Nina Z. Moore

A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2

Tissue inhibitor of metalloproteinases-3 (TIMP3) is one of four members of a family of proteins that were originally classified according to their ability to inhibit matrix metalloproteinases (MMP). TIMP3, which encodes a potent angiogenesis inhibitor, is mutated in Sorsby fundus dystrophy, a macular degenerative disease with submacular choroidal neovascularization. In this study we demonstrate the ability of TIMP3 to inhibit vascular endothelial factor (VEGF)–mediated angiogenesis and identify the potential mechanism by which this occurs: TIMP3 blocks the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling and angiogenesis. This property seems to be independent of its MMP-inhibitory activity, indicating a new function for this molecule.

Central neuromodulation for refractory pain.

Chronic neuropathic pain affects 8.2% of adults, extrapolated to roughly 18 million people every year in the United States. Patients who have pain that cannot be controlled with pharmacologic management or less invasive techniques can be considered for deep brain stimulation or motor cortex stimulation. These techniques are not currently approved by the Food and Drug Administration for chronic pain and are, thus, considered off-label use of medical devices for this patient population. Conclusive effectiveness studies are still needed to demonstrate the best targets as well as the reliability of the results with these approaches.

Flow diverter treatment of intracranial vertebral artery dissecting pseudoaneurysms

Introduction Intracranial vertebral dissecting pseudoaneurysms are a rare, but increasingly recognized, cause of subarachnoid hemorrhage and ischemic stroke. The risks of aneurysm re-rupture and associated morbidity are high. The use of flow diverter stents for the treatment of these aneurysms has not been well studied. Objective To report our data and provide a summarized review of literature using flow diverter stents for the treatment of intracranial vertebral artery dissecting pseudoaneurysms. Methods We performed a retrospective analysis of flow diverter stents used for the treatment of intracranial vertebral artery dissecting pseudoaneurysms. Clinical, imaging, procedural, and follow-up data were collected. Results We identified eight vertebral dissecting pseudoaneurysms in seven patients (5 (71.4%) female; median age 47 years (IQR 46–52)) who had undergone treatment with flow diverter stents. In 4/7 patients (57.1%) the aneurysm had ruptured; however, only one was treated in the acute phase. Median size of the largest diameter of the aneurysm was 6.3 mm (IQR 4.2–8.8), and 7/8 aneurysms (87.5%) were treated with a single flow diverter device. Three aneurysms were concurrently coiled. Angiographic complete occlusion was seen in 6/8 (75%) aneurysms at a median follow-up of 14 months (IQR 7.7–20.2). Two patients had periprocedural strokes with transient neurologic deficits. All patients had a good clinical outcome (modified Rankin Scale score ≤2). There were no re-treatments or aneurysm ruptures during the follow-up period. Conclusions Our experience suggests that flow diverter stent treatment of intracranial vertebral artery dissecting pseudoaneurysms is safe, and associated with good occlusion rates and favorable clinical outcomes.

Treatment of an Anterior Inferior Cerebellar Artery Aneurysm With Microsurgical Trapping and In Situ Posterior Inferior Cerebellar Artery to Anterior Inferior Cerebellar Artery Bypass: Case Report

BACKGROUND Anterior inferior cerebellar artery (AICA) aneurysms are rare lesions whose treatment can involve microsurgical and/or endovascular techniques. Such treatment can be challenging and may carry a significant risk of neurological morbidity. OBJECTIVE To demonstrate a case involving a complex AICA aneurysm that was treated with a unique microsurgical approach involving trapping the aneurysm and performing in Situ bypass from the posterior inferior cerebellar artery (PICA) to the distal AICA. The nuances of AICA aneurysms and revascularization strategies are discussed. METHODS The aneurysm and the distal segments of AICA and PICA were exposed with a retrosigmoid and far lateral approach. A side-to-side anastomosis was performed between the adjacent caudal loops of PICA and AICA. The AICA aneurysm was then treated by trapping the aneurysm-bearing segment of the parent vessel between 2 clips. RESULTS A postoperative angiogram demonstrated a patent PICA-AICA bypass and complete occlusion of the AICA aneurysm. There were no complications, and the patient made an excellent recovery. CONCLUSION The combination of parent vessel sacrifice and bypass remains an excellent option for certain difficult-to-treat aneurysms. This case involving PICA-AICA bypass to treat an AICA aneurysm serves as an example of the neurosurgeons ability to develop unique solutions that take advantage of individual anatomy.

