Long-term safety of MRI-guided administration of AAV2-GDNF and gadoteridol in the putamen of individuals with Parkinson's disease.

Direct putaminal infusion of adeno-associated virus vector (serotype 2) (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene was studied in a phase I clinical trial of participants with advanced Parkinson's disease (PD). Convection-enhanced delivery of AAV2-GDNF with a surrogate imaging tracer (gadoteridol) was used to track infusate distribution during real-time intraoperative magnetic resonance imaging (iMRI). Pre-, intra-, and serial postoperative (up to 5 years after infusion) MRI were analyzed in 13 participants with PD treated with bilateral putaminal co-infusions (52 infusions in total) of AAV2-GDNF and gadoteridol (infusion volume, 450 mL per putamen). Real-time iMRI confirmed infusion cannula placement, anatomic quantification of volumetric perfusion within the putamen, and direct visualization of off-target leakage or cannula reflux (which permitted corresponding infusion rate/cannula adjustments). Serial post-treatment MRI assessment (n = 13) demonstrated no evidence of cerebral parenchyma toxicity in the corresponding regions of AAV2-GDNF and gadoteridol co-infusion or surrounding regions over long-term follow-up. Direct confirmation of key intraoperative safety and efficacy parameters underscores the safety and tissue targeting value of real-time imaging with co-infused gadoteridol and putative therapeutic agents (i.e., AAV2-GDNF). This delivery-imaging platform enhances safety, permits delivery personalization, improves therapeutic distribution, and facilitates assessment of efficacy and dosing effect.

Sex differences in thrombosis as it affects acute ischemic stroke.

Ischemic stroke is a devastating health problem, affecting approximately 800,000 patients in the US every year, making it the leading cause of combined death and disability in the country. Stroke has historically been thought of as predominantly impacting men, however it is becoming increasingly clear that stroke affects women to a greater degree than men. Indeed, women have worse outcomes compared to men following ischemic stroke. Recent clinical advances have shown great promise in acute stroke therapy, with the use of mechanical endovascular thrombectomy (with and without recombinant tissue plasminogen activator; rtPA) greatly improving outcomes. This observation makes it clear that removal of clots and reperfusion, either mechanically or pharmacologically, is critical for improving outcomes of patients following acute ischemic stroke. Despite these promising advances, long-term neurological sequelae persist in the post-stroke population. This review focuses on mechanisms of thrombosis (clot formation) as it pertains to stroke and important sex differences in thrombosis and responses to treatment. Finally, we describe recent data related to new therapeutic approaches to thrombolysis, with a particular focus on von Willebrand Factor (vWF).

Negative pressure wound therapy in spinal fusion patients.

Post-operative wound complications are some of the most common acute complications following spine surgery. These surgical site infections (SSI) contribute to increased healthcare related costs. Negative pressure wound therapy (NPWT) has long been used for treatment of soft tissue injury or defects. NPWT may reduce the incident of SSI following spinal fusion procedures; however, its potential applications need further clarification. Thus, we conducted a retrospective analysis of two cohorts to compare NPWT to traditional sterile dressings following spinal fusions in regards to post-operative outcomes. Following institutional review board approval, 42 patients who had a NPWT were matched by type of surgery to 42 patients who had traditional dressings. A retrospective chart-review was completed. Outcome measures, particularly SSI and need for reoperation, were analyzed using one-way ANOVA for both univariate and multivariate analysis. When controlled for sex and body-mass index, the use of a NPWT was independently correlated with decreased SSI (P = .035). Superficial dehiscence, seroma, need for additional outpatient care, and need for operative revision were all found to occur at higher rates in the traditional dressing cohort. Closed incisional negative pressure wound therapy provides a cost-effective method of decreasing surgical site infection for posterior elective spine surgeries.

Real-time ultrasound guidance in the endoscopic endonasal resection of a retro-odontoid pannus: Technical note and case illustration.

