Gene therapy for intracranial aneurysms: systemic review.

Treatment of intracranial aneurysms is currently limited to invasive surgical and endovascular modalities, and some aneurysms are not treatable with these methods. Identification and targeting of specific molecular pathways involved in the pathogenesis of aneurysms may improve outcomes. Low frequency somatic variants found in cancer related genes have been linked to intracranial aneurysm development. In particular, mutations in the PDGFRB gene lead to constitutively activated ERK and nuclear factor κB signaling pathways, which can be targeted with tyrosine kinase inhibitors. In this review, we describe how low frequency somatic variants in oncogenic and other genes affect the pathogenesis of aneurysm development, with a focus on gene therapy applications, such as endovascular in situ delivery of chemotherapeutics.

Chordoma: current concepts, management, and future directions.

Chordoma is a rare bone cancer that is aggressive, locally invasive, and has a poor prognosis. Chordomas are thought to arise from transformed remnants of notochord and have a predilection for the axial skeleton, with the most common sites being the sacrum, skull base, and spine. The gold standard treatment for chordomas of the mobile spine and sacrum is en-bloc excision with wide margins and postoperative external-beam radiation therapy. Treatment of clival chordomas is unique from other locations with an enhanced emphasis on preservation of neurological function, typified by a general paradigm of maximally safe cytoreductive surgery and advanced radiation delivery techniques. In this Review, we highlight current standards in diagnosis, clinical management, and molecular characterisation of chordomas, and discuss current research.

Advances in meningioma genomics, proteomics, and epigenetics: insights into biomarker identification and targeted therapies.

Meningiomas are a heterogeneous group of tumors, defined histo-pathologically by World Health Organization (WHO) grading. The WHO grade of meningiomas does not always correlate with clinical aggressiveness. Despite maximal surgical resection and adjuvant radiation, a subset of tumors are clinically aggressive; displaying early recurrence and invasion. Current methods for identifying aggressive meningiomas solely focus on genomics, proteomics, or epigenetics and not a combination of all for developing a real-time clinical biomarker. Improved methods for the identification of these outlying tumors can facilitate better classification and potentially adjuvant treatment planning. Understanding the pathways of oncogenesis using multiple markers driving aggressive meningiomas can provide a foundation for targeted therapies, which currently do not exist.

Patterns of Failure After Stereotactic Radiosurgery for Recurrent High-Grade Glioma: A Single Institution Experience of 10 Years.

BACKGROUND: Stereotactic radiosurgery (SRS) is a treatment modality that is frequently used as salvage therapy for small nodular recurrent high-grade gliomas (HGG). Due to the infiltrative nature of HGG, it is unclear if this highly focused technique provides a durable local control benefit. OBJECTIVE: To determine how demographic or clinical factors influence the pattern of failure following SRS for recurrent high-grade gliomas. METHODS: We retrospectively reviewed clinical, radiographic, and follow-up information for 47 consecutive patients receiving SRS for recurrent HGG at our institution between June 2006 and July 2016. All patients initially presented with an HGG (WHO grade III and IV). Following SRS for recurrence, all patients experienced treatment failure, and we evaluated patterns of local, regional, and distant failure in relation to the SRS 50% isodose line. RESULTS: Most patients with recurrent HGG developed "in-field" treatment failure following SRS (n = 40; 85%). Higher SRS doses were associated with longer time to failure (hazards ratio = 0.80 per 1 Gy increase; 95% confidence interval 0.67-0.96; P = .016). There was a statistically significant increase in distant versus in-field failure among older patients (P = .035). This effect was independent of bevacizumab use (odds ratio = 0.54, P = 1.0). CONCLUSION: Based on our experience, the majority of treatment failures after SRS for recurrent HGG were "in-field." Older patients, however, presented with more distant failures. Our results indicate that higher SRS doses delivered to a larger area as fractioned or unfractioned regimen may prolong time to failure, especially in the older population.

Pipeline Embolization Device as primary treatment for blister aneurysms and iatrogenic pseudoaneurysms of the internal carotid artery.

