Transforaminal Lumbar Interbody Fusion Versus Posterolateral Fusion Alone in the Treatment of Grade 1 Degenerative Spondylolisthesis

Neurosurgery 93:186–197, 2023

Transforaminal lumbar interbody fusion (TLIF) and posterolateral fusion (PLF) alone are two operations performed to treat degenerative lumbar spondylolisthesis. To date, it is unclear which operation leads to better outcomes.

OBJECTIVE: To compare TLIF vs PLF alone regarding long-term reoperation rates, complications, and patient-reported outcome measures (PROMs) in patients with degenerative grade 1 spondylolisthesis.

METHODS: A retrospective cohort study using prospectively collected data between October 2010 and May 2021 was undertaken. Inclusion criteria were patients aged 18 years or older with grade 1 degenerative spondylolisthesis undergoing elective, single-level, open posterior lumbar decompression and instrumented fusion with ≥1-year follow-up. The primary exposure was presence of TLIF vs PLF without interbody fusion. The primary outcome was reoperation. Secondary outcomes included complications, readmission, discharge disposition, return to work, and PROMs at 3 and 12 months postoperatively, including Numeric Rating Scale-Back/Leg and Oswestry Disability Index. Minimum clinically important difference of PROMs was set at 30% improvement from baseline.

RESULTS: Of 546 patients, 373 (68.3%) underwent TLIF and 173 underwent (31.7%) PLF. Median follow-up was 6.1 years (IQR = 3.6-9.0), with 339 (62.1%) >5-year follow-up. Multivariable logistic regression showed that patients undergoing TLIF had a lower odds of reoperation compared with PLF alone (odds ratio = 0.23, 95% CI = 0.54-0.99, P = .048). Among patients with >5-year follow-up, the same trend was seen (odds ratio = 0.15, 95% CI = 0.03-0.95, P = .045). No differences were observed in 90-day complications (P = .487) and readmission rates (P = .230) or minimum clinically important difference PROMs.

CONCLUSION: In a retrospective cohort study from a prospectively maintained registry, patients with grade 1 degenerative spondylolisthesis undergoing TLIF had significantly lower long-term reoperation rates than those undergoing PLF.

Rehemorrhage of brainstem cavernous malformations: a benchmark approach to individualized risk and severity assessment

J Neurosurg 139:94–105, 2023

Brainstem cavernous malformations (BSCMs) represent a unique subgroup of cavernous malformations with more hemorrhagic presentation and technical challenges. This study aimed to provide individualized assessment of the rehemorrhage clustering risk of BSCMs after the first symptomatic hemorrhage and to identify patients at higher risk of neurological deterioration after new hemorrhage, which would help in clinical decision-making.

METHODS A total of 123 consecutive BSCM patients with symptomatic hemorrhage were identified between 2015 and 2022, with untreated follow-up > 12 months or subsequent hemorrhage during the untreated follow-up. Nomograms were proposed to individualize the assessment of subsequent hemorrhage risk and neurological status (determined by the modified Rankin Scale [mRS] score) after future hemorrhage. The least absolute shrinkage and selector operation (LASSO) regression was used for feature screening. The calibration curve and concordance index (C-index) were used to assess the internal calibration and discrimination performance of the nomograms. Cross-validation was further performed to validate the accuracy of the nomograms.

RESULTS Prior hemorrhage times (adjusted OR [aOR] 6.78 per ictus increase) and Zabramski type I or V (OR 11.04) were associated with rehemorrhage within 1 year. A lower mRS score after previous hemorrhage (aOR 0.38 for a shift to a higher mRS score), Zabramski type I or V (OR 3.41), medulla or midbrain location (aOR 2.77), and multiple cerebral cavernous malformations (aOR 11.76) were associated with worsened neurological status at subsequent hemorrhage. The nomograms showed good accuracy and discrimination, with a C-index of 0.80 for predicting subsequent hemorrhage within 1 year and 0.71 for predicting neurological status after subsequent hemorrhage, which were maintained in cross-validation.

CONCLUSIONS An individualized approach to risk and severity assessment of BSCM rehemorrhage was feasible with clinical and imaging features.

Pediatric Vagus Nerve Stimulation: Case Series Outcomes and Future Directions

Neurosurgery 92:1043–1051, 2023

Vagus nerve stimulation (VNS) is a neuromodulatory procedure most extensively studied as an adjunct to medically refractory epilepsy. Despite widespread adoption and decades of clinical experience, clinical predictors of response to VNS remain unclear. OBJECTIVE: To evaluate a retrospective cohort of pediatric patients undergoing VNS at our institution to better understand who may benefit from VNS and identify factors which may predict response to VNS.

METHODS: We conducted a retrospective cohort study examining pediatric patients undergoing VNS over nearly a 20-year span at a single institution. Presurgical evaluation, including demographics, clinical history, and diagnostic electroencephalogram, and imaging findings were examined. Primary outcomes included VNS response.

