Seizure after surgical treatment of chronic subdural hematoma-Associated factors and effect on outcome.

Introduction: Chronic subdural hematoma (cSDH) is becoming more prevalent due to population aging and the increasing use of antithrombotic drugs. Postoperative seizure in cSDH have a negative effect on outcome, and there currently no consensus regarding prophylactic anti-epileptic drug (AED) treatment. The objective of this study was to evaluate predisposing and triggering factors associated with postoperative epileptic seizure in patients with cSDH. Methods: All patients, who were surgically treated for cSDH in a single tertiary care center between 2015 and 2019, were considered for inclusion. Relevant patient- and hematoma-specific characteristics were retrospectively extracted from hospital records. Paroxysmal events categorized by the treating physician as suspected postoperative seizures were noted. The clinical outcome was extracted from the last available follow-up visit and classified according to the Glasgow outcome scale (GOS). Results: Of the included 349 patients, 54 (15.5%) developed suspected postoperative epileptic complications in the form of early seizure (≤ 7 days) in 11 patients (3.2%) and late seizure (>7 days) in 43 patients (12.3%). In the logistic regression analysis, solely depressed brain volume (supratentorial volume (ml) not filled with re-expanded brain) was independently associated with postoperative seizure (odds ratio [OR] 1.006, 95% CI: 1.001-1.011; p = 0.034). The occurrence of postoperative seizure (OR 6.210, 95% CI: 2.704-14.258; p < 0.001) and preoperative Markwalder grading (OR 2.919, 95% CI: 1.538-5.543; p = 0.001) were independently associated with unfavorable (GOS1-3) outcome. Conclusion: Larger postoperative depressed brain volume was the only factor independently associated with suspected postoperative seizure, and it could help identify a subgroup of patients with higher susceptibility to epileptic events. Based on our data, no formal recommendation can be made regarding the prophylactic use of anti-epileptic drugs. Nevertheless, the relative safety of new generation AEDs and the detrimental effect of postoperative seizure on outcome may justify its use in a selected patient population.

MRI appearance of chronic subdural hematoma.

Objective: We aimed to describe the magnetic resonance imaging (MRI) characteristics of chronic subdural hematoma (cSDH) and to ascribe MRI patterns. Methods: A total of 20 patients having 27 subdural hematomas underwent contrast-enhanced (CE) MRI of the brain at our institution between April 2019 and May 2021. The images were independently evaluated by two experienced neuroradiologists with regard to imaging characteristics on T1w, T2w, T2*-GRE, FLAIR, diffusion-weighted magnetic resonance imaging (DWI), and CE images. Results: The signal characteristics of cSDH on T1- and T2-weighted images were rather heterogeneous. The majority of hematomas (74%) had internal septations. Surprisingly, contrast enhancement along the outer membrane adjacent to the cranium was noticed in all hematomas. There was also contrast enhancement along the inner membrane adjacent to the brain in more than one-third of the hematomas (37%). In approximately two-thirds of the cSDH (62%), there was a mass-like enhancement of the hematoma. Most hematomas (89%) were partially hypointense on T2*-GRE and/or susceptibility-weighted imaging (SWI). Restricted diffusion was detected in approximately one-third of the hematomas (33%). Conclusion: Consistent contrast enhancement along the outer membrane, triangular-shaped contrast enhancement at the borders of the cSDH, and infrequent enhancement of the inner membrane may help to distinguish cSDH from other entities such as empyema and tumors. Mass-like enhancement may refer to non-solid hematomas and could be an indicator for hematoma growth and a possible surrogate for successful endovascular embolization. Restricted diffusion in a subdural mass is not specific for empyema but may also be found in cSDH.

Risk factors of recurrence in chronic subdural hematoma and a proposed extended classification of internal architecture as a predictor of recurrence.

