Guido Wilms

Postoperative Adjuvant Dendritic Cell–Based Immunotherapy in Patients with Relapsed Glioblastoma Multiforme

Purpose: To investigate the therapeutic role of adjuvant vaccination with autologous mature dendritic cells (DC) loaded with tumor lysates derived from autologous, resected glioblastoma multiforme (GBM) at time of relapse. Experimental Design: Fifty-six patients with relapsed GBM (WHO grade IV) were treated with at least three vaccinations. Children and adults were treated similarly in three consecutive cohorts, with progressively shorter vaccination intervals per cohort. Feasibility and toxicity were assessed as well as effect of age, extent of resection, Karnofsky Performance Score, and treatment cohort on the progression-free (PFS) and overall survival (OS) using univariable and multivariable analysis. Results: Since the prevaccine reoperation, the median PFS and OS of the total group was 3 and 9.6 months, respectively, with a 2-year OS of 14.8%. Total resection was a predictor for better PFS both in univariable analysis and after correction for the other covariates. For OS, younger age and total resection were predictors of a better outcome in univariable analysis but not in multivariable analysis. A trend to improved PFS was observed in favor of the faster DC vaccination schedule with tumor lysate boosting. Vaccine-related edema in one patient with gross residual disease before vaccination was the only serious adverse event. Conclusion: Adjuvant DC-based immunotherapy for patients with relapsed GBM is safe and can induce long-term survival. A trend to PFS improvement was shown in the faster vaccination schedule. The importance of age and a minimal residual disease status at the start of the vaccination is underscored.

Early endovascular treatment of ruptured cerebral aneurysms in patients in very poor neurological condition.

OBJECTIVE In patients in very poor neurological condition (World Federation of Neurosurgical Societies Grade V) with aneurysmal subarachnoid hemorrhage, early surgery to prevent rebleeding and to allow appropriate treatment of complications is often difficult. The aim of the present study was to evaluate whether early endovascular treatment followed by aggressive proactive treatment of complications (prophylactic hypervolemic hemodilution, hypertensive treatment in the event of systemic hypotension, and appropriate treatment of intracranial hypertension) is an acceptable management strategy for these patients. METHODS We prospectively studied 11 consecutive patients who presented with acutely ruptured aneurysms and were in very poor neurological condition after resuscitation (World Federation of Neurosurgical Societies Grade V) but did not have a significant intracerebral hemorrhage. These patients received endovascular treatment with Guglielmi detachable coils (Boston Scientific/Target, Fremont, CA). Follow-up consisted of a clinical evaluation based on the Glasgow Outcome Scale. A control angiogram was obtained after 6 months in patients with favorable outcomes to evaluate the occlusion of the aneurysm. RESULTS There were no deaths or complications directly related to the procedure. Two patients died as a consequence of increased intracranial pressure. The mean follow-up of the surviving patients was 12 months. Two patients had early rebleeding after the coiling and required further treatment. Four patients had good outcomes, two patients were moderately disabled, and three patients were severely disabled. CONCLUSION This study demonstrates that early endovascular treatment of acutely ruptured cerebral aneurysms in patients evaluated as World Federation of Neurosurgical Societies Grade V allows for aggressive treatment of intracranial hypertension and vasospasm. More than half of the patients had favorable outcomes. Therefore, early endovascular treatment seems to be a valuable alternative to early surgery in patients who present with a very poor clinical grade after subarachnoid hemorrhage. The results of this study are promising but must be interpreted with caution, because a small number of patients were studied.

Magnetic resonance angiography in suspected cerebral vasculitis

The purpose of this study was to determine the technical capacity and diagnostic accuracy of 3D time-of-flight magnetic resonance angiography (MRA) in suspected cerebral vasculitis in a retrospective analysis of MRA and digital subtraction angiography (DSA) in 14 young patients with clinical and/or radiological suspicion of cerebral vasculitis. A total of nine arteries were evaluated in each patient. Consensus review of DSA by three observers was the reference standard. The sensitivity for detecting a stenosis varied from 62 to 79% for MRA and from 76 to 94% for DSA, depending on the observer. The specificity for detecting a stenosis varied from 83 to 87% for MRA and from 83 to 97% for DSA. Using the criterion “more than two stenoses in at least two separate vascular distributions” to consider the examination as being true positive, the false-positive rates for MRA and DSA were comparable. MRA plays a role as the first angiographical examination in the diagnostic work-up of suspected cerebral vasculitis. When more than two stenoses in at least two separate vascular distributions are depicted on MRA, DSA is not expected to add a significant diagnostic contribution in a patient with suspected cerebral vasculitis. DSA remains necessary when MRA is normal or when less than three stenoses are seen.

