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Cortex; a Journal Devoted To the Study... Sep 2023It has been suggested that Gerstmann's syndrome is the result of subcortical disconnection rather than emerging from damage of a multifunctional brain region within the...
It has been suggested that Gerstmann's syndrome is the result of subcortical disconnection rather than emerging from damage of a multifunctional brain region within the parietal lobe. However, patterns of white matter tract disconnection following parietal damage have been barely investigated. This single case study allows characterising Gerstmann's syndrome in terms of disconnected networks. We report the case of a left parietal patient affected by Gerstmann's tetrad: agraphia, acalculia, left/right orientation problems, and finger agnosia. Lesion mapping, atlas-based estimation of probability of disconnection, and DTI-based tractography revealed that the lesion was mainly located in the superior parietal lobule, and it caused disruption of both intraparietal tracts passing through the inferior parietal lobule (e.g., tracts connecting the angular, supramarginal, postcentral gyri, and the superior parietal lobule) and fronto-parietal long tracts (e.g., the superior longitudinal fasciculus). The lesion site appears to be located more superiorly as compared to the cerebral regions shown active by other studies during tasks impaired in the syndrome, and it reached the subcortical area potentially critical in the emergence of the syndrome, as hypothesised in previous studies. Importantly, the reconstruction of tracts connecting regions within the parietal lobe indicates that this critical subcortical area is mainly crossed by white matter tracts connecting the angular gyrus and the superior parietal lobule. Taken together, these findings suggest that this case study might be considered as empirical evidence of Gerstmann's tetrad caused by disconnection of intraparietal white matter tracts.
Topics: Humans; Gerstmann Syndrome; White Matter; Parietal Lobe; Brain; Agnosia
PubMed: 37478549
DOI: 10.1016/j.cortex.2023.05.016 -
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 -
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 -
The Journal of Neuroscience : the... Aug 2023Semaphorins and Plexins form ligand/receptor pairs that are crucial for a wide range of developmental processes from cell proliferation to axon guidance. The ability of...
Semaphorins and Plexins form ligand/receptor pairs that are crucial for a wide range of developmental processes from cell proliferation to axon guidance. The ability of semaphorins to act both as signaling receptors and ligands yields a multitude of responses. Here, we describe a novel role for Semaphorin-6D (Sema6D) and Plexin-A1 in the positioning and targeting of retinogeniculate axons. In or mutant mice of either sex, the optic tract courses through, rather than along, the border of the dorsal lateral geniculate nucleus (dLGN), and some retinal axons ectopically arborize adjacent and lateral to the optic tract rather than defasciculating and entering the target region. We find that Sema6D and Plexin-A1 act together in a dose-dependent manner, as the number of the ectopic retinal projections is altered in proportion to the level of Sema6D or Plexin-A1 expression. Moreover, using retinal electroporation of Sema6D or Plexin-A1 shRNA, we show that Sema6D and Plexin-A1 are both required in retinal ganglion cells for axon positioning and targeting. Strikingly, nonelectroporated retinal ganglion cell axons also mistarget in the tract region, indicating that Sema6D and Plexin-A1 can act non-cell-autonomously, potentially through axon-axon interactions. These data provide novel evidence for a dose-dependent and non-cell-autonomous role for Sema6D and Plexin-A1 in retinal axon organization in the optic tract and dLGN. Before innervating their central brain targets, retinal ganglion cell axons fasciculate in the optic tract and then branch and arborize in their target areas. Upon deletion of the guidance molecules Plexin-A1 or Semaphorin-6D, the optic tract becomes disorganized near and extends within the dorsal lateral geniculate nucleus. In addition, some retinal axons form ectopic aggregates within the defasciculated tract. Sema6D and Plexin-A1 act together as a receptor-ligand pair in a dose-dependent manner, and non-cell-autonomously, to produce this developmental aberration. Such a phenotype highlights an underappreciated role for axon guidance molecules in tract cohesion and appropriate defasciculation near, and arborization within, targets.