BACKGROUND: Blood blister type aneurysms (BBAs) and pseudoaneurysms create a unique treatment challenge. Despite many advances in open surgical and endovascular techniques, this subset of patients retains relatively high rates of morbidity and mortality. Recently, BBAs have been treated with flow-diverting stents such as the Pipeline Embolization Device (PED) with overall positive results. METHODS: Four patients presented with dissecting internal carotid artery (ICA) aneurysms treated with the PED (two BBAs presenting with subarachnoid hemorrhage (SAH), two pseudoaneurysms after injury during endoscopic trans-sphenoidal tumor surgery). RESULTS: Three patients had a successful angiographic and neurological outcome. One patient with a BBA re-ruptured during initial PED placement, again in the postoperative period, and later died. Primary PED treatment involved telescoping stents in two patients and coil embolization supplementation in one patient. CONCLUSIONS: The PED should be used selectively in the setting of acute SAH. Dual antiplatelet therapy can complicate hydrocephalus management, and the lack of immediate aneurysm occlusion creates the risk of short-term re-rupture. PED treatment for iatrogenic ICA pseudoaneurysms can provide a good angiographic and neurological outcome.

Management of meningiomas invading the major dural venous sinuses: operative technique, results, and potential benefit for higher grade tumors.

OBJECTIVE: The optimal surgical management of meningiomas involving the major venous sinuses represents a therapeutic dilemma. The decision is whether to leave a fragment of the lesion and have a higher recurrence rate, especially for World Health Organization classification II/III tumors, or to attempt total removal and potentially increase risk to the venous circulation. We present the surgical strategies we follow in managing meningiomas involving the major venous sinuses and the potential benefit of these techniques for higher grade tumors. METHODS: Between 2005 and 2013, 38 patients underwent operations. Preoperative and postoperative data were retrospectively analyzed. The surgical strategies based on sinus invasion are discussed. RESULTS: Meningiomas involved the superior sagittal sinus (26 patients), Torcular Herophili (5), transverse (5), or sigmoid sinus (2 patients). In 13 patients, the sinus was totally occluded, in 9 subtotally (50%-95%), and in 14 patients partially (<50%), whereas two tumors involved the outer layer of the sinus wall. Twenty-seven patients had World Health Organization classification grade I meningiomas and 11 grade II. A gross total resection was achieved in 86.9% of patients, and sinus reconstruction followed in 21 cases: 13 by direct suture and 8 using a patch. Postoperatively, the sinus was patent (52.4%), or narrow but patent (33.3%) in 85.7% of these patients. No deaths and one major postoperative complication occurred, and the mean postoperative KPS score was 88.9±15.3. Two recurrences (5.3%) occurred during a mean follow-up of 26.05 months. CONCLUSIONS: The surgical strategies presented, achieving minimal morbidity, support the practice of aggressive removal of tumors invading the sinus, particularly in the case of higher grade meningiomas.

Cerebrovascular bypass and aneurysm trapping for the treatment of an A2-segment anterior cerebral artery pseudoaneurysm and herniation through a skull base defect following trauma.

Fractures of the anterior skull base can lead to pseudoaneurysm formation as a result of direct injury to a vessel wall. Pseudoaneurysms in this location are challenging to treat, as both perforator and distal blood supply must be maintained. Additionally, traumatic skull base fractures can lead to a rare condition of cerebral blood vessel herniation through the bony defect, further complicating treatment planning. Treatment of these lesions is essential to (1) prevent the occurrence of potentially fatal subarachnoid hemorrhage and (2) prevent dissection from propagating and compromising blood flow to distal vessels, perforators, and even parent vessels. We present a unique case of a traumatic proximal anterior cerebral artery pseudoaneurysm, herniating through a skull base defect. Treatment consisted of aneurysm trapping and bypass with skull base reconstruction.

Incidence of cerebrospinal fluid leak following petrosectomy and analysis of avoidance techniques.

A cerebrospinal fluid (CSF) leak following skull base surgery can lead to meningitis, impaired wound healing, and often requires re-operation and/or CSF diversion. Thirty-two patients underwent a presigmoid, transpetrosal approach to skull base aneurysms and tumors. A vascularized temporalis muscle flap was utilized during the closure of the initial skull base reconstruction in 18 of the 32 patients. A temporary CSF diversion was utilized in 23 of the 32 patients. A permanent shunt was placed in eight patients. One patient developed a postoperative CSF leak from the contralateral ear due to a congenital abnormality in the middle ear. Another patient, who did not have a vascularized temporalis muscle flap reconstruction, developed a postoperative CSF leak in the context of an operation for recurrent tumor and prior radiation treatment. CSF diversion and vascularized temporalis muscle flaps are effective in preventing the development of postoperative CSF leaks following petrosectomy.