Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Intracranial aneurysms in patients with acute ischemic stroke prevalence and influence on mechanical thrombectomy over 14 years in a tertiary-care center.

INTRODUCTION: The prevalence of intracranial aneurysms (IA) in patients with acute ischemic stroke (AIS) requiring mechanical thrombectomy (MT) is unclear. OBJECTIVE: To describe the prevalence of IA in patients with AIS and their influence on MT. MATERIALS & METHODS: This is a retrospective cohort study on all patients admitted with a diagnosis of AIS from January 2008 to March 2022 at a tertiary academic center. The records were reviewed for demographic, clinical, imaging, and outcomes data. Only patients who had CTA at admission were included in this analysis. RESULTS: Among 2265 patients admitted with AIS, this diagnosis was confirmed in 2113 patients (93.3 %). We included 1111 patients (52.6 %) who had head CTA and 321 (28.9 %) who underwent MT. The observed prevalence of aneurysms on CTA was 4.5 % (50/1111 patients), and 8 (16 %) had multiple aneurysms. MT was performed in 7 patients harboring IAs: 6 ipsilateral (5 proximal and 1 distal to the occlusion)and 1 contralateral aneurysm.. The patient with a contralateral aneurysm had a TICI 2B score In patients with ipsilateral aneurysms, TICI 2B or 3 was achieved in 3 cases (50 %), which is significantly lower than historical control of MT (91.6 %) without IA (p = 0.01). No aneurysms ruptured during MT. The aneurysm noted distal to the occlusion was mycotic. CONCLUSION: In this analysis, the observed prevalence of IA in patients with AIS was 4.5%. Ipsilateral aneurysms (proximal or distal to the occlusion site) deserve particular attention, given the potential risk of rupture during MT. Aneurysms located distal to the occlusion were mycotic and the rate of recanization in patients with ipsilateral aneurysms was low compared to historical controls. Further studies are needed to improve the outcomes in patients with IA requiring MT.

Long-Term Safety and Efficacy of Pipeline Embolization Device in Anterior and Posterior Circulation Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: Flow diversion using the pipeline embolization device (PED) has been a paradigm shift for anterior circulation (AC) aneurysms. However, only a few studies report the long-term (≥1 year) angiographic and clinical outcomes for posterior circulation (PC) aneurysms. This study aims to compare the long-term safety and efficacy of treatment of AC and PC aneurysms with PED. METHODS: The databases included Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane, and Scopus. Studies with at least 10 patients and 1-year follow-up were included. Twenty-four studies met our inclusion criteria. A random effect meta-analysis was performed to estimate the ischemic and hemorrhagic complications. A meta-analysis of proportions was performed to estimate the pooled rates of long-term complete aneurysmal occlusion, symptomatic stroke, aneurysmal rupture, and intracranial hemorrhage. RESULTS: There were 1952 aneurysms, of which 1547 (79.25%) were in the AC and 405 (20.75%) in the PC. The 1-year occlusion rate was 78% in AC compared to 73% in PC aneurysms (P < 0.01). The symptomatic infarct rate was 5% in AC compared to 13% in PC (P < 0.01). While the rupture rate was 1% in AC compared to 4% in PC (P = 0.01), the rate of intracranial hemorrhage was 2% for both (P = 0.99). CONCLUSIONS: The long-term occlusion rate after PED was higher in AC aneurysms, and the cumulative incidence of stroke and aneurysm rupture was higher in PC aneurysms.

Oncolytic viral therapy: a review and promising future directions.

