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Jonathan G. Hobbs, Jacob S. Young and Julian E. Bailes

Sports-related concussions (SRCs) are traumatic events that affect up to 3.8 million athletes per year. The initial diagnosis and management is often instituted on the field of play by coaches, athletic trainers, and team physicians. SRCs are usually transient episodes of neurological dysfunction following a traumatic impact, with most symptoms resolving in 7–10 days; however, a small percentage of patients will suffer protracted symptoms for years after the event and may develop chronic neurodegenerative disease. Rarely, SRCs are associated with complications, such as skull fractures, epidural or subdural hematomas, and edema requiring neurosurgical evaluation. Current standards of care are based on a paradigm of rest and gradual return to play, with decisions driven by subjective and objective information gleaned from a detailed history and physical examination. Advanced imaging techniques such as functional MRI, and detailed understanding of the complex pathophysiological process underlying SRCs and how they affect the athletes acutely and long-term, may change the way physicians treat athletes who suffer a concussion. It is hoped that these advances will allow a more accurate assessment of when an athlete is truly safe to return to play, decreasing the risk of secondary impact injuries, and provide avenues for therapeutic strategies targeting the complex biochemical cascade that results from a traumatic injury to the brain.

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Jacob N. Young, Blaine S. Nashold Jr. and Eric R. Cosman

✓ A new insulated radiofrequency electrode for making nucleus caudalis dorsal root entry zone lesions reduces the incidence of ataxia.

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Ramin A. Morshed, Jacob S. Young, Seunggu J. Han, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Many surgical approaches have been described for lesions within the mesial temporal lobe (MTL), but there are limited reports on the transcortical approach for the resection of tumors within this region. Here, the authors describe the technical considerations and functional outcomes in patients undergoing transcortical resection of gliomas of the MTL.

METHODS

Patients with a glioma (WHO grades I–IV) located within the MTL who had undergone the transcortical approach in the period between 1998 and 2016 were identified through the University of California, San Francisco (UCSF) tumor registry and were classified according to tumor location: preuncus, uncus, hippocampus/parahippocampus, and various combinations of the former groups. Patient and tumor characteristics and outcomes were determined from operative, radiology, pathology, and other clinical reports that were available through the UCSF electronic medical record.

RESULTS

Fifty patients with low- or high-grade glioma were identified. The mean patient age was 46.8 years, and the mean follow-up was 3 years. Seizures were the presenting symptom in 82% of cases. Schramm types A, C, and D represented 34%, 28%, and 38% of the tumors, and the majority of lesions were located at least in part within the hippocampus/parahippocampus. For preuncus and preuncus/uncus tumors, a transcortical approach through the temporal pole allowed for resection. For most tumors of the uncus and those extending into the hippocampus/parahippocampus, a corticectomy was performed within the middle and/or inferior temporal gyri to approach the lesion. To locate the safest corridor for the corticectomy, language mapping was performed in 96.9% of the left-sided tumor cases, and subcortical motor mapping was performed in 52% of all cases. The mean volumetric extent of resection of low- and high-grade tumors was 89.5% and 96.0%, respectively, and did not differ by tumor location or Schramm type. By 3 months’ follow-up, 12 patients (24%) had residual deficits, most of which were visual field deficits. Three patients with left-sided tumors (9.4% of dominant-cortex lesions) experienced word-finding difficulty at 3 months after resection, but 2 of these patients demonstrated complete resolution of symptoms by 1 year.

CONCLUSIONS

Mesial temporal lobe gliomas, including larger Schramm type C and D tumors, can be safely and aggressively resected via a transcortical equatorial approach when used in conjunction with cortical and subcortical mapping.

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Ramin A. Morshed, Jacob S. Young, Seunggu J. Han, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Greater extent of resection (EOR) improves overall survival and progression-free survival for patients with low- and high-grade glioma. While resection for newly diagnosed insular gliomas can be performed with minimal morbidity, perioperative morbidity is not clearly defined for patients undergoing a repeat resection for recurrent insular gliomas. In this study the authors report on tumor characteristics, tumor EOR, and functional outcomes in patients undergoing reoperation for recurrent insular glioma.

