Corpus Callosum Research Articles

Associations of haematological and inflammatory biomarkers with brain volume in patients with sickle cell anaemia: A cross-sectional retrospective study.

Sickle cell disease is a genetic disorder characterised by abnormal haemoglobin production. This study aims to investigate the associations between haematological and inflammatory biomarkers and brain volumes in patients with sickle cell anaemia and compare brain structure between patients with sickle cell anaemia and healthy controls. This retrospective cross-sectional study included 130 participants (70 sickle cell anaemia patients and 60 healthy controls) who underwent brain MRI examinations at King Fahad Central Hospital between January 2010 and October 2022. Demographic data and haematological and inflammatory biomarkers were collected to examine their relationships with brain volumes. Brain volumes were measured using FreeSurfer. Specific haematological and inflammatory biomarkers were correlated with brain volume in patients with sickle cell anaemia, p < 0.05. Sickle cell anaemia patients exhibited smaller volumes in the brainstem, corpus callosum and amygdala compared to healthy controls. Males had significantly higher iron levels (p < 0.001) and larger various brain structure volumes (p < 0.05) than females. This study demonstrates significant associations between specific biomarkers and brain volume in sickle cell anaemia patients, underscoring the importance of monitoring these biomarkers for early detection and management of neurological complications in sickle cell anaemia.

The shape of the corpus callosum is different in bipolar disorder.

Bipolar disorder (BD) is a recurrent chronic disorder characterised by fluctuations in mood and energy disposition. Diseases could lead to degenerative alterations in brain structures such as corpus callosum (CC). Studies demonstrated that abnormalities in CC are associated with BD symptoms. The present study aims to analyse the CC of the patients with statistical shape analysis (SSA) and compare the findings with healthy controls. Forty-one BD patients and 41 healthy individuals in similar age groups, which included 23 female and 18 male subjects, participated in the study. CC was marked with landmarks on the mid-sagittal images of each individual. The mean 'Procrustes' point was calculated, and shape deformations were analysed with thin-plate spline analysis. Significant differences were observed in the shape of CC between the two groups, where maximum CC deformation was observed in posterior region marks in BD patients. There was no significant difference between the CC area of the BD patients and controls. CC analysis conducted with SSA revealed significant differences between patients and healthy controls. The study findings emphasised the abnormal distribution of white matter in CC and the variable subregional nature of CC in BD patients. This study may enable the development of more targeted and effective treatment strategies by taking into account biological factors and understanding the differences in the brain regions of individuals with BD.

Septo-optic dysplasia plus: A case report for reviewing and recognizing this condition

Septo-optic dysplasia is a congenital neurological condition with multifactorial etiology, characterized by septum pellucidum agenesis and/or corpus callosum dysgenesis, hypoplasia of the chiasm or optic nerves, and hormonal dysfunction with pituitary or hypothalamic alterations. Diagnosis requires two of these criteria and magnetic resonance is the imaging test of choice. Most cases present with abnormalities of cortical development in the form known as septo-optic dysplasia plus. While seizures and neurodevelopmental disorders are the dominant neurological manifestations, this entity is highly heterogeneous and has multiple clinical and radiological findings to consider. We present the case of a 35-year-old man with a history of cranioencephalic trauma in childhood and remission for refractory focal epilepsy associated with cognitive deficit. During the initial examination, the simple cranial tomography showed septum pellucidum agenesis and corpus callosum dysgenesis. Brain magnetic resonance imaging revealed agenesis of the septum pellucidum, irregularity and anomalous thickening of the cerebral cortex in frontal lobes and perisylvian region, heterotopic gray matter in frontal lobes and left fronto-insular region, mild supratentorial ventriculomegaly, atypical appearance of the corpus callosum rostrum, and hypoplasia of the chiasm and optic nerves. Although agenesis of the septum pellucidum was the key finding in this case, it is not present in all patients. The relevance of magnetic resonance imaging for the detailed evaluation of other involved structures, highlighting optic nerve hypoplasia, is fundamental in the radiologist’s diagnostic workup and this entity recognition.

