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OBJECTIVE In patients with temporal lobe epilepsy (TLE) with a nonlesional and nonepileptogenic hippocampus (HC), in order to preserve functionally intact brain tissue, the HC is not resected. However, some patients experience postoperative memory decline, possibly due to disruption of the extrahippocampal memory network and secondary hippocampal volume (HV) loss. The purpose of this study was to determine the extent of hippocampal atrophy ipsilateral and contralateral to the side of the surgery and its relation to memory outcomes. METHODS Hippocampal volume and verbal as well as visual memory performance were retrospectively examined in 55 patients (mean age ± standard deviation [SD] 30 ± 15 years, 25 female, 31 left) before and 5 months after surgery within the temporal lobe that spared the entire HC. HV was extracted based on prespecified templates, and resection volumes were also determined. RESULTS HV loss was found both ipsilateral and contralateral to the side of surgery (P

Elderly patients constitute an expanding part of our society. Due to a continuously increasing life expectancy, an optimal quality of life is expected even into advanced age. Glioblastoma (GBM) is more common in older patients, but they are still often withheld from efficient treatment due to worry of worse tolerance and have a significantly worse prognosis compared to younger patients. Our retrospective observational study aimed to investigate the therapeutic benefit from a second resection in recurrent glioblastoma of elderly patients. We included a cohort of 39 elderly patients (> 65 years) with a second resection as treatment option in the case of a tumor recurrence. A causal inference model was built by multiple non- and semiparametric models, which was used to identify matched patients from our elderly GBM database which comprises 538 patients. The matched cohorts were analyzed by a Cox-regression model adjusted by time-dependent covariates. The Cox-regression analysis showed a significant survival benefit (Hazard Ratio: 0.6, 95% CI 0.36–0.9, p-value = 0.0427) for the re-resected group (18.0 months, 95% CI 13.97–23.2 months) compared to the group without re-resection (10.1 months, 95% CI 8.09–20.9 months). No differences in the co-morbidities or hemato-oncological side effects during chemotherapy could be detected. Anesthetic- and surgical complications were rare and comparable to the complication rate of patients undergoing the first-line resection. Taken together, in elderly patients, re-resection is an acceptable treatment option in the recurrent state of a glioblastoma. The individual evaluation of the patients′ medical status as well as the chances of withstanding general anesthesia needs to be done in close interdisciplinary consultation. If these requirements are met, elderly patients benefit from a re-resection.

Background Anaplastic meningiomas are rare tumors with a poor prognosis, even after complete surgical resection and radiotherapy. There has been limited evidence with respect to the clinical factors and their effects on the course of the disease. Various retrospective studies have not been able to provide clear evidence of standardized treatment, usually presenting contradictory results. The aim of this study was to evaluate the prognostic factors influencing the progression-free survival (PFS) and overall survival (OS) of anaplastic meningiomas, with a particular focus on the roles of the extent of resection and postoperative adjuvant radiotherapy. Methods Between October 2001 and March 2016, 36 patients with anaplastic meningiomas were treated in our Department of Neurosurgery, of whom 11 underwent gross total resection (GTR) and 18 subtotal resection. Twenty-one patients received postoperative adjuvant radiotherapy, and 8 were treated with surgery alone. GTR (Simpson grades I and II) was associated with significantly improved PFS (P = 0.01) and OS (P = 0.004). Furthermore, adjuvant radiotherapy showed an improvement in PFS (P = 0.01) but not in OS (P = 0.16). Conclusions The extent of resection in anaplastic meningiomas is correlated with a better outcome. However, resection alone is not sufficient for the long-term control of anaplastic meningiomas. Adjuvant radiotherapy is an essential component in the adjuvant treatment of anaplastic meningiomas, including for patients undergoing GTR. Further investigations through which to improve adjuvant therapy options are necessary to improve meningioma therapy.

BACKGROUND Hemodynamic alterations of extracranial veins are considered an etiologic factor in multiple sclerosis (MS). However, ultrasound and MRI studies could not confirm a pathophysiological link. Because of technical challenges using standard diagnostics, information about the involvement of superficial intracranial veins in proximity to the affected brain in MS is scarce. PURPOSE To comprehensively investigate the hemodynamics of intracranial veins and of the venous outflow tract in MS patients and controls. STUDY TYPE Prospective. POPULATION Twenty-eight patients with relapsing-remitting MS (EDSS1.9 ± 1.1; range 0-3) and 41 healthy controls. FIELD STRENGTH/SEQUENCE 3T/2D phase-contrast and time-resolved 4D flow MRI, extra- and transcranial sonography. ASSESSMENT Hemodynamics within the superficial and deep intracranial venous system and outflow tract including the internal, basal, and great cerebral vein, straight, superior sagittal, and transverse sinuses, internal jugular and vertebral veins. Sonography adhered to the chronic cerebrospinal venous insufficiency (CCSVI) criteria. STATISTICAL TESTS Multivariate repeated measure analysis of variance, Student's two-sample t-test, chi-square, Fisher's exact test; separate analysis of the entire cohort and 32 age- and sex-matched participants. RESULTS Multi- and univariate main effects of the factor group (MS patient vs. control) and its interactions with the factor vessel position (lower flow within dorsal superior sagittal sinus in MS, 3 ± 1 ml/s vs. 3.8 ± 1 ml/s; P < 0.05) in the uncontrolled cohort were attributable to age-related differences. Age- and sex-matched pairs showed a different velocity gradient in a single segment within the deep cerebral veins (great cerebral vein, vena cerebri magna [VCM] 7.6 ± 1.7 cm/s; straight sinus [StS] 10.5 ± 2.2 cm/s vs. volunteers: VCM 9.2 ± 2.3 cm/s; StS 10.2 ± 2.3 cm/s; P = 0.01), reaching comparable velocities instantaneously downstream. Sonography was not statistically different between groups. DATA CONCLUSION Consistent with previous studies focusing on extracranial hemodynamics, our comprehensive analysis of intracerebral venous blood flow did not reveal relevant differences between MS patients and controls. Level of Evidence 1. Technical Efficacy Stage 3. J. Magn. Reson. Imaging 2020;51:205-217.

PurposeThe aim of this study was the development and external validation of a logistic regression model to differentiate gliosarcoma (GSC) and glioblastoma multiforme (GBM) on standard MR imaging.MethodsA univariate and multivariate analysis was carried out of a logistic regression model to discriminate patients histologically diagnosed with primary GSC and an age and sex-matched group of patients with primary GBM on presurgical MRI with external validation.ResultsIn total, 56 patients with GSC and 56 patients with GBM were included. Evidence of haemorrhage suggested the diagnosis of GSC, whereas cystic components and pial as well as ependymal invasion were more commonly observed in GBM patients. The logistic regression model yielded a mean area under the curve (AUC) of 0.919 on the training dataset and of 0.746 on the validation dataset. The accuracy in the validation dataset was 0.67 with a sensitivity of 0.85 and a specificity of 0.5.ConclusionsAlthough some imaging criteria suggest the diagnosis of GSC or GBM, differentiation between these two tumour entities on standard MRI alone is not feasible.

Acta neurochirurgica 163(4), 937-945 (2021). doi:10.1007/s00701-020-04623-z special issue: "Tumor - Glioma", Published by Springer, Wien [u.a.]

