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5-ALA fluorescence for intraoperative visualization of spinal ependymal tumors and identification of unexpected residual tumor tissue: experience in 31 patients

Matthias Millesi, Barbara Kiesel, Vanessa Mazanec, Lisa I. Wadiura, Adelheid Wöhrer, Johannes Herta, Stefan Wolfsberger, Klaus Novak, Julia Furtner, Karl Rössler, Engelbert Knosp, and Georg Widhalm

OBJECTIVE

Gross-total resection (GTR) is the treatment of choice in the majority of patients suffering from spinal ependymal tumors. In such tumors, the extent of resection (EOR) is considered the key factor for tumor recurrence and thus patient prognosis. However, incomplete resection is not uncommon and leads to increased risk of tumor recurrence. One important cause of incomplete resection is insufficient intraoperative visualization of tumor tissue as well as residual tumor tissue. Therefore, the authors investigated the value of 5-aminolevulinic acid (5-ALA)–induced fluorescence in a series of spinal ependymal tumors for improved tumor visualization.

METHODS

Adult patients who underwent preoperative 5-ALA administration and surgery for a spinal ependymal tumor were included in this study. For each tumor, a conventional white-light microsurgical resection was performed. Additionally, the fluorescence status (strong, vague, or no fluorescence) and fluorescence homogeneity (homogenous or inhomogeneous) of the spinal ependymal tumors were evaluated during surgery using a modified neurosurgical microscope. In intramedullary tumor cases with assumed GTR, the resection cavity was investigated for potential residual fluorescing foci under white-light microscopy. In cases with residual fluorescing foci, these areas were safely resected and the corresponding samples were histopathologically screened for the presence of tumor tissue.

RESULTS

In total, 31 spinal ependymal tumors, including 27 intramedullary tumors and 4 intradural extramedullary tumors, were included in this study. Visible fluorescence was observed in the majority of spinal ependymal tumors (n = 25, 81%). Of those, strong fluorescence was noted in 23 of these cases (92%), whereas vague fluorescence was present in 2 cases (8%). In contrast, no fluorescence was observed in the remaining 6 tumors (19%). Most ependymal tumors demonstrated an inhomogeneous fluorescence effect (17 of 25 cases, 68%). After assumed GTR in intramedullary tumors (n = 15), unexpected residual fluorescing foci within the resection cavity could be detected in 5 tumors (33%). These residual fluorescing foci histopathologically corresponded to residual tumor tissue in all cases.

CONCLUSIONS

This study indicates that 5-ALA fluorescence makes it possible to visualize the majority of spinal ependymal tumors during surgery. Unexpected residual tumor tissue could be detected with the assistance of 5-ALA fluorescence in approximately one-third of analyzed intramedullary tumors. Thus, 5-ALA fluorescence might be useful to increase the EOR, particularly in intramedullary ependymal tumors, in order to reduce the risk of tumor recurrence.

In Journal of Neurosurgery: Spine Publish Before Print

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Clinical and genomic factors associated with seizures in meningiomas

Trisha P. Gupte, Chang Li, Lan Jin, Kanat Yalcin, Mark W. Youngblood, Danielle F. Miyagishima, Ketu Mishra-Gorur, Amy Y. Zhao, Joseph Antonios, Anita Huttner, Declan McGuone, Nicholas A. Blondin, Joseph N. Contessa, Yawei Zhang, Robert K. Fulbright, Murat Gunel, Zeynep Erson-Omay, and Jennifer Moliterno

OBJECTIVE

The association of seizures with meningiomas is poorly understood. Moreover, any relationship between seizures and the underlying meningioma genomic subgroup has not been studied. Herein, the authors report on their experience with identifying clinical and genomic factors associated with preoperative and postoperative seizure presentation in meningioma patients.

METHODS

Clinical and genomic sequencing data on 394 patients surgically treated for meningioma at Yale New Haven Hospital were reviewed. Correlations between clinical, histological, or genomic variables and the occurrence of preoperative and postoperative seizures were analyzed. Logistic regression models were developed for assessing multiple risk factors for pre- and postoperative seizures. Mediation analyses were also conducted to investigate the causal pathways between genomic subgroups and seizures.

RESULTS

Seventeen percent of the cohort had presented with preoperative seizures. In a univariate analysis, patients with preoperative seizures were more likely to have tumors with a somatic NF2 mutation (p = 0.020), WHO grade II or III tumor (p = 0.029), atypical histology (p = 0.004), edema (p < 0.001), brain invasion (p = 0.009), and worse progression-free survival (HR 2.68, 95% CI 1.30–5.50). In a multivariate analysis, edema (OR 3.11, 95% CI 1.46–6.65, p = 0.003) and atypical histology (OR 2.00, 95% CI 1.03–3.90, p = 0.041) were positive predictors of preoperative seizures, while genomic subgroup was not, such that the effect of an NF2 mutation was indirectly mediated through atypical histology and edema (p = 0.012). Seizure freedom was achieved in 83.3% of the cohort, and only 20.8% of the seizure-free patients, who were more likely to have undergone gross-total resection (p = 0.031), were able to discontinue antiepileptic drug use postoperatively. Preoperative seizures (OR 3.54, 95% CI 1.37–9.12, p = 0.009), recurrent tumors (OR 2.89, 95% CI 1.08–7.74, p = 0.035), and tumors requiring postoperative radiation (OR 2.82, 95% CI 1.09–7.33, p = 0.033) were significant predictors of postoperative seizures in a multivariate analysis.

CONCLUSIONS

Seizures are relatively common at meningioma presentation. While NF2-mutated tumors are significantly associated with preoperative seizures, the association appears to be mediated through edema and atypical histology. Patients who undergo radiation and/or have a recurrence are at risk for postoperative seizures, regardless of the extent of resection. Preoperative seizures may indeed portend a more potentially aggressive molecular entity and challenging clinical course with a higher risk of recurrence.

In Journal of Neurosurgery Publish Before Print

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Correlation of vertebral trabecular attenuation in Hounsfield units and the upper instrumented vertebra with proximal junctional failure after surgical treatment of degenerative lumbar disease

Qi Wang, Chi Wang, Xiaobo Zhang, Fanqi Hu, Wenhao Hu, Teng Li, Yan Wang, and Xuesong Zhang

OBJECTIVE

The aim of this study was to investigate whether bone mineral density (BMD) measured in Hounsfield units (HUs) is correlated with proximal junctional failure (PJF).

METHODS

A retrospective study of 104 patients with adult degenerative lumbar disease was performed. All patients underwent posterior instrumented fusion of 4 or more segments and were followed up for at least 2 years. Patients were divided into two groups on the basis of whether they had mechanical complications of PJF. Age, sex ratio, BMI, follow-up time, upper instrumented vertebra (UIV), lower instrumented vertebra, and vertebral body osteotomy were recorded. The spinopelvic parameters were measured on early postoperative radiographs. The HU value of L1 trabecular attenuation was measured on axial and sagittal CT scans. Statistical analysis was performed to compare the difference of continuous and categorical variables. Receiver operating characteristic (ROC) curve analysis was used to obtain attenuation thresholds. A Kaplan-Meier curve and log-rank test were used to analyze the differences in PJF-free survival. Multivariate analysis via a Cox proportional hazards model was used to analyze the risk factors.

RESULTS

The HU value of L1 trabecular attenuation in the PJF group was lower than that in the control group (p < 0.001). The spinopelvic parameter L4–S1 lordosis was significantly different between the groups (p = 0.033). ROC curve analysis determined an optimal threshold of 89.25 HUs (sensitivity = 78.3%, specificity = 80.2%, area under the ROC curve = 0.799). PJF-free survival significantly decreased in patients with L1 attenuation ≤ 89.25 HUs (p < 0.001, log-rank test). When L1 trabecular attenuation was ≤ 89.25 HUs, PJF-free survival in patients with the UIV at L2 was the lowest, compared with patients with their UIV at the thoracolumbar junction or above (p = 0.028, log-rank test).

CONCLUSIONS

HUs could provide important information for surgeons to make a treatment plan to prevent PJF. L1 trabecular attenuation ≤ 89.25 HUs measured by spinal CT scanning could predict the incidence of PJF. Under this condition, the UIV at L2 significantly increases the incidence of PJF.