Treatment Outcomes of A Randomized Trial of Unruptured Brain Arteriovenous Malformation-Eligible Unruptured Brain Arteriovenous Malformation Patients.

BACKGROUND The guideline for treating unruptured brain arteriovenous malformations (ubAVMs) remains controversial. A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) reported lower risk of stroke or death with conservative management compared to interventional treatment. There were numerous limitations to the study, including short follow-up period and disproportionate number of patients treated with surgery and embolization. OBJECTIVE To evaluate whether treatment of ARUBA-eligible patients have acceptable outcomes at our institution. METHODS Retrospective analysis was performed on 673 patients with brain AVMs treated at our institution between 2001 and 2014. One hundred five patients were ARUBA eligible and included in the study. Patients were divided into the microsurgery or Gamma Knife Radiosurgery (GKS; Elekta, Stockholm, Sweden) arm depending on their final treatment. Mean follow-up period was 43 mo (range 4-136 mo). Primary outcome was stroke or death. RESULTS A total of 8 (7.6%) patients had a stroke or died. The overall risk of stroke or death was 11.4% (5 of 44 patients) for the microsurgery arm and 4.9% (3 of 61 patients) for the GKS arm. The annual rates of stroke or death were 2.1%, 4.0%, and 1.2% for the entire patient cohort, microsurgery arm, and GKS arm, respectively. AVM obliteration rates at the end of the follow-up period were 95.5% and 47.5% for the microsurgery and GKS arms, respectively. CONCLUSION We report a lower overall risk of stroke or death in our ARUBA-eligible patients following treatment than ARUBA. Our results suggest that microsurgery and GKS may be appropriate treatments for patients with ubAVM.

BrainPath-Mediated Resection of a Ruptured Subcortical Arteriovenous Malformation

BACKGROUND Although tubular retractor systems have gained popularity for other indications, there have been few reports of their use for arteriovenous malformation (AVM) surgery. A patient was diagnosed with a ruptured 1.2-cm subcortical AVM after presenting with intracerebral hemorrhage in the right frontal lobe and anterior basal ganglia. The characteristics of this AVM made it amenable to resection using a tubular retractor. OBJECTIVE To demonstrate the feasibility and safety of AVM resection using a tubular retractor system. METHODS Resection of the ruptured 1.2-cm subcortical AVM was performed utilizing the BrainPathTM (NICO corp, Indianapolis, Indiana) tubular retractor system. RESULTS The BrainPathTM approach provided sufficient visualization and surgical freedom to permit successful AVM resection and hematoma evacuation. Postoperative imaging demonstrated near total hematoma removal and angiographic obliteration of the AVM. There were no complications, and the patient made an excellent recovery. CONCLUSION Tubular retractors warrant consideration for accessing small, deep, ruptured AVMs. The nuances of such systems and their role in AVM surgery are discussed.

Spinal Vascular Malformation Surgery

Spinal vascular malformation surgery can be a daunting challenge for neurosurgeons. Possibly complicated by anterior location, intermixed with normal spinal vasculature and having little neurologic reserve room for mistake, spinal AVMs must be approached with careful planning, consideration of preoperative embolization, and use of intraoperative diagnostic tools to improve success. Some progress in improving resection strategy has been made with the use of new intraoperative tools and invasive and noninvasive neuroimaging.

