Mild Atrophy Research Articles

Pathological study of progressive supranuclear palsy the cases with mutations in Bassoon.

Clinical diagnosis of progressive supranuclear palsy (PSP) is difficult due to various phenotypes. Neuropathologically, PSP is defined by neuronal loss in the basal ganglia and brainstem with widespread occurrence of neurofibrillary tangles (NFTs) and accumulation of phosphorylated tau protein in neurons and glial cells in the brain. We previously identified the point mutation p.Pro3866Ala in the Bassoon (BSN) gene in a Japanese family with PSP-like syndrome. We newly detected BSN mutations in two autopsied PSP cases carrying p.Thr2542Met and p.Glu2759Gly, respectively. The case with p.Thr2542Met mutation showed neurological symptoms including behavioral abnormalities, cognitive dysfunction, and parkinsonism. Brain magnetic resonance imaging (MRI) showed atrophy of the midbrain tegmentum and hippocampus. Pathologically, moderate to severe loss of neurons with gliosis was also found in the substantia nigra, and there was an almost complete loss of neurons with gliosis in the transitional zone of the cornu ammonis (CA) 1 region to the subiculum. NFTs were observed in the globus pallidus, subthalamic nucleus, substantia nigra, and CA1. 4R tau-dominant tauopathy was detected. The case with p.Glu2759Gly mutation showed neurological symptoms, including right-dominant motor impairment, right limping gait, postural instability, and cognitive dysfunction. Brain MRI showed mild atrophy of the midbrain tegmentum and left-dominant parietal lobe atrophy. Pathologically, NFTs were detected in the globus pallidus, subthalamic nucleus, substantia nigra, thalamus, putamen, and brainstem tegmentum. Most neurons were immunopositive for four-repeat tau, whereas only a few of them harbored three-repeat tau-positive NFTs in the hippocampus. We showed the results of a pathological study of PSP cases with BSN mutations; these were two new cases. The clinical phenotypes were similar to the first case in the point of neurological symptoms. Accumulation of four-repeat tau was dominant. Further autopsies of BSN mutation cases and further elucidation of the molecular biological mechanism are desirable.

Case report: Double mutations in a patient with early-onset Alzheimer’s disease in China, PSEN2 and IDE variants

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by gradual cognitive decline. Early-onset Alzheimer’s disease (EOAD) is defined as AD occurring before age 65. The main pathogenic gene variants associated with EOAD include PSEN1, PSEN2, and APP. IDE gene has been identified as a risk factor in the pathogenesis of AD. In this study, we report a 33-year-old male with mutations in the PSEN2 gene (c.640G > T, p.V214L) and IDE gene (c.782G > A, p.R261Q). PSEN2 V214L has been reported in five previous cases, and no reported cases have carried IDE R261Q. He had progressive memory decline, his sister carried the same gene mutations but had no clinical manifestations. Neuroimaging revealed mild cortical atrophy. The concentration of Aβ42 in cerebrospinal fluid (CSF) was obviously decreased. In silico predictive models suggested that these mutations are damaging. Our findings indicate that mutations in the PSEN2 and IDE genes may disrupt the normal functioning of their respective proteins, contributing to the pathogenesis of AD.

A case of X-Linked adrenoleukodystrophy caused by a novel mutation with singular clinical manifestation: unilateral lower limb weakness.

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene, leading to the accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues. It primarily affects the central nervous system white matter and the adrenal cortex. Clinical manifestations include myeloneuropathy, leukodystrophy, and adrenal insufficiency. Reliable methods for diagnosis include VLCFAs and genetic testing. We report the case of a 31-year-old male X-ALD patient who mainly presented with unilateral lower limb weakness. Adrenal insufficiency was not observed, and there was no evidence of peripheral nerve involvement in nerve conduction studies. MRI revealed only mild atrophy of thoracic spinal cord without other relevant abnormalities. Ultimately, Next-Generation Sequencing (NGS) and VLCFAs testing confirmed the diagnosis of X-ALD, and the NGS indicated a novel missense mutation.

