Central Nervous System Disorders Research Articles

Selective neuronal expression of progranulin is sufficient to provide neuroprotective and anti-inflammatory effects after traumatic brain injury

Progranulin (PGRN), which is produced in neurons and microglia, is a neurotrophic and anti-inflammatory glycoprotein. Human loss-of-function mutations cause frontotemporal dementia, and PGRN knockout (KO) mice are a model for dementia. In addition, PGRN KO mice exhibit severe phenotypes in models of traumatic or ischemic central nervous system (CNS) disorders, including traumatic brain injury (TBI). It is unknown whether restoration of progranulin expression in neurons (and not in microglia) might be sufficient to prevent excessive TBI-evoked brain damage. To address this question, we generated mice with Nestin-Cre-driven murine PGRN expression in a PGRN KO line (PGRN-KONestinGrn) to rescue PGRN in neurons. PGRN expression analysis in primary CNS cell cultures from naïve mice and in (non-) injured brain tissue from PGRN-KONestinGrn revealed expression of PGRN in neurons but not in microglia. After experimental TBI, examination of the structural brain damage at 5 days post-injury (dpi) showed that the TBI-induced loss of brain tissue and hippocampal neurons was exacerbated in PGRN-KOGrnflfl mice (PGRN knockout with the mGrn fl-STOP-fl allele, Cre-negative), as expected, whereas the tissue damage in PGRN-KONestinGrn mice was similar to that in PGRN-WT mice. Analysis of CD68+ immunofluorescent microglia and Cd68 mRNA expression showed that excessive microglial activation was rescued in PGRN-KONestinGrn mice, and the correlation of brain injury with Cd68 expression suggested that Cd68 was a surrogate marker for excessive brain injury caused by PGRN deficiency. The results show that restoring neuronal PGRN expression was sufficient to rescue the exacerbated neuropathology of TBI caused by PGRN deficiency, even in the absence of microglial PGRN. Hence, endogenous microglial PGRN expression was not essential for the neuroprotective or anti-inflammatory effects of PGRN after TBI in this study.Graphical

Chemical Composition of Clay Soil Analysis and Potential Health Risks: Experimental Study in Tshwane District, Gauteng Province

The practise of geophagy is common amongst women of childbearing age from different geographic locations, including South Africa, regardless of their social and economic status such as their level of education, race, marital status, income or occupation. This study aimed to examine the women of childbearing age in Tshwane District, Gauteng Province, South Africa. An experimental study was conducted at the laboratory to examine the chemical composition of clay soil ingested by geophagic women of childbearing age. Thirty-nine clay soil samples were collected from study participants attending antenatal care services and family planning at public healthcare facilities of Tshwane District, Gauteng Province, and subjected to geochemical analysis. The concentrations of vanadium, manganese, chromium, and barium were detected in quantities exceeding 100 mg/kg in almost all samples. Cadmium, mercury and silver were detected in low concentrations below 1 mg/kg in all samples. The practice of geophagy amongst women of childbearing age has been reported to be associated with detrimental health outcomes and risks such as iron deficiency anaemia, constipation, shortness of breath, maternal and childhood mortalities and morbidities, neurological and central nervous system disorder, death, appendicitis, cancers, teratogenic risks, and ulcers. The chemical composition of clay soil eaten by geophagic women of childbearing age contains potentially harmful substances, thus the practise of geophagy is toxic and should be discouraged to protect public health.

Cerebrospinal fluid L-lactate as a diagnostic marker for infectious-inflammatory disorders in the central nervous system of cattle.

Bacterial infection of the central nervous system (CNS) poses a clinical challenge and is a leading cause of neurological disorders in cattle. Human studies have demonstrated an increase in cerebrospinal fluid (CSF) L-lactate levels in bacterial meningitis. The aims of this study were to establish a Reference Interval (RI) for L-lactate in bovine CSF and assess its potential as a biomarker for detecting infectious-inflammatory disorders. CSF L-lactate was measured in the field using a commercially available lactate monitor. The RI for CSF L-lactate was calculated on healthy animals; univariate and receiver operating characteristic (ROC) analyses were performed to disclose an association between CSF L-lactate levels and interpretation of CSF in sick animals. Twenty-seven healthy cattle and 86 sick cattle with either CNS infectious-inflammatory disorders (47/86) or CNS disorders of other etiology (39/86) were included in this prospective study. The RI for CSF L-lactate was 1.1-2.4 mmol/L. The concentration was higher in the cattle with neutrophilic pleocytosis and the area under the ROC curve was 0.92 compared to other animals. Based on a cut-off of 3.15 mmol/L, CSF L-lactate had diagnostic sensitivity and specificity for neutrophilic pleocytosis of 93 and 80%, respectively. This is the first study to determine a RI for CSF L-lactate in cattle. Elevated CSF L-lactate levels indicated neutrophilic pleocytosis, which is often manifested in acute bacterial infection. The present findings may aid in diagnosis and correct use of antimicrobial drugs.

