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Endocrine Reviews May 2024Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Fröhlich, advances in molecular genetic laboratory techniques... (Review)
Review
Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Fröhlich, advances in molecular genetic laboratory techniques have allowed us to elucidate various components of the intricate neurocircuitry governing appetite and weight regulation connecting the hypothalamus, pituitary gland, brainstem, adipose tissue, pancreas, and gastrointestinal tract. On a background of an increasing prevalence of population-level common obesity, the number of survivors of congenital (eg, septo-optic dysplasia, Prader-Willi syndrome) and acquired (eg, central nervous system tumors) hypothalamic disorders is increasing, thanks to earlier diagnosis and management as well as better oncological therapies. Although to date the discovery of several appetite-regulating peptides has led to the development of a range of targeted molecular therapies for monogenic obesity syndromes, outside of these disorders these discoveries have not translated into the development of efficacious treatments for other forms of HyOb. This review aims to summarize our current understanding of the neuroendocrine physiology of appetite and weight regulation, and explore our current understanding of the pathophysiology of HyOb.
Topics: Humans; Obesity; Hypothalamic Diseases; Appetite; Neurosecretory Systems; Animals; Hypothalamus; Body Weight
PubMed: 38019584
DOI: 10.1210/endrev/bnad033 -
Journal of Clinical Medicine Jul 2023Granulomatosis with polyangiitis (GPA), formerly referred to as Wegener's disease, is a form of ANCA-associated vasculitis. It manifests mainly in the kidneys and the...
Granulomatosis with polyangiitis (GPA), formerly referred to as Wegener's disease, is a form of ANCA-associated vasculitis. It manifests mainly in the kidneys and the upper respiratory tract, but ocular involvement is not uncommon. In this article, four cases with ocular manifestations are presented with comprehensive photographic documentation. We describe the way to proper diagnosis, which may be long, the possible treatment, and the final outcomes. Our patients had the following ocular manifestations of GPA: retinal vasculitis, anterior necrotizing scleritis, medial orbital wall and orbital floor erosion with middle face deformation, compressive optic neuropathy due to retrobulbar inflammatory mass, and the abscess of the eyelids, inflammatory intraorbital mass causing exophthalmos and diplopia. This manuscript includes the description of severe forms of GPA, the initial signs and symptoms, relapses, and difficulties in achieving remission. The extraocular involvement is described with diagnostic modalities and laboratory findings. One of the reported cases was diagnosed by an ophthalmologist on the basis of ocular symptoms in the early stages of the disease. Our outcomes are compared with those discussed in the literature.
PubMed: 37445483
DOI: 10.3390/jcm12134448 -
Journal of Neurology, Neurosurgery, and... Mar 2024Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis rarely causes visible lesions in conventional MRI, yet advanced imaging detects extensive white matter damage. To...
BACKGROUND
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis rarely causes visible lesions in conventional MRI, yet advanced imaging detects extensive white matter damage. To improve prognostic capabilities, we evaluate the T1-weighted/T2-weighted (T1w/T2w) ratio, a measure of white matter integrity computable from clinical MRI sequences, in NMDAR encephalitis and examine its associations with cognitive impairment.
METHODS
T1-weighted and T2-weighted MRI were acquired cross-sectionally at 3 Tesla in 53 patients with NMDAR encephalitis (81% women, mean age 29 years) and 53 matched healthy controls. Quantitative and voxel-wise group differences in T1w/T2w ratios and associations with clinical and neuropsychological outcomes were assessed. P-values were false discovery rate (FDR) adjusted where multiple tests were conducted.
RESULTS
Patients with NMDAR encephalitis had significantly lower T1w/T2w ratios across normal appearing white matter (p=0.009, Hedges' g=-0.51), which was associated with worse verbal episodic memory performance (r=0.39, p=0.005, p(FDR)=0.026). White matter integrity loss was observed in the corticospinal tract, superior longitudinal fascicle, optic radiation and callosal body with medium to large effects (Cohen's d=[0.42-1.17]). In addition, patients showed decreased T1w/T2w ratios in the hippocampus (p=0.002, p(FDR)=0.005, Hedges' g=-0.62), amygdala (p=0.002, p(FDR)=0.005, Hedges' g=-0.63) and thalamus (p=0.010, p(FDR)=0.019, Hedges' g=-0.51).
CONCLUSIONS
The T1w/T2w ratio detects microstructural changes in grey and white matter of patients with NMDAR encephalitis that correlate with cognitive performance. Computable from conventional clinical MRI sequences, this measure shows promise in bridging the clinico-radiological dissociation in NMDAR encephalitis and could serve as an imaging outcome measure in clinical trials.