Topics: Animals; Mice; Axons; Ligands; Retinal Ganglion Cells; Semaphorins
PubMed: 37344233
DOI: 10.1523/JNEUROSCI.0072-22.2023 -
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 -
Radiology Case Reports Aug 2023Glioma has been previously known as the most common adult brain tumor. Glioma of the optic pathway is predominated by low-grade neoplasms. High-grade glioma in adults is...
Glioma has been previously known as the most common adult brain tumor. Glioma of the optic pathway is predominated by low-grade neoplasms. High-grade glioma in adults is extremely rare. In this study, we present the case of a 46-year-old male patient who developed glioblastoma of the optic chiasm extending along the optic tract. This study aims to discuss several common differential diagnoses of nontumor diffuse lesions in the optic pathway and their clinical symptoms and magnetic resonance imaging findings, which could help navigate management.
PubMed: 37273722
DOI: 10.1016/j.radcr.2023.05.010 -
Journal of Neurotrauma Oct 2023Repetitive mild traumatic brain injuries (rmTBIs) are serious trauma events responsible for the development of numerous neurodegenerative disorders. A major challenge in...
Fixed Time-Point Analysis Reveals Repetitive Mild Traumatic Brain Injury Effects on Resting State Functional Magnetic Resonance Imaging Connectivity and Neuro-Spatial Protein Profiles.
Repetitive mild traumatic brain injuries (rmTBIs) are serious trauma events responsible for the development of numerous neurodegenerative disorders. A major challenge in developing diagnostics and treatments for the consequences of rmTBI is the fundamental knowledge gaps of the molecular mechanisms responsible for neurodegeneration. It is both critical and urgent to understand the neuropathological and functional consequences of rmTBI to develop effective therapeutic strategies. Using the Closed-Head Impact Model of Engineered Rotational Acceleration, or CHIMERA, we measured neural changes following injury, including brain volume, diffusion tensor imaging, and resting-state functional magnetic resonance imaging coupled with graph theory and functional connectivity analyses. We determined the effect of rmTBI on markers of gliosis and used NanoString-GeoMx to add a digital-spatial protein profiling analysis of neurodegenerative disease-associated proteins in gray and white matter regions. Our analyses revealed aberrant connectivity changes in the thalamus, independent of microstructural damage or neuroinflammation. We also identified distinct changes in the levels of proteins linked to various neurodegenerative processes including total and phospho-tau species and cell proliferation markers. Together, our data show that rmTBI significantly alters brain functional connectivity and causes distinct protein changes in morphologically intact brain areas.
Topics: Humans; Brain Concussion; Neurodegenerative Diseases; Diffusion Tensor Imaging; Brain; Brain Injuries, Traumatic; Magnetic Resonance Imaging
PubMed: 37051703
DOI: 10.1089/neu.2022.0464 -
Internal Medicine (Tokyo, Japan) Oct 2023We encountered a 37-year-old Japanese man with KIF1A-associated neurological disorder (KAND) who exhibited motor developmental delay, intellectual disability, and slowly...
We encountered a 37-year-old Japanese man with KIF1A-associated neurological disorder (KAND) who exhibited motor developmental delay, intellectual disability, and slowly progressive cerebellar ataxia, hypotonia, and optic neuropathy. Pyramidal tract signs were evident late in this case. At 30 years old, the patient developed a neurogenic bladder. A molecular diagnosis revealed a uniallelic missense de novo variant (p.L278P) of KIF1A. Serial neuroradiological studies revealed atrophy of the cerebellum at an early age, and cerebral hemisphere atrophy progressed slowly over a 22-year observation period. Our study suggests that the primary etiology of KAND may be acquired, long-standing neurodegeneration rather than congenital hypoplasia.
Topics: Adult; Humans; Male; Atrophy; Cerebellum; East Asian People; Intellectual Disability; Kinesins; Mutation, Missense; Neurodegenerative Diseases
PubMed: 36889712
DOI: 10.2169/internalmedicine.1184-22