Clinical trial links oncolytic immunoactivation to survival in glioblastoma.

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV)3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318 ).

Depressed skull fracture compressing eloquent cortex causing focal neurologic deficits.

BACKGROUND: Depressed skull fractures are typically the consequence of high-impact injuries with inward buckling of the cranium. The majority of depressed skull fractures are managed conservatively in the absence of dural violation, sinus involvement, significant underlying hematoma, depressed fragment greater than 1 cm, wound infection, or gross wound contamination. Even in the presence of any of the aforementioned criteria, cranioplasty is typically considered an urgent procedure rather than a neurosurgical emergency. Rarely, a depressed fracture fragment can cause focal neurologic deficit(s) due to direct compression of the underlying eloquent cortex. CASE DESCRIPTION: A 40-year-old male presented to the emergency department after a mechanical fall with a left central facial nerve palsy, left hemiplegia, left hemianesthesia, and fixed right gaze deviation. The neurologic deficits observed were attributed to a combination of blunt force trauma to the head (i.e., coup-contrecoup injury) and the depressed fracture fragment compressing the underlying eloquent cortex. He underwent emergent cranioplasty with fragment elevation within 2 hours of the traumatic injury. At 6-month follow-up, he regained full neurologic function without any residual deficits. CONCLUSIONS: Our experience highlights a rare indication for emergent cranioplasty with an excellent functional outcome attributable to immediate fracture elevation and decompression of eloquent cortex.

Natural History of Traumatic Encephaloceles: A Systematic Literature Review.

Encephaloceles rarely develop following traumatic skull fractures. Given their low incidence, the clinical presentations and management strategies of these lesions are confined to case reports and limited case series. A systematic literature review was performed using PubMed, Ovid, and Web of Science databases to identify relevant articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 37 articles met inclusion criteria, including the case presented herein. These articles reported 52 traumatic encephaloceles. Mean patient age was 25.3 years (range 6 mo-66 y) with a male predominance (63%, 33/52). The most common bony defects resulting in encephalocele formation were the orbital roof (52%, 27/52), ethmoid (35%, 18/52), and sphenoid (10%, 5/52). Mean time from traumatic injury to initial presentation was 21.3 months (range 0 d-36 y) with a bimodal distribution split between immediately following the traumatic injury (57%, 26/46) or in a delayed manner (43%, 20/46). Common presentations of orbital roof, frontonasal, and temporal bone encephaloceles were exophthalmos (85%, 23/27), cerebrospinal fluid rhinorrhea (71%, 17/24), and hearing loss (100%, 4/4), respectively. Operative approach, repair technique, and materials used for encephalocele reduction were highly variable. Surgical intervention afforded definitive symptomatic improvement or resolution in the majority of cases (89%, 42/47). Clinical outcomes did not differ between orbital, frontonasal, or temporal bone encephaloceles ( P =0.438). Traumatic encephaloceles are a rare entity with diverse presenting symptomatology dependent upon the location of fracture dehiscence. Surgical intervention affords symptomatic improvement in the majority of cases irrespective of encephalocele location, time to presentation, or operative approach.

Prostate-Specific Membrane Antigen as Target for Neuroimaging of Central Nervous System Tumors.

Introduction: Positron emission tomography (PET) imaging with prostate-specific membrane antigen- (PSMA-) binding tracers has been found incidentally to demonstrate uptake in CNS tumors. Following the encouraging findings of several such case reports, there is a growing interest in the potential application of PSMA-targeted PET imaging for diagnostics, theranostics, and monitoring of CNS tumors. This is a systematic literature review on PSMA-binding tracers in CNS tumors. Methods: A PubMed search was conducted, including preclinical and clinical reports. One hundred and twelve records were identified, and after screening, 56 were included in the final report. Results: Tissue studies demonstrated PSMA expression in tumor vascular endothelial cells, without expression in normal brain tissue, though the extent and intensity of staining varied by anti-PSMA antibody and methodology. Most included studies reported on gliomas, which showed strong PSMA ligand uptake and more favorable tumor to background ratios than other PET tracers. There are also case reports demonstrating PSMA ligand uptake in prostate cancer brain metastases, nonprostate cancer brain metastases, and meningiomas. We also review the properties of the various PSMA-binding radiotracers available. Therapeutic and theranostic applications of PSMA-binding tracers have been studied, including labeled alpha- and beta-ray emitting isotopes, as well as PSMA targeting in directing MRI-guided focused ultrasound. Conclusions: There is a potential application for PSMA-targeted PET in neuro-oncology as a combination of diagnostic and therapeutic use, as a theranostic modality for managing CNS tumors. Further research is needed regarding the mechanism(s) of PSMA expression in CNS tumors and its differential performance by tumor type.

Comparison of Amino Acid PET to Advanced and Emerging MRI Techniques for Neurooncology Imaging: A Systematic Review of the Recent Studies.

Introduction: Standard neuroimaging protocols for brain tumors have well-known limitations. The clinical use of additional modalities including amino acid PET (aaPET) and advanced MRI (aMRI) techniques (including DWI, PWI, and MRS) is emerging in response to the need for more accurate detection of brain tumors. In this systematic review of the past 2 years of the literature, we discuss the most recent studies that directly compare or combine aaPET and aMRI for brain tumor imaging. Methods: A PubMed search was conducted for human studies incorporating both aaPET and aMRI and published between July 2018 and August 2020. Results: A total of 22 studies were found in the study period. Recent studies of aaPET with DWI showed a superiority of MET, FET, FDOPA, and AMT PET for detecting tumor, predicting recurrence, diagnosing progression, and predicting survival. Combining modalities further improved performance. Comparisons of aaPET with PWI showed mixed results about spatial correlation. However, both modalities were able to detect high-grade tumors, identify tumor recurrence, differentiate recurrence from treatment effects, and predict survival. aaPET performed better on these measures than PWI, but when combined, they had the strongest results. Studies of aaPET with MRS demonstrated that both modalities have diagnostic potential but MET PET and FDOPA PET performed better than MRS. MRS suffered from some data quality issues that limited analysis in two studies, and, in one study that combined modalities, overall performance actually decreased. Four recent studies compared aaPET with emerging MRI approaches (such as CEST imaging, MR fingerprinting, and SISTINA), but the initial results remain inconclusive. Conclusions: aaPET outperformed the aMRI imaging techniques in most recent studies. DWI and PWI added meaningful complementary data, and the combination of aaPET with aMRI yielded the best results in most studies.

Preoperative functional MRI use in neurooncology patients: a clinician survey.

OBJECTIVE: Functional MRI (fMRI) is increasingly being investigated for use in neurosurgical patient care. In the current study, the authors characterize the clinical use of fMRI by surveying neurosurgeons' use of and attitudes toward fMRI as a surgical planning tool in neurooncology patients. METHODS: A survey was developed to inquire about clinicians' use of and experiences with preoperative fMRI in the neurooncology patient population, including example case images. The survey was distributed to all neurosurgical departments with a residency program in the US. RESULTS: After excluding incomplete surveys and responders that do not use fMRI (n = 11), 50 complete responses were included in the final analysis. Responders were predominantly from academic programs (88%), with 20 years or more in practice (40%), with a main area of practice in neurooncology (48%) and treating an adult population (90%). All 50 responders currently use fMRI in neurooncology patients, mostly for low- (94%) and high-grade glioma (82%). The leading decision factors for ordering fMRI were location of mass in dominant hemisphere, location in a functional area, motor symptoms, and aphasia. Across 10 cases, language fMRI yielded the highest interrater reliability agreement (Fleiss' kappa 0.437). The most common reasons for ordering fMRI were to identify language laterality, plan extent of resection, and discuss neurological risks with patients. Clinicians reported that fMRI results were not obtained when ordered a median 10% of the time and were suboptimal a median 27% of the time. Of responders, 70% reported that they had ever resected an fMRI-positive functional site, of whom 77% did so because the site was "cleared" by cortical stimulation. Responders reported disagreement between fMRI and awake surgery 30% of the time. Overall, 98% of responders reported that if results of fMRI and intraoperative mapping disagreed, they would rely on intraoperative mapping. CONCLUSIONS: Although fMRI is increasingly being adopted as a practical preoperative planning tool for brain tumor resection, there remains a substantial degree of discrepancy with regard to its current use and presumed utility. There is a need for further research to evaluate the use of preoperative fMRI in neurooncology patients. As fMRI continues to gain prominence, it will be important for clinicians to collectively share best practices and develop guidelines for the use of fMRI in the preoperative planning phase of brain tumor patients.

Hyperosmolar Therapy in Pediatric Severe Traumatic Brain Injury-A Systematic Review.

OBJECTIVES: Traumatic brain injury is a leading cause of hospital visits for children. Hyperosmolar therapy is often used to treat severe traumatic brain injury. Hypertonic saline is used predominantly, yet there remains disagreement about whether hypertonic saline or mannitol is more effective. DATA SOURCES: Literature search was conducted using Pubmed, Cochrane, and Embase. Systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. STUDY SELECTION: Retrospective and prospective studies assessing use of hyperosmolar therapy in pediatric patients with severe traumatic brain injury were included. DATA EXTRACTION: Two independent authors performed article review. Two-thousand two-hundred thirty unique articles were initially evaluated, 11 were included in the final analysis, with a total of 358 patients. Study quality was assessed using Modified Newcastle-Ottawa Scale and Jadad score. DATA SYNTHESIS: Of the 11 studies, all evaluated hypertonic saline and four evaluated both hypertonic saline and mannitol. Nine reported that hypertonic saline lowered intracranial pressure and two reported that mannitol lowered intracranial pressure. The studies varied significantly in dose, concentration, and administrations schedule for both hypertonic saline and mannitol. Five studies were prospective, but only one directly compared mannitol to hypertonic saline. The prospective comparison study found no difference in physiologic outcomes. Clinical outcomes were reported using different measures across studies. For hypertonic saline-treated patients, mechanical ventilation was required for 6.9-9 days, decompressive craniectomy was required for 6.25-29.3% of patients, ICU length of stay was 8.0-10.6 days, in-hospital mortality was 10-48%, and 6-month mortality was 7-17%. In mannitol-treated patients, ICU length of stay was 9.5 days, in-hospital mortality was 56%, and 6-month mortality was 19%. CONCLUSIONS: Both hypertonic saline and mannitol appear to lower intracranial pressure and improve clinical outcomes in pediatric severe traumatic brain injury, but the evidence is extremely fractured both in the method of treatment and in the evaluation of outcomes. Given the paucity of high-quality data, it is difficult to definitively conclude which agent is better or what treatment protocol to follow.

Evaluating the Utility of Repeat Computed Tomography Scans in Patients with Isolated Mild Traumatic Subarachnoid Hemorrhage.

BACKGROUND: Traumatic subarachnoid hemorrhage (tSAH) is a common consequence of head trauma. Treatment of patients with tSAH commonly involves serial computed tomography (CT) scans to assess for expansile hemorrhage. However, growing evidence suggests that these patients rarely deteriorate or require neurosurgical intervention. We assessed the utility of repeat CT scans in adult patients with isolated tSAH and an intact initial neurological examination. METHODS: Patients presenting to Mass General Brigham hospitals with tSAH between 2000 and 2021 were eligible for inclusion in this retrospective cohort study. Patients were excluded if subarachnoid hemorrhage was nontraumatic, they experienced another form of intracerebral hemorrhage, or they had a documented Glasgow Coma Scale score of ≤12 and/or poor presenting neurological examination. Univariate and multivariate regression models were used for statistical analysis. RESULTS: Overall, 405 patients were included (191 male). The most common mechanism of trauma was fall from standing (58%). The mean number of total CT scans for all patients was 2.3, with 329 patients (80%) receiving ≥2 scans. In 309 patients, no significant neurological symptoms were present. No patients developed acute neurological deterioration or required neurosurgical intervention related to their bleed, although 5 patients had mild hemorrhagic expansion on follow-up imaging. CONCLUSIONS: In this study, repeat imaging rarely demonstrated meaningful hemorrhagic expansion in this cohort of neurologically intact patients with isolated tSAH. In these patients with mild traumatic brain injury, excessive CT scans are perhaps unlikely to affect patient management and may present unnecessary burden to patients and hospital systems.