Phytochemical and pharmacological evaluation of bacopa monniera for anti – anxiety activity

Anxiety, a common emotional response to stress, involves numerous brain regions and neurotransmitters, including the amygdala, prefrontal cortex, and hippocampus, and is partially by genetic, environmental, and biological factors. This study evaluates Bacopa monnieri, a herb known in Ayurvedic medicine for its cognitive-enhancing and adaptogenic properties, as a potential anti-anxiety agent. The plant's ethanolic extract revealed a variety of phytochemicals, including alkaloids, flavonoids, and saponins. Acute toxicity studies indicated a high safety margin with an LD50 exceeding 2000 mg/kg body weight. The anti-anxiety effects were assessed using three established models. In the Elevated Plus-Maze Test, Bacopa monnieri significantly reduced anxiety levels in mice, comparable to the standard anxiolytic benzodiazepine. The Hole-Board Test showed increased head-dipping and rearing behaviors, while reducing immobility, suggesting anxiolytic activity. The Light-Dark Exploration Test demonstrated the herb's ability to decrease anxiety-related behaviors, including a reduction in rearing in dark compartments and increased exploration of light areas. These findings provide scientific validation for Bacopa monnieri's traditional use in treating anxiety and support its potential as an effective and safe anti-anxiety agent in managing central nervous system disorders.

Potential Neuroprotective Effects of Alpinia officinarum Hance (Galangal): A Review.

Background/Objectives: This review aims to provide a detailed understanding of the current evidence on Alpinia officinarum Hance (A. officinarum) and its potential therapeutic role in central nervous system (CNS) disorders. CNS disorders encompass a wide range of disorders affecting the brain and spinal cord, leading to various neurological, cognitive and psychiatric impairments. In recent years, natural products have emerged as potential neuroprotective agents for the treatment of CNS disorders due to their outstanding bioactivity and favourable safety profile. One such plant is A. officinarum, also known as lesser galangal, a perennial herb from the Zingiberaceae family. Its phytochemical compounds such as flavonoids and phenols have been documented to have a powerful antioxidants effect, capable of scavenging free radicals and preventing oxidative damage. Methods: In this review, we critically evaluate the in vitro and in vivo studies and examine the mechanisms by which A. officinarum exerts its neuroprotective effect. Results: Several studies have confirmed that A. officinarum exerts its neuroprotective effects by reducing oxidative stress and cell apoptosis, promoting neurite outgrowth, and modulating neurotransmitter levels and signalling pathways. Conclusions: Although previous studies have shown promising results in various models of neurological disorders, the underlying mechanisms of A. officinarum in Alzheimer's (AD) and Parkinson's disease (PD) are still poorly understood. Further studies on brain tissue and cognitive and motor functions in animal models of AD and PD are needed to validate the results observed in in vitro studies. In addition, further clinical studies are needed to confirm the safety and efficacy of A. officinarum in CNS disorders.

Gaining insights into the physicochemical properties and sequence space of blood–brain barrier penetrating peptides

The blood–brain barrier (BBB) poses a significant obstacle to the administration of drugs to the brain for the development of therapies of central nervous system (CNS) disorders. Blood-brain barrier penetrating peptides (BBBPps) are a group of peptides that can traverse the BBB by different processes without causing harm to the BBB. These peptides show promise as potential drugs for CNS ailments. Nevertheless, the process of identifying BBBPps using experimental approaches is both time-consuming and labour-intensive. To discover additional BBBPps as potential treatments for CNS diseases, it is critical to develop insilico methods that can distinguish BBBPps from non- BBBPps rapidly and precisely. In the current work, machine learning aided models are developed for accurate prediction of BBBPps using physicochemical and evolutionary information. The best model achieved an accuracy of 84.8 % by using 5-fold cross-validation and 79.8 % based on the holdout testing set on a reduced set of features. Further an extensive analysis is carried out for the black box models using model agnostic interpretation approaches to infer the physicochemical and sequence space of BBBPps. Basic amino acids and conservation of Arginine and Lysine are found to be more favoured in BBBPps. Further, basic amino acid property group and its interactions with other features are found to be prominent important interactions.