RESULTS: Two hundred ninety-seven subjects were studied. The mean age at surgery was 10.1 (SD = 4.9, range = 0.8-25.3) years; length of follow-up was a mean of 4.6 years (SD = 3.5, median = 3.9 years, range 1 day-16.1 years). There was no association between demographic factors, epilepsy etiology, or genetic basis and VNS outcomes. There was an association between reduction in main seizure type with positive MRI finding. Of all MRI findings analyzed, brain atrophy was significantly associated with worse VNS outcomes, whereas dysplastic hippocampus and chronic periventricular leukomalacia findings were found to be associated with improved outcomes. Increased seizure semiology variability and seizure type were also associated with improved seizure outcomes.

CONCLUSION: Predicting response to VNS remains difficult, leading to incompletely realized benefits and suboptimal resource utilization. Specific MRI findings and increased seizure semiology variability and type can help guide clinical decision making and patient counseling.

Occurrence, Risk Factors, and Consequences of Postoperative Ischemia After Glioma Resection

Neurosurgery 92:125–136, 2023

Postoperative ischemia can lead to neurological deficits and is a known complication of glioma resection. There is inconsistency in documented incidence of ischemia after glioma resection, and the precise cause of ischemia is often unknown.

OBJECTIVE: To assess the incidence of postoperative ischemia and neurological deficits after glioma resection and to evaluate their association with potential risk factors.

METHODS: One hundred thirty-nine patients with 144 surgeries between January 2012 and September 2014 for World Health Organization (WHO) 2016 grade II-IV diffuse supratentorial gliomas with postoperative MRI within 72 hours were retrospectively included. Patient, tumor, and perioperative data were extracted from the electronic patient records. Occurrence of postoperative confluent ischemia, defined as new confluent areas of diffusion restriction, and new or worsened neurological deficits were analyzed univariably and multivariably using logistic regression models.

RESULTS: Postoperative confluent ischemia was found in 64.6% of the cases. Occurrence of confluent ischemia was associated with an insular location (P = .042) and intraoperative administration of vasopressors (P = .024) in multivariable analysis. Glioma location in the temporal lobe was related to an absence of confluent ischemia (P = .01). Any new or worsened neurological deficits occurred in 30.6% and 20.9% at discharge from the hospital and at first follow-up, respectively. Occurrence of ischemia was significantly associated with the presence of novel neurological deficits at discharge (P = .013) and after 3 months (P = .024).

CONCLUSION: Postoperative ischemia and neurological deficit were significantly correlated. Intraoperative administration of vasopressors, insular glioma involvement, and absence of temporal lobe involvement were significantly associated with postoperative ischemia.

Medication intake and hemorrhage risk in patients with familial cerebral cavernous malformations

J Neurosurg 137:1088–1094, 2022

The objective of this study was to analyze the impact of medication intake on hemorrhage risk in patients with familial cerebral cavernous malformation (FCCM).

METHODS The authors’ institutional database was screened for patients with FCCM who had been admitted to their department between 2003 and 2020. Patients with a complete magnetic resonance imaging (MRI) data set, evidence of multiple CCMs, clinical baseline characteristics, and follow-up (FU) examination were included in the study. The authors assessed the influence of medication intake on first or recurrent intracerebral hemorrhage (ICH) using univariate and multivariate logistic regression adjusted for age and sex. The longitudinal cumulative 5-year risk of hemorrhage was calculated by applying Kaplan-Meier and Cox regression analyses adjusted for age and sex.

RESULTS Two hundred five patients with FCCMs were included in the study. Multivariate Cox regression analysis revealed ICH as a predictor for recurrent hemorrhage during the 5-year FU. The authors also noted a tendency toward a decreased association with ICH during FU in patients on statin medication (HR 0.22, 95% CI 0.03–1.68, p = 0.143), although the relationship was not statistically significant. No bleeding events were observed in patients on antithrombotic therapy. Kaplan-Meier analysis and log-rank test showed a tendency toward a low risk of ICH during FU in patients on antithrombotic therapy (p = 0.085), as well as those on statin therapy (p = 0.193). The cumulative 5-year risk of bleeding was 22.82% (95% CI 17.33%–29.38%) for the entire cohort, 31.41% (95% CI 23.26%–40.83%) for patients with a history of ICH, 26.54% (95% CI 11.13%–49.7%) for individuals on beta-blocker medication, 6.25% (95% CI 0.33%–32.29%) for patients on statin medication, and 0% (95% CI 0%–30.13%) for patients on antithrombotic medication.

CONCLUSIONS ICH at diagnosis was identified as a risk factor for recurrent hemorrhage. Although the relationships were not statistically significant, statin and antithrombotic medication tended to be associated with decreased bleeding events.

