsy who underwent stereoelectroencephalography.A large-scale clinical trial(NCT03643016)is underway to further assess VEP,which is expected to enroll 356 patients prospectively.As supporting evidence accumulates,the clinical application of VEP has the potential to improve clinical practice,leading to better outcomes and qualities of life of patients.

Advances in brain imaging of neuropathic pain

To review the literature on the use of brain imaging, including functional magnetic resonance imaging （fMRI）, positron emission tomography （PET）, magnetic resonance spectroscopy （MRS） and voxel-based morphometry （VBM） in investigation of the activity in diverse brain regions that creates and modulates chronic neuropathic pain. Data sources English literatures from January 1, 2000 to July 31, 2007 that examined human brain activity in chronic neuropathic pain were accessed through MEDLINE/CD ROM, using PET, fMRI, VBM, MRS and receptor binding. Study selection Published articles about the application of fMRI, PET, VBM, MRS and chronic neuropathic pain were selected. Data extraction Data were mainly extracted from 40 representative articles as the research basis. Results The PET studies suggested that spontaneous neuropathic pain is associated with changes in thalamic activity. Both PET and fMRI have been used to investigate the substrate of allodynia. The VBM demonstrated that brain structural changes are involved in chronic neuropathic pain, which is not seen in a matched control group. However, the results obtained had a large variety, which may be due to different pain etiology, pain distribution, lesion tomography, symptoms and stimulation procedures. Conclusions Application of the techniques of brain imaging plays a very important role in the study of structural and functional reorganization in patients with neuropathic pain. However, a unique “pain matrix” has not been defined. Future studies should be conducted using a prospective longitudinal research design, which would guarantee the control for many confounding factors.

A study of medial and lateral temporal lobe epilepsy based on stereoelectroencephalography

Background:Patients with temporal lobe epilepsy(TLE)originating from different seizure onset zones had distinct electrophysiological characteristics and surgical outcomes.In this study,we aimed to investigate the relationship between the origin and prognosis of TLE,and the stereoelectroencephalography(SEEG)features.Methods:Thirty patients with TLE,who underwent surgical treatment in our functional neurosurgery department from January 2016 to December 2017,were enrolled in this study.All patients underwent anterior temporal lobectomy after an invasive preoperative evaluation with SEEG.Depending on the epileptic focus location,patients were divided into those with medial temporal lobe seizures(MTLS)and those with lateral temporal lobe seizures(LTLS).The Engel classification was used to evaluate operation effectiveness,and the Kaplan-Meier analysis was used to detect seizure-free duration.Results:The mean follow-up time was 25.7±4.8 months.Effectiveness was 63.3%for Engel I(n=19),13.3%for Engel II,3.3%for Engel III,and 20.0%for Engel IV.According to the SEEG,60.0%(n=18)had MTLS,and 40.0%(n=12)had LTLS.Compared with the MTLS group,the operation age of those with LTLS was significantly greater(26.9±6.9 vs.29.9±12.5 years,t=-0.840,P=0.009)with longer epilepsy duration(11.9±6.0 vs.17.9±12.1 years,t=-1.801,P=0.038).Patients with MTLS had a longer time interval between ictal onset to seizure(67.3±59.1 s vs.29.3±24.4 s,t=2.017,P=0.008).The most common SEEG ictal pattern was a sharp/spike-wave rhythm in the MTLS group(55.6%)and low-voltage fast activity in the LTLS group(58.3%).Compared with the LTLS group,patients with MTLS had a more favorable prognosis(41.7%vs.77.8%,P=0.049).Post-operative recurrence was more likely to occur within three months after the operation for both groups,and there appeared to be a stable longterm outcome.Conclusion:Patients with MTLS,who accounted for three-fifths of patients with TLE,showed a more favorable surgical outcome.

