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Objective: Interhemispheric neurons in the motor section of the corpus callosum have an inhibitory effect on neurons of the contralateral motor cortex. Three quarters of patients with amyotrophic laterals sclerosis (ALS) show impaired transcallosal inhibition. We aimed to investigate whether structural changes co-occur with this functional impairment and to explore its phenotypic correlates., Methods: The demographic, clinical, and neuropsychological data of 127 ALS patients were analysed. Transcallosal inhibition was assessed with an ipsilateral silent period (iSP) protocol using transcranial magnetic stimulation. Patients were categorised based on an iSP response or its loss, and the groups were characterised by demographic, clinical, and neuropsychological variables. Diffusion-weighted images from a subset of 63 patients were analysed using tractography, and white matter (WM) structural integrity metrics were compared across groups., Results: 54 % of patients displayed iSP loss. The average free-water-corrected fractional anisotropy values within the callosal tract between the primary motor cortices were lower for patients with iSP loss compared to patients with an iSP response. There were no group differences based on other diffusivity metrics. The groups did not differ regarding any of the demographic, clinical, or neuropsychological variables., Interpretation: We found reduced WM integrity in the motor section of the corpus callosum that differentiated ALS patients with iSP loss from patients with an iSP response, but with a small effect size. Nevertheless, the underlying pathological substrate and potential genetic drivers for these structural and functional changes in a subset of ALS patients remain to be satisfactorily investigated., Competing Interests: Declaration of competing interest S.T. served on advisory boards of Lilly, Eisai, and Biogen, and is member of the independent data safety and monitoring board of the ENVISION study (Biogen)., (Copyright © 2024. Published by Elsevier B.V.)

Hydrocephalus is a clinical and neurologic condition characterized by an abnormal accumulation of cerebrospinal fluid (CSF). Currently, idiopathic Normal Pressure Hydrocephalus (iNPH) is recognized as a late-onset neurologic disorder defined by a clinical triad of gait disturbance, urinary incontinence, and dementia. Imaging studies often reveal a disproportionate increase in subarachnoid space and ventricular size relative to brain volume, with normal CSF pressure during lumbar puncture. Recent developments in neuroimaging have led to the establishment of criteria for diagnosing and managing iNPH, incorporating the concept of Disproportionately Enlarged Subarachnoid-space Hydrocephalus (DESH). Distinguishing iNPH from the natural neurological aging process and other forms of dementia, wherein brain atrophy and hydrocephalus ex vacuo can be observed, can present challenges for both neurologists and neuroradiologists. Despite DESH becoming a radiologic criterion for diagnosing iNPH in some guidelines, its recognition remains limited., Competing Interests: Declaration of competing interest There is no conflict of interest on this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chronic cerebral hypoperfusion (CCH) has been acknowledged as a potential contributor to cognitive dysfunction and brain injury, causing progressive demyelination of white matter, oligodendrocytes apoptosis and microglia activation. Nervonic acid (NA), a naturally occurring fatty acid with various pharmacological effects, has been found to alleviate neurodegeneration. Nonetheless, evidence is still lacking on whether NA can protect against neurological dysfunction resulting from CCH. To induce CCH in mice, we employed the right unilateral common carotid artery occlusion (rUCCAO) method, followed by oral administration of NA daily for 28 days after the onset of hypoperfusion. We found that NA ameliorated cognitive function, as evidenced by improved performance of NA-treated mice in both novel object recognition test and Morris water maze test. Moreover, NA mitigated demyelination and loss of oligodendrocytes in the corpus callosum and hippocampus of rUCCAO-treated mice, and prevented oligodendrocyte apoptosis. Furthermore, NA protected primary cultured murine oligodendrocytes against oxygen-glucose deprivation (OGD)-induced cell death in a concentration-dependent manner. These findings indicated that NA promotes oligodendrocyte maturation both in vivo and in vitro. Our findings suggest that NA offers protective effects against cerebral hypoperfusion, highlighting its potential as a promising treatment for CCH and related neurological disorders., Competing Interests: Declaration of competing interest The authors declare no competing financial interests or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Maldevelopment of the posterior corpus callosum is common in spina bifida myelomeningocele (SBM) due to hydrocephalus-related hypoplasia and congenital partial hypogenesis. This study examined the relations of macro- and microstructural integrity of the interhemispheric temporal tract in SBM and auditory interhemispheric transfer using consonant-vowel dichotic listening., Method: We collected T ₁-weighted and diffusion tensor imaging data from 46 individuals with SBM and 15 typically developing individuals. Probabilistic tractography was used to isolate the interhemispheric white matter connecting auditory processing regions in both hemispheres. Interhemispheric transfer was assessed with a dichotic listening task., Results: Although the typically developing group and the group with SBM showed the normative right-ear advantage, fewer participants showed a right-ear advantage in the group with SBM. The absence of the right-ear advantage was largely in the subgroup with hypogenesis of the splenium or severe posterior hypoplasia. Sex, anterior commissure cross-sectional area, and number of shunt pathways visible on magnetic resonance imaging predicted right-ear superiority., Conclusions: Interhemispheric transfer is disrupted in individuals with SBM and hypogenesis or severe hypoplasia of the posterior corpus callosum. Preservation of interhemispheric transfer is related to expected connections through the posterior corpus callosum and possibly compensatory pathways in the anterior commissure. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Few studies have quantitatively analyzed the imaging disparities between multiple sclerosis (MS) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to compare the imaging characteristics of MS and CADASIL in middle-aged patients., Materials and Methods: This retrospective study used a single-center database and included patients aged 40-60 years with MS and CADASIL who underwent the designated imaging protocol including 3D T1-weighted imaging and fluid attenuated inversion recovery (FLAIR), diffusion tensor imaging and susceptibility-weighted imaging between January 2018 and March 2023. Patients with MRI-detected macrobleeds were excluded., Results: A total of 27 patients with MS (mean age, 46.7 years ± 4.4, 8 men) and 30 patients with CADASIL (mean age, 51.6 years ± 5.8, 14 men) were included. No significant differences were observed in the Fazekas grades of white matter lesions (WMLs). Patients with CADASIL exhibited greater external capsule involvement (56.7% vs.18.5 %; p = 0.006), whereas the MS group had more lesions in the corpus callosum (81.5% vs. 53.3 %, p = 0.02) and brainstem (74.1% vs. 46.7 %, p = 0.04). The CADASIL group exhibited a higher incidence of microbleeds (12.07 vs. 0.11, p = 0.001). The WMLs in the MS group exhibited a lower T1 lesion/cerebrospinal fluid signal index (2.206 vs. 2.882, p < 0.001). A value of ≤2.57 demonstrated a sensitivity of 92.6 % and a specificity of 90.0 % in differentiating MS. Patients with MS had a thinner corpus callosum (7.18 mm vs 7.86 mm, p = 0.04), while patients with CADASIL showed significantly higher mean diffusivity (0.8776 × 10 -3 vs. 0.7637 × 10 -3 mm2/s, p = 0.03) and lower fractional anisotropy (0.7581 vs. 0.8389, p = 0.04) in the splenium of the corpus callosum., Conclusion: Middle-aged patients with MS and CADASIL showed comparable Fazekas grades for WMLs. However, lesion distribution, T1 signal characteristics, and splenic diffusivity changes can help differentiate between MS and CADASIL., Competing Interests: Declaration of competing interest The authors have nothing to disclose. The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a clinical-radiological syndrome characterized by transient central nervous system symptoms and a reversible lesion in the splenium of the corpus callosum (SCC) on magnetic resonance (MR). We reported a case of adult-onset MERS with uncommon presentation and reviewed the existing literature., Methods: We described a case of adult-onset MERS with uncommon symptoms and signs and performed a systematic review of case series including more than four patients of adult-onset (> 14 years old) MERS, from January 2000 to December 2022. We summarized the clinical, laboratory, imaging and therapy data., Results: We included seven eligible studies for a total of 51 adult-onset MERS patients. Neurological manifestations were preceded by prodromal symptoms in most of the patients (88%), mainly with fever (78%). Headache was the most common symptom (50%), followed by seizures (22%) and disturbance of consciousness (22%). Inflammatory changes on cerebrospinal fluid were present in a half of patient, so defining encephalitis cases. Clinal recovery, was achieved in all patients but two with severe disturbance of consciousness who required ventilator support in the acute phase. MR showed isolated lesion in the SCC in 92% of patients, while 8% of patients showed also extracallosal lesions, all the lesions resolved or improved on follow-up imaging., Conclusions: MERS is a form of encephalitis/encephalopathy with a broad range of central nervous system manifestation, often with mild symptoms, such as headache alone, that can lead to overlooked some cases, with an excellent prognosis in most patient., (© 2024. Fondazione Società Italiana di Neurologia.)

