Balloon assisted Woven endobridge deployment (BAWD): A safety and efficacy study.

BACKGROUND: Balloon-assisted deployment/remodelling is a proven adjunctive technique for coil embolization of intracranial aneurysms, and it may be a helpful adjunct in delivering the Woven EndoBridge (WEB) device. OBJECTIVE: To evaluate the safety, efficacy and feasibility of balloon-assisted WEB deployment in both ruptured and unruptured intracranial aneurysms in both typical and atypical locations. METHODS: Patients who underwent treatment of ruptured and unruptured intracranial aneurysms with the BAWD technique were retrospectively identified from a prospectively maintained database at two neurointerventional centres. Patient demographics, aneurysm characteristics, technical procedure details, clinical and imaging outcomes were reviewed. RESULTS: Thirty-three aneurysms (23 women) were identified with a median age of 58 years. There were 15 (45.5%) ruptured aneurysms, 25 (64.3%) in the anterior circulation and 12 (36.4%) aneurysms having an atypical location for WEB treatment. The average aneurysm size was 6.8 mm (greatest dimension), 4.6 mm (height) and 4.5 mm (width), and 25 (75.8%) aneurysms had a wide neck morphology. One patient died (3.0%) secondary to a procedure-related complication, and there was no procedure-related permanent morbidity. Complete and adequate aneurysm occlusion on mid-term follow-up DSA was 85.2% and 92%, respectively. CONCLUSION: Balloon-assisted WEB deployment appears to be a safe and effective technique that may increase the utility of the WEB device. Further prospective studies on BAWD should be considered.

A case study of a long-term glioblastoma survivor with unmethylated MGMT and hypermutated genotype.

Effective treatments that extend survival of malignant brain tumor glioblastoma (GBM) have not changed in more than a decade; however, there exists a minority patient group (<5%) whose survival is longer than 3 yr. We herein present a case report of a long-term surviving 51-yr-old female diagnosed with a MGMT unmethylated GBM. The patient was progression-free for 23 mo. Fresh primary and recurrent tumor samples were collected and processed for patient-derived model development. Whole-genome sequencing (WGS) was performed concurrently with additional standard of care diagnostics. WGS revealed a hypermutated genotype in the germline tissue and in both the primary and recurrent tumor samples. Specific to the matched tumors, an average of 30 cancer driver genes were mutated. Noteworthy was the identification of a nonsynonymous mutation in the POLE gene. As a possible instigator of the hypermutational genotype observed in the tumors, we identified nonsynonymous germline mutations within the mismatch repair genes, MLH1 and PMS2 Mutations within these genes are often indicative of the pan-cancer phenotype known as Lynch syndrome; however, their pathogenicity remains unreported. We performed a drug screen of 165 compounds, which identified one compound, YM155, an experimental survivin inhibitor, that showed effectivity to the patient-derived cell lines of both tumors. Treatment selection based on a patient's genome to individualize treatment for GBM patients could potentially be useful in the clinic. This is a promising avenue for further translational research, with larger databases and integrated platforms to increase the efficiency of analyzing and interpreting the individual genomic data of GBM.

Association Between IDH1 and IDH2 Mutations and Preoperative Seizures in Patients with Low-Grade Versus High-Grade Glioma: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with brain tumors, particularly gliomas, commonly present with seizures. Higher incidence of seizure has been reported in low-grade gliomas and tumors located within the temporal and insular area. The association between IDH1 and IDH2 mutations with preoperative seizures in glioma and the magnitude of this association in low-grade versus high-grade gliomas are unclear. To clarify this relationship, a systematic review and meta-analysis was performed. METHODS: Following accepted guidelines and systematic review recommendations, electronic searches were performed in journal databases up to May 2017. Data were extracted and pooled via meta-analysis. RESULTS: We compared 782 patients with IDH1 and IDH2 mutations with 803 patients with wild-type IDH1 and IDH2 before surgery. There was a significant difference in seizure incidence between the IDH1 mutation group (61.6%) and wild-type IDH1 group (32.1%) (odds ratio 2.76; 95% confidence interval, 1.26-6.02; I2 = 73%; P = 0.01). Similar findings were observed in analysis of IDH1 and IDH2 mutations (odds ratio 2.74; 95% confidence interval, 1.74-4.33; I2 = 58%; P < 0.0001). The difference remained in both mutation groups (IDH1, IDH1 and IDH2) with grade II gliomas but not with grade III and IV gliomas. Patients with grade II gliomas showed a higher rate of IDH1 and IDH2 mutations and seizures than patients with grade III and IV gliomas. CONCLUSIONS: This study demonstrated a significant association of IDH1 and IDH2 mutations with incidence of preoperative seizures. This association was significant only in patients with low-grade glioma (grade II) and not in patients with higher grade gliomas (grade III and IV).