BMC cancer 20, 818 (2020). doi:10.1186/s12885-020-07290-6, Published by BioMed Central, London

The aim of this study was to evaluate whether ganglioglioma (GGL), dysembryoplastic neuroepithelial tumour (DNET) and FCD (focal cortical dysplasia) are distinguishable through diffusion tensor imaging. Additionally, it was investigated whether the diffusion measures differed in the perilesional (pNAWM) and in the contralateral normal appearing white matter (cNAWM). Six GGLs, eight DNETs and seven FCDs were included in this study. Quantitative diffusion measures, that is, axial, radial and mean diffusivity and fractional anisotropy, were determined in the lesion identified on isotropic T2 or FLAIR-weighted images and in pNAWM and cNAWM, respectively. DNET differed from FCD in mean diffusivity, and GGL from FCD in radial diffusivity. Both types of glioneuronal tumours were different from pNAWM in fractional anisotropy and radial diffusivity. For identifying the tumour edges, threshold values for tumour-free tissue were investigated with receiver operating characteristic analyses: tumour could be separated from pNAWM at a threshold ≤ 0.32 (fractional anisotropy) or ≥ 0.56 (radial diffusivity) *10–3 mm2/s (area under the curve 0.995 and 0.990 respectively). While diffusion parameters of FCDs differed from cNAWM (radial diffusivity (*10–3 mm/s2): 0.74 ± 0.19 vs. 0.43 ± 0.05; corrected p-value

The purpose of this study is to map spatial metabolite differences across three molecular subgroups of glial tumors, defined by the IDH1/2 mutation and 1p19q-co-deletion, using magnetic resonance spectroscopy. This work reports a new MR spectroscopy based classification algorithm by applying a radiomics analytics pipeline. 65 patients received anatomical and chemical shift imaging (5 × 5 × 20 mm voxel size). Tumor regions were segmented and registered to corresponding spectroscopic voxels. Spectroscopic features were computed (n = 860) in a radiomic approach and selected by a classification algorithm. Finally, a random forest machine-learning model was trained to predict the molecular subtypes. A cluster analysis identified three robust spectroscopic clusters based on the mean silhouette widths. Molecular subgroups were significantly associated with the computed spectroscopic clusters (Fisher’s Exact test p

We aimed to modify our previously published method for arterial input function measurements for evaluation of cerebral perfusion (dynamic susceptibility contrast MRI) such that it can be applied in humans in a clinical setting. Similarly to our previous work, a conventional measurement sequence for dynamic susceptibility contrast MRI is extended with an additional measurement slice at the neck. Measurement parameters at this slice were optimized for the blood signal (short echo time, background suppression, magnitude and phase images). Phase-based evaluation of the signal in the carotid arteries is used to obtain quantitative arterial input functions. In all pilot measurements, quantitative arterial input functions were obtained. The resulting absolute perfusion parameters agree well with literature values (gray and white matter mean values of 46 and 24 mL/100 g/min, respectively, for cerebral blood flow and 3.0% and 1.6%, respectively, for cerebral blood volume). The proposed method has the potential to quantify arterial input functions in the carotid arteries from a direct measurement without any additional normalization.

Antero-inferior temporal lobe meningoencephaloceles are a rare, but increasingly recognized cause of drug-resistant temporal lobe epilepsy (TLE). In order to evaluate whether these lesions are related to idiopathic intracranial hypertension (IIH), we analyzed clinical and MRI findings of a cohort of patients undergoing presurgical work-up. Seizure onset in the anterior temporal lobe was proven by EEG electrodes in 22 patients, and in 21 patients, anterior temporal lobectomy (mostly with sparing of the hippocampus) was performed. MRI signs of IIH (in particular empty sella) and the volumes of the ventricles and external CSF spaces were determined and related to the body mass index (BMI) and clinical outcome. Six of seven obese (BMI > 30 kg/m2) compared to four of 15 non-obese patients had partial empty or empty sella (p = 0.007). Bilateral lesions were found in all obese and 11 patients. Seizure freedom (Engel class 1A) was achieved in 12 of 21 patients (5 obese compared to 7 non-obese patients). BMI was related to the volume of the external CSF spaces (r = 0.467), and age at seizure onset was higher in obese patients. Roughly a third of patients with temporal lobe epilepsy due to antero-inferior meningoencephaloceles is obese and has MRI signs of idiopathic intracranial hypertension.

The APOE ε4 allele increases the risk for sporadic Alzheimer's disease and modifies brain activation patterns of numerous cognitive domains. We assessed cognitively intact older adults with a letter n-back task to determine if previously observed increases in ε4 carriers' working-memory-related brain activation are compensatory such that they serve to maintain working memory function. Using multiple regression models, we identified interactions of APOE variant and age in bilateral hippocampus independently from task performance: ε4 carriers only showed a decrease in activation with increasing age, suggesting high sensitivity of fMRI data for detecting changes in Alzheimer's disease-relevant brain areas before cognitive decline. Moreover, we identified ε4 carriers to show higher activations in task-negative medial and task-positive inferior frontal areas along with better performance under high working memory load relative to non-ε4 carriers. The increased frontal recruitment is compatible with models of neuronal compensation, extends on existing evidence, and suggests that ε4 carriers require additional neuronal resources to successfully perform a demanding working memory task.

The biology of recurrent glioblastoma multiforme (GBM) is a dynamic process influenced by selection pressure induced by different antitumoural therapies. The poor clinical outcome of tumours in the recurrent stage necessitates the development of effective therapeutic strategies. Checkpoint-inhibition (PD1/PD-L1 Inhibition) is a hallmark of immunotherapy being investigated in ongoing clinical trials. The purpose of this study was to analyse the PD-L1 expression in de-novo and recurrent glioblastoma multiforme and to explore associated genetic alterations and clinical traits. We show that PD-L1 expression was reduced in recurrent GBM in comparison to de-novo GBM. Additionally, patients who received an extended dose of temozolomide (TMZ) chemotherapy showed a significantly reduced level of PD-L1 expression in the recurrence stage compared to the corresponding de-novo tumour. Our findings may provide an explanation for potentially lower response to immunotherapy in the recurrent stage due to the reduced expression of the therapeutic target PD-L1.

Background Mesiotemporal lobe epilepsy is one of the most frequent causes for pharmacoresistant epilepsy. Different surgical approaches to the mesiotemporal area are used. Objective To analyze epileptological and neuropsychological results as well as complications of different surgical strategies. Methods This retrospective study is based on a consecutive series of 458 patients all harboring pharmacoresistant mesiotemporal lobe epilepsy. Following procedures were performed: standard anterior temporal lobectomy, anterior temporal or key-hole resection, extended lesionectomy, and transsylvian and subtemporal selective amygdalohippocampectomy. Postoperative outcome was evaluated according to different surgical procedures. Results Overall, 1 yr after surgery 315 of 432 patients (72.9%) were classified Engel I; in particular, 72.8% were seizure-free after anterior temporal lobectomy, 76.9% after key-hole resection, 84.4% after extended lesionectomy, 70.3% after transylvian selective amygdalohippocampectomy, and 59.1% after subtemporal selective amygdalohippocampectomy. No significant differences in seizure outcome were found between different resective procedures, neither in short-term nor long-term follow-up. There was no perioperative mortality. Permanent morbidity was encountered in 4.4%. There were no significant differences in complications between different resection types. In the majority of patients, selective attention improved following surgery. Patients after left-sided operations performed significantly worse regarding verbal memory as compared to right-sided procedures. However, surgical approach had no significant effect on memory outcome. Conclusion Different surgical approaches for mesiotemporal epilepsy analyzed resulted in similar epileptological, neuropsychological results, and complication rates. Therefore, the approach for the individual patient does not only depend on the specific localization of the epileptogenic area, but also on the experience of the surgeon.

