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Stereo-electroencephalography (SEEG) is inherently-three-dimensional and can be modeled using source localization. This study aimed to assess the validity of ictal SEEG source localization.The dominant frequency at ictal onset was used for source localization in the time and frequency domains using rotating dipoles and current density maps. Validity was assessed by concordance with the epileptologist-defined seizure onset zone (conventional SOZ) and the surgical treatment volume (TV) of seizure-free versus non-seizure-free patients.Source localization was performed on 68 seizures from 27 patients. Median distance to nearest contact in the conventional SOZ was 7 (IQR 6-12) mm for time-domain dipoles. Current density predicted ictal activity with up to 86 % (60-87 %) accuracy. Distance from time-domain dipoles to the TV was smaller (P = 0.045) in seizure-free (2 [0-4] mm) versus non-seizure-free (12 [2-17] mm) patients, and predicted surgical outcome with 91 % sensitivity and 63 % specificity. Removing near-field data from contacts within the TV negated outcome prediction (P = 0.51).Source localization of SEEG accurately mapped ictal onset compared with conventional interpretation. Proximity of dipoles to the TV predicted seizure outcome when near-field recordings were analyzed.Ictal SEEG source localization is useful in corroborating the epileptogenic zone, assuming near-field recordings are obtained.

Background Endoscopic third ventriculostomy (ETV) is a widely accepted treatment for obstructive hydrocephalus. For most practitioners, this procedure will be performed without navigation guidance. Without such guidance, the complications associated with the procedure have ranged from 1% to 8%. We hypothesized that the discrepancy between the surface bony anatomy and internal cranial anatomy contributes to the morbidities associated with ETV. We tested this hypothesis by comparing the position of the entry point defined by the classic Kocher's point relative to the ideal entry point that would result in no manipulation of the endoscope defined by frame-based stereotaxis. Methods The cranial computed tomography scan of 58 patients who had undergone frame-based stereotactic ETV was reformatted into 3-dimensional renderings. The location of this entry point was compared with the Kocher point, as determined by the external bony anatomy. Results Overall, >70% of the burr holes that provided an ideal trajectory to the third ventricle were ≥0.5 cm from the Kocher point in both the sagittal and the coronal planes. Median deviations of 0.74 and 0.81 cm in the coronal (P Conclusion The use of stereotactic endoscopic techniques increase the safety of third ventriculostomy by adding precision and reducing otherwise unnecessary surgical maneuvering.

Efforts to improve epilepsy surgery outcomes have led to increased interest in the study of electroencephalographic oscillations outside the conventional EEG bands. These include fast activity above the gamma band, known as high frequency oscillations (HFOs), and infraslow activity (ISA) below the delta band, sometimes referred to as direct current (DC) or ictal baseline shifts (IBS). HFOs in particular have been extensively studied as potential biomarkers for epileptogenic tissue in light of evidence showing that resection of brain tissue containing HFOs is associated with good surgical outcomes. Not all HFOs are conclusively pathological, however, as they can be recorded in nonepileptic tissue and induced by cognitive, visual, or motor tasks. Consequently, efforts to distinguish between pathological and physiological HFOs have identified several traits specific to pathological HFOs, such as coupling with interictal spikes, association with delta waves, and stereotypical morphologies. On the opposite end of the EEG spectrum, sub-delta oscillations have been shown to co-localize with the seizure onset zones (SOZ) and appear in a narrower spatial distribution than activity in the conventional EEG frequency bands. In this report, we review studies that implicate HFOs and ISA in ictogenesis and discuss current limitations such as inter-observer variability and poor standardization of recording techniques. Furthermore, we propose that HFOs and ISA should be analyzed in addition to activity in the conventional EEG band during intracranial presurgical EEG monitoring to identify the best possible surgical margin.