Oncolytic viral therapy is quickly emerging as a promising subset of immunotherapy, which theoretically can target tumor cells while sparing surrounding healthy cells by harnessing the replication machinery of viruses with tropism for tumor cells, resulting in direct oncolysis, and by transforming immunologically "cold" tumor into areas that elicit the host's immune response. This review provides an overview of oncolytic viral therapy until the present day, starting with the original concept in 1912. The general mechanism of oncolytic viruses (OVs) depends on selectively integrating them into tumor cells based on genetic engineering of viral genomic material, inducing oncolysis and eliciting the host's innate immune response. Moreover, a major component of oncolytic viral therapy has been herpes simplex virus, with talimogene laherparepvec being the only FDA-approved oncolytic viral therapy for the treatment of melanomas. This review explores the characteristics, advantages, disadvantages, and therapeutic uses of several DNA and RNA viral families. A snapshot of the oncolytic viral treatments used in the most recent and advanced clinical trials is also provided. Lastly, the challenges of implementing oncolytic viral therapy are explored, both at a molecular and clinical level, with a highlight of promising future directions. In particular, the lack of an optimal delivery method based on tumor type for oncolytic viral therapy poses a significant obstacle, even in clinical studies. Intrathecal continuous delivery of OVs is a promising prospect, potentially by adapting the novel continuous irrigation and drainage IRRAflow catheter. Further exploration and testing of the IRRAflow catheter should be undertaken.

Extent of Surgical Resection as a Predictor of Tumor Progression in Skull Base Chordomas: A Multicenter Volumetric Analysis.

INTRODUCTION: Skull-base chordomas are aggressive tumors with a propensity for recurrence/progression. Even with standard of care (SoC), 5-year recurrence rates are variable (19%-54%). This high recurrence/progression rate correlates with increased morbidity and mortality. We sought to analyze a multicenter cohort of skull base chordomas to identify predictors of progression in patients receiving SoC. METHODS: The [Blinded]-Neurosurgery data registry was queried for skull base chordomas treated from 2008-2020. Patients with the histopathologic diagnosis of chordoma were included. The cohort was composed of patients with preoperative and postoperative magnetic resonance imaging. Tumor volume and radiologic characteristics were obtained from axial T2 sequences using a Digital Imaging and Communications in Medicine viewer. Survival analysis was performed using Kaplan-Meier method, and time-to-event multivariate regression was performed to identify independent predictors of progression. RESULTS: The cohort included 195 patients, of which 66 patients met inclusion criteria; median age was 44, and 28 (42%) were females. Fifty-four (82%) received SoC, 7 (11%) resection only, and 5 (8%) radiotherapy only. Median preoperative and postoperative tumor volumes were 11.55 cm3 (0.33-54.89) and 0.34 cm3 (0-42.52), respectively. Recurrence rate with SoC was 37%. Postoperative tumor volume (P = 0.010) correlated with progression. A postoperative volume of >4.9 cm3 (P = 0.044), ≤81.3% of tumor resection (P = 0.02), and lower-clivus location (P < 0.005) correlated with decreased time to progression. CONCLUSIONS: Skull base chordomas can be challenging to resect. Even though maximal resection and radiotherapy improve rate of tumor progression, many of these lesions eventually recur. We have identified a postoperative tumor volume of ≥4.9 cm3 and extent of resection of ≤81.3% in this cohort as predictors of progression in patients receiving SoC.

Safety and Feasibility of a Fast-Track Pathway for Neurosurgical Craniotomy Patients: Bypassing the Intensive Care Unit.

Objective: To describe the safety and feasibility of a fast-track pathway for neurosurgical craniotomy patients receiving care in a neurosciences progressive care unit (NPCU). Patients and Methods: Traditionally, most craniotomy patients are admitted to the neurosciences intensive care unit (NSICU) for postoperative follow-up. Decreased availability of NSICU beds during the coronavirus disease-2019 delta surge led our team to establish a de-novo NPCU to preserve capacity for patients requiring high level of care and would bypass routine NSICU admissions. Patients were selected a priori by treating neurosurgeons on the basis of the potential need for high-level ICU services. After operation, selected patients were transferred to the postoperative care unit, where suitability for NPCU transfer was reassessed with checklist-criteria. This process was continued after the delta surge. Results: From July 1, 2021 to September 30, 2022, 57 patients followed the NPCU protocol. Thirty-four (59.6%) were women, and the mean age was 56 years. Fifty-seven craniotomies for 34 intra-axial and 23 extra-axial lesions were performed. After assessment and application of the checklist-criteria, 55 (96.5%) were transferred to NPCU, and only 2 (3.5%) were transferred to ICU. All 55 patients followed in NPCU had good safety outcomes without requiring NSICU transfer. This saved $143,000 and led to 55 additional ICU beds for emergent admissions. Conclusion: This fast-track craniotomy protocol provides early experience that a surgeon-selected group of patients may be suitably monitored outside the traditional NSICU. This system has the potential to reduce overall health care expenses, increase capacity for NSICU bed availability, and change the paradigm of NSICU admission.

