Pub Date : 2025-03-01DOI: 10.1016/j.dscb.2025.100204
André Aires Fernandes , Fátima Hierro , Frederico Garret , Andreia Costa , Carolina Soares
Introduction
The link between reversible posterior encephalopathy syndrome (PRES) and certain drugs is well documented, especially for immunosuppressive and/or cytotoxic drugs. Metamizole is a non-opioid analgesic whose exact mechanism of action is still not fully understood, but it seems to involve the inhibition of prostaglandin synthesis. Prostaglandins are important vasoactive molecules involved in either arterial vasoconstriction and vasodilation, thus may promote loss of autoregulation of vascular circulation.
Methods
Description of a case of PRES after metamizole intake.
Results
An 18-year-old female with no significant medical history presented to the emergency department with new-onset generalized tonic-clonic seizures and visual disturbances. After reviewing the patient's medical records and brain MRI findings, the diagnosis of PRES was suspected, and classical precipitants were ruled out. However, the ingestion of metamizole was found to be the only plausible precipitating factor. The patient was treated with nimodipine 60 mg every 4 h and started on levetiracetam 500 mg twice daily. She was discharged asymptomatic and normotensive. The follow-up brain MRI performed three months after discharge was unremarkable.
Conclusions
This case-report may suggest a new pharmacological precipitant associated with PRES. Our hypothesis is that endothelial dysfunction resulting from the inhibition of the prostaglandin pathway may lead to the disruption of blood-brain barrier permeability, resulting in the loss of autoregulation of vascular circulation.
{"title":"Reversible posterior encephalopathy syndrome and metamizole: A new pharmacological precipitant?","authors":"André Aires Fernandes , Fátima Hierro , Frederico Garret , Andreia Costa , Carolina Soares","doi":"10.1016/j.dscb.2025.100204","DOIUrl":"10.1016/j.dscb.2025.100204","url":null,"abstract":"<div><h3>Introduction</h3><div>The link between reversible posterior encephalopathy syndrome (PRES) and certain drugs is well documented, especially for immunosuppressive and/or cytotoxic drugs. Metamizole is a non-opioid analgesic whose exact mechanism of action is still not fully understood, but it seems to involve the inhibition of prostaglandin synthesis. Prostaglandins are important vasoactive molecules involved in either arterial vasoconstriction and vasodilation, thus may promote loss of autoregulation of vascular circulation.</div></div><div><h3>Methods</h3><div>Description of a case of PRES after metamizole intake.</div></div><div><h3>Results</h3><div>An 18-year-old female with no significant medical history presented to the emergency department with new-onset generalized tonic-clonic seizures and visual disturbances. After reviewing the patient's medical records and brain MRI findings, the diagnosis of PRES was suspected, and classical precipitants were ruled out. However, the ingestion of metamizole was found to be the only plausible precipitating factor. The patient was treated with nimodipine 60 mg every 4 h and started on levetiracetam 500 mg twice daily. She was discharged asymptomatic and normotensive. The follow-up brain MRI performed three months after discharge was unremarkable.</div></div><div><h3>Conclusions</h3><div>This case-report may suggest a new pharmacological precipitant associated with PRES. Our hypothesis is that endothelial dysfunction resulting from the inhibition of the prostaglandin pathway may lead to the disruption of blood-brain barrier permeability, resulting in the loss of autoregulation of vascular circulation.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100204"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.dscb.2025.100206
Ashmita Das , Durlav Chowdhury , Dilip Sharma , Rahul Manna , Surendra H. Bodakhe
The literature documents the ability of oxysterols and TGFβ to cause fibrotic damage in the brain. Our study explores the potential mechanisms of oxysterol interactions with fibrotic mediators in Alzheimer's disease. It focuses on peripherally formed oxysterols and their effects on TGFβ hyperactivation in an experimental rodent model of Alzheimer's disease. We fed experimental rats a high-cholesterol diet for eight weeks and evaluated their cognitive abilities weekly using Hebb's Williams and Radial arm mazes. Using ELISA, we measured plasma and brain oxysterols, transforming growth factor β, amyloid β, matrix metalloproteinase-9, claudin-5, and ATP Binding Cassette Transporter A1 expressions biweekly. The concentrations high density lipoprotein, low density lipoprotein, aspartate aminotransferase, and alanine transaminase were assessed using diagnostic kits, while the antioxidant profile was determined using UV spectroscopy. Our results indicated a synergistic increase in oxysterols, transforming growth factor β, amyloid β, matrix metalloproteinase-9, low density lipoprotein, aspartate aminotransferase, and alanine transaminase, with a concomitant decrease in the experimental animals' Claudin-5, ATP Binding Cassette Transporter A1, high density lipoprotein and antioxidant regulations. These findings suggest that a high-cholesterol diet may lead to oxysterol buildup, resulting in amyloid β accumulation due to transforming growth factor β hyperactivation. In conclusion, our study highlights the need to explore the role of oxysterols in the pathogenesis of Alzheimer's disease. By uncovering potential mechanisms underlying the interplay of oxysterols with fibrotic mediators, our study may pave the way for developing novel therapeutic approaches to manage Alzheimer's disease.
