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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.
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Líquido Cefalorraquidiano , Neoplasias Meníngeas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/secundário , Injeções EspinhaisRESUMO
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.
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There is limited evidence of N-butyl cyanoacrylate (n-BCA) use in endovascular embolization of traumatic face and neck vessel injuries. We investigated the safety and effectiveness of n-BCA for this purpose. We retrospectively analyzed consecutive patients presenting to a Level 1 trauma center between April 2021 and July 2022. We included patients aged ≥ 18 years old with any vessel injury in the face and neck circulation requiring n-BCA embolization. The primary endpoint was n-BCA effectiveness defined as immediate control of active bleeding post-embolization. In total, 13 patients met the inclusion criteria. The median decade of life was 3 (IQR 3 - 5) with a male predominance (n = 11, 84.6%). Median Glasgow Coma Scale score on presentation was 15 (IQR 3-15). Eleven patients suffered gunshot wound injuries; two patients suffered blunt injuries. Injured vessels included facial artery (n = 6, 46.2%), buccal branch artery (n = 3, 23.1%), internal maxillary (n = 5, 38.5%), cervical internal carotid artery (n = 1, 7.7%), and vertebral artery (n = 1, 7.7%). All patients were treated with 1:2 n-BCA to ethiodol mixture with immediate extravasation control. No bleeding recurrence or need for retreatment occurred. One patient died in-hospital (7.7%). Patients were discharged to home (n = 8, 61.5%), day rehabilitation (n = 1, 7.7%), or acute rehabilitation (n = 3, 23.1%). One patient developed a right posterior cerebral artery infarct with hemorrhagic transformation. To our knowledge, this is the first study demonstrating the safety and effectiveness of n-BCA liquid embolism in traumatic vessel injuries, especially penetrating gunshot wounds.
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BACKGROUND: Middle meningeal artery (MMA) embolization for subdural hematomas (SDH) and dural arteriovenous fistulas (dAVFs) has gained momentum in the neuroendovascular space. However, there is variability in the technique for safe and effective embolization. The aim of this report is to describe the technical feasibility and clinical performance of using Zoom™ 45 catheter for MMA access to facilitate embolization. METHODS: We analyzed all cases of MMA embolization in which the Zoom™ 45 catheter was used and performed in our institution from February 2021 to March 2023 for SDH and dAVFs. RESULTS: A total of 32 patients were included. Mean age was 64.0 ± 18.0 years, 75.0% (4/32) were male, and 56.7% (17/30), were black. The technical success was achieved in 93.8% (30/32) of cases, with selective embolization utilizing microcatheter directly into frontal and parietal branches for most patients (96.9%, 31/32). Identification of dangerous collaterals, such as lacrimal and petrous branches, prior to embolization, was achieved in most patients (96.9%, 31/32). Bilateral MMA embolization was done in 50.0% (16/32) of patients. The transradial approach and transfemoral approach were used in 53.1% (17/32) and 46.9% (15/32) of patients, respectively. The most common embolization material was n-butyl cyanoacrylate (84.4%, 27/32). There were no access site complications or complications related to the MMA embolization procedures and used devices. CONCLUSIONS: The use of Zoom™ 45 Catheter seems to be technically feasible, safe, and effective for facilitating MMA access for embolization in the context of SDH and dAVFs.
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Purpose of Review: Sleep disorders among refugees are common yet understudied. Interventions are difficult in resource-limited settings where most of these populations live. A systematic review of sleep disorders in refugee populations is warranted to identify prevalence, comorbidities, and the limitations of the current state of sleep health among refugees. Recent Findings: Sleep disturbances, particularly insomnia and nightmares, occur with a higher prevalence among refugees. Diseases associated with insomnia in this population included fibromyalgia, posttraumatic stress disorder, depression, and anxiety. Risk factors include trauma, migration, lower socioeconomic status, lower educational level, and settlement in areas with a high influx of new residents or proximity to conflict. Only a few partially successful therapies were identified. Summary: This review identifies the high prevalence of the disturbed sleep in this population and its risk factors. It proposes ways of increasing awareness of it in this vulnerable population as a first step toward remediation.
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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.
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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.
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Background: Spinal cord stimulation (SCS) involves the utilization of an implantable neurostimulation device, stereotypically used in the treatment of patients with chronic neuropathic pain. While these devices have been shown to have significant clinical benefits, there have also been documented potential complications, including the risk of infection, fractured electrodes, electrode migration, and lack of symptom improvement. In addition, there has been minimal documentation on gastrointestinal (GI) side effects after SCS implantation. Case Description: A 42-year-old patient with chronic axial and radicular neuropathic pain in her back and left leg status post multiple lumbar surgeries underwent implantation of an open paddle lead in the T8-T9 region. After the procedure, the patient endorsed a 50% decrease in pain at the 6-week follow-up with no further concerns. However, at the 18 months follow-up, the patient endorsed severe constipation when the SCS was turned on, leading to subsequent evaluation by gastroenterology, motility studies, and a thorough bowel regimen. Symptoms persisted, and the patient ultimately opted for the removal of the SCS implant at 21 months after the initial surgery. Conclusion: While the exact mechanism behind the GI side effects endorsed in this patient is unknown, current literature postulates a variety of theories, including a SCS-induced parasympathetic blockade of the GI tract. Further, investigation is needed to determine the exact effects of SCS on the GI tract.
