Cerebrospinal Fluid Volume Research Articles

Association between choroid plexus volume and cognitive function in community-dwelling older adults without dementia: a population-based cross-sectional analysis

BackgroundAn increase in choroid plexus (CP) volume may be associated with cognitive decline in older individuals without dementia. In this study, we aimed to clarify whether CP volume can serve as an imaging marker of cognitive decline, determine how strongly CP volume is associated with cognitive decline, and explore factors associated with CP volume in older adults.MethodsWe measured CP volume, brain parenchyma, and cerebrospinal fluid (CSF) spaces associated with disproportionately enlarged subarachnoid space hydrocephalus (DESH), an imaging feature of normal-pressure hydrocephalus, in community-dwelling older adults aged ≥ 65 years without dementia.ResultsIn 1,370 participants, lower Mini-Mental State Examination (MMSE) scores were significantly associated with higher CP volume, even after adjusting for DESH-related CSF space and brain parenchymal volume. CP volume was more strongly associated with MMSE scores than DESH-related CSF space and brain parenchymal volume. History of smoking, white matter hyperintensity, enlarged perivascular spaces, age, body mass index, and diabetes mellitus were also associated with increased CP volume.ConclusionsCP volume may be a highly sensitive imaging marker of cognitive decline in community-dwelling older adults without dementia, as it is linked to cognitive decline independently of brain parenchyma and CSF volumes. Our findings emphasize the importance of investigating CP volume increase to maintain cognitive function in older individuals. Accordingly, further longitudinal studies are required.

Characterization of Morphological Brain Changes in Generalized Epilepsy Using Region-based Morphometry

Magnetic Resonance Imaging has been widely involved in detecting morphological brain changes in generalized epilepsy at voxel level. It is believed that region-based morphometry could provide better characterizations for macro structural changes in the brain with comparative advantages than voxel-based morphometry. The aim of this study is to detect regional brain changes associated with generalized epilepsy and to test the potential of regional brain changes in classification of patients with generalized epilepsy and non-epileptic subjects. 45 patients and 46 non-epileptic subjects were scanned using a 3 Tesla MRI scanner and 3D T1 weighted images were obtained. Images were pre-processed and region based structural metrics (grey matter volumes, white matter volumes, cerebrospinal fluid volumes, cortical gyrification, and sulcus depth) were developed using Computational Anatomical Toolbox (CAT12). Two sample t-tests were used to perform the univariate analyses and results were corrected for multiple comparisons (FDR corrected, p < 0.05). Grey matter volume reductions were detected in cerebellum, frontal lobe, temporal lobe, thalamus, and hippocampal region while bilateral white matter volume reductions were reported in cerebellum. In contrast, cerebrospinal fluid volume increments in left lateral ventricle were also detected. Reduced regional gyrification was detected in left posterior ramus of the lateral sulcus and reduced sulcal depths were detected in occipital pole, cuneus, and posterior ramus of the lateral sulcus in patients. Furthermore, pattern analysis revealed that each metric shows different discriminative abilities to distinguish patients with generalized epilepsy and non-epileptic subjects (Classification accuracy: 61.1%, 62.2%, 58.8%, 61.1% and 60% for GMV, WMV, CSFV, Cortical gyrification and sulcal depth respectively). In conclusion, this study provides a comprehensive understanding about regional structural changes (cortical and subcortical) associated with generalized epilepsy under region-based morphometry. However, pattern analyses do not provide adequate discriminative power and therefore the clinical utility of findings is limited.

The normalization trend of ventricular morphology after lateral ventricular tumor resection without additional diversion

