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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.

Manual interactions with objects are supported by tactile signals from the hand. This tactile feedback can be restored in brain-controlled bionic hands via intracortical microstimulation (ICMS) of somatosensory cortex (S1). In ICMS-based tactile feedback, contact force can be signaled by modulating the stimulation intensity based on the output of force sensors on the bionic hand, which in turn modulates the perceived magnitude of the sensation. In the present study, we gauged the dynamic range and precision of ICMS-based force feedback in three human participants implanted with arrays of microelectrodes in S1. To this end, we measured the increases in sensation magnitude resulting from increases in ICMS amplitude and participant’s ability to distinguish between different intensity levels. We then assessed whether we could improve the fidelity of this feedback by implementing “biomimetic” ICMS-trains, designed to evoke patterns of neuronal activity that more closely mimic those in natural touch, and by delivering ICMS through multiple channels at once. We found that multi-channel biomimetic ICMS gives rise to stronger and more distinguishable sensations than does its single-channel counterpart. We conclude that multi-channel biomimetic ICMS conveys finely graded force feedback that more closely approximates the sensitivity conferred by natural touch.

OBJECTIVE The authors aimed to examine the relationship between mesial temporal subregion ablation volume and seizure outcome in a diverse cohort of patients who underwent stereotactic laser amygdalohippocampotomy (SLAH) for mesial temporal lobe epilepsy (MTLE). METHODS Seizure outcomes and pre- and postoperative images were retrospectively reviewed in patients with MTLE who underwent SLAH at a single institution. Mesial temporal subregions and the contrast-enhancing ablation volume were manually segmented. Pre- and postoperative MR images were coregistered to assess anatomical ablation. Postoperative MRI and ablation volumes were also spatially normalized, enabling the assessment of seizure outcome with heat maps. RESULTS Twenty-eight patients with MTLE underwent SLAH, 15 of whom had mesial temporal sclerosis (MTS). The rate of Engel class I outcome at 1 year after SLAH was 39% overall: 47% in patients with MTS and 31% in patients without MTS. The percentage of parahippocampal gyrus (PHG) ablated was higher in patients with an Engel class I outcome (40% vs 25%, p = 0.04). Subregion analysis revealed that extent of ablation in the parahippocampal cortex (35% vs 19%, p = 0.03) and angular bundle (64% vs 43%, p = 0.02) was positively associated with Engel class I outcome. The degree of amygdalohippocampal complex (AHC) ablated was not associated with seizure outcome (p = 0.30). CONCLUSIONS Although the AHC was the described target of SLAH, seizure outcome in this cohort was associated with degree of ablation for the PHG, not the AHC. Complete coverage of both the AHC and PHG is technically challenging, and more work is needed to optimize seizure outcome after SLAH.

BackgroundAnterior capsulotomy is a well-established treatment for refractory obsessive–compulsive disorder (OCD). MRI-guided laser interstitial thermal therapy (LITT) allows creation of large, sharply demarcated lesions with the safeguard of real-time imaging.ObjectiveTo characterise the outcomes of laser anterior capsulotomy, including radiographical predictors of improvement.MethodsPatients with severe OCD refractory to pharmacotherapy and cognitive–behavioural therapy underwent bilateral anterior capsulotomy via LITT. The primary outcome was per cent reduction in Yale-Brown Obsessive–Compulsive Scale (Y-BOCS) score over time. Lesion size was measured on postablation MRI. Disconnection of the anterior limb of the internal capsule (ALIC) was assessed via individual and normative tractography.ResultsEighteen patients underwent laser anterior capsulotomy. Median follow-up was 6 months (range 3–51 months). Time occupied by obsessions improved immediately (median Y-BOCS item 1 score 4–1, p=0.002). Mean (±SD) decrease in Y-BOCS score at last follow-up was 46%±32% (16±11 points, pConclusionsLaser anterior capsulotomy resulted in immediate, marked improvement in OCD symptom severity. Larger lesions permit greater disconnection of prefrontal–subcortical pathways involved in OCD. The importance of greater disconnection is presumably related to variation in ALIC structure and the complex role of the PFC in OCD.