Neurological event prediction for patients with symptomatic cerebral cavernous malformation: the BLED 2 score

J Neurosurg 137:344–351, 2022

Retrospective patient cohort studies have identified risk factors associated with recurrent focal neurological events in patients with symptomatic cerebral cavernous malformations (CCMs). Using a prospectively maintained database of patients with CCMs, this study identified key risk factors for recurrent neurological events in patients with symptomatic CCM. A simple scoring system and risk stratification calculator was then created to predict future neurological events in patients with symptomatic CCMs.

METHODS This was a dual-center, prospectively acquired, retrospectively analyzed cohort study. Adult patients who presented with symptomatic CCMs causing focal neurological deficits or seizures were uniformly treated and clinically followed from the time of diagnosis onward. Baseline variables included age, sex, history of intracerebral hemorrhage, lesion multiplicity, location, eloquence, size, number of past neurological events, and duration since last event. Stepwise multivariable Cox regression was used to derive independent predictors of recurrent neurological events, and predictive accuracy was assessed. A scoring system based on the relative magnitude of each risk factor was devised, and KaplanMeier curve analysis was used to compare event-free survival among patients with different score values. Subsequently, 1-, 2-, and 5-year neurological event rates were calculated for every score value on the basis of the final model.

RESULTS In total, 126 (47%) of 270 patients met the inclusion criteria. During the mean (interquartile range) follow-up of 54.4 (12–66) months, 55 patients (44%) experienced recurrent neurological events. Multivariable analysis yielded 4 risk factors: bleeding at presentation (HR 1.92, p = 0.048), large size ≥ 12 mm (HR 2.06, p = 0.016), eloquent location (HR 3.01, p = 0.013), and duration ≤ 1 year since last event (HR 9.28, p = 0.002). The model achieved an optimism-corrected c-statistic of 0.7209. All factors were assigned 1 point, except duration from last event which was assigned 2 points. The acronym BLED 2 summarizes the scoring system. The 1-, 2-, and 5-year risks of a recurrent neurological event ranged from 0.6%, 1.2%, and 2.3%, respectively, for patients with a BLED 2 score of 0, to 48%, 74%, and 93%, respectively, for patients with a BLED 2 score of 5.

CONCLUSIONS The BLED 2 risk score predicts prospective neurological events in symptomatic CCM patients.

Complications of degenerative lumbar spondylolisthesis and stenosis surgery in patients over 80 s

Acta Neurochirurgica (2022) 164:923–931

Degenerative spondylolisthesis (DS) is a debilitating condition that carries a high economic burden. As the global population ages, the number of patients over 80 years old demanding spinal fusion is constantly rising. Therefore, neurosurgeons often face the important decision as to whether to perform surgery or not in this age group, commonly perceived at high risk for complications.

Methods Six hundred seventy-eight elder patients, who underwent posterolateral lumbar fusion for DS (performed in three different centers) from 2012 to 2020, were screened for medical, early and late surgical complications and for the presence of potential preoperative risk factors. Patients were divided in three categories based on their age: (1) 60–69 years, (2) 70–79 years, (3) 80 and over. Multiple logistic regression was used to determine the predictive power of age and of other risk factors (i.e., ASA score; BMI; sex; presence or absence of insulin-dependent and -independent diabetes, use of anticoagulants, use of antiaggregants and osteoporosis) for the development of postoperative complications.

Results In univariate analysis, age was significantly and positively correlated with medical complications. However, when controls for other risk factors were added in the regressions, age never reached significance, with the only noticeable exception of cerebrovascular accidents. ASA score and BMI were the two risk factors that significantly correlated with the higher numbers of complication rates (especially medical).

Conclusion Patients of different age but with comparable preoperative risk factors share similar postoperative morbidity rates. When considering octogenarians for lumbar arthrodesis, the importance of biological age overrides that of chronological.

Risk factors for polyetheretherketone cage subsidence following minimally invasive transforaminal lumbar interbody fusion

Acta Neurochirurgica (2021) 163:2557–2565

Interbody cage subsidence is a postoperative complication leading to poor outcomes after minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). This study aimed to identify risk factors of cage subsidence in lumbar spinal diseases after MIS-TLIF using polyetheretherketone (PEEK) cage.

Methods In this retrospective cohort study, plain radiographs and three-dimensional computed tomography (3D-CT) performed 12 months after MIS-TLIF were evaluated, and the risk of cage subsidence was calculated with odds ratio (OR), confidence interval (CI), and logistic regression analysis.

