Preclinical and clinical role of interleukin-6 in the development of delayed cerebral vasospasm and neuronal cell death after subarachnoid hemorrhage: towards a potential target therapy?

Delayed cerebral vasospasm (DCVS), early brain injury (EBI), and delayed cerebral ischemia (DCI) are devastating complications after aneurysmal subarachnoid hemorrhage (SAH). Interleukin (IL)-6 seems to be an important interleukin in the inflammatory response after SAH, and many studies describe a strong correlation between IL-6 and worse outcome. The aim of this study was to systematically review preclinical and clinical studies that evaluated systemic and cerebral IL-6 levels after SAH and their relation to DCVS, neuronal cell death, and DCI. We conducted two systematic literature searches using PubMed to identify preclinical and clinical studies evaluating the role of IL-6 after SAH. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 61 and 30 preclinical and clinical articles, respectively, were included in the systematic reviews. Of the preclinical studies in which IL-6 was measured in cerebrospinal fluid (CSF), parenchyma, and systemically, 100%, 94.4%, and 81.3%, respectively, showed increased expression of IL-6 after SAH. Preclinical results were mirrored by clinical findings in which elevated levels of IL-6 in CSF and plasma were found after SAH, correlating with DCVS, DCI, and worse outcome. Only two preclinical studies analyzed the direct inhibition of IL-6, which resulted in reduced DCVS and neuronal cell death. IL-6 is a marker of intracranial inflammation and plays a role in the pathophysiology of DCVS and DCI after SAH in preclinical animal models and clinical studies. Its inhibition might have therapeutic potential to improve the outcome of SAH patients.

Randomized study comparing 3D virtual reality and conventional 2D on-screen teaching of cerebrovascular anatomy.

OBJECTIVE: Performing aneurysmal clipping requires years of training to successfully understand the 3D neurovascular anatomy. This training has traditionally been obtained by learning through observation. Currently, with fewer operative aneurysm clippings, stricter work-hour regulations, and increased patient safety concerns, novel teaching methods are required for young neurosurgeons. Virtual-reality (VR) models offer the opportunity to either train a specific surgical skill or prepare for an individual surgery. With this study, the authors aimed to compare the spatial orientation between traditional 2D images and 3D VR models in neurosurgical residents or medical students. METHODS: Residents and students were each randomly assigned to describe 4 aneurysm cases, which could be either 2D images or 3D VR models. The time to aneurysm detection as well as a spatial anatomical description was assessed via an online questionnaire and compared between the groups. The aneurysm cases were 10 selected patient cases treated at the authors' institution. RESULTS: Overall, the time to aneurysm detection was shorter in the 3D VR model compared to 2D images, with a trend toward statistical significance (25.77 ± 37.26 vs 45.70 ± 51.94 seconds, p = 0.052). No significant difference was observed for residents (3D VR 24.47 ± 40.16 vs 2D 33.52 ± 56.06 seconds, p = 0.564), while in students a significantly shorter time to aneurysm detection was measured using 3D VR models (26.95 ± 35.39 vs 59.16 ± 44.60 seconds, p = 0.015). No significant differences between the modalities for anatomical and descriptive spatial mistakes were observed. Most participants (90%) preferred the 3D VR models for aneurysm detection and description, and only 1 participant (5%) described VR-related side effects such as dizziness or nausea. CONCLUSIONS: VR platforms facilitate aneurysm recognition and understanding of its spatial anatomy, which could make them the preferred method compared to 2D images in the years to come.

Cervical Radiculopathy Caused by a Vertebral Artery Loop: Is a Focused Fluoroscopic-Guided Cervical Epidural Steroid Injection a Possible Treatment Modality?

