Cerebral White Matter Lesions Research Articles

Grade prediction of lesions in cerebral white matter using a convolutional neural network.

We established a diagnostic method for cerebral white matter lesions using MRI images and examined the relationship between the MRI images and the medical checkup data. There were approximately 25 MRI images for each patient's head, from the top of the head to near the eyes. To order these images, we defined the unit of axial for convenience. We varied conditions, such as the location and extent of the images to be loaded, into a convolutional neural network model and verified the changes in discrimination performance on the test data. Co-occurrence network diagrams were also used to determine the relationship between the grade of cerebral white matter lesions and the biochemical test items, which were treated as categorical variables, the progression of cerebral white matter lesions, and patient health status. The convolutional neural network showed the highest discrimination performance when the images were loaded into the model with 80 pixels per side, axial from 9 to 15, along with FLAIR and T1-weighted images. The area under the curve for each grade was 0.9814 for grade 0, 0.9800 for grade 1, 0.9905 for grade 2, 0.9977 for grade 3, and 0.9998 for grade 4. In the co-occurrence network diagram, patients with no or mild cerebral white matter lesions, such as grade 0 and grade 1, had near normal blood pressure, whereas grade 2 patients were closer to (isolated) systolic hypertension. This indicates that patients with higher-grade cerebral white matter lesions tend to experience more severe hypertension.

Cerebrospinal fluid neurofilament light chain levels in children with acquired demyelinating syndrome

ObjectiveTo study the cerebrospinal fluid (CSF) neurofilament light chain (NfL) in pediatric acquired demyelinating syndrome (ADS) and its association with factors of laboratory and imaging results.MethodsWe analyzed clinical data from children with ADS collected from May 2020 to January 2021 at the Department of Neurology of Guangzhou Women and Children's Medical Center. Enzyme-linked immunosorbent assays were used to detect the CSF NfL of patients.ResultsThirty pediatric ADS patients (17 male, 13 female) were included in the study. The most frequent diagnosis was uncategorized ADS (36.7%, 11/30), followed by acute disseminating encephalomyelitis (ADEM) (23.3%, 7/30), myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) (20.0%, 6/30), NMO (6.7%, 2/30), multiple sclerosis (MS) (6.7%, 2/30), and neuromyelitis optic spectrum disorders (NMOSD) (6.7%, 2/30). The median CSF NfL for the first time was 7,425.28 pg/ml (interquartile range, 1,273.51, >10,000 pg/ml). CSF NfL increase over normal value (<290.00 pg/ml for people younger than 30 years old) was seen in 98.7% of patients. Patients were divided into uncategorized ADS, ADEM, MOGAD, and MS/NMO/NMOSD groups, with no significant difference in CSF NfL between each group. The CSF NfL positively correlated with the immunoglobulin (Ig) G (ρ = 0.473) and IgE (ρ = 0.366). However, the CSF NfL did not correlate with CSF white blood count and CSF protein. Furthermore, there was no significant difference between patients with oligoclonal bands positive and without. The CSF NfL negatively correlated with interferon γ (ρ = −0.501), CD45 + CD3+ T (ρ = −0.466), CD45 + CD3 + CD4+ T (ρ = −0.466), and CD45 + CD3 + CD8+ T cells (ρ = −0.521). However, it did not correlate with CD45 + CD19+ B cells. CSF NfL in patients with cerebral white matter lesions in MRI was higher than in patients without. Moreover, the CSF NfL positively correlated with the number of brain MRI locations (ρ = 0.362). Nine patients underwent multiple detections of CSF NfL, and their CSF NfL for the last detection was not significantly different from the first.ConclusionsThe CSF NfL increases significantly in pediatric ADS, and it can be a biomarker of neuro-axonal injury and a good indication of the extent of lesions.

Potentiation of cortico-spinal output via targeted electrical stimulation of the motor thalamus

Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for therapies aimed at improving volitional muscle activation. Here we hypothesize that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby immediately potentiating motor output. To test this hypothesis, we identify optimal thalamic targets and stimulation parameters that enhance upper-limb motor-evoked potentials and grip forces in anesthetized monkeys. This potentiation persists after white matter lesions. We replicate these results in humans during intra-operative testing. We then design a stimulation protocol that immediately improves strength and force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions.

Evaluating cochlear implant outcomes in DFNA9 subjects: a comprehensive study on cerebral white matter lesions and vestibular abnormalities.