Resumption of Antithrombotic Agents in Chronic Subdural Hematoma: A Systematic Review and Meta-analysis.

BACKGROUND: The clinical decision whether and when to resume antithrombotics in patients with chronic subdural hematomas (CSDH) postoperatively is limited by a lack of quality evidence exploring this topic. Our study aims to assess the available evidence of patient complication outcomes, specifically hemorrhagic and thromboembolic events, following the resumption or non-resumption of antithrombotic agents postoperatively in CSDH patients already on these agents before CSDH. METHODS: We followed recommended PRISMA guidelines for systematic reviews. Electronic database searches were performed to identify included studies. Data were extracted and analyzed using meta-analysis. RESULTS: Eight studies were included for analysis. The most common indication for antithrombotic treatment before onset of CSDH was atrial fibrillation (29.6%), followed by prosthetic heart valve (16.6%), recent myocardial infarction (14.1%), prior stroke or transient ischemic attack (11.6%), and finally venous thromboembolism (8.3%). The overall hemorrhagic complication rate was 14.8% in the resumption group versus 18.6% in the no resumption group (P = 0.591). This did not differ between early (<2 weeks) versus late (>1 month) resumption (15% vs. 18.6%, P = 0.97). The rate of thromboembolism however was statistically lower in those who resumed antithrombotics (2.9% vs. 6.8%, P<0.001). There was a non-significant trend towards higher thromboembolic rates with early resumption (5.3% vs. 2.1%, P = 0.23). CONCLUSIONS: The decision to resume antithrombotics postoperatively in the clinical management of CSDH patients is a complex one and should therefore be a highly individualized process. Our meta-analysis demonstrates that in selected cases, it is feasible to resume early antithrombotic treatment without additional hemorrhagic or thromboembolic risk.

Gliomatosis cerebri: Prognosis based on current molecular markers.

This study aims to review the literature and identify key molecular markers affecting the prognosis of Gliomatosis cerebri (2) to evaluate the level of evidence and identify outstanding markers requiring further study. A literature search was conducted across 5 major databases using the key terms: "Molecular markers" AND "Gliomatosis cerebri" OR "diffuse astrocytoma." Critical appraisal and data presentation was performed inline with the PRISMA guidelines. Following search strategy implementation, 11 studies were included in the final review process. Our data demonstrates significant prognostic value associated with IDH1132H mutation and variable evidence surrounding the role of INA expression, MGMT promoter methylation and other factors. However, there are significant limitations in the level of evidence obtained. As the genetic basis for the pathogenesis of Gliomatosis cerebri continues to widen, there is little data on markers aside from IDH1 mutation available. IDH1132H mutation has been demonstrated to have significant effect on survival, particularly in patients with Gliomatosis cerebri type 2.

Endoscopic Endonasal versus Microsurgical Transsphenoidal Approach for Growth Hormone-Secreting Pituitary Adenomas-Systematic Review and Meta-Analysis.

BACKGROUND: The pituitary adenoma causing acromegaly is typically resected through a transsphenoidal approach and visualized with an operating microscope or endoscope. We undertook a systematic review and meta-analysis examining the clinical efficacy of endoscopic and microsurgical approaches. METHODS: Relevant studies using either endoscopic or microscopic transsphenoidal approaches for growth hormone pituitary adenomas were identified until February 2016. Data were extracted and analyzed according to predefined clinical end points. RESULTS: We identified 31 studies, in which 950 patients underwent endoscopic transsphenoidal resection and 2137 patients underwent microsurgical transsphenoidal resection. Patients undergoing microsurgery were less likely to present with hypothyroidism (10.7% vs. 19.1%, P = 0.033, 462 vs. 156 patients) and less likely to have macroadenomas (66.9% vs. 83.8%, P ≤ 0.001, 1484 vs. 884 patients); adenomas with cavernous sinus invasion (21.3% vs. 44.4%, P = 0.036, 592 vs. 558 patients); and a lower mean tumor volume (17.84 vs. 20.54 mm3, P = 0.012, 158 vs. 248 patients). Patients treated via the endoscopic approach were more likely to achieve remission for noninvasive macroadenomas (83.8% vs. 66.9%, P ≤ 0.001, 115 vs. 365 patients). Sinusitis (15.6% vs. 2.6%, P < 0.001, 241 vs. 295 patients) and intraoperative cerebrospinal fluid leak (21.6% vs. 1.0%, P = 0.022, 697 vs. 127 patients) were more common in patients treated endoscopically, and meningitis (0.7% vs. 1.7%, P = 0.027, 511 vs. 1513 patients) was more common in patients undergoing a microsurgical approach. CONCLUSIONS: Our study shows the clinical utility of the endoscopic approach and demonstrates potential benefits including increased remission rates with noninvasive macroadenomas and a lower rate of meningitis.

