Connectivity alteration in thalamic nuclei and default mode network-related area in memory processes in mesial temporal lobe epilepsy using magnetoencephalography.

This work aimed to investigate the involvement of the thalamic nuclei in mesial temporal lobe epilepsy (MTLE) and identify the influence of interictal epileptic discharges on the neural basis of memory processing by evaluating the functional connectivity (FC) between the thalamic nuclei and default mode network-related area (DMNRA) using magnetoencephalography. Preoperative datasets of nine patients with MTLE with seizure-free status after surgery and those of nine healthy controls were analyzed. The FC between the thalamic nuclei (anterior nucleus [ANT], mediodorsal nucleus [MD], intralaminar nuclei [IL]), hippocampus, and DMNRA was examined for each of the resting, pre-spike, spike, and post-spike periods in the delta to ripple bands using magnetoencephalography. The FC between the ANT, MD, hippocampus, and medial prefrontal cortex increased in the gamma to ripple bands, whereas the FC between the ANT, IL, and DMNRA decreased in the delta to beta bands, compared with that of the healthy controls at rest. Compared with the rest period, the pre-spike period had significantly decreased FC between the ANT, MD, and DMNRA in the ripple band. Different FC changes between the thalamic nuclei, hippocampus, and DMNRA of specific connections in a particular band may reflect impairment or compensation in the memory processes.

Clinical Impacts of Stereotactic Electroencephalography on Epilepsy Surgery and Associated Issues in the Current Situation in Japan.

Stereotactic electroencephalography (SEEG) is receiving increasing attention as a safe and effective technique in the invasive evaluation for epileptogenic zone (EZ) detection. The main clinical question is whether the use of SEEG truly improves outcomes. Herein, we compared outcomes in our patients after three types of intracranial EEG (iEEG): SEEG, the subdural electrode (SDE), and a combined method using depth and strip electrodes. We present here our preliminary results from two demonstrative cases. Several international reports from large epilepsy centers found the following clinical advantages of SEEG: 1) three-dimensional analysis of structures, including bilateral and multilobar structures; 2) low rate of complications; 3) less pneumoencephalopathy and less patient burden during postoperative course, which allows the initiation of video-EEG monitoring immediately after implantation and does not require resection to be performed in the same hospitalization; and 4) a higher rate of good seizure control after resection. In other words, SEEG more accurately identified the EZ than the SDE method. We obtained similar results in our preliminary experiences under limited conditions. In Japan, as of August 2022, dedicated electrodes and SEEG accessories have not been approved and the use of the robot arm is not widespread. The Japanese medical community is hopeful that these issues will soon be resolved and that the experience with SEEG in Japan will align with that of large epilepsy centers internationally.

[Seizure Semiology and Functional Anatomy in the Cerebral Cortex].

Understanding the semiology and underlying anatomy of each seizure is essential for epilepsy surgeons. According to the International League Against Epilepsy(ILAE)classification in 2017, seizure types are classified as focal, generalized, or unknown onset, all of which are further classified as motor or non-motor onset. Impairment of awareness is involved in consciousness systems(consisting of subcortical structures such as the thalamus and upper brain stem)and cortical structures(including the frontoparietal association cortices). Seizures with motor features are divided into elementary symptoms for which myoclonic, clonic, and tonic expressions reflect the somatotopy of the primary motor cortex; and integrated or gestural motor expression representing activation of the motor association cortex. A rostrocaudal gradient is demonstrated in hyperkinetic movements in frontal lobe epilepsy. Non-motor epileptic features should be understood together with auras, which correspond to focal aware seizures and hold crucial localizing semiologic values. The correlation between functional anatomy and seizure semiology is justified by invasive recordings such as stereotactic electroencephalography and subdural recordings, and also confirmed by seizure outcomes after resection of supposed epileptogenic zones. In addition to the conventional localization theory, it is necessary to consider the neural network theory for further recognition of the functionally anatomical basis in an incomprehensible demonstration of seizures.

