Neurological Impairment Research Articles

Intraventricular antibiotics for severe central nervous system infections: a case series.

Severe central nervous system infections (CNSI), including community-acquired CNSI (CA-CNSI) and healthcare-associated ventriculitis and meningitis (HAVM), present high morbidity and mortality. Intraventricular antibiotic treatment (IVT) is advisable for these infections, though evidence is limited. We retrospectively analyzed data on 27 patients who received IVT for severe CA-CNSI and HAVM over 10 years, assessing clinical and paraclinical features, such as baseline severity and functional outcome, antibiotics, microbiological and laboratory data. Comparisons were made between patients affected by CNSI and HAVM and those with favorable and unfavorable outcomes, based on the modified Rankin scale.Gram-positive organisms dominated in CA-CNSI (64%), while gram-negative organisms were more frequent in HAVM (64%). Patients received a median of 30 days of intravenous antibiotics and 11 days of IVT, with no significant difference between CA-CNSI and HAVM. IVT-associated toxicity was rare. Patients with favorable outcomes (64%) had higher initial cerebrospinal fluid- white blood cell count (CSF-WBC), that decreased more rapidly than in patients with unfavorable outcomes. CSF-WBC dynamics did not differ between CA-CNSI and HAVM patients.Rapid decline in CSF-WBC after initiation of IVT was associated with favorable outcome. Despite severe neurological impairment at admission, most survivors achieved favorable long-term outcomes.

Paradoxical deterioration during treatment of tuberculous meningitis responded to infliximab but not to steroids

Paradoxical deterioration in patients with tuberculous meningitis is a significant diagnostic and treatment challenge. We present the case of a 55-year-old previously healthy male, human immunodeficiency virus (HIV)-negative, presenting with headache, fever, agitation and slurred speech, who was ultimately diagnosed with tuberculous meningoencephalitis confirmed by cerebrospinal fluid polymerase chain reaction positive for Mycobacterium tuberculosis complex. After initiation of a standard antitubercular therapy combined with glucocorticoids, the patient experienced an initial neurological improvement. However, after 3 months of therapy, he had a major stroke with neurological deterioration, clinically and radiologically attributable to a paradoxical deterioration or an immune reconstruction syndrome as described in HIV-positive patients. Due to the persistence of inflammatory symptoms and radiological evidence of worsening tuberculomas despite ongoing antituberculosis therapy, off-label use of the tumour necrosis factor (TNF) inhibitor infliximab was initiated. The patient received three doses of infliximab at 5 mg/kg at monthly intervals, which led to marked clinical and radiological improvement. Follow-up magnetic resonance imaging showed regression of lesions, and the patient was eventually discharged with a significant recovery of motor and speech functions. This case underscores the potential of TNF inhibitors in managing severe cases of paradoxical deterioration in patients with tuberculous meningitis, challenging existing treatment paradigms and suggesting a need for further research into the pathophysiology and treatment of this condition.

MULTICENTER EXTERNAL VALIDATION OF THE ACCURACY OF COMPUTED TOMOGRAPHY CRITERIA FOR DETECTING THORACOLUMBAR POSTERIOR LIGAMENTOUS COMPLEX INJURY

Background and Objective Recent studies have proposed computed tomography (CT) criteria for posterior ligamentous complex (PLC) injury: disrupted if ? 2 CT findings, indeterminate if single finding, and intact if 0 CT findings. The study aims to validate the CT criteria for PLC injury externally. Methods Three level 1 trauma centers enrolled 614 consecutive patients with acute thoracolumbar fractures (T1- L5) who received Computed tomography (CT) and magnetic resonance imaging (MRI). Three reviewers from each center were the patients from the respective center for sessed CT for facet joint malalignment, horizontal laminar fracture, spinous process fracture, and interspinous widening and MRI for disrupted PLC. The primary outcome is the diagnostic accuracy of CT criteria (0,1, ? 2 findings) in detecting disrupted PLC on MRI using all CT readings. Subgroup analysis for each participating center and reviewer was done. The inter-reader agreement on PLC status on MRI and CT criteria was assessed using Fleiss Kappa (k). Results The positive predictive value (PPV) for PLC injury was 0 findings, 3%; single positive CT, 43%; ? 2 CT findings, 94%, and was consistent among different centers and reviewers. The AUC for ? 1 CT findings in detecting PLC injury ranged from 90% to 97%, indicating excellent discrimination for all centers. The inter-reader k on PLC status by MRI and CT criteria was substantial (k >0.60). Conclusions This study externally validates the previously proposed CT criteria for PLC injury. ? 2 positive CT findings or 0 CT findings can be used as criteria for a disrupted PLC (B-type injury) or intact PLC (A-type injuries), respectively, without added MRI. A single CT finding implies indeterminate PLC status and the need for further MRI assessment. The CT criteria will potentially guide MRI indications and treatment decisions for burst fractures in patients without neurological impairment.

