Validating EEG source imaging using intracranial electrical stimulation.

Electrical source imaging is used in presurgical epilepsy evaluation and in cognitive neurosciences to localize neuronal sources of brain potentials recorded on EEG. This study evaluates the spatial accuracy of electrical source imaging for known sources, using electrical stimulation potentials recorded on simultaneous stereo-EEG and 37-electrode scalp EEG, and identifies factors determining the localization error. In 11 patients undergoing simultaneous stereo-EEG and 37-electrode scalp EEG recordings, sequential series of 99-110 biphasic pulses (2 ms pulse width) were applied by bipolar electrical stimulation on adjacent contacts of implanted stereo-EEG electrodes. The scalp EEG correlates of stimulation potentials were recorded with a sampling rate of 30 kHz. Electrical source imaging of averaged stimulation potentials was calculated utilizing a dipole source model of peak stimulation potentials based on individual four-compartment finite element method head models with various skull conductivities (range from 0.0413 to 0.001 S/m). Fitted dipoles with a goodness of fit of ≥80% were included in the analysis. The localization error was calculated using the Euclidean distance between the estimated dipoles and the centre point of adjacent stimulating contacts. A total of 3619 stimulation locations, respectively, dipole localizations, were included in the evaluation. Mean localization errors ranged from 10.3 to 26 mm, depending on source depth and selected skull conductivity. The mean localization error increased with an increase in source depth (r(3617) = [0.19], P = 0.000) and decreased with an increase in skull conductivity (r(3617) = [-0.26], P = 0.000). High skull conductivities (0.0413-0.0118 S/m) yielded significantly lower localization errors for all source depths. For superficial sources (<20 mm from the inner skull), all skull conductivities yielded insignificantly different localization errors. However, for deeper sources, in particular >40 mm, high skull conductivities of 0.0413 and 0.0206 S/m yielded significantly lower localization errors. In relation to stimulation locations, the majority of estimated dipoles moved outward-forward-downward to inward-forward-downward with a decrease in source depth and an increase in skull conductivity. Multivariate analysis revealed that an increase in source depth, number of skull holes and white matter volume, while a decrease in skull conductivity independently led to higher localization error. This evaluation of electrical source imaging accuracy using artificial patterns with a high signal-to-noise ratio supports its application in presurgical epilepsy evaluation and cognitive neurosciences. In our artificial potential model, optimizing the selected skull conductivity minimized the localization error. Future studies should examine if this accounts for true neural signals.

Factors influencing the detection of treatable epileptogenic lesions on MRI. A randomized prospective study.

BACKGROUND: To prospectively analyze factors associated with detecting epileptogenic lesions on MRI within the work-sharing process of neurologists, epileptologists, radiologists and neuroradiologists. METHODS: We assembled four sets of six MRI scans, each set representing five typical epileptogenic lesions (hippocampal sclerosis or limbic encephalitis; focal cortical dysplasias; periventricular nodular or other heterotopias; long-term epilepsy associated tumors; gliotic scar, hemosiderin or cavernoma), and non - lesional epilepsy. At professional conferences, we invited neurologists, epileptologists, radiologists, and neuroradiologists to read two out of four MRI sets, one of which was presented with a clinical focus hypothesis. Participants were randomly assigned to MRI sets. Effects of examiners' specialty, duration of training and professional experience on detection rate of epileptogenic lesions were investigated. RESULTS: Fourty-eight neurologists, 22 epileptologists, 20 radiologists and 21 neuroradiologists read 1323 MRI scans. Overall, 613 of 1101 (55.7%) epileptogenic lesions were detected. Long-term epilepsy associated tumors (182/221, 82.4%) were found more frequently than gliotic scar, hemosiderin or cavernoma (157/220, 71.4%), hippocampal sclerosis or limbic encephalitis (141/220, 64.1%), nodular heterotopia (68/220, 30.9%) and focal cortical dysplasias (65/220, 29.5%, p < 0.001). Provision of a focus hypothesis improved the detection of hippocampal sclerosis or limbic encephalitis (86/110, 78.2% vs 55/110, 50%, p < 0.001) and focal cortical dysplasias (40/110, 36.4% vs 25/110, 22.7%, p = 0.037). Neuroradiologists and epileptologists were more likely than radiologists and neurologists to be amongst the most successful readers. In multivariable analysis, type of epileptogenic lesion, specialty of MRI reader, and provision of focus hypothesis predicted correct identification of epileptogenic lesions. CONCLUSIONS: Epileptogenic lesions are often not recognized on MRI even by expert readers. Their detection can be improved by providing a focus hypothesis. These results stress the need for training in the MRI characteristics of epilepsy - specific pathology, and, most importantly, interdisciplinary communication between neurologists/epileptologists and (neuro)radiologists to improve detection of epileptogenic lesions.

