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Immunotherapy has revolutionized the treatment of many tumors. However, most glioblastoma (GBM) patients have not, so far, benefited from such successes. With the goal of exploring ways to boost anti-GBM immunity, we developed a B cell-based vaccine (BVax) that consists of 4-1BBL+ B cells activated with CD40 agonism and IFNγ stimulation. BVax migrates to key secondary lymphoid organs and is proficient at antigen cross-presentation, which promotes both the survival and the functionality of CD8+ T cells. A combination of radiation, BVax, and PD-L1 blockade conferred tumor eradication in 80% of treated tumor-bearing animals. This treatment elicited immunological memory that prevented the growth of new tumors upon subsequent reinjection in cured mice. GBM patient-derived BVax was successful in activating autologous CD8+ T cells; these T cells showed a strong ability to kill autologous glioma cells. Our study provides an efficient alternative to current immunotherapeutic approaches that can be readily translated to the clinic., Competing Interests: Disclosures: C. Lee-Chang and M. Lesniak reported a patent to a B cell–based vaccine for glioma and other cancers, which is pending. No other disclosures were reported., (© 2020 Lee-Chang et al.)

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a cause of dementia that can be reversed when treated timely with cerebrospinal fluid (CSF) diversion. Understanding CSF dynamics throughout the development of hydrocephalus is crucial to identify prognostic markers to estimate benefit/risk to shunts., Objective: To explore the cerebral aqueduct CSF flow dynamics with phase-contrast magnetic resonance imaging (MRI) in a novel rodent model of adult chronic communicating hydrocephalus., Methods: Kaolin was injected into the subarachnoid space at the convexities in Sprague-Dawley adult rats. 11.7-T Bruker MRI was used to acquire T2-weighted images for anatomic identification and phase-contrast MRI at the cerebral aqueduct. Aqueductal stroke volume (ASV) results were compared with the ventricular volume (VV) at 15, 60, 90, and 120 days., Results: Significant ventricular enlargement was found in kaolin-injected animals at all times (P < 0.001). ASV differed between cases and controls/shams at every time point (P = 0.004, 0.001, 0.001, and <0.001 at 15, 60, 90, and 120 days, respectively). After correlation between the ASV and the VV, there was a significant correlation at 15 (P = 0.015), 60 (P = 0.001), 90 (P < 0.001), and 120 days. Moreover, there was a significant positive correlation between the VV expansion and the aqueductal CSF stroke between 15 and 60 days., Conclusions: An initial active phase of rapid ventricular enlargement shows a strong correlation between the expansion of the VV and the increment in the ASV during the first 60 days, followed by a second phase with less ventricular enlargement and heterogeneous behavior in the ASV. Further correlation with complementary data from intracranial pressure and histologic/microstructural brain parenchyma assessments are needed to better understand the ASV variations after 60 days., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Normal pressure hydrocephalus (NPH) is an underdiagnosed and undertreated condition affecting the elderly population and with costs associated with its surgical management reported to be less than those associated with conservative management., Objective: To determine if the rate of diagnosis of NPH has improved over the last decade, the rate of treatment has increased, and if surgical treatment costs and socioeconomic factors related to receipt of treatment have changed over time compared with conservative therapy., Methods: A retrospective study based on data from a nationally representative random sample of 2,378,637 Medicare beneficiaries (2006-2010) was performed. Shunt surgery, shunt revision, replacement, and removal were analyzed as independent variables., Results: A total of 2321 patients with NPH were included, with 580 (24.99%) receiving a first shunt procedure. The adjusted effect of the procedure is that total 5-year expenditures are $11,676 more per patient (P < 0.001) than expenditures associated with nonsurgical management. Shunt revision ($22,715, P < 0.01) and/or replacement ($46,607, P < 0.001) add significantly to 5-year expenditures. Socioeconomic factors including African American race (P = 0.006); age 75-79 years (P = 0.024), 80-84 years (P < 0.001), and ≥85 years (P < 0.001); and Medicaid (P < 0.001) have significant negative associations with shunt surgery., Conclusions: There was a 1.66-fold increase in the rate of diagnosis of NPH, from 0.12% in 1999 to 0.2% in 2008. The total costs per surgical patient rose by approximately 145% to 160% comparing 2001 and 2010. This increase was mainly due to hospital (by 167% to 168%) and home health costs (by 118% to 148%). Providing appropriate care across the socioeconomic spectrum warrants further study and requires identifying the factors that limit access to care., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: The pathophysiology of normal-pressure hydrocephalus and the correlation with its symptomatology is not well understood., Objective: To monitor and evaluate the enlargement patterns of the ventricular system for each ventricle and its correlation with the presenting symptoms., Methods: Bilateral kaolin injection into the subarachnoid space overlying the cranial convexities was done in 18 adult rats. Magnetic resonance imaging was performed on an 11.7-T scanner 15, 60, 90, and 120 days after injection. Volumes of the ventricular system were measured for each ventricle and correlated with biweekly behavioral findings., Results: There was a progressive increase in the ventricular volume for the lateral ventricles since day 15 in the kaolin-injected animals. There was a nonsignificant trend in volume growth for the third ventricle, but its enlargement was synchronous with the lateral ventricles. No significant change for the fourth ventricle. No symptoms were detected in the first 60 days. Association was found between the ventricular volume and locomotor changes. In addition, the odds of locomotor symptoms increased by 3% for every additional cubic millimeter of volume in the left (P < 0.001) and right (P = 0.023) ventricles, and for the total magnetic resonance imaging volume by 1% (P = 0.013)., Conclusions: Expansion of the lateral ventricles maintained similar proportions over time, accompanied by a synchronous third ventricular expansion with less proportion and a nonsignificant fourth enlargement. Lateral ventricles enlarged most in those animals that were to develop late locomotor deterioration. Further research using this animal model combined with different radiologic imaging techniques, such as diffusion tensor imaging and perfusion studies, is recommended., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In the late 19th century, Dr. William B. Coley introduced the theory that infections may aid in the treatment of malignancy. With the creation of Coley's toxin, reports of remission during viral illnesses for systemic malignancies soon emerged. A few decades after this initial discovery, Austrian physicians performed intravascular injections of Clostridium to induce oncolysis in patients with glioblastoma. Since then, suggestions between improved survival and infectious processes have been reported in several patients with glioma, which ultimately marshaled the infamous use of intracerebral Enterobacter. These early observations of tumor regression and concomitant infection piloted a burgeoning field focusing on the use of pathogens in molecular oncology.