This study assessed whether the Fazekas score could account for the variability in cochlear implantation (CI) outcomes among individuals with DFNA9 and evaluated signal loss in the semicircular canals (SCCs) on magnetic resonance imaging (MRI) among individuals with DFNA9. This retrospective cross-sectional study included CI recipients with DFNA9. Pre-implantation MRI-scans were reviewed to determine the Fazekas score, localizing and grading cerebral white matter lesions (WML), and identify abnormalities in the SCCs. CI performance was assessed by evaluating phoneme scores one year post-implantation. The function of the SCCs was evaluated using rotatory chair testing with electronystagmography (ENG) and the video Head Impulse Test (vHIT). Forty-five subjects (49 ears) were enrolled. The phoneme scores significantly improved from 35% (IQR 11-50) pre-implantation to 84% (IQR 76-90) one year post-implantation. No correlation was observed between the Fazekas score and the one-year post-implantation phoneme score (rsp=0.003, p = 0.986). Signal loss in at least one SCCs was detected in 97.7% of subjects and 77.8% of ears. There was no correlation between vestibular test results and fluid signal loss in the SCCs on MRI. Most individuals with DFNA9 show improved speech recognition with CI. The observed variability in CI outcomes was not linked to the Fazekas score. Additionally, our study confirms a high prevalence of focal sclerosis in DFNA9. Recognizing the limitations of this study, further research is needed to explore the predictive role of the Fazekas score on CI outcomes and its relationship with vestibular function.

Exploration of a comprehensive index for predicting cognitive impairment in patients with cerebral small vessel disease and white matter lesions

Background & Objective: The objective of this study was to explore the risk factors for cognitive impairment in patients with cerebral small vessel disease (CSVD), and to construct a predictive model for cognitive impairment in CSVD patients, providing personalized diagnostic and treatment strategies for patients. Methods: Clinical data and blood indicators of CSVD patients admitted to the Department of Neurology at the Second Affiliated Hospital of Shandong First Medical University from February 2022 to February 2023 were collected. Additionally, these patients underwent cranial MRI examinations and completed neurological and psychological assessments, including the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Based on the MoCA and MMSE results, the patients were divided into the cognitive impairment group and the normal cognitive group. Clinical data, blood indicators, and white matter lesion (WML) grades were compared between the two groups. Univariate logistic regression analysis was performed to identify the risk factors for cognitive impairment in CSVD patients. Using MoCA assessment results as the gold standard and several clinical indicators as independent variables, a logistic regression model was constructed. Predicted values were calculated based on this model, and a receiver operating characteristic (ROC) curve for the comprehensive diagnosis of multiple variables was plotted to evaluate the model’s accuracy. Results: A total of 134 CSVD patients were included, and cognitive impairment occurred in 98 cases, with an incidence rate of 73.13%, while 36 patients did not have cognitive impairment. Univariate logistic regression analysis of the collected variables identified eight factors: age, education level, hypertension, diabetes, cerebral hemorrhage, low-density lipoprotein cholesterol (LDL-C), hyperhomocysteine (HHCY), and WML grading. Multivariate logistic regression analysis identified age, LDL-C, and WML grading as the final predictive factors, establishing a combined diagnostic model to predict the probability of cognitive impairment in patients. The constructed ROC curve for the comprehensive diagnosis of multiple variables yielded an area under the curve of 0.870, indicating good accuracy. To facilitate clinical diagnosis, the combined diagnostic model was simplified into an L score calculation formula, with the optimal cutoff value of 5.223. When the L score is <5.223, the patient can be considered not having cognitive impairment, while an L score >5.223 indicates cognitive impairment, allowing for the prediction of the risk of cognitive impairment in patients. Conclusion: Age, education level, hypertension, diabetes, cerebral hemorrhage, LDL-C, HHCY, and WML grading are related risk factors for cognitive impairment in CSVD patients. Age, LDL-C, and WML grading are independent risk factors for cognitive impairment in CSVD patients. The clinical predictive model for cognitive impairment in cerebral small vessel disease, constructed using the final predictive factors, showed good performance and clinical utility. It facilitates individualized risk assessment for cognitive impairment in CSVD patients and allows for targeted follow-up observation for high-risk individuals.

