Brain Abnormalities Research Articles

Oxidative Stress-mediated Loss of Hippocampal Parvalbumin Interneurons Contributes to Memory Precision Decline After Acute Sleep Deprivation.

Sleep is pivotal to memory consolidation, and sleep deprivation (SD) after learning can impede this process, leading to memory disorders. In the present study, we aimed to explore the effects of acute sleep deprivation (ASD) on memory disorders and the underlying mechanisms. ASD model was induced by subjecting the mice to 6h of SD following fear conditioning training. Different cohorts were used for behavioral, biochemical, and electrophysiological tests. Here, we showed that memory precision decline was induced by ASD, concomitant with a notable elevation in oxidative stress within PV interneurons, loss of PV, and disturbed neuronal oscillation in the CA1 region. Notably, chemogenetic activation of PV interneurons effectively ameliorated abnormal gamma oscillation and memory precision decline observed in ASD mice. Meanwhile, chemogenetic inhibition of PV interneurons successfully mimicked the abnormal brain oscillations and memory precision decline observed in ASD mice. Additionally, prior administration of the antioxidant medication N-acetylcysteine effectively reversed memory precision decline and mitigated PV loss and abnormal oscillation triggered by ASD. Collectively, our findings indicated that ASD increased oxidative stress in PV interneurons, thereby disrupting neural oscillation in the CA1 and ultimately leading to memory precision decline.

A rotenone organotypic whole hemisphere slice model of mitochondrial abnormalities in the neonatal brain.

Mitochondrial abnormalities underscore a variety of neurologic injuries and diseases and are well-studied in adult populations. Clinical studies identify critical roles of mitochondria in a wide range of developmental brain injuries, but models that capture mitochondrial abnormalities in systems representative of the neonatal brain environment are lacking. Here, we develop an organotypic whole-hemisphere (OWH) brain slice model of mitochondrial dysfunction in the neonatal brain. We extended the utility of complex I inhibitor rotenone (ROT), canonically used in models of adult neurodegenerative diseases, to inflict mitochondrial damage in OWH slices from term-equivalent rats. We quantified whole-slice health over 6days of exposure for a range of doses represented in ROT literature. We identified 50nM ROT as a suitable exposure level for OWH slices to inflict injury without compromising viability. At the selected exposure level, we confirmed exposure- and time-dependent mitochondrial responses showing differences in mitochondrial fluorescence and nuclear localization using MitoTracker imaging in live OWH slices and dysregulated mitochondrial markers via RT-qPCR screening. We leveraged the regional structures present in OWH slices to quantify cell density and cell death in the cortex and the midbrain regions, observing higher susceptibilities to damage in the midbrain as a function of exposure and culture time. We supplemented these findings with analysis of microglia and mature neurons showing time-, region-, and exposure-dependent differences in microglial responses. We demonstrated changes in tissue microstructure as a function of region, culture time, and exposure level using live-video epifluorescence microscopy of extracellularly diffusing nanoparticle probes in live OWH slices. Our results highlight severity-, time-, and region-dependent responses and establish a complimentary model system of mitochondrial abnormalities for high-throughput or live-tissue experimental needs.

Clinical efficacy of low-dose Perampanel correlates with neurophysiological changes in familial adult myoclonus epilepsy 2.