In Journal of Neurosurgery: Spine Publish Before Print

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Effectiveness of the Chiari Health Index for Pediatrics instrument in measuring postoperative health-related quality of life in pediatric patients with Chiari malformation type I

Georgina E. Sellyn, Alan R. Tang, Shilin Zhao, Madeleine Sherburn, Rachel Pellegrino, Stephen R. Gannon, Bradley S. Guidry, Travis R. Ladner, John C. Wellons III, and Chevis N. Shannon

OBJECTIVE

The authors’ previously published work validated the Chiari Health Index for Pediatrics (CHIP), a new instrument for measuring health-related quality of life (HRQOL) for pediatric Chiari malformation type I (CM-I) patients. In this study, the authors further evaluated the CHIP to assess HRQOL changes over time and correlate changes in HRQOL to changes in symptomatology and radiological factors in CM-I patients who undergo surgical intervention. Strong HRQOL evaluation instruments are currently lacking for pediatric CM-I patients, creating the need for a standardized HRQOL instrument for this patient population. This study serves as the first analysis of the CHIP instrument’s effectiveness in measuring short-term HRQOL changes in pediatric CM-I patients and can be a useful tool in future CM-I HRQOL studies.

METHODS

The authors evaluated prospectively collected CHIP scores and clinical factors of surgical intervention in patients younger than 18 years. To be included, patients completed a baseline CHIP captured during the preoperative visit, and at least 1 follow-up CHIP administered postoperatively. CHIP has 2 domains (physical and psychosocial) comprising 4 components, the 3 physical components of pain frequency, pain severity, and nonpain symptoms, and a single psychosocial component. Each CHIP category is scored on a scale, with 0 indicating absent and 1 indicating present, with higher scores indicating better HRQOL. Wilcoxon paired tests, Spearman correlations, and linear regression models were used to evaluate and correlate HRQOL, symptomatology, and radiographic factors.

RESULTS

Sixty-three patients made up the analysis cohort (92% Caucasian, 52% female, mean age 11.8 years, average follow-up time 15.4 months). Dural augmentation was performed in 92% of patients. Of the 63 patients, 48 reported preoperative symptoms and 42 had a preoperative syrinx. From baseline, overall CHIP scores significantly improved over time (from 0.71 to 0.78, p < 0.001). Significant improvement in CHIP scores was seen in patients presenting at baseline with neck/back pain (p = 0.015) and headaches (p < 0.001) and in patients with extremity numbness trending at p = 0.064. Patients with syringomyelia were found to have improvement in CHIP scores over time (0.75 to 0.82, p < 0.001), as well as significant improvement in all 4 components. Additionally, improved CHIP scores were found to be significantly associated with age in patients with cervical (p = 0.009) or thoracic (p = 0.011) syrinxes.

CONCLUSIONS

The study data show that the CHIP is an effective instrument for measuring HRQOL over time. Additionally, the CHIP was found to be significantly correlated to changes in symptomatology, a finding indicating that this instrument is a clinically valuable tool for the management of CM-I.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Letter to the Editor. Intracranial pressure monitoring: challenge beyond the threshold numerical value

Nícollas Nunes Rabelo, Mateus Gonçalves de Sena Barbosa, Matheus Pereira Silva Lemos, Sérgio Brasil, and Gustavo Frigieri

In Journal of Neurosurgery Publish Before Print

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Letter to the Editor. The COVID-19 pandemic and the inequities of the neurosurgery match

Michael D. White, Brandon M. Fox, and Nitin Agarwal

In Journal of Neurosurgery Publish Before Print

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Long-term stability of fusiform dilatation of the internal carotid artery following surgery adjacent to the circle of Willis: report of 2 cases