Purpose Epileptiform activity limited to deep sources such as the hippocampus currently lacks reliable scalp correlates. Recent studies, however, have found that a subset of hippocampal interictal discharges may be associated with visible scalp signals, suggesting that some types of hippocampal activity may be monitored noninvasively. The purpose of this study is to characterize the relationship between these scalp waveforms and the underlying intracranial activity. Methods Paired intracranial and scalp EEG recordings obtained from 16 patients were used to identify hippocampal interictal discharges. Discharges were grouped by waveform shape, and spike-triggered averages of the intracranial and scalp signals were calculated for each group. Cross-correlation of intracranial and scalp spike-triggered averages was used to determine their temporal relationship, and topographic maps of the scalp were generated for each group. Results Cross-correlation of intracranial and scalp correlates resulted in two classes of scalp waveforms-those with and without time delays from the associated hippocampal discharges. Scalp signals with no delay showed topographies with a broad field with higher amplitudes on the side ipsilateral to the discharges and a left-right flip in polarity-observations consistent with the volume conduction of a single unilateral deep source. In contrast, scalp correlates with time lags showed rotational dynamics, suggesting synaptic propagation mechanisms. Conclusions The temporal relationship between the intracranial and scalp signals suggests that both volume conduction and synaptic propagation contribute to these scalp manifestations. Furthermore, the topographic evolution of these scalp waveforms may be used to distinguish spikes that are limited to the hippocampus from those that travel to or engage other brain areas.

Motor (M1) and somatosensory (S1) cortex play a critical role in motor control but the nature of the signaling between these structures is not known. To fill this gap, we recorded – in three human participants whose hands were paralyzed as a result of a spinal cord injury – the responses evoked in the hand and arm representations of primary motor cortex (M1) while we delivered ICMS to the somatosensory cortex (S1). We found that ICMS of S1 activated some M1 neurons at short, fixed latencies, locked to each pulse in a manner consistent with monosynaptic activation. However, most of the changes in M1 firing rates were much more variable in time, suggesting a more indirect effect of the stimulation. The spatial pattern of M1 activation varied systematically depending on the stimulating electrode: S1 electrodes that elicited percepts at a given hand location tended to activate M1 neurons with movement fields at the same location. However, the indirect effects of S1 ICMS on M1 were strongly context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS was used to convey tactile feedback about object interactions. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption could be minimized with biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, reduces sustained stimulation, and has been shown to convey useful contact-related information.SignificanceMotor (M1) and somatosensory (S1) cortex play a critical role in motor control but the nature of the signaling between these structures is not known. To fill this gap, we recorded from M1 while delivering intracortical microstimulation (ICMS) to S1 of three human participants, whose hands were paralyzed by spinal cord injury. We found that ICMS activates M1 and that the motor fields of activated M1 neurons match the sensory fields of the stimulated S1 electrodes. These findings have important implications for using ICMS to convey tactile feedback for brain-controlled bionic hands. Indeed, the ICMS-evoked M1 activity worsens control of the hand. Fortunately, this effect is minimized by using biomimetic tactile feedback, which emphasizes contact transients and reduces sustained ICMS.