Familial adult myoclonus epilepsy (FAME) management relies on antiseizure medications (ASMs), which inadequately address myoclonus and cortical tremor. This study evaluates Perampanel (PER), an AMPA-receptor antagonist, for treating FAME symptoms. Fifteen FAME2 patients participated in an observational prospective study. They received up to 6 mg daily of PER and underwent Unified-Myoclonus-Rating-Scale (UMRS) before and after treatment. Neurophysiological evaluations, including somatosensory evoked potentials (SEPs) and transcranial magnetic stimulation (TMS), assessed PER's impact on cortical glutamatergic excitatory and GABAergic inhibitory circuits. PER treatment significantly reduced UMRS total scores (p = 0.001) and action-myoclonus subscores (p = 0.002), irrespective of disease duration, age at onset, or testing time (p >0.05). Patients with more severe baseline myoclonus demonstrated significant improvements. Neurophysiological assessments revealed a PER-induced decrease in sensorimotor hyperexcitability, characterized by diminished N33 amplitudes, attenuated glutamatergic facilitation, and enhanced GABAergic inhibition in the motor cortex. In conclusion, low-dose PER is well tolerated and effective in alleviating myoclonus in FAME2 patients, supported by its modulatory effects on glutamatergic and GABAergic neuronal circuits. Plain Language Summary: This study investigated the effects of low-dose perampanel in individuals with Familial Adult Myoclonus Epilepsy2 (FAME2), a hereditary condition characterized by epilepsy and tremors. Perampanel, an antiepileptic drug, blocks AMPA receptors in the brain, reducing excessive neural activity that causes seizures and abnormal movements. The results showed significant symptom improvement, which correlated with changes in brain activity as measured by neurophysiological tests. This study suggests that perampanel helps regulate abnormal brain signals and may help managing FAME2 symptoms.

Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis.

Integrin heterodimers containing an Integrin alpha V subunit are essential for development and play critical roles in cell adhesion and signaling. We identified biallelic variants in the gene coding for Integrin alpha V (ITGAV) in three independent families (two patients and four fetuses) that either caused abnormal mRNA and the loss of functional protein or caused mistargeting of the integrin. This led to eye and brain abnormalities, inflammatory bowel disease, immune dysregulation, and other developmental issues. Mechanistically, the reduction of functional Integrin αV resulted in the dysregulation of several pathways including TGF-β-dependent signaling and αVβ3-regulated immune signaling. These effects were confirmed using immunostaining, RNA sequencing, and functional studies in patient-derived cells. The genetic deletion of itgav in zebrafish recapitulated patient phenotypes including retinal and brain defects and the loss of microglia in early development as well as colitis in juvenile zebrafish with reduced SMAD3 expression and transcriptional regulation. Taken together, the ITGAV variants identified in this report caused a previously unknown human disease characterized by brain and developmental defects in the case of complete loss-of-function and atopy, neurodevelopmental defects, and colitis in cases of incomplete loss-of-function.

Abnormal changes of brain function and structure in patients with T2DM-related cognitive impairment: a neuroimaging meta-analysis and an independent validation.

Type 2 diabetes mellitus (T2DM) seriously threatens human health and the quality of life, cognitive impairment is considered as a common complication of T2DM. Neuroimaging meta-analysis found brain functional and structural abnormality in patients with T2DM. Therefore, the purpose of the meta-analysis was to identify brain regions of patients with T2DM-related cognitive impairment (T2DM-CI) where functional and structural indicators changed together or could not synchronize. A literature screening of neuroimaging studies on cognitive impairment in T2DM was conducted from 1 January 2007 to 26 May 2023 in PubMed, Web of Science, Cochrane Library, and Medline databases. The functional indicators we studied were amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and degree centrality (DC), while the structural indicator was gray matter (GM), which included gray matter volume (GMV) and cerebral cortical thickness. Studies reporting ALFF, ReHo, DC and GM abnormalities between T2DM-CI and healthy controls (HCs) were selected and their significant peak coordinates (x, y, z) and effect size (t-value) were extracted to perform a meta-analysis using anisotropic effect size sign differential mapping (AES-SDM) 5.15 software. Moreover, the brain regions with significant differences obtained from meta-analysis were saved as masks and then validated in our data. Total 19 studies and 20 datasets were involved in this study. Compared to HCs, combining ALFF, ReHo, and DC measurements, the brain activity of the left anterior cingulate/paracingulate gyri (ACC.L, BA24) in T2DM-CI patients increased significantly, while the brain activity of the left lingual gyrus (LING.L, BA18) in T2DM-CI patients decreased significantly. The GM indicator of the right superior temporal gyrus (STG.R, BA42) and left inferior occipital gyrus (IOG.L, BA19) in T2DM-CI patients decreased significantly. Meta-regression analysis showed the negative relationship between the brain activity reduction in LING.L and the percentage of female patients, as well as the negative relationship between GM reduction in IOG.L and T2DM duration. Furthermore, we validated a decrease in brain activity in the LING.L of T2DM-CI patients in our independent dataset. The decrease of brain activity in LING.L and the decrease of GM in IOG.L were closely related to visual impairment in T2DM-CI patients. These abnormal brain regions may be the main targets for future research, early intervention can delay the further development of cognitive impairment in T2DM patients and improve their quality of life, which also provided early biomarkers for clarifying the mechanism of cognitive impairment in T2DM.

