Time course of tumorigenesis of a newly developed sporadic hemangioblastoma in an elderly patient: illustrative case.

BACKGROUND: von Hippel-Lindau disease-associated hemangioblastomas (HBs) account for 20%-30% of all HB cases, with the appearance of new lesions often observed in the natural course of the disease. By comparison, the development of new lesions is rare in patients with sporadic HB. OBSERVATIONS: A 65-year-old man underwent clipping for an unruptured aneurysm of the anterior communicating artery. Fourteen years later, follow-up magnetic resonance imaging (MRI) revealed a strongly enhanced mass in the right cerebellar hemisphere, diagnosed as a sporadic HB. A retrospective review of MRI studies obtained over the follow-up period revealed the gradual development of peritumoral edema and vascularization before mass formation. LESSONS: Newly appearing high-intensity T2 lesions in the cerebellum may represent a preliminary stage of tumorigenesis. Careful monitoring of these patients would be indicated, which could provide options for early treatment to improve patient outcomes.

Higher abundance of Campylobacter in the oral microbiome of Japanese patients with moyamoya disease.

Genetic factors alone cannot explain the pathophysiology of moyamoya disease (MMD), and environmental factors such as an immune response are thought to be involved. Oral and gut microbiomes have attracted attention as environmental factors in the pathophysiology of some vascular and autoimmune diseases. However, the relationship between MMD and these microbiomes is yet to be thoroughly investigated. This prospective case-control study aimed to compare the microbiomes of Japanese patients with MMD with those of healthy individuals to identify the specific bacteria involved in MMD. Saliva and fecal samples were collected from 16 patients with MMD who had not undergone revascularization surgery. Fifteen healthy individuals were matched for age, sex, and body mass index. The microbiomes were determined using 16S rRNA sequencing and analyzed using QIIME2. Differentially abundant microbes were identified using LEfSE and ANCOM-BC. In the oral microbiome, the two analytical methods showed that Campylobacter was more abundant in patients with MMD than in healthy individuals. Differences in the gut microbiome were smaller than those in the oral microbiome. In conclusion, the oral microbiome profiles of patients with MMD significantly differ from those of healthy individuals. Campylobacter spp. could be a substantial environmental factor in the pathophysiology of MMD.

Efficacy of Spinal Cord Stimulation Using Differential Target Multiplexed Stimulation for Intractable Pain of Hereditary Neuropathy with Liability to Pressure Palsies: A Case Report.

Hereditary neuropathy with liability to pressure palsies is an extremely rare genetic disorder; it is an autosomal dominant disorder with a high incidence of neuropathic and/or musculoskeletal pain. A case of achieving pain relief by spinal cord stimulation using differential target multiplexed stimulation for a 44-year-old female patient with hereditary neuropathy with liability to pressure palsies who was experiencing severe pain in her back, face, and all four limbs is presented. In her early teens, the initial symptoms were numbness and weakness of a limb after movement, which improved spontaneously. Transient pain in her back followed by systemic and persistent muscle weakness and pain developed. Deletion of the gene for peripheral myelin protein 22 was detected by peripheral nerve biopsy. The diagnosis of hereditary neuropathy with liability to pressure palsies was made in her early thirties. A spinal cord stimulation trial was performed because her severe pain continued despite administering many medications. Therefore, two spinal cord stimulation systems were implanted at the C3-5 and Th8-9 levels by two procedures. Pain in her back, arms, and legs decreased from 8 to 1, 5 to 1, and 6 to 2 on the numerical rating scale, respectively. Furthermore, opioid usage was tapered. The pain of hereditary neuropathy with liability to pressure palsies has a complicated pathogenesis and is resistant to pharmacological treatment. Spinal cord stimulation using differential target multiplexed stimulation may be a viable treatment option.

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.

Secondary aneurysmal bone cyst of the frontal bone with fibrous dysplasia showing rapid expansion: a case report.

A 19-year-old woman presented with swelling of the left forehead without pain. She did not have any relevant past or family history. Computed tomography showed destruction of the outer cortex of the frontal bone. A solitary mass lesion with a fluid collection was detected with magnetic resonance imaging. Because the swelling of the left forehead had enlarged rapidly with osteolytic changes, surgical removal of the lesion was performed. The lesion appeared to be enveloped in a fibrous capsule. The soft lesion was removed from the frontal bone. The outer frontal bone was absent, although the inner frontal bone was preserved. Then, the frontal bone was resected with margins from the edge of the erosion. The dura mater under the lesion was intact. A cranioplasty was performed using titanium mesh. On histological examination, the trabecular bones revealed irregular shapes and arrangements, indicating fibrous dysplasia. There was a continuous high-cell-concentration pathological lesion outside the fibrous dysplasia. There were numerous cells, such as mononuclear cells, osteoclast-like multinucleated giant cells, foam cells, and red blood cells. The osteoclast-like multinucleated giant cells and other cells did not show significant nuclear atypia. Immunostaining with H3.3G34W was negative, and the ubiquitin-specific peptidase 6/Tre-2 gene showed no rearrangements. The histopathological diagnosis was secondary aneurysmal bone cyst with fibrous dysplasia. Additional postsurgical therapy was not performed. There has been no evidence of recurrence of the lesion for two years.

