Radiotherapy of spinal cord gliomas : A retrospective mono-institutional analysis.

BACKGROUND: Due to the rarity of spinal cord gliomas, no consensus has been reached regarding the optimal treatment strategy. The aim of the present retrospective study was to identify patient and tumor characteristics and to evaluate the effectiveness of radiotherapy within this setting. PATIENTS AND METHODS: Patients diagnosed with spinal cord gliomas between 2003 and 2013 and treated at the Department of Radiation Oncology, University of Munich, were retrospectively analyzed. Overall survival was estimated with the Kaplan-Meier method and univariate analysis was performed by log-rank testing. RESULTS: A total of 16 patients were identified. The cohort consisted of seven primary spinal cord gliomas and eight cases of metastases of cerebral gliomas. Median follow-up was 42 months and median total radiation dose was 45.0 Gy. In all, 62.5 % of patients received a simultaneous chemotherapy with temozolomide. The median overall survival was 6 months (95% CI: 0-27.5 months). Surgical resection of the tumor was a significant predictor of improved survival, compared with radiotherapy alone (p = 0.001). Patients with the diagnosis of a primary spinal cord glioma survived significantly longer than those presenting with a metastatic deposit from a cerebral glioma (p < 0.001). A statistically significant dose-response relationship at dose levels of ≥ 45 Gy vs. < 45 Gy could be derived (p < 0.001). Simultaneous chemotherapy did not influence survival outcome. CONCLUSION: Despite the aggressive treatment in the present study, the prognosis for spinal cord gliomas was still poor, with a median overall survival of 6 months. To the best of our knowledge, this is the largest study reporting the results of simultaneous chemoradiation in spinal cord gliomas. A combined chemoradiation treatment seems feasible and can be considered as a new treatment option in the management of spinal cord gliomas.

Ruptured basilar artery perforator aneurysms--treatment regimen and long-term follow-up in eight cases.

INTRODUCTION: Basilar artery (BA) perforator aneurysms may lead to severe subarachnoid hemorrhage (SAH). The acute management is uncertain. The anatomic approach is challenging both for coiling and clipping, and flow diverter stenting may be dangerous due to the required antiplatelet therapy. We report on our experiences in eight patients. METHODS: We retrospectively analyzed eight patients with ruptured BA perforator aneurysm, including clinical characteristics, imaging data, treatment regimen, clinical course, and long-term outcome. RESULTS: Patients presented with major SAH and World Federation of Neurosurgical Societies (WFNS) scores of I in three, II in two, and V in three cases. In four patients, the aneurysm was detected in the initial angiography, in four only in follow-up angiography. Five patients were treated conservatively and three patients had endovascular therapy. In the conservative group, the aneurysm spontaneously thrombosed in three cases. One patient suffered from a re-SAH and stayed permanently dependent due to an associated perforator stroke (modified Rankin Scale (mRS) 5). The remaining four patients recovered well (mRS 0 and 1 in two cases, each) including three patients also exhibiting perforator strokes. Regarding the endovascular group, one parent vessel was an angioma feeder and embolized with Onyx. The second aneurysm spontaneously thrombosed periinterventionally. The third patient underwent coiling. Two parent vessels were occluded postinterventionally, resulting in perforator strokes. Final mRS scores were 0, 2, and 2, respectively. CONCLUSION: Conservative management of ruptured BA aneurysms might be a first-line treatment option with common spontaneous aneurysm occlusion, low rate of re-SAH, and promising clinical outcome.

Re-irradiation and bevacizumab in recurrent high-grade glioma: an effective treatment option.