METHODS

Adult patients with insular gliomas (WHO grades II–IV) who underwent index resection followed by reoperation were identified through the University of California San Francisco Brain Tumor Center. Treatment history and functional outcomes were collected retrospectively from the electronic medical record. Pre- and postoperative tumor volumes were quantified using software with region-of-interest analysis based on FLAIR and T1-weighted postgadolinium sequences from pre- and postoperative MRI.

RESULTS

Forty-four patients (63.6% male, 36.4% female) undergoing 49 reoperations for recurrent insular tumors were identified with a median follow-up of 741 days. Left- and right-sided tumors comprised 52.3% and 47.7% of the cohort, respectively. WHO grade II, III, and IV gliomas comprised 46.9%, 28.6%, and 24.5% of the cohort, respectively. Ninety-five percent (95.9%) of cases involved language and/or motor mapping. Median EOR of the insular component of grade II, III, and IV tumors were 82.1%, 75.0%, and 94.6%, respectively. EOR during reoperation was not impacted by Berger-Sanai insular zone or tumor side. At the time of reoperation, 44.9% of tumors demonstrated malignant transformation to a higher WHO grade. Ninety-day postoperative assessment confirmed that 91.5% of patients had no new postoperative deficit attributable to surgery. Of those with new deficits, 3 (6.4%) had a visual field cut and 1 (2.1%) had hemiparesis (strength grade 1–2/5). The presence of a new postoperative deficit did not vary with EOR.

CONCLUSIONS

Recurrent insular gliomas, regardless of insular zone and pathology, may be reoperated on with an overall acceptable degree of resection and safety despite their anatomical and functional complexities. The use of intraoperative mapping utilizing asleep or awake methods may reduce morbidity to acceptable rates despite prior surgery.

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Stephen T. Magill, Jacob S. Young, Ricky Chae, Manish K. Aghi, Philip V. Theodosopoulos and Michael W. McDermott

OBJECTIVE

Prior studies have investigated preoperative risk factors for meningioma; however, no association has been shown between meningioma tumor size and tumor grade. The objective of this study was to investigate the relationship between tumor size and grade in a large single-center study of patients undergoing meningioma resection.

METHODS

A retrospective chart review of patients undergoing meningioma resection at the University of California, San Francisco, between 1985 and 2015 was performed. Patients with incomplete information, spinal meningiomas, multiple meningiomas, or WHO grade III meningiomas were excluded. The largest tumor dimension was used as a surrogate for tumor size. Univariate and multivariate logistic regression models were used to investigate the relationship between tumor grade and tumor size. A recursive partitioning analysis was performed to identify groups at higher risk for atypical (WHO grade II) meningioma.

RESULTS

Of the 1113 patients identified, 905 (81%) had a WHO grade I tumor and in 208 (19%) the tumors were WHO grade II. The median largest tumor dimension was 3.6 cm (range 0.2–13 cm). Tumors were distributed as follows: skull base (n = 573, 51%), convexity/falx/parasagittal (n = 431, 39%), and other (n = 109, 10%). On univariate regression, larger tumor size (p < 0.001), convexity/falx/parasagittal location (p < 0.001), and male sex (p < 0.001) were significant predictors of WHO grade II pathology. After controlling for interactions, multivariate regression found male sex (OR 1.74, 95% CI 1.25–2.43), size 3–6 cm (OR 1.69, 95% CI 1.08–2.66), size > 6 cm (OR 3.01, 95% CI 1.53–5.94), and convexity/falx/parasagittal location (OR 1.83, 95% CI 1.19–2.82) to be significantly associated with WHO grade II. Recursive partitioning analysis identified male patients with tumors > 3 cm as a high-risk group (32%) for WHO grade II meningioma.

CONCLUSIONS

Larger tumor size is associated with a greater likelihood of a meningioma being WHO grade II, independent of tumor location and male sex, which are known risk factors.

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Fara Dayani, Jacob S. Young, Alexander Bonte, Edward F. Chang, Philip Theodosopoulos, Michael W. McDermott, Mitchel S. Berger and Manish K. Aghi

OBJECTIVE

Butterfly glioblastoma (bGBM) is a rare type of GBM, characterized by a butterfly pattern on MRI studies because of its bihemispheric involvement and invasion of the corpus callosum (CC). There is a profound gap in the knowledge regarding the optimal treatment approach as well as the safety and survival benefits of resection in treating this aggressive brain tumor. In this retrospective study, authors add to our understanding of these tumors by identifying the clinical characteristics and outcomes of patients with bGBM.

