Adult-type and Pediatric-type Diffuse Gliomas : What the Neuroradiologist Should Know.

The classification of diffuse gliomas into the adult type and the pediatric type is the new basis for the diagnosis and clinical evaluation. The knowledge for the neuroradiologist should not remain limited to radiological aspects but should be based additionally on the current edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS). This classification defines the 11 entities of diffuse gliomas, which are included in the 3 large groups of adult-type diffuse gliomas, pediatric-type diffuse low-grade gliomas, and pediatric-type diffuse high-grade gliomas. This article provides a detailed overview of important molecular, morphological, and clinical aspects for all 11 entities, such as typical genetic alterations, age distribution, variability of the tumor localization, variability of histopathological and radiological findings within each entity, as well as currently available statistical information on prognosis and outcome. Important differential diagnoses are also discussed.

Topographic Mapping of Isolated Thalamic Infarcts Using Vascular and Novel Probabilistic Functional Thalamic Landmarks.

PURPOSE: We aimed to re-evaluate the relationship between thalamic infarct (TI) localization and clinical symptoms using a vascular (VTM) and a novel functional territorial thalamic map (FTM). METHODS: Magnetic resonance imaging (MRI) and clinical data of 65 patients with isolated TI were evaluated (female n = 23, male n = 42, right n = 23, left n = 42). A VTM depicted the known seven thalamic vascular territories (VT: inferolateral, anterolateral, inferomedial, posterior, central, anteromedian, posterolateral). An FTM was generated from a probabilistic thalamic nuclei atlas to determine six functionally defined territories (FT: anterior: memory/emotions; ventral: motor/somatosensory/language; medial: behavior/emotions/nociception, oculomotor; intralaminar: arousal/pain; lateral: visuospatial/somatosensory/conceptual and analytic thinking; posterior: audiovisual/somatosensory). Four neuroradiologists independently assigned diffusion-weighted imaging (DWI) lesions to the territories mapped by the VTM and FTM. Findings were correlated with clinical features. RESULTS: The most frequent symptom was a hemisensory syndrome (58%), which was not specific for any territory. A co-occurrence of hemisensory syndrome and hemiparesis had positive predictive values (PPV) of 76% and 82% for the involvement of the inferolateral VT and ventral FT, respectively. Thalamic aphasia had a PPV of 63% each for involvement of the anterolateral VT and ventral FT. Neglect was associated with involvement of the inferolateral VT/ventral FT. Interrater reliability for the assignment of DWI lesions to the VTM was fair (κ = 0.36), but good (κ = 0.73) for the FTM. CONCLUSION: The FTM revealed a greater reproducibility for the topographical assignment of TI than the VTM. Sensorimotor hemiparesis and neglect are predictive for a TI in the inferolateral VT/ventral FT. The hemisensory syndrome alone does not allow any topographical assignment.

Reliability of Instant Messaging-Based Evaluation of Brain Imaging in Acute Stroke.

BACKGROUND: The use of instant messenger applications among physicians has become common in acute stroke management, especially in developing countries. Photos or video sequences of brain computed tomography (CT) scans are being sent to receive real-time support in assessing radiological findings. We analyzed whether instant messaging-based evaluation is precise enough to extract relevant information from the images. METHODS: In this prospective study, anonymized videos and photos of CT and CT angiography scans of patients with symptoms of acute stroke were recorded from the diagnostic monitor using a smartphone. Two neurologists and 2 neuroradiologists performed evaluation of the images using WhatsApp. The gold standard was set by 2 experienced neuroradiologists who evaluated the CT images with their full radiological equipment. Statistical analysis included the calculation of Cohen kappa (κ). RESULTS: A total of 104 brain images (derived from 81 patients) were included. All 4 raters performed with a perfect (κ=1) interobserver reliability in diagnosing intracerebral hemorrhage. For subarachnoid hemorrhage, interobserver reliability was slightly lower (raters 1, 2, and 3, κ=1; rater 4, κ=0.88). For diagnosing stroke mimics, interobserver reliability showed considerable variations (κ between 0.32 and 1). Alberta Stroke Program Early CT Score differences overall were comparable between raters and did not exceed 3 to 4 points without noticeable outliers. All raters performed with a moderate-to-substantial interobserver reliability for detecting large vessel occlusions (κ=0.48 in rater 1, κ=0.62 in rater 2, and κ=0.63 in raters 3 and 4). CONCLUSIONS: Stroke neurologists can reliably extract information on intracerebral hemorrhage from CT images recorded via smartphone and sent through instant messaging tools. Remote diagnosis of early infarct signs and stroke mimics was less reliable. We developed a standard for the acquisition of images, taking data protection into account.