Re-irradiation has been shown to be a meaningful option for recurrent high-grade glioma (HGG) patients. Furthermore, bevacizumab exerts certain activity in combination with chemotherapy/as monotherapy and was safely tested in combination with radiotherapy in several previous studies. To our knowledge, this is the largest cohort of patients treated with both re-irradiation and bevacizumab to date. After receiving standard radiotherapy (with or without TMZ) patients with recurrent HGG were treated with bevacizumab (10 mg/kg intravenously at d1 and d15) during re-irradiation. Median prescribed radiation dose during re-treatment was 36 Gy, conventionally fractionated. Datasets of 71 re-irradiated patients were retrospectively analyzed. Patients either received bevacizumab (N = 57) or not (N = 14; other substances (N = 4) and sole radiation (N = 10)). In patients receiving bevacizumab, both post-recurrence survival (PRS) (median 8.6 vs. 5.7 months; p = 0.003, log-rank test) and post-recurrence progression-free survival (PR-PFS, 5.6 vs. 2.5 months; p = 0.005, log-rank test; PFS-6 42.1 % for the bevacizumab group) were significantly increased which was confirmed by multivariate analysis. KPS, re-surgery, MGMT methylation status, sex, WHO grade, tumor volume and age were no significant predictors for neither PR-PFS nor PRS (univariate analysis). Re-irradiation with bevacizumab remains a feasible and highly effective treatment schedule. Studies on further salvage strategies and timing of sequential treatment options versus observation are warranted.

Pseudo-subarachnoid haemorrhage due to chronic hypoxaemia: case report and review of the literature.

BACKGROUND: The specificity of computed tomography (CT) for subarachnoid haemorrhage (SAH) is very high. However, physicians should be aware of rare false positive findings, also referred to as "pseudo-SAH". We present an unusual case in which such a finding was caused by chronic hypoxaemia. CASE PRESENTATION: A 37-year-old male patient presented with headaches. His CT-scan showed multiple confluent subarachnoid hyperattenuations, which mimicked SAH. However, the headache was chronic and had no features typical for SAH. The patient suffered from severe chronic hypoxaemia due to congenital heart failure. On CT-angiography diffuse intracranial vessel proliferation was found and laboratory results revealed a highly raised level of haematocrit, which had both probably developed as compensatory mechanisms. A combination of these findings explained the subarachnoid hyperdensities. Magnetic resonance imaging (MRI) showed no signs of SAH and visualized hypoxaemia in cerebral veins. A diagnosis of pseudo-SAH was made. The patient's symptoms were likely due to a secondary headache attributed to hypoxia and/or hypercapnia. Therapy was symptomatic. CONCLUSIONS: Severe chronic hypoxaemia should be recognised as a rare cause of pseudo-SAH. Clinical evaluation and MRI help differentiate SAH from pseudo-SAH.

Focal subarachnoid haemorrhage mimicking transient ischaemic attack--do we really need MRI in the acute stage?

BACKGROUND: Acute non-traumatic focal subarachnoid haemorrhage (fSAH) is a rare transient ischaemic attack (TIA)-mimic. MRI is considered to be indispensable by some authors in order to avoid misdiagnosis, and subsequent improper therapy. We therefore evaluated the role of CT and MRI in the diagnosis of fSAH patients by comparing our cases to those from the literature. METHODS: From 01/2010 to 12/2012 we retrospectively identified seven patients with transient neurological episodes due to fSAH, who had received unenhanced thin-sliced multiplanar CT and subsequent MRI within 3 days on a 1.5 T scanner. MRI protocol included at least fast-field-echo (FFE), diffusion-weighted imaging (DWI), T2-weighted fluid-attenuated inversion recovery (FLAIR) and time-of-flight (TOF) MRA sequences. By using MRI as gold-standard, we re-evaluated images and data from recent publications regarding the sensitivity to detect fSAH in unenhanced CT. RESULTS: fSAH was detected by CT and by FFE and FLAIR on MRI in all of our own cases. However, DWI and T2w-spin-echo sequences revealed fSAH in 3 of 7 and 4 of 6 cases respectively. Vascular imaging was negative in all cases. FFE-MRI revealed additional multiple microbleeds and superficial siderosis in 4 of 7 patients and 5 of 7 patients respectively. Including data from recently published literature CT scans delivered positive results for fSAH in 95 of 100 cases (95%), whereas MRI was positive for fSAH in 69 of 69 cases (100%). CONCLUSIONS: Thin-sliced unenhanced CT is a valuable emergency diagnostic tool to rule out intracranial haemorrhage including fSAH in patients with acute transient neurological episodes if immediate MRI is not available. However, MRI work-up is crucial and mandatorily has to be completed within the next 24-72 hours.

Patient reported long-term outcome after endovascular therapy of indirect dural carotid cavernous fistulas.