Safety and efficacy of the pipeline embolization device for treatment of small vs. large aneurysms: a systematic review and meta-analysis.

Flow diversion with the pipeline embolization device (PED) is increasingly used to treat intracranial aneurysms with high obliteration rates and low morbidity. However, long-term (≥ 1 year) angiographic and clinical outcomes still require further investigation. The aim of this study was to compare the occlusion and complication rates for small (< 10 mm) versus large (10-25 mm) aneurysms at long-term following treatment with PED. A systematic review and meta-analysis were performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We conducted a comprehensive search of English language databases including Ovid MEDLINE and Epub Ahead of Print, In-Process, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Our studies included a minimum of 10 patients treated with PED for small vs. large aneurysms and with at least 12 months of follow-up. The primary safety endpoint was the rate of clinical complications measured by the occurrence of symptomatic stroke (confirmed clinically and radiographically), intracranial hemorrhage, or aneurysmal rupture. The primary efficacy endpoint was the complete aneurysm occlusion rate. Our analysis included 19 studies with 1277 patients and 1493 aneurysms. Of those, 1378 aneurysms met our inclusion criteria. The mean age was 53.9 years, and most aneurysms were small (89.75%; N = 1340) in women (79.1%; N = 1010). The long-term occlusion rate was 73% (95%, CI 65 to 80%) in small compared to 84% (95%, CI 76 to 90%) in large aneurysms (p < 0.01). The symptomatic thromboembolic complication rate was 5% (95%, CI 3 to 9%) in small compared to 7% (95%, CI 4 to 13%) in large aneurysms (p = 0.01). The rupture rate was 2% vs. 4% (p = 0.92), and the rate of intracranial hemorrhage was 2% vs. 4% (p = 0.96) for small vs. large aneurysms, respectively; however, these differences were not statistically significant. The long-term occlusion rate after PED treatment is higher in large vs. small aneurysms. Symptomatic thromboembolic rates with stroke are also higher in large vs. small aneurysms. The difference in the rates of aneurysm rupture and intracranial hemorrhage was insignificant. Although the PED seems a safe and effective treatment for small and large aneurysms, further studies are required to clarify how occlusion rate and morbidity are affected by aneurysm size.

Association between immunohistochemical markers and tumor progression following resection of spinal chordomas: a multicenter study.

OBJECTIVE: Chordomas are slow-growing tumors derived from notochord remnants. Despite margin-negative excision and postoperative radiation therapy, spinal chordomas (SCs) often progress. The potential of immunohistochemical (IHC) markers, such as epithelial membrane antigen (EMA), combined with machine learning algorithms to predict long-term (≥ 12 months) postoperative tumor progression, has been understudied. The authors aimed to identify IHC markers using trained tree-based algorithms to predict long-term (≥ 12 months) postoperative tumor progression. METHODS: The authors reviewed the records of patients who underwent resection of SCs between January 2017 and June 2021 across the Mayo Clinic enterprise. Demographics, type of treatment, histopathology, and other relevant clinical factors were abstracted from each patient's record. Low tumor progression was defined as more than a 94.3-mm3 decrease in the tumor size at the latest radiographic follow-up. Decision trees and random forest classifiers were trained and tested to predict the long-term volumetric progression after an 80/20 data split. RESULTS: Sixty-two patients diagnosed with and surgically treated for SC were identified, of whom 31 were found to have a more advanced tumor progression based on the tumor volume change cutoff of 94.3 mm3. The mean age was 54.3 ± 13.8 years, and most patients were male (62.9%) and White (98.4%). The most common treatment modality was subtotal resection with radiation therapy (35.5%), with proton beam therapy being the most common (71%). Most SCs were sacrococcygeal (41.9%), followed by cervical (32.3%). EMA-positive SCs had a postoperative progression risk of 67%. Pancytokeratin-positive SCs had a progression rate of 67%; however, patients with S100 protein-positive SCs had a 54% risk of progression. The accuracy of this model in predicting the progression of unseen test data was 66%. Pancytokeratin (mean minimal depth = 1.57), EMA (mean minimal depth = 1.58), cytokeratin A1/A3 (mean minimal depth = 1.59), and S100 protein (mean minimal depth = 1.6) predicted the long-term volumetric progression. Multiway variable importance plots show the relative importance of the top 10 variables based on three measures of varying significance and their predictive role. CONCLUSIONS: These IHC variables with tree-based machine learning tools successfully demonstrate a high capacity to identify a patient's tumor progression pattern with an accuracy of 66%. Pancytokeratin, EMA, cytokeratin A1/A3, and S100 protein were the IHC drivers of a low tumor progression. This shows the power of machine learning algorithms in analyzing and predicting outcomes of rare conditions in a small sample size.

