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Background and Purpose: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort. Methods: For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0–2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders. Results: The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 [95% CI, 4.0–10.4]), followed by the second attempt (adjusted odds ratio, 4.56 [95% CI, 2.7–7.7]), and finally the third (adjusted odds ratio, 3.16 [95% CI, 1.8–5.6]). Conclusions: Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03356392.

PurposeThe Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.ParticipantsAll centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Findings to dateCurrently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.Future plansThis collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.

BackgroundWide necked bifurcation aneurysms (WNBA) are among the most difficult aneurysms to treat. Very low dome-to-neck (DTN) and aspect ratios provide an even greater challenge in the management of WNBAs. We present the safety and efficacy profile for endovascular clip system (eCLIPs) device in the treatment of this subset of WNBAs with very unfavorable morphologies.MethodsIn our case series, 24 patients treated at 12 international centers were taken from a larger prospective voluntary post-marketing registry of 65 patients treated with the eCLIPs device and coiling. Those who had WNBAs at either the carotid or basilar terminus with a DTN ratio ResultsThe eCLIPs device was successfully deployed in 23 cases (96%). One patient (4.2%) died due to guidewire perforation distal to the implant site. No other complications were documented. After a mean follow-up of 15.8 months (range 3–40 months), good radiologic outcomes (modified Raymond–Roy classification (MRRC) scores of 1 or 2) were documented in 20 of 21 patients (95%) with follow-up data. The lone patient with an MRRC score of 3 showed coiled compaction after incomplete neck coverage with the device.ConclusionOur series of patients with aneurysms having adverse DTN and aspect ratios demonstrated that the eCLIPs device has a safety and efficacy profile comparable with currently available devices in the treatment of WNBAs.

To describe our experience with mechanical thrombectomy (MTE) of acute distal posterior cerebral artery (PCA) occlusions, either isolated or in combination with more proximal vessel occlusions regarding recanalization rates, MTE techniques, and procedural safety. From the prospectively maintained stroke thrombectomy databases of two institutions, all consecutive patients subjected to MTE of acute distal PCA occlusion (P2 and 3 segments) between July 2013 and May 2020 were retrospectively identified. Imaging data and angiographic features, as well as patients’ demographic and clinical data were evaluated. 35 consecutive patients were included in the study. In 17 patients MTE of isolated acute distal PCA occlusion was performed. 9 patients had combined basilar artery (BA) and distal PCA occlusion on stroke imaging and 3 had embolic distal PCA occlusion following MTE for BA occlusion. 6 patients harbored distal PCA occlusions in combination with carotid-T occlusion and a dominant posterior communicating artery. The median NIHSS at presentation was 14 (IQR 8 – 27). 25 patients (71.4%) had occlusions of the P2 and 10 patients (28.6%) of the P3 segment. Successful recanalization (TICI 2b/3) was achieved in 31 patients (88.6%). 10 patients (28.6%) were treated with a direct contact aspiration technique, while a stent retriever was used in 25 patients (71.4%). No complication attributable to distal PCA MTE occurred. Good outcome (mRS ≤ 2) was achieved in 14 patients (46.7%) and mortality was 22.9%. MTE for acute distal PCA occlusion in the setting of different occlusion patterns appears both safe and angiographically effective. Yet, clinical effectiveness remains to be determined.

To evaluate the diagnostic performance of magnetic resonance imaging (MRI) alone in comparison to positron emission tomography/ magnetic resonance imaging (PET/MRI) in patients with meningiomas. 57 patients with a total of 112 meningiomas of the brain were included. PET/MRI, including a fully diagnostic contrast enhanced MRI and PET, were acquired. PET/MRI was used as reference standard. The size and location of meningiomas was recorded. Likelihood-ratio chi-square tests were used to calculate p-values within logistic regression in order to compare different models. A multi-level logistic regression was applied to comply the hierarchical data structure. Multi-level regression adjusts for clustering in data was performed. The majority (n = 103) of meningiomas could be identified based on standard MRI sequences compared to PET/MRI. MRI alone achieved a sensitivity of 95% (95% CI 0.78, 0.99) and specificity of 88% (95% CI 0.58, 0.98). Based on intensity of contrast medium uptake, 97 meningiomas could be diagnosed with intense uptake (93.75%). Sensitivity was lowest with 74% for meningiomas 2cm3 and highest with 100% for meningiomas 0.5–1.0 cm3. Petroclival meningiomas showed lowest sensitivity with 88% compared to sphenoidal meningiomas with 94% and orbital meningiomas with 100%. Specificity of meningioma diagnostic with MRI was high with 100% for sphenoidal and hemispherical-dural meningiomas and meningiomas with 0.5–1.0 and 1.0–2.0 cm3. Overall MRI enables reliable detection of meningiomas compared to PET/MRI. PET/MRI imaging offers highest sensitivity and specificity for small or difficult located meningiomas. Charité (3093)

Background Patients aged ≥90 were excluded or under‐represented in past thrombectomy trials; thus, uncertainty remains whether treatment benefits can be expected regardless of age. This study investigates outcome and safety of thrombectomy in nonagenarians to improve decision making in a real‐world setting. Methods and Results All currently available data of patients aged ≥90 enrolled in the GSR‐ET (German Stroke Registry–Endovascular Treatment) were combined with a smaller cohort from 3 tertiary stroke centers. Baseline characteristics, procedural (Thrombolysis in Cerebral Infarction scale) and functional outcomes (modified Rankin Scale; mRS ), as well as complications (symptomatic intracranial hemorrhage, serious adverse events; SAEs) were analyzed. Good functional outcome was defined as mRS ≤3 at 90‐days. 203 patients with anterior circulation stroke and prestroke mRS ≤3 were included. The rate of successful recanalization (Thrombolysis in Cerebral Infarction scale ≥2b) was 75.9% (154/203). Good functional outcome ( mRS ≤3) was observed in 21.6% (41 of 193) at 90‐days. In‐hospital mortality was 27.1% (55 of 203) and increased significantly at 90 days to 48.9% (93 of 190; P CI , 1.01–3.70; P =0.046) and initial National Institute of Health Stroke Scale (adjusted odds ratio, 0.85; 95% CI , 0.76–0.97; P =0.014) as independent predictors for good outcome. Patients with successful recanalization had a significant ( P =0.001) shift of mRS distribution with higher rates of good functional outcomes (23.8% [34 of 143] versus 14.9% [7 of 47]) and lower mortality at 90‐days (46.8% [67 of 143] versus 55.3% [26 of 47]). Conclusions Despite high mortality and less frequent favorable outcome, our data suggest that thrombectomy is still effective and safe for nonagenarians. Decision making for thrombectomy in patients aged ≥90 should be based on a case‐by‐case basis with regard to initial National Institute of Health Stroke Scale and Alberta Stroke Program Early CT Score.

Purpose To evaluate diffusion abnormalities of the retina and optic nerve in patients with central retinal artery occlusion (CRAO) using standard stroke diffusion-weighted magnetic resonance imaging (DWI). Methods In this case-control study, DWI scans of patients with nonarteritic CRAO were retrospectively assessed for acute ischemia of the retina and optic nerve. Two neuroradiologists, blinded for patient diagnosis, randomly evaluated DWI of CRAO patients and controls (a collective of stroke and transient ischemic attack [TIA] patients) for restrictions of the retina and optic nerve. We calculated statistical quality criteria and analyzed inter-rater reliability using unweighted Kappa statistics. Results 20 CRAO patients (60,6 ± 17 years) and 20 controls (60,7 ± 17 years) were included in the study. Sensitivity, specificity, positive and negative predictive values for retinal DWI restrictions were 75%/80%/79%/76% (reader 1) and 75%/100%/100%/80% (reader 2), respectively. Unweighted Kappa was κ = 0,70 (95% CI 0,48‑0,92), indicating “substantial” interrater reliability. In comparison, sensitivity, specificity, PPV and NPV (positive and negative predictive values) for restrictions of the optic nerve in CRAO were 55%/70%/65%/61% (reader 1) and 25%/100%/100%/57% (reader 2). Inter-rater reliability was “fair” with unweighted Kappa κ = 0,32 (95% CI 0,09‑0,56). Conclusions Retinal diffusion restrictions were present in a majority of CRAO patients and detectable with reasonable sensitivity, high specificity and substantial inter-rater reliability. Further studies are necessary to study time dependency of retinal diffusion restrictions, improve image quality and investigate the reliability of retinal DWI to discern CRAO from other causes of acute loss of vision.