{"title":"A high cholesterol diet accelerates Alzheimer's progression by promoting fibrotic damage in rats","authors":"Ashmita Das , Durlav Chowdhury , Dilip Sharma , Rahul Manna , Surendra H. Bodakhe","doi":"10.1016/j.dscb.2025.100206","DOIUrl":"10.1016/j.dscb.2025.100206","url":null,"abstract":"<div><div>The literature documents the ability of oxysterols and TGFβ to cause fibrotic damage in the brain. Our study explores the potential mechanisms of oxysterol interactions with fibrotic mediators in Alzheimer's disease. It focuses on peripherally formed oxysterols and their effects on TGFβ hyperactivation in an experimental rodent model of Alzheimer's disease. We fed experimental rats a high-cholesterol diet for eight weeks and evaluated their cognitive abilities weekly using Hebb's Williams and Radial arm mazes. Using ELISA, we measured plasma and brain oxysterols, transforming growth factor β, amyloid β, matrix metalloproteinase-9, claudin-5, and ATP Binding Cassette Transporter A1 expressions biweekly. The concentrations high density lipoprotein, low density lipoprotein, aspartate aminotransferase, and alanine transaminase were assessed using diagnostic kits, while the antioxidant profile was determined using UV spectroscopy. Our results indicated a synergistic increase in oxysterols, transforming growth factor β, amyloid β, matrix metalloproteinase-9, low density lipoprotein, aspartate aminotransferase, and alanine transaminase, with a concomitant decrease in the experimental animals' Claudin-5, ATP Binding Cassette Transporter A1, high density lipoprotein and antioxidant regulations. These findings suggest that a high-cholesterol diet may lead to oxysterol buildup, resulting in amyloid β accumulation due to transforming growth factor β hyperactivation. In conclusion, our study highlights the need to explore the role of oxysterols in the pathogenesis of Alzheimer's disease. By uncovering potential mechanisms underlying the interplay of oxysterols with fibrotic mediators, our study may pave the way for developing novel therapeutic approaches to manage Alzheimer's disease.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><div>This case report describes the clinical case of a patient with Canavan Syndrome, a condition characterized by high mortality in infancy, who reached the age of 32. The article focuses on the patient's medical history, clinical and instrumental evaluations, and the treatment administered, then compares the patient's clinical history with that of other individuals affected by the same disease, and finally assesses the various treatment options and future therapeutic prospects for this condition. Canavan disease is a rare, progressive, autosomal recessive disorder that begins in infancy or early childhood [<span><span>1</span></span>,<span><span>2</span></span>]. It is caused by genetic mutation in the aspartoacylase (ASPA) gene, which encodes a metabolic enzyme synthesized by oligodendrocytes in the brain. ASPA mutations lead to a deficiency of the enzyme aspartoacylase resulting in accumulation of N-Acetylaspartic acid in the brain. This accumulation will result in oligodendrocyte dysfunction, axonal myelin degeneration and cerebral spongiform changes [<span><span>3</span></span>]. Sufficient data is unavailable to calculate the prevalence [<span><span>4</span></span>]. The neonatal form is the most common (85–90%) and is usually associated with the most severe symptoms while a less severe atypical Canavan disease (10%-15%) is associated with onset from infancy to adolescence, milder development delay, with or without regression. Typical features of the neonatal form include lethargy, listlessness, weak cry and suck, a lack of head control when the baby is pulled from a lying to a sitting position, hypotonia, poor visual tracking or blindness, vomiting, and seizures. Macrocephaly becomes prominent by the age of three to six months, and hypotonia eventually progresses to spasticity, hyperreflexia, extensor plantar responses, and tonic extensor spasms. It can also be present blindness due to optic atrophy. [<span><span>5</span></span>] No consensus clinical diagnostic criteria for Canavan disease have been established. Diagnosis is based on compatible clinical features and neuroimaging findings (spongiform degeneration and edema of the white matter, brain enlargement) associated with elevated levels of urine NAA and, on proton magnetic resonance spectroscopy (1/H-MRS), an increase in NAA, a reduction in Cr and choline, and an increase in lactate levels [<span><span>6</span></span>,<span><span>7</span></span>]. The molecular diagnosis of Canavan disease is established in a proband with biallelic pathogenic variant in the ASPA gene identified by molecular genetic testing [<span><span>8</span></span>]. There is no cure for Canavan disease. Supportive treatment is recommended, in particular to provide adequate hydration and nutrition, managing the risk of infections and protecting the airway [<span><span>6</span></span>]. Prognosis is variable, although most people with the neonatal/infantile form die in the first two decades of life. [<span><
{"title":"A rare case of a long-lived patient with Canavan syndrome","authors":"Giuseppe Liardi , Salvatore Dongiovanni , Michelangelo Carucci , Valentina Andreozzi , Connye Mattera , Federica Quadro , Gennaro Calafiore , Sabrina Gentile , Nicoletta Liardi","doi":"10.1016/j.dscb.2025.100200","DOIUrl":"10.1016/j.dscb.2025.100200","url":null,"abstract":"<div><div>This case report describes the clinical case of a patient with Canavan Syndrome, a condition characterized by high mortality in infancy, who reached the age of 32. The article focuses on the patient's medical history, clinical and instrumental evaluations, and the treatment administered, then compares the patient's clinical history with that of other individuals affected by the same disease, and finally assesses the various treatment options and future therapeutic prospects for this condition. Canavan disease is a rare, progressive, autosomal recessive disorder that begins in infancy or early childhood [<span><span>1</span></span>,<span><span>2</span></span>]. It is caused by genetic mutation in the aspartoacylase (ASPA) gene, which encodes a metabolic enzyme synthesized by oligodendrocytes in the brain. ASPA mutations lead to a deficiency of the enzyme aspartoacylase resulting in accumulation of N-Acetylaspartic acid in the brain. This accumulation will result in oligodendrocyte dysfunction, axonal myelin degeneration and cerebral spongiform changes [<span><span>3</span></span>]. Sufficient data is unavailable to calculate the prevalence [<span><span>4</span></span>]. The neonatal form is the most common (85–90%) and is usually associated with the most severe symptoms while a less severe atypical Canavan disease (10%-15%) is associated with onset from infancy to adolescence, milder development delay, with or without regression. Typical features of the neonatal form include lethargy, listlessness, weak cry and suck, a lack of head control when the baby is pulled from a lying to a sitting position, hypotonia, poor visual tracking or blindness, vomiting, and seizures. Macrocephaly becomes prominent by the age of three to six months, and hypotonia eventually progresses to spasticity, hyperreflexia, extensor plantar responses, and tonic extensor spasms. It can also be present blindness due to optic atrophy. [<span><span>5</span></span>] No consensus clinical diagnostic criteria for Canavan disease have been established. Diagnosis is based on compatible clinical features and neuroimaging findings (spongiform degeneration and edema of the white matter, brain enlargement) associated with elevated levels of urine NAA and, on proton magnetic resonance spectroscopy (1/H-MRS), an increase in NAA, a reduction in Cr and choline, and an increase in lactate levels [<span><span>6</span></span>,<span><span>7</span></span>]. The molecular diagnosis of Canavan disease is established in a proband with biallelic pathogenic variant in the ASPA gene identified by molecular genetic testing [<span><span>8</span></span>]. There is no cure for Canavan disease. Supportive treatment is recommended, in particular to provide adequate hydration and nutrition, managing the risk of infections and protecting the airway [<span><span>6</span></span>]. Prognosis is variable, although most people with the neonatal/infantile form die in the first two decades of life. [<span><","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100200"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.dscb.2025.100199
G. Nunn , G. Simkovics , K. Hird , K. Beer , I. Cooper , M. Needham
