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Item The SMART Registry: Long-Term Results on the Utility of the Penumbra SMART COIL System for Treatment of Intracranial Aneurysms and Other Malformations(Frontiers Media, 2021-04-13) Spiotta, Alejandro M.; Park, Min S.; Bellon, Richard J.; Bohnstedt, Bradley N.; Yoo, Albert J.; Schirmer, Clemens M.; DeLeacy, Reade A.; Fiorella, David J.; Woodward, B. Keith; Hawk, Harris E.; Nanda, Ashish; Zaidat, Osama O.; Sunenshine, Peter J.; Liu, Kenneth C.; Kabbani, Mouhammed R.; Snyder, Kenneth V.; Sivapatham, Thinesh; Dumont, Travis M.; Reeves, Alan R.; Starke, Robert M.; SMART Registry Investigators; Neurological Surgery, School of MedicineIntroduction: Penumbra SMART COIL® (SMART) System is a novel generation embolic coil with varying stiffness. The study purpose was to report real-world usage of the SMART System in patients with intracranial aneurysms (ICA) and non-aneurysm vascular lesions. Materials and Methods: The SMART Registry is a post-market, prospective, multicenter registry requiring ≥75% Penumbra Coils, including SMART, PC400, and/or POD coils. The primary efficacy endpoint was retreatment rate at 1-year and the primary safety endpoint was the procedural device-related serious adverse event rate. Results: Between June 2016 and August 2018, 995 patients (mean age 59.6 years, 72.1% female) were enrolled at 68 sites in the U.S. and Canada. Target lesions were intracranial aneurysms in 91.0% of patients; 63.5% were wide-neck and 31.8% were ruptured. Adjunctive devices were used in 55.2% of patients. Mean packing density was 32.3%. Procedural device-related serious adverse events occurred in 2.6% of patients. The rate of immediate post-procedure adequate occlusion was 97.1% in aneurysms and the rate of complete occlusion was 85.2% in non-aneurysms. At 1-year, the retreatment rate was 6.8%, Raymond Roy Occlusion Classification (RROC) I or II was 90.0% for aneurysms, and Modified Rankin Scale (mRS) 0-2 was achieved in 83.1% of all patients. Predictors of 1-year for RROC III or retreatment (incomplete occlusion) were rupture status (P < 0.0001), balloon-assisted coiling (P = 0.0354), aneurysm size (P = 0.0071), and RROC III immediate post-procedure (P = 0.0086) in a model that also included bifurcation aneurysm (P = 0.7788). Predictors of aneurysm retreatment at 1-year was rupture status (P < 0.0001). Conclusions: Lesions treated with SMART System coils achieved low long-term retreatment rates.Item Lumbar Ganglioneuroma Presenting With Scoliosis(Springer Nature, 2021-07-31) Gaddipati, Ravi; Ma, Joanna; Dayawansa, Samantha; Shan, Yuan; Huang, Jason H.; Garrett, David; Qaiser, Rabia; Neurological Surgery, School of MedicineGanglioneuromas are rare, benign tumors arising from the sympathetic nervous system. The presentation of the tumor is variable and may be associated with scoliosis. Few reports of ganglioneuroma associated with scoliosis exist and most involve the thoracic spine. Here, we present a 13-year-old female with scoliosis who was found to have a lumbar ganglioneuroma. The patient was treated with a subtotal resection and lumbar spinal fusion to correct her scoliosis in a single-stage operation. The patient's symptoms and scoliosis markedly improved following treatment without any complications. Additionally, we conducted an up-to-date literature review of ganglioneuromas associated with scoliosis that have been published in the last 20 years. We discuss variations in clinical presentation and surgical approach.Item 7,8-Dihydroxyflavone accelerates recovery of Brown-Sequard syndrome in adult female rats with spinal cord lateral hemisection(Elsevier, 2022) Lin, Xiaojing; Zhao, Tingbao; Mei, Guiping; Liu, Ruoxu; Li, Chenyi; Wang, Xiaowen; Qu, Zixuan; Lin, Shide; Walker, M. J.; Yi, Xueqing; Zhang, Peng; Tseng, Kuang-Wen; Xu, Xiao-Ming; Lin, Cheng-Hsien; Sun, Gang; Neurological Surgery, School of MedicineBackground: 7,8-Dihydroxyflavone (DHF) mimicks the physiological action of brain-derived neurotrophic factor (BDNF). Since local BDNF delivery to the injured spinal cord enhanced diaphragmatic respiratory function, we aimed to ascertain whether DHF might have similar beneficial effects after Brown-Sequard