Shunts that are used for the treatment of hydrocephalus have a propensity towards malfunction, however, diagnosing a shunt malfunction can sometimes be a challenge. The purpose of this study was to investigate whether ultrasound technology can be safely and effectively used to assess for distal shunt malfunction. This was a prospective cohort study at a single institution. Eighteen adult patients that received a radionuclide shunt patency study also underwent an ultrasound shunt patency study. Ultrasound with Doppler technology was used to visualize flow through the shunt tubing following manual compression of the shunt reservoir. A peak flow speed was recorded and the results were compared to the results of the radionuclide shunt patency study. A Receiver Operating Characteristic (ROC) curve comparing the ultrasound to the radionuclide shunt patency study was generated, revealing an Area Under the Curve (AUC) of 0.95 (95% CI: 0.84-1.00). The ultrasound test performed maximally with a cutoff speed of ≤10cm/s as the criteria for malfunction, with a sensitivity of 100.00%, specificity of 90.91%, accuracy of 94.44%, positive likelihood ratio of 11.000 and negative likelihood ratio of 0.000 using the radionuclide study results as criteria for comparison. Overall, ultrasound has the potential to be a safe, quick, available and cost-effective screening test for patients with suspected distal shunt malfunction. The high sensitivity of the test makes it an attractive option for use as a screening method that could potentially reduce the number of cases requiring radionuclide shunt patency study., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study is to evaluate long-term treatment outcome and toxicities among vestibular schwannoma (VS) patients treated with hypofractionated stereotactic radiotherapy (HSRT)., Methods: 383 patients with unilateral VS treated with HSRT (25 Gy, five fractions) between 1995 and 2007 were retrospectively reviewed. Treatment failure was defined as requiring salvage microsurgery. Posttreatment new/progressive clinical symptoms or increases in baseline tumor volume (BTV) due to treatment effect or progression were noted. Symptom outcomes were reported as baseline and posttreatment ± improvement, respectively. Symptoms were grouped by cranial nerve (CN) VII or CNVIII. Audiometry was assessed baseline and posttreatment hearing. Patients were grouped as having greater than serviceable hearing [Gardner Robertson (GR) score 1-2] or less than non-serviceable hearing (GR score 3-5) by audiometry., Results: Median follow-up was 72.0 months. Nine (2.3%) experienced treatment failure. At last follow-up, 74 (19.3%) had new/progressive symptoms and were categorized as radiologic non-responders, whereas 300 (78.3%) had no tumor progression and were grouped as radiologic responders. Average pretreatment BTV for treatment failures, radiologic non-responders, and radiologic responders was 2.11, 0.44, and 1.87 cm 3 , respectively. Pretreatment CNVII and CNVIII symptoms were present in 9.4 and 93.4% of patients, respectively. Eight (24%) with pre-HSRT CNVII and 37 (10%) with pre-HSRT CNVIII symptoms recovered CN function post-HSRT. Thirty-five (9%) and 36 (9.4%) experienced new CNVII and CNVIII deficit, respectively, after HSRT. Of these, 20 (57%) and 18 (50%) recovered CNVII and CNVIII function, respectively, after HSRT. Evaluable audiograms were available in 199 patients. At baseline and at last follow-up, 65.8 and 36.2% had serviceable hearing, respectively. Fifty-one percent had preservation of serviceable hearing at last follow-up., Conclusion: Treatment of VS with HSRT is effective with treatment success in 97.7% and an acceptable toxicity profile. Less than one-third of patients experience any new CNVII or CNVIII deficit posttreatment. Greater than 50% of patients with serviceable hearing at baseline maintained hearing function. Improved methods to differentiate treatment effect and tumor progression are needed.

OBJECTIVE Factors associated with emergency department admission and/or shunt revision for idiopathic intracranial hypertension (IIH) are unclear. In this study, the associations of several factors with emergency department admission and shunt revision for IIH were explored. METHODS The authors performed a retrospective review of 31 patients (169 total emergency department visits) who presented to the emergency department for IIH-related symptoms between 2003 and 2015. Demographics, comorbidities, symptoms, IIH diagnosis and treatment history, ophthalmological examination, diagnostic lumbar puncture (LP), imaging findings, and data regarding admission and management decisions were collected. Multivariable general linear models regression analysis was performed to assess the predictive factors associated with admission and shunt revision. RESULTS Thirty-one adult patients with a history of shunt placement for IIH visited the emergency department a total of 169 times for IIH-related symptoms, with a median of 3 visits (interquartile range 2-7 visits) per patient. Five patients had more than 10 emergency department visits. Baseline factors associated with admission included male sex (OR 10.47, 95% CI 2.13-51.56; p = 0.004) and performance of an LP (OR 3.10, 95% CI 1.31-7.31; p = 0.01). Contrastingly, older age at presentation (OR 0.94, 95% CI 0.90-0.99; p = 0.01), and a greater number of prior emergency department visits (OR 0.94, 95% CI 0.89-0.99; p = 0.02) were slightly protective against admission. The presence of papilledema (OR 11.62, 95% CI 3.20-42.16; p < 0.001), Caucasian race (OR 40.53, 95% CI 2.49-660.09 p = 0.009), and systemic hypertension (OR 7.73, 95% CI 1.11-53.62; p = 0.03) were independent risk factors for shunt revision. In addition, a greater number of prior emergency department visits (OR 0.86, 95% CI 0.77-0.96; p = 0.009) and older age at presentation (OR 0.93, 95% CI 0.87-0.99; p = 0.02) were slightly protective against shunt revision, while there was suggestive evidence that presence of a programmable shunt (OR 0.23, 95% CI 0.05-1.14; p = 0.07) was a protective factor against shunt revision. Of note, location of the proximal catheter in the ventricle or lumbar subarachnoid space was not significantly associated with admission or shunt revision in the multivariable analyses. CONCLUSIONS The decision to admit a shunt-treated patient from the emergency department for symptoms related to IIH is challenging. Knowledge of factors associated with the need for admission and/or shunt revision is required. In this study, factors such as male sex, younger age at presentation, lower number of prior emergency department visits, and performance of a diagnostic LP were independent predictors of admission. In addition, papilledema was strongly predictive of the need for shunt revision, highlighting the importance of an ophthalmological examination for shunt-treated adults with IIH who present to the emergency department.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a devastating condition that affects the elderly population. Although ventriculoatrial (VA) shunts can be used to manage iNPH, concerns for associated cardiopulmonary and renal complications have decreased their use. However, the rate of these complications is not well understood within this population of patients., Patients and Methods: A retrospective review of the electronic medical records of patients diagnosed with iNPH by the senior author between 1993 and 2015 was performed. Demographic information and baseline symptoms were assessed. Complications including infection, shunt obstruction, overdrainage, cardiopulmonary events, renal dysfunction, and shunt revision were recorded. Complication rates were compared between VA and VP shunted patients. Statistical analysis using Chi-square test, Fisher's exact test, logistic regression, Wald t-test, Poisson regression, ANOVA, and ANCOVA was performed., Results: 496 Patients, including 150 receiving VA shunts and 346 receiving VP shunts, were included in the study. The median age was 74 and 73 for VA and VP shunted patients, respectively, with slight male predominance in both (58.0% and 58.4% for VA and VP groups, respectively). A total of 36.0% of VA shunted patients and 42.5% of VP shunted patients experienced at least one post-operative complication. Overdrainage was the most commonly experienced complication in both VA (27.4%) and VP patients (19.9%). Infection occurred in only 2.0% of patients, and renal complications occurred in 1.3%. No patients had cardiopulmonary complications. VA shunted patients were significantly less likely to experience shunt obstruction and require shunt revision compared to VP shunted patients (p=0.008 and <0.001, respectively). Only dizziness and gait disturbance at baseline were correlated with a shorter time to revision in VA shunted patients (p=0.002 for both)., Conclusion: Although cardiopulmonary and renal complications are serious concerns associated with VA shunt placement, they were uncommon in patients with iNPH. VA shunted patients were less likely to experience shunt obstruction and require shunt revision compared to VP shunted patients. Therefore, VA shunts should be considered as an alternative primary treatment option in the iNPH population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The pathogenesis of adult chronic hydrocephalus is not fully understood, and the temporal relationship between development of the radiological changes and neurological deterioration is unknown., Objective: To clarify the progression of radiological-histological changes and subsequent clinical manifestations of adult chronic hydrocephalus., Methods: Kaolin was injected bilaterally into the subarachnoid space overlying the cranial convexities in 20 adult rats. Magnetic resonance imaging (MRI) was obtained by using an 11.7 T scanner at 14, 60, 90, and 120 days after kaolin injection. Locomotor, gait, and cognitive evaluations were performed independently. Kaolin distribution and the associated inflammatory and fibrotic responses were histologically analyzed., Results: Evans index of ventriculomegaly showed significant progressive growth in ventricular size over all time points examined. The greatest enlargement occurred within the first 2 months. Evans index also correlated with the extent of kaolin distribution by MRI and by pathological examination at all time points. First gait changes occurred at 69 days, anxiety at 80, cognitive impairment at 81, and locomotor difficulties after 120 days. Only locomotor deterioration was associated with Evans index or the radiological evaluation of kaolin extension. Inflammatory/fibrotic response was histologically confirmed over the cranial convexities in all rats, and its extension was associated with ventricular size and with the rate of ventricular enlargement., Conclusion: Kaolin injected into the subarachnoid space over the cerebral hemispheres of adult rats produces an inflammatory/fibrotic response leading in a slow-onset communicating hydrocephalus that is initially asymptomatic. Increased ventricular size eventually leads to gait, memory, and locomotor impairment closely resembling the course of human adult chronic hydrocephalus., Abbreviation: NPH, normal pressure hydrocephalus.

OBJECTIVE A growing body of evidence suggests that longer durations of preoperative symptoms may correlate with worse postoperative outcomes following cerebrospinal fluid (CSF) diversion for treatment of idiopathic normal pressure hydrocephalus (iNPH). The aim of this study is to determine whether the duration of preoperative symptoms alters postoperative outcomes in patients treated for iNPH. METHODS The authors conducted a retrospective review of 393 cases of iNPH involving patients treated with ventriculoperitoneal (VP) shunting. The duration of symptoms prior to the operative intervention was recorded. The following outcome variables were assessed at baseline, 6 months postoperatively, and at last follow-up: gait performance, urinary continence, and cognition. RESULTS The patients' median age at shunt placement was 74 years. Increased symptom duration was significantly associated with worse gait outcomes (relative risk (RR) 1.055 per year of symptoms, p = 0.037), and an overall absence of improvement in any of the classic triad symptomology (RR 1.053 per year of symptoms, p = 0.033) at 6 months postoperatively. Additionally, there were trends toward significance for symptom duration increasing the risk of having no 6-month postoperative improvement in urinary incontinence (RR 1.049 per year of symptoms, p = 0.069) or cognitive symptoms (RR 1.051 per year of symptoms, p = 0.069). However, no statistically significant differences were noted in these outcomes at last follow-up (median 31 months). Age stratification by decade revealed that prolonging symptom duration was significantly associated with lower Mini-Mental Status Examination scores in patients aged 60-70 years, and lack of cognitive improvement in patients aged 70-80 years. CONCLUSIONS Patients with iNPH with longer duration of preoperative symptoms may not receive the same short-term benefits of surgical intervention as patients with shorter duration of preoperative symptoms. However, with longer follow-up, the patients generally reached the same end point. Therefore, when managing patients with iNPH, it may take longer to see the benefits of CSF shunting when patients present with a longer duration of preoperative symptoms.