Aim Evaluation of a semiautomatic software algorithm for magnetic resonance imaging (MRI)-based assessment of cerebral metastases in cancer patients. Material and Methods Brain metastases (n = 131) in 38 patients, assessed by contrast-enhanced MRI, were retrospectively evaluated at two timepoints (baseline, follow-up) by two experienced neuroradiologists in a blinded manner. The response assessment in neuro-oncology (RANO) criteria for brain metastases (RANO-BM) were applied by means of a software (autoRANO-BM) as well as manually (manRANO-BM) at an interval of 3 weeks. Results The average diameter of metastases was 12.03 mm (SD ± 6.66 mm) for manRANO-BM and 13.97 mm (SD ± 7.76 mm) for autoRANO-BM. Diameter figures were higher when using semiautomatic measurements (median = 11.8 mm) as compared to the manual ones (median = 10.2 mm; p = 0.000). Correlation coefficients for intra-observer variability were 0.993 (autoRANO-BM) and 0.979 (manRANO-BM). The interobserver variability (R1/R2) was 0.936/0.965 for manRANO-BM and 0.989/0.998 for autoRANO-BM. A total of 19 lesions (15%) were classified differently when using semiautomatic measurements. In 14 cases with suspected disease progression by manRANO-BM a stable course was found according to autoRANO-BM. Conclusion Computerized measuring techniques can aid in the assessment of cerebral metastases by reducing examiner-dependent effects and may consequently result in a different classification according to RANO-BM criteria.

Purpose To describe our single-center experience of mechanical thrombectomy (MTE) via a direct carotid puncture (DCP) with regard to indication, time metrics, procedural details, as well as safety and efficacy aspects. Methods DCP thrombectomy cases performed at our center were retrospectively identified from a prospectively maintained institutional MTE database. Various patient (age, sex, stroke cause, comorbidities), clinical (NIHSS, mRS), imaging (occlusion site, ASPECT score), procedural (indication for DCP, time from DCP to reperfusion, materials used, technical nuances), and outcome data (NIHSS, mRS) were tabulated. Results Among 715 anterior circulation MTEs, 12 DCP-MTEs were identified and analyzed. Nine were left-sided M1 occlusions, one right-sided M1 occlusion, and two right-sided M2 occlusions. DCP was successfully carried out in 91.7%; TICI 2b/3-recanalization was achieved in 83.3% via direct lesional aspiration and/or stent-retrieval techniques. Median time from DCP to reperfusion was 23 min. Indications included futile transfemoral catheterization attempts of the cervical target vessels as well as iliac occlusive disease. Neck hematoma occurred in 2 patients, none of which required further therapy. Conclusion MTE via DCP in these highly selected patients was reasonably safe, fast, and efficient. It thus represents a valuable technical extension of MTE, especially in patients with difficult access.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

OBJECTIVE A direct comparison of intraoperative CT (iCT), cone-beam CT (CBCT), and robotic cone-beam CT (rCBCT) has been necessary to identify the ideal imaging solution for each individual user’s need. Herein, the authors sought to analyze workflow, handling, and performance of iCT, CBCT, and rCBCT imaging for navigated pedicle screw instrumentation across the entire spine performed within the same surgical environment by the same group of surgeons. METHODS Between 2014 and 2018, 503 consecutive patients received 2673 navigated pedicle screws using iCT (n = 1219), CBCT (n = 646), or rCBCT (n = 808) imaging during the first 24 months after the acquisition of each modality. Clinical and demographic data, workflow, handling, and screw assessment and accuracy were analyzed. RESULTS Intraoperative CT showed image quality and workflow advantages for cervicothoracic cases, obese patients, and long-segment instrumentation, whereas CBCT and rCBCT offered independent handling, around-the-clock availability, and the option of performing 2D fluoroscopy. All modalities permitted reliable intraoperative screw assessment. Navigated screw revision was possible with each modality and yielded final accuracy rates > 92% in all groups (iCT 96.2% vs CBCT 92.3%, p < 0.001) without a difference in the accuracy of cervical pedicle screw placement or the rate of secondary screw revision surgeries. CONCLUSIONS Continuous training and an individual setup of iCT, CBCT, and rCBCT has been shown to permit safe and precise navigated posterior instrumentation across the entire spine with reliable screw assessment and the option of immediate revision. The perceived higher image quality and larger scan area of iCT should be weighed against the around-the-clock availability of CBCT and rCBCT technology with the option of single-handed robotic image acquisition.

To describe the clinical and radiological characteristics, frequency, technical aspects and outcome of endovascular treatment of acute basilar artery occlusion (ABO) in the setting of vertebrobasilar steno-occlusive disease. Retrospective analysis of databases of two universitary stroke centers including all consecutive patients from January 2013 until May 2017 undergoing thrombectomy for a) acute stroke due to basilar artery occlusion and either significant basilar artery stenosis or vertebral artery stenosis/occlusion as well as b) presumed embolic basilar artery occlusions. Demographics, stroke characteristics, time metrics, recanalization results and outcome were recorded. Interventional strategies were evaluated concerning the thrombectomy technique, additional angioplasty, type of approach with respect to lesion pattern (ipsilateral to steno-occlusive VA lesion: dirty road or contralateral: clean road) and sequence of actions. Out of 157 patients treated for ABO 38 (24.2%) had associated significant vertebrobasilar steno-occlusive lesions. An underlying significant basilar artery stenosis was present in 23.7% and additionally significant steno-occlusive vertebral lesions were present in 81.5%. Thrombectomy was performed with primary aspiration in 15.8% and with stent-retrievers in 84.2%. Successful revascularization (TICI 2b-3) was achieved in 86.8%. In 52.6% additional stent angioplasty was performed, in 7.9% balloon angioplasty only. The clean road approach was used in 22.5% of cases, the dirty road in 77.4%. Final modified Rankin scale (mRS) was 0–2 in 6 patients (15.8%) and 3–5 in 32 (84.2%). The in-hospital mortality was 36.8%. There were no statistically significant differences in outcome compared to presumed cases of embolisms. Endovascular treatment of ABO with underlying significant vertebrobasilar steno-occlusive lesions is effective and reasonably safe. Specific procedural strategies apply depending on individual patient pathology and anatomy. Although high rates of recanalization can be achieved, outcomes tend to be poor.

Background: Cerebellar infarction is exceedingly rare in neonates, usually occurring after traumatic birth. Lifelong sequelae can result from cerebellar damage with disorders of motor function, ataxia, and also cognitive dysfunction. Objectives/Methods: We report the clinical presentation of a preterm triplet infant delivered by elective cesarean who showed peripheral facial palsy immediately after birth. Results: Tonic seizures with high-voltage discharges over the contralateral cerebral hemisphere and secondary generalization were successfully treated with phenobarbital. Transnuchal ultrasound through the foramen magnum and subsequent MRI examinations revealed infarction of the left cerebellar hemisphere. Conclusions: In newborn infants, acute cerebellar stroke may have direct epileptogenic potential.