We describe a case of a patient suffering with cervical radiculopathy due to vertebral artery loop with nerve root compression, treated with an epidural steroid injection. A 37-year-old man presented with a 2-year history of right-sided radicular pain along the C7 dermatome. Imaging showed a right-sided loop of the vertebral artery at the V1-V2 transition with contact on the C7 nerve root. The pain was resistant to conservative treatment, and the decision was made to perform a focused fluoroscopy-guided translaminar epidural steroid injection near the C7 nerve root. The procedure was uneventful, and the symptoms resolved completely after the procedure. Targeted epidural steroid injection might be a useful and safe diagnostic and therapeutic approach in patients affected by cervical radiculopathy due to a VA loop. To our knowledge, this is the first case of a VA loop associated with cervical radiculopathy treated with this technique.

Cerebral venous thrombosis requiring invasive treatment for elevated intracranial pressure in women with combined hormonal contraceptive intake: risk factors, anatomical distribution, and clinical presentation.

OBJECTIVE Women taking combined hormonal contraceptives (CHCs) are generally considered to be at low risk for cerebral venous thrombosis (CVT). When it does occur, however, intensive care and neurosurgical management may, in rare cases, be needed for the control of elevated intracranial pressure (ICP). The use of nonsurgical strategies such as barbiturate coma and induced hypothermia has never been reported in this context. The objective of this study is to determine predictive factors for invasive or surgical ICP treatment and the potential complications of nonsurgical strategies in this population. METHODS The authors conducted a 2-center, retrospective chart review of 168 cases of CVT in women between 2000 and 2012. Eligible patients were classified as having had a mild or a severe clinical course, the latter category including all patients who underwent invasive or surgical ICP treatment and all who had an unfavorable outcome (modified Rankin Scale score ≥ 3 or Glasgow Outcome Scale score ≤ 3). The Mann-Whitney U-test was used for continuous parameters and Fisher's exact test for categorical parameters, and odds ratios were calculated with statistical significance set at p ≤ 0.05. RESULTS Of the 168 patients, 57 (age range 16-49 years) were determined to be eligible for the study. Six patients (10.5%) required invasive or surgical ICP treatment. Three patients (5.3%) developed refractory ICP > 30 mm Hg despite early surgical decompression; 2 of them (3.5%) were treated with barbiturate coma and induced hypothermia, with documented infectious, thromboembolic, and hemorrhagic complications. Coma on admission, thrombosis of the deep venous system with consecutive hydrocephalus, intraventricular hemorrhage, and hemorrhagic venous infarction were associated with a higher frequency of surgical intervention. Coma, quadriparesis on admission, and hydrocephalus were more commonly seen among women with unfavorable outcomes. Thrombosis of the transverse sinus was less common in patients with an unfavorable outcome, with similar distribution in patients needing invasive or surgical ICP treatment. CONCLUSIONS The need for invasive or surgical ICP treatment in women taking CHCs who have CVT is partly predictable on the basis of the clinical and radiological findings on admission. The use of nonsurgical treatments for refractory ICP, such as barbiturate coma and induced hypothermia, is associated with systemic infectious and hematological complications and may worsen morbidity in this patient population. The significance of these factors should be studied in larger multicenter cohorts.

Chiari malformation presenting with subarachnoid hemorrhage: a case report.

Chiari malformations (CM) are often diagnosed in childhood and younger adults, with an incidence of only 0.77% in adult populations. Patients with CM may develop syringomyelia and increased intracranial pressure (ICP) due to cerebrospinal fluid (CSF) obstruction and altered fluid dynamics at the cervicomedullary junction. We describe the case of a 65-year-old female presenting with an angionegative subarachnoid hemorrhage (SAH) with concomitant new diagnosis of CM type I with syringomyelia. After ruling out any aneurysm or vascular malformations, she underwent a suboccipital craniectomy for a Chiari decompression with a C1 laminectomy. There were no complications with the surgery and her symptoms improved. This case report highlights the unusual presentation of a CM.

Intraoperative View of a Multinodal, Paralysis-Inducing Spinal Melanocytoma: Case Report and Literature Review.