Decreased Brain pH Underlies Behavioral and Brain Abnormalities Induced by Chronic Exposure to Glucocorticoids in Mice.

Depressed patients may exhibit glucocorticoid hypersecretion, suggesting that elevated levels of glucocorticoids may play an important role in the pathophysiology of depression. Some postmortem brain studies have shown decreased pH and increased lactate levels in psychiatric patients, implying involvement of these factors in the pathogenesis. To investigate the effects of glucocorticoids on brain pH and lactate levels, and their roles in depressive symptoms, brain pH and lactate were examined in mice treated with corticosterone (CORT), the major bioactive glucocorticoid in rodents. A single administration of CORT decreased hippocampal pH after 24 h. Three weeks of CORT treatment decreased pH in the prefrontal cortex (PFC), striatum, and hippocampus (HC), whereas intake of pH 9.0 drinking water increased pH in these brain regions. pH and lactate levels were correlated in the PFC and HC of mice treated with CORT for 3 weeks. The suppression of body weight gain and decrease in adrenal weight observed after 3 weeks of CORT treatment were not alleviated by pH 9.0 water. However, an increase in immobility time in the forced swim test and a decrease in neurogenesis in the hippocampus were alleviated. The decrease in brain pH and increase in immobility time in the forced swim test and a decrease in neurogenesis in the hippocampus induced by CORT treatment were abolished by co-treatment with the glucocorticoid receptor (GR) antagonist mifepristone. These findings indicate that decreased brain pH via GRs may be related to glucocorticoid-induced depression-like behavior and decreased hippocampal neurogenesis.

Antisecretory Factor 16 (AF16): A Promising Avenue for the Treatment of Traumatic Brain Injury—An In Vitro Model Approach

Traumatic brain injury (TBI) is caused by an external mechanical force to the head, resulting in abnormal brain functioning and clinical manifestations. Antisecretory factor (AF16) is a potential therapeutic agent for TBI treatment due to its ability to inhibit fluid secretion and decrease inflammation, intracranial pressure, and interstitial fluid build-up, key hallmarks presented in TBI. Here, we investigated the effect of AF16 in an in vitro model of neuronal injury, as well as its impact on key components of the autophagy pathway and mitochondrial dynamics. N2Awt cells were treated with AF16, injured using a scratch assay, and analysed using confocal microscopy, correlative light and electron microscopy (CLEM), flow cytometry, and western blotting. Our results reveal that AF16 enhances autophagy activity, regulates mitochondrial dynamics, and provides protection as early as 6 h post-injury. Fluorescently labelled AF16 was observed to localise to lysosomes and the autophagy compartment, suggesting a role for autophagy and mitochondrial quality control in conferring AF16-associated neuronal protection. This study concludes that AF16 has potential as a therapeutic agent for TBI treatment through is regulation of autophagy and mitochondrial dynamics.

Hypermethioninemia due to methionine adenosyltransferase I/III deficiency and brain damage

Background and objectivesMethionine adenosyltransferase I/III deficiency used to be considered a relatively benign disease. This study aims to elucidate the clinical characteristics of methionine adenosyltransferase I/III deficiency patients with neurological manifestations.MethodsThe clinical data, blood amino acids, plasma total homocysteine, gene variants, brain imaging, treatments and outcomes of 15 patients with methionine adenosyltransferase I/III deficiency were retrospectively analyzed.ResultsOf these 15 patients, 10 demonstrated neurological abnormalities, with delayed language development, learning difficulties or abnormal brain imaging findings. Eleven patients were identified by newborn screening. Patients with demyelination showed significantly higher blood methionine concentrations at baseline (1102 vs. 396 µmol/L), and their blood methionine remained markedly elevated despite a low-methionine diet. Their plasma total homocysteine was normal to moderate elevated. One patient underwent liver transplantation aged 8 years, which reduced his serum methionine concentration to normal. Compound heterozygous and homozygous MAT1A variants were identified from the patients. Among the 21 variants observed, nine have been reported previously, while 12 were novel.ConclusionsMethionine adenosyltransferase I/III deficiency is not just a benign disease. Severe persistent hypermethioninemia can cause brain injuries, especially in the white matter. Liver transplantation may be a potential treatment option for refractory methionine adenosyltransferase I/III deficiency.