Human accomplishments depend on learning, and effective learning depends on consolidation. Consolidation is the process whereby new memories are gradually stored in an enduring way in the brain so that they can be available when needed. For factual or event knowledge, consolidation is thought to progress during sleep as well as during waking states, and to be mediated by interactions between hippocampal and neocortical networks. However, consolidation is difficult to observe directly, but rather is inferred through behavioral observations. Here, we investigated overnight memory change by measuring electrical activity in and near the hippocampus. Electroencephalographic (EEG) recordings were made in five patients from electrodes implanted to determine whether a surgical treatment could relieve their seizure disorders. One night, while each patient slept in a hospital monitoring room, we recorded electrophysiological responses to 10-20 specific sounds that were presented very quietly, to avoid arousal. Half of the sounds had been associated with objects and their precise spatial locations that patients learned before sleep. After sleep, we found systematic improvements in spatial recall, replicating prior results. We assume that when the sounds were presented during sleep, they reactivated and strengthened corresponding spatial memories. Notably, the sounds also elicited oscillatory intracranial EEG activity, including increases in theta, sigma, and gamma EEG bands. Gamma responses, in particular, were consistently associated with the degree of improvement in spatial memory exhibited after sleep. We thus conclude that this electrophysiological activity in the hippocampus and adjacent medial temporal cortex reflects sleep-based enhancement of memory storage.Significance StatementSleep contributes to memory consolidation, we presume, because memories are replayed during sleep. Understanding this aspect of consolidation can help with optimizing normal learning in many contexts, and with treating memory disorders and other diseases. Here, we systematically manipulated sleep-based processing using targeted memory reactivation; brief sounds coupled with pre-sleep learning were quietly presented again during sleep, producing (a) recall improvements for specific spatial memories associated with those sounds, and (b) physiological responses in the sleep EEG. Neural activity in the hippocampus and adjacent medial temporal cortex was thus found in association with memory consolidation during sleep. These findings advance understanding of consolidation by linking beneficial memory changes during sleep to both memory reactivation and specific patterns of brain activity.

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.

Objective Corpus callosotomy is an effective palliative treatment for drug-resistant Lennox-Gastaut syndrome (LGS). Laser interstitial thermal therapy has been increasingly used in the treatment of epilepsy. Here, we assess the safety and effectiveness of minimally invasive stereotactic laser anterior corpus callosotomy (SLACC) for drop attacks in LGS. Methods We reviewed sequential cases of patients with medically intractable LGS who underwent SLACC using a two-cannula technique between November 2014 and July 2019. Pre- and postoperative magnetic resonance imaging was used to measure the anteroposterior length of callosal ablation (contrast-enhancing lesion) and estimated disconnection (gap in tract projections on diffusion tensor imaging). Patients were followed longitudinally to assess clinical outcomes. Results Ten patients were included in this study. The median age was 33 (range = 11-52) years, median duration of epilepsy was 26 (range = 10-49) years, and median duration of postoperative follow-up was 19 (range = 6-40) months. In the anteroposterior direction, 53 ± 7% (mean ± SD) of the corpus callosum was ablated and 62 ± 19% of the corpus callosum was estimated to be disconnected. Six (60%) of 10 patients achieved >80% seizure reduction, two (20%) of whom became seizure-free. Eight (80%) patients had >80% reduction in drop attacks, five (50%) of whom became free of drop attacks. Three patients subsequently underwent laser posterior callosotomy with further improvement in drop attacks and/or overall seizure frequency. One patient had an asymptomatic intracerebral hemorrhage along the cannula tract. One patient developed significant aggression after becoming seizure-free. Significance Seizure outcomes following SLACC were comparable to previously reported outcomes of open callosotomy, with reasonable safety profile. SLACC appears to be an effective alternative to open anterior corpus callosotomy with minimal postoperative discomfort and a short recovery period.

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.