Lactobacillus Helveticus Improves Controlled Cortical Impact Injury-Generated Neurological Aberrations by Remodeling of Gut-Brain Axis Mediators.

Considerable studies augured the potential of gut microbiota-based interventions in brain injury-associated complications. Based on our earlier study results, we envisaged the sex-specific neuroprotective effect of Lactobacillus helveticus by remodeling of gut-brain axis. In this study, we investigated the effect of L. helveticus on neurological complications in a mouse model of controlled cortical impact (CCI). Adult, male and female, C57BL/6 mice underwent CCI surgery and received L. helveticus treatment for six weeks. Sensorimotor function was evaluated via neurological severity score and rotarod test. Long-term effects on anxiety-like behavior and cognition were assessed using the elevated-zero maze (EZM) and novel object recognition test (NORT). Brain perilesional area, blood, colon, and fecal samples were collected post-CCI for molecular biology analysis. CCI-operated mice displayed significant neurological impairments at 1-, 3-, 5-, and 7-days post-injury (dpi) and exhibited altered behavior in EZM and NORT compared to sham-operated mice. However, these behavioral changes were ameliorated in mice receiving L. helveticus. GFAP, Iba-1, TNF-α, and IL-1β expressions and corticotrophin-releasing hormone (CRH) levels were elevated in the perilesional cortex of CCI-operated male/female mice. These elevated biomarkers and decreased BDNF levels in both male/female mice were modified by L. helveticus treatment. Additionally, L. helveticus treatment restored altered short-chain fatty acids (SCFAs) levels in fecal samples and improved intestinal integrity but did not affect decreased plasma levels of progesterone and testosterone in CCI mice. These results indicate that L. helveticus exerts beneficial effects in the CCI mouse model by mitigating inflammation and remodeling of gut microbiota-brain mediators.

Cell inspired delivery system equipped with natural membrane structures in applications for rescuing ischemic stroke.

Ischemic stroke (IS), accounting for 87 % of stroke incidences, constitutes a paramount health challenge owing to neurological impairments and irreversible tissue damage arising from cerebral ischemia. Chief among therapeutic obstacles are the restrictive penetration of the blood-brain barrier (BBB) and insufficient targeting precision, hindering the accumulation of drugs in ischemic brain areas. Motivated by the remarkable capabilities of natural membrane-based delivery vehicles in achieving targeted delivery and traversing the BBB, thanks to their biocompatible architecture and bioactive components, numerous membrane-engineered systems such as cells, cell membranes and extracellular vesicles have emerged as promising platforms to augment IS treatment efficacy with the help of nanotechnology. This review consolidates the primary pathological manifestations following IS, elucidates the unique functionalities of natural membrane drug delivery systems (DDSs) with nanotechnology, as well as delineates the structural characteristics of various natural membranes alongside rational design strategies employed. The review illuminates both the potential and challenges encountered when employing natural membrane DDSs in IS drug therapy, offering fresh perspectives and insights for devising efficacious and practical delivery systems tailored to IS intervention.

Equine assisted services - an intervention in the motor disorders of a child with cytomegalovirus sequelae

Cytomegalovirus infection (CMV) represents the most prevalent infection correlated with congenital neurological impairment. After infection occurs several factors contribute for the child to have motor development deficits and possibly present several neurological manifestations. Equine assisted services- therapeutic and educational method that uses the horse within an interdisciplinary approach has shown positive results in the intervention of neurological dysfunctions. The objective to analyze the effect of equine assisted services on the gross motor function of a participant with sequelae caused by CMV infection. A quantitative and descriptive case study. It consisted of assessments pre- and post-equine assisted services interventions using the Gross Motor Function Measure (GMFM). The child participating in the study is classified as level III according to the Gross Motor Function Classification System (GMFCS). The results indicate a percentage increase in the total average between the pre- and post-intervention assessments, with results of 31.9 and 50.3%, respectively, and evolution in three of the five dimensions assessed through the GMFM, which are: lying and rolling, sitting, crawling and kneeling. It is concluded that equine assisted services are an effective tool for improving gross motor function of a participant with sequelae caused by cytomegalovirus infection.