Dorsal root entry zone coagulation for treatment of deafferentation pain syndromes

Background Deafferentation pain is a kind of chronic pain syndrome and hard to manipulate. To evaluate the effectiveness and safety of junctional dorsal root entry zone （DREZ） coagulation, 23 consecutive patients with intractable deafferentation pain syndrome were studied.Methods Twenty-three patients underwent junctional DREZ coagulation （C5-T1 for upper extremities and L2-S1 for lower extremities） under general anesthesia. The pain severity was evaluated by the short McGill pain questionnaire （MPQ） and the visual analog scale （VAS）, and the depression and anxiety of patients were assessed by Hamilton rating scale for depression （HRSD）, Hamilton anxiety scale （HAMA）, self-rating anxiety scale （SAS） and self-rating depression scale （SDS）.Results All the patients experienced significant pain reduction immediately after surgery. The scales of short MPQ and VAS at pre-operation, 6-month and 12-month follow-up were 31.5±3.4 and 8.8±1.5, 6.5±1.9 and 2.5±2.2, 7.1±2.1 and 2.9±1.9, respectively. The postoperative scores comparing to pre-operative scores showed a statistically significant difference （P 〈0.01）. The depression and anxiety state was also significantly relieved. At 12-month follow-up 6 patients had complete pain relief, 11 had excellent results with more than 75% pain relief, 17 had good results with more than 50% pain relief （73.9%）. The main postoperative complications were transient slight hemiplegia （8）, hypesthesia and paresthesia （15）, a bearing down feeling of affected extremity （6）, and deep sensory disability in the lower limbs （4） on the operated side. Because of the long time and prone position of the operation, 13 cases had a transient hyperalgesia in the upper chest. Conclusion DREZ coagulation is a safe and effective procedure in the treatment of deafferentation pain syndromes.

Deep Brain Stimulation of the Globus Pallidus Internus in Patients with Intractable Tourette Syndrome： A 1-year Follow-up Study

Background： Deep brain stimulation （DBS） has been a promising treatment for patients with refractory Tourette syndrome （TS） for more than a decade. Despite successful DBS treatment of TS in more than 100 patients worldwide, studies with a large patient sample and long-term follow-up assessments are still scarce. Accordingly, we investigated the clinical efficacy and safety of globus pallidus internus （GPi） DBS in the treatment of intractable TS in 24 patients with a 1-year follow-up assessment. Methods： Bilateral/unilateral GPi-DBS was performed in 24 patients with TS. We evaluated symptoms of tics and obsessive-compulsive disorder （OCD） through the Yale Global Tic Severity Scale （YGTSS） and Yale-Brown Obsessive-compulsive Scale （Y-BOCS）. We used the Wechsler Adult Intelligence Scale-Revised in China （WAIS-RC） to evaluate the safety of the treatment. We conducted follow-up assessments of all patients for at least 12 months （12-99 months）. Results： Symptoms of tics and OCD were significantly relieved at a 12-month follow-up assessment. The mean YGTSS score was 74.04 ± 11.52, 49.83 ± 10.91, 32.58 ± 7.97, and 31.21 ± 8.87 at baseline, 3, 6, and 12 months, respectively. The mean YGTSS scores obtained at the follow-up assessments were significantly different from the baseline （P 〈 0.05）. The improvement in motor tics was superior to that in phonic tics. The mean Y-BOCS scores were 21.61 ± 4.97, 18 ± 4.58, 14.39 ± 3.99, and 13.78 ± 4.56 at baseline, 3, 6, and 12 months, respectively （P 〈 0.05）. We observed a remarkable improvement in psychiatric comorbidities, such as OCD and attention-deficit hyperactivity disorder, after the procedure. WAIS-RC scores were comparable before and after the operation. There were no severe postoperative complications. Conclusion： GPi-DBS appears to comprehensively alleviate tic symptoms and psychiatric comorbidities in patients with TS, thus significantly improving patients＇ quality of life.