Therapeutically resected, adult brain segments were maintained and characterized for an extended period to study glioblastoma progression and treatment in its almost natural environment., When it comes to the human brain, models that closely mimic in vivo conditions are lacking. Living neuronal tissue is the closest representation of the in vivo human brain outside of a living person. Here, we present a method that can be used to maintain therapeutically resected healthy neuronal tissue for prolonged periods without any discernible changes in tissue vitality, evidenced by immunohistochemistry, genetic expression, and electrophysiology. This method was then used to assess glioblastoma (GBM) progression in its natural environment by microinjection of patient-derived tumor cells into cultured sections. The result closely resembles the pattern of de novo tumor growth and invasion, drug therapy response, and cytokine environment. Reactive transformation of astrocytes, as an example of the cellular nonmalignant tumor environment, can be accurately simulated with transcriptional differences similar to those of astrocytes isolated from acute GBM specimens. In a nutshell, we present a simple method to study GBM in its physiological environment, from which valuable insights can be gained. This technique can lead to further advancements in neuroscience, neuro-oncology, and pharmacotherapy.

Objective:To distinguish white matter remodeling directly induced by stroke lesion from that evoked by remote network dysfunction, using spatial neglect as a model.Methods:We examined 24 visual neglect/extinction patients and 17 control patients combining comprehensive analyses of diffusion tensor metrics and global fiber tracking with neuropsychological testing in the acute (6.3 ± 0.5 days poststroke) and chronic (134 ± 7 days poststroke) stroke phases.Results:Compared to stroke controls, patients with spatial neglect/extinction displayed longitudinal white matter alterations with 2 defining signatures: (1) perilesional degenerative changes characterized by congruently reduced fractional anisotropy and increased radial diffusivity (RD), axial diffusivity, and mean diffusivity, all suggestive of direct axonal damage by lesion and therefore nonspecific for impaired attention network and (2) transneuronal changes characterized by an increased RD in contralesional frontoparietal and bilateral occipital connections, suggestive of primary periaxonal involvement; these changes were distinctly related to the degree of unrecovered neglect symptoms in chronic stroke, hence emerging as network-specific alterations.Conclusions:The present data show how stroke entails global alterations of lesion-spared network architecture over time. Sufficiently large lesions of widely interconnected association cortex induce distinct, large-scale structural reorganization in domain-specific network connections. Besides their relevance to unrecovered domain-specific symptoms, these effects might also explain mechanisms of domain-general deficits in stroke patients, pointing to potential targets for therapeutic intervention.

// Dieter Henrik Heiland 1, 5 , Jakob Worner 2 , Jan Gerrit Haaker 1, 5 , Daniel Delev 1, 5 , Nils Pompe 2 , Bianca Mercas 1, 5 , Pamela Franco 1, 5 , Annette Gabelein 1, 5 , Sabrina Heynckes 1, 5 , Dietmar Pfeifer 3, 5 , Stefan Weber 2 , Irina Mader 4, 5 and Oliver Schnell 1, 5 1 Department of Neurosurgery, Medical Center, University of Freiburg, Freiburg, Germany 2 Institute of Physical Chemistry, Faculty of Chemistry and Pharmacy, University of Freiburg, Freiburg, Germany 3 Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, University of Freiburg, Freiburg, Germany 4 Department of Neuroradiology, Medical Center, University of Freiburg, Freiburg, Germany 5 Faculty of Medicine, University of Freiburg, Freiburg, Germany Correspondence to: Dieter Henrik Heiland, email: dieter.henrik.heiland@uniklinik-freiburg.de Keywords: metabolomics, transcriptomics, network analysis, glioblastoma multiforme, WGCNA Received: January 02, 2017 Accepted: February 23, 2017 Published: March 24, 2017 ABSTRACT The purpose of this study was to map the landscape of metabolic-transcriptional alterations in glioblastoma multiforme. Omic-datasets were acquired by metabolic profiling (1D-NMR spectroscopy n=33 Patient) and transcriptomic profiling (n=48 Patients). Both datasets were analyzed by integrative network modeling. The computed model concluded in four different metabolic-transcriptomic signatures containing: oligodendrocytic differentiation, cell-cycle functions, immune response and hypoxia. These clusters were found being distinguished by individual metabolism and distinct transcriptional programs. The study highlighted the association between metabolism and hallmarks of oncogenic signaling such as cell-cycle alterations, immune escape mechanism and other cancer pathway alterations. In conclusion, this study showed the strong influence of metabolic alterations in the wide scope of oncogenic transcriptional alterations.

A patient is reported with reversible pure alexia in the context of migraine with aura. Following previous, anecdotal reports, the present study is the first to formally assess word reading, writing, and other linguistic and visual processing and to compare these to a patient with stroke-related pure alexia. The reading impairment, suggestive of letter-by-letter reading, was observed across 7 days but had remitted at a 3-month follow-up. The deficit also affected recognition of letters, suggesting a functional impairment at the level of letter recognition, not just word reading. It went along with reversible abnormalities in diffusion-weighted and fluid-attenuated inversion recovery imaging in areas known to be involved in word reading.

// Dieter Henrik Heiland 1 , Theo Demerath 2, 6 , Elias Kellner 3 , Valerij G. Kiselev 3 , Dietmar Pfeifer 4 , Oliver Schnell 1 , Ori Staszewski 5 , Horst Urbach 2 , Astrid Weyerbrock 1 , Irina Mader 2 1 Department of Neurosurgery, Medical Center University of Freiburg, Freiburg, Germany 2 Department of Neuroradiology, Medical Center University of Freiburg, Freiburg, Germany 3 Medical Physics, Department of Radiology, Medical Center University of Freiburg, Freiburg, Germany 4 Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center University of Freiburg, Freiburg, Germany 5 Department of Neuropathology, Medical Center University of Freiburg, Freiburg, Germany 6 Department of Radiology, Kantonsspital, Medical Center Universtiy of Basel, Switzerland Correspondence to: Dieter Henrik Heiland, email: dieter.henrik.heiland@uniklinik-freiburg.de Keywords: radiogenomics, CBV, vessel size imaging, WGCNA, glioblastoma Received: April 27, 2016 Accepted: July 28, 2016 Published: August 23, 2016 ABSTRACT The purpose of this study was to investigate the molecular background of cerebral blood volume (CBV) and vessel size (VS) of capillaries in glioblastoma multiforme (GBM). Both parameters are derived from extended perfusion MR imaging. A prospective case study including 21 patients (median age 66 years, 10 females) was performed. Before operation, CBV and VS of contrast enhancing tumor were assessed. Tissue was sampled from the assessed areas under neuronavigation control. After RNA extraction, transcriptional data was analyzed by Weighted Gene Co-Expression Network Analysis (WGCNA) and split into modules based on its network affiliations. Gene Set Enrichment Analysis (GSEA) identified biological functions or pathways of the genetic modules. These were applied on 484 GBM samples of the TCGA database. Ten modules were highly correlated to CBV and VS. One module was exclusively associated to VS and highly correlated to hypoxia, another one exclusively to CBV showing strong enrichments in the Epithelial Growth Factor (EGF) pathway and Epithelial-to-Mesenchymal-Transition (EMT). Moreover, patients with increased CBV and VS predominantly showed a mesenchymal gene-expression, a finding that could be corroborated by TCGA data. In conclusion, CBV and VS mirror different genetic pathways and reflect certain molecular subclasses of GBM.