Madeline B. Karsten and R. Michael Scott

Fusiform dilatation of the internal carotid artery (FDCA) is a known postoperative imaging finding after craniopharyngioma resection. FDCA has also been reported following surgery for other lesions in the suprasellar region in pediatric patients and is thought to be due to trauma to the internal carotid artery (ICA) wall during tumor dissection. Here, the authors report 2 cases of pediatric patients with FDCA. Case 1 is a patient in whom FDCA was visualized on follow-up scans after total resection of a craniopharyngioma; this patient’s subsequent scans and neurological status remained stable throughout a 20-year follow-up period. In case 2, FDCA appeared after resection and fenestration of a giant arachnoid cyst in a 3-year-old child, with 6 years of stable subsequent follow-up, an imaging finding that to the authors’ knowledge has not previously been reported following surgery for arachnoid cyst fenestration. These cases demonstrate that surgery involving dissection adjacent to the carotid artery wall in pediatric patients may lead to the development of FDCA. On very long-term follow-up, this imaging finding rarely changes and virtually all patients remain asymptomatic. Neurointerventional treatment of FDCA in the absence of symptoms or significant late enlargement of the arterial ectasia does not appear to be indicated.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Lumbar alignment and patient-reported outcomes after single-level transforaminal lumbar interbody fusion for degenerative lumbar spondylolisthesis with and without local coronal imbalance

Wei Pan, Jia-li Zhao, Jin Xu, Ming Zhang, Tao Fang, Jing Yan, Xin-hong Wang, and Quan Zhou

OBJECTIVE

The purpose of this study was to compare the preoperative radiographic features of degenerative lumbar spondylolisthesis (DLS) with and without local coronal imbalance (LCI) and to investigate the surgical outcomes of transforaminal lumbar interbody fusion (TLIF) in the treatment of DLS with LCI at the spondylolisthesis level. DLS with scoliotic disc wedging and/or lateral listhesis at the same involved segment, as well as LCI, constitutes a distinct subgroup. However, previous studies concerning surgical outcomes focused mainly on sagittal profiles. There is a paucity of valid data regarding lumbar coronal alignment and patient-reported outcomes (PROs) after surgery in DLS with LCI.

METHODS

The authors reviewed consecutive patients who received TLIF for L4/5 DLS between 2009 and 2018. Patients were assigned to the LCI and non-LCI groups based on preoperative radiographs. Demographics, radiographic parameters related to both sagittal and coronal alignment, and PROs were compared between the 2 groups.

RESULTS

There were 21 patients in the LCI and 80 in the non-LCI group. Compared with the non-LCI group, the LCI group was characterized by lower preoperative lumbar lordosis on sagittal alignment (38.3° vs 43.7°, p < 0.05), higher lumbar Cobb angle on coronal alignment (12.4° vs 5.1°, p < 0.05), and worse lumbar coronal balance (18.5 mm vs 6.8 mm, p < 0.05). After surgery, lumbar alignment in the sagittal and coronal planes was significantly improved in the LCI group, whereas no significant changes occurred in the non-LCI group. Scores on the preoperative Oswestry Disability Index and the visual analog scale for back pain and leg pain scores were significantly higher in the LCI group, whereas no differences were found between the 2 groups in the postoperative evaluation (p > 0.05).

CONCLUSIONS

DLS with LCI constitutes a distinct subgroup characterized by coronal malalignment and loss of whole lumbar lordosis, which may result in worse PROs. The TLIF procedure allows the reconstruction of the coronal and sagittal lumbar profile and achievement of satisfactory PROs.

In Journal of Neurosurgery: Spine Publish Before Print

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The mediums of dissemination of knowledge and illustration in neurosurgery: unraveling the evolution

Bharath Raju, Fareed Jumah, Vinayak Narayan, Anika Sonig, Hai Sun, and Anil Nanda

The earliest evidence of man’s attempts in communicating ideas and emotions can be seen on cave walls and ceilings from the prehistoric era. Ingenuity, as well as the development of tools, allowed clay tablets to become the preferred method of documentation, then papyrus and eventually the codex. As civilizations advanced to develop structured systems of writing, knowledge became a power available to only those who were literate. As the search to understand the intricacies of the human brain moved forward, so did the demand for teaching the next generation of physicians. The different methods of distributing information were forced to advance, lest the civilization falls behind. Here, the authors present a historical perspective on the evolution of the mediums of illustration and knowledge dissemination through the lens of neurosurgery. They highlight how the medium of choice transitioned from primitive clay pots to cutting-edge virtual reality technology, aiding in the propagation of medical literature from generation to generation across the centuries.