Aspiration secondary to impaired swallow function, or dysphagia, is one of the major causes of mortality in patients with Parkinson’s disease (PD). Dysphagia usually does not respond well to medications. Despite its effectiveness on motor fluctuation, dyskinesia and tremor in patients with PD, deep brain stimulation (DBS) is not as effective on axial symptoms of balance, freezing of gait (FOG), speech and swallow function. Studies even raise concerns about axial symptoms under usual high-frequency stimulation (HFS) of the subthalamic nucleus (STN), particularly ON medication.1 STN DBS has various effects on swallow function.2–4 Swallowing involves multiple phases, with oral and pharyngeal phases most critical for bolus clearance and airway protection. However, the impact of different oral textures on aspiration with or without DBS in patients with PD has not been studied.2 Fast-flowing liquids may be more likely to aspirate before and during the swallow, although with less risk of post-swallow aspiration of residue compared with more viscous solids. Dynamic changes in swallow parameters have not been well characterised either.2 A comprehensive evaluation in a randomised double-blind study under various DBS conditions over time is therefore of significant importance. We hypothesised that liquids would more likely yield aspiration than solids, regardless of DBS conditions and assessment timing, and that swallowing measures could worsen in a year. ### Standard protocol approval, registrations and patient consents The study was approved by the institutional review board, with written consents by patients.3 Unlike our previous publications in which only the whole aspiration events (a combination of liquid and solid bolus) were reported using the Penetration-Aspiration Scale (PAS) on the videofluoroscopic swallow study (VFSS),3 the current study (1) further delineated the impact of different oral textures (liquid vs solid bolus) on aspiration and (2) characterised the swallow dynamics across oral and pharyngeal phases, based on the previously obtained VFSS …

Neurosurgery, and in particular academic neurosurgery, has, despite the tremendous progress in the last 100 years, not found its clear and solidly anchored home within the medical specialties. This stems from its dichotomic origin. Complicating the picture, these origins are different on different continents. In the USA, neurosurgery was established as a new specialty by Harvey Cushing—a surgeon—and neurosurgery hence for a long time was a surgical subspecialty dwelling on the technical aspects of neurosurgery and, to be fair on some pathophysiology, but not really on central nervous system (CNS) biology. In Europe, neurosurgery also branched off neurology with Otfried Foerster being an eminent neurologist, before turning to the surgical armamentarium to treat neurological disease. Ironically, Cushing and Foerster visited each other and showed admiration for their respective work. So to simplify things and use these two paradigmatic figures as opposite ends of the spectrum, we can: 1. Outline the answer to the question posed in the title and look at the pros and cons of each description. 2. Maybe more important we can analyse the development of neurosurgery in the last decade and predict which name will be appropriate extrapolating into the future. 3. Semantics or impact: we can determine what the structural framework of neurosurgery should be to associate it with the correct description. Neurosurgery has come a long way since the days of fairly gross CNS tissue manipulation to remove lesions, occlude vascular malformations or even ablate tissue for movement disorders and has moved to delicate microsurgical manipulation—but it is still manipulation—and neuromodulation. The future will likely be different and adaptation be necessary if neurosurgery does not want to fall victim to ‘creative destruction’ like Schumpeter.1–3 Subspecialisation in neurosurgery is the inevitable trend to increase expertise, and analysing its development most likely allows an answer to my first point. …

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.

Objective: To assess the seizure outcomes of stereotactic laser amygdalohippocampectomy (SLAH) in consecutive patients with mesial temporal lobe epilepsy (mTLE) in a single center and identify scalp EEG and imaging factors in the presurgical evaluation that correlate with post-surgical seizure recurrence.Methods: We retrospectively reviewed the medical and EEG records of 30 patients with drug-resistant mTLE who underwent SLAH and had at least 1 year of follow-up. Surgical outcomes were classified using the Engel scale. Univariate hazard ratios were used to evaluate the risk factors associated with seizure recurrence after SLAH.Results: The overall Engel class I outcome after SLAH was 13/30 (43%), with a mean postoperative follow-up of 48.9 ± 17.6 months. Scalp EEG findings of interictal regional slow activity (IRSA) on the side of surgery (HR = 4.05, p = 0.005) and non-lateralizing or contra-lateralizing seizure onset (HR = 4.31, p = 0.006) were negatively correlated with postsurgical seizure freedom. Scalp EEG with either one of the above features strongly predicted seizure recurrence after surgery (HR = 7.13, p < 0.001) with 100% sensitivity and 71% specificity.Significance: Understanding the factors associated with good or poor surgical outcomes can help choose the best candidates for SLAH. Of the variables assessed, scalp EEG findings were the most clearly associated with seizure outcomes after SLAH.

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.