Background Freehand ventricular catheter placement may represent limited accuracy for the surgeon's intent to achieve primary optimal catheter position. Objective To investigate the accuracy of a ventricular catheter guide assisted by a simple mobile health application (mhealth app) in a multicenter, randomized, controlled, simple blinded study (GAVCA study). Methods In total, 139 eligible patients were enrolled in 9 centers. Catheter placement was evaluated by 3 different components: number of ventricular cannulation attempts, a grading scale, and the anatomical position of the catheter tip. The primary endpoint was the rate of primary cannulation of grade I catheter position in the ipsilateral ventricle. The secondary endpoints were rate of intraventricular position of the catheter's perforations, early ventricular catheter failure, and complications. Results The primary endpoint was reached in 70% of the guided group vs 56.5% (freehand group; odds ratio 1.79, 95% confidence interval 0.89-3.61). The primary successful puncture rate was 100% vs 91.3% (P = .012). Catheter perforations were located completely inside the ventricle in 81.4% (guided group) and 65.2% (freehand group; odds ratio 2.34, 95% confidence interval 1.07-5.1). No differences occurred in early ventricular catheter failure, complication rate, duration of surgery, or hospital stay. Conclusion The guided ventricular catheter application proved to be a safe and simple method. The primary endpoint revealed a nonsignificant improvement of optimal catheter placement among the groups. Long-term follow-up is necessary in order to evaluate differences in catheter survival among shunted patients.

Low-profile intracranial stents are characterized by a miniaturized design that enables deployment via a 0.0165″ or 0.017″ internal diameter microcatheter, which is typically intended for coil delivery. This study analyzed the incidence, clinical relevance and risk factors of thromboembolic events (TEE) occurring during low-profile stent-assisted coiling of intracranial aneurysms. This was a retrospective, multicenter analysis of consecutive patients who underwent stent-assisted aneurysm coiling (SAC) with the laser-cut Acandis Acclino and Neuroform Atlas stents. The study evaluated the incidence of symptomatic and asymptomatic TEEs and the impact on functional outcome. Risk factors for TEEs were determined by univariate and bivariate logistic regression analyses. Among 131 procedures (mean patient age 56.5 ± 12.8 years, mean aneurysm size: 6.7 ± 3.9 mm) TEEs occurred in 14 cases (10.7%) of which 2 patients (1.5%) developed ischemic stroke, while the remaining TEEs remained asymptomatic. Multivariate analysis revealed Y‑stenting as potential risk factor for TEEs (odds ratio: 3.9, 95% confidence interval: 1.0–16.5; p = 0.08). The use of SAC with low-profile intracranial stents is associated with a favorable safety profile; however, Y‑stenting may carry an increased risk of TEEs, which needs to be considered during treatment planning.

Background Process optimization in computed tomography (CT) and telemedicine. Purpose To compare image quality and objective diagnostic accuracy of medical-grade and consumer-grade digital displays/computer terminals for detection of intracranial aneurysms. Material and Methods Four radiologists with different levels of experience retrospectively read a total of 60 patients including 30 cases of proven therapy-naïve intracranial aneurysm detectable on a medical-grade grayscale calibrated display. They had 5 min per case reading the first 20 datasets using only axial slices, the next 20 patients using axial slices and multiplanar reconstructions (MPRs), and the last 20 patients using axial slices, MPRs, and maximum intensity projections (MIPs). Three months after the first reading session on a medical-grade display, they read all datasets again under the same standardized conditions but on a consumer-grade display. Diagnostic performance, subjective diagnostic confidence, and reading speed were analyzed and compared. Readers rated image quality on a five-point Likert scale. Results Diagnostic accuracy did not differ significantly with areas under the curve of 0.717–0.809 for all readers on both display devices. Sensitivity and specificity did not increase significantly when adding MPRs and/or MIPs. Reading speed was similar with both devices. There were no significant differences in subjective image quality scores, and overall inter-reader variability of all subjective parameters correlated positively between the two devices ( P Conclusion Diagnostic accuracy and readers’ diagnostic confidence in detecting and ruling out intracranial aneurysm were similar on commercial-grade and medical-grade displays. Additional reconstructions did not increase sensitivity/specificity or reduce the time needed for diagnosis.

Percutaneous paraspinal pedicle screw implantation (PPSI) reduces soft tissue trauma, blood loss, and postoperative pain but remains technically challenging and associated with radiation exposure and implant-related artefacts. Here, we determined the feasibility, screw accessibility, and the accuracy of navigated PPSI in the thoraco-lumbar sacral spine using intraoperative computed tomography (iCT) and robotic cone-beam CT (CBCT) imaging. Between 2015 and 2018, 465 percutaneous paraspinal pedicle screws were implanted in 75 patients using iCT- or CBCT-based spinal navigation with 230 screws connected to rod reducers during screw assessment imaging (iCT 198; CBCT 32). Clinical and demographic data, intraoperative screw accessibility, and screw accuracy were analyzed and compared to a case-matched cohort of 75 patients undergoing navigated implantation of 481 pedicle screws through an open midline approach. Both iCT and CBCT permitted reliable assessment of each implanted screw, regardless of artifacts caused by rod reducers. Although overall accuracy for correct placement was comparable between PPSI and open surgery (PPSI 96.6%; Open 94.2%), PPSI compared favorably to open surgery regarding complete placement within the pedicle (PPSI 90.1%; Open 75.1%; p

Objective Clinical data on the new Neuroform Atlas stent for treatment of intracranial aneurysms is limited. We report our experience in stent-assisted coiling procedures of complex, predominantly wide-necked aneurysms. Methods This is a retrospective study of consecutive patients treated with the Neuroform Atlas stent between August 2014 and November 2018 at three German tertiary care centers. We evaluated the complication rate, clinical outcome and angiographic result at mid-term follow-up. Results Thirty-seven aneurysms (elective: 23, previous subarachnoid hemorrhage: 14) were treated in 37 patients (mean age: 59.4 years, 62.2% females). Stent-assisted coiling was successful in all cases, achieving immediate complete aneurysm occlusion by coiling in 83.8% and neck remnants in 16.2%. At 6-month angiographic follow-up, complete aneurysm occlusion was obtained in 80.8% (21/26), neck remnants in 11.5% (3/26) and aneurysm remnants in 7.7% (2/26). Retreatment was necessary in 7.7%. Ischemic stroke occurred in one patient (2.7%). At 6-month clinical follow-up, procedure-related permanent morbidity was 2.7%. Conclusions Our results demonstrate that treatment of intracranial aneurysms with the Neuroform Atlas stent is associated with low morbidity and a high aneurysm occlusion rate at mid-term follow-up. Further studies will be necessary to confirm our results.

Neuroimaging has seen a paradigm shift away from a formal description of local activity patterns towards studying distributed brain networks. The recently defined framework of the 'human connectome' enables global analysis of parts of the brain and their interconnections. Deep brain stimulation (DBS) is an invasive therapy for patients with severe movement disorders aiming to retune abnormal brain network activity by local high frequency stimulation of the basal ganglia. Beyond clinical utility, DBS represents a powerful research platform to study functional connectomics and the modulation of distributed brain networks in the human brain. We acquired resting-state functional MRI in 20 patients with Parkinson's disease with subthalamic DBS switched on and off. An age-matched control cohort of 15 subjects was acquired from an open data repository. DBS lead placement in the subthalamic nucleus was localized using a state-of-the art pipeline that involved brain shift correction, multispectral image registration and use of a precise subcortical atlas. Based on a realistic 3D model of the electrode and surrounding anatomy, the amount of local impact of DBS was estimated using a finite element method approach. On a global level, average connectivity increases and decreases throughout the brain were estimated by contrasting on and off DBS scans on a voxel-wise graph comprising eight thousand nodes. Local impact of DBS on the motor subthalamic nucleus explained half the variance in global connectivity increases within the motor network (R = 0.711, P < 0.001). Moreover, local impact of DBS on the motor subthalamic nucleus could explain the degree to how much voxel-wise average brain connectivity normalized towards healthy controls (R = 0.713, P < 0.001). Finally, a network-based statistics analysis revealed that DBS attenuated specific couplings known to be pathological in Parkinson's disease. Namely, coupling between motor thalamus and motor cortex was increased while striatal coupling with cerebellum, external pallidum and subthalamic nucleus was decreased by DBS. Our results show that resting state functional MRI may be acquired in DBS on and off conditions on clinical MRI hardware and that data are useful to gain additional insight into how DBS modulates the functional connectome of the human brain. We demonstrate that effective DBS increases overall connectivity in the motor network, normalizes the network profile towards healthy controls and specifically strengthens thalamo-cortical connectivity while reducing striatal control over basal ganglia and cerebellar structures.