Intraventricular tumors frequently provoke alterations in ventricular morphology. This study aims to quantificational assess perioperative dynamic fluctuations in the cerebrospinal fluid (CSF) volume within the lateral ventricles of patients harboring lateral ventricular tumors. A retrospective review encompassing 90 patients who underwent surgical intervention for lateral ventricular tumors at our institution was undertaken. Comprehensive observations at multiple perioperative time points were conducted, and LVCV analyses were performed to delineate the longitudinal dynamic alterations in ventricular morphology. Additionally, LVCV measurements were juxtaposed with data from 19 healthy subjects to stratify patients into two cohorts: those exhibiting preoperative increased LVCV and those without such changes. After surgical excision of intraventricular tumors, alterations in LVCV were compared between these cohorts, with a factor analysis undertaken specifically among patients demonstrating increased LVCV to elucidate potential influencing variables. 40 patients (44.4%) diagnosed with intraventricular tumors presenting with enlarged preoperative LVCV [74.6 (49.3–101.8) cm3] compared with the normal subject group, and the LVCV demonstrated a significant postoperative [41.3 (27.6–67.5) cm3] reduction in 3 months (p < 0.001). Meanwhile, 50 patients (55.6%) without LVCV enlargement [14.5 (8.1–21.0) cm3] experienced a notable increase following surgery in 3 months [20.2 (14.1–33.3) cm3, p = 0.002]. Preoperative increased LVCV is an important factor leading to the increased LVCV postoperatively (p = 0.022, OR = 26.239), however, compared to healthy subjects, both groups exhibited a trend toward normalization of LVCV value postoperatively (p = 0.165, p = 0.072, respectively). Following appropriate surgical excision of the tumor, the preoperative increased LVCV associated with intraventricular tumors does not hinder the normalization trend of ventricular morphology. Not all ventricular dilation requires preventive long-term external ventricular drainage and aggressive ventriculoperitoneal shunt treatment.

Anatomical Characteristics of Cervicomedullary Compression on MRI Scans in Children with Achondroplasia.

This retrospective study assessed anatomical characteristics of cervicomedullary compression in children with achondroplasia. Twelve anatomical parameters were analyzed (foramen magnum diameter and area; myelon area; clivus length; tentorium and occipital angles; brainstem volume outside the posterior fossa; and posterior fossa, cerebellum, supratentorial ventricular system, intracranial cerebrospinal fluid, and fourth ventricle volumes) from sagittal and transversal T1- and T2-weighted magnetic resonance imaging (MRI) scans from 37 children with achondroplasia aged ≤ 4 years (median [range] 0.8 [0.1-3.6] years) and compared with scans from 37 children without achondroplasia (median age 1.5 [0-3.9] years). Mann-Whitney U testing was used for between-group comparisons. Foramen magnum diameter and area were significantly smaller in children with achondroplasia compared with the reference group (mean 10.0 vs. 16.1 mm [p < 0.001] and 109.0 vs. 160.8 mm2 [p = 0.005], respectively). The tentorial angle was also steeper in children with achondroplasia (mean 47.6 vs. 38.1 degrees; p < 0.001), while the clivus was significantly shorter (mean 23.5 vs. 30.3 mm; p < 0.001). Significant differences were also observed in myelon area, occipital angle, fourth ventricle, intracranial cerebrospinal fluid and supratentorial ventricular volumes, and the volume of brainstem protruding beyond the posterior fossa (all p < 0.05). MRI analysis of brain structures may provide a standardized value to indicate decompression surgery in children with achondroplasia.

Neuroprotective Effects of Rapid Local Ischemic Postconditioning in Successful Endovascular Thrombectomy Patients.

We aim to assess the efficacy of rapid local ischemic postconditioning (RL-IPostC) following successful reperfusion in patients with acute ischemic stroke with anterior circulation large vessel occlusion who underwent endovascular thrombectomy. We conducted an ambidirectional cohort study with 78 prospectively enrolled patients with RL-IPostC and endovascular thrombectomy and 129 retrospectively enrolled patients with endovascular thrombectomy. The RL-IPostC procedure involved 5 cycles of 15-s balloon inflation and deflation in the ipsilateral internal carotid artery. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes included excellent outcomes (modified Rankin Scale score, 0-1) and early therapeutic response. Imaging outcomes involved infarct volume changes and cerebral edema measurements. Outcomes were compared with postpropensity score matching (1:1) and assessed using univariable and multivariable regression models. In the matched cohort of 136 patients (mean age, 71±14 years; 70 men [51%]), RL-IPostC was associated with a higher rate of functional independence (adjusted odds ratio, 2.47 [95% CI, 1.10-5.68]; P=0.030). The RL-IPostC group exhibited significantly reduced infarct volumes at 24 hours (difference, -12.2 [95% CI, -23.9 to -0.53]; P=0.041) and less infarct growth (difference, -12.2 [95% CI, -23.9 to -0.45]; P=0.042). Furthermore, RL-IPostC correlated with lower increases in net water uptake (difference, -0.04 [95% CI, -0.07 to -0.01]; P=0.018), lower decrease cerebrospinal fluid volume (difference, -7.75 [95% CI, -11.7 to -3.84]; P<0.001), and reduced midline shift at 24 hours (difference, -1.39 [95% CI, -2.48 to -0.30]; P=0.013). RL-IPostC tends to promote functional independence and reduces infarct growth and cerebral edema in patients with acute ischemic stroke post-reperfusion.