Melanocytomas arising from the leptomeningeal melanocytes within the central nervous system are a rare occurrence, accounting for 0.06%-0.1% of brain tumors and having an incidence of 1/10 million people per year.1-14 Here, we describe the case of 68-year-old male presenting with bilateral lower extremity weakness progressing to paralysis and urinary incontinence (Video 1). Upon examination, this gentleman had no sensation below T11. Magnetic resonance imaging showed multiple contrast-enhancing lesions with a major intradural lesion at level T11 arising from the ventrolateral surface and causing severe spinal cord compression. The multifocal nature of this tumor further adds to its rarity. Interdisciplinary indication for surgical resection of the intradural lesion was made. This was accomplished through a T11 laminectomy and concomitant T11-12 stabilization with neuromonitoring. Pathologic analysis of the resected tumor identified an S100+, HMB45+, pigmented melanocytoma. No complications occurred during the procedure. The patient was discharged to rehabilitation with persistent neurologic deficits. Routine follow-up is indicated given the high rates of recurrence and the multiple remaining tumor nodules.14.

Cerebral Aneurysm and Interleukin-6: a Key Player in Aneurysm Generation and Rupture or Just One of the Multiple Factors?

Intracranial aneurysm (IA) rupture is a common cause of subarachnoid hemorrhage (SAH) with high mortality and morbidity. Inflammatory interleukins (IL), such as IL-6, play an important role in the occurrence and rupture of IA causing SAH. With this review we aim to elucidate the specific role of IL-6 in aneurysm formation and rupture in preclinical and clinical studies. IL-6 is a novel cytokine in that it has pro-inflammatory and anti-inflammatory signaling pathways. In preclinical and clinical studies of IA formation, elevated and reduced levels of IL-6 are reported. Poor post-rupture prognosis and increased rupture risk, however, are associated with higher levels of IL-6. By better understanding the relationships between IL-6 and IA formation and rupture, IL-6 may serve as a biomarker in high-risk populations. Furthermore, by better understanding the IL-6 signaling mechanisms in IA formation and rupture, IL-6 may optimize surveillance and treatment strategies. This review examines the association between IL-6 and IA, while also suggesting future research directions.

O-Arm Accuracy and Radiation Exposure in Adult Deformity Surgery.

OBJECTIVE: In long thoracolumbar deformity surgery, accurate screw positioning is critical for spinal stability. We assessed pedicle and pelvic screw accuracy and radiation exposure in patients undergoing long thoracolumbar deformity fusion surgery (≥4 levels) involving 3-dimensional fluoroscopy (O-Arm/Stealth) navigation. METHODS: In this retrospective single-center cohort study, all patients aged >18 years who underwent fusion in 2016-2018 were reviewed. O-Arm images were assessed for screw accuracy. Effective radiation doses were calculated. The primary outcome was pedicle screw accuracy (Heary grade). Secondary outcomes were pelvic fixation screw accuracy, radiation exposure, and screw-related perioperative and postoperative complications or revision surgery within 3 years. RESULTS: Of 1477 pedicle screws placed in 91 patients (mean 16.41 ± 5.6 screws/patient), 1208 pedicle screws (81.8%) could be evaluated by 3-dimensional imaging after placement. Heary Grade I placement was achieved in 1150 screws (95.2%), Grade II in 47 (3.9%), Grade III in 10 (0.82%), Grade IV in 1 (0.08%), and Grade V in 0; Grade III-V were replaced intraoperatively. One of 60 (1.6%) sacroiliac screws placed showed medial cortical breach and was replaced. The average O-Arm-related effective dose was 29.54 ± 14.29 mSv and effective dose/spin was 8.25 ± 2.65 mSv. No postoperative neurological worsening, vascular injuries, or revision surgeries for screw misplacement were recorded. CONCLUSIONS: With effective radiation doses similar to those in interventional neuroendovascular procedures, the use of O-Arm in multilevel complex deformity surgery resulted in high screw accuracy, no need for surgical revision because of screw malposition, less additional imaging, and no radiation exposure for the surgical team.

The role of IL-6 in TBI and PTSD, a potential therapeutic target?