Vagus nerve size determined via ultrasonography is associated with white matter lesions in patients with vascular risk factors

PurposeThe cross-sectional area (CSA) of the cervical vagus nerve (VN), as assessed through ultrasonography, might be linked to autonomic nervous system dysfunction. Hypertension is the primary factor associated with cerebral white matter lesions (WMLs), but there is also evidence of a connection with autonomic nervous system dysfunction. However, the associations between WMLs and VN size are unclear. Our objective was to investigate the associations between WMLs and VN size in patients with vascular risk factors.MethodsThe CSA of the VN was evaluated using carotid ultrasonography in patients with a history of stroke (acute or chronic) and comorbidities (n = 196, 70.2 ± 12.7 years). Common carotid artery (CCA) intima-media thickness and interadventitial diameter (IAD) were also measured. The severity of the WMLs was assessed by the Fazekas classification and Scheltens’ scale.ResultsThe CSA of the right VN (2.08 ± 0.65 mm2) was significantly greater than that of the CSA of the left VN (1.56 ± 0.44 mm2) (P < 0.001). Multiple linear regression analyses revealed that older age, hypertension, increased right CCA IAD, and decreased CSA of the right VN (standardized partial regression coefficient [β] − 0.226; P < 0.001) were independently associated with the severity of WMLs (Scheltens’ scale). A decreased CSA of the left VN was also associated with the severity of WMLs (β = − 0.239; P < 0.001).ConclusionVN size determined via ultrasonography was associated with the severity of WMLs. While these findings do not establish a causal relationship, they suggest that autonomic nervous system dysfunction is involved in the progression of WMLs.

The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage.

Subarachnoid hemorrhage leads to a series of pathological changes, including vascular spasm, cellular apoptosis, blood-brain barrier damage, cerebral edema, and white matter injury. Microglia, which are the key immune cells in the central nervous system, maintain homeostasis in the neural environment, support neurons, mediate apoptosis, participate in immune regulation, and have neuroprotective effects. Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage. Moreover, microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage. Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury. This provides new targets and ideas for the treatment of subarachnoid hemorrhage. However, an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking. This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm, neuroinflammation, neuronal apoptosis, blood-brain barrier disruption, cerebral edema, and cerebral white matter lesions. It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage. Currently, microglia in subarachnoid hemorrhage are targeted with TLR inhibitors, nuclear factor-κB and STAT3 pathway inhibitors, glycine/tyrosine kinases, NLRP3 signaling pathway inhibitors, Gasdermin D inhibitors, vincristine receptor α receptor agonists, ferroptosis inhibitors, genetic modification techniques, stem cell therapies, and traditional Chinese medicine. However, most of these are still being evaluated at the laboratory stage. More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.

The association of structural versus load-dependent large artery stiffness mechanisms with cerebrovascular damage and cortical atrophy in humans.

Large central arterial stiffness is a risk factor for cerebrovascular damage and subsequent progression of neurodegenerative diseases, including Alzheimer's disease and dementia. However, arterial stiffness is determined by both the intrinsic components of the arterial wall (structural stiffness) and the load (i.e., arterial blood pressure) exerted upon it by the blood (load-dependent stiffness). This study aimed to determine the degree to which structural and/or load-dependent mechanisms of central arterial stiffness are associated with cerebrovascular damage. Among 128 healthy individuals (aged 63±6, age range: 50-80 years, 42% men), aortic and carotid artery stiffness was measured via carotid-femoral pulse wave velocity and B-mode ultrasonography, respectively. Using participant-specific exponential models, both aortic and carotid artery stiffness were standardized to a reference blood pressure to separate their structural and load-dependent stiffness mechanisms. Magnetic resonance imaging was used to derive total, periventricular, and deep cerebral white matter lesion volume (WMLV) and global cortical thickness. After adjusting for common cardiovascular disease risk factors, a 1 m/s increase in structural aortic stiffness was associated with 15% greater total WMLV (95% confidence interval [CI] = 0.01, 0.27, P = 0.036), 14% greater periventricular WMLV (95%CI = 0.004, 0.25, P = 0.044) and 0.011mm lower cortical thickness (95%CI = -0.022, -1.18, P = 0.028). No association was observed between structural carotid stiffness and WMLVs (total, periventricular, and deep), and neither aortic nor carotid load-dependent stiffness was associated with WMLVs or cortical thickness. Structural, not load-dependent, mechanisms of aortic stiffness are related to cerebrovascular-related white matter damage.