Syndrome in a rat model of spinal cord lateral hemisection (HX) at the 9th thoracic (T9) vertebral level. Methods: Three sets of adult female rats were included: sham+vehicle group, T9HX+vehicle group and T9HX+DHF group. On the day of surgery, HX+DHF group received DHF (5 mg/kg) while HX+vehicle group received vehicle. Neurobehavioral function, morphology of motor neurons innervating the tibialis anterior muscle and the transmission in descending motor pathways were evaluated. Results: Adult female rats received T9 HX had paralysis and loss of proprioception on the same side as the injury and loss of pain and temperature on the opposite side. We found that, in this model of Brown-Sequard syndrome, reduced cord dendritic arbor complexity, reduced cord motoneuron numbers, enlarged cord lesion volumes, reduced motor evoked potentials, and cord astrogliosis and microgliosis were noted after T9HX. All of the above-mentioned disorders showed recovery by Day 28 after surgery. Therapy with DHF significantly accelerated the electrophysiological, histological and functional recovery in these T9HX animals. Conclusions: Our data provide a biological basis for DHF as a neurotherapeutic agent to improve recovery after a Brown-Sequard syndrome. Such an effect may be mediated by synaptic plasticity and glia-mediated inflammation in the spared lumbar motoneuron pools to a T9HX.Item Regeneration of Propriospinal Axons in Rat Transected Spinal Cord Injury through a Growth-Promoting Pathway Constructed by Schwann Cells Overexpressing GDNF(MDPI, 2024-07-08) Du, Xiaolong; Zhang, Shengqi; Khabbaz, Aytak; Cohen, Kristen Lynn; Zhang, Yihong; Chakraborty, Samhita; Smith, George M.; Wang, Hongxing; Yadav, Amol P.; Liu, Naikui; Deng, Lingxiao; Neurological Surgery, School of MedicineUnsuccessful axonal regeneration in transected spinal cord injury (SCI) is mainly attributed to shortage of growth factors, inhibitory glial scar, and low intrinsic regenerating capacity of severely injured neurons. Previously, we constructed an axonal growth permissive pathway in a thoracic hemisected injury by transplantation of Schwann cells overexpressing glial-cell-derived neurotrophic factor (SCs-GDNF) into the lesion gap as well as the caudal cord and proved that this novel permissive bridge promoted the regeneration of descending propriospinal tract (dPST) axons across and beyond the lesion. In the current study, we subjected rats to complete thoracic (T11) spinal cord transections and examined whether these combinatorial treatments can support dPST axons’ regeneration beyond the transected injury. The results indicated that GDNF significantly improved graft–host interface by promoting integration between SCs and astrocytes, especially the migration of reactive astrocyte into SCs-GDNF territory. The glial response in the caudal graft area has been significantly attenuated. The astrocytes inside the grafted area were morphologically characterized by elongated and slim process and bipolar orientation accompanied by dramatically reduced expression of glial fibrillary acidic protein. Tremendous dPST axons have been found to regenerate across the lesion and back to the caudal spinal cord which were otherwise difficult to see in control groups. The caudal synaptic connections were formed, and regenerated axons were remyelinated. The hindlimb locomotor function has been improved.Item Adenoid Cystic Carcinoma (ACC) Infiltrating the Skull Base: A Systematic Review of Clinical Characteristics and Management Strategies(IIAR, 2022-09-03) Bin-Alamer, Othman; Haider, Ali S.; Chaudhary, Adhiraj; Balasubramanian, Kishore; Breeding, Tessa; Palmisciano, Paolo; Haider, Maryam; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Yu, Kenny; Neurological Surgery, School of MedicineBackground/Aim: To systematically review the patient characteristics and management approaches of adenoid cystic carcinoma (ACC) infiltrating the skull base. Materials and Methods: According to PRISMA guidelines, PubMed, Scopus, and Cochrane were searched to retrieve studies reporting management protocols and survival outcomes of patients with skull base ACCs. Patient characteristics, management strategies, and outcomes were investigated. Results: The