Brain MRI Research Articles

Cognitive impact and brain structural changes in long COVID patients: a cross-sectional MRI study two years post infection in a cohort from Argentina

Abstract Objective Long COVID is a condition characterised by persistent symptoms after a SARS-CoV-2 infection, with neurological manifestations being particularly frequent. Existing research suggests that long COVID patients not only report cognitive symptoms but also exhibit measurable cognitive impairment. Neuroimaging studies have identified structural alterations in brain regions linked to cognitive functions. However, most of these studies have focused on patients within months of their initial infection. This study aims to explore the longer-term cognitive effects and brain structural changes in long COVID patients, approximately two years post-infection, in a cohort from San Martín, Buenos Aires, Argentina. Methods We conducted a cross-sectional study involving 137 participants: 109 with long COVID symptoms and 28 healthy controls. The participants underwent an initial clinical assessment, completed a structured questionnaire and standardised scales, underwent a cognitive assessment, and had a brain MRI scan. Structural MRI images were processed via FreeSurfer and FSL to obtain volumetric measures for subcortical and cortical regions, along with regional cortical thickness. Differences between groups for these variables were analysed using ANCOVA, with permutation tests applied to correct for multiple comparisons. Results Long COVID patients reported persistent cognitive symptoms such as memory problems and brain fog, with higher levels of fatigue and reduced quality of life compared to controls. Despite subjective cognitive complaints, cognitive tests did not reveal significant differences between groups, except for the TMT-A (p = 0.05). MRI analysis revealed decreased volume in the cerebellum (p = 0.03), lingual gyrus (p = 0.04), and inferior parietal regions (p = 0.03), and reduced cortical thickness in several areas, including the left and right postcentral gyri (p = 0.02, p = 0.03) and precuneus (p = 0.01, p = 0.02). Conclusions This study highlights the enduring impact of long COVID on quality of life and physical activity, with specific brain structural changes identified two years post-infection. Although cognitive tests did not show clear impairment, the observed brain atrophy and significant reduction in quality of life emphasize the need for comprehensive interventions and further longitudinal studies to understand the long-term effects of long COVID on cognition and brain health.

Cerebral vascular shunting and oxygen metabolism in sickle cell disease.

Patients with sickle cell disease (SCD) are at elevated risk of silent cerebral infarcts and strokes; however, they frequently lack established stroke risk factors (e.g., macrovascular arterial steno-occlusion) and as such the mechanisms underlying such events are incompletely characterized. This study evaluated cerebral metabolism with respect to imaging markers of vascular shunting in 143 SCD participants, including 73 pediatric (6-17 years) and 70 adult (18-40 years) participants. Participants completed clinical and cerebral imaging assessments using 3-Tesla brain MRI to quantify cerebral hemo-metabolic measures. Vascular shunting was assessed in each patient using a previously published ordinal venous hyperintensity score (VHS=0, 1, or 2) on cerebral blood flow-weighted MRI. Relationships between age group (pediatric versus adults) and hemo-metabolic measures for varying VHS were investigated using two-way ANOVA. Participants with VHS=2, indicative of the most rapid arterio-venous transit, had significantly reduced blood oxygen content (CaO2=10.90±1.69 ml O2/100ml blood), oxygen extraction fraction (OEF=33.52±5.54%), and cerebral metabolic rate of oxygen consumption (CMRO2=2.91±0.69 ml O2/100g tissue/min) compared to their counterparts with VHS=0 (CaO2=12.42±1.58 ml O2/100ml blood; OEF=39.03±3.80%; CMRO2=3.77±0.84 ml O2/100g tissue/min) or VHS=1 (CaO2=11.86±1.73 ml O2/100ml blood; OEF=36.37±5.11%; CMRO2=3.59±0.78 ml O2/100g tissue/min). Both pediatric and adult SCD patients presenting with greater imaging evidence of vascular shunting had mildly reduced OEF and CMRO2. These findings highlight that imaging markers of vascular shunting are associated with significant, albeit mild, evidence of reduced OEF and CMRO2 in patients with SCD.

Interhypothalamic adhesions: prevalence, structure, and location-based classification map in pediatric patients undergoing MRI.