Analysis of clinical phenotypes and genetic variations in two pedigrees affected with Weiss-Kruszka syndrome.

Weiss-Kruszka syndrome (WSKA) is a rare autosomal dominant syndrome characterized by multiple congenital anomalies caused by variants in the zinc finger protein 462 gene (ZNF462). About 40 cases of Weiss-Kruszka syndrome have been reported worldwide, and the aim of this study was to investigate the genetic causes of three patients from two Weiss-Kruszka syndrome family pedigrees with the aim of accumulating more data on the disease. To explore the clinical and genetic characteristics of two pedigrees with Weiss-Kruszka syndrome. The clinical data and family history of patients and family members of two pedigrees with Weiss-Kruszka syndrome were collected, and the pathogenic genes of the patients were analysed by whole-exon sequencing. Suspicious variants were verified by Sanger sequencing verification and bioinformatics prediction. Proband 1 has developmental delay, autistic behaviour, and abnormal electroencephalogram results. WES revealed a classical heterozygous c.6696-2A > C splice variant of the ZNF462 gene, which was detected in neither parent. This position was conserved, and the variant was predicted to be deleterious. Minigene assays revealed that three types of aberrantly spliced mRNAs were produced. MRI of proband 2 suggested dysplasia of the corpus callosum with the formation of hemispheric cleft cysts, with a teardrop-like appearance in the lateral ventricle. WES revealed that a heterozygous c.4891C > T:p. The Glu1631Ter nonsense variant of the ZNF462 gene was inherited from her mother. According to the guidelines of the American Society of Medical Genetics and combined with its clinical manifestations, c.6696-2A > C and c.4891C > T:p. Glu1631Ter was determined to be a possible pathogenic variant. The c.6696-2A>C and c.4891C > T:p.Glu1631Ter of the ZNF462 gene likely underlies Weiss-Kruszka syndrome in children (foetus), which enriches the variant spectrum of Chinese patients with Weiss-Kruszka syndrome and provides a basis for prenatal diagnosis and genetic counselling.

White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals.

Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group. In a mega-analysis, we investigated the associations between BMI, diagnosis or medication and FA. Lower FA was associated with both BD and BMI in six white matter tracts, including the corpus callosum and thalamic radiation. Higher BMI or BD were uniquely associated with lower FA in three and six white matter tracts, respectively. People not receiving lithium treatment had a greater negative association between FA and BMI than people treated with lithium in the posterior thalamic radiation and sagittal stratum. In three tracts BMI accounted for 10.5 to 17% of the negative association between the number of medication classes other than lithium and FA. Both overweight/obesity and BD demonstrated lower FA in some of the same regions. People prescribed lithium had a weaker association between BMI and FA than people not on lithium. In contrast, greater weight contributed to the negative associations between medications and FA. Obesity may add to brain alterations in BD and may play a role in effects of medications on the brain.

Altered callosal morphology in post-stroke cognitive impairment

Stroke is the second leading cause of death and cognitive impairment. Post-stroke cognitive impairment (PSCI) is one of the most common sequelae among stroke survivors, yet its underlying neural mechanisms remain largely unclear. The corpus callosum (CC) plays a crucial role in interhemispheric integration and hemispheric segregation, with changes in CC morphology potentially overlapping with the spectrum of PSCI. This study aimed to investigate the morphological changes in the CC and their diagnostic value in PSCI patients. Structural MRI, neurobehavioral, and clinical data were collected from 104 PSCI patients and 54 demographically matched healthy controls. Significant reductions in CC area, circularity, and genu thickness were observed in PSCI patients, with these changes strongly correlating with global cognitive function. Subgroup analysis revealed that CC circularity significantly decreased when lesions were located in the posterior circulation, while both CC area and circularity markedly decreased with anterior circulation lesions. Receiver Operating Characteristic analyses identified the midbody areas of the CC as having high diagnostic value, with area under the curve values of 0.748 and 0.746, respectively. Further validation analyses suggest that the transcallosal fibers in these CC subregions are connected to the premotor, dorsal attention, and frontoparietal system. These findings show that areal CC atrophy in PSCI patients, particularly in regions with transcallosal connections to the premotor cortex and frontoparietal network, parallels global cognitive impairment. This suggests that CC morphology may serve as a potential imaging marker for the diagnosis and prognosis of PSCI.

Accelerated remyelination and immune modulation by the EBI2 agonist 7α,25-dihydroxycholesterol analogue in the cuprizone model

SummaryResearch indicates a role for EBI2 receptor in remyelination, demonstrating that its deficiency or antagonism inhibits this process. However, activation of EBI2 with its endogenous ligand, oxysterol 7α,25-dihydroxycholesterol (7α,25OHC), does not enhance remyelination beyond the levels observed in spontaneously remyelinating tissue. We hypothesized that the short half-life of the natural ligand might explain this lack of beneficial effects and tested a synthetic analogue, CF3-7α,25OHC, in the cuprizone model. The data showed that extending the bioavailability of 7α,25OHC is sufficient to accelerate remyelination in vivo. Moreover, the analogue, in contrast to the endogenous ligand, upregulated brain expression of Ebi2 and the synthesis of 15 lipids in the mouse corpus callosum. Mechanistically, the increased concentration of oxysterol likely disrupted its gradient in demyelinated areas of the brain, leading to the dispersion of infiltrating EBI2-expressing immune cells rather than their accumulation in demyelinated regions. Remarkably, the analogue CF3-7α,25OHC markedly decreased the lymphocyte and monocyte counts mimicking the key mechanism of action of some of the most effective disease-modifying therapies for multiple sclerosis. Furthermore, the Cd4+ transcripts in the cerebellum and CD4+ cell number in the corpus callosum were reduced compared to vehicle-treated mice. These findings suggest a mechanism by which EBI2/7α,25OHC signalling modulates the immune response and accelerates remyelination in vivo.

Demyelination and impaired oligodendrogenesis in the corpus callosum following lead exposure.

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 4wk) 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 20wk) 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.

White Matter Function and Network Abnormalities in Patients with Diabetic Retinopathy.

This study aims to explore changes in white matter function and network connectivity in individuals with DR. This study included 46 patients with DR and 43 age- and gender-matched healthy control (HC) participants were enrolled in the study. The aim was to investigate inter-group differences in white matter (WM) function and to analyze changes in the WM network among DR patients. Increased degree centrality (DC) values were observed in the middle cerebellar peduncle and genu of the corpus callosum, while higher fractional amplitude of low-frequency fluctuations (fALFF) values were found in the left superior corona radiata, right anterior corona radiata, and right superior longitudinal fasciculus. Conversely, reduced regional homogeneity (ReHo) values were noted in the left posterior thalamic radiation among patients with DR compared to HC, with statistical correction applied The SVM classification accuracy for distinguishing between DR and HC patients based on WM measures indicated values of 81.52%, 80.43%, and 89.13% for DC, fALFF, and ReHo, respectively, with respective area under the curve (AUC) values of 0.87, 0.85, and 0.93. Furthermore, alterations were detected within specific brain regions including the body of corpus callosum (BCC), splenium of corpus callosum (SCC), genu of corpus callosum (GCC), left posterior thalamic radiation (PTR), right anterior corona radiata (ACR), and right posterior corona radiata (PCR) in the DR group compared to HCs, with an intra-network decrease in connectivity. Interestingly, the left superior longitudinal fasciculus (SLF) within the DR group exhibited an intra-network increase compared to the HC group. DR exhibited abnormal white matter functional alterations, particularly affecting the fiber pathways linking the visual network to the sensory-motor network.

