Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pa...Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-targe...Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.展开更多
Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple rol...Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.展开更多
Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann c...Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.展开更多
Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves ...Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.展开更多
Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives ...Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.展开更多
Amyotrophic lateral sclerosis(ALS),also known as Lou Geh rig's disease,is a progressive neurodegenerative disorder that affects motor neurons in the brain and spinal cord.This leads to muscle weakness,paralysis,an...Amyotrophic lateral sclerosis(ALS),also known as Lou Geh rig's disease,is a progressive neurodegenerative disorder that affects motor neurons in the brain and spinal cord.This leads to muscle weakness,paralysis,and ultimately,respiratory failure(Cha and Kim,2022).展开更多
Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(ALS)are neurodegenerative diseases with significant overlapping attributes.While these neurod...Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(ALS)are neurodegenerative diseases with significant overlapping attributes.While these neurodegenerative diseases affect different neuronal populations(with FTD affecting neurons of the frontal and temporal lobes,and ALS affecting upper and lower motor neurons),these two diseases are complexly intertwined.FTD and ALS exist on a disease spectrum,with shared genetic causes,clinical presentations,and pathologies.展开更多
Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b...Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated by infiltrating immune cells(Hauser and Cree, 2020).展开更多
Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons,clinically marked by muscle atrophy and weakness.Although the clinical course is ...Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons,clinically marked by muscle atrophy and weakness.Although the clinical course is highly variable,the average time from the onset of symptoms to the need for respiratory support or death is 3-5 years.ALS is the most prevalent motor neuron disease in adults,occurring at a rate of 2 per 100,000 individuals and affecting 5.4 per 100,000 individuals overall.展开更多
This editorial discusses a case report recently published in the World Journal of Clinical Cases.The report describes the clinical presentation,imaging,diagnosis,and treatment of a patient with tuberous sclerosis comp...This editorial discusses a case report recently published in the World Journal of Clinical Cases.The report describes the clinical presentation,imaging,diagnosis,and treatment of a patient with tuberous sclerosis complex(TSC)combined with primary lymphedema(PLE).Additionally,it retrospectively analyzes the data of 16 previously reported cases of children with TSC combined with PLE to summarize the epidemiology,genetic diagnosis,and current main treatments of these patients.The report also speculates on the pathological and physiological mechanisms underlying TSC combined with PLE.TSC combined with PLE is rare;therefore,the report provides a theoretical basis for understanding the pathophysiological mechanisms and treatment options for patients with TSC and PLE.Comprehensive clinical management of TSC is essential due to the diverse and multiorgan nature of its manifestations,often requiring a multidisciplinary approach for newly diagnosed cases.展开更多
Amyotrophic lateral sclerosis(ALS)is a devastating neurological disease characterized by the accumulation of aberrant proteins in motor neurons of the brain and spinal cord.Patients with ALS develop skeletal muscle we...Amyotrophic lateral sclerosis(ALS)is a devastating neurological disease characterized by the accumulation of aberrant proteins in motor neurons of the brain and spinal cord.Patients with ALS develop skeletal muscle weakness,resulting in death from respiratory paralysis,which usually occurs 2-4 years after clinical onset(Goutman et al.,2022).展开更多
Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity an...Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.展开更多
Macrophage migration inhibitory factor(MIF):MIF acts as a pleiotropic inflammatory mediator,playing regulatory roles in innate and adaptive immunity,neuroinflammation,neuroendocrine functions,and nervous system develo...Macrophage migration inhibitory factor(MIF):MIF acts as a pleiotropic inflammatory mediator,playing regulatory roles in innate and adaptive immunity,neuroinflammation,neuroendocrine functions,and nervous system development(Matejuk et al.,2024).In recent years,MIF has attra cted significant inte rest from research groups as a potential target for the treatment of various neurodegenerative diseases,including Alzheimer's disease,Parkinson's disease,multiple sclerosis,and glioblastoma(Matejuk et al.,2024).展开更多
