Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO): An Open-Label, Dose-Escalation Phase I/II Trial.

BACKGROUND: The median time to recurrence of glioblastoma (GB) following multimodal treatment is ∼7 mo. Nearly all cancers recur locally, suggesting that augmenting local treatments may improve outcomes. OBJECTIVE: To investigate whether intraoperative radiotherapy (IORT) to the resection cavity is safe and effective. METHODS: INTRAGO was a phase I/II trial to evaluate the safety and tolerability of IORT with 20 to 40 Gy of low-energy photons in addition to standard radiochemotherapy (ClinicalTrials.gov ID, NCT02685605). The primary endpoint was safety as per occurrence of dose-limiting toxicities. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). We also performed an exploratory analysis of the local PFS (L-PFS), defined as recurrence within 1 cm of the treated margin. RESULTS: Fifteen patients were treated at 3 dose levels. Of these, 13 underwent incomplete resection, 6 had unresected satellites, and 3 did not receive per-protocol treatment (PPT). The MGMT promoter was unmethylated in 10 patients. The median follow-up was 13.8 mo. The majority of grade 3 to 5 adverse events were deemed unrelated to IORT. Five cases of radionecrosis were observed, 2 were classified as grade 3 events. Other grade 3 events judged related to radiotherapy (external-beam radiotherapy and/or IORT) were wound dehiscence (n = 1), CSF leakage (n = 1), cyst formation (n = 1). No IORT-related deaths occurred. The median PFS was 11.2 mo (95% confidence interval [CI]: 5.4-17.0) for all patients and 11.3 mo (95% CI: 10.9-11.6) for those receiving PPT. The median L-PFS was 14.3 mo (95% CI: 8.4-20.2) for all patients and 17.8 mo (95% CI: 9.7-25.9) for those receiving PPT. The median OS was 16.2 mo (95% CI: 11.1-21.4) for all patients and 17.8 mo (95% CI: 13.9-21.7) for those receiving PPT. CONCLUSION: These data suggest that IORT is associated with manageable toxicity. Considering the limitations of a 15-patient phase I/II trial, further studies aimed at assessing an outcome benefit are warranted.

Pregnancy and delivery in moyamoya vasculopathy: experience of a single European institution.

Moyamoya vasculopathy (MMV) is a stenoocclusive cerebrovascular disease frequently affecting adolescent females. Thus, the management of pregnancy is of major interest for physicians dealing with MMV patients. However, clinical data concerning pregnant MMV patients is lacking. Our aim was to analyze the course of pregnancy in our European MMV patient cohort. We retrospectively identified MMV patients with a history of pregnancy who were treated in our institution. We analyzed demographic data, clinical symptoms, treatment, and detailed history of pregnancies. We identified 31 MMV patients (81% moyamoya disease (MMD), 6% unilateral MMD, 13% quasi MMD) with a history of pregnancy resulting in a total of 60 pregnancies and 48 deliveries. Ninety-four percent of the patients became symptomatic by ischemic events and 6% by headache. Eighty-one and nineteen percent of the patients experienced their pregnancies prior to (first group) or after the diagnosis (second group), respectively. In the first group, the mean age at first delivery and bypass treatment were 24 ± 4 and 42 ± 10, respectively. Eight percent of these patients were diagnosed as MMV due to ischemic events during perinatal period. In the second group, the mean age at first delivery and bypass treatment were 26 ± 7 and 23 ± 6, respectively. No cerebral events were reported within perinatal period in this group. All previously operated patients continued their aspirin medication at least until the 3rd trimester. The majority of the pregnancies occurred prior to diagnosis in our European patient cohort. Our data indicates a protective effect of surgical treatment for avoiding cerebral events during pregnancy and delivery for already diagnosed patients.

Combined stereotactic biopsy and stepping-source interstitial irradiation of glioblastoma multiforme.