Magnetic resonance-guided focused ultrasound thalamotomy restored distinctive resting-state networks in patients with essential tremor.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy ameliorates symptoms in patients with essential tremor (ET). How this treatment affects canonical brain networks has not been elucidated. The purpose of this study was to clarify changes of brain networks after MRgFUS thalamotomy in ET patients by analyzing resting-state networks (RSNs). METHODS: Fifteen patients with ET were included in this study. Left MRgFUS thalamotomy was performed in all cases, and MR images, including resting-state functional MRI (rsfMRI), were taken before and after surgery. MR images of 15 age- and sex-matched healthy controls (HCs) were also used for analysis. Using rsfMRI data, canonical RSNs were extracted by performing dual regression analysis, and the functional connectivity (FC) within respective networks was compared among pre-MRgFUS patients, post-MRgFUS patients, and HCs. The severity of tremor was evaluated using the Clinical Rating Scale for Tremor (CRST) score pre- and postoperatively, and its correlation with RSNs was examined. RESULTS: Preoperatively, ET patients showed a significant decrease in FC in the sensorimotor network (SMN), primary visual network (VN), and visuospatial network (VSN) compared with HCs. The decrease in FC in the SMN correlated with the severity of tremor. After MRgFUS thalamotomy, ET patients still exhibited a significant decrease in FC in a small area of the SMN, but they exhibited an increase in the cerebellar network (CN). In comparison between pre- and post-MRgFUS patients, the FC in the SMN and the VSN significantly increased after treatment. Quantitative evaluation of the FCs in these three groups showed that the SMN and VSN increased postoperatively and demonstrated a trend toward those of HCs. CONCLUSIONS: The SMN and CN, which are considered to be associated with the cerebello-thalamo-cortical loop, exhibited increased connectivity after MRgFUS thalamotomy. In addition, the FC of the visual network, which declined in ET patients compared with HCs, tended to normalize postoperatively. This could be related to the hypothesis that visual feedback is involved in tremor severity in ET patients. Overall, the analysis of the RSNs by rsfMRI reflected the pathophysiology with the intervention of MRgFUS thalamotomy in ET patients and demonstrated a possibility of a biomarker for successful treatment.

Cutoff values for the best management strategy for magnetic resonance-guided focused ultrasound ablation for essential tremor.

OBJECTIVE: The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) ablation for essential tremor (ET) is well known; however, no prognostic factors have been established. The authors aimed to retrospectively investigate MRgFUS ablation outcomes and associated factors and to define the cutoff values for each prognostic factor. METHODS: Sixty-four Japanese patients who underwent unilateral ventral intermediate nucleus thalamotomy with MRgFUS for ET were included. Follow-up evaluations were performed at 1 week and 1, 3, 6, 12, and 24 months postoperatively. Tremor suppression was evaluated using the Clinical Rating Scale for Tremor (CRST), and adverse effects were recorded postoperatively. Outcome-associated factors were examined preoperatively, intraoperatively, and postoperatively using multivariate analyses. The cutoff values for the prognostic factors were calculated using receiver operating characteristics. RESULTS: Percentage improvements in the CRST scores of the affected upper limb were 82.4%, 72.2%, 68.6%, and 65.9% at 1, 3, 6, and 12 months, respectively. Preoperatively, a high skull density ratio (SDR) (p ≤ 0.047), low CRST part B score (used to assess tremors during several tasks) (cutoff value 25, p ≤ 0.041), and nonoccurrence of resting tremors (p = 0.027) were significantly associated with improved tremor control. An intraoperatively high maximum mean temperature (cutoff value 52.5°C, p ≤ 0.047), postoperatively large lesion (cutoff value 3.9 mm in the anterior-posterior direction, p ≤ 0.002; cutoff value 5.0-5.55 mm in the superior-inferior direction, p ≤ 0.026), and small transducer focus correction (p ≤ 0.015) were also associated with improved tremor control. No valid cutoff value was found for SDR. Adverse effects (limb weakness, sensory disturbance, ataxia/walking disturbance, dysgeusia, dysarthria, and facial swelling) occurred transiently and were associated with high SDR, high temperature, high number of sonication sessions, large lesion, and occurrence of resting tremor. Patients who developed leg weakness experienced greater percentage improvement in tremors at 3 months postoperatively than those who did not. CONCLUSIONS: MRgFUS ablation could be used to achieve good tremor control with acceptable adverse effects in Japanese patients with ET. The relatively low SDR in Asian ethnic groups as compared with that of Western populations makes treatment difficult; however, the cutoff values obtained in this study may be useful for achieving good treatment outcomes even in such patients. Clinical trial registration no.: UMIN000026952 (University Hospital Medical Information Network). ABBREVIATIONS: ACPC = anterior commissure-posterior commissure; AP = anterior to posterior; CRST = Clinical Rating Scale for Tremor; ET = essential tremor; MRgFUS = magnetic resonance-guided focused ultrasound; PC = posterior commissure; PSA = posterior subthalamic area; RL = right to left; ROC = receiver operating characteristic; SDR = skull density ratio; SI = superior to inferior; T2WI = T2-weighted imaging; VIM = ventral intermediate nucleus.