PURPOSE Achieving higher spatial resolution and improved brain coverage while mitigating in-plane susceptibility artifacts in the assessment of perfusion parameters, such as cerebral blood volume, in echo planar imaging (EPI)-based dynamic susceptibility contrast weighted cerebral perfusion measurements. METHODS PEAK-EPI, an EPI sequence with interleaved readout trajectories and three different strategies for autocalibration-signal acquisition (inplace, dynamic extra and extra) is presented. Performance of each approach is analyzed in vivo based on flip angle variation induced dynamics, assessing temporal fidelity, temporal SNR and g-factors. All approaches are compared with conventional GRAPPA reconstructions. PEAK-EPI with inplace autocalibration-signal at R = 5 is then compared with the standard clinical EPI protocol in six patients, using two half-dose dynamic susceptibility contrast weighted cerebral perfusion measurements per subject. RESULTS PEAK-EPI acquisition facilitates a substantial increase of spatial resolution at a higher number of slices per TR and provides improved SNR compared to conventional GRAPPA. High dependency of the resulting reconstruction quality on the type of autocalibration-signal acquisition is observed. PEAK-EPI with inplace autocalibration-signal achieves high temporal fidelity and initial feasibility is shown. CONCLUSION The obtained high resolution cerebral blood volume maps reveal more detailed information than in corresponding standard EPI measurements and facilitate detailed delineation of tumorous tissue. Magn Reson Med 77:2153-2166, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

To differentiate between abnormal tumor vessels and regular brain vasculature using new quantitative measures in time-of-flight (TOF) MR angiography (MRA) data. In this work time-of-flight (TOF) MR angiography data are acquired in 11 glioma patients to quantify vessel abnormality. Brain vessels are first segmented with a new algorithm, efficient monte-carlo image-analysis for the location of vascular entity (EMILOVE), and are then characterized in three brain regions: tumor, normal-appearing contralateral brain, and the total brain volume without the tumor. For characterization local vessel orientation angles and the dot product between local orientation vectors are calculated and averaged in the 3 regions. Additionally, correlation with histological and genetic markers is performed. Both the local vessel orientation angles and the dot product show a statistically significant difference (p

BMC cancer 19, 117 (2019). doi:10.1186/s12885-019-5308-y, Published by BioMed Central, London

According to the 2016 WHO classification lower-grade gliomas consist of three groups: IDH-mutated and 1p/19q co-deleted, IDH-mutated and IDH-wildtype tumors. The aim of this study was to evaluate the impact of surgical therapy for lower-grade gliomas with a particular focus on the molecular subgroups. This is a bi-centric retrospective analysis including 299 patients, who underwent treatment for lower-grade glioma between 1990 and 2016. All tumors were re-classified according to the 2016 WHO classification. Data concerning baseline and tumor characteristics, overall survival, different treatment modalities and functional outcome were analyzed. A total of 112 (37.5%) patients with IDH-mutation and 1p/19q co-deletetion, 86 (28.8%) patients with IDH-mutation and 101 (33.8%) patients with IDH-wildtype tumors were identified. The median overall survival (mOS) differed significantly between the groups (p

Background Although frontal lobe resections account for one-third of intralobar resections in pediatric epilepsy surgery, there is a dearth of information regarding long-term seizure freedom, overall cognitive and adaptive functioning. Objective To identify outcome predictors and define the appropriate timing for surgery. Methods We retrospectively analyzed the data of 75 consecutive patients aged 10.0 ± 4.9 yr at surgery that had an 8.1 yr mean follow-up. Results Etiology comprised focal cortical dysplasia (FCD) in 71% and benign tumors in 16% cases. All patients but one had a magnetic resonance imaging-visible lesion. At last follow-up, 63% patients remained seizure-free and 37% had discontinued antiepileptic drugs. Presurgical predictors of seizure freedom were a shorter epilepsy duration, strictly regional epileptic discharges in electroencephalography (EEG), and an epileptogenic zone and/or lesion distant from eloquent cortex. Postsurgical predictors were the completeness of resection and the lack of early postoperative seizures or epileptic discharges in EEG. Higher presurgical overall cognitive and adaptive functioning was related to later epilepsy onset and to a sublobar epileptogenic zone and/or lesion. Following surgery, scores remained stable in the majority of patients. Postsurgical gains were determined by higher presurgical performance and tumors vs FCD. Conclusion Our findings highlight the favorable long-term outcomes following frontal lobe epilepsy surgery in childhood and adolescence and underline the importance of early surgical intervention in selected candidates. Early postsurgical relapses and epileptic discharges in EEG constitute key markers of treatment failure and should prompt timely reevaluation. Postsurgical overall cognitive and adaptive functioning is stable in most patients, whereas those with benign tumors have higher chances of improvement.

Background and purpose GTV definition for re-irradiation treatment planning in recurrent glioblastoma (rGBM) is usually based on contrast-enhanced MRI (GdT1w-MRI) and, for an increased specificity, on amino acid PET. Diffusion-weighted (DWI) MRI and ADC maps can reveal regions of high cellularity as surrogate for active tumor. The objective of this study was to compare the localization and quality of diffusion restriction foci (GTV-ADClow) with FET-PET (GTV-PET) and GdT1w-MRI (GTV-GdT1w-MRI). Material and methods We prospectively evaluated 41 patients, who received a fractionated stereotactic re-irradiation for rGBM. GTV-PET was generated automatically (tumor-to-background ratio 1.7–1.8) and manually customized. GTV-ADClow was manually defined based on DWI data (3D diffusion gradients, b = 0, 1000 s/mm2) and parametric ADC maps. The localization of recurrence was correlated with initial GdT1w-MRI and PET data. Results In 30/41 patients, DWI-MRI showed areas with restricted diffusion (mean ADC-value 0.74 ± 0.22 mm2/s). 66% of GTVs-ADClow were located outside the GdT1w-MRI volume and 76% outside increased FET uptake regions. Furthermore, GTVs-ADClow were only partially included in the high dose volume and received in mean 82% of the reference dose. An adjusted volume including GdT1w-MRI, PET-positive and restricted diffusion areas would imply a GTV increase of 48%. GTV-PET and GdT1w-MRI correlated better with the localization of re-recurrence in comparison to GTV-ADClow. Conclusion Unexpectedly, GTV-ADClow overlapped only partially with FET-PET and GdT1w-MRI in rGBM. Moreover, GTV-ADClow correlated poorly with later rGBM-recurrences. Seeing as a restricted diffusion is known to correlate with hypercellularity, this imaging discrepancy could only be further explained in histopathological studies.

Objective Spatial neglect can either spontaneously resolve or persist after stroke; the latter is associated with a poorer outcome. We aimed to investigate the neural correlates and predictors of favorable versus poor recovery from neglect in acute stroke. Methods In addition to neuropsychological testing, we explored task-related functional magnetic resonance imaging activation and functional connectivity in 34 patients with neglect and/or extinction. Patients were examined at 2 to 3 days (acute phase I) and 8 to 10 days (acute phase II), and some of them at 4 to 6 months (chronic phase) poststroke. Results Course of recovery was predicted by the strength of functional connectivity between the right parietal and left prefrontal and parietal regions, as early as acute phase I. During acute phase II, favorable recovery from neglect was associated with increased activation in the left prefrontal and right parietal regions, an effect not observed at any time point in patients with poor acute recovery. The extent of neglect amelioration correlated with activation gain in the right attention centers; stronger activation of their left functional homologues correlated with better spatial processing in the neglected hemispace during both of the acute examination phases. Interpretation System excitability and early recruitment of contralesional functional homologues represented specific features of favorable recovery in acute stroke. In severe strokes leading to neglect, contralesional functional homologues support recovery by modulating the preserved ipsilesional network, and initial functional connectivity between them might predict recovery course and help to identify patients with potentially poor recovery requiring more intensive early rehabilitation.