Patients diagnosed with glioblastoma multiforme receiving stereotactic biopsy only either due to tumor localization or impaired clinical status face a devastating prognosis with very short survival times. One strategy to provide an initial cytoreductive and palliative therapy at the time of the stereotactic biopsy is interstitial irradiation through the pre-defined trajectory of the biopsy channel. We designed a novel treatment planning system and evaluated the treatment potential of a fixed-source and a stepping-source algorithm for interstitial radiosurgery on non-spherical glioblastoma in direct adjacency to risk structures. Using both setups, we show that radiation doses delivered to 100% of the gross tumor volume shifts from sub-therapeutic (10-12 Gy) to sterilizing single doses (25-30 Gy) when using the stepping source algorithm due to improved sparing of organs-at-risk. Specifically, the maximum doses at the brain stem were 100% of the PTV dose when a fixed central source and 38% when a stepping-source algorithm was used. We also demonstrated precision of intracranial target points and stability of superficial and deep trajectories using both a phantom and a body donor study. Our setup now for the first time provides a basis for a clinical proof-of-concept trial and may widen palliation options for patients with limited life expectancy that should not undergo time-consuming therapies.

Immediate Titanium Mesh Implantation for Patients with Postcraniotomy Neurosurgical Site Infections: Safe and Aesthetic Alternative Procedure?

BACKGROUND: Surgical site infection (SSI) is one of the main complications after craniotomy. The incidence is up to 11% in the literature. The established procedure is debridement, removal of the bone flap, and delayed cranioplasty. Delayed cranioplasty has several disadvantages. A promising approach is the immediate titanium mesh implantation at the time of wound revision. We report our experience with this technique regarding outcome measured by reinfection rates and patient satisfaction. METHODS: Patients treated in our department from January 2013 to October 2014 with SSI after craniotomy for brain tumor, trauma, or vascular pathologies were prospectively collected. In all these patients, immediate titanium mesh implantation after bone flap removal was performed. Primary outcome parameters were the reinfection rate and patient satisfaction via self-designed questionnaires in a follow-up period >3 months. RESULTS: Twenty-four patients were included within the study period. Main risk factors causing SSI were previous steroid medication (62.5%), cranial radiation therapy (42%), cerebrospinal fluid fistula after initial surgery (12.5%), and diabetes mellitus (25%). The follow-up was >3 months after titanium mesh cranioplasty (mean 4.6 months; range 3-6 months). No recurrent infection was detected in the study group. In 2 cases, reoperation was necessary. The returning questionnaires showed a high satisfaction rate with the cosmetic result. CONCLUSIONS: Our small series seems to confirm that immediate titanium mesh implantation for patients with postcraniotomy SSI is a cost-effective, safe, and cosmetically suitable alternative to delayed cranioplasty in selected patients without hydrocephalus or persistent cerebrospinal fluid fistula.

Hepatotoxicity by combination treatment of temozolomide, artesunate and Chinese herbs in a glioblastoma multiforme patient: case report review of the literature.

Glioblastoma multiforme (GBM) represents an aggressive tumor type with poor prognosis. The majority of GBM patients cannot be cured. There is high willingness among patients for the compassionate use of non-approved medications, which might occasionally lead to profound toxicity. A 65-year-old patient with glioblastoma multiforme (GBM) has been treated with radiochemotherapy including temozolomide (TMZ) after surgery. The treatment outcome was evaluated as stable disease with a tendency to slow tumor progression. In addition to standard medication (ondansetron, valproic acid, levetiracetam, lorazepam, clobazam), the patient took the antimalarial drug artesunate (ART) and a decoction of Chinese herbs (Coptis chinensis, Siegesbeckia orientalis, Artemisia scoparia, Dictamnus dasycarpus). In consequence, the clinical status deteriorated. Elevated liver enzymes were noted with peak values of 238 U/L (GPT/ALAT), 226 U/L (GOT/ASAT), and 347 U/L (γ-GT), respectively. After cessation of ART and Chinese herbs, the values returned back to normal and the patient felt well again. In the literature, hepatotoxicity is well documented for TMZ, but is very rare for ART. Among the Chinese herbs used, Dictamnus dasycarpus has been reported to induce liver injury. Additional medication included valproic acid and levetiracetam, which are also reported to exert hepatotoxicity. While all drugs alone may bear a minor risk for hepatotoxicity, the combination treatment might have caused increased liver enzyme activities. It can be speculated that the combination of these drugs caused liver injury. We conclude that the compassionate use of ART and Chinese herbs is not recommended during standard radiochemotherapy with TMZ for GBM.