External ventricular drains and risk of freehand placement: A systematic review and meta-analysis.

OBJECTIVE: External ventricular drains (EVDs) are used to monitor and treat elevated intracranial pressure. EVDs are often placed blindly without the use of imaging guidance, and successful placement with respect to pass attempts and final catheter location may suffer as a result of this freehand technique. METHODS: A systematic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane databases to identify studies pertaining to freehand EVD placement through March 30, 2022. Studies were included if they reported percentage of EVDs placed successfully on the first pass attempt, or final catheter location as defined by the Kakarla Grading System. Pooled weighted incidence estimates and 95% confidence intervals (95%CI) were calculated using a random effects model. RESULTS: Of the 2964 results returned from the literature search, 39 studies were included in this meta-analysis. These studies reported on 6313 EVDs placed via freehand technique in 6070 patients with the following respective incidence: successful EVD placement on the first attempt (78%, 95%CI: 67-86%); placement with a Kakarla Grade of 1 (optimal location) (72%, 95%CI: 66-77%); hemorrhage (7%, 95%CI: 6-10%), and infection (5%, 95%CI: 3-8%). CONCLUSIONS: Only 78% of EVDs in this meta-analysis were placed successfully on the first pass, and only 72% of final placements were deemed optimal. This represents a relatively high rate of suboptimal outcomes with respect to EVD placement, which could potentially be avoided with the use of navigation-assisted placement techniques.

Central Nervous System Lymphoproliferative Disorder Secondary to Methotrexate: A Systematic Literature Review and Case Illustration.

BACKGROUND: Methotrexate is an immunosuppressant commonly used to treat inflammatory conditions, such as rheumatoid arthritis. However, albeit exceedingly rare, it can have serious adverse effects within the central nervous system (CNS), such as methotrexate-associated lymphoproliferative disorder (MTX-LPD). Literature describing the natural history, treatment options, and clinical outcomes of patients with CNS MTX-LPD remains sparse. METHODS: We present a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a case illustration of CNS MTX-LPD. RESULTS: A systematic review of the literature revealed 12 published cases of CNS MTX-LPD, plus the case presented herein, for a total of 13 included cases. The most common indication for MTX was rheumatoid arthritis. The most common treatment for the LPD was MTX cessation (12, 92.3%), adjunct chemotherapy (2, 15.4%), total tumor resection (3, 23.1%), or steroid therapy (1, 7.7%). Treatment usually led to improvement of neurological symptoms (9, 69.2%) along with regression of the lesions (3, 23.1%) with no recurrence (6, 46.2%). Death was reported in four cases (30.8%) with a mean time from onset of 11 months. CONCLUSIONS: CNS MTX-LPD should be considered in the differential diagnosis for patients who are taking MTX presenting with neurologic symptoms, as immediate withdrawal of MTX has demonstrated good prognosis.

External Ventricular Drains versus Intraparenchymal Pressure Monitors in the Management of Moderate to Severe Traumatic Brain Injury: Experience at Two Academic Centers over a Decade.

OBJECTIVE: The choice between external ventricular drain (EVD) and intraparenchymal monitor (IPM) for managing intracranial pressure in moderate-to-severe traumatic brain injury (msTBI) patients remains controversial. This study aimed to investigate factors associated with receiving EVD versus IPM and to compare outcomes and clinical management between EVD and IPM patients. METHODS: Adult msTBI patients at 2 similar academic institutions were identified. Logistic regression was performed to identify factors associated with receiving EVD versus IPM (model 1) and to compare EVD versus IPM in relation to patient outcomes after controlling for potential confounders (model 2), through odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of 521 patients, 167 (32.1%) had EVD and 354 (67.9%) had IPM. Mean age, sex, and Injury Severity Score were comparable between groups. Epidural hemorrhage (EDH) (OR 0.43, 95% CI 0.21-0.85), greater midline shift (OR 0.90, 95% CI 0.82-0.98), and the hospital with higher volume (OR 0.14, 95% CI 0.09-0.22) were independently associated with lower odds of receiving an EVD whereas patients needing a craniectomy were more likely to receive an EVD (OR 2.04, 95% CI 1.12-3.73). EVD patients received more intense medical treatment requiring hyperosmolar therapy compared to IPM patients (64.1% vs. 40.1%). No statistically significant differences were found in patient outcomes. CONCLUSIONS: While EDH, greater midline shift, and hospital with larger patient volume were associated with receiving an IPM, the need for a craniectomy was associated with receiving an EVD. EVD patients received different clinical management than IPM patients with no significant differences in patient outcomes.

Supratentorial Neurenteric Cysts: Systematic Literature Review and Case Report.

BACKGROUND: Neurenteric cysts (NC) are uncommon congenital lesions with histopathologic properties derived from the gastrointestinal or respiratory tract. They are typically located in the intradural extramedullary compartment but rarely seen in the supratentorial region. The occurrence of supratentorial NCs (S-NC) presents an interesting quandary regarding their embryopathogenesis. METHODS: We present a case report and systematic literature review on S-NCs following PRISMA guidelines. RESULTS: A 57-year-old woman presented with a seizure and paresthesias of the face, hands, and feet. Magnetic resonance imaging showed a right temporo-occipital cystic lesion, which was managed with surgical resection. Histologically, the cyst was type A. The patient was without recurrence at 10 months. Including this case, 88 S-NCs have been reported in the literature. Common presenting symptoms are headaches and seizures. They were mostly treated with craniotomy, preferably with gross total resection, although subtotal resection may be necessary because of adhesions. Resection usually led to symptom improvement (61%). Malignant transformation was seen in 3%. Recurrence was seen in 17%, with a mean time to recurrence of 4.2 years, and was significantly more common after subtotal resection than gross total resection. CONCLUSIONS: If surgically resected, the cyst wall specimen should be sent for pathology review, because of the potential risk for malignancy. If conservatively managed, serial imaging is warranted to track for changes that may indicate transformation. The embryopathogenesis of these rare congenital lesions remains incompletely understood, but the most comprehensive theory involves enteric cell migration to the neuroectoderm during embryogenesis.

Supratentorial cortical ependymoma: A systematic literature review and case illustration.

Cortical ependymomas are currently not considered a subgroup of supratentorial ependymomas; however, there is a growing body of literature investigating the natural history of these lesions compared to supratentorial ependymomas. We performed a systematic literature review of cortical ependymomas with a focus on the natural history, clinical characteristics, and clinical outcomes of these lesions as compared to supratentorial ependymomas. Our search revealed 153 unique cases of cortical ependymomas. The mean age on presentation was 21.2 years. Males and females comprised 58.8% (90/153) and 41.2% (63/153) of cases, respectively. The most common presenting symptom was seizure activity occurring in 44.4% of the cohort (68/153). The recently recognized C11orf95-RELA fusion was identified in 13.7% of the cohort (21/153) and 95.5% of cases (21/22) reporting molecular characterization. World Health Organization grades 2 and 3 were reported in 52.3% (79/151) and 47.7% (72/151) of cases, respectively. The frontal lobe was involved in the majority of cases (54.9%, 84/153). Gross total resection was achieved in 80.4% of cases (123/153). Tumor recurrence was identified in 27.7% of cases (39/141). Mean clinical follow-up was 41.3 months. Mean overall survival of patients who expired was 27.4 months whereas mean progression-free survival was 15.0 months. Comparatively, cortical ependymomas with C11orf95-RELA fusions and supratentorial ependymomas with C11orf95 RELA fusions exhibited differing clinical outcomes. Further studies with larger sample sizes are necessary to investigate the significance of RELA fusions on survival in cortical ependymomas and to determine whether cortical ependymomas with C11orf95-RELA fusions should be classified as a distinct entity.

