Stent-Assisted Coiling Using Leo+ Baby Stent

Background!#!Stent-assisted coiling is well-established for treatment of cerebral aneurysms. The technique enables treatment of wide-neck, bifurcation and recurrent aneurysms with high packing rates. While described in extenso for laser cut stents, the results of patients treated with the Leo+ Baby (Balt, Montmorency, France) braided microstent are presented.!##!Material and methods!#!Patients were included if treated with a Leo+ Baby and with digital subtraction angiography (DSA) follow-up available of at least 6 months. Data were evaluated for successful deployment, aneurysm occlusion according to the modified Raymond-Roy classification (MRRC), stent patency and procedure-related morbidity and mortality.!##!Results!#!A total of 81 patients were included and Leo+ Baby deployment was successful in all cases. Coils were used in 80 cases. In 1 case 2 stents were used stent-in-stent without additional coiling. Initial aneurysm occlusion rates were MRRC!##!Conclusion!#!The results confirm that stent-assisted coiling with the Leo+ Baby stent is safe and efficient for treatment of wide neck or recurrent cerebral aneurysms. Spontaneous progressive aneurysm occlusion over 6 months supports the theory of considerable flow-modulating effects of Leo+ Baby

Classification of Primary Cerebral Lymphoma and Glioblastoma Featuring Dynamic Susceptibility Contrast and Apparent Diffusion Coefficient

This study aimed to differentiate primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) via multimodal MRI featuring radiomic analysis. MRI data sets of patients with histological proven PCNSL and GBM were analyzed retrospectively. Diffusion-weighted imaging (DWI) and dynamic susceptibility contrast (DSC) perfusion imaging were evaluated to differentiate contrast enhancing intracerebral lesions. Selective (contrast enhanced tumor area with the highest mean cerebral blood volume (CBV) value) and unselective (contouring whole contrast enhanced lesion) Apparent diffusion coefficient (ADC) measurement was performed. By multivariate logistic regression, a multiparametric model was compiled and tested for its diagnostic strength. A total of 74 patients were included in our study. Selective and unselective mean and maximum ADC values, mean and maximum CBV and ratioCBV as quotient of tumor CBV and CBV in contralateral healthy white matter were significantly larger in patients with GBM than PCNSL; minimum CBV was significantly lower in GBM than in PCNSL. The highest AUC for discrimination of PCNSL and GBM was obtained for selective mean and maximum ADC, mean and maximum CBV and ratioCBV. By integrating these five in a multiparametric model 100% of the patients were classified correctly. The combination of perfusion imaging (CBV) and tumor hot-spot selective ADC measurement yields reliable radiological discrimination of PCNSL from GBM with highest accuracy and is readily available in clinical routine

DSC Brain Perfusion Using Advanced Deconvolution Models in the Diagnostic Work-Up of Dementia and Mild Cognitive Impairment: A Semiquantitative Comparison with HMPAO-SPECT-Brain Perfusion

Background: SPECT (single-photon emission-computed tomography) is used for the detection of hypoperfusion in cognitive impairment and dementia but is not widely available and related to radiation dose exposure. We compared the performance of DSC (dynamic susceptibility contrast) perfusion using semi- and fully adaptive deconvolution models to HMPAO-SPECT (99mTc-hexamethylpropyleneamine oxime-SPECT). Material and Methods: Twenty-seven patients with dementia of different subtypes including frontotemporal dementia (FTD) and mild cognitive impairment (MCI) received a multimodal diagnostic work-up including DSC perfusion at a clinical 3T high-field scanner and HMPAO-SPECT. Nineteen healthy control individuals received DSC perfusion. For calculation of the hemodynamic parameter maps, oscillation-index standard truncated singular value decomposition (oSVD, semi-adaptive) as well as Bayesian parameter estimation (BAY, fully adaptive) were performed. Results: Patients showed decreased cortical perfusion in the left frontal lobe compared to controls (relative cerebral blood volume corrected, rBVc: 0.37 vs. 0.27, p = 0.048, adjusted for age and sex). Performance of rBVc (corrected for T1 effects) was highest compared to SPECT for detection of frontal hypoperfusion (sensitivity 83%, specificity 80% for oSVD and BAY, area under curve (AUC) = 0.833 respectively, p < 0.05) in FTD and MCI. For nonleakage-corrected rBV and for rBF (relative cerebral blood flow), sensitivity of frontal hypoperfusion was above 80% for oSVD and for BAY (rBV: sensitivity 83%, specificity 75%, AUC = 0.908 for oSVD and 0.917 for BAY, p < 0.05 respectively; rBF: sensitivity 83%, specificity 65%, AUC = 0.825, p < 0.05 for oSVD). Conclusion: Advanced deconvolution DSC can reliably detect pathological perfusion alterations in FTD and MCI. Hence, this widely accessible technique has the potential to improve the diagnosis of dementia and MCI as part of an interdisciplinary multimodal imaging work-up. Advances in knowledge: Advanced DSC perfusion has a high potential in the work-up of suspected dementia and correlates with SPECT brain perfusion results in dementia and MCI

Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis

Background: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. Methods: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). Results: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (<= 48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. Conclusions: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials

Characteristics in Non-Vitamin K Antagonist Oral Anticoagulant-Related Intracerebral Hemorrhage

Background and Purpose Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany. Imaging, clinical characteristics, and 3-months modified Rankin Scale (mRS) outcomes were compared in NOAC- versus VKA-related ICH patients. Propensity score matching was conducted to adjust for clinically relevant differences in baseline parameters. Subgroup analyses were performed regarding NOAC agent, dosing and present clinically relevant anticoagulatory activity (last intake 30 ng/mL). Results Despite older age in NOAC patients, there were no relevant differences in clinical and hematoma characteristics between NOAC- and VKA-related ICH regarding baseline hematoma volume (median [interquartile range]: NOAC, 14.7 [5.1-42.3] mL versus VKA, 16.4 [5.8-40.6] mL; P=0.33), rate of hematoma expansion (NOAC, 49/146 [33.6%] versus VKA, 235/688 [34.2%]; P=0.89), and the proportion of patients with unfavorable outcome at 3 months (mRS, 4-6: NOAC 126/179 [70.4%] versus VKA 473/682 [69.4%]; P=0.79). Subgroup analyses revealed that NOAC patients with clinically relevant anticoagulatory effect had higher rates of intraventricular hemorrhage (n/N [%]: present 52/109 [47.7%] versus absent 9/35 [25.7%]; P=0.022) and hematoma expansion (present 35/90 [38.9%] versus absent 5/30 [16.7%]; P=0.040), whereas type of NOAC agent or different NOAC-dosing regimens did not result in relevant differences in imaging characteristics or outcome. Conclusions If effectively anticoagulated, there are no differences in hematoma characteristics and functional outcome among patients with NOAC- or VKA-related ICH. Clinical Trial Registratio

Management of therapeutic anticoagulation in patients with intracerebral haemorrhage andmechanical heart valves

Aims Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH. Methods and results We pooled individual patient- data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no-TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate-ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67-35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA-timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33-21.37; P < 0.01). The hazard for the composite-balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10-5.70; P = 0.03). Conclusion Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing-between least risks for thromboembolic and haemorrhagic complications-provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk

Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage

Objective To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)associated ICH. Methods Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC. Results IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04-1.93) vs non-LDSH: 1.32 (0.33-3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38-4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4-6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume <4.4 mL: 0.18 (0.04-0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS <4: 0.29 (0.11-0.78); p=0.014) were significantly associated with fewer IHC. Conclusions Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention

Association of Surgical Hematoma Evacuation vs Conservative Treatment With Functional Outcome in Patients With Cerebellar Intracerebral Hemorrhage

IMPORTANCE The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established. OBJECTIVE To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH. DESIGN, SETTING, AND PARTICIPANTS Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015). EXPOSURE Surgical hematoma evacuation vs conservative treatment. MAIN OUTCOMES AND MEASURES The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH. RESULTS Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm(3) vs 18.8 cm(3)). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], -3.7% [95% CI, -8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm(3) was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume = 15 cm(3), 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02). CONCLUSIONS AND RELEVANCE Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume