Anti-aquaporin-4 immunoglobulin G/anti-myelin oligodendrocyte glycoprotein immunoglobulin G double-positive paraneoplastic neurological syndrome in a patient with triple-negative breast cancer.

We report a rare case of paraneoplastic neurological syndrome with dual seropositivity of anti-aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in a 40 year-old woman with metastatic triple-negative breast cancer. She received multiple lines of anti-neoplastic treatment, including immunotherapy with pembrolizumab, as well as cytotoxic chemotherapy. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis followed by left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid analysis during both episodes showed normal glucose and protein, and elevated white blood cell count. Cytology was negative for malignancy. Cerebrospinal fluid was positive for neuromyelitis optica immunoglobulin G antibody anti-aquaporin-4, and autoimmune myelopathy panel was positive for myelin oligodendrocyte glycoprotein antibody. The patient had significant clinical and radiographic improvement after completion of five cycles of plasmapheresis followed by intravenous immunoglobulin. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every 6 months and daily low-dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case shows that these antibodies can occur concurrently and cause clinical features, such as both neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease, in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or cerebrospinal fluid profile negative for leptomeningeal carcinomatosis.

Age-stratified comorbid and pharmacologic analysis of patients with glioblastoma.

Background: Increased age is a strong and unfavorable prognostic factor for patients with glioblastoma (GBM). However, the relationships between stratified patient age, comorbidities, and medications have yet to be explored in GBM patient survival analyses. Objective: To evaluate co-morbid conditions, tumor-related symptoms, medication prescriptions, and subject age for patients with GBM and to establish potential targets for prospective studies. Methods: Electronic health records for 565 patients with IDHwt GBM were evaluated at a single center between January 1, 2000 and August 9, 2021 were retrospectively assessed. Data were stratified by MGMT promoter methylation status when available and were used to construct multivariable time-dependent cox models and intra-cohort hazards. Results: Younger (<65 years of age) but not older (≥65 years) GBM patients demonstrated a worse prognosis with movement related disabilities (P < 0.0001), gait/balance difficulty (P = 0.04) and weakness (P = 0.007), as well as psychiatric conditions, mental health disorders (P = 0.002) and anxiety (P = 0.001). In contrast, older but not younger GBM patients demonstrated a worse prognosis with epilepsy (P = 0.039). Both groups had worse survival with confusion/altered mental status (P = 0.023 vs < 0.000) and an improved survival with a Temozolomide prescription. Older but not younger GBM patients experienced an improved hazard with a prescription of ace-inhibitor medications (P = 0.048). Conclusion: Age-dependent novel associations between clinical symptoms and medications prescribed for co-morbid conditions were demonstrated in patients with GBM. The results of the current work support future mechanistic studies that investigate the negative relationship(s) between increased age, comorbidities, and drug therapies for differential clinical decision-making across the lifespan of patients with GBM.

The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Cerebral arterial vasospasm complicating supratentorial meningioma resection: illustrative cases.

BACKGROUND: Cerebral arterial vasospasm is a rare complication after supratentorial meningioma resection. The pathophysiology of this condition may be similar to vasospasm after aneurysmal subarachnoid hemorrhage, and treatment options may be similar. OBSERVATIONS: The authors present two cases of cerebral vasospasm after supratentorial meningioma resection and perform a systematic literature review of similar cases. LESSONS: Cerebral arterial vasospasm after supratentorial meningioma resection may be associated with significant morbidity due to cerebral ischemia if not addressed in a timely manner. Treatment paradigms may be adopted from the management of arterial vasospasm associated with subarachnoid hemorrhage.

Risk Factors Associated with Spinal Cord Ischemia During Aortic Aneurysm Repair.