Iatrogenic Leptomeningeal Carcinomatosis Following Craniotomy for Resection of Metastatic Serous Ovarian Carcinoma: A Systematic Literature Review and Case Report.

Metastasis of ovarian carcinoma to the central nervous system occurs in <2% of cases and classically localizes within the brain parenchyma. Moreover, leptomeningeal spread of these tumors is an exceedingly rare phenomenon. Here, we conduct a systematic review of the current literature on the natural history, treatment options, and proposed pathogenic mechanisms of leptomeningeal carcinomatosis in ovarian carcinoma. We also report a case of a 67-year-old female with stage IV metastatic ovarian serous carcinoma initially confined to the peritoneal cavity with a stable disease burden over the course of three years. Follow-up imaging demonstrated an intracranial lesion, which was resected via craniotomy, and pathology was consistent with the original diagnosis. Three months after surgery, she developed rapidly progressive dizziness, generalized weakness, fatigue, and ataxia. Repeat MRI demonstrated interval development of extensive and diffusely enhancing dural nodularity, numerous avidly enhancing supratentorial and infratentorial lesions, enhancement of the bilateral trigeminal nerves, internal auditory canals, and exit wound from the surgical site into the posterior aspect of the right-sided neck musculature consistent with diffuse leptomeningeal dissemination. The present case highlights that leptomeningeal dissemination of ovarian carcinoma is a potential yet rare consequence following surgical resection of an ovarian parenchymal metastasis. Progressive clinical symptomatology that develops postoperatively in this patient population should prompt urgent workup to rule out leptomeningeal disease and an expedited radiation oncology consultation if identified.

Decreased Incidence of CSF Leaks after Skull Base Fractures in the 21st Century: An Institutional Report.

Objectives Cerebrospinal fluid (CSF) leaks are a possible complication in patients with skull base fractures (SBFs). The widely cited incidence of CSF leaks is 10 to 30% in SBF patients; however, this estimate is based only on a few outdated studies. A recent report found CSF leaks in <2% SBF patients, suggesting the incidence may be lower now. To investigate this, we report here our institutional series. Design This study is a retrospective chart review. Setting The study was conducted at two major academic medical centers (2000-2018). Participants Adult patients with SBF were included in this study. Main Outcome Measures Variables included age, gender, CSF leak within 90 days, management regimen, meningitis within 90 days, and 1-year mortality. Results Among 4,944 patients with SBF, 199 (4%) developed a CSF leak. SBF incidence was positively correlated with year of clinical presentation ( r -squared 0.78, p < 0.001). Among CSF leaks, 42% were conservatively managed, 52% were treated with lumbar drain, and 7% required surgical repair. Meningitis developed in 28% CSF leak patients. The 1-year mortality for all SBF patients was 11%, for patients with CSF leaks was 12%, and for patients with meningitis was 16%. Conclusion In the largest institutional review of SBF patients in the 21st century, we found CSF leak incidence to be 4%. This is lower than the widely cited range of 10 to 30%. Nevertheless, morbidity and mortality associated with this complication remains clinically significant, and SBF patients should continue to be monitored for CSF leaks. We provide here our institutional treatment algorithm for these patients that may help to inform the treatment strategy at other institutions.

The low utility of routine cranial imaging after pediatric shunt revision.