Pharmacological Chaperone Therapy for Fabry Disease

Pharmacological chaperone therapy (PCT) structurally stabilizes mutant enzyme proteins and increases their activity. Although ease of oral administration and effectiveness in patients with central nervous system disorders serve as advantages, PCT is effective only for patients with amenable mutations because its efficacy depends on gene mutations. PCT, which prevents progression of Fabry cardiomyopathy and nephropathy, was approved in Japan in 2018. It is expected that PCT will also be developed for lysosomal diseases that cause central nervous system disorders in the future.

Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling

ABSTRACTProteoglycans and their proteolytic fragments diffuse into biological fluids such as plasma, serum, urine, or synovial fluid, where they can be detected by antibodies or mass‐spectrometry. Neopeptides generated by the proteolysis of proteoglycans are recognized by specific neoepitope antibodies and can act as a proxy for the activity of certain proteases. Proteoglycan and proteoglycan fragments can be potentially used as prognostic, diagnostic, or theragnostic biomarkers for several diseases characterized by dysregulated extracellular matrix remodeling such as osteoarthritis, rheumatoid arthritis, atherosclerosis, thoracic aortic aneurysms, central nervous system disorders, viral infections, and cancer. Here, we review the main mechanisms accounting for the presence of soluble proteoglycans and their fragments in biological fluids, their potential application as diagnostic, prognostic, or theragnostic biomarkers, and highlight challenges and opportunities ahead of their clinical translation.

656P AAV gene therapy in the Pompe canine model demonstrates correction of the muscle and CNS disorder with immune tolerance to human GAA.

656P AAV gene therapy in the Pompe canine model demonstrates correction of the muscle and CNS disorder with immune tolerance to human GAA.

Advancements and mechanisms of stem cell-based therapies for spinal cord injury in animals.

Spinal cord injury (SCI) is a neurodegenerative disorder of the central nervous system (CNS) that can lead to permanent loss of sensation and voluntary movement beyond the affected area. Extensive preclinical and clinical trials have been conducted to evaluate the safety and effectiveness of stem cells for the treatment of various CNS diseases or disorders, including SCI. However, several challenges hinder nerve cell regeneration in the injured spinal cord, such as extensive cell loss, limited neural cell regeneration capacity, axonal disruption, and the presence of growth-inhibiting molecules, particularly astroglial scarring or glial scars at the injury site in chronic cases. These obstacles pose significant challenges for physicians in restoring normal motor and sensory nerve function in both humans and animals following SCI. This review focuses on SCI pathogenesis, the mechanisms underlying the therapeutic potential of Mesenchymal Stem Cells (MSCs) in SCI, and the potential of stem cell-based therapies as promising avenues for treatment. This review article also included relevant preclinical and clinical data from animal studies.

The Antidiabetic Drug Metformin Attenuated Depressive and Anxietylike Behaviors and Oxidative Stress in the Brain in a Rodent Model of Inflammation Induced by Lipopolysaccharide in Male Rats.

Inflammation is considered to be a link between diabetes and central nervous system (CNS) disorders, including depression and anxiety. Metformin is suggested to have antioxidant, anti-inflammatory, and mood-improving effects. The aim of the current research was to investigate the effects of the antidiabetic drug metformin on depressive- and anxiety- like behaviors and oxidative stress in the brain in a rodent model of inflammation induced by lipopolysaccharide (LPS) in male rats. The rats were treated as follows: (1) Vehicle instead of metformin and lipopolysaccharide, (2) Lipopolysaccharide (1 mg/ kg) + vehicle instead of metformin, (3-5) Lipopolysaccharide + 50, 100, or 150 mg/ kg of metformin. After the behavioral tests, including open field (OF), elevated pulse maze (EPM), and force swimming (FS) tests, the brains were removed, and malondialdehyde (MDA), nitric oxide (NO) metabolites, total thiol, catalase (CAT) activity, interleukin-6 (IL-6) and superoxide dismutase (SOD) activity were determined. In the EPM, metformin increased the open arm time and entry and decreased closed arm time and entry. In the FS test, metformin lowered the immobility and increased active time compared to lipopolysaccharide. In the OF test, metformin increased total crossing and total distance, time spent, traveled distance, and crossing number in the central zone. As a result of metformin administration, IL-6, MDA, and NO metabolites were decreased while thiol content, SOD, and CAT activity were increased. The results indicated that the well-known antidiabetic drug metformin attenuated depressive- and anxiety-like behaviors induced by inflammation in rats. These beneficial effects are suggested to be due to their attenuating effects on neuroinflammation, oxidative stress, and NO in the brain.

