Bifocal extra- and intradural melanocytoma of the spine: case report and literature review

Background: Spinal melanocytoma is one of the most infrequent space-occupying lesions of the central nervous system. To the best of our knowledge, this is the first report of primary bifocal intradural melanocytoma of heterogenous pathological grade to date. Case description: We report the case of a 43-year old patient with primary bifocal melanocytoma, clinically and radiologically resembling benign schwannoma. The patient presented with myeloradiculopathy of the left C3 dermatome. Magnetic resonance imaging of the upper spine revealed two space-occupying lesions with paraspinal extension, initially diagnosed as neurofibroma. Definitive histopathological classification of both lesions was melanocytoma. Both tumours were only partially removed due to adherence to surrounding structures. The patient underwent stereotactic external beam irradiation (EBR). Follow-up at 1year after surgery revealed no recurrence and the patient remained free of symptoms. The clinical, radiological and pathological features of this rare tumour entity are presented and the available literature is reviewed. Conclusions: Intradural melanocytoma, although exceedingly rare, requires a thorough work-up to exclude malignant melanoma. With only two previous reports of multifocal melanocytoma published in the literature, standard therapy has not yet been established and complete surgical removal remains the modality of choice. Patients should be closely monitored to detect local recurrence or malignant degeneration. EBR may be considered in cases where total excision is not achievable and reduces risk of local recurrence

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

Ictal semiology of epileptic seizures with insulo-opercular genesis

Objective!#!Epileptic seizures with insular genesis are often difficult to distinguish from those originating in the temporal lobe due to their complex and variable semiology. Here, we analyzed differentiating characteristics in the clinical spectrum of insulo-opercular seizures.!##!Methods!#!Ictal semiology in patients with a diagnosis of insulo-opercular epilepsy (IOE) based on imaging of epileptogenic lesions or electrophysiological evidence of an insulo-opercular seizure origin was retrospectively analyzed and compared to age-matched controls with mesial temporal lobe epilepsy (MTE).!##!Results!#!Forty-six IOE and 46 matched MTE patients were included. The most prominent ictal features in IOE were focal motor phenomena in 80.4% of these patients. Somatosensory sensations, version, tonic and clonic features, when present, were more frequent contralateral to the SOZ in MTE patients, while they occurred about equally often ipsilateral and contralateral to the SOZ in IOE patients. Ipsilateral manual automatisms were significantly more frequent in MTE patients than in IOE (p = 0.010). Multivariate analysis correctly identified IOE in 78.3% and MTE in 84.8% using five semiologic features (Chi-square = 53.79 with 5 degrees of freedom, p < 0.0001). A subanalysis comparing patients with purely insular lesions with MTE patients using only the earliest ictal signs showed that somatosensory sensations are significantly more frequent in insular epilepsy (p = 0.010), while automatisms were significantly more frequent in MTE patients (p = 0.06).!##!Significance!#!Our study represents the first in-depth analysis of ictal semiology in IOE compared to MTE. Use of these differentiating characteristics can serve for a correct syndrome classification and to steer appropriate diagnostic and local therapeutic procedures

A whole-brain 3D myeloarchitectonic atlas: Mapping the Vogt-Vogt legacy to the cortical surface

Building precise and detailed parcellations of anatomically and functionally distinct brain areas has been a major focus in Neuroscience. Pioneer anatomists parcellated the cortical manifold based on extensive histological studies of post-mortem brain, harnessing local variations in cortical cyto-and myeloarchitecture to define areal bound-aries. Compared to the cytoarchitectonic field, where multiple neuroimaging studies have recently translated this old legacy data into useful analytical resources, myeloarchitectonics, which parcellate the cortex based on the organization of myelinated fibers, has received less attention. Here, we present the neocortical surface-based myeloarchitectonic atlas based on the histology-derived maps of the Vogt-Vogt school and its 2D translation by Nieuwenhuys. In addition to a myeloarchitectonic parcellation, our package includes intracortical laminar pro-files of myelin content based on Vogt-Vogt-Hopf original publications. Histology-derived myelin density mapped on our atlas demonstrated a close overlap with in vivo quantitative MRI markers for myelin and relates to cytoar-chitectural features. Complementing the existing battery of approaches for digital cartography, the whole-brain myeloarchitectonic atlas offers an opportunity to validate imaging surrogate markers of myelin in both health and disease.11Nsciescopu

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

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

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

Enhanced serum creatine kinase after neurosurgery in lateral position and intraoperative neurophysiological monitoring

OBJECTIVE: Several cases of highly elevated serum levels of creatine kinase (CK) after surgical interventions have been described in the literature. A consensus on possible risk factors is still lacking. We therefore studied CK-levels in a large population of patients undergoing neurosurgical interventions and sought to determine possible risk factors. METHODS: We retrospectively analyzed 150 elective neurosurgical interventions where pre- and postoperative CK serum levels were determined. The cases were selected such that 50 patients were operated in lateral position and 100 in prone or supine position. During the hospital stay, routine clinical diagnostics were conducted, including medical status and laboratory examinations. RESULTS: In the patient group (median age 50, 63 male) there were 129 cranial and 21 spinal interventions. In 55 cases, intraoperative neurophysiological monitoring (IONM) was performed so that in these patients muscles were not relaxed pharmacologically. In a linear regression model, the maximal postoperative CK-level increased compared to baseline (p<0.001). While age and obesity were not identified as risk factors, the CK-level was enhanced after surgery in lateral position (p<0.001) and if IONM was performed (p=0.04). CONCLUSIONS: The strong association of postoperative serum CK-level with intraoperative positioning and IONM may be related to the elevated body pressure on the operating table in the lateral position, in particular if muscles are not relaxed pharmacologically, which was the case if intraoperative monitoring was performed. In these cases special care has to be taken for the positioning and during the peri-operative management

Bifocal extra- and intradural melanocytoma of the spine: case report and literature review

BACKGROUND: Spinal melanocytoma is one of the most infrequent space-occupying lesions of the central nervous system. To the best of our knowledge, this is the first report of primary bifocal intradural melanocytoma of heterogenous pathological grade to date. CASE DESCRIPTION: We report the case of a 43-year old patient with primary bifocal melanocytoma, clinically and radiologically resembling benign schwannoma. The patient presented with myeloradiculopathy of the left C3 dermatome. Magnetic resonance imaging of the upper spine revealed two space-occupying lesions with paraspinal extension, initially diagnosed as neurofibroma. Definitive histopathological classification of both lesions was melanocytoma. Both tumours were only partially removed due to adherence to surrounding structures. The patient underwent stereotactic external beam irradiation (EBR). Follow-up at 1 year after surgery revealed no recurrence and the patient remained free of symptoms. The clinical, radiological and pathological features of this rare tumour entity are presented and the available literature is reviewed. CONCLUSIONS: Intradural melanocytoma, although exceedingly rare, requires a thorough work-up to exclude malignant melanoma. With only two previous reports of multifocal melanocytoma published in the literature, standard therapy has not yet been established and complete surgical removal remains the modality of choice. Patients should be closely monitored to detect local recurrence or malignant degeneration. EBR may be considered in cases where total excision is not achievable and reduces risk of local recurrences