CAR‑T cell therapy has been implemented as clinical routine treatment option during the last decade. Despite beneficial outcomes in many patients severe side effects and toxicities are seen regularly that can compromise the treatment success.Literature review: CAR T‑cell therapy, toxicities and their management RESULTS: The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) are seen regularly after CAR T‑cell treatment. CRS symptoms can range from mild flu-like symptoms to severe organ dysfunction requiring vasopressor therapy, mechanical ventilation and other intensive care support. ICANS symptoms usually develop later and can range from disorientation and aphasia to potentially life-threatening brain edema. IL‑6 is a key factor in the pathophysiology of CRS. The pathophysiology of ICANS is not fully understood. The ASTCT consensus grading is recommended to stratify patients for different management options. An interdisciplinary team including hematologist, intensivist, neurologists and other specialties is needed to optimize the treatment.Severe and potentially life-threatening toxicities occur regularly after CAR T‑cell therapy. Treatment strategies for CRS and ICANS still need to be evaluated prospectively. Due to the increasing number of patients treated with CAR T‑cells the number of patients requiring temporary intensive care management due to CRS and ICANS is expected to increase during the next years.HINTERGRUND: Die Therapie mit Chimeric-antigen-receptor(CAR)-T-Zellen hat sich als neue Therapieform in der Onkologie etabliert. Im Rahmen einer Therapie mit CAR-T-Zellen kommt es regelhaft zu schweren Nebenwirkungen.Review der Literatur zu CAR-T-Zell-Therapie, Toxizitäten und Nebenwirkungsmanagement ERGEBNIS: Das „cytokine release syndrome“ (CRS) und das „immune effector cell-associated neurotoxicity syndrome“ (ICANS) treten regelhaft im Rahmen einer Therapie mit CAR-T-Zellen auf. Das CRS kann von einer milden grippeähnlichen Symptomatik bis hin zu einem Multiorganversagen führen. Bei ICANS kann sich letztendlich ein lebensbedrohliches Hirnödem entwickeln. Bei der Pathophysiologie des CRS spielt insbesondere das Interleukin‑6 eine entscheidende Rolle. Die Pathophysiologie des ICANS ist nicht vollständig verstanden. Das Management richtet sich nach dem Schweregrad gemäß Grading der American Society for Transplantation and Cellular Therapy (ASTCT). Beim CRS werden Tocilizumab und Kortikosteroide, für das ICANS Kortikosteroide empfohlen.Nach einer CAR-T-Zell-Therapie kommt es regelhaft zu potenziell lebensbedrohlichen Komplikationen. Weitergehende Therapieansätze sind bislang nicht gut untersucht. Eine interdisziplinäre Zusammenarbeit zwischen Intensivmediziner*innen, Hämatolog*innen, Neurolog*innen und Ärzt*innen anderer Fachabteilungen ist von entscheidender Bedeutung. Aufgrund der steigenden Patientenzahlen ist von einer Zunahme an Patienten mit Notwendigkeit einer intensivmedizinischen Behandlung im Rahmen einer CAR-T-Zelltherapie auszugehen.

To determine clinical and intracranial EEG correlates of rhythmic temporal theta bursts of drowsiness (RTTBD) and assess its clinical significance in patients with temporal lobe epilepsy (TLE). A retrospective review of simultaneous scalp and intracranial video-EEG recordings from 28 patients with TLE was evaluated for epilepsy surgery. Scalp RTTBD patterns were identified and their clinical and intracranial EEG correlates were then determined on video-EEG recording using depth and subdural electrodes. Thirty-one RTTBD patterns on scalp EEG were observed in six (21%) of the 28 patients. Five (16%) of the RTTBD patterns occurred during wakefulness and 26 (84%) occurred during drowsiness and light sleep. The mean duration of RTTBD was 10 seconds (range: 3-28 seconds). RTTDB consistently correlated with hippocampal ictal discharges and was time-locked to the hippocampal seizures in which the ictal discharges evolved into rhythmic theta frequency (4-7-Hz) range. Ictal automatisms were observed during five (16%) RTTBD patterns, while cognitive impairment was observed in four (13%) of the 31 RTTBD patterns. Our findings show that scalp EEG correlates of hippocampal ictal discharges can resemble RTTBD and may be associated with ictal symptoms and cognitive impairment, indicating that RTTBD may rarely be an ictal EEG pattern in patients with TLE.

