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Journal of Pediatric Endocrinology &... May 2024Wolfram syndrome is characterised by insulin-dependent diabetes (IDDM), diabetes insipidus (DI), optic atrophy, sensorineural deafness and neurocognitive disorders. The...
OBJECTIVES
Wolfram syndrome is characterised by insulin-dependent diabetes (IDDM), diabetes insipidus (DI), optic atrophy, sensorineural deafness and neurocognitive disorders. The DIDMOAD acronym has been recently modified to DIDMOAUD suggesting the rising awareness of the prevalence of urinary tract dysfunction (UD). End stage renal disease is the commonest cause of mortality in Wolfram syndrome. We present a case series with main objective of long term follow up in four children having Wolfram syndrome with evaluation of their urodynamic profile.
METHODS
A prospective follow up of four genetically proven children with Wolfram syndrome presenting to a tertiary care pediatric diabetes clinic in Pune, India was conducted. Their clinical, and urodynamic parameters were reviewed.
RESULTS
IDDM, in the first decade, was the initial presentation in all the four children (three male and one female). Three children had persistent polyuria and polydipsia despite having optimum glycemic control; hence were diagnosed to have DI and treated with desmopressin. All four patients entered spontaneous puberty. All patients had homozygous mutation in WFS1 gene; three with exon 8 and one with exon 6 novel mutations. These children with symptoms of lower urinary tract malfunction were further evaluated with urodynamic studies; two of them had hypocontractile detrusor and another had sphincter-detrusor dyssynergia. Patients with hypocontractile bladder were taught clean intermittent catheterization and the use of overnight drain.
CONCLUSIONS
We report a novel homozygous deletion in exon 6 of WFS-1 gene. The importance of evaluation of lower urinary tract malfunction is highlighted by our case series. The final bladder outcome in our cases was a poorly contractile bladder in three patients.
Topics: Adolescent; Child; Female; Humans; Male; Diabetes Mellitus, Type 1; Follow-Up Studies; Membrane Proteins; Mutation; Prognosis; Prospective Studies; Urodynamics; Wolfram Syndrome
PubMed: 38465704
DOI: 10.1515/jpem-2023-0531 -
Frontiers in Aging Neuroscience 2024The aim of our study was to examine the alterations in microstructure in patients with coronary artery disease (CAD) and cognitive impairment (CI) using diffusion...
OBJECT
The aim of our study was to examine the alterations in microstructure in patients with coronary artery disease (CAD) and cognitive impairment (CI) using diffusion kurtosis imaging (DKI). Additionally, we aimed to investigate the potential correlation between DKI parameters and cognitive function.
MATERIALS AND METHODS
A total of 28 CAD patients and 30 healthy controls (HC) were prospectively enrolled in our study. All participants underwent routine and diffusion sequences of head imaging. DKE software was utilized to generate various diffusion kurtosis imaging parameters (DKI), including kurtosis fractional anisotropy (KFA), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), and mean diffusivity (MD). Nonparametric tests were conducted using tract-based spatial statistics (TBSS) to compare the parameter values between the two groups. The parameter values of the significantly different fiber tracts were extracted and correlated with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores.
RESULTS
Compared to the HC group, patients with coronary artery disease exhibited significant reductions in FA values in the bilateral Superior corona radiata, bilateral Anterior corona radiata, bilateral Posterior corona radiata, corpus callosum, left Posterior thalamic radiation, right Posterior limb of internal capsule, Anterior limb of internal capsule, and Cerebral peduncle, as well as in the left Superior longitudinal fasciculus. Additionally, KFA values decreased in the bilateral Anterior corona radiata, bilateral Anterior limb of internal capsule, and Genu of the corpus callosum. The MK values decreased in the right Posterior corona radiata, Retrolenticular part of the internal capsule, Posterior thalamic radiation (including optic radiation), Superior longitudinal fasciculus, and left Posterior thalamic radiation (including optic radiation). Moreover, the RK values decreased in the bilateral Retrolenticular part of the internal capsule, right Posterior thalamic radiation (including optic radiation), and Superior longitudinal fasciculus, as well as in the left Superior longitudinal fasciculus and Posterior thalamic radiation (including optic radiation) ( < 0.01, TFCE corrected), while no significant differences were observed in other parameter values ( > 0.01, TFCE corrected). The FA values of the right posterior limb of the internal capsule ( = 0.610, = 0.001) and the right cerebral peduncle ( = 0.622, < 0.001) were positively correlated with MMSE scores. Additionally, a significant correlation between kurtosis and diffusion coefficient parameters (FA and KFA) was observed.
CONCLUSION
CAD patients showed radial shrinkage and complexity of brain white matter microstructure. Whole-brain white matter analysis based on TBSS DKI can objectively reflect the characteristics of white matter damage in CAD patients, providing a basis for the auxiliary diagnosis of CAD with CI.