Characterization of Clinical and Radiological Features of Quasi-Moyamoya Disease among European Caucasians Including Surgical Treatment and Outcome.

BACKGROUND: Moyamoya disease (MMD) associated with a potentially underlying disease, such as genetic disorders or other coexisting hematological pathologies, is called quasi-MMD. This very rare disease has been characterized mainly in Asian countries, so far. As MMD reveals several significant ethnic differences, the question is raised whether characteristics of quasi-MMD would also vary among different ethnic backgrounds. Here, we report a series of 61 patients with quasi-MMD and highlight the specific clinical features of this rare disease among European Caucasians. METHODS: We retrospectively identified 61 European Caucasians with quasi-MMD who were treated in our institution between 1997 and 2014. We analyzed demographic data, clinical symptoms, associated diseases, angiographic characteristics and functional hemodynamic studies. RESULTS: Thirty-three percent of our patients were juvenile. We observed an overall female predominance of 2.8:1. Seventy-nine percent presented with a typical quasi-MMD with more pronounced unilateral and atypical quasi-MMD in pediatric population (unilateral/atypical: pediatric patients 20/15%, adults 7/7%). We identified a wide range of associated diseases. Overall, 84 and 8% of our cohort presented initially with ischemic and hemorrhagic manifestation, respectively. The hemorrhagic manifestation of quasi-MMD occurred however only in adults. Angiographic analysis revealed steno-occlusive involvement of the posterior circulation (in addition to the anterior circulation) in 31% with a higher involvement in pediatric patients (40%) compared to adults (27%). CONCLUSIONS: The characterization of our European Caucasian cohort reveals several differences when compared to reported Asian quasi-MMD cohorts and also compared to European Caucasian MMD cohort. We conclude that quasi-MMD represents a distinct disease with different ethnic clinical features.

Is There an Influence of Routine Daily Transcranial Doppler Examination on Clinical Outcome in Patients After Aneurysmal Subarachnoid Hemorrhage?

BACKGROUND: Transcranial Doppler (TCD) is widely used as a daily routine method to detect vasospasm in patients after aneurysmal subarachnoid hemorrhage (aSAH); however, there are only limited data about the real benefit of this examination. Therefore, the clinical outcome of 2 cohorts with and without daily TCD after aSAH was assessed. METHODS: All patients included in this study received a standardized diagnostic and treatment protocol. Fifty patients admitted with aSAH from January 2013 to December 2013 received daily TCD measurements; 39 patients admitted from January 2014 to September 2014 received no TCD measurements. Data on clinical grade (Hunt and Hess grade), severity of bleeding (Barrow Neurological Institute grade), localization of aneurysm, and angiographic or clinically relevant vasospasm were collected prospectively. The Glasgow Outcome Scale, modified Rankin Scale, and the National Institute of Health Stroke Scale were used as clinical outcome parameters. RESULTS: Patient baseline characteristics and clinical data were comparable; treatment modality of the aneurysm was not different between the groups (P = 0.7756). No significant difference between the Hunt and Hess grade (P = 0.818) and the Barrow Neurological Institute grade (P = 0.1551) was observed. There was also no significance concerning the incidence of angiographic or clinically relevant vasospasm between both groups (P = 0.5842 and P = 0.7933). Glasgow Outcome Scale, mRS, and National Institute of Health Stroke Scale as the primary outcome parameters showed no significant difference in morbidity and mortality between both groups (mortality P = 0.8544). CONCLUSIONS: With the limitation of an explorative cohort study, the results indicate that routine TCD studies do not improve the overall outcome of patients after aSAH.