Growing evidence indicates that non-neuronal oligodendrocyte plays an important role in Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In patient's brain, the impaired myelin structure is a pathological feature with the observation of TDP-43 in cytoplasm of oligodendrocyte. However, the mechanism underlying the gain of function by TDP-43 in oligodendrocytes, which are vital for the axonal integrity, remains unclear. Recently, we found that the primate-specific cleavage of truncated TDP-43 fragments occurred in cytoplasm of monkey neural cells. This finding opened up the avenue to investigate the myelin integrity affected by pathogenic TDP-43 in oligodendrocytes. In current study, we demonstrated that the truncated TDP-35 in oligodendrocytes specifically, could lead to the dysfunctional demyelination in corpus callosum of monkey. As a consequence of the interaction of myelin regulatory factor with the accumulated TDP-35 in cytoplasm, the downstream myelin-associated genes expression was downregulated at the transcriptional level. Our study aims to investigate the potential effect on myelin structure injury, affected by the truncated TDP-43 in oligodendrocyte, which provided the additional clues on the gain of function during the progressive pathogenesis and symptoms in TDP-43 related diseases., (© 2024 The Author(s). Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

The corpus callosum is an oligodendrocyte-enriched brain region, replenished by newborn oligodendrocytes from oligodendrocyte progenitor cells (OPCs) in subventricular zone (SVZ). Lead (Pb) exposure has been associated with multiple sclerosis, a disease characterized by the loss of oligodendrocytes. This study aimed to investigate the effects of Pb exposure on oligodendrogenesis in SVZ and myelination in the corpus callosum. Adult female mice were used for a disproportionately higher prevalence of multiple sclerosis in females. Acute Pb exposure (one ip-injection of 27 mg Pb/kg as PbAc2 24 hr before sampling) caused mild Pb accumulation in the corpus callosum. Ex vivo assay using isolated SVZ tissues collected from acute Pb-exposed brains showed a diminished oligodendrogenesis in SVZ-derived neurospheres compared with controls. In vivo subchronic Pb exposure (13.5 mg Pb/kg by daily oral gavage 4 wk) revealed significantly decreased newborn BrdU+/MBP+ oligodendrocytes in the corpus callosum, suggesting demyelination. Mechanistic investigations indicated decreased Rictor in SVZ OPCs, defective self-defense pathways, and reactive gliosis in the corpus callosum. Given the interwined pathologies between multiple sclerosis and Alzheimer's disease, the effect of Pb on myelination was evaluated in AD-modeled APP/PS1 mice. Myelin MRI on mice following chronic exposure (1,000 ppm Pb in drinking water as PbAc2 for 20 wk) revealed a profound demyelination in the corpus callosum compared with controls. Immunostaining of the choroid plexus showed diminished signaling molecule (Klotho, OTX2) expressions in Pb-treated animals. These observations suggest that Pb caused demyelination in the corpus callosum, likely by disrupting oligodendrogenesis from SVZ OPCs. Pb-induced demyelination represents a crucial pathogenic pathway in Pb neurotoxicity, including multiple sclerosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study., Methods and Materials: This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (V rel ) and tumor migration distance (d migration ). Covariables evaluated included: corpus callosum involvement, extent of surgery, O 6 -methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status., Results: The median V rel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median d migration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant V rel reduction at F20 (P = .03) and smaller d migration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant V rel reduction at F10 (P = .001) and F20 (P = .001) and a smaller d migration at F10 (P = .03) and F20 (P = .002). O 6 -Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with V rel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with d migration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007)., Conclusions: Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Reduced graphene oxide (rGO) has unique physicochemical properties that make it suitable for therapeutic applications in neurodegenerative scenarios. This study investigates the therapeutic potential of rGO in a cuprizone-induced demyelination model in mice through histomorphological techniques and analysis of biochemical parameters. We demonstrate that daily intraperitoneal administration of rGO (1 mg ml -1 ) for 21 days tends to reduce demyelination in the Corpus callosum by decreasing glial cell recruitment during the repair mechanism. Additionally, rGO interferes with oxidative stress markers in the brain and liver indicating potential neuroprotective effects in the central nervous system. No significant damage to vital organs was observed, suggesting that multiple doses could be used safely. However, further long-term investigations are needed to understand rGO distribution, metabolism, routes of action and associated challenges in central neurodegenerative therapies. Overall, these findings contribute to the comprehension of rGO effects in vivo , paving the way for possible future clinical research., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Previous studies have shown that cerebral ischemia can cause white matter injury in the brain. This study aimed to investigate the potential mechanism of electroacupuncture (EA) at the Baihui (GV20) and Zusanli (ST36) acupoints in protecting white matter. Sprague-Dawley rats were used to establish permanent middle cerebral artery occlusion (pMCAO) rat models. Comprehensive motor functions were assessed using the mesh experiment. Morphological changes in the myelin sheath were assessed with Luxol fast blue staining. Morphological changes in oligodendrocytes and myelinated axons were evaluated using Nissl staining. The expressions of high-mobility group box 1 protein (HMGB1) and the receptor for advanced glycation end products (RAGE) in the corpus callosum were detected by immunohistochemical staining and Western blot analysis. pMCAO caused severe injury to the corpus callosum, evidenced by significant loss of white matter fibers and myelinated axons, and induced overexpression of HMGB1 and RAGE in the corpus callosum. EA treatment significantly improved comprehensive motor function alleviated white matter damage, and downregulated the expression of HMGB1 and RAGE. Its effects were comparable to those of FPS-ZM1, a RAGE receptor inhibitor. In conclusion, EA effectively improves comprehensive motor function in rats with cerebral infarction and alleviates corpus callosum injury. This effect may be related to the inhibition of HMGB1 and RAGE overexpression., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

A 47-year-old woman with a history of substance abuse, depression, and insomnia experienced a collapse. Upon arrival at the hospital, the patient displayed low systolic blood pressure, confusion, dehydration, and renal failure. Urine tests confirmed an amphetamine and opioid overdose. Her condition fluctuated with reduced consciousness, myoclonic movements, fever, and suspected psychogenic seizures. Brain magnetic resonance imaging revealed abnormalities in the splenium of the corpus callosum, which later resolved. The patient's condition gradually improved without any specific treatment. This unique case represents the first report of mild encephalopathy/encephalitis with reversible splenial lesions associated with amphetamine and opioid use.

Background: Marchiafava-Bignami disease (MBD) is an exceptionally rare condition, a fact that should pique the professional curiosity of medical practitioners. In recent years, case reports of this disease have been infrequent, and no comprehensive analysis or summary of the characteristics of the published cases has been conducted., Methods: We collected the medical records of three patients treated at our hospital from March 2022 to March 2023. Furthermore, we searched PubMed for "case reports" from January 2017 to March 2023 and included 30 cases. By retrospectively analyzing these 33 cases, we summarized the characteristics of the disease., Results: Based on our analysis, we found that MBD primarily affects middle-aged men and typically has an acute or subacute onset, with the primary clinical manifestations being disturbances of consciousness, speech disorders, cognitive impairment, and psychiatric or behavioral abnormalities, often leading to misdiagnosis of psychiatric disorders. Most patients have a history of alcohol consumption or malnutrition. Head CT or MRI revealed symmetric lesions in the corpus callosum, with the splenium being the most commonly affected area. Lesions might also involve white matter outside the corpus callosum, and a wider range of lesions suggested a poor prognosis. However, the prognosis is generally favorable with timely and adequate administration of B vitamins, providing reassurance to medical professionals and patients alike., Conclusion: The early recognition and treatment of Marchiafava-Bignami disease are paramount, as they can significantly improve the prognosis. This underscores the critical need for prompt clinical intervention in the early stages of the disease, instilling a sense of urgency and significance in the work of medical professionals., (© 2024. The Author(s).)

Background: The Coronavirus disease 19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a threat to human health. Although the COVID-19 pandemic is finished, some peoples are still suffering from this disease. Herein, we report the first case of SARS-CoV-2-associated Guillain-Barré syndrome (GBS) presenting as polyneuritis cranialis (PNC) and acute panautonomic neuropathy (APN) variants, accompanied by mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) and hyponatremia., Case Presentation: A 32-year-old female patient with symptoms indicating multiple cranial nerve involvement, as well as sympathetic and parasympathetic nervous system dysfunction, was diagnosed as SARS-CoV-2-associated GBS presenting as PNC and APN variants, accompanied by MERS and hyponatremia. Following treatment with immunoglobulin, methylprednisolone, and symptomatic care, the patient's inflammatory cytokines and serum sodium became normal. However, some residual symptoms such as postural hypotension, fatigue, and mild dysarthria persisted at the 9-month follow-up., Conclusion: This case highlights the unique presentation of SARS-CoV-2 infection. The involvement of both the central nervous system (CNS) and the peripheral nervous system (PNS) in this case underscores the complex neurological manifestations of COVID-19. Although the exact underlying pathogenesis of this case is unclear, inflammatory cytokines, particularly IL-6, may be implicated. Further research is needed to better understand the mechanisms underlying these complications and to optimize treatment strategies for affected patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Si, Li and Du.)

Glial cell dysfunction results in myelin loss and leads to subsequent motor and cognitive deficits throughout the demyelinating disease course.Therefore, in various therapeutic approaches, significant attention has been directed toward glial-restricted progenitor (GRP) transplantation for myelin repair and remyelination, and numerous studies using exogenous GRP injection in rodent models of hypomyelinating diseases have been performed. Previously, we proposed the transplantation of canine glial-restricted progenitors (cGRPs) into the double-mutant immunodeficient, demyelinated neonatal shiverer mice (shiverer/Rag2 -/- ). The results of our previous study revealed the myelination of axons within the corpus callosum of transplanted animals; however, the extent of myelination and lifespan prolongation depended on the transplantation site (anterior vs. posterior). The goal of our present study was to optimize the therapeutic effect of cGRP transplantation by using a multisite injection protocol to achieve a broader dispersal of donor cells in the host and obtain better therapeutic results. Experimental analysis of cGRP graft recipients revealed a marked elevation in myelin basic protein (MBP) expression and prominent axonal myelination across the brains of shiverer mice. Interestingly, the proportion of galactosyl ceramidase (GalC) positive cells was similar between the brains of cGRP recipients and control mice, implying a natural propensity of exogenous cGRPs to generate mature, myelinating oligodendrocytes. Moreover, multisite injection of cGRPs improved mice survival as compared to non-transplanted animals.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) that led to brain atrophy. The purpose of this study was to investigate the effects of pre-and post-conditioning with exercise on demyelination and brain morphology. Thirty male rats were randomly divided into five groups (n = 6 per group), consisting of a healthy control group (Control), an MS group, and three exercise groups: the group that performed the exercise protocol (running on a treadmill 5 days/week for 6 weeks) before the MS induction (EX + MS), the group that performed the exercise protocol during the MS induction (MS + EX), and the group that performed the exercise protocol before and during the MS induction (EX + MS + EX). The expression of Myelin basic protein (MBP), and demyelination in the corpus callosum and the volume, weight, length, width, and height of the brain were measured. The EX + MS + EX showed a significant increase in the expression of MBP compared to other MS groups (**p < 0.01) as well as a significant decrease in the area of demyelination of the corpus callosum compared to MS and MS + EX groups (**p < 0.01). However, there were no significant differences between the MS group and exercised groups for brain morphology. The exercise showed neuroprotective effects, as evidenced by decreased areas of demyelination and improved MBP expression., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Ciguatera is a food poisoning caused by marine organisms and has a polymoprhic clinic. Differential diagnoses need to be eliminated., Observation: A patient was hospitalized for a febrile syndrome a few days after the appearance of clinical signs suggestive of ciguatera after consuming lagoon fish. He also presented with central neurological signs and brain MRI revealed a lesion of the corpus callosum. A skin infection linked to the scratching lesions was the cause of this febrile state and a diagnosis of CLOCCS was made based on the lesions on MRI., Conclusion: A central neurological involvement in ciguatera is possible but rare, CLOCCS may be one of them. On the other hand, a febrile syndrome should lead to consider an differential diagnosis or a complication., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

A juvenile coyote (Canis latrans) was presented to a wildlife rehabilitation center with intermittent circling, hypernatremia, and elevated blood urea nitrogen. Diagnostic testing supported a diagnosis of hypodipsic hypernatremia. Postmortem magnetic resonance imaging (MRI) and necropsy revealed marked hypoplasia of the corpus callosum, a finding not previously reported in a free-ranging animal., (© Wildlife Disease Association 2024.)

Primary nocturnal enuresis (PNE) is a common childhood disorder with abnormal sleep or arousal. The corpus callosum (CC) continues to develop into adulthood and plays an important role in sleep arousal. This study aimed to evaluate the microstructure of the CC in children with PNE. Diffusion tensor imaging (DTI) indices were extracted throughout the CC and its seven subregions were compared between the children with PNE and healthy children (HC). The correlation between abnormal DTI indices of the CC and cognitive condition was also tested. Compared to HC, decreased fiber number (NF) (F = 8.492, P FDR = 0.032) and fractional anisotropy (FA) value (F = 8.442, P FDR = 0.040) were found in the posterior midbody of the CC, increased RD was found in the posterior midbody (F = 6.888, P FDR = 0.040) and isthmus (F = 7.967, P FDR = 0.040) in children with PNE. The reduction of FA value was more obvious in boys than girls with PNE. In children with PNE, there was a significant positive correlation between the NF of the posterior midbody and full IQ (r = 0.322, P = 0.025) and between the FA value and the general knowledge memory (r = 0.293, P = 0.043). This study provides imaging evidence for abnormalities in the microstructure of the CC in children with PNE, especially in male PNE, which might affect the children's cognitive performance., Competing Interests: Declarations Ethics approval and informed consent The study protocol was approved by the Ethics Committee of Tianjin Children’s Hospital, with written informed consent from all subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Competing interests The authors declare no competing interests. Conflict of interest No potential conflicts of interest relevant to this article were reported., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The neurodevelopmental toxicity of anesthetics has been confirmed repeatedly, and esketamine is now widely used in pediatric surgeries. Oligodendrocyte precursor cells (OPCs) evolved into mature oligodendrocytes (OLs) and formed myeline sheath during the early brain development. In this study, we investigated whether esketamine exposure interrupted development of OPCs and induced hypomyelination in rats. Further we explored the roles of PI3K/Akt phosphorylation in OPCs development and myelination. Sprague Dawley rats with different ages (postnatal day (P) 1, 3, 7 and 12) were exposed to 40mg/kg esketamine. Progesterone treatment was given (16 mg/kg per day for 3 days) 24 h after esketamine exposure via the intraperitoneal route. Corpus callosum tissues were collected at P8 or P14 for western blot and immunofluorescence analyses. Esketamine exposure at P7 and P12 significantly reduced myelin basic protein (MBP) expression and CC1+ OLs number in corpus callosum. Esketamine exposure at P7 not only aggravated the mature OLs apoptosis, also decreased the OPCs proliferation and differentiation, which was related with dephosphorylation of PI3K/Akt. Progesterone was able to promote OPCs differentiation and ameliorate esketamine-induced hypomyelination by enhancing PI3K/Akt phosphorylation. Stage-dependent abnormality of OPCs/OLs after esketamine leads to the esketamine-induced hypomyelination. Esketamine interrupted OPCs evolution via PI3K/Akt signaling pathway, which can be ameliorated by progesterone.