PURPOSE: Patient-reported long-term follow-up after endovascular treatment of indirect carotid cavernous fistulas is important, but rarely addressed in literature. We report on this issue with a special focus on the patient's view and its impact on the indication evaluation process. METHODS: We retrospectively reviewed the records of all patients (n = 33) with a minimum follow-up interval of at least 36 and up to 166 months after endovascular treatment of an indirect carotid cavernous fistula (Barrow B-D) at our institution (treated from 01/2003 to 06/2015). We determined treatment details including primary therapy success and complication rate and quote the patient's subjective perception of the long-term treatment success using a standardized interview form. RESULTS: As a primary result the fistula was completely occluded in 25/33 cases (76%), while a downgrading was achieved in 8/33 (24%) of the cases. Secondary occlusion was observed in three out of eight patients (38%). In the long-term interview (response rate: 91%, median follow-up interval: 114 months) 87% of the patients reported high satisfaction with the long-term therapy result. Endovascular treatment achieved a sustainable relief from all eye-related symptoms in 89% and from pulsatile tinnitus in 57% of the cases. CONCLUSIONS: In addition to good results in terms of angiographic and clinical cure, endovascular treatment is also perceived as beneficial by most of the patients. This is another important argument in favor of an endovascular treatment.

Endovascular therapy of direct dural carotid cavernous fistulas - A therapy assessment study including long-term follow-up patient interviews.

PURPOSE: Endovascular embolization nowadays is a well-established treatment option for direct carotid cavernous fistulas (dCCF, Barrow Type A). There are many publications on the complication and success rates of this method. However, little is known on the patients´ opinion on the treatment result after several years. We report on this issue also including the "pioneer patients" treated almost two decades ago. METHODS: We retrospectively reviewed the records of all patient (n = 25) with a more than 24 months follow-up interval after endovascular treatment of a dCCF at our institution from 01/1999 to 08/2018. We determined primary therapy success, complication rate, state of the fistula in the last imaging follow-up and quoted the patient's subjective perception of the long-term treatment success using a standardized interview form. RESULTS: Occlusion rate in the last imaging follow up was 96% (24/25) with a complication rate of 8% (2/25). The response rate on our interview request was 96% (24/25) with a rate of considered feedback of 84% (21/25 patients). Duration of our observation interval for the patient reported outcome was 143 months / 11 years (median, range: 35-226 m / 2-18 y). Most of them (21/25, 84%) felt they benefited from the treatment. CONCLUSIONS: Endovascular supply of dCCF is a highly effective treatment method leading to a sustainable therapy success with long-lasting stable subjective benefit even to our "pioneer patients" treated almost two decades ago.

Significant improvement of the quality of bystander first aid using an expert system with a mobile multimedia device.

OBJECTIVE: Better quality bystander first-aid could improve outcome rates for emergency victims significantly. In this case-control study, we hypothesised that expert knowledge presented step-by-step to untrained helpers using a personal digital assistant (PDA), would improve the quality of bystanders basic life support. METHOD: We confronted 101 lay-helpers with two standard emergency situations. (1) An unconscious trauma victim with severe bleeding. (2) Cardiopulmonary resuscitation (CPR). Performance was assessed using an Objective Structured Clinical Examination (OSCE). One group was supported by a PDA providing visual and audio instructions, whereas the control group acted only with their current knowledge. The expert system was programmed in HTML-code and displayed on the PDA's Internet browser. RESULTS: The maximum score obtainable was 24 points corresponding to optimal treatment. The control group without the PDA reached 14.8+/-3.5 (mean value+/-standard deviation), whereas the PDA supported group scored significantly higher (21.9+/-2.7, p<0.01). The difference in performance was measurable in all criteria tested and particularly notable in the items: placing in recovery position, airway management and quality of CPR. CONCLUSION: The PDA based expert system increased the performance of untrained helpers supplying emergency care significantly. Since Internet compatible mobile devices have become widely available, a significant quality improvement in bystander first-aid seems possible.

Endovascular therapy of low- and intermediate-grade intracranial lateral dural arteriovenous fistulas: a detailed analysis of primary success rates, complication rates, and long-term follow-up of different technical approaches.