BACKGROUND: The risk of spinal cord ischemia (SCI) with aortic aneurysm repair can cause significant neurological morbidity. Prevention of SCI is critical. We sought to identify risk factors that predispose to SCI that may guide strategies to mitigate the occurrence of SCI during and following these procedures. METHODS: This study includes all adults who underwent atraumatic, unruptured, thoracic, and suprarenal aortic aneurysm repairs (endovascular or open) at our institution over 11 years (2010-2020). Our database included patient demographics, aneurysm anatomic features, and operative characteristics and an extreme gradient boost (XGB) machine method was used to develop a predictive model for SCI. The model was trained on an 80% randomly stratified cohort of the data and tested on the remaining 20% testing cohort. Shapley values were used to determine the most important predictive factors of SCI and decision trees were used to identify risk factor threshold values and highest risk factor combinations. RESULTS: Information was collected for 174 adult patients undergoing thoracic and suprarenal aortic repair from 2010 to 2020. Fifty eight percent of the patients were male. Ninety seven (55.7%) patients had open aortic repair and 87 (44.3%) had endovascular repair. Twenty seven (15%) of all patients had major complications and were considered to have SCI. The XGB model converged over the training cohort with a testing cohort accuracy of 0.841 [Sensitivity = 75%, Specificity = 68%] and area under the curve of receiver operating characteristic of 0.774. The XGB model identified older age (> 65 years), history of neurologic disease, hyperlipidemia, diabetes, coronary artery disease, heart failure, poor renal function, < 6 months since last aortic repair, chronic anticoagulant use, preoperational anemia (Hemoglobin < 9), thrombocytopenia (platelet < 90,000), coagulopathy (prothrombin time > 15s and activated partial thromboplastin time > 40s), hypotension (mean arterial pressure < 70 mm Hg), longer operations (> 100 min), aneurysms longer than 5 cm, and anatomic location of aneurysm caudal to T-11 as risk factors for SCI in all types of aortic repair. Diabetic and heart failure patients undergoing longer operations (> 100 min) with thrombocytopenia or aneurysms longer than 5 cm were at the highest risk. CONCLUSIONS: The XGB model accurately identified risk factors of SCI with aortic aneurysm repair that may guide patient selection, timing of surgery, and strategies to minimize the risk of SCI.

Cerebrospinal Fluid Shunting for Idiopathic Intracranial Hypertension: A Systematic Review, Meta-Analysis, and Implications for a Modern Management Protocol.

BACKGROUND: Cerebrospinal fluid (CSF) shunting is widely used in refractory idiopathic intracranial hypotension (IIH). Although multiple reviews have assessed its efficacy compared with other surgical treatments, there is no detailed analysis that evaluates the clinical outcomes after CSF shunting. OBJECTIVE: To conduct a meta-analysis of the clinical impact of CSF shunting for refractory IIH and use this in conjunction with existing information on other treatment modalities to develop a modern management protocol. METHODS: PubMed and Embase were systematically searched for studies describing CSF shunting for medically refractory IIH. Relevant information including study characteristics, patient demographics, clinical outcomes, periprocedural complications, and long-term outcomes were subjected to meta-analysis. RESULTS: Fifteen studies published between 1988 and 2019 met our inclusion and exclusion criteria, providing 372 patients for analysis. The mean age was 31.2 years (range 0.5-71) with 83.6% being female. The average follow-up was 33.9 months (range 0-278 months). The overall rate of improvement in headache, papilledema, and visual impairment was 91% (95% CI 84%-97%), 96% (95% CI 85%-100%), and 85% (95% CI 72%-95%), respectively. Of 372 patients, 155 had 436 revisions; the overall revision rate was 42% (95% CI 26%-59%). There was no significant correlation between average follow-up duration and revision rates in studies ( P = .627). Periprocedural low-pressure headaches were noted in 74 patients (20%; 95% CI 11%-32%). CONCLUSION: CSF shunting for IIH is associated with significant improvement in clinical symptoms. Shunting rarely causes periprocedural complications except overdrainage-related low-pressure headache. However, CSF shunting has a relatively high revision rate.

Survival benefit of concomitant chemoradiation in adult supratentorial primary glioblastoma. A propensity score weighted population-based analysis.

