Christina Wendl

Fluorescein sodium-guided resection of cerebral metastases—experience with the first 30 patients

BackgroundSurgical resection is a key element of the multidisciplinary treatment of cerebral metastases (CMs). Recent studies have highlighted the importance of complete resection of CMs for improving recurrence-free and overall survival rates. This study presents the first data on the use of fluorescein sodium (FL) under the dedicated surgical microscope filter YELLOW 560xa0nm (Zeiss Meditec, Germany) in patients with CM.MethodsThirty patients with CMs of different primary cancers were included (15 females, 15 males; mean age 61.1xa0years); 200xa0mg of FL was intravenously injected directly before CM resection. A YELLOW 560xa0nm filter was used for microsurgical tumor resection and resection control. Surgical reports were evaluated regarding the degree of fluorescent staining, postoperative MRIs regarding the extent of resection [gadolinium (Gd)-enhanced T1-weighted sequence] and the postoperative courses regarding any adverse effects.ResultsMost patients (90.0xa0%, nu2009=u200927) showed bright fluorescent staining, which markedly enhanced tumor visibility. Three patients (10.0xa0%) (two with adenocarcinoma of the lung and one with melanoma of the skin) showed no or only insufficient FL staining. Another three patients (10.0xa0%) showed residual tumor tissue in the postoperative MRI examination. In two other patients, radiographic examination could not exclude the possibility of very small areas of residual tumor tissue. Thus, gross-total resection was achieved in 83.3xa0% (nu2009=u200925) of patients. No adverse effects were registered over the postoperative course.ConclusionsFL and the YELLOW 560xa0nm filter are safe and practical tools for the resection of CM, but further prospective research is needed to confirm that this advanced technique will improve the quality of CM resection.

Continuous intra-arterial nimodipine infusion in patients with severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a feasibility study and outcome results.

BackgroundSevere cerebral vasospasm is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. No causative treatment is yet available and hypertensive hypervolemic therapy (HHT) is often insufficient to avoid delayed cerebral ischemia and neurological deficits. We compared patients receiving continuous intra-arterial infusion of the calcium-antagonist nimodipine with a historical group treated with HHT and oral nimodipine alone.MethodsBetween 0.5 and 1.2xa0mg/h of nimodipine were continuously administered by intra-arterial infusion via microcatheters either into the internal carotid or vertebral artery or both, depending on the areas of vasospasm. The effect was controlled via multimodal neuromonitoring and transcranial Doppler sonography. Outcome was determined by means of the Glasgow Outcome Scale at discharge and 6xa0months after the hemorrhage and compared to a historical control group.ResultsTwenty-one patients received 28 intra-arterial nimodipine infusions. Six months after discharge, the occurrence of cerebral infarctions was significantly lower (42.6xa0%) in the nimodipine group than in the control group (75.0xa0%). This result was reflected by a significantly higher proportion (76.0xa0%) of patients with good outcome in the nimodipine-treated group, when compared to 10.0xa0% good outcome in the control group. Median GOS was 4 in the nimodipine group and 2 in the control group (pu2009=u20090.001).ConclusionsContinuous intra-arterial nimodipine infusion is an effective treatment for patients with severe cerebral vasospasm who fail to respond to HHT and oral nimodipine alone. Key to the effective administration of continuous intra-arterial nimodipine is multimodal neuromonitoring and the individual adaptation of dosage and time of infusion for each patient.

Fluorescein sodium-guided surgery in cerebral lymphoma.

OBJECTIVESnGrowth and progress of primary central nervous lymphoma (PCNSL) severely disrupt the blood brain barrier (BBB). Such disruptions can be intraoperatively visualized by injecting fluorescein sodium (FL) and applying a YELLOW 560 nm surgical microscope filter. Here, we report a small cohort of patients with PCNSL that mimicked high grade gliomas (HGG) or cerebral metastases (CM), who had been operated on with the use of FL.nnnPATIENTS AND METHODSnRetrospectively, seven patients with PCNSL were identified, who had been operated on by means of microsurgery after intravenous FL injection. The surgical reports were screened for statements on the grade of fluorescent staining in the tumor area. One representative case was chosen to show the staining under white light as well as under filtered light at different distances to the tumor area.nnnRESULTSnAll patients had shown bright and homogenous fluorescent staining of the tumor (n=7. 100%). No adverse effects had been observed.nnnCONCLUSIONnSimilar to patients with HGG or CM, patients with PCNSL may benefit from use of FL and the dedicated YELLOW 560 nm filter in open surgery.