Dexmedetomidine Inhibits Hippocampal Neuronal Damage Caused by Persistent Isoflurane-Induced Hypotension in Rat Model of Chronic Cerebral Hypoperfusion.

Purpose The purpose of this study was to investigate the effect of dexmedetomidine (DEX) on hypotension-induced neuronal damage in a chronic cerebral hypoperfusion (CCH) model of rats, an established model of cerebral white matter lesions (WML) in humans, which is prevalent in the elderly and closely related to cognitive decline. Methods The CCH model rats were randomly assigned to one of four groups: normotension + no DEX (NN) group (n = 6), normotension + DEX (ND) group (n = 6), hypotension + no DEX (HN) group (n = 6), or hypotension + DEX (HD) group (n = 6). Under isoflurane anesthesia, mean arterial blood pressure was maintained at or above 80 mmHg (normotension) or below 60 mmHg (hypotension) for a duration of two hours. The DEX groups received 50 μg of DEX intraperitoneally. Two weeks later, the Y-maze test and, after preparing brain slices, immunohistochemical staining were performed using antibodies against neuronal nuclei (NeuN), microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adapter molecule 1 (Iba1). Results Behavioral observations showed no significant differences among the groups. Significant reductions of both NeuN-positive cells and the MAP2-positive area were found in the hippocampal CA1 in the HN group compared with NN and ND groups, but not in the HD group. GFAP and Iba-1-positive areas were significantly increased in the HN group, but not in the HD group. Conclusion DEX significantly ameliorated hypotension-induced neuronal damage and both astroglial and microglial activation in the CA1 region of CCH rats.

Parenchymal Neuro-Behçet's disease or Comorbid Behçet's disease with multiple sclerosis: A discriminative analysis of a complex clinical entity

BackgroundPatients with Behçet's disease (BD) may rarely manifest with cerebral white matter lesions resembling multiple sclerosis (MS). This may result in misdiagnosis due to diagnostic difficulties between parenchymal neuro-BD (pNBD) and MS. This study aims to elucidate the distinguishing features of patients with comorbid BD and MS (BD+MS) in comparison to those with pNBD and MS alone by focusing on clinical and laboratory features. We also aimed to identify the distinctive characteristics of BD+MS patients by comparing them to patients with pNBD and MS. MethodsThe methodology of this study involved a retrospective analysis of patient records followed in the Department of Neurology at the Istanbul Faculty of Medicine, Istanbul University. The study population included patients diagnosed with pNBD, MS, and a comorbid condition of BD and MS (BD+MS). We assessed clinical, radiological, and laboratory data, including disease onset, annual relapse rates, Expanded Disability Status Scale (EDSS) progression, and cerebrospinal fluid examination. Several parameters were examined between the pNBD, MS, and BD+MS patient groups to find similarities and differences between subgroups. ResultsOur study included 1,764 patients: 172 with pNBD, 1,574 with MS, and 18 with BD+MS. A predominance of females was noted in the BD+MS (72%, p < 0.001) and MS (69 %, p < 0.001) groups compared to pNBD (30 %). The median age at the onset of neurological symptoms was 35.5 (IQR: 16.8) years for BD+MS, 34.6 (13.6) years for pNBD, and 27.6 (13.3) years for MS (BD+MS vs. MS; p = 0.3, pNBD vs. MS, p = 0.7). Additionally, the number of attacks was notably different, with BD+MS patients experiencing a median of 3.5 (2.0) attacks compared to 3.0 (3.0) for MS patients and only 1.0 (1.0) for pNBD patients, suggesting a more active disease course in the MS and BD+MS groups compared to pNBD (p < 0.001). The median annualized relapse rate for BD+MS was 0.3 (0.2), which was lower than the rate of 0.4 (0.4) in MS (p = 0.048) and equivalent to the rate of 0.2 (0.3) in pNBD (p = 0.2). The time to the first relapse was similar to those with BD+MS and MS, but considerably shorter than in individuals with pNBD (p < 0.0001). The cerebrospinal fluid (CSF) analysis showed no significant differences in neutrophil and lymphocyte counts between BD+MS and MS patients but elevated levels in pNBD patients (p < 0.05). CSF protein levels were consistent across all groups (p = 0.1 and p = 0.7). Oligoclonal bands were detected in all patients with BD+MS, in the majority of MS patients (83.6 %), and a small percentage of pNBD patients (19.7 %), showing a notable distinction between the BD+MS and pNBD groups (p < 0.001). ConclusionOur study underscores the need for a skeptical approach in diagnosing and treating patients with BD who exhibit symptomatic MS-like MRI lesions. Our findings suggest that BD+MS is a distinct clinical entity, warranting specific diagnostic and treatment approaches. Our findings highlight that BD patients with MS-like lesions meeting MS diagnostic criteria should be managed as patients with comorbid MS and BD rather than pNBD.

