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Abstract Objective Guyon’s canal syndrome is caused by compression of the ulnar nerve at the wrist, occasionally requiring decompression surgery. In recent times, minimally invasive approaches have gained popularity. The aim of this study was to assess the efficacy and safety of ultrasound-guided thread release for transecting the palmar ligament in Guyon’s canal without harming surrounding structures, in a cadaveric specimen model. Methods After ethical approval, thirteen ultrasound-guided thread releases of Guyon’s canal were performed on the wrists of softly embalmed anatomic specimens. Cadavers showing injuries or prior operations at the hand were excluded. Subsequently, the specimens were dissected, and the outcome of the interventions and potential damage to adjacent anatomical structures as well as ultrasound visibility were evaluated with a score from one to three. Results Out of 13 interventions, a complete transection was achieved in ten cases (76.9%), and a partial transection was documented in three cases (23.1%). Irrelevant lesions on the flexor tendons were observed in two cases (15.4%), and an arterial branch was damaged in one (7.7%). Ultrasound visibility varied among specimens, but essential structures were delineated in all cases. Conclusion Ultrasound-guided thread release of Guyon’s canal has shown promising first results in anatomic specimens. However, further studies are required to ensure the safety of the procedure. Relevance statement Our study showed that minimally invasive ultrasound-guided thread release of Guyon’s canal is a feasible approach in the anatomical model. The results may provide a basis for further research and refinement of this technique. Key points • In Guyon’s canal syndrome, the ulnar nerve is compressed at the wrist, often requiring surgical release. • We adapted and tested a minimally invasive ultrasound-guided thread release technique in anatomic specimens. • The technique was effective; however, in one specimen, a small anatomic branch was damaged. Graphical Abstract

Background/Objectives: Digital subtraction angiography (DSA) is the gold standard in the diagnosis of cerebral vasospasm, frequently observed after subarachnoid hemorrhage (SAH). However, less-invasive methods, such as computed tomography angiography (CTA), may be equally accurate. To further clarify comparability, this study evaluated the reliability of CTA in detecting cerebral vasospasm. Methods: This retrospective study included 51 patients with SAH who underwent both CTA and DSA within 24 h. The smallest diameter of the proximal cerebral arterial segments was measured in both modalities at admission and during the vasospasm period. The mean difference in diameter, the intraclass correlation coefficient (ICC) of CTA and DSA, the difference in grade of vasospasm and sensitivity, the specificity and the positive predictive value (PPV) for CTA were calculated. Results: A total of 872 arterial segments were investigated. At time of admission, arterial diameters were significantly smaller on CTA compared to DSA in all segments (−0.26 ± 0.12 mm; p < 0.05). At time of suspected vasospasm (day 9 ± 5), these differences remained significant only for the M1 segment (−0.18 ± 0.37 mm, p = 0.02), the P1 segment (−0.13 ± 0.24 mm, p = 0.04) and the basilar artery (−0.20 ± 0.37 mm, p = 0.0.04). The ICC between CTA and DSA was good (0.5–0.8). The sensitivity of CTA for predicting angiographic vasospasm was 99%, the specificity was 50% and the PPV was 92%. Conclusions: Arterial diameters measured on CTA may underestimate the arterial caliber observed in DSA; however, these absolute differences were minor. Importantly, vessel diameter alone does not fully reflect malperfusion, requiring additional imaging techniques such as CT perfusion.

Abstract Studies in comparative neuroanatomy and of the fossil record demonstrate the influence of socio-ecological niches on the morphology of the cerebral cortex, but have led to oftentimes conflicting theories about its evolution. Here, we study the relationship between the shape of the cerebral cortex and the topography of its function. We establish a joint geometric representation of the cerebral cortices of ninety species of extant Euarchontoglires, including commonly used experimental model organisms. We show that variability in surface geometry relates to species’ ecology and behaviour, independent of overall brain size. Notably, ancestral shape reconstruction of the cortical surface and its change during evolution enables us to trace the evolutionary history of localised cortical expansions, modal segregation of brain function, and their association to behaviour and cognition. We find that individual cortical regions follow different sequences of area increase during evolutionary adaptations to dynamic socio-ecological niches. Anatomical correlates of this sequence of events are still observable in extant species, and relate to their current behaviour and ecology. We decompose the deep evolutionary history of the shape of the human cortical surface into spatially and temporally conscribed components with highly interpretable functional associations, highlighting the importance of considering the evolutionary history of cortical regions when studying their anatomy and function.