YTHDF1 gene inhibits epilepsy progression by epigenetic activation of PTEN gene

Epilepsy is a common chronic neurological disorder with high prevalence that profoundly affects millions of people worldwide. Inflammatory dysregulation affects central nervous system disorders including epilepsy, and YTHDF1, the most common "reader" of m6A and m6A-binding protein, can attenuate the inflammatory response and activate PTEN, and here we aimed to investigate its effect on epilepsy through epigenetics. All mice were injected intraperitoneally with 12 mg/kg of sea manic acid to establish an epilepsy model, and the epileptic behaviors of the mice were classified into 6 grades; epileptic behaviors of grade 3 or above were defined as seizures, and consecutive epileptic seizures of more than 30 min were considered as successful modeling. Mouse behavior was examined using the Morris Water Maze tracking assay; inflammatory factors IL-6, TNF-α, and IL-1β were detected by qPCR/WB/ELISA; cell activity was analyzed by CCK-8; apoptotic markers were identified by immunofluorescence assay and Western blot analysis. YTHDF1 knockout mice have poor spatial memory capacity and sensitivity to external stimuli. Under the influence of YTHDF1, the neuroinflammation and nseuron death decreased. YTHDF1 works by repressing the production of pro-inflammatory cytokines and the activation of astrocytes. It was found that YTHDF1 epigenetically activates PTEN through m6A modification, activates glial cells and represses pro-inflammatory cytokines production and inhibits the development of epilepsy.

A validated high-performance liquid chromatography-ultraviolet method for the determination of valproic acid derivatives in pharmaceutical formulations with a microbiological suitability evaluation

Valproic acid and its derivatives are common drugs used in the treatment of epilepsy, a result of CNS disorders. Because the molecular structure of valproic acid, as a fatty acid, does not contain any chromophore groups, its peak response demanded special conditions to be detected in HPLC, ensuring the best precision results. Still, the current approach illustrates simple, validated procedures for conduction. The conducted chromatographic system consists of the BDS Hypersil C8, 150 × 4.6 mm, 5 µm column using a mobile phase of acetonitrile: phosphate buffer (4:6) at a detection wavelength of 215 nm at room temperature. A full method validation study was conducted and approved to ensure precise, repeatable, and accurate results by implementing system suitability parameters. In microbiological terms, a suitability test is used to validate microbiological testing methods, ensuring their efficacy despite potential interference from antimicrobial properties in the tested materials. The HPLC-UV developed and validated analytical method was evaluated, and it was found to be sensitive for use in the detection of low concentrations of methylparaben, propylparaben, and valproate with an optimum run time of six minutes. limit of detection (LODs) were statistically estimated and found to be 2.27 µg/mL, 39.77 ng/mL, and 1.84 µg/mL for methylparaben, propylparaben, and valproate, respectively. Additionally, the method demonstrated a high recovery of methylparaben, propylparaben, and valproate with an excellent closed-accuracy range (98.84% - 101.34%). An excellent regression coefficient (r) of 0.99924, 0.99998, and 0.99997 for methylparaben, valproate, and propylparaben, respectively, was achieved. Assay determination of various pharmaceutical dosage forms in the local market was implemented, yielding admirable results.

MGlu4R, mGlu7R, and mGlu8R allosteric modulation for treating acute and chronic neurodegenerative disorders.