Altered sleep and inflammation are related to outcomes in neonatal encephalopathy.

Immune dysregulation and delayed onset of sleep wake cycling (SWC) are associated with worse outcome in neonatal encephalopathy (NE), however the association between sleep and immune dysfunction in NE remains unclear. Aimed to evaluate association of sleep and systemic inflammation with outcomes in NE. Amplitude-integrated electroencephalography (aEEG) recordings were collected on infants undergoing therapeutic hypothermia (TH). Duration to onset of (SWC) and sleep quality (SQ) were examined. Blood samples collected during the first 2 days of life. Thirteen pro- and anti-inflammatory serum cytokines were quantified. Adverse outcome defined as death or abnormal MRI brain. Earlier onset of SWC and better SQ had less adverse outcomes. SQ provided better prognostic value and showed better interobserver agreement compared to duration to SWC. Better SQ associated with lower cytokines EPO and interleukin (IL)-1β. In infants with unfavourable outcome, shorter duration to SWC was associated with higher EPO and better SQ was associated with lower TNF-α. Earlier onset of SWC or better SQ showed less systemic inflammation and fewer adverse outcomes. SQ during TH provided better prognostic information than time of onset of SWC. Modulation of circadian rhythm in infants with NE may have an immunomodulatory role, leading to improved outcomes.

Peri-injury symptomatology as predictors of brain computed tomography (CT) scan abnormalities in mild traumatic brain injury (mTBI)

ObjectiveThis study aimed to identify predictors of brain CT abnormalities in patients who sustained a mild traumatic brain injury (mTBI).MethodsRetrospective observational cohort of adult patients with mTBI (Glasgow Coma Score 13–15) that occurred within the preceding 24 h.Results2548 (91%) of the cohort had a brain CT and 698 (27%) demonstrated abnormal findings. The most frequently observed CT abnormalities were bleeding (638, 25%) and fractures (190, 7.4%). Multivariate logistic regression analysis revealed several significant predictors associated with the presence of brain CT abnormalities including older age [P < 0.0001], male sex [P < 0.0001], loss of consciousness [P = 0.0041], associated vomiting [P = 0.0011], alteration of consciousness (AOC) [P = 0102], and GCS score [P < 0.0001]. This was a robust model with an R² of 14.2%.ConclusionIn this retrospective analysis, older age, male sex, the presence of loss of consciousness or alteration in consciousness, lower GCS score, and associated vomiting were found to be significant predictors of having an abnormal brain CT. These findings highlight the importance of considering these factors when determining the necessity of brain CT scans in patients with mTBI and suggest that existing clinical decision rules may be limited. These findings may also help to inform clinical decision rules. Early identification of individuals at a higher risk of CT abnormalities may assist in appropriate management and allocation of healthcare resources.

Volumetric Integrated Classification Index: An Integrated Voxel-Based Morphometry and Machine Learning Interpretable Biomarker for Post-Traumatic Stress Disorder.