Key points Standardised fetal MRI delivers reproducible quantitative whole lung radiomics features. 2D lung ROI radiomics features are not representative of the whole fetal lung. Whole lung radiomics features are better reproducible than 2D ROI features. Whole lung radiomics features are more sensitive to subtle differences between normal and pathological fetal lung development compared to 2D lung ROI features. Fetal MRI whole lung radiomics may improve non-invasive in-vivo lung development assessment.

The analysis of fetal MRI data and follow-up language assessments reveal that temporal sulcus depth asymmetry is a potential biomarker for maturity and integrity of neural correlates of language.

The ability to plan is an important part of the set of the cognitive skills called “executive functions.” To be able to plan actions in advance is of great importance in everyday life and constitutes one of the major key features for academic as well as economic success. The present study aimed to investigate the neuroanatomical correlates of planning in normally developing children, as measured by the cortical thickness of the prefrontal cortex. Eighteen healthy children and adolescents underwent structural MRI examinations and the Tower of London (ToL) task. A multiple regression analysis revealed that the cortical thickness of the right caudal middle frontal gyrus (cMFG) was a significant predictor of planning performance. Neither the cortical thickness of any other prefrontal area nor gender were significantly associated with performance in the ToL task. The results of the present exploratory study suggest that the cortical thickness of the right, but not the left cMFG, is positively correlated with performance in the ToL task. We, therefore, conclude that increased cortical thickness may be more beneficial for higher-order processes, such as information integration, than for lower-order processes, such as the analysis of external information.

Abstract The methionine (M)—valine (V) polymorphic codon 129 of the prion protein gene (PRNP) plays a central role in both susceptibility and phenotypic expression of sporadic Creutzfeldt-Jakob diseases (sCJD). Experimental transmissions of sCJD in humanized transgenic mice led to the isolation of five prion strains, named M1, M2C, M2T, V2, and V1, based on two major conformations of the pathological prion protein (PrPSc, type 1 and type 2), and the codon 129 genotype determining susceptibility and propagation efficiency. While the most frequent sCJD strains have been described in codon 129 homozygosis (MM1, MM2C, VV2) and heterozygosis (MV1, MV2K, and MV2C), the V1 strain has only been found in patients carrying VV. We identified six sCJD cases, 4 in Catalonia and 2 in Italy, carrying MV at PRNP codon 129 in combination with PrPSc type 1 and a new clinical and neuropathological profile reminiscent of the VV1 sCJD subtype rather than typical MM1/MV1. All patients had a relatively long duration (mean of 20.5 vs. 3.5 months of MM1/MV1 patients) and lacked electroencephalographic periodic sharp-wave complexes at diagnosis. Distinctive histopathological features included the spongiform change with vacuoles of larger size than those seen in sCJD MM1/MV1, the lesion profile with prominent cortical and striatal involvement, and the pattern of PrPSc deposition characterized by a dissociation between florid spongiform change and mild synaptic deposits associated with coarse, patch-like deposits in the cerebellar molecular layer. Western blot analysis of brain homogenates revealed a PrPSc type 1 profile with physicochemical properties reminiscent of the type 1 protein linked to the VV1 sCJD subtype. In summary, we have identified a new subtype of sCJD with distinctive clinicopathological features significantly overlapping with those of the VV1 subtype, possibly representing the missing evidence of V1 sCJD strain propagation in the 129MV host genotype.