Multiple Sclerosis(MS)poses significant health risks.Patients may face neurodegeneration,mobility issues,cognitive decline,and a reduced quality of life.Manual diagnosis by neurologists is prone to limitations,making ...Multiple Sclerosis(MS)poses significant health risks.Patients may face neurodegeneration,mobility issues,cognitive decline,and a reduced quality of life.Manual diagnosis by neurologists is prone to limitations,making AI-based classification crucial for early detection.Therefore,automated classification using Artificial Intelligence(AI)techniques has a crucial role in addressing the limitations of manual classification and preventing the development of MS to advanced stages.This study developed hybrid systems integrating XGBoost(eXtreme Gradient Boosting)with multi-CNN(Convolutional Neural Networks)features based on Ant Colony Optimization(ACO)and Maximum Entropy Score-based Selection(MESbS)algorithms for early classification of MRI(Magnetic Resonance Imaging)images in a multi-class and binary-class MS dataset.All hybrid systems started by enhancing MRI images using the fusion processes of a Gaussian filter and Contrast-Limited Adaptive Histogram Equalization(CLAHE).Then,the Gradient Vector Flow(GVF)algorithm was applied to select white matter(regions of interest)within the brain and segment them from the surrounding brain structures.These regions of interest were processed by CNN models(ResNet101,DenseNet201,and MobileNet)to extract deep feature maps,which were then combined into fused feature vectors of multi-CNN model combinations(ResNet101-DenseNet201,DenseNet201-MobileNet,ResNet101-MobileNet,and ResNet101-DenseNet201-MobileNet).The multi-CNN features underwent dimensionality reduction using ACO and MESbS algorithms to remove unimportant features and retain important features.The XGBoost classifier employed the resultant feature vectors for classification.All developed hybrid systems displayed promising outcomes.For multiclass classification,the XGBoost model using ResNet101-DenseNet201-MobileNet features selected by ACO attained 99.4%accuracy,99.45%precision,and 99.75%specificity,surpassing prior studies(93.76%accuracy).It reached 99.6%accuracy,99.65%precision,and 99.55%specificity in binary-class classification.These results demonstrate the effectiveness of multi-CNN fusion with feature selection in improving MS classification accuracy.展开更多
Objective As the core unit of the limbic system,the hippocampus is involved in the regulation of higher neural activity by integrating emotional encoding and memory storage functions.In the pathological process of epi...Objective As the core unit of the limbic system,the hippocampus is involved in the regulation of higher neural activity by integrating emotional encoding and memory storage functions.In the pathological process of epilepsy,structural remodeling and functional disorders in this region have become the focus of research,and the existing evidence mostly focuses on hippocampal sclerosis,a typical neurodegenerative change.However,there is still a lack of systematic analysis of the pathological subtypes under the International League Against Epilepsy(ILAE)classification system in cross-scale molecular events such as epigenetic regulation and microbiome-brain axis.By integrating clinical cohort data and experimental model evidence,this article focuses on the association characteristics between hippocampal sclerosis subtypes and seizure patterns,and reveals the formation of abnormal hippocampal network and the cascading effect of abnormal hippocampus-related neurotransmitters in the formation of epileptogenic network.The study found that specific pathological subtypes showed a significant correspondence with seizure frequency and drug sensitivity,suggesting that hippocampal sclerosis drives epilepsy progression through multidimensional molecular events.In the future,it is necessary to combine spatial transcriptome and targeted metabolomics technology to analyze the cell interaction network in the hippocampal microenvironment,so as to provide a theoretical basis for the development of subtype-specific antiepileptic strategies.展开更多