PTSD is a complex mental health condition triggered by individuals' traumatic experiences, with long-term and broad impacts on sufferers' psychological health and quality of life. Despite decades of research providing partial understanding of the pathobiological aspects of PTSD, precise neurobiological markers and imaging indicators remain challenging to pinpoint. This study employed VBM analysis and machine learning algorithms to investigate structural brain changes in PTSD patients. Data were sourced ADNI-DoD database for PTSD cases and from the ADNI database for healthy controls. Various machine learning models, including SVM, RF, and LR, were utilized for classification. Additionally, the VICI was proposed to enhance model interpretability, incorporating SHAP analysis. The association between PTSD risk genes and VICI values was also explored through gene expression data analysis. Among the tested machine learning algorithms, RF emerged as the top performer, achieving high accuracy in classifying PTSD patients. Structural brain abnormalities in PTSD patients were predominantly observed in prefrontal areas compared to healthy controls. The proposed VICI demonstrated classification efficacy comparable to the optimized RF model, indicating its potential as a simplified diagnostic tool. Analysis of gene expression data revealed significant associations between PTSD risk genes and VICI values, implicating synaptic integrity and neural development regulation. This study reveals neuroimaging and genetic characteristics of PTSD, highlighting the potential of VBM analysis and machine learning models in diagnosis and prognosis. The VICI offers a promising approach to enhance model interpretability and guide clinical decision-making. These findings contribute to a better understanding of the pathophysiological mechanisms of PTSD and provide new avenues for future diagnosis and treatment.

Maternal Immune Activation and Child Brain Development: A Longitudinal Population-based Multimodal Neuroimaging study

Maternal Immune Activation (MIA) has been hypothesized to have an adverse effect on child neurodevelopment, but only a few neuroimaging studies have been performed to date, mostly in neonates. In this population-based cohort study, we investigated the association between MIA and multiple neuroimaging modalities depicting brain development from childhood to adolescence. We used data of mother-child pairs from the Generation R Study. To define our exposure, we measured IL-1β, IL-6, IL-17a, IL-23 and IFN-γ, and CRP at two time points during pregnancy. Given that levels of these 5 cytokines were highly correlated, we were able to compute a Cytokine index. We used multiple brain imaging modalities as outcomes, encompassing global and regional measures of brain morphology (structural MRI, volume, n=3,295), white matter microstructure (diffusion MRI, FA and MD, n=3,267), and functional connectivity (functional MRI, graph theory measures and network-level connectivity, n=2,914) at child mean ages 10 and 14 years. We performed mixed-effects models using the child's age as continuous time variable. We found no significant association or time interaction between MIA and any neuroimaging outcomes in children over time. These associations were similar for the Cytokine index, CRP, and individual cytokines. We observed no evidence for differential effects of timing of prenatal MIA or child sex after multiple testing correction. This longitudinal population-based study reports no evidence for an association between MIA and child brain development in the general population. Our findings differ from prior research in neonates showing structural and functional brain abnormalities after MIA.

Polytetrafluoroethylene (PTFE) Microplastics Affect Angiogenesis and Central Nervous System (CNS) Development of Duck Embryo

Prolonged exposure to teratogens is known to cause neural tube defects (NTDs), a severe malformation of the central nervous system (CNS) that significantly contributes to global infant mortality. In recent years, exposure to nanoplastics (NPs) has been linked to faulty neural crest closure and altered neurulation by altering cellular adhesion molecules and accumulation of plastic particles in the neural tube leading to NTDs. However, research on the influence of various types of microplastics (MPs) on malformations of the CNS are still limited. In this study, we investigated whether MPs of polytetrafluoroethylene (PTFE)—a type of plastic commonly used as non-stick coatings of cooking utensils can affect angiogenesis and CNS development using ducks as model organisms. PTFE MPs were administered on Day 3 of duck embryo development at varying concentrations (0.01 mg/ml, 0.1 mg/ml, 1 mg/ml, and 5 mg/ml), and angiogenesis was evaluated using a chorioallantoic membrane (CAM) assay. Gross morphology and histology of the spinal column and brain were analyzed on Days 8 and 18, respectively. FTIR confirmed PTFE's structure, while SEM and DLS analyses showed particle sizes between 300 nm and 5 μm, classifying them as MPs. High concentrations (5 mg/ml) of PTFE MPs treated on duck embryos resulted in a 35% mortality rate and reduced vascular density, suggesting anti-angiogenic effects. Brain and spinal abnormalities, such as encephalomalacia and spinal cord discontinuities were observed in the PTFE-treated embryos. Based on these results, PTFE is an anti-angiogenic and teratogenic agent affecting the development of duck embryos.

