SummaryBackgroundIntracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.MethodsIn a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.FindingsOf 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).InterpretationIn this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects i...

The clinical, radiological, and operative factors of recurrent chronic subdural hematoma (CSDH) were retrospectively analyzed in 116 patients with CSDH in 134 hemispheres, treated by one burr hole surgery. The correlation of recurrence was evaluated with personal and clinical factors such as age, sex, history of head injury, and interval from onset of initial symptoms to hospitalization; laboratory findings such as bleeding tendency and liver function; computed tomography (CT) findings such as hematoma density and brain atrophy; and operative findings such as additional procedures and postoperative residual air. The recurrence group (RG) included 10 hemispheres (7.5%) in 10 patients (8.6%). The interval from onset of symptoms to hospitalization was significantly shorter in the RG than in the nonrecurrence group (NRG). Headache was more frequently seen in the RG than in the NRG. Density of hematoma on CT was classified into five types: Low, iso, and high density, niveau, and mixed, and the incidence of recurrence was 0%, 2.3%, 17.2%, 12.5%, and 6.5%, respectively. Larger amounts of residual air in the postoperative hematoma cavity were associated with recurrence of CSDH. CSDH that progresses rapidly in the acute stage and appears as high density on preoperative CT is associated with a high incidence of recurrence. Intraoperative air invasion to the hematoma cavity should be avoided to prevent recurrence.

Summary:Purpose: To test the sensitivity of extracranial magnetoencephalography (MEG) for epileptic spikes in different cerebral sites.Methods: We simultaneously recorded MEG and electrocorticography (ECoG) by using subdural electrodes with 1-cm interelectrode distances for one patient with lateral frontal epilepsy and one patient with basal temporal epilepsy. We analyzed MEG spikes associated with ECoG spikes and compared the maximal amplitude and number of electrodes involved. We estimated and evaluated the locations and moments of the equivalent current dipoles (ECDs) of MEG spikes.Results: In patient 1, MEG detected 100 (53%) of 188 ECoG lateral frontal spikes, including 31 (46%) of 67 spikes that activated three subdural electrodes. MEG spike amplitudes correlated with ECoG spike amplitudes and the number of electrodes activated (p < 0.01). ECDs were perpendicular to the superior frontal sulcus. In patient 2, MEG detected 31 (26%) of 121 ECoG basal temporal spikes, but none that activated only three subdural electrodes. ECDs were localized in the entorhinal and parahippocampal gyri, oriented perpendicular to those basal temporal cortical surfaces. The ECD strength was 136.6 ± 71.5 nAm in the frontal region, but 274.5 ± 150.6 nAm in the temporal region (p < 0.01).Conclusions: When lateral frontal ECoG spikes extend >3 cm 2 across the fissure, MEG can detect >50%, correlating with spatial activation and voltage. In the basal temporal region, MEG requires higher-amplitude discharges over a more extensive area. MEG shows a significantly higher sensitivity to lateral convexity epileptic discharges than to discharges in isolated deep basal temporal regions. Key Words: Magnetoencephalography-Electrocorticography-Epilepsy-Extent of epileptic spikes-Sensitivity.Magnetoencephalography (MEG) measures the extracranial magnetic fields generated by intraneuronal electric currents with superconducting quantum interference devices (1). Extracranial magnetic fields result from intracranial tangential currents, such as neuronal activity, in the fissural cortex, which makes up two thirds of the surface of the human brain (2). During MEG analysis, magnetic field recordings are fitted to an equivalent current dipole (ECD) model to localize sources of intracranial activity, such as epileptic spikes; the spike source locations are then overlaid onto magnetic resonance (MR) images of corresponding areas of the brain. Because magnetic fields are relatively unaffected by the different electrical conductivities of the brain, cerebral spinal fluid, skull, and skin, MEG can accurately localize the source of intraneuronal electric currents that contribute to extracranial magnetic fields (3).Electroencephalography (EEG) dipole recordings delineate both radial and tangential currents (4). However, the electrical fields, as measured by EEG, are affected by the conductivities of different tissues.MEG has clinical application for patients with partial epilepsy. Neurosurgeons use advanced multisensor helmet-shaped, whole-head neuromagnetomete...