The impact of body position on neurofluid dynamics: present insights and advancements in imaging.

The intricate neurofluid dynamics and balance is essential in preserving the structural and functional integrity of the brain. Key among these forces are: hemodynamics, such as heartbeat-driven arterial and venous blood flow, and hydrodynamics, such as cerebrospinal fluid (CSF) circulation. The delicate interplay between these dynamics is crucial for maintaining optimal homeostasis within the brain. Currently, the widely accepted framework for understanding brain functions is the Monro-Kellie's doctrine, which posits a constant sum of intracranial CSF, blood flow and brain tissue volumes. However, in recent decades, there has been a growing interest in exploring the dynamic interplay between these elements and the impact of external factors, such as daily changes in body position. CSF circulation in particular plays a crucial role in the context of neurodegeneration and dementia, since its dysfunction has been associated with impaired clearance mechanisms and accumulation of toxic substances. Despite the implementation of various invasive and non-invasive imaging techniques to investigate the intracranial hemodynamic or hydrodynamic properties, a comprehensive understanding of how all these elements interact and are influenced by body position remains wanted. Establishing a comprehensive overview of this topic is therefore crucial and could pave the way for alternative care approaches. In this review, we aim to summarize the existing understanding of intracranial hemodynamic and hydrodynamic properties, fundamental for brain homeostasis, along with factors known to influence their equilibrium. Special attention will be devoted to elucidating the effects of body position shifts, given their significance and remaining ambiguities. Furthermore, we will explore recent advancements in imaging techniques utilized for real time and non-invasive measurements of dynamic body fluid properties in-vivo.

Transcranial low-level laser stimulation in the near-infrared-II region (1064 nm) for brain safety in healthy humans

BackgroundThe use of near-infrared lasers for transcranial photobiomodulation (tPBM) offers a non-invasive method for influencing brain activity and is beneficial for various neurological conditions. However, comprehensive quantitative studies on its safety are lacking. ObjectiveThis study aims to investigate the safety of 1064-nm laser-based tPBM across brain structure, brain function, neural damage, cognitive ability and tolerance. MethodsWe employed a multimodal approach, using magnetic resonance imaging (MRI), electroencephalogram (EEG), biochemical analyses, and cognitive testing to quantitatively assess the potential adverse effects of tPBM on brain structure or function, neurons, glial cells, and executive function (EF). Additionally, a detailed questionnaire was used to evaluate subjective tolerance. ResultsAt the whole-brain structural level, no significant variations in gray matter, white matter, or cerebrospinal fluid volume or density were observed as a result of tPBM. There was no increase in neuron-specific enolase (NSE) or S100β levels suggesting no neuronal damage, but an unexpected significant reduction in NSE was detected which requires further study to assess its implications. EEG, analyzed through power spectra and expert evaluation, revealed no potential disease-inducing effects. A series of cognitive tests demonstrated no impairment in any of the EF components. Furthermore, the questionnaire data revealed minimal discomfort across fatigue, itching, pain, burning, warmth, dizziness, and drowsiness. ConclusionsOur data indicate that 1064 nm laser tPBM does not induce adverse effects on brain structure or function, nor does it impair cognitive abilities. tPBM is safe for specific parameters, highlighting its good tolerability.

A Histopathologic Correlation Study Evaluating Glymphatic Function in Brain Tumors by Multiparametric MRI.

This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage by leveraging advanced MRI techniques to explore the relationships among tumor characteristics, glymphatic function, and aquaporin-4 (AQP4) expression levels. In a prospective cohort from March 2022 to April 2023, patients with glioblastoma, brain metastases, and aggressive meningiomas, alongside age- and sex-matched healthy controls, underwent 3.0T MRI, including diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index and multiparametric MRI for quantitative brain mapping. Tumor and peritumor tissues were analyzed for AQP4 expression levels via immunofluorescence. Correlations among MRI parameters, glymphatic function (DTI-ALPS index), and AQP4 expression levels were statistically assessed. Among 84 patients (mean age: 55 ± 12 years; 38 males) and 59 controls (mean age: 54 ± 8 years; 23 males), patients with brain tumor exhibited significantly reduced glymphatic function (DTI-ALPS index: 2.315 vs. 2.879; P = 0.001) and increased cerebrospinal fluid volume (201.376 cm³ vs. 115.957 cm³; P = 0.001). A negative correlation was observed between tumor volume and the DTI-ALPS index (r: -0.715, P < 0.001), whereas AQP4 expression levels correlated positively with peritumoral brain edema volume (r: 0.989, P < 0.001) and negatively with proton density in peritumoral brain edema areas (ρ: -0.506, P < 0.001). Our findings highlight the interplay among tumor-induced compression, glymphatic dysfunction, and altered fluid dynamics, demonstrating the utility of DTI-ALPS and multiparametric MRI in understanding the pathophysiology of tumor-related cerebral edema. These insights provide a radiological foundation for further neuro-oncological investigations into the glymphatic system. See related commentary by Surov and Borggrefe, p. 4813.