White matter biomarker for predicting de novo Parkinson's disease using tract-based spatial statistics: a machine learning-based model.

Parkinson's disease (PD) is an irreversible, chronic degenerative disease of the central nervous system, potentially associated with cerebral white matter (WM) lesions. Investigating the microstructural alterations within the WM in the early stages of PD can help to identify the disease early and enable intervention to reduce the associated serious threats to health. This study selected 227 cases from the Parkinson's Progression Markers Initiative (PPMI) database, including 152 de novo PD patients and 75 normal controls (NC). Whole-brain voxel analysis of the WM was performed using the tract-based spatial statistics (TBSS) method. The WM regions with statistically significant differences (P<0.05) between the PD and NC groups were identified and used as masks. The mask was applied to each case's fractional anisotropy (FA) image to extract voxel values as feature vectors. Geometric dimensionality reduction was then applied to eliminate redundant values in the feature vectors. Subsequently, the cases were randomly divided into a training group (158 cases, including 103 PD patients and 55 NC) and a test group (69 cases, including 49 PD patients and 20 NC). The least absolute shrinkage and selection operator (LASSO) regression algorithm was employed to extract the minimal set of relevant features, then the random forest (RF) algorithm was utilized for classification using 5-fold cross validation. The resulting model was further integrated with clinical factors to create a comprehensive prediction model. In comparison to the NC group, the FA values in PD patients exhibited a statistically significant decrease (P<0.05), indicating the presence of widespread WM lesions across multiple brain regions. Moreover, the PD prediction model, constructed based on these WM lesion regions, yielded prediction accuracy (ACC) and area under the receiver operating characteristic (ROC) curve (AUC) values of 0.778 and 0.865 in the validation set, and 0.783 and 0.831 in the test set, respectively. Furthermore, the performance of the integrated model showed some improvement, with ACC and AUC values in the test set reaching 0.804 and 0.844, respectively. The quantitative calculation of WM lesion area on FA images using the TBSS method can serve as a neuroimaging biomarker for diagnosing and predicting early PD at the individual level. When integrated with clinical variables, the predictive performance improves.

Transcript Profiles of Microglia/Macrophage Cells at the Borders of Chronic Active and Subpial Gray Matter Lesions in Multiple Sclerosis.

Microglia/macrophages line the border of demyelinated lesions in both cerebral white matter and the cortex in the brains of multiple sclerosis patients. Microglia/macrophages associated with chronic white matter lesions are thought to be responsible for slow lesion expansion and disability progression in progressive multiple sclerosis, whereas those lining gray matter lesions are less studied. Profiling these microglia/macrophages could help to focus therapies on genes or pathways specific to lesion expansion and disease progression. We compared the morphology and transcript profiles of microglia/macrophages associated with borders of white matter (WM line) and subpial gray matter lesions (GM line) using laser capture microscopy. We performed RNA sequencing on isolated cells followed by immunocytochemistry to determine the distribution of translational products of transcripts increased in WM line microglia. Cells in the WM line appear activated, with shorter processes and larger cell bodies, whereas those in the GM line appear more homeostatic, with smaller cell bodies and multiple thin processes. Transcript profiling revealed 176 genes in WM lines and 111 genes in GM lines as differentially expressed. Transcripts associated with immune activation and iron homeostasis were increased in WM line microglia, whereas genes belonging to the canonical Wnt signaling pathway were increased in GM line microglia. We propose that the mechanisms of demyelination and dynamics of lesion expansion are responsible for differential transcript expression in WM lines and GM lines, and posit that increased expression of the Fc epsilon receptor, spleen tyrosine kinase, and Bruton's tyrosine kinase, play a key role in regulating microglia/macrophage function at the border of chronic active white matter lesions. ANN NEUROL 2024;95:907-916.