7289 An interesting case of Diabetes Mellitus Type 1 induced Renal Tubal Acidosis Type 1

Abstract Disclosure: R. Ripa: None. A. Itani: None. S.K. Patel: None. Introduction: Renal Tubular Acidosis (RTA) are a group of disorders that involve dysfunctional transporters and channels in the renal system. These disorders can be acquired (idiopathic, medication side effects, and medical disorders) or inherited. The most common type worldwide is type 4 RTA, the main cause is diabetic nephropathy leading to hypoaldosteronism. The association of type 1 RTA with diabetes has rarely been reported in studies. Here, we report the presentation, diagnosis and management of a rare case of type 1 RTA in a patient with a history of diabetes mellitus type 1. Case: A male in his 50s with a 30-year history of uncontrolled type 1 diabetes mellitus on insulin pump and coronary artery disease presented to his cardiologist with worsening chest pain, fatigue, polyuria, weight loss of 15 lbs, and recent insulin pump change. Blood tests revealed serum bicarbonate of 10 mmol/L and he was sent to the hospital. On examination, he was hypotensive and bradycardic with dry mouth and decreased skin turgor. His blood tests were consistent with type 1 RTA, he was treated with intravenous fluids containing bicarbonate plus potassium and transitioned to oral potassium citrate on discharge. He underwent renal biopsy as work up was unrevealing for a cause of type 1 RTA. Biopsy revealed normal glomeruli with negative immunofluorescence and Congo red stain. The biopsy, however, did show mild patchy chronic interstitial fibrosis with lymphocytes and mild tubular atrophy. At one year follow up, he remained on oral potassium citrate with resulting serum bicarbonate of 26 mmol/L and a normal renal function. Discussion: Diabetes mellitus can lead to a variety of renal pathologies, specifically metabolic acidosis that can be either seen as diabetic ketoacidosis or hyporeninemic hypoaldosteronism (Type 4 RTA). In our patient, despite being a diabetic, he did not present with either elevated anion gap, ketonuria or hyperkalemic hyperchloremic acidosis typical of type 4 RTA. He was noted to have hypokalemic hyperchloremic acidosis, with a positive urine anion gap, and an alkaline urine, all characteristic of type 1 RTA. Acquired distal RTA occurs more commonly due to certain medications or autoimmune diseases as in Sjögren’s syndrome. The relationship between distal RTA and Sjögren’s syndrome has already been established, unlike the relationship with type 1 diabetes. There have been few case reports of distal RTA in association with type 1 diabetes mellitus, implying a possible autoimmune pathology. Prior case reports also not only had patients who were insulin dependent, but diabetes was present for more than a decade at least suggesting chronicity of disease is needed. Traditional management consists of alkaline therapy and treatment of the underlying disease, or removal of offending medication. In this case, we hope to highlight distal RTA in a diabetic who doesn’t meet criteria for DKA or type 4 RTA. Presentation: 6/1/2024

Novel insights into presenilin 1 mutation associated with a distinctive dementia phenotype and cotton wool plaques.

The mutations in the presenilin 1 gene (PSEN1) are the main cause of familial Alzheimer's disease. PSEN1 mutations affect amyloid-beta peptide production, which accumulates in the brain as senile plaque and cotton wool plaques (CWPs) and relates to other neurodegenerative disorders. Here we report the second case of the PSEN1 G266S mutation, which showed distinctive neuropathological features, including abundant CWPs. Lewy body pathology, and altered amyloid-beta production. Using the proband's samples, we performed genetic analysis of the PSEN1, APP, MAPT, and APOE genes, histopathological and immunohistochemical analysis of the brain tissue, and biochemical analysis of Aβ production in COS cells transfected with wild-type or mutant PSEN1. The patient presented with memory loss, abnormal behavior, and visual hallucinations. Brain scans showed reduced blood flow, mild atrophy, and white matter lesions. Genetic analysis revealed a heterozygous mutation at codon 266 (G266S) of PSEN1 and polymorphism of MAPT (Q230R). The brain had many CWPs, severe cerebral amyloid angiopathy (CAA), senile plaque, Lewy bodies, and neurites. Electron microscopy displayed myelinated fiber degeneration, mitochondrial damage, and amyloid fibrils in the white matter. The production level of Aβ42 in PSEN1 G266S-transfected cells significantly increased. Our findings suggest that the PSEN1 G266S mutation may cause a heterogeneous clinical and pathological phenotype, influenced by other genetic or environmental factors.