Neuroprotection, defined as safeguarding neurons from damage and death by inhibiting diverse pathological mechanisms, continues to be a promising approach for managing a range of central nervous system (CNS) disorders, including acute conditions such as ischemic stroke and traumatic brain injury (TBI) and chronic neurodegenerative diseases like Parkinson's disease (PD), Alzheimer's disease (AD), and multiple sclerosis (MS). These pathophysiological conditions involve excessive glutamatergic (Glu) transmission activity, which can lead to excitotoxicity. Inhibiting this excessive Glu transmission has been proposed as a potential therapeutic strategy for treating the CNS disorders mentioned. In particular, ligands of G protein-coupled receptors (GPCRs), including metabotropic glutamatergic receptors (mGluRs), have been recognized as promising options for inhibiting excessive Glu transmission. This review discusses the complex interactions of mGlu receptors with their subtypes, including the formation of homo- and heterodimers, which may vary in function and pharmacology depending on their protomer composition. Understanding these intricate details of mGlu receptor structure and function enhances researchers' ability to develop targeted pharmacological interventions, potentially offering new therapeutic avenues for neurological and psychiatric disorders. This review also summarizes the current knowledge of the neuroprotective potential of ligands targeting group III mGluRs in preclinical cellular (in vitro) and animal (in vivo) models of ischemic stroke, TBI, PD, AD, and MS. In recent years, experiments have shown that compounds, especially those activating mGlu4 or mGlu7 receptors, exhibit protective effects in experimental ischemia models. The discovery of allosteric ligands for specific mGluR subtypes has led to reports suggesting that group III mGluRs may be promising targets for neuroprotective therapy in PD (mGlu4R), TBI (mGlu7R), and MS (mGlu8R).

Biological function of sialic acid and sialylation in human health and disease.

Sialic acids are predominantly found at the terminal ends of glycoproteins and glycolipids and play key roles in cellular communication and function. The process of sialylation, a form of post-translational modification, involves the covalent attachment of sialic acid to the terminal residues of oligosaccharides and glycoproteins. This modification not only provides a layer of electrostatic repulsion to cells but also serves as a receptor for various biological signaling pathways. Sialylation is involved in several pathophysiological processes. Given its multifaceted involvement in cellular functions, sialylation presents a promising avenue for therapeutic intervention. Current studies are exploring agents that target sialic acid residues on sialoglycans or the sialylation process. These efforts are particularly focused on the fields of cancer therapy, stroke treatment, antiviral strategies, and therapies for central nervous system disorders. In this review, we aimed to summarize the biological functions of sialic acid and the process of sialylation, explore their roles in various pathophysiological contexts, and discuss their potential applications in the development of novel therapeutics.

A Comprehensive Review of Molecular Mechanisms, Pharmacokinetics, Toxicology and Plant Sources of Juglanin: Current Landscape and Future Perspectives.

Juglanin (kaempferol 3-O-α-L-arabinofuranoside) is a flavonol glycoside occurring in many plants, including its commercial sources Juglans regia, Polygonum aviculare and Selliguea hastata. Recent extensive studies have explored the potential of using juglanin in various pathological conditions, including cardiovascular disorders, central nervous and skeletal system disorders, metabolic syndrome, hepatic injury, and cancers. The results indicated a wide range of effects, like anti-inflammatory, anti-oxidant, anti-fibrotic, anti-thrombotic, anti-angiogenic, hepatoprotective, hypolipidemic, hypoglycemic, anti-apoptotic (normal cells), and pro-apoptotic (cancer cells). The health-promoting properties of juglanin can be attributed to its influence on many signaling pathways, associated with SIRT1, AMPK, Nrf2, STING, TLR4, MAPKs, NF-κB, AKT, JAK, and their downstream genes. This review primarily summarizes the current knowledge of molecular mechanisms, pharmacokinetics, biocompatibility, and human use safety of juglanin. In addition, the most promising new plant sources and other existing challenges and prospects have also been reviewed and discussed, aiming to provide direction and rationale for the further development and broader pharmaceutical application of juglanin.

An Overview of the Components, Techniques, and Innovation Used for Fast-Dissolving Films.

Fast-dissolving films (FDFs) stand as a cornerstone in modern pharmaceutical innovation, heralded for their unrivaled convenience, patient adherence, and the swift onset of action. Within the realm of this paper lies a meticulous exploration of FDFs, delving deep into their intricate formulation intricacies, manufacturing methodologies, and diverse therapeutic applications. The formulation journey traverses the meticulous selection of film-forming polymers, plasticizers, taste-masking agents, and active pharmaceutical ingredients (APIs), each element meticulously calibrated to achieve optimal efficacy. Diverse production techniques, spanning solvent casting, hot melt extrusion, and spray drying, are scrutinized with precision, shedding light on their inherent advantages and nuanced limitations. Beyond the realm of formulation and manufacturing, this review embarks on an expansive voyage into the vast therapeutic landscape that FDFs traverse. From the treatment areas of central nervous system disorders to the realms of cardiovascular diseases, allergies, and pain management, the versatility and adaptability of FDFs emerge as a beacon of hope for patients and practitioners alike. Yet, amidst the brilliance of FDFs, inherent challenges linger, from stability concerns to the intricate dance of bioavailability and the ever-watchful eye of regulatory scrutiny. However, within these challenges lies the fertile ground for future research and development endeavors, beckoning forth a new era of innovation and advancement in the realm of rapidly dissolving films. This study stands as an indispensable compass, guiding researchers, pharmaceutical scientists, and practitioners toward the forefront of FDF development and implementation.