Objective: We investigated the effects of adding regions to current dissemination in space (DIS) criteria for multiple sclerosis (MS)., Methods: Participants underwent brain, optic nerve, and spinal cord MRI. Baseline DIS was assessed by 2017 McDonald criteria and versions including optic nerve, temporal lobe, or corpus callosum as a fifth region (requiring 2/5), a version with all regions (requiring 3/7) and optic nerve variations requiring 3/5 and 4/5 regions. Performance was evaluated against MS diagnosis (2017 McDonald criteria) during follow-up., Results: Eighty-four participants were recruited (53F, 32.8 ± 7.1 years). 2017 McDonald DIS criteria were 87% sensitive (95% CI: 76-94), 73% specific (50-89), and 83% accurate (74-91) in identifying MS. Modified criteria with optic nerve improved sensitivity to 98% (91-100), with specificity 33% (13-59) and accuracy 84% (74-91). Criteria including temporal lobe showed sensitivity 94% (84-98), specificity 50% (28-72), and accuracy 82% (72-90); criteria including corpus callosum showed sensitivity 90% (80-96), specificity 68% (45-86), and accuracy 85% (75-91). Criteria adding all three regions (3/7 required) had sensitivity 95% (87-99), specificity 55% (32-76), and accuracy 85% (75-91). When requiring 3/5 regions (optic nerve as the fifth), sensitivity was 82% (70-91), specificity 77% (55-92), and accuracy 81% (71-89); with 4/5 regions, sensitivity was 56% (43-69), specificity 95% (77-100), and accuracy 67% (56-77)., Interpretation: Optic nerve inclusion increased sensitivity while lowering specificity. Increasing required regions in optic nerve criteria increased specificity and decreased sensitivity. Results suggest considering the optic nerve for DIS. An option of 3/5 or 4/5 regions preserved specificity, and criteria adding all three regions had highest accuracy., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Magnetic resonance imaging (MRI) brain abnormalities have been reported in the corpus callosum (CC) of patients with adult-onset hypothyroidism. However, no study has directly compared CC-specific morphological or functional alterations among subclinical hypothyroidism (SCH), overt hypothyroidism (OH), and healthy controls (HC). Moreover, the association of CC alterations with cognition and emotion is not well understood., Methods: Demographic data, clinical variables, neuropsychological scores, and MRI data of 152 participants (60 SCH, 37 OH, and 55 HC) were collected. This study investigated the clinical performance, morphological and functional changes of CC subregions across three groups. Moreover, a correlation analysis was performed to explore potential relationships between these factors., Results: Compared to HC, SCH and OH groups exhibited lower cognitive scores and higher depressive/anxious scores. Notably, rostrum and rostral body volume of CC was larger in the SCH group. Functional connectivity between rostral body, anterior midbody and the right precentral and dorsolateral superior frontal gyrus were increased in the SCH group. In contrast, the SCH and OH groups exhibited a decline in functional connectivity between splenium and the right angular gyrus. Within the SCH group, rostrum volume demonstrated a negative correlation with Montreal Cognitive Assessment and visuospatial/executive scores, while displaying a positive correlation with 24-item Hamilton Depression Rating Scale scores. In the OH group, rostral body volume exhibited a negative correlation with serum thyroid stimulating hormone levels, while a positive correlation with serum total thyroxine and free thyroxine levels., Conclusions: This study suggests that patients with different stages of adult-onset hypothyroidism may exhibit different patterns of CC abnormalities. These findings offer new insights into the neuropathophysiological mechanisms in hypothyroidism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Identifying white matter (WM) microstructural similarities and differences between major depressive disorder (MDD) and bipolar disorder (BD) is an important way to understand the potential neuropathological mechanism in emotional disorders. Numerous diffusion tensor imaging (DTI) studies over recent decades have confirmed the presence of WM anomalies in these two affective disorders, but the results were inconsistent. This study aimed to determine the statistical consistency of DTI findings for BD and MDD by using the coordinate-based meta-analysis (CBMA) approach., Methods: We performed a systematic search of tract-based spatial statistics (TBSS) studies comparing MDD or BD with healthy controls (HC) as of June 30, 2024. The seed-based d- mapping (SDM) was applied to investigate fractional anisotropy (FA) changes. Meta-regression was then used to analyze the potential correlations between demographics and neuroimaging alterations., Results: Regional FA reductions in the body of the corpus callosum (CC) were identified in both of these two diseases. Besides, MDD patients also exhibited decreased FA in the genu and splenium of the CC, as well as the left anterior thalamic projections (ATP), while BD patients showed FA reduction in the left median network, and cingulum in addition to the CC., Conclusions: The results highlighted that altered integrity in the body of CC served as the shared basis of MDD and BD, and distinct microstructural WM abnormalities also existed, which might induce the various clinical manifestations of these two affective disorders. The study was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number: CRD42022301929., (© 2024 The Author(s). Published by IMR Press.)

Background: Reversible splenial lesion syndrome (RESLES) is known as a neuro-imaging syndrome with recurrent but reversible lesion of the corpus callosum, characterized by nonspecific but usually mild encephalopathies and specific imaging manifestations.There are few published reports in the field of oncology., Case Presentation: A 33-year-old female with right breast cancer and with no particular family history was admitted to hospital with high fever and severe headache, after receiving adjuvant radiotherapy. Blood routine test upon admission suggested neutropenia, considering myelosuppression associated with radiotherapy. There were no definite findings of common pathogenic microorganism, and no imaging indication of certain infectious sites other than a likely reversible corpus callosum syndrome suggested by brain MRI, which was relieved after systemic antibiotic therapy and granulocyte colony-stimulating factor injection., Conclusions: Reversible splenial lesion syndrome is a kind of clinical-imaging syndrome with multiple clinical manifestations and etiologies. This breast cancer patient after postoperative adjuvant radiotherapy develops a complication of RESLES that rings an alarm bell to the oncologists not to easily recognize the corpus callosum lesion as infarction or metastasis. Meanwhile, the potential pathogenic mechanisms need to be explored further., (© 2024. The Author(s).)