METHODS

An institutional database was reviewed for GBM cases treated in the period from 2004 to 2014. Records were reviewed to identify adult patients with bGBM. Cases of GBM with invasion of the CC without involvement of the contralateral hemisphere and bilateral GBMs without involvement of the CC were excluded from the study. Patient and tumor characteristics were gleaned from the medical records, and volumetric analysis was performed using T1-weighted MRI studies.

RESULTS

From among 1746 cases of GBM, 39 cases of bGBM were identified. Patients had a mean age of 57.8 years at diagnosis. Headache and confusion were the most common presenting symptoms (48.7% and 33.3%, respectively). The median overall survival was 3.2 months from diagnosis with an overall 6-month survival rate of 38.1%. Age, Karnofsky Performance Status at diagnosis, preoperative tumor volume, postoperative tumor volume, and extent of resection were found to significantly impact survival in the univariate analysis. On multivariate analysis, preoperative tumor volume and treatment approach of resection versus biopsy were identified as independent prognostic factors regardless of the patient-specific characteristics of age and KPS at diagnosis. Resection and biopsy were performed in 35.9% and 64.1% of patients, respectively. Resection was found to confer a better prognosis than biopsy (HR 0.37, p = 0.009) with a minimum extent of resection of 86% to observe survival benefits (HR 0.054, p = 0.03). The rate of persistent neurological deficits from resection was 7.14%. Patients younger than 70 years had a better prognosis (HR 0.32, p = 0.003). Patients undergoing resection and receiving adjuvant chemoradiation had a better prognosis than patients who lacked one of the three treatment modalities (HR = 0.34, p = 0.015).

CONCLUSIONS

Resection of bGBM is associated with low persistent neurological deficits, with improvement in survival compared to biopsy. A more aggressive treatment approach involving aggressive resection and adjuvant chemoradiation has significant survival benefits and improves outcome.

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Andrew J. Gogos, Jacob S. Young, Matheus P. Pereira, Ramin A. Morshed, Matthew B. Potts, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Although most patients with low-grade glioma (LGG) present after a seizure, a small proportion is diagnosed after neuroimaging is performed for a sign or symptom unrelated to the tumor. While these tumors invariably grow, some surgeons argue for a watchful waiting approach. Here, the authors report on their experience in the surgical treatment of patients with incidental LGG (iLGG) and describe the neurological outcomes, survival, and complications.

METHODS

Relevant cases were identified from a prospective registry of patients undergoing glioma resection at the University of California, San Francisco, between 1997 and 2019. Cases were considered iLGG when the lesion was noted on imaging performed for a reason unrelated to the tumor. Demographic, clinical, pathological, and imaging data were extracted from the electronic medical record. Tumor volumes, growth, and extent of resection were calculated from pre- and postoperative volumetric FLAIR sequences.

RESULTS

One hundred thirteen of 657 (17.2%) first-time resections for LGG were for incidental lesions. The most common reasons for the discovery of an iLGG were headaches (without mass effect, 34.5%) or trauma (16.8%). Incidental tumors were no different from symptomatic lesions in terms of laterality or location, but they were significantly smaller (22.5 vs 57.5 cm3, p < 0.0001). There was no difference in diagnosis between patients with iLGG and those with symptomatic LGG (sLGG), incorporating both molecular and pathological data. The median preoperative observation time for iLGG was 3.1 months (range 1 month–12 years), and there was a median growth rate of 3.9 cm3/year. Complete resection of the FLAIR abnormality was achieved in 57% of patients with incidental lesions but only 23.8% of symptomatic lesions (p < 0.001), and the residual volumes were smaller for iLGGs (2.9 vs 13.5 cm3, p < 0.0001). Overall survival was significantly longer for patients with incidental tumors (median survival not reached for patients with iLGG vs 14.6 years for those with sLGG, p < 0.0001). There was a 4.4% rate of neurological deficits at 6 months.