Activation of Platelets and Occurrence of Cerebral Vasospasm and Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage in a Prospective Pilot-Trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) often leads to poor outcome. The aim of the study was to assess platelet function in patients after SAH. METHODS: In this prospective observational study in patients suffering from SAH, platelet count and aggregability were assessed by multiple electrode aggregometry (MEA) over 14 days. RESULTS: In 12 of 18 patients, cerebral vasospasms (CVS) were diagnosed; of those, five developed delayed cerebral ischemia (DCI). We observed a significant increase in the platelet count compared to baseline from day 8 onwards (p < 0.037) and, in patients with CVS and DCI, a significant difference in outcome classified by the mRS (p = 0.047). Repeated measures ANOVA determined no differences in platelet aggregability in patients with or without CVS/DCI. CONCLUSIONS: Besides an increase in platelet count, we detected no increase in platelet aggregability. Nevertheless, patients after SAH may have increased platelet aggregability, which is not reflected by MEA.

Neurotoxicity of subarachnoid Gd-based contrast agent accumulation: a potential complication of intraoperative MRI?

OBJECTIVE: Intraoperative MRI with Gd-based contrast agent (GBCA) improves the extent of resection of contrast-enhancing brain tumors. Signal changes of CSF due to perioperative GBCA leakage in the subarachnoid space have been reported. However, although GBCA potentially exhibits neurotoxic effects, so far no associated complications have been described. In this case series, the authors report a single-center cohort of patients with subarachnoid GBCA extravasation after intraoperative MRI and discuss potential neurotoxic complications and potential ways of avoiding them. METHODS: All patients with CSF signal increase on unenhanced T1-weighted and FLAIR images on postoperative MRI, who had previously undergone tumor resection with use of intraoperative MRI, were retrospectively included and compared with a control cohort. The control group was matched in age, tumor characteristics, and extent of resection; comparisons were made regarding postoperative seizures and ICU stay. A subgroup with initially diagnosed malignant glioma was additionally analyzed for potential delay of initiation of adjuvant treatment and overall survival. RESULTS: Seven patients with postoperative GBCA accumulation in the subarachnoid space were identified; 5 presented with focal seizures and altered mental status postoperatively. Poor patient condition led to extended ICU stay and prolonged delay of the initiation of adjuvant treatment in patients with newly diagnosed malignant glioma. Overall survival was reduced compared to the matched control group. CONCLUSIONS: The results suggest that there might be a risk of neurotoxic complications if GBCA that is intravenously applied during neurosurgery leaks into the subarachnoid space. Patients with highly vascularized tumors with intraoperative bleeding seem to be especially at risk for GBCA accumulation and neurotoxic complications. Therefore, awareness of the potential risk of complicating GBCA leakage is mandatory in the application of intraoperative GBCA.

Abusive head trauma: experience improves diagnosis.