Background: Timely detection of intraorbital and skull base wooden foreign bodies is crucial. Wooden foreign bodies are difficult to detect on imaging. The radiologist may fail to identify wooden foreign bodies on two thirds of initial scans and can miss them in almost one third of total cases., Case Description: A 66-year-old woman sustained a penetrating injury through the left upper eyelid with a small tree branch. The branch was immediately removed in the field, and she was provided with prompt medical care at a local hospital. Initial computed tomography (CT) scan diagnosis was "posttraumatic sinusitis," and this was treated empirically with vancomycin and piperacillin/tazobactam. On the eighth day after injury, she developed progressive swelling and pain of her eyelid with left trigeminal/supraorbital numbness and complete left ophthalmoplegia. A new CT scan showed an open "track" from the region of the left upper orbit/superior rectus to the contralateral sphenoid sinus, which raised suspicion for a retained foreign body. Further imaging confirmed the suspicion. Endoscopic sinus surgery was performed with extraction of the wooden object and evacuation of the left orbital infection., Conclusions: This case indicates that intraorbital and skull base wooden foreign bodies are elusive, demanding a high index of suspicion from both clinicians and radiologists to identify retained material in the setting of ocular or sinus trauma. For better identification of wooden foreign bodies, bone windows on CT should have a width of -1000 Hounsfield units with a soft tissue window level of -500 Hounsfield units., (Published by Elsevier Inc.)

Placement of a ventriculoperitoneal (VP) shunt is the treatment of choice for communicating hydrocephalus; however, the extent to which VP shunting is able to relieve symptoms in patients who had previously been treated with cerebrospinal fluid diverting therapy at an outside institution remains unclear. A retrospective review of patients with idiopathic normal pressure hydrocephalus treated with VP shunts at a single institution between 1993 and 2013 was conducted. Patients were classified as having received a primary VP shunt if they had not been previously treated with a VP shunt, ventriculoatrial shunt, lumboperitoneal shunt, or endoscopic third ventriculostomy. Patients were classified as having received a salvage VP shunt if they had been previously treated by one of these four modalities at an outside institution prior to their presentation to our institution. There were 357 patients who received a primary shunt and 33 patients who received a salvage shunt. Patients who had a salvage shunt placed had significantly higher odds of requiring a future revision (54% versus 41%; odds ratio=2.85; 95% confidence interval [CI]: 1.24-6.57; p=0.014). Patients who received a salvage shunt had statistically significantly lower rates of gait improvement at 6months in comparison to patients who received a primary shunt (relative risk=0.35; 95% CI: 0.14-0.87; p=0.025). Despite these findings, there was no significant difference at last follow-up in improvement in gait, continence, and cognition, indicating that outcomes for patients requiring a salvage shunt were comparable to patients receiving a primary shunt., (Published by Elsevier Ltd.)

Introduction: Early treatment of normal pressure hydrocephalus (NPH) yields better postoperative outcomes. Our current tests often fail to detect significant changes at early stages. We developed a new scoring system (LP log score) to determine if this tool is more sensitive in detecting clinical differences than current tests., Material and Methods: Sixty-two consecutive new patients with suspected idiopathic NPH were studied. Secondary, previously treated and obstructive cases were not included. We collected age, pre- and post-lumbar puncture (LP) Tinetti, Timed Up and Go (TUG) Test, European NPH scale, and LP log scores. The LP log score is recorded at baseline and for seven consecutive days after removing 40 cc of cerebrospinal fluid (CSF) via LP. We studied the diagnostic accuracy of the tests for surgical indication., Results: The post-LP log showed improvement in 90% of people with good baseline gait tests and in 93% of people who did not show any pre-LP and post-LP change in gait tests. Sensitivity, specificity, and accuracy to detect intention to treat when positive post-LP improvements were 4%, 100%, and 24%, respectively, for TUG, 21%, 86%, and 34%, respectively, for the Tinetti Mobility Test, 66%, 29%, and 58%, respectively, for Medical College of Virginia (MCV) grade, and 98%, 33%, and 85%, respectively, for LP log score. Pre-LP and post-LP TUG improvement and pre-LP and post-LP Tinetti improvement were not associated with a surgical indication (p > 0.05). LP log improvement was associated with surgical indication odds ratio (OR): 24.5 95% CI (2.4-248.12) (p = 0.007)., Conclusions: LP log showed better sensitivity, diagnostic accuracy, and association with surgical indication than the current diagnostic approach. An LP log may be useful detecting NPH patients at earlier stages and, therefore, yield better surgical outcomes.

Objective: Few studies have focused on predictive factors of ventriculoperitoneal (VP) shunt revision in patients with idiopathic normal pressure hydrocephalus (iNPH). This study aims to determine whether comorbidities and baseline symptoms are associated with the need for shunt revision., Methods: A retrospective review of patients with iNPH treated with VP shunts by the senior author from 1993 to 2013 was conducted. Demographics and baseline symptoms were compared between patients with and without shunt revision. The need for revision, total number of revisions, and time to first revision were examined. Statistical analysis was performed using simple logistic, linear, and Poisson regression, and a multivariate analysis was performed., Results: A total of 347 patients with iNPH who received VP shunts were included. One hundred patients (28.8%) required shunt revision, with an average of 1.38 ± 0.76 revisions per patient. Mean time to revision was 19.2 ± 31.7 months. Gait and cognitive symptoms were associated with fewer revisions (incidence rate ratio, 0.45 and 0.67; P = 0.03 and 0.004, respectively). Headaches and urinary incontinence showed a greater time to revision (32.0 and 12.0 months; P = 0.014 and <0.0005, respectively). Gait instability demonstrated decreased time to revision (P < 0.0005)., Conclusions: Preoperative symptoms, such as headaches, gait instability, cognitive decline, and urinary incontinence, were significantly correlated with number of revisions and time to first revision. These factors should be considered during the initial counseling of prognosis for patients with iNPH receiving VP shunts., (Published by Elsevier Inc.)