Interhypothalamic adhesions (IHAs) have been reported only in the pediatric population, with unknown prevalence and histological composition. We aim to demonstrate their prevalence, assess their persistence through longitudinal imaging, classify IHAs by anatomical distribution, explore their structure, and report associated pathologies. A retrospective review was conducted on consecutive pediatric brain MRI studies obtained between January 2012, and December 2013. The presence of an IHA was only confirmed when observed on at least two planes. For each IHA, cross-sectional area was calculated, and signal intensities were measured at the center on sagittal T2WIs. Signal intensities were also measured in both cerebral white matter and gray matter for normalization and comparison. Patient demographics and clinical information were collected from electronic charts. Out of 1550 patients (0-17.9 years), 33 (19 males, 14 females) had an IHA, resulting in a 2.13% prevalence. Follow-up images were available for 19 IHA-positive patients, and IHAs were again seen in 92% of the follow-up scans (71/77). Normalized IHA signal highly correlated with normalized gray matter signal (r = 0.83, P < 0.001), but not with normalized white matter signal (r = -0.16, p = 0.494). Common co-occurring pathologies included hydrocephalus (n = 9), prematurity (n = 8), and corpus callosum abnormalities (n = 7). All type 3 IHAs (3/3) were accompanied by pituitary pathologies. IHAs have a prevalence of 2.13% in our cohort, and the majority persist in longitudinal studies. They showed gray matter signal intensity and Type 3 IHAs exclusively accompanied pituitary abnormalities.

Development and Evaluation of Automated Artificial Intelligence-Based Brain Tumor Response Assessment in Patients with Glioblastoma.

To develop and evaluate an automated, AI-based, volumetric brain tumor MRI response assessment algorithm on a large cohort of patients treated at a high-volume brain tumor center. We retrospectively analyzed data from 634 patients treated for glioblastoma at a single brain tumor center over a 5-year period (2017-2021). The mean age was 56 +/-13 years. 372/634 (59%) patients were male, and 262/634 (41%) patients were female. Study data consisted of 3,403 brain MRI exams and corresponding standardized, radiologist-based brain tumor response assessments (BT-RADS). An artificial intelligence (AI)-based brain tumor response assessment algorithm was developed using automated, volumetric tumor segmentation. AI-based response assessments were evaluated for agreement with radiologist-based response assessments and ability to stratify patients by overall survival. Metrics were computed to assess the agreement using BTRADS as the ground-truth, fixed-time point survival analysis was conducted to evaluate the survival stratification, and associated P-values were calculated. For all BT-RADS categories, AI-based response assessments showed moderate agreement with radiologists' response assessments (F1 = 0.587-0.755). Kaplan-Meier survival analysis revealed statistically worse overall fixed time point survival for patients assessed as image worsening equivalent to RANO progression by human alone compared to by AI alone (log-rank P=0.007). Cox proportional hazard model analysis showed a disadvantage to AI-based assessments for overall survival prediction (P=0.012). AI-based volumetric glioblastoma MRI response assessment following BT-RADS criteria yielded moderate agreement for replicating human response assessments and slightly worse stratification by overall survival. GBM＝ Glioblastoma; RANO＝ Response Assessment in Neuro-Oncology; BTRADS＝ Brain Tumor Reporting and Data System; NLP = Natural Language Processing.

The impact of Prophylactic cranial irradiation on the prognosis of patients with limited-stage small cell lung cancer in the MRI era.

To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of MRI surveillance. Limited-stage SCLC patients with complete remission (CR) or partial remission (PR) of tumor after definitive chemo-radiotherapy (CRT) were retrospectively analyzed. Survival data were calculated by Kaplan-Meier methods, Cox proportional hazards model was applied for multivariate prognostic analysis. Between June 2002 and January 2017, 620 patients with limited-stage SCLC were accrued in our study. After CRT, 228 (36.8%) patients achieved CR, of whom, 29 patients did not receive PCI, among the rest 199 patients, 172 (86.4%) received brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 25.6 months, the cumulative BM rate was 17.1% and 37.9% in patients who received or did not receive PCI (P = 0.011). The median survival time was 30.2 months and 30.5 months, respectively and the 1 -, 3 -, 5-year survival rates were 93.7%, 42.9%, 35.8% and 83.4%, 46.5%, 41.9%, respectively (P = 0.98). Multivariate analysis indicated that baseline KPS ≥ 90 was a favorable independent prognostic factor for OS in CR patients (HR: 0.33, 95% CI: 0.23-0.46, P = 0.000). After CRT, 392 (63.2%) patients achieved PR, 53 cases did not receive PCI and 310 (91.4%) of the remaining 339 patients received brain MRI before PCI. With a median follow-up time of 15.5 months, the cumulative brain metastasis rate was 12.7% and 46.2% respectively (P = 0.000). The median survival time was 25.7 months and 18.6 months, respectively. The 1 -, 3 -, and 5-year survival rates were 87.6%, 40.2%, 29.2% and 75.7%, 16.7%, 10.3% (P = 0.000). Baseline KPS ≥ 90 (HR: 0.32, 95% CI: 0.25-0.41, P = 0.000) and PCI (HR: 0.57, 95% CI: 0.41-0.79, P = 0.001) were favorable prognostic factors for OS in PR patients. In this study, PCI significantly reduced the incidence of BM in patients with limited-stage SCLC who were evaluated as CR and PR after CRT, but it has no significantly positive impact on overall survival in CR patients. Further prospective randomized studies were warranted.