Properties of oscillatory neuronal activity in the basal ganglia and thalamus in patients with Parkinson’s disease

Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.Methods:Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus(STN)DBS(n=11),unilateral pallidotomy(n=9)and unilateral thalamotomy(n=9)were studied.Microelectrode recordings in the STN,globus pallidus internus(GPi)and ventral oral posterior/ventral intermediate of thalamus(Vop/Vim)were performed.Electromyography of the contralateral limbs was recorded.Single unit characteristics including interspike intervals were analyzed.Spectral and coherence analyses were assessed.Mean spontaneous firing rate(MSFR)of neurons was calculated.Analysis of variance and χ^(2) test were performed.Results:Of 76 STN neurons,39.5% were 4–6 Hz band oscillatory neurons and 28.9% were β frequency band(βFB)oscillatory neurons.The MSFR was 44.2±7.6 Hz.Of 62 GPi neurons,37.1% were 4–6 Hz band oscillatory neurons and 27.4% were βFB neurons.The MSFR was 80.9±9.6 Hz.Of 44 Vop neurons,65.9% were 4–6 Hz band oscillatory neurons and 9%were βFB neurons.The MSFR was 24.4±4.2 Hz.Of 30 Vim oscillatory neurons,70% were 4–6 Hz band oscillatory neurons and 13.3% were β FB neurons.The MSFR was 30.3±3.6 Hz.Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim(P<0.05).Conversely,the proportion of 4–6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi(P<0.05).The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons(P<0.005).Conclusion:The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism.β oscillatory activity is more prominent in basal ganglia than in thalamus suggesting that the activity likely results from dopaminergic depletion.While both basal ganglia and thalamus have tremor activity,the thalamus appears to play a more important role in tremor production,and basal ganglia β oscillatory activity might be the trigger.

Subthalamic deep brain stimulation for Parkinson＇s disease： correlation of active contacts and electrophysiologically mapped subthalamic nucleus

Background Subthalamic deep brain stimulation （STN-DBS） has been shown to be effective in the treatment of Parkinson＇s disease. The site for permanent stimulation is still in debate. This study aimed to assess the position of active contacts in relation to the subthalamic nucleus. Methods We reviewed the location of 40 electrodes in 34 patients who underwent STN-DBS. The position of electrode was evaluated by postoperative magnetic resonance imaging （MRI）. The position of active contacts was compared with the subthalamic nucleus （STN） determined by intraoperative electrophysiological mapping and postoperative MRI. Results The average position of the 40 active contacts was （11.7±1.2） mm lateral, （0.6±1.3） mm anterior, and （0.7±1.4） mm vertical to the midcommissural point. The dorsal margin of the STN was （11.6±1.1） mm lateral, （0.2±1.1） mm anterior, and （1.3±1.1） mm vertical to the midcommissural point. When compared with the dorsal margin of the STN, the active contacts were located more dorsally （P=0.033） and anteriorly （P=-0.012）, no significant difference was found in the lateral direction （P=0.107）. When compared with the position of the STN, 26 （65%） of active contacts were located in the region dorsal to the STN, only 13 （32.5%） were located in the upper two-thirds portion of STN. Conclusions The site for permanent stimulation appears to be in the subthalamic region dorsal to the STN, close to the dorsal margin of the STN. Besides the dorsal portion of the STN, other structures such as fields of Forel H and zona incerta may also be involved in the therapeutic benefit of deep brain stimulation.

Role of the Hippocampus in Distinct Memory Traces: Timing of Match and Mismatch Enhancement Revealed by Intracranial Recording

A previous functional magnetic resonance imaging study reported evidence for parallel memory traces in the hippocampus： a controlled match signal detecting matches to internally-generated goal states and an automatic mismatch signal identifying unpredicted perceptual novelty. However, the timing information in this process is unknown. In the current study, facilitated by the high spatial and temporal resolution of intracranial recording from human patients, we confirmed that the left posterior hippocampus played an important role in the goal match enhancement effect, in which combinations of object identity and location were involved. We also found that this effect happened within 520 ms to 735 ms after the probe onset, ＊150 ms later than the perceptual mismatch enhancement found bilaterally in both the anterior and posterior hippocampus. More specifically, the latency of the perceptual mismatch enhancement effect of the right hippocampus was positively correlated with the performance accuracy. These results suggested that the hippocampus is crucial in working memory if features binding with location are involved in the task and the goal match enhancement effect happens after perceptual mismatch enhancement, implying the dissociation of different components of working memory at the hippocampus. Moreover, single trial decoding results suggested that theintracranial field potential response in the right hippocampus can classify the match or switch task. This is consistent with the findings that the right hippocampal activity observed during the simulation of the future events may reflect the encoding of the simulation into memory.

