Genetic Variants and Persistent Impairment Following Mild Traumatic Brain Injury: A Systematic Review.

OBJECTIVE: The purpose of this review is to systematically assess primary research publications on known genetic variants, which modify the risk for symptoms or dysfunction persisting 30 days or more following mild traumatic brain injury (mTBI). SUMMARY OF REVIEW: A search of PubMed and Embase from inception through June 2022 identified 42 studies that associated genetic variants with the presence of symptoms or cognitive dysfunction 30 days or more following mTBI. Risk of bias was assessed for each publication using the Newcastle Ottawa Scale (NOS). Fifteen of the 22 studies evaluating apolipoprotein E (APOE) ɛ4 concluded that it was associated with worse outcomes and 4 of the 8 studies investigating the brain-derived neurotrophic factor (BDNF) reported the Val66Met allele was associated with poorer outcomes. The review also identified 12 studies associating 28 additional variants with mTBI outcomes. Of these, 8 references associated specific variants with poorer outcomes. Aside from analyses comparing carriers and noncarriers of APOE ɛ4 and BDNF Val66Met, most of the reviewed studies were too dissimilar, particularly in terms of specific outcome measures but also in genes examined, to allow for direct comparisons of their findings. Moreover, these investigations were observational and subject to varying degrees of bias. CONCLUSIONS: The most consistent finding across articles was that APOE ɛ4 is associated with persistent post-mTBI impairment (symptoms or cognitive dysfunction) more than 30 days after mTBI. The sparsity of other well-established and consistent findings in the mTBI literature should motivate larger, prospective studies, which characterize the risk for persistent impairment with standardized outcomes in mTBI posed by other genetic variants influencing mTBI recovery.

Woven EndoBridge versus stent-assisted coil embolization for the treatment of ruptured wide-necked aneurysms: A multicentric experience.

BACKGROUND: The potentially higher risk of hemorrhagic complications is of concern in stent-assisted coiling (SAC) of ruptured wide-necked intracranial aneurysms (IAs). The Woven EndoBridge (WEB) is considered an appealing alternative since antiplatelet therapy is not required. Herein, we aimed to compare the safety and effectiveness of WEB vs. SAC for the treatment of ruptured wide-necked IAs. METHODS: This was an international cross-sectional study of consecutive patients treated for ruptured wide-neck IAs with WEB or SAC at four high-volume neurovascular centers between 2019 and 2022. Primary and secondary efficacy outcomes were radiographic aneurysm occlusion at follow-up and functional status at last follow-up. Safety outcomes included periprocedural hemorrhagic/ischemia-related complications. RESULTS: One hundred five patients treated with WEB and 112 patients treated with SAC were included. The median procedure duration of endovascular treatment was shorter for WEB than for SAC (69 vs. 76 min; p = 0.04). There were no significant differences in complete aneurysm occlusion rates (SAC: 64.5% vs. WEB: 60.9%; adjusted OR [aOR] = 0.70; 95%CI 0.34-1.43; p = 0.328). SAC had a significantly higher risk of complications (23.2% vs. 9.5%, p = 0.009), ischemic events (17% vs. 6.7%, p = 0.024), and EVD hemorrhage (16% vs. 0%, p = 0.008). The probability of procedure-related complications across procedure time was significantly lower with WEB compared with SAC (aOR = 0.40; 95%CI 0.20-1.13; p = 0.03). CONCLUSION: WEB and SAC demonstrated similar obliteration rates at follow-up when used for embolization of ruptured wide-necked IAs. However, SAC showed higher rates of procedure-related complications primarily driven by ischemic events and higher rates of EVD hemorrhage. The overall treatment duration was shorter for WEB than for SAC.

Responsive Thalamic Neurostimulation: A Systematic Review of a Promising Approach for Refractory Epilepsy.