Machine Learning Models to Forecast Outcomes of Pituitary Surgery: A Systematic Review in Quality of Reporting and Current Evidence.

BACKGROUND: The complex nature and heterogeneity involving pituitary surgery results have increased interest in machine learning (ML) applications for prediction of outcomes over the last decade. This study aims to systematically review the characteristics of ML models involving pituitary surgery outcome prediction and assess their reporting quality. METHODS: We searched the PubMed, Scopus, and Web of Knowledge databases for publications on the use of ML to predict pituitary surgery outcomes. We used the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) to assess report quality. Our search strategy was based on the terms "artificial intelligence", "machine learning", and "pituitary". RESULTS: 20 studies were included in this review. The principal models reported in each article were post-surgical endocrine outcomes (n = 10), tumor management (n = 3), and intra- and postoperative complications (n = 7). Overall, the included studies adhered to a median of 65% (IQR = 60-72%) of TRIPOD criteria, ranging from 43% to 83%. The median reported AUC was 0.84 (IQR = 0.80-0.91). The most popular algorithms were support vector machine (n = 5) and random forest (n = 5). Only two studies reported external validation and adherence to any reporting guideline. Calibration methods were not reported in 15 studies. No model achieved the phase of actual clinical applicability. CONCLUSION: Applications of ML in the prediction of pituitary outcomes are still nascent, as evidenced by the lack of any model validated for clinical practice. Although studies have demonstrated promising results, greater transparency in model development and reporting is needed to enable their use in clinical practice. Further adherence to reporting guidelines can help increase AI's real-world utility and improve clinical practice.

Management of Poor-Grade Aneurysmal Subarachnoid Hemorrhage and Key Pearls for Achieving Favorable Outcomes: An Illustrative Case.

Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high patient mortality. Despite recent advances in management strategies, the prognosis for poor-grade aSAH remains dismal. We present a challenging case of a patient presenting with poor-grade aSAH. A 46-year-old female presented to the emergency department after losing consciousness following a sudden headache. The examination showed a dilated left pupil and a Glasgow Coma Scale of 4. Imaging revealed a ruptured anterior communicating artery (ACoM) aneurysm, after which the patient was subsequently taken to the neuro-interventional radiology suite. We showed that carefully managing blood pressure and intracranial pressure (ICP) makes it possible to achieve a favorable outcome and reduce the risk of secondary brain injury in aSAH, regardless of patient presentation. We propose maintaining blood pressure at <160 mmHg prior to intervention, after which it can be permitted to increase to 160-240 mmHg for the purpose of preventing vasospasm. Additionally, transcranial doppler (TCD) is essential to detect vasospasm due to the subtility of symptoms in patients with aSAH. Once identified, vasospasm can be successfully treated with balloon angioplasty. Finally, targeted temperature management (TTM), mannitol, hypertonic saline, and neuromuscular paralysis are essential for the postoperative management of ICP levels.

MIS lateral retroperitoneal transpsoas approach allows gross total resection of a giant L4 schwannoma.