Prognostic value of high-frequency oscillations combined with multimodal imaging methods for epilepsy surgery

Background:The combination of high-frequency oscillations(HFOs)with single-mode imaging methods has been proved useful in identifying epileptogenic zones,whereas few studies have examined HFOs combined with multimodal imaging methods.The aim of this study was to evaluate the prognostic value of ripples,an HFO subtype with a frequency of 80 to 200 Hz is combined with multimodal imaging methods in predicting epilepsy surgery outcome.Methods:HFOs were analyzed in 21 consecutive medically refractory epilepsy patients who underwent epilepsy surgery.All patients underwent positron emission tomography(PET)and deep electrode implantation for stereo-electroencephalography(SEEG);11 patients underwent magnetoencephalography(MEG).Sensitivity,specificity,positive predictive value,negative predictive value,and accuracy in predicting surgical outcome were calculated for ripples combined with PET,MEG,both PET and MEG,and PET combined with MEG.Kaplan-Meier survival analyses were conducted in each group to estimate prognostic value.Results:The study included 13 men and 8 women.Accuracy for ripples,PET,and MEG alone in predicting surgical outcome was 42.9%,42.9%,and 81.8%,respectively.Accuracy for ripples combined with PET and MEG was the highest.Resection of regions identified by ripples,MEG dipoles,and combined PET findings was significantly associated with better surgical outcome(P<0.05).Conclusions:Intracranial electrodes are essential to detect regions which generate ripples and to remove these areas which indicate good surgical outcome for medically intractable epilepsy.With the assistance of presurgical noninvasive imaging examinations,PET and MEG,for example,the SEEG electrodes would identify epileptogenic regions more effectively.

Functional hemispherectomy for patients with adult-onset Rasmussen’s encephalitis

Background:Surgical treatment for patients with adult-onset Rasmussen’s encephalitis(A-RE)is rarely reported.We investigated the clinical and surgical features of two patients with A-RE who underwent functional hemispherectomy.Case presentation:The data of clinical manifestations,neuroimaging,surgical treatment and surgical outcomes of two patients with A-RE was reviewed.The two patients initially presented with recurrent partial seizures or secondly generalized tonic clonic seizures.Gradually,the patients showed unilateral limb paralysis as well as chronic focal epileptic status.Both patients underwent functional hemispherectomy and achieved seizure freedom in the followup.The contralateral neurological deficits improved gradually after rehabilitation and were acceptable for the selfcare of daily living.The living quality improved prominently after surgery.Conclusions:Despite the risk of hemiplegia,functional hemispherectomy may be a choice for patients with A-RE for favorable seizure control and improved quality of life in selected patients.

Intranasal administration nanosystems for brain-targeted drug delivery

The existence of the blood-brain barrier(BBB)restricts the entry of drugs from the circulation into the central nervous system(CNS),which severely affects the treatment of neurological diseases,including glioblastoma,Parkinson’s disease(PD),and Alzheimer’s disease(AD).With the advantage of bypassing the BBB and avoiding systemic distribution,intranasal administration has emerged as an alternative method of delivering drugs to the brain.Drug delivery directly to the brain using intranasal nanosystems represents a new paradigm for neurological disease treatment because of its advantages in improving drug solubility and stability in vivo,enabling targeted drug delivery and controlled release,and reducing non-specific toxicity.And it has shown efficacy in animal models and clinical applications.Herein,this review describes the mechanisms of intranasal delivery of brain-targeted drugs,the properties of nanosystems for intranasal administration(e.g.,liposomes,nanoemulsions,and micelles),and strategies for intranasal drug delivery to enhance brain-targeted drug delivery.Recent applications of nanosystems in intranasal drug delivery and disease treatment have been comprehensively reviewed.Although encouraging results have been reported,significant challenges still need to be overcome to translate these nanosystems into clinics.Therefore,the future prospects of intranasal drug delivery nanosystems are discussed in depth,expecting to provide useful insights and guidance for effective neurological disease treatment.