Abstract 4119428: Monosialoganglioside-containing nanoliposomes protect against acute and chronic ischemic stroke injury

Background: Stroke remains a leading cause of mortality and disability. The narrow temporal window and limited availability of, and eligibility for thrombolytic therapy or endovascular thrombectomy are major therapeutic limitations in treating stroke. Neuroprotective therapies that could be given early to replace or augment these existing therapies are needed to improve stroke outcomes. We showed that monosialoganglioside (GM1) containing nanoliposomes composed of phosphatidylcholine, cholesterol and GM1 (70/25/5% molar ratios, NLGM1) protect against hypoxic injury likely through Nrf2-dependent upregulation of antoxidant enzymes. Aims: To test if post-occlusion NLGM1 treatment could reduce 1) acute stroke injury following middle cerebral artery occlusion (MCAO) and 2) chronic injury following photothrombotic (PT) stroke injury. Methods: 20 week old C57BL/6 mice underwent MCAO for 60 minutes and then injected with saline or NLGM1 (1 or 2 mg IV) prior to reperfusion. Neurologic deficit score and brain infarct % area were measured the next day. Separately, mice underwent PT injury followed by injection of saline or NLGM1 (1 or 2 mg immediately and 2 hours post-injury) and cognitive/behavior tests done 1-90 days post injury. Results: Following MCAO, there was reduced neurologic impairment, infarct volume and brain edema with NLGM1 versus saline control (Fig. 1). Following PT injury, there was reduced neurologic, cognitive and motor impairment from Day 2-90 post-injury with NLGM1 versus saline control (Fig. 2). In both stroke models, there was no difference in efficacy between 1 and 2 mg NLGM1 doses. Conclusions: Treatment of mice with NLGM1 following MCAO or PT stroke injury resulted in improved structural (infarct size, edema) and functional (cognitive, behavior, motor) outcomes in the acute (MCAO) and chronic (PT) timeframes. NLGM1 is a potential novel therapeutic agent for stroke.

Abstract 4120716: Aspirin plus clopidogrel versus aspirin alone in patients with mild-to-moderate stroke: A systematic review and meta-analysis

Background: Studies have shown that dual antiplatelet therapy (DAPT) is superior to aspirin monotherapy in patients with minor stroke or transient ischemic attacks. However, there is limited evidence regarding the efficacy and safety of DAPT in mild-to-moderate stroke. Aims: We conducted a systematic review and meta-analysis to evaluate whether DAPT is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Methods: PubMed/MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from inception till March 2024 for published randomized controlled trials (RCTs) and observational studies that compared aspirin plus clopidogrel versus aspirin monotherapy in patients with mild-to-moderate stroke. R version 4.3.2 was used to calculate risk ratios (RRs) with 95% confidence intervals (95% CIs). Results: A total of 4 studies reporting data for 15,173 patients were included. DAPT was associated with a reduced risk of early neurological deterioration (END) (RR: 0.55, 95% CI: 0.28 to 1.05, p = 0.07 Figure 1A) and recurrent ischemic stroke (RR: 0.65, 95% CI: 0.41 to 1.04, p = 0.07 Figure 1B) without reaching statistical significance. The risk of recurrent hemorrhagic stroke (RR: 0.94, 95% CI: 0.47 to 1.86, p = 0.86 Figure 2A), all-cause death (RR: 0.75, 95% CI: 0.52 to 1.08 Figure 2B), or myocardial infarction (RR: 0.83, 95% CI: 0.45 to 1.54 Figure 2C) was comparable across the two groups. DAPT was not associated with an increased risk of any bleeding event (RR: 0.70, 95% CI: 0.36 to 1.36 Figure 2D). Conclusion: DAPT possibly reduces the risk of END and recurrent ischemic stroke as compared to aspirin monotherapy in mild or moderate stroke without increasing the risk of bleeding events.