The research aims to study the therapeutic impact of HEK293-XPack-Olig2 cell-derived exosomes on remyelination of the corpus callosum in a cuprizone-induced demyelinating disease model. A lentiviral vector expressing Olig2 was constructed using XPack technology. The highly abundant Olig2 exosomes (ExoOs) were isolated by centrifugation for subsequent experiments. Western blot, nanoparticle tracking analysis (NTA), and electron microscopy showed no significant difference in particle size and morphology between Exos and ExoOs, and a high level of Olig2 expression could be detected in ExoOs, indicating that exosome modification by XPack technology was successful. The Black Gold/Fluromyelin staining analysis showed that the ExoOs group significantly reduced the demyelination area in the corpus callosum compared to the PBS and Exos groups. Additionally, the PDGFRα/APC staining of the demyelinating region revealed an increase in APC + oligodendrocytes and a decrease in PDGFRα + oligodendrocyte progenitor cells (OPCs) in the ExoOs group. Furthermore, there was evident myelin regeneration in the demyelinated areas after ExoOs treatment, with better g-ratio and a higher number of intact myelin compared to the other treatment groups. The level of Sox10 expression in the brain tissue of the ExoOs group were higher compared to those of the PBS and Exos groups. The demyelination process can be significantly slowed down by the XPack-modified exosomes, the differentiation of OPCs promoted, and myelin regeneration accelerated under pathological conditions. This process is presumed to be achieved by changing the expression level of intracellular differentiation-related genes after exosomes transport Olig2 enriched into oligodendrocyte progenitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Intravital 2P-microscopy enables the longitudinal study of brain tumor biology in superficial mouse cortex layers. Intravital microscopy of the white matter, an important route of glioblastoma invasion and recurrence, has not been feasible, due to low signal-to-noise ratios and insufficient spatiotemporal resolution. Here, we present an intravital microscopy and artificial intelligence-based analysis workflow (Deep3P) that enables longitudinal deep imaging of glioblastoma up to a depth of 1.2 mm. We find that perivascular invasion is the preferred invasion route into the corpus callosum and uncover two vascular mechanisms of glioblastoma migration in the white matter. Furthermore, we observe morphological changes after white matter infiltration, a potential basis of an imaging biomarker during early glioblastoma colonization. Taken together, Deep3P allows for a non-invasive intravital investigation of brain tumor biology and its tumor microenvironment at subcortical depths explored, opening up opportunities for studying the neuroscience of brain tumors and other model systems., (© 2024. The Author(s).)

Background and Objectives: Childhood cerebral adrenoleukodystrophy (C-ALD) is a severe inflammatory demyelinating disease that must be treated at an early stage to prevent permanent brain injury and neurocognitive decline. In standard clinical practice, C-ALD lesions are detected and characterized by a neuroradiologist reviewing anatomical MRI scans. We aimed to assess whether diffusion tensor imaging (DTI) is sensitive to the presence and severity of C-ALD lesions and to investigate associations with neurocognitive outcomes after hematopoietic cell therapy (HCT)., Methods: In this retrospective cohort study, we analyzed high-resolution anatomical MRI, DTI, and neurocognitive assessments from boys with C-ALD undergoing HCT at the University of Minnesota between 2011 and 2021. Longitudinal DTI data were compared with an age-matched group of boys with ALD and no lesion (NL-ALD). DTI metrics were obtained for atlas-based regions of interest (ROIs) within 3 subdivisions of the corpus callosum (CC), corticospinal tract (CST), and total white matter (WM). Between-group baseline and slope differences in fractional anisotropy (FA) and axial (AD), radial (RD), and mean (MD) diffusivities were compared using analysis of covariance accounting for age, MRI severity (Loes score), and lesion location., Results: Among patients with NL-ALD (n = 14), stable or increasing FA, stable AD, and stable or decreasing RD and MD were generally observed during the 1-year study period across all ROIs. In comparison, patients with mild posterior lesions (Loes 1-2; n = 13) demonstrated lower baseline FA in the CC splenium (C-ALD 0.50 ± 0.08 vs NL-ALD 0.58 ± 0.04; p BH = 0.022 adjusted Benjamini-Hochberg p -value), lower baseline AD across ROIs (e.g., C-ALD 1.34 ± 0.03 ×10 -9 m 2 /s in total WM vs NL-ALD 1.38 ± 0.04 ×10 -9 m 2 /s; p BH = 0.005), lower baseline RD in CC body and CST, and lower baseline MD across ROIs except CC splenium. Longitudinal slopes in CC splenium showed high sensitivity and specificity in differentiating early C-ALD from NL-ALD. Among all patients with C-ALD (n = 38), baseline Loes scores and DTI metrics were associated with post-HCT neurocognitive functions, including processing speed (e.g., FA WM Spearman correlation coefficient R = 0.64) and visual-motor integration (e.g., FA WM R = 0.71)., Discussion: DTI was sensitive to lesion presence and severity as well as clinical neurocognitive effects of C-ALD. DTI metrics quantify C-ALD even at an early stage.

Multiple sclerosis (MS) is a debilitating demyelinating disease characterized by remyelination failure attributed to inadequate oligodendrocyte precursor cells (OPCs) differentiation and aberrant astrogliosis. A comprehensive cell atlas reanalysis of clinical specimens brings to light heightened clusterin (CLU) expression in a specific astrocyte subtype links to active lesions in MS patients. Our investigation reveals elevated astrocytic CLU levels in both active lesions of patient tissues and female murine MS models. CLU administration stimulates primary astrocyte proliferation while concurrently impeding astrocyte-mediated clearance of myelin debris. Intriguingly, CLU overload directly impedes OPC differentiation and induces OPCs and OLs apoptosis. Mechanistically, CLU suppresses PI3K-AKT signaling in primary OPCs via very low-density lipoprotein receptor. Pharmacological activation of AKT rescues the damage inflicted by excess CLU on OPCs and ameliorates demyelination in the corpus callosum. Furthermore, conditional knockout of CLU emerges as a promising intervention, showcasing improved remyelination processes and reduced severity in murine MS models., (© 2024. The Author(s).)

Background: Mirror movements (MM) are commonly caused by a defect of interhemispheric pathways also affected in multiple sclerosis (MS), particularly the corpus callosum. We investigated the prevalence of MM in MS in relation to functional and morphological callosal fiber integrity by transcranial magnetic stimulation (TMS), magnetic resonance imaging (MRI), as well as fatigue., Methods: In 21 patients with relapsing-remitting MS and 19 healthy controls, MM were assessed and graded (Woods and Teuber scale: MM 1-4) using a bedside test. Fatigue was evaluated using the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire. TMS measured ipsilateral silent period latency and duration. MRI assessed callosal atrophy by measuring the normalized corpus callosum area (nCCA), corpus callosum index (CCI), and lesion volume., Results: MS patients had significantly more often and pronounced MM compared to healthy controls (p = 0.0002) and nCCA was significantly lower (p = 0.045) in MRI studies. Patients with higher MM scores (MM > 1 vs. MM 0/1) showed significantly more fatigue (higher FSMC sum score, p = 0.04, motor score, p = 0.01). In TMS and MRI studies, no significant differences were found between patients with MM 0/1 and those with MM > 1 (ipsilateral silent period measurements, CCA, CCI and lesion volume)., Conclusions: MM are common in MS and can easily be detected through bedside testing. As MM are associated with fatigue, they might indicate fatigue in MS. It is possible that other cerebral structures, in addition to the corpus callosum, may contribute to the origin of MM in MS., (© 2024. The Author(s).)