This cross-sectional study aimed to explore the relationships between physical disability, depression, and wellbeing in people with inclusion body myositis, a rare and progressively disabling muscle disease. The study investigated the relative influence of physical disability and depression on an individual's wellbeing. The Neuromuscular Symptom Score, Personal Wellbeing Index, and Patient Health Questionnaire surveys were used as measures of physical disability, wellbeing, and depression respectively. Surveys were administered via an online questionnaire to inclusion body myositis patients across Australia. One hundred and one participants completed the study. Linear regression identified that depression scores were significantly correlated with wellbeing, however physical disability scores were not, with a negative predictive value of depression for wellbeing (-2.7513, p < 0.001) and a positive predictive value of disability for wellbeing (0.0575, p = 0.764). Moderate to severe depression was reported in 78.2 % of participants, and all but one participant reported reduced wellbeing. The study found that depression scores are a stronger predictor of wellbeing versus physical disability in inclusion body myositis. The study also identified a high prevalence of depression and reduced wellbeing in participants, highlighting the significance of the impact of mental health in people living with this disease.
{"title":"Mind over matter? A cross-sectional study exploring the influence of depression versus physical disability on patient-reported wellbeing in inclusion body myositis","authors":"G. Nunn , G. Simkovics , K. Hird , K. Beer , I. Cooper , M. Needham","doi":"10.1016/j.dscb.2025.100199","DOIUrl":"10.1016/j.dscb.2025.100199","url":null,"abstract":"<div><div>This cross-sectional study aimed to explore the relationships between physical disability, depression, and wellbeing in people with inclusion body myositis, a rare and progressively disabling muscle disease. The study investigated the relative influence of physical disability and depression on an individual's wellbeing. The Neuromuscular Symptom Score, Personal Wellbeing Index, and Patient Health Questionnaire surveys were used as measures of physical disability, wellbeing, and depression respectively. Surveys were administered via an online questionnaire to inclusion body myositis patients across Australia. One hundred and one participants completed the study. Linear regression identified that depression scores were significantly correlated with wellbeing, however physical disability scores were not, with a negative predictive value of depression for wellbeing (-2.7513, <em>p</em> < 0.001) and a positive predictive value of disability for wellbeing (0.0575, <em>p</em> = 0.764). Moderate to severe depression was reported in 78.2 % of participants, and all but one participant reported reduced wellbeing. The study found that depression scores are a stronger predictor of wellbeing versus physical disability in inclusion body myositis. The study also identified a high prevalence of depression and reduced wellbeing in participants, highlighting the significance of the impact of mental health in people living with this disease.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100199"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.dscb.2025.100202
Ramakrishnan Veerabathiran, B.K. Iyshwarya
Epilepsy is a neurological illness that affects over 50 million individuals worldwide. An epileptic disease is a neurological condition characterized by frequent seizures. Seizures occur when brain activity spikes abruptly and abnormally, altering movement, perception, or behavior. Several genes may be associated with epilepsy, according to research currently being conducted. We sought to identify the genes associated with sudden, unexpected mortality in epilepsy and malformations of the cortical development related to epilepsy. Detailed analyses of each gene process have been conducted better to understand its probable mechanism and relationship to epilepsy. Since analyzing family studies and refining computational methods, we have better understood how genetics may influence epilepsy. Although genetic factors may play a role in epilepsy development, the origins and consequences of epilepsy are still unknown. The study of genes associated with epilepsy is necessary to understand better how genetics and epilepsy are connected. Several epilepsy genes have been identified due to advances in genetic research. These insights enable genetic diagnostics to be incorporated into clinical practice and assist in diagnosing and treating epilepsy.