PURPOSE: The diagnosis of abusive head trauma (AHT) is complex and neuroimaging plays a crucial role. Our goal was to determine whether non-neuroradiologists with standard neuroradiology knowledge perform as well as neuroradiologists with experience in pediatric neuroimaging in interpreting MRI in cases of presumptive AHT (pAHT). METHODS: Twenty children were retrospectively evaluated. Patients had been diagnosed with pAHT (6 patients), non-abusive head trauma-NAHT (5 patients), metabolic diseases (3 patients), and benign enlargement of the subarachnoid spaces (BESS) (6 patients). The MRI was assessed blindly, i.e., no clinical history was given to the 3 non-neuroradiologists and 3 neuroradiologists from 2 different institutions. RESULTS: Blindly, neuroradiologists demonstrated higher levels of sensitivity and positive predictive value in the diagnosis of pAHT (89%) than non-neuroradiologists (50%). Neuroradiologists chose correctly pAHT as the most probable diagnosis 16 out of 18 times; in contrast, non-neuroradiologists only chose 9 out of 18 times. In our series, the foremost important misdiagnosis for pAHT was NAHT (neuroradiologists twice and non-neuroradiologists 5 times). Only victims of motor vehicle accidents were blindly misdiagnosed as pAHT. No usual household NAHT was not misdiagnosed as pAHT. Neuroradiologists correctly ruled out pAHT in all cases of metabolic diseases and BESS. CONCLUSION: MRI in cases of suspected AHT should be evaluated by neuroradiologists with experience in pediatric neuroimaging. Neuroradiologists looked beyond the subdural hemorrhage (SDH) and were more precise in the assessment of pAHT and its differential diagnosis than non-neuroradiologists were. It seems that non-neuroradiologists mainly assess whether or not a pAHT is present depending on the presence or absence of SDH.

Invasive Mold Infection of the Central Nervous System in Immunocompromised Children.

Background: Due to the difficulties in the definite diagnosis, data on brain imaging in pediatric patients with central nervous system (CNS)-invasive mold infection (IMD) are scarce. Our aim was to describe brain imaging abnormalities seen in immunocompromised children with CNS-IMD, and to analyze retrospectively whether specific imaging findings and sequences have a prognostic value. Methods: In a retrospective study of 19 pediatric patients with proven or probable CNS-IMD, magnetic resonance imaging (MRI)-findings were described and analyzed. The results were correlated with outcome, namely death, severe sequelae, or no neurological sequelae. Results: 11 children and 8 adolescents (11/8 with proven/probable CNS-IMD) were included. Seven of the patients died and 12/19 children survived (63%): seven without major neurological sequelae and five with major neurological sequelae. Multifocal ring enhancement and diffusion restriction were the most common brain MRI changes. Diffusion restriction was mostly seen at the core of the lesion. No patient with disease limited to one lobe died. Perivascular microbleeding seen on susceptibility weighted imaging (SWI) and/or gradient-echo/T2* images, as well as infarction, were associated with poor prognosis. Conclusions: The presence of infarction was related to poor outcome. As early microbleeding seems to be associated with poor prognosis, we suggest including SWI in routine diagnostic evaluation of immunocompromised children with suspected CNS-IMD.

Flat Panel Computed Tomography Pooled Blood Volume and Infarct Prediction in Endovascular Stroke Treatment.

Background and Purpose- Patients with large-vessel stroke frequently need to be transferred to comprehensive stroke centers for endovascular treatment. An update of physiological perfusion parameters and stroke progression on arrival is desirable. We examined the reliability of preinterventional pooled blood volume (PBV)-maps acquired by flat-panel detector computed tomography (CT) in the interventional angiography suite. Methods- The volumes of preinterventional perfusion deficit in flat-panel detector CT-PBV source images were compared with final infarct volume on follow-up multislice-CT after endovascular treatment of 29 consecutive patients with occlusion of the middle cerebral artery (MCA) or the distal internal carotid artery (ICA). Results- Endovascular treatment was successful in 26 patients (Thrombolysis in Cerebral Infarction, 2b-3). Overall, the median preinterventional PBV-deficit was 9×larger than median final infarct volume on multislice-CT (86.4 mL [10.3; 111.6] versus 9.6 mL [3.6; 36.8]). This was especially evident in the subgroup of successful recanalization (PBV-deficit: 87.5 mL [10.6; 115.1], final infarct: 8.7 mL [3.6; 29]). In futile recanalization, the final infarct tended to be underestimated (PBV-deficit: 86.4 mL [5.9; -] and final infarct: 116.4 mL [3.5; -]). Conclusions- Flat panel detector CT-PBV is not reliable in predicting the final infarct volume and should not be used in clinical decision making for endovascular treatment of acute cerebral artery occlusions.

Complete Restitution of the Ischemic Penumbra after Successful Thrombectomy : A Pilot Study Using Quantitative MRI.