Background and Objectives: Odontoidectomy is a surgical procedure indicated in the setting of various pathologies, with the main goal of decompressing the ventral brain stem and spinal cord as a result of irreducible compression at the craniovertebral junction. The endoscopic endonasal approach has been increasingly used as an alternative to the transoral approach as it provides a straightforward, panoramic, and direct approach to the odontoid process. In addition, intraoperative ultrasound (US) guidance is a technique that can optimize safety and surgical outcomes in this context. It is used as an adjunct to neuronavigation and provides intraoperative confirmation of decompression of craniovertebral junction structures in real time. The authors aim to present the use and safe application of real-time intraoperative US guidance during endonasal endoscopic resection of a retro-odontoid pannus. Methods: A retrospective chart review of a single case was performed and presented herein as a case report and narrated operative video. Results: A minimally invasive US transducer was used intraoperatively to guide the resection of a retro-odontoid pannus and confirm spinal cord decompression in real time. Postoperative examination of the patient revealed immediate neurological improvement. Conclusions: Intraoperative ultrasonography is a well described and useful modality in neurosurgery. However, the use of intraoperative US guidance during endonasal endoscopic approaches to the craniovertebral junction has not been previously described. As demonstrated in this technical note, the authors show that this imaging modality can be added to the ever-evolving armamentarium of neurosurgeons to safely guide the decompression of neural structures within the craniocervical junction with good surgical outcomes.

C1-2 facet disarticulation for correction of iatrogenic cervical kyphosis following occipital-cervical fusion.

The patient is a 69-year-old woman with a history of atlantoaxial instability and cervical pain who underwent an occipital-cervical fusion at an outside hospital. Five days following the procedure she required a PEG tube due to progressive dysphagia. Compared with preoperative imaging, x-ray shows cervical spine hyperextension with a significant decrease in the occipital-C2 angle. A swallow test confirmed aspiration and pharyngeal phase functional impairment. Two-stage surgery consisted of hardware removal, drilling the fused right C1-2 facet, reinstrumentation, and halo placement. The swallowing test confirmed there is no aspiration. We proceeded with rod placement. The patient recovered completely. The video can be found here: https://youtu.be/YzdJrOm46Y4.

Direct convective delivery of adeno-associated virus gene therapy for treatment of neurological disorders.

Molecular biological insights have led to a fundamental understanding of the underlying genomic mechanisms of nervous system disease. These findings have resulted in the identification of therapeutic genes that can be packaged in viral capsids for the treatment of a variety of neurological conditions, including neurodegenerative, metabolic, and enzyme deficiency disorders. Recent data have demonstrated that gene-carrying viral vectors (most often adeno-associated viruses) can be effectively distributed by convection-enhanced delivery (CED) in a safe, reliable, targeted, and homogeneous manner across the blood-brain barrier. Critically, these vectors can be monitored using real-time MRI of a co-infused surrogate tracer to accurately predict vector distribution and transgene expression at the perfused site. The unique properties of CED of adeno-associated virus vectors allow for cell-specific transgene manipulation of the infused anatomical site and/or widespread interconnected sites via antero- and/or retrograde transport. The authors review the convective properties of viral vectors, associated technology, and clinical applications.

Acute presentation of spinal gouty arthritis: A case report and review of literature.

BACKGROUND: Gout is an inflammatory arthritis that results from faulty purine metabolism, affecting approximately 4% of adults in the US, and predominately affects people in the fourth decade of life. Further, spinal gout is rarely the first presentation of gout, especially in younger individuals. CASE DESCRIPTION: A 26-year-old male came to the emergency room with acute lower extremity numbness and weakness. The MR demonstrated an enhancing epidural lesion at T6-T8 in the mid-thoracic spine. He subsequently underwent a decompressive laminectomy and fusion at levels T6-T9, resulting in full recovery 1 year later. The pathology demonstrated needle-like monosodium urate crystals consistent with the diagnosis of spinal gouty arthritis. CONCLUSION: Gout rarely initially presents in a young adult in the spine. Here, we reviewed the case of spinal gout in a 26-year-old male who successfully underwent spinal surgery.

Real-Time Magnetic Resonance Imaging During Convective Gene Therapy Perfusion of the Brain.

This article discusses use of intraoperative MRI in convective gene therapy perfusion.

Intraosseous Orbital Cavernous Hemangioma with Frontal Extension and Dural Involvement.

Primary intraosseous cavernous hemangiomas are rare skull lesions that are not typically known to involve the orbital bones or the dura. We describe a rare case of a fronto-orbital bone cavernous hemangioma with extension into the dura. A 68-year-old female presented with a one-year history of diplopia with discomfort around her left orbit. Magnetic resonance images demonstrated a mass in the left frontal skull extending into the orbital rim. The patient underwent a craniotomy for tumor resection. Dural invasion was found intraoperatively. Gross total resection and reconstruction were achieved. On the postoperative follow-up, the patient was asymptomatic.  Primary calvarial intraosseous cavernous hemangiomas are most commonly located in the frontal and parietal bones. These lesions typically involve only the outer table of the skull. In lesions involving the orbit and dura, excision with cranioplasty can provide symptomatic relief with good cosmetic outcomes.