Epileptic Activity Increases Cerebral Amino Acid Transport Assessed by 18F-Fluoroethyl-l-Tyrosine Amino Acid PET: A Potential Brain Tumor Mimic

O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) PET is a well-established method increasingly used for diagnosis, treatment planning, and monitoring in gliomas. Epileptic activity, frequently occurring in glioma patients, can influence MRI findings. Whether seizures also affect 18F-FET PET imaging is currently unknown. The aim of this retrospective analysis was to investigate the brain amino acid metabolism during epileptic seizures by 18F-FET PET and to elucidate the pathophysiologic background. Methods: Ten patients with 11 episodes of serial seizures or status epilepticus, who underwent MRI and 18F-FET PET, were studied. The main diagnosis was glioma World Health Organization grade II–IV (n = 8); 2 patients suffered from nonneoplastic diseases. Immunohistochemical assessment of LAT1/LAT2/CD98 amino acid transporters was performed in seizure-affected cortex (n = 2) and compared with glioma tissues (n = 3). Results: All patients exhibited increased seizure-associated strict gyral 18F-FET uptake, which was reversible in follow-up studies or negative shortly before and without any histologic or clinical signs of tumor recurrence. 18F-FET uptake corresponded to structural MRI changes, compatible with cortical vasogenic and cytotoxic edema, partial contrast enhancement, and hyperperfusion. Patients with prolonged postictal symptoms lasting up to 8 wk displayed intensive and widespread (≥ 1 lobe) cortical 18F-FET uptake. LAT1/LAT2/CD98 was strongly expressed in neurons and endothelium of seizure-affected brains and less in reactive astrocytosis. Conclusion: Seizure activity, in particular status epilepticus, increases cerebral amino acid transport with a strict gyral 18F-FET uptake pattern. Such periictal pseudoprogression represents a potential pitfall of 18F-FET PET and may mimic brain tumor. Our data also indicate a seizure-induced upregulation of neuronal, endothelial, and less astroglial LAT1/LAT2/CD98 amino acid transporter expression.

Use of the pCONus as an adjunct to coil embolization of acutely ruptured aneurysms

Introduction Coil embolization of ruptured aneurysms has become the standard treatment in many situations. However, certain aneurysm morphologies pose technical difficulties and may require the use of adjunctive devices. Objective To present our experience with the pCONus, a new neck bridging device, as an adjunct to coil embolization for acutely ruptured aneurysms and discuss the technical success, angiographic and clinical outcomes. Methods We conducted a retrospective review of our database of prospectively collected data to identify all patients who presented with acute subarachnoid hemorrhage that required adjunctive treatment with the pCONus in the acute stage. We searched the database between April 2011 and April 2016. Results 21 patients were identified (13 male, 8 female) with an average age of 54.6u2005years (range 31–73). 8 aneurysms were located at the basilar artery tip, 7 at the anterior communicating artery, 4 at the middle cerebral artery bifurcation, 1 pericallosal, and 1 basilar fenestration. 61.8% patients achieved modified Raymond–Roy classification I or II at immediate angiography, with 75% of patients having completely occluded aneurysms or stable appearance at initial follow-up. There were no repeat aneurysmal ruptures and two device-related complications (no permanent morbidity). Four patients in our cohort died. Conclusions Use of the pCONus is safe and effective in patients with acutely ruptured aneurysms and carries a high rate of technical success.

Fluorescein sodium-guided resection of cerebral metastases—an update

BackgroundCerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identification of tumor tissue. In 2012, we started evaluating fluorescein (FL) with the dedicated microscope filter in cerebral metastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients.MethodsNinety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60xa0years, range, 25–85xa0years); 5xa0mg/kg bodyweight of FL was intravenously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control.The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events.ResultsNinety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL staining. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (nu2009=u200979) of patients. No adverse events were registered during the postoperative course.ConclusionsFL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

Early postoperative tumor progression predicts clinical outcome in glioblastoma—implication for clinical trials

Molecular markers define the diagnosis of glioblastoma in the new WHO classification of 2016, challenging neuro-oncology centers to provide timely treatment initiation. The aim of this study was to determine whether a time delay to treatment initiation was accompanied by signs of early tumor progression in an MRI before the start of radiotherapy, and, if so, whether this influences the survival of glioblastoma patients. Images from 61 patients with early post-surgery MRI and a second MRI just before the start of radiotherapy were examined retrospectively for signs of early tumor progression. Survival information was analyzed using the Kaplan–Meier method, and a Cox multivariate analysis was performed to identify independent variables for survival prediction. 59 percent of patients showed signs of early tumor progression after a mean time of 24.1xa0days from the early post-surgery MRI to the start of radiotherapy. Compared to the group without signs of early tumor progression, which had a mean time of 23.3xa0days (pu2009=u20090.685, Student’s t test), progression free survival was reduced from 320 to 185xa0days (HR 2.3; CI 95% 1.3–4.0; pu2009=u20090.0042, log-rank test) and overall survival from 778 to 329xa0days (HR 2.9; CI 95% 1.6–5.1; pu2009=u20090.0005). A multivariate Cox regression analysis revealed that the Karnofsky performance score, O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, and signs of early tumor progression are prognostic markers of overall survival. Early tumor progression at the start of radiotherapy is associated with a worse prognosis for glioblastoma patients. A standardized baseline MRI might allow for better patient stratification.