Objective To describe the spatio-temporal dynamics and interactions during linguistic and memory tasks. Methods Event-related electrocorticographic (ECoG) spectral patterns obtained during cognitive tasks from 26 epilepsy patients (aged: 9–60 y) were analyzed in order to examine the spatio-temporal patterns of activation of cortical language areas. ECoGs (1024 Hz/channel) were recorded from 1567 subdural electrodes and 510 depth electrodes chronically implanted over or within the frontal, parietal, occipital and/or temporal lobes as part of their surgical work-up for intractable seizures. Six language/memory tasks were performed, which required responding verbally to auditory or visual word stimuli. Detailed analysis of electrode locations allowed combining results across patients. Results Transient increases in induced ECoG gamma power (70–100 Hz) were observed in response to hearing words (central superior temporal gyrus), reading text and naming pictures (occipital and fusiform cortex) and speaking (pre-central, post-central and sub-central cortex). Conclusions Between these activations there was widespread spatial divergence followed by convergence of gamma activity that reliably identified cortical areas associated with task-specific processes. Significance The combined dataset supports the concept of functionally-specific locally parallel language networks that are widely distributed, partially interacting in succession to serve the cognitive and behavioral demands of the tasks.

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.

ObjectiveRefractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive–compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016.DesignHere we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses.ConclusionInterest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

As methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in humans are a global challenge. In Mecklenburg and Western Pomerania (Germany) 1,517 patients who underwent surgical interventions were systematically screened for MRSA and MSSA colonization on the day of hospital admission and discharge. Demographic data, risk factors and colonization status of the (i) nose, (ii) throat, (iii) groin, and (iv) thorax or site of surgical intervention were determined. Of the 1,433 patients who were included for further evaluation, 331 (23.1%) were colonized with MSSA, while only 17 (1.2%) were MRSA carriers on the day of hospital admission. A combination of nose, throat and groin swabs returned a detection rate of 98.3% for MSSA/MRSA. Trauma patients had lower prevalence of MRSA/MSSA (OR 0.524, 95% CI: 0.37–0.75; p

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.

ZusammenfassungSeit der Etablierung der klinischen Beatmungsmedizin gewinnt die Entwöhnung langzeitbeatmeter Patienten vom Respirator (Weaning) zunehmend an Bedeutung. Vor diesem Hintergrund wurden ab den 1980iger Jahren Zentren geschaffen, die speziell auf das Weaning von Patienten von der maschinellen Beatmung ausgerichtet waren.In dem Artikel werden die strukturelle Entwicklung sowie die Ergebnisse aus den letzten zehn Jahren (2006 – 2015) des Weaningzentrums der Universitätsmedizin Greifswald dargestellt. Dazu wurden die Daten von 616 Patienten ausgewertet. Über die Jahre zeigt sich eine Verschiebung der zur Beatmung führenden Grunderkrankung, wobei der Anteil kardiochirurgischer Patienten rückläufig war und die Patienten mit Pneumonie/Sepsis zugenommen haben. Im Zeitverlauf haben die Tage mit Beatmung vor Aufnahme (p = 0,004) als auch die Beatmungstage im Weaningzentrum (p = 0,02) signifikant abgenommen. Ungeachtet des hohen APACHE-II-Scores bei stationärer Aufnahme konnte der Prozentsatz erfolgreich entwöhnter Patienten von 62,7 % (2006 – 10) auf 77,3 % (2011 – 2015) signifikant gesteigert werden (p Die Ergebnisse bei der Betreuung der Patienten im Weaningzentrum Greifswald bewegen sich auf vergleichbarem Niveau anderer deutscher Weaningzentren.