Microstructural integrity of affective neurocircuitry in patients with dissociative seizures is associated with emotional task performance, illness severity and trauma history.

PURPOSE: To identify variations in white matter tract integrity related to behavioural control in response to emotional stimuli in patients with dissociative seizures (DS) and healthy controls (HC), and examine associations with illness characteristics and psychological trauma history. METHODS: Twenty DS patients and 20 HC completed an emotional go/no-go task and questionnaires, and then underwent diffusion tensor imaging (DTI). RESULTS: Patients had higher false alarm rates in response to negative emotional stimuli than HC. Task performance was correlated with self-reported difficulties in emotional awareness and regulation in everyday life. White matter analysis using tract-based spatial statistics revealed no between-group differences. In patients, fractional anisotropy (FA) in the right uncinate fasciculus, right and left fornix/stria terminalis, and corpus callosum were correlated with task performance. Similar results were found for radial diffusivity (RD), but not mean (MD) or axial diffusivity (AD). In HC, task performance was associated with AD and RD of fewer and smaller clusters in the corpus callosum and right fornix/stria terminalis, and none for FA or MD. Probabilistic tractography of thus identified tracts revealed that mean FA values were correlated with illness parameters (right fornix/stria terminalis with age at onset; posterior corpus callosum with seizure frequency), and psychological trauma history (traumatic experiences during adolescence with anterior corpus callosum). CONCLUSIONS: Patients with DS show impaired behavioural control in response to emotional stimuli. Microstructural variations in task-related neurocircuitry show associations with illness parameters and psychological trauma history. Future studies using psychiatric controls should examine the specificity of these findings.

Twenty-year follow-up of a pilot/phase II trial on the Bonn protocol for primary CNS lymphoma.

OBJECTIVE: To determine whether a fraction of patients with primary CNS lymphoma (PCNSL) had been cured by systemic and intraventricular methotrexate- and cytarabine-based chemotherapy (Bonn protocol) after a very long-term follow-up of nearly 20 years. METHODS: Sixty-five patients (median age 62 years, range 27-75; median Karnofsky performance score 70, range 20-90) had been treated with systemic and intraventricular polychemotherapy without whole brain radiotherapy from September 1995 until December 2001. All patients still alive in 2019 were contacted and interviewed on their current life situation. RESULTS: Median follow-up for surviving patients was 19.6 years (17.5-23.3 years). Out of 65 patients, 11 (17%) were still alive. Six of those never experienced any relapse. For the whole study population, median overall survival (OS) was 4.4 years (95% confidence interval [CI] 2.9-5.9); for patients ≤60 years, 11.0 years (95% CI 4.8-17.0). The 10-year OS rate for the entire cohort was 29% and the estimated 20-year OS rate was 19%. Four late relapses were observed after 9.8, 10.3, 13.3, and 21.0 years. CONCLUSION: At a median follow-up of 19.6 years, 17% of patients were alive and free of tumor; however, even after response for decades, an inherent risk of relapse, either systemic or cerebral, characterizes the biology of PCNSL. CLASSIFICATION OF EVIDENCE: This work provides Class III evidence that PCNSL treatment with methotrexate-based polychemotherapy including intraventricular therapy is associated with long-term disease control in some patients.

Intravenous Thrombolysis Facilitates Successful Recanalization with Stent-Retriever Mechanical Thrombectomy in Middle Cerebral Artery Occlusions.