Introduction: Responsive neurostimulation is an evolving therapeutic option for patients with treatment-refractory epilepsy. Open-loop, continuous stimulation of the anterior thalamic nuclei is the only approved modality, yet chronic stimulation rarely induces complete seizure remission and is associated with neuropsychiatric adverse effects. Accounts of off-label responsive stimulation in thalamic nuclei describe significant improvements in patients who have failed multiple drug regimens, vagal nerve stimulation, and other invasive measures. This systematic review surveys the currently available data supporting the use of responsive thalamic neurostimulation in primary and secondary generalized, treatment-refractory epilepsy. Materials and Methods: A systematic review was performed using the following combination of keywords and controlled vocabulary: ("Seizures"[Mesh] AND "Thalamus"[Mesh] AND "Deep Brain Stimulation"[Mesh]) OR (responsive neurostim* AND (thalamus[MeSH])) OR [responsive neurostimulation AND thalamus AND (epilepsy OR seizures)]. In addition, a search of the publications listed under the PubMed "cited by" tab was performed for all publications that passed title/abstract screening in addition to manually searching their reference lists. Results: Ten publications were identified describing a total of 29 subjects with a broad range of epilepsy disorders treated with closed-loop thalamic neurostimulation. The median age of subjects was 31 years old (range 10-65 years). Of the 29 subjects, 15 were stimulated in the anterior, 11 in the centromedian, and 3 in the pulvinar nuclei. Excluding 5 subjects who were treated for 1 month or less, median time on stimulation was 19 months (range 2.4-54 months). Of these subjects, 17/24 experienced greater than or equal to 50%, 11/24 least 75%, and 9/24 at least 90% reduction in seizures. Although a minority of patients did not exhibit significant clinical improvement by follow-up, there was a general trend of increasing treatment efficacy with longer periods on closed-loop thalamic stimulation. Conclusion: The data supporting off-label closed-loop thalamic stimulation for refractory epilepsy is limited to 29 adult and pediatric patients, many of whom experienced significant improvement in seizure duration and frequency. This encouraging progress must be verified in larger studies.

Dataset on flow diversion procedures performed with the Pipeline Embolization Device, Pipeline Flex, and Surpass Streamline for intracranial aneurysms.

Flow diversion is an evolving endovascular modality for treating intracranial aneurysms. Although rare, serious adverse events following flow diversion may include ischemic stroke, intracranial hemorrhage, or delayed rupture of the treated aneurysm. This dataset describes 141 flow diversion procedures performed with the Pipeline Embolization Device, Pipeline Flex, or Surpass Streamline on 126 subjects with intracranial aneurysms [1]. The retrospective data were collected from electronic medical records at two large tertiary centers. Baseline patient data included age, sex, and medical comorbidities. The dataset also describes aneurysm characteristics including laterality, anatomic location, morphology, dome height, and neck width. In addition, digital subtraction images showing the internal carotid artery tortuosity were included for aneurysms in the anterior cerebral circulation [2]. Procedural data include case duration, radiation exposure, number of flow diverters deployed, and complications encountered during deployment. In addition, data related to the duration of hospitalization and postoperative adverse events are included. Finally, time to follow up and rates of total aneurysm obliteration at first and second postoperative visits are included. This data is propensity score matching are included. This data is presented as a starting point for future prospective comparisons in the safety and efficacy of flow diverters as more devices become approved and commercially available.

Neurological Sequelae of COVID-19.

BACKGROUND: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders. OBJECTIVE: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments. METHODS: A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "Neurology", "Neurological Manifestations", "Neuropsychiatric Manifestations", "Stroke", "Encephalopathy", "Headache", "Guillain-Barre syndrome", "Depression", "Anxiety", "Encephalitis", "Seizure", "Spasm", and "ICUAW". Another search was carried out for "Long-COVID" and "Post-Acute COVID-19" and "Neurological Manifestations" or "Neuropsychiatric Manifestations". Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients. RESULTS: A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.

Pipeline Embolization Device and Pipeline Flex Versus Surpass Streamline Flow Diversion in Intracranial Aneurysms: A Retrospective Propensity Score-Matched Study.

OBJECTIVE: To compare safety and efficacy profiles in aneurysms treated with Pipeline Embolization Device or Pipeline Flex versus Surpass Streamline flow diverters (FDs). METHODS: Patients who underwent flow diversion for aneurysm treatment at 2 centers were included. Covariates comprised patient demographics, comorbidities, and aneurysm characteristics. Metrics included number of devices, adjuvant device use, case duration, and radiation exposure. Outcomes included periprocedural complications and radiographic results at follow-up. Propensity score-matched pairs were generated using demographic and aneurysm characteristics to verify the outcomes in equally sized groups. RESULTS: The majority of 141 flow diversion procedures performed on 126 patients were in the anterior circulation (96%) and unruptured (93%). Operators experienced more complications placing Surpass FDs compared with Pipelines (18.2% vs. 3.1%, P = 0.005) but used fewer Surpass devices per case (1 device in all Surpass cases and range for Pipeline cases 1-7; P < 0.001). Ballooning was more frequent for Surpass (29.5% vs. 2.1%, P < 0.001). There were no differences in mortality (2.1% vs. 0, P = 1.00), intracranial hemorrhage (3.1% vs. 0, P = 0.551), or stroke (4.2% vs. 6.8%, P = 0.680). Rates of aneurysm obliteration at follow-up were similar. Propensity-matched pairs had no differences in FD deployment complications or perioperative events, yet the significant differences remained for adjuvant balloon use and number of FDs deployed. CONCLUSIONS: While the devices demonstrated similar safety and efficacy profiles, deployment of the Surpass Streamline was more technically challenging than Pipeline Embolization Device or Pipeline Flex. Prospective cohort studies are needed to corroborate these findings.