Multitier Network Analysis Using Resting-state Functional MRI for Epilepsy Surgery.

Resting-state functional MRI (rs-fMRI) has been utilized to visualize large-scale brain networks. We evaluated the usefulness of multitier network analysis using rs-fMRI in patients with focal epilepsy. Structural and rs-fMRI data were retrospectively evaluated in 20 cases with medically refractory focal epilepsy, who subsequently underwent surgery. First, structural changes were examined using voxel-based morphometry analysis. Second, alterations in large-scale networks were evaluated using dual-regression analysis. Third, changes in cortical hubs were analyzed and the relationship between aberrant hubs and the epileptogenic zone (EZ) was evaluated. Finally, the relationship between the hubs and the default mode network (DMN) was examined using spectral dynamic causal modeling (spDCM). Dual-regression analysis revealed significant decrease in functional connectivity in several networks including DMN in patients, although no structural difference was seen between groups. Aberrant cortical hubs were observed in and around the EZ (EZ hubs) in 85% of the patients, and a strong degree of EZ hubs correlated to good seizure outcomes postoperatively. In spDCM analysis, facilitation was often seen from the EZ hub to the contralateral side, while inhibition was seen from the EZ hub to nodes of the DMN. Some cognition-related networks were impaired in patients with focal epilepsy. The EZ hub appeared in the vicinity of EZ facilitating connections to distant regions in the early phase, which may eventually generate secondary focus, while inhibiting connections to the DMN, which may cause cognitive deterioration. Our results demonstrate pathological network alterations in epilepsy and suggest that earlier surgical intervention may be more effective.

A case report: Dual-lead deep brain stimulation of the posterior subthalamic area and the thalamus was effective for Holmes tremor after unsuccessful focused ultrasound thalamotomy.

Holmes tremor is a symptomatic tremor that develops secondary to central nervous system disorders. Stereotactic neuromodulation is considered when the tremors are intractable. Targeting the ventral intermediate nucleus (Vim) is common; however, the outcome is often unsatisfactory, and the posterior subthalamic area (PSA) is expected as alternative target. In this study, we report the case of a patient with intractable Holmes tremor who underwent dual-lead deep brain stimulation (DBS) to stimulate multiple locations in the PSA and thalamus. The patient was a 77-year-old female who complained of severe tremor in her left upper extremity that developed one year after her right thalamic infarction. Vim-thalamotomy using focused ultrasound therapy (FUS) was initially performed but failed to control tremor. Subsequently, we performed DBS using two leads to stimulate four different structures. Accordingly, one lead was implanted with the aim of targeting the ventral oralis nucleus (Vo)/zona incerta (Zi), and the other with the aim of targeting the Vim/prelemniscal radiation (Raprl). Electrode stimulation revealed that Raprl and Zi had obvious effects. Postoperatively, the patient achieved good tremor control without any side effects, which was maintained for two years. Considering that she demonstrated resting, postural, and intention/action tremor, and Vim-thalamotomy by FUS was insufficient for tremor control, complicated pathogenesis was presumed in her symptoms including both the cerebellothalamic and the pallidothalamic pathways. Using the dual-lead DBS technique, we have more choices to adjust the stimulation at multiple sites, where different functional networks are connected. Intractable tremors, such as Holmes tremor, may have complicated pathology, therefore, modulating multiple pathological networks is necessary. We suggest that the dual-lead DBS (Vo/Raprl and Vim/Zi) presented here is safe, technically feasible, and possibly effective for the control of Holmes tremor.