BACKGROUND: This population study aims to assess the impact of the implementation of the original Stupp protocol on overall survival in patients with new-diagnosed supratentorial primary GBM. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to study the survival of histologically confirmed adult supratentorial GBM patients diagnosed between 1998 and 2016. Kaplan-Meier, and a univariate and propensity-score weighted multivariate Cox proportional hazard model adjusted for age at diagnosis, sex, race, marital status and extent of resection was used to assess the survival of patients prior to implementation of the Stupp protocol in 2005 (Pre-Stupp) and following implementation of the Stupp Protocol until 2016 (Post Stupp). RESULTS: Overall, 6390 patients satisfied inclusion exclusion criteria. Median survival times were 13 months for the Pre-Stupp and 15 months for Post-Stupp groups (P<0.001). The 1-, 2-, 5- and 10-year survival rates for the Pre-Stupp group were 51%, 18%, 5% and 2% respectively compared to 59%, 27%, 8% and 4% on the Post-Stupp group. Propensity-score weighted analysis showed a lower mortality risk for patients who underwent concomitant chemoradiation during the Post-Stupp era (HR=0.77, 95% CI 0.62-0.94). There was a 42% relative reduction in the risk of death for patients treated during the Post-Stupp era. CONCLUSIONS: This population-based propensity-score study with long-term follow-up suggests that the implementation of the Stupp protocol in 2005 had a positive impact on the survival of patients with supratentorial GBM. This "real-world" analysis validates the results of the original randomized control trial on which this protocol is based.

Glioblastoma as an age-related neurological disorder in adults.

BACKGROUND: Advanced age is a major risk factor for the development of many diseases including those affecting the central nervous system. Wild-type isocitrate dehydrogenase glioblastoma (IDHwt GBM) is the most common primary malignant brain cancer and accounts for ≥90% of all adult GBM diagnoses. Patients with IDHwt GBM have a median age of diagnosis at 68-70 years of age, and increasing age is associated with an increasingly worse prognosis for patients with this type of GBM. METHODS: The Surveillance, Epidemiology, and End Results, The Cancer Genome Atlas, and the Chinese Glioma Genome Atlas databases were analyzed for mortality indices. Meta-analysis of 80 clinical trials was evaluated for log hazard ratio for aging to tumor survivorship. RESULTS: Despite significant advances in the understanding of intratumoral genetic alterations, molecular characteristics of tumor microenvironments, and relationships between tumor molecular characteristics and the use of targeted therapeutics, life expectancy for older adults with GBM has yet to improve. CONCLUSIONS: Based upon the results of our analysis, we propose that age-dependent factors that are yet to be fully elucidated, contribute to IDHwt GBM patient outcomes.

Socioeconomic Disparities in Non-Small Cell Lung Cancer With Brain Metastases at Presentation: A Population-Based Study.

OBJECTIVE/BACKGROUND: The purpose of this study was to characterize the impact of household income disparities in the survival of patients with non-small cell lung cancer (NSCLC) presenting with brain metastasis on a population-based level. METHODS: This is a population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2016 including 15,808 NSCLC patients presenting with brain metastasis. RESULTS: This study comprises 15,808 adult patients with NSCLC presenting with brain metastases having an age range 64 ± 10 years with 51% male, 76% white, 52% married, 61% insured, and with 85% of lung adenocarcinoma histopathology. The 1-, 2- and 5-year survival rates for living in the lower household income quartile were 21%, 10%, and 3%, respectively, for the second quartile 24%, 10%, and 3%; for the third quartile 28%, 14%, and 4%; and for the top quartile 31%, 17%, and 4%, respectively. Multivariate Cox proportional hazard analysis showed that living in a higher quartile household income county is associated with increased survival (P < 0.0001), hazard ratio 0.87, 95% confidence interval (0.82-0.92). CONCLUSIONS: This population-based study suggests that living in higher median household income counties is associated with increased survival time and reduced risk of mortality for patients with NSCLC who have brain metastases present at diagnosis, independent of other factors. These findings underscore the importance of ensuring adequate and easy access to care for all patients, irrespective of their economic background.

Effectiveness of a Standardized External Ventricular Drain Placement Protocol for Infection Control.