Abstract Su1204: Impact of Hypothermia vs. Normothermia Temperature Management Based on Body Temperature at Hospital Arrival on 30-Day Neurological Outcomes in Out-of-Hospital Cardiac Arrest Patients: A Nationwide, Retrospective Study in Japan

Introduction: Temperature management (TM) to prevent fever is crucial to mitigate neurological deterioration post-cardiac arrest. Whether hypothermic TM (h-TM) is superior or equal to normothermic TM (n-TM) after out-of-hospital cardiac arrest (OHCA) is debatable, prompting ongoing effects to identify patients who might benefit more from h-TM. We hypothesized that effect of TM would differ based on body temperature at hospital arrival. Aim: Explore which post-cardiac arrest patient subsets might benefit from h-TM by stratifying them based on body temperature at hospital arrival. Methods: This retrospective, observational study used data from the OHCA registry in Japan. Patients 18 years and older who experienced OHCA due to medical cause and received TM in the intensive care unit were included. Primary outcome measure was 30-day favorable neurological outcomes, defined as a Cerebral Performance Category score of 1 or 2. Patients were stratified into groups based on body temperature at hospital arrival: normothermia (36.0-38.0°C), hypothermia (<36.0°C), and hyperthermia (>38.0°C). Effect of TM post-cardiac arrest (h-TM [32-34°C] or n-TM [35-36°C]) was evaluated in each stratified group. Univariable and multivariable logistic regression analysis was used for comparison. Adjusted odds ratio (OR) for favorable neurological outcome with h-TM was calculated using n-TM as a reference. Hyperthermia was excluded from multivariable analyses due to small sample size. Results: We analyzed 3,044 patients, 1,273 in the normothermia group, 1,747 in the hypothermia group, and 24 in the hyperthermia group. Numbers of patients with favorable neurological outcomes were as follows: 530/1,273 (41.6%) in the normothermia group, 584/1,747 (33.4%) in the hypothermia group, and 4/24 (16.7%) in the hyperthermia group. There were no differences in favorable 30-day neurological outcomes between h-TM and n-TM in any stratified group in the univariable analysis: normothermia (h-TM 323/785 [41.2%] vs. n-TM 207/488 [42.4%], p=0.66); hypothermia (411/1,185 [34.7%] vs. 173/562 [30.8%], p=0.11); hyperthermia (3/13 [23.1%] vs. 1/11 [9.1%], p=0.59). Multivariable analysis also showed no differences: normothermia (OR: 0.96, 95% CI: 0.72-1.26), hypothermia (OR: 1.10, 95% CI: 0.85-1.42). Conclusion: TM (h-TM vs. n-TM) did not significantly affect 30-day neurological outcomes, regardless of initial temperature at hospital arrival.

4-Phenylbutyric acid mitigates ER stress-induced neurodegeneration in the spinal cords of a GM2 gangliosidosis mouse model.

Sandhoff disease (SD), a fatal and rare lysosomal storage disorder (LSD), is caused by a deficiency of the enzyme β-hexosaminidase B and leads to severe accumulation of GM2 gangliosides in lysosomes, primarily within the central nervous system (CNS). This accumulation results in severe neurological impairment, lower motor neuron disease, and death. Currently, there are no effective therapies available for SD. Here, we explored the role of endoplasmic reticulum (ER) stress in the spinal cord during disease progression in an established mouse model of SD and revealed the beneficial outcome of off-label treatment with the FDA-approved drug, 4-phenylbutyric acid (4-PBA). We analyzed the expression and localization of ER stress and cellular apoptosis markers, which revealed significant upregulation of these factors within motor neurons. Additionally, we observed a > 50% reduction in neuronal numbers throughout all spinal cord regions. Our studies also tested the impact of the chemical chaperone 4-PBA on ER stress in mice, and following administration, we observed significant improvements in motor neuromuscular function and life span throughout disease progression. 4-PBA treatment significantly reduced apoptosis in spinal cord neurons and increased the number of choline acetyltransferase (ChAT)-positive neurons, with little effect on astrogliosis or sensory interneurons. Overall, this study provides strong evidence for the role of chronic ER stress in the pathophysiology of SD and highlights 4-PBA as a promising therapeutic treatment for SD and potentially other related LSDs.