Dysembryoplastic neuroepithelial tumors： magnetic resonance imaging and magnetic resonance spectroscopy evaluation

Background Dysembryoplastic neuroepithelial tumor （DNT） is a rare benign neoplasm of the central nervous system affecting young people. A correct preoperative diagnosis is helpful for planning surgical strategies and improving prognosis. The purpose of this study was to characterize DNTs using magnetic resonance imaging （MRI） and magnetic resonance spectroscopy （MRS） and to analyze the value of these two techniques in the diagnosis of DNTs. Methods MR images of 13 patients with DNTs were reviewed retrospectively; and five of the patients also underwent MRS. Tumors were confirmed by surgery. The distribution, extension and signal features of the lesions were assessed, and the MRS results were analyzed. Results All tumors were supratentorial. The cortex was the main area involved, with nine tumors located in the temporal lobe, three in the frontal lobe, and one on the boundary between the temporal and occipital lobes. All cases had decreased signal intensity on Tl-weighted MR images and increased signal intensity on T2-weighted images. On fluid attenuated inversion recovery weighted images, the hyperintense ＂ring sign＂ and internal septation of the lesion were seen in 9 cases. Eight tumors had well-demarcated borders. Peritumoral edema or mass effect was absent in all cases. A contrast enhancement examination was performed in 9 cases. Contrast enhancement was absent in five cases, and four cases showed significant enhancement. The MRS showed a low N-acetylaspartate peak and a lack of elevated choline-containing component （Cho） or Cho-Cr ratio （Cho/Cr） in five patients. Conclusions The MRI findings of DNTs were stereotypical. The combination of MRI and MRS techniques were helpful in making a correct presurgical diagnosis.

Microsurgical dorsal root entry zone coagulation for chronic neuropathic pain due to spinal cord and/or cauda equina injuries

Chronic pain is a major problem for patients suffering from spinal cord injury （SCI）.The prevalence of SCI-related pain ranges from 48% to 94% depending on the method of data acquisition and type of pain considered.1 SCI-related neuropathic pain is classified into three subtypes：above-,at-,and below-lesion-level pain.After SCI,it is believed that the dorsal horn of the injured spinal cord expressed increased electrical activity.2 Thus,the neurosurgical procedures for coagulation in the dorsal root entry zone （DREZ） have proved to be most effective in chronic neuropathic pain due to SCI.The aim of this study was to describe the effect and safety ofmicrosurgical DREZ coagulation in treating chronic SCI-related neuropathic pain.

Brain glucose metabolic changes associated with chronic spontaneous pain due to brachial plexus avulsion： a preliminary positron emission tomography study

Background Previous brain imaging studies suggested that the brain activity underlying the perception of chronic pain may differ from that underlying acute pain. To investigate the brain regions involved in chronic spontaneous pain due to brachial plexus avulsion （BPA）, fluorine-18^fluorodeoxyglucose （18^F-FDG） positron emission tomography （PET） scanning was applied to determine the glucose metabolic changes in patients with pain due to BPA.Methods Six right-handed patients with chronic spontaneous pain due to left-BPA and twelve right-handed age- and sex-matched healthy control subjects participated in the 18^F-FDG PET study. The patients were rated by visual analog scale （VAS） during scanning and Hamilton depression scale and Hamilton anxiety scale after scanning. Statistical parametric mapping 2 （SPM2） was applied for data analysis. Results Compared with healthy subjects, the patients had significant glucose metabolism decreases in the right thalamus and SI （P 〈0.001, uncorrected）, and significant glucose metabolism increases in the right orbitofrontal cortex （OFC） （BAll）, left rostral insula cortex and left dorsolateral prefrontal cortex （DLPFC） （BA10/46） （P 〈0.001, uncorrected）. Conclusion These findings suggest that the brain areas involved in emotion, attention and internal modulation of pain may be related to the chronic spontaneous pain due to BPA.