Background:Epilepsy is a disease characterized by unprovoked seizures,and it affects around 70 million people worldwide.Standard treatment is ineffective in one third of all epilepsy patients.Temporal Lobe Epilepsy wi...Background:Epilepsy is a disease characterized by unprovoked seizures,and it affects around 70 million people worldwide.Standard treatment is ineffective in one third of all epilepsy patients.Temporal Lobe Epilepsy with Hippocampal Sclerosis(TLE-HS)is the most drug-resistant form of epilepsy,and it also impacts physical,mental,and psychological well-being of patients.Carum carvi extract has demonstrated anti-convulsant,anti-depressant,and anxiolytic properties.This study was designed to investigate if Carum carvi extract can alleviate depression and memory loss symptoms in a TLE-HS animal model.Methods:Male Sprague Dawley rats were used to create a model of TLE-HS and Carum carvi extract treatment,along with appropriate controls,was used to test the efficacy of this herbal extract in reducing the symptoms of depression and memory loss.Results:Forced swim test showed that Carum carvi extract treated TLE-HS rats resulted in significant improvement of the symptoms of depression.However,novel object recognition test showed that memory improvement did not occur.Conclusion:Depression significantly impacts the quality of life in TLE-HS patients,and this study has shown that Carum carvi extract should be explored further as an adjuvant treatment for TLE-HS patients to improve their quality of life.展开更多
Objective:To investigate the diagnostic value of magnetic resonance imaging(MRI)in patients with Modic changes and endplate sclerosis of the lumbar spine.Methods:A total of 66 patients with lumbar spine diseases who u...Objective:To investigate the diagnostic value of magnetic resonance imaging(MRI)in patients with Modic changes and endplate sclerosis of the lumbar spine.Methods:A total of 66 patients with lumbar spine diseases who underwent MRI and CT diagnostic examinations at the hospital from May 2024 to April 2025 were included in this study.The MRI findings of Modic changes were compared between Type I and Type II patients,and the presence or absence of endplate sclerosis signals and the HU value ratio on CT were analyzed.The pathological characteristics of Modic changes in Type I and Type II patients were observed.The imaging features of Modic changes in patients with lumbar spine diseases were analyzed.Results:Modic changes were present in 34 patients,with a total of 204 endplates evaluated,of which 74 were affected.MRI classification showed:Type I in 8 cases(10.81%),Type I/II mixed in 10 cases(13.51%),Type II in 51 cases(68.92%),and Type II/III mixed in 5 cases(6.76%).In CT reconstruction images,26 endplates with Modic changes on MRI showed sclerosis in the vertebral body,presenting high-density sclerotic features.These sclerotic areas did not exhibit distinct signal characteristics on MRI but pathologically demonstrated Type II Modic changes concurrently with fatty degeneration and sclerosis;In patients with Modic changes of Type I and Type II,regardless of the presence or absence of endplate sclerosis,the sagittal T1/T2 signal intensity ratio showed no statistically significant difference(P>0.05).However,the HU value ratio in Type II changes with sclerotic regions(2.74±0.61)was significantly higher than that in regions without sclerosis(1.16±0.23),with a statistically significant difference(P<0.05).Conclusion:CT reconstruction images of patients with lumbar Modic changes clearly demonstrate endplate sclerosis,a phenomenon closely associated with the bone marrow repair process.MRI has limited sensitivity for detecting sclerosis,potentially due to the following factors:first,differences in the radiographic characterization of endplate mineral content;second,the specific influence of different Modic types on signal intensity.This suggests that MRI classification should be combined with CT features for comprehensive interpretation.展开更多
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
基金Private DonationLa Trobe Research Focus AreasMultiple Sclerosis Australia,Grant/Award Number:20-032。
文摘Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32271292,31872723,32200778,and 22377089)the Jiangsu Students Innovation and Entrepre-neurship Training Program,China(Program No.:202210285081Z)+6 种基金the Project of MOE Key Laboratory of Geriatric Diseases and Immunology,China(Project No.:JYN202404)Proj-ect Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,Natural Science Foundation of Jiangsu Province,China(Project No.:BK20220494)Suzhou Medical and Health Technology Innovation Project,China(Grant No.:SKY2022107)the Clinical Research Center of Neuro-logical Disease in The Second Affiliated Hospital of Soochow University,China(Grant No.:ND2022A04)State Key Laboratory of Drug Research(Grant No.:SKLDR-2023-KF-05)Jiangsu Shuang-chuang Program for Doctor,Young Science Talents Promotion Project of Jiangsu Science and Technology Association(Program No.:TJ-2023-019)Young Science Talents Promotion Project of Suzhou Science and Technology Association,Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and startup funding(Grant Nos.:NH21500221,NH21500122,and NH21500123)to Qifei Cong.
文摘Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.