Schaaf-Yang Syndrome Presenting with Prolonged Hyperthermia in a Child: A Case Report

Introduction: Schaaf-Yang syndrome (SYS) is a rare autosomal dominant disorder, first identified in 2013, resulting from mutations in the paternal allele of the MAGEL2 gene. Schaaf-Yang syndrome exhibits clinical features similar to those of Prader-Willi syndrome (PWS), including hypotonia, joint contractures, developmental delay, and intellectual disability. However, SYS is also characterized by unique manifestations, such as recurrent hyperthermia, feeding difficulties, respiratory distress, and seizures. This case report describes the first SYS case identified in Iran. Case Presentation: A one-year-old female, born to consanguineous parents, presented with recurrent episodes of hyperthermia, respiratory distress, and seizures since the neonatal period. Despite initial empirical treatment with broad-spectrum antibiotics for suspected infections, her symptoms persisted. Physical examination revealed hypotonia, camptodactyly, and hand contractures. Genetic testing confirmed SYS with a MAGEL2 gene mutation (c.1923dupC, p.V643Gfs*70) and probable pathogenic variants in ASPM and KIF7. The hyperthermia was attributed to hypothalamic dysfunction, a hallmark of SYS, rather than an infectious cause. The patient remains under follow-up without specific pharmacological intervention. Conclusions: This case emphasizes the importance of considering SYS in patients presenting with unexplained fever, seizures, and neurodevelopmental delays. Early genetic testing is crucial for diagnosing SYS and differentiating it from conditions such as PWS or infection-related disorders. Timely diagnosis can improve management strategies and help reduce the risk of lasting neurological impairments associated with this genetic disorder.

Upregulation of C1QC as a Mediator of Blood-Brain Barrier Damage in Type 2 Diabetes Mellitus.

The blood-brain barrier (BBB) is a neurovascular structure that safeguards the brain by inhibiting the passage of harmful substances. In individuals with type 2 diabetes mellitus (T2DM), the heightened blood glucose may cause damage to endothelial cells and neurons, increase collagen protein content, and elevate BBB permeability. Although the impact of blood glucose regulation on the structure and function of BBB has been documented, the exact mechanism remains incompletely elucidated. The primary aim of this investigation was to uncover the pivotal dysregulation of specific genes observed within the cerebral microvascular endothelial cells of diabetic patients, with a particular focus on understanding its biological implications in the disruption of the BBB. By integrating bioinformatics analysis, we identified C1QC as a potential upregulated marker. The expression level of C1QC was subsequently verified in both in vivo and in vitro models. Our experiments have discovered that, under diabetic conditions, suppressing C1QC leads to the mitigation of BBB damage. The presence of a high level of C1QC, through its binding to discoidin domain receptor 2 (DDR2), may trigger the activation of its downstream MMP9, a calcium-dependent enzyme that is capable of degrading protein components in the extracellular matrix, consequently leading to the structural and functional disruption of BBB. In summary, the findings of this study indicate that the aberrantly upregulated expression of C1QC may exert deleterious effects on the BBB under diabetes. To alleviate neurological impairments in individuals with T2DM, C1QC may emerge as a promising therapeutic target worthy of further investigation.

Abstract Su505: Impact of a Targeted Automated External Defibrillator (AED) Program on Survival After Ventricular Fibrillation Cardiac Arrest in the Sao Paulo Metropolitan Subway System: A Landmark Initiative in Latin America

The targeted Automated External Defibrillator (AED) program in the Sao Paulo Metro has yielded promising results in improving survival rates for individuals experiencing out-of-hospital cardiac arrest (OHCA) due to ventricular arrhythmias. A longitudinal observational study conducted from September 2006 to November 2023 assessed the program's impact on survival outcomes. The implementation of the full program led to a significant improvement in survival to hospital discharge with minimal neurological impairment (0% vs. 43%, P=0.001). These findings underscore the importance of a targeted AED program in improving survival outcomes for OHCA, particularly in densely populated urban environments such as the Sao Paulo Metro. The short interval between arrest and defibrillation emerged as a critical factor in achieving favorable long-term, neurologically intact survival rates. The success of this program advocates for the strategic expansion of targeted AED initiatives in other large Latin American cities, emphasizing the potential to save lives and enhance public health outcomes through proactive emergency medical response measures.