Primary cytomegalovirus (CMV) infection during pregnancy is associated with an increased risk of congenital CMV (cCMV). Hyperimmune globulin (HIG) therapy has been proposed as a potential prophylaxis to reduce maternal–fetal transmission. Data on whether the administration of HIG every 2 weeks offers benefits over HIG administration every 4 weeks are lacking. This was a retrospective analysis including pregnant women with primary CMV infection diagnosed in the first or early second trimester between 2010 and 2022 treated with HIG every 4 weeks (300 IE HIG per kg) or every 2 weeks (200 IE HIG per kg), respectively. In total, 36 women (4 weeks: n = 26; 2 weeks: n = 10) and 39 newborns (4 weeks: n = 29; 2 weeks: n = 10) were included. The median gestational age at the first HIG administration was 13.1 weeks. There was no significant difference in the cCMV rates between the women who received HIG every 4 versus every 2 weeks (n = 8/24 [33.3%] vs. 3/10 [30.0%]; p = 0.850). An abnormal fetal ultrasound was present in three fetuses and fetal magnetic resonance imaging (MRI) anomalies in four fetuses were related to cCMV infection, with no significant difference in the frequency between the two groups. A larger study will be needed to determine whether HIG administration every 2 instead of every 4 weeks improves the maternal–fetal transmission rates.

Developmental gene expression data from medulloblastoma (MB) suggest that WNT-MB originates from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH MB arise from cerebellar precursor matrix regions. This study aimed to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group. A review of the institutional database identified 58 out of 72 pediatric patients who were operated for an MB at our department between 1996 and 2020 that had a detailed operative report and a surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings. Using the intraoperatively defined STO, “correct” prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08–0.48) for WNT-MB, 0.86 (95% CI 0.49–0.97) for SHH-MB and 0.73 (95% CI 0.57–0.85) for non-WNT/non-SHH MB. The present study demonstrated a limited predictive value of the intraoperatively observed STO for the prediction of the molecular group of MB.

Abstract Objective White matter lesions (WML) in multiple sclerosis (MS) differ from vascular WML caused by Fabry disease (FD). However, in atypical cases the discrimination can be difficult and may vary between individual raters. The aim of this study was to evaluate interrater reliability of WML differentiation between MS and FD patients. Materials and methods Brain MRI scans of 21 patients with genetically confirmed FD were compared to 21 matched patients with MS. Pseudonymized axial FLAIR sequences were assessed by 6 blinded raters and attributed to either the MS or the FD group to investigate interrater reliability. Additionally, localization of WML was compared between the two groups. Results The median age of patients was 46 years (IQR 35–58). Interrater reliability was moderate with a Fleiss' Kappa of 0.45 (95%CI 0.3–0.59). Overall, 85% of all ratings in the MS group and 75% in the FD group were correct. However, only 38% of patients with MS and 33% of patients with FD were correctly identified by all 6 raters. WML involving the corpus callosum (p

The 22q11.2 deletion syndrome (22q11.2 DS) is known as the most common microdeletion syndrome. Due to its variable clinical phenotype, prenatal diagnosis can be challenging. The aim of this retrospective study was to evaluate the clinical course and pregnancy outcome of cases with prenatally diagnosed 22q11.2 deletion syndrome (DS) as well as to evaluate the role of prenatal magnetic resonance imaging (MRI) and postmortem examination. In total, 21 cases who underwent prenatal ultrasound examination and pregnancy care at the Department of Obstetrics and Gynecology at the Medical University of Vienna between 2012 and 2022 were included. The majority of the cases were genetically diagnosed using fluorescent in situ hybridization (FISH). The median gestational age (GA) at genetic diagnosis was 23.0 weeks (IQR 21.4–24.8 weeks). CHDs were detected in all fetuses and the most common extracardiac manifestation was thymus hypo/aplasia followed by genitourinary anomalies. Prenatal magnetic resonance imaging (MRI) revealed additional diagnostic information in three of ten cases. Overall, 14 patients opted for drug-induced TOP, of which 9 cases had a feticide prior to the induction of labor. The majority of craniofacial malformations were only detected by autopsy. In conclusion, the majority of cases prenatally diagnosed with 22q11.2 DS had an absent or hypoplastic thymus noted antenatally in addition to the detected CHD, and almost half of the cases had another extracardiac malformation of predominantly genitourinary origin. Furthermore, prenatal MRIs confirmed previously detected malformations, but only provided additional diagnostic information in three out of ten cases, whereas postmortem examination diagnosed most of the craniofacial anomalies and should always be conducted, serving as an important quality indicator for prenatal imaging.