The incidence of venous thromboembolism following surgical resection of intracranial and intraspinal meningioma. A systematic review and retrospective study.

INTRODUCTION: Historically, the development of venous thromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary thromboembolism (PE) was cited as a higher post-operative risk for patients harboring meningiomas. However, recent literature has suggested that there may be no elevated risk for VTE among these patients. The authors perform both a retrospective review of their own cases as well as a systematic review of the literature in order to determine the frequency of the VTE and rate of post-operative hemorrhage in this patient population. METHODOLOGY: Patients undergoing surgery for intracranial and spinal meningioma from 2012 to 2019 were retrospectively reviewed for patient demographics, clinical characteristics, and post-operative complications. Logistic regression was used to determine risk factors for the development of VTE. Additionally, a PubMed search was performed to identify patients addressing this topic. RESULTS: Our retrospective review included 189 patients who underwent 197 operations. The rate of VTE for patients receiving LMWH was 3.55 % vs. 4.06 % for those not receiving LMWH. There were no observed hemorrhages after initiation of LMWH. Multivariate analysis found tumor volume, history of DVT, and length of hospital stay as independent risk factors for VTE. In the systematic review, 11 papers describing 28,954 patients were included. The risk of developing a VTE with or without LMWH was 2.71 % versus 4.07 %, respectively. The hemorrhage risk was 2.23 % on LMWH versus 4.20 % not on LMWH. DISCUSSION: In several heterogeneous series of all types of neurosurgical procedures, the reported rate of VTE was 11.1 %. In our review of the literature, the VTE rate of 2.71 % was similar to our cohort's rate of 3.55 %, for patients administered LMWH postoperatively. Higher rates of VTE with meningiomas may not be the case as once thought. Regular use of LMWH appears to be a safe, but it also did not necessarily lower the rates of VTE in our cohort. The use of routine lower-extremity duplex ultrasound, mechanical prophylaxis, and early mobilization, may have contributed to these lower rates of VTEs in patients with meningiomas.

Predictors of reoperation and noninfectious complications following craniotomy for cerebral abscess.

OBJECTIVES: There is a paucity of literature that examines predictors of reoperation and noninfectious complications following treatment of cerebral abscess with craniotomy. The goal of the present study is to identify predictors for each of these outcomes. PATIENTS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database 2012-2016 file was the data source. Patients were identified using a combination of CPT and ICD-9/10 codes. Exclusions included missing age/gender, secondary surgery, and absent length of stay information. Univariate followed by multivariable analysis using logistic regression was used to identify significant predictors of reoperation and noninfectious postoperative complications (p < 0.05). RESULTS: 166 patients met the above criteria. Median age was 56 (IQR 44-65) and 68.1% of patients were men. The 30-day reoperation rate was 18.1% and increasing white blood cell count (WBC) was identified as a significant risk factor for reoperation (odds ratio [OR] 1.10, 95% CI 1.02-1.19, p = 0.013). Noninfectious complications occurred at a rate of 20.5% at 30 days. Significant predictors were ASA classification ≥4 (OR 4.13, 95% CI 1.74-9.81, p = 0.001), smoking (OR 3.04, 95% CI 1.18-7.78, p = 0.020), and increasing WBC count (OR 1.11, 95% CI 1.03-1.20, p = 0.007). Emergency case status, abscess location (supratentorial versus infratentorial), nor chronic steroid use demonstrated a significant relationship with the studied outcomes. CONCLUSION: Increasing preoperative WBC count predicts both reoperation and noninfectious complications following craniotomy for cerebral abscess. Less modifiable predictors for noninfectious complications which may help anticipate operative risk are smoking and high ASA classification.