Metronomic chemotherapy with daily low-dose temozolomide and celecoxib in elderly patients with newly diagnosed glioblastoma multiforme: a retrospective analysis.

Chemotherapy is often omitted in elderly patients with glioblastoma multiforme due to a fear of side effects. We applied metronomic chemotherapy with low-dose temozolomide and celecoxib (LD-TEM/CEL) during and after external beam radiotherapy (EBRT) and here report on how this regimen compares to standard temozolomide radiochemotherapy (SD-TEM) in elderly patients. We retrospectively analyzed records of 146 patients aged 65 years and older that underwent EBRT. Factors of interest were age, performance status, comorbidities, MGMT status, therapy (resection/biopsy, radiotherapy/dose, chemotherapy/regimen/dose), progression-free (PFS) and overall survival (OS) status. Irrespective of the regimen, addition of chemotherapy more than doubled median survival rates (EBRT only: 4.2 months; EBRT + LD-TEM/CEL: 8.5 months; EBRT + SD-TEM: 10.8 months; p ≤ 0.008). Although patients receiving metronomic LD-TEM/CEL were significantly older (62 % were ≥75 years vs. 22 %; p < 0.001), had significantly lower performance scores (50 % had a KPS <70 vs. 28 %; p = 0.049) and were significantly more comorbid (73 % had ≥4 comorbidities vs. 37 %; p = 0.002) than patients of the SD-TEM group, there were no significant differences in PFS and OS. Independent of other factors, omission of chemotherapy significantly impairs progression-free and overall survival. With all the limitations of a retrospective analysis, our data suggest that metronomic chemotherapy with LD-TEM/CEL may be equieffective and eventually better tolerated than SD-TEM. It may be offered to elderly patients that are not eligible for standard chemotherapy.

MR angiography follow-up 10 years after cryptogenic nonperimesencephalic subarachnoid hemorrhage.

OBJECTIVES: Long-term magnetic resonance angiography (MRA) follow-up studies regarding cryptogenic nonperimesencephalic subarachnoid hemorrhage (nSAH) are scarce. This single-centre study identified all patients with angiographically verified cryptogenic nSAH from 1998 to 2007: The two main objectives were to prospectively assess the incidence of de novo aneurysm with 3.0-MRI years after cryptogenic nSAH in patients without evidence for further hemorrhage, and retrospectively assess patient demographics and outcome. METHODS: From prospectively maintained report databases all patients with angiographically verified cryptogenic nSAH were identified. 21 of 29 patients received high-resolution 3T-MRI including time-of-flight and contrast-enhanced angiography, 10.2 ± 2.8 years after cryptogenic nSAH. MRA follow-up imaging was compared with initial digital subtraction angiography (DSA) and CT/MRA. Post-hemorrhage images were related to current MRI with reference to persistent lesions resulting from delayed cerebral ischemia (DCI) and post-hemorrhagic siderosis. Patient-based objectives were retrospectively abstracted from clinical databases. RESULTS: 29 patients were identified with cryptogenic nSAH, 17 (59%) were male. Mean age at time of hemorrhage was 52.9 ± 14.4 years (range 4 - 74 years). 21 persons were available for long-term follow-up. In these, there were 213.5 person years of MRI-follow-up. No de novo aneurysm was detected. Mean modified Rankin Scale (mRS) during discharge was 1.28. Post-hemorrhage radiographic vasospasm was found in three patients (10.3%); DCI-related lesions occurred in one patient (3.4%). Five patients (17.2%) needed temporary external ventricular drainage; long-term CSF shunt dependency was necessary only in one patient (3.4%). Initial DSA retrospectively showed a 2 x 2 mm aneurysm of the right distal ICA in one patient, which remained stable. Post-hemorrhage siderosis was detected 8.1 years after the initial bleeding in one patient (4.8%). CONCLUSION: Patients with cryptogenic nSAH have favourable outcomes and do not exhibit higher risks for de novo aneurysms. Therefore the need for long-term follow up after cryptogenic nSAH is questionable.