Sex differences in brain MRI using deep learning toward fairer healthcare outcomes

This study leverages deep learning to analyze sex differences in brain MRI data, aiming to further advance fairness in medical imaging. We employed 3D T1-weighted Magnetic Resonance images from four diverse datasets: Calgary-Campinas-359, OASIS-3, Alzheimer's Disease Neuroimaging Initiative, and Cambridge Center for Aging and Neuroscience, ensuring a balanced representation of sexes and a broad demographic scope. Our methodology focused on minimal preprocessing to preserve the integrity of brain structures, utilizing a Convolutional Neural Network model for sex classification. The model achieved an accuracy of 87% on the test set without employing total intracranial volume (TIV) adjustment techniques. We observed that while the model exhibited biases at extreme brain sizes, it performed with less bias when the TIV distributions overlapped more. Saliency maps were used to identify brain regions significant in sex differentiation, revealing that certain supratentorial and infratentorial regions were important for predictions. Furthermore, our interdisciplinary team, comprising machine learning specialists and a radiologist, ensured diverse perspectives in validating the results. The detailed investigation of sex differences in brain MRI in this study, highlighted by the sex differences map, offers valuable insights into sex-specific aspects of medical imaging and could aid in developing sex-based bias mitigation strategies, contributing to the future development of fair AI algorithms. Awareness of the brain's differences between sexes enables more equitable AI predictions, promoting fairness in healthcare outcomes. Our code and saliency maps are available at https://github.com/mahsadibaji/sex-differences-brain-dl.

Common protein-altering variant in GFAP is associated with white matter lesions in the older Japanese population.

The genetic architecture of white matter lesions (WMLs) in Asian populations has not been well-characterized. Here, we performed a genome-wide association study (GWAS) to identify loci associated with the WML volume. Brain MRI and DNA samples were collected from 9479 participants in the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD). The GWAS confirmed three known WML-associated loci (SH3PXD2A, GFAP, and TRIM47). The lead variant of GFAP was a common missense variant (p.D295N) in East Asians. Meta-GWAS using the publicly available summary statistics of UK Biobank identified one previously unreported locus 6q23.2 (SLC2A12). Integration with expression quantitative trait locus data implied the newly identified locus affects SLC2A12 expression. The effect sizes of 20 lead variants at the WML-associated loci were moderately correlated between JPSC-AD and UK Biobank. These results indicate that the alteration in GFAP protein caused by the common missense variant in East Asians influences the WML volume.

Neuroinflammation modifies the relationship between stress and perivascular spaces in an elderly population with different levels of cognitive impairment

BackgroundPerivascular spaces (PVS) are fluid-filled spaces surrounding the brain parenchymal vasculature. Literature suggests that PVS may play a significant role in aging and neurological disorders, including Alzheimer’s disease (AD). The aim of this study is to investigate whether the relationship between MRI-visible PVS and stress is influenced by neuroinflammation in an elderly population with different levels of cognitive impairment.MethodsUsing brain MRI scans acquired at 1.5 T, PVS were quantified in a cohort of 461 individuals, consisting of cognitively healthy controls (n = 48), people with mild cognitive impairment (MCI, n = 322) and Alzheimer’s disease (AD, n = 91). PVS volume fraction was calculated in the basal ganglia and centrum semiovale using a semi-automated segmentation approach. Stress was quantified with levels of salivary cortisol. Inflammatory biomarkers measured from plasma included cytokines, matrix metalloproteinases and C-reactive protein. General linear models were used to test the relationship between PVS and cortisol, when interacting with inflammatory markers. This was done on the whole cohort and within each clinical cognitive group.ResultsIn the centrum semiovale, higher inflammation levels reduced the relationship of cortisol with PVS. In basal ganglia, higher levels of C-reactive protein reduced the negative relationship of cortisol with PVS. All analyses were accounted for age, sex, body mass index (BMI) and total hippocampal volume. There was a significant interaction effect between cortisol and C-reactive protein on PVS volume fraction in the MCI group.DiscussionThese findings suggest an influence of neuroinflammation on the PVS structure in Alzheimer’s disease spectrum, and offer insight for better understanding physiological processes of cognitive impairment onset.