{"title":"Identification of novel epilepsy genetics and development of advanced diagnostic approaches","authors":"Ramakrishnan Veerabathiran, B.K. Iyshwarya","doi":"10.1016/j.dscb.2025.100202","DOIUrl":"10.1016/j.dscb.2025.100202","url":null,"abstract":"<div><div>Epilepsy is a neurological illness that affects over 50 million individuals worldwide. An epileptic disease is a neurological condition characterized by frequent seizures. Seizures occur when brain activity spikes abruptly and abnormally, altering movement, perception, or behavior. Several genes may be associated with epilepsy, according to research currently being conducted. We sought to identify the genes associated with sudden, unexpected mortality in epilepsy and malformations of the cortical development related to epilepsy. Detailed analyses of each gene process have been conducted better to understand its probable mechanism and relationship to epilepsy. Since analyzing family studies and refining computational methods, we have better understood how genetics may influence epilepsy. Although genetic factors may play a role in epilepsy development, the origins and consequences of epilepsy are still unknown. The study of genes associated with epilepsy is necessary to understand better how genetics and epilepsy are connected. Several epilepsy genes have been identified due to advances in genetic research. These insights enable genetic diagnostics to be incorporated into clinical practice and assist in diagnosing and treating epilepsy.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100202"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prader-Willi Syndrome is typically caused by paternal deletion of chromosome 15q11-q13. It involves multiple systems and is commonly associated with hypotonia, global developmental delay, and endocrine abnormalities. Seizures are less frequently reported in individuals with Prader-Willi syndrome. Here, we present a rare case of a 3-year-old boy presenting with early-onset tonic seizures, global developmental delay, and an EEG showing a Lennox-Gastaut Syndrome-like pattern. Notably, brain MRI results were normal. This case represents previously unreported co-occurrence of Lennox-Gastaut Syndrome in a pediatric patient with Prader-Willi Syndrome.
{"title":"Lennox-gastaut syndrome in a pediatric patient with prader-willi syndrome: A case report and review","authors":"Raidah Albaradie , Sharook Alhawaj , Wojod Alothman , Shahid Bashir","doi":"10.1016/j.dscb.2025.100201","DOIUrl":"10.1016/j.dscb.2025.100201","url":null,"abstract":"<div><div>Prader-Willi Syndrome is typically caused by paternal deletion of chromosome 15q11-q13. It involves multiple systems and is commonly associated with hypotonia, global developmental delay, and endocrine abnormalities. Seizures are less frequently reported in individuals with Prader-Willi syndrome. Here, we present a rare case of a 3-year-old boy presenting with early-onset tonic seizures, global developmental delay, and an EEG showing a Lennox-Gastaut Syndrome-like pattern. Notably, brain MRI results were normal. This case represents previously unreported co-occurrence of Lennox-Gastaut Syndrome in a pediatric patient with Prader-Willi Syndrome.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100201"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alzheimer's disease is a neurodegenerative disorder which impacts millions of individuals worldwide, is driven by cholinergic neuron degeneration. The current research examined taxifolin's neuroprotective effects against scopolamine-induced dementia in rats.
Methods
Twenty male Sprague-Dawley rats were assigned into four groups (5 rats/group). Group I (control group) and Group II (disease group) received saline intraperitoneally for five days. Group III (treatment group) received taxifolin (5 mg/kg, i.p.) for five days. Group IV (positive control) received donepezil (2 mg/kg, i.p.) for five days. Except Group I all the other Groups received scopolamine (2 mg/kg, i.p.) on day five. Cognitive abilities were evaluated using the Y-maze, Morris water maze, and Cook's pole climbing tests. Post-euthanasia, brain samples were analysed for acetylcholinesterase activity, oxidative stress markers (lipid peroxidation, nitrite levels), antioxidant enzymes (superoxide dismutase, catalase, reduced glutathione), and inflammation (myeloperoxidase activity). Molecular docking was performed to evaluate taxifolin's binding with acetylcholinesterase. In silico studies were done to analyse pharmacokinetic and toxicological properties of taxifolin.