Summary Background Moraxella catarrhalis is a common agent causing upper and lower respiratory tract infections, particularly of ventilated patients. The bacteria are transmitted between humans by direct and indirect contacts. However, reports of nosocomial outbreaks by this pathogen are scarce. Aim To analyse M. catarrhalis strains isolated during an outbreak in a medical rehabilitation centre to reveal their clonal relationship and to elucidate potential transmission routes. Methods Extensive environmental and medical staff sampling was performed. Phenotypic and genotypic analyses of 15 isolates were executed, including repetitive element palindromic polymerase chain reaction (repPCR) and whole-genome sequencing. Furthermore, an intensified hygiene regimen was installed. Findings The clonal nature of nine patient isolates and a simultaneous presence of separate entities including a strain isolated from a physician during staff screening was confirmed. Although neither asymptomatic carriers among the staff persons nor outbreak strain-contaminated fomites were identified for a specific intervention, the outbreak ceased due to maximum general and specific hygiene precautions. Retrospective analysis showed the increasing prevalence of M. catarrhalis strains over a period of two years before the incidence. Since then and after returning to the regular hygiene regimen, only one patient with a phenotypically diverse M. catarrhalis isolate has been documented. Conclusion The first M. catarrhalis outbreak involving nine patients of a neurological and trauma rehabilitation centre was reported. Potential transmission pathways were discussed. Comprehensive outbreak analyses insinuated the extension of routine laboratory storage time for defined species.

Purpose To determine the usefulness of the first-hour sleep EEG recording in identifying interictal epileptiform discharges (IEDs) during long-term video-EEG monitoring. Method We retrospectively reviewed 255 consecutive patients who underwent continuous long-term video-EEG monitoring in the adult epilepsy monitoring unit (EMU) at the University of Chicago. The complete video-EEG recording was reviewed, and the occurrence of IEDs was determined for each patient. We compared the occurrence of IEDs observed during the first-hour sleep EEG recordings with the occurrence of IEDs observed during the complete video-EEG recordings. Results Overall, IEDs were observed in 134 (53%) of 255 patients during the full long-term video-EEG recording with a mean duration of 4 days. IEDs were identified in the first-hour sleep EEG in 125 (49%) of 225 patients. Comparing to reviewing full records, the first hour sleep EEG identified IEDs in 125 (93%) of 134 patients. Of the IED subtypes, the first-hour sleep EEG identified 92 (94%) of 98 patients with temporal lobe IEDs, 11 (92%) of 12 patients with frontal lobe IEDs, 3 (100%) of 3 patients with parietal lobe IEDs, 1(50%) of the 2 patients with occipital lobe IEDs, 16 (94%) of 17 patients with generalized IEDs, and 2 (100%) 2 patients with multi-focal IEDs. Conclusions The first-hour sleep EEG reliably predicts the occurrence of IEDs during the long-term video-EEG recording, and therefore can be a time-efficient tool for identifying patients with IEDs during long-term video-EEG recording in the adult epilepsy monitoring unit.

To identify scalp EEG correlates of hippocampal spikes in patients with mesial temporal lobe epilepsy (mTLE).We recorded scalp and intracranial EEG simultaneously in 20 consecutive surgical candidates with mTLE. Hippocampal spikes were identified from depth electrodes during the first hour of sleep on the first night of recording in the epilepsy monitoring unit, and their scalp EEG correlates were identified.Hippocampal spiking rates varied widely from 101 to 2187 (556 ± 672, mean ± SD) spikes per hour among the subjects. Of the 16,398 hippocampal spikes observed in this study, 492 (3.0%) of hippocampal spikes with extensive involvement of lateral temporal cortex were associated with scalp interictal epileptiform discharges (IEDs) including spikes and sharp waves; 198 (1.2%) of hippocampal spikes with limited involvement of lateral temporal cortex were associated with sharp transients or sharp slow waves, and 78 (0.05%)of hippocampal spikes with no lateral temporal involvement were associated with small sharp spikes (SSS). SSS were not correlated with independent temporal neocortical spikes.There are morphologically heterogeneous scalp EEG correlates of hippocampal spikes including SSS, sharp transients, sharp slow waves, spikes, and sharp waves. SSS correlate with hippocampal spikes and are likely an EEG marker for mTLE. These findings have important clinical implications for the diagnosis and localization of mTLE, and provide new perspectives on criteria for defining scalp IEDs.