Efficacy and Safety of the Natural Killer T Cell-Stimulatory Glycolipid OCH-NCNP1 for Patients With Relapsing Multiple Sclerosis: Protocol for a Randomized Placebo-Controlled Clinical Trial.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system that causes myelin sheath damage and axonal degeneration. The glycolipid (2S, 3S, 4R)-1-O-(α-d-galactosyl)-2-tetracosanoylamino-1,3,4-nonaetriol (OCH-NCNP1 or OCH) exerts an immunoregulatory action that suppresses T helper (Th)1 cell-mediated immune responses through natural killer T cell activation, selective interleukin-4 production, and Th2 bias induction in human CD4-positive natural killer T cells. This trial aims to investigate the efficacy and safety of the immunomodulator OCH in patients with relapsing MS through 24-week repeated administration. This protocol describes a double-blind, multicenter, placebo-controlled, randomized phase II clinical trial that was initiated in September 2019. The participants were randomly assigned to either a placebo control group or an OCH-NCNP1 group and the investigational drug (3.0 mg) was orally administered once weekly for the 24-week duration. Major inclusion criteria are as follows: patients had been diagnosed with relapsing MS (relapsing-remitting and/or secondary progressive MS) based on the revised McDonald criteria or were diagnosed with MS by an attending physician as noted in their medical records; patients with at least two medically confirmed clinical exacerbations within 24 months prior to consent or one exacerbation within 12 months prior to consent; patients with at least one lesion suspected to be MS on screening magnetic resonance imaging (MRI); and patients with 7 points or less in the Expanded Disability Status Scale during screening. Major exclusion criteria are as follows: diagnosis of neuromyelitis optica and one of optic neuritis, acute myelitis, and satisfying at least two of the following three items: (1) spinal cord MRI lesion extending across at least three vertebral bodies, (2) no brain MRI lesions during onset (at least four cerebral white matter lesions or three lesions, one of which is around the lateral ventricle), and (3) neuromyelitis optica-immunoglobulin G or antiaquaporin-4 antibody-positive. Outcome measures include the primary outcome of MRI changes (the percentage of subjects with new or newly expanded lesions at 24 weeks on T2-weighted MRI) and the secondary outcomes annual relapse rate (number of recurrences per year), relapse-free period (time to recurrence), sustained reduction in disability (SRD) occurrence rate, period until SRD (time to SRD occurrence), no evidence of disease activity, and exploratory biomarkers from phase I trials (such as gene expression, cell frequency, and intestinal and oral microbiome). We plan to enroll 30 patients in the full analysis set. Enrollment was closed in June 2021 and the study analysis was completed in March 2023. This randomized controlled trial will determine whether OCH-NCNP1 is effective and safe in patients with MS as well as provide evidence for the potential of OCH-NCNP1 as a therapeutic agent for MS. ClinicalTrials.gov NCT04211740; https://clinicaltrials.gov/study/NCT04211740. DERR1-10.2196/46709.

Anti-leucine-rich Glioma-inactivated 1 Protein-antibody Positive Encephalitis with Extensive Unilateral Cerebral Cortex and White Matter Lesions.

Encephalitis caused by antibodies targeting the leucine-rich glioma-inactivated 1 protein receptor, which belongs to the anti-voltage-gated potassium channel receptor complex, is characterized by hyponatremia, progressive cognitive impairment, seizures, and psychiatric disorders. The patient initially presented with faciobrachial dystonic seizures and subsequently developed encephalopathy. Brain magnetic resonance imaging revealed atypical unilateral hyperintense signals in the cerebral cortex and white matter. Intravenous corticosteroid pulse therapy effectively improved faciobrachial dystonic seizures and brain lesions.

Age-related decline in cerebral oxygen consumption in multiple sclerosis

Cerebral oxygen metabolism is altered in relapsing-remitting multiple sclerosis (RRMS), possibly a result of disease related cerebral atrophy with subsequent decreased oxygen demand. However, MS inflammation can also inhibit brain metabolism. Therefore, we measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) using MRI phase contrast mapping and susceptibility-based oximetry in 44 patients with early RRMS and 36 healthy controls. Cerebral atrophy and white matter lesion load were assessed from high-resolution structural MRI. Expanded Disability Status Scale (EDSS) scores were collected from medical records. The CMRO2 was significantly lower in patients (−15%, p = 0.002) and decreased significantly with age in patients relative to the controls (−1.35 µmol/100 g/min/year, p = 0.036). The lower CMRO2 in RRMS was primarily driven by a higher venous oxygen saturation in the sagittal sinus (p = 0.007) and not a reduction in CBF (p = 0.69). There was no difference in cerebral atrophy between the groups, and no correlation between CMRO2 and MS lesion volume or EDSS score. Therefore, the progressive CMRO2 decline observed before the occurrence of significant cerebral atrophy and despite adequate CBF supports emerging evidence of dysfunctional cellular respiration as a potential pathogenic mechanism and therapeutic target in RRMS.