review encompassed 17 studies involving 171 patients, with a female predominance (57.9%) and a mean age of 49±7.12 years. ACCs mostly infiltrated the paranasal sinus (22.2%), cavernous sinus (8.8%), and nasopharynx (7.1%). Perineural invasion was reported in 6.4% of cases. Facial pain, nasal obstruction, and facial paresthesia were the most common symptoms. Surgical resection (45.6%) was favored over biopsy (12.2%). Employing the free flap technique (4.7%), surgical reconstruction of the bony defect after resection was performed using abdominal and anterior thigh muscle grafts in 1.8% of patients each. As adjuvant management, 22.8% of cases had radiotherapy and 14.6% received chemotherapy. Recurrence of skull base ACCs occurred in 26.9% of cases during a mean follow up-time of 30.8±1.8 months. Conclusion: Skull base ACCs pose a surgical challenge mainly due to their proximity to critical neurovascular structures and aggressive behavior. Surgical resection and radiotherapy are shown to be safe and effective treatment modalities. The dismal prognosis and limited data on non-surgical strategies highlight the need for further evaluation of the current management paradigm and upraising innovative therapies to improve patient mortality and quality of life.Item Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury: a randomized controlled study(Wolters Kluwer, 2024) Zhu, Hui; Guest, James D.; Dunlop, Sarah; Xie, Jia-Xin; Gao, Sujuan; Luo, Zhuojing; Springer, Joe E.; Wu, Wutian; Young, Wise; Poon, Wai Sang; Liu, Song; Gao, Hongkun; Yu, Tao; Wang, Dianchun; Zhou, Libing; Wu, Shengping; Zhong, Lei; Niu, Fang; Wang, Xiaomei; Liu, Yansheng; So, Kwok-Fai; Xu, Xiao-Ming; Neurological Surgery, School of MedicineFor patients with chronic spinal cord injury, the conventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection, pressure sores, osteoporosis, and deep vein thrombosis. Surgery is rarely performed on spinal cord injury in the chronic phase, and few treatments have been proven effective in chronic spinal cord injury patients. Development of effective therapies for chronic spinal cord injury patients is needed. We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal cord injury to compare intensive rehabilitation (weight-bearing walking training) alone with surgical intervention plus intensive rehabilitation. This clinical trial was registered at ClinicalTrials.gov (NCT02663310). The goal of surgical intervention was spinal cord detethering, restoration of cerebrospinal fluid flow, and elimination of residual spinal cord compression. We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement, reduced spasticity, and more rapid bowel and bladder functional recovery than weight-bearing walking training alone. Overall, the surgical procedures and intensive rehabilitation were safe. American Spinal Injury Association Impairment Scale improvement was more common in T7–T11 injuries than in T2–T6 injuries. Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.Item Image-based assessment of natural killer cell activity against glioblastoma stem cells(Wiley, 2024) Du, Yuanning; Metcalfe, Samuel; Akunapuram, Shreya; Ghosh, Sugata; Spruck, Charles; Richardson, Angela M.; Cohen‐Gadol, Aaron A.; Shen, Jia; Neurological Surgery, School of MedicineGlioblastoma (GBM) poses a significant challenge in oncology and stands as the most aggressive form of brain cancer. A primary contributor to its relentless nature is the stem-like cancer cells, called glioblastoma stem cells (GSCs). GSCs have the capacity for self-renewal and tumorigenesis, leading to frequent GBM recurrences and complicating treatment modalities. While natural killer (NK) cells exhibit potential in targeting and eliminating stem-like cancer cells, their efficacy within the GBM microenvironment is limited due to constrained infiltration and function. To address this limitation, novel investigations focusing on boosting NK cell activity against GSCs are imperative. This study presents two streamlined image-based assays assessing NK cell migration and cytotoxicity towards GSCs. It details protocols and explores the strengths and limitations of these methods. These assays could aid in identifying novel targets to enhance