A case of cognitive impairment in an ex-boxer

ABSTRACT Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease related to the long-term consequences of repetitive cranial trauma. However, the CTE clinical phenotype has yet to be clearly defined. A 63-year-old man visited the hospital due to memory impairment. He was a former boxer. He scored 23 points on the Mini-Mental State Examination (MMSE). Magnetic resonance imaging (MRI) of the brain showed mild hippocampal atrophy. Reduced perfusion is identified in the bilateral frontal and parietotemporal lobes in cerebral blood flow on single photon emission computed tomography (SPECT). From detailed history taking, neuropsychological testing and neuroimaging, our case has not only suggestive probable CTE but also comorbid Alzheimer’s disease (AD). The diagnosis process of CTE is complex; therefore, detailed longitudinal history taking, neuropsychological testing and imaging were important.

A - 102 Neuropsychological Insights into Kearns-Sayre Syndrome: a Case Study

Abstract Objective Kearns-Sayre Syndrome (KSS) is a genetic mitochondrial and neuromuscular condition with multisystemic effects, including the eyes, heart, muscles, and cognition. Very little is known regarding the cognitive profile of patients with KSS, and existing studies have presented mixed findings. Results in one study revealed impairments in visuospatial abilities and attention, while another study found impairments in global cognition and word-finding. Interestingly, both studies revealed impairments in executive functions. Method This abstract presents the case of a 46-year-old right-handed, African American female diagnosed with KSS in 2021. Symptoms of KSS first appeared in 2010 with progressive vision loss and bilateral ptosis. Genetic testing revealed MT-T1 mutation consistent with KSS. Electroretinography findings revealed mild cone atrophy and mild-to-moderate concentric visual field defects. Attentional difficulties were noted in 2016 and resulted in a diagnosis of ADHD. Memory problems were first noticed in 2016 and have persisted since then. Magnetic resonance imaging results from May 2023 revealed no structural abnormalities in the brain. Results A comprehensive neuropsychological evaluation completed in March 2024 revealed mostly intact neurocognitive functioning. Notably, performance on memory and visuospatial measures were within normal limits. However, poor performance was revealed on one measure of executive functioning. Conclusions It remains unclear whether the poor performance seen on a measure of executive functioning reflects a true cognitive deficit or just chance variation. Even so, with little information regarding the cognitive profile of KSS, baseline neuropsychological testing should be considered to monitor related cognitive changes over time.

B - 109 Long-Term Cognitive Effects of Combined Opioid/Non-Opioid Use

Abstract Objective Chronic pain is estimated to afflict 25–50% of community-dwelling older adults (Cravello et al., 2019). Despite the growing epidemic, opioids remain commonly prescribed analgesics, and approximately 10% of older adults with intermittent opioid use become chronic users (Ramachandran et al., 2021). This is concerning given an observed association between cognitive decline and prescription opioid use within this population (Warner et al., 2022). In efforts to reduce opioid consumption, opioid/non-opioid combinations have been used (Pergolizzi et al., 2023); however, the long-term cognitive impact of such alternatives has not been investigated. Thus, the current case report investigates the neurocognitive outcome following longtime opioid/non-opioid combination cessation in the context of chronic pain. Method A 69-year-old Black woman with approximate 30-year history of chronic pain underwent neuropsychological re-evaluation 2 years post-initial assessment and 1.5 years after stopping combined hydromorphone/clonidine use via intrathecal pump. Baseline MRI brain revealed mild diffuse atrophy and punctate nonspecific T2 white matter hyperintensities. CT head approximately 1 year later was unremarkable. Results Neuropsychological re-assessment approximately 2 years post-baseline evaluation revealed significantly declined performances on speed-mediated tasks (e.g., oral numeric sequencing, fluency) amid an otherwise grossly stable, albeit globally impaired, cognitive profile. Conclusions This study elucidates the impact of a 1.5-year period of abstinence from 13 years of combined intrathecal opioid/non-opioid use. Overall, results suggest that cognitive performance, even following this abstinence period, is not improved. Thus, while opioid/non-opioid therapies may reduce opioid exposure, deleterious cognitive effects persist. This study highlights the importance of non-opioid analgesics in efforts to attenuate cognitive impairment risk.

Phenotypic variability related to dominant UCHL1 mutations: about three families with optic atrophy and ataxia.