Minimally invasive percutaneous fixation techniques for metastatic spinal disease.

OBJECTIVE: Surgical treatment of spinal metastasis is generally a palliative procedure. Although minimally invasive surgical (MIS) techniques are supposedly less morbid than open techniques, there is a lack of stratification of MIS techniques based on anticipated longevity. A simple stratification into three percutaneous surgical techniques based on modified Tokuhashi score is here proposed. METHODS: Patients recommended for spinal surgery for metastatic spinal disease between 2009 and 2012 and operated on by the senior author (RJM) were retrospectively reviewed. One of three MIS techniques was offered based on estimated survival using a modified Tokuhashi score. Technique #1 is suitable for patients with predicted short longevity (<6 months). Using a mini-open midline or paramedian decompression and percutaneous screw fixation, the goal here is for rapid mobilization and minimization of hospitalization. Technique #2 is suitable for patients with predicted medium longevity (6-12 months). They are suitable for decompression and/or cement vertebral body replacement and a two levels stabilization. Technique #3 is suitable for patients with predicted long term survival survival (>12 months). In these patients, the primary goal of surgery is a wide local or marginal resection of tumor, decompression of the neurological elements and a robust stabilization construct. They are suitable for an open 360°decompression, vertebral body reconstruction and a multilevel stabilization. RESULTS: The study included eight patients with a mean age of 59 years (range, 36-72 years). Mean modified Tokuhashi score was 10 (range, 7-13) with three patients in the short term, two in the medium term and three in the long term survival category. Mean blood loss was 700 mL (range, 100-1200 mL), mean operating time 280 min (range, 120-360 min) and length of stay in the hospital was on average 13 days (range, 3-30 days). CONCLUSION: The authors present three minimally invasive technique options for the management of spinal metastatic disease corresponding to three clinical prognostic categories. In this small series, MIS techniques resulted in speedy recovery, minimal morbidity and no mortality.

Durable thrombosis in a rat model of arteriovenous malformation treated with radiosurgery and vascular targeting.

OBJECT: Radiosurgical treatment of brain arteriovenous malformations (AVMs) has the significant shortcomings of being limited to lesions smaller than 3 cm in diameter and of a latency-to-cure time of up to 3 years. A possible method of overcoming these limitations is stimulation of thrombosis by using vascular targeting. Using an animal model of AVM, the authors examined the durability of the thrombosis induced by the vascular-targeting agents lipopolysaccharide and soluble tissue factor conjugate (LPS/sTF). METHODS: Stereotactic radiosurgery or sham radiation was administered to 32 male Sprague-Dawley rats serving as an animal model of AVM; 24 hours after this intervention, the rats received an intravenous injection of LPS/sTF or normal saline. The animals were killed at 1, 7, 30, or 90 days after treatment. Immediately beforehand, angiography was performed, and model AVM tissue was harvested for histological analysis to assess rates of vessel thrombosis. RESULTS: Among rats that received radiosurgery and LPS/sTF, induced thrombosis occurred in 58% of small AVM vessels; among those that received radiosurgery and saline, thrombosis occurred in 12% of small AVM vessels (diameter < 200 µm); and among those that received LPS/sTF but no radiosurgery, thrombosis occurred at an intermediate rate of 43%. No systemic toxicity or intravascular thrombosis remote from the target region was detected in any of the animals. CONCLUSIONS: Vascular targeting can increase intravascular thrombosis after radiosurgery, and the vessel occlusion is durable. Further work is needed to refine this approach to AVM treatment, which shows promise as a way to overcome the limitations of radiosurgery.

Molecular responses of brain endothelial cells to radiation in a mouse model.

Although most small arteriovenous malformations (AVM) are curable, over 90% of large lesions are untreatable with current surgery or radiosurgery. Endothelial cells (EC) are believed to be pivotal in the resulting vascular changes after AVM are irradiated, although their role is not fully understood. Elucidating the molecular effects of radiation on EC may allow development of new therapies that modulate the response of AVM to radiation. Cultured murine cerebral EC (bEnd.3) were exposed to a single 25 Gy dose of ionising radiation from a linear accelerator. Expression of the membrane proinflammatory and thrombotic molecules E-selectin, tissue factor (TF) and thrombomodulin (TM) were examined by immunofluorescent staining at times up to three weeks post irradiation. We found that E-selectin is significantly down regulated in the first 24 hours after irradiation. Later there is no significant difference in expression of this molecule between irradiated and non-irradiated groups. TM expression was significantly increased at all times, and the staining intensity of TF remained unchanged three weeks post irradiation. These results contribute to a greater understanding of the proinflammatory and thrombotic changes caused by irradiating normal brain EC.

