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## The meningioma surface factor: a novel approach to quantify shape irregularity on preoperative imaging and its correlation with WHO grade

### OBJECTIVE

Atypical and anaplastic meningiomas account for 20% of all meningiomas. An irregular tumor shape on preoperative MRI has been associated with WHO grade II–III histology. However, this subjective allocation does not allow quantification or comparison. An objective parameter of irregularity could substantially influence resection strategy toward a more aggressive approach. Therefore, the aim of this study was to objectively quantify the level of irregularity on preoperative MRI and predict histology based on WHO grade using this novel approach.

### METHODS

A retrospective study on meningiomas resected between January 2010 and December 2018 was conducted at two neurosurgical centers. This novel approach relies on the theory that a regularly shaped tumor has a smaller surface area than an irregularly shaped tumor with the same volume. A factor was generated using the surface area of a corresponding sphere as a reference, because for a given volume a sphere represents the shape with the smallest surface area possible. Consequently, the surface factor (SF) was calculated by dividing the surface area of a sphere with the same volume as the tumor with the surface area of the tumor. The resulting value of the SF ranges from > 0 to 1. Finally, the SF of each meningioma was then correlated with the corresponding histopathological grading.

### RESULTS

A total of 126 patients were included in this study; 60.3% had a WHO grade I, 34.9% a WHO grade II, and 4.8% a WHO grade III meningioma. Calculation of the SF demonstrated a significant difference in SFs between WHO grade I (SF 0.851) and WHO grade II–III meningiomas (SF 0.788) (p < 0.001). Multivariate analysis identified SF as an independent prognostic factor for WHO grade (OR 0.000009, 95% CI 0.000–0.159; p = 0.020).

### CONCLUSIONS

The SF is a proposed mathematical model for a quantitative and objective measurement of meningioma shape, instead of the present subjective assessment. This study revealed significant differences between the SFs of WHO grade I and WHO grade II–III meningiomas and demonstrated that SF is an independent prognostic factor for WHO grade.

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## Middle meningeal artery embolization for chronic subdural hematoma in cancer patients with refractory thrombocytopenia

### OBJECTIVE

Surgical evacuation of chronic subdural hematoma (SDH) in cancer patients is often contraindicated owing to refractory thrombocytopenia. Middle meningeal artery embolization (MMAE) recently emerged as a potential alternative to surgical evacuation for patients with chronic SDH. The goal of this study was to evaluate the safety and efficacy of MMAE for chronic SDH in cancer patients with refractory thrombocytopenia.

### METHODS

A multiinstitutional registry was reviewed for clinical and radiographic outcomes of cancer patients with transfusion-refractory thrombocytopenia and baseline platelet count < 75 K/µl, who underwent MMAE for chronic SDH.

### RESULTS

MMAE was performed on a total of 31 SDHs in 22 patients, with a mean ± SD (range) platelet count of 42.1 ± 18.3 (9–74) K/µl. At the longest follow-up, 24 SDHs (77%) had reduced in size, with 15 (48%) showing > 50% reduction. Two patients required surgical evacuation after MMAE. There was only 1 procedural complication; however, 16 patients (73%) ultimately died of cancer-related complications. Median survival was significantly longer in the 16 patients with improved SDH than the 6 patients with worsened SDH after MMAE (185 vs 24 days, p = 0.029). Length of procedure, technical success rate, SDH size reduction, and complication rate were not significantly differ between patients who underwent transfemoral and transradial approaches.

### CONCLUSIONS

Transfemoral or transradial MMAE is a potential therapeutic option for thrombocytopenic cancer patients with SDH. However, treatment benefit may be marginal for patients with high disease burden and limited life expectancy. A prospective trial is warranted to address these questions.

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## The neurosurgical management of sinonasal malignancies involving the anterior skull base: a 28-year experience at The MD Anderson Cancer Center

### OBJECTIVE

Sinonasal malignancies that extend to the anterior skull base frequently require neurosurgical intervention. The development of techniques for craniofacial resection revolutionized the management of these neoplasms, but modern and long-term data are lacking, particularly those related to the incorporation of endoscopic techniques and novel adjuvant chemotherapeutics into management schema. The present study was performed to better define the utility of surgical management and to determine factors related to outcome.