An Association Between Fetal Subarachnoid Space and Various Pathologies Using MR Imaging

Background/Objectives: This study aimed to explore a relationship between the fetal subarachnoid space (SAS) width and various fetal pathologies, employing fetal brain MRI scans. Methods: A retrospective collection of fetal brain MRI scans of 78 fetuses was performed with sonographic indications of microcephaly, macrocephaly, or fetal growth restriction (FGR), during a 7-year period at a single tertiary center. The SAS width (named the SAS index) was manually measured in millimeters in ten specific anatomical locations (four in the axial plane and six in the coronal plane), and then converted to centiles by comparing it to (previously collected) data of apparently healthy fetuses. We evaluated the median SAS centiles using the Kruskal–Wallis and Mann–Whitney U tests for statistical comparison. Results: Seventy-eight subjects (mean gestational age of MRI scan 34.2 ± 2.2 weeks) were evaluated. The median SAS centiles were consistently higher in the macrocephaly group compared to the microcephaly group in all ten anatomical locations (statistically significant except coronal left inferior temporal gyri). Most pronounced difference was displayed in the insula gyri (axial and coronal). The median SAS centiles were higher in the microcephaly group when compared with FGR across all ten anatomical locations (all were statistically significant except for coronal frontal and insula gyri), and the maximal difference was found in the frontal gyri of both planes. The median SAS indexes (IQR) of the three groups in millimeters: macrocephaly 91.55 (86.35–101.05), microcephaly 59.46 (50.00–66.91), and FGR 53.21 (49.71–59.10), p &lt; 0.001. Conclusions: We found a statistically significant association between the fetal subarachnoid space and various fetal pathologies: macrocephaly, microcephaly, and FGR.

Case report: The effect of induction targeted therapies in stage III driver mutants non-small cell lung cancer

BackgroundOver the past decade, progress in the diagnosis and treatment of Non-Small Cell Lung Cancer (NSCLC) has led to the identification of many targeted mutations. This has enhanced PFS and OS in both advanced and early-stage NSCLC. The current standard of care for stage III NSCLC varies, and it may combine chemotherapy with either immunotherapy or radiotherapy. This study evaluated the role of induction targeted therapies in patients with driver mutations and inoperable NSCLC.MethodsThis is a single-center, retrospective study assessing the efficacy of targeted therapy in resectable stage III NSCLC patients who are EGFR or ALK-positive, using patient records, PET-CT, brain MRI staging, and mediastinal lymph node evaluation.ResultsBetween January 2020 and February 2024, we identified four patients with either EML4-ALK fusions (2/4) or EGFR mutations (2/4) who underwent treatment with brigatinib or osimertinib before surgery. All patients experienced clinical benefits. Of the two patients with ALK fusion, one responded almost completely, while the other exhibited a notable partial response. Among the patients with EGFR mutations, one had a complete response and the other displayed a significant partial response. All four patients subsequently underwent lobectomy surgical resection.ConclusionsThis case series highlights the potential of targeted therapies for resectable NSCLC in the neoadjuvant setting. Further research is required to confirm their benefits, assess their safety and efficacy, and determine optimal timing and sequencing.

White Matter Hyperintensities and Cognitive Functions in People With the R544C Variant of the NOTCH3 Gene Without Stroke or Dementia.