²³Na-MRI of recurrent glioblastoma multiforme after intraoperative radiotherapy: technical note.

INTRODUCTION: We report the first case of an intraoperative radiotherapy (IORT) in a patient with recurrent glioblastoma multiforme (GBM) who was followed up with a novel magnetic resonance imaging (MRI) method-(23)Na-MRI-in comparison to a standard contrast-enhanced (1)H-MRI and (18)F-FET-PET. METHODS: A 56-year-old female patient with diagnosed GBM in July 2012 underwent tumor resection, radiochemotherapy, and three cycles of chemotherapy. After a relapse, 6 months after the initial diagnosis, an IORT was recommended which was performed in March 2013 using the INTRABEAM system (Carl Zeiss Meditec AG, Germany) with a 3-cm applicator and a surface dose of 20 Gy. Early post-operative contrast-enhanced and 1-month follow-up (1)H-MRI and a (18)F-FET-PET were performed. In addition, an IRB-approved (23)Na-MRI was performed on a 3.0-T MR scanner (MAGNETOM TimTrio, Siemens Healthcare, Germany). RESULTS: After re-surgery and IORT in March 2013, only a faint contrast enhancement but considerable surrounding edema was visible at the medio-posterior resection margins. In April 2013, new and progressive contrast enhancement, edema, (23)Na content, and increased uptake in the (18)F-FET-PET were visible, indicating tumor recurrence. Increased sodium content within the area of contrast enhancement was found in the (23)Na-MRI, but also exceeding this area, very similar to the increased uptake depicted in the (18)F-FET-PET. The clearly delineable zone of edema in both examinations exhibits a lower (23)Na content compared to areas with suspected proliferating tumor tissue. CONCLUSION: (23)Na-MRI provided similar information in the suspicious area compared to (18)F-FET-PET, exceeding conventional (1)H-MRI. Still, (23)Na-MRI remains an investigational technique, which is worth to be further evaluated.

INTRAGO: intraoperative radiotherapy in glioblastoma multiforme­a phase I/II dose escalation study.

BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent primary malignant brain tumor in adults. Despite multimodal therapies, almost all GBM recur within a narrow margin around the initial resected lesion. Thus, novel therapeutic intensification strategies must target both, the population of dispersed tumor cells around the cavity and the postoperative microenvironment. Intraoperative radiotherapy (IORT) is a pragmatic and effective approach to sterilize the margins from persistent tumor cells, abrogate post-injury proliferative stimuli and to bridge the therapeutic gap between surgery and radiochemotherapy. Therefore, we have set up INTRAGO, a phase I/II dose-escalation study to evaluate the safety and tolerability of IORT added to standard therapy in newly diagnosed GBM. In contrast to previous approaches, the study involves the application of isotropic low-energy (kV) x-rays delivered by spherical applicators, providing optimal irradiation properties to the resection cavity. METHODS/DESIGN: INTRAGO includes patients aged 50 years or older with a Karnofsky performance status of at least 50% and a histologically confirmed (frozen sections) supratentorial GBM. Safety and tolerability (i.e., the maximum tolerated dose, MTD) will be assessed using a classical 3 + 3 dose-escalation design. Dose-limiting toxicities (DLT) are wound healing deficits or infections requiring surgical intervention, IORT-related cerebral bleeding or ischemia, symptomatic brain necrosis requiring surgical intervention and early termination of external beam radiotherapy (before the envisaged dose of 60 Gy) due to radiotoxicity. Secondary end points are progression-free and overall survival. TRIAL REGISTRATION: The study is registered with clinicaltrials.gov, number: NCT02104882 (Registration Date: 03/26/2014).

Collateralization and ischemia in hemodynamic cerebrovascular insufficiency.