In this surgical video, the authors present a successful minimally invasive (MIS) lateral retroperitoneal transpsoas approach for resection of an L4 nerve root schwannoma. They describe the surgical approach in detail, with special emphasis on patient positioning for an orthogonal view, as well as technical nuances throughout the procedure. Using a sequential tubular retractor, they performed a microscopic dissection of the lesion. The tumor was debulked and the tumor capsule was disconnected from the surrounding tissue. During dissection, direct stimulation identified a functional nerve root that was carefully dissected from the tumor capsule. The tumor was then removed en bloc. The video can be found here: https://stream.cadmore.media/r10.3171/2022.3.FOCVID2220.

A deep learning model for discriminating true progression from pseudoprogression in glioblastoma patients.

INTRODUCTION: Glioblastomas (GBMs) are highly aggressive tumors. A common clinical challenge after standard of care treatment is differentiating tumor progression from treatment-related changes, also known as pseudoprogression (PsP). Usually, PsP resolves or stabilizes without further treatment or a course of steroids, whereas true progression (TP) requires more aggressive management. Differentiating PsP from TP will affect the patient's outcome. This study investigated using deep learning to distinguish PsP MRI features from progressive disease. METHOD: We included GBM patients with a new or increasingly enhancing lesion within the original radiation field. We labeled those who subsequently were stable or improved on imaging and clinically as PsP and those with clinical and imaging deterioration as TP. A subset of subjects underwent a second resection. We labeled these subjects as PsP, or TP based on the histological diagnosis. We coregistered contrast-enhanced T1 MRIs with T2-weighted images for each patient and used them as input to a 3-D Densenet121 model and using five-fold cross-validation to predict TP vs PsP. RESULT: We included 124 patients who met the criteria, and of those, 63 were PsP and 61 were TP. We trained a deep learning model that achieved 76.4% (range 70-84%, SD 5.122) mean accuracy over the 5 folds, 0.7560 (range 0.6553-0.8535, SD 0.069) mean AUROCC, 88.72% (SD 6.86) mean sensitivity, and 62.05% (SD 9.11) mean specificity. CONCLUSION: We report the development of a deep learning model that distinguishes PsP from TP in GBM patients treated per the Stupp protocol. Further refinement and external validation are required prior to widespread adoption in clinical practice.

Intracranial Aneurysms in Loeys-Dietz Syndrome: A Multicenter Propensity-Matched Analysis.

BACKGROUND: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by a classic triad of hypertelorism, bifid uvula and/or cleft palate, and generalized arterial tortuosity. There are limited data on the prevalence and rupture risk of intracranial aneurysms (IAs) in the setting of LDS, with no established guidelines. OBJECTIVE: To analyze the prevalence and rupture risk of IA in LDS. METHODS: Electronic medical records of patients with a confirmed diagnosis of LDS and available cerebrovascular imaging were reviewed. Patients were divided into 2 groups based on the presence of IA. Unmatched and propensity-matched analyses were used to identify potential risk factors for aneurysm formation. RESULTS: Records of 1111 patients were screened yielding a total of 60 patients with a diagnosis of LDS. Eighteen (30%) patients had IA, 4 (22.2%) of whom had multiple aneurysms for a total of 24 IAs. Twenty-three (95.8%) aneurysms were located in the anterior circulation; none of them were ruptured. On unmatched analysis, age ( P = .015), smoking history ( P = .034), hypertension ( P = .035), and number of extracranial aneurysms ( P < .001) were significantly higher in patients with IA. After matching for age, sex, race, stroke history, family history, and extracranial aneurysms, smoking history ( P = .009) remained significant. CONCLUSION: Patients with LDS have an increased risk of IAs, especially with a history of smoking. The prevalence rate of IAs in our series was 30%. Screening imaging should be considered at diagnosis, and patients should be encouraged to abstain from smoking. Further studies are needed to elucidate the risk of IA rupture and treatment considerations in this unique population.

The early infiltrative phase of GBM hypothesis: are molecular glioblastomas histological glioblastomas in the making? A preliminary multicenter study.