Motion correction is an essential preprocessing step in functional Magnetic Resonance Imaging (fMRI) of the fetal brain with the aim to remove artifacts caused by fetal movement and maternal breathing and consequently to suppress erroneous signal correlations. Current motion correction approaches for fetal fMRI choose a single 3D volume from a specific acquisition timepoint with least motion artefacts as reference volume, and perform interpolation for the reconstruction of the motion corrected time series. The results can suffer, if no low-motion frame is available, and if reconstruction does not exploit any assumptions about the continuity of the fMRI signal. Here, we propose a novel framework, which estimates a high-resolution reference volume by using outlier-robust motion correction, and by utilizing Huber L2 regularization for intra-stack volumetric reconstruction of the motion-corrected fetal brain fMRI. We performed an extensive parameter study to investigate the effectiveness of motion estimation and present in this work benchmark metrics to quantify the effect of motion correction and regularised volumetric reconstruction approaches on functional connectivity computations. We demonstrate the proposed framework’s ability to improve functional connectivity estimates, reproducibility and signal interpretability, which is clinically highly desirable for the establishment of prognostic noninvasive imaging biomarkers. The motion correction and volumetric reconstruction framework is made available as an open-source package of NiftyMIC.

ObjectiveCardiac and extra-cardiac anomalies in 46 pre-natally diagnosed cases of heterotaxy were compared to post-natal anatomical patterns in order to reveal discordant findings. Second, the outcome of these fetuses was evaluated.MethodsFetuses with heterotaxy, diagnosed in a tertiary referral centre, were analysed retrospectively. Based on the foetal abdominal situs view, right atrial isomerism (RAI) and left atrial isomerism (LAI) were defined as foetal sub-types. Post-natally, discordant anatomical patterns for broncho-pulmonary branching, atrial appendage morphology, and splenic status were further clarified with CT scans. In summary, the spectrum of pre-natally and post-natally detected cardiac and extra-cardiac anomalies is systematically reviewed. Necessary surgical interventions and mid-long-term outcomes were compared between the two sub-types in surviving infants.ResultsA total of 46 fetuses with heterotaxy were included; LAI was diagnosed in 29 (63%) fetuses and RAI was diagnosed in 17 (37%) fetuses. Extra-cardiac anomalies were noted in 35% of fetuses. Seven out of the 29 fetuses (24%) with LAI had atrio-ventricular block (AVB) and four of these cases presented with hydrops. Twenty nine out of the 46 participating fetuses (63%) were live births, with 62% in the LAI group and 65% in the RAI group. Five fetuses were lost to follow-up. At the age of 1 year, the overall survival of live births [estimate (95% CI)] was 67% (48; 92%) in patients with LAI and 55% (32; 94%) in patients with RAI. At the age of 5 years, the estimates were 67% (48; 92%) in the LAI group and 46% (24–87%) in the RAI group. The median survival (first quartile; third quartile) was 11.1 (0.1; 14) years for patients with LAI and 1.3 (0.09; NA) years for patients with RAI. Of 17 children who had undergone cardiac surgery, five (29%) children achieved a bi-ventricular repair and 12 (70%) children achieved a uni-ventricular palliation. Three were primarily palliated, but converted to bi-ventricular thereafter. Foetal subtype definition of heterotaxy based on the abdominal situs and post-natal thoracic imaging studies showed a discordant pattern of broncho-pulmonary branching and atrial appendage anatomy in 40% of our live-born children.ConclusionHeterotaxy is a rare and complex condition with significant morbidity and mortality related to severe cardiac and extra-cardiac associations. Accurate pre-natal diagnosis can help identify the fetuses at risk and allow for timely intervention in a multi-disciplinary setting. Further studies are warranted to shed light on the exact sub-type definition in fetuses with heterotaxy and the presence of discordant post-natal patterns.