BACKGROUND: Moyamoya disease and atherosclerotic cerebrovascular occlusive disease lead to hemodynamic impairment of cerebral blood flow. One major differentiation between both disease entities lies in the collateralization pathways. The clinical implications of the collateralization pathways for the development of hemodynamic ischemia remain unknown. The aim was to characterize collateralization and ischemia patterns in patients with chronic hemodynamic compromise. METHODS: Hemodynamic compromise was verified using acetazolamide-stimulated xenon-CT or SPECT in 54 patients [30 moyamoya and 24 atherosclerotic cerebrovascular disease (ACVD)]. All patients received MRI to differentiate hemodynamic ischemia into anterior/posterior cortical border zone infarction (CBI), inferior border zone infarction (IBI) or territorial infarction (TI). Digital subtraction angiography was applied to evaluate collateralization. Collateralization was compared and correlated with the localization of ischemia and number of vascular territories with impaired cerebrovascular reserve capacity (CVRC). RESULTS: MM patients showed collateralization significantly more often via pericallosal anastomosis and the posterior communicating artery (flow in the anterior-posterior direction; MM: 95%/95% vs. ACVD: 23%/12%, p < 0.05). ACVD patients demonstrated collateralization via the anterior and posterior communicating arteries (flow in the posterior-anterior direction, MM: 6%/5% vs. ACVD: 62%/88%, p < 0.05). Patterns of infarction were comparable (aCBI: MM: 36% vs. ACVD: 35%; pCBI: MM: 10% vs. ACVD: 20%; IBI: MM: 35% vs. ACVD: 41%; TI: MM: 13% vs. ACVD: 18%). The number and localization of vascular territories with impaired CVRC were comparable. CONCLUSIONS: Despite significant differences in collateralization, the infarct patterns and severity of CVRC impairment do not differ between MMV and ACVD patients. Cerebral collateralization does not allow reaching conclusions about the localization of cerebral ischemia or severity of impaired CVRC in chronic hemodynamic impairment.

Approaches to temporal lobe lesions: a proposal for classification.

BACKGROUND: Tumor surgery in the temporal region is challenging due to anatomical complexity and the versatility of surgical approaches. The aim was to categorize temporal lobe tumors based on anatomical, functional, and vascular considerations and to devise a systematic field manual of surgical approaches. METHODS: Tumors were classified into four main types with assigned approaches: Type I-lateral: transcortical; type II-polar: pterional/transcortical; type III-central: transsylvian/trans-opercular; type IV-mesial: transsylvian/trans-cisternal if more anterior (=Type IV A), and supratentorial/infraoccipital if more posterior (=type IV B). 105 patients have been operated on prospectively using the advocated guidelines. Outcomes were evaluated. CONCLUSION: Systematic application of the proposed classification facilitated a tailored approach, with gross total tumor resection of 88 %. Neurological and surgical morbidity were less than 10 %. The proposed classification may prove a valuable tool for surgical planning.

Risk profile in extracranial/intracranial bypass surgery--the role of antiplatelet agents, disease pathology, and surgical technique in 168 direct revascularization procedures.

OBJECTIVE: Cerebral revascularization procedures are a treatment option in moyamoya disease patients, but recent studies failed to show an immediate benefit in cerebrovascular atherosclerotic disease. To facilitate optimal efficacy of the procedure, a detailed characterization of a representative perioperative complication rate and the role of potential risk factors such as underlying pathology, antiplatelet therapy, and the type of surgery performed is warranted and the purpose of this study. METHODS: We included 158 consecutive patients with moyamoya disease or cerebrovascular atherosclerotic disease undergoing 168 direct revascularization procedures. Type of disease, antiplatelet therapy, coagulation disorders, surgical technique, intraoperative complications, postoperative imaging, the need for revision, and outcome at time of discharge were analyzed. RESULTS: Complication rate was low, with a high patency rate of 97%. Six hemispheres (3.6%) needed to undergo surgical revision; early morbidity was 10.7% with no mortality, with evidence of ischemia in 6.9% of patients. Type of pathology treated and surgical technique did not influence outcome. Antiplatelet treatment was not associated with an increased risk for hemorrhage or revision, but improved outcome (P < 0.05). Ischemia, hemorrhage, and the need for revision aggravated outcome at time of discharge. CONCLUSION: Extra-/intracranial bypass surgery remains a treatment option in patients with moyamoya disease, although its use in the context of atherosclerotic disease was recently put into question. Regardless, a detailed characterization of perioperative risk factors is needed to optimize a potential long-term benefit of surgery. At a high-volume center, the complication rate is low independent from the underlying pathology with a high patency rate. Antiplatelet treatment does not increase the risk of hemorrhagic complications, but may improve outcome. Longer follow-up is required to adequately assess the true efficacy of revascularization on stroke prevention.