NOTCH3 pathologic variants cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which presents with stroke and dementia and is characterized by white matter hyperintensities (WMHs) on brain MRI. The R544C variant is a common pathologic variant in Taiwan, but not all carriers exhibit significant symptoms. We investigated whether WMHs occur before clinical symptoms in carriers with pathogenic variants, examined factors associated with WMHs, and explored their relationship with cognitive functions. We enrolled 63 R544C carriers without overt clinical disease (WOCD) and 37 age-matched and sex-matched noncarriers as controls from the Taiwan Precision Medicine Initiative data set. All participants underwent clinical interviews, comprehensive neuropsychological assessments, and brain MRI. We calculated total and regional WMH volumes, determined the age at which WMHs began increasing in carriers, and examined the relationship between WMHs and neuropsychological performance. Factors associated with WMH volumes were analyzed using multivariable linear regression models. Compared with controls, R544C carriers WOCD had increased WMH volume, except in the occipital and midbrain areas, and showed a rapid increase in WMHs starting at age 48. They scored lower on the Mini-Mental State Examination (median = 28.4 vs 29.0, p = 0.048), Montreal Cognitive Assessment (MoCA) (median = 28.3 vs 29.0, p = 0.013), and memory and executive function tests than controls. After adjusting for age, sex, and education, MoCA scores were associated with whole-brain (r = -0.387, padj = 0.008) and regional WMHs (all padj < 0.05) except in the midbrain area. Age (β = 0.034, 95% CI 0.021-0.046, p < 0.001), hypercholesterolemia (β = 0.375, 95% CI 0.097-0.653, p = 0.009), and the vascular risk factor (VRF) index (β = 0.132, 95% CI 0.032-0.242, p = 0.019) were associated with the WMH severity in carriers. Our study revealed that WMHs are extensively distributed in R544C carriers WOCD. They exhibited a rapid increase in WMHs beginning at age 48, approximately 7 years earlier than the reported age at symptomatic onset. Age was the strongest predictive factor of WMHs, and VRF, particularly hypercholesterolemia, might be modifying factors of WMHs.

Abstract 4122507: Fetal Socioeconomic and Environmental Exposures Influence Fetal Brain Growth and Risk of Neonatal Brain Injury in Congenital Heart Disease

Introduction: Fetuses with CHD have smaller total brain volume (TBV) and are at risk for acquired brain white matter injury (WMI), both of which are linked to neurodevelopmental impairments. Social determinants of health (SDOH) and other fetal environmental factors have been linked to fetal brain health in other populations. Our aim was to test our hypothesis that these exposures influence fetal brain growth and postnatal WMI risk in severe CHD. Methods: Our prospective longitudinal cohort study enrolled fetuses with severe CHD to undergo fetal brain MRI and postnatal pre-operative brain MRI. Participants completed home environment surveys on individual SDOH and exposures. Community SDOH metrics were determined using Child Opportunity Index (COI) based on home address. An ‘at risk’ fetus composite was created if there was exposure to: personal/household smoking, welfare/food stamps, or poverty. TBV was calculated at both time points. Presence/degree of WMI was determined on postnatal MRI. Repeated measures analysis and logistic regression were performed to determine association between individual and community SDOH metrics with rate of TBV growth and risk of WMI. Results: 55 participants enrolled (54 fetal scans: mean GA 33.9 wks, 95%CI: 33.7,34.1; 47 neonatal scans: mean GA 39.3 wks 95%CI: 38.9,39.6). Fetal sex, smoking exposure, and several individual SDOH were associated with TBV growth. Adjusting for fetal sex and GA at scan, rate of TBV growth was slower with smoking exposure (coeff: -5.2, 95%CI: -10.3, -0.2, p= 0.04) and trended towards significance for those with welfare/food stamps or poverty. ‘At risk’ fetuses had slower rate of TBV growth than those without risk (coeff: -2.5, 95%CI: -5.0, -0.07, p= 0.04) (Figure 1). There were lower odds of pre-operative WMI with high COI compared to low after adjusting for GA at scan (OR= 0.16, 95%CI: 0.03, 0.9, p= 0.04). Conclusion: Smoking exposure and individual-level SDOH influence brain growth, while community COI is associated with risk of postnatal pre-op WMI in CHD. Our findings identify targets for intervention to optimize brain growth and outcomes in the CHD population, including smoking cessation programs, and nutritional and needs assessment during pregnancy.

Abstract 4126731: Cumulative Cardiovascular Health in Young Adulthood and Systemic Target Organ Damage: The Coronary Artery Risk Development In Young Adults (CARDIA) Study

Introduction: Cardiovascular health (CVH) in young adulthood (YA) is strongly associated with subclinical and clinical outcomes in later life. Longitudinal patterns of CVH exposure through YA (e.g., cumulative CVH exposure) may be particularly important. However, no studies have assessed cumulative CVH in YA and its association with target organ damage (TOD). Methods: CVH was defined using Life’s Essential 8 (LE8) score. CARDIA participants (ppts) with CVH assessed at ≥3 exams over 20 years of follow-up in YA (year [Y]0 to Y20 exams; mean ages 25 to 45 years) were included. Cumulative LE8 scores (cumLE8; higher = better CVH over time) were calculated as the sum of LE8 scores through YA carried forward between exams measured as point*years. Eight markers of TOD (listed in Results) were measured at subsequent exams (Y20 or Y25) including cardiac, renal, pulmonary, and neurologic markers. Associations of cumLE8 with markers of TOD were assessed using partial effects regression models adjusted for race, sex, and maximal education. Results: There were 3,485 ppts (43.4% men, 46.2% Black) with mean cumLE8 score of 1,448.6 (SD 211.4) point*years. Higher cumLE8 in YA was linearly associated with lower measures of cardiac (left ventricular mass index, carotid intima media thickness, prevalence of coronary artery calcium), renal (estimated glomerular filtration rate [eGFR] in men), and neurologic damage (proportion of white matter hyperintensity on brain MRI) ( Figure ). Higher cumLE8 was also linearly associated with better lung function (forced expiratory volume in 1 second, forced vital capacity). Urine albumin-creatinine ratio (in men and women) and eGFR (in women) were non-linearly associated with cumLE8. Conclusions: Our findings underscore the importance of high cumLE8 in YA and its association with reduced onset of TOD later in life. Primordial prevention strategies are needed to achieve and maintain high CVH through the critical period of YA.

Association of Seizure Foci and Location of Tau and Amyloid Deposition and Brain Atrophy in Patients With Alzheimer Disease and Seizures.

Alzheimer disease (AD) is associated with a 2 to 3-fold increased risk of developing late-onset focal epilepsy, yet it remains unclear how development of focal epilepsy in AD is related to AD pathology. The objective of this study was to examine spatial relationships between the epileptogenic zone and tau deposition, amyloid deposition, and brain atrophy in individuals with AD who developed late-onset, otherwise unexplained focal epilepsy. We hypothesized that if network hyperexcitability is mechanistically linked to AD pathology, then there would be increased tau and amyloid deposition within the epileptogenic hemisphere. In this cross-sectional study, we performed tau and amyloid PET imaging, brain MRI, and overnight scalp EEG in individuals with early clinical stages of AD who developed late-onset, otherwise unexplained focal epilepsy (AD-Ep). Participants were referred from epilepsy and memory disorders clinics at our institutions. We determined epilepsy localization based on EEG findings and seizure semiology. We quantified tau deposition, amyloid deposition, and atrophy across brain regions and calculated asymmetry indices for these measures. We compared findings in AD-Ep with those in a control AD group without epilepsy (AD-NoEp). The AD-Ep group included 8 individuals with a mean age of 69.5 ± 4.2 years at PET imaging. The AD-NoEp group included 14 individuals with a mean age of 71.7 ± 9.8 years at PET imaging. In AD-Ep, we found a highly asymmetric pattern of tau deposition, with significantly greater tau in the epileptogenic hemisphere. Amyloid deposition and cortical atrophy were also greater in the epileptogenic hemisphere, although the magnitudes of asymmetry were reduced compared with tau. Compared with AD-NoEp, the AD-Ep group had significantly greater tau asymmetry and trends toward greater asymmetry of amyloid and atrophy. AD-Ep also had significantly greater amyloid burden bilaterally and trends toward greater tau burden within the epileptogenic hemisphere, compared with AD-NoEp. Our results reveal a spatial association between the epileptogenic focus and tau deposition, amyloid deposition, and neurodegeneration in early clinical stages of AD. Within the limitations of a cross-sectional study with small sample sizes, these findings contribute to our understanding of the clinicopathologic heterogeneity of AD, demonstrating an association between focal epilepsy and lateralized pathology in AD.

The fork sign: a new cortical landmark in the human brain

Abstract In the cerebral cortex, establishing the precise relationship between functional areas and the macroscopic anatomy of gyri and sulci has a paramount importance for the field of neuroimaging and neurosurgical interventions. The anatomical orientation should start with the identification of anatomical landmarks to set the anatomo-functional boundaries. The human central sulcus region stands out as a well-defined structural and functional unit housing the primary motor and sensory cortices and is considered as key region to be identified during brain surgery. While useful anatomical landmarks have been discovered, especially in the axial plane, the identification of this region in the sagittal plane remains sometimes difficult. Using cadaveric whole brains and multimodal analysis of MRI brain scans, we systematically observed a tuning fork shaped sulco-gyral configuration centered around the gyral continuum bridging the precentral gyrus with the middle frontal gyrus. We provide evidence that this “Fork sign” is a consistent morphological feature visible on the lateral surface of the brain and a reliable radioanatomical landmark for identifying central sulcus region structures on sagittal MRI images, including the motor hand area.

