Myeloarchitectonic cortical parcellation data for contemporary neuroimaging - the Vogt-Vogt legacy in the 21st century.

Obtaining precise and detailed parcellations of the human brain has been a major focus of neuroscience research. Here, we present a multimodal dataset, MYATLAS, based on histology-derived myeloarchitectonic parcellations for use with contemporary neuroimaging analyses software. The core of MYATLAS is a novel 3D neocortical, surface-based atlas derived from legacy myeloarchitectonic histology studies. Additionally, we provide digitized quantitative laminar profiles of intracortical myelin content derived from postmortem photometric data, cross-correlated with in vivo myeloarchitectonic features obtained by quantitative MRI mapping. Moreover, congregated, digitized and quality-improved Vogt-Vogt legacy histology data is made available. Finally, to allow for cross-modality correlations, maps of quantitative myelin estimates and corresponding von Economo-Koskinas' cytoarchitectonic features are also included. We share all necessary surface and volume-based registration files as well as shell scripts to facilitate applications of MYATLAS to future in vivo MRI studies.

Temporal Expression Pattern of Hemoxygenase-1 Expression and Its Association with Vasospasm and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Red blood cell-induced cerebral inflammation and toxicity has been shown to be attenuated by induction of the heme-catalyzing enzyme, hemoxygenase-1 (HO-1), in animal models of subarachnoid hemorrhage (SAH). Although inflammatory mechanisms leading to secondary neuronal injury in SAH are becoming increasingly well understood, markers of cerebral inflammation have so far not been implemented in clinical prediction models of SAH. METHODS: In this biomarker observational study, HO-1 messenger ribonucleic acid (mRNA) expression levels were determined in cerebrospinal fluid (CSF) and blood of 66 patients with aneurysmal SAH on days 1, 7, and 14 after the SAH event. HO-1 mRNA expression was determined via real time polymerase chain reaction (PCR), and relative expression changes were quantified in comparison with expression levels in nonhemorrhagic control CSF. Subarachnoid blood burden, as well as presence of vasospasm and delayed cerebral ischemia (DCI), were recorded. Short and long-term clinical outcomes were assessed using the Modified Rankin Scale at discharge and 1 year after the SAH event. RESULTS: CSF HO-1 expression levels showed a significant increase over the 14-day observation period (p < 0.001, F = 22.53) and correlated with intracranial hematoma burden (ρ = 0.349, p = 0.025). In multivariate analyses, CSF HO-1 expression levels did not reach significance as independent predictors of outcome. Vasospasm on computed tomographic angiography was associated with lower CSF HO-1 expression levels on day 7 after SAH (n = 53, p = 0.010), whereas patients with DCI showed higher CSF HO-1 expression levels on day 14 after SAH (n = 21, p = 0.009). CONCLUSIONS: HO-1 expression in CSF in patients with SAH follows a distinct temporal induction pattern and is dependent on intracranial hematoma burden. CSF HO-1 expression was unable to predict functional outcome. Associations of early low HO-1 expression with vasospasm and late elevated HO-1 expression with DCI may point to detrimental effects of late HO-1 induction, warranting the need for further investigation in a larger study population.

Patients with Subarachnoid Hemorrhage Exhibit Disturbed Expression Patterns of the Circadian Rhythm Gene Period-2.

Circadian rhythm gene expression in cerebral pacemaker regions is regulated by a transcriptional-translational feedback loop across the 24-h day-night cycle. In preclinical models of subarachnoid hemorrhage (SAH), cyclic gene expression is disrupted. Stabilization of circadian rhythm gene expression attenuates susceptibility to ischemic damage in both neuronal and myocardial tissues. In this clinical observational study, circadian rhythm gene Period-2 (Per2) mRNA expression levels were determined from blood leukocytes and cerebrospinal fluid (CSF) cells via real-time PCR on days 1, 7 and 14 after aneurysm rupture in 49 patients with spontaneous SAH. CSF Per2 expression was markedly suppressed immediately after SAH and remained suppressed over the course of two weeks of ICU treatment. Short-term mortality as well as occurrence of delirium was associated with greater extent of Per2 suppression on day 1 after SAH. Patients that developed delayed cerebral ischemia exhibited comparatively lower Per2 expression levels on day 7 after SAH, while presence of vasospasm remained unaffected. However, Per2 expression did not differ in patient groups with favourable or non-favourable functional neurological outcome (modified Rankin Scales 1-3 vs. 4-6). While our findings suggest a potential protective effect of stable circadian rhythm gene expression on the extent of ischemic damage, this effect was confined to the early disease course and was not reflected in patients' functional neurological outcome.

Contributions of Imaging to Neuromodulatory Treatment of Drug-Refractory Epilepsy.

Epilepsy affects about 1% of the world's population, and up to 30% of all patients will ultimately not achieve freedom from seizures with anticonvulsive medication alone. While surgical resection of a magnetic resonance imaging (MRI) -identifiable lesion remains the first-line treatment option for drug-refractory epilepsy, surgery cannot be offered to all. Neuromodulatory therapy targeting "seizures" instead of "epilepsy" has emerged as a valuable treatment option for these patients, including invasive procedures such as deep brain stimulation (DBS), responsive neurostimulation (RNS) and peripheral approaches such as vagus nerve stimulation (VNS). The purpose of this review is to provide in-depth information on current concepts and evidence on network-level aspects of drug-refractory epilepsy. We reviewed the current evidence gained from studies utilizing advanced imaging methodology, with a specific focus on their contributions to neuromodulatory therapy.

Accuracy and practical aspects of semi- and fully automatic segmentation methods for resected brain areas.

