Cerebrospinal fluid-administered therapies for leptomeningeal metastases from solid tumors.

Aims/purpose: Leptomeningeal metastases (LM) are associated with substantial morbidity and mortality. Several approaches are used to treat LM, including intrathecally administered therapies. We consolidated current studies exploring intrathecal therapies for LM treatment. Patients & methods: A review of clinical trials using intrathecal agents was conducted with outcomes tabulated and trends described. 48 trials met the inclusion criteria. Initial investigations began with cytotoxic agents; following this were formulations with longer cerebrospinal fluid half-lives, targeted antibodies and radionucleotides. Results & conclusion: Outcomes were not reported consistently. Survival, when reported, remained poor. Intrathecal therapies for LM remain a viable option. Their use can be informed by an understanding of efficacy, safety and toxicity. They may be an important component of future LM treatments.

This paper summarizes the findings from 48 clinical trials conducted since the 1970s about the treatment of leptomeningeal metastases through an intrathecal approach (administering drugs directly into the cerebrospinal fluid ­ a fluid that surrounds the brain and spinal cord). The results of these studies suggest that although these therapies show promise for the future, they currently do not clearly and consistently report a benefit. Further work is needed to explore the possible use of these treatments.

Building Team Medicine in the Management of CNS Metastases.

CNS metastases are often terminal for cancer patients and occur at an approximately 10-fold higher rate than primary CNS tumors. The incidence of these tumors is approximately 70,000-400,000 cases annually in the US. Advances that have occurred over the past two decades have led to more personalized treatment approaches. Newer surgical and radiation techniques, as well as targeted and immune therapies, have enanled patient to live longer, thus increasing the risk for the development of CNS, brain, and leptomeningeal metastases (BM and LM). Patients who develop CNS metastases have often been heavily treated, and options for future treatment could best be addressed by multidisciplinary teams. Studies have indicated that patients with brain metastases have improved survival outcomes when cared for in high-volume academic institutions using multidisciplinary teams. This manuscript discusses a multidisciplinary approach for both parenchymal brain metastases as well as leptomeningeal metastases implemented in three academic institutions. Additionally, with the increasing development of healthcare systems, we discuss optimizing the management of CNS metastases across healthcare systems and integrating basic and translational science into our clinical care to further improve outcomes. This paper summarizes the existing therapeutic approaches to the treatment of BM and LM and discusses novel and emerging approaches to optimizing access to neuro-oncologic care while simultaneously integrating multidisciplinary teams in the care of patients with BM and LM.

Current Updates on the Diagnosis and Management of Multiple Sclerosis for the General Neurologist.

Multiple sclerosis (MS) is an immune-driven disease that affects the central nervous system and is characterized by acute-on-chronic demyelination attacks. It is a major cause of global neurological disability, and its prevalence has increased in the United States. Conceptual understandings of MS have evolved over time, including the identification of B cells as key factors in its pathophysiology. The foundation of MS management involves preventing flares so as to avoid long-term functional decline. Treatments may be categorized into low-, middle-, and high-efficacy medications based on their efficacy in relapse prevention. With 24 FDA-approved treatments for MS, individual therapy is chosen based on distinct mechanisms and potential side effects. This review provides a detailed update on the epidemiology, diagnosis, treatment advances, and major ongoing research investigations in MS.

From the ER to the OR: Initial Evaluation of Primary Central Nervous System Lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare, often curable neoplasm, often initially presenting in acute care settings by nonneuroscience specialized physicians. Delays in the recognition of specific imaging findings, lack of appropriate specialist consultation, and urgent incorrect medication administration can delay necessary diagnosis and treatment. REVIEW SUMMARY: In this paper, the reader is moved quickly from the initial presentation to the diagnostic surgical intervention for PCNSL in a manner analogous to the experience of clinicians in the frontline setting. We review the clinical presentation of PCNSL, its radiographic features, the effect of prebiopsy steroids, and the role of a biopsy in the diagnosis. In addition, this paper revisits the role of surgical resection for PCNSL and investigational diagnostic studies for PCNSL. CONCLUSION: PCNSL is a rare tumor that is associated with high morbidity and mortality. However, with appropriate identification of clinical signs, symptoms, and key radiographic findings, the early suspicion of PCNSL can lead to steroid avoidance and timely biopsy for rapid administration of the potentially curative chemoimmunotherapy. Surgical resection presents the potential for improving outcomes for patients with PCNSL, however, this remains controversial. Further research into PCNSL presents the opportunity for better outcomes and longer livelihoods for patients.

Cognitive Impairment in Liver Transplant Recipients With a History of Cirrhosis: A Systematic Review.

Cognitive impairment is common among patients with cirrhosis and may persist post-transplantation. This systematic review seeks to (1) describe the prevalence of cognitive impairment in liver transplant (LT) recipients with a history of cirrhosis, (2) describe risk factors for this population, and (3) describe associations between post-transplant cognitive impairment and quality outcome measures. Methods: Studies in PubMed, Embase, Scopus, PsychINFO, and the Cochrane Database of Controlled Trials were included through May 2022. Inclusion criteria included (1) population - LT recipient, age ≥18 y, (2) exposure - history of cirrhosis before transplant, and (3) outcome - cognitive impairment after transplant (per validated cognitive testing). Exclusion criteria included (1) wrong study type, (2) abstract-only publication, (3) full-text unavailable, (4) wrong population, (5) wrong exposure, and (6) wrong outcome. The risk of bias was assessed using the Newcastle-Ottawa Scale and the Appraisal tool for Cross-Sectional Studies. The Grading of Recommendations, Assessment, Development, and Evaluations system was used to assess evidence certainty. Data from individual tests were categorized into six cognitive domains: attention, executive function, working memory, long-term memory, visuospatial, and language. Results: Twenty-four studies were included covering 847 patients. Follow-up ranged from 1 mo to 1.8 y after LT. Studies had a median of 30 (interquartile range 21.5-50.5) patients. The prevalence of cognitive impairment after LT ranged from 0% to 36%. Forty-three unique cognitive tests were used, the most common being the Psychometric Hepatic Encephalopathy Score. The most frequently assessed cognitive domains were attention (10 studies) and executive function (10 studies). Conclusions: The prevalence of cognitive impairment after LT varied across studies depending on cognitive tests utilized and follow-up duration. Attention and executive function were most impacted. Generalizability is limited due to small sample size and heterogeneous methodology. Further studies are needed to examine differences in the prevalence of post-LT cognitive impairment by etiology, risk factors, and ideal cognitive measures.