Background:Iron rim lesions (IRLs) represent chronic lesion activity and are associated with a more severe disease course in multiple sclerosis (MS). How the iron rims around the lesions arise in patients with MS (pwMS), and whether peripheral hemolysis may be a source of iron in rim associated macrophages, is unclear.ObjectiveTo determine a potential correlation between peripheral hemolysis parameters and IRL presence in pwMS.MethodsThis retrospective study included pwMS, who underwent a 3T brain MRI between 2015 and 2020 and had a blood sample drawn at ± 2 weeks. Patients with vertigo served as a control group.ResultsWe analyzed 75 pwMS (mean age 37.0 years [SD 9.0], 53.3% female) and 43 controls (mean age 38.3 years [SD 9.8], 51.2% female). Median number of IRLs was 1 (IQR 4), 28 (37.3%) pwMS had no IRLs. IRL patients showed significantly higher Expanded Disability Status Scale (EDSS) compared to non-IRL patients (median EDSS 2.3 [IQR 2.9] vs. 1.3 [IQR 2.9], p = 0.017). Number of IRLs correlated significantly with disease duration (rs = 0.239, p = 0.039), EDSS (rs = 0.387, p < 0.001) and Multiple Sclerosis Severity Scale (MSSS) (rs = 0.289, p = 0.014). There was no significant difference in hemolysis parameters between non-IRL, IRL patients (regardless of gender and/or disease type) and controls, nor between hemolysis parameters and the number of IRLs. Total brain volume was associated with fibrinogen (β= −0.34, 95% CI −1.32 to −0.145, p = 0.016), and absolute cortical and total gray matter volumes were associated with hemoglobin (β = 0.34, 95% CI 3.39–24.68, p = 0.011; β = 0.33, 95% CI 3.29–28.95, p = 0.015; respectively).ConclusionOur data do not suggest an association between hemolysis parameters and IRL presence despite a significant association between these parameters and markers for neurodegeneration.

IntroductionNeurogenic thoracic outlet syndrome (NTOS) is a complex entity that comprises various clinical presentations, which are all believed to result from mechanical stress to the brachial plexus. Causes for the stress can include fibrous bands, spanning from the transverse processes, stump, or cervical ribs to the pleural cupula. The aim of this case series is to document how the combined potential of high-resolution neurography, including high-resolution ultrasound (HRUS), and magnetic resonance imaging (MRI) can be used to identify, anatomical compression sites, such as stump ribs and their NTOS associated ligamentous bands.Materials and MethodsRetrospective chart and image reviews identified patients, who underwent HRUS between 2011 and 2021 and the diagnosis of NTOS caused by accessory ligaments was subsequently confirmed by radiological imaging (MRI) and/or surgical exploration.ResultsSixteen patients were included in this study. In all cases, a ligament extending from the tip of a stump rib to the pleural cupula could be depicted. In all cases, these structures led to compression of the lower trunk of the brachial plexus. All surgically explored cases confirmed the radiological findings.ConclusionThis case-series demonstrates that HRUS and MRI can directly and reliably visualize accessory costocupular ligaments and a stump rib in patients with symptoms of NTOS. HRUS may be used as the first imaging modality to diagnose suspected NTOS.

Purpose Impairment of cognitive functions is commonly observed in temporal lobe epilepsy (TLE). The aim of this study was to assess visuospatial memory functions and memory-related networks using an adapted version of Roland’s Hometown Walking (RHWT) functional MRI (fMRI) task in patients with TLE. Methods We used fMRI to study activation patterns based on a visuospatial memory paradigm in 32 TLE patients (9 right; 23 left) and also within subgroups of lesional and non-lesional TLE. To test for performance, a correlational analysis of fMRI activation patterns and out-of-scanner neuropsychological visuospatial memory testing was performed. Additionally, we assessed memory-related networks using functional connectivity (FC). Results Greater contralateral than ipsilateral mesiotemporal (parahippocampal gyrus/hippocampus) activation was observed in left (n = 23)/right (n = 9) TLE. In lesional left TLE (n = 17), significant activations were seen in right more than left mesiotemporal areas (parahippocampal gyrus), while non-lesional left TLE patients (n = 6) showed significant bilateral (left>right) activations in mesiotemporal structures (parahippocampal gyrus). In left TLE, visuospatial cognitive testing correlated with fMRI activations in left (parahippocampal gyrus) and right mesiotemporal structures (hippocampus), characterized by greater fMRI activation being associated with better memory scores. In right TLE, higher scores in visuospatial memory testing were associated with greater fMRI activations in left and right insular regions. FC patterns of memory-related networks differ in right and left TLE. Conclusion While TLE in general leads to asymmetrical mesiotemporal activation, lesion-induced and non-lesional TLE patients reveal different memory fMRI activation patterns. In right TLE, insular regions try to compensate for impaired right mesiotemporal structures during the performance of visuospatial tasks. Underlying functional visuospatial memory networks differ in right and left TLE.