Ubiquitin C-terminal hydrolase L1 (UCHL1) has been associated with a severe, complex autosomal recessive spastic paraplegia (HSP79) [1] [2] [3][4]. More recently, UCHL1 loss of function (LoF) variants have been associated to an autosomal dominant disease characterized by late-onset spastic ataxia, neuropathy, and frequent optic atrophy [5]. Routine clinical care whole-genome (WGS) and exome (ES) sequencing. We present three families with autosomal dominant UCHL1-related disorder. The clinical phenotype mainly associated optic atrophy, mixed cerebellar and sensory ataxia, and possible hearing loss. We delineated two major phenotypes, even within the same family: (1) juvenile severe optic atrophy followed by a later-onset ataxia, or (2) late-onset ataxia with asymptomatic or mild optic atrophy. The families harboured three novel heterozygous variants in UCHL1: two loss of function (p.Lys115AsnfsTer40; c.171_174 + 7del11), and one missense (p.Asp176Asn) involving the catalytic site of the protein and potentially altering the adjacent splice site. We confirm the existence of dominantly inherited UCHL1 pathogenic variants. We describe a considerable intrafamilial phenotypic variability, with two main phenotypes. Optic atrophy was consistently present, but with varying degrees of severity. Neither delayed motor or intellectual development, nor dysmorphic features were part of the dominant phenotype in comparison with the autosomal recessive form. The molecular mechanism appears to be haploinsufficiency. UCHL1 monoallelic variants should therefore be considered in any case of early-onset optic atrophy or in late-onset complex ataxic syndrome with asymptomatic optic atrophy.

Sub-acute dermal toxicity of Jatropha curcas Linn. leaf extract coated silver nanoparticles (SNPs) in wistar rats

The application of different nanoparticles is underway in the development of phyto-medicines. Silver nanoparticles (AgNPs) are commonly used as coating agents to treat various bacterial and viral diseases. Their safety and potential toxicity necessitate further research to explore the development of nanoparticles coated herbal drugs. The Azadirachta indica (neem) 5% leaf extract and silver nitrate was used to prepare the silver nanoparticles (SNPs) with the biological reduction (green synthesis) method [1]. The application of silver nanoparticles (SNPs) coated with J. carcus leaf extract (JcLE) on Wistar rats showed no adverse sign of toxicity on hematological parameters except an increase in the neutrophil count and increased in total erythrocyte count (TEC) on 28th day. Similarly, serum biochemical values exhibited an increase in aspartate aminotransferase (AST/SGOT) and alanine transaminase (ALT/SGPT) with JcLE-coated SNPs in treated groups. The histopathology revealed that there was no alteration in skin architecture, however, minimal alteration was observed in the liver and kidney with dilatation of the central vein and sinusoidal space, fatty change in the liver, multifocal necrobiotic changes, cystic degeneration and mild focal glomerular atrophy and hyaline cast in the lumen of tubules of kidney. It indicates the proper absorption and excretion of SNPs from the body. There was no significant effect on hematological parameters in the rats treated with J. curcas leaf extract-coated SNP. However, the serum biochemical analysis revealed a toxic effect on the kidney.

Expanding the Mutational Landscape and Clinical Phenotype of CHD2-Related Encephalopathy.

To present a case series of novel CHD2 variants in patients presenting with genetic epileptic and developmental encephalopathy. CHD2 gene encodes an ATP-dependent enzyme, chromodomain helicase DNA-binding protein 2, involved in chromatin remodeling. Pathogenic variants in CHD2 are linked to early-onset conditions such as developmental and epileptic encephalopathy, drug-resistant epilepsies, and neurodevelopmental disorders. Approximately 225 diagnosed patients from 28 countries exhibit various allelic variants in CHD2, including small intragenic deletions/insertions and missense, nonsense, and splice site variants. We present the molecular and clinical characteristics of 17 unreported individuals from 17 families with novel pathogenic or likely pathogenic variants in CHD2. All individuals presented with severe global developmental delay, childhood-onset myoclonic epilepsy, and additional neuropsychiatric features, such as behavioral including autism, ADHD, and hyperactivity. Additional findings include abnormal reflexes, hypotonia and hypertonia, motor impairment, gastrointestinal problems, and kyphoscoliosis. Neuroimaging features included hippocampal signal alterations (4/10), with additional volume loss in 2 cases, inferior vermis hypoplasia (7/10), mild cerebellar atrophy (4/10), and cerebral atrophy (1/10). Our study broadens the geographic scope of CHD2-related phenotypes, providing valuable insights into the prevalence and clinical characteristics of this genetic disorder in previously underrepresented populations.

Indocyanine green fluorescence imaging as a predictor of long-term testicular atrophy in testicular torsion: a pilot study.