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Background: Spinal cord stimulation (SCS) consists of the implantation of neuromodulatory devices in the spinal cord to treat refractory neuropathic pain. Although SCS technology has been proven of immense clinical benefit, complications remain including refractory pain, infection risk, and electrode migration or displacement. Till date, there are minimal reports of allergic side effects following SCS implantation. Case Description: In the first case, a 36-year-old male with chronic axial and radicular neuropathic pain in underwent implantation of an open paddle lead and generator. Within 1-3 h of activating the SCS, he developed diffuse raised erythematous hives. Over time, the SCS had immense clinical benefit for his pain reduction; however, he continued to experience recurrent hives and various other allergic reactions including facial flushing and photosensitivity. Four years later, he ultimately opted to retain the device for its clinical pain benefits. In the second case, a 35-year-old female with acute, intractable bilateral occipital neuralgia and a past medical history of Type 1 Chiari Malformation status-post-posterior fossa decompression underwent implantation of an occipital nerve stimulator (ONS). At 1-month follow-up, she began to experience pruritus across the back of her head and along the subcutaneous course of the lead. At 8 months, she continued to experience persistent symptoms, ultimately opting for device removal. Conclusion: Although allergic reactions to implanted neurostimulation systems are rare, and mechanisms not completely understood, existing studies posit multiple theories surrounding the pathophysiology of allergic reactions to these devices, such as delayed hypersensitivity reactions or contact dermatitis. Further research is needed to elucidate the cutaneous and immunologic side effects of SCS and ONS devices.
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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.
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Neoplasias do Sistema Nervoso Central , Linfoma , Humanos , Linfoma/diagnóstico por imagem , Linfoma/terapia , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/terapia , Esteroides/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Sistema Nervoso Central/patologiaRESUMO
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.
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Despite increasing diversity in research recruitment, research finding reporting by gender, race, ethnicity, and sex has remained up to the discretion of authors. This study developped and piloted tools to standardize the inclusive reporting of gender, race, ethnicity, and sex in health research. A modified Delphi approach was used to develop standardized tools for the inclusive reporting of gender, race, ethnicity, and sex in health research. Health research, social epidemiology, sociology, and medical anthropology experts from 11 different universities participated in the Delphi process. The tools were pilot tested on 85 health research manuscripts in top health research journals to determine inter-rater reliability of the tools. The tools each spanned five dimensions for both sex and gender as well as race and ethnicity: Author inclusiveness, Participant inclusiveness, Nomenclature reporting, Descriptive reporting, and Outcomes reporting for each subpopulation. The sex and gender tool had a median score of 6 and a range of 1-15 out of 16 possible points. The percent agreement between reviewers piloting the sex and gender tool was 82%. The interrater reliability or average Cohen's Kappa was 0.54 with a standard deviation of 0.33 demonstrating moderate agreement. The race and ethnicity tool had a median score of 1 and a range of 0-15 out of 16 possible points. Race and ethnicity were both reported in only 25.8% of studies evaluated. Most studies that reported race reported only the largest subgroups; White, Black, and Latinx. The percent agreement between reviewers piloting the race and ethnicity tool was 84 and average Cohen's Kappa was 0.61 with a standard deviation of 0.38 demonstrating substantial agreement. While the overall dimension scores were low (indicating low inclusivity), the interrater reliability measures indicated moderate to substantial agreement for the respective tools. Efforts in recruitment alone will not provide more inclusive literature without improving reporting.
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BACKGROUND: Transitional care programs establish comprehensive outpatient care after hospitalization. This scoping review aimed to define participant characteristics and structure of transitional care programs for injured adults as well as associated readmission rates, cost of care, and follow-up adherence. METHODS: We conducted a scoping review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews standard. Information sources searched were Medline, the Cochrane Library, CINAHL, and Scopus Plus with Full Text. Eligibility criteria were systematic reviews, clinical trials, and observational studies of transitional care programs for injured adults in the United States, published in English since 2000. Two independent reviewers screened all full texts. A data charting process extracted patient characteristics, program structure, readmission rates, cost of care, and follow-up adherence for each study. RESULTS: A total of 10 studies described 9 transitional care programs. Most programs (60%) were nurse/social-worker-led post-discharge phone call programs that provided follow-up reminders and inquired regarding patient concerns. The remaining 40% of programs were comprehensive interdisciplinary case-coordination transitional care programs. Readmissions were reduced by 5% and emergency department visits by 13% among participants of both types of programs compared to historic data. Both programs improved follow-up adherence by 75% compared to historic data. CONCLUSION: Transitional care programs targeted at injured patients vary in structure and may reduce overall health care use.