Phase-contrast MRI analysis of cerebral blood and CSF flow dynamic interactions

BackgroundFollowing the Monro-Kellie doctrine, the Cerebral Blood Volume Changes (CB_VC) should be mirrored by the Cerebrospinal Fluid Volume Changes (CSF_VC) at the spinal canal. Cervical level is often chosen to estimate CB_VC during the cardiac cycle. However, due to the heterogeneity in the anatomy of extracranial internal jugular veins and their high compliance, we hypothesize that the intracranial level could be a better choice to investigate blood and cerebrospinal fluid (CSF) interactions. This study aims to determine which level, intracranial or extracranial, is more suitable for measuring arterial and venous flows to study cerebral blood and CSF dynamics interactions.MethodsThe spinal CSF and cerebral blood flow measured at intracranial and extracranial levels were quantified using cine phase-contrast magnetic resonance imaging (PC-MRI) in 38 healthy young adults. Subsequently, CSF_VC and CB_VC were calculated, and by linear regression analysis (R2 and slope), the relationship between CB_VC at both levels and the spinal CSF_VC was compared. The differences between extracranial and intracranial measurements were assessed using either a paired Student’s t-test or Wilcoxon’s test, depending on the normality of the data distribution.ResultsThe CB_VC amplitude was significantly higher at the extracranial level (0.89 ± 0.28 ml/CC) compared to the intracranial level (0.73 ± 0.19 ml/CC; p < 0.001). CSF oscillations through the spinal canal do not completely balance blood volume changes. The R2 and the slope values obtained from the linear regression analysis between CSF and blood flows were significantly higher in magnitude for the intracranial CB_VC (R2: 0.82 ± 0.16; slope: − 0.74 ± 0.19) compared to the extracranial CB_VC (R2: 0.47 ± 0.37; slope: -0.36 ± 0.33; p < 0.001). Interestingly, extracranial CB_VC showed a greater variability compared to intracranial CB_VC.ConclusionOur results confirmed that CSF does not completely and instantaneously balance cerebral blood expansion during the cardiac cycle. Nevertheless, the resting volume is very small compared to the total intracranial volume. To our knowledge, this study is the first to demonstrate these findings using cerebral blood flow measured intracranially below the Circle of Willis. Additionally, our findings show that cerebral arterial and venous flow dynamic measurements during the cardiac cycle obtained by PC-MRI at the intracranial plane strongly correlate with CSF oscillations measured in the spinal canal. Therefore, the intracranial vascular plane is more relevant for analyzing cerebral blood and CSF interactions during the cardiac cycle compared to measurements taken at the cervical vascular level.

ENDOSCOPIC THIRD VENTRICULOSTOMY VS VENTRICULOPERITONEAL SHUNT IN OBSTRUCTIVE HYDROCEPHALUS IN TERMS OF POST-OPERATIVE COMPLICATIONS

: Obstructive Hydrocephalus is a condition characterized by increased cerebrospinal fluid (CSF) volume within the brain's ventricular system, leading to clinical deterioration and disability. Without treatment, it can be fatal. Two primary treatment modalities are Ventriculoperitoneal Shunting (VPS) and Endoscopic Third Ventriculostomy (ETV), with ongoing debate over the superiority of one approach over the other. Objective: To compare the complications associated with Ventriculoperitoneal Shunting (VPS) and Endoscopic Third Ventriculostomy (ETV) in patients with obstructive hydrocephalus. Methods: A randomized controlled trial was conducted at a tertiary care hospital from April 15, 2024, to September 15, 2024. A total of 100 patients diagnosed with obstructive hydrocephalus were randomly allocated into two groups: 50 patients received VPS treatment, and 50 received ETV. Complications, including surgical site infection, seizures, hematoma, and CSF leakage, were recorded and analyzed. Results: Complications were observed in 36% (n=18) of patients in the VPS group compared to 16% (n=8) in the ETV group, with a statistically significant difference (p=0.023). Surgical site infections occurred in 8% (n=4) of VPS patients, while no infections were reported in the ETV group. Seizures were significantly more common in the VPS group, affecting 26% (n=13) compared to 8% (n=4) in the ETV group (p=0.017). Hematoma formation was observed in 4% (n=2) of VPS patients and 6% (n=3) of ETV patients. CSF leakage occurred in 4% (n=2) of VPS patients and 2% (n=1) of ETV patients. Conclusion: Endoscopic Third Ventriculostomy (ETV) demonstrated a significantly lower complication rate compared to Ventriculoperitoneal Shunting (VPS) in the management of obstructive hydrocephalus. These findings support ETV as a safer alternative with fewer associated complications.