Neuroendoscopic evacuation of intraventricular empyema using a side-cutting aspiration device

Pyogenic ventriculitis is a rare but severe post-neurosurgical complication. The infection is often resistant to antibiotic treatment alone. Continuous intraventricular irrigation has been suggested but the technique is cumbersome, increases the risk for secondary infection, and is inadequate in removing adherent purulence. We used a novel neuroendoscopic approach assisted with a side-cutting aspiration device to treat four cases of post-neurosurgical pyogenic ventriculitis. Ventricular empyema was cleared in all patients and three of the four patients had favorable outcomes.

Microsurgical Repair of Ruptured Aneurysms Associated with Moyamoya-Pattern Collateral Vessels of the Middle Cerebral Artery: A Report of Two Cases

BACKGROUND Patients with Moyamoya or other intracranial steno-occlusive disease are at risk for developing aneurysms associated with flow through collateral vessels. Because these lesions are rare, the optimal management remains unclear. Here, we describe 2 cases of microsurgical repair of ruptured collateral vessel aneurysms associated with middle cerebral artery (MCA) occlusion. CASE DESCRIPTION The first patient was a 61-year-old man who presented with right frontal and intraventricular hemorrhage. Angiography revealed chronic right M1 occlusion and a 3-mm spherical lenticulostriate aneurysm. The frontal lobe hematoma was evacuated to reveal the aneurysm, which was safely cauterized and resected by coagulating and dividing the lenticulostriate parent vessel. The procedure was carried out with neuronavigation guidance and intraoperative neuromonitoring. The patient was discharged with no neurologic deficits. The second patient was a 53-year-old woman who presented with subarachnoid and intracerebral hemorrhage. Computed tomography angiogram showed a 2-mm saccular MCA aneurysm. Emergency left decompressive hemicraniectomy and hematoma evacuation were performed. The aneurysm, arising from a small collateral type vessel, was safely clipped without complications. Postoperative angiography revealed absence of the superior MCA trunk with a dense network of collateral vessels at the site of the clipped aneurysm. The patient recovered well and was ambulating independently 6 months postoperatively. No rebleeding occurred in the 2 patients. CONCLUSIONS Our experience suggests that patients with MCA occlusion can harbor associated aneurysms related to flow through collateral vessels and can present with hemorrhage. Microsurgical repair of these aneurysms can be performed safely to prevent rebleeding.

Minimally Invasive Hemorrhage Evacuation

With new therapies and interventions in the ischemic stroke realm leading to improved outcomes, attention is turning to treatment of hemorrhagic stroke therapies that strive to improve both morbidity and mortality. The thought that “time is brain” likely also applies to damage to neural structures neighboring hemorrhagic clots and efforts to create a method for hemorrhagic clot evacuation while minimizing damage to still intact brain tissue is actively being investigated. Open surgical evacuation, when tested against initial medical management only, was shown to improve outcomes in traumatic intracerebral hemorrhage (ICH) but had a small outcome advantage in spontaneous lobar hemorrhage and no advantage to the larger group of spontaneous ICH in the STITCH, STICH II, and STICH trials, respectively, performed in the United Kingdom. Although the reason for a lack of significant difference in open surgical evacuation compared with medically managed therapy is not known definitively, it is felt that perhaps the damage to the brain during surgical evacuation or incomplete evacuation may contribute to the lack of significant improvement from medically managed patients. New treatment techniques are now being explored to improve the access to the clot while minimizing the effect on the intervening brain tissue. These new, minimally invasive techniques range from image-guided placement of brain catheters that use chemical thrombolysis to stereotactic placement of brain tubular access devices that allow for minimal disruption of tissue while being able to access the clot under visualization. These minimally invasive techniques have shown some positive results with the outcomes of the Minimally Invasive Surgery and rtTPA for Intracerebral Hemorrhage Evacuation (MISTIE) trials I and II demonstrating that the intraparenchymal clot can be safely