OBJECT Endoscopic third ventriculostomy (ETV) is the treatment of choice for obstructive hydrocephalus; however, the success of ETV in patients who have previously undergone shunt placement remains unclear. The present study analyzed 103 adult patients with aqueductal stenosis who underwent ETV for obstructive hydrocephalus and evaluated the effect of previous shunt placement on post-ETV outcomes. METHODS This study was a retrospective review of 151 consecutive patients who were treated between 2007 and 2013 with ETV for hydrocephalus. One hundred three (68.2%) patients with aqueductal stenosis causing obstructive hydrocephalus were included in the analysis. Postoperative ETV patency and aqueductal and cisternal flow were assessed by high-resolution, gradient-echo MRI. Post-ETV Mini-Mental State Examination, Timed Up and Go, and Tinetti scores were compared with preoperative values. Univariate and multivariate analyses were performed comparing the post-ETV outcomes in patients who underwent a primary (no previous shunt) ETV (n = 64) versus secondary (previous shunt) ETV (n = 39). RESULTS The majority of patients showed significant improvement in symptoms after ETV; however, no significant differences were seen in any of the quantitative tests performed during follow-up. Symptom recurrence occurred in 29 (28.2%) patients after ETV, after a median of 3.0 (interquartile range 0.8-8.0) months post-ETV failure. Twenty-seven (26.2%) patients required surgical revision after their initial ETV. Patients who received a secondary ETV had higher rates of symptom recurrence (p = 0.003) and surgical revision (p = 0.003), particularly in regard to additional shunt placement/revision post-ETV (p = 0.005). These differences remained significant after multivariate analysis for both symptom recurrence (p = 0.030) and surgical revision (p = 0.043). CONCLUSIONS Patients with obstructive hydrocephalus due to aqueductal stenosis exhibit symptomatic improvement after ETV, with a relatively low failure rate. Patients with a primary history of shunt placement who undergo ETV as a secondary intervention are at increased risk of symptom recurrence and need for surgical revision post-ETV.

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder that classically presents with a triad of progressive gait impairment, urinary incontinence, and cognitive deterioration. Treatment predominantly involves ventriculoperitoneal (VP) shunting, but one alternative is ventriculoatrial (VA) shunting. This study sought to describe and evaluate the clinical outcomes of patients with iNPH primarily treated with VA shunting., Materials and Methods: A retrospective review of patients with iNPH who were treated with VA shunting at a single institution, from 2003 to 2013, was performed., Results: 58 patients with iNPH underwent primary VA shunting at a median age of 74 (IQR: 70-80) years. The most common comorbidities included hypertension (n=39, 67%) and diabetes mellitus (n=11, 19%). Median duration of symptoms prior to VA shunting was 24 (IQR: 12-36) months. All patients had gait impairment, 52 (90%) had cognitive decline, and 43 (74%) had urinary incontinence. Forty-three (74%) patients had all three symptoms. At a median last follow-up of 16 (IQR: 7-26) months, median iNPH score improved from 6 to 3 (p<0.0001), mini mental status exam (MMSE) tended to increase from 26 to 29 (p=0.082), timed up-and-go (TUG) improved from 18 to 13s (p<0.0001), and Tinetti score improved from 19 to 25 (p<0.0001) after VA shunting. 78% of patients had improvement in at least one of their symptoms with 66% of patients having improvement in gait, 53% having improvement in their cognition, and 52% having improved urinary incontinence. A total of 21 patients (36%) had improvement in all 3 symptoms., Conclusions: There were significant improvements in functional outcomes as evaluated via the iNPH score, TUG, and Tinetti score, while improvement in MMSE trended toward significance. Patients also had improvement of clinical symptoms related to gait, urinary function and cognition. These results suggest that VA shunting can be an effective primary treatment alternative to VP shunting for iNPH., (Published by Elsevier B.V.)

Background: Despite advancements in materials and techniques used for cranial reconstruction, complication rates following reconstructive cranioplasty remain significant., Methods: In this study, the authors assessed the association of perioperative anticoagulation use and/or a hypercoagulable state with minor (i.e., not requiring surgical intervention) and major (i.e., surgical intervention required) complications after reconstructive cranioplasty for large skull defects. A retrospective cohort review of 108 consecutive cranioplasties performed between 2011 and 2014 was conducted. A multiple logistic regression analysis was performed to identify the adjusted association between the predictor variables and complications., Results: Twenty-three primary (21.3 percent) and 85 secondary (78.7 percent) cranioplasties were performed on 94 patients with a median age of 50 years (interquartile range, 38 to 63 years). Median full-thickness calvarial defect size was 154 cm (interquartile range, 104 to 230 cm). Eleven minor (10.2 percent) and 18 major postoperative complications (16.7 percent) occurred in 26 cases (24.1 percent). Multiple logistic regression analysis revealed that coagulation status (i.e., perioperative use of anticoagulation therapy or hypercoagulable state) was statistically significant in predicting minor complications (OR, 7.8; 95 percent CI, 2.4 to 25.2; p = 0.001). Of note, the odds of a minor complication were an order of magnitude higher when both perioperative anticoagulation and a hypercoagulable state were present., Conclusion: To the authors' knowledge, this is the first study to document that the use of perioperative anticoagulant therapy for patients with thromboembolic conditions is a positive predictor of complications following cranioplasty reconstruction., Clinical Question/level of Evidence: Therapeutic, III.

Background: Endoscopic third ventriculostomy (ETV) is commonly used to treat obstructive hydrocephalus. Closure of the stoma can be associated with symptom recurrence and need for further surgical intervention., Objective: To describe the use of a side-cutting aspiration device for treatment of aqueductal stenosis in patients undergoing ETV., Methods: A retrospective review of 30 consecutive adults with aqueductal stenosis treated with ETV using an adjunct side-cutting aspiration device between 2011 and 2013 was performed. Patients included in the study ranged from 35 to 64 years of age. ETV success was determined by the absence of stoma closure (aqueductal and cisternal flow assessed by high-resolution, gradient-echo magnetic resonance imaging), post-ETV symptom recurrence, and need for subsequent surgical intervention., Results: Patients treated by using a side-cutting aspirator had no observed stoma closure (0%) and a 10% (n = 3) rate of post-ETV symptom recurrence. Three patients (10%) demonstrated a need for surgical revision following initial ETV with the side-cutting aspirator., Conclusion: Adult patients with obstructive hydrocephalus secondary to aqueductal stenosis exhibited a low rate of stoma closure with the use of a side-cutting aspiration device, and a rate of complications comparable to the known literature. Likewise, patients treated with a side-cutting aspirator may have lower symptom recurrence post-ETV and require fewer revisions in comparison with the known literature. As such, a side-cutting aspirator may be considered as a useful adjunct to traditional ETV for the treatment of obstructive hydrocephalus secondary to aqueductal stenosis.

Background: Shunted patients with idiopathic intracranial hypertension (IIH) often present to the emergency department (ED) for symptoms related to their disease. Although brain imaging with computed tomography (CT) is often performed, particularly in the current medicolegal environment, its utility during these ED visits is unclear., Methods: The ED visits of all shunted adult patients with IIH from 2003-2015 were retrospectively reviewed. ED visits not related to IIH were excluded from our study., Results: Thirty-one patients visited the ED 171 times for IIH symptoms. Five patients had greater than 10 ED visits. Twenty-five (81%) patients had 131 visits involving a CT scan, while six (19%) patients were not scanned. The majority of scans (n = 126, 96%) showed no change; five (4%) scans detected new noncritical pathologies. On the basis of CT findings alone, treatment changes occurred in three (2.3%) instances. Of the 131 visits with a CT scan, twenty-five (19%) visits resulted in management changes; of the 40 ED visits without a CT scan, four (10%) visits resulted in a management change (P = 0.23)., Conclusions: In our cohort, CT imaging rarely showed a change in pathology or affected the management of patients with IIH. There was no difference in the rate of management changes between those patients who underwent a CT scan and those who did not. Given the risk of cumulative radiation exposure and cost of CT scans, CT imaging should be used when there is concern for visual dysfunction and the utility of CT imaging in the ED for the workup of other symptoms related to IIH must be explored further., (Published by Elsevier Inc.)

OBJECT The number of patients with spinal tumors is rapidly increasing; spinal metastases develop in more than 30% of cancer patients during the course of their illness. Such lesions can significantly decrease quality of life, often necessitating treatment. Stereotactic radiosurgery has effectively achieved local control and symptomatic relief for these patients. The authors determined prognostic factors that predicted pain palliation and report overall institutional outcomes after spine stereotactic body radiation therapy (SBRT). METHODS Records of patients who had undergone treatment with SBRT for either primary spinal tumors or spinal metastases from June 2008 through June 2013 were retrospectively reviewed. Data were collected at the initial visit just before treatment and at 1-, 3-, 6-, and 12-month follow-up visits. Collected clinical data included Karnofsky Performance Scale scores, pain status, presence of neurological deficits, and prior radiation exposure at the level of interest. Radiation treatment plan parameters (dose, fractionation, and target coverage) were recorded. To determine the initial extent of epidural spinal cord compression (ESCC), the authors retrospectively reviewed MR images, assessed spinal instability according to the Bilsky scale, and evaluated lesion progression after treatment. RESULTS The study included 99 patients (mean age 60.4 years). The median survival time was 9.1 months (95% CI 6.9-17.2 months). Significant decreases in the proportion of patients reporting pain were observed at 3 months (p < 0.0001), 6 months (p = 0.0002), and 12 months (p = 0.0019) after treatment. Significant decreases in the number of patients reporting pain were also observed at the last follow-up visit (p = 0.00020) (median follow-up time 6.1 months, range 1.0-56.6 months). Univariate analyses revealed that significant predictors of persistent pain after intervention were initial ESCC grade, stratified by a Bilsky grade of 1c (p = 0.0058); initial American Spinal Injury Association grade of D (p = 0.011); initial Karnofsky Performance Scale score, stratified by a score of 80 (p = 0.002); the presence of multiple treated lesions (p = 0.044); and prior radiation at the site of interest (p < 0.0001). However, when multivariate analyses were performed on all variables with p values less than 0.05, the only predictor of pain at last follow-up visit was a prior history of radiation at the site of interest (p = 0.0038), although initial ESCC grade trended toward significance (p = 0.073). Using pain outcomes at 3 months, at this follow-up time point, pain could be predicted by receipt of radiation above a threshold biologically effective dose of 66.7 Gy. CONCLUSIONS Pain palliation occurs as early as 3 months after treatment; significant differences in pain reporting are also observed at 6 and 12 months. Pain palliation is limited for patients with spinal tumors with epidural extension that deforms the cord and for patients who have previously received radiation to the same site. Further investigation into the optimal dose and fractionation schedule are needed, but improved outcomes were observed in patients who received radiation at a biologically effective dose (with an a/b of 3.0) of 66.7 Gy or higher.