White Matter Lesion Volumes on 3-T MRI in People With MS Who Had Followed a Diet and Lifestyle Program for More Than 10 Years.

Background: Cerebral white matter lesion (WML) formation in people with multiple sclerosis (pwMS) is linked to the death of myelin-producing oligodendrocytes. Current MS treatment strategies focus on limiting WML accumulation and disability. Using a pathology-supported genetic testing (PSGT) program, we identified specific risk factors for MS, categorized as deficiencies and aggravators. We developed a novel clinical methodology to mitigate these risk factors, including personalized lifestyle interventions and optimization of cerebral nutrients to prevent oligodendrocyte demise and promote remyelination. Objective: To conduct a pilot case-control study over a 10-year period to ascertain whether the PSGT Program can reduce or prevent WML formation in pwMS. Methods: MRI was performed at baseline as well as after an interval period of at least 10 years or longer in 22 pwMS. WML volumes were determined using Sequence Adaptive Multimodal SEGmentation (SAMSEG) software, part of FreeSurfer 7.2. Other variables included age at MRI, disease duration, disability status, and medication. Results: PwMS (n = 13) who had followed the PSGT program for more than 10 years, had significantly smaller lesion volumes (mm3) compared to pwMS who did not adhere to the program (n = 9) (4950 ± 5303 vs. 17934 ± 11139; p = 0.002). WML volumes were significantly associated (p = 0.02) with disability (EDSS) but not with age (p = 0.350), disease duration (p = 0.709), or Interferon-β treatment (p = 0.70). Conclusion: Dietary and lifestyle changes may lower the risk of developing cerebral WMLs in pwMS and potentially slow disease progression. Larger studies are required to confirm the effectiveness of such interventions in pwMS.

U-fiber analysis: a toolbox for automated quantification of U-fibers and white matter hyperintensities.

Whether white matter hyperintensities (WMHs) involve U-fibers is of great value in understanding the different etiologies of cerebral white matter (WM) lesions. However, clinical practice currently relies only on the naked eye to determine whether WMHs are in the vicinity of U-fibers, and there is a lack of good neuroimaging tools to quantify WMHs and U-fibers. Here, we developed a multimodal neuroimaging toolbox named U-fiber analysis (UFA) that can automatically extract WMHs and quantitatively characterize the volume and number of WMHs in different brain regions. In addition, we proposed an anatomically constrained U-fiber tracking scheme and quantitatively characterized the microstructure diffusion properties, fiber length, and number of U-fibers in different brain regions to help clinicians to quantitatively determine whether WMHs in the proximal cortex disrupt the microstructure of U-fibers. To validate the utility of the UFA toolbox, we analyzed the neuroimaging data from 246 patients with cerebral small vessel disease (cSVD) enrolled at Zhongshan Hospital between March 2018 and November 2019 in a cross-sectional study. According to the manual judgment of the clinician, the patients with cSVD were divided into a WMHs involved U-fiber group (U-fiber-involved group, 51 cases) and WMHs not involved U-fiber group (U-fiber-spared group, 163 cases). There were no significant differences between the U-fiber-spared group and the U-fiber-involved group in terms of age (P=0.143), gender (P=0.462), education (P=0.151), Mini-Mental State Examination (MMSE) scores (P=0.151), and Montreal Cognitive Assessment (MoCA) scores (P=0.411). However, patients in the U-fiber-involved group had higher Fazekas scores (P<0.001) and significantly higher whole brain WMHs (P=0.046) and deep WMH volumes (P<0.001) compared to patients in the U-fiber-spared group. Moreover, the U-fiber-involved group had higher WMH volumes in the bilateral frontal [P(left) <0.001, P(right) <0.001] and parietal lobes [P(left) <0.001, P(right) <0.001]. On the other hand, patients in the U-fiber-involved group had higher mean diffusivity (MD) and axial diffusivity (AD) in the bilateral parietal [P(left, MD) =0.048, P(right, MD) =0.045, P(left, AD) =0.015, P(right, AD) =0.015] and right frontal-parietal regions [P(MD) =0.048, P(AD) =0.027], and had significantly reduced mean fiber length and number in the right parietal [P(length) =0.013, P(number) =0.028] and right frontal-parietal regions [P(length) =0.048] compared to patients in the U-fiber-spared group. Our results suggest that WMHs in the proximal cortex may disrupt the microstructure of U-fibers. Our tool may provide new insights into the understanding of WM lesions of different etiologies in the brain.