AIM: Several factors influence the outcome after acute ischemic stroke secondary to proximal occlusions of cerebral vessels. Among others, noneligibility for intravenous thrombolysis (IVT) and incomplete revascularization have been identified as predictors of unfavorable outcome. The aim of this study was to investigate whether concomitant IVT influences the revascularization efficacy in mechanical thrombectomy (MT). METHODS: This study conducted a retrospective analysis of all consecutive patients presenting with an anterior circulation stroke due to large-artery occlusion with imaging evidence who were treated with MT between July 2012 and December 2013 at 2 high-volume stroke centers. Imaging data were regraded and re-evaluated according to the modified Treatment in Cerebral Ischemia scale and its respective vessel occlusion site definitions. Clinical end points included National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale; imaging and procedural measures were technical end points. RESULTS: We identified 93 patients who presented with an occlusion of the middle cerebral artery (MCA): of these patients, 66 (71%) received IVT. We did not find statistically significant differences in the baseline NIHSS score, time from symptom onset to groin puncture, and age when comparing the IVT group with the non-IVT group. The rate of successful recanalizations (modified Treatment in Cerebral Ischemia score ≥ 2b) was significantly higher in patients with MCA occlusion and concomitant IVT (P = .01). Stepwise logistic regression identified IVT and thrombus length as predictive factors for successful mechanical recanalization (P = .004, P = .002). CONCLUSION: IVT and thrombus length are predictive factors for a successful recanalization in MT for acute ischemic stroke with underlying MCA occlusion.

Direct aspiration first pass technique for the treatment of acute ischemic stroke: initial experience at a European stroke center.

INTRODUCTION: Over the past decade, endovascular techniques for the treatment of acute ischemic stroke have emerged significantly. However, revascularization rates are limited at approximately 80%, and mechanical thrombectomy procedures still last about 1 h. Therefore, we investigated the novel direct aspiration first pass technique for its efficacy and safety. METHODS: Our neurointerventional database was screened for patients who received mechanical thrombectomy for acute ischemic stroke using the Penumbra 5MAX ACE aspiration catheter on an intention to treat basis between November 2013 and June 2014. Procedural data, including modified Thrombolysis in Cerebral Infarction (mTICI) score, procedural timings, and complications, as well as clinical data at admission and discharge, were analyzed. RESULTS: 54 patients received mechanical thrombectomy using the 5MAX ACE. Median age was 69 (39-94) years (54% were men). Baseline National Institutes of Health Stroke Scale (NIHSS) score was 15 (2-27) and 44/54 (81%) patients received intravenous thrombolysis. Vessel occlusion sites were 91% anterior circulation and 9% posterior circulation. A successful revascularization result (mTICI ≥2b) was achieved in 93% of cases whereas direct aspiration alone was successful in 30/54 (56%) cases; among these, median time from groin puncture to revascularization was 30 min (9-113). Symptomatic intracranial hemorrhage occurred in 2/54 (4%) patients, and embolization to new territories in 3/54 (6%). Median NIHSS at discharge was 6 (0-24); 46% of patients were independent at discharge. CONCLUSIONS: The direct aspiration first pass technique proofed to be fast, effective, and safe. Promising revascularization results can be achieved quickly in more than 50% of patients using this technique as the firstline option. Nevertheless, stent retrievers are still warranted in approximately 40% of cases to achieve a favorable revascularization result.

Multicenter clinical experience in over 125 patients with the Penumbra Separator 3D for mechanical thrombectomy in acute ischemic stroke.