INTRODUCTION: Placement of an external ventricular drain (EVD) is a common procedure routinely completed at bedside by neurosurgical residents. A standardized protocol for placement and maintenance of an EVD is potentially useful. METHODS: This single-institution retrospective review analyzed all patients who underwent placement of an EVD over a 5-year span using a standardized protocol. RESULTS: A total of 428 EVDs in 381 patients were placed as per this protocol. Overall compliance with the practice protocol was 98.7%. Overall, our infection rate was 1.86% (8 external ventricular drain-related infection [ERIs] over 428 EVDs). There was no difference in age for the ERI cases (median 55, range (50.5-60.5), compared with the non-ERI cases (median of 53, range [38-65]) (P = 0.512). Indications for placement of EVD were hemorrhage (51.9%, n = 198), tumor (16.2%, n = 62), trauma (12.8%, n = 49), hydrocephalus (11.5%, n = 44), cerebellar stroke (2.8%, n = 11), infection (3.1%, n = 12), unknown (1.3%, n = 5). Most EVDs (77.6%, n = 296) were placed bedside by second-year residents (median PGY level 2, interquartile range 1-2.75). Computed tomography confirmed placement in the ipsilateral frontal horn in 72% (n = 277) of EVDs. EVD-related complications were noted in 8.3% of EVDs (n = 32, with 8 infections and 24 tract hemorrhages). The median EVD duration was 10 days; duration of EVD had no statistically significant impact on the risk of an ERI (P = 1). Only replacement of an EVD was associated with an increased risk of infection. CONCLUSIONS: Adherence to a standard EVD placement protocol is useful in maintaining a low risk of ERI regardless of the duration of catheter utilization. Replacement of the catheter through the same access hole as the original catheter is associated with an increased risk of ERI.

Dandy's hemispherectomies: historical vignette.

To better understand Walter Dandy's intentions and the historical context of his work on hemispherectomy, the authors reviewed his original 1928 publication. Gliomas were considered incurable at that time. Presuming that the loss of motor function denoted a lack of useful tissue in that hemisphere, he pioneered radical removal of the involved cerebral hemisphere. Of the 5 patients operated on by Dandy, 1 died within 48 hours of hemorrhage because of a displaced vascular clip; 1 died of pneumonia in 2 weeks; 2 died of tumor recurrence, at 3 months and 3.5 years, respectively; and a fifth patient was lost to follow-up beyond the 2nd postoperative week. The authors queried the Thomson Reuters Web of Science and Scopus. A total of 88 papers fulfilled inclusion criteria. Half of these papers (44/88) were published after 2012. Only 11% of papers (10/88) quoted Dandy's paper accurately; half of them were published before 1997. Most publications (76% [67/88]) quoted Dandy incorrectly, all of them from 1997 and later. In the remaining 11 papers (13%), the accuracy of the quotes was unclear. The authors found a trend toward more accurate citation in earlier papers. Critically reviewing Dandy's report, with an understanding of the historical context, allows a better understanding of his intentions and the value of his contribution.

Lumbar Drains for Vascular Procedures: An Institutional Protocol Review and Guidelines.

BACKGROUND: Aortic disease requiring open or endovascular repair may result in spinal cord injury in approximately 2%-10% of patients. Cerebrospinal fluid diversion using lumbar drains (LDs) has been validated as a protective measure to mitigate this complication. METHODS: This single-institution retrospective study analyzed the implementation of a standardized protocol and subsequent educational intervention for LDs for aortic vascular procedures over a 4-year period. RESULTS: In 2016-2019, 45 patients had LDs placed for open or endovascular procedures; group 1 included 19 patients with LDs placed before protocol implementation, and group 2 included 26 patients with LDs placed as per the institutional protocol. Demographics and procedural details in both groups were similar. However, there was a significant difference in the number of patients who had emergent versus planned placement of the LD (group 1, 89.5%; group 2, 50%; P < 0.01), volume of cerebrospinal fluid drained (group 1, 453 mL; group 2, 197 mL; P < 0.01), and compliance with 10 mL/hour drainage recommendation (group 1, 68.4%; group 2, 100%; P < 0.01). In group 1, 5 (31.6%) patients experienced neurological complications compared with only 1 (3.8%) in group 2. LD-related complications occurred 3 patients (15.8%) in group 1, whereas none occurred in group 2. Survey results suggested increased health care worker protocol familiarity with educational interventions. CONCLUSIONS: Implementation of an institutional protocol for LDs for open or endovascular procedures is feasible and beneficial. Educational modules improve familiarity among all health care providers, which can improve patient care and complication avoidance.

Hypertrophic cranial pachymeningitis and orbital apex syndrome secondary to infection of the eye: illustrative case.