Child Neurology: Acute Necrotizing Encephalopathy of Childhood Associated With Dengue: Good Neurologic Outcome Despite a Fulminant Presentation.

Acute necrotizing encephalopathy of childhood (ANEC) is characterized by a rapidly progressive encephalopathy after a viral febrile illness, with multiple, symmetrical lesions in the brain including the thalami. Acute dengue fever is a known, but rare, trigger for ANEC. The clinical course of ANEC is usually fulminant and is associated with high morbidity and mortality. We describe here a prospective cohort of 5 children who presented with ANEC associated with dengue infection characterized by encephalopathy within the first week of fever, followed by a rapidly deteriorating sensorium requiring intensive care unit admission. Dengue fever was diagnosed based on a positive nonstructural protein 1 antigen test. ANEC was diagnosed based on characteristic MRI brain findings including the "trilaminar sign" in bilateral thalami combined with clinical features of severe encephalopathy, thrombocytopenia, and transaminitis. All the children required prolonged hospital stay (mean duration 30 days), with 4 of 5 children requiring mechanical ventilation (mean duration 21 days). All the children received immunomodulation with IV methylprednisolone either alone or followed by IV immunoglobulin. Although these children were bedridden at discharge (modified Rankin Scale, mRS score 4 or 5), they showed a consistent recovery in follow-up. At 6 months of follow-up, all the children were fully independent in activities of daily living (mRS scores 1-2). These cases highlight good neurologic outcomes in children with ANEC associated with dengue despite a catastrophic presentation and a protracted hospital course. The most common residual neurologic deficits noted were hand tremors and extrapyramidal dysarthria.

Abstract 4119116: Percutaneous Aspiration of Mitral Valve Endocarditis using the AngioVac Device

Case Description: A 68-year-old man with end-stage renal disease on dialysis, peripheral vascular disease with metatarsal amputations, atrial fibrillation and type 1 diabetes was admitted for foot osteomyelitis secondary to MSSA bacteremia. Transesophageal echocardiogram revealed mobile mitral valve vegetations up to 1.8cm on the atrial aspect of the posterior mitral valve leaflet which prolapsed through the mitral valve during diastole. Ejection fraction was 60% and there was trivial-mild mitral regurgitation without valvular destruction or peri-annular extension into the mitral annulus. MRI brain showed bilateral cerebral and cerebellar hemispheric infarcts, consistent with acute embolic stroke. He was at high risk for both recurrent embolism and operative mortality (STS risk score 51%) due to his comorbidities and risk of hemorrhagic conversion of stroke. After shared decision making, percutaneous aspiration of the mitral vegetation was performed with AngioVac (Fig). Cerebral embolism protection devices were deployed prior to AngioVac evacuation of the mass. There was no residual mitral regurgitation and only a small vegetation strand remained (Fig). Surgical pathology confirmed MSSA endocarditis. Blood cultures remained negative, and the patient did not suffer from recurrent embolic events. The patient underwent revision metatarsal amputation and was discharged with a 6-week course of IV cefazolin. Discussion: Infective endocarditis with high embolic risk is life-threatening and challenging to treat in patients with high surgical risk. We illustrate a case of percutaneous vegetation aspiration using the AngioVac device in our patient who suffered from embolic strokes due to MSSA mitral valve endocarditis. Meta-analyses have shown clinically successful debulking in 90% of cases, with 82% of patients able to clear bacteremia with AngioVac. Although most commonly used in right-sided lesions, percutaneous debulking of left-sided endocarditis with AngioVac and cerebral protection can be considered as a treatment strategy in select patients with prohibitive surgical risk.