Results A total of 114 patients (mean age, 65 years) and 135 levels were included in this study: 80 (59.3%) with and 55 (40.7%) without cage subsidence. Multifidus atrophy showed the strongest association with PEEK cage subsidence (p < 0.001). Compared to those with normal mass, the odds of PEEK cage subsidence were 76.0 (95% CI: 3.9–1472.9) for severe atrophy. The factors significantly associated with cage subsistence were posterior cage position (OR = 4.2; p = 0.005), cage height ≥ 12 mm (OR = 7.6; p = 0.008), use of an autograft mixed with demineralized bone matrix (DBM) (OR = 5.8; p = 0.002), body mass index (BMI) > 27.5 kg/m2 (OR = 4.2; p = 0.03), and titanium-coated PEEK (Ti-PEEK) cage-type (OR = 38.4, p = 0.02).

Conclusions In MIS-TLIF with a PEEK cage, the factors associated with an increased risk of cage subsidence were higher BMI, increased severity of multifidus muscle atrophy, Ti-coated PEEK cage-type, cage height ≥ 12 mm, use of DBM mixed autograft, and posterior cage position.

Risk factors for reoperation after lumbar total disc replacement at short-, mid-, and long-term follow-up


The reoperation rate following TDR (Total Disc replacement) has been established at short- and mid-term time points through the Food and Drug Administration Investigational Device Exemption (FDA IDE) trials. However, these trials include highly selected centers and surgeons with strict governance of indications. The utilization of TDR throughout the community needs further analysis.


To identify the risk factors for lumbar spine reoperation in patients undergoing lumbar total disc replacement (TDR) at short-, mid-, and long-term follow-up.


This study is a multi-center retrospective cohort study utilizing the New York Statewide Planning and Research Cooperative System database.


We identified 1,368 patients who underwent an elective primary lumbar TDR in New York State between January 1, 2005 and September 30, 2013.


The primary functional outcome of interest was lumbar reoperation, specifically the evaluation of independent risk factors for lumbar reoperation at a minimum of 2 years, with sub-analyses performed at 5 and ten years.


International Classification of Diseases, Ninth revision codes were utilized to identify patients undergoing a primary lumbar TDR. We excluded patients with primary/revision lumbar fusion procedures and revision disc replacement procedures. Hospital academic status was determined by the Accreditation Council for Graduate Medical Education. Unique encrypted patient identifiers allowed for longitudinal follow-up for reoperation. Logistic regression models compared reoperation and no-reoperation cohorts, and were performed on sub-analyses for significant univariate predictors of reoperation.


Between January 2005 and September 2013, 1368 patients underwent a primary lumbar TDR. Reoperation occurred in 8.8% by 2 years, 15.8% by 5 years, and 19.5% by ten years. Diabetics were more likely to have reoperations (7.5% vs 3.8%, p=.013). Teaching hospitals experienced a decreased reoperation rate compared to nonteaching hospitals at 2-year (5.0% vs 10.5%, p=.002), 5-year (10.7% vs 17.9%, p=.002) and 10-year (11.7% vs 21.9%, p=.045) follow-up. Lumbar fusion was the most common reoperation (14.2%).


We identified an 8.8% reoperation rate after inpatient lumbar TDR at 2-years, 15.8% at 5-years, and 19.5% at 10-years. When stratifying by teaching status, reoperation rates at teaching centers align with those reported in FDA IDE studies. Diabetes was the only patient factor influencing reoperation rate. There is a growing consensus that lumbar TDR is a durable and appropriate surgical option for lumbar degenerative disc disease. Proper indications are crucial to obtaining good outcomes with lumbar TDR.


A clinical study of ocular motor nerve functions after petroclival meningioma resection

Acta Neurochirurgica (2020) 162:1249–1257

Ocular motor dysfunction is one of the most common postoperative complications of petroclival meningioma. However, its incidence, recovery rate, and independent risk factors remain poorly explored.

Methods: A prospective analysis of 31 petroclival meningiomas was performed. Operative approaches were selected by utilizing a new 6-region classification of petroclival meningiomas we proposed. Two scores were used to evaluate the functions of the oculomotor and abducens nerves. Pearson correlation analysis and binary logistic regression analysis were used to identify independent risk factors for intraoperative oculomotor and abducens nerve injury.

Results: Postoperative new-onset dysfunctions in the pupillary light reflex and eye/eyelid movements as well as abducens paralysis were detected in eight (25.8%), ten (32.3%) and twelve (38.7%) cases, respectively. Their corresponding recovery rates after 6 months of follow-up were 75% (6/8), 80% (8/10), and 83.3% (10/12), respectively, and their mean times to start recovery were 4.03, 2.43, and 2.5 months, respectively. Tumor invasion into the suprasellar region/sphenoid sinus was the only risk factor for dysfunctions in both the pupillary light reflex (p = 0.001) and eye/ eyelid movements (p = 0.002). Intraoperative utilization of the infratrigeminal interspace was the only risk factor for dysfunction in eyeball abduction movement (p = 0.004).