Apraxia is a debilitating cognitive motor disorder that frequently occurs after left hemisphere stroke and affects tool-associated and imitative skills. However, the severity of the apraxic deficits varies even across patients with similar lesions. This variability raises the question whether regions outside the left hemisphere network typically associated with cognitive motor tasks in healthy subjects are of additional functional relevance. To investigate this hypothesis, we explored regions where functional magnetic resonance imaging activity is associated with better cognitive motor performance in patients with left hemisphere ischaemic stroke. Thirty-six patients with chronic (>6 months) large left hemisphere infarcts (age ± standard deviation, 60 ± 12 years, 29 male) and 29 control subjects (age ± standard deviation, 72 ± 7, 15 male) were first assessed behaviourally outside the scanner with tests for actual tool use, pantomime and imitation of tool-use gestures, as well as for meaningless gesture imitation. Second, functional magnetic resonance imaging activity was registered during the passive observation of videos showing tool-associated actions. Voxel-wise linear regression analyses were used to identify areas where behavioural performance was correlated with functional magnetic resonance imaging activity. Furthermore, lesions were delineated on the magnetic resonance imaging scans for voxel-based lesion–symptom mapping. The analyses revealed two sets of regions where functional magnetic resonance imaging activity was associated with better performance in the clinical tasks. First, activity in left hemisphere areas thought to mediate cognitive motor functions in healthy individuals (i.e. activity within the putative ‘healthy’ network) was correlated with better scores. Within this network, tool-associated tasks were mainly related to activity in supramarginal gyrus and ventral premotor cortex, while meaningless gesture imitation depended more on the anterior intraparietal sulcus and superior parietal lobule. Second, repeating the regression analyses with total left hemisphere lesion volume as additional covariate demonstrated that tool-related skills were further supported by right premotor, right inferior frontal and left anterior temporal areas, while meaningless gesture imitation was also driven by the left dorso-lateral prefrontal cortex. In summary, tool-related and imitative skills in left hemisphere stroke patients depend on the activation of spared left hemisphere regions that support these abilities in healthy individuals. In addition, cognitive motor functions rely on the activation of ipsi- and contralesional areas that are situated outside this ‘healthy’ network. This activity may explain why some patients perform surprisingly well despite large left brain lesions, while others are severely impaired. * Abbreviations : ATL = : anterior temporal lobe BOLD = : blood oxygen level-dependant IFG = : inferior frontal gyrus IPL = : inferior parietal lobule MCA = : middle cerebral artery PFC = : prefrontal cortex PMC = : premotor cortex SMG = : supramarginal gyrus SPL = : superior parietal lobule VLSM = : voxel-based lesion–symptom mapping

Reliable performance in working memory (WM) critically depends on the ability to resist proactive interference (PI) from previously relevant WM contents. Both WM performance and PI susceptibility are subject to cognitive decline at older adult age. However, the behavioral and neural processes underlying these co-evolving developmental changes and their potential interdependencies are not yet understood. Here, we investigated PI using a recent-probes WM paradigm and functional MRI in a cross-sectional sample of younger (n=18, 10 female, 23.4 ± 2.7 years) and older adults (n=18, 10 female, 70.2 ± 2.7 years). As expected, older adults showed lower WM performance and higher PI susceptibility than younger adults. Resolution of PI activated a mainly bilateral frontal network across all participants. Significant interactions with age indicated reduced neural activation in older adults for PI resolution. A second analysis in a selection of younger and older adults (n=12 each) with matched WM performance also revealed significant differences in PI between both age groups and - on a descriptive level - again a hypo-activation of the older adults' PI network. But the differential effect of age on the neural PI effects did not reach significance in this smaller sample most likely to the reduced statistical power. However, given the highly similar patterns in both the overall and the WM-matched samples, we propose that the hypo-activation of the PI network in the older adults may not be attributable to age-related differences in overall WM performance, hence suggesting that higher PI susceptibility in older adult age does not directly depend on their lower WM performance.

A large spectrum of possible diagnoses must be taken into consideration when a contrast-enhancing lesion of the pontomedullary region is found on MRI. Among these diagnoses are neoplastic, inflammatory, and infectious, as well as vascular pathologies. The authors report a rare case of an intracranial dural arteriovenous fistula (DAVF) with perimedullary spinal venous drainage (Cognard Type V) that initially presented as a unilateral contrast-enhancing pontomedullary lesion mimicking a brainstem neoplasm in a 76-year-old man. Following occlusion of the DAVF by transarterial embolization that resulted in clinical and radiological improvement, the fistula recurred 10 months later and was finally cured by a combined endovascularand surgical approach that resulted in complete occlusion. Clinical symptoms and MRI findings gradually improved following this treatment. A literature review on the MRI findings of Cognard Type V DAVF was performed. Centrally located medullary or pontomedullary edema represents the typical imaging finding, while unilateral edema as seen in the authors’ patient is exceptionally rare. The hallmark imaging finding suggestive of DAVF consisting of perimedullary engorged vessels may not always be present or may only be very subtly visible. Therefore, the authors suggest performing contrast-enhanced MR angiography or even digital subtraction angiography in the presence of an unclear edematous brainstem lesion before scheduling stereotactic biopsy.

Several major association fiber tracts are known to be part of the language processing system. There is evidence that high angular diffusion-based MRI is able to separate these fascicles in a constant way. In this study, we wanted to proof this thesis using a novel whole brain “global tracking” approach and to test for possible lateralization. Global tracking was performed in six healthy right-handed volunteers for the arcuate fascicle (AF), the medial longitudinal fascicle (MdLF), the inferior fronto-occipital fascicle (IFOF), and the inferior longitudinal fascicle (ILF). These fiber tracts were characterized quantitatively using the number of streamlines (SL) and the mean fractional anisotropy (FA). We were able to characterize the AF, the MdLF, the IFOF, and the ILF consistently in six healthy volunteers using global tracking. A left-sided dominance (LI > 0.2) for the AF was found in all participants. The MdLF showed a left-sided dominance in four participants (one female, three male). Regarding the FA, no lateralization (LI > 0.2) could be shown in any of the fascicles. Using a novel global tracking algorithm we confirmed that the courses of the primary language processing associated fascicles can consistently be differentiated. Additionally we were able to show a streamline-based left-sided lateralization in the AF of all right-handed healthy subjects.