Techniques, Indications, and Outcomes in Magnetic Resonance-guided Focused Ultrasound Thalamotomy for Tremor.

Magnetic resonance (MR)-guided focused ultrasound surgery (MRgFUS) is the latest minimally invasive stereotactic procedure, and thalamotomy using this novel modality has demonstrated its effectiveness and safety, especially for patients with essential tremor (ET) and Parkinson's disease (PD). In Japan, the application of MRgFUS to treat ET and PD has recently been covered by health insurance. Technically, the transducer with 1024 elements emits ultrasound beams, which are then focused on the target with a phase control, resulting in optimal ablation by thermal coagulation. The technical advantages of MRgFUS are continuous intraoperative monitoring of clinical symptoms and MR images and fine adjustment of the target by the steering function. Postoperative tremor control is compatible with other modalities, although long-term follow-up is necessary. The adverse effects are usually transient and acceptable. Prognostic factors for good tremor control include high temperature and large lesion size. A high skull density ratio is a factor to achieve high temperature and large lesioning, but it may not be necessary and sufficient for clinical outcomes. For patients with advanced symptoms such as bilateral tremor or head/neck tremor, deep brain stimulation may be recommended because of the adjustability of stimulation and the possibility of bilateral treatment. Patients have high expectations of MRgFUS because of its non-invasiveness. To perform this treatment safely and effectively, physicians need to understand the technological aspects, the physiological principles. To choose the appropriate modality, physicians also should recognize the clinical advantages and disadvantages of MRgFUS compared to other modalities.

Distributed source analysis of magnetoencephalography using a volume head model combined with statistical methods improves focus diagnosis in epilepsy surgery.

Deep-seated epileptic focus estimation using magnetoencephalography is challenging because of its low signal-to-noise ratio and the ambiguity of current sources estimated by interictal epileptiform discharge (IED). We developed a distributed source (DS) analysis method using a volume head model as the source space of the forward model and standardized low-resolution brain electromagnetic tomography combined with statistical methods (permutation tests between IEDs and baselines and false discovery rate between voxels to reduce variation). We aimed to evaluate the efficacy of the combined DS (cDS) analysis in surgical cases. In total, 19 surgical cases with adult and pediatric focal epilepsy were evaluated. Both cDS and equivalent current dipole (ECD) analyses were performed in all cases. The concordance rates of the two methods with surgically identified epileptic foci were calculated and compared with surgical outcomes. Concordance rates from the cDS analysis were significantly higher than those from the ECD analysis (68.4% vs. 26.3%), especially in cases with deep-seated lesions, such as in the interhemispheric, fronto-temporal base, and mesial temporal structures (81.8% vs. 9.1%). Furthermore, the concordance rate correlated well with surgical outcomes. In conclusion, cDS analysis has better diagnostic performance in focal epilepsy, especially with deep-seated epileptic focus, and potentially leads to good surgical outcomes.

Anatomo-electro-clinical correlations of hypermotor seizures with amygdala enlargement: Hippocampal seizure origin identified using stereoelectroencephalography.

•A drug-resistant epilepsy case showed hypermotor seizures and amygdala enlargement.•Seizure onset zone was the hippocampus, not amygdala, as revealed by SEEG.•The enlarged amygdala pathology was classified as FCD type I.•Selective amygdalohippocampectomy led to good outcomes.

Three types of dural suturing for closure of CSF leak after endoscopic transsphenoidal surgery.