CONCLUSIONS

The authors present the largest cohort of iLGGs. Patient age, tumor location, and molecular genetics were not different between iLGGs and sLGGs. Incidental tumors were smaller, a greater extent of resection could be achieved, and overall survival was improved compared to those for patients with sLGG. Operative morbidity and rates of neurological deficit were acceptably low; thus, the authors advocate upfront surgical intervention aimed at maximal safe resection for these incidentally discovered lesions.

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Andrew J. Gogos, Jacob S. Young, Ramin A. Morshed, Lauro N. Avalos, Roger S. Noss, Javier E. Villanueva-Meyer, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Maximal safe resection of gliomas near motor pathways is facilitated by intraoperative mapping. The authors and other groups have described the use of bipolar or monopolar direct stimulation to identify functional tissue, as well as transcranial or transcortical motor evoked potentials (MEPs) to monitor motor pathways. Here, the authors describe their initial experience using all 3 modalities to identify, monitor, and preserve cortical and subcortical motor systems during glioma surgery.

METHODS

Intraoperative mapping data were extracted from a prospective registry of glioma resections near motor pathways. Additional demographic, clinical, pathological, and imaging data were extracted from the electronic medical record. All patients with new or worsened postoperative motor deficits were followed for at least 6 months.

RESULTS

Between January 2018 and August 2019, 59 operations were performed in 58 patients. Overall, patients in 6 cases (10.2%) had new or worse immediate postoperative deficits. Patients with temporary deficits all had at least Medical Research Council grade 4/5 power. Only 2 patients (3.4%) had permanently worsened deficits after 6 months, both of which were associated with diffusion restriction consistent with ischemia within the corticospinal tract. One patient’s deficit improved to 4/5 and the other to 4/5 proximally and 3/5 distally in the lower limb, allowing ambulation following rehabilitation. Subcortical motor pathways were identified in 51 cases (86.4%) with monopolar high-frequency stimulation, but only in 6 patients using bipolar stimulation. Transcranial or cortical MEPs were diminished in only 6 cases, 3 of which had new or worsened deficits, with 1 permanent deficit. Insula location (p = 0.001) and reduction in MEPs (p = 0.01) were the only univariate predictors of new or worsened postoperative deficits. Insula location was the only predictor of permanent deficits (p = 0.046). The median extent of resection was 98.0%.

CONCLUSIONS

Asleep triple motor mapping is safe and resulted in a low rate of deficits without compromising the extent of resection.

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Anthony T. Lee, Claire Faltermeier, Ramin A. Morshed, Jacob S. Young, Sofia Kakaizada, Claudia Valdivia, Anne M. Findlay, Phiroz E. Tarapore, Srikantan S. Nagarajan, Shawn L. Hervey-Jumper and Mitchel S. Berger

OBJECTIVE

Gliomas are intrinsic brain tumors with the hallmark of diffuse white matter infiltration, resulting in short- and long-range network dysfunction. Preoperative magnetoencephalography (MEG) can assist in maximizing the extent of resection while minimizing morbidity. While MEG has been validated in motor mapping, its role in speech mapping remains less well studied. The authors assessed how the resection of intraoperative electrical stimulation (IES)–negative, high functional connectivity (HFC) network sites, as identified by MEG, impacts language performance.

METHODS

Resting-state, whole-brain MEG recordings were obtained from 26 patients who underwent perioperative language evaluation and glioma resection that was guided by awake language and IES mapping. The functional connectivity of an individual voxel was determined by the imaginary coherence between the index voxel and the rest of the brain, referenced to its contralesional pair. The percentage of resected HFC voxels was correlated with postoperative language outcomes in tasks of increasing complexity: text reading, 4-syllable repetition, picture naming, syntax (SYN), and auditory stimulus naming (AN).