Abstract Background Few safety data of concurrent stereotactic radiosurgery and targeted therapy (TT) or immunotherapy (IT) are available. The aim of the study was to evaluate the outcome of melanoma patients with brain metastases (MBM) after Gamma Knife Radiosurgery (GKRS) in relation to IT/TT. Methods We evaluated 182 MBM patients, who were treated with GKRS in the modern radiosurgical and oncological era. Results The median time between the initial melanoma diagnosis and occurrence of MBM was 2.4 years. The median overall survival time was 5.4 years after melanoma diagnosis. The estimated median survival after the initial diagnosis of MBM was 1.0 year (95% CI = 0.7‐1.2 years). Patients treated with anti‐PD‐1 or a combination of anti‐CTLA‐4/PD‐1 showed a significantly longer survival after first GKRS compared to all other forms of treatment. In addition, patients treated with anti‐PD‐1, anti‐CTLA‐4, or a combination of anti‐CTLA‐4/PD‐1 showed a significantly longer time to new MBM after GKRS1 compared to patients treated with other forms and combinations of the oncological therapy. The occurrence of hemorrhage or radiation reaction/necrosis after GKRS did not show any statistically significant differences in relation to IT/TT. Conclusion In MBM patients, complications after GKRS are not significantly increased if IT/TT treatment is performed at the time of or after radiosurgery. Further, a clear benefit in distant control and survival is seen in MBM patients treated with GKRS and checkpoint inhibitors. Thus, concomitant treatment of MBM with GKRS and IT/TT seems to be a safe and powerful treatment option although further prospective studies should be conducted.

Introduction: Botulinumtoxin associated muscle denervation (BNTMD) can be detected by magnet resonance imaging (MRI), MRI may provide further insights into the exact timeline of BNTMD and the potential impact and timing of physical exercise. We aimed to assess the time interval until detection of BNTMD by MRI and whether immediate physical exercise after intramuscular BNT injection has a measurable effect on clinical parameters and the intramuscular denervation dynamics illustrated by MRI.Materials and Methods: Eleven age-matched patients were randomized to an “exercise” or “no-exercise” group. Eighty mouse-units of incobotulinumtoxin were injected into the spastic biceps muscle. MRI of the injected region, hand-held dynamometry of elbow flexor strength and clinical rating scales (mAS, CGI-I) were conducted in predefined intervals.Results: We could not detect BNTMD within 24 h but 7 days after injection independent of group allocation (exercise n = 6, no-exercise n = 5). Denervation signs were more diffuse and spread into adjacent muscles in patients having received exercise. We could not detect differences concerning clinical measures between the two groups.Conclusions: Physical exercise might influence BNTMD dynamics and promote propagation of T2-MR muscle denervation signs from the injected site into adjacent muscles.Trial registration:clinicaltrialsregister.eu, Identifier 2017-003117-25.