Phosphorylated tau in cerebrospinal fluid-derived extracellular vesicles in Alzheimer’s disease: a pilot study

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder characterized by brain aggregation of β-amyloid (Aβ) peptides and phosphorylated tau (P-tau) proteins. Extracellular vesicles (EVs) can be isolated and studied for potential roles in disease. While several studies have tested plasma-derived EVs in AD, few have analyzed EVs from cerebrospinal fluid (CSF), which are potentially more closely related to brain changes. This study included 20 AD patients and 20 cognitively unimpaired (CU) participants. Using a novel EV isolation method based on acoustic trapping, we isolated and purified EVs from minimal CSF volumes. EVs were lysed and analyzed by immunoassays for P-tau217 and P-tau181. Isolation was confirmed through transmission electron microscopy and the presence of EV-specific markers (CD9, CD63, CD81, ATP1A3). Nanoparticle tracking analysis revealed a high variance in EV distribution. AD patients exhibited increased P-tau181 and decreased P-tau217 in EVs, leading to a higher EV P-tau181/P-tau217 ratio compared to CU. No significant differences in EV counts or sizes were observed between AD and CU groups. This study is the first to use acoustic trapping to isolate EVs from CSF and demonstrates differential P-tau content in AD-derived EVs, warranting further research to understand the relationship between these EV changes and brain pathology.

Deep Proteome Analysis of Cerebrospinal Fluid from Pediatric Patients with Central Nervous System Cancer.

The cerebrospinal fluid (CSF) is a key matrix for discovery of biomarkers relevant for prognosis and the development of therapeutic targets in pediatric central nervous system malignancies. However, the wide range of protein concentrations and age-related differences in children makes such discoveries challenging. In addition, pediatric CSF samples are often sparse and first prioritized for clinical purposes. The present work focused on optimizing each step of the proteome analysis workflow to extract the most detailed proteome information possible from the limited CSF resources available for research purposes. The strategy included applying sequential ultracentrifugation to enrich for extracellular vesicles (EV) in addition to analysis of a small volume of raw CSF, which allowed quantification of 1351 proteins (+55% relative to raw CSF) from 400 μL CSF. When including a spectral library, a total of 2103 proteins (+240%) could be quantified. The workflow was optimized for CSF input volume, tryptic digestion method, gradient length, mass spectrometry data acquisition method and database search strategy to quantify as many proteins a possible. The fully optimized workflow included protein aggregation capture (PAC) digestion, paired with data-independent acquisition (DIA, 21 min gradient) and allowed 2989 unique proteins to be quantified from only 400 μL CSF, which is a 340% increase in proteins compared to analysis of a tryptic digest of raw CSF.

The Relationship Between Physical Activity and Non-Modifiable Risk Factors on Alzheimer's Disease and Brain Health Markers: A UK Biobank Study.