OBJECTIVE Sinus-preserving (SP) embolization techniques augment endovascular treatment options for intracranial lateral dural arteriovenous fistulas (DAVFs). The authors aimed to perform a retrospective comparison of their primary success rates, complication rates, and long-term follow-up with those of sinus-occluding (SO) treatment variants in the collective of low- and intermediate-grade lateral DAVFs (Cognard Types I-IIb). METHODS Clinical symptoms, complication rates, and Cognard grading prior to and after endovascular DAVF treatment using different technical approaches was retrospectively analyzed in 36 patients with lateral DAVF Cognard Types I-IIb. The long-term success rate was determined by a standardized questionnaire. RESULTS The SO approaches offered a higher rate of definitive fistula occlusion (93% SO vs 71% SP) but were accompanied by a significantly higher complication rate (33% or 20% SO vs 0% SP). The patients interviewed reported very high satisfaction with their health in long-term follow-up in both groups. CONCLUSIONS A higher rate of definitive fistula occlusion in the SO group was attained at the price of a significantly higher complication rate. The SP approaches offered a good primary success rate in combination with a very low complication rate. Despite some limitations of the data (e.g., a small sample size) the authors thus recommend an SP variant as the primary therapeutic option for the endovascular treatment of low- and intermediate-grade DAVFs. The SO approaches should be restricted to cases in which SP treatment does not achieve a downgrading to no worse than Cognard Type IIa.

Intracranial Aneurysms Treated by Flow-Diverting Stents: Long-Term Follow-Up with Contrast-Enhanced Magnetic Resonance Angiography.

PURPOSE: Long-term data on aneurysm treatment with flow-diverting stents are still sparse, and follow-up protocols differ widely between institutions. We present long-term results, with a focus on the usefulness of contrast-enhanced MR angiography (ceMRA). MATERIALS AND METHODS: Interventions and follow-up imaging of patients with aneurysms treated by flow-diverting stents ("Pipeline," "Silk" and "FRED" models) without additional coiling were analyzed. All MRI scans included dedicated two-phase ceMRA. Aneurysm occlusion rates, size of the aneurysmal sac and complications were evaluated on MRI and digital subtraction angiography (DSA), where available. The ability of ceMRA to depict aneurysm occlusion and stent patency was graded on a three-point scale. RESULTS: Twenty-five patients with 102 MRI scans were included. The median duration of follow-up was 830 days. Aneurysm occlusion rates were 52% at 3 months (10 of 19 patients), 72% at 6 months (18/25) and 84% overall (21/25). Shrinkage of the aneurysmal sac was found in 19 patients (76%) and in 12 cases to <50% of the original size (48%). CeMRA assessability of aneurysmal occlusion was graded as good in all cases. When compared to DSA (18 cases), ceMRA had a sensitivity of 100% and specificity of 91% regarding aneurysm remnant detection. Assessability of the stent lumen varied and was limited in most cases. CONCLUSIONS: Flow-diverter treatment achieves high occlusion rates and can cause major aneurysm shrinkage. CeMRA is highly valuable regarding imaging of the aneurysmal sac. There are limitations regarding the assessability of the stent lumen on ceMRA. LEVEL OF EVIDENCE: Level 4, Case Series.

Early treatment of complex located pediatric low-grade gliomas using iodine-125 brachytherapy alone or in combination with microsurgery.

To analyze efficacy, functional outcome, and treatment toxicity of low-dose rate I-125 brachytherapy (SBT) alone or in combination with best safe resection (in case of larger tumor volumes) as first-line treatment for pediatric low-grade gliomas (PLGGs) not suitable for complete resection. Consecutively treated (2000-2014) complex located circumscribed WHO grade I/II PLGGs were included. For small tumors (≤4 cm in diameter) SBT alone was performed; for larger tumors best safe resection and subsequent SBT was chosen. Temporary Iodine-125 seeds were used (median reference dose: 54 Gy). Treatment response was estimated with the modified MacDonald criteria. Analysis of functional outcome included ophthalmological, endocrinological and neurological evaluation. Survival was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from proportional hazards models. Toxicity was categorized according to the Common Terminology Criteria for Adverse Events. Fifty-eight patients were included treated either with SBT alone (n = 39) or with SBT plus microsurgery (n = 19). Five-year progression-free survival was 87%. Two patients had died due to tumor progression. Among survivors, improvement/stabilization/deterioration of functional deficits was seen in 20/14/5 patients, respectively. Complete/partial response had beneficial impact on functional scores (P = 0.02). The 5-year estimated risk to receive adjuvant radiotherapy/chemotherapy was 5.2%. The overall early (delayed) toxicity rate was 8.6% (10.3%), respectively. No permanent morbidity occurred. In complex located PLGGs, early SBT alone or combined with best safe resection preserves/improves functional scores and results in tumor control rates usually achieved with complete resection. Long-term analysis is necessary for confirmation of these results.