Variations of the superior sagittal sinus and bridging veins in human dissections and computed tomography venography.

OBJECTIVES: The aim of the present study was to examine the superior sagittal sinus (SSS) and bridging veins (BVs) from an anatomical, neurosurgical and radiological perspective. METHODS: Computed tomography venographies (CTVs) of 30 patients and 9 cadaveric dissections of human SSS were analyzed. RESULTS: CTV and cadavers showed most BVs emptying into the SSS close by (±3 cm) and distal to the coronary suture (74% in CTV, 62% in cadavers). CONCLUSIONS: Important anatomical information can be drawn from cerebral CTV for neurosurgical preoperative planning.

Method of aneurysm treatment does not affect clot clearance after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Patients undergoing neurosurgical clipping or endovascular coiling of a ruptured aneurysm may differ in their risk of vasospasm. OBJECTIVE: Because clot clearance affects vasospasm, we tested the hypothesis that clot clearance differs in patients depending on method of aneurysm treatment. METHODS: Exploratory analysis was performed on 413 patients from CONSCIOUS-1, a prospective randomized trial of clazosentan for the prevention of angiographic vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). Clot clearance was measured by change in Hijdra score between baseline computed tomography and one performed 24 to 48 hours after aneurysm treatment. Angiographic vasospasm was assessed by the use of catheter angiography 7 to 11 days after SAH, and delayed ischemic neurological deficit (DIND) was determined clinically. Extended Glasgow Outcome Score (GOSE) was assessed 3 months after SAH, and poor outcome was defined as death, vegetative state, or severe disability. Multivariable ordinal and binary logistic regression were used. RESULTS: There was no significant difference in the rate of clot clearance between patients undergoing clipping or coiling (P = .56). Coiling was independently associated with decreased severity of angiographic vasospasm (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.33-0.86), but not with DIND or GOSE. Greater clot clearance decreased the risk of severe angiographic vasospasm (OR 0.86, 95% CI 0.81-0.91), whereas higher baseline Hijdra score predicted increased angiographic vasospasm (OR 1.17, 95% CI 1.11-1.23) and poor GOSE (OR 1.09, 95% CI 1.04-1.14). CONCLUSION: Aneurysm coiling and increased clot clearance were independently associated with decreased severity of angiographic vasospasm in multivariate analysis, although no differences in clot clearance were seen between coiled and clipped patients.

Experience in using the excimer laser-assisted nonocclusive anastomosis nonocclusive bypass technique for high-flow revascularization: Mannheim-Helsinki series of 64 patients.