The periventricular crossroads have been described as transient structures of the fetal brain where major systems of developing fibers intersect. The triangular parietal crossroad constitutes one major crossroad region. By combining in vivo and post-mortem fetal MRI with histological and immunohistochemical methods, we aimed to characterize these structures.Data from 529 in vivo and 66 post-mortem MRI examinations of fetal brains between gestational weeks (GW) 18–39 were retrospectively reviewed. In each fetus, the area adjacent to the trigone of the lateral ventricles at the exit of the posterior limb of the internal capsule (PLIC) was assessed with respect to signal intensity, size, and shape on T2-weighted images. In addition, by using in vivo diffusion tensor imaging (DTI), the main fiber pathways that intersect in these areas were identified. In order to explain the in vivo features of the parietal crossroads (signal intensity and developmental profile), we analyzed 23 post-mortem fetal human brains, between 16 and ​40 GW of age, processed by histological and immunohistochemical methods. The parietal crossroads were triangular-shaped areas with the base in the continuity of the PLIC, adjacent to the germinal matrix and the trigone of the lateral ventricles, with the tip pointing toward the subplate. These areas appeared hyperintense to the subplate, and corresponded to a convergence zone of the developing external capsule, the PLIC, and the fronto-occipital association fibers. They were best detected between GW 25–26, and, at term, they became isointense to the adjacent structures. The immunohistochemical results showed a distinct cellular, fibrillar, and extracellular matrix arrangement in the parietal crossroads, depending on the stage of development, which influenced the MRI features.The parietal crossroads are transient, but important structures in white matter maturation and their damage may be indicative of a poor prognosis for a fetus with regard to neurological development. In addition, impairment of this region may explain the complex neurodevelopmental deficits in preterm infants with periventricular hypoxic/ischemic or inflammatory lesions.

The purpose of this study was to establish a non-invasive clinical PET/MR protocol using [18F]-labeled deoxyglucose (FDG) that provides physicians with regional metabolic rate of glucose (MRGlc) values and to clarify the contribution of absolute quantification to clinical management of patients with non-lesional extratemporal lobe epilepsy (ETLE). The study included a group of 15 patients with non-lesional ETLE who underwent a dynamic FDG PET study using a fully-integrated PET/MRI system (Siemens Biograph). FDG tracer uptake images were converted to MRGlc (μmol/100 g/min) maps using an image derived input function that was extracted based on the combined analysis of PET and MRI data. In addition, the same protocol was applied to a group of healthy controls, yielding a normative database. Abnormality maps for ETLE patients were created with respect to the normative database, defining significant hypo- or hyper-metabolic regions that exceeded ±2 SD of normal regional mean MRGlc values. Abnormality maps derived from MRGlc images of ETLE patients contributed to the localization of hypo-metabolic areas against visual readings in 53% and increased the confidence in the original clinical readings in 33% of all cases. Moreover, quantification allowed identification of hyper-metabolic areas that are associated with frequently spiking cortex, rarely acknowledged in clinical readings. Overall, besides providing some confirmatory information to visual readings, quantitative PET imaging demonstrated only a moderate impact on clinical management of patients with complex pathology that leads to epileptic seizures, failing to provide new decisive information that would have changed classification of patients from being rejected to being considered for surgical intervention.

Abstract Background Epilepsy occurs in up to 90 % of all individuals with tuberous sclerosis complex (TSC). In 67 % disease onset is during childhood. In ≥ 50 % seizures are refractory to currently available treatment options. The mTOR-Inhibitor Everolimus (Votubia®) was approved for the treatment of subependymal giant cell astrocytoma (SEGA) and renal angiomyolipoma (AML) in Europe in 2011. It’s anticonvulsive/antiepileptic properties are promising, but evidence is still limited. Study aim was to evaluate the efficacy and safety of Everolimus in children and adolescents with TSC-associated epilepsies. Methods Inclusion-criteria of this investigator-initiated, single-center, open, prospective study were: 1) the ascertained diagnosis of TSC; 2) age ≤ 18 years; 3) treatment indication for Votubia® according to the European Commission guidelines; 4) drug-resistant TSC-associated epilepsy, 5) prospective continuous follow-up for at least 6 months after treatment initiation and 6) informed consent to participate. Votubia® was orally administered once/day, starting with 4.5 mg/m2 and titrated to achieve blood trough concentrations between 5 and 15 ng/ml. Primary endpoint was the reduction in seizure frequency of ≥ 50 % compared to baseline. Results Fifteen patients (nine male) with a median age of six (range; 1–18) years fulfilled the inclusion criteria. 26 % (4/15) had TSC1, 66 % (10/15) had TSC2 mutations. In one patient no mutation was found. Time of observation after treatment initiation was median 22 (range; 6–50) months. At last observation, 80 % (12/15) of the patients were responders, 58 % of them (7/12) were seizure free. The overall reduction in seizure frequency was 60 % in focal seizures, 80 % in generalized tonic clonic seizures and 87 % in drop attacks. The effect of Everolimus was seen already at low doses, early after treatment initiation. Loss of efficacy over time was not observed. Transient side effects were seen in 93 % (14/15) of the patients. In no case the drug had to be withdrawn. Conclusion Everolimus seems to be an effective treatment option not only for SEGA and AML, but also for TSC-related epilepsies. Although there are potential serious side effects, treatment was tolerated well by the majority of patients, provided that patients are under close surveillance of epileptologists who are familiar with immunosuppressive agents.