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder affecting the central nervous system. Evidence suggests that age-related neurodegeneration contributes to disability progression during the chronic stages of MS. Aging is characterized by decreased regeneration potential and impaired myelin repair in the brain. It is hypothesized that accelerated cellular aging contributes to the functional decline associated with neurodegenerative diseases. We assessed the impact of aging on myelin content in the corpus callosum (CC) and compared aging with the long-term demyelination (LTD) consequents induced by 12 weeks of feeding with a cuprizone (CPZ) diet. Initially, evaluating myelin content in 2-, 6-, and 18-month-old mice revealed a reduction in myelin content, particularly at 18 months. Myelin thickness was decreased and the g-ratio increased in aged mice. Although a lower myelin content and higher g-ratio were observed in LTD model mice, compared to the normally aged mice, both aging and LTD exhibited relatively similar myelin ultrastructure. Our findings provide evidence that LTD exhibits the hallmarks of aging such as elevated expression of senescence-associated genes, mitochondrial dysfunction, and high level of oxidative stress as observed following normal aging. We also investigated the senescence-associated β-galactosidase activity in O4 + late oligodendrocyte progenitor cells (OPCs). The senescent O4 + /β-galactosidase + cells were elevated in the CPZ diet. Our data showed that the myelin degeneration in CC occurs throughout the lifespan, and LTD induced by CPZ accelerates the aging process which may explain the impairment of myelin repair in patients with progressive MS., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: The most compact portion of the corpus callosum (CC) is the corpus splenium (CS)., Purpose: To evaluate the connection between clinical and demographic features to determine whether neuroimaging findings will be permanent or temporary in CS patients., Material and Methods: We enrolled 93 patients (age range = 18-86 years) with CS lesions. Demographic and clinical information were recorded. We examined the lesions depending on the location. Group 1 (n = 20) had lesions limited to the CS (egg-shaped or round); group 2 (n = 15) had "boomerang sign" lesions; and group 3 (n = 58) had splenium involvement in conditions affecting the whole brain (Boomerang sign+ plus)., Results: Group 1 had a lower mean age, shorter disease duration, and fewer persistent lesions than others ( P  < 0.01, P  < 0.001, and P  < 0.001, respectively). The mean disease onset age (in years) in group 1 was higher than that of the other groups ( P  < 0.045). Group 2 had lower potassium (K) ( P  < 0.003) and red cell distribution width levels ( P  < 0.029) than the other groups. Age <41.5 years ( P  < 0.001), age at illness initiation <48.5 years ( P  < 0.002), disease duration <5.5 months ( P  < 0.001), and eosinophil level <0.29 uL ( P 0.014) all point to temporary lesions., Conclusion: Cases with limited CS lesions have younger onset ages, lower disease onset ages, and shorter disease durations. Age, age of disease onset, disease duration, and eosinophil level are risk variables that affect whether CS lesions are permanent or temporary., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Demyelination is the loss of myelin in CNS, resulting in damaged myelin sheath. Oxidative stress and neuroinflammation play a key role in inducing demyelinating diseases like MS; hence, controlling oxidative stress and neuroinflammation is important. Cuprizone (CPZ), a copper chelator, generates oxidative stress and neuroinflammation, thereby inducing demyelination. Therefore, the CPZ-induced demyelinating mouse model (CPZ model) is widely used in research. The present study was intended to unravel a mechanism of inhibition of demyelination by arsenic in a CPZ model, which is otherwise known for its toxicity. We investigated an alternative mechanism of inhibition of demyelination by arsenic through the reversal of SOD1 activity employing in silico analysis, analytical chemistry techniques, and in vitro and in vivo experiments. In vivo experiments showed protection of body weight, survivability, and myelination of the corpus callosum in CPZ and arsenic-co-exposed animals, where neuroinflammation was apparently not involved. In vitro experiments revealed that arsenic-mediated reversal of impaired SOD1 activity leads to reduced cellular ROS levels and better viability of primary oligodendrocytes. Reversal of SOD1 activity was also observed in the corpus callosum tissue isolated from experimental animals. In silico and analytical chemistry studies revealed that similar to copper, arsenic can potentially bind to CPZ and thereby make the copper freely available for SOD1 activity. Suitable neurobehavior tests further validated the protective effect of arsenic. Taken together, the present study revealed that arsenic protects oligodendrocytes and demyelination of corpus callosum by reversing CPZ-induced impaired SOD1 activity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Optic Aphasia (OA) and Associative Visual Agnosia (AVA) are neuropsychological disorders characterized by impaired naming on visual presentation. From a cognitive point of view, while stimulus identification is largely unimpaired in OA (where access to semantic knowledge is still possible), in AVA it is not. OA has been linked with right hemianopia and disconnection of the occipital right-hemisphere (RH) visual processing from the left hemisphere (LH) language areas.In this paper, we describe the case of AA, an 81-year-old housewife suffering from a deficit in naming visually presented stimuli after left occipital lesion and damage to the interhemispheric splenial pathway. AA has been tested through a set of tasks assessing different levels of visual object processing. We discuss behavioral performance as well as the pattern of lesion and disconnection in relation to a neurocognitive model adapted from Luzzatti and colleagues (1998). Despite the complexity of the neuropsychological picture, behavioral data suggest that semantic access from visual input is possible, while a lesion-based structural disconnectome investigation demonstrated the splenial involvement.Altogether, neuropsychological and neuroanatomical findings support the assumption of visuo-verbal callosal disconnection compatible with a diagnosis of OA., (© 2024. The Author(s).)

Objectives: To determine the prevalence of abnormalities of the corpus callosum (AbnCC) in a non-selected population, to propose a systematic screening protocol for AbnCC in all populations through direct assessment, and to describe the follow-up and prognosis of all AbnCC cases diagnosed in our clinical setting., Methods: This was a retrospective review of the prevalence of AbnCC over 11 years. We included a sagittal assessment of the corpus callosum (CC) in the second-trimester scan. AbnCC was classified into complete agenesis of CC (ACC) and dysgenesis of CC (DCC; including small, partial agenesis, thick and with lipoma)., Results: Of the 38,586 second-trimester scans performed during our screening, 43 cases of AbnCC were detected (prevalence of 0.8/1000). Of the AbnCC cases, 10 cases were identified as ACC (29.40%) and 24 as DCC (70.59%). Follow-up investigations showed that in the 43 cases with AbnCC, 76.5% had other associated ultrasound abnormalities, 26.5% had genetic abnormalities, 11.8% had other MRI abnormalities, and 25% of the children had neurodevelopmental delays (8.8% of the total), which were severe in only one case., Conclusions: AbnCC is found in approximately 0.8/1000 of cases in an unselected population. The findings suggest that systematic and direct assessment of the CC as part of screening ultrasound in the second trimester of gestation should be recommended as a routine practice., (© 2024 John Wiley & Sons Ltd.)

Background: Wernicke's encephalopathy (WE) is an acute neurological syndrome resulting from thiamine (vitamin B1) deficiency. It has been recognized increasingly in non-alcoholic patients, such as in the condition of malnutrition. Recent literature has shed light on uncommon symptoms and neuroimaging findings., Case Report: We reported a case of a 44-year-old male who initially presented with bilateral hearing loss, and exhibited abnormality in the splenium of the corpus callosum on magnetic resonance imaging (MRI) diffusion-weighted imaging sequence. On the following day the patient developed new symptoms, including unstable walking, double vision and hallucination. The subsequent brain MRI demonstrated lesions involving periaqueductal grey matter and bilateral medial thalamus, indicating the diagnosis of WE. Empirical treatment with intravenous thiamine resulted in complete clinical and radiological resolution., Conclusion: To the best of our knowledge, the current case is the first report of WE in literature with uncommon but reversible manifestations. This case warns us to maintain a heightened level of suspicion for WE in malnourished patients with neurological deficits, despite the possibility of atypical presentations encompassing bilateral hearing disturbances and unusual neuroradiological results. Early diagnosis and timely administration of thiamine in WE are likely to lead to a favorable outcome and full recovery., (© 2024. Fondazione Società Italiana di Neurologia.)

Here we described an 18-year-old woman who were initially misdiagnosed as psychiatric disorders in a psychiatric institution. She was transferred to our neurological ward because of impaired consciousness. Neuronal antibody testing confirmed the diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Cerebral magnetic resonance imaging (MRI) revealed a concomitant disorder named reversible splenial lesion syndrome (RESLES). After administration of combined immunotherapy, the patient recovered completely 3 months after discharge. To our knowledge, co-occurrence of RESLES and anti-NMDAR encephalitis was only described in two patients with teratoma and we provide another case without teratoma. We highlight that anti-NMDAR antibodies can be added to the multiple causes of RESLES. It is therefore imperative for clinicians to detect anti-neuronal antibodies in patients with RESLES to avoid missed diagnosis., (© 2024. Fondazione Società Italiana di Neurologia.)