Chronic subdural hematomas (cSDHs) constitute one of the most prevalent intracranial disease entities requiring surgical treatment. Although mostly taking a benign course, recurrence after treatment is common and associated with additional morbidity and costs. Aim of this study was to develop hematoma-specific characteristics associated with risk of recurrence. All consecutive patients treated for cSDH in a single university hospital between 2015 and 2019 were retrospectively considered for inclusion. Size, volume, and midline shift were noted alongside relevant patient-specific factors. We applied an extended morphological classification system based on internal architecture in CT imaging consisting of eight hematoma subtypes. A logistic regression model was used to assess the classification's performance on predicting hematoma recurrence. Recurrence was observed in 122 (32.0%) of 381 included patients. Apart from postoperative depressed brain volume (OR 1.005; 95% CI 1.000 to 1.010; p = 0.048), neither demographic nor factors related to patient comorbidity affected recurrence. The extended hematoma classification was identified as a significant predictor of recurrence (OR 1.518; 95% CI 1.275 to 1.808; p < 0.001). The highest recurrence rates were observed in hematomas of the homogenous (isodense: 41.4%; hypodense: 45.0%) and sedimented (50.0%) types. Our results support that internal architecture subtypes might represent stages in the natural history of chronic subdural hematoma. Detection and treatment at a later stage of spontaneous repair can result in a reduced risk of recurrence. Based on their high risk of recurrence, we advocate follow-up after treatment of sedimented and homogenous hematomas.

Progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome in seven patients with sarcoidosis: a critical discussion of treatment and prognosis.

Progressive multifocal leukoencephalopathy (PML) is a subacute brain infection by the opportunistic John Cunningham (JC) virus. Herein, we describe seven patients with PML, lymphopenia, and sarcoidosis, in three of whom PML was the first manifestation of sarcoidosis. At onset, the clinical picture comprised rapidly progressive spastic hemi- or limb pareses as well as disturbances of vision, speech, and orientation. Cerebral magnetic resonance imaging showed T2-hyperintense, confluent, mainly supratentorial lesions. Four patients developed punctate contrast enhancement as a radiological sign of an immune reconstitution inflammatory syndrome (IRIS), three of them having a fatal course. In the cerebrospinal fluid, the initial JC virus load (8-25,787 copies/ml) did not correlate with interindividual severity; however, virus load corresponded to clinical dynamics. Brain biopsies (n = 2), performed 2 months after symptom onset, showed spotted demyelination and microglial activation. All patients had lymphopenia in the range of 270-1150/µl. To control JC virus, three patients received a combination of mirtazapine and mefloquine, another two patients additionally took cidofovir. One patient was treated with cidofovir only, and one patient had a combined regimen with mirtazapine, mefloquine, cidofovir, intravenous interleukin 2, and JC capsid vaccination. To treat sarcoidosis, the four previously untreated patients received prednisolone. Three patients had taken immunosuppressants prior to PML onset, which were subsequently stopped as a potential accelerator of opportunistic infections. After 6-54 months of follow up, three patients reached an incomplete recovery, one patient progressed, but survived so far, and two patients died. One further patient was additionally diagnosed with lung cancer, which he died from after 24 months. We conclude that the combination of PML and sarcoidosis is a diagnostic and therapeutic challenge. PML can occur as the first sign of sarcoidosis without preceding immunosuppressive treatment. The development of IRIS might be an indicator of poor outcome.

Development of a Polymer-Based Biodegradable Neurovascular Stent Prototype: A Preliminary In Vitro and In Vivo Study.

Biodegradable stents are not established in neurovascular interventions. In this study, mechanical, radiological, and histological characteristics of a stent prototype developed for neurovascular use are presented. The elasticity and brittleness of PLA 96/4, PLDL 70/30, PCL, and PLGA 85/15 and 10/90 polymers in in vitro experiments are first analyzed. After excluding the inapt polymers, degradability and mechanical characteristics of 78 PLGA 85/15 and PLGA 10/90 stent prototypes are analyzed. After excluding PLGA 10/90 stents because of rapid loss of mass PLGA 85/15 stents in porcine in vivo experiments are analyzed. Angiographic occlusion rates 7 d, 1 month, 3 months, and 6 months after stent implantation are assessed. Histological outcome measures are the presence of signs of inflammation, endothelialization, and the homogeneity of degradation after six months. One case of stent occlusion occurs within the first 7 d. There is a prominent foreign-body reaction with considerable mononuclear and minor granulocytic inflammation combined with incomplete fragmental degradation of the struts. It is possible to produce a stent prototype with dimensions that fit the typical size of carotid arteries. Major improvements concerning thrombogenicity, degradation, and inflammatory response are required to produce biodegradable stents that are suitable for neurovascular interventions.

Genetic Imbalance in Patients with Cervical Artery Dissection.