This literature review focuses on the role of IL-6 in TBI or PTSD-induced neuroinflammation. While TBI and PTSD are widely prevalent, these diagnoses are particularly common amongst veterans. Given the role of IL-6 in neuroprotection acutely, compared to detrimental chronically, targeting this cytokine at specific time points may be beneficial in modulating neuroinflammation. Current treatments for TBI or PTSD are variably affective. By reviewing the role of IL-6 in these two diagnoses, future studies can focus on therapeutics to treat neuroinflammation and ultimately reduce the devastating impacts of neuroinflammation on cognition in PTSD and TBI.

Microclots in subarachnoid hemorrhage: an underestimated factor in delayed cerebral ischemia?

Subarachnoid hemorrhage has a poor prognosis due to the wide array of associated complications such as vasospasm, early brain injury, cortical spreading depression, oxidative stress, inflammation, and apoptosis. Each of these complications increases the risk of delayed cerebral ischemia (DCI), but recent research has suggested microclots play a substantial role in DCI incidence. This review will focus on the underlying inflammatory and coagulative mechanisms of microthrombosis while also outlining the current literature relating microclot burden to DCI. With a better understanding DCI pathophysiology as it relates to microthrombosis, more effective therapies can be developed in the future to improve clinical outcomes of SAH.

L4 Corpectomy: Surgical Approaches and Mitigating the Risk of Femoral Nerve Injuries.

OBJECTIVE: Because of the challenging anatomic location, corpectomies are performed less often at the fourth lumbar vertebral body than at other levels. Our objective was to review the literature of L4 corpectomy and anterior column reconstruction. METHODS: A literature search in the Medline/PubMed database was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify all relevant cases and cases series describing corpectomies of the L4 vertebral body using "lumbar" AND "corpectomy" as search terms. We present an illustrative case to describe the technique. RESULTS: We identified 18 articles with 30 patients who met the search criteria. Including our case illustration, the most common approach used was the lateral retroperitoneal approach (n = 17, 54.8%), of which 8 (26.7%) were performed via a transpsoas approach. Seven (23%) patients underwent corpectomy through a posterior approach, 4 (12.9%) through an anterior retroperitoneal approach, and 3 (10%) through combined anterior and lateral retroperitoneal. The overall complications rate was 19.3% including 1 case each of femoral nerve injury and iatrogenic lumbar nerve root injury. CONCLUSIONS: Corpectomies of the L4 vertebral body are challenging. None of the various approaches described clearly demonstrates any superiority in mitigating the risk of neural complications. Decision making about which surgical approach to use should be based on patient-specific characteristics.

Solitary manifestations of primary B-lymphoblastic lymphoma of the spine: Systematic literature review with case illustration.

BACKGROUND: Given the locally destructive osteolytic nature of primary B-cell lymphoblastic lymphoma (B-LBL) of the spine, careful attention is needed to identify clinical signs and symptoms as well as radiological findings of spinal instability because these lesions may warrant resection, decompression, and instrumentation with posterolateral fusion. Our objective was to summarize the presenting symptoms, clinical features, potential treatment modalities, and clinical outcome of cases described in the literature. METHODS: We undertook a systematic literature review to identify all relevant cases and case series describing primary manifestations B-LBL of the spine using Pubmed/Medline. We summarized the findings in accordance with the PRISMA guidelines. We also present a case illustration. RESULTS: Together with our case, 9 cases of primary B-LBL of the spine were identified in 6 male and 3 female patients (age 8-58 years, median 31 years). Back pain was the most common symptom, and five patients also had neurological signs of spinal cord compression. T1-weighted MRI contrast enhancement was seen in 5 cases. Surgery was performed in 5 patients with progression of neurological deficits. Steroid treatment was also given in 3 patients preoperatively. Seven patients had chemotherapy after diagnosis. During follow-up of 1 month to 1 year, 2 cases of recurrence and 4 cases of complete remission were noted; however, with the short follow-up time, patient prognosis overall remains unclear. CONCLUSIONS: Primary B-LBL of the spine represents a rare clinical entity whose management mandates a multidisciplinary approach. Careful attention must be paid to the neurological status of the patient, as well as to imaging that may highlight potential local instability of the spine.