PURPOSE: Precise segmentation of brain lesions is essential for neurological research. Specifically, resection volume estimates can aid in the assessment of residual postoperative tissue, e.g. following surgery for glioma. Furthermore, behavioral lesion-symptom mapping in epilepsy relies on accurate delineation of surgical lesions. We sought to determine whether semi- and fully automatic segmentation methods can be applied to resected brain areas and which approach provides the most accurate and cost-efficient results. METHODS: We compared a semi-automatic (ITK-SNAP) with a fully automatic (lesion_GNB) method for segmentation of resected brain areas in terms of accuracy with manual segmentation serving as reference. Additionally, we evaluated processing times of all three methods. We used T1w, MRI-data of epilepsy patients (n = 27; 11 m; mean age 39 years, range 16-69) who underwent temporal lobe resections (17 left). RESULTS: The semi-automatic approach yielded superior accuracy (p < 0.001) with a median Dice similarity coefficient (mDSC) of 0.78 and a median average Hausdorff distance (maHD) of 0.44 compared with the fully automatic approach (mDSC 0.58, maHD 1.32). There was no significant difference between the median percent volume difference of the two approaches (p > 0.05). Manual segmentation required more human input (30.41 min/subject) and therefore inferring significantly higher costs than semi- (3.27 min/subject) or fully automatic approaches (labor and cost approaching zero). CONCLUSION: Semi-automatic segmentation offers the most accurate results in resected brain areas with a moderate amount of human input, thus representing a viable alternative compared with manual segmentation, especially for studies with large patient cohorts.

Functional Networks in Epilepsy Presurgical Evaluation.

Continuing advancements in neuroimaging methodology allow for increasingly detailed in vivo characterization of structural and functional brain networks, leading to the recognition of epilepsy as a disorder of large-scale networks. In surgical candidates, analysis of functional networks has proved invaluable for the identification of eloquent brain areas, such as hemispherical language dominance. More recently, connectome-based biomarkers have demonstrated potential to further inform clinical decision making in drug-refractory epilepsy. This article summarizes current evidence on epilepsy as a network disorder, emphasizing potential benefits of network analysis techniques for preoperative assessments and resection planning.

Neuroprotection after Hemorrhagic Stroke Depends on Cerebral Heme Oxygenase-1.

(1) Background: A detailed understanding of the pathophysiology of hemorrhagic stroke is still missing. We hypothesized that expression of heme oxygenase-1 (HO-1) in microglia functions as a protective signaling pathway. (2) Methods: Hippocampal HT22 neuronal cells were exposed to heme-containing blood components and cell death was determined. We evaluated HO-1-induction and cytokine release by wildtype compared to tissue-specific HO-1-deficient (LyzM-Cre.Hmox1 fl/fl) primary microglia (PMG). In a study involving 46 patients with subarachnoid hemorrhage (SAH), relative HO-1 mRNA level in the cerebrospinal fluid were correlated with hematoma size and functional outcome. (3) Results: Neuronal cell death was induced by exposure to whole blood and hemoglobin. HO-1 was induced in microglia following blood exposure. Neuronal cells were protected from cell death by microglia cell medium conditioned with blood. This was associated with a HO-1-dependent increase in monocyte chemotactic protein-1 (MCP-1) production. HO-1 mRNA level in the cerebrospinal fluid of SAH-patients correlated positively with hematoma size. High HO-1 mRNA level in relation to hematoma size were associated with improved functional outcome at hospital discharge. (4) Conclusions: Microglial HO-1 induction with endogenous CO production functions as a crucial signaling pathway in blood-induced inflammation, determining microglial MCP-1 production and the extent of neuronal cell death. These results give further insight into the pathophysiology of neuronal damage after SAH and the function of HO-1 in humans.

Visual field defects following different resective procedures for mesiotemporal lobe epilepsy.

INTRODUCTION: One of the most common side effects of mesiotemporal lobe resection in patients with medically intractable epilepsy are visual field defects (VFD). While peripheral defects usually remain unnoticed by patients, extended VFD influence daily life activities and can, in particular, affect driving regulations. This study had been designed to evaluate frequency and extent of VFD following different surgical approaches to the mesiotemporal area with respect to the ability to drive. MATERIALS AND METHODS: This study comprises a consecutive series of 366 patients operated at the Epilepsy Center in Freiburg for intractable mesiotemporal lobe epilepsy from 1998 to 2016. The following procedures were performed: standard anterior temporal lobectomy (ATL: n=134; 37%), anterior temporal or keyhole resection (KH: n=53; 15%), and selective amygdalohippocampectomy via the transsylvian (tsAHE: n=145; 40%) and the subtemporal (ssAHE: n=34; 9%) approach. Frequency and extent of postoperative VFD were evaluated in relation to different surgical procedures. According to the German driving guidelines, postoperative VFD were classified as driving-relevant VFD with the involvement of absolute, homonymous central scotoma within 20° and driving-irrelevant VFD with either none or exclusively minor VFD sparing the center. RESULTS: Postoperative visual field examinations were available in 276 of 366 cases. Postoperative VFD were observed in 202 of 276 patients (73%) and were found to be driving-relevant in 133 of 276 patients (48%), whereas 69 patients (25%) showed VFD irrelevant for driving. Visual field defects were significantly less likely following ssAHE compared with other temporal resections, and if present, they were less frequently driving-relevant (p<0.05), irrespective of the side of surgery. CONCLUSION: Subtemporal sAHE (ssAHE) caused significantly less frequently and less severely driving-relevant VFD compared with all other approaches to the temporal lobe, irrespective of the side of surgery.