基金supported by the National Natural Science Foundation of China,Nos.82060219,82271234the Natural Science Foundation of Jiangxi Province,Nos.20212ACB216009,20212BAB216048+1 种基金Jiangxi Province Thousands of Plans,No.jxsq2019201023Youth Team Project of the Second Affiliated Hospital of Nanchang University,No.2019YNTD12003(all to FH)。
文摘Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.
基金support from the Miami Project to Cure Paralysis,the Buoniconti Fund,and the Interdisciplinary Stem Cell Institute(to AK,WDD,JDG,and ADL)the unconditional support of Dean Henri Ford of the Leonard M.Miller School of Medicine at the University of Miami.
文摘Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.
文摘Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.
基金supported by the National Natural Science Foundation of China,Nos.82071426,81873784Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(all to DF)。
文摘Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.
基金supported by the BK21 FOUR(Fostering Outstanding Universities for Research)the Basic Science Research Program through the National Research Foundation of Korea(NRF)+2 种基金the Regional Innovation Mega Project Program through the Korea Innovation Foundation funded by the Ministry of Education(MOE)the Ministry of Science and ICT(MSIT)(NRF-2022R1A2C1004204,RS-2023-00219563,2023-DD-UP-0007)the Soonchunhyang University Research Fund(to KK)。
文摘Amyotrophic lateral sclerosis(ALS),also known as Lou Geh rig's disease,is a progressive neurodegenerative disorder that affects motor neurons in the brain and spinal cord.This leads to muscle weakness,paralysis,and ultimately,respiratory failure(Cha and Kim,2022).
基金funded by a senior research fellowship from Alzheimer’s Research UK (ARUK-SRF2022A-005)funded by a PhD studentship from Alzheimer’s Society (571)+1 种基金supported by the UK Dementia Research Institute through UK DRI Ltd.principally funded by the UK Medical Research Council
文摘Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(ALS)are neurodegenerative diseases with significant overlapping attributes.While these neurodegenerative diseases affect different neuronal populations(with FTD affecting neurons of the frontal and temporal lobes,and ALS affecting upper and lower motor neurons),these two diseases are complexly intertwined.FTD and ALS exist on a disease spectrum,with shared genetic causes,clinical presentations,and pathologies.
文摘Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated by infiltrating immune cells(Hauser and Cree, 2020).
基金funded by Fondazione AriSLA ETS(Fondazione di ricerca per la SLA ETS),ReNicALS project to SAsupported by#NEXTGENERATIONEU(NGEU)and funded by the Ministry of University and Research(MUR),National Recovery and Resilience Plan(NRRP),project MNESYS(PE0000006)-A Multiscale Integrated Approach to the Study of the Nervous System in Health and Disease(DN.1553 October 11,2022)。
文摘Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons,clinically marked by muscle atrophy and weakness.Although the clinical course is highly variable,the average time from the onset of symptoms to the need for respiratory support or death is 3-5 years.ALS is the most prevalent motor neuron disease in adults,occurring at a rate of 2 per 100,000 individuals and affecting 5.4 per 100,000 individuals overall.
文摘This editorial discusses a case report recently published in the World Journal of Clinical Cases.The report describes the clinical presentation,imaging,diagnosis,and treatment of a patient with tuberous sclerosis complex(TSC)combined with primary lymphedema(PLE).Additionally,it retrospectively analyzes the data of 16 previously reported cases of children with TSC combined with PLE to summarize the epidemiology,genetic diagnosis,and current main treatments of these patients.The report also speculates on the pathological and physiological mechanisms underlying TSC combined with PLE.TSC combined with PLE is rare;therefore,the report provides a theoretical basis for understanding the pathophysiological mechanisms and treatment options for patients with TSC and PLE.Comprehensive clinical management of TSC is essential due to the diverse and multiorgan nature of its manifestations,often requiring a multidisciplinary approach for newly diagnosed cases.
基金supported in port by the JSPS KAKENHI(grant number 22K07539 to MS)funded by Mitsubishi Tanabe Pharma Corporation。
文摘Amyotrophic lateral sclerosis(ALS)is a devastating neurological disease characterized by the accumulation of aberrant proteins in motor neurons of the brain and spinal cord.Patients with ALS develop skeletal muscle weakness,resulting in death from respiratory paralysis,which usually occurs 2-4 years after clinical onset(Goutman et al.,2022).