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Cuidado Transicional , Adulto , Humanos , Alta do Paciente , Assistência ao Convalescente , Hospitalização , Assistência AmbulatorialRESUMO
Background: The optimal antiplatelet therapy regimen for certain neuroendovascular procedures remains unclear. This study investigates the safety and feasibility of intravenous dose-adjusted cangrelor in patients undergoing acute neuroendovascular interventions. Methods: We conducted a retrospective chart review of all consecutive patients on intravenous cangrelor for neuroendovascular procedures between September 1, 2020, and March 13, 2022. We also conducted an updated systematic review and meta-analysis using PubMed, Scopus, Web of Science, Embase and the Cochrane Library up to February 22, 2023. Results: In our cohort, a total of 76 patients were included [mean age (years): 57.2 ± 18.2, males: 39 (51.3), Black: 49 (64.5)]. Cangrelor was most used for embolization and intracranial stent placement (n = 24, 32%). Approximately 44% of our patients had a favorable outcome with a modified Rankin Scale (mRS) score of 0 to 2 at 90 days (n = 25/57); within 1 year, 8% of patients had recurrent or new strokes (n = 5/59), 6% had symptomatic intracranial hemorrhage [sICH] (4/64), 3% had major extracranial bleeding events (2/64), and 3% had a gastrointestinal bleed (2/64). In our meta-analysis, 11 studies with 298 patients were included. The pooled proportion of sICH and intraprocedural thromboembolic complication events were 0.07 [95% CI 0.04 to 1.13] and 0.08 [95% CI 0.05 to 0.15], respectively. Conclusion: Our study found that intravenous cangrelor appears to be safe and effective in neuroendovascular procedures, with low rates of bleeding and ischemic events. However, further research is needed to compare different dosing and titration protocols of cangrelor and other intravenous agents.
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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.
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BACKGROUND: Civilian extremity trauma with vascular injury carries a significant risk of morbidity, limb loss, and mortality. We aim to describe the trends in extremity vascular injury repair and compare outcomes between trauma and vascular surgeons. METHODS: We performed a single-center retrospective review of patients 18 years or older with extremity vascular injury requiring surgical intervention between January 2009 and December 2019. Demographics, injury characteristics, operative course, and hospital course were analyzed. Descriptive statistics were used to examine management trends, and outcomes were compared for arterial repairs. Multivariate regression was used to evaluate surgeon specialty as a predictor of complications, readmission, vascular outcomes, and mortality. RESULTS: A total of 231 patients met our inclusion criteria; 80% were male with a median age of 29 years. The femoral vessels were most commonly injured (39.4%), followed by the popliteal vessels (26.8%). Trauma surgeons performed the majority of femoral artery repairs (82%), while vascular surgeons repaired the majority of popliteal artery injuries (84%). Both had a similar share of brachial artery repairs (36% vs. 39%, respectively). There were no differences in complications, readmission, vascular outcomes, and mortality. Median time from arrival to operating room was significantly shorter for trauma surgeons. There was a significant downward trend between 2009 and 2017 in the proportion of total and femoral vascular procedures performed by trauma surgeons. On multivariate regression, surgical specialty was not a significant predictor of need for vascular reintervention, prophylactic or delayed fasciotomies, postoperative complications, or readmissions. CONCLUSION: Traumas surgeons arrived quicker to the operating and had no difference in short-term clinical outcomes of brachial and femoral artery repairs compared with patients treated by vascular surgeons. Over the last decade, there has been a significant decline in the number of open vascular repairs done by trauma surgeons. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level IV.
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Cirurgiões , Lesões do Sistema Vascular , Adulto , Feminino , Humanos , Masculino , Artéria Poplítea/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/métodos , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/cirurgiaRESUMO
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.
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Estimulação Encefálica Profunda , Eletrodos Implantados , Humanos , Imageamento Tridimensional , Técnicas Estereotáxicas , Tomografia Computadorizada por Raios XRESUMO
Neuropathic facial pain can be exceedingly difficult to manage with conventional therapies. Since this pain may be excruciating and often debilitating and some patients do not respond or do not tolerate conventional treatments, the interest in neuromodulation therapies is increasing. One of the most commonly used neuromodulation therapies, spinal cord stimulation, has recently shown promise in treating facial pain. We reviewed the current literature to determine usefulness of spinal cord stimulation in management of refractory facial pain. Our review indicates that for some patients with intractable pain in portions of the face, cervical spinal cord stimulation may be effective at reducing pain.