### METHODS

Patients who underwent surgery between 1993 and 2020 were included in this retrospective cohort study. Only patients with greater than 6 months of clinical and radiological follow-up were included. Outcome measures included progression, survival, and treatment-related complications.

### RESULTS

Two hundred twenty-five patients were included. The mean clinical follow-up was 6.5 years. The most common histological diagnosis was olfactory neuroblastoma (33%). Overall, metastatic disease and brain invasion were present in 8% and 19% of patients, respectively, at the time of surgery. A lumbar drain was used in 54% of patients. When stratified by decade, higher-stage disease at surgery became more frequent over time (15% of patients had metastatic disease in the 3rd decade of the study period vs 4% in the 1st decade). Despite the inclusion of patients with progressively higher-stage disease, median overall survival (OS) remained stable in each decade at approximately 10 years (p = 0.16). OS was significantly worse in patients with brain invasion (p = 0.006) or metastasis at the time of surgery (p = 0.014). Complications occurred after 28% of operations, but typically resulted in no long-term negative sequelae. Use of a lumbar drain was a significant predictor of complications (p = 0.02). Permanent ophthalmological disabilities were observed after 4% of surgical procedures. One patient died during the perioperative period. Finally, major complications (Clavien-Dindo grade ≥ IIIb) decreased from 27% of patients in the 1st decade to 10% in the 3rd decade (p = 0.007).

### CONCLUSIONS

The surgical management of sinonasal malignancies with anterior skull base involvement is effective and generally safe. Surgical management, however, is only one facet of the overall multimodal management paradigms created to optimize patient outcomes. Survival outcomes have remained stable despite more extensive disease at surgery in patients who have presented in recent decades. The safety of such surgery has improved over time owing to the incorporation of endoscopic surgical techniques and the avoidance of lumbar spinal drainage with open resection.

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## New interinstitutional, multimodal presurgical evaluation protocol associated with improved seizure freedom for poorly defined cases of focal epilepsy in children

### OBJECTIVE

In an attempt to improve postsurgical seizure outcomes for poorly defined cases (PDCs) of pediatric focal epilepsy (i.e., those that are not visible or well defined on 3T MRI), the authors modified their presurgical evaluation strategy. Instead of relying on concordance between video-electroencephalography and 3T MRI and using functional imaging and intracranial recording in select cases, the authors systematically used a multimodal, 3-tiered investigation protocol that also involved new collaborations between their hospital, the Montreal Children’s Hospital, and the Montreal Neurological Institute. In this study, the authors examined how their new strategy has impacted postsurgical outcomes. They hypothesized that it would improve postsurgical seizure outcomes, with the added benefit of identifying a subset of tests contributing the most.

### METHODS

Chart review was performed for children with PDCs who underwent resection following the new strategy (i.e., new protocol [NP]), and for the same number who underwent treatment previously (i.e., preprotocol [PP]); ≥ 1-year follow-up was required for inclusion. Well-defined, multifocal, and diffuse hemispheric cases were excluded. Preoperative demographics and clinical characteristics, resection volumes, and pathology, as well as seizure outcomes (Engel class Ia vs > Ia) at 1 year postsurgery and last follow-up were reviewed.

### RESULTS

Twenty-two consecutive NP patients were compared with 22 PP patients. There was no difference between the two groups for resection volumes, pathology, or preoperative characteristics, except that the NP group underwent more presurgical evaluation tests (p < 0.001). At 1 year postsurgery, 20 of 22 NP patients and 10 of 22 PP patients were seizure free (OR 11.81, 95% CI 2.00–69.68; p = 0.006). Magnetoencephalography and PET/MRI were associated with improved postsurgical seizure outcomes, but both were highly correlated with the protocol group (i.e., independent test effects could not be demonstrated).

### CONCLUSIONS

A new presurgical evaluation strategy for children with PDCs of focal epilepsy led to improved postsurgical seizure freedom. No individual presurgical evaluation test was independently associated with improved outcome, suggesting that it may be the combined systematic protocol and new interinstitutional collaborations that makes the difference rather than any individual test.

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## Outcome after resective epilepsy surgery in the elderly

### OBJECTIVE

The objective of this study was to compare complications, seizures, and neuropsychological outcomes after resective epilepsy surgery in patients ≥ 60 years of age who underwent operations to younger and matched controls.