This pilot study evaluated indocyanine green-guided near-infrared fluorescence (ICG-NIRF) imaging of testicular blood flow to predict long-term testicular atrophy after testicular torsion (TT) surgery. The subjects of this retrospective study were patients who underwent surgery for TT at our hospital between December, 2020 and July, 2022. After detorsion, testicular blood flow was evaluated by ICG-NIRF imaging and classified into three categories: fluorescence detected, no fluorescence detected, and fluorescence detected only in the tunica albuginea vessels. Testicular volume was measured by ultrasonography up to 12months after surgery to evaluate long-term outcomes. Twelve patients were included in this analysis. We found a 100% correlation between the absence of ICG-NIRF signals and subsequent testicular atrophy. In three patients without an ICG-NIRF signal, the median testis size 12months postoperatively was significantly smaller (16.5% of the contralateral testis; range 13-20%) than that in six patients with an ICG-NIRF signal (96%; 89-115%) (p = 0.013). Mild atrophy (74.5%; 73-76%) was also observed in the three patients for whom an ICG-NIRF signal was detected only in the tunica albuginea vessels. Our pilot study highlights the potential of ICG-NIRF imaging as a prognostic tool for guiding surgical decision-making for patients with TT, by predicting postoperative testicular atrophy.

Magnetic resonance imaging pattern recognition of metabolic and neurodegenerative encephalopathies in dogs and cats.

Metabolic/neurodegenerative encephalopathies encompass a wide list of conditions that share similar clinical and magnetic resonance imaging (MRI) characteristics, challenging the diagnostic process and resulting in numerous tests performed in order to reach a definitive diagnosis. The aims of this multicentric, retrospective and descriptive study are: (I) to describe the MRI features of dogs and cats with metabolic/neurodegenerative encephalopathies; (II) to attempt an MRI recognition pattern classifying these conditions according to the involvement of grey matter, white matter or both; and (III) to correlate the MRI findings with previous literature. A total of 100 cases were recruited, comprising 81 dogs and 19 cats. These included hepatic encephalopathy (20 dogs and three cats), myelinolysis (five dogs), intoxications (seven dogs and one cat), thiamine deficiency (two dogs and seven cats), hypertensive encephalopathy (three dogs and two cats), neuronal ceroid lipofuscinosis (11 dogs and one cat), gangliosidosis (three dogs and two cats), fucosidosis (one dog), L-2-hydroxyglutaric aciduria (13 dogs and one cat), Lafora disease (11 dogs), spongiform leukoencephalomyelopathy (one dog) and cerebellar cortical degeneration (four dogs and two cats). None of the hepatic encephalopathies showed the previously described T1-weighted hyperintensity of the lentiform nuclei. Instead, there was involvement of the cerebellar nuclei (8/23), which is a feature not previously described. Dogs with myelinolysis showed novel involvement of a specific white matter structure, the superior longitudinal fasciculus (5/5). Thiamine deficiency affected numerous deep grey nuclei with novel involvement of the oculomotor nuclei (3/9), thalamic nuclei, subthalamus and cerebellar nuclei (1/9). Cats with hypertensive encephalopathy had a more extensive distribution of the white matter changes when compared to dogs, extending from the parietal and occipital lobes into the frontal lobes with associated mass effect and increased brain volume. Lysosomal storage disease showed white matter involvement only, with neuronal ceroid lipofuscinosis characterised by severe brain atrophy when compared to gangliosidosis and fucosidosis. All patients with L-2-hydroxyglutaric aciduria had a characteristic T2-weighted hyperintense swelling of the cerebral and cerebellar cortical grey matter, resulting in increased brain volume. Lafora disease cases showed either normal brain morphology (5/11) or mild brain atrophy (6/11). Dogs with cerebellar cortical degeneration had more marked cerebellar atrophy when compared to cats. This study shows the important role of MRI in distinguishing different metabolic/neurodegenerative encephalopathies according to specific imaging characteristics.