BACKGROUND: Hypertrophic cranial pachymeningitis is a rare inflammatory disorder characterized by thickening of the dura mater and multiple cranial neuropathies. Although an infectious etiology may be present, often no specific cause is discovered. OBSERVATIONS: The authors described a 71-year-old man with progressive right eye vision loss, ptosis, and complete ophthalmoplegia with imaging findings suggestive of hypertrophic cranial pachymeningitis. Extensive studies, including cerebrospinal fluid studies, showed negative results. Blood serum, cell-free evaluation, and paraffin-embedded dural tissue testing had positive results for Pseudomonas aeruginosa, which allowed treatment tailored to the organism and a salutary clinical outcome. LESSONS: The constellation of neurological and radiological findings may make a diagnosis difficult in an inflammatory setting. The most precise methodology for establishing a diagnosis involves sampling the dura and testing it for infectious pathology. However, if results are inconclusive, further cell-free serum sampling with next-generation sequencing is a viable option for identifying pathogens with infectious concerns. This case highlighted the importance of multimodality studies for identifying a targetable pathogen.

Fetal Bovine Collagen Grafts for Repair of Tegmen Defects and Encephaloceles Via Middle Cranial Fossa Approach.

To evaluate the use of commercially available allogenic dural graft materials made of fetal bovine collagen, we present an analysis of our case series with use of autologous and allogenic graft materials. Patients who underwent surgical repair of a tegmen tympani defect associated with ipsilateral conductive hearing loss and cerebrospinal fluid (CSF) otorrhea using a middle cranial fossa (MCF) approach from 2004 to 2018 at Loyola University Medical Center were included. Resolution of CSF otorrhea, audiologic outcomes, facial nerve preservation, and surgical complications was analyzed. Thirty-three patients with an average age of 55.3 years (range: 21-78, standard deviation [SD]: 12.9) and body mass index of 34.4 (range: 22-51, SD: 7.4) underwent an MCF repair of a tegmen and dural defect. All patients presented with CSF otorrhea and conductive hearing loss ipsilateral to the defect. Repairs were made with combinations of allograft and autograft in 17 cases, allograft only in 15 cases, and autograft only in 5 cases. Improvement in hearing was noted in 33 cases, and resolution of CSF otorrhea was noted in 36 cases; one patient required repeat surgery which resolved CSF otorrhea. Three patients had minor complications; all these were in the autograft group. The MCF approach coupled with the use of fetal bovine collagen grafts is a safe and viable method to repair tegmen tympani and associated dural defects with salutary outcomes and low morbidity.

What is New in Neuro-oncology?

Neuro-oncology is a rapidly developing field. A continuous evolution in the understanding of the molecular underpinnings of central nervous system tumors has helped reconfigure the classification of brain tumors. More importantly, it has laid the path forward for the development and investigation of new therapeutics. The authors discuss the classification of brain tumors and novel therapies in brain tumors as well as promising treatments underway.

Acute Neurological Complications of Brain Tumors and Immune Therapies, a Guideline for the Neuro-hospitalist.

PURPOSE OF REVIEW: Patients with brain tumors presenting to the emergency room with acute neurologic complications may warrant urgent investigations and emergent management. As the neuro-hospitalist will likely encounter this complex patient population, an understanding of the acute neurologic issues will have value. RECENT FINDINGS: We discuss updated information and management regarding various acute neurologic complications among neuro-oncology patients and neurologic complications of immunotherapy. Understanding of the acute neurologic complications associated with central nervous system tumors and with common contemporary cancer treatments will facilitate the neuro-hospitalist management of these patient populations. While there are aspects analogous to the diagnosis and management in the non-oncologic population, a number of unique features discussed in this review should be considered.

Brachial Plexitis After Stem Cell Transplant.

BACKGROUND: Brachial plexitis is characterized by acute onset pain followed by weakness due to dysfunction of the nerves constituting the brachial plexus. The exact pathophysiology of this condition remains unknown but it is known to follow acute infections, such as a viral illness. CASE DESCRIPTION: We describe a case of idiopathic brachial plexitis in a patient after a peripheral stem cell transplant. The acute denervation of nerves in the brachial plexus may be due to reconstitution of his immune system. This is a rare entity and can be a diagnostic dilemma. CONCLUSIONS: Brachial plexitis may follow peripheral stem cell transplantation. Awareness of this phenomenon is helpful to clinicians involved in the care of these patients.