Glutamatergic alteration is one of the potential mechanisms of depression. However, there is no consensus on whether glutamate metabolism changes affect the myelin structure of depression in mouse models. Glutamate chemical exchange saturation transfer (GluCEST) is a novel and powerful molecular imaging technique that can visualize glutamate distribution. In this study, we used the GluCEST imaging technique to look at glutamate levels in mice under chronic unpredictable mild stress (CUMS) and how they relate to demyelination. The CUMS mice were exposed to different stress factors for 6 weeks. Evaluated of depression in CUMS mice by behavioral tests. MRI scans were then performed, including T2-mapping, GluCEST, and diffusion tensor imaging (DTI) sequences. Brain tissues were collected for Luxol Fast Blue staining and immunofluorescence staining to analyze the changes in the myelin sheath. Artificially sketched regions of interest (ROI) (corpus callosum, hippocampus, and thalamus) were used to calculate the GluCEST value, fractional anisotropy (FA), and T2 value. Compared with the control group, the GluCEST value in the ROIs of CUMS mice significantly decreased. Similarly, the FA value in ROIs was lower in the CUMS group than in the CTRL group, but the T2 value did not differ significantly between the two groups. The histological results showed that ROIs in the CUMS group had demyelination compared with the CTRL group, indicating that DTI was more sensitive than T2 mapping in detecting myelin abnormalities. Furthermore, the GluCEST value in the ROIs correlates positively with the FA value. These findings suggest that altered glutamate metabolism may be one of the important factors leading to demyelination in depression, and GluCEST is expected to serve as an imaging biological marker for the diagnosis of demyelination in depression., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Chronic restrain stress (CRS) induces depression-like behaviors and demyelination in the brain; however, the relationship between these depression-like behaviors and demyelination remains unclear. Arketamine, the (R)-enantiomer of ketamine, has shown rapid antidepressant-like effects in CRS-exposed mice., Methods: We examined whether arketamine can improve both depression-like behaviors and demyelination in the brains of CRS-exposed mice. Additionally, we investigated the role of transforming growth factor β1 (TGF-β1) in the beneficial effects of arketamine., Results: A single dose of arketamine (10 mg/kg) improved both depression-like behavior and demyelination in the corpus callosum of CRS-exposed mice. Correlations were found between depression-like behaviors and demyelination in this region. Furthermore, pretreatment with RepSox, an inhibitor of TGF-β1 receptor, significantly blocked the beneficial effects of arketamine on depression-like behaviors and demyelination in CRS-exposed mice. Finally, a single intranasal administration of TGF-β1 ameliorated both depression-like behaviors and demyelination in CRS-exposed mice., Limitations: The precise mechanisms by which TGF-β1 contributes to the effects of arketamine remain unclear., Conclusions: These data suggest that CRS-induced demyelination in the corpus callosum may contribute to depression-like behaviors, and that arketamine can mitigate these changes through a TGF-β1-dependent mechanism., Competing Interests: Declaration of competing interest Dr. Hashimoto is the inventor of filed patent applications on “The use of R-ketamine in the treatment of psychiatric diseases”, “(S)-norketamine and salt thereof as pharmaceutical”, “R-ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder”, “Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases”, and “R-ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder” by the Chiba University. Dr. Hashimoto has also received speakers' honoraria, consultant fee, or research support from Otsuka. Other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: RESLES (Reversible splenial lesion syndrome) can be observed secondary to various diseases, and intramyelinic edema may play a crucial role in the pathogenesis of SCC (Splenium of the corpus callosum). Some studies have suggested that hypoxic-ischaemic encephalopathy may constitute a risk factor for SCC lesions. However, the potential impact of high-altitude environments on SCC, especially during chronic exposure, remain obscure., Methods: Our study included 19 patients who satisfied the diagnostic criteria of RESLES at high altitudes. Ten low-altitude patients with RESLES were included as controls. All participants received MRI (Magnetic resonance imaging) scans twice. Routine blood tests, liver, kidney and thyroid function, coagulation function, electrolytes and vitamins were detected during hospitalization and before discharge. In addition, the patients were followed up in May 2023., Results: Hypoxic environments at high altitudes may increase the risk of RESLES. The two groups showed different clinical symptoms. High-altitude patients had significantly higher CRP levels than low-altitude patients. The lesion size in high-altitude patients showed a positive correlation with SaO 2 levels. However, the patients at low altitudes had positive correlation trends between lesion size and several inflammatory markers (WBC, NEU and CRP). All patients had a benign prognosis that may not be affected by the use of prednisone acetate., Conclusions: Hypoxic environments at high altitudes may play a role in the aetiology of RESLES. Additionally, RESLES is a reversible disease and the administration of glucocorticoids may be dispensable for its treatment.

Rationale: Critical illness-associated cerebral microbleeds (CI-aCMBs) are emerging as significant radiographic findings in patients with hypoxic ischemic injuries. Their occurrence, particularly in the corpus callosum, warrants a closer examination due to the potential implications for neurological outcomes in critically ill patients. We aim to describe a rare case of CI-aCMBs within the corpus callosum following cardiac arrest with the goal of bolstering the scientific literature on this topic., Patient Concerns: A 34-year-old man with a history of polysubstance abuse was found unconscious and experienced a pulseless electrical activity (PEA) cardiac arrest after a suspected drug overdose. Post-resuscitation, the patient exhibited severe respiratory distress, acute kidney injury, and profound neurological deficits., Diagnoses: Initial magnetic resonance imaging scans post-cardiac arrest showed no acute brain abnormalities. However, subsequent imaging revealed extensive cerebral microbleeds predominantly in the corpus callosum, diagnosed as CI-aCMBs. These findings were made in the absence of high signal intensity on T2-weighted images, suggesting a unique pathophysiological profile of microhemorrhages., Interventions: The patient underwent targeted temperature management (TTM) and supportive care in the intensive care unit after cardiac arrest., Outcomes: He was subsequently extubated and had significant recovery without any neurological deficits., Lessons: CI-aCMBs is a rare radiographic finding after cardiac arrest. These lesions may be confined to the corpus callosum and the long-term clinical and radiographic sequelae are still largely unknown., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The corpus callosum, the largest white matter inter-hemispheric pathway, is involved in language and communication. In a cohort of 15 children and adolescents (8-15 years) with developmental absence of the corpus callosum (AgCC), this study aimed to describe language and everyday communication functioning, and explored the role of anatomical factors, social risk, and non-verbal IQ in these outcomes. Standardised measures of language and everyday communication functioning, intellectual ability and social risk were used. AgCC classification and anterior commissure volume, a potential alternative pathway, were extracted from T1-weighted images. Participants with AgCC showed reduced receptive and expressive language compared with test norms, and high rates of language and communication impairments. Complete AgCC, higher social risk and lower non-verbal IQ were associated with communication difficulties. Anterior commissure volume was not associated with language and communication. Recognising heterogeneity in language and communication functioning enhances our understanding and suggests specific focuses for potential interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite improved management of traumatic brain injury (TBI), it still leads to lifelong sequelae and disability, particularly in children. Chronic neuroinflammation (the so-called tertiary phase), in particular, microglia/macrophage and astrocyte reactivity, is among the main mechanisms suspected of playing a role in the generation of lesions associated with TBI. The role of acute neuroinflammation is now well understood, but its persistent effect and impact on the brain, particularly during development, are not. Here, we investigated the long-term effects of pediatric TBI on the brain in a mouse model., Methods: Pediatric TBI was induced in mice on postnatal day (P) 7 by weight-drop trauma. The time course of neuroinflammation and myelination was examined in the TBI mice. They were also assessed by magnetic resonance, functional ultrasound, and behavioral tests at P45., Results: TBI induced robust neuroinflammation, characterized by acute microglia/macrophage and astrocyte reactivity. The long-term consequences of pediatric TBI studied on P45 involved localized scarring astrogliosis, persistent microgliosis associated with a specific transcriptomic signature, and a long-lasting myelination defect consisting of the loss of myelinated axons, a decreased level of myelin binding protein, and severe thinning of the corpus callosum. These results were confirmed by reduced fractional anisotropy, measured by diffusion tensor imaging, and altered inter- and intra-hemispheric connectivity, measured by functional ultrasound imaging. In addition, adolescent mice with pediatric TBI showed persistent social interaction deficits and signs of anxiety and depressive behaviors., Conclusions: We show that pediatric TBI induces tertiary neuroinflammatory processes associated with white matter lesions and altered behavior. These results support our model as a model for preclinical studies for tertiary lesions following TBI., (Copyright © 2024. Published by Elsevier Inc.)