In Journal of Neurosurgery Publish Before Print

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Multicenter assessment of surgical outcomes in adult spinal deformity patients with severe global coronal malalignment: determination of target coronal realignment threshold

Thomas J. Buell, Justin S. Smith, Christopher I. Shaffrey, Han Jo Kim, Eric O. Klineberg, Virginie Lafage, Renaud Lafage, Themistocles S. Protopsaltis, Peter G. Passias, Gregory M. Mundis Jr., Robert K. Eastlack, Vedat Deviren, Michael P. Kelly, Alan H. Daniels, Jeffrey L. Gum, Alex Soroceanu, D. Kojo Hamilton, Munish C. Gupta, Douglas C. Burton, Richard A. Hostin, Khaled M. Kebaish, Robert A. Hart, Frank J. Schwab, Shay Bess, Christopher P. Ames, and the International Spine Study Group (ISSG)

OBJECTIVE

The impact of global coronal malalignment (GCM; C7 plumb line–midsacral offset) on adult spinal deformity (ASD) treatment outcomes is unclear. Here, the authors’ primary objective was to assess surgical outcomes and complications in patients with severe GCM, with a secondary aim of investigating potential surgical target coronal thresholds for optimal outcomes.

METHODS

This is a retrospective analysis of a prospective multicenter database. Operative patients with severe GCM (≥ 1 SD above the mean) and a minimum 2-year follow-up were identified. Demographic, surgical, radiographic, health-related quality of life (HRQOL), and complications data were analyzed.

RESULTS

Of 691 potentially eligible operative patients (mean GCM 4 ± 3 cm), 80 met the criteria for severe GCM ≥ 7 cm. Of these, 62 (78%; mean age 63.7 ± 10.7 years, 81% women) had a minimum 2-year follow-up (mean follow-up 3.3 ± 1.1 years). The mean ASD–Frailty Index was 3.9 ± 1.5 (frail), 50% had undergone prior fusion, and 81% had concurrent severe sagittal spinopelvic deformity with GCM and C7–S1 sagittal vertical axis (SVA) positively correlated (r = 0.313, p = 0.015). Surgical characteristics included posterior-only (58%) versus anterior-posterior (42%) approach, mean fusion of 13.2 ± 3.8 levels, iliac fixation (90%), 3-column osteotomy (36%), operative duration of 8.3 ± 3.0 hours, and estimated blood loss of 2.3 ± 1.7 L. Final alignment and HRQOL significantly improved (p < 0.01): GCM, 11 to 4 cm; maximum coronal Cobb angle, 43° to 20°; SVA, 13 to 4 cm; pelvic tilt, 29° to 23°; pelvic incidence–lumbar lordosis mismatch, 31° to 5°; Oswestry Disability Index, 51 to 37; physical component summary of SF-36 (PCS), 29 to 37; 22-Item Scoliosis Research Society Patient Questionnaire (SRS-22r) Total, 2.6 to 3.5; and numeric rating scale score for back and leg pain, 7 to 4 and 5 to 3, respectively. Residual GCM ≥ 3 cm was associated with worse SRS-22r Appearance (p = 0.04) and SRS-22r Satisfaction (p = 0.02). The minimal clinically important difference and/or substantial clinical benefit (MCID/SCB) was met in 43%–83% (highest for SRS-22r Appearance [MCID 83%] and PCS [SCB 53%]). The severity of baseline GCM (≥ 2 SD above the mean) significantly impacted postoperative SRS-22r Satisfaction and MCID/SCB improvement for PCS. No significant partial correlations were demonstrated between GCM or SVA correction and HRQOL improvement. There were 89 total complications (34 minor and 55 major), 45 (73%) patients with ≥ 1 complication (most commonly rod fracture [19%] and proximal junctional kyphosis [PJK; 18%]), and 34 reoperations in 22 (35%) patients (most commonly for rod fracture and PJK).

CONCLUSIONS

Study results demonstrated that ASD surgery in patients with substantial GCM was associated with significant radiographic and HRQOL improvement despite high complication rates. MCID improvement was highest for SRS-22r Appearance/Self-Image. A residual GCM ≥ 3 cm was associated with a worse outcome, suggesting a potential coronal realignment target threshold to assist surgical planning.

In Journal of Neurosurgery: Spine Publish Before Print