Conclusions: Dysfunctions of the oculomotor and abducens nerves recovered within 6 months postoperatively. Tumor extension into the suprasellar region/sphenoid sinus was the only risk factor for oculomotor nerve paralysis. Eye/eyelid movements were more sensitive than the pupillary light reflex in reflecting nerve dysfunctions. Intraoperative utilization of the infratrigeminal interspace was the only risk factor for abducens nerve paralysis.

Unruptured intracranial aneurysm growth trajectory: occurrence and rate of enlargement in 520 longitudinally followed cases

J Neurosurg 132:1077–1087, 2020

As imaging technology has improved, more unruptured intracranial aneurysms (UIAs) are detected incidentally. However, there is limited information regarding how UIAs change over time to provide stratified, patient-specific UIA follow-up management. The authors sought to enrich understanding of the natural history of UIAs and identify basic UIA growth trajectories, that is, the speed at which various UIAs increase in size.

METHODS From January 2005 to December 2015, 382 patients diagnosed with UIAs (n = 520) were followed up at UCLA Medical Center through serial imaging. UIA characteristics and patient-specific variables were studied to identify risk factors associated with aneurysm growth and create a predicted aneurysm trajectory (PAT) model to differentiate aneurysm growth behavior.

RESULTS The PAT model indicated that smoking and hypothyroidism had a large effect on the growth rate of large UIAs (≥ 7 mm), while UIAs < 7 mm were less influenced by smoking and hypothyroidism. Analysis of risk factors related to growth showed that initial size and multiplicity were significant factors related to aneurysm growth and were consistent across different definitions of growth. A 1.09-fold increase in risk of growth was found for every 1-mm increase in initial size (95% CI 1.04–1.15; p = 0.001). Aneurysms in patients with multiple aneurysms were 2.43-fold more likely to grow than those in patients with single aneurysms (95% CI 1.36–4.35; p = 0.003). The growth rate (speed) for large UIAs (≥ 7 mm; 0.085 mm/month) was significantly faster than that for UIAs < 3 mm (0.030 mm/month) and for males than for females (0.089 and 0.045 mm/month, respectively; p = 0.048).

CONCLUSIONS Analyzing longitudinal UIA data as continuous data points can be useful to study the risk of growth and predict the aneurysm growth trajectory. Individual patient characteristics (demographics, behavior, medical history) may have a significant effect on the speed of UIA growth, and predictive models such as PAT may help optimize follow-up frequency for UIA management.

Comprehensive analysis of perforator territory infarction on postoperative diffusion-weighted imaging in patients with surgically treated unruptured intracranial saccular aneurysms

J Neurosurg 132:1088–1095, 2020

Perforator territory infarction (PTI) is still a major problem needing to be solved to achieve good outcomes in aneurysm surgery. However, details and risk factors of PTI diagnosed on postoperative MRI remain unknown. The authors aimed to investigate the details of PTI on postoperative diffusion-weighted imaging (DWI) in patients with surgically treated unruptured intracranial saccular aneurysms (UISAs).

METHODS The data of 848 patients with 1047 UISAs were retrospectively evaluated. PTI was diagnosed on DWI, which was performed the day after aneurysm surgery. Clinical and radiological characteristics were compared between UISAs with and without PTI. Poor outcome was defined as an increase in 1 or more modified Rankin Scale scores at 12 months after aneurysm surgery.

RESULTS Postoperative DWI was performed in all cases, and it revealed PTI in 56 UISA cases (5.3%). Forty-three PTIs occurred without direct injury and occlusion of perforators (43 of 56, 77%). Poor outcome was more frequently observed in the PTI group (17 of 56, 30%) than the non-PTI group (57 of 1047, 5.4%) (p < 0.0001). Thalamotuberal arteries (p < 0.01), lateral striate arteries (p < 0.01), Heubner’s artery (p < 0.01), anterior median commissural artery (p < 0.05), terminal internal carotid artery perforators (p < 0 0.01), and basilar artery perforator (p < 0 0.01) infarctions were related to poor outcome by adjusted residual analysis. On multivariate analysis, statin use (OR 10, 95% CI, 3.3–31; p < 0.0001), specific aneurysm locations (posterior communicating artery [OR 4.1, 95% CI 2.1–8.1; p < 0.0001] and basilar artery [OR 3.1, 95% CI 1.1–8.9; p = 0.031]), larger aneurysm size (OR 1.1, 95% CI 1.1–1.2; p = 0.043), and permanent decrease of motor evoked potential (OR 38, 95% CI 3.1–468; p = 0.0045) were related to PTI.

CONCLUSIONS Despite efforts to avoid PTI, it occurred even without direct injury, occlusion of perforators, or evoked potential abnormality. Therefore, surgical treatment of UISAs, especially with the aforementioned risk factors of PTI, should be more carefully considered. The evaluation of PTI in the territory of the above-mentioned perforators could be useful in helping predict the clinical course in patients after aneurysm surgery.