Ripe Musa sapientum Peels Exhibit Neuroprotection Against Lead Acetate-Induced Brain Damage in Wistar Rats

Objective: Human health has continued to be at risk from lead exposure. This study explored the antioxidative potential of ethanol extract of ripe Musa sapientum peels to protect against lead acetate-induced neuronal insult in female wistar rats. Methods: Thirty adult female rats (120-160 g) were randomly divided into six groups (n = 5): Group 1 (control group) received 10 mL/kg of distilled water; Group 2 received 100 mg/kg lead acetate. Group 3 received 2.5 mg/kg of donepezil. Groups 4 to 6 received 100, 200, and 400 mg/kg ethanol extract of ripe M sapientum, respectively, via oral gavage. Groups 2 to 5 were co-treated with 100 mg/kg lead acetate for 21 days. Neurobehavioral parameter, biochemical and histological analyses of the hippocampus were determined. Recognition memory was evaluated using Novel Object Recognition Test. Results: There was a significant ( p < 0.05) increase in total exploration, discrimination index, and percentage alternation in the ethanol extract M sapientum-treated groups compared with the lead acetate-induced group. M sapientum ethanol extract and dopamine significantly ( p < 0.05) reduced acetylcholinesterase enzyme (AChE) and malondialdehyde (MDA) activities in a dose-dependent manner and significantly ( p < 0.05) increased superoxide dismutase activity (SOD) dose dependently, respectively. In the histopathological analysis of the hippocampal area, there were mild vacuolation (V), mild degeneration as well as mild granular cell atrophy in the treated groups, suggesting that M sapientum may have neuroprotective properties. Conclusion: Ethanol extract of ripe M sapientum peels enhanced cognitive functions and may be beneficial in preventing neurodegenerative disorders via antioxidant mechanism.

Protective evaluation of the commercialized porcine reproductive and respiratory syndrome virus vaccines in piglets challenged by NADC34-like strain.

In China, the porcine reproductive and respiratory syndrome virus (PRRSV) has undergone several variations over the decades and contributed to the diversity of the clinical epidemic PRRSV strains. This has complicated the prevention and control of PRRS. In particular, the efficacy of the currently available commercial vaccines against the highly pathogenic NADC34-like strains is unclear. Therefore, the objective of this study was to evaluate the protection efficacy of three commercial PRRS modified-live virus (MLV) vaccines derived from classical PRRS VR2332 MLV and R98 MLV against challenge with a heterologous NADC34-like PRRSV strain, JS2021NADC34, which has high pathogenicity in pigs. PRRSV- and antibody-free piglets were immunized with the PRRS VR2332 MLV vaccine or either of two R98 MLV vaccines (from different manufacturers) and were challenged with the JS2021NADC34 strain 28 days after immunization. Rectal temperature, clinical symptoms, viremia and viral shedding from the nose, gross lesions in the thymus and lungs, microscopic lesions and viral distribution in the lungs, as well as the humoral immune response and mortality rates were recorded over a 14-day post-challenge period. The results showed that PRRS VR2332 MLV had better efficacy against the JS2021NADC34 challenge than PRRS R98 MLV, with vaccinated piglets in the former group showing transient and mild symptoms, mild pathological lesions in the lungs, mild thymic atrophy, and low viral levels in sera and nasal swabs, as well as better growth performance and a 100% survival rate. In contrast, two PRRS R98 MLVs exhibited limited efficacy against the JS2021NADC34 challenge, with the piglets in two R98 groups showing obvious clinical symptoms and pathological changes in the lungs and thymus; moreover, there were two deaths caused by PRRS in two R98 groups, respectively. Despite this, the mortality rate was lower than that of the unvaccinated piglets that were challenged with JS2021NADC34. The cumulative results demonstrate that PRRS VR2332 MLV was partly effective against the highly pathogenic PRRSV NADC34-like strain based on the observations over the 14-day post-challenge period. Thus, it might be a viable option among the commercially available vaccines for control of NADC34-like virus infections in swine herds.

Distinct virtual histology of grey matter atrophy in four neuroinflammatory diseases.