### METHODS

Charts of 2243 patients were screened for operated patients in the authors’ center between 2000 and 2015. Patients with available postsurgical follow-up data who were operated on at the age of 60 years or older and matched (by gender, histopathology, and side of surgery) controls who were between 20 and 40 years of age at the time of surgery were included. Outcomes regarding postoperative seizure control were scored according to the Engel classification and group comparisons were performed by using chi-square statistics.

### RESULTS

Data of 20 older patients were compared to those of 60 younger controls. Postoperative seizure control was favorable in the majority of the elderly patients (Engel classes I and II: 75% at 12 months, 65% at last follow-up), but the proportion of patients with favorable outcome tended to be larger in the control group (Engel classes I and II: 90% at 12 months, p = 0.092; 87% at last follow-up, p = 0.032, chi-square test). The surgical complication rate was higher in the elderly population (65% vs 27%, p = 0.002), but relevant persistent deficits occurred in 2 patients of each group only. Neuropsychological and behavioral assessments displayed considerable preoperative impairment and additional postoperative worsening, particularly of verbal skills, memory (p < 0.05), and mood in the elderly.

### CONCLUSIONS

The overall favorable postsurgical outcome regarding seizure control and the moderate risk of disabling persistent neurological deficits in elderly patients supports the view that advanced age should not be a barrier per se for resective epilepsy surgery and underscores the importance of an adequate presurgical evaluation and of referral of elderly patients to presurgical assessment.

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## Outcomes of epilepsy surgery in the older population: not too old, not too late

### OBJECTIVE

The prevalence of epilepsy in the older adult population is increasing. While surgical intervention in younger patients is supported by level I evidence, the safety and efficacy of epilepsy surgery in older individuals is less well established. The aim of this study was to evaluate seizure freedom rates and surgical outcomes in older epilepsy patients.

### METHODS

The authors’ institutional electronic database was queried for patients older than 50 who had undergone epilepsy surgery during 2002–2018. Cases were grouped into 50–59, 60–69, and 70+ years old. Seizure freedom at the last follow-up constituted the primary outcome of interest. The institutional analysis was supplemented by a literature review and meta-analysis (random effects model) of all published studies on this topic as well as by an analysis of complication rates, mortality rates, and cost data from a nationwide administrative database (Vizient Inc., years 2016–2019).

### RESULTS

A total of 73 patients (n = 16 for 50–59 years, n = 47 for 60–69, and n = 10 for 70+) were treated at the authors’ institution. The median age was 63 years, and 66% of the patients were female. At a median follow-up of 24 months, seizure freedom was 73% for the overall cohort, 63% for the 50–59 group, 77% for the 60–69 group, and 70% for the 70+ group. The literature search identified 15 additional retrospective studies (474 cases). Temporal lobectomy was the most commonly performed procedure (73%), and mesial temporal sclerosis was the most common pathology (52%), followed by nonspecific gliosis (19%). The pooled mean follow-up was 39 months (range 6–114.8 months) with a pooled seizure freedom rate of 65% (95% CI 59%–72%). On multivariable meta-regression analysis, an older mean age at surgery (coefficient [coeff] 2.1, 95% CI 1.1–3.1, p < 0.001) and the presence of mesial temporal sclerosis (coeff 0.3, 95% CI 0.1–0.6, p = 0.015) were the most important predictors of seizure freedom. Finally, analysis of the Vizient database revealed mortality rates of 0.5%, 1.1%, and 9.6%; complication rates of 7.1%, 10.1%, and 17.3%; and mean hospital costs of $31,977,$34,586, and \$40,153 for patients aged 50–59, 60–69, and 70+ years, respectively.

### CONCLUSIONS

While seizure-free outcomes of epilepsy surgery are excellent, there is an expected increase in morbidity and mortality with increasing age. Findings in this study on the safety and efficacy of epilepsy surgery in the older population may serve as a useful guide during preoperative decision-making and patient counseling.

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## Predictors of functional recovery following surgery for foot drop due to degenerative lumbar disease

### OBJECTIVE

Surgery for foot drop secondary to lumbar degenerative disease is not always associated with postoperative functional improvement. It is still unclear whether early decompression results in better functional recovery and how soon surgery should be performed. This study aimed to evaluate predicting factors that affect short- and long-term recovery outcomes and to explore the relationship between timing of lumbar decompression and recovery from foot drop in an attempt to identify a cutoff time from symptom onset until decompression for optimal functional improvement.