CTIM-09. INB-200: FULLY ENROLLED PHASE 1 STUDY OF GENE-MODIFIED AUTOLOGOUS GAMMA-DELTA (ΓΔ) T CELLS IN NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) PATIENTS RECEIVING MAINTENANCE TEMOZOLOMIDE (TMZ)

Abstract IN8bio’s DeltEx drug resistant immunotherapy (DRI), comprising TMZ-resistant γδ T cells engineered to express methylguanine-DNA methyltransferase (MGMT), enables γδ T cells to target upregulated NKG2D ligands on tumor cells in real time during alkylating chemotherapy exposure. Updated results from the fully enrolled Phase 1 trial evaluating DRI in adult newly diagnosed GBM subjects with IDH wild type and mutant tumors, adequate organ function and KPS ≥ 70%. Cohorts (C) 1, 2 and 3 received 1, 3 or 6 doses (1 x 107 DRI cells/dose) into the resection cavity with 150 mg/m2 of IV TMZ on Day 1 of each of 6 Stupp maintenance cycles. The primary endpoint is safety and secondary endpoints include survival; immunologic correlative analyses are included. Dose limiting toxicities (DLTs) are defined as treatment related ≥ grade (G) 3 cardiopulmonary or hepatic toxicity, G4 toxicity exceeding 72 hours or neurologic deterioration that exceeds 2 weeks. A total of 23 subjects were enrolled and 13 dosed (61% male; median age 68 (range: 21-74); 92% IDH-WT, 54% MGMT unmethylated). No DLTs, cytokine release syndrome (CRS), neurotoxicity (ICANS) or treatment related deaths were reported. The most common adverse events were decreased WBC/platelet count, asthenia, fatigue, hydrocephalus, headache, decreased appetite, urinary tract infection, thrombosis and balance disorder with ≥G3 platelet count decreased in 23% and WBC/ neutrophil/ lymphocyte count decreased in 7.7% each. Peripheral TMZ-based lymphodepletion was maintained for up to 1 year evidenced by near or below normal range T, B, and NK subsets. With median follow-up of 10.8 months, 83% of subjects exceeded the median 7 month Progression Free Survival (PFS) of the Stupp regimen alone, had manageable toxicity with a continued encouraging trend in PFS. Subject with IDH mutant tumor remains progression free for > 35 months. Long-term follow-up for durability of PFS and OS continues.

Exploring non-canonical targets in Alzheimer’s disease: a departure from the norm

AbstractAlzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized by neurological impairments such as visual and sensory difficulties, motor dysfunction, sphincter issues, incoordination, gait abnormalities, and cognitive decline. Despite advances in understanding AD pathophysiology and the expansion of therapeutic options over the past three decades, the disease remains incurable. Current therapies, even those specifically targeting AD, often fail to significantly alter its progression, underscoring the need for innovative treatment approaches beyond symptomatic relief. This calls for a re-examination of AD pathology to identify potential therapeutic targets that go beyond conventional strategies. This review highlights four of the most promising non-canonical therapeutic targets: oligodendrocytes, the blood–brain barrier (BBB), neuroimmunometabolism, and the coagulation system. These components are crucial for maintaining the integrity and proper function of neurons and the brain, playing key roles in the progression of AD. Oligodendrocytes, for example, are essential for myelination and neuronal support, while BBB dysfunction can lead to impaired clearance of toxic proteins. Neuroimmunometabolism offers insights into how metabolic processes influence immune responses in the brain and dysregulation of the coagulation system has been linked to increased neuroinflammation and vascular abnormalities in AD. Recent discoveries in these fields provide new avenues for understanding the disease and identifying potential therapeutic targets. By exploring these non-canonical pathways, future research may offer breakthroughs in treating AD, moving beyond symptomatic management towards disease-modifying strategies.