Cavernous sinus aneurysms: risk of growth over time and risk factors

J Neurosurg 132:22–26, 2020

Cavernous internal carotid artery (ICA) aneurysms are frequently diagnosed incidentally and the benign natural history of these lesions is well known, but there is limited information assessing the risk of growth in untreated patients. The authors sought to assess and analyze risk factors in patients with cavernous ICA aneurysms and compare them to those of patients with intracranial berry aneurysms in other locations.

METHODS Data from consecutive patients who were diagnosed with a cavernous ICA aneurysm were retrospectively reviewed. The authors evaluated patients for the incidence of cavernous ICA aneurysm growth and rupture. In addition, the authors analyzed risk factors for cavernous ICA aneurysm growth and compared them to risk factors in a population of patients diagnosed with intracranial berry aneurysms in locations other than the cavernous ICA during the same period.

RESULTS In 194 patients with 208 cavernous ICA aneurysms, the authors found a high risk of aneurysm growth (19.2% per patient-year) in patients with large/giant aneurysms. Size was significantly associated with higher risk of growth. Compared to patients with intracranial berry aneurysms in other locations, patients with cavernous ICA aneurysms were significantly more likely to be female and have a lower incidence of hypertension.

CONCLUSIONS Aneurysms of the cavernous ICA are benign lesions with a negligible risk of rupture but a definite risk of growth. Aneurysm size was found to be associated with aneurysm growth, which can be associated with new onset of symptoms. Serial follow-up imaging of a cavernous ICA aneurysm might be indicated to monitor for asymptomatic growth, especially in patients with larger lesions.


A Meta-Analysis of Risk Factors for the Formation of de novo Intracranial Aneurysms

Neurosurgery, Volume 85 (4) 2019, 454–465

Understanding the risk factors for the formation of de novo intracranial aneurysms (IAs) is important for patients who have ever suffered a cerebral aneurysm.

OBJECTIVE: To estimate the risk factors for the development of a de novo IA to identify which patients need more aggressive surveillance after aneurysm treatment.

METHODS: We followed the preferred reporting items for systematic reviews and metaanalyses guidelines and searched the PubMed, CENTRAL, EMBASE, and LILACS databases using the key words cerebral aneurysms, de novo, IAs, risk factors combined using and/or. The search was performed in July 2017.We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using RevMan 5.3 (Cochrane, London, United Kingdom) to evaluate risk factors. Statistical significance was set at P < .05.

RESULTS: The analysis included 14 studies involving 6389 patients, of whom 197 patients had de novo IAs. The main risk factors for formation included sex (OR = 1.82, 95% CI [1.30,2.56], P = .0005, female vs male), age <40 yr (OR = 2.96, 95% CI [1.76,4.96], P < .0001), family history (OR = 2.05, 95% CI [1.07,3.93], P = .03), smoking history (OR = 2.73, 95% CI [1.81,4.12], P < .0001), and multiple saccular intracranial aneurysms (sIAs) at first diagnosis (OR = 2.10, 95% CI [1.12,3.91], P = .02), internal carotid artery (ICA) as the initial site (OR = 2.58, 95% CI [1.43,4.68], P = .002). Heterogeneous analysis showed that these I 2 were less than 50% and the results were reliable.

CONCLUSION: Observational evidence identified multiple clinical and anatomic risk factors for the formation of de novo IAs, including female sex, age <40 yr, family history, smoking history, multiple sIAs at first diagnosis, and IC as the initial site. More aggressive long-term angiographic follow-up with digital subtraction angiography, computed tomography angiography, or magnetic resonance angiography is recommended for these patients.

Prerupture Intracranial Aneurysm Morphology in Predicting Risk of Rupture

Neurosurgery 84:132–140, 2019

Maximal size and other morphological parameters of intracranial aneurysms (IAs) are used when deciding if an IA should be treated prophylactically. These parameters are derived from postrupture morphology. As time and rupture may alter the aneurysm geometry, possiblemorphological predictors of a rupture should be established in prerupture aneurysms.

OBJECTIVE: To identify morphological parameters of unruptured IAs associated with later rupture.

METHODS: Nationwide matched case-control study. Twelve IAs that later ruptured were matched 1:2 with 24 control IAs that remained unruptured during a median follow-up time of 4.5 (interquartile range, 3.7-8.2) yr. Morphological parameters were automatically measured on 3-dimensional models constructed from angiograms obtained at time of diagnosis. Cases and controls were matched by aneurysm location and size, patient age and sex, and the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from another aneurysm, and site of aneurysm) score did not differ between the 2 groups.

RESULTS: Only inflow angle was significantly different in cases vs controls in univariate analysis (P = .045), and remained significant in multivariable analysis. Maximal size correlated with size ratio in both cases and controls (P = .015 and <.001, respectively). However, maximal size and inflow angle were correlated in cases but not in controls (P = .004. and .87, respectively).