Association between brain imaging biomarkers and continuous glucose monitoring-derived glycemic control indices in Japanese patients with type 2 diabetes mellitus

IntroductionAlthough type 2 diabetes mellitus (T2DM) is associated with alterations in brain structure, the relationship between glycemic control indices and brain imaging markers remains unclear. This study aimed to investigate...

A nomogram for predicting cerebral white matter lesions in elderly men.

This study aimed to develop a nomogram tool to predict cerebral white matter lesions (WMLs) in elderly men. Based on a retrospective cohort from January 2017 to December 2019, a multivariate logistic analysis was performed to construct a nomogram for predicting WMLs. The nomogram was further validated using a follow-up cohort between January 2020 and December 2022. The calibration curve, receiver operating characteristics (ROC) curves, and the decision curves analysis (DCA) were used to evaluate discrimination and calibration of this nomogram. A total of 436 male patients were enrolled in this study, and all 436 patients were used as the training cohort and 163 follow-up patients as the validation cohort. A multivariate logistic analysis showed that age, cystatin C, uric acid, total cholesterol, platelet, and the use of antiplatelet drugs were independently associated with WMLs. Based on these variables, a nomogram was developed. The nomogram displayed excellent predictive power with the area under the ROC curve of 0.951 [95% confidence interval (CI), 0.929-0.972] in the training cohort and 0.915 (95% CI, 0.864-0.966) in the validation cohort. The calibration of the nomogram was also good, as indicated by the Hosmer-Lemeshow test with p-value of 0.594 in the training cohort and 0.178 in the validation cohort. The DCA showed that the nomogram holds good clinical application value. We have developed and validated a novel nomogram tool for identifying elderly men at high risk of WMLs, which exhibits excellent predictive power, discrimination, and calibration.

Construction and validation of a nomogram model to predict symptomatic intracranial hemorrhage after intravenous thrombolysis in elderly population with severe white matter lesions

Background and Objective: Elderly people are at high prevalence of atherosclerotic cerebral infarction. Cerebral white matter lesions (WMLs) increase the risk of bleeding after intravenous thrombolysis (IVT) although they may also require the IVT. The aim of this study is to develop a clinical nomogram model for post-IVT symptomatic intracranial hemorrhage (sICH), with the aim to prevent sICH in elderly patients with severe WMLs when IVT is being considered. Methods: This is a large single-center retrospective analysis study of elderly patients with severe WMLs receiving IVT from January 2018 to December 2022. Univariate and multi-factor logistic regression analysis were used to construct nomogram model, and a series of validations were performed on the model. Results: More than 2,000 patients with IVT were screened for inclusion in this study after cranial magnetic resonance imaging evaluation. Out of these, 163 elderly patients had cerebral WMLs, and 25 had sICH. In univariate analysis, history of hypertension (p=0.037), hyperlipidemia (p&lt;0.001), NIHSS score before IVT (p&lt;0.001), low-density lipoprotein levels (p=0.016), cholesterol levels (p=0.020), platelet count (p=0.006), systolic blood pressure (p&lt;0.001), diastolic blood pressure (p&lt;0.001) were significantly associated with sICH. In a multifactorial analysis, the NIHSS score before IVT (OR 42.056 CI 7.308-242.012, p&lt;0.001), and diastolic blood pressure (OR 1.050 CI 1.002-1.100, p=0.040) were found to be significantly associated with sICH after IVT. The four most significant risk factors from logistic regression are subsequently fitted to create a predictive model. The accuracy was verified using calibration curves, decision curves, and clinical impact curves, and the model was considered to have strong stability. Conclusions: The NHISS score before IVT and diastolic blood pressure are independent risk factors for sICH after IVT in elderly patients with severe WMLs. The models are highly accurate and can be applied clinically to provide a reliable predictive basis for IVT in elderly patients with severe WMLs.