The ability to recognize and respond to actions performed by others is fundamental for a wide range of activities involving social interactions. However, despite an enormous number of functional imaging studies, a precise delineation of the brain regions crucial for distinct aspects of action recognition has remained elusive. Moreover, the degree of overlap between regions involved in active action performance is controversial. To elucidate these issues, 98 acute stroke patients (68 male, age mean ± SD, 65 ± 13 years) were examined in the acute period after stroke (mean ± SD 4.4 ± 2 days after symptom onset). First, action recognition was assessed with a newly designed test which required patients to distinguish between correctly and incorrectly performed tool-associated actions depicted in short videos. Errors categories comprised conceptual (e.g., spreading jam on toast with a paint brush), and spatio-temporal errors (orientation of the tool, hand configuration, and movement kinematics). Second, actual use of tools was probed using an established test which, in analogy to the error categories for action recognition, included separate measures for the ability to match tools and recipients (e.g., hammer – nail; conceptual score), and for the quality of the executed action (e.g., hammering; spatio-temporal score). Lesions were delineated on diffusion-weighted scans for voxel-based lesion-symptom mapping. Impaired recognition of conceptual errors was associated mainly with lesions to the anterior middle temporal gyrus as well as to the caudal middle frontal gyrus. Conversely, the detection of spatio-temporal errors depended on the posterior superior temporal gyrus and sulcus, inferior parietal lobule (IPL) and ventral premotor cortex (vPMC). Analyses for distinct spatio-temporal error subcategories revealed that superior temporal lesions specifically affected the recognition of kinematic and tool orientation errors, while inferior parietal and premotor damage selectively impaired the discrimination of hand configurations. Lastly, compared to the recognition of conceptual and spatio-temporal errors, both active tool-recipient matching and action execution, respectively, were more dependent on the IPL and vPMC; conversely, action recognition deficits were more strongly associated with occipito-temporal and superior temporal lesions. The results demonstrate that action recognition is enabled by a network of dissociable regions that are specialized for the processing of distinct action features. While the decoding of conceptual action aspects relies mainly on anterior temporal regions, IPL and vPMC mediate the recognition of hand configurations, and the posterior superior temporal lobe is crucial for the processing of movement kinematics and tool orientation. Our findings show that, with the exception of the hand configuration, action recognition does not rely on the fronto-parietal regions that subserve the performance of actual tool use.

Inhibition is not a unitary construct, as different inhibition-related functions have been disentangled. The present single-case study compares performance of a patient with bilateral lesions in the inferior frontal gyrus (IFG) and anterior insula to healthy age-matched controls in different inhibition-related tasks. Particular focus was on the resolution of proactive interference that is supposed to rely on bilateral IFG and anterior insula. Two working memory tasks previously proven sensitive to deficits in proactive interference (recent-probes, n-back) and two tasks measuring behavioral inhibition (verb generation task, Stroop task) were administered. Against expectations, the patient did not show any deficits in measures of proactive interference. However, compared to controls, she demonstrated considerably reduced performance in both measures of behavioral inhibition, thus resulting in a classical dissociation between proactive interference and behavioral inhibition. Although performance improved during the chronic phase post stroke, the overall pattern of a classical dissociation between proactive interference and behavioral inhibition remained stable across time. Taken together, the present data support the role of the IFG in inhibition-related functions, but a direct relationship between lesions in the IFG and difficulties in resolution of proactive interference could not be corroborated.

Purpose To compare the vessel size and the cerebral blood volume in human gliomas with histopathology. Vessel size imaging (VSI) is a dynamic susceptibility contrast method for the assessment of the vessel size in normal and pathological tissue. Previous publications in rodents showed a satisfactory conformity with the vessel size derived from histopathology. To assess the clinical value, further, the progression-free interval was determined and correlated. Materials and Methods Twenty-five gliomas (WHO grade °II [n = 10], °III [n = 3], °IV [n = 12]) were prospectively included and received a stereotaxic biopsy after VSI. The vessel size and the cerebral blood volume (CBV) were calculated in regions of interest at the tumor edge and correlated with the vessel size measured by histopathology. Results Both VSI and CBV showed a good correlation with the vessel size in histopathology (up to r = 0.84, P < 0.001, and r = 0.62, P < 0.001, respectively). Slope and offset of the linear regression (y = 0.77x + 0.36 μm) suggest that the size of normal capillaries is overestimated with VSI, while for grossly enlarged vessels an underestimation occurs. Both VSI and CBV were negatively correlated with the progression-free interval (r = –0.57, P = 0.008, and r = –0.50, P = 0.025, respectively). Conclusion The correlation between VSI and vessel size from histopathology is in good accordance with the animal studies. The overestimation of small capillary sizes is also known from the animal trials. Vessel size and CBV showed similar results, both for the correlation with the histopathological vessel size and the progression-free interval. J. Magn. Reson. Imaging 2015;42:1117–1125.

The evolving and highly heterogeneous nature of malignant brain tumors underlies their limited response to therapy and poor prognosis. In addition to genetic alterations, highly dynamic processes, such as transcriptional and metabolic reprogramming, play an important role in the development of tumor heterogeneity. The current study reports an adaptive mechanism in which the metabolic environment of malignant glioma drives transcriptional reprogramming. Multiregional analysis of a glioblastoma patient biopsy revealed a metabolic landscape marked by varying stages of hypoxia and creatine enrichment. Creatine treatment and metabolism was further shown to promote a synergistic effect through upregulation of the glycine cleavage system and chemical regulation of prolyl-hydroxylase domain. Consequently, creatine maintained a reduction of reactive oxygen species and change of the α-ketoglutarate/succinate ratio, leading to an inhibition of HIF signaling in primary tumor cell lines. These effects shifted the transcriptional pattern toward a proneural subtype and reduced the rate of cell migration and invasion in vitro. Implications: Transcriptional subclasses of glioblastoma multiforme are heterogeneously distributed within the same tumor. This study uncovered a regulatory function of the tumor microenvironment by metabolism-driven transcriptional reprogramming in infiltrating glioma cells. Mol Cancer Res; 16(4); 655–68. ©2018 AACR.

Objective The stereotactic suboccipital-transcerebellar approach is widely regarded as technically demanding requiring substantial modifications of the standard stereotactic methods thus often making a transfrontal approach preferable. In this comprehensive series we aim to present our experience with the stereotactic suboccipital-transcerebellar approach to lesions of the brainstem or cerebellum using two standard stereotactic systems. Patients and Methods In the period of 2000–2015 overall 80 patients (mean age 43.95 ± 23.76 years) with lesions of the brainstem or cerebellum underwent stereotactic surgery for diagnostic or therapeutic purposes via a suboccipital approach. In 59 patients stereotactic surgery was performed using the Riechert-Mundinger Stereotactic Frame, the Leksell Stereotactic Frame was used in 21 patients. For both frames standard systems were used without modification. Retrospective analysis of intraoperative stereotactic technique, achievement of the predefined surgical objectives and perioperative complications was carried out. Results In this series, the stereotactic suboccipital-transcerebellar approach proved to be feasible with two standard stereotactic systems. Using either frame the predefined surgical objective was achieved in 90.0%. A verified neuropathological diagnosis was obtained in 89.6%. Minor transient perioperative complications occurred in 8.75%. There was no surgery-related permanent morbidity or mortality. Conclusion In this comprehensive series the stereotactic suboccipital-transcerebellar approach using a standard stereotactic system proved to be a favorable stereotactic approach with a high diagnostic success rate and no surgery-related permanent morbidity.