Modifiable (physical activity) and non-modifiable (sex and genotype) risk factors interact to affect Alzheimer's disease (AD) risk. Further investigation is necessary to understand if these factors influence brain volume and cognition. The study aimed to assess the effect of physical activity, APOE genotype, and sex on AD risk, brain volume, and cognition. UK Biobank data from 2006 to 2023 was accessed. Physical activity was measured by accelerometers, and International Physical Activity Questionnaire. Outcomes were AD incidence; brain volume (ventricular cerebrospinal fluid and total brain); and cognition (executive function, memory, visuospatial ability, processing speed, and reaction time). Logistic and linear regression models were conducted. 69,060 participants met inclusion criteria (mean age: 62.28 years, SD: 7.84; 54.64% female). Higher self-reported (OR = 0.63, 95% CI [0.40, 1.00], p = 0.047) and accelerometer-assessed (OR = 0.96 [0.93, 0.98], p = 0.002) physical activity was associated with lower disease incidence. Smaller ventricular cerebrospinal fluid volume (β= - 65.43 [- 109.68, - 17.40], p = 0.007), and larger total brain volume (β= 4398.46 [165.11, 8631.82], p < 0.001) was associated with increased accelerometer-assessed and self-reported physical activity respectively. Both brain volume analyses were moderated by sex. Increased accelerometer-assessed physical activity levels were associated with faster reaction time (β= - 0.43 [- 0.68, - 0.18], p = 0.001); though poorer visuospatial ability (β= - 0.06 [- 0.09, - 0.03], p < 0.001), and executive function (β= 0.49 [0.31, 0.66], p < 0.001; β= 0.27 [0.10, 0.45], p = 0.002) was related to self-reported physical activity levels. Higher levels of physical activity reduce AD risk independently of non-modifiable risk factors. Moderation of sex on brain volume highlighted the importance of incorporating non-modifiable risk factors in analysis.

Parasagittal dural volume correlates with cerebrospinal fluid volume and developmental delay in children with autism spectrum disorder

BackgroundThe parasagittal dura, a tissue that lines the walls of the superior sagittal sinus, acts as an active site for immune-surveillance, promotes the reabsorption of cerebrospinal fluid, and facilitates the removal of metabolic waste products from the brain. Cerebrospinal fluid is important for the distribution of growth factors that signal immature neurons to proliferate and migrate. Autism spectrum disorder is characterized by altered cerebrospinal fluid dynamics.MethodsIn this retrospective study, we investigated potential correlations between parasagittal dura volume, brain structure volumes, and clinical severity scales in young children with autism spectrum disorder. We employed a semi-supervised two step pipeline to extract parasagittal dura volume from 3D-T2 Fluid Attenuated Inversion Recovery sequences, based on U-Net followed by manual refinement of the extracted parasagittal dura masks.ResultsHere we show that the parasagittal dura volume does not change with age but is significantly correlated with cerebrospinal fluid (p-value = 0.002), extra-axial cerebrospinal fluid volume (p-value = 0.0003) and severity of developmental delay (p-value = 0.024).ConclusionsThese findings suggest that autism spectrum disorder children with severe developmental delay may have a maldeveloped parasagittal dura that potentially perturbs cerebrospinal fluid dynamics.

Tetraspanins, GLAST and L1CAM Quantification in Single Extracellular Vesicles from Cerebrospinal Fluid and Serum of People with Multiple Sclerosis.

Objective: This study aimed to unravel the single tetraspanin pattern of extracellular vesicles (EVs), L1CAM+ and GLAST+ EV levels as diagnostic biomarkers to stratify people with multiple sclerosis (pwMS), specifically relapsing-remitting (RRMS) and primary progressive (PPMS). Methods: The ExoView platform was used to directly track single EVs using a clinically feasible volume of cerebrospinal fluid (CSF) and serum samples. This technology allowed us to examine the patterns of classical tetraspanin and quantify the levels of L1CAM and GLAST proteins, commonly used to immunoisolate putative neuron- and astrocyte-derived EVs. Results: The tetraspanin EV pattern does not allow us to differentiate RRMS, PPMS and non-MS donors neither in CSF nor serum, but this was associated with the type of biofluid. L1CAM+ and GLAST+ EVs showed a very low presence of tetraspanin proteins. Additionally, a significant decrease in the particle count of L1CAM+ EVs was detected in L1CAM-captured spots, and L1CAM+ and GLAST+ EVs decreased in GLAST-captured spots in the CSF from PPMS subjects compared to RRMS. Interestingly, only GLAST+ EVs exhibited a lower quantity in the CSF from PPMS compared to both MS and non-MS samples. Finally, GLAST+ EVs demonstrated a medium negative and significative correlation with GFAP levels-a biomarker of MS progression, astrocyte damage and neurodegenerative processes. Conclusions: ExoView technology could track neural EV biomarkers and be potentially useful in the diagnostic evaluation and follow-up of pwMS. GLAST+ EVs might provide insights into the etiology of PPMS and could offer small windows to elucidate the molecular mechanisms behind its clinical presentation.