Abnormal intrinsic brain functional network dynamics in patients with retinal detachment based on graph theory and machine learning

Backgroundand purpose: The investigation of functional plasticity and remodeling of the brain in patients with retinal detachment (RD) has gained increasing attention and validation. However, the precise alterations in the topological configuration of dynamic functional networks are still not fully understood. This study aimed to investigate the topological structure of dynamic brain functional networks in RD patients. MethodsWe recruited 32 patients with RD and 33 healthy controls (HCs) to participate in resting-state fMRI. Employing the sliding time window analysis and K-means clustering method, we sought to identify dynamic functional connectivity (dFC) variability patterns in both groups. The investigation into the topological structure of whole-brain functional networks utilized a graph theoretical approach. Furthermore, we employed machine learning analysis, selecting altered topological properties as classification features to distinguish RD patients from HCs. ResultsAll participants exhibited four distinct states of dynamic functional connectivity. Compared to the healthy control (HC) group, patients with RD experienced a significant reduction in the number of transitions among these four states. Additionally, the dynamic topological properties of RD patients demonstrated notable changes in both global and node-specific characteristics, with these changes correlating with clinical parameters. The support vector machine (SVM) model used for classification achieved an accuracy of 0.938, an area under the curve (AUC) of 0.988, and both sensitivity and specificity of 0.937. ConclusionThe alterations in the topological properties of the brain in RD patients may indicate the integration function and information exchange efficiency of the whole brain network were reduced. In addition, the topological properties hold considerable promise for distinguishing between RD and HCs.

A microglia-containing cerebral organoid model to study early life immune challenges.

Prenatal infections and activation of the maternal immune system have been proposed to contribute to causing neurodevelopmental disorders (NDDs), chronic conditions often linked to brain abnormalities. Microglia are the resident immune cells of the brain and play a key role in neurodevelopment. Disruption of microglial functions can lead to brain abnormalities and increase the risk of developing NDDs. How the maternal as well as the fetal immune system affect human neurodevelopment and contribute to NDDs remains unclear. An important reason for this knowledge gap is the fact that the impact of exposure to prenatal risk factors has been challenging to study in the human context. Here, we characterized a model of cerebral organoids (CO) with integrated microglia (COiMg). These organoids express typical microglial markers and respond to inflammatory stimuli. The presence of microglia influences cerebral organoid development, including cell density and neural differentiation, and regulates the expression of several ciliated and mesenchymal cell markers. Moreover, COiMg and organoids without microglia show similar but also distinct responses to inflammatory stimuli. Additionally, IFN-γ induced significant transcriptional and structural changes in the cerebral organoids, that appear to be regulated by the presence of microglia. Specifically, interferon-gamma (IFN-γ) was found to alter the expression of genes linked to autism. This model provides a valuable tool to study how inflammatory perturbations and microglial presence affect neurodevelopmental processes.

A Novel Mutation of FOXC1 (P136L) in an Axenfeld-Rieger Syndrome Patient With a Systematized Delusion of Jealousy: A Case Report and Literature Review.

The main features of Axenfeld-Rieger Syndrome (ARS) are ocular, auditory, neurological, and morphological brain abnormalities. Mutations in forkhead box protein C1 (FOXC1) are among the responsible genes causing ARS, but neuropsychiatric features have rarely been reported. The case of an ARS patient (a 77-year-old man) with delusions of jealousy and impairment of working memory, in addition to the main clinical features, glaucoma and leukoencephalopathy, is presented. The mutation in the patient's genome was found with whole exome sequencing and in silico analysis using PolyPhen-2 and SIFT. Furthermore, AlphaFold2 and PyMOL were used to predict the protein structure based on the mutation. A novel mutation at the forkhead domain of FOXC1 gene (c.408C>A, p.Phe136Leu) was found and confirmed in the patient's family, and it was predicted to cause protein damage; the SIFT score was 0, meaning deleterious, and the PolyPhen2 result also indicated damaging (score: 0.997). The predicted protein structure based on the novel mutation was different from that of the native structure. In the literature review, 6 of 95 (6.3%) cases showed neuropsychiatric features. Of them, 5 of 6 (83.3%) mutations were located in the forkhead domain. A novel mutation was found in the FOXC1 gene (c.408C>A, p.Phe136Leu), which possibly induces delusions of jealousy and impairment of working memory, as well as features of ARS, by changing the protein structure. Mutations in that domain of the FOXC1 gene may be important not only for ocular abnormalities but also for brain function.

