Stephanie Tritt

A benchmark approach to hemorrhage risk management of cavernous malformations

Objective Despite the low annual risk of hemorrhage associated with a cavernous malformation (CM) (0.6%–1.1% per year), the risk of rehemorrhage rate and severity of neurologic deficits is significantly higher; therefore, we aimed to evaluate the rupture risk of CMs depending on various factors. Methods We retrospectively analyzed medical records of all patients with CM admitted to our institution between 1999 and April 2016. Cavernoma volume, location of the lesion, existence of a developmental venous anomaly (DVA), number of cavernomas, and patient characteristics (sex, age, hypertension, and antithrombotic therapy) were assessed. Results One hundred fifty-four patients with CM were included; 89 (58%) ruptured CMs were identified. In statistical univariable analysis, the existence of a DVA was significantly higher in the ruptured cavernoma group (p < 0.001; odds ratio [OR] 4.6). A multivariable analysis of all included independent risk factors designated young age (<45 years) (p < 0.05; OR 2.2), infratentorial location (p < 0.01; OR 2.9), and existence of a DVA (p < 0.0001; OR 4.7) with significantly higher risk of rupture in our patient cohort. A separate analysis of these anatomical locations, supratentorial vs infratentorial, indicated that the existence of a DVA (p < 0.01; OR 4.16) in ruptured supratentorial cases and CM volume (≥1 cm3) (p < 0.0001; OR 3.5) in ruptured infratentorial cases were significant independent predictors for hemorrhage. Conclusions Young age (<45 years), infratentorial location, and the presence of a DVA are associated with a higher hemorrhage risk. CM volume (≥1 cm3) and the existence of a DVA were independently in accordance with the anatomical location high risk factors for CM rupture.

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.

MRI-detection rate and incidence of lumbar bleeding sources in 190 patients with non-aneurysmal SAH

Background Up to 15% of all spontaneous subarachnoid hemorrhages (SAH) have a non-aneurysmal SAH (NASAH). The evaluation of SAH patients with negative digital subtraction angiography (DSA) is sometimes a diagnostic challenge. Our goal in this study was to reassess the yield of standard MR-imaging of the complete spinal axis to rule out spinal bleeding sources in patients with NASAH. Methods We retrospectively analyzed the spinal MRI findings in 190 patients with spontaneous NASAH, containing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH, diagnosed by computer tomography (CT) and/or lumbar puncture (LP), and negative 2nd DSA. Results 190 NASAH patients were included in the study, divided into PM-SAH (n = 87; 46%) and NPM-SAH (n = 103; 54%). Overall, 23 (22%) patients had a CT negative SAH, diagnosed by positive LP. MR-imaging of the spinal axis detected two patients with lumbar ependymoma (n = 2; 1,05%). Both patients complained of radicular sciatic pain. The detection rate raised up to 25%, if only patients with radicular sciatic pain received an MRI. Conclusion Routine radiological investigation of the complete spinal axis in NASAH patients is expensive and can not be recommended for standard procedure. However, patients with clinical signs of low-back/sciatic pain should be worked up for a spinal pathology.

Biopsies of pediatric brainstem lesions display low morbidity but strong impact on further treatment decisions.

OBJECTIVE The course of malignant brain stem gliomas in childhood is rarely positive. Because of limited therapeutic options and potentially hazardous biopsies oncologist often relay on MRI diagnoses only for further therapy decisions. In this study we show that brain stem biopsies display a low morbidity rate and neuropathological assessment has a considerable impact on further treatment decision. METHODS Within 18-months five children with brainstem symptoms and the radiological diagnosis of a malignant brainstem glioma, were identified. From this time point it was possible to analyze all samples with the 450K methylome analysis. Other neuropathological techniques included classical histology with immunohistochemistry. Surgery was performed as biopsy, either microsurgical, frame-guided (Leksell), robot-assisted (ROSA) or navigated (BrainLab, two children). RESULTS Mean age of the children was 7.5years (range: newborn to 12years). There was no biopsy-related morbidity or mortality. The mean number of taken samples was 12 (range: 1-25). Histologic diagnosis could be established in all children, however, 450K methylome diagnosis was positive in only two out of five patients. CONCLUSION Despite the technically difficult biopsies, all specimens were sufficient for immunohistochemical diagnosis, however, 450K methylome analysis could only be better established where multiple small samples were taken, instead of few larger ones. Based on the preoperative radiological diagnosis suggesting malignant brainstem glioma, all children would have been treated with combined radiation and temozolomid chemotherapy. Nevertheless, due to the availability of histology and molecular diagnostics, individualized therapy could be performed, preventing in two out of five children from unnecessary radiation and chemotherapy.