PubMed: 38425783
DOI: 10.3389/fnagi.2024.1301826 -
Postgraduate Medicine Mar 2024To evaluate adverse events (AEs) in pediatric patients with rheumatologic diseases being treated with approved or off-label biologic agents (BAs). (Observational Study)
Observational Study
OBJECTIVES
To evaluate adverse events (AEs) in pediatric patients with rheumatologic diseases being treated with approved or off-label biologic agents (BAs).
METHODS
This observational, retrospective, multicenter study was conducted from 2010 to 2022 in patients under 18 years of age with rheumatic diseases who were receiving interleukin-1 antibodies (Anti-IL1), interleukin-6 antibodies (Anti-IL6), and tumor necrosis factor alpha inhibitors (anti-TNF). Efficacy, AEs, and timing of AEs were collected from electronic medical records.
RESULTS
Three hundred and fifteen BAs were prescribed to 237 patients. Fifty AEs occurred in 44 patients (18.6%). Anti-TNF exposure was present in 8 (72.2%) of 11 patients with latent tuberculosis (TB) and in all 7 patients with herpes infections. Four of 6 patients (66.7%) with recurrent upper respiratory tract infections and 7 of 8 patients (87.5%) with local skin reactions were on Anti-IL1. The cutoff value for latent TB development was determined as 23.5 months by ROC analysis (AUC: 0.684 ± 0.072, = 0.038, 95% CI: 0.54-0.82). In patients who used BA for 23.5 months or more, the risk of latent TB was 5.94-fold ( = 0.024, 95% CI: 1.26-27.97). Drug rash with eosinophilia and systemic symptoms (DRESS) occurred in 2 patients on anakinra, and anaphylaxis occurred in 1 patient on anti-IL6. There were no cases of malignancy or death in any patient.
CONCLUSION
The physician should be vigilant for latent TB in patients exposed to BA for more than 2 years. While local skin reactions are more prevalent in patients receiving anti-IL1, severe skin reactions such as DRESS may also occur.
Topics: Humans; Male; Female; Rheumatic Diseases; Child; Retrospective Studies; Adolescent; Child, Preschool; Antirheumatic Agents; Latent Tuberculosis; Interleukin-1; Interleukin-6; Tumor Necrosis Factor-alpha; Biological Factors
PubMed: 38415679
DOI: 10.1080/00325481.2024.2325333 -
Neurobiology of Disease Apr 2024White matter (WM) tract formation and axonal pathfinding are major processes in brain development allowing to establish precise connections between targeted structures....
White matter (WM) tract formation and axonal pathfinding are major processes in brain development allowing to establish precise connections between targeted structures. Disruptions in axon pathfinding and connectivity impairments will lead to neural circuitry abnormalities, often associated with various neurodevelopmental disorders (NDDs). Among several neuroimaging methodologies, Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) technique that has the advantage of visualizing in 3D the WM tractography of the whole brain non-invasively. DTI is particularly valuable in unpinning structural tract connectivity defects of neural networks in NDDs. In this study, we used 3D DTI to unveil brain-specific tract defects in two mouse models lacking the Nr2f1 gene, which mutations in patients have been proven to cause an emerging NDD, called Bosch-Boonstra-Schaaf Optic Atrophy (BBSOAS). We aimed to investigate the impact of the lack of cortical Nr2f1 function on WM morphometry and tract microstructure quantifications. We found in both mutant mice partial loss of fibers and severe misrouting of the two major cortical commissural tracts, the corpus callosum, and the anterior commissure, as well as the two major hippocampal efferent tracts, the post-commissural fornix, and the ventral hippocampal commissure. DTI tract malformations were supported by 2D histology, 3D fluorescent imaging, and behavioral analyses. We propose that these interhemispheric connectivity impairments are consistent in explaining some cognitive defects described in BBSOAS patients, particularly altered information processing between the two brain hemispheres. Finally, our results highlight 3DDTI as a relevant neuroimaging modality that can provide appropriate morphometric biomarkers for further diagnosis of BBSOAS patients.
Topics: Humans; Mice; Animals; Diffusion Tensor Imaging; White Matter; Brain; Magnetic Resonance Imaging; Optic Atrophy
PubMed: 38408685
DOI: 10.1016/j.nbd.2024.106455 -
Current Issues in Molecular Biology Feb 2024Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. In our previous studies, we showed that wheat bran extract (WBE) reduced...
Inhibition of Glial Activation and Subsequent Reduction in White Matter Damage through Supplementation with a Combined Extract of Wheat Bran, Citrus Peel, and Jujube in a Rat Model of Vascular Dementia.
Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. In our previous studies, we showed that wheat bran extract (WBE) reduced white matter damage in a rat VaD model and improved memory in a human clinical trial. However, starch gelatinization made the large-scale preparation of WBE difficult. To simplify the manufacturing process and increase efficacy, we attempted to find a decoction containing an optimum ratio of wheat bran, sliced citrus peel, and sliced jujube (WCJ). To find an optimal ratio, the cell survival of C6 (rat glioma) cultured under hypoxic conditions (1% O) was measured, and apoptosis was assessed. To confirm the efficacies of the optimized WCJ for VaD, pupillary light reflex, white matter damage, and the activation of astrocytes and microglia were assessed in a rat model of bilateral common carotid artery occlusion (BCCAO) causing chronic hypoperfusion. Using a combination of both searching the literature and cell survival experiments, we chose 6:2:1 as the optimal ratio of wheat bran to sliced citrus peel to sliced jujube to prepare WCJ. We showed that phytic acid contained only in wheat bran can be used as an indicator component for the quality control of WCJ. We observed in vitro that the WCJ treatment improved cell survival by reducing apoptosis through an increase in the Bcl-2/Bax ratio. In the BCCAO experiments, the WCJ-supplemented diet prevented astrocytic and microglial activation, mitigated myelin damage in the corpus callosum and optic tract, and, consequently, improved pupillary light reflex at dosages over 100 mg/kg/day. The results suggest that the consumption of WCJ can prevent VaD by reducing white matter damage, and WCJ can be developed as a safe, herbal medicine to prevent VaD.
PubMed: 38392214
DOI: 10.3390/cimb46020096 -
Pediatric Dermatology Feb 2024IgA vasculitis (IgAV), formerly known as Henoch-Scholein purpura, is a small vessel vasculitis, most commonly seen in pediatric patients, that can affect numerous...
IgA vasculitis (IgAV), formerly known as Henoch-Scholein purpura, is a small vessel vasculitis, most commonly seen in pediatric patients, that can affect numerous internal organs including the kidneys, lungs, gastrointestinal tract, and the central nervous system (CNS). CNS manifestations of this condition include hypertensive encephalopathy, thrombosis, optic neuropathy, seizures, CNS vasculitis, and a more recently described phenomenon known as posterior reversible encephalopathy syndrome (PRES). Symptoms of PRES include hypertension, altered mental status, and seizures caused by vasogenic disruption of the blood-brain barrier, and the condition is diagnosed by characteristic edema-related gray-white matter changes in the parieto-occipital lobes on magnetic resonance imaging. Herein, we present a rare case of PRES as a presenting sign of IgAV to increase awareness about this unusual association.
PubMed: 38368940
DOI: 10.1111/pde.15569 -
The Journal of Comparative Neurology Feb 2024Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system (CNS) of vertebrates. Immunohistochemical techniques with specific...
Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system (CNS) of vertebrates. Immunohistochemical techniques with specific antibodies against GABA or against its synthesizing enzyme, glutamic acid decarboxylase (GAD) allowed characterizing GABAergic neurons and fibers in the CNS. However, studies on the CNS distribution of GABAergic neurons and fibers of bony fishes are scant and were done in teleost species. With the aim of understanding the early evolution of this system in bony vertebrates, we analyzed the distribution of GABA-immunoreactive (-ir) and GAD-ir neurons and fibers in the CNS of a basal ray-finned fish, the Siberian sturgeon (Chondrostei, Acipenseriformes), using immunohistochemical techniques. Our results revealed the presence and distribution of GABA/GAD-ir cells in different regions of the CNS such as olfactory bulbs, pallium and subpallium, hypothalamus, thalamus, pretectum, optic tectum, tegmentum, cerebellum, central grey, octavolateralis area, vagal lobe, rhombencephalic reticular areas, and the spinal cord. Abundant GABAergic innervation was observed in most brain regions, and GABAergic fibers were very abundant in the hypothalamic floor along the hypothalamo-hypophyseal tract and neurohypophysis. In addition, GABA-ir cerebrospinal fluid-contacting cells were observed in the alar and basal hypothalamus, saccus vasculosus, and spinal cord central canal. The distribution of GABAergic systems in the sturgeon brain shows numerous similarities to that observed in lampreys, but also to those of teleosts and tetrapods.
Topics: Animals; Brain; Central Nervous System; Fishes; Spinal Cord; gamma-Aminobutyric Acid
PubMed: 38335045
DOI: 10.1002/cne.25590 -
BioRxiv : the Preprint Server For... Jan 2024Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific signs and vulnerabilities. Aging not only...
Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific signs and vulnerabilities. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following repetitive mild traumatic brain injuries (rmTBIs). In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and Neurite Orientation Dispersion and Density Imaging (NODDI). Utilizing the CHIMERA model, we conducted rmTBIs or sham (control) procedures on young (2.5-3 months old) and aged (22-month-old) male and female mice to model high risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposing effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean, radial, axial diffusivity, fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Inflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in aged animals. These findings provide a comprehensive understanding of the intricate interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBIs.
PubMed: 38328104
DOI: 10.1101/2024.01.25.577316