Lateral Suboccipital Craniotomy With C1-C2 Hemilaminectomies and C1-C3 Fusion for the Treatment of a C1-C2 Synovial Cyst Causing Spinal Cord Compression: 2-Dimensional Operative Video.

Atlantoaxial synovial cysts are a rare cause of cervical myelopathy. Here we describe a case of a 26-yr-old woman who presented with progressively decreasing right arm and leg strength and associated gait imbalance. On examination, she had diffuse weakness in the right upper and lower extremities, a positive right-sided Hoffman sign, and clonus in the right lower extremity. Computed tomography demonstrated an os odontoideum and a retro-odontoid cyst. Magnetic resonance imaging demonstrated a T1 hypointense, T2 hyperintense, slightly rim-enhancing retro-odontoid cyst causing a marked narrowing of the spinal canal, with resultant flattening and leftward deviation of the spinal cord. The patient consented to undergo cyst fenestration via a right suboccipital craniotomy and right C1-C2 hemilaminectomies, along with a C1-C3 instrumented posterior spinal fusion. This approach was chosen because it allows for cyst fenestration and instrumentation of the hypermobile cervical spine within the same incision. After the dura was opened and the arachnoid was dissected, the cyst was visualized compressing the spinal cord. The cyst was fenestrated just inferior to the C1 nerve rootlets, resulting in immediate egress of a gelatinous content; thereafter, all accessible cyst wall portions were removed. Fusion was performed with lateral mass screws at C1 and C3 and pars screws at C2. Pathological analysis described the cyst content as reactive fibrovascular tissue with cholesterol deposition. There were no complications associated with the procedure, and the patient's right-sided weakness had nearly resolved by postoperative day 1. Patient consent was granted for publication.

Augmented Reality Fluorescence Imaging in Cerebrovascular Surgery: A Single-Center Experience with Thirty-Nine Cases.

BACKGROUND: Several intraoperative imaging methods exist in cerebrovascular surgery to visualize and analyze the vascular anatomy flow. A new method based on multispectral fluorescence (MFL) imaging of indocyanine green (ICG) video angiography (VA) allows real-time, augmented reality (AR) visualization of blood flow superimposed on white-light microscopic images. We describe our single-center experience using MFL AR in cerebrovascular surgery. METHODS: Case descriptions are provided of cerebrovascular surgery with intraoperative use of MFL AR images performed at our institution from June 2018 to April 2020. MFL superimposes the blood flow in real time on white-light microscopic images. We used MFL AR imaging as well as standard ICG-VA visualization and intraoperative digital subtraction angiography (DSA) as a control. RESULTS: A total of 39 cases (33 aneurysm clippings, 4 arteriovenous malformations, and 2 external carotid-internal carotid bypass surgeries), were performed using MFL technology-based AR visualization of ICG. MFL AR imaging and DSA showed a high correlation concerning aneurysm occlusion and vessel patency. In arteriovenous malformation resection surgery, MFL AR imaging facilitated early identification of the feeding arteries and draining veins. Because of increased sensitivity of MFL AR, a reduced dose of ICG could be used, allowing repeated intraoperative imaging. There were no postoperative complications, side effects, or technical problems related to the use of MFL AR imaging. CONCLUSIONS: MFL AR is an easy-to-use adjunct in cerebrovascular surgery and shows a high correlation with intraoperative DSA. No interruption of the surgery is necessary because MFL AR images of the blood flow are superimposed in real time on white-light microscopic images.

Early permanent cerebrospinal fluid diversion in aneurysmal subarachnoid hemorrhage: does a lower rate of nosocomial meningitis outweigh the risk of delayed cerebral vasospasm related morbidity?