Gray matter (GM) atrophies were observed in multiple sclerosis, neuromyelitis optica spectrum disorders (both anti-aquaporin-4 antibody-positive [AQP4+], and -negative [AQP4-] subtypes NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Revealing the pathogenesis of brain atrophy in these disorders would help their differential diagnosis and guide therapeutic strategies. To determine the neurobiological underpinnings of GM atrophies in multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, and MOGAD, we conducted a virtual histology analysis that links T1-weighted image derived GM atrophy and gene expression using a multicenter cohort of 324 patients with multiple sclerosis, 197 patients with AQP4+ NMOSD, 75 patients with AQP4- NMOSD, 47 patients with MOGAD, and 2,169 healthy controls (HCs). First, interregional GM atrophy profiles across the cortical and subcortical regions were determined by Cohen's d between patients with multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, MOGAD and HCs. Then, the GM atrophy profiles were spatially correlated with the gene expressions extracted from the Allen Human Brain Atlas, respectively. Finally, we explored the virtual histology of clinical feature relevant GM atrophy by subgroup analysis that stratified by physical disability, disease duration, number of relapses, lesion burden, and cognitive function. Multiple sclerosis showed severe widespread GM atrophy pattern, mainly involving subcortical nuclei and brainstem. AQP4+ NMOSD showed obvious widespread GM atrophy pattern, predominately located in occipital cortex as well as cerebellum. AQP4- NMOSD showed mild widespread GM atrophy pattern, mainly located in frontal and parietal cortices. MOGAD showed GM atrophy mainly involving the frontal and temporal cortices. High expression of genes specific to microglia, astrocytes, oligodendrocytes, and endothelial cells in multiple sclerosis, S1 pyramidal cells in AQP4+ NMOSD, as well as S1 and CA1 pyramidal cells in MOGAD had spatial correlations with GM atrophy profiles were observed, while no atrophy profile related gene expression was found in AQP4- NMOSD. Virtual histology of clinical feature relevant GM atrophy mainly pointed to the shared neuronal and endothelial cells among the four neuroinflammatory diseases. The unique underlying virtual histology patterns were microglia, astrocytes, and oligodendrocytes for multiple sclerosis; astrocytes for AQP4+ NMOSD; and oligodendrocytes for MOGAD. Neuronal and endothelial cells were shared potential targets across these neuroinflammatory diseases. These findings might help their differential diagnosis and optimal therapeutic strategies.

Post-Ictal Mania: A Case Report with Literature Revue

IntroductionWhile postictal mania is a well-recognized clinical condition, it has received less research attention compared to other postictal manifestations.ObjectivesDrawing upon an analysis of a case report that underscores the clinical and therapeutic challenges associated with comorbid epilepsy and mania, a literature review was carried out to investigate the connection between these two disorders.MethodsWe illustrate a case of comorbidity between mania and epilepsy and provide a concise review of the literature summarizing the key characteristics of this association.ResultsThis case pertains to Mr. M, a 44-year-old male with a history of frontal epilepsy characterized by secondary partial generalization, which was partially controlled with sodium valproate. He was admitted to our service due to acute agitation following a loss of consciousness lasting a few minutes.Upon admission, the patient exhibited symptoms of mental confusion. A neurological examination did not uncover any abnormalities. Brain computed tomography revealed mild frontal atrophy. Video electroencephalography conducted during the interictal period and outside the episodes of confusion did not reveal any abnormalities. The patient was restarted on sodium valproate (20 mg/kg/day) and clonazepam (2 mg/day). Following a lucid interval of ten days, the patient started to manifest psychiatric symptoms, which included irritability, hostility towards his spouse, increased talkativeness, thought pressure, and an unusual sense of familiarity, raising suspicion of post-ictal mania.ConclusionsBased on this clinical case and the existing scientific literature, post-ictal mania occupies a distinct position among the mental disorders observed in the post-ictal period. Therefore, clinicians must be aware of these conditions to facilitate accurate diagnosis and appropriate management.Disclosure of InterestNone Declared

Revealing the heterogeneity of plasma protein and cognitive decline trajectory among Mild Cognitive Impairment patients by clustering of brain atrophy features

Alzheimer's disease (AD) is suggested to be a heterogeneous disorder, but limited studies explore the heterogeneity of the Mild Cognitive Impairment (MCI) stage. This study aimed to tackle such problems using the CIMLR (Cancer Integration via Multikernel Learning) algorithm to cluster brain structural features extracted from T1-weighted Magnetic Resonance Images of MCI patients from Alzheimer's Disease Neuroimaging Initiative. The demographic and cognitive results, characteristics of brain structural features, plasma biomarkers, and longitudinal cognitive trajectory were analyzed for each cluster. The CIMLR clustering analysis revealed four distinct clusters. Cluster 1 is the oldest group but has had mild atrophy and moderate progression with elevated Tumor Necrosis Factor Receptor 2 level; and low Brain-Derived Neurotrophic Factor and CD40 Ligand levels. Cluster 2 showed the highest risk for aggressive MCI progression, with abnormal Leptin, Adiponectin, and Creatine kinase-MB values. Cluster 3 exhibited a low level of Monokine Induced by Gamma Interferon and mild atrophy that shared similar patterns with Cluster 1. Cluster 4 represented the healthiest group during longitudinal tracking, with the mildest Parahippocampal atrophy, which was found to be positively correlated with cognitive impairment and amino acid levels. The longitudinal analyses showed the potential of Hepatocyte Growth Factor as a marker for slow cognitive impairment; Cortisol and Neurofilament Light Polypeptide as prognosis markers for aggressive MCI progression. These findings may lay out new suggestions for further research contributing to the accurate diagnosis and precision medicine for dementia and AD.