While it has been shown that cerebellar tumor lesions have an impact on cognitive functions, the extent to which they shape distant neuronal pathways is still largely undescribed. Thus, the present neuroimaging study was designed to investigate different aspects of cognitive function and their neuronal correlates in patients after childhood cerebellar tumor surgery. An alertness task, a working memory task and an incompatibility task were performed by 11 patients after childhood cerebellar tumor surgery and 17 healthy controls. Neuronal correlates as reflected by alterations in functional networks during tasks were assessed using group independent component analysis. We were able to identify eight networks involved during task performance: default mode network, precuneus, anterior salience network, executive control network, visual network, auditory and sensorimotor network and a cerebellar network. For the most 'basic' cognitive tasks, a weaker task-modulation of default mode network, left executive control network and the cerebellar network was observed in patients compared to controls. Results for higher-order tasks are in line with a partial restoration of networks responsible for higher-order task execution. Our results provide tentative evidence that the synchronicity of brain activity in patients was at least partially restored in the course of neuroplastic reorganization, particularly for networks related to higher-order cognitive processes. The complex activation patterns underline the importance of testing several cognitive functions to assess the specificity of cognitive deficits and neuronal reorganization processes after brain lesions.

Association fibers connect different cortical areas within the same hemisphere and constitute an essential anatomical substrate for a diverse range of higher cognitive functions. So far a comprehensive description of the prenatal in vivo morphology of these functionally important pathways is lacking. In the present study, diffusion tensor imaging (DTI) and tractography were used to visualize major association fiber tracts and the fornix in utero in preselected non-motion degraded DTI datasets of 24 living unsedated fetuses between 20 and 34 gestational weeks (GW). The uncinate fasciculus and inferior fronto-occipital fasciculus were depicted as early as 20 GW, while in vivo 3D visualization of the inferior longitudinal fasciculus, cingulum and fornix was successful in older fetuses during the third trimester. Provided optimal scanning conditions, in utero DTI and tractography have the potential to provide a more accurate anatomical definition of developing neuronal networks in the human fetal brain. Knowledge about the normal prenatal 3D association tract morphology may serve as reference for their assessment in common developmental diseases.

ObjectivesIn cases of "spina bifida," a detailed prenatal imaging assessment of the exact morphology of neural tube defects (NTD) is often limited. Due to the diverse clinical prognosis and prenatal treatment options, imaging parameters that support the prenatal differentiation between open and closed neural tube defects (ONTDs and CNTDs) are required. This fetal MR study aims to evaluate the clivus-supraocciput angle (CSA) and the maximum transverse diameter of the posterior fossa (TDPF) as morphometric parameters to aid in the reliable diagnosis of either ONTDs or CNTDs.MethodsThe TDPF and the CSA of 238 fetuses (20-37 GW, mean: 28.36 GW) with a normal central nervous system, 44 with ONTDS, and 13 with CNTDs (18-37 GW, mean: 24.3 GW) were retrospectively measured using T2-weighted 1.5 Tesla MR -sequences.ResultsNormal fetuses showed a significant increase in the TDPF (r = .956; pConclusionsThe skull base morphology in fetuses with ONTDs differs significantly from cases with CNTDs and normal controls. This is the first study to show that the CSA changes during gestation and that it is a reliable imaging biomarker to distinguish between ONTDs and CNTDs, independent of the morphology of the spinal defect.

ObjectivesEye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed.MethodsDynamic SSFP sequences were acquired in 72 singleton fetuses (17-40 GW, three age groups [17-23 GW, 24-32 GW, 33-40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid.ResultsIn 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3-45%.ConclusionsIn human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations.