Immunity in malignant brain tumors: Tumor entities, role of immunotherapy, and specific contribution of myeloid cells to the brain tumor microenvironment.

Malignant brain tumors lack effective treatment, that can improve their poor overall survival achieved with standard of care. Advancement in different cancer treatments has shifted the focus in brain tumor research and clinical trials toward immunotherapy-based approaches. The investigation of the immune cell landscape revealed a dominance of myeloid cells in the tumor microenvironment. Their exact roles and functions are the subject of ongoing research. Current evidence suggests a complex interplay of tumor cells and myeloid cells with competing functions toward support vs. control of tumor growth. Here, we provide a brief overview of the three most abundant brain tumor entities: meningioma, glioma, and brain metastases. We also describe the field of ongoing immunotherapy trials and their results, including immune checkpoint inhibitors, vaccination studies, oncolytic viral therapy, and CAR-T cells. Finally, we summarize the phenotypes of microglia, monocyte-derived macrophages, border-associated macrophages, neutrophils, and potential novel therapy targets.

Immune checkpoint blockade induces distinct alterations in the microenvironments of primary and metastatic brain tumors.

In comparison with responses in recurrent glioblastoma (rGBM), the intracranial response of brain metastases (BrM) to immune checkpoint blockade (ICB) is less well studied. Here, we present an integrated single-cell RNA-Seq (scRNA-Seq) study of 19 ICB-naive and 9 ICB-treated BrM samples from our own and published data sets. We compared them with our previously published scRNA-Seq data from rGBM and found that ICB led to more prominent T cell infiltration into BrM than rGBM. These BrM-infiltrating T cells exhibited a tumor-specific phenotype and displayed greater activated/exhausted features. We also used multiplex immunofluorescence and spatial transcriptomics to reveal that ICB reduced a distinct CD206+ macrophage population in the perivascular space, which may modulate T cell entry into BrM. Furthermore, we identified a subset of progenitor exhausted T cells that correlated with longer overall survival in BrM patients. Our study provides a comprehensive immune cellular landscape of ICB's effect on metastatic brain tumors and offers insights into potential strategies for improving ICB efficacy for brain tumor patients.

Lumbar Epidural Cavernous Hemangioma: A Case Report and Review of the Literature.

Pure epidural cavernous hemangioma (ECH) of the spine are rare and account for only 4% of all epidural spinal lesions. We report a case of epidural cavernoma at L3/4 presenting with L4 radiculopathy. Radiological, intraoperative findings and histopathology are presented. We present the case of a 56-year-old man who was admitted with a right L4 radiculopathy including an M4 paresis of the right leg, hypoesthesia L4, and radicular pain. Magnetic resonance imaging (MRI) confirmed an extradural lesion L3/4 partially expanding into the right intervertebral foramen. The lesion had a heterogeneous signal, isointense on T1-weighted and hyperintense on proton density (PD) and T2-weighted images. At surgery, an epidural, ovoid, gray-red, soft mass, lightly adherent to the dura and extending to the right L4 foramen was observed. Findings in the histological examination indicated a cavernous hemangioma without signs of hemorrhage. Symptoms and paresis improved rapidly after surgery. The follow-up MRI showed complete resection of the lesion with no signs of radicular compression. Spinal ECH should be considered as a cause of chronic lumbar radiculopathy with atypical radiological findings. Early diagnosis and total removal of the spinal ECH might prevent hemorrhage and neurological deficits. Fewer than 50 cases of lumbar epidural spinal hemangioma have been reported until today, and our case report is adding valuable knowledge to the existing literature.

Preoperative ODI and Intake of Analgesics Predict Outcome after Lumbar Microdiskectomy: Results from a Prospective Register.

BACKGROUND: Lumbar disk herniation (LDH) typically causes leg pain and neurologic deficits, but can also be a source of low back pain (LBP). Lumbar microdiskectomy (LMD) is among the most common neurosurgical procedures to relieve radicular symptoms. It is important for both surgeon and patient to understand potential predictors of outcome after LMD. The aim of this study was to investigate if the presence and intensity of preoperative LBP, the ODI score, and analgesic intake can predict the outcome of patients undergoing LMD. METHODS: This is a single-center retrospective study based on the analysis of prospectively acquired data of patients in the SwissDisc Registry. A total of 685 surgeries on 640 patients who underwent standardized LMD at our institution to treat LDH were included in this study. We performed multivariable linear regression analysis to determine preoperative predictors for patient outcomes based on the Oswestry Disability Index (ODI) scores, recorded on average 39.77 (±33.77) days after surgery. RESULTS: Our study confirmed that surgery overall improves patient degree of disability as measured by ODI score. Following model selection using Aikake Information Criterion (AIC), we observed that higher preoperative ODI scores (ß: 0.020 [95% CI: 0.008 to 0.031]) and higher number of analgesic medication usage by patients prior to surgery (ß: 0.236 [95% CI: 0.057 to 0.415]) were both associated with an increased postoperative ODI score. CONCLUSION: LDH surgery generally improves patient degree of disability. The analysis of patients with a high preoperative ODI score and increased intake of analgesics before surgery predicted a worsening of patients' disability after LMD in this subgroup.

The Impact of Aspirin in Brain Tumor Surgery: To Stop or Not to Stop?

Given the lack of guidelines regarding perioperative management of neurosurgical patients taking antiplatelet medication, a break of aspirin intake for elective brain surgery is recommended. To the best of our knowledge, only three clinical studies have been published comparing re-bleeding rates in patients undergoing elective brain surgery with and without aspirin. We present a case of an 81-year-old woman who was admitted for elective craniotomy and brain metastases resection. She presented with a right-sided hemianopsia for > two weeks and further investigation by magnetic resonance imaging (MRI) showed the left occipital lesion. For primary cardiovascular prevention, the patient was prescribed prophylactic low-dose aspirin 100 mg. A platelet function test on the day of admission detected highly pathological values. Surgery was scheduled the next day, and aspirin intake was paused. The platelet function test was repeated the morning before surgery. Interestingly, the test showed a 20% above-normal level platelet function. Craniotomy and tumor resection were performed in a routine fashion and no increased bleeding tendency was reported intraoperatively. Postoperatively, the right-sided hemianopsia was immediately regressive. MRI performed 24 hours after surgery demonstrated a complete tumor resection without any signs of rebleeding. The patient was discharged five days after surgery without any neurological deficits. The literature is limited and guidelines are missing on the topic of management of antiplatelet medication in elective brain surgery. As confirmed by the present case and a review of the literature, elective craniotomy and tumor resection under antiplatelet medication may be considered in certain cases with risk and benefit stratification. More data and randomized controlled trials are needed to confirm these findings.

Effectiveness of an Annular Closure Device to Prevent Recurrent Lumbar Disc Herniation: A Secondary Analysis With 5 Years of Follow-up.

Importance: Patients with large annular defects following lumbar microdiscectomy for disc herniation are at increased risk for symptomatic recurrence and reoperation. Objective: To determine whether a bone-anchored annular closure device in addition to lumbar microdiscectomy resulted in lower reherniation and reoperation rates vs lumbar microdiscectomy alone. Design, Setting, and Participants: This secondary analysis of a multicenter randomized clinical trial reports 5-year follow-up for enrolled patients between December 2010 and October 2014 at 21 clinical sites. Patients in this study had a large annular defect (6-10 mm width) following lumbar microdiscectomy for treatment of lumbar disc herniation. Statistical analysis was performed from November to December 2020. Interventions: Lumbar microdiscectomy with additional bone-anchored annular closure device (device group) or lumbar microdiscectomy only (control group). Main Outcomes and Measures: The incidence of symptomatic reherniation, reoperation, and adverse events as well as changes in leg pain, Oswestry Disability Index, and health-related quality of life when comparing the device and control groups over 5 years of follow-up. Results: Among 554 randomized participants (mean [SD] age: 43 [11] years; 327 [59%] were men), 550 were included in the modified intent-to-treat efficacy population (device group: n = 272; 270 [99%] were White); control group: n = 278; 273 [98%] were White) and 550 were included in the as-treated safety population (device group: n = 267; control group: n = 283). The risk of symptomatic reherniation (18.8% [SE, 2.5%] vs 31.6% [SE, 2.9%]; P < .001) and reoperation (16.0% [SE, 2.3%] vs 22.6% [SE, 2.6%]; P = .03) was lower in the device group. There were 53 reoperations in 40 patients in the device group and 82 reoperations in 58 patients in the control group. Scores for leg pain severity, Oswestry Disability Index, and health-related quality of life significantly improved over 5 years of follow-up with no clinically relevant differences between groups. The frequency of serious adverse events was comparable between the treatment groups. Serious adverse events associated with the device or procedure were less frequent in the device group (12.0% vs 20.5%; difference, -8.5%; 95% CI, -14.6% to -2.3%; P = .008). Conclusions and Relevance: In patients who are at high risk of recurrent herniation following lumbar microdiscectomy owing to a large defect in the annulus fibrosus, this study's findings suggest that annular closure with a bone-anchored implant lowers the risk of symptomatic recurrence and reoperation over 5 years of follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT01283438.

Neoadjuvant PD-1 blockade induces T cell and cDC1 activation but fails to overcome the immunosuppressive tumor associated macrophages in recurrent glioblastoma.

Primary brain tumors, such as glioblastoma (GBM), are remarkably resistant to immunotherapy, even though pre-clinical models suggest effectiveness. To understand this better in patients, here we take advantage of our recent neoadjuvant treatment paradigm to map the infiltrating immune cell landscape of GBM and how this is altered following PD-1 checkpoint blockade using high dimensional proteomics, single cell transcriptomics, and quantitative multiplex immunofluorescence. Neoadjuvant PD-1 blockade increases T cell infiltration and the proportion of a progenitor exhausted population of T cells found within the tumor. We identify an early activated and clonally expanded CD8+ T cell cluster whose TCR overlaps with a CD8+ PBMC population. Distinct changes are also observed in conventional type 1 dendritic cells that may facilitate T cell recruitment. Macrophages and monocytes still constitute the majority of infiltrating immune cells, even after anti-PD-1 therapy. Interferon-mediated changes in the myeloid population are consistently observed following PD-1 blockade; these also mediate an increase in chemotactic factors that recruit T cells. However, sustained high expression of T-cell-suppressive checkpoints in these myeloid cells continue to prevent the optimal activation of the tumor infiltrating T cells. Therefore, future immunotherapeutic strategies may need to incorporate the targeting of these cells for clinical benefit.

Linear accelerator-based radiosurgery for trigeminal neuralgia: comparative outcomes of frame-based and mask-based techniques.

OBJECTIVE: Precise and accurate targeting is critical to optimize outcomes after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). The aim of this study was to compare the outcomes after SRS for TN in which two different techniques were used: mask-based 4-mm cone versus frame-based 5-mm cone. METHODS: The authors performed a retrospective review of patients who underwent SRS for TN at their institution between 1996 and 2019. The Barrow Neurological Institute (BNI) pain score and facial hypesthesia scale were used to evaluate pain relief and facial numbness. RESULTS: A total of 234 patients were included in this study; the mean age was 67 years. In 97 patients (41.5%) radiation was collimated by a mask-based 4-mm cone, whereas a frame-based 5-mm cone was used in the remaining 137 patients (58.5%). The initial adequate pain control rate (BNI I-III) was 93.4% in the frame-based 5-mm group, compared to 87.6% in the mask-based 4-mm group. This difference between groups lasted, with an adequate pain control rate at ≥ 24 months of 89.9% and 77.8%, respectively. Pain relief was significantly different between groups from initial response until the last follow-up (≥ 24 months, p = 0.02). A new, permanent facial hypesthesia occurred in 30.3% of patients (33.6% in the frame-based 5-mm group vs 25.8% in the mask-based 4-mm group). However, no significant association between the BNI facial hypesthesia score and groups was found. Pain recurrence occurred earlier (median time to recurrence 12 months vs 29 months, p = 0.016) and more frequently (38.1% vs 20.4%, p = 0.003) in the mask-based 4-mm than in the frame-based 5-mm group. CONCLUSIONS: Frame-based 5-mm collimator SRS for TN resulted in a better long-term pain relief with similar toxicity profiles to that seen with mask-based 4-mm collimator SRS.

Value of 3-Dimensional Digital Subtraction Angiography for Detection and Classification of Intracranial Aneurysm Remnants After Clipping.

BACKGROUND: The current gold standard for evaluation of the surgical result after intracranial aneurysm (IA) clipping is two-dimensional (2D) digital subtraction angiography (DSA). While there is growing evidence that postoperative 3D-DSA is superior to 2D-DSA, there is a lack of data on intraoperative comparison. OBJECTIVE: To compare the diagnostic yield of detection of IA remnants in intra- and postoperative 3D-DSA, categorize the remnants based on 3D-DSA findings, and examine associations between missed 2D-DSA remnants and IA characteristics. METHODS: We evaluated 232 clipped IAs that were examined with intraoperative or postoperative 3D-DSA. Variables analyzed included patient demographics, IA and remnant distinguishing characteristics, and 2D- and 3D-DSA findings. Maximal IA remnant size detected by 3D-DSA was measured using a 3-point scale of 2-mm increments. RESULTS: Although 3D-DSA detected all clipped IA remnants, 2D-DSA missed 30.4% (7 of 23) and 38.9% (14 of 36) clipped IA remnants in intraoperative and postoperative imaging, respectively (95% CI: 30 [ 12, 49] %; P-value .023 and 39 [23, 55] %; P-value = <.001), and more often missed grade 1 (< 2 mm) clipped remnants (odds ratio [95% CI]: 4.3 [1.6, 12.7], P-value .005). CONCLUSION: Compared with 2D-DSA, 3D-DSA achieves a better diagnostic yield in the evaluation of clipped IA. Our proposed method to grade 3D-DSA remnants proved to be simple and practical. Especially small IA remnants have a high risk to be missed in 2D-DSA. We advocate routine use of either intraoperative or postoperative 3D-DSA as a baseline for lifelong follow-up of clipped IA.

Incidence and clinical impact of vertebral endplate changes after limited lumbar microdiscectomy and implantation of a bone-anchored annular closure device.

BACKGROUND: An annular closure device (ACD) could potentially prevent recurrent herniation by blocking larger annular defects after limited microdiscectomy (LMD). The purpose of this study was to analyze the incidence of endplate changes (EPC) and outcome after LMD with additional implantation of an ACD to prevent reherniation. METHODS: This analysis includes data from a) RCT study-arm of patients undergoing LMD with ACD implantation and b) additional patients undergoing ACD implantation at our institution. Clinical findings (VAS, ODI), radiological outcome (reherniation, implant integrity, volume of EPC) and risk factors for EPC were assessed. RESULTS: Seventy-two patients (37 men, 47 ± 11.63yo) underwent LMD and ACD implantation between 2013-2016. A total of 71 (99%) patients presented with some degree of EPC during the follow-up period (14.67 ± 4.77 months). In the multivariate regression analysis, localization of the anchor was the only significant predictor of EPC (p = 0.038). The largest EPC measured 4.2 cm3. Reherniation was documented in 17 (24%) patients (symptomatic: n = 10; asymptomatic: n = 7). Six (8.3%) patients with symptomatic reherniation underwent rediscectomy. Implant failure was documented in 19 (26.4%) patients including anchor head breakage (n = 1, 1.3%), dislocation of the whole device (n = 5, 6.9%), and mesh dislocation into the spinal canal (n = 13, 18%). Mesh subsidence within the EPC was documented in 15 (20.8%) patients. Seven (9.7%) patients underwent explantation of the entire, or parts of the device. CONCLUSION: Clinical improvement after LMD and ACD implantation was proven in our study. High incidence and volume of EPC did not correlate with clinical outcome. The ACD might prevent disc reherniation despite implant failure rates. Mechanical friction of the polymer mesh with the endplate is most likely the cause of EPC after ACD.

Intraoperative findings, complications, and short-term results after lumbar microdiscectomy with or without implantation of annular closure device.

BACKGROUND: Standard microscopic lumbar discectomy (MLD) is a short operation with minimal blood loss, and a low rate of peri- and intraoperative complications. The objective of this study was to evaluate intraoperative findings, complications, and early postoperative neurological outcome (< 105 days) in patients undergoing MLD with or without implantation of an annular closure device (ACD). METHODS: This study is based on data analysis of a post-marketing, prospective, multicenter RCT in Europe including patients undergoing standard MLD with or without implantation of an ACD (Barricaid®, Intrinsic Therapeutics, Inc., Woburn, MA). Enrollment of 554 patients in 21 centers in Europe (Germany, Switzerland, Austria, Belgium, The Netherlands, and France) started in 2010 and was completed in October 2014, with 276 patients randomized to the ACD group and 278 to the control group. RESULTS: Mean operation time was 70 min in the ACD group and 52 min in the control group (p < 0.0001). Intraoperative fluoroscopy time was 24 s in the ACD group and 7 s in the control group (p < 0.0001). Average blood loss was 94.2 ml in the ACD group and 64.7 ml in the control group (p = 0.0001). Serious device- or procedure-related adverse events occurred in 3.7% (10/272) of the ACD group and 7.9% (22/278) of the control group. Dural injuries occurred in 13 (4.8%) patients in the ACD group and 7 (2.5%) in the control group. There was one device-related nerve root injury resulting in a nerve root amputation. Surgical complications included 3 hematomas in the ACD group and 4 in the control group; 3 infections occurred in both groups. Device migrations were documented in 3 patients in the ACD group. Patients in the ACD group (n = 7, 2.6%) underwent fewer reoperations compared with that in the control group (n = 16, 5.8%, OR = 2.3 (0.9-5.7)). Mean VAS leg pain at 3 months was 11.9 in the ACD and 15.1 in the control group, respectively. CONCLUSION: Short-term outcome after MLD with or without implantation of ACD was similar in both groups. Patients included in the ACD group underwent fewer reoperations in the first 3 months after surgery. Nevertheless, longer operation time, higher amount of blood loss, and risk of nerve root lesion during device implantation should be considered additional risks in patients undergoing ACD implantation after MLD.

Risk factors for early reherniation after lumbar discectomy with or without annular closure: results of a multicenter randomized controlled study.

BACKGROUND: Reherniation after lumbar discectomy is classified as a failure and occurs in 3 to 18% of cases. Various risk factors for reherniation such as age, sex, body mass index, smoking, and size of annular defect have been reported. The aim of this study was to identify risk factors for early reherniation after one-level lumbar discectomy with or without annular closure within 3 months after surgery. METHODS: This study is based on data analysis of a prospective, multicenter randomized controlled trial in Europe. Patients included underwent standard lumbar discectomy-with or without implantation of an annular closure device (ACD). Enrollment of 554 patients in 21 centers in Europe (Germany, Switzerland, Austria, Belgium, The Netherlands, and France) started in 2010 and was completed in October 2014. A total of 276 patients were randomized to the ACD group (ACG) and 278 patients to the control group (CG). RESULTS: Four (1.5%) symptomatic reherniations occurred in the ACG and 18 (6.5%) in the CG. In the overall population, a significant correlation was found with recurrent herniation for disc degeneration (Pfirrmann p = 0.009) and a trend for current smoker status (p = 0.07). In CG, age ≥ 50 years (p = 0.05) and disc degeneration (Pfirrmann p = 0.026, Kellgren and Lawrence p = 0.013) were predictive factors for reherniation. CONCLUSION: In the current study, risk factors for early recurrent disc herniation after lumbar discectomy were age ≥ 50 years and moderate disc degeneration. The annular closure device reduced the risk of early reherniation. TRIAL REGISTRATION: Clinicaltrials.gov NCT01283438.

Changing the paradigm of intracranial hypertension in brain tumor patients: a study based on non-invasive ICP measurements.

BACKGROUND: The ultrasound based non-invasive ICP measurement method has been recently validated. Correlation of symptoms and signs of intracranial hypertension with actual ICP measurements in patients with large intracranial tumors is controversial. The purpose of this study was to assess ICP in patients with brain tumors, presenting with neurological signs and symptoms of elevated ICP and to further evaluate the value and utility of non-invasive ICP monitoring. METHODS: Twenty patients underwent non-invasive ICP measurement using a two-depth transcranial Doppler ultrasound designed to simultaneously compare pulse dynamics in the proximal (intracranial), and the distal (extracranial) intraorbital segments of the ophthalmic artery through the closed eyelid. RESULTS: Forty-eight measurements were analyzed. Radiological characteristics included tumor volume (range = 5.45-220.27cm3, mean = 48.81 cm3), perilesional edema (range = 0-238.27cm3, mean = 74.40 cm3), and midline shift (mean = 3.99 mm). All ICP measurements were in the normal range of 7-16 mmHg (ICPmean: 9.19 mmHg). The correlation of demographics, clinical and radiological variables in a bivariate association, showed a statistically significant correlation with neurological deficits and ICPmax (p = 0.02) as well as ICPmean (p = 0.01). The correlation between ICP and neurological deficits, showed a negative value of the estimate. The ICP was not increased in all cases, whether ipsilateral nor contralateral to the tumor. The multivariate model analysis demonstrated that neurological deficits were associated with lower ICPmax values, whereas maximum tumor diameter was associated with larger ICPmax values. CONCLUSIONS: This study demonstrated that ICP in patients with intracranial tumors and mass effect is not necessarily increased. Therefore, clinical signs of intracranial hypertension do not necessarily reflect increased ICP.

Endovascular Temporary Balloon Occlusion for Microsurgical Clipping of Posterior Circulation Aneurysms.

Based on the relationship between the posterior clinoid process and the basilar artery (BA) apex it may be difficult to obtain proximal control of the BA using temporary clips. Endovascular BA temporary balloon occlusion (TBO) can reduce aneurysm sac pressure, facilitate dissection/clipping, and finally lower the risk of intraoperative rupture. We present our experience with TBO during aneurysm clipping of posterior circulation aneurysms within the setting of a hybrid operating room (hOR). We report one case each of a basilar tip, posterior cerebral artery, and superior cerebellar artery aneurysm that underwent surgical occlusion under TBO within an hOR. Surgical exposure of the BA was achieved with a pterional approach and selective anterior and posterior clinoidectomy. Intraoperative digital subtraction angiography (iDSA) was performed prior, during, and after aneurysm occlusion. Two patients presented with subarachnoid hemorrhage and one patient presented with an unruptured aneurysm. The intraluminal balloon was inserted through the femoral artery and inflated in the BA after craniotomy to allow further dissection of the parent vessel and branches needed for the preparation of the aneurysm neck. No complications during balloon inflation and aneurysm dissection occurred. Intraoperative aneurysm rupture prior to clipping did not occur. The duration of TBO varied between 9 and 11 min. Small neck aneurysm remnants were present in two cases (BA and PCA). Two patients recovered well with a GOS 5 after surgery and one patient died due to complications unrelated to surgery. Intraoperative TBO within the hOR is a feasible and safe procedure with no additional morbidity when using a standardized protocol and setting. No relevant side effects or intraoperative complications were present in this series. In addition, iDSA in an hOR facilitates the evaluation of the surgical result and 3D reconstructions provide documentation of potential aneurysm remnants for future follow-up.

Clinical Implications of Vertebral Endplate Disruptions After Lumbar Discectomy: 3-Year Results from a Randomized Trial of a Bone-Anchored Annular Closure Device.

OBJECTIVE: Vertebral endplate disruptions (VEPD) are common findings on imaging after lumbar surgery. The objective of this study was to explore the clinical implications of VEPD development following lumbar discectomy with or without implant with a bone-anchored annular closure device (ACD). METHODS: This was a multicenter randomized controlled trial of patients with large postsurgical annular defects after limited lumbar discectomy who were randomized to additionally receive an ACD or no additional treatment. VEPD were identified on computed tomography and confirmed by an imaging core laboratory. Clinical outcomes included recurrent herniation, reoperation, Oswestry Disability Index, leg pain, and back pain. Patient follow-up in this study was 3 years. RESULTS: In the ACD group (n=272), the risk of reoperation was lower in patients with vs without VEPD (8% vs 24%, p<0.01), but no other clinical outcomes differed when stratified by VEPD prevalence or size. In the Control group (n=278), the risk of symptomatic reherniation was higher in patients with VEPD (41% vs 23%, p<0.01) and patients with the largest VEPD had the highest reoperation rates. Patient-reported outcomes were not associated with VEPD prevalence or size in the Control group. CONCLUSION: VEPD had no significant influence on patient-reported outcomes at 3 years after lumbar discectomy. VEPD increased the risk of recurrence in patients treated with lumbar discectomy only, but had no negative influence in patients treated with the ACD.

Comparison of Intra- and Postoperative 3-Dimensional Digital Subtraction Angiography in Evaluation of the Surgical Result After Intracranial Aneurysm Treatment.

BACKGROUND: Postoperative three-dimensional digital subtraction angiography (3D-DSA) is the gold standard in evaluating intracranial aneurysm (IA) remnants after clipping. Should intraoperative 3D-DSA image quality be equally good as postoperative 3D-DSA, it could supplant the latter as standard of care for follow-up of clipped IA. OBJECTIVE: To directly compare the quality of assessment of clipped IA by intraoperative and postoperative 3D-DSA. METHODS: From a prospective cohort of 221 consecutive patients who underwent craniotomy for IA treatment in a hybrid operating room, we retrospectively studied 26 patients who had both intraoperative and postoperative 3D-DSA imaging of their clipped aneurysm. Comparison of intraoperative and postoperative 3D-DSA images (blinded for review) included parameters that affected image quality and differences between the 2 periods. RESULTS: In the 26 patients with 32 clipped IAs, the mean interval was 11 ± 7 mo between intraoperative and postoperative imaging 3D-DSA examinations. Reconstruction with multiple clips was used in 14 (44%) cases. Of 15 remnants, 9 (60%) were small (<2 mm). In comparing intraoperative and postoperative 3D-DSA, no discordance or discrepancy in assessment of the surgical result was noted for any clipped IA, and overall imaging quality was excellent for both modalities. Factors affecting minor differences in image quality were not identified. CONCLUSION: Compared with postoperative 3D-DSA, intraoperative 3D-DSA images achieved equally high quality and effective, immediate interpretation of the surgical clipping result. With comparable imaging quality and no discordant findings, intraoperative 3D-DSA could replace postoperative 3D-DSA to become the standard of care in IA surgery.

Three-year results from a randomized trial of lumbar discectomy with annulus fibrosus occlusion in patients at high risk for reherniation.

BACKGROUND: A larger defect in the annulus fibrosus following lumbar discectomy is a well-known risk factor for reherniation. Procedures intended to prevent reherniation by sealing or occluding the annular defect warrant study in high-risk patients. This study sought to determine 3-year results of lumbar discectomy with a bone-anchored annular closure device (ACD) or lumbar discectomy only (controls) in patients at high risk for reherniation. METHODS: This multicenter randomized trial enrolled patients with sciatica due to lumbar intervertebral disc herniation who failed conservative treatment. Patients with large annular defects after lumbar limited microdiscectomy were intraoperatively randomly assigned to receive ACD or control. Clinical and imaging follow-up was performed at routine intervals over 3 years. Main outcomes included rate of reherniations, reoperations, and endplate changes; leg and back pain scores on a visual analogue scale; Oswestry Disability Index (ODI); Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the SF-36; and adverse events adjudicated by a data safety monitoring board. RESULTS: Among 554 randomized patients, the modified intent-to-treat population consisted of 272 patients in which ACD implantation was attempted and 278 receiving control; device implantation was not attempted in 4 patients assigned to ACD. Outcomes at 3 years favored ACD for symptomatic reherniation (14.8% vs. 29.5%; P < 0.001), reoperation (11.0% vs. 19.3%; P = 0.007), leg pain (21 vs. 30; P < 0.01), back pain (23 vs. 30; P = 0.01), ODI (18 vs. 23; P = 0.02), PCS (47 vs. 44; P < 0.01), and MCS (52 vs. 49; P < 0.01). The frequency of all-cause serious adverse events was comparable between groups (42.3% vs. 44.5%; P = 0.61). CONCLUSIONS: The addition of a bone-anchored ACD in patients with large annular defects following lumbar discectomy reduces the risk of reherniation and reoperation, and has a similar safety profile over 3-year follow-up compared with lumbar limited discectomy only. TRIAL REGISTRATION: ClinicalTrials.gov NCT01283438.

Validation of Noninvasive Absolute Intracranial Pressure Measurements in Traumatic Brain Injury and Intracranial Hemorrhage.

BACKGROUND: Increased intracranial pressure (ICP) causes secondary damage in traumatic brain injury (TBI), and intracranial hemorrhage (ICH). Current methods of ICP monitoring require surgery and carry risks of complications. OBJECTIVE: To validate a new instrument for noninvasive ICP measurement by comparing values obtained from noninvasive measurements to those from commercial implantable devices through this pilot study. METHODS: The ophthalmic artery (OA) served as a natural ICP sensor. ICP measurements obtained using noninvasive, self-calibrating device utilizing Doppler ultrasound to evaluate OA flow were compared to standard implantable ICP measurement probes. RESULTS: A total of 78 simultaneous, paired, invasive, and noninvasive ICP measurements were obtained in 11 ICU patients over a 17-mo period with the diagnosis of TBI, SAH, or ICH. A total of 24 paired data points were initially excluded because of questions about data independence. Analysis of variance was performed first on the 54 remaining data points and then on the entire set of 78 data points. There was no difference between the 2 groups nor was there any correlation between type of sensor and the patient (F[10, 43] = 1.516, P = .167), or the accuracy and precision of noninvasive ICP measurements (F[1, 43] = 0.511, P = .479). Accuracy was [-1.130; 0.539] mm Hg (CL = 95%). Patient-specific calibration was not needed. Standard deviation (precision) was [1.632; 2.396] mm Hg (CL = 95%). No adverse events were encountered. CONCLUSION: This pilot study revealed no significant differences between invasive and noninvasive ICP measurements (P < .05), suggesting that noninvasive ICP measurements obtained by this method are comparable and reliable.