基金The lab of AK obtained support from the Interdisciplinary Center for Clinical Research(IZKF)Jena(MSPProject ID:MSP09)+2 种基金DG and MJA B were supported by the Circular Vision project,which has received funding from the European Union's Horizon 2020 research and innovation program(Grant agreement No.899417)the Ministerio de Ciencia e Innovoción,Spain(Grant No.PID2020-119715GB-I00/AEI/10.13039/501100011033)the Instituto de Salud CarlosⅢ,Infrastructure of Precision Medicine associated with Science and Technology(IMPaCT)of the Strategic Action in Health(iDATAMP)(to MJAB)。
文摘Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.
基金supported by grants from the Israel Science Foundation(ISF#284/19)German Israeli Foundation(GIF#I-116-415.6-2016)(to AI)。
文摘Macrophage migration inhibitory factor(MIF):MIF acts as a pleiotropic inflammatory mediator,playing regulatory roles in innate and adaptive immunity,neuroinflammation,neuroendocrine functions,and nervous system development(Matejuk et al.,2024).In recent years,MIF has attra cted significant inte rest from research groups as a potential target for the treatment of various neurodegenerative diseases,including Alzheimer's disease,Parkinson's disease,multiple sclerosis,and glioblastoma(Matejuk et al.,2024).
文摘Multiple Sclerosis(MS)poses significant health risks.Patients may face neurodegeneration,mobility issues,cognitive decline,and a reduced quality of life.Manual diagnosis by neurologists is prone to limitations,making AI-based classification crucial for early detection.Therefore,automated classification using Artificial Intelligence(AI)techniques has a crucial role in addressing the limitations of manual classification and preventing the development of MS to advanced stages.This study developed hybrid systems integrating XGBoost(eXtreme Gradient Boosting)with multi-CNN(Convolutional Neural Networks)features based on Ant Colony Optimization(ACO)and Maximum Entropy Score-based Selection(MESbS)algorithms for early classification of MRI(Magnetic Resonance Imaging)images in a multi-class and binary-class MS dataset.All hybrid systems started by enhancing MRI images using the fusion processes of a Gaussian filter and Contrast-Limited Adaptive Histogram Equalization(CLAHE).Then,the Gradient Vector Flow(GVF)algorithm was applied to select white matter(regions of interest)within the brain and segment them from the surrounding brain structures.These regions of interest were processed by CNN models(ResNet101,DenseNet201,and MobileNet)to extract deep feature maps,which were then combined into fused feature vectors of multi-CNN model combinations(ResNet101-DenseNet201,DenseNet201-MobileNet,ResNet101-MobileNet,and ResNet101-DenseNet201-MobileNet).The multi-CNN features underwent dimensionality reduction using ACO and MESbS algorithms to remove unimportant features and retain important features.The XGBoost classifier employed the resultant feature vectors for classification.All developed hybrid systems displayed promising outcomes.For multiclass classification,the XGBoost model using ResNet101-DenseNet201-MobileNet features selected by ACO attained 99.4%accuracy,99.45%precision,and 99.75%specificity,surpassing prior studies(93.76%accuracy).It reached 99.6%accuracy,99.65%precision,and 99.55%specificity in binary-class classification.These results demonstrate the effectiveness of multi-CNN fusion with feature selection in improving MS classification accuracy.
文摘Objective As the core unit of the limbic system,the hippocampus is involved in the regulation of higher neural activity by integrating emotional encoding and memory storage functions.In the pathological process of epilepsy,structural remodeling and functional disorders in this region have become the focus of research,and the existing evidence mostly focuses on hippocampal sclerosis,a typical neurodegenerative change.However,there is still a lack of systematic analysis of the pathological subtypes under the International League Against Epilepsy(ILAE)classification system in cross-scale molecular events such as epigenetic regulation and microbiome-brain axis.By integrating clinical cohort data and experimental model evidence,this article focuses on the association characteristics between hippocampal sclerosis subtypes and seizure patterns,and reveals the formation of abnormal hippocampal network and the cascading effect of abnormal hippocampus-related neurotransmitters in the formation of epileptogenic network.The study found that specific pathological subtypes showed a significant correspondence with seizure frequency and drug sensitivity,suggesting that hippocampal sclerosis drives epilepsy progression through multidimensional molecular events.In the future,it is necessary to combine spatial transcriptome and targeted metabolomics technology to analyze the cell interaction network in the hippocampal microenvironment,so as to provide a theoretical basis for the development of subtype-specific antiepileptic strategies.