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.

Unique vascular structures of a radicular arteriovenous fistula at the craniocervical junction along the first cervical spinal nerve: A case report.

Background: An arteriovenous fistula (AVF) at the craniocervical junction (CCJ) is a rare vascular malformation. Definitive diagnosis and curative treatment of CCJ AVF are challenging. Case Description: A 77-year-old man presented with subarachnoid hemorrhage. Cerebral angiography showed an AVF at the CCJ, which drained into a radicular vein. The lesion was fed by a vertebral artery, anterior and lateral spinal arteries (LSAs), and the occipital artery (OA). There were two unique structures: the LSA originating from the posterior inferior cerebellar artery of the extracranial V3 segment and the OA feeding the shunt. Curative treatment involved two steps: endovascular embolization of feeders using Onyx and surgical shunt disconnection. Feeding arteries were blackened by Onyx, which helped identify the location of the shunt. The shunt was located behind the first cervical (C1) spinal nerve, and the draining vein was confirmed on the deep side of the nerve. A clip was applied to the draining vein distal to the shunt. Tiny vessels supplying the shunt were then coagulated referring to blackened arteries. Conclusion: A radicular AVF at the CCJ along the C1 spinal nerve had unique vascular structures. Definitive diagnosis and curative treatment were achieved by combining endovascular embolization using Onyx and direct surgery.

[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.

Long noncoding RNA profile of the intracranial artery in patients with moyamoya disease.

OBJECTIVE: Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the internal carotid artery (ICA) and secondary formation of collateral vessels. Revascularization surgery is performed in patients with MMD to prevent stroke; however, the pathogenesis of MMD remains unknown. Recently, long noncoding RNAs (lncRNAs) have been found to play a key role in gene regulation and are implicated in various vascular diseases. However, the lncRNA expression profile in MMD lesions has not been investigated. In this study the authors aimed to determine the characteristics of lncRNA expression in MMD lesions. METHODS: The authors collected microsamples of the middle cerebral artery (MCA) from patients with MMD (n = 21) and patients with control conditions (n = 11) who underwent neurosurgical treatment. Using microarray experiments, the authors compared the profiles of lncRNA expression in the MCAs of the MMD and control patient groups and identified differentially expressed lncRNAs (fold change > 2, q < 0.05). In addition, the neighboring coding genes, whose transcription can be regulated in cis by the identified differentially expressed lncRNAs, were investigated and Gene Ontology (GO) analysis was applied to predict associated biological functions. RESULTS: The authors detected 308 differentially expressed lncRNAs (fold change > 2, q < 0.05), including 306 upregulated and 2 downregulated lncRNAs in the MCA from patients with MMD. Regarding the prediction of biological function, GO analyses with possible coding genes whose transcription was regulated in cis by the identified differentially expressed lncRNAs suggested involvement in the antibacterial humoral response, T-cell receptor signaling pathway, positive regulation of cytokine production, and branching involved in blood vessel morphogenesis. CONCLUSIONS: The profile of lncRNA expression in MMD lesions was different from that in the normal cerebral artery, and differentially expressed lncRNAs were identified. This study provides new insights into the pathophysiology of MMD.

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.

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.

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.

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.

[Magnetic Resonance-guided Focused Ultrasound Ablation:Techniques and Neurological Applications].

Magnetic resonance(MR)-guided focused ultrasound ablation(FUS)is a minimally invasive technique for targeted tissue thermo-ablation and is promising for neuromodulation in various neurological disorders. The effectiveness and safety of this technique have been recognized worldwide. In Japan, the applications of FUS for the treatment of essential tremors and Parkinson's disease have recently been covered under health insurance. The FUS system is composed of a phased-array transducer with 1024 elements, with a beam of ultrasound emerging from each element. The phase and amplitude of the beam are computed and controlled to focus on the target with the calculation of computed tomography(CT)profiles, resulting in optimal thermo-ablation. To utilize FUS safely and effectively, a deep understanding of the physics of this technology is necessary. Furthermore, the technique should be compared with other options including deep brain stimulation(DBS)and radiofrequency thermo-ablation. Although FUS has received attention because of minimally invasive characteristics and a possibility of procedural target refinement, DBS has some advantages on bilateral implantation, a potential of postoperative adjustment, and control of head/leg tremors. In this article, we first reviewed the physics of FUS and demonstrated the typical treatment protocols. Second, we reviewed the outcomes from the existing literature, and revealed the advantages and disadvantages of this procedure, with the evaluation of the optimal condition for FUS.

[Electrical Stimulation Mapping of Multilingualism].

Language mapping is commonly practiced in brain tumors and epilepsy surgeries. It is done by direct electrical stimulation of the brain during awake craniotomy or by placing subdural electrodes on the brain's surface, or both. Studies of the language mapping in bi- or multi-lingual patients have concluded that they have both "language-specific areas," in which symptoms are evoked upon stimulation in one specific language and not in the other languages, and "common areas" or "overlapping areas," in which positive findings are evoked in all languages evaluated. The distribution of the pattern of language areas associated with each language, however, varies widely from patient to patient due to multiple factors such as the age of language acquisition, the language proficiency level, the amount of exposure to each language, the location of the lesions, the duration of the diseases, and other factors. Language mapping in bi- or multi-lingual patients should be done by screening all languages the patient speaks.

Solitary fibrous tumor/hemangiopericytoma treated with temozolomide plus bevacizumab: a report of four cases and literature review.

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a rare tumor derived from mesenchymal tissue. Although standard chemotherapy for SHT/HPC has not been established, temozolomide plus bevacizumab (TMZ+Bev) therapy for SFT/HPC has been reported. The effectiveness and safety of TMZ+Bev (temozolomide 150 mg/m2 orally on days 1-7 and days 15-21 and bevacizumab 5 mg/kg intravenously on day 8 and day 22 on a 28-day cycle), which was administered from December 2013 until April 2019 to four patients with SFT/HPC, were retrospectively analyzed. Four patients with SFT/HPC received TMZ+Bev. The age of the patients ranged from 41 to 75 years. Two were male, and the primary tumor sites were the meninges in three patients and the pleura in one. One achieved partial response; the others, stable disease (SD). The progression-free survival time ranged from 9.4 to 29.6 months according to RECIST v1.1. One patient died 59 months after using TMZ+Bev, and the others survived for 17 to 64 months. All patients experienced Grade 3 or higher lymphopenia, and three had Grade 3 or higher leukopenia and neutropenia. One patient subsequently received doxorubicin; another, pazopanib. TMZ+Bev therapy for SFT/HPC is safe and effective for maintaining long-term SD.

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.

Subsecond EEG-fMRI analysis for presurgical evaluation in focal epilepsy.

OBJECTIVE: The authors recently reported a novel subsecond analysis method of analyzing EEG-functional MRI (fMRI) to improve the detection rate of epileptic focus. This study aims to validate the utility of this method for presurgical evaluation in pharmacoresistant focal epilepsy. METHODS: Among 13 patients with focal epilepsy undergoing presurgical examinations including simultaneous EEG-fMRI at 3T, 11 patients had interictal epileptiform discharges (IEDs) during fMRI. The authors used the sequence of topographic maps during the IEDs as a reference to obtain subsecond fMRI activation maps with the same temporal resolution as the EEG data, and constructed "spike-and-slow-wave-activation-summary" (SSWAS) maps that showed the activation frequency of voxels during IEDs. Clusters were defined by thresholding the SSWAS maps (voxel value > 10), and those containing voxels with the top 3 highest activation frequencies were considered significant. Significant hemodynamic responses using conventional event-related (ER) analysis and SSWAS maps were compared with the resection areas and surgical outcomes at 1 year after surgery. RESULTS: Using ER analysis, 4 (36%) of 11 patients had significant hemodynamic responses. One of 4 patients had significant hemodynamic responses in the resection area and good surgical outcome. Using SSWAS maps, 10 (91%) of 11 patients had significant hemodynamic responses. Six of 10 patients had significant hemodynamic responses in the resection area, and 5 of the 6 patients achieved good surgical outcomes. The remaining 4 patients had significant hemodynamic responses distant from the resection area, and only 1 of the 4 patients achieved good surgical outcomes. The sensitivity, specificity, positive predictive value, and negative predictive value of SSWAS maps were 83.3%, 75.0%, 83.3%, and 75.0%, respectively. CONCLUSIONS: This study demonstrated the clinical utility of SSWAS maps for presurgical evaluation of pharmacoresistant focal epilepsy. The findings indicated that subsecond EEG-fMRI analysis may help surgeons choose the resection areas that could lead to good surgical outcomes.