Neuroimaging has seen a paradigm shift from a formal description of local activity patterns toward studying distributed brain networks. The recently defined framework of the ‘human connectome’ allows to globally analyse parts of the brain and their interconnections. Deep brain stimulation (DBS) is an invasive therapy for patients with severe movement disorders aiming to retune abnormal brain network activity by local high frequency stimulation of the basal ganglia. Beyond clinical utility, DBS represents a powerful research platform to study functional connectomics and the modulation of distributed brain networks in the human brain. We acquired resting-state functional MRI in twenty Parkinson’s disease (PD) patients with subthalamic DBS switched ON and OFF. An age-matched control cohort of fifteen subjects was acquired from an open data repository. DBS lead placement in the subthalamic nucleus (STN) was localized using a state-of-the art pipeline that involved brain shift correction, multispectral image registration and use of a precise subcortical atlas. Based on a realistic 3D model of the electrode and surrounding anatomy, the amount of local impact of DBS was estimated using a finite element method approach. On a global level, average connectivity increases and decreases throughout the brain were estimated by contrasting ON and OFF DBS scans on a voxel-wise graph comprising eight thousand nodes. Local impact of DBS on the sensorimotor STN explained half the variance in global connectivity increases within the sensorimotor network (R = 0.711, p < 0.001). Moreover, local impact of DBS on the motor STN could explain the degree of how much voxel-wise average brain connectivity normalized toward healthy controls (R = 0.713, p < 0.001). Finally, a network based statistics analysis revealed that DBS attenuated specific couplings that are known to be pathological in PD. Namely, coupling between motor thalamus and sensorimotor cortex was increased and striatal coupling with cerebellum, external pallidum and STN was decreased by DBS.Our results show that rs-fMRI may be acquired in DBS ON and OFF conditions on clinical MRI hardware and that data is useful to gain additional insight into how DBS modulates the functional connectome of the human brain. We demonstrate that effective DBS increases overall connectivity in the motor network, normalizes the network profile toward healthy controls and specifically strengthens thalamo-cortical connectivity while reducing striatal control over basal ganglia and cerebellar structures.

Background: There is a need to examine the effects of different types of oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) on perihematomal edema (PHE), which is gaining considerable appeal as a biomarker for secondary brain injury and clinical outcome. Methods: In a large multicenter approach, computed tomography-derived imaging markers for PHE (absolute PHE, relative PHE (rPHE), edema expansion distance (EED)) were calculated for patients with OAC-ICH and NON-OAC-ICH. Exploratory analysis for non-vitamin-K-antagonist OAC (NOAC) and vitamin-K-antagonists (VKA) was performed. The predictive performance of logistic regression models, employing predictors of poor functional outcome (modified Rankin scale 4–6), was explored. Results: Of 811 retrospectively enrolled patients, 212 (26.14%) had an OAC-ICH. Mean rPHE and mean EED were significantly lower in patients with OAC-ICH compared to NON-OAC-ICH, p-value 0.001 and 0.007, whereas, mean absolute PHE did not differ, p-value 0.091. Mean EED was also significantly lower in NOAC compared to NON-OAC-ICH, p-value 0.05. Absolute PHE was an independent predictor of poor clinical outcome in NON-OAC-ICH (OR 1.02, 95%CI 1.002–1.028, p-value 0.027), but not in OAC-ICH (p-value 0.45). Conclusion: Quantitative markers of early PHE (rPHE and EED) were lower in patients with OAC-ICH compared to those with NON-OAC-ICH, with significantly lower levels of EED in NOAC compared to&nbsp, NON-OAC-ICH. Increase of early PHE volume did not increase the likelihood of poor outcome in OAC-ICH, but was independently associated with poor outcome in NON-OAC-ICH. The results underline the importance of etiology-specific treatment strategies. Further prospective studies are needed.

ObjectiveTo investigate whether spreading depolarization (SD)-related variables at 2 different time windows (days 1–4 and 5–8) after aneurysmal subarachnoid hemorrhage (aSAH) correlate with the stereologically determined volume of early focal brain injury on the preinterventional CT scan.MethodsIn this observational multicenter study of 54 patients, volumes of unaffected brain tissue, ventricles, cerebellum, aSAH, intracerebral hemorrhage, and focal parenchymal hypodensity were stereologically estimated. Patients were electrocorticographically monitored using subdural electrodes for 81.8 hours (median) (interquartile range: 70.6–90.5) during days 1–4 (n = 54) and for 75.9 (59.5–88.7) hours during days 5–8 (n = 51). Peak total SD-induced depression duration of a recording day (PTDDD) and peak numbers of (1) SDs, (2) isoelectric SDs, and (3) spreading depressions of a recording day were determined following the recommendations of the Co-Operative Studies on Brain Injury Depolarizations.ResultsThirty-three of 37 patients with early focal brain injury (intracerebral hemorrhage and/or hypodensity) in contrast to 7 of 17 without displayed SDs during days 1–4 (sensitivity: 89% [95% confidence interval, CI: 75%–97%], specificity: 59% [CI: 33%–82%], positive predictive value: 83% [CI: 67%–93%], negative predictive value: 71% [CI: 42%–92%], Fisher exact test, p < 0.001). All 4 SD-related variables during days 1–4 significantly correlated with the volume of early focal brain injury (Spearman rank order correlations). A multiple ordinal regression analysis identified the PTDDD as the most important predictor.ConclusionsOur findings suggest that early focal brain injury after aSAH is associated with early SDs and further support the notion that SDs are a biomarker of focal brain lesions.

Objective A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion. Methods ENDOSTROKE is an investigator-initiated multicenter registry for patients undergoing EVT. This analysis includes 148 consecutive patients with BA occlusion, with 59% having received intravenous thrombolysis prior to EVT. Recanalization (defined as Thrombolysis in Cerebral Infarction [TICI] score 2b–3) and collateral status (using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral grading system) were assessed by a blinded core laboratory. Good (moderate) outcome was defined as a modified Rankin Scale score of 0 to 2 (0–3) assessed after at least 3 months (median time to follow-up = 120 days). Results Thirty-four percent had good and 42% had moderate clinical outcome; mortality was 35%. TICI 2b–3 recanalization was achieved by 79%. Age, hypertension, National Institutes of Health Stroke Scale scores, collateral status, and the use of magnetic resonance imaging prior to EVT predicted clinical outcome, the latter 3 remaining independent predictors in multivariate analysis. Independent predictors of recanalization were better collateral status and the use of a stent retriever. However, recanalization did not significantly predict clinical outcome. Interpretation Beside initial stroke severity, the collateral status predicts clinical outcome and recanalization in BA occlusion. Our data suggest that the use of a stent retriever is associated with high recanalization rates, but recanalization on its own does not predict outcome. The role of other modifiable factors, including the choice of pretreatment imaging modality and time issues, warrants further investigation. Ann Neurol 2015;77:415–424