Association of ambient air pollution with cognitive functioning and markers of structural brain damage: The Maastricht study

IntroductionGiven the absence of curative interventions and the rising global incidence of dementia, research is increasingly focusing on lifestyle factors for prevention. However, identifying shared environmental risk for dementia, next to individual factors, is crucial for optimal risk reduction strategies. Therefore, in the present study we investigated the association between air pollution, cognitive functioning, and markers of structural brain damage. MethodsWe used cross-sectional data from 4,002 participants of The Maastricht Study on volumetric markers of brain integrity (white and grey matter volume, cerebrospinal fluid volume, white matter hyperintensities volume, presence of cerebral small vessel disease) and cognitive functioning (memory, executive functioning and attention, processing speed, overall cognition). Individuals were matched by postal code of residence to nationwide data on air pollution exposure (particulate matter < 2.5 μm (PM2.5), particulate matter <10 μm (PM10), nitrogen dioxide (NO2), soot). Potentia linear and non-linear associations were investigated with linear, logistic, and restricted cubic splines regression. All analyses were adjusted for demographic characteristics and a compound score of modifiable dementia risk and protective factors. ResultsExposure to air pollutants was not related to cognitive functioning and most brain markers. We found curvilinear relationships between high PM2.5 exposures and grey matter and cerebrospinal fluid volume. Participants in the low and high range of exposure had lower grey matter volume. Higher cerebrospinal fluid volumes were only associated with high range of exposure, independent of demographic and individual modifiable dementia risk factors. After additional post hoc analyses, controlling for urbanicity, the associations for grey matter volume became non-significant. In men only, higher exposure to all air pollutants was associated with lower white matter volumes. No significant associations with white matter hyperintensities volume or cerebral small vessel disease were observed. DiscussionOur findings suggest that higher PM2.5 exposure is associated with more brain atrophy.

Utility and performance of cell blocks in cerebrospinal fluid cytology: Experience at two teaching hospitals.

Cytology cell blocks (CBs) are not routinely made for cerebrospinal fluid (CSF) specimens. The goal of this study was to identify when CSF CB preparation improves diagnostic performance. Under institutional review board approval, a retrospective review of CSF cytology cases was conducted at a tertiary university-based hospital and an affiliated county hospital. Patient history, CSF volume, final diagnosis, use of stains, and whether the CB was contributory was determined from the cytopathology report. CSF nucleated cell count data was obtained from the medical record. A total of 69 CSF specimens with CBs from January 2006 to March 2023 were identified from 61 patients. The median CSF volume was 8mL (interquartile range, 4-13mL; range, 1-800mL), with immunohistochemical stains performed on 29 (42%) cases. Per cytology report, CB was contributory in 23 cases (33%), not contributory in 34 cases (49%), and not discussed in 12 cases (17%). The median volume was 8mL for cases in which CB was contributory, not contributory, or not discussed. There was no difference in average nucleated cell counts between cases in which CB was contributory versus not contributory (73.9 vs. 40.0, p=.175). CBs for CSF samples were contributory in a subset (33%) of cases. The authors were unable to identify any specific pre-analytic factors, including specimen volume and average nucleated cell counts, for cases in which CB was contributory. Further evaluation is needed to identify if there are scenarios in which CSF CBs should be routinely prepared.

Olfactory Bulb Volume and Asymmetry as Predictors of Executive Dysfunction in Adolescents with Congenital Heart Disease.