### METHODS

The authors collected demographic, clinical, and radiographic data on patients who underwent surgery for foot drop due to lumbar degenerative disease. Clinical data included tibialis anterior muscle (TAM) strength before and after surgery, duration of preoperative motor weakness, and duration of radicular pain until surgery. TAM strength was recorded at the immediate postoperative period and 1 month after surgery while long-term follow-up on functional outcomes were obtained at ≥ 2 years postsurgery by telephone interview. Data including degree and duration of preoperative motor weakness as well as the occurrence of pain and its duration were collected to analyze their impact on short- and long-term outcomes.

### RESULTS

The majority of patients (70%) showed functional improvement within 1 month postsurgery and 40% recovered to normal or near-normal strength. Univariate analysis revealed a trend toward lower improvement rates in patients with preoperative weakness of more than 3 weeks (33%) compared with patients who were operated on earlier (76.5%, p = 0.034). In a multivariate analysis, the only significant predictor for maximal strength recovery was TAM strength before surgery (OR 6.80, 95% CI 1.38–33.42, p = 0.018). Maximal recovery by 1 month after surgery was significantly associated with sustained long-term functional improvement (p = 0.006).

### CONCLUSIONS

Early surgery may improve the recovery rate in patients with foot drop caused by lumbar degenerative disease, yet the strongest predictor for the extent of recovery is the severity of preoperative TAM weakness. Maximal recovery in the short-term postoperative period is associated with sustained long-term functional improvement and independence.

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## Predictors of long-term clinical outcomes in adult patients after lumbar total disc replacement: development and validation of a prediction model

### OBJECTIVE

Long-term outcomes of single-level lumbar arthroplasty are understood to be very good, with the most recent Investigational Device Exemption (IDE) trial showing a < 5% reoperation rate at the close of the 7-year study. This post hoc analysis was conducted to determine whether specific patients from the activL IDE data set had better outcomes than the mean good outcome of the IDE trial, as well as to identify contributing factors that could be optimized in real-world use.

### METHODS

Univariable and multivariable logistic regression models were developed using the randomized patient set (n = 283) from the activL trial and used to identify predictive factors and to derive risk equations. The models were internally validated using the randomized patient set and externally validated using the nonrandomized patient set (n = 52) from the activL trial. Predictive power was assessed using area under the receiver operating characteristic curve analysis.

### RESULTS

Two factors were significantly associated with achievement of better than the mean outcomes at 7 years. Randomization to receive the activL device was positively associated with better than the mean visual analog scale (VAS)–back pain and Oswestry Disability Index (ODI) scores, whereas preoperative narcotics use was negatively associated with better than the mean ODI score. Preoperative narcotics use was also negatively associated with return to unrestricted full-time work. Other preoperative factors associated with positive outcomes included unrestricted full-time work, working manual labor after index back injury, and decreasing disc height. Older age, greater VAS–leg pain score, greater ODI score, female sex, and working manual labor before back injury were identified as preoperative factors associated with negative outcomes. Preoperative BMI, VAS–back pain score, back pain duration ≥ 1 year, SF-36 physical component summary score, and recreational activity had no effect on outcomes.

### CONCLUSIONS

Lumbar total disc replacement for symptomatic single-level lumbar degenerative disc disease is a well-established option for improving long-term patient outcomes. Discontinuing narcotics use may further improve patient outcomes, as this analysis identified associations between no preoperative narcotics use and better ODI score relative to the mean score of the activL trial at 7 years and increased likelihood of return to work within 7 years. Other preoperative factors that may further improve outcomes included unrestricted full-time work, working manual labor despite back injury, sedentary work status before back injury, and randomization to receive the activL device. Tailoring patient care before total disc replacement may further improve patient outcomes.

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## Quick cell-free DNA testing for the prediction of postconcussion syndrome: a single-center prospective pilot trial

### OBJECTIVE

Mild traumatic brain injury (mTBI) is a major cause of emergency room (ER) admission. Thirty percent of mTBI patients have postconcussion syndrome (PCS), and 15% have symptoms for over a year. This population is underdiagnosed and does not receive appropriate care. The authors proposed a fast and inexpensive fluorometric measurement of circulating cell-free DNA (cfDNA) as a biomarker for PCS. cfDNA is a proven, useful marker of a variety of acute pathological conditions such as trauma and acute illness.