Objective: Early permanent cerebrospinal fluid (CSF) diversion for hydrocephalus during the first 2 weeks after aneurysmal subarachnoid hemorrhage (aSAH) shortens the duration of external ventricular drainage (EVD) and reduces EVD-associated infections (EVDAI). The objective of this study was to detect any association with symptomatic delayed cerebral vasospasm (DCVS), or delayed cerebral ischemia (DCI) by the time of hospital discharge. Methods: We used a single-center dataset of aSAH patients who had received a permanent CSF diversion. We compared an 'early group' in which the procedure was performed up to 14 days after the ictus, to a 'late group' in which it was performed from the 15th day onward. Results: Among 274 consecutive aSAH patients, 39 (14%) had a permanent CSF diversion procedure with a silver-coated EVD. While the blood clot burden was similarly distributed, patients with early permanent CSF diversion (20 out of 39; 51%) had higher levels of consciousness on admission. Early permanent CSF diversion was associated with less colonized catheter, a shorter duration of extracorporeal CSF diversion (OR 0.73, 95%CI 0.58-0.92 per EVD day), and a lower rate of EVDAI (OR 0.08, 95%CI 0.01-0.80). The occurrence of CSF diversion device obstruction, the rate of symptomatic DCVS or detected DCI on computed tomography and the likelihood of a poor outcome at discharge did not differ between the two groups. Discussion: Early permanent CSF diversion lowers the occurrence of catheter colonization and infectious complication without affecting DCVS-related morbidity in good-grade aSAH patients. These findings need confirmation in larger prospective multicenter cohorts. Abbreviations: aSAH: aneurysmal subarachnoid hemorrhage; BNI: Barrow Neurological Institute Scale; CSF: Cerebrospinal fluid; DCVS: Delayed Cerebral Vasospasm; DCI: Delayed Cortical Ischemia; EKNZ: Ethik-Kommission Nordwest Schweiz; EVD: External ventricular drain; EVDAI: External ventricular drain-associated infections; GCS: Glasgow Coma Scale; IRB: Institutional Review Board; IVH: Inraventricular hemorrhage; mRS: Modified Rankin Scale; SOS: Swiss Study of Subarachnoid Hemorrhage Registry; WFNS: World Federation Neurological-Surgeon Scale.

Direct Oral Anticoagulants in Patients Undergoing Spine Surgery.

OBJECTIVE: Despite increasing use of direct oral anticoagulants (DOACs), guidelines for their perioperative use in spine surgery are still lacking. The main goal of our study was to analyze the occurrence of postoperative bleeding events and possible confounders in patients treated with DOACs who undergo spine surgery. METHODS: Of 2777 patients undergoing spine surgery at our institution, 82 (2.9%) were treated with DOACs. The primary endpoint was postoperative bleeding events. Secondary outcome measures were postoperative thromboembolic events and anemia, hematologic findings, perioperative packed red blood cell substitution, operative time, hospital length of stay, morbidity, and mortality. Subanalysis of possible confounders affecting the rates of bleeding was also performed. Additionally, correlation of bleeding event rates and preoperative and postoperative discontinuation of DOACs was analyzed. RESULTS: Overall postoperative bleeding events rate was 4.9% (n = 4). Preoperative DOAC discontinuation time of <24 hours increased significantly the rate of perioperative packed red blood cell substitution (P = 0.007). Treatment with concomitant blood thinners showed a trend toward higher incidence of bleeding events (P = 0.066), whereas pre-existing kidney failure increased significantly rates of postoperative anemia (P = 0.014). The rate of postoperative thromboembolic events was 4.9% (n = 4); all events occurred with DOAC resumption >72 hours postoperatively. CONCLUSIONS: Short preoperative discontinuation time of DOACs, even <24 hours, may be justified, considering an increased risk of perioperative packed red blood cell substitution. Care should be taken with patients treated with concomitant blood thinners and patients with pre-existing kidney disease. Postoperative DOAC resumption >72 hours may increase risk of thromboembolic events.