BACKGROUND: Genetic and environmental risk factors are assumed to contribute to the susceptibility to cervical artery dissection (CeAD). To explore the role of genetic imbalance in the etiology of CeAD, copy number variants (CNVs) were identified in high-density microarrays samples from the multicenter CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study and from control subjects from the CADISP study and the German PopGen biobank. Microarray data from 833 CeAD patients and 2040 control subjects (565 subjects with ischemic stroke due to causes different from CeAD and 1475 disease-free individuals) were analyzed. Rare genic CNVs were equally frequent in CeAD-patients (16.4%; n=137) and in control subjects (17.0%; n=346) but differed with respect to their genetic content. Compared to control subjects, CNVs from CeAD patients were enriched for genes associated with muscle organ development and cell differentiation, which suggests a possible association with arterial development. CNVs affecting cardiovascular system development were more common in CeAD patients than in control subjects (p=0.003; odds ratio (OR) =2.5; 95% confidence interval (95% CI) =1.4-4.5) and more common in patients with a familial history of CeAD than in those with sporadic CeAD (p=0.036; OR=11.2; 95% CI=1.2-107). CONCLUSION: The findings suggest that rare genetic imbalance affecting cardiovascular system development may contribute to the risk of CeAD. Validation of these findings in independent study populations is warranted.

Imaging of Ventriculoperitoneal Shunt Complications: Comparison of Whole Body Low-Dose Computed Tomography and Radiographic Shunt Series.

OBJECTIVE: To determine diagnostic value and radiation exposure of low-dose computed tomography (LD-CT) compared to radiographic shunt series (SS) for the detection of ventriculoperitoneal (VP) shunt complications. METHODS: Fourteen VP shunts were implanted in 7 swine cadavers. Mechanical complications were induced in 50% of VP shunts. Low-dose CT (80 kVp, 10 mAs, Pitch = 1.5) and SS were acquired. Dose area product (DAP) and effective doses for SS and LD-CT were collected. Scoring of diagnostic confidence and blinded readings of SS and CT data were performed. RESULTS: The sensitivity of LD-CT was high (0.97; 95% confidence interval, 0.91-1.00) with excellent interobserver agreement (κ = 0.88). Similarly, the sensitivity of SS was high (0.82; 95% confidence interval, 0.68-0.95) with good interobserver agreement (κ = 0.68). In contrast, LD-CT was associated with significantly higher diagnostic confidence (4.64 ± 0.41 vs 2.71 ± 0.73; P < 0.01) and significantly lower radiation exposure (effective dose: 0.26 mSv vs 1.06 mSv; DAP: 265.4 µGym vs 724.8 µGym; P < 0.001). CONCLUSIONS: For the assessment of suspected VP shunt complications, LD-CT provides excellent sensitivity and higher diagnostic confidence with lower radiation exposure compared with SS.

Molecular Ultrasound Imaging of αvß3-Integrin Expression in Carotid Arteries of Pigs After Vessel Injury.

OBJECTIVES: Interventions such as balloon angioplasty can cause vascular injury leading to platelet activation, thrombus formation, and inflammatory response. This induces vascular smooth muscle cell activation and subsequent re-endothelialization with expression of αvß3-integrin by endothelial cells and vascular smooth muscle cell. Thus, poly-N-butylcyanoacrylate microbubbles (MBs) targeted to αvß3-integrin were evaluated for monitoring vascular healing after vessel injury in pigs using molecular ultrasound imaging. MATERIALS AND METHODS: Approval for animal experiments was obtained. The binding specificity of αvß3-integrin-targeted MB to human umbilical vein endothelial cells was tested with fluorescence microscopy. In vivo imaging was performed using a clinical ultrasound system and an 8-MHz probe. Six mini pigs were examined after vessel injury in the left carotid artery. The right carotid served as control. Uncoated MB, cDRG-coated MB, and αvß3-integrin-specific cRGD-coated MB were injected sequentially. Bound MBs were assessed 8 minutes after injection using ultrasound replenishment analysis. Measurements were performed 2 hours, 1 and 5 weeks, and 3 and 6 months after injury. In vivo data were validated by immunohistochemistry. RESULTS: Significantly stronger binding of cRGD-MB than MB and cDRG-MB to human umbilical vein endothelial cells was found (P < 0.01). As vessel injury leads to upregulation of αvß3-integrin, cRGD-MBs bound significantly stronger (P < 0.05) in injured carotid arteries than at the counter side 1 week after vessel injury and significant differences could also be observed after 5 weeks. After 3 months, αvß3-integrin expression decreased to baseline and binding of cRGD-MB was comparable in both vessels. Values remained at baseline also after 6 months. CONCLUSIONS: Ultrasound imaging with RGD-MB is promising for monitoring vascular healing after vessel injury. This may open new perspectives to assess vascular damage after radiological interventions.