Topics: Humans; Female; Adult; Male; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Magnetic Resonance Imaging; White Matter; Hippocampus; Biomarkers
PubMed: 37798094
DOI: 10.1136/jnnp-2023-332069 -
Pediatric Nephrology (Berlin, Germany) Feb 2024Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common birth defects worldwide and a major cause of kidney failure in children.... (Review)
Review
Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common birth defects worldwide and a major cause of kidney failure in children. Extra-renal manifestations are also common. This study reviewed diseases associated with the Genomics England CAKUT-associated gene panel for ocular anomalies. In addition, each gene was examined for expression in the human retina and an ocular phenotype in mouse models using the Human Protein Atlas and Mouse Genome Informatics databases, respectively. Thirty-four (54%) of the 63 CAKUT-associated genes (55 'green' and 8 'amber') had a reported ocular phenotype. Five of the 6 most common CAKUT-associated genes (PAX2, EYA1, SALL1, GATA3, PBX1) that represent 30% of all diagnoses had ocular features. The ocular abnormalities found with most CAKUT-associated genes and with five of the six commonest were coloboma, microphthalmia, optic disc anomalies, refraction errors (astigmatism, myopia, and hypermetropia), and cataract. Seven of the CAKUT-associated genes studied (11%) had no reported ocular features but were expressed in the human retina or had an ocular phenotype in a mouse model, which suggested further possibly-unrecognised abnormalities. About one third of CAKUT-associated genes (18, 29%) had no ocular associations and were not expressed in the retina, and the corresponding mouse models had no ocular phenotype. Ocular abnormalities in individuals with CAKUT suggest a genetic basis for the disease and sometimes indicate the affected gene. Individuals with CAKUT often have ocular abnormalities and may require an ophthalmic review, monitoring, and treatment to preserve vision.
Topics: Child; Mice; Animals; Humans; Kidney; Urinary Tract; Vesico-Ureteral Reflux; Urogenital Abnormalities
PubMed: 37468646
DOI: 10.1007/s00467-023-06068-9 -
International Journal of Ophthalmology 2023To describe the clinical and radiologic features of retrolaminar migration silicone oil (SiO) and observe the dynamic position of ventricular oil accumulation in supine...
AIM
To describe the clinical and radiologic features of retrolaminar migration silicone oil (SiO) and observe the dynamic position of ventricular oil accumulation in supine and prone.
METHODS
For this retrospective study, 29 patients who had a history of SiO injection treatment and underwent unenhanced head computed tomography (CT) were included from January 2019 to October 2022. The patients were divided into migration-positive and negative groups. Clinical history and CT features were compared using Whitney and Fisher's exact tests. The dynamic position of SiO was observed within the ventricular system in supine and prone. CT images were visually assessed for SiO migration along the retrolaminar involving pathways for vision (optic nerve, chiasm, and tract) and ventricular system.
RESULTS
Intraocular SiO migration was found in 5 of the 29 patients (17.24%), with SiO at the optic nerve head (=1), optic nerve (=4), optic chiasm (=1), optic tract (=1), and within lateral ventricles (=1). The time interval between SiO injection and CT examination of migration-positive cases was significantly higher than that of migration-negative patients (22.8±16.5mo 13.1±2.6mo, <0.001). The hyperdense lesion located in the frontal horns of the right lateral ventricle migrated to the fourth ventricle when changing the position from supine to prone.
CONCLUSION
Although SiO retrolaminar migration is unusual, the clinician and radiologist should be aware of migration routes. The supine combined with prone examination is the first-choice method to confirm the presence of SiO in the ventricular system.
PubMed: 37724262
DOI: 10.18240/ijo.2023.09.20 -
Frontiers in Neuroscience 2023Sleep deprivation (SD) causes several adverse functional outcomes, and understanding the associated processes can improve quality of life. Although the effects of SD on...
Sleep deprivation (SD) causes several adverse functional outcomes, and understanding the associated processes can improve quality of life. Although the effects of SD on neuronal activity in several brain regions have been identified, a comprehensive evaluation of the whole brain is still lacking. Hence, we performed SD using two different methods, gentle handling and a dedicated chamber, in targeted recombination in active populations 2 (TRAP2) mice crossed with Rosa-ZsGreen reporter mice and visualized cellular activity in the whole brain. Using the semi-automated post-imaging analysis tool Slice Histology Alignment, Registration, and Cell Quantification (SHARCQ), the number of activated cells was quantified. From the analysis of 14 brain regions, cellular activity was significantly increased in the olfactory areas and decreased in the medulla by the two SD methods. From the analysis of the further subdivided 348 regions, cellular activity was significantly increased in the vascular organ of the lamina terminalis, lateral hypothalamic area, parabigeminal nucleus, ventral tegmental area, and magnocellular reticular nucleus, and decreased in the anterior part of the basolateral amygdalar nucleus, nucleus accumbens, septohippocampal nucleus, reticular nucleus of the thalamus, preoptic part of the periventricular hypothalamic nucleus, ventromedial preoptic nucleus, rostral linear nucleus raphe, facial motor nucleus, vestibular nuclei, and some fiber tracts (oculomotor nerve, genu of corpus callosum, and rubrospinal tract) by the two SD methods. Two subdivided regions of the striatum (caudoputamen and other striatum), epithalamus, vascular organ of the lamina terminalis, anteroventral preoptic nucleus, superior colliculus optic layer, medial terminal nucleus of the accessory optic tract, pontine gray, and fiber tracts (medial lemniscus, columns of the fornix, brachium of the inferior colliculus, and mammillary peduncle) were differentially affected by the two SD methods. Most brain regions detected from these analyses have been reported to be involved in regulating sleep/wake regulatory circuits. Moreover, the results from the connectivity analysis indicated that the connectivity of cellular activity among brain regions was altered by SD. Together, such a comprehensive analysis of the whole brain is useful for understanding the mechanisms by which SD and/or sleep disruption affects brain function.