Summary:Purpose: To characterize the epileptogenic zone in neocortical epilepsy (NE) by using magnetoencephalography (MEG).Methods: We defined and compared locations of single and multiple clusters of equivalent current dipoles (ECDs) for interictal spikes with MRI findings, ictal-onset zones (IOZs) from subdural electroencephalography (SDEEG), resected areas, and postsurgical outcomes of 20 patients who underwent cortical resection for medically intractable NE.Results: Fourteen patients had single clusters; six had multiple clusters. Overlap of clusters and IOZs defined group A (nine patients), in which a single cluster coincided with the IOZ; group B1 (four patients), in which a single cluster was within or partially overlapped the IOZ; group B2 (five patients), in which multiplecluster sections overlapped IOZs; group C (two patients; one single; one multiple), in which no overlap was seen. More single clusters (nine of 14) than multiple clusters (none of six) coincided with the IOZ (p = 0.014). More patients with single clusters (10 of 14) than patients with multiple clusters (one of six) had seizure-free outcomes (p = 0.049). Eight of nine patients in group A, versus three of 11 in groups B1, B2, and C, achieved seizure-free outcomes (p = 0.0098). Correlations between MRI findings and postsurgical outcomes were not statistically significant; eight of 13 patients with single lesions, one of four with no lesions, and two of three with multifocal lesions had seizure-free outcomes.Conclusions: In neocortical epilepsy, MEG ECD clusters correlated with SDEEG IOZs. Single clusters indicated discrete epileptogenic zones that required complete resection for seizurefree outcome. Multiple clusters necessitated that the multiple or extensive epileptogenic zones be completely identified and delineated by SDEEG.

Intraoperative FNMEP monitoring can be useful for predicting facial nerve function after skull base surgery. This new method is a valuable adjunct to conventional facial nerve monitoring.

Magnetoencephalography spike source clusters indicate an epileptic zone requiring complete excision. Coexisting scatters remote from clusters are nonepileptogenic and do not require excision. Scatters alone, however, should be examined by ECoG; an epileptic zone may exist within these distributions.

S urgical removal of tumors located in the skull base or deep intracranial regions requires a high order of anatomical knowledge that can be obtained only through a large number of surgical experiences and has therefore been recognized as a challenging category in the neurosurgical field. Object. In this paper, the authors' goal was to report their novel presurgical simulation method applying interactive virtual simulation (IVS) using 3D computer graphics (CG) data and microscopic observation of color-printed plaster models based on these CG data in surgery for skull base and deep tumors.Methods. For 25 operations in 23 patients with skull base or deep intracranial tumors (meningiomas, schwannomas, epidermoid tumors, chordomas, and others), the authors carried out presurgical simulation based on 3D CG data created by image analysis for radiological data. Interactive virtual simulation was performed by modifying the 3D CG data to imitate various surgical procedures, such as bone drilling, brain retraction, and tumor removal, with manipulation of a haptic device. The authors also produced color-printed plaster models of modified 3D CG data by a selective laser sintering method and observed them under the operative microscope.Results. In all patients, IVS provided detailed and realistic surgical perspectives of sufficient quality, thereby allowing surgeons to determine an appropriate and feasible surgical approach. Surgeons agreed that in 44% of the 25 operations IVS showed high utility (as indicated by a rating of "prominent") in comprehending 3D microsurgical anatomies for which reconstruction using only 2D images was complicated. Microscopic observation of color-printed plaster models in 12 patients provided further utility in confirming realistic surgical anatomies.Conclusions. The authors' presurgical simulation method applying advanced 3D imaging and modeling techniques provided a realistic environment for practicing microsurgical procedures virtually and enabled the authors to ascertain complex microsurgical anatomy, to determine the optimal surgical strategies, and also to efficiently educate neurosurgical trainees, especially during surgery for skull base and deep tumors. (http://thejns.org/doi/abs/10.3171/2013.3.JNS121109) keY WorDs • neurosurgery • presurgical simulation • skull base tumor • surgical anatomy • 3D imaging • oncology Abbreviations used in this paper: CAD = computer-aided designing; CG = computer graphics; CN = cranial nerve; CPA = cerebellopontine angle; CTA = CT angiography; DSA = digital subtraction angiography; IAC = internal auditory canal; IVS = interactive virtual simulation; MRA = MR angiography.

Epithelioid glioblastoma is a rare aggressive variant of glioblastoma (GBM) characterized by a dismal prognosis of about 6 months and frequent leptomeningeal dissemination. A recent study has revealed that 50% of epithelioid GBMs harbor three genetic alterations – BRAF V600E mutation, TERT promoter mutations, and homozygous deletions of CDKN2A/2B . Emerging evidence support the effectiveness of targeted therapies for brain tumors with BRAF V600E mutation. Here we describe a dramatic radiographical response to combined therapy with BRAF and MEK inhibitors in a patient with epithelioid GBM harboring BRAF V600E mutation, characterized by thick spinal dissemination. From relapsed tumor procured at autopsy, we established a cell line retaining the BRAF V600E mutation, TERT promoter mutation and CDKN2A/2B loss. Intracranial implantation of these cells into mice resulted in tumors closely resembling the original, characterized by epithelioid tumor cells and dissemination, and invasion into the perivascular spaces. We then confirmed the efficacy of treatment with BRAF and MEK inhibitor both in vitro and in vivo. Epithelioid GBM with BRAF V600E mutation can be considered a good treatment indication for precision medicine, and this patient-derived cell line should be useful for prediction of the tumor response and clarification of its biological characteristics. Electronic supplementary material The online version of this article (10.1186/s40478-019-0774-7) contains supplementary material, which is available to authorized users.