Ultrathin visible-light OCT endomicroscopy for in vivo ultrahigh-resolution neuroimaging in deep brain

Deep-brain neuroimaging, a task that demands high-resolution imaging techniques for visualizing intricate brain structures, assessing deep-seated disease histopathology, and offering real-time intervention guidance, is challenged by the resolution-depth trade-off of current methods. We propose an optical coherence tomography (OCT) endomicroscopy device for high-resolution in vivo imaging of deep brain microstructures and histopathology. A unique liquid shaping technique enables the direct fabrication of a microlens on the fiber tip of the imaging probe, optimizing imaging performance parameters, such as longitudinal focal shift, focused spot size, and working distance. In addition, a broadband visible-light source enhances axial resolution and OCT imaging contrast. As a result, the first monolithic visible-light OCT (vis-OCT) endomicroscope, with a submillimeter outer diameter (∼0.4 mm), is presented, achieving an ultrahigh resolution of 1.4 μm axial × 4.5 μm transverse in air. This compact probe allows minimally invasive in vivo deep-brain imaging in mice at a depth of 7.2 mm. Key regions in the mouse deep brain, such as the isocortex, corpus callosum, and caudate putamen, were successfully identified using our vis-OCT endomicroscope. In addition, we examined the myeloarchitectures and cytoarchitectures in the isocortex. Our findings demonstrate that the vis-OCT endomicroscope offers enhanced visualization of myelinated axon fibers and nerve fiber bundles compared to its 800 nm counterpart. This vis-OCT endomicroscope, overcoming resolution and imaging depth limitations of conventional methods, offers a novel tool for minimally invasive, ultrahigh-resolution in vivo deep brain neuroimaging.

Microstructural analysis does not support altered interhemispheric wiring of the human anterior commissure in corpus callosum dysgenesis

BackgroundIndividuals with corpus callosum dysgenesis (CCD) lack the clear disconnection syndrome that is characteristic of individuals in whom the corpus callosum has been surgically severed. One potential explanation for this paradox is that the anterior commissure undergoes neuroplastic remodeling in CCD to improve interhemispheric communication between the brain hemispheres. MethodsA cohort of sixteen individuals with CCD (and sixteen sex and age-matched neurotypical controls) underwent multi-shell diffusion magnetic resonance high-field imaging (dMRI) at 7-Tesla to assess the anatomy of the anterior commissure for evidence of neuroplasticity. ResultsNo significant group-wise differences in midsagittal anterior commissure volumes were detected between the CCD and control cohorts, although there were CCD individuals within the cohort who exhibited volumes that were either substantially larger or smaller than their neurotypical counterparts. Axonal intracellular volume fractions were reduced across the CCD white matter, including regions of the anterior commissure, and tractographic analyses were unable to identify any novel connections projecting through the anterior commissure that were unique to CCD individuals. Finally, variances in the neuroanatomy of the anterior commissure in the CCD cohort did not correlate with performance on neuropsychological tasks that are highly dependent upon interhemispheric communication. ConclusionsThe results of this study indicate that there are individuals within the CCD population in whom it is unlikely that the anterior commissure is the primary substrate for interhemispheric communication. Consequently, other, presently unknown, compensatory mechanisms are likely involved in supporting this function.