Variants of the basal vein of Rosenthal and perimesencephalic nonaneurysmal hemorrhage

BACKGROUND The cause of perimesencephalic nonaneurysmal SAH or PMH is not known. Earlier studies reported a possible contribution of a primitive variant of the BVR in the pathogenesis of PMH. We compared the variants of BVR in a case control study between patients with PMH and aneurysmal SAH by studying the venous phase of the DSA. METHODS Two observers reviewed the DSAs of 59 patients with PMH and 59 patients with aneurysmal SAH. The variants of BVR were classified into (1) normal continuous: BVR is continuous with the deep middle cerebral vein and drains mainly into the VG; (2) normal discontinuous: drainage anterior to uncal veins and posterior to the VG; and (3) primitive variant: drainage into veins other than the VG. RESULTS One hundred eighteen patients were enrolled, with a mean age of 49 +/- 12 years. There were 31 men and 28 women in each group. Patients with PMH were older than patients with aneurysmal SAH (52 vs 46, P = .01). Primitive variants were found in 21% on the left side and 29% on the right side (P = .27). There was no association between PMH and the presence of a primitive variant on the left (25% in PMH vs 19% in aneurysmal SAH, P = .65) or on the right side (31% in PMH vs 30% in aneurysmal SAH, P = .92) in univariate analysis. After correction for age and sex, variants on neither side were associated with PMH (OR: 1.4, P = .53 for left variants and 1.2, P = .67 for right variants). CONCLUSIONS In this large controlled study, we were unable to confirm a contribution of a primitive variant of the BVR in the pathogenesis of PMH.

Endovascular Shunt Reduction in the Management of Transjugular Portosystemic Shunt-Induced Hepatic Encephalopathy: Preliminary Experience with Reduction Stents and Stent-Grafts

OBJECTIVE The purpose of this study was to retrospectively evaluate the safety, feasibility, and midterm clinical outcome of the use of three types of reduction stents inserted to manage transjugular intrahepatic portosystemic shunt (TIPS)-induced hepatic encephalopathy refractory to medical treatment. CONCLUSION The use of a covered reduction stent-graft results in a greater increase in portosystemic gradient immediately after reduction than does use of a bare reduction stent. Relief of TIPS-induced hepatic encephalopathy tends to be greater in patients with reduction stent-grafts than in those with bare reduction stents.

Pain experience during internal spermatic vein embolization for varicocele: comparison of two cyanoacrylate glues

The purpose of this study was to evaluate possible pain sensation differences in patients after retrograde varicocele embolization either with n-butyl-(2)-cyanoacrylate (NBCA) or with n-butyl-(2)-cyanoacrylate + methacryloxysulfolane (NBCA-MS). Transcatheter varicocele embolization was performed in 64 consecutive patients (62 left, two bilateral). Embolization was done with NBCA (n=32) or NBCA-MS (n=32). Immediately after the procedure, patients were asked to evaluate pain during embolization using a visual analog scale (VAS). Statistical analysis was done with Student’s t test. Mean pain score on VAS was 3.23 (range: 0–8) for NBCA and 3.28 (range 0–9) for NBCA-MS. This difference was not significant (P=0.932). Independently of the type of glue, no difference in pain sensation (P value 0.421) was found between patients younger than 18 (n=29) and patients older than 18 years of age (n=35) (younger than18, mean 3.52; older than 18, mean 3.05). No difference in mean pain experience level (P=0.323) was seen in 11 patients with vessel wall perforation (23.4%) during the procedure (3.89; range: 0–8.5) in comparison with those without perforation (mean pain sensation level: 3.13; range: 0–9). No difference in pain experience was found after transcatheter varicocele embolization either with NBCA or NBCA-MS. Age and vessel wall perforation have no influence on pain sensation independently of the type of glue.

Symptomatic Internal Carotid Artery Dissecting Pseudoaneurysm: Endovascular Treatment by Stent-Graft

Dissecting pseudoaneurysm of the extracranial portion of the internal carotid artery (ICA) is a usually benign complication of spontaneous ICA dissection. We report a case in which pseudoaneurysm volume enlarged progressively and new clinical symptoms developed 9 months following disease onset. Placement of a coronary stent-graft resulted in immediate complete resolution of clinical symptoms and radiologic restoration of normal flow.

Magnetic resonance imaging-based endovascular versus medical stroke treatment for symptom onset up to 12 h

Background Recent trials have shown a clear benefit of endovascular therapy for stroke patients presenting within 6 h after stroke onset. Imaging-based selection may identify a cohort with a favorable response to endovascular therapy, in an even later time window. Aims We performed an indirect comparison between outcomes seen in DEFUSE 2, a prospective cohort study of patients who received a baseline MRI before endovascular therapy, and a control group from AXIS 2 receiving standard medical care up to 12 h after symptom onset. Methods Patients from AXIS 2 with a confirmed large vessel occlusion were selected as a control group for DEFUSE 2-patients. The primary endpoint was good functional outcome at day 90 (Modified Rankin Score 0–2). We performed a stratified analysis based on the presence of the target mismatch for both studies and reperfusion status in DEFUSE 2. Results We compared good functional outcome in 108 patients from AXIS 2 and 99 patients from DEFUSE 2. In DEFUSE 2-patients with the target mismatch profile in whom reperfusion was achieved, the rate of good functional outcome was increased compared to target mismatch patients in AXIS 2, 54% versus 29% (OR 3.2, 95% CI 1.1–9.4). In target mismatch patients treated between 6 and 12 h after stroke onset, this association between study and good functional outcome remained present (OR 9.0, 95% CI 1.1–75.8). Conclusions This indirect comparison suggests that endovascular treatment resulting in substantial reperfusion is associated with improved outcome in target mismatch patients even beyond 6 h after stroke onset. Confirmation is needed from future clinical trials that randomize patients beyond the 6 h time window.

Fatal brain necrosis in primary HIV infection

In November, 2004, a 31-year-old man was admitted toour hospital with a prominent morbilliform rash,pharyngitis, and a fever (40oC). He had been well until2 weeks earlier, when he developed a fever, rash, anddiarrhoea. HIV serology from 4 days earlier wasnegative. Neurological examination on admission wasnormal. However, 3 days later, he became lethargic andhad a tonic-clonic seizure, necessitating intubation andmechanical ventilation. There was no evidence ofhypoxia or hypotension. HIV screening tests done onadmission were positive, indicating seroconversion. HIVwestern blot was indeterminate; p24 antigen was morethan 200 pg/mL, plasma HIV-1 RNA was greater than500000 copies per mL, and peripheral bloodlymphocytes were 4·6 10

Long-lasting, complete exclusion of a large galenic dural arteriovenous fistula after clipping of the central venous aneurysm of the vein of galen: case report.

BACKGROUND AND IMPORTANCE: Galenic dural arteriovenous fistulas (DAVFs) are a subtype of the rare falcotentorial DAVFs with a high risk of hemorrhage and an aggressive clinical course. Microsurgical treatment is often necessary because endovascular obliteration will rarely completely obliterate the DAVF. CLINICAL PRESENTATION: We present a unique case of a complex, ruptured galenic DAVF in which the key point of the fistula was formed by a large venous aneurysm of the vein of Galen. A session of embolization of the falcotentorial feeding vessels followed by additional surgical transsection of the remaining tentorial arterial feeders failed to exclude the galenic DAVF. Direct clipping of the venous aneurysm through a unilateral occipital craniotomy for a posterior interhemispheric transtentorial approach resulted in an ongoing radiological complete obliteration in this patient, who made an uneventful complete recovery after 2 subarachnoid hemorrhages, which he suffered before this definitive treatment. CONCLUSION: Direct interruption of the fistula key point by clipping of the venous aneurysm, rather than interruption of the feeding vessels, was mandatory for complete exclusion of this complex galenic DAVF.