Common sequelae for patients with congenital heart disease (CHD) are neurodevelopmental disabilities including executive function, attention, and socio-emotional deficits. Although these are common diagnoses for patients with CHD, limited research has investigated the mechanistic underpinnings of these findings. Our previous research examined the association between abnormal respiratory ciliary motion and brain abnormalities in infants with CHD. Results suggested that abnormal ciliary motion correlated to a spectrum of subtle dysplasia, notably within the olfactory bulb (OB)1. Our current study investigates whether OB anomalies predict neurodevelopmental outcomes for pediatric patients with CHD. We hypothesize that adolescents with CHD who exhibit aberrant morphological measurements in the OB are more likely to suffer from executive functional deficits. A prospective, observational study of 54 CHD and 75 healthy subjects, ages 6-25 years old, was completed under the supervision of a senior pediatric neuroradiologist. T2 3D Space and T2 Blade 2MM MRI images were manually segmented to extract volumetric bilateral regions of the OB and cerebrospinal fluid (CSF) using ITK-SNAP. Imaging metrics were correlated to OB asymmetry, CSF to OB ratio, total CSF volume, total OB volume, and independent left and right CSF and OB volumes. Linear regression was used to evaluate MRI morphologic measurements with co-variates: CHD status, sex, MRI age, and segmenter. Executive function was determined by the Behavioral Rating Inventory of Executive Function (BRIEF) Parent Report and Delis-Kaplan Executive Function System (D-KEFS) for subjects ages 6-16. Cognition and olfactory function were measured with the NIH Toolbox Cognitive Battery and Odor Identification Test, respectively. No statistically significant results were reported between cohorts for asymmetry of OB, CSF to OB ratio, total CSF volume, total OB volume, nor between independent left and right CSF and OB volumes. Increased OB volume was associated with worse outcomes on the BRIEF Parent Report (p≤0.03). Asymmetry of OB predicted poorer executive functioning as reported by parents on the BRIEF (p≤0.05). Overall, the CHD cohort demonstrated worse scores on the BRIEF Parent Report compared to controls. Across groups, no significant association was reported for olfaction function measured by the NIH Toolbox Odor Identification Test on a limited subset of participants. As survival rates for CHD improve, there is an increased risk of long-term neurodevelopmental impairments. Our findings identify adolescents who are at risk for executive dysfunction, particularly those showing increased OB volume and/or asymmetry of the OB. This is particularly concerning for the CHD population with atypical OB morphology, who also exhibit significantly poorer outcomes on the BRIEF Parent Report and face a higher overall risk. Increased OB volume and OB asymmetry are olfactory-based biomarkers that may help identify at-risk CHD patients earlier, enabling more timely intervention and support.

Brain Volumetric Analysis Using Artificial Intelligence Software in Premanifest Huntington's Disease Individuals from a Colombian Caribbean Population.

Background and objectives: The premanifest phase of Huntington's disease (HD) is characterized by the absence of motor symptoms and exhibits structural changes in imaging that precede clinical manifestation. This study aimed to analyze volumetric changes identified through brain magnetic resonance imaging (MRI) processed using artificial intelligence (AI) software in premanifest HD individuals, focusing on the relationship between CAG triplet expansion and structural biomarkers. Methods: The study included 36 individuals descending from families affected by HD in the Department of Atlántico. Sociodemographic data were collected, followed by peripheral blood sampling to extract genomic DNA for quantifying CAG trinucleotide repeats in the Huntingtin gene. Brain volumes were evaluated using AI software (Entelai/IMEXHS, v4.3.4) based on MRI volumetric images. Correlations between brain volumes and variables such as age, sex, and disease status were determined. All analyses were conducted using SPSS (v. IBM SPSS Statistics 26), with significance set at p < 0.05. Results: The analysis of brain volumes according to CAG repeat expansion shows that individuals with ≥40 repeats evidence significant increases in cerebrospinal fluid (CSF) volume and subcortical structures such as the amygdalae and left caudate nucleus, along with marked reductions in cerebral white matter, the cerebellum, brainstem, and left pallidum. In contrast, those with <40 repeats show minimal or moderate volumetric changes, primarily in white matter and CSF. Conclusions: These findings suggest that CAG expansion selectively impacts key brain regions, potentially influencing the progression of Huntington's disease, and that AI in neuroimaging could identify structural biomarkers long before clinical symptoms appear.

Investigating the effect of brain atrophy on transcranial direct current stimulation: A computational study using ADNI dataset

BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that uses weak electrical currents to modulate brain activity, thus potentially aiding the treatment of brain diseases. Although tDCS offers convenience, it yields inconsistent electric-field distributions among individuals. This inconsistency may be attributed to certain factors, such as brain atrophy. Brain atrophy is accompanied by increased cerebrospinal fluid (CSF) volume. Owing to the high electrical conductivity of CSF, its increased volume complicates current delivery to the brain, thus resulting in greater inter-subject variability. ObjectiveWe aim to investigate the differences in tDCS-induced electric fields between groups with different severities of brain atrophy. MethodsWe classified 180 magnetic resonance images into four groups based on the presence of Alzheimer's disease and sex. We used two montages, i.e., F-3 & Fp-2 and TP-9 & TP-10, to target the left rostral middle frontal gyrus and the hippocampus/amygdala complex, respectively. Differences between the groups in terms of regional volume variation, stimulation effect, and correlation were analyzed. ResultsSignificant differences were observed in the geometrical variations of the CSF and two target regions. Electric fields induced by tDCS were similar in both sexes. Unique patterns were observed in each group in the correlation analysis. ConclusionOur findings show that factors such as brain atrophy affect the tDCS results and that the factors present complex relationships. Further studies are necessary to better understand the relationships between these factors and optimize tDCS as a therapeutic tool.