OBJECTIVE: Postoperative routine imaging is common after pediatric ventricular shunt revision, but the benefit of scanning in the absence of symptoms is questionable. In this study, the authors aimed to assess how often routine scanning results in a change in clinical management after shunt revision. METHODS: The records of a large, tertiary pediatric hospital were retrospectively reviewed for all consecutive cases of pediatric shunt revision between July 2013 and July 2018. Postoperative imaging was classified as routine (i.e., in the absence of symptoms, complications, or other direct indications) or nonroutine. Reinterventions within 30 days were assessed in these groups. RESULTS: Of 387 included shunt revisions performed in 232 patients, postoperative imaging was performed in 297 (77%), which was routine in 244 (63%) and nonroutine in 53 (14%). Ninety revisions (23%) underwent any shunt-related procedure after postoperative imaging, including shunt reprogramming (n = 35, 9%), shunt tap (n = 10, 3%), and a return to the operating room (OR; n = 58, 15%). Of the 244 cases receiving routine imaging, 241 did not undergo a change in clinical management solely based on routine imaging findings. The remaining 3 cases returned to the OR, accounting for 0.8% (95% CI 0.0%-1.7%) of all cases or 1.2% (95% CI 0.0%-2.6%) of cases that received routine imaging. Furthermore, 27 of 244 patients in this group returned to the OR for other reasons, namely complications (n = 12) or recurrent symptoms (n = 15); all arose after initial routine imaging. CONCLUSIONS: The authors found a low yield to routine imaging after pediatric shunt revision, with only 0.8% of cases undergoing a change in management based on routine imaging findings without corresponding clinical findings. Moreover, routine imaging without abnormal findings was no guarantee of an uneventful postoperative course. Clinical monitoring can be considered as an alternative in asymptomatic, uncomplicated patients.

Extra-Axial Fluid Collections After Decompressive Craniectomy: Management, Outcomes, and Treatment Algorithm.

BACKGROUND: Extra-axial fluid collections (EACs) frequently develop after decompressive craniectomy. Management of EACs remains poorly understood, and information on how to predict their clinical course is inadequate. We aimed to better characterize EACs, understand predictors of their resolution, and delineate the best treatment paradigm for patients. METHODS: We reviewed patients who developed EACs after undergoing decompressive craniectomy for treatment of refractory intracranial pressure elevations. We excluded patients who had an ischemic stroke, as EACs in these patients have a different clinical course. We performed univariate analysis and multiple linear regression to find variables associated with earlier resolution of EACs and stratified our analyses by EAC phenotype (complicated vs. uncomplicated). We conducted a systematic review to compare our findings with the literature. RESULTS: Of 96 included patients, 73% were male, and median age was 42.5 years. EACs resolved after a median of 60 days. Complicated EACs were common (62.5%) and required multiple drainage methods before cranioplasty. These were not associated with a protracted course or increased risk of death (P > 0.05). Early bone flap restoration with simultaneous drainage was independently associated with earlier resolution of EACs (ß = 0.56, P < 0.001). Systematic review confirmed lack of standardized direction with respect to EAC management. CONCLUSIONS: Our analyses reveal 2 clinically relevant phenotypes of EAC: complicated and uncomplicated. Our proposed treatment algorithm involves replacing the bone flap as soon as it is safe to do so and draining refractory EACs aggressively. Further studies to assess long-term clinical outcomes of EACs are warranted.

The Impact of Age and Severity on Dementia After Traumatic Brain Injury: A Comparison Study.

BACKGROUND: Growing evidence associates traumatic brain injury (TBI) with increased risk of dementia, but few studies have evaluated associations in patients younger than 55 yr using non-TBI orthopedic trauma (NTOT) patients as controls to investigate the influence of age and TBI severity, and to identify predictors of dementia after trauma. OBJECTIVE: To investigate the relationship between TBI and dementia in an institutional group. METHODS: Retrospective cohort study (2000-2018) of TBI patients aged 45 to 100 yr vs NTOT controls. Primary outcome was dementia after TBI (followed ≤10 yr). Cox proportional hazards models were used to assess risk of dementia; logistic regression models assessed predictors of dementia. RESULTS: Among 24 846 patients, TBI patients developed dementia (7.5% vs 4.6%) at a younger age (78.6 vs 82.7 yr) and demonstrated higher 10-yr mortality than controls (27% vs 14%; P < .001). Mild TBI patients had higher incidence of dementia (9%) than moderate/severe TBI (5.4%), with lower 10-yr mortality (20% vs 31%; P < .001). Risk of dementia was significant in all mild TBI age groups, even 45 to 54 yr (hazard ratio 4.1, 95% CI 2.7-7.8). A total of 10-yr cumulative incidence was higher in mild TBI (14.4%) than moderate/severe TBI (11.3%) and controls (6.8%) (P < .001). Predictors of dementia include TBI, sex, age, hypertension, hyperlipidemia, stroke, depression, anxiety, and Injury Severity Score. CONCLUSION: Mild and moderate/severe TBI patients experienced higher incidence of dementia, even in the youngest group (45-54 yr old), than NTOT controls. All TBI patients, especially middle-aged adults with minor injury who are more likely to be overlooked, should be monitored for dementia.