BACKGROUND: The excimer laser-assisted nonocclusive anastomosis (ELANA) technique enables large-caliber bypass revascularization without temporary occlusion of the parent artery. OBJECTIVE: To present the surgical experience of 2 bypass centers using ELANA in the treatment of complex intracranial lesions. METHODS: Between July 2002 and December 2007, 64 consecutive patients (37 in Germany and 27 in Finland) were selected for high-flow bypass surgery with ELANA. Modified Rankin Scale, a bypass success rate, and the success rate of the laser arteriotomy were assessed. RESULTS: In 66 surgeries for 64 intent-to-treat patients, 58 ELANA procedures were completed successfully. A favorable outcome (postoperative modified Rankin Scale score less than or equal to preoperative modified Rankin Scale) at 3 months was achieved in 43 of 56 patients (77%) with anterior circulation lesions (37 of the 43 patients had aneurysms, 4 had ischemia, and 2 received a bypass before tumor removal) and only in 2 of 8 patients (25%) with posterior circulation aneurysms. Perioperative (< 7 days) mortality for anterior and posterior circulation aneurysms was 6% and 50%, respectively. At the 3-month follow-up, 12% and 63% of patients with anterior and posterior circulation aneurysms, respectively, were dead. The success rate of the laser arteriotomy was 70%. Another 14% were retrieved manually after a nearly complete laser arteriotomy. CONCLUSION: The ELANA procedure requires a meticulous and careful operative technique. Morbidity and especially mortality rates, usually unrelated to ELANA, are comparable to those of contemporary series of conventional high-flow revascularization operations. This underscores the overall complexity of treating neurovascular pathologies by high-flow bypasses.

Delayed cerebral ischemia and spreading depolarization in absence of angiographic vasospasm after subarachnoid hemorrhage.

It has been hypothesized that vasospasm is the prime mechanism of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Recently, it was found that clusters of spreading depolarizations (SDs) are associated with DCI. Surgical placement of nicardipine prolonged-release implants (NPRIs) was shown to strongly attenuate vasospasm. In the present study, we tested whether SDs and DCI are abolished when vasospasm is reduced or abolished by NPRIs. After aneurysm clipping, 10 NPRIs were placed next to the proximal intracranial vessels. The SDs were recorded using a subdural electrode strip. Proximal vasospasm was assessed by digital subtraction angiography (DSA). 534 SDs were recorded in 10 of 13 patients (77%). Digital subtraction angiography revealed no vasospasm in 8 of 13 patients (62%) and only mild or moderate vasospasm in the remaining. Five patients developed DCI associated with clusters of SD despite the absence of angiographic vasospasm in three of those patients. The number of SDs correlated significantly with the development of DCI. This may explain why reduction of angiographic vasospasm alone has not been sufficient to improve outcome in some clinical studies.

The use of nicardipine prolonged release implants (NPRI) in microsurgical clipping after aneurysmal subarachnoid haemorrhage: comparison with endovascular treatment.

BACKGROUND: Nicardipine prolonged release implants (NPRI) have been shown to decrease the incidence of cerebral vasospasm and infarcts significantly in patients after aneurysmal subarachnoid haemorrhage (SAH) following microsurgical clipping. Yet, the comparison with results after endovascular coiling is lacking. This study was conducted to determine the differences in the incidence of cerebral vasospasm and infarctions between those two treatment modalities METHODS: The design of this investigation reflects a case-control study; 27 patients suffering from acute SAH were treated by microsurgical clipping and received an intracisternal implantation of NPRI. Twenty-seven matching consecutive patients after microsurgical treatment without implantation of NPRI or endovascular treatment, respectively, served as controls. The incidence of angiographic vasospasm and cerebral infarctions were documented. RESULTS: All groups were comparable concerning demographics and severity of SAH. Twenty-four of 81 patients developed angiographic vasospasm (>33% constriction). The incidence of vasospasm was 48%, 44% and 11% for patients after endovascular treatment, microsurgical clipping without NPRI and microsurgical clipping with NPRI, respectively. New cerebral infarctions occurred in 28%, 22% and 7% of the treated patients, respectively. A good clinical recovery 1 year after the initial bleeding (modified Rankin scale 0-2) was seen in 48%, 50% and 77% of the treated patients, respectively. CONCLUSION: The use of NPRI during microsurgical clipping was confirmed to be safe and effective. Patients who received intracisternally implanted NPRI during clipping after aneurysmal SAH yielded significantly lower vasospasm and infarction rates, and showed a better clinical outcome when compared with clipping without NPRI and also when compared with endovascular coiling.