BACKGROUND: The aim of this study was to assess reperfusion and clinical outcome of treatment with the self-expanding retrievable Separator 3D in revascularization of acute ischemic stroke. The three-dimensional (3D) device secures thrombus with direct aspiration and supports debulking of the clot. METHODS: At two centers, 129 consecutive stroke patients with National Institutes of Health Stroke Scale (NIHSS) scores ≥5 were treated with mechanical thrombectomy using the Separator 3D as a component of the Penumbra System within 8 h of symptom onset; modified Treatment in Cerebral Infarction (mTICI) revascularization scores, NIHSS score on admission and discharge, mortality rates, and modified Rankin Scale (mRS) outcomes at 90 days were evaluated. RESULTS: A total of 129 vessels in 129 patients were treated. Occlusions were located in the middle cerebral artery (MCA, 48%), internal carotid artery (ICA, 33%), cervical ICA-MCA (3%), and vertebrobasilar arteries (16%). Intravenous thrombolytic therapy with recombinant tissue plasminogen activator was given to 78% of patients. Median NIHSS was 15 prior to treatment. Reperfusion to mTICI 2b or 3 was successful in 96/129 (74%) target arterial lesions, with more than half of cases (51%) achieving mTICI 3. The mean time from arterial puncture to revascularization was 65 min. At 90 days, the symptomatic intracranial hemorrhage rate was 4%, all cause mortality was 32%, and 43/99 patients (43%) achieved functional independence with an mRS score of ≤2. CONCLUSIONS: The results suggest that the Separator 3D enables safe and effective revascularization of occluded large arteries in acute stroke intervention, leading to a high rate of functional independence at 90 days.

Lumbar juxta-facet joint cysts in association with facet joint orientation, -tropism and -arthritis: A case-control study.

OBJECTIVE: To assess the association between juxta-facet-joint cysts (JFC) occurrence at the lumbar spine and Facet Joint (FJ) orientation, -tropism and -arthritis. METHODS: Study group, 36 consecutive patients with JFC and the same number of controls, with degenerative diseases without JFC were match paired for demographics and spine segment. Parameter assessment was by T2-weighted axial MRI scans. JFC diagnosis was confirmed histopathologically. Group comparison was by Student's t-test for continuous variables and X(2) for categorical variables. RESULTS: Nineteen female and 17 male patients, aged between 45 and 85 years (mean 67.19 ± 10.3 years) had a mean JFC size of 9.26 ± 4.8mm occurring most frequently in the segment L4-L5 (75% n=25) and on the left side (61%). Mean FJ orientation of the study group was significantly more coronal compared to controls (left side 42° vs 36°, p<0.02*, 95% confidence interval: 0.9-11.5 and right side 43° vs 37°, p<0.02*, 95% confidence interval: 0.6-10.6 respectively). However, individual intersegmental analysis for study group patients showed the JFC bearing side to be significantly more sagittally oriented 40° ± 11.2° compared to 45° ± 13.2° for the side without FJC (p<0.03*, 95% confidence interval: 8.1-1.7). 50% of the study group showed FJ asymmetry compared to 30% in controls, with a trend for FJ tropism (p<0.07). Severe (grade 3) FJ arthritis was significantly more predominant in the study group 23/33 (p<0.001*) as compared to controls. CONCLUSIONS: Compared to a control group, JFC occurrence is associated with significant higher rates of arthritis and coronally orientated FJ. At intersegment comparison within the same patient cysts located in more sagittally orientated FJ and the asymmetric segments show a trend for FJ tropism.

Endovascular stroke therapy at nighttime and on weekends-as fast and effective as during normal business hours?