Results
Scopolamine caused memory impairment, altered the brain's histopathology, increased acetylcholinesterase activity, lipid peroxidation, nitrite levels, and myeloperoxidase activity, while altering antioxidant enzymes. Taxifolin pre-treatment reversed these alterations, improving cognitive function, reducing oxidative stress and inflammation, and restoring antioxidant enzymes. Molecular docking showed taxifolin inhibited acetylcholinesterase with a docking score of 55, while in silico studies revealed favourable pharmacokinetic and toxicological profiles.
Conclusion
Taxifolin effectively mitigates scopolamine-induced cognitive and biochemical impairments, suggesting its potential as a therapeutic candidate for Alzheimer's disease. Further studies are required to validate these findings.
{"title":"Unravelling the neuroprotective effects of taxifolin against scopolamine-induced dementia in male Sprague Dawley rats: A comprehensive preclinical investigation","authors":"Heena Chauhan , Bhavya Nakum , Udit Chaube , Bhagawati Saxena","doi":"10.1016/j.dscb.2025.100203","DOIUrl":"10.1016/j.dscb.2025.100203","url":null,"abstract":"<div><h3>Background/objective</h3><div>Alzheimer's disease is a neurodegenerative disorder which impacts millions of individuals worldwide, is driven by cholinergic neuron degeneration. The current research examined taxifolin's neuroprotective effects against scopolamine-induced dementia in rats.</div></div><div><h3>Methods</h3><div>Twenty male Sprague-Dawley rats were assigned into four groups (5 rats/group). <strong>Group I (control group)</strong> and <strong>Group II (disease group)</strong> received saline intraperitoneally for five days. <strong>Group III (treatment group)</strong> received taxifolin (5 mg/kg, <em>i.p.</em>) for five days. <strong>Group IV (positive control)</strong> received donepezil (2 mg/kg, <em>i.p.</em>) for five days. Except Group I all the other Groups received scopolamine (2 mg/kg, <em>i.p.</em>) on day five. Cognitive abilities were evaluated using the Y-maze, Morris water maze, and Cook's pole climbing tests. Post-euthanasia, brain samples were analysed for acetylcholinesterase activity, oxidative stress markers (lipid peroxidation, nitrite levels), antioxidant enzymes (superoxide dismutase, catalase, reduced glutathione), and inflammation (myeloperoxidase activity). Molecular docking was performed to evaluate taxifolin's binding with acetylcholinesterase. <em>In silico</em> studies were done to analyse pharmacokinetic and toxicological properties of taxifolin.</div></div><div><h3>Results</h3><div>Scopolamine caused memory impairment, altered the brain's histopathology, increased acetylcholinesterase activity, lipid peroxidation, nitrite levels, and myeloperoxidase activity, while altering antioxidant enzymes. Taxifolin pre-treatment reversed these alterations, improving cognitive function, reducing oxidative stress and inflammation, and restoring antioxidant enzymes. Molecular docking showed taxifolin inhibited acetylcholinesterase with a docking score of 55, while <em>in silico</em> studies revealed favourable pharmacokinetic and toxicological profiles.</div></div><div><h3>Conclusion</h3><div>Taxifolin effectively mitigates scopolamine-induced cognitive and biochemical impairments, suggesting its potential as a therapeutic candidate for Alzheimer's disease. Further studies are required to validate these findings.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100203"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.dscb.2025.100205
Dr Amina Hameed, Dr Khurram Khaliq Bhinder, Dr Aroosa Kanwal, Dr Namrah Khalid, Dr Ranam Akhtar
The absence of the vermis and the continuity of the cerebellar hemispheres, dentate nuclei, and superior cerebellar peduncles are the hallmarks of rhombencephalosynapsis, a congenital disorder of the cerebellum. It has varying degrees of neurological damage and can occur as a single aberration (rare) or as a component of a larger brain malformation. We present a case of a young adult with two year history of unusual behaviors and falls, who on MRI was diagnosed with rhombencephalosynapsis. Our case demonstrates the common characteristics of RES and the critical function of MRI in diagnosis and treatment.