PURPOSE: Endovascular thrombectomy is highly effective in patients with proximal large artery occlusion but the relevance of reperfusion injury after recanalization is a matter of debate. The aim of this study was to investigate potential residual metabolic distress and microstructural tissue damage or edema after reperfusion using quantitative oxygen-sensitive T2' and T2-mapping in patients successfully treated by thrombectomy. METHODS: Included in this study were 11 patients (mean age 70 ± 11.4 years) with acute ischemic stroke due to internal carotid artery and/or middle cerebral artery occlusion. Quantitative T2 and T2' (1/T2' = 1/T2* - 1/T2) were determined within the ischemic core and hypoperfused but salvaged tissue with delayed time-to-peak (TTP) in patients before and after successful thrombectomy and compared to a control region within the unaffected hemisphere. RESULTS: Decreased T2' values within hypoperfused tissue before thrombectomy showed a normalization after recanalization (p < 0.01). In formerly hypoperfused but salvaged tissue, T2 values increased significantly after thrombectomy (p < 0.05) but did not differ from reference values in the control region. In salvaged tissue, increases of quantitative T2' and T2 to follow-up were more pronounced in areas with severe TTP delay. CONCLUSION: After successful recanalization, T2' re-increased back to normal in formerly hypoperfused areas as a sign of prompt normalization of oxygen metabolism. Furthermore, quantitative T2 in the formerly hypoperfused tissue did not differ from reference values in unaffected tissue. These results indicate complete restitution of salvaged tissue after reperfusion and support the overall safety of endovascular thrombectomy with respect to microstructural tissue integrity.

Invasive EEG-electrodes in presurgical evaluation of epilepsies: Systematic analysis of implantation-, video-EEG-monitoring- and explantation-related complications, and review of literature.

INTRODUCTION: Stereoelectroencephalography (sEEG) is a diagnostic procedure for patients with refractory focal epilepsies that is performed to localize and define the epileptogenic zone. In contrast to grid electrodes, sEEG electrodes are implanted using minimal invasive operation techniques without large craniotomies. Previous studies provided good evidence that sEEG implantation is a safe and effective procedure; however, complications in asymptomatic patients after explantation may be underreported. The aim of this analysis was to systematically analyze clinical and imaging data following implantation and explantation. RESULTS: We analyzed 18 consecutive patients (mean age: 30.5 years, range: 12-46; 61% female) undergoing invasive presurgical video-EEG monitoring via sEEG electrodes (n = 167 implanted electrodes) over a period of 2.5 years with robot-assisted implantation. There were no neurological deficits reported after implantation or explantation in any of the enrolled patients. Postimplantation imaging showed a minimal subclinical subarachnoid hemorrhage in one patient and further workup revealed a previously unknown factor VII deficiency. No injuries or status epilepticus occurred during video-EEG monitoring. In one patient, a seizure-related asymptomatic cross break of two fixation screws was found and led to revision surgery. Unspecific symptoms like headaches or low-grade fever were present in 10 of 18 (56%) patients during the first days of video-EEG monitoring and were transient. Postexplantation imaging showed asymptomatic and small bleedings close to four electrodes (2.8%). CONCLUSION: Overall, sEEG is a safe and well-tolerated procedure. Systematic imaging after implantation and explantation helps to identify clinically silent complications of sEEG. In the literature, complication rates of up to 4.4% in sEEG and in 49.9% of subdural EEG are reported; however, systematic imaging after explantation was not performed throughout the studies, which may have led to underreporting of associated complications.

Introducing the New 3.5/28 Microstent Retriever for Recanalization of Distal Cerebral Arteries in Acute Stroke: Preliminary Results.