Impact of image denoising on image quality, quantitative parameters and sensitivity of ultra-low-dose volume perfusion CT imaging.

OBJECTIVES: To examine the impact of denoising on ultra-low-dose volume perfusion CT (ULD-VPCT) imaging in acute stroke. METHODS: Simulated ULD-VPCT data sets at 20 % dose rate were generated from perfusion data sets of 20 patients with suspected ischemic stroke acquired at 80 kVp/180 mAs. Four data sets were generated from each ULD-VPCT data set: not-denoised (ND); denoised using spatiotemporal filter (D1); denoised using quanta-stream diffusion technique (D2); combination of both methods (D1 + D2). Signal-to-noise ratio (SNR) was measured in the resulting 100 data sets. Image quality, presence/absence of ischemic lesions, CBV and CBF scores according to a modified ASPECTS score were assessed by two blinded readers. RESULTS: SNR and qualitative scores were highest for D1 + D2 and lowest for ND (all p ≤ 0.001). In 25 % of the patients, ND maps were not assessable and therefore excluded from further analyses. Compared to original data sets, in D2 and D1 + D2, readers correctly identified all patients with ischemic lesions (sensitivity 1.0, kappa 1.0). Lesion size was most accurately estimated for D1 + D2 with a sensitivity of 1.0 (CBV) and 0.94 (CBF) and an inter-rater agreement of 1.0 and 0.92, respectively. CONCLUSION: An appropriate combination of denoising techniques applied in ULD-VPCT produces diagnostically sufficient perfusion maps at substantially reduced dose rates as low as 20 % of the normal scan. KEY POINTS: Perfusion-CT is an accurate tool for the detection of brain ischemias. The high associated radiation doses are a major drawback of brain perfusion CT. Decreasing tube current in perfusion CT increases image noise and deteriorates image quality. Combination of different image-denoising techniques produces sufficient image quality from ultra-low-dose perfusion CT.

Metal artifact reduction for flat panel detector intravenous CT angiography in patients with intracranial metallic implants after endovascular and surgical treatment.

BACKGROUND: Flat panel detector CT angiography with intravenous contrast agent injection (IV CTA) allows high-resolution imaging of cerebrovascular structures. Artifacts caused by metallic implants like platinum coils or clips lead to degradation of image quality and are a significant problem. OBJECTIVE: To evaluate the influence of a prototype metal artifact reduction (MAR) algorithm on image quality in patients with intracranial metallic implants. METHODS: Flat panel detector CT after intravenous application of 80 mL contrast agent was performed with an angiography system (Artis zee; Siemens, Forchheim, Germany) using a 20 s rotation protocol (200° rotation angle, 20 s acquisition time, 496 projections). The data before and after MAR of 26 patients with a total of 34 implants (coils, clips, stents) were independently evaluated by two blinded neuroradiologists. RESULTS: MAR improved the assessability of the brain parenchyma and small vessels (diameter <1 mm) in the neighborhood of metallic implants and at a distance of 6 cm (p<0.001 each, Wilcoxon test). Furthermore, MAR significantly improved the assessability of parent vessel patency and potential aneurysm remnants (p<0.005 each, McNemar test). MAR, however, did not improve assessability of stented vessels. CONCLUSIONS: When an intravenous contrast protocol is used, MAR significantly ameliorates the assessability of brain parenchyma, vessels, and treated aneurysms in patients with intracranial coils or clips.

High-Pitch Low-Dose Whole-Body Computed Tomography for the Assessment of Ventriculoperitoneal Shunts in a Pediatric Patient Model: An Experimental Ex Vivo Study in Rabbits.