Aquaporin-4 Immunoglobulin G-seropositive Neuromyelitis Optica Spectrum Disorder MRI Characteristics: Data Analysis from the International Real-World PAMRINO Study Cohort.

Background Patients with neuromyelitis optica spectrum disorder (NMOSD) are often seropositive for antibodies against aquaporin-4 (AQP4). The importance of MRI monitoring in this disease requires evaluation. Purpose To profile MRI features from a large international cohort with AQP4 immunoglobulin G (IgG)-seropositive NMOSD (from the Parallel MRI in NMOSD [PAMRINO] study) and to evaluate and confirm existing knowledge regarding the incidence, location, and longitudinal development of characteristic lesions in the central nervous system associated with AQP4-IgG-seropositive NMOSD. Materials and Methods In this retrospective study (from August 2016 to January 2019), MRI and clinical data were collected from 17 NMOSD expert sites in 11 countries across four continents. Clinical features and lesions identified at cross-sectional and longitudinal MRI were assessed. No formal statistical tests were used to compare observations; however, means, SDs, and 95% CIs are reported when evaluating lesion frequencies. Results Available T1-weighted and T2-weighted MRI scans in patients with AQP4-IgG-seropositive NMOSD (n = 525) were read. Among the 525 patients, 320 underwent cerebral MRI examinations with T2-weighted hyperintense cerebral (264 of 320; 82.5%), cerebellar (44 of 320; 13.8%), and brainstem (158 of 321 [49.2%], including one lesion observed at cervical spinal cord [SC] MRI) lesions. Lesions in the optic nerves, analyzed from 152 MRI examinations, were mainly found in the central (81 of 92; 88%) and posterior (79 of 92; 86%) sections (bilaterally in 39 of 92; 42%). Longitudinally extensive transverse myelitis was the predominant SC lesion pattern (upper compartment from 322 MRI examinations, 133 of 210 [63.3%]; and lower compartment from 301 MRI examinations, 149 of 212 [70.3%]). However, nonlongitudinal extensive transverse myelitis lesions were also observed frequently (105 of 210; 50.0%) in the cervical SC. Clinical data (n = 349; mean age, 44 years ± 14 [SD]; 202 female patients) and acute lesions at contrast-enhanced (CE) MRI (n = 58, performed within 30 days of the last attack) were evaluated. CE lesions were detected in the cerebrum (eight of 13; 62%), optic nerves (14 of 19; 74%), or chiasm (three of four; 75%) within 15 days of any relapse. In the upper SC (29 of 44; 66%), CE lesions were frequently observed up to 20 days after a clinical myelitis event. Conclusion A high incidence of abnormal brain MRI examinations and nonlongitudinal extensive SC lesions was found in patients in PAMRINO with AQP4-IgG-seropositive NMOSD. © RSNA, 2024 Supplemental material is available for this article.

Frequency-Specific Alternations in the Amplitude of Fluctuations in Tension-Type Headache: A Machine Learning Study.

Brain neural signal at different frequency bands relates to different functions. However, the frequency-specific properties of spontaneous brain activity in tension-type headache (TTH)-the most rampant primary headache-remain largely unknown. We investigated the local neural activity of 33 TTH patients and 31 healthy controls (HCs) in the conventional frequency band and two sub-frequency bands (slow-4 and slow-5 frequency band), employing fractional amplitude of low-frequency fluctuations (fALFF), percent amplitude fluctuations (PerAF) and Wavelet-ALFF analytic methods. Using age as covariate, we performed two sample t-test to compare the between-group differences of each metrics in each frequency band. Support vector machine (SVM) was conducted to classify TTH patients and HCs on the basis of altered spontaneous brain activities. TTH patients showed lower fALFF values in the left cerebellar lobule X, left parahippocampal gyrus, and right supplementary motor area in slow-5 band. TTH patients showed lower PerAF in the left fusiform and cerebellar regions in three bands. Altered Wavelet-ALFF values in the right thalamus, left anterior cingulum gyrus, superior parietal gyrus and middle and parietal frontal regions in three frequency bands were detected. And the SVM classifier obtained an overall accuracy of 77.38%, 82.38%, and 95% based on fALFF, PerAF, and Wavelet ALFF values, respectively. TTH patients exhibited abnormal neural activity in various brain regions. The abnormal brain activities serve as powerful features for distinguishing TTH patients. This preliminary exploration provides a novel insight into the underlying mechanism of TTH.