EOLP-02. END-OF-LIFE CHALLENGES IN NEURO-ONCOLOGICAL PATIENT CARE: A YOUNGNOA SURVEY

Abstract BACKGROUND Malignant brain tumors inevitably relapse, almost always causing significant functional and neurological impairments. Thus, palliative care is crucial in managing individuals with malignant brain tumors. It is essential for neuro-oncologists to be well-prepared to openly communicate about and meet the palliative needs of these patients. With this survey, we sought to evaluate palliative care practices in Germany and their impact on the treatment of neuro-oncological patients. METHODS We conducted an anonymous, interdisciplinary survey targeting palliative care practices among neuro-oncologists in Germany, all members of the Neuro-oncology Working Group of the German Cancer Society. The questionnaire, designed in close coordination with board-certified palliative care specialists, was distributed to 450 physicians. It collected personal information and assessed respondents’ knowledge of and access to palliative care structures. The survey was conducted online from March 31 to April 30, 2023. RESULTS Ninety-two physicians completed the survey. Of these, 81 (88%) reported feeling comfortable with end-of-life conversations, while 11 (12%) did not. No significant differences were observed between the two subgroups regarding their level of medical education (p=0.7140), workplace (p=0.4966), sex (p=0.9999), medical specialty (p=0.5478), or region of practice (p=0.9999). However, those comfortable with end-of-life discussions had significantly more palliative care training either during specialty training (p=0.0475) or through active participation in palliative care courses (p=0.0254). Further detailed analysis is in progress. CONCLUSIONS The survey indicates that while the majority of participants are comfortable with end-of-life discussions, a clear correlation exists between their comfort level and the extent of palliative care training received. This highlights the critical need for enhanced and targeted palliative care education within neuro-oncology training programs to prepare physicians for the complex communication and care challenges in neuro-oncological palliation. Further analysis will continue to explore additional educational and systemic factors that could increase the quality of palliative care in neuro-oncology.

RADT-32. FREQUENT MULTIFOCAL INTRATUMORAL HEMORRHAGE IN MULTIPLE BRAIN METASTASES FROM HEPATOCELLULAR CARCINOMA

Abstract OBJECTIVE Brain metastasis (BM) rarely occurs in hepatocellular carcinoma (HCC); however, it frequently causes intratumoral hemorrhage (ITH). We investigated the clinical manifestations of ITH in patients with multiple BMs from HCC (HCC-BM). METHODS Patients who underwent treatment for multiple BMs with more than two metastatic sites were retrospectively reviewed and those diagnosed with HCC-BM were further analyzed. The multifocality of hemorrhage was classified into two groups, spatial and temporal multifocality, according to the radiological findings. The characteristics of multifocal hemorrhage in HCC were compared with those of BMs from other cancer types. RESULTS Fifteen out of 636 (2.36%) cases of multiple BMs were due to HCC metastasis. Out of 15 HCC-BM cases, 13 (86.7%) presented multifocal hemorrhage and 1 presented unifocal hemorrhage during the follow-up period. Spatial and temporal multifocality were observed in 9 and 5 cases, respectively, among 13 cases of multifocal hemorrhage. Among 636 cases of multiple BMs, HCC cases showed the highest frequency of multifocal hemorrhage, and HCC was significantly associated with multifocal hemorrhage compared with other primary-site cancer types (30/621 cases, 4.8%). Out of 15 patients with multiple HCC-BMs, 12 underwent whole-brain irradiation (WBI), and their median overall survival was 147 days. In one patient (8.3%), although treatment was stopped due to neurological deterioration by ITH, local BM control was favorable after the completion of WBI, and the only cause of death in six patients who completed WBI and were radiologically followed up until death was the progression of extracranial lesions. CONCLUSIONS Multiple HCC-BMs frequently present with multifocal ITH compared with BMs from other cancer types. Despite poor treatment outcome, WBI may show favorable local control considering the potential hemorrhagic event by tiny metastases that would not be detected radiologically. Immediate commencement of treatment before hemorrhage progression will be required for the treatment of multiple HCC-BMs.