OBJECTIVE: The aim of this study was to assess the diagnostic value of whole-body low-dose (LD) computed tomography (CT) for the detection of ventriculoperitoneal (VP) shunt complications in pediatric patients compared with radiographic shunt series (SS) in an ex vivo rabbit animal model. METHODS: In the first step, 2 optimized LD-CT imaging protocols, with high pitch (pitch, 3.2), low tube voltages (70 kVp and 80 kVp), and using both filtered back projection and iterative reconstruction, were assessed on a 16-cm solid polymethylmethacrylate phantom regarding signal-to-noise ratio and radiation dose. Taking both radiation dose and signal-to-noise ratio into account, the LD-CT protocol (80 kVp; 4 mA; pitch, 3.2) was identified as most appropriate and therefore applied in this study.After identification of appropriate LD-CT protocol, 12 VP shunts were implanted in 6 rabbit cadavers (mean weight, 5.1 kg). Twenty-four mechanical complications (extracranial and extraperitoneal malpositioning, breakages, and disconnections) were induced in half of the VP shunts. Low-dose CT and conventional SS were acquired in standard fashion. Dose-area products (DAPs) for SS and LD-CT were collected; effective radiation doses for both SS and LD-CT were estimated using CT-Expo (v. 2.3.1.) and age-specific effective dose (ED) estimates. Qualitative scoring of diagnostic confidence on a 5-point Likert scale (1, very low diagnostic confidence; 5, excellent diagnostic confidence) and blinded readings of both SS and LD-CTs were performed. RESULTS: Among the 24 VP shunt complications, LD-CT yielded excellent sensitivity and specificity for the detection of VP shunt complications (sensitivity, 0.98; specificity, 1; 95% confidence interval, 0.92-1) with excellent interobserver agreement (κ = 0.90). Shunt series yielded good sensitivity and specificity (sensitivity, 0.75; specificity, 1; 95% confidence interval, 0.58-0.92) with moderate interobserver agreement (κ = 0.56). No false-positive findings were registered. Compared with SS, LD-CT yielded significantly lower ED and DAPs (ED, 0.039 vs 0.062 mSv; DAP, 20.5 vs 26.3; P < 0.05). CONCLUSIONS: In this experimental ex vivo pediatric patient model, LD-CT yields excellent sensitivity for the detection of VP shunt complications at higher diagnostic confidence and lower radiation exposure compared with SS.

Effects of radiation dose reduction in Volume Perfusion CT imaging of acute ischemic stroke.

PURPOSE: To examine the influence of radiation dose reduction on image quality and sensitivity of Volume Perfusion CT (VPCT) maps regarding the detection of ischemic brain lesions. METHODS AND MATERIALS: VPCT data of 20 patients with suspected ischemic stroke acquired at 80 kV and 180 mAs were included. Using realistic reduced-dose simulation, low-dose VPCT datasets with 144 mAs, 108 mAs, 72 mAs and 36 mAs (80 %, 60 %, 40 % and 20 % of the original levels) were generated, resulting in a total of 100 datasets. Perfusion maps were created and signal-to-noise-ratio (SNR) measurements were performed. Qualitative analyses were conducted by two blinded readers, who also assessed the presence/absence of ischemic lesions and scored CBV and CBF maps using a modified ASPECTS-score. RESULTS: SNR of all low-dose datasets were significantly lower than those of the original datasets (p < .05). All datasets down to 72 mAs (40 %) yielded sufficient image quality and high sensitivity with excellent inter-observer-agreements, whereas 36 mAs datasets (20 %) yielded poor image quality in 15 % of the cases with lower sensitivity and inter-observer-agreements. CONCLUSION: Low-dose VPCT using decreased tube currents down to 72 mAs (40 % of original radiation dose) produces sufficient perfusion maps for the detection of ischemic brain lesions. KEY POINTS: • Perfusion CT is highly accurate for the detection of ischemic brain lesions • Perfusion CT results in high radiation exposure, therefore low-dose protocols are required • Reduction of tube current down to 72 mAs produces sufficient perfusion maps.

Feasibility, Safety, and Efficacy of Flow-Diverting Stent-Assisted Microsphere Embolization of Fusiform and Sidewall Aneurysms.