Familial adult-onset neuronal intranuclear inclusion disease: A case report and literature review.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with highly variable clinical manifestations, making diagnosis challenging. Recent advancements in genetic and pathological testing, such as the identification of GGC repeat expansions in the NOTCH2NLC gene, have improved diagnostic accuracy, but familial cases remain underreported. This report details 3 cases of familial adult-onset NIID in 2 sisters and 1 brother. The older sister experienced episodic encephalopathy and autonomic dysfunction for over 40 years, while the younger sister presented similar symptoms 5 years ago. The brother also developed episodic encephalopathy 5 years ago. Brain diffusion-weighted imaging (DWI) for all 3 patients revealed hyperintensity at the corticomedullary junction and corpus callosum. Skin biopsies from the older sister and brother confirmed the presence of p62 antibody-positive intranuclear inclusion bodies in sweat gland cells and fibroblasts. Genetic testing showed 146 and 133 GGC repeats in the NOTCH2NLC gene in the older sister and brother, respectively. All 3 patients were diagnosed with NIID based on clinical, radiological, and genetic findings. The patients received hormonal therapy, circulation-enhancing treatments, and rehydration therapy during acute episodes. All 3 patients showed significant improvement in symptoms following treatment, with a return to baseline function after hospital discharge. Proper management of NIID includes prompt recognition of symptoms, adequate rest, and avoidance of triggers such as fatigue, infections, and stress, which may reduce the frequency of episodic attacks. Early diagnosis and targeted symptomatic treatment are essential for improving patient outcomes.

Repeated high-dose esketamine in early postnatal rats leads to behavioural deficits with long-term modifications in white matter microstructural integrity

Esketamine is commonly used for sedation or general anaesthesia in infants and young children. However, repeated esketamine administration during periods of rapid brain growth and development may result in various pathophysiological and cognitive changes. Therefore, this study aimed to investigate the influence of recurrent esketamine exposure on long-term behavioural and white matter consequences. Seven-day-old (P7) male rats were allocated to control, high-, and low-dose groups. Behavioural paradigm assessment was conducted at P25–29. Diffusion tensor imaging revealed long-term effects on water diffusivity in the splenium and cingulum white matter of the corpus callosum at P30. Subsequent two-dimensional structure-tensor analysis of brain tissue sections stained with Luxol fast blue (LFB) showed marked changes in the white matter microstructure in rats after multiple exposures to varying esketamine doses. High-dose esketamine significantly reduced activity time and total distance in the open-field experiment. High-dose esketamine exposure might lead to impaired short-term memory in rats. Additionally, the high-dose group showed prolonged immobility time during the forced swimming test. On the balance beam, the high-dose group displayed more right turns and right-foot slips and lower time spent on the rotating bar, indicating motor defects, than did the other groups. Diffusion tensor imaging demonstrated a decreased water molecule diffusion ability in the corpus callosum in the high-dose group. LFB staining indicated microstructural differences in the white matter of animals in the high-dose group. These findings suggest that behavioural deficits in high-dose esketamine-treated rats are at least partially attributed to changes in the white matter microstructure.

Phospholipase D Family Member 4 Regulates Microglial Phagocytosis and Remyelination via the AKT Pathway in a Cuprizone-Induced Multiple Sclerosis Mouse Model.

Remyelination is an endogenous repair process that is often deficient in multiple sclerosis (MS). Stimulation of remyelination is thought to help limit the progression of MS. This study aimed to investigate the expression pattern and function of a microglial phagocytosis-related gene, phospholipase D family member 4 (PLD4), in a cuprizone (CPZ)-induced MS mouse model. The extent of remyelination was assessed using LFB staining. Myelin phagocytosis assay was used to investigate the effect of Pld4 on microglial phagocytic activity. Pld4 was upregulated in the corpus callosum during demyelination and remyelination. AAV9-mediated Pld4 deficiency impaired remyelination and reduced the number of Olig2-positive cells. In the corpus callosum of Pld4-deficient mice, the microglial phagocytosis marker MAC2 was reduced, accompanied by inhibition of TrkA/AKT signaling. Similarly, the phagocytosis assay showed that Pld4 knockdown significantly inhibited myelin debris phagocytosis by BV2 cells. The AKT activator SC79 reversed the Pld4 deficiency-induced inhibition of microglial phagocytic activity and rescued the impaired remyelination in Pld4-deficient mice. PLD4 is upregulated in CPZ-induced MS and modulates microglial phagocytosis and remyelination via the AKT pathway. Our findings provide experimental evidence for a better understanding of the molecular mechanism of MS.