Cerebrotendinous Xanthomatosis (CTX) Disease Prevalance in Patients with Autism Spectrum Disorder (ASD): A Prospective Observational Study

Background: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive congenital metabolic disorder which is characterized by the impairment of the enzymatic activity of sterol 27-hydroxylase. CTX, a rare neurodegenerative disease of sterol metabolism, can affect multiple systems, including the nervous system.It has been demonstrated that many congenital metabolic diseases like CTX are associated with Autism Spectrum Disorder (ASD). The aim of this study is to identify the prevalence of CTX disease in patients with ASD. Method: The clinical conditions of all patients were evaluated using the Mignarri Scoring Index. A socio-demographic form and Gilliam Autism Rating Scale-2 were applied to all participants. Results: In total, 101 children and adolescents with ASD were analyzed for genes. Following genetic analyses, four patients with mutations in the CYP27A1 gene, two homozygous variants and two different heterozygous mutations were identified. Most common symptom was diarrhea. 67.3% of all patients and 3 in 4 cases with CYP27A1 gene mutation had gone through psychiatric evaluation. A family history of a psychiatric disorder was present in 19.8% of all cases and in 75% of cases with mutations.Moreover, all mutant cases had comorbid Oppositional Defiant Disorder (ODD). 81.2% of all patients and all mutant patients were diagnosed with a behavioral disorder. Conclusion: psychiatric manifestations ranging from personality changes to behavioral disorders might accompany CTX. Better understanding and knowledge of the CTX disease by distinguishing specific psychiatric and systemic symptoms might help prevent missed diagnoses, progressive neurological deterioration and permanent disability through early initiation of chenodeoxycholic acid treatment.

Relevance of optic nerve B-mode sonography in multiple sclerosis diagnosis and follow-up

Abstract Background Among young people, multiple sclerosis (MS) accounts for the majority of non-traumatic neurological impairments. Almost all MS patients develop optic neuritis as the illness progresses. In MS, the optic nerve (ON) is vulnerable to demyelinating injury and is considered “eloquent” in comparison with the brain. Thus, it serves as a clinical model for MS. Since the eye is a suitable target for ultrasonography due to its high-water content, non-invasive trans-orbital sonography (TOS) can determine the optic nerve sheath diameter (ONSD). This research aimed to determine the effectiveness of ON ultrasonography as a simple, low-cost method for diagnosing and following up MS patients, facilitating their treatment plan. It correlates the findings of ONSD using TOS and visual-evoked potential (VEP), the number of magnetic resonance imaging (MRI) black holes, and other clinically significant parameters in 30 relapsing–remitting MS (RRMS) patients versus 30 controls. Results We examined a total of 120 eyes. The ONSD values at 3 mm, 5 mm, and myelination index were significantly lower in the patients (4.7 ± 0.3, 5.5 ± 0.3, and 0.86 ± 0.03, respectively) versus the controls (5.6 ± 0.3, 6.2 ± 0.4, and 0.90 ± 0.03, respectively) (p < 0.001 in each). The mean P 100 latency was significantly delayed in the patients (125.5 ± 6.1 ms) than the controls (100.2 ± 3.3 ms), (p < 0.001). The mean VEP amplitude was significantly lower in the patients (4.9 ± 0.7 μV) than the controls (6.8 ± 0.8 μV) (p < 0.001). There was a highly significant positive correlation between the ONSD and P 100 amplitude, and highly significant negative correlations between the ONSD and disease duration, number of optic neuritis attacks, EDSS, MRI black holes number, and P 100 latency. Conclusions Trans-orbital sonography is a practical and easily accessible approach for assessing ON atrophy in MS. It can measure axonal loss and brain atrophy indirectly and is a reliable paraclinical diagnostic tool, suggesting that ONSD could be a biomarker of disease activity.

Advancing ischemic stroke diagnosis and clinical outcome prediction using improved ensemble techniques in DSC-PWI radiomics.

Ischemic stroke is a leading global cause of death and disability and is expected to rise in the future. The present diagnostic techniques, like CT and MRI, have some limitations in distinguishing acute from chronic ischemia and in early ischemia detection. This study investigates the function of ensemble models based on the dynamic radiomics features (DRF) from the dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) ischemic stroke diagnosis, neurological impairment assessment, and modified Rankin Scale (mRS) outcome prediction). DRF is extracted from the 3D images, features are selected, and dimensionality is reduced. After that, ensemble models are applied. Two model structures were developed: a voting classifier with 6 bagging classifiers and a stacking classifier based on 4 bagging classifiers. The ensemble models were evaluated on three core tasks. The Stacking_ens_LR model performed best for ischemic stroke detection, the LR Bagging model for NIH Stroke Scale (NIHSS) prediction, and the NB Bagging model for outcome prediction. These outcomes illustrate the strength of ensemble models. The work showcases the role of ensemble models and DRF in the stroke management process.