BACKGROUND: Treatment of wide-necked internal carotid artery aneurysms is frequently associated with incomplete occlusion and high recurrence rates. Furthermore, platinum coils cause strong beam-hardening artifacts, hampering subsequent image analyses. OBJECTIVE: To assess the feasibility, safety, and efficacy of flow-diverting, stent-assisted microsphere embolization of fusiform and sidewall aneurysms in vitro and in vivo. METHODS: Using a recirculating pulsatile in vitro flow model, 5 different aneurysm geometries (inner/outer curve, narrow/wide neck, and fusiform) were treated (each n = 1) by flow-diverting stent (FDS) implantation and subsequent embolization through a jailed microcatheter using calibrated microspheres (500-900 µm) larger than the pores of the FDS mesh. Treatment effects were analyzed angiographically and by micro computed tomography. The fluid of the in vitro model was filtered to ensure that no microspheres evaded the aneurysm. The experiment was repeated once in vivo. RESULTS: In vitro, all 5 aneurysms were safely and completely occluded by FDS-assisted microsphere embolization. Virtually complete aneurysm occlusion was confirmed by angiography and micro computed tomography. No microspheres escaped into the circulation. The experiment was successfully repeated in 1 pig with a sidewall aneurysm generated by vessel occlusion. An embolic protection system placed distally of the FDS in vitro and in vivo (each n = 1) contained no microspheres after the embolization. Thus, no microspheres were lost in the circulation, and the use of an embolic protection system seems feasible to provide additional safety. CONCLUSION: FDS-assisted microsphere embolization of fusiform and sidewall aneurysms is feasible and yields virtually complete aneurysm occlusion while avoiding coil-associated beam-hardening artifacts.

Evaluation of whole body Ultralow-Dose CT for the assessment of ventriculoperitoneal shunt complications: an experimental ex-vivo study in a swine model.

OBJECTIVE: To evaluate the suitability of whole body Ultralow-dose CT (ULD-CT) as a diagnostic tool for the evaluation of ventriculoperitoneal shunt (VP-shunt) complications with special regards to radiation dose and image quality. METHODS: Fourteen VP-shunts were implanted in 7 swine cadavers (weight: 55-70 kg). Twenty-two mechanical complications (extracranial and extraperitoneal malpositioning, breakages, disconnections) were induced in nine VP-shunts. Ten ULD-CT scans with different parameters (tube voltage: 80, 100, 120 kV; tube current: 20 or 50 mAs; Pitch (P): 1 or 1.5) were acquired; the combination of 120 kV and 50 mAs was omitted. Radiation dose estimation, blinded readings, and quantitative and qualitative assessment of the CT-data were performed. RESULTS: Effective radiation doses varied between 0.44 ± 0.06 and 2.55 ± 0.35 mSv. ULD-CT protocols provided a mean sensitivity (i.e., correctly detected shunt complications) of 98.2 %. Unnoticed or incorrectly identified complications did not exceed one complication (4.5 %) in any ULD-CT protocol. Diagnostic confidence was sufficient for all ULD-CT protocols except for protocols with 80 kV and 20 mAs. CONCLUSIONS: ULD-CT allows accurate detection of VP-shunt complications at radiation doses similar or lower than reported for a radiographic shunt series. At the tested radiation dose levels, ULD-CT thus provides an alternative to a radiographic shunt series. KEY POINTS: • Ultralow-dose CT accurately detects Ventriculoperitoneal Shunt complications. • Radiation dosage is similar or lower than reported for a radiographic shunt series. • Ultralow-dose CT potentially shortens the diagnostic process when shunt complications are suspected.

Postinterventional subarachnoid haemorrhage after endovascular stroke treatment with stent retrievers.

INTRODUCTION: The purpose of this paper is to investigate the clinical significance of postinterventional subarachnoid hyperdensities (PSH) after endovascular mechanical thrombectomy in acute ischemic stroke. METHODS: We analysed clinical and radiological data of 113 consecutive patients who received postinterventional CT scans within 4.5 h after mechanical thrombectomy. RESULTS: PSH was present in 27 of 113 patients (24%). Extravasation of contrast agent was observed during intervention in only 6 of 27 cases (22%). There was consecutive haemorrhagic transformation in four patients with PSH (p = 0.209, Fisher's exact test). Preinterventional predictors for the occurrence of PSH in our series were a long interval between clinical onset and recanalization (p = 0.028), a long procedure time (p = 0.010), and a high number of recanalization attempts (p = 0.001). PSH had no significant impact on clinical outcome (modified Rankin Scale) at discharge (p = 0.419) or at 3 months (p = 0.396). There were no significant correlations between PSH and thrombectomy devices (Solitaire: p = 0.433, Trevo Pro: p = 0.124). CONCLUSION: PSH after endovascular mechanical thrombectomy in acute ischemic stroke are likely to occur in complicated cases in which more than one revascularisation attempt is performed. PSH per se do not appear to be associated with an impaired clinical outcome or an elevated risk for consecutive haemorrhage.