OBJECTIVETranscranial color-coded duplex sonography (TCCS) is a reliable tool that is used to assess vasospasm in the M1 segment of the middle cerebral artery (MCA) after subarachnoid hemorrhage (SAH). A distinct increase in blood flow velocity (BFV) is the principal criterion for vasospasm. The MCA/internal carotid artery (ICA) index (Lindegaard Index) is also widely used to distinguish between vasospasm and cerebral hyperperfusion. However, extracranial ultrasonography assessment of the neck vessels might be difficult in an intensive care unit. Therefore, the authors evaluated whether the relationship of intracranial arterial to venous BFV might indicate vasospasm with similar or even better accuracy.METHODSPatients who presented between 2008 and 2015 with aneurysmal SAH were prospectively enrolled in the study. Digital subtraction angiography (DSA) and TCCS were performed within 24 hours of each other to assess vasospasm 8–10 days after SAH. The following different TCCS parameters were analyzed to assess vasospasm in the MCA and were compared with the gold-standard DSA parameters: 1) mean time-averaged maximum BFV (Vmean) of the MCA, 2) peak systolic velocity (PSV) of the MCA, 3) the Lindegaard Index using Vmean as well as PSV, and 4) a new arteriovenous index (AVI) between the MCA and the basal vein of Rosenthal using Vmean and PSV. The best cutoff values for these parameters to distinguish vasospasm from normal perfusion or hyperperfusion were calculated using receiver operating characteristic curve analysis. Sensitivity, specificity, positive predictive value, and negative predictive value as well as the overall accuracy for each cutoff value were analyzed.RESULTSA total of 102 patients (mean age 52 ± 12 years) were evaluated. Bilateral MCA assessment by TCCS was successful in all patients. In 6 cases (3%), the BFV of the basal vein of Rosenthal could not be analyzed. The AVI could not be calculated in 50 of 204 cases (25%) because the insonation quality was very low in one of the ICAs. An AVI > 10 for Vmean and an AVI > 12 for systolic velocity provided the highest accuracies of 87% and 86%, respectively. Regarding the Lindegaard Index, the accuracy was highest using a threshold of > 3 for the mean BFV (84%) as well as systolic BFV (80%). BFVs in the MCA of ≥ 120 cm/sec (Vmean) and ≥ 200 cm/sec (PSV) predicted vasospasm with accuracies of 84% and 83%, respectively. A combined analysis of the MCA BFV and the AVI led to a slight increase in specificity (Vmean, 94%; PSV, 93%) and positive predictive value (Vmean, 88%; PSV 86%) without further improvement in accuracy (Vmean, 88%; PSV, 84%).CONCLUSIONSThe intracranial AVI is a reliable parameter that can be used to assess vasospasm after SAH. Its reliability for differentiating vasospasm and hyperperfusion is slightly higher than that for the established Lindegaard Index, and this method has the additional advantage of a remarkably lower failure rate.

International journal of stroke 12(4), 412-415 (2017). doi:10.1177/1747493016677986, Published by Sage, London

Background: Multiple sclerosis (MS) is a chronic disease characterized by CNS lesions causing physical and cognitive impairment. Using psychophysical testing, an olfactory disorder is diagnosed in 15-38.5% of patients with MS. Olfactometry permits objective testing of the sensory nerve function. Methods: The study looked at 20 patients with MS. Clinical, olfactory (chemosensory evoked potentials), and MRI data (volume of the bulbus olfactorius (BO), olfactory brain (OB), lesions in the CNS) were analyzed. Results: 25 percent of patients were hyposmic, exhibiting higher OB lesion volumes and smaller bulb volumes. H2S and CO2 latencies and the BO volume (inversely) correlated with the volume and number of MS lesions of the olfactory brain in all patients. Patients with a smaller olfactory bulb volume exhibited longer H2S latencies (p = 0.025). Conclusion: A relationship between olfactory bulb volume, olfactory brain lesion load, and objective olfactory function testing in MS patients was investigated in all patients. Our data shows that brain damage characteristic of MS, including reduced bulb volume, causes an increase in chemosensory potential latencies and an olfactory function deficit.

Background Cerebrospinal fluid (CSF) examination is considered important in the diagnosis of neurosarcoidosis, however, data on whether and how CSF parameters may be related to MRI findings and clinical disease activity of patients with neurosarcoidosis are scarce. Objective To correlate CSF findings in patients with neurosarcoidosis with MRI findings and clinical disease activity. Material and methods Results of 51 comprehensive CSF examinations of 25 patients with probable or definite neurosarcoidosis according to the Zajicek-criteria were analyzed retrospectively. Results Patients with diffuse leptomeningeal gadolinium enhancement on MRI had significantly higher cell counts (≥ 50 cells/μl in 80%), total protein (≥ 200 mg/dl in 80%), CSF/serum albumin quotients (QAlb, ≥ 30 in 80%), and lactate (≥ 30 mg/dl in 70%), but significantly lower glucose levels (≤ 40 mg/dl in 67%) than patients without leptomeningeal enhancement. Irrespective of MRI findings, activated lymphocytes and plasma cells were detected in the initial CSF examination in 60% and 47% of patients, and an intrathecal synthesis of IgG, IgA, and IgM in 22%, 29%, and 22%. Patients with clinically active disease had significantly higher CSF cell counts, total protein, QAlb, and lactate, but significantly lower glucose levels than patients with stable disease. Conclusion CSF abnormalities in neurosarcoidosis are most pronounced in patients with diffuse leptomeningeal enhancement on MRI. CSF analyses may thus aid in the distinction of different radiographic and pathologic manifestations of neurosarcoidosis. Furthermore, CSF examinations may allow monitoring disease activity in patients with neurosarcoidosis.

DYTCA is a syndrome that is characterized by predominant dystonia and mild cerebellar ataxia. We examined two affected siblings with healthy, consanguineous, Turkish parents. Both patients presented with a combination of childhood-onset cerebellar ataxia, dystonia, and sensory axonal neuropathy. In the brother, dystonic features were most pronounced in the legs, while his sister developed torticollis. Routine diagnostic investigations excluded known genetic causes. Biochemical analyses revealed a mitochondrial respiratory chain complex IV and a coenzyme Q10 deficiency in a muscle biopsy. By exome sequencing, we identified a homozygous missense mutation (c.154A >C; p.Thr52Pro) in both patients in exon 2 of the COX20 (FAM36A) gene, which encodes a complex IV assembly factor. This variant was confirmed by Sanger sequencing, was heterozygous in both parents, and was absent from 427 healthy controls. The exact same mutation was recently reported in a patient with ataxia and muscle hypotonia. Among 128 early-onset dystonia and/or ataxia patients, we did not detect any other patient with a COX20 mutation. cDNA sequencing and semi-quantitative analysis were performed in fibroblasts from one of our homozygous mutation carriers and six controls. In addition to the exchange of an amino acid, the mutation led to a shift in splicing. In conclusion, we extend the phenotypic spectrum of a recently identified mutation in COX20 to a recessively inherited, early-onset dystonia-ataxia syndrome that is characterized by reduced complex IV activity. Further, we confirm a pathogenic role of this mutation in cerebellar ataxia, but this mutation seems to be a rather rare cause.

