Chirag D. Gandhi

Heparin crosslinked chitosan microspheres for the delivery of neural stem cells and growth factors for central nervous system repair.

An effective paradigm for transplanting large numbers of neural stem cells after central nervous system (CNS) injury has yet to be established. Biomaterial scaffolds have shown promise in cell transplantation and in regenerative medicine, but improved scaffolds are needed. In this study we designed and optimized multifunctional and biocompatible chitosan-based films and microspheres for the delivery of neural stem cells and growth factors for CNS injuries. The chitosan microspheres were fabricated by coaxial airflow techniques, with the sphere size controlled by varying the syringe needle gauge and the airflow rate. When applying a coaxial airflow at 30 standard cubic feet per hour, ∼300μm diameter spheres were reproducibly generated that were physically stable yet susceptible to enzymatic degradation. Heparin was covalently crosslinked to the chitosan scaffolds using genipin, which bound fibroblast growth factor-2 (FGF-2) with high affinity while retaining its biological activity. At 1μgml(-1) approximately 80% of the FGF-2 bound to the scaffold. A neural stem cell line, GFP+RG3.6 derived from embryonic rat cortex, was used to evaluate cytocompatibility, attachment and survival on the crosslinked chitosan-heparin complex surfaces. The MTT assay and microscopic analysis revealed that the scaffold containing tethered FGF-2 was superior in sustaining survival and growth of neural stem cells compared to standard culture conditions. Altogether, our results demonstrate that this multifunctional scaffold possesses good cytocompatibility and can be used as a growth factor delivery vehicle while supporting neural stem cell attachment and survival.

Endovascular therapy of acute ischemic stroke: Report of the Standards of Practice Committee of the Society of NeuroInterventional Surgery

Objective To summarize and classify the evidence for the use of endovascular techniques in the treatment of patients with acute ischemic stroke. Methods Recommendations previously published by the American Heart Association (AHA) (Guidelines for the early management of adults with ischemic stroke (Circulation 2007) and Scientific statement indications for the performance of intracranial endovascular neurointerventional procedures (Circulation 2009)) were vetted and used as a foundation for the current process. Building on this foundation, a critical review of the literature was performed to evaluate evidence supporting the endovascular treatment of acute ischemic stroke. The assessment was based on guidelines for evidence based medicine proposed by the Stroke Council of the AHA and the University of Oxford, Centre for Evidence Based Medicine (CEBM). Procedural safety, technical efficacy and impact on patient outcomes were specifically examined.

Head, neck, and brain tumor embolization guidelines

Background Management of vascular tumors of the head, neck, and brain is often complex and requires a multidisciplinary approach. Peri-operative embolization of vascular tumors may help to reduce intra-operative bleeding and operative times and have thus become an integral part of the management of these tumors. Advances in catheter and non-catheter based techniques in conjunction with the growing field of neurointerventional surgery is likely to expand the number of peri-operative embolizations performed. The goal of this article is to provide consensus reporting standards and guidelines for embolization treatment of vascular head, neck, and brain tumors. Summary This article was produced by a writing group comprised of members of the Society of Neurointerventional Surgery. A computerized literature search using the National Library of Medicine database (Pubmed) was conducted for relevant articles published between 1 January 1990 and 31 December 2010. The article summarizes the effectiveness and safety of peri-operative vascular tumor embolization. In addition, this document provides consensus definitions and reporting standards as well as guidelines not intended to represent the standard of care, but rather to provide uniformity in subsequent trials and studies involving embolization of vascular head and neck as well as brain tumors. Conclusions Peri-operative embolization of vascular head, neck, and brain tumors is an effective and safe adjuvant to surgical resection. Major complications reported in the literature are rare when these procedures are performed by operators with appropriate training and knowledge of the relevant vascular and surgical anatomy. These standards may help to standardize reporting and publication in future studies.

Treatment of ruptured lenticulostriate artery aneurysms

OBJECTnLenticulostriate artery (LSA) aneurysms are rarely reported in the literature, making management decisions challenging. Conservative, endovascular, and surgical treatments have been described primarily through case reports and reports of individual authors experiences. The purpose of this study is to report neurological outcomes in a single-institution experience of ruptured lenticulostriate aneurysms treated surgically.nnnMETHODSnThe authors have conducted a retrospective review of all cases involving patients with ruptured LSA aneurysms who presented to the Mt. Sinai Hospital neurosurgical service between September 2001 and January 2007.nnnRESULTSnOver 5.4 years, the authors treated 6 patients with 7 LSA aneurysms-6 ruptured and 1 unruptured. The Hunt and Hess grade on admission ranged from I to IV, with subarachnoid hemorrhage in 5 of the 6 patients. Catheter angiography confirmed the presence of the aneurysms, and all patients underwent a pterional craniotomy and clipping or resection of the aneurysm, performed by a single surgeon. Associated risk factors in our series of patients included hypertension, cocaine abuse, and intracranial occlusive disease suggestive of moyamoya disease. Two types of LSA aneurysms were identified. The mean size of the 6 ruptured aneurysms was 3.2 mm. The LSA was preserved in 3 of 6 patients, but LSA preservation did not correlate with development of a postoperative infarct, clinically or radiologically. In patients with ruptured aneurysms, the mean modified Rankin Scale score at discharge was 1.7. The 3 patients in whom the LSA was sacrificed had good outcomes, suggesting that loss of the artery is clinically well tolerated.nnnCONCLUSIONSnThis case series demonstrates that surgical treatment of ruptured LSA aneurysms can be an appropriate, effective, and safe therapy.