{"title":"Rare case of rhombencephalosynapsis (RES); Case report and literature review","authors":"Dr Amina Hameed, Dr Khurram Khaliq Bhinder, Dr Aroosa Kanwal, Dr Namrah Khalid, Dr Ranam Akhtar","doi":"10.1016/j.dscb.2025.100205","DOIUrl":"10.1016/j.dscb.2025.100205","url":null,"abstract":"<div><div>The absence of the vermis and the continuity of the cerebellar hemispheres, dentate nuclei, and superior cerebellar peduncles are the hallmarks of rhombencephalosynapsis, a congenital disorder of the cerebellum. It has varying degrees of neurological damage and can occur as a single aberration (rare) or as a component of a larger brain malformation. We present a case of a young adult with two year history of unusual behaviors and falls, who on MRI was diagnosed with rhombencephalosynapsis. Our case demonstrates the common characteristics of RES and the critical function of MRI in diagnosis and treatment.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100205"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-17DOI: 10.1016/j.dscb.2025.100198
Anika Siamin Oyshi , Mohammad Hasan , Md. Khabir Uddin Ahamed , Md. Sydur Rahman , Md. Mahfuzul Haque , Mahmudul Alam
Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent mental disorder affecting both adults and children, frequently leading to academic difficulties. This study aims to improve the diagnosis of ADHD in children by using resting-state Functional Magnetic Resonance Imaging (fMRI) data. The method use seed coherence to identify functional connections between specific seed areas and all brain voxels, focusing on Default Mode Network (DMN) regions pertinent to the diagnosis of ADHD. Convolutional Neural Networks (CNNs) are utilized in classification tasks because of their capacity to learn intricate spatial hierarchies. The research utilizes fMRI scans from the ADHD 200 - Global Competitive dataset, comprising 776 subjects from three prominent data centers. The methodology entails data preparation, feature extraction via seed-based correlation, and classification with Convolutional Neural Networks (CNNs). Three classifiers were assessed: a Neural Network (Keras Sequential Model), a Support Vector Machine (SVM), and a Random Forest Classifier. The optimal outcome was achieved by the neural network, which harmonized precision, recall, and F1 scores, attaining an accuracy of 97 %. The SVM demonstrated considerable accuracy at 83 %, however the Random Forest Classifier exhibited a mere 50 % accuracy, underscoring the necessity for enhancement. These results underscore the merits and shortcomings of each classifier and offer suggestions for enhancement. The paper highlights the significance of Neural Networks for attaining precise and equitable forecasts, proposes enhancements for the Support Vector Machine, and stresses the imperative of optimizing the Random Forest Classifier. This study enhances ADHD diagnosis by methodically employing neuroimaging techniques and assessing several classifiers, leading to a reliable diagnostic system.
{"title":"Attention Deficit Hyperactivity Disorder identification: FMRI data analyzed with CNN and seed-based approach","authors":"Anika Siamin Oyshi , Mohammad Hasan , Md. Khabir Uddin Ahamed , Md. Sydur Rahman , Md. Mahfuzul Haque , Mahmudul Alam","doi":"10.1016/j.dscb.2025.100198","DOIUrl":"10.1016/j.dscb.2025.100198","url":null,"abstract":"<div><div>Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent mental disorder affecting both adults and children, frequently leading to academic difficulties. This study aims to improve the diagnosis of ADHD in children by using resting-state Functional Magnetic Resonance Imaging (fMRI) data. The method use seed coherence to identify functional connections between specific seed areas and all brain voxels, focusing on Default Mode Network (DMN) regions pertinent to the diagnosis of ADHD. Convolutional Neural Networks (CNNs) are utilized in classification tasks because of their capacity to learn intricate spatial hierarchies. The research utilizes fMRI scans from the ADHD 200 - Global Competitive dataset, comprising 776 subjects from three prominent data centers. The methodology entails data preparation, feature extraction via seed-based correlation, and classification with Convolutional Neural Networks (CNNs). Three classifiers were assessed: a Neural Network (Keras Sequential Model), a Support Vector Machine (SVM), and a Random Forest Classifier. The optimal outcome was achieved by the neural network, which harmonized precision, recall, and F1 scores, attaining an accuracy of 97 %. The SVM demonstrated considerable accuracy at 83 %, however the Random Forest Classifier exhibited a mere 50 % accuracy, underscoring the necessity for enhancement. These results underscore the merits and shortcomings of each classifier and offer suggestions for enhancement. The paper highlights the significance of Neural Networks for attaining precise and equitable forecasts, proposes enhancements for the Support Vector Machine, and stresses the imperative of optimizing the Random Forest Classifier. This study enhances ADHD diagnosis by methodically employing neuroimaging techniques and assessing several classifiers, leading to a reliable diagnostic system.