Clinical significance of post-interventional cerebral hyperdensities after endovascular mechanical thrombectomy in acute ischaemic stroke.

INTRODUCTION: This study aims to investigate the clinical significance of post-interventional cerebral hyperdensities (PCHD) after endovascular mechanical thrombectomy in acute ischaemic stroke. METHODS: Data of 102 consecutive patients who received post-interventional CT scans within 4.5 h after mechanical thrombectomy were analysed retrospectively. RESULTS: Sixty-two of 102 patients (60.8 %) had PCHD on their post-interventional CT scans. The most common site of PCHD was the basal ganglia. PCHD were persisting in 13 of 62 patients (21.0 %), and transient in the remaining 49 patients (79.0 %) within 24 h. Four patients with PCHD and four patients without PCHD suffered from parenchymal haemorrhage. Neither ASA nor Clopidogrel, Tirofiban or rtPA were risk factors for PCHD. Final infarction size was congruent with or bigger than areas of PCHD in 93.3 % of cases in our series. CONCLUSION: PCHD was not a risk factor for parenchymal haemorrhage in our series. The occurrence of PCHD was strongly related to the prior presence of infarction. PCHD was also a strong predictor for final infarction size.

Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression.

Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication-based mechanisms such fork stalling and template switching or microhomology-mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients' fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele-specific LMNB1 expression levels.

Copy number variation in patients with cervical artery dissection.

Cervical artery dissection (CeAD) occurs in healthy young individuals and often entails ischemic stroke. Skin biopsies from most CeAD-patients show minor connective tissue alterations. We search for rare genetic deletions and duplication that may predispose to CeAD. Forty-nine non-traumatic CeAD-patients with electron microscopic (EM) alterations of their dermal connective tissue (EM+ patients) and 21 patients with normal connective tissue in skin biopsies (EM- patients) were analyzed. Affymetrix 6.0 microarrays (Affymetrix) from all patients were screened for copy number variants (CNVs). CNVs absent from 403 control subjects and from 2402 published disease-free individuals were considered as CeAD-associated. The genetic content of undentified CNVs was analyzed by means of the Gene Ontology (GO) Term Mapper to detect associations with biological processes. In 49 EM+ patients we identified 13 CeAD-associated CNVs harboring 83 protein-coding genes. In 21 EM- patients we found five CeAD-associated CNVs containing only nine genes (comparison of CNV gene density between the groups: Mann-Whitney P=0.039). Patients' CNVs were enriched for genes involved in extracellular matrix organization (COL5A2, COL3A1, SNTA1, P=0.035), collagen fibril organization COL5A2, COL3A1, (P=0.0001) and possibly for genes involved in transforming growth factor beta (TGF)-beta receptor signaling pathway (COL3A1, DUPS22, P=0.068). We conclude that rare genetic variants may contribute to the pathogenesis of CeAD, in particular in patients with a microscopic connective tissue phenotype.

Spontaneous arterial dissection: phenotype and molecular pathogenesis.

Arterial dissection (AD) is defined as the longitudinal splitting up of the arterial wall caused by intramural bleeding. It can occur as a spontaneous event in all large and medium sized arteries. The histological hallmark of AD is medial degeneration. Histological investigations, gene expression profiling and proteome studies of affected arteries reveal disturbances in many different biological processes including inflammation, proteolytic activity, cell proliferation, apoptosis and smooth muscle cell (SMC) contractile function. Medial degeneration can be caused by various rare dominant Mendelian disorders. Genetic linkage analysis lead to the identification of mutations in different disease-causing genes involved in the biosynthesis of the extracellular matrix (FBN1, COL3A1), in transforming growth factor (TGF) beta signaling (FBN1, TGFBR1, TGFBR2) and in the SMC contractile system (ACTA2, MYH11). Genome wide association studies suggest that the CDKN2A/CDKN2B locus plays a role in the etiology AD and other arterial diseases.