Diagnostic MRI Score to Differentiate Susac Syndrome from Primary Angiitis of the Central Nervous System and Multiple Sclerosis.

Susac syndrome (SuS), multiple sclerosis (MS), and primary angiitis of the central nervous system (PACNS) present diagnostic challenges due to overlapping clinical features. We aimed to enhance diagnostic precision by developing the SPAMS (SuS, PACNS, MS) score, a practical radiological tool. This multicenter study included 99 patients (43 SuS, 37 MS, 19 PACNS) from South American countries. Relevant MRI features were identified through an elastic-net model determined key variables. The SPAMS score assigned 2 points for snowball lesions, 1 point for spokes-like lesions, or if there are more than 4 lesions in the corpus callosum, corpus callosum involvement, or cerebellar involvement. It subtracted 1 point if gadolinium-enhancing lesions or 4 points if Dawson's fingers are present. Bootstrapping validated the optimal cutoff at 2 points, exhibiting a diagnostic performance of area under the curve = 0.931, sensitivity = 88%, specificity = 89%, positive predictive value = 88%, negative predictive value = 89%, and accuracy = 88%. When specific MRI findings coexisted, the SPAMS score differentiated SuS from MS and PACNS. Access to MRI and standard protocol sequences makes it a valuable tool for timely diagnosis and treatment, potentially preventing disability progression and severe clinical outcomes. ANN NEUROL 2024;96:846-854.

White matter organization abnormalities in adults with 47,XXX: a 7 Tesla MRI study

47,XXX (Triple X syndrome) is a sex chromosome aneuploidy characterized by the presence of a supernumerary X chromosome in affected females, and has been associated with a variable cognitive, behavioral, and psychiatric phenotype. Alterations in brain gray matter structure and function have been reported, but less is known about white matter (WM) organization in 47,XXX. Therefore, we conducted 7 T diffusion tensor imaging and characterized fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of 22 adult women with 47,XXX and 22 age-matched typically developing females using tract-based spatial statistics. Relationships between phenotypic traits and WM organization characteristics in 47,XXX were also investigated. Adults with 47,XXX showed lower axial diffusivity in the body of the corpus callosum and the right superior longitudinal fasciculus. WM organization variability was not associated with IQ and social cognition and social functioning deficits in 47,XXX. Our findings indicate an effect of a supernumerary X chromosome in adult women on axonal integrity of the body of the corpus callosum and the right superior longitudinal fasciculus. These findings provide additional insight into the role of the X chromosome on WM organization. Future research is warranted to explore the clinical significant impact of altered WM organization in 47,XXX.

Prognostic nomogram model based on quantitative metrics of subregions surrounding residual cavity in glioblastoma patients

BackgroundThe hyperintensity area surrounding the residual cavity on postoperative fluid-attenuated inversion recovery (FLAIR) image is a potential site for glioblastoma (GBM) recurrence. This study aimed to develop a nomogram using quantitative metrics from subregions of this area, prior to chemoradiotherapy (CRT), to predict early GBM recurrence.MethodsAdult patients with GBM diagnosed between October 2018 and October 2022 were retrospectively analyzed. Quantitative metrics, including the mean, maximum, minimum, median values, and standard deviation of FLAIR signal intensity (SI) (measured using 3D-Slicer software), were extracted from the following subregions surrounding the residual cavity on post-contrast T1-weighted (CE-T1WI)-FLAIR fusion images: the enhancing region (ER), non-enhancing region (NER), and combined ER + NER. Independent prognostic factors were identified using Cox regression and least absolute shrinkage and selection operator (LASSO) analyses and were incorporated into the prediction nomogram model. The model’s performance was evaluated using the C-index, calibration curves, and decision curves.ResultsA total of 129 adult GBM patients were enrolled and randomly assigned to a training (n = 90) and a validation cohorts (n = 39) in a 7:3 ratio. Sixty-nine patients experienced postoperative recurrence. Cox regression analysis identified subventricular zone involvement, the median FLAIR intensity in the ER, the rFLAIR (relative FLAIR intensity compared to the contralateral normal region) of ER + NER, and corpus callosum involvement as independent prognostic factors. For predicting recurrence within 1 year after surgery, the nomogram model had a C-index of 0.733 in the training cohort and 0.746 in the validation cohort. Based on the nomogram score, post-operative GBM patients could be stratified into high- and low-risk for recurrence.ConclusionsNomogram models which based on quantitative metrics from FLAIR hyperintensity subregions may serve as potential markers for assessing GBM recurrence risk. This approach could enhance clinical decision-making and provide an alternative method for recurrence estimation in GBM patients.