Systemic and CSF Interleukin-1α Expression in a Rabbit Closed Cranium Subarachnoid Hemorrhage Model: An Exploratory Study.

BACKGROUND: The inflammatory pathway in cerebrospinal fluid (CSF) leads to delayed cerebral vasospasm (DCVS) and delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). The role of IL-1α has never been evaluated in a rabbit SAH model. The aim of our study is to analyze systemic and CSF changes of IL-1α, and to evaluate potential associations with the onset of DCVS in a rabbit closed cranium SAH model. Methods: 17 New Zealand white rabbits were randomized into two groups, SAH (n = 12) and sham (n = 5). In the first group, SAH was induced by extracranial-intracranial shunting from the subclavian artery into the cerebral cistern of magna under intracranial pressure (ICP) monitoring. The sham group served as a control. The CSF and blood samples for IL-1α measurement were taken at day zero before SAH induction and at day three. RESULTS: There was a significant increase of ICP (p = 0.00009) and a decrease of cerebral perfusion pressure (CPP) (p = 0.00089) during SAH induction. At follow up, there was a significant increase of systemic IL-1α in the SAH as compared with the sham group (p = 0.042). There was no statistically significant difference in the CSF values in both groups. The CSF IL-1α values showed a correlation trend of DCVS. CONCLUSIONS: Systemic IL-1α levels are elevated after SAH induction in a rabbit SAH model.

Novel Oral Anticoagulants in Patients Undergoing Cranial Surgery.

BACKGROUND: The number of patients treated with novel oral anticoagulants (NOACs) is increasing. Despite growing clinical relevance, guidelines on the perioperative management of neurosurgical patients treated with NOACs are still lacking. The aim of this study was to analyze the occurrence of postoperative bleeding events and factors that might influence bleeding rates in these patients. METHODS: Out of 1353 consecutive patients undergoing cranial neurosurgical procedures, 30 (2.2%) received NOACs preoperatively. The rates of perioperative and postoperative intracranial bleeding events, rate of postoperative thromboembolic events, hematologic findings, morbidity, and mortality were reviewed. A subanalysis of factors influencing the bleeding risk of these patients and the bleeding rate depending on the preoperative discontinuation time of NOACS, with cutoff of 24 and 48 hours, was performed as well. RESULTS: The rate of perioperative bleeding was 13.3% (n = 4 of 30). Postoperative bleeding led to death in 2 patients. The median discontinuation time was significantly shorter in the patients experiencing a bleeding event compared to those without a bleeding event (1.5 days [range 0-3 days] vs. 11 days [range, 0-120 days]). The rate of perioperative thromboembolic events was 3.3% (n = 1), and overall mortality was 13.3% (n = 4). CONCLUSIONS: The postoperative bleeding rate in patients undergoing cranial surgery treated with NOACs was 13.3%. A shorter preoperative discontinuation time seems to have a significant effect on bleeding rate. Further studies evaluating the management and postsurgical outcomes of these patients are warranted.

Thalidomide Embryopathy as Possible Cause of Anterior Sacral Meningocele: A Case Report.

A 54-year-old male presented with a sudden burning sensation during urination and left flank pain. Apart from having congenital facial palsy and malformation of the inner right ear that was linked to thalidomide embryopathy, the patient has always been in good health. Urine examination showed the presence of a urinary tract infection. An abdominal ultrasound revealed a large cyst in the lower abdomen, which on MRI corresponded to a large anterior sacral meningocele (ASM) with sacral agenesis at S1/S2. After antibiotic treatment and the spontaneous passage of a kidney stone, the symptoms resolved. This suggests that the patient's acute symptoms were caused by the urolithiasis and not the ASM. Thalidomide is teratogenic between days 17 and 30 after conception. The neural tube closes between days 20 and 36, therefore, thalidomide embryopathy was the possible cause of ASM in this patient. Birth Defects Research 109:1390-1392, 2017.© 2017 Wiley Periodicals, Inc.