Functional outcome after infectious encephalitis: a longitudinal multicenter prospective cohort study.

ObjectivesWe aimed to describe longitudinal functional outcome among survivors after an infectious encephalitis (IE) and to analyze risk factors for poor functional outcome. MethodsPatients included in the prospective ENCEIF cohort (France, 2016-2019) were followed-up at 6 months and one year after hospital discharge for assessment of i) functional outcome using modified Rankin scale (mRS); ii) cognitive function and abilities to perform activities of daily living. Risk factors for poor outcome on the full distribution of mRS were estimated using multivariable mixed ordinal regression analysis with time between hospital discharge and follow-up as a covariate. ResultsOur follow-up study included 322 patients with 896 mRS evaluations. Median age was 66 [50-74] years, 197/322 were male (61%) and 35/322 were immunocompromised (11%). Causative agents were herpes simplex virus 1 (HSV-1) in 95/322 cases (30%), varicella zoster virus (VZV) in 46/322 cases (14%), others documented IE in 90/322 cases (28%) and unknown in 91/322 cases (28%). Intensive care unit (ICU) admission was necessary for 117/322 patients (36%). Brain imaging was abnormal in 180/311 (58%) of patients.At 6 months, 95/287 (33%) had fully recovered and 181/287 (63%) had persisting symptoms. At 12 months, 124/253 (49%) had fully recovered and 108/253 (43%) had persisting symptoms. The proportion of patients who improved was 41% (117/287) during the first 6 months, and 24% (52/218) between 6 and 12 months. Factors significantly associated with poor functional outcome were age, immunosuppression, ICU admission, abnormal brain imaging and causative agents, notably HSV-1. Follow-up visit during the first 120 days did not detect significant change in functional outcome, but was strongly associated with better outcome at the subsequent evaluation. ConclusionsAfter IE, improvement may take several months. Functional outcome is associated with baseline health status (age, immunosuppression), abnormal brain imaging, ICU admission, and causative agent.

Identification of asymmetrical abnormalities in functional connectivity and brain network topology for migraine sufferers: A preliminary study based on resting-state fMRI data

Research on the neural mechanisms underlying brain asymmetry in patients with migraine patients using fMRI is insufficient. This study proposed using lateralized algorithms for functional connectivity and brain network topology and investigated changes in their lateralization in patients with migraine. In study 1, laterality indices of functional connectivity (LFunctionCorr) and brain network topological properties (LBetweennessCentrality, LDegree, and LStrength) were defined. Differences between migraineurs and normal subjects were compared at whole-brain, half-brain, and region levels. In study 2, laterality indices were used to classify migraine and were validated using independent samples and the segment method for repeatability. In study 3, abnormal brain regions related to migraine were extracted based on the classification results and differences analysis. Study 1 found no significant differences related to in for migraine at the whole-brain level; however, significant differences were identified at the half-brain level for the hemispheric lateralization of the LFunctionCorr, while 11 significantly different brain regions were also identified at the brain region level. Furthermore, the classification accuracy in study 2 was 0.9366. With repeated validation, the accuracy reached 0.8561. Furthermore, after extending the samples according to the segmentation strategy, the classification accuracies were improved to 0.9408 and 0.8585. Study 3 identified 10 crucial brain regions with asymmetrical specificity based on laterality indices distributed across the visual network, the frontoparietal control network, the default mode network, the salience/ventral attention network and the limbic system. The results revealed novel insights and avenues for research into the mechanisms of migraine asymmetry and showed that the laterality indices could be used as a potential diagnostic imaging marker for migraine.