Three dimensional CT angiography versus digital subtraction angiography in the detection of intracranial aneurysms in subarachnoid hemorrhage

Introduction Ruptured intracranial aneurysms are responsible for over 90% of cases of spontaneous subarachnoid hemorrhage (SAH). Conventional digital subtraction angiography (DSA) remains the gold standard for diagnosing the source of SAH. A prospective study is presented wherein SAH patients underwent three dimensional CT angiography (CTA) prior to DSA in order to assess the specificity and sensitivity of this non-invasive modality to detect aneurysms. Methods 179 consecutive patients with spontaneous SAH presented over 36u2005months, as identified by screening CT and CTA. Patients with negative CTA findings underwent DSA within 24u2005h of presentation. All patients who were determined to have angiographically negative SAH underwent follow-up DSA 2u2005weeks later. Results Of the 179 patients screened by CTA, 13 (7%) were negative for aneurysms or other vascular lesions (arteriovenous malformation or dural fistula) on CTA and underwent DSA. No new lesions were identified on six vessel angiography, resulting in a 0% false negative rate (sensitivity 100%, predictive value 100%). MRI to rule out thrombosed aneurysms and repeat angiography at the 2 week follow-up were negative. Conclusions Sensitivity and specificity were higher than previously reported, suggesting that CTA may be used as an initial screening tool in lieu of DSA. Further studies are necessary to determine if CTA can supplant DSA in ruling out all forms of vascular disease in idiopathic SAH.

True aneurysms of the posterior communicating artery: a systematic review and meta-analysis of individual patient data.

OBJECTIVEnTo review and analyze systematically the reported cases of true posterior communicating artery (PCoA) aneurysm.nnnMETHODSnA retrospective review of the published literature was performed, and a meta-analysis of individual patient data was conducted.nnnRESULTSnPooled data showed that true PCoA aneurysms represent about 1.3% (95% confidence interval [CI] 0.8%, 1.7%) of all intracranial aneurysms and 6.8% (95% CI 4.3%, 9.2%) of all PCoA aneurysms. Mean patient age was 53.5 years (53.5 years ± 15.4), and age range was 23-79 years. Of the 49 patients reported in the literature, 44 (89.8%) were reported as ruptured, and 4 (10.2%) were reported as unruptured. There were no significant differences in ruptured status between age (P = 0.321), left vs right aneurysm (P = 0.537), and shape of aneurysm (P = 0.408). No significant differences in complication rates were found between rupture status (P = 0.27), and operative modalities (P = 0.878). The mean ages of patients who had no complications and patients who had complications were 53 years (53 years ± 2.59) vs 53.2 years (53.2 years ± 5.02) (P = 0.972).nnnCONCLUSIONSnTrue PCoA aneurysms represent about 1.3% of all intracranial aneurysms and 6.8% of all PCoA aneurysms. They are more prone to rupture compared with their counterpart junctional aneurysms. When surgical management is indicated, a good understanding of the location and configuration of the aneurysm neck before surgical treatment is critical in the successful treatment of these lesions.

Current endovascular treatment options of dural venous sinus thrombosis: a review of the literature

Dural venous sinus thrombosis, although relatively rare, has the propensity to cause potentially fatal conditions, such as stroke. This review presents the current endovascular treatment and management options for dural venous sinus thrombosis and provides current recommendations. Select databases were utilized for an exhaustive literature search with key search terms in efforts to obtain all relevant cases to endovascular treatment of dural venous sinus thrombosis. Recommendations for management options include initially the use of anticoagulation. For patients with a poor prognosis, local thrombolysis with urokinase or recombinant tissue plasminogen activator should be initiated. Ultimately, if the patient is not a good candidate for local or systemic thrombolysis, treatment via rheolytic thrombectomy should be employed.