Multiple sclerosis treatment options are increasing. Evidence-based patient information (EBPI) are therefore crucial to enable patient involvement in decision making. Based on earlier work on decision support, patient information handbooks on 8 MS immunotherapies were developed, piloted and evaluated with support from the German Clinical Competence Network MS and the German MS Society.Handbooks were structured according to EBPI concepts. Drafts were commented by patient representatives and neurologists with an MS expertise. Executive boards of the German MS Society and the Competence Network as well as pharmaceutical companies' feedback was included. Handbooks were distributed among MS neurologists by the German MS Society. Evaluation followed applying a mixed methods approach with interviews, focus groups and surveys. One survey addressed persons with MS (pwMS) based on a questionnaire included in each handbook. Neurologists who received printed patient handbooks were invited to give feedback in a second survey.Eight handbooks were developed providing absolute and relative risk information in numbers and figures as well as monitoring needs and drug fact boxes. Despite the high amount of information and the display of low absolute risk reduction rates of treatments, handbooks were overall appreciated by pwMS (n=107) and mostly also by physicians (n=24). For more than 70% of the pwMS the information was new, understandable and supportive for decision making. But patients felt uncomfortable with relative risk information. However, response rates in the evaluation were low, exposing the challenges when implementing EBPI into clinical care. Therefore, conclusions must be considered preliminary.EBPI on immunotherapies for MS seem feasible and are appreciated by patients and treating neurologists but more implementation research is needed.

Objective Mesial temporal lobe epilepsy (mTLE) is the most common type of focal epilepsy, but often lacks scalp EEG correlates. We ask if hippocampal epileptiform discharges that are characteristic of mTLE are associated with small sharp spikes (SSS) recorded on scalp EEG. SSS are considered benign waveforms, so are not currently used as markers of epilepsy. Methods To determine if there is a relationship between SSS and hippocampal discharges, simultaneous scalp and hippocampal depth electrode EEGs were recorded from 27 patients being evaluated for possible mTLE. Scalp EEG waveforms were assessed at the time of hippocampal discharges identified on intracranial hippocampal depth electrodes. Results 15 of 27 patients had SSS on scalp EEG that were time locked to hippocampal epileptiform discharges measured intracranially. These hippocampal spikes tended to have overlying high frequency oscillations and to co-localize with a seizure onset zone, suggesting that they were pathological discharges. Conclusions There is a tight coupling between a subset of pathological hippocampal discharges and SSS. Significance SSS can be scalp EEG markers of mTLE rather than normal EEG variants.

Glutamic acid decarboxylase (GAD) antibody-associated encephalitis causes both acute seizures and chronic epilepsy with predominantly temporal lobe onset. This condition is challenging in diagnosis and management, and the incidence of GAD antibody (Ab)-related epilepsy could be much higher than commonly believed. Imaging and CSF evidence of inflammation along with typical clinical presentations, such as adult onset temporal lobe epilepsy (TLE) with unexplained etiology, should prompt testing for the diagnostic antibodies. High serum GAD Ab titer (≥2000U/mL or ≥20nmol/L) and evidence of intrathecal anti-GAD Ab synthesis support the diagnosis. Unlike other immune-mediated epilepsies, antiglutamic acid decarboxylase 65 (GAD65) antibody-mediated epilepsy is often poorly responsive to antiepileptic drugs (AEDs) and only moderately responsive to immune therapy with steroids, intravenous immunoglobulin (IVIG), or plasma exchange (PLEX). Long-term treatment with more aggressive immunosuppressants such as rituximab (RTX) and/or cyclophosphamide is often necessary and may be more effective than current immunosuppressive approaches. The aim of this review is to review the physiology, pathology, clinical presentation, related ancillary tests, and management of GAD Ab-associated autoimmune epilepsy by searching the keywords and to promote the recognition and the initiation of proper therapy for this condition.