PubMed: 37928729
DOI: 10.3389/fnins.2023.1252689 -
Neural Regeneration Research Nov 2023Data from studies analyzing the differentiation and functional connectivity of embryonic neural tissue grafted into the mammalian nervous system has led to the clinical...
Data from studies analyzing the differentiation and functional connectivity of embryonic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients with neurodegenerative disease. While some success has been achieved, ethical concerns have led to a search for alternative therapeutic strategies, mostly exploring the use of neural precursors or neurons derived from pluripotent stem cells to replace damaged host neurons and restore lost circuitries. These more recent studies address questions of graft viability, differentiation, and connectivity similar to those posed by researchers in earlier fetal transplant work, thus reviews of the fetal graft literature may inform and help guide ongoing research in the stem cell/organoid field. This brief review describes some key observations from research into the transplantation of neural tissue into the rat visual system, focusing on grafts of the fetal superior colliculus (tectal grafts) into neonatal or adult hosts. In neonate hosts, grafts quickly develop connections with the underlying host midbrain and attain a morphology typical of mature grafts by about 2 weeks. Grafts consistently contain numerous localized regions which, based on neurofibrillar staining, neuronal morphology (Golgi), neurochemistry, receptor expression, and glial architecture, are homologous to the stratum griseum superficiale of normal superior colliculus. These localized "patches" are also seen after explant culture and when donor tectal tissue is dissociated and reaggregated prior to transplantation. In almost all circumstances, host retinal innervation is restricted to these localized patches, but only those that are located adjacent to the graft surface. Synapses are formed and there is evidence of functional drive. The only exception occurs when Schwann cells are added to dissociated tecta prior to reaggregation. In these co-grafts, the peripheral glia appear to compete with local target factors and host retinal ingrowth is more widespread. Other afferent systems (e.g., host cortex, serotonin) show different patterns of innervation. The host cortical input originates more from extrastriate regions and establishes functional excitatory synapses with grafted neurons. Finally, when grafted into optic tract lesions in adult rat hosts, spontaneously regrowing host retinal axons retain the capacity to selectively innervate the localized patches in embryonic tectal grafts, showing that the specific affinities between adult retinal axons and their targets are not lost during regeneration. While the research described here provides some pertinent information about development and plasticity in visual pathways, a more general aim is to highlight how the review of the extensive fetal graft literature may aid in an appreciation of the positive (and negative) factors that influence survival, differentiation, connectivity and functionality of engineered cells and organoids transplanted into the central nervous system.
PubMed: 37282449
DOI: 10.4103/1673-5374.371348 -
Stroke Sep 2023Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts... (Observational Study)
Observational Study
BACKGROUND
Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts may become relevant for compensation or recovery of function.
METHODS
We used the ENIGMA Stroke Recovery data set, a multicenter, retrospective, and cross-sectional collection of patients with upper limb impairment during the chronic phase of stroke to test the relevance of tracts in individuals with less and more severe (laterality index of CST fractional anisotropy ≥0.25) CST damage in an observational study design. White matter integrity was quantified using fractional anisotropy for the CST, the superior longitudinal fascicle, and the callosal fibers interconnecting the primary motor cortices between hemispheres. Optic radiations served as a control tract as they have no a priori relevance for the motor system. Pearson correlation was used for testing correlation with upper limb motor function (Fugl-Meyer upper extremity).
RESULTS
From 1235 available data sets, 166 were selected (by imaging, Fugl-Meyer upper extremity, covariates, stroke location, and stage) for analyses. Only individuals with severe CST damage showed a positive association of fractional anisotropy in both callosal fibers interconnecting the primary motor cortices ([21]=0.49; 0.025) and superior longitudinal fascicle ([21]=0.51; .018) with Fugl-Meyer upper extremity.
CONCLUSIONS
Our data support the notion that individuals with more severe damage of the CST depend on residual pathways for achieving better upper limb outcome than those with less affected CST.
Topics: Humans; Cross-Sectional Studies; Retrospective Studies; White Matter; Stroke; Upper Extremity; Pyramidal Tracts; Recovery of Function
PubMed: 37465999
DOI: 10.1161/STROKEAHA.123.043713