OBJECTIVE: Transsphenoidal surgery (TSS) is commonly used for anterior skull base surgery, especially in the sella turcica (sellar) region. However, because of its anatomical position, CSF leakage is a major complication of this approach. The authors introduced a new grading reconstruction strategy for anterior skull base surgery with continuous dural suturing in 2013. In this paper the authors report on their methods and results. METHODS: All patients with sellar or anterior skull base lesions that were removed with TSS or extended TSS by a single neurosurgeon between April 2013 and March 2017 at Nagoya University Hospital and several cooperating hospitals were retrospectively identified. Three methods of suturing dura were considered, depending on the dural defect. RESULTS: There were 176 TSS cases (141 conventional TSS cases and 35 extended endoscopic TSS cases) and 76 cases of Esposito's grade 2 or 3 intradural high-flow CSF leakage. In the high-flow CSF leak group, there were 3 cases of CSF leakage after the operation. The rates of CSF leakage after surgery corresponding to grades 2 and 3 were 2.9% (1/34) and 4.7% (2/42), respectively. CONCLUSIONS: Dural suturing is a basic and key method for reconstruction of the skull base, and continuous suturing is the most effective approach. Using this approach, the frequency of cases requiring a nasoseptal flap and lumbar drainage can be reduced.

Application of Awake Surgery for Epilepsy in Clinical Practice.

Epilepsy surgery aims to control epilepsy by resecting the epileptogenic region while preserving function. In some patients with epileptogenic foci in and around functionally eloquent areas, awake surgery is implemented. We analyzed the surgical outcomes of such patients and discuss the clinical application of awake surgery for epilepsy. We examined five consecutive patients, in whom we performed lesionectomy for epilepsy with awake craniotomy, with postoperative follow-up > 2 years. All patients showed clear lesions on magnetic resonance imaging (MRI) in the right frontal (n = 1), left temporal (n = 1), and left parietal lobe (n = 3). Intraoperatively, under awake conditions, sensorimotor mapping was performed; primary motor and/or sensory areas were successfully identified in four cases, but not in one case of temporal craniotomy. Language mapping was performed in four cases, and language areas were identified in three cases. In one case with a left parietal arteriovenous malformation (AVM) scar, language centers were not identified, probably because of a functional shift. Electrocorticograms (ECoGs) were recorded in all cases, before and after resection. ECoG information changed surgical strategy during surgery in two of five cases. Postoperatively, no patient demonstrated neurological deterioration. Seizure disappeared in four of five cases (Engel class 1), but recurred after 2 years in the remaining patient due to tumor recurrence. Thus, for patients with epileptogenic foci in and around functionally eloquent areas, awake surgery allows maximal resection of the foci; intraoperative ECoG evaluation and functional mapping allow functional preservation. This leads to improved seizure control and functional outcomes.

[Usefulness and Problems of Intraoperative Monitoring for Unruptured Aneurysm Surgery with the Motor Evoked Potential].

It has been pointed out that the motor evoked potential(MEP)with a subdural electrode is useful in the intraoperative monitoring for unruptured aneurysm surgery. However, in some cases, we experienced postoperative ischemic complications despite evaluating the motor function via MEP monitoring. Herein, we have reported the usefulness and problems of intraoperative monitoring with MEP to evaluate brain dysfunction caused by insufficiency of cerebral blood flow. Out of 279 aneurysm surgery procedures, we performed MEP monitoring in 142 cases and successfully recorded in 126 cases. We compared the ischemic complication rate of the group for which MEP was monitored with that of the group for which MEP was not monitored. The whole ischemic complication rate was decreased in the group that underwent MEP monitoring. Thus, it was suggested that MEP monitoring was useful for avoiding ischemic complications. In internal carotid artery aneurysms, the amplitude of MEP changed and recovered in 2 cases and disappeared in one case. In anterior cerebral artery aneurysms, the amplitude of MEP changed and recovered in 2 cases. In middle cerebral artery aneurysms, the amplitude of MEP changed and recovered in 5 cases. We could avoid ischemic complications by intraoperative MEP monitoring in many cases. However, in some cases, we found ischemic complications that were not detected by MEP monitoring with a subdural electrode. In these cases, transcranial stimulation in combination with subdural electrode might be effective in avoiding ischemic complications that might occur after dural closure.