Objective We hypothesize that procedure deployment rates and technical performance with minimally invasive surgery and thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE) can be enhanced in post-trial clinical practice, per Phase III trial results and lessons learned. Materials and Methods We identified ICH patients and those who underwent MISTIE procedure between 2017–2021 at a single site, after completed enrollments in the Phase III trial. Deployment rates, complications and technical outcomes were compared to those observed in the trial. Initial and final hematoma volume were compared between site measurements using ABC/2, MISTIE trial reading center utilizing manual segmentation, and a novel Artificial Intelligence (AI) based volume assessment. Results Nineteen of 286 patients were eligible for MISTIE. All 19 received the procedure (6.6% enrollment to screening rate 6.6% compared to 1.6% at our center in the trial; p=0.0018). Sixteen patients (84%) achieved evaculation target 70% removal, compared to 59.7% in the trial surgical cohort (p=0.034). No poor catheter placement occurred and no surgical protocol deviations. Limitations of ICH volume assessments using the ABC/2 method were shown, while AI based methodology of ICH volume assessments had excellent correlation with manual segmentation by experienced reading centers. Conclusions Greater procedure deployment and higher technical success rates can be achieved in post-trial clinical practice than in the MISTIE III trial. AI based measurements can be deployed to enhance clinician estimated ICH volume. Clinical outcome implications of this enhanced technical performance cannot be surmised, and will need assessment in future trials.

Background Current treatment of a trapped temporal horn consists primarily of ventriculo-peritoneal (VP) shunting. Objective As a less invasive alternative, we examined an endoscopic-stereotactic approach to connect the trapped temporal horn with the prepontine cistern. Methods Six patients with different etiology of entrapment were studied. Using frame-based stereotaxy, image fusion and endoscopy a Rickham catheter was placed connecting both compartments. Results After median follow-up of 22.1 ± 7.8 months all patients improved symptomatically and the size of the temporal horn was normalized. No morbidity was encountered. Conclusion Endoscopic-stereotactic internal shunting of trapped temporal horns into the prepontine cistern can be done with favorable risk profile, and it offers an elegant alternative to traditional VP shunting, by avoiding the inherent complications.

The objective of this study was to determine the association of sleep with sudden unexpected death in epilepsy (SUDEP).We conducted a systematic review and meta-analysis based on literature search from databases PubMed, Web of Science, and Scopus using keywords "SUDEP", or "sudden unexpected death in epilepsy", or "sudden unexplained death in epilepsy". Sudden unexpected death in epilepsy was considered to occur during sleep if the patient was found in bed, if the SUDEP cases were documented as in sleep, or if the patient was found at bedside on the bedroom floor.Circadian pattern was documented in 880 of the 1025 SUDEP cases in 67 studies meeting the inclusion and exclusion criteria. Of the 880 SUDEP cases, 69.3% occurred during sleep and 30.7% occurred during wakefulness. Sudden unexpected death in epilepsy was significantly associated with sleep as compared to wakefulness (P0.001). In the subgroup of 272 cases in which circadian pattern and age were documented, patients 40years old or younger were more likely to die in sleep than those older than 40years (OR: 2.0; 95% CI=1.0, 3.8; P=0.05). In the subgroup of 114 cases in which both circadian pattern and body position at the time of death were documented, 87.6% (95% CI=81.1%, 94.2%) of patients who died during sleep were in the prone position, whereas 52.9% (95% CI=24.7%, 81.1%) of patients who died during wakefulness were in the prone position. Patients with nocturnal seizures were 6.3 times more likely to die in a prone position than those with diurnal seizures (OR: 6.3; 95% CI=2.0, 19.5; P=0.002).There is a strong association of SUDEP with sleep, suggesting that sleep is a significant risk factor for SUDEP. Although the risks of SUDEP associated with sleep are unknown and likely multifactorial, the prone position might be an important contributory factor.

Highlights • FFEVF associated with a higher (~50%) risk of medication resistant epilepsy. • Surgery in the familial epilepsies has been of benefit in some patients. • LITT can be an effective treatment for medically refractory NPRL3-related epilepsy., Introduction: NPRL3 gene mutations cause autosomal dominant familial focal epilepsy of variable foci (FFEVF) and is characterized by focal epilepsy arising from different brain regions including temporal, frontal, parietal and occipital lobes. About 50% of patients with NPRL3 related epilepsy are resistant to medical treatment. Method: We present a case of 27 years old man with NPRL3 related focal drug-resistant epilepsy. Stereotactic EEG showed two independent seizure foci, namely, left hippocampus and left orbitofrontal cortices. He underwent laser interstitial thermal therapy for ablating both foci in the same procedure that led to seizure cessation. Conclusion: laser interstitial thermal therapy can be an effective treatment for drug resistant NPRL3 related focal epilepsy with better tolerance and less morbidity as compared to open surgical resection, particularly in those with multiple seizure foci.