Divergence in the epidemiological estimates of traumatic brain injury in the United States: comparison of two national databases.

OBJECTIVE: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the US, but the true incidence of TBI is unknown. METHODS: The National Trauma Data Bank National Sample Program (NTDB NSP) was queried for 2007 and 2013, and population-based weighted estimates of TBI-related emergency department (ED) visits, hospitalizations, and deaths were calculated. These data were compared to the 2017 Centers for Disease Control and Prevention (CDC) report on TBI, which used the Healthcare Cost and Utilization Project's National ("Nationwide" before 2012) Inpatient Sample and National Emergency Department Sample. RESULTS: In the NTDB NSP the incidence of TBI-related ED visits was 59/100,000 in 2007 and 62/100,000 in 2013. However, in the CDC report there were 534/100,000 in 2007 and 787/100,000 in 2013. The CDC estimate for ED visits was 805% higher in 2007 and 1169% higher in 2013. In the NTDB NSP, the incidence of TBI-related deaths was 5/100,000 in 2007 and 4/100,000 in 2013. In the CDC report, the incidence was 18/100,000 in both years. The CDC estimate for deaths was 260% higher in 2007 and 325% higher in 2013. CONCLUSIONS: The databases disagreed widely in their weighted estimates of TBI incidence: CDC estimates were consistently higher than NTDB NSP estimates, by an average of 448%. Although such a discrepancy may be intuitive, this is the first study to quantify the magnitude of disagreement between these databases. Given that research, funding, and policy decisions are made based on these estimates, there is a need for a more accurate estimate of the true national incidence of TBI.

Comparison of minor head trauma management in the emergency departments of a United States and Italian Children's hospital.

BACKGROUND: Pediatric head trauma management varies between emergency departments globally. Here we aim to compare the pediatric minor head trauma management between a US and Italian hospital. METHODS: We conducted a retrospective chart review of children 0-18 years old presenting after minor head trauma (Glasgow Coma Scale 14-15) from two emergency departments, in Boston, Massachusetts, United States and Trieste, Italy, between January and December 2013. Frequencies of demographic, clinical, and management characteristic were calculated. We compared rate ratios for characteristics of patients receiving cranial computed tomography (CT) scans between the two populations. RESULTS: There were 1783 patients in Boston, Massachusetts and 183 patients in Trieste, Italy. Patients in Boston had more reported neurologic symptoms (61.2%) than in Trieste (6%) (p < 0.001). More CT scans were ordered on the patients in Boston (17.3% vs. 6.6%) (p < 0.001), while more children were hospitalized in Trieste (55.7% vs. 8.6%) (p < 0.001). Patients with neurological symptoms more commonly had a CT scan in Trieste (45.5%) than in Boston (23.5%) (RR 0.52, 95% CI 0.27, 1.00), while more patients without neurological symptoms had CTs in Boston (7.5%) than in Trieste (4.1%) (RR 1.85, 95% CI 0.86, 4.00). Assignment of triage levels and definitions of head injury severity varied considerably between the two hospitals, resulting in dissimilar populations presenting to the two hospitals, and thus, differences in the management of these children. CONCLUSION: The population of head trauma patients and the management of pediatric minor head trauma differs between Boston and Trieste, with a preference for CT scans in Boston and a preference for hospitalization in Trieste. Clinical guidelines used at each institution likely lead to this variation in care influenced by the different patient populations and institutional resources.