PATH-31. COMPLETE TUMOR DISAPPEARANCE ON BRAIN MRI AFTER STANDARD CHEMORADIATION THERAPY FOR A MOLECULAR GLIOBLASTOMA

Abstract INTRODUCTION Glioblastoma (GBM) is the most aggressive brain tumor. The WHO CNS5 classification has newly incorporated three molecular criteria in diagnosing molecular GBM, including a concurrent gain of chromosome 7 and loss of chromosome 10 (+7/-10), TERT promoter mutation, or EGFR amplification. Despite new classification, the Stupp protocol remains the standard of care for all GBMs. However, it is unclear if the treatment response of the molecular GBM with low grade features is the same as the limited response of the traditional histopathological GBM. CASE REPORT A 74-year-old male presented in August of 2023 with new onset left-sided facial numbness. The numbness resolved spontaneously that day. Brain MRI was notable for a diffuse left frontal T2/Flair hyperintense lesion extending across the corpus callosum into the right frontal lobe without definite enhancement. Brain biopsy from 8 sites of the tumor demonstrated a subset of areas with mild hyper-cellularity, suggesting a low-density infiltrating glioma. However, TERT promoter mutation (-124C&amp;gt;T), was detected along with wild-type IDH1, supporting molecular GBM. Studies also found unmethylated MGMT gene promotor. Brain MRIs after 3 and 6 months showed no tumor progression. The patient has remained asymptomatic apart from baseline mild forgetfulness. He was started on the 6-week standard concomitant temozolomide and radiation therapy. Follow-up brain MRI after the above treatment showed complete imaging resolution of the tumor. DISCUSSION It is very rare for complete imaging resolution of GBM on brain MRI after standard 6-week chemoradiation therapy. Our case suggests that molecular GBM with low-grade features on imagine and pathology might have a better response to the standard treatment than traditional histopathological GBM even though the molecular GBM patient has unfavorable prognostic factors such as unmethylated MGMT and older age (&amp;gt;70 years old). Our experience emphasizes the heterogenous response of molecular GBM to the current standard treatment.

NCOG-08. A RARE PRIMARY CNS T-CELL LYMPHOMA CASE: 12-YEAR FOLLOW-UP AFTER CHEMOTHERAPY

Abstract INTRODUCTION Primary central nervous system (CNS) T-cell lymphoma (PCNSTL) is a rare hematological malignancy. There is mere literature to guide the treatment. CASE REPORT This study is an update on our previously reported case at SNO in 2012 after a 12-year follow-up, detailing the long-term outcome of our chemotherapy treatment for a case of PCNSTL. In 2011, a 26-year-old immunocompetent patient presented with severe headache, vomiting, and lethargy. The brain MRI found more than a dozen masses on his bilateral cerebral hemispheres. Brain biopsy discovered T-cell lymphoma. The patient was started biweekly high-dose-methotrexate (HD-MTX) in 2011. After three doses, there was no noticeable improvement on his brain MRI. His treatment was switched to HD-MTX plus high dose cytarabine regimen (Ferreri et al, The Lancet, 2009). The patient could not tolerate cytarabine; thus, was changed back to HD-MTX. The patient responded to the rest of HD-MTX well. He completed 8 doses of biweekly HD-MTX induction therapy and 2 doses of monthly HD-MTX maintenance therapy. His brain MRI showed complete resolution of enhancement on one-year follow-up image. The patient has been off-treatment and monitored under surveillance of brain MRIs since 2012. He has had no lymphoma recurrence over the past 12 years. His physical functions have been preserved with a Karnofsky Performance Status scale of 80%. Neuropsychological evaluations in 2015, 2018, and 2023 showed mild cognitive impairment with gradual improvements in his working memory and semantic fluency. His Mini-Mental Status Exam scores have remained stable to mild improvement, recording 27/30 in 2015, 26/30 in 2018, 27/30 in 2023 and 28/30 in 2024. DISCUSSION The patient, who is now 38 years old, has surpassed a 12-year survival mark. Our experience emphasizes the feasibility of treating PCNSTL through chemotherapy only, which might be potentially beneficial in surviving and preserving major aspects of brain function.

Malignant sarcomatous transformation of calvarial fibrous dysplasia: illustrative case.

Fibrous dysplasia (FD) is a nonheritable genetic disorder characterized by abnormal osteogenesis, resulting in benign bone lesions in one or multiple bones. Despite their predominantly benign nature, these lesions can transform into malignant neoplasms, resulting in pain, swelling, disfigurement, and even death. The authors report a case of malignant sarcomatous transformation in an adult patient with a history of craniofacial FD. A 61-year-old male with a history of systemic FD presented with a rapidly enlarging cranial mass that had recently started becoming painful to touch. Magnetic resonance imaging of the brain displayed extensive FD changes throughout the calvarium and a large dysplastic mass in the right parietal bone with extension into the underlying epidural space, resulting in severe mass effect. The patient subsequently underwent radical resection and complex soft tissue reconstruction. The pathology confirmed high-grade undifferentiated pleomorphic sarcoma, for which the patient subsequently underwent an adjuvant chemotherapy regimen. Malignant sarcomatous transformation of craniofacial FD most often results in the formation of an osteosarcoma in the maxilla, with the temporal and sphenoid bones also being common sites of such transformations. Although treatment begins with radical resection, the efficacy of adjuvant chemotherapy and radiation remains controversial. https://thejns.org/doi/10.3171/CASE24537.