INTRODUCTION: There is only limited data on the influence of the admission time (normal business hours versus nighttime and weekends) on procedural timings, revascularization efficacy, and outcome after mechanical thrombectomy. We investigated whether the admission time has an impact on the above-mentioned factors. METHODS: Our neurointerventional database was screened for all mechanical thrombectomies in anterior circulation acute ischemic stroke between 07/13 and 06/14. Outcome measures were procedural timings and clinical and demographic data; we compared patients who were admitted at normal business hours (Monday to Friday 8:00-18:00) to those admitted at night or at the weekend. RESULTS: 98 patients were identified. Of them, 52 (53%) were admitted during normal business hours, the remainder at night or at weekend. There was no statistically significant difference between the groups regarding the time from symptom-onset to admission, baseline National Institutes of Health Stroke Scale (NIHSS) or IVT-rate. There was a significant difference between groups for door-to-reperfusion timing, favoring patients admitted during normal business hours (146 versus 165 min, p = 0.02). Door-to-groin-puncture and groin-puncture-to-reperfusion time did not differ significantly. The rate of successful revascularizations (mTICI ≥ 2b) and the rate of favorable clinical outcome at discharge (mRS ≤ 2) did not differ between groups (77% versus 78% and 37% versus 35%, respectively). CONCLUSIONS: There was a statistically significant prolongation of door-to-reperfusion timings for patients admitted during nighttime and weekends; it went along neither with a lower rate of successful revascularizations nor with a lower rate of favorable outcome in our series. ABBREVIATIONS: AFatrial fibrillationAISacute ischemic strokeCTAcomputed tomography angiographyDMdiabetes mellitusENTembolization to new territoryEVTendovascular therapyHLPhyperlipoproteinemiaHTNhypertensionIQRinter-quartile rangeIVTintravenous thrombolysismRSmodified Rankin ScaleMTmechanical thrombectomyNIHSSNational Institutes of Health Stroke Scalen.s.not significantsICHsymptomatic intracranial hemorrhage.

Low-profile Visualized Intraluminal Support device (LVIS Jr) as a novel tool in the treatment of wide-necked intracranial aneurysms: initial experience in 32 cases.

BACKGROUND AND PURPOSE: The focus of this study was to determine ease of deployment, safety and effectiveness of the LVIS Jr device. METHODS: A retrospective analysis was performed of 32 cases comprising 34 aneurysms in which the LVIS Jr device was used for stent-assisted coil embolization of intracranial aneurysms from February to October 2012, including all clinical and angiographic data as well as mid-term follow-up (1-12 months of treatment). RESULTS: The median age of the patients was 54 years (range 21-76) and 19 (59%) were women. The aneurysms were ruptured in 12/34 cases (35.3%); 26 (76.4%) were located within the anterior circulation and the remaining 8 (23.5%) were located in the posterior circulation. Eleven of the 34 aneurysms (32.3%) were treated with a Y-stent configuration. Immediate total occlusion was observed in 16/34 (47%), near total occlusion (90-95%) in 5/34 (14.7%) and a 'dog ear' or subtotal occlusion in 12/34 (35.2%). A single aneurysm was treated without coil embolization. Complications occurred in 5/34 cases (15%), including two cases of in-stent thrombosis. CONCLUSIONS: Implantation of the LVIS Jr device as a support device for stent-assisted coil embolization seems to be safe and effective. The LVIS Jr device can also be implanted in a Y-stent configuration, offering a novel technique with a potentially lower risk of thromboembolic complications compared with other devices.

Complications of mechanical thrombectomy for acute ischemic stroke-a retrospective single-center study of 176 consecutive cases.

INTRODUCTION: There is only very limited data about complications in mechanical thrombectomy for acute ischemic stroke. The purpose of this study was to evaluate the frequency and the clinical relevance of procedure-related complications in mechanical thrombectomy. METHODS: We conducted a retrospective analysis of 176 consecutive acute ischemic stroke cases that were treated with mechanical thrombectomy. Primary outcome measures included the following: symptomatic intracranial hemorrhage (sICH), vessel dissection, emboli to new vascular territories, vasospasm, and stent dislocation/occlusion whenever appropriate. Secondary outcome measures included mTICI score, time from symptom onset to revascularization, and time from groin puncture to revascularization as well as the early clinical outcome at discharge. RESULTS: Complications occurred in 20/176 patients (11 %) comprising 23 adverse events at the following rates: sICH 8/176 (5 %), emboli to new vascular territories 4/176 (2 %); vessel dissection 3/176 (2 %); vasospasm of the access vessel 5/176 (3 %); stent dislocation in 1/42 (2 %); and stent occlusion in 2/42 (5 %). Two out of 20 (10 %) suffered from two or more procedure-related complications. There was a statistically significant correlation of complications with time from groin puncture to revascularization, unfavorable revascularization results, and unfavorable clinical outcome. CONCLUSION: Overall, the frequency of procedure-related complications lies within acceptable limits for an emergency procedure. The endovascular treatment does not seem to add significantly to the stroke patients' risk of sICH but implies an innate risk of stroke in an initially uninvolved territory. Furthermore, a prolonged endovascular procedure beyond an hour is correlated with higher complication rates, which underlines the importance of a swift and complete revascularization.