Cardiovascular Health in St. Louis Bosnian-Americans.

In Bosnia and Herzegovina, cardiovascular disease accounts for nearly 50% of deaths. Cardiovascular health of resettled Bosnian-Americans has not been well-characterized. Our study aimed to quantify cardiovascular risk in Bosnian-Americans in St. Louis, the largest non-European center of resettlement. Seven community screenings focused on Bosnian-Americans were held. Cardiovascular risk was calculated to stratify individuals into low (<10%), moderate (10-20%), and high (>20%) risk. Those with self-reported coronary heart disease (CHD) or risk equivalent were considered high-risk. Two-hundred fifty Bosnian-Americans were screened; 51% (n = 128) consented to the IRB-approved study. Twenty-one percent were smokers, 33% obese, and 33% had hypertension. Excluding risk equivalent individuals, 5.7% of subjects were high-risk, increasing to 26.6% when including high-risk equivalents. Lipid abnormalities include elevated triglycerides (29.0%) and low HDL (50.0%). Compared to general American population studies, Bosnian-Americans have greater ten-year hard CHD risk. A community-based approach identified potential culturally-based lifestyle interventions including diet, exercise, and smoking.

Recurrent hemorrhage in hemangioblastoma involving the posterior fossa: Case report.

BACKGROUND: Hemangioblastomas (HGBs) are the most common primary intra-axial posterior fossa tumor in adults. Although spontaneous hemorrhage of these tumors is exceedingly rare, despite their vascular nature, we describe a case of recurrent hemorrhage with associated tonsillar herniation, and demonstrate that a surgical approach can provide a suitable outcome. CASE DESCRIPTION: A 54-year-old female with von Hippel-Lindau (VHL) syndrome presented with acute loss of consciousness and Glasgow Coma Scale (GCS) was 4. Computed tomographic (CT) images demonstrated large volume subarachnoid hemorrhage of the posterior fossa with intraventricular extension and intraparenchymal hemorrhage involving the right cerebellar tonsil. Magnetic resonance imaging (MRI) displayed three lesions in the posterior fossa, two near the hemorrhage site. Patient underwent suboccipital craniectomy with a decent recovery followed by radiosurgery as she refused resection. A second hemorrhage occurred ultimately prompting surgical resection of the three posterior fossa lesions, with a reasonable postoperative course. CONCLUSION: Hemorrhage of HGBs of the posterior fossa can present in conjunction of tonsillar herniation. Re-hemorrhage appears to be likely if prior acute hemorrhage has occurred. A stepwise approach of surgical decompression and resection may provide the best outcome.

Awake High-Flow Extracranial to Intracranial Bypass for Complex Cerebral Aneurysms: Institutional Clinical Trial Results.

OBJECTIVE: Assess the potential added benefit to patient outcomes of "awake" neurological testing when compared with standard neurophysiologic testing performed under general endotracheal anesthesia. METHODS: Prospective study of 30 consecutive adult patients who underwent awake high flow extracranial to intracranial (HFEC-IC) bypass. Clinical neurological and neurophysiologic findings were recorded. Primary outcome measures were the incidence of stroke/cerebrovascular accident (CVA), length of stay, discharge to rehabilitation, 30-day modified Rankin scale score, and death. An analysis was also performed of a retrospective control cohort (n = 110 patients who underwent HFEC-IC for internal carotid artery (ICA) aneurysms under standard general endotracheal anesthesia). RESULTS: Five patients (16.6%) developed clinical awake neurological changes (4, contralateral hemiparesis; 1, ipsilateral visual changes) during the 10-minute ICA occlusion test. These patients had 2 kinks in the graft, 1 vasospasm, 1 requiring reconstruction of the distal anastomosis, and 1 developed blurring of vision that reversed after the removal of the distal permanent clip on the ICA. Three of these 5 patients had asynchronous clinical "awake" neurological and neurophysiologic changes. Two patients (7%) developed CVA. Median length of stay was 4 days. Twenty-eight of 30 patients were discharged to home. Median modified Rankin scale score was 1. There were no deaths in this series. Absolute risk reduction in the awake craniotomy group (n = 30) relative to control retrospective group (n = 110) was 7% for CVA, 9% for discharge to rehabilitation, and 10% for graft patency. CONCLUSIONS: Temporary ICA occlusion during HFEC-IC bypass for ICA aneurysms in conjunction with awake intraoperative clinical testing was effective in detecting a subset of patients (n = 3, 10%) in whom neurological deficit was not detected by neurophysiologic monitoring alone.