NK cell activity towards GSCs, facilitating the development of NK cell-based immunotherapy for improved GBM treatment.Item Giant diffuse cerebellar AVM: managing ultimate intraoperative challenges(American Association of Neurological Surgeons, 2021-01-01) Hendricks, Benjamin K.; Cohen-Gadol, Aaron A.; Neurological Surgery, School of MedicineSurgery within the posterior cranial fossa uniquely requires excellence in microsurgical technique, given the complexity of the neurovascular structures housed within this region. Arteriovenous malformations (AVMs) within this region represent the greatest surgical challenge because of the difficulty in resecting an AVM completely while preserving the highly eloquent surrounding structures. The AVM in this video exemplifies a surgeon's "most challenging case," a surgery that spanned two stages, including 14 hours of resection, but concluded with complete resection despite the complexity of deep arterial and dural feeders. The video can be found here: https://youtu.be/WNBuwFHSrQ0.Item Aircraft noise, like heat stress, causes cognitive impairments via similar mechanisms in male mice(Elsevier, 2021) Sun, Gang; Lin, Xiaojing; Yi, Xueqing; Zhang, Peng; Liu, Ruoxu; Fu, Bo; Sun, Yating; Li, Jing; Jiao, Shuxin; Tian, Tian; Xu, Xiao-Ming; Tseng, Kuang-Wen; Lin, Cheng-Hsien; Neurological Surgery, School of MedicineTo our knowledge, little evidence is available about effects of aircraft noise (AN), a non-chemical stressor, on cognitive function. Again, it is unknown whether or not the heat stress (HS)-induced cognitive deficits can be exacerbated by AN. The adult male mice were assigned to four groups: group 1 mice exposed to non-HS (24-26 °C 2 h daily for 4 consecutive days) and white noise (WN) (2 h daily for 4 consecutive days), group 2 mice exposed to WN and HS (32-34 °C 2 h daily for 4 consecutive days), group 3 mice exposed to AN and non-HS (2 h daily for 4 consecutive days) and group 4 mice exposed to AN and HS (2 h daily for consecutive 4 days). Cognitive function were determined by passive avoidance, Y-maze, Morris water maze, and novel object recognition tests. Gut barrier and blood-brain-barrier (BBB) permeability, upload of lipopolysaccharide (LPS) translocation, systemic and central inflammation, and stress reactions were examined. Heat stressed mice displayed both increased stress reactions and learning and memory loss. Heat stress also caused gut barrier hyperpermeability, increased upload of LPS translocation, systemic inflammation, BBB disruption and hippocampal neuroinflammation. Aircraft noise stressed mice did not display systemic inflammation but caused gut barrier hyperpermeability, increased upload of LPS translocation, increased stress reactions, BBB disruption, hippocampal neuroinflammation and cognitive deficits. Aircraft noise exposure further exacerbated the heat stress-induced cognitive deficits and its complications. Our data suggest that AN, like HS, causes cognitive impairments via similar mechanisms in male mice.Item Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations(Wolters Kluwer, 2023) Chesnut, Randall M.; Aguilera, Sergio; Buki, Andras; Bulger, Eileen M.; Citerio, Giuseppe; Cooper, D. Jamie; Diaz Arrastia, Ramon; Diringer, Michael; Figaji, Anthony; Gao, Guoyi; Geocadin, Romergryko G.; Ghajar, Jamshid; Harris, Odette; Hawryluk, Gregory W. J.; Hoffer, Alan; Hutchinson, Peter; Joseph, Mathew; Kitagawa, Ryan; Manley, Geoffrey; Mayer, Stephan; Menon, David K.; Meyfroidt, Geert; Michael, Daniel B.; Oddo, Mauro; Okonkwo, David O.; Patel, Mayur B.; Robertson, Claudia; Rosenfeld, Jeffrey V.; Rubiano, Andres M.; Sahuquillo, Juain; Servadei, Franco; Shutter, Lori; Stein, Deborah M.; Stocchetti, Nino; Taccone, Fabio Silvio; Timmons, Shelly D.; Tsai, Eve C.; Ullman, Jamie S.; Videtta, Walter; Wright, David W.; Zammit, Christopher; Neurological Surgery, School of MedicineBackground: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. Objective: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion. Methods: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression. Results: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations. Conclusion: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.