Nanoparticles in CNS Therapeutics: Pioneering Drug Delivery Advancements.

The incidence of Central Nervous System (CNS) disorders, including Parkinson's disease, Alzheimer's disease, stroke, and malignancies, has risen significantly in recent decades, contributing to millions of deaths annually. Efficacious treatment of these disorders requires medicines targeting the brain. The Blood-Brain Barrier (BBB) poses a formidable challenge to effective drug delivery to the brain, hindering progress in CNS therapeutics. This review explores the latest developments in nanoparticulate carriers, highlighting their potential to overcome BBB limitations. This study aimed to evaluate and summarise the critical factors and pathways in the nanoparticle- based central nervous system's targeted drug delivery. An extensive literature search was conducted, comprising the initial development of nanoparticle- based central nervous system-targeted drug delivery approaches to the latest advancements using various online search tools. The properties of nanoparticles, such as type of nanoparticles, size, shape, surface charge, hydrophobicity, and surface functionalisation, along with properties of the blood-brain barrier during normal and pathological conditions and their impact on the delivery of nanoparticles across the BBB, are identified and discussed here. Important properties and pathways that determine the penetration of nanoparticles across the central nervous system are reviewed in this article, along with recent advances in the field.

Innovative glycochenodeoxycholic Acid-Acrylamide Nanopolymer carriers: Regulating upper critical solution temperature on neurorehabilitation

Neurorehabilitation focuses on restoring function in patients with central and peripheral nervous system disorders, yet effective therapeutic options remain scarce. This study introduces a novel nanocopolymer, CaCO3-PAAm-GDCA, synthesized through reversible addition-fragmentation chain transfer polymerization of glycodeoxycholic acid, acrylamide, and CaCO3. This nanocopolymer exhibits a sharp and reversible insoluble-to-soluble transition in water at a temperature related to its upper critical solution temperature (UCST), which can be finely adjusted to a practical range around 37 °C, suitable for biomedical applications. The addition of β-cyclodextrin (β-CD) modulates this transition temperature by forming host-guest complexes, further enhancing the copolymer’s adaptability. When loaded with compound 1, the resulting CaCO3-PAAm-GDCA@1 significantly promoted the proliferation of damaged neuronal HT22 cells and inhibited ferroptosis through the modulation of Nrf2 and GPX4 pathways. This study provides a strong foundation for the development of neuroprotective drugs, highlighting the potential of tailored nanocopolymers in advanced neurorehabilitation therapies.

Acute disseminated encephalomyelitis in a five-year-old girl: a case report

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating central nervous system disorder with a predilection to early childhood. ADEM is generally considered a monophasic disease. However, recurrence has been described and defined as multiphasic disseminated encephalomyelitis (MDEM). ADEM often occurs after infection or immunization and is clinically defined as acute polyfocal neurological deficits, including encephalopathy. Many times, ADEM is a diagnosis of exclusion, and early diagnosis and treatment are the keys to favorable outcomes. Magnetic resonance imaging (MRI) typically demonstrates reversible, large, ill-defined white matter lesions of the brain and often also the spinal cord, along with frequent involvement of thalami and basal ganglia. CSF analysis may reveal mild pleocytosis and elevated protein but is generally negative for intrathecal oligoclonal bands. We report a case of five years six-month- old girl who presented with fever, vomiting, headache, and cough for seven days. She had one episode of involuntary passage of urine. The child was lethargic at presentation and was unable to stand or walk. Clinical features and investigations, including MRI brain and spine, were suggestive of ADEM. She was started on Inj. Methylprednisolone followed by oral prednisolone in tapering dose for four weeks. Clinical improvement was seen in the form of improvement in activity and power in limbs. The child improved with normal neurological function on day three of inj methylprednisolone. On follow-up for six months, the child did not have any relapse and had complete neurological and radiological recovery.