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100198"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Influenza cerebellitis is an extremely rare disease with limited understanding of its clinical course, treatment, and neurological outcomes. An 8-year-old girl presented with fever and was diagnosed with type A influenza. She later developed altered mental status on day three, leading to hospitalization on day four. Upon hospitalization, cerebrospinal fluid (CSF) analysis revealed increased white blood cell counts and protein levels, and magnetic resonance imaging (MRI) showed high-intensity signals at the splenium of the corpus callosum (SCC), suggestive of mild encephalitis/encephalopathy with a reversible splenial lesion. However, arterial spin labeling (ASL) revealed increased cerebellar blood flow, raising suspicion of acute cerebellitis. Intravenous methylprednisolone pulse therapy was administered. Despite fever resolution, the patient's impaired consciousness persisted. MRI on day eight showed new lesions in the bilateral cerebellar hemisphere, white matter, and dentate nuclei instead of splenial lesion disappearance, suggesting acute cerebellitis. The patient received intravenous immunoglobulin G and repeated methylprednisolone pulse therapy, which led to gradual improvement. MRI on day 32 revealed lesion resolution. The patient was discharged with neurological sequelae (dysarthria and slight dysmetria), which improved completely after two months. This is the second reported pediatric case of influenza cerebellitis with a reversible SCC lesion, which presented with atypical neutrophilic pleocytosis on CSF analysis and unique findings on initial MRI. This case highlights the importance of early diagnosis and treatment of influenza cerebellitis. Repeat MRI, including ASL, should be considered in suspected cases of influenza-related encephalitis/encephalopathy. Further research is needed to establish optimal diagnostic and treatment strategies for influenza cerebellitis.
{"title":"Acute cerebellitis with a reversible splenial lesion in a pediatric patient with influenza","authors":"Yuki Kawashima , Rui Aoyagi , Yusa Nagai , Masahiro Noda , Kunihiro Oba , Tatsuo Katori , Masashi Ogasawara","doi":"10.1016/j.dscb.2025.100197","DOIUrl":"10.1016/j.dscb.2025.100197","url":null,"abstract":"<div><div>Influenza cerebellitis is an extremely rare disease with limited understanding of its clinical course, treatment, and neurological outcomes. An 8-year-old girl presented with fever and was diagnosed with type A influenza. She later developed altered mental status on day three, leading to hospitalization on day four. Upon hospitalization, cerebrospinal fluid (CSF) analysis revealed increased white blood cell counts and protein levels, and magnetic resonance imaging (MRI) showed high-intensity signals at the splenium of the corpus callosum (SCC), suggestive of mild encephalitis/encephalopathy with a reversible splenial lesion. However, arterial spin labeling (ASL) revealed increased cerebellar blood flow, raising suspicion of acute cerebellitis. Intravenous methylprednisolone pulse therapy was administered. Despite fever resolution, the patient's impaired consciousness persisted. MRI on day eight showed new lesions in the bilateral cerebellar hemisphere, white matter, and dentate nuclei instead of splenial lesion disappearance, suggesting acute cerebellitis. The patient received intravenous immunoglobulin G and repeated methylprednisolone pulse therapy, which led to gradual improvement. MRI on day 32 revealed lesion resolution. The patient was discharged with neurological sequelae (dysarthria and slight dysmetria), which improved completely after two months. This is the second reported pediatric case of influenza cerebellitis with a reversible SCC lesion, which presented with atypical neutrophilic pleocytosis on CSF analysis and unique findings on initial MRI. This case highlights the importance of early diagnosis and treatment of influenza cerebellitis. Repeat MRI, including ASL, should be considered in suspected cases of influenza-related encephalitis/encephalopathy. Further research is needed to establish optimal diagnostic and treatment strategies for influenza cerebellitis.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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