CONCLUSION: A straighter inflow angle may predispose an aneurysm to changes that further increase risk of rupture. Traditional parameters of aneurysm morphology may be of limited value in predicting IA rupture.



External validation of cerebral aneurysm rupture probability model with data from two patient cohorts

Acta Neurochirurgica (2018) 160:2425–2434

For a treatment decision of unruptured cerebral aneurysms, physicians and patients need to weigh the risk of treatment against the risk of hemorrhagic stroke caused by aneurysm rupture. The aim of this study was to externally evaluate a recently developed statistical aneurysm rupture probability model, which could potentially support such treatment decisions.

Methods Segmented image data and patient information obtained from two patient cohorts including 203 patients with 249 aneurysms were used for patient-specific computational fluid dynamics simulations and subsequent evaluation of the statistical model in terms of accuracy, discrimination, and goodness of fit. The model’s performance was further compared to a similaritybased approach for rupture assessment by identifying aneurysms in the training cohort that were similar in terms of hemodynamics and shape compared to a given aneurysm from the external cohorts.

Results When applied to the external data, the model achieved a good discrimination and goodness of fit (area under the receiver operating characteristic curve AUC = 0.82), which was only slightly reduced compared to the optimism-corrected AUC in the training population (AUC = 0.84). The accuracy metrics indicated a small decrease in accuracy compared to the training data (misclassification error of 0.24 vs. 0.21). The model’s prediction accuracy was improved when combined with the similarity approach (misclassification error of 0.14).

Conclusions The model’s performance measures indicated a good generalizability for data acquired at different clinical institutions. Combining the model-based and similarity-based approach could further improve the assessment and interpretation of new cases, demonstrating its potential use for clinical risk assessment.

Subarachnoid hemorrhage after surgical treatment of unruptured intracranial aneurysms

J Neurosurg 129:490–497, 2018

Only a few previous studies have investigated subarachnoid hemorrhage (SAH) after surgical treatment in patients with unruptured intracranial aneurysms (UIAs). Given the improvement in long-term outcomes of embolization, more extensive data are needed concerning the true rupture rates after microsurgery in order to provide reliable information for treatment decisions. The purpose of this study was to investigate the incidence of and risk factors for postoperative SAH in patients with surgically treated UIAs.

METHODS Data from 702 consecutive patients harboring 852 surgically treated UIAs were evaluated. Surgical treatments included neck clipping (complete or incomplete), coating/wrapping, trapping, proximal occlusion, and bypass surgery. Clippable UIAs were defined as UIAs treated by complete neck clipping. The annual incidence of postoperative SAH and risk factors for SAH were studied using Kaplan-Meier survival analysis and Cox proportional hazards regression models.

RESULTS The patients’ median age was 64 years (interquartile range [IQR] 56–71 years). Of 852 UIAs, 767 were clippable and 85 were not. The mean duration of follow-up was 731 days (SD 380 days). During 1708 aneurysm years, there were 4 episodes of SAH, giving an overall average annual incidence rate of 0.23% (95% CI 0.12%–0.59%) and an average annual incidence rate of 0.065% (95% CI 0.0017%–0.37%) for clippable UIAs (1 episode of SAH, 1552 aneurysmyears). Basilar artery location (adjusted hazard ratio [HR] 23, 95% CI 2.0–255, p = 0.0012) and unclippable UIA status (adjusted HR 15, 95% CI 1.1–215, p = 0.046) were significantly related to postoperative SAH. An excellent outcome (modified Rankin Scale score of 0 or 1) was achieved in 816 (95.7%) of 852 cases overall and in 748 (98%) of 767 clippable UIAs at 12 months.

CONCLUSIONS In this large case series, microsurgical treatment of UIAs was found to be safe and effective. Aneurysm location and unclippable morphologies were related to postoperative SAH in patients with surgically treated UIAs.


Characteristics of Unruptured Compared to Ruptured Intracranial Aneurysms: A Multicenter Case–Control Study

Neurosurgery 83:43–52, 2018

Only a minority of intracranial aneurysms rupture to cause subarachnoid hemorrhage.

OBJECTIVE: To test the hypothesis that unruptured aneurysms have different characteristics and risk factor profiles compared to ruptured aneurysms.

METHODS: We recruited patients with unruptured aneurysms or aneurysmal subarachnoid hemorrhages at 22 UK hospitals between 2011 and 2014. Demographic, clinical, and imaging data were collected using standardized case report forms. We compared risk factors using multivariable logistic regression.