Direct carotid cavernous sinus fistulae: vessel reconstruction using flow-diverting implants.

PurposeRetrospective evaluation of our experience with the use of flow diverters (FD) for the endovascular treatment of direct carotid-cavernous sinus fistulae (diCCF).MethodsBetween 2011 and 2015, 14xa0consecutive patients with 14xa0diCCF were treated with FD alone or in combination with other implants in axa0single institution.ResultsAxa0total of 21xa0sessions were performed in 14xa0patients. FD placement was technically successful in all cases without an adverse event. Patients were treated with FD alone (nxa0= 5), FD and covered stents (nxa0= 2), FD and coils (nxa0= 7). Axa0total of 59xa0FD (24xa0Pipeline Embolization Device, Medtronic; 35xa0p64 Flow Modulation Device, phenox), 291xa0coils, and 3xa0stent grafts were used. Three of 14xa0diCCF were completely occluded after the 1stxa0session, axa0minor residual shunt was found in 7/14, and in the remaining 4/14 patients, the shunt volume was reduced significantly. The mean follow-up period encompassed 20xa0months. Additional treatment included transvenous coil occlusion (nxa0= 3) and/or further FD deployment (nxa0= 5). An asymptomatic internal carotid artery (ICA) occlusion was encountered in 2xa0patients, related to an interruption of antiaggregation. At the last follow-up, 10/14xa0patients were free from ocular symptoms (71u2009%), 2xa0had residual exophthalmos, and no patient had clinical deterioration.ConclusionThe usage of FD for the treatment of diCCF is straightforward. Injury of the cranial nerves can be avoided. In most cases, ocular symptoms improve. Several FD layers and/or an adjunctive venous coil occlusion are required. Complete occlusion of axa0diCCF may take weeks or months and long-term antiaggregation is required. In the future, axa0flexible stent graft might be axa0better solution.

Recurrence rates and functional outcome after resection of intrinsic intramedullary tumors

INTRODUCTIONnIntramedullary tumors account for 2-4% of all CNS neoplasms. Surgical resection is challenging because of aggravated neurological impairment in up to 64% of patients. We analyzed a consecutive series of patients with intramedullary tumors and focused on the extent of resection, functional outcome, and tumor recurrence.nnnMETHODSn53 patients (23 women and 30 men; mean age 46.3 years) were included who had undergone microsurgical resection for intramedullary spinal tumors. We reviewed the patient records for tumor size, edema, intratumoral hemorrhage, consistency, midline detection, resection method, extent of resection, histopathology, and recurrence. Outcome was measured by the Karnofsky Score (KPI), the McCormick score (MCS), and the Medical Research Council Neurological Performance Score (MRC-NPS).nnnRESULTSnThe most frequent diagnosis was ependymoma (37.7%), lymphoma (13.2%) and astrocytoma (11.3%). The majority of tumors were located in the thoracic spine (62.2%). Gross total resection was achieved in 73.6% and most successful in patients with ependymal histology (p<0.01). Tumor recurrence - observed in 11.3% - was significantly associated with age >65 years, astrocytic histology, higher tumor grades, and higher Ki-67 labeling. At follow-up, MCS and MRC-NPS showed significantly better results than prior to resection (p<0.001), and pain and sensory deficits had improved in 67.9% and 64.2% of patients, respectively. Microsurgical resection improved the neurological status significantly. Pain and sensory deficits showed higher improvement rates than paresis and vegetative dysfunction.nnnCONCLUSIONnOur data help identify patients at risk of tumor recurrence and classify the course of postoperative neurological performance.

Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage

BackgroundLong-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects.MethodsAll patients treated with CIAN therapy for at least 5xa0days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2xa0days before the beginning and 5xa0days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy.ResultsData from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5xa0±xa04.5xa0days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4–5) 6xa0months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation of a previous antiinfective therapy or the onset of antibiotics which was in line with a significant increase of C-reactive protein and white blood cell count. Obstipation was observed in 22 patients (78.6%). Ten patients (35.7%) even showed insufficient defecation on at least seven consecutive days. Compared to the situation before, ICP was significantly higher during the whole period of CIAN therapy.ConclusionsLong-term CIAN therapy is associated with diverse side effects. The leading problems are an impairment of the hemodynamic situation and cardiac problems, an increase in infectious complications, a worsening of the motility of the gastrointestinal tract, and rising ICP values. Teams on neurointensive care units must be aware of these side effects to avoid that the beneficial effects of CIAN therapy on CV reported elsewhere are foiled by the problems this technique can be associated with.