BACKGROUND AND PURPOSE: To describe our first experience using a small stent retriever specifically designed for thrombectomy in cerebral arteries with a small caliber (Acandis APERIO® 3.5/28) in patients with acute ischemic stroke. MATERIALS AND METHODS: All patients with an acute ischemic stroke, who underwent endovascular recanalization using the APERIO® thrombectomy device with a diameter of 3.5 mm, were identified in retrospect and included in the present analysis. Demographic and clinical data as well as data on the procedures performed were collected (patient sex, mean age, NIHSS, mRS, TICI score, and complications). RESULTS: Stent retriever-based thrombectomy with the Aperio® 3.5/28 alone (n = 10 vessels) or in combination with other devices (n = 13 vessels) was performed in 22 acute stroke patients with embolic occlusions of distal branches of the anterior and posterior circulations (median NIHSS = 8.5). For vessels treated with the Aperio® 3.5/28, we achieved a TICI 2b/3 reperfusion rate of 73.9%. One patient suffered a symptomatic intracerebral hemorrhage after thrombectomy; otherwise, no procedure-related complications were seen. CONCLUSION: Our data suggest that mechanical thrombectomy of distal cerebral artery occlusions with the Aperio® 3.5/28 is feasible and in general safe, thus offering a promising option for endovascular stroke therapy. However, multicentric studies with larger patient cohorts are necessary to evaluate the clinical benefit.

A Network-Wide Stroke Team Program Reduces Time to Treatment for Endovascular Stroke Therapy in a Regional Stroke-Network.

BACKGROUND AND PURPOSE: Driven by the positive results of randomized, controlled trials of endovascular stroke therapies (EVT) in stroke patients with large vessel occlusion, different approaches to speed up the workflow for EVT candidates are currently being implemented worldwide. We aimed to assess the effect of a simple stroke network-wide workflow improvement project, primarily focusing on i.v. thrombolysis, on process times for patients undergoing EVT. METHODS: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow improvement program for i.v. thrombolysis with the main components of implementing a binding team-based algorithm at every stroke unit of the regional network, educating all stroke teams about non-technical skills and providing a stroke-specific simulation training. Before and after the intervention we recorded periprocedural process times, including patients undergoing EVT at the 3 EVT-capable centers (January - June 2015, n = 80 vs. July 2015 - June 2016, n = 184). RESULTS: In this multi-centric evaluation of 268 patients receiving EVT, we observed a relevant shortening of the median time from symptom onset to EVT specifically in patients requiring secondary transfer by almost an hour (300 min, 25-75% interquartile range [IQR] 231-381 min to 254 min, IQR 215.25-341 min; p = 0.117), including a reduction of the median door-to-groin time at the EVT-capable center in this patient group by 15.5 min (59 min, IQR 35-102 min to 43.5 min, IQR 27.75-81.25 min; p = 0.063). In patients directly admitted to an EVT-capable center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR 83.5-170.5 min to 114.5 min, IQR 66.5-151 min; p = 0.167), but a considerable heterogeneity between the centers was observed (p < 0.001). CONCLUSIONS: We show that a simple network-wide workflow improvement program primarily directed at fast i.v. thrombolysis also accelerates process times for EVT candidates and is a promising measure to improve the performance of an entire stroke network.

Bevacizumab as a last-line treatment for glioblastoma following failure of radiotherapy, temozolomide and lomustine.

In previous trials, bevacizumab failed to prolong the overall survival time in newly diagnosed glioblastoma and at the first recurrence. Randomized clinical trials at the second or further recurrence following the failure of radiotherapy, temozolomide and lomustine, and retrospective analyses focusing on this specific cohort, are not yet available. A total of 62 patients with glioblastoma who received bevacizumab after the failure of standard care, including radiotherapy, temozolomide and lomustine, were retrospectively identified. Patient characteristics, previous treatment details, concomitant therapy, response based on the Response Assessment in Neuro-Oncology criteria, and progression-free survival (PFS) and overall survival (OS) times and rates were evaluated. Furthermore, the PFS and OS times and rates were analyzed for responders and non-responders. Of the patients, 54.8% (n=34) responded to treatment [complete response (CR) 3.2%, n=2; partial response (PR) 51.6%, n=32]. The median PFS time was 3.5 months and the median OS time was 7.5 months. The PFS rate at 6 months was 21.5% and the OS rate at 12 months was 11.5%. Responders (CR or PR) experienced a superior median PFS time compared with non-responders (i.e. stable or progressive disease; 5.4 vs. 1.9 months; P<0.0001) and a superior PFS rate at 6 months (34.9 vs. 7.1%; P<0.0001). The median OS time (8.6 vs. 6.4 months; P<0.0001) and OS rate at 12 months (21.3 vs. 0%; P<0.0001) were also superior in patients who exhibited a response to bevacizumab treatment. In conclusion, the objective response rate and the PFS and OS times and rates indicate that bevacizumab has activity in patients with glioblastoma following the failure of radiotherapy, temozolomide, and lomustine. A randomized trial comparing bevacizumab with best supportive care in these patients is advised.