Eclampsia is characterized by seizures, coma, or focal neurological deficits in pregnant women with pre-eclampsia. It is not known if brain lesions are caused by vasospasm with hypoperfusion or by hypertension-induced breakdown of cerebrovascular autoregulation with hyperperfusion [1–3]. Ultrasound studies reported an increase of flow velocities and assumed vasospasm but did not prove it by a pathological middle cerebral artery (MCA)/internal carotid artery (ICA) (Lindegaard)-index in combination with angiography [4, 5]. However, also cerebral hyperperfusion and decreased resistance (vasodilatation) of intracerebral arteries have been reported in eclampsia [5, 6]. Low intracranial Doppler resistance and pulsatility indices predict a high risk of developing pre-eclampsia [6]. It is not clear if raised intracranial blood flow velocities are due to vasospasm or hyperperfusion [7]. Serial and multimodal investigations have been requested to improve the understanding of eclampsia [4]. A 34-year-old pregnant patient developed arterial hypertension (up to 200/140 mmHg) and proteinuria (2 ?). After two epileptic seizures (focal and generalized tonic– clonic), she was admitted to our hospital at her 37th week of pregnancy with the diagnosis of eclampsia. She suffered from pulsating headache of maximal intensity. Her neurological examination was regular. Ultrasound showed partial placental abruption. She gave birth to a healthy male infant weighing 2,955 g by emergency cesarean section. Seizures ceased with short-term clobazepam and long-term carbamazepine. CRP, AST, ALT, LDH, and leukocytes were transiently increased (Table 1). EEG showed bilateral intermittent slow theta waves and sharp transients. One day postpartum, MRI (T2 and fluid-attenuated inversion recovery FLAIR) showed multifocal, non-confluating, non-enhancing hyperintensities in both cerebral hemispheres without diffusion restriction, indicating vasogenic edema (Fig. 1a). MRA detected multifocal irregular lumen constrictions of bilateral anterior, middle, and posterior cerebral arteries (Fig. 1c). The follow-up brain MRI and MRA demonstrated complete normalization after 1 year (Fig. 1b, d). Global cerebral blood flow (GCBF) was measured as the sum of blood volume flow in both internal carotid and vertebral arteries [8]. Cerebral blood flow velocities (CBFV) and pulsatility were assessed by transcranial duplex ultrasound (DUS). Three days postpartum, CBFV of all intracranial arteries were raised, and both MCA/ICA indices and GCBF were increased; the pulsatility index of both ICAs was decreased (Table 1; Fig. 1e). Ten days postpartum, intracranial peak systolic flow velocities, MCA/ICA indices, and GCBF decreased (Table 1). Twenty days postpartum, blood flow velocities, MCA/ICA J. E. Roehl and S. J. Schreiber contributed equally to this article.

Although often reversible, fatal outcome in posterior reversible encephalopathy syndrome (PRES) is well known. However, data on predictors of PRES-associated in-hospital death are scarce. In this study, we aimed to investigate predictors of in-hospital death in a large cohort. Radiological report databases between January 1999 and February 2015 were retrospectively searched for patients with PRES. Patients were included if they met criteria for PRES after detailed investigation of clinical charts and imaging studies. Various clinical, paraclinical and brain MRI data as well as data on in-hospital mortality were analyzed. 151 patients were included into the study, 64% were female. Seventeen (11.2%) patients died during hospital stay. In univariate analyses, higher age (p = 0.04), higher levels of C-reactive protein (p < 0.001), etiology of PRES (sepsis and chemotherapy; p = 0.02), altered coagulation (p = 0.002), altered mental state at onset (p = 0.03), and subarachnoid hemorrhage (SAH; p = 0.01) were related to in-hospital death. In multivariate analyses adjusted for age and sex, elevated CRP levels (OR 1.1 95% CI 1.1–1.2), altered coagulation (OR 5.1 95% CI 1.8–14.7), subarachnoid hemorrhage (OR 10.1 95% CI 2.2–46.1) and altered mental state (OR 3.3; 95% CI 1.1–9.4) were independently associated with in-hospital death. Altered mental state, subarachnoid hemorrhage as well as the higher levels of CRP and altered coagulation were significantly more frequent in patients who died in hospital. However, prospective studies are warranted to establish predictors of fatality in patients with PRES.

Introduction: The endovascular treatment (EVT) of cerebral ischemia in the case of large vessel occlusion has been established over recent years. Randomized trials showed a positive impact on the clinical outcome of endovascular treatment in addition to thrombolysis with respect to clinical outcome and safety, so that this therapeutic option will be implemented in future guidelines. The role of EVT in patients treated with oral anticoagulants remains uncertain. Hypothesis: We assessed the hypothesis that application of EVT is safe with regard to the occurrence of intracranial bleeding and clinical outcome in patients taking anticoagulants. Methods: The ENDOSTROKE-Registry is a commercially independent, prospective observational study in 12 stroke centers in Germany and Austria launched in January 2011. An online tool served for data acquisition of pre-specified variables concerning endovascular stroke therapy. Results: Data from 815 patients (median age 70, 57% male) undergoing EVT and known anticoagulation status were analyzed. A total of 85 (median age 76, 52% male) patients (10.4%) took oral anticoagulants prior to EVT. Anticoagulation status as measured with INR was 2.0-3.0 in 24 patients (29%), Conclusion: The application of endovascular treatment in patients taking oral anticoagulants is safe and should be considered in acute stroke treatment as an important alternative to contraindicated intravenous thrombolysis.

Despite its high prevalence among patients with aneurysmal subarachnoid hemorrhage (aSAH) and high risk of delayed cerebral ischemia (DCI), the Fisher grade 3 category remains a poorly studied subgroup. The aim of this cohort study has been to investigate the prognostic value of the Hijdra sum scoring system for the functional outcome in patients with Fisher grade 3 aSAH, in order to improve the risk stratification within this Fisher category. Initial CT scans of 72 prospectively enrolled patients with Fisher grade 3 aSAH were analyzed, and cisternal, ventricular, and total amount of blood were graded according to the Hijdra scale. Additionally, space-occupying subarachnoid blood clots were assessed. Outcome was evaluated after 6 months. Within the subgroup of Fisher grade 3, aSAH patients with an unfavorable outcome showed a significantly larger cisternal Hijdra sum score (HSS: 21.1 ± 5.2) than patients with a favorable outcome (HSS: 17.6 ± 5.9; p = 0.009). However, both the amount of ventricular blood (p = 0.165) and space-occupying blood clots (p = 0.206) appeared to have no prognostic relevance. After adjusting for the patient’s age, gender, tobacco use, clinical status at admission, and presence of intracerebral hemorrhage, the cisternal and total HSS remained the only independent parameters included in multivariate logistic regression models to predict functional outcome (p

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.

Patients with transient global amnesia (TGA) present with a characteristic clinical syndrome although other differential diagnoses have to be considered. Diffusion-weighted imaging (DWI) represents a highly specific diagnostic tool in the context of TGA; however, standard clinical DWI often fails to detect the small characteristic hippocampal lesions. The diagnostic success of DWI sequences in TGA patients was analyzed with respect to slice thickness and time interval between symptom onset. Magnetic resonance imaging (MRI) studies of 198 patients with clinically diagnosed TGA were retrospectively analyzed. All DWI studies were grouped according to the slice thickness applied (3 mm, 5 mm and 6 mm). The three groups were assessed for group-specific detection rates of hippocampal lesions with diffusion restriction. In addition the detection rates were evaluated with respect to the time interval between TGA symptom onset and MRI examination. A significant increase in detection rates (about 8.4% per mm) was found when thinner slices were acquired (44.7% for 3 mm, 27.1% for 5 mm and 19.6% for 6 mm slice thickness). The detection rate was highest (up to 80%) when MRI was performed 2 days after TGA symptom onset. The MRI protocol in patients with TGA should include a DWI sequence with a slice thickness of 3 mm or less. The examination should be performed on day 2 after symptom onset to fully exploit the diagnostic value of DWI which represents a sensitive and specific diagnostic tool for patients with TGA.