Some studies have shown that low frequency stimulation (LFS, most commonly 60 Hz), compared to high frequency stimulation (HFS, most commonly 130 Hz), has beneficial effects, short-term or even long-term, on improving freezing of gait (FOG) and other axial symptoms, including speech and swallowing function, in Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN DBS). However, other studies failed to confirm this. It seems not clear what determines the difference in response to LFS. Differences in study design, such as presence or absence of FOG, exact LFS used (60 Hz versus 80 Hz), study size, open label versus randomized double blind assessment, retrospective versus prospective evaluation, medication On or Off state, total electric energy delivered maintained or not with the change in frequency, and the location of active contacts could all potentially affect the results. This mini-review goes over the literature with the aforementioned factors in mind, focusing on the effect of LFS versus HFS on FOG and other axial symptoms in PD with bilateral STN DBS, in an effort to extract the essential data to guide our clinical management of axial symptoms and explore the potential underlying mechanisms as well. Overall, LFS of 60 Hz seems to be consistently effective in patients with FOG at the usual HFS in regards to improving FOG, speech, swallowing function and other axial symptoms, though LFS could reduce tremor control in some patients. Whether LFS simply addresses the axial symptoms in the context of HFS or has other beneficial effects requires further studies, along with the mechanism.

Vor dem Hintergrund unterschiedlicher Lebenserwartung und Pravalenz von kardiovaskularen Risikofaktoren in den alten und neuen Bundeslandern der Bundesrepublik Deutschland nach der Wiedervereinigung wurde eine umfassende epidemiologische Studie in Vorpommern geplant. Diese Studie erfasst seit 1997 in funfjahrigen Abstanden die Pravalenz von kardiovaskularen Risikofaktoren sowie subklinische und manifeste Erkrankungen. Die 3. Wiederholungsuntersuchung (SHIP-3) wurde zwischen 2014 – 2016 erfolgreich durchgefuhrt. Parallel wurde 2008 – 2012 eine zweite, unabhangige, reprasentative Bevolkerungsstichprobe (SHIP-TREND) untersucht, wobei aktuell die 1. Verlaufsuntersuchung (SHIP-TREND-1) gestartet wurde. Die vorliegende Arbeit beschreibt die untersuchten Kohorten, die methodischen Ansatze der Qualitatssicherung bei der Erfassung pneumologisch relevanter Daten und gibt eine Ubersicht zu den bisher publizierten pneumologischen Daten. Somit soll interessierten Arbeitsgruppen die Moglichkeit gegeben werden, gezielte Kooperationen fur zukunftige Untersuchungen aufzubauen und die vorliegenden Daten fur gemeinsame Analysen zu nutzen.

Acute symptomatic seizures have been reported in sporadic cases in patients with COVID-19.1 2 However, a recent large retrospective cohort study suggested that there was no increased risk of acute symptomatic seizures in these patients.3 As such, the association of seizures with COVID-19 has not been established. Admittedly, EEG studies have been significantly underused due to exposure concerns, and epileptiform activity has seldom been identified in this patient population. The aims of this study were to determine the prevalence of epileptiform activity and to assess the risk of seizures in patients with COVID-19. We retrospectively reviewed consecutive patients with COVID-19 from 1 March to 27 May 2020 in a single institution. Patients were included if they were (1) ≥18 years of age, (2) positive for nasal swab SARS-CoV-2 RNA qualitative PCR test and (3) underwent EEG monitoring. Patients with a prior active diagnosis of epilepsy were excluded. Patient data regarding demographics, medical history, neuroimaging, laboratory tests, complications, mortality, metabolic profiles and treatment were extracted from electronic medical records. COVID-19 disease severity was categorised according to WHO guideline into (1) non-severe: absence of viral pneumonia or hypoxia, or clinical signs of pneumonia but SpO2 of >90% on room air; (2) severe: clinical pneumonia, respiratory rate of >30 and SpO2 of

