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.
Jonathan G. Hobbs, Jacob S. Young, and Julian E. Bailes
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.
Alexander F. Haddad, Jacob S. Young, and Manish K. Aghi
The treatment for glioblastoma (GBM) has not seen significant improvement in over a decade. Immunotherapies target the immune system against tumor cells and have seen success in various cancer types. However, the efficacy of immunotherapies in GBM thus far has been limited. Systemic immunotherapies also carry with them concerns surrounding systemic toxicities as well as penetration of the blood-brain barrier. These concerns may potentially limit their efficacy in GBM and preclude the use of combinatorial immunotherapy, which may be needed to overcome the severe multidimensional immune suppression seen in GBM patients. The use of viral vectors to deliver immunotherapies directly to tumor cells has the potential to improve immunotherapy delivery to the CNS, reduce systemic toxicities, and increase treatment efficacy. Indeed, preclinical studies investigating the delivery of immunomodulators to GBM using viral vectors have demonstrated significant promise. In this review, the authors discuss previous studies investigating the delivery of local immunotherapy using viral vectors. They also discuss the future of these treatments, including the reasoning behind immunomodulator and vector selection, patient safety, personalized therapies, and the need for combinatorial treatment.
Jacob S. Young, Ramin A. Morshed, John P. Andrews, Soonmee Cha, and Mitchel S. Berger
Prosopagnosia is a rare neurological condition characterized by the impairment of face perception with preserved visual processing and cognitive functioning and is associated with injury to the fusiform gyrus and inferior longitudinal fasciculus (ILF). Reports of this clinical impairment following resection of right temporal lobe diffuse gliomas in the absence of contralateral injury are exceedingly scarce and not expected as a complication of surgery.
The authors describe the case of a young female patient found to have an incidental diffuse glioma in the right inferior temporal lobe despite evidence of preoperative ILF disruption by the tumor. Following resection of the lesion, despite the preoperative disruption to the ILF by the tumor, the patient developed prosopagnosia. There was no evidence of contralateral, left-sided ILF injury.
Given the significant functional impairment associated with prosopagnosia, neurosurgeons should be aware of the exceedingly rare possibility of a visual-processing deficit following unilateral and, in this case, right-sided inferior temporal lobe glioma resections. More investigation is needed to determine whether preoperative testing can determine dominance of facial-processing networks for patients with lesions in the right inferior posterior temporooccipital lobe and whether intraoperative mapping could help prevent this complication.
Ramin A. Morshed, Jacob S. Young, Seunggu J. Han, Shawn L. Hervey-Jumper, and Mitchel S. Berger
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.
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.
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.
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.
Ramin A. Morshed, Jacob S. Young, Seunggu J. Han, Shawn L. Hervey-Jumper, and Mitchel S. Berger
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.
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.
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.
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.
Eric J. Chalif, Ramin A. Morshed, Jacob S. Young, Alexander F. Haddad, Saket Jain, and Manish K. Aghi
Decision-making in how to manage pituitary adenomas (PAs) in the elderly (age ≥ 65 years) can be challenging given the benign nature of these tumors and concerns about surgical morbidity in these patients. In this study involving a large multicenter national registry, the authors examined treatment trends and surgical outcomes in elderly compared to nonelderly patients.
The National Cancer Data Base (NCDB) was queried for adults aged ≥ 18 years with PA diagnosed by MRI (in observed cases) or pathology (in surgical cases) from 2004 to 2016. Univariate and multivariate logistic regressions were used to evaluate the prognostic impact of age and other covariates on 30- and 90-day postsurgical mortality (30M/90M), prolonged (≥ 5 days) length of inpatient hospital stay (LOS), and extent of resection.
A total of 96,399 cases met the study inclusion criteria, 27% of which were microadenomas and 73% of which were macroadenomas. Among these cases were 25,464 elderly patients with PA. Fifty-three percent of these elderly patients were treated with surgery, 1.9% underwent upfront radiotherapy, and 44.9% were observed without treatment. Factors associated with surgical treatment compared to observation included younger age, higher income, private insurance, higher Charlson-Deyo comorbidity (CD) score, larger tumor size, and receiving treatment at an academic hospital (each p ≤ 0.01). Elderly patients undergoing surgery had increased rates of 30M (1.4% vs 0.6%), 90M (2.8% vs 0.9%), prolonged LOS (26.1% vs 23.0%), and subtotal resection (27.2% vs 24.5%; each p ≤ 0.01) compared to those in nonelderly PA patients. On multivariate analysis, age, tumor size, and CD score were independently associated with worse postsurgical mortality. High-volume facilities (HVFs) had significantly better outcomes than low-volume facilities: 30M (0.9% vs 1.8%, p < 0.001), 90M (2.0% vs 3.5%, p < 0.001), and prolonged LOS (21.8% vs 30.3%, p < 0.001). A systematic literature review composed of 22 studies demonstrated an elderly PA patient mortality rate of 0.7%, which is dramatically lower than real-world NCDB outcomes and speaks to substantial selection bias in the previously published literature.
The study findings confirm that elderly patients with PA are at higher risk for postoperative mortality than younger patients. Surgical risk in this age group may have been previously underreported in the literature. Resection at HVFs better reflects these historical rates, which has important implications in elderly patients for whom surgery is being considered.
Alexander F. Haddad, Jacob S. Young, Jun Yeop Oh, Hideho Okada, and Manish K. Aghi
Low-grade gliomas (LGGs), which harbor an isocitrate dehydrogenase (IDH) mutation, have a better prognosis than their high-grade counterparts; nonetheless, they remain incurable and impart significant negative impacts on patients’ quality of life. Although immunotherapies represent a novel avenue of treatment for patients with LGGs, they have not yet been successful. Accurately selecting and evaluating immunotherapies requires a detailed understanding of LGG tumor immunology and the underlying tumor immune phenotype. A growing body of literature suggests that LGGs significantly differ in their immunology from high-grade gliomas, highlighting the importance of investigation into LGG immunology specifically. In this review, the authors aimed to discuss relevant research surrounding the LGG tumor immune microenvironment, including immune cell infiltration, tumor immunogenicity, checkpoint molecule expression, the impact of an IDH mutation, and implications for immunotherapies, while also briefly touching on current immunotherapy trials and future directions for LGG immunology research.
Stephen T. Magill, Jacob S. Young, Ricky Chae, Manish K. Aghi, Philip V. Theodosopoulos, and Michael W. McDermott
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.
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.
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.
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.
Alexander F. Haddad, Jacob S. Young, Ramin A. Morshed, S. Andrew Josephson, Soonmee Cha, and Mitchel S. Berger
Lower-grade insular gliomas often appear as expansile and infiltrative masses on magnetic resonance imaging (MRI). However, there are nonneoplastic lesions of the insula, such as demyelinating disease and vasculopathies, that can mimic insular gliomas.
The authors report two patients who presented with headaches and were found to have mass lesions concerning for lower-grade insular glioma based on MRI obtained at initial presentation. However, on the immediate preoperative MRI obtained a few weeks later, both patients had spontaneous and complete resolution of the insular lesions.
Tumor mimics should always be in the differential diagnosis of brain masses, including those involving the insula. The immediate preoperative MRI (within 24–48 hours of surgery) must be compared carefully with the initial presentation MRI to assess interval change that suggests tumor mimics to avoid unnecessary surgical intervention.