Posterior fossa AVMs: Increased risk of bleeding and worse outcome compared to supratentorial AVMs

Infratentorial AVMs are often considered as potentially hazardous as they are thought to present more often with hemorrhage, may harbor AVM-associated aneurysms more frequently and to be associated with poor outcome. The aim of our study is to compare features of supratentorial and infratentorial AVMs. We retrospectively analyzed 316 consecutive patients with cerebral AVM presenting to our neurovascular center between 2005 and 2015. Location and angioarchitecture of the AVM including AVM-associated aneurysms, bleeding events, and outcome during follow up were analyzed. Outcome was assessed using the modified Rankin Scale (mRS) and stratified into favorable (mRS 0-2) and unfavorable (mRS 3-6). 41.6% of the patients with a supratentorial AVM (stAVM) and 69.2% of the patients with an infratentorial AVM (itAVM) were presented with a hemorrhage initially (p < .001). Patients with itAVMs were older at presentation (mean 48.1 vs. 37.9 years, p < .001). ItAVMs furthermore were smaller (95.1% <3 cm nidus-diameter, p < .001) and had lower Spetzler-Martin-Grades (p = .04). Associated aneurysms were more frequent in itAVMs (38.5% vs. 20.7%, p < .004) and were associated with an increased risk of hemorrhage at presentation (30.9% vs. 18.7%, p = .013). Outcome was poor in 10.8% of the patients with stAVM and in 28.3% of patients with itAVM (p < .001). The risk of a new hemorrhage-associated deficit was significantly higher in itAVMs (p < .001). Most posterior fossa AVMs are associated with an increased hemorrhage rate. Thus they are a predictor for poor outcome and should be treated even if unruptured to maintain good neurological function.

Positive influence of partial resection on overall survival of patients with overlapping glioblastomas

OBJECTIVES Patients with overlapping glioblastomas (former known as gliomatosis cerebri according to the 2007 WHO classification) have a poor prognosis. Most of the patients undergo biopsy to confirm histopathological diagnosis. Treatment comprises chemotherapy, radiation and combination of both. We determined whether resection of the contrast enhancing tumor parts leads to a prolonged survival. PATIENTS AND METHODS We performed a retrospective analysis and included 31 patients with overlapping glioblastomas (OG) who showed WHO IV in the initial histopathological examination. All patients fulfilled criteria of overlapping glioblastomas in the MRI according to WHO criteria (3 or more lobes were affected). We evaluated Karnofsky performance score (KPS), gender, age, IDH-1_R132H status, MGMT promotor methylation status, proliferation index, postoperative therapy, biopsy vs. partial resection and extent of resection as possible factors affecting overall survival (OAS). A matched pair analysis was performed between the biopsy and resection group on basis of age, KPS and combined radio-chemotherapy. RESULTS 10 Patients underwent resection of the contrast enhancing tumor parts, 21 patients underwent stereotactic biopsy. All included patients showed contrast enhancing lesions in the MRI. Median age was 61 years in the biopsy-group and 53 in the partial resection (PR) group. We found a significant correlation between OAS and age <50 (p=0.02). Median KPS was 80 in the STX group vs. 100 in the PR group. KPS above 80 was significantly associated with longer OAS (p=0.02). Median survival was 174days in the STX group compared to 446days in the PR group (p=0.05). Also the matched pair analysis showed significant p-values for resection. CONCLUSION Partial resection might have a positive impact on overall survival of patients with overlapping glioblastomas (former known as gliomatosis cerebri), although the prognosis remains limited.