RESULTS

Overall, 70% of patients (14/20) in whom any HFC tissue was resected developed an early postoperative language deficit (mean 2.3 days, range 1–8 days), compared to 33% of patients (2/6) in whom no HFC tissue was resected (p = 0.16). When bifurcated by the amount of HFC tissue that was resected, 100% of patients (3/3) with an HFC resection > 25% displayed deficits in AN, compared to 30% of patients (6/20) with an HFC resection < 25% (p = 0.04). Furthermore, there was a linear correlation between the severity of AN and SYN decline with percentage of HFC sites resected (p = 0.02 and p = 0.04, respectively). By 2.2 months postoperatively (range 1–6 months), the correlation between HFC resection and both AN and SYN decline had resolved (p = 0.94 and p = 1.00, respectively) in all patients (9/9) except two who experienced early postoperative tumor progression or stroke involving inferior frontooccipital fasciculus.

CONCLUSIONS

Imaginary coherence measures of functional connectivity using MEG are able to identify HFC network sites within and around low- and high-grade gliomas. Removal of IES-negative HFC sites results in early transient postoperative decline in AN and SYN, which resolved by 3 months in all patients without stroke or early tumor progression. Measures of functional connectivity may therefore be a useful means of counseling patients about postoperative risk and assist with preoperative surgical planning.

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Ankush Chandra, Jacob S. Young, Cecilia Dalle Ore, Fara Dayani, Darryl Lau, Harsh Wadhwa, Jonathan W. Rick, Alan T. Nguyen, Michael W. McDermott, Mitchel S. Berger and Manish K. Aghi

OBJECTIVE

Glioblastoma (GBM) carries a high economic burden for patients and caregivers, much of which is associated with initial surgery. The authors investigated the impact of insurance status on the inpatient hospital costs of surgery for patients with GBM.

METHODS

The authors conducted a retrospective review of patients with GBM (2010–2015) undergoing their first resection at the University of California, San Francisco, and corresponding inpatient hospital costs.

RESULTS

Of 227 patients with GBM (median age 62 years, 37.9% females), 31 (13.7%) had Medicaid, 94 (41.4%) had Medicare, and 102 (44.9%) had private insurance. Medicaid patients had 30% higher overall hospital costs for surgery compared to non-Medicaid patients ($50,285 vs $38,779, p = 0.01). Medicaid patients had higher intensive care unit (ICU; p < 0.01), operating room (p < 0.03), imaging (p < 0.001), room and board (p < 0001), and pharmacy (p < 0.02) costs versus non-Medicaid patients. Medicaid patients had significantly longer overall and ICU lengths of stay (6.9 and 2.6 days) versus Medicare (4.0 and 1.5 days) and privately insured patients (3.9 and 1.8 days, p < 0.01). Medicaid patients had similar comorbidity rates to Medicare patients (67.8% vs 68.1%), and both groups had higher comorbidity rates than privately insured patients (37.3%, p < 0.0001). Only 67.7% of Medicaid patients had primary care providers (PCPs) versus 91.5% of Medicare and 86.3% of privately insured patients (p = 0.009) at the time of presentation. Tumor diameter at diagnosis was largest for Medicaid (4.7 cm) versus Medicare (4.1 cm) and privately insured patients (4.2 cm, p = 0.03). Preoperative (70 vs 90, p = 0.02) and postoperative (80 vs 90, p = 0.03) Karnofsky Performance Scale (KPS) scores were lowest for Medicaid versus non-Medicaid patients, while in subgroup analysis, postoperative KPS score was lowest for Medicaid patients (80, vs 90 for Medicare and 90 for private insurance; p = 0.03). Medicaid patients had significantly shorter median overall survival (10.7 months vs 12.8 months for Medicare and 15.8 months for private insurance; p = 0.02). Quality-adjusted life year (QALY) scores were 0.66 and 1.05 for Medicaid and non-Medicaid patients, respectively (p = 0.036). The incremental cost per QALY was $29,963 lower for the non-Medicaid cohort.

CONCLUSIONS

Patients with GBMs and Medicaid have higher surgical costs, longer lengths of stay, poorer survival, and lower QALY scores. This study indicates that these patients lack PCPs, have more comorbidities, and present later in the disease course with larger tumors; these factors may drive the poorer postoperative function and greater consumption of hospital resources that were identified. Given limited resources and rising healthcare costs, factors such as access to PCPs, equitable adjuvant therapy, and early screening/diagnosis of disease need to be improved in order to improve prognosis and reduce hospital costs for patients with GBM.