Background: Posterior reversible encephalopathy syndrome (PRES) is a serious maternal complication in pregnancy, but data on the clinicoradiological differences to other etiologies of PRES are scarce. In this study, we aimed to investigate the clinical and imaging characteristics of PRES in preeclampsia-eclampsia patients compared with other predisposing diseases in a large cohort. Methods: We retrospectively reviewed the radiological report data bases between January 1999 and August 2010 for patients with PRES. Patients fulfilling the criteria for PRES after detailed investigation of clinical charts and imaging studies were separated into patients with eclampsia-preeclampsia and other predisposing causes. Various imaging features at onset of symptoms and on follow-up as well as clinical and paraclinical data were analyzed. Results: A total of 24 patients with preeclampsia-eclampsia associated PRES and 72 patients with PRES of other predisposing causes were included into the study. In preeclampsia-eclampsia patients, headaches were significantly more frequent as initial PRES-related symptom (P

PURPOSE: To examine possible causes for olfactory and gustatory dysfunction in MS patients in a prospective study with MRI. MATERIALS AND METHODS: 30 MS patients (21 women, 11 men, 22 - 65 years, O 42 years) were examined by MRI. The olfactory bulb (OB) and olfactory brain volume was correlated with the number and volume of MS lesions in the olfactory brain and the non-olfactory brain. Olfactory testing was performed using the Threshold-Discrimination-Identification Test (TDI), and gustatory function was tested using the Taste-Strips-Test (TST). RESULTS: 33 % of the MS patients displayed olfactory dysfunction (8 % of the control group), and 17 % displayed gustatory dysfunction (5 % of the control group). There was a correlation between the olfactory brain volume and the number (r = -0.38, p < 0.05) and volume (r = -0.38, p < 0.05) of MS lesions in the olfactory brain. The olfactory brain volume correlated with the number of MS lesions in the non-olfactory brain (r = -0.48, p < 0.05). The volume of the left OB correlated with the volume of MS lesions in the olfactory brain (r = -0.42, p < 0.05), the number (r = 0.37, p < 0.05) and volume (r = 0.4, p < 0.05) of lesions in the left part of the olfactory brain and with the TST score (r = -0.45, p < 0.05). The TST score correlated with the volume of lesions in the left (r = -0.45, p < 0.05) and right part (r = -0.53, p < 0.05) of the olfactory brain. The TST score correlated with the number of lesions in the non-olfactory brain (r = -0.48, p < 0.05). CONCLUSION: The correlation between a higher number and volume of MS lesions in the olfactory brain with a decreased OB and olfactory brain volume could help to explain olfactory and gustatory dysfunction in MS patients. Just the left OB correlated with the number and volume of lesions in the olfactory brain. Manual segmentation was a suitable method for measuring OB and olfactory brain volume.

Functional connectivity analysis of resting-state functional magnetic resonance imaging data (fcrs-fMRI) has been shown to be a robust non-invasive method for localization of functional networks (without using specific tasks) and to be promising for presurgical planning. However, in order to transfer the approach to everyday clinical practice, fcrs-fMRI needs to be further validated and made easily accessible to neurosurgeons. This paper addresses the latter by presenting a software tool designed for neurosurgeons for analyzing and visualizing fcrs-fMRI data. A prototypical interactive visualization tool was developed to enable neurosurgeons to explore functional connectivity data and evaluate its usability. The implementation builds upon LIPSIA, an established software package for the assessment of functional neuroimaging data, and integrates the selection of a region-of-interest with the computation and visualization of functionally connected areas. The tool was used to explore data from a healthy participant and eight brain lesion patients. The usability of the software was evaluated with four neurosurgeons previously unacquainted with the methodology, who were asked to identify prominent, large-scale cortical networks. With this novel tool, previously published findings, such as tumor displacement of the sensorimotor cortex and other disturbances of functional networks, were reproduced. The neurosurgeons were able to consistently obtain results similar to the results of an expert, with the exception of the language network. Immediate feedback helped to pinpoint functional networks quickly and intuitively, with even inexperienced users requiring less than 3 min per network. Although fcrs-fMRI is a nascent method still undergoing evaluation with respect to established standards, the interactive software is nonetheless a promising tool for non-invasive exploration of individual functional connectivity networks in neurosurgical practice, both for well-known networks and for those less typically addressed.

Background and Purpose: Experimental and clinical data suggest that overactivation of the sympathetic nerve system (SNS) is an essential mediator of stroke-induced immunodepression, which in turn increases susceptibility to post-stroke infections. In a post hoc analysis of the PANTHERIS (Preventive Antibacterial Treatment in Acute Stroke) trial, we investigated the impact of distinct lesion patterns on SNS activation, immunodepression, and frequency of post-stroke infections. Methods: Stroke volume, stress hormone levels, and immune function were determined on day 1 after stroke onset. Stroke localization was graded using the Alberta Stroke Programme Early CT score (ASPECTS). In univariate analysis, we investigated the impact of clinical (National Institutes of Health Stroke Scale, NIHSS) and imaging stroke characteristics (lesion volume, lateralization, localization grading) on autonomous nervous system activity (norepinephrine, cortisol), immune competence (monocytic HLA-DR expression), and the frequency of post-stroke infections. In a logistic regression model, we tested for independent factors that might increase susceptibility to post-stroke infections. Results: In a single-factor analysis, large stroke volume, lesions affecting distinct regions of the MCA cortex, and SNS activation (elevated norepinephrine levels) were associated with an impaired immune function (reduced mHLA-DR expression) and a higher susceptibility to post-stroke infections. Multivariate analysis identified increased levels of norepinephrine and infarction of the anterior MCA cortex as independent risk factors of post-stroke infections. Neither stroke severity nor stroke volume was independently associated with post-stroke infections. Conclusions: Apart from sympathetic activation, our data suggest that ischemic lesion in the anterior MCA cortex may be a major determinant of stroke-associated infection. This finding has to be confirmed in larger prospective studies.

Object Multiloculated hydrocephalus remains a challenging condition to treat in the pediatric hydrocephalic population. In a retrospective study, the authors reviewed their experience with navigated endoscopy to treat multiloculated hydrocephalus in children. Methods Between April 2004 and September 2008, navigated endoscopic procedures were performed in 16 children with multiloculated hydrocephalus (median age 8 months, mean age 16.1 ± 23.3 months). In all patients preoperative MR imaging was used for planning entry sites and trajectories of the endoscopic approach for cyst perforation and catheter positioning. Intraoperatively, a rigid endoscope was tracked by the navigation system. For all children the total number of operative procedures, navigated endoscopic procedures, implanted ventricular catheters, and drained compartments were recorded. In addition, postoperative complications and radiological follow-up data were analyzed. Results In 16 children, a total of 91 procedures were performed to treat multiloculated hydrocephalus, including 29 navigated endoscopic surgeries. Finally, 21 navigated procedures involved 1 ventricular catheter and 8 involved 2 catheters for CSF diversion via the shunt. The average number of drained compartments in a shunt was 3.6 ± 1.7 (range 2–9 compartments). In 9 patients (56%) a navigated endoscopic procedure constituted the last procedure within the follow-up period. One additional surgery was necessary in 3 patients (19%) after navigated endoscopy, and in 4 patients (25%) 2 further procedures were necessary after navigated endoscopy. Serial follow-up MR imaging demonstrated evidence of sufficient CSF diversion in all patients. Conclusions Navigated endoscopic surgery is a safe and effective treatment option for multiloculated hydrocephalus. The combination of the endoscopic approach and neuronavigation further refines preoperative planning and intraoperative orientation. The aim of treatment is to drain as many compartments as possible and as soon as possible, thereby establishing sufficient CSF drainage with few ventricular catheters in single shunt systems. Close clinical and radiological follow-up is mandatory because multiple revisions are likely.