Diagnosis by combination of endoscopic findings helps differentiate non-Helicobacter pylori Helicobacter-infected gastritis from Helicobacter pylori-infected gastritis.

The characteristic endoscopic findings of non-Helicobacter pylori Helicobacter (NHPH) gastritis, including white marbled appearance and crack-like mucosa, have been reported. However, these findings can also manifest in H. pylori (HP)-infected gastritis. This study compared NHPH gastritis and mild atrophic HP gastritis to identify features that may enhance NHPH diagnosis. A total of 2087 patients underwent upper gastrointestinal endoscopy and were histologically evaluated by multiple gastric mucosal biopsies according to the updated Sydney System (USS) at Shinshu University Hospital between 2005 and 2023. Among them, nine patients were classified into the NHPH group and 134 patients with HP infection and mild atrophy were classified into the HP group for retrospective comparisons of endoscopic findings and clinicopathological characteristics. All nine patients in the NHPH group (eight males [89%], median ± standard deviation [SD] age: 49 ± 13.0 years) were infected with H. suis. The 134 patients in the HP group contained 70 men (52%) and had a median ± SD age of 35 ± 19.9 years. Endoscopic findings were statistically comparable for white marbled appearance (three patients [33%] in the NHPH group and 37 patients [31%] in the HP group) and crack-like mucosa (three patients [33%] and 27 patients [20%], respectively). Diffuse redness was significantly less frequent in the NHPH group (one patient [14%] vs. 97 patients [72%], p < 0.001). White marbled appearance or crack-like mucosa without diffuse redness was significantly more common in the NHPH group (56% vs. 13%, p = 0.004), with a sensitivity and specificity of 56% and 87%, respectively. Mean USS neutrophil infiltration and Helicobacter density scores were significantly higher in the HP group (both p < 0.01), which might have influenced the endoscopic findings of diffuse redness. When endoscopic findings of white marbled appearance or cracked-like mucosa are present, evaluation for diffuse redness may contribute to a more accurate diagnosis of NHPH gastritis.

Brain volume loss in Japanese patients with multiple sclerosis is present in the early to middle stage of the disease

BackgroundTo determine which disease-modifying therapies should be used in patients with multiple sclerosis (MS), identifying patients at high and low risk for brain volume loss (BVL) is important. Although the BVL rate in MS is nearly constant from early to late disease onset, regardless of the disease stage, individual differences have been noted. Moreover, as disease duration increases, the risk of chronic progression increases, and brain atrophy becomes more noticeable. Therefore, measuring prognosis using a classification that considers BVL rate and disease duration is appropriate. We aimed to investigate the BVL in Japanese patients with MS. MethodsHerein, with an observational period of approximately 3.5 years, 82 Japanese patients with MS were included. The volumes and annualised volume changes (AVCs) of the grey matter (GM) and whole brain were evaluated using icobrain ms. ResultsWhole-brain AVCs varied, especially among patients with a disease duration within approximately 16 years. Cluster analysis using two variables, disease duration and whole-brain AVC, identified the SM (short to middle duration and mild atrophy rates), SS (short to middle duration and severe atrophy rates), and L (long duration) groups. The optimal cut-off values for disease duration and whole-brain AVC to discriminate among the three groups were 15.8 years and −0.43%, respectively. Compared with the SM group, the SS group had higher Multiple Sclerosis Severity Scale (MSSS) and Expanded Disability Status Scale (EDSS) scores, lower information processing speed (IPS), higher lesion loads, higher whole-brain and GM volume loss, and higher GM atrophy rates. Moreover, among the 63 patients with MS included in the SM and SS groups, whole-brain AVCs were significantly correlated with the EDSS and MSSS scores and IPS. ConclusionBVL rates vary, especially among Japanese patients with MS with short to middle disease duration, and BVL degree is associated with poor prognosis.