PURPOSE: The presence of necrosis or microvascular proliferation was previously the hallmark for glioblastoma (GBM) diagnosis. The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/-10 copy changes. We hypothesize that these tumors are early histological GBM and will eventually develop the classic histological features. METHODS: Medical records from 65 consecutive patients diagnosed with molGBM at three tertiary-care centers from our institution were retrospectively reviewed from November 2017-October 2021. Only patients who underwent reoperation for tumor recurrence and whose tissue at initial diagnosis and recurrence was available were included in this study. The detailed clinical, histopathological, and radiographic scenarios are presented. RESULTS: Five patients were included in our final cohort. Three (60%) patients underwent reoperation for recurrence in the primary site and 2 (40%) underwent reoperation for distal recurrence. Microvascular proliferation and pseudopalisading necrosis were absent at initial diagnosis but present at recurrence in 4 (80%) patients. Radiographically, all tumors showed contrast enhancement, however none of them showed the classic radiographic features of GBM at initial diagnosis. CONCLUSIONS: In this manuscript we present preliminary data for a hypothesis that molGBMs are early histological GBMs diagnosed early in their natural history of disease and will eventually develop necrosis and microvascular proliferation. Further correlative studies are needed in support of this hypothesis.

Treatment of recurrent and persistent Cushing's disease after first transsphenoidal surgery: lessons learned from an international meta-analysis.

PURPOSE: Transsphenoidal surgery (TSS) is the first-line treatment for patients with Cushing's Disease (CD). Recurrence rates after a first TSS range between 3 and 22% within 3 years. Management of recurrent or persistent CD may include repeat TSS or stereotactic radiosurgery (SRS). We performed a meta-analysis to explore the overall efficacy of TSS and SRS for patients with CD after an initial surgical intervention. METHODS: EMBASE, PubMed, SCOPUS, and Cochrane databases were searched from their dates-of-inception up to December 2021. Inclusion criteria were comprised of patients with an established diagnosis of CD who presented with persistent or biochemically recurrent disease after a first TSS for tumor resection and were treated with a second TSS or SRS. RESULTS: Search criteria yielded 2,116 studies of which 37 articles from 15 countries were included for analysis. Mean age ranged between 29.9 and 47.9 years, and mean follow-up was 11-104 months. TSS was used in 669 (67.7%) patients, while SRS was used in 320 (32.4%) patients, and remission rates for CD were 59% (95%CI 0.49-0.68) and 74% (95%CI 0.54-0.88), respectively. There was no statistically significant difference in the remission rate between TSS and SRS (P = 0.15). The remission rate of patients with recurrent CD undergoing TSS was 53% (95%CI 0.32-0.73), and for persistent CD was 41% (95%CI 0.28-0.56) (P = 0.36). CONCLUSION: Both TSS and SRS are possible approaches for the treatment of recurrent or persistent CD after a first TSS. Our data show that either TSS or SRS represent viable treatment options to achieve remission for this subset of patients.

Cerebral venous thrombosis during the COVID-19 Pandemic: A multi-center experience.

OBJECTIVE: To describe the clinical characteristics and outcomes of CVT in patients with history of recent COVID-19 infection or vaccination. METHODS: We reviewed demographic, clinical, and radiographic characteristics of non-pyrogenic, non-traumatic CVT cases at our multi-center institution between March 2020 and December 2021. Patients were grouped according to their history of recent COVID-19 infection or vaccination into group-I (+COVID-19 association) and group-II (-COVID-19 association). RESULTS: Fifty-one patients with CVT were included, of which 14 (27.4%) had a positive COVID-19 association: 10 with infection and 4 with mRNA-COVID-vaccine. Nine patients in group-I had COVID-19 infection or vaccine within 30 days of CVT diagnosis, including 3 patients with active infection at the time of CVT diagnosis. Half of the patients in group-I (n = 7,50.0%) and 32.4% (n = 12) of group-II were male, and mean age was 52.6 years in group-I and 51.4 years in group-II. Fever at presentation was noted in one patient who had active COVID infection (I=1 (7.1%), II= 0 (0%)). Higher rates of comorbidities were observed in group-II: hypertension (I= 2 (14.3%), II= 13 (35.1%)), deep venous thrombosis(I=1(7.1%), II= 10 (27.0%)), pulmonary emboli (I=1(7.1%), II= 8(21.6%)), or stroke(I=0(0%), II= 6(16.4%)). Three patients had thrombocytopenia at the time of CVT diagnosis (5.4%) and most patients (n = 37, 72.5%) were treated medically with anticoagulation. Complication rate during hospitalization was 17.6% (n = 6), and no mortality was noted. CONCLUSION: Twenty-seven percent of CVT patients were associated with COVID-19 infection or vaccination, and the majority presented within 30 days of infection/vaccination.