基金supported by the URC Aga Khan University(Project ID:212003)Pakistan Science Foundation(Project Code:710110-201-20001-500-53413-0000).
文摘Background:Epilepsy is a disease characterized by unprovoked seizures,and it affects around 70 million people worldwide.Standard treatment is ineffective in one third of all epilepsy patients.Temporal Lobe Epilepsy with Hippocampal Sclerosis(TLE-HS)is the most drug-resistant form of epilepsy,and it also impacts physical,mental,and psychological well-being of patients.Carum carvi extract has demonstrated anti-convulsant,anti-depressant,and anxiolytic properties.This study was designed to investigate if Carum carvi extract can alleviate depression and memory loss symptoms in a TLE-HS animal model.Methods:Male Sprague Dawley rats were used to create a model of TLE-HS and Carum carvi extract treatment,along with appropriate controls,was used to test the efficacy of this herbal extract in reducing the symptoms of depression and memory loss.Results:Forced swim test showed that Carum carvi extract treated TLE-HS rats resulted in significant improvement of the symptoms of depression.However,novel object recognition test showed that memory improvement did not occur.Conclusion:Depression significantly impacts the quality of life in TLE-HS patients,and this study has shown that Carum carvi extract should be explored further as an adjuvant treatment for TLE-HS patients to improve their quality of life.
基金Key Laboratory of Spinal Degenerative Diseases,Xianyang City(Project No.:L2023-CXNL-CXPT-ZDSYS-010)Key Technology Innovation Team Project for Minimally Invasive Spinal Surgery,Xianyang City(Grant No.:L2022CXNLTD002)University-level Scientific Research Project,Shaanxi University of Traditional Chinese Medicine(Project No.:2020FS06).
文摘Objective:To investigate the diagnostic value of magnetic resonance imaging(MRI)in patients with Modic changes and endplate sclerosis of the lumbar spine.Methods:A total of 66 patients with lumbar spine diseases who underwent MRI and CT diagnostic examinations at the hospital from May 2024 to April 2025 were included in this study.The MRI findings of Modic changes were compared between Type I and Type II patients,and the presence or absence of endplate sclerosis signals and the HU value ratio on CT were analyzed.The pathological characteristics of Modic changes in Type I and Type II patients were observed.The imaging features of Modic changes in patients with lumbar spine diseases were analyzed.Results:Modic changes were present in 34 patients,with a total of 204 endplates evaluated,of which 74 were affected.MRI classification showed:Type I in 8 cases(10.81%),Type I/II mixed in 10 cases(13.51%),Type II in 51 cases(68.92%),and Type II/III mixed in 5 cases(6.76%).In CT reconstruction images,26 endplates with Modic changes on MRI showed sclerosis in the vertebral body,presenting high-density sclerotic features.These sclerotic areas did not exhibit distinct signal characteristics on MRI but pathologically demonstrated Type II Modic changes concurrently with fatty degeneration and sclerosis;In patients with Modic changes of Type I and Type II,regardless of the presence or absence of endplate sclerosis,the sagittal T1/T2 signal intensity ratio showed no statistically significant difference(P>0.05).However,the HU value ratio in Type II changes with sclerotic regions(2.74±0.61)was significantly higher than that in regions without sclerosis(1.16±0.23),with a statistically significant difference(P<0.05).Conclusion:CT reconstruction images of patients with lumbar Modic changes clearly demonstrate endplate sclerosis,a phenomenon closely associated with the bone marrow repair process.MRI has limited sensitivity for detecting sclerosis,potentially due to the following factors:first,differences in the radiographic characterization of endplate mineral content;second,the specific influence of different Modic types on signal intensity.This suggests that MRI classification should be combined with CT features for comprehensive interpretation.