Objectives: Shunt series and shunt patency studies can be performed in the emergency department (ED) to evaluate for shunt malfunction in patients with idiopathic intracranial hypertension (IIH). Here, we examine the utility of these studies in this specific patient population., Methods: We retrospectively reviewed the ED visits of all shunted patients diagnosed with IIH from 2003 to 2014. ED visits for symptoms not related to the patient's IIH were excluded from the study. Collected variables included demographics, symptoms, IIH diagnosis and treatment history, imaging findings, and management changes., Results: Twenty-five (81%) patients had a total of 105 visits involving a shunt series, with four (3.9%) showing problems with the catheter. The majority of shunt series (n=101, 96%) showed no catheter pathology. Based on results of the shunt series alone, in 3 instances, management changes in the form of shunt revision or shunt reprogramming occurred. Of the 105 visits with a shunt series, 17 (16%) resulted in a change in management as compared to 12 out of 66 (18%) visits without a shunt series (p=0.83). Nine patients had a total of 10 visits involving a shunt patency study: five were normal, four were abnormal, and one was inconclusive. Based on findings on the shunt patency study alone, changes in management leading to shunt adjustment or revision occurred in 4 instances. Of the 10 visits with shunt patency studies, 5 resulted in a change in management as compared to 24 out of 161 visits without a shunt patency study (p=0.014)., Conclusions: Shunt series detected catheter pathology only 3.9% of the time, and there was no difference in the rate of management changes between those patients who underwent a shunt series and those who did not. There was a significant difference in the rate of management changes in patients who received shunt patency studies as compared to those who did not. Shunt series may not be a useful screening tool to be used universally to diagnose shunt malfunction in IIH patients in the ED, and should be utilized when there is concern for impending visual loss. Shunt patency studies should be reserved for patients with inconclusive diagnostic imaging and clinical findings to decide whether to proceed to surgical exploration and revision., (Published by Elsevier B.V.)

We evaluated if patients with idiopathic normal pressure hydrocephalus (iNPH) showed functional improvement after primary endoscopic third ventriculostomy (ETV). The efficacy of ETV for iNPH remains controversial. We retrospectively reviewed 10 consecutive patients treated between 2009 and 2011 with ETV for iNPH. Seven patients with a median age of 73 years (range: 60-80) who underwent a primary ETV for iNPH were included for analysis. Median follow-up was 39 months (range: 26-46). Post-ETV stoma and aqueductal and cisternal flows were confirmed via high resolution, gradient echo and phase contrast MRI. Post-ETV timed up and go (TUG) and Tinetti performance oriented mobility assessment scores were compared to pre- and post-lumbar puncture (LP) values. A second LP was performed if ETV failed to sustain the observed improvement after initial LP. Patients who demonstrated ETV failure were subsequently shunted. Compared to pre-LP TUG and Tinetti values of 14.00 seconds (range: 12.00-23.00) and 22 (range: 16-24), post-LP scores improved to 11.00 seconds (range: 8.64-15.00; p=0.06) and 25 (range: 24-28; p=0.02), respectively. ETV failed to sustain this improvement with slight worsening between pre-LP and post-ETV TUG and Tinetti scores. Improvement from pre-LP assessment was regained after shunting and at last follow-up with TUG and Tinetti scores of 12.97 seconds (range: 9.00-18.00; p=0.250) and 25 (range: 18-27; p=0.07), and 11.87 seconds (range: 8.27-18.50; p=0.152) and 23 (range: 18-26; p=0.382), respectively. Despite stoma patency, ETV failed to sustain functional improvement seen after LP, however, improvement was regained after subsequent shunting suggesting that shunt placement remains the preferred treatment for iNPH., (Published by Elsevier Ltd.)

Objective: To report five patients who underwent lumbopleural (LPl) shunting for the treatment of idiopathic intracranial hypertension (IIH) and to describe the considerations, complications, and outcomes related to this rarely described procedure., Methods: The clinical data of five patients treated with LPl shunting over a 23-year period were retrospectively analyzed. Factors including the age at diagnosis of IIH, age at time of LPl shunting, body mass index (BMI), reason for LPl shunt placement, number of revisions before LPl shunt placement, valve type, time to first revision, presence of overdrainage and its management, complications and their management, survival time of LPl shunt, and clinical course at last follow-up were analyzed., Results: All patients were morbidly obese females with an average of 4.6 shunt revisions before an LPl shunt. The average overall survival time of the LPl shunt was 48 months. Two patients experienced failure of their LPl shunts with subsequent replacement within the first year. Four patients experienced complications related to shunt overdrainage, requiring placement of an antisiphon device (ASD) or additional valve. One patient developed a symptomatic pleural effusion, and one patient developed a small pneumothorax, which was managed conservatively., Conclusions: LPl shunting, though rarely used, is a viable option in the treatment of IIH refractory to standard peritoneal shunting. When pursuing this treatment, a valve and ASD are recommended to mitigate the risks of overdrainage and pleural effusion. Chest imaging should be obtained if the patient becomes symptomatic but can be deferred if the patient remains asymptomatic and is doing well., (Published by Elsevier Inc.)

Object: To evaluate the effectiveness of stereotactic navigation in enhancing the accuracy of ventricular shunt placement in patients with hydrocephalus., Methods: A retrospective cohort study at a single institution by a single surgeon was performed. Consecutive patients who underwent implantation of a ventricular shunt for the management of hydrocephalus between July 2001 and December 2011 were included in the study, totaling 535 patients. Patients were classified as either having optimal or sub-optimal placement of the shunt into the ventricle. Multiple logistic regression analysis was used., Results: Overall, 93.8% of patients were found to have optimal shunt placement. On multivariate analysis, navigation use was not significantly associated with improved accuracy of shunt placement (odds ratio [OR] = 0.54; 95% confidence interval [CI] = 0.19-1.54; p = 0.25). Pseudotumor cerebri diagnosis was significantly associated with increased odds of sub-optimal shunt placement (OR = 6.41; 95% CI = 1.90-21.59; p=0.003)., Conclusions: CT guided navigation did not significantly improve the accuracy of ventricular shunt placement in adults with hydrocephalus for an experienced surgeon. Further studies are required to assess the utility of CT guided navigation for less experienced surgeons and patients with small or dysmorphic ventricles., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Unlabelled: Pituitary adenomas are usually solitary lesions. Rarely, patients may present with two distinct pituitary tumors. We report a case of synchronous secretory pituitary adenomas in a woman who initially presented with elevated prolactin levels. She was initially treated with cabergoline, but, after many years, she began developing symptoms consistent with acromegaly. Imaging revealed two distinct tumors within the pituitary gland. Endocrinological investigation confirmed acromegaly. At the time of surgery, two separate tumors were identified and resected. Pathological analysis demonstrated one tumor as a prolactinoma, and the other tumor as a GH-secreting adenoma. Postoperatively, her GH and IGF1 levels normalized, while the prolactin level remained slightly above normal. This case highlights that GH and prolactin level elevation is not always from co-secretion by the same adenoma., Learning Points: Synchronous pituitary adenomas represent <0.5% of pituitary tumors requiring surgery.In the setting of elevated GH and prolactin levels, one cannot assume that they are co-secreted by the same adenoma.A careful study of hormonal workup and pre-operative imaging is necessary for synchronous pituitary adenomas to assure resection of both tumors.