Predictive Value of Pooled Cerebral Blood Volume Mapping for Final Infarct Volume in Patients with Major Artery Occlusions. A Retrospective Analysis.

PURPOSE: Detection of ischemic core and collateral status is helpful to predict clinical success of thrombectomy in acute cerebral artery occlusion. Angiographic flat panel detector computed tomography (CT) with pooled blood volume (PBV) data acquisition was described to be helpful to estimate ischemic core in stroke patients prior to thrombectomy and to depict cerebral vessels. We therefore retrospectively evaluated preinterventional PBV data of a large collective of ischemic stroke patients prior to thrombectomy to test its predictive value on final infarct considering PBV maps and collateral status. METHODS: We used PBV data from 101 patients with acute cerebral artery occlusion prior to successful thrombectomy to reconstruct PBV maps and collateral status maps. Suspected ischemic core and collateral status were correlated to final infarct on follow-up multislice CT. Furthermore, the influence of time window and patient age was taken into consideration. RESULTS: In 75.2% (95% confidence interval CI 66-82%), suspected ischemic core (PBV) matched with final infarct and in 24.8% (95% CI 17-34%) final infarct was overestimated. In all patients, collateral status could be evaluated, and the better the collateral status, the smaller the final infarct (p = 0.016). Although not statistically significant, poor collaterals seem to be a risk factor for overestimation of final infarct on PBV maps. In patients >80 years old predictive value of PBV and collateral status is better than in patients ≤80 years old (p = 0.04). Increasing time window did not have significant impact on predictive value of PBV and collateral status. CONCLUSION: The PBV data are useful to expeditiously exclude infarct growth and estimate collateral status prior to thrombectomy after a longer interval between initial multislice CT magnetic resonance imaging (MRI) and intervention. However, because of overestimating final infarct in 25% of patients, PBV data presuming large infarct should not be used as the only basis for excluding patients from effective stroke treatment at this point in time.

Early diffusion-weighted MRI lesions after treatment of unruptured intracranial aneurysms: a prospective study.

OBJECTIVE Diffusion-weighted MRI was used to assess periprocedural lesion load after repair of unruptured intracranial aneurysms (UIA) by microsurgical clipping (MC) and endovascular coiling (EC). METHODS Patients with UIA were assigned to undergo MC or EC according to interdisciplinary consensus and underwent diffusion-weighted imaging (DWI) 1 day before and 1 day after aneurysm treatment. Newly detected lesions by DWI after treatment were the primary end point of this prospective study. Lesions detected by DWI were categorized as follows: A) 1-3 DWI spots < 10 mm, B) > 3 DWI spots < 10 mm, C) single DWI lesion > 10 mm, or D) DWI lesion related to surgical access. RESULTS Between 2010 and 2014, 99 cases were included. Sixty-two UIA were treated by MC and 37 by EC. There were no significant differences between groups in age, sex, aneurysm size, occurrence of multiple aneurysms in 1 patient, or presence of lesions detected by DWI before treatment. Aneurysms treated by EC were significantly more often located in the posterior circulation (p < 0.001). Diffusion-weighted MRI detected new lesions in 27 (43.5%) and 20 (54.1%) patients after MC and EC, respectively (not significant). The pattern of lesions detected by DWI varied significantly between groups (p < 0.001). Microembolic lesions (A and B) found on DWI were detected more frequently after EC (A, 14 cases; B, 5 cases) than after MC (A, 5 cases), whereas C and D were rare after EC (C, 1 case) and occurred more often after MC (C, 12 cases and D, 10 cases). No procedure-related unfavorable outcomes were detected. CONCLUSIONS According to the specific techniques, lesion patterns differ between MC and EC, whereas the frequency of new lesions found on DWI is similar after occlusion of UIA. In general, the lesion load was low in both groups, and lesions were clinically silent. Clinical trial registration no.: NCT01490463 ( clinicaltrials.gov ).