### METHODS

Thirty mTBI patients were recruited for this prospective single-center trial. At admission, patients completed questionnaires and blood was drawn to obtain cfDNA. At 3–4 months after injury, 18 patients returned for cognitive assessments with questionnaires and the Color Trails Test (CTT). The fast SYBR Gold assay was used to measure cfDNA.

### RESULTS

Seventeen men and 13 women participated in this trial. The mean ± SD age was 50.9 ± 13.9 years. Of the 18 patients who returned for cognitive assessment, one-third reported working fewer hours, 4 (22.2%) changed their driving patterns, and 5 (27.7%) reduced or stopped performing physical activity. The median cfDNA level of the mTBI group was greater than that of the matched healthy control group (730.5 vs 521.5 ng/ml, p = 0.0395). Admission cfDNA concentration was negatively correlated with performance on the CTT1 and CTT2 standardized tests (r = −0.559 and −0.599), meaning that greater cfDNA level was correlated with decreased cognitive performance status. The performance of the patients with normal cfDNA level included in the mTBI group was similar to that of the healthy participants. In contrast, the increased cfDNA group (> 800 ng/ml) had lower scores on the CTT tests than the normal cfDNA group (p < 0.001). Furthermore, patients with moderate/severe cognitive impairment according to CTT1 results had a greater median cfDNA level than the patients with scores indicating mild impairment or normal function (1186 vs 473.5 ng/ml, p = 0.0441, area under the receiver operating characteristic curve = 0.8393).

### CONCLUSIONS

The data from this pilot study show the potential to use cfDNA, as measured with a fast test, as a biomarker to screen for PCS in the ER. A large-scale study is required to establish the value of cfDNA as an early predictor of PCS.

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## Retrolabyrinthine transsigmoid approach to complex parabrainstem tumors in the posterior fossa

### OBJECTIVE

The surgical management of large and complex tumors of the posterior fossa poses a formidable challenge in neurosurgery. The standard retrosigmoid craniotomy approach has been performed at most neurosurgical centers; however, the retrosigmoid approach may not provide enough working space without significant retraction of the cerebellum. The transsigmoid approach provides wider and shallower surgical fields; however, there have been few clinical and no cadaveric studies on its usefulness. In the present study, the authors describe the transsigmoid approach in clinical cases and cadaveric specimens.

### METHODS

For the clinical study, the authors retrospectively reviewed the medical records and operative charts of patients who had been surgically treated for parabrainstem tumors using the transsigmoid approach between 1997 and 2019. They analyzed patient demographic and clinical data, as well as surgical and clinical outcomes. In the cadaveric study, they compared the surgical views obtained in different approaches (retrosigmoid, presigmoid, retrolabyrinthine, and transsigmoid) and measured the sigmoid sinus width at the level of the endolymphatic sac and the distance between the anterior edge of the sigmoid sinus and the endolymphatic sac on 35 sides in 19 cadaveric specimens.

### RESULTS

A total of 21 patients (6 males and 15 females) with a mean age of 42.2 (range 15–67) years were included in the clinical study. Eleven patients had meningioma, 7 had vestibular schwannoma, 2 had hemangioblastoma, and 1 had epidermoid cyst. Gross-total, near-total, and subtotal removal were achieved in 7 (33.3%), 3 (14.3%), and 11 (52.4%) patients, respectively. In the cadaveric study, 19 cadaveric specimens were used. The sigmoid sinus was cut in the middle, and the incision was extended from the retrosigmoid to the presigmoid dura. The dura was then retracted upward and downward like opening a door. The results indicated that this technique can widen the operative field anteriorly by approximately 2 cm as compared to the retrosigmoid approach and provides a better view anterior to the brainstem.

### CONCLUSIONS

The transsigmoid approach is useful for complex parabrainstem tumors in the posterior fossa because it provides a wider and shallower operative view with less retraction of the cerebellum. This enables safer tumor removal with less damage to important structures in the posterior fossa, resulting in better operative and clinical outcomes.