Background: Many children with severe traumatic brain injury (TBI) receive magnetic resonance imaging (MRI) during hospitalization. There are insufficient data on how different patterns of injury on early MRI inform outcomes., Methods: Children (3-17 years) admitted in 2010-2021 for severe TBI (Glasgow Coma Scale [GCS] score < 9) were identified using our site's trauma registry. We used multivariable modeling to determine whether the hemorrhagic diffuse axonal injury (DAI) grade and the number of regions with restricted diffusion (subcortical white matter, corpus callosum, deep gray matter, and brainstem) on MRI obtained within 7 days of injury were independently associated with time to follow commands and with Functional Independence Measure for Children (WeeFIM) scores at the time of discharge from inpatient rehabilitation. We controlled for the clinical variables age, preadmission cardiopulmonary resuscitation, pupil reactivity, motor GCS score, and fever (> 38 °C) in the first 12 h., Results: Of 260 patients, 136 (52%) underwent MRI within 7 days of injury at a median of 3 days (interquartile range [IQR] 2-4). Patients with early MRI were a median age of 11 years (IQR 7-14), 8 (6%) patients received cardiopulmonary resuscitation, 19 (14%) patients had bilateral unreactive pupils, the median motor GCS score was 1 (IQR 1-4), and 82 (60%) patients had fever. Grade 3 DAI was present in 46 (34%) patients, and restricted diffusion was noted in the corpus callosum in 75 (55%) patients, deep gray matter in 29 (21%) patients, subcortical white matter in 23 (17%) patients, and the brainstem in 20 (15%) patients. After controlling for clinical variables, an increased number of regions with restricted diffusion, but not hemorrhagic DAI grade, was independently associated with longer time to follow commands (hazard ratio 0.68, 95% confidence interval 0.53-0.89) and worse WeeFIM scores (estimate β - 4.67, 95% confidence interval - 8.33 to - 1.01)., Conclusions: Regional restricted diffusion on early MRI is independently associated with short-term outcomes in children with severe TBI. Multicenter cohort studies are needed to validate these findings and elucidate the association of early MRI features with long-term outcomes in children with severe TBI., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Studies suggest that amyotrophic lateral sclerosis (ALS) compromises the integrity of white matter fiber tracts, primarily affecting motor fibers. However, it remains uncertain whether the integrity of these fibers influences the risk of ALS. We performed bidirectional two-sample Mendelian randomization (MR) and multivariable MR analyses to evaluate the associative relationships between the integrity of fiber tracts [including the corticospinal tract (CST) and corpus callosum (CC)] and the risk of ALS. Genetic instrumental variables for specific fiber tracts were obtained from published genome-wide association studies (GWASs), including 33,292 European individuals from five diffusion magnetic resonance imaging (dMRI) datasets. Summary-level GWAS data for ALS were derived from 27,205 ALS patients and 110,881 controls. The MR results suggested that an increase in the first principal component (PC1) of fractional anisotropy (FA) in the genu of the CC (GCC) was correlated with an increased risk of ALS (P FDR  = 0.001, odds ratio = 1.363, 95% confidence interval 1.178-1.577). Although other neuroimaging phenotypes [mean diffusivity in the CST, radial diffusivity (RD) in the CST, FA in the GCC, PC1 in the body of the CC (BCC), PC1 in the CST, and RD in the GCC] did not pass correction, they were also considered to have suggestive associations with the risk of ALS. No evidence revealed that ALS caused changes in the integrity of fiber tracts. In summary, the results of this study provide genetic support for the potential association between the integrity of specific fiber tracts and the risk of ALS. Greater fiber integrity in the GCC and BCC may be a risk factor for ALS, while greater fiber integrity in the CST may have a protective effect on ALS. This study provides insights into ALS development., (© 2024. The Author(s).)

Headache and neurological deficits with cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is a rare condition characterised by recurrent episodes of headache and transient neurological deficits. This case report presents a young patient initially diagnosed with hemiplegic migraine, having a normal brain CT, with focal cerebral perfusion mismatch not restricted to a single vascular territory on CT angiography. Brain MRI revealed a cytotoxic lesion of the splenium in the corpus callosum (CLOCC), a feature also reported in migraine. However, recurrent headaches with neurological deficits prompted further investigations with CSF analysis and brain MRI, confirming HaNDL and demonstrating reversibility of CLOCC. Recognising HaNDL as a differential diagnosis is essential in patients with recurrent headaches with focal neurological deficits, given the differences in therapeutic approach. The relationship between migraine and HaNDL is not fully understood, but they may share a pathophysiological link. Awareness of this is crucial for accurate diagnosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Multiple sclerosis (MS) is an irreversible progressive CNS pathology characterized by the loss of myelin (i.e. demyelination). The lack of myelin is followed by a progressive neurodegeneration triggering symptoms as diverse as fatigue, motor, locomotor and sensory impairments and/or bladder, cardiac and respiratory dysfunction. Even though there are more than fourteen approved treatments for reducing MS progression, there are still no cure for the disease. Thus, MS research is a very active field and therefore we count with different experimental animal models for studying mechanisms of demyelination and myelin repair, however, we still lack a preclinical MS model assembling demyelination mechanisms with relevant clinical-like signs., Results: Here, by inducing the simultaneous demyelination of both callosal and cerebellar white matter fibers by the double-site injection of lysolecithin (LPC), we were able to reproduce CNS demyelination, astrocyte recruitment and increases levels of proinflammatory cytokines levels along with motor, locomotor and urinary impairment, as well as cardiac and respiratory dysfunction, in the same animal model. Single site LPC-injections either in corpus callosum or cerebellum only, fails in to reproduce such a complete range of MS-like signs., Conclusion: We here report that the double-site LPC injections treatment evoke a complex MS-like mice model. We hope that this experimental approach will help to deepen our knowledge about the mechanisms of demyelinated diseases such as MS., (© 2024. The Author(s).)

Background: Tic disorder is a neuropsychiatric disorder characterized by involuntary movements or vocalizations. Previous studies utilizing diffusion-weighted imaging to explore white-matter alterations in tic disorders have reported inconsistent results regarding the affected tracts. We aimed to address this gap by employing a novel tractography technique for more detailed analysis., Methods: We analyzed MRI data from 23 children with tic disorders and 23 healthy controls using TRActs Constrained by UnderLying Anatomy (TRACULA), an advanced automated probabilistic tractography method. We examined fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity in 42 specific significant white matter tracts., Results: Our findings revealed notable differences in the children with tic disorders compared to the control group. Specifically, there was a significant reduction in FA in the parietal part and splenium of the corpus callosum and the left corticospinal tract. Increased RD was observed in the temporal and splenium areas of the corpus callosum, the left corticospinal tract, and the left acoustic radiation. A higher mean diffusivity was also noted in the left middle longitudinal fasciculus. A significant correlation emerged between the severity of motor symptoms, measured by the Yale Global Tic Severity Scale, and FA in the parietal part of the corpus callosum, as well as RD in the left acoustic radiation., Conclusion: These results indicate a pattern of reduced interhemispheric connectivity in the corpus callosum, aligning with previous studies and novel findings in the diffusion indices changes in the left corticospinal tract, left acoustic radiation, and left middle longitudinal fasciculus. Tic disorders might involve structural abnormalities in key white matter tracts, offering new insights into their pathogenesis., (© 2024. The Author(s).)