Increased 68Ga-DOTATATE uptake in PET imaging discriminates meningioma and tumor-free tissue.

UNLABELLED: Meningiomas are known to express somatostatin receptor 2 (SSTR2). PET using the SSTR2 analog (68)Ga-DOTATATE has recently been introduced for imaging of meningiomas. However, a systematic correlation between (68)Ga-DOTATATE uptake, SSTR2 expression, and histology (including tumor-free scar tissue) is still lacking. For elucidation, we conducted this prospective study. METHODS: Twenty-one adult patients with primary (n = 12) or recurrent (n = 9) meningiomas were prospectively enrolled. Preoperative MR imaging and (68)Ga-DOTATATE PET scans were fused and used for a spatially precise neuronavigated tissue-sampling procedure during tumor resection. Histopathologic diagnosis included immunohistochemical determination of SSTR2 expression. At each individual sampling site, the maximum standardized uptake value (SUVmax) of (68)Ga-DOTATATE was correlated with MR imaging findings, histology, and semiquantitative SSTR2 expression. RESULTS: One hundred fifteen samples (81 tumor, 34 tumor-free) were obtained. There was a significant positive correlation between SUVmax and SSTR2 expression. Receiver-operating characteristic analysis revealed a threshold of 2.3 for SUVmax to discriminate between tumor and nontumoral tissue. Regarding the detection of tumor tissue, PET imaging showed a higher sensitivity (90% vs. 79%; P = 0.049), with specificity and positive predictive values similar to MR imaging, for both de novo and recurrent tumors. CONCLUSION: (68)Ga-DOTATATE uptake correlates with SSTR2 expression and offers high diagnostic accuracy to delineate meningioma from tumor-free tissue even in recurrent tumors after previous therapy. Our findings substantiate an important role for (68)Ga-DOTATATE PET in meningioma management.

Irradiation and bevacizumab in high-grade glioma retreatment settings.

PURPOSE: Reirradiation is a treatment option for recurrent high-grade glioma with proven but limited effectiveness. Therapies directed against vascular endothelial growth factor have been shown to exert certain efficacy in combination with chemotherapy and have been safely tested in combination with radiotherapy in a small cohort of patients. To study the feasibility of reirradiation combined with bevacizumab treatment, the toxicity and treatment outcomes of this approach were analyzed retrospectively. PATIENTS AND METHODS: After previous treatment with standard radiotherapy (with or without temozolomide) patients with recurrent malignant glioma received bevacizumab (10 mg/kg intravenous) on Day 1 and Day 15 during radiotherapy. Maintenance therapy was selected based on individual considerations, and mainly bevacizumab-containing regimens were chosen. Patients received 36 Gy in 18 fractions. RESULTS: The data of the medical charts of the 30 patients were analyzed retrospectively. All were irradiated in a single institution and received either bevacizumab (n = 20), no additional substance (n = 7), or temozolomide (n = 3). Reirradiation was tolerated well, regardless of the added drug. In 1 patient treated with bevacizumab, a wound dehiscence occurred. Overall survival was significantly better in patients receiving bevacizumab (p = 0.03, log-rank test). In a multivariate proportional hazards Cox model, bevacizumab, Karnovsky performance status, and World Health Organization grade at relapse turned out to be the most important predictors for overall survival. CONCLUSION: Reirradiation with bevacizumab is a feasible and effective treatment for patients with recurrent high-grade gliomas. A randomized trial is warranted to finally answer the question whether bevacizumab adds substantial benefit to a radiotherapeutic retreatment setting.