Isolated central nervous system relapse of systemic lymphoma (SCNSL): clinical features and outcome of a retrospective analysis.

We analyzed clinical outcome of patients with an isolated central nervous system lymphoma (CNSL) relapse after systemic non-Hodgkin's lymphoma (NHL). All 23 patients with an isolated secondary CNSL (SCNSL) treated at two institutions from 04/2003-12/2007 were included into this analysis. At cerebral relapse, 15/23 patients were treated with a regimen consisting of high-dose methotrexate (Bonn protocol). After a median follow-up of 6.5 months (range 1-68), 15/23 (65%) patients with SCNSL had relapsed or progressed. HD (high-dose)- methotrexate (MTX) chemotherapy according to the Bonn protocol is effective concerning response rates; however, overall survival of patients with SCNSL seems to be impaired in comparison to relapses in primary CNSL (PCNSL).

Neurologic complications after intrathecal liposomal cytarabine in combination with systemic polychemotherapy in primary CNS lymphoma.

Intrathecal application of liposomal cytarabine (Ara-C) (DepoCyte(®)) has been associated with neurotoxicity when applied as part of a polychemotherapy regimen. Patients with primary central nervous system lymphoma treated with high-dose systemic methotrexate (MTX)- and Ara-C-based polychemotherapy including six cycles of liposomal Ara-C (50 mg intrathecally every 3 weeks) were prospectively monitored for neurotoxic side-effects. Between November 2005 and February 2009, 149 intrathecal applications of liposomal cytarabine (DepoCyte(®)) were carried out in 33 patients, 7 (21%) of whom developed an incomplete conus medullaris/cauda equina syndrome with incontinence for bladder (6) and bowel function (3) or lumbosacral polyradicular paresis (1), resolving only incompletely over a follow-up period of 9-30 months. In six of these seven patients, lumbosacral magnetic resonance imaging (MRI) was negative for leptomeningeal infiltration or arachnoiditis. Cerebrospinal fluid (CSF) analysis performed in six of these seven patients showed normal cell count in all and increased total protein in four of them. One patient among these seven suffered a seizure without other identifiable causes. Conus/cauda syndrome has to be considered as a serious potential neurotoxic side-effect in patients receiving liposomal Ara-C as part of a multimodal regimen including high-dose systemic MTX and Ara-C.

Diagnosis of leptomeningeal disease in diffuse large B-cell lymphomas of the central nervous system by flow cytometry and cytopathology.

Reliable detection of leptomeningeal disease has the potential of facilitating the diagnosis of central nervous system (CNS) lymphoma and is important for therapeutic considerations. Currently, the standard diagnostic procedure for the detection of lymphoma in the cerebrospinal fluid is cytopathology. To improve the limited specificity and sensitivity of cytopathology, flow cytometry has been suggested as an alternative. Here, we evaluated multi-parameter flow cytometry in combination with conventional cytopathology in cerebrospinal fluid (CSF) samples from 30 patients with primary CNS lymphoma and seven patients with secondary CNS lymphoma. Overall, in 11 of 37 (29.7%) patients with CNS lymphoma, lymphoma cells were detected in CSF by flow cytometry, while cytopathology was less sensitive displaying unequivocally malignant CSF cells in only seven of all 37 (18.9%) patients. Six (16.2%) patients showed cytopathological results suspicious of lymphoma; however, in only one of these patients, the diagnosis of CSF lymphoma cells could be confirmed by flow cytometry. In primary CNS lymphomas (PCNSL), seven of 30 (23.3%) patients were positive for CSF lymphoma cells in flow cytometry, in contrast to four (13.3%) patients with PCNSL with definitely positive cytopathology. In summary, our results suggest that multi-parameter flow cytometry increases the sensitivity and specificity of leptomeningeal disease detection in CNS lymphomas. Both methods should be applied concurrently for complementary diagnostic assessment in patients with CNS lymphoma.