The vagus nerve stimulator (VNS) has been shown to provide a safe, albeit costly, treatment for intractable epilepsy. We aimed to analyze the incidence, timing, and clinical/demographic associations of revision surgery post-VNS implantation in epilepsy patients. The Thomson Reuters MarketScan database, containing data from 23-50million individuals, was used. Epilepsy patients receiving VNS implantations from 2003 to 2009 were identified by Current Procedural Terminology and International Classification Of Diseases Ninth Revision codes. Incidence and timing of subsequent implant-related surgeries were recorded. Events were described using time-to-event methodology, with Kaplan-Meier failure estimation/Cox proportional hazard models adjusted for clinical/demographic factors. In 1234 patients, average incidence of revision surgeries over 6years of follow-up were

Objective The objectives of this study were to determine the incidence of peri-ictal prone position in patients with generalized convulsive seizures (GCS) and to further assess the risk of sudden unexpected death in epilepsy (SUDEP) associated with the prone position. Method We retrospectively reviewed the video-EEG data of 308 GCS in 193 patients who underwent long-term video-EEG monitoring in two epilepsy centers. We determined the peri-ictal (preictal, ictal, and/or postictal) body positions. Results A peri-ictal prone position was observed in 12 (6.2%) of 193 patients and 13 (4.2%) of 308 GCS. In 5 (1.6%) of 308 GCS, patients in nonprone positions at seizure onset turned into the prone position during versive seizures. In 8 (2.6%) of 308 GCS, patients were sleeping prone at seizure onset. Peri-ictal intervention with body repositioning was provided in 11 of 12 patients and 12 of the 13 GCS. Repositioning was not provided during the remaining seizure; the patient died in the prone position. In the subset of 96 GCS without ictal intervention, patients in a supine position at seizure onset remained in the supine position at seizure termination in 57 (98.3%) of 58 GCS. Patients sleeping prone at seizure onset remained in the prone position at seizure termination in 4 (80%) of 5 GCS. Conclusion Our data suggest that the incidence of peri-ictal prone position in patients with GCS is low. Both prone sleeping and forced ictal version may result in postictal prone position. Although avoiding prone sleeping may reduce the SUDEP risk, influencing forced ictal version may be difficult in the absence of supervision.