Molybdenum cofactor deficiency is an autosomal recessive inborn error of metabolism, which results from mutations in genes involved in Moco biosynthesis. Moco serves as a cofactor of several enzymes, including sulfite oxidase. MoCD is clinically characterized by intractable seizures and severe, rapidly progressing neurodegeneration leading to death in early childhood in the majority of known cases. Here we report a patient with an unusual late disease onset and mild phenotype, characterized by a lack of seizures, normal early development, a decline triggered by febrile illness and a subsequent dystonic movement disorder. Genetic analysis revealed a homozygous c.1338delG MOCS1 mutation causing a frameshift (p.S442fs) with a premature termination of the MOCS1AB translation product at position 477 lacking the entire MOCS1B domain. Surprisingly, urine analysis detected trace amounts (1% of control) of the Moco degradation product urothione, suggesting a residual Moco synthesis in the patient, which was consistent with the mild clinical presentation. Therefore, we performed bioinformatic analysis of the patient’s mutated MOCS1 transcript and found a potential Kozak-sequence downstream of the mutation site providing the possibility of an independent expression of a MOCS1B protein. Following the expression of the patient’s MOCS1 cDNA in HEK293 cells we detected two proteins: a truncated MOCS1AB protein and a 22.4 kDa protein representing MOCS1B. Functional studies of both proteins confirmed activity of MOCS1B, but not of the truncated MOCS1AB. This finding demonstrates an unusual mechanism of translation re-initiation in the MOCS1 transcript, which results in trace amounts of functional MOCS1B protein being sufficient to partially protect the patient from the most severe symptoms of MoCD.

Background: Schizophreniform syndromes can be divided into primary forms from polygenic causes or secondary forms due to immunological, epileptiform, monogenic, or degenerative causes. Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a secondary immunological form associated with increased thyroid antibodies, such as anti-thyroid peroxidase antibodies, and shows a good response to corticosteroids. Case presentation: We present the case of a 41-year-old woman suffering from a schizophreniform syndrome. Starting at the age of 35, she developed psychotic exacerbations with formal thought disorder, acoustic hallucinations, cenesthopathic experiences, and loss of ego boundaries. At the same time, she began to suffer from chronic sexual delusions and olfactory hallucinations, which did not respond to neuroleptic medication. Her levels of anti-thyroid peroxidase antibodies were slightly increased, and the blood–brain barrier was disturbed. An electroencephalogram (EEG) showed intermittent generalized slowing, and cerebral magnetic resonance imaging (cMRI) depicted mild temporolateral atrophy. High-dose corticosteroid treatment led to convincing improvement of attentional performance and the disappearance of delusions and olfactory hallucinations. Conclusion: SREAT can mimic typical symptoms of schizophreniform syndromes. The increased titer of anti-thyroid peroxidase antibodies in combination with the EEG slowing, blood–brain barrier dysfunction, and the cMRI alterations were the basis for suspecting an immunological cause in our patient. Chronic delusions, olfactory hallucinations, and cognitive deficits were successfully treated with corticosteroids. The occurrence of secondary immunological forms of schizophreniform syndromes demonstrates the need for innovative immunosuppressive treatment options.

ObjectiveTo report 3 patients with multiple sclerosis showing severe activation of disease during immunotherapy with alemtuzumab.MethodsRetrospective case series.ResultsPatient 1, a 21-year-old woman, developed severe cognitive impairment, sight deterioration, severe gait ataxia, urinary retention, and extensive progression of cerebral lesion load, including new lesions that exhibited gadolinium ring enhancement and dominance of CD19/20-positive B lymphocytes, 6 months after induction of alemtuzumab. Patient 2, a 28-year-old man, developed left-sided hemihypesthesia and ∼60 new cerebral and spinal lesions including lesions with gadolinium ring enhancement 6 months after induction of alemtuzumab. Patient 3, a 37-year-old woman, developed ataxia and numbness of the left thigh, 16 new gadolinium-positive supratentorial lesions, and partly ring-enhancing and dominance of CD19/20-positive B lymphocytes 6 months after induction of alemtuzumab.ConclusionThis is a case series reporting severe activation of disease during immunotherapy with alemtuzumab. All patients showed onset of symptoms 6 months after induction of alemtuzumab, strikingly similar MRI lesion morphology, and unexpected high total B cell count, which may suggest a B-cell-mediated activation of disease. Whether this is due to different rates of B- and T cell repopulation has to be the subject of further research. Moreover, further effects on the interactions between the adaptive and innate immunity as well as between B and T cell lineages might explain the observed disease activation.

Apraxia is a cognitive disorder of skilled movements that characteristically affects the ability to imitate meaningless gestures, or to pantomime the use of tools. Despite substantial research, the neural underpinnings of imitation and pantomime have remained debated. An influential model states that higher motor functions are supported by different processing streams. A dorso-dorsal stream may mediate movements based on physical object properties, like reaching or grasping, whereas skilled tool use or pantomime rely on action representations stored within a ventro-dorsal stream. However, given variable results of past studies, the role of the two streams for imitation of meaningless gestures has remained uncertain, and the importance of the ventro-dorsal stream for pantomime of tool use has been questioned. To clarify the involvement of ventral and dorsal streams in imitation and pantomime, we performed voxel-based lesion-symptom mapping in a sample of 96 consecutive left-hemisphere stroke patients (mean age ± SD, 63.4 ± 14.8 years, 56 male). Patients were examined in the acute phase after ischaemic stroke (after a mean of 5.3, maximum 10 days) to avoid interference of brain reorganization with a reliable lesion-symptom mapping as best as possible. Patients were asked to imitate 20 meaningless hand and finger postures, and to pantomime the use of 14 common tools depicted as line drawings. Following the distinction between movement engrams and action semantics, pantomime errors were characterized as either movement or content errors, respectively. Whereas movement errors referred to incorrect spatio-temporal features of overall recognizable movements, content errors reflected an inability to associate tools with their prototypical actions. Both imitation and pantomime deficits were associated with lesions within the lateral occipitotemporal cortex, posterior inferior parietal lobule, posterior intraparietal sulcus and superior parietal lobule. However, the areas specifically related to the dorso-dorsal stream, i.e. posterior intraparietal sulcus and superior parietal lobule, were more strongly associated with imitation. Conversely, in contrast to imitation, pantomime deficits were associated with ventro-dorsal regions such as the supramarginal gyrus, as well as brain structures counted to the ventral stream, such as the extreme capsule. Ventral stream involvement was especially clear for content errors which were related to anterior temporal damage. However, movement errors were not consistently associated with a specific lesion location. In summary, our results indicate that imitation mainly relies on the dorso-dorsal stream for visuo-motor conversion and on-line movement control. Conversely, pantomime additionally requires ventro-dorsal and ventral streams for access to stored action engrams and retrieval of tool-action relationships.

Microelectrocorticography (µECoG) provides insights into the cortical organization with high temporal and spatial resolution desirable for better understanding of neural information processing. Here we evaluated the use of µECoG for detailed cortical recording of somatosensory evoked potentials (SEPs) in an ovine model. The approach to the cortex was planned using an MRI-based 3D model of the sheep's brain. We describe a minimally extended surgical procedure allowing placement of two different µECoG grids on the somatosensory cortex. With this small craniotomy, the frontal sinus was kept intact, thus keeping the surgical site sterile and making this approach suitable for chronic implantations. We evaluated the procedure for chronic implantation of an encapsulated µECoG recording system. During acute and chronic recordings, significant SEP responses in the triangle between the ansate, diagonal, and coronal sulcus were identified in all animals. Stimulation of the nose, upper lip, lower lip, and chin caused a somatotopic lateral-to-medial, ipsilateral response pattern. With repetitive recordings of SEPs, this somatotopic pattern was reliably recorded for up to 16 weeks. The findings of this study confirm the previously postulated ipsilateral, somatotopic organization of the sheep's sensory cortex. High gamma band activity was spatially most specific in the comparison of different frequency components of the somatosensory evoked response. This study provides a basis for further acute and chronic investigations of the sheep's sensory cortex by characterizing its exact position, its functional properties, and the surgical approach with respect to macroanatomical landmarks.