RESULTS: A total of 2334 patients (1729 with aneurysmal subarachnoid hemorrhage, 605 with unruptured aneurysms) were included (mean age 54.22 yr). In multivariable analyses, the following variables were independently associated with rupture status: black ethnicity (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.29-4.56, compared to white) and aneurysm location (anterior cerebral artery/anterior communicating artery [OR 3.21; 95% CI 2.34-4.40], posterior communicating artery [OR 3.92; 95% CI 2.67-5.74], or posterior circulation [OR 3.12; 95% CI 2.08-4.70], compared to middle cerebral artery). The following variables were inversely associated with rupture status: antihypertensive medication (OR 0.65; 95% CI 0.49-0.84), hypercholesterolemia (0.64 OR; 95% CI 0.48-0.85), aspirin use (OR 0.28; 95% CI 0.20-0.40), internal carotid artery location (OR 0.53; 95% CI 0.38-0.75), and aneurysm size (per mm increase; OR 0.76; 95% CI 0.69-0.84).

CONCLUSION: We show substantial differences in patient and aneurysm characteristics between ruptured and unruptured aneurysms. These findings support the hypothesis that different pathological mechanisms are involved in the formation of ruptured aneurysms and incidentally detected unruptured aneurysms. The potential protective effect of aspirin might justify randomized prevention trials in patients with unruptured aneurysms.


A novel score to predict shunt dependency after aneurysmal subarachnoid hemorrhage

J Neurosurg 128:1273–1279, 2018

Feasible clinical scores for predicting shunt-dependent hydrocephalus (SDHC) after aneurysmal subarachnoid hemorrhage (aSAH) are scarce. The chronic hydrocephalus ensuing from SAH score (CHESS) was introduced in 2015 and has a high predictive value for SDHC. Although this score is easy to calculate, several early clinical and radiological factors are required. The authors designed the retrospective analysis described here for external CHESS validation and determination of predictive values for the radiographic Barrow Neurological Institute (BNI) scoring system and a new simplified combined scoring system.

METHODS Consecutive data of 314 patients with aSAH were retrospectively analyzed with respect to CHESS parameters and BNI score. A new score, the shunt dependency in aSAH (SDASH) score, was calculated from independent risk factors identified with multivariate analysis.

RESULTS Two hundred twenty-five patients survived the initial phase after the hemorrhage, and 27.1% of these patients developed SDHC. The SDASH score was developed from results of multivariate analysis, which revealed acute hydrocephalus (aHP), a BNI score of ≥ 3, and a Hunt and Hess (HH) grade of ≥ 4 to be independent risk factors for SDHC (ORs 5.709 [aHP], 6.804 [BNI], and 4.122 [HH]; p < 0.001). All 3 SDHC scores tested (CHESS, BNI, and SDASH) reliably predicted chronic hydrocephalus (ORs 1.533 [CHESS], 2.021 [BNI], and 2.496 [SDASH]; p ≤ 0.001). Areas under the receiver operating curve (AUROC) for CHESS and SDASH were comparable (0.769 vs 0.785, respectively; p = 0.447), but the CHESS and SDASH scores were superior to the BNI grading system for predicting SDHC (BNI AUROC 0.649; p = 0.014 and 0.001, respectively). In contrast to CHESS and BNI scores, an increase in the SDASH score coincided with a monotonous increase in the risk of developing SDHC.

CONCLUSIONS The newly developed SDASH score is a reliable tool for predicting SDHC. It contains fewer factors and is more intuitive than existing scores that were shown to predict SDHC. A prospective score evaluation is needed.

Risk Factors for Readmission with Cerebrospinal Fluid Leakage Within 30 Days of Vestibular Schwannoma Surgery

Neurosurgery 82:630–637, 2018

Cerebrospinal fluid (CSF) leak is a well-recognized complication after surgical resection of vestibular schwannomas and is associated with a number of secondary complications, including readmission and meningitis. OBJECTIVE: To identify risk factors for and timing of 30-d readmission with CSF leak.

METHODS: Patients who had undergone surgical resection of a vestibular schwannoma from 1995 to 2010 were identified in the California Office of Statewide Health Planning and Development database. The most common admission diagnoses were identified by International Classification of Disease, ninth Revision, diagnosis codes, and predictors of readmission with CSF leak were determined using logistic regression.

RESULTS: A total of 6820 patients were identified. CSF leak, though a relatively uncommon cause of admission after discharge (3.52% of all patients), was implicated in nearly half of 490 readmissions (48.98%). Significant independent predictors of readmission with CSF leak were male sex (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.32-2.25), first admission at a teaching hospital (OR 3.32, 95% CI 1.06-10.39), CSF leak during first admission (OR 1.84, 95% CI 1.33-2.55), obesity during first admission (OR 2.10, 95% CI 1.20-3.66), and case volume of first admission hospital (OR of log case volume 0.82, 95% CI 0.70-0.95). Median time to readmission was 6 d from hospital discharge.

CONCLUSION: This study has quantified CSF leak as an important contributor to nearly half of all readmissions following vestibular schwannoma surgery. We propose that surgeons should focus on technical factors that may reduce CSF leakage and take advantage of potential screening strategies for the detection of CSF leakage prior to first admission discharge.

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