Corpus callosum structure and auditory interhemispheric transfer in spina bifida myelomeningocele.

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. We collected T₁-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. 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. 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).

SRPK3 Is Essential for Cognitive and Ocular Development in Humans and Zebrafish, Explaining X-Linked Intellectual Disability.

Intellectual disability is often the outcome of neurodevelopmental disorders and is characterized by significant impairments in intellectual and adaptive functioning. X-linked intellectual disability (XLID) is a subset of these disorders caused by genetic defects on the X chromosome, affecting about 2 out of 1,000 males. In syndromic form, it leads to a broad range of cognitive, behavioral, ocular, and physical disabilities. Employing exome or genome sequencing, here we identified 4 missense variants (c.475C > G; p.H159D, c.1373C > A; p.T458N, and c.1585G > A; p.E529K, c.953C > T; p.S318L) and a putative truncating variant (c.1413_1414del; p.Y471*) in the SRPK3 gene in 9 XLID patients from 5 unrelated families. To validate SRPK3 as a novel XLID gene, we established a knockout (KO) model of the SRPK3 orthologue in zebrafish. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Together, these data indicate a pathological role of SRPK3 in neurodevelopmental disorders. In post-fertilization day 5 larvae (free swimming stage), KO zebrafish exhibited severe deficits in eye movement and swim bladder inflation, mimicking uncontrolled ocular movement and physical clumsiness observed in human patients. In adult KO zebrafish, cerebellar agenesis and behavioral abnormalities were observed, recapitulating human phenotypes of cerebellar atrophy and intellectual disability. Overall, these results suggest a crucial role of SRPK3 in the pathogenesis of syndromic X-linked intellectual disability and provide new insights into brain development, cognitive and ocular dysfunction in both humans and zebrafish. ANN NEUROL 2024;96:914-931.

Sonic Hedgehog Is an Early Oligodendrocyte Marker During Remyelination.

Failure of myelin regeneration by oligodendrocytes contributes to progressive decline in many neurological diseases. Here, using in vitro and in vivo rodent models, functional blockade, and mouse brain demyelination, we demonstrate that Sonic hedgehog (Shh) expression in a subset of oligodendrocyte progenitor cells precedes the expression of myelin basic protein (MBP), a major myelin sheath protein. Primary cultures of rodent cortical oligodendrocytes show that Shh mRNA and protein are upregulated during oligodendrocyte maturation before the upregulation of MBP expression. Importantly, almost all MBP-positive cells are Shh positive during differentiation. During remyelination, we identify a rapid induction of Shh mRNA and peptide in oligodendroglial cells present in the demyelinated corpus callosum of mice, including a population of PDGFRα-expressing cells. Shh invalidation by an adeno-associated virus strategy demonstrates that the downregulation of Shh impairs the differentiation of oligodendrocytes in vitro and decreases MBP and myelin proteolipid protein expression in the demyelinated mouse brain at late stages of remyelination. We also report a parallel expression of Shh and MBP in oligodendroglial cells during early post-natal myelination of the mouse brain. Thus, we identify a crucial Shh signal involved in oligodendroglial cell differentiation and remyelination, with potential interest in the design of better-targeted remyelinating therapeutic strategies.