Introduction: Atypical choroid plexus papilloma is a rare tumour, recently defined by the World Health Organisation and with very few cases reported to date. Choroid plexus tumours are rare intraventricular neoplasms originating from choroid plexus epithelium, with benign papillomas being more frequent than carcinomas. Most of these lesions appear in children, mainly located in the lateral ventricles. Those arising from the fourth ventricle are more frequent in adulthood. Surgery with complete resection can be curative in papillomas, with 5-year survival rates close to 100% and occasional recurrences. Radical surgery in carcinomas is difficult and usually requires adjuvant therapy, prognosis is worse and survival rates are lower. We report a case of atypical choroid plexus papilloma in adulthood located in the fourth ventricle, describing the different therapeutic options and reviewing the existing literature., Case Report: 38-year old male with an atypical choroid plexus papilloma located in the fourth ventricle, totally resected by posterior fossa craniectomy and telovellar approach., Conclusion: Atypical choroid plexus papillomas are associated with an increased risk of recurrence or malignant transformation when compared to "typical" papillomas. At present, complete surgical excision and close follow-up seems to be the most reliable treatment. Adjuvant chemotherapy or radiotherapy should be considered in cases of partial resection, recurrence or dissemination., (Copyright © 2011 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.)

Extracranial metastases secondary to intracranial neoplasm are extremely rare. The incidence of extraneural metastases of brain tumours is estimated to be less than 0.4%. The authors report a case of postoperative intracranial glioblastoma spreading to the skin in an adult patient. In this case, the radiological images and surgical findings suggest that the potential dissemination mechanism is as a result of infiltration through the surgical wound site. The primary tumour-upon coming into contact with the dura and the skin-mimicked the characteristics of both tissues. This case supports the theory of risk of spread through the durotomy site, although this phenomenon is extremely rare. Both the specific pathogenic mechanisms as well as the ideal and effective management have not been established yet and require further investigation.

BACKGROUND. The rarest location of pilocytic astrocytoma is intramedullary. Gliomas represent up to 24 - 30% of intramedullary tumors in adulthood and are second only after ependymomas. Leptomeningeal dissemination through cerebrospinal fluid is unusual and occurs predominantly in medulloblastomas, ependymoblastomas, central neuroblastomas, ependymomas, germ cell tumors and high-grade gliomas. The majority of spinal cord gliomas reporting metastasis were anaplastic astrocytomas or glioblastomas multiforme and relatively few were low-grade gliomas. The incidence of leptomeningeal spread of low-grade tumors is rare. A rare cranial extension of brain leptomeningeal dissemination in an intramedullary pilocytic astrocytoma during adulthood is reported. CASE REPORT. A 51 year-old-man with a recurrent intramedullary mass at C5-C7 level operated 4 times with all pathological anatomy reports describing the lesion as Pilocytic Astrocytoma developed, after 15 years from the diagnosis, visual hallucinations and his level of consciousness worsened to Glasgow coma score 13/15. The MRI showed highly enhanced cranial and spinal leptomeninges and paquimeninges with a micro nodular-granulomatous aspect associated with intense affectation of basal cisterns, subarachnoid spaces and convexity of both cerebral hemispheres suggestive of leptomeningeal spread of the spinal mass. The patient expired after three days. CONCLUSION. Leptomeningeal spread is a rare phenomenon and when it happens usually doesn't change the primary tumor's behavior. In our case the aggressiveness could be explained by a potential malignization of the primary tumor that it was not documented because of the partial resections from the lasts surgeries or instead the tumor was actually a monomorphous pilomyxoid tumor.

Background: Around 600 spinal epidural hematoma cases have been previously reported. Incidence of paraplegia after epidural anesthesia varies between 0,0005 and 0,02%. Several possible etiologies have been described in the literature, including surgery, trauma, anticoagulant therapy, arteriovenous malformations, pregnancy and lumbar puncture. Spinal and epidural anesthesic procedures represent the tenth most common cause. But in combination with anticoagulant therapy, the forementioned procedures increase its incidence until reaching the fifth most common etiological group. We report the case of an 80 year-old-man with a cervical epidural hematoma who had a good outcome with conservative management., Case Report: 80 year-old-man that developed intense cervicalgia with lower limbs weakness showing complete paraplegia and arreflexia 2 hours after analgesic treatment with epidural cervical infiltration for cervicoartrosis. Cervical MRI showed epidural cervical hematoma between C4 and T1 levels. The patient is transferred to our facilities in order to perform surgery. But after showing fast recovery, medical conservative management was elected. After one month, the patient's condition has improved showing no neurological deficits and complete resorption is seen in MRI., Conclusions: Nowadays, trend is to perform surgery in patients with spinal hematoma and significant neurological deterioration during the first hours. However, good neurological outcomes can be achieved with conservative management, in well selected patients with non progressive, incomplete and partial deficits. Presently, we can not predict which is the best treatment for each case.