Successful endovascular and surgical treatment of spinal extradural metameric arteriovenous malformation. Case report.

A report of successful combined endovascular and surgical management of an unusual case of metameric (juvenile) spinal arteriovenous malformation (AVM) is presented. The malformation had extradural and paraspinal components, but no intradural elements. It had caused rapid neurological deterioration to near-complete paraplegia prior to treatment (American Spinal Injury Association [ASIA] Grade C). A combination of endovascular occlusion of major feeding vessels and excision of the malformation resulted in a complete neurological recovery (ASIA Grade E). The authors conclude that selected metameric AVMs can be successfully treated with multimodal therapy. This case further illustrates the fact that not all spinal vascular malformations are easily categorized.

Intracranial haemorrhage in pregnancy.

Intracranial haemorrhage (ICH) is a rare, yet potentially devastating event in pregnancy. There is a risk of maternal mortality or morbidity and a significant risk to the unborn child. The risk of haemorrhage increases during the third trimester and is greatest during parturition and the puerperium. ICH can be extradural, subdural, subarachnoid or intraparenchymal. Causes of bleeding include trauma, arteriovenous malformations, aneurysms, preeclampsia/eclampsia and venous thrombosis. Urgent neurosurgical conditions generally outweigh obstetric considerations in management decisions, although anaesthetic and surgical modifications can be made to minimize adverse effects to the fetus.

Spinal cord glioblastoma multiforme induced by radiation after treatment for Hodgkin disease. Case report.

The authors report on a 26-year-old man with a very rare case of radiation-induced intramedullary spinal cord glioblastoma multiforme, which developed several years after radiotherapy for Hodgkin disease.

Concussion clinic referral demographics and recommendations: a retrospective analysis.

OBJECTIVE: To review the demographic factors, mechanism of injury and treatment recommendations for patients attending a concussion clinic in New Zealand. METHODS: Retrospective analysis of data for all patients attending a concussion clinic in a single centre over a 2-year period. Data was collected via an electronic database and written clinical records. RESULTS: Data from a total of 161 patients was collected; 8 patients did not attend clinic appointments, yet their mechanism of injury was available from referral notes. 42 (26%) patients were diagnosed as not having a mild traumatic brain injury (TBI). Of the remainder, 72 (47%) had a mild TBI and 36 (22%) had moderate or severe TBI; 21% of attendees were injured in sporting accidents with 19% injured in motor vehicle accidents and 17% in falls. More treatment recommendations were made in those patients diagnosed with TBI than those with no TBI (p=0.038). Occupational therapy was the most commonly recommended treatment. CONCLUSIONS: Considering the high number of injuries with mild TBI that occur every year, there was a relatively small number seen in the Wellington area concussion clinic. Only half of clinic attendees had had a mild TBI. Treatment recommendations were similar throughout patient diagnostic groups; occupational therapy input was probably offered because it was resourced by the clinic funder. Further research is required into return to work, emotional and cognitive outcomes.

Post-clipping cerebrovascular compliance in an infant with bilateral anterior circulation aneurysms

We present an uncommon case of an infant 12 months, presenting with a seizure due to subarachnoid hemorrhage secondary to an anterior circulation aneurysm. Following angiography, a right A1/A2 junction aneurysm was clipped by a right pterional approach. Angiography 5 months after clipping revealed loss of flow in the right anterior cerebral artery and a de novo L A1/A2 aneurysm, which was electively clipped by a left pterional approach. Follow angiography 5 monthslater showed loss left anterior cerebral artery flow and the anterior cerebral artery territory perfused by posterior cerebral arteries. Cerebral angiography 8 months later did not show further aneurysms and demostrated the posterior circulation vessels perfusing the anterior circulation vascular territory The child remains neurologically intact

Post-clipping cerebrovascular compliance in an infant with bilateral anterior circulation aneurysms

We present an uncommon case of an infant 12 months, presenting with a seizure due to subarachnoid hemorrhage secondary to an anterior circulation aneurysm. Following angiography, a right A1/A2 junction aneurysm was clipped by a right pterional approach. Angiography 5 months after clipping revealed loss of flow in the right anterior cerebral artery and a de novo L A1/A2 aneurysm, which was electively clipped by a left pterional approach. Follow angiography 5 monthslater showed loss left anterior cerebral artery flow and the anterior cerebral artery territory perfused by posterior cerebral arteries. Cerebral angiography 8 months later did not show further aneurysms and demostrated the posterior circulation vessels perfusing the anterior circulation vascular territory The child remains neurologically intact (AU)