Maya Ta Maya Ho (Love is Love): A Qualitative Study on LGBTQI+ Experiences in Hospice & Palliative Care in Nepal.

OBJECTIVE(S): LGBTQI+ disparities in hospice and palliative care have been vastly underrecognized in medical practice and research. This may result in LGBTQI+ community members distrusting health care professionals, avoiding encounters due to fears of discrimination or mistreatment, and seldom disclosing their identities to health care professionals. LGBTQI+ patients often lack familial emotional and caregiver support, a central theme of hospice and palliative care - for example, older LGBTQI+ people are twice as likely as cisgender heterosexual people to live alone and four times as likely to not have children. LGBTQI+ populations are also highly intersectional; therefore, members may be further stigmatized. Blue Diamond Society is a non-governmental organization in Nepal that specializes in LGBTQI+ advocacy and patient care. Our main objective in this study was to explore Nepali LGBTQI+ patients' experiences in hospice and palliative care. METHODS: 29 interviews were conducted with patients, health care professionals, family members, and administrators involved with Blue Diamond Society (BDS), a Nepali NGO that serves Nepal's LGBTQI+ community. Questions were developed based on open-ended questioning to abstract relevant life and health history information pertaining to experiences with BDS and palliative care. These interviews were translated and transcribed verbatim. Qualitative Content analysis was conducted to identify prevalent themes. RESULTS: Four themes were identified: Fear of Dying without Family; Understanding Oneself and Sense of Community; Patient as Advocate; and Intersectionality and Eliminating Reductionism. CONCLUSIONS: This study elucidated themes inherent to the experiences of LGBTQI+ Nepali people receiving palliative and hospice care, ultimately describing the unique needs of LGBTQI+ Nepali patients in palliative and hospice care settings. In doing so, this study presents an intersectional focus on palliative and hospice care, elaborating on challenges specific to a deeply marginalized community that remains underrepresented in academia. Findings from this study describe an expanded notion of "palliation" to embody "whole-person care," that is, the palliation of social and structural pain, in addition to the more traditional conceptions of palliation as purely physical, emotional, and/or spiritual. This study also identified the importance of acknowledging and affirming the intersectional marginalization at which LGBTQI+ Nepalis live, ranging from experiences with socioeconomic status, family and communal conflict, ethnicity, race, sex, gender, sexual orientation, age, and environmental resource scarcity. In further understanding and improving upon intersectional LGBTQI+ cultural humility, this study provides opportunities for further research on cross-cultural LGBTQI+ patient needs in hospice and palliative care in a variety of resource settings.

American Society of Clinical Oncology 2021 Annual Meeting updates on primary brain tumors and CNS metastatic tumors.

In this report, select key studies presented at the American Society of Clinical Oncology (ASCO) 2021 annual meeting are reviewed. Two major phase III randomized controlled trials were presented at the meeting: GEINO 1401 and EORTC 1709/CCTG CE.8. Both are reviewed in this report. Moreover, important phase II trials, including Alliance A0716701, and key phase I trials are included. All trials presented cover important advances in the understanding of primary brain tumor management. In addition, case series papers, trials in progress and select work on exploratory CSF biomarkers are reviewed. Altogether, research presented at ASCO 2021 highlights important advances in neuro-oncologic topics that may inform future research and practice.

Intraoperative Computed Tomography for Registration of Stereotactic Frame in Frame-Based Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) electrode placement utilizing a frame-based technique requires registration of the stereotactic frame with computed tomography (CT) or magnetic resonance (MR) imaging. This traditionally has been accomplished with a conventional CT scanner. In recent years, intraoperative CT has become more prevalent. OBJECTIVE: To compare the coordinates obtained with intraoperative CT and conventional CT for registration of the stereotactic frame for DBS. METHODS: Patients undergoing DBS electrode placement between 2015 and 2017, who underwent both conventional and intraoperative CT for registration of the stereotactic frame, were included for analysis. The coordinates for the stereotactic target, anterior commissure, and posterior commissure for each CT method were recorded. The mean, maximum, minimum, and standard deviation of the absolute difference for each of the paired coordinates was calculated. Paired t-tests were performed to test for statistical significance of the difference. The directional difference as well as the vector error between the paired coordinates was also calculated. RESULTS: The mean absolute difference between conventional and intraoperative CT for the coordinate pairs was less than 0.279 mm or 0.211 degrees for all coordinate pairs analyzed. This was not statistically significant for any of the coordinate pairs. Moreover, the maximum absolute difference between all coordinate pairs was 1.04 mm. CONCLUSION: Intraoperative CT imaging provides stereotactic frame registration coordinates that are similar to those obtained by a standard CT scanner. This may save time and hospital resources by obviating the need for the patient to go to the radiology department for a CT scan.