Vertebral augmentation: report of the Standards and Guidelines Committee of the Society of NeuroInterventional Surgery

Vertebroplasty and kyphoplasty are minimally invasive image-guided procedures that involve the injection of cement (typically polymethylmethacrylate (PMMA)) into a vertebral body. Kyphoplasty involves inflation of a balloon tamp to create a cavity within the vertebral body into which cement is subsequently injected. The majority of these vertebral augmentation procedures are performed to relieve back pain from osteoporotic or cancer-related vertebral compression fractures and to reinforce the vertebral body with neoplasm or vascular tumor. The primary goal of vertebroplasty and kyphoplasty is to reduce back pain and to improve patients functional status, and the secondary goal is stabilization of a vertebra weakened by fracture or neoplasia.nn### Osteoporotic vertebral fracturesnnOsteoporosis is a common disease that causes significant morbidity and incurs a significant healthcare cost to the community. The major osteoporotic fractures involve the hip, vertebra, proximal humerus and distal forearm; the lifetime osteoporotic fracture risk at age 50 is approximately one in two women and one in five men.1 The lifetime incidence of symptomatic osteoporotic vertebral fractures in women at age 50 is estimated at 10–15%1; once a vertebral fracture occurs, there is a 20% risk of another vertebral fracture within 12u2005months.2nnMost osteoporotic vertebral compression fractures are asymptomatic or result in minimal pain; only a third of vertebral fractures result in medical attention.3 Conservative medical therapy is therefore appropriate for the vast majority of vertebral compression fractures since most acute back pain symptoms are mild and subside over a period of 6–8u2005weeks as the fracture heals. The goals of conservative therapy are pain reduction (with analgesics and/or bed rest), improvement in functional status (with orthotic devices and physical therapy) and prevention of future fractures (with vitamin D, calcium supplementation and antiresorptive agents).nnHowever, conservative treatment for those with severe pain or limitation of function is not benign. It …

Salvage endoscopic nasoseptal flap repair of persistent cerebrospinal fluid leak after open skull base surgery

PURPOSEnPersistent cerebrospinal fluid (CSF) rhinorrhea after open skull base surgery can be challenging to manage due to the risk of meningitis, brain abscess, surgical morbidity associated with revision craniotomy, and the lack of available healthy autologous tissue after failure of a pericranial flap. Given the recent success of the vascularized pedicled nasoseptal flap (PNSF) for reconstruction after endoscopic skull base surgery, we have adopted this technique as a salvage method to treat recalcitrant CSF rhinorrhea after previous open skull base surgery in order to avoid revision craniotomy. To our knowledge, use of the PNSF in this setting has not been previously described in the literature.nnnMETHODSnA retrospective analysis was performed on 4 patients who underwent endoscopic endonasal PNSF repair of persistent CSF rhinorrhea after having undergone previous open transcranial skull base operation. Pathologies consisted of one sinonasal anterior skull base squamous cell carcinoma, one recurrent petrosal skull base meningioma, and 2 traumatic gunshot wounds to the head.nnnRESULTSnAll 4 patients underwent successful repair of CSF rhinorrhea without complications using the salvage endoscopic endonasal PNSF technique after a mean follow-up of 21.5 months.nnnCONCLUSIONSnIn patients who have undergone previous open skull base surgery as the primary approach, persistent CSF rhinorrhea can be safely repaired using the vascularized PNSF via an endoscopic endonasal approach. This minimally invasive strategy has the advantage of providing new healthy vascularized tissue for skull base reconstruction while avoiding revision craniotomy.

Endovascular treatment for acute ischemic stroke in octogenarians compared with younger patients: a meta-analysis.

Background Little is known about the safety and efficacy of endovascular therapy for acute ischemic stroke in octogenarians. Aim We performed a systematic review and meta-analysis of published studies comparing outcomes of octogenarians and younger patients after endovascular treatment for acute ischemic stroke. Methods A computerized search of the medical literature from 1990 to 2012 was performed to identify comparative studies of endovascular treatment of ischemic stroke patients 80 years or older and younger patients. Data on clinical outcomes, mortality, symptomatic intracerebral hemorrhage, and recanalization were abstracted. Results Data from eight studies with 2729 patients were included in the final analysis. Good functional outcome defined as modified Rankin score 2 or less within 90 days was more common in younger patients compared with octogenarians [odds ratio 2·694; 95% confidence interval 1·941–3·740, P < 0·001). Symptomatic hemorrhage and death were significantly more come in patients 80 years or older (odds ratio 1·604; 95% confidence interval 1·013–2·540, P = 0·04 and odds ratio 3·695; 95% confidence interval 2·517–5·424, P < 0·001, respectively). Successful recanalization defined as Thrombolysis in Myocardial Infarction (TIMI) 2–3 was seen less frequently in older patients; however, this did not reach statistical significance (odds ratio 0·814; 95% confidence interval 0·522–1·269, P = 0·364). Conclusion Formal meta-analysis showed that octogenarians are less likely to achieve functional independence and have higher rates of mortality and intracerebral hemorrhage following endovascular treatment for ischemic stroke compared with younger patients. Decisions regarding endovascular treatment of elderly patients should be individualized until randomized controlled trials are available.