Objective Assessing the impact of image noise (IN) levels, scout scan dose and lens shield use on image quality and radiation exposure in neck multislice CT (MSCT) when using z -axis dose modulation (DM). Methods Neck MSCT phantom studies with/without z -axis DM were performed by using different IN levels (S.D. 7.5–30 HU) and scout scan tube currents (7.5–50 mA) on Toshiba Aquilion scanners (16-/64-slice). Image quality indices were evaluated by two radiologists and radiation exposure parameters calculated. Cadaveric phantom measurements elucidated lens shield interactions with DM efficacy. The lowest dose scan protocol with diagnostic image quality was introduced into the clinical imaging routine and retrospectively evaluated in 20 age-matched patients undergoing neck MSCT with/without DM. Results The highest image noise level in DM neck studies with comparable image quality to standard neck CT amounted to 20 HU, resulting in a mean tube current of 50 mAs (CTDI w 6.3 mGy). DM reduced effective dose by 35% and organ dose figures (lens, thyroid) by 33%. Scout scan dose lowering to 20 mA resulted in an effective dose (ED) decrease of 0.06 mSv (5%). Avoiding lens shield placement during scout scan effected an organ dose decrease of 20%. Overall contour sharpness and image contrast did not differ significantly (DM/without DM) whereas image noise was rated higher in DM neck CT studies ( p Conclusions z -Axis dose modulation, as assessed on 16- and 64-slice Toshiba Aquilion scanners, is effective and mandatory in neck MSCT. DM efficacy can be enhanced by optimising scout scan doses and lens shield use.

Neuroimaging studies have revealed gray matter abnormalities in schizophrenia in various regions of the brain. It is, however, still unclear whether such abnormalities are already present in individuals at ultra-high risk (UHR) for transition into psychosis. We investigated this issue using voxel-based morphometry of structural magnetic resonance images (MRI) and compared UHR patients with first-episode patients with schizophrenia and healthy controls. Gray matter volume maps from high-resolution MR T1-weighted whole brain images were analyzed in a cross-sectional study in 30 UHR patients, 23 first-episode schizophrenic patients and 29 controls. UHR patients showed significantly lower gray matter volume in the cingulate gyrus bilaterally, in the right inferior frontal and right superior temporal gyrus, as well as in the left and right hippocampus in comparison to healthy subjects. First-episode patients with schizophrenia showed smaller gray matter volume in the cingulate cortex bilaterally, in the left orbitofrontal gyrus, in the right inferior frontal and superior temporal gyrus, in the right temporal pole, in the left and right hippocampus, in the left parahippocampus, left amygdala, and in the left fusiform gyrus compared to the UHR patients. This study provides further evidence that gray matter brain volume, especially in the anterior cingulate cortex, is already reduced in the prodromal state of schizophrenia.

The term cortical spreading depolarization (CSD) describes a wave of mass neuronal depolarization associated with net influx of cations and water. Clusters of prolonged CSDs were measured time-locked to progressive ischaemic damage in human cortex. CSD induces tone alterations in resistance vessels, causing either transient hyperperfusion (physiological haemodynamic response) in healthy tissue; or hypoperfusion [inverse haemodynamic response = cortical spreading ischaemia (CSI)] in tissue at risk for progressive damage, which has so far only been shown experimentally. Here, we performed a prospective, multicentre study in 13 patients with aneurysmal subarachnoid haemorrhage, using novel subdural opto-electrode technology for simultaneous laser-Doppler flowmetry (LDF) and direct current-electrocorticography, combined with measurements of tissue partial pressure of oxygen (ptiO(2)). Regional cerebral blood flow and electrocorticography were simultaneously recorded in 417 CSDs. Isolated CSDs occurred in 12 patients and were associated with either physiological, absent or inverse haemodynamic responses. Whereas the physiological haemodynamic response caused tissue hyperoxia, the inverse response led to tissue hypoxia. Clusters of prolonged CSDs were measured in five patients in close proximity to structural brain damage as assessed by neuroimaging. Clusters were associated with CSD-induced spreading hypoperfusions, which were significantly longer in duration (up to 144 min) than those of isolated CSDs. Thus, oxygen depletion caused by the inverse haemodynamic response may contribute to the establishment of clusters of prolonged CSDs and lesion progression. Combined electrocorticography and perfusion monitoring also revealed a characteristic vascular signature that might be used for non-invasive detection of CSD. Low-frequency vascular fluctuations (LF-VF) (f < 0.1 Hz), detectable by functional imaging methods, are determined by the brain's resting neuronal activity. CSD provides a depolarization block of the resting activity, recorded electrophysiologically as spreading depression of high-frequency-electrocorticography activity. Accordingly, we observed a spreading suppression of LF-VF, which accompanied spreading depression of high-frequency-electrocorticography activity, independently of whether CSD was associated with a physiological, absent or inverse haemodynamic response. Spreading suppressions of LF-VF thus allow the differentiation of progressive ischaemia and repair phases in a fashion similar to that shown previously for spreading depressions of high-frequency-electrocorticography activity. In conclusion, it is suggested that (i) CSI is a novel human disease mechanism associated with lesion development and a potential target for therapeutic intervention in stroke; and that (ii) prolonged spreading suppressions of LF-VF are a novel 'functional marker' for progressive ischaemia.

The purpose of this study was to correlate magnetic resonance imaging (MRI)-based lesion load assessment with clinical disability in early relapsing remitting multiple sclerosis (RRMS). Seventeen untreated patients (ten women, seven men; mean age 33.0 ± 7.9 years) with the initial diagnosis of RRMS were included for cross-sectional as well as longitudinal (24 months) clinical and MRI-based assessment in comparison with age-matched healthy controls. Conventional MR sequences, MR spectroscopy (MRS) and magnetisation transfer imaging (MTI) were performed at 1.5 T. Lesion number and volume, MRS and MTI measurements for lesions and normal appearing white matter (NAWM) were correlated to clinical scores [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC)] for monitoring disease course after treatment initiation (interferon β-1a). MTI and MRS detected changes [magnetisation transfer ratio (MTR), N-acetylaspartate (NAA)/creatine ratio] in NAWM over time. EDSS and lesional MTR increases correlated throughout the disease course. Average MTR of NAWM raised during the study (p < 0.05) and correlated to the MSFC score (r = 0.476, p < 0.001). At study termination, NAA/creatine ratio of NAWM correlated to the MSFC score (p < 0.05). MTI and MRS were useful for initial disease assessment in NAWM. MTI and MRS correlated with clinical scores, indicating potential for monitoring the disease course and gaining new insights into treatment-related effects.

Rationale and Objectives The authors report study protocols and initial clinical experience in assessing patients with acute and chronic cerebrovascular disorders using the recently introduced technique of volume computed tomography (VCT). Materials and Methods Thirteen patients with presumptive cerebrovascular insufficiency underwent VCT using a 320-slice scanner (detector width, 160 mm), including time-resolved whole-brain perfusion and cerebral angiography (four-dimensional computed tomographic angiography [CTA] and computed tomographic perfusion [CTP]). Unenhanced cranial CT (cCT) and helical cervicocranial CT (three-dimensional CTA) were added according to clinical requirements. Study protocols are presented, and image quality, data management, and radiation exposure issues are discussed. Results In 12 of 13 patients, the procedure was performed successfully on admission; in the other patient, the study was aborted for clinical reasons and repeated. Total scan time amounted to about 5 minutes, and data reconstruction times were up to 10 minutes. About 9000 primary images were generated, partially in the enhanced Digital Imaging and Communications in Medicine format, thus requiring new data postprocessing and management strategies. Image artifacts restricted the use of single-rotation cCT and incremental VCT (three-dimensional CTA). Overall exposure figures (computed tomographic dose index and dose-length product) were increased by 65% on average when three-dimensional CTA was added to volume cCT and four-dimensional CTA and CTP (5.0 mSv and 2178 mGy · cm, respectively). Conclusion Preliminary clinical experience indicates that whole-brain four-dimensional CTA and CTP is a robust technique that provides relevant clinical information with respect to whole-brain perfusion as well as cerebral hemodynamics. The exposure benefit of deriving time-resolved perfusion and vessel images from one source data set is compromised when adding three-dimensional CTA to the protocol. Other acquisition techniques specific to VCT, such as single-rotation cCT and incremental three-dimensional CTA, suffer from restrictions in terms of image quality at present.