We present a patient with chronic postmenopausal estrogen intake with presence of Kayser-Fleischer ring in the cornea and Alzheimer's disease and discuss the pathophysiological mechanisms of estrogen intake and copper accumulation in various tissues, including the central nervous system. Sonography was compatible with copper accumulation in the basal ganglia, but the patient showed no clinical signs of Wilson's disease. Magnetic resonance imaging and positron emission tomography revealed a typical pattern for Alzheimer's disease. We propose increased copper levels as a direct effect of estrogen intake due to an augmented ATP7A-mRNA in the intestine. Moreover, we discuss the impact of elevated free serum copper on accompanying Alzheimer's disease, knowing that copper plays a crucial role in the formation of amyloid plaques and tau aggregation. This might offer a partial explanation for the observation that postmenopausal estrogen therapy is associated with a higher risk of mild cognitive impairment and Alzheimer's disease.

Background In contrast to the abundance of seizure outcome reports in epilepsy surgery for glioneuronal tumors in childhood and adolescence, there is a dearth of information regarding cognitive outcomes. Objective To investigate the seizure and cognitive outcome of children and adolescents that underwent resective surgery for glioneuronal tumor-associated refractory epilepsy and determine their predictive factors. Methods We retrospectively analyzed the presurgical findings, resection types, and outcomes over 1.3 to 12.3 years (mean, 7.3) of 29 consecutive patients, who underwent resection in 2000 to 2011. The mean age at epilepsy onset was 7.9 years (range, 0-15.4), the mean age at surgery was 11.7 years (range, 2.6-17.3), and the mean epilepsy duration to surgery was 3.8 years (range, 0.3-15.3). Etiology comprised 13 dysembryoplastic neuroepithelial tumors and 16 gangliogliomas, with additional focal cortical dysplasia in 5 cases. Results Eighty-six percent of children were seizure free 12 months after surgery; at final follow-up, 76% remained seizure free and 62% had discontinued antiepileptic drugs. Gross total resection was related to significantly higher rates of seizure freedom. Higher presurgical cognitive functioning (full-scale IQ, verbal IQ) was related to shorter epilepsy duration to surgery independent of age at epilepsy onset, thus determining postsurgical functioning. Improvements in verbal IQ, performance IQ, and visual memory as well as a trend toward improvement in full-scale IQ were established after surgery. Despite individual losses in full-scale IQ, verbal or visual memory, no deterioration was noted in any cognitive variable on a group level. Conclusion Completeness of resection predisposes to favorable outcomes regarding seizure alleviation. Whereas cognitive functioning deteriorates with time in glioneuronal tumor-related refractory epilepsy, surgery is linked to improvement rather than to deterioration on a group level.

Visual neglect results from dysfunction within the spatial attention network. The structural connectivity in undamaged brain tissue in neglect has barely been investigated until now. In the present study, we explored the microstructural white matter characteristics of the contralesional hemisphere in relation to neglect severity and recovery in acute stroke patients. We compared age-matched healthy subjects and three groups of acute stroke patients (9 ± 0.5 days after stroke): (i) patients with nonrecovered neglect (n = 12); (ii) patients with rapid recovery from initial neglect (within the first week post-stroke, n = 7), (iii) stroke patients without neglect (n = 17). We analyzed the differences between groups in grey and white matter density and fractional anisotropy (FA) and used fiber tracking to identify the affected fibers. Patients with nonrecovered neglect differed from those with rapid recovery by FA-reduction in the left inferior parietal lobe. Fibers passing through this region connect the left-hemispheric analogues of the ventral attention system. Compared with healthy subjects, neglect patients with persisting neglect had FA-reduction in the left superior parietal lobe, optic radiation, and left corpus callosum/cingulum. Fibers passing through these regions connect centers of the left dorsal attention system. FA-reduction in the identified regions correlated with neglect severity. The study shows for the first time white matter changes within the spatial attention system remote from the lesion and correlating with the extent and persistence of neglect. The data support the concept of neglect as disintegration within the whole attention system and illustrate the dynamics of structural-functional correlates in acute stroke. Hum Brain Mapp 35:4678–4692, 2014. © 2014 Wiley Periodicals, Inc.

Purpose We recently presented a method for the quantitative measurement of the arterial input function which allows for determination of absolute cerebral blood flow (CBF) values without adjustable parameters. The aim of the present work is to estimate absolute CBF values by using this new technique and to compare it with the gold standard for cerebral perfusion, positron emission tomography. Methods Pigs (13) were comparatively investigated by each method performing multiple measurement runs. The reproducibility of both methods was assessed by a voxel-wise correlation of repeated measurements. An intersubject evaluation was performed on median whole-brain CBF estimates. Results The mean CBF (MRI) was for gray matter, the mean CBF (positron emission tomography) was for gray and white matter. The reproducibility for MRI correlated with r = 0.85 and , for positron emission tomography with r = 0.76 and . The correlation for the median whole-brain CBF in MRI and positron emission tomography was r = 0.60 and P = 0.04. Conclusions The proposed method allows for determination of quantitative CBF without normalization factors. The relatively low estimates of absolute CBF most likely results from the higher age of the pigs as compared to other studies. The intermediate correlation between both methods is caused by physiological intraindividual fluctuations of the CBF and by a limited reproducibility of both methods. Magn Reson Med 72:1723–1734, 2014. © 2013 Wiley Periodicals, Inc.

Language deficits are regularly found in cortical neurodegenerative diseases. The progression of language deficits shows a considerable inter-individual variability even within one diagnostic group. We aimed at detecting patterns of altered diffusion as well as atrophy of cerebral gray and white matter which underlie ongoing language-related deterioration in patients with cortical neurodegenerative diseases. Diffusion tensor imaging and T1-weighted MRI data of 26 patients with clinically diagnosed neurodegenerative disorders were acquired at baseline and 14 months later in this prospective study. Language functions were assessed with a confrontation naming test and the Token Test. Diffusion and voxel-based morphometric measures were calculated and correlates of language performance were evaluated. Across all patients, the naming impairment was related to diffusion (false discovery rate-corrected P

BACKGROUND AND PURPOSE: Fiber tractography is increasingly used in the preoperative evaluation of endangered fiber bundles. From a clinical point of view, an accurate and methodologically transparent procedure is desired. Our aim was to evaluate the recently described global tracking algorithm compared with other established methods, such as deterministic and probabilistic tractography. MATERIALS AND METHODS: Twenty patients, candidates for excision of epileptogenic lesions, were subjected to higher-angular resolution diffusion imaging–based fiber tractography. Seed points were created without manual bias, predominantly by FreeSurfer and voxel-based atlases. We focused on 2 important fiber bundles, namely the descending motor pathways and the optic radiation. Postoperatively, the accuracy of the predicted fiber route was controlled by structural MR imaging and by inflicted functional deficits. RESULTS: Among the 3 evaluated methods, global tracking was the only method capable of reconstructing the full extent of the descending motor pathways, including corticobulbar fibers from the area of face representation. Still, probabilistic tractography depicted the optic radiation better, especially the Meyer loop. The deterministic algorithm performed less adequately. CONCLUSIONS: The probabilistic method seems to be the best balance between computational time and effectiveness and seems to be the best choice in most cases, particularly for the optic radiation. If, however, a detailed depiction of the fiber anatomy is intended and tract crossings are implicated, then the computationally time-consuming global tracking should be preferred.