Mesenchymal stem cell therapy for focal epilepsy: A systematic review of preclinical models and clinical studies.

Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: (("mesenchymal") AND ("stem cell")) AND (("epilepsy") OR ("convulsion") OR ("seizures")). This review followed Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ-aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.

The survival outcomes of molecular glioblastoma IDH-wildtype: a multicenter study.

PURPOSE: Histological diagnosis of glioblastoma (GBM) was determined by the presence of necrosis or microvascular proliferation (histGBM). The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM, WHO grade 4) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/- 10 copy changes. The objective of this study was to explore and compare the survival outcomes between histGBM and molGBM. METHODS: Medical records for patients diagnosed with GBM at the three tertiary care academic centers of our institution from November 2017 to October 2021. Only patients who underwent adjuvant chemoradiation were included. Patients without molecular feature testing or with an IDH mutation were excluded. Univariable and multivariable analyses were performed to evaluate progression-free (PFS) and overall- survival (OS). RESULTS: 708 consecutive patients were included; 643 with histGBM and 65 with molGBM. Median PFS was 8 months (histGBM) and 13 months (molGBM) (p = 0.0237) and median OS was 21 months (histGBM) versus 26 months (molGBM) (p = 0.435). Multivariable analysis on the molGBM sub-group showed a worse PFS if there was contrast enhancement on MRI (HR 6.224 [CI 95% 2.187-17.714], p < 0.001) and a superior PFS on patients with MGMT methylation (HR 0.026 [CI 95% 0.065-0.655], p = 0.007). CONCLUSIONS: molGBM has a similar OS but significantly longer PFS when compared to histGBM. The presence of contrast enhancement and MGMT methylation seem to affect the clinical behavior of this subset of tumors.

Motor Cortex Stimulation for Pain: A Narrative Review of Indications, Techniques, and Outcomes.

BACKGROUND: Motor cortex stimulation (MCS) was introduced in 1985 and has been tested extensively for different types of peripheral and central neuropathic pain syndromes (eg, central poststroke pain, phantom limb pain, trigeminal neuropathic pain, migraines, etc). The motor cortex can be stimulated through different routes, including subdural, epidural, and transcranial. OBJECTIVES: In this review, we discuss the current uses, surgical techniques, localization techniques, stimulation parameters, and clinical outcomes of patients who underwent chronic MCS for treatment-resistant pain syndromes. MATERIALS AND METHODS: A broad literature search was conducted through PubMed to include all articles focusing on MCS for pain relief (keywords: subdural, epidural, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, motor cortex stimulation, pain). LITERATURE REVIEW: Epidural MCS was the most widely used technique and had varying response rates across studies. Long-term efficacy was limited, and pain relief tended to decrease over time. Subdural MCS using similar stimulation parameters demonstrated similar efficacy to epidural stimulation and less invasive methods, such as repetitive transcranial magnetic stimulation (rTMS), which have been shown to provide adequate pain relief. rTMS and certain medications (ketamine and morphine) have been shown to predict the long-term response to epidural MCS. Complications tend to be rare, the most reported being seizures during subdural or epidural stimulation or hardware infection. CONCLUSIONS: Scientific evidence supports the use of MCS for treatment of refractory neuropathic pain syndromes. Further studies are warranted to elucidate the specific indications and stimulation protocols that are most amenable to the different types of MCS.