Summary Background Besides the use of temozolomide and radiotherapy for patients with favourable methylation status, little progress has been made in the treatment of adult glioblastoma. Local control of the disease by complete removal increases time to progression and survival. We assessed the efficacy and safety of a locally applied adenovirus-mediated gene therapy with a prodrug converting enzyme (herpes-simplex-virus thymidine kinase; sitimagene ceradenovec) followed by intravenous ganciclovir in patients with newly diagnosed resectable glioblastoma. Methods For this international, open-label, randomised, parallel group multicentre phase 3 clinical trial, we recruited patients from 38 sites in Europe. Patients were eligible if they were aged 18–70 years, had newly diagnosed supratentorial glioblastoma multiforme amenable to complete resection, and had a Karnofsky score of 70 or more at screening. We used a computer-generated randomisation sequence to allocate patients in a one-to-one ratio (with block sizes of four) to receive either surgical resection of the tumour and intraoperative perilesional injection of sitimagene ceradenovec (1 × 10 12 viral particles) followed by ganciclovir (postoperatively, 5 mg/kg intravenously twice a day) in addition to standard care or resection and standard care alone. Temozolomide, not being standard in all participating countries at the time of the study, was allowed at the discretion of the treating physician. The primary endpoint was a composite of time to death or re-intervention, adjusted for temozolamide use, assessed by intention-to-treat (ITT) analysis. This trial is registered with EudraCT, number 2004-000464-28. Findings Between Nov 3, 2005, and April 16, 2007, 250 patients were recruited and randomly allocated: 124 to the experimental group and 126 to the standard care group, of whom 119 and 117 patients, respectively, were included in the ITT analyses. Median time to death or re-intervention was longer in the experimental group (308 days, 95% CI 283–373) than in the control group (268 days, 210–313; hazard ratio [HR] 1·53, 95% CI 1·13–2·07; p=0·006). In a subgroup of patients with non-methylated MGMT , the HR was 1·72 (95% CI 1·15–2·56; p=0·008). However, there was no difference between groups in terms of overall survival (median 497 days, 95% CI 369–574 for the experimental group vs 452 days, 95% CI 437–558 for the control group; HR 1·18, 95% CI 0·86–1·61, p=0·31). More patients in the experimental group had one or more treatment-related adverse events those in the control group (88 [71%] vs 51 [43%]). The most common grade 3–4 adverse events were hemiparesis (eight in the experimental group vs three in the control group) and aphasia (six vs two). Interpretation Our findings suggest that use of sitimagene ceradenovec and ganciclovir after resection can increase time to death or re-intervention in patients with newly diagnosed supratentorial glioblastoma multiforme, although the intervention did not improve overall survival. Locally delivered gene therapy for glioblastoma should be further developed, especially for patients who are unlikely to respond to standard chemotherapy. Funding Ark Therapeutics Ltd.

Introduction To determine the predictive value of the first hour sleep EEG recording in identifying patients with interictal epileptiform discharges (IEDs) during long-term video-EEG monitoring in an adult epilepsy monitoring unit. Methods We retrospectively reviewed 255 consecutive patients who underwent continuous long-term video-EEG monitoring in the University of Chicago EMU. The complete video-EEG recording was reviewed, and the occurrence of IEDs was determined for each patient. We compared the occurrence of IEDs observed during the first hour sleep EEG recordings with the occurrence of IEDs observed during the complete long-term video-EEG recordings; inclusive of the first hour of sleep. Results Overall, IEDs were observed in 134(53%) of 255 patients during the full long-term video-EEG recording with a duration of 4 ± 0.8 days. IEDs were identified in the first hour sleep EEG recording in 125 (sensitivity 93%) of the 134 patients. IEDs were found in the first hour sleep EEG recording in 92 (94%) of 98 patients with temporal lobe epilepsy, 11 (92%) of 12 patients with frontal lobe epilepsy, 3 (100%) of 3 patients with parietal lobe epilepsy, 1 (50%) of the 2 patients with occipital lobe epilepsy, and 15 (88%) of the 17 patients with generalized epilepsy. The ictal onset in remaining 2 patients with multi-focal IEDs could not be localized due to muscle artifacts. The negative predictive value of the first hour EEG was 93%. Conclusion The first hour of sleep EEG recording reliably predicts the occurrence of interictal epileptiform activity in a long-term video-EEG recording, and therefore can be used efficiently for identifying patients with IEDs during long-term video-EEG recording in the adult epilepsy monitoring unit.

Background Entrapped temporal horn syndrome secondary to obstructive neoplastic lesions is most frequently treated by surgical excision of the offending lesion. Here we describe an alternate approach involving temporal horn to prepontine cistern shunting followed by radiosurgery of the offending lesion. Methods A 41-year-old woman with a history of meningiomatosis presented with progressive, incapacitating headache. Magnetic resonance imaging (MRI) showed growth of a right trigone meningioma, causing entrapment of the right temporal horn. A ventricular catheter was placed using frame-based stereotaxy and image fusion computed tomography/MRI to connect the entrapped lateral ventricle to the prepontine cistern. The patient reported complete resolution of her symptoms after the procedure. Results Postoperative MRI revealed decompression of the temporal horn. The trigonal meningioma was treated with stereotactic radiosurgery. The patient remained asymptomatic at the 2-year follow-up. Conclusions Trapped temporal horn syndrome secondary to obstructive neoplastic lesions can be treated by internal shunting followed by radiosurgery.