OBJECTIVEThe authors sought to perform a preliminary assessment of the safety and effectiveness of stereotactic laser interstitial thermal therapy (LITT) for patients with cerebral cavernous malformation (CCM)–related epilepsy.METHODSThe authors retrospectively analyzed 6 patients with CCM-related epilepsy who underwent LITT. Pre-, intra-, and postoperative brain MRI studies were used to characterize preoperative CCM volume, ablation volume, and postablation hemosiderin volume. Clinical outcomes were assessed postoperatively during clinic follow-up visits or phone interviews.RESULTSLITT was performed in 7 CCMs in 6 patients. Two patients had familial CCM disease with multifocal lesions. Four treated CCMs were extratemporal, and 3 were in or near the visual pathways. The median follow-up was 25 (range 12–39) months. Five of 6 (83%) patients achieved seizure freedom (Engel I classification), of whom 4 (67%) were Engel IA and 1 was Engel IC after a single seizure on postoperative day 4. The remaining patient had rare seizures (Engel II). One patient had a nondisabling visual field deficit. There were no hemorrhagic complications. All patients were discharged within 24 hours postablation. MRI 3–11 months after ablation demonstrated expected focal necrosis and trace hemosiderin-related T2 hypointensity measuring 9%–44% (median 24%) of the original lesion volume, with significant (p = 0.04) volume reduction.CONCLUSIONSLITT is a minimally invasive option for treating CCM-related epilepsy with seizure outcomes comparable to those achieved with open lesionectomy. The precision of LITT allows for the obliteration of eloquent, deep, small, and multifocal lesions with low complication rates, minimal postoperative discomfort, and short hospital stays. In this study the feasibility and benefits of this method were demonstrated in 2 patients with multifocal lesions.

BACKGROUND The natural history and management of dural ectasia in Neurofibromatosis 1 (NF1) is still largely unknown. Dural ectasias are one of the common clinical manifestations of NF1; however, the treatment options for dural ectasias remain unstudied. OBJECTIVE To investigate the natural history, diagnosis, management, and outcome of the largest case series of patients with NF1-associated dural ectasia to date. METHODS Records from our NF1 clinic were reviewed to identify NF1 patients with computed tomography or magnetic resonance imaging evidence of dural ectasia(s) to determine their clinical course. Demographics, symptoms, radiographic and histopathologic findings, treatment, and clinical course were assessed. RESULTS Thirty-four of 37 patients were managed without surgery. Of the 18 initially asymptomatic patients, 5 (27.8%) progressed to symptoms attributable to a dural ectasia (onset of 2.7% per patient-year). Three patients required surgical intervention because of extraspinal mass effect. All 3 initially improved but had symptom recurrence within 2 yr. Reoperation involved shunt placement for cerebrospinal fluid (CSF) diversion. On imaging review, 26 (76.5%) of the nonsurgical patients harbored an associated nearby plexiform neurofibroma. Pathology of one surgical case revealed dural infiltration by diffuse neurofibroma. CONCLUSION Using the largest NF1-associated dural ectasia group to date, we report the first symptom-onset rate for nonsurgical patients. In the few cases requiring surgery for decompression, primary resection, and patching of ectasias failed, subsequently requiring CSF shunting. We demonstrate imaging evidence of nearby plexiform neurofibroma in a majority of cases, which, when combined with histopathology, provides a novel explanation for the formation of dural ectasias.

While multiple trials have employed stereotactic stem cell transplantation, injection techniques have received little critical attention. Precise cell delivery is critical for certain applications, particularly when targeting deep nuclei. Ten patients with a history of ischemic stroke underwent CT-guided stem cell transplantation. Cells were delivered along 3 tracts adjacent to the infarcted area. Intraoperative air deposits and postoperative T2-weighted MRI fluid signals were mapped in relation to calculated targets. The deepest air deposit was found 4.5 ± 1.0 mm (mean ± 2 SEM) from target. The apex of the T2-hyperintense tract was found 2.8 ± 0.8 mm from target. On average, air pockets were found anterior (1.2 ± 1.1 mm, p = 0.04) and superior (2.4 ± 1.0 mm, p