Pattern Of Degeneration Research Articles

The Use of a Resurfacing Capitate Pyrocarbon Implant in Conjunction with a Proximal Row Carpectomy: A Systematic Review

AbstractDegenerative wrist disease may have varying etiologies, but solutions to deal with this debilitating condition center around several common management pathways. Once nonoperative measures have been exhausted, generally there is a choice between motion sparing procedures or a total wrist arthrodesis. The appropriateness of motion sparing procedures will be dictated by the extent and pattern of degeneration, and midcarpal arthrosis is typically a contraindication to a proximal row carpectomy. One solution to this problem is to employ a Resurfacing Capitate Pyrocarbon Implant. This study aimed to investigate the prevalence and effectiveness of this operation by systematically reviewing the literature. The findings of this review support the use of this implant in the setting of degenerative wrist disease, with reported outcomes comparable to similar operations. However, this is based on overall low numbers of reported outcomes with a reasonable chance of bias. Level of Evidence III.

Progressive Encephalomyelitis With Rigidity and Myoclonus With Glycine Receptor and GAD65 Antibodies: Case Report and Potential Mechanisms.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder that can be associated with antibodies against surface antigens (glycine receptor (GlyR), dipeptidyl-peptidase-like-protein-6) and intracellular antigens (glutamate decarboxylase (GAD65), amphiphysin). We report clinico-pathologic findings of a PERM patient with coexisting GlyR and GAD65 antibodies. A 75-year-old man presented with myoclonus and pain of the legs, subsequently developed severe motor symptoms, hyperekplexia, a pronounced startle reflex, hallucinations, dysautonomia, and died 10 months after onset despite extensive immunotherapy, symptomatic treatment, and continuous intensive care support. Immunotherapy comprised corticosteroids, IVIG, plasmapheresis, immunoadsorption, cyclophosphamide, and bortezomib. Intensive care treatment and permanent isoflurane sedation was required for more than 20 weeks. CNS tissue revealed neuronal loss, astrogliosis and microgliosis, representing a pallido-nigro-dentato-bulbar-spinal degeneration pattern, specifically along GlyR and GAD expression sites. Neurons showed pSTAT1, MHC class I, and GRP78 upregulation. Inflammation was moderate and characterized by CD8+ T cells and single CD20+/CD79a+ B/plasma cells. Focal tau-positive thread-like deposits were detected in gliotic brainstem areas. In the spinal cord, GlyR, glycine transporter-2, and GAD67 expression were strongly reduced. A possible potentiating effect of pathogenic GlyR antibodies together with T cells directed against neurons may have led to the severe and progressive clinical course.

A novel three-dimensional method for detailed analysis of RGC central projections under acute ocular hypertension

Normal perception of visual information relies not only on the quantity and quality of retinal ganglion cells (RGCs), but also on the integrity of the visual pathway, within which RGC central projection predominates. However, the exact changes of RGC central projection under particular pathological conditions remain to be elucidated. Here, we report a whole-brain clearing method modified from iDISCO for 3D visualization of RGC central projection. The CTB-labeled RGC central projection was visualized three-dimensionally with minimized both fluorescence quenching and the time taken. For observation of RGC axonal degeneration pattern under pathological conditions, we took acute ocular hypertension (AOH) as an example. Mice were intracamerally irrigated, and fluorescent signal in brain subregions where RGC axons projected to were quantified. The novel methodology is well-applied for rapid clearing and observation of RGC central projection in C57BL/6J, showing damaged RGC central projection on the AOH side and the most statistically significant degeneration in the superior colliculi (SC). Detailed analysis also revealed a distinct injury pattern among lateral geniculate nuclei (LGN) subregions, with the parvocellular part of the pregeniculate nuclei (PrGPC) being more vulnerable compared with the magnocellular part (PrGMC). The intracranial retrograde labeling of RGC subgroups based on brain damage variation showed PrGPC-projecting RGCs (Plgn RGC) being smaller than PrGMC-projecting RGCs (Mlgn RGC) in size and less in number, yet more vulnerable in terms of degeneration under AOH. Our data revealed the methodology for visualizing selective neuronal vulnerability under AOH, and in the meantime provided novel approach for future mechanisms exploration regarding RGC degeneration.

A novel alpha-synuclein G14R missense variant is associated with atypical neuropathological features.

Parkinson's disease (PD) affects millions of people worldwide, but only 5-10% of patients suffer from a monogenic form of the disease with Mendelian inheritance. SNCA, the gene encoding for the protein alpha-synuclein (aSyn), was the first to be associated with familial forms of PD and, since then, several missense variants and multiplications of the SNCA gene have been established as rare causes of autosomal dominant forms of PD. A patient carrying aSyn missense mutation and his family members were studied. We present the clinical features, genetic testing - whole exome sequencing (WES), and neuropathological findings. The functional consequences of this aSyn variant were extensively investigated using biochemical, biophysical, and cellular assays. The patient exhibited a complex neurodegenerative disease that included generalized myocloni, bradykinesia, dystonia of the left arm and apraxia. WES identified a novel heterozygous SNCA variant (cDNA 40G>A; protein G14R). Neuropathological examination showed extensive atypical aSyn pathology with frontotemporal lobar degeneration (FTLD) and nigral degeneration pattern with abundant ring-like neuronal inclusions, and few oligodendroglial inclusions. Sanger sequencing confirmed the SNCA variant in the healthy, elderly parent of the patient patient suggesting incomplete penetrance. NMR studies suggest that the G14R mutation induces a local structural alteration in aSyn, and lower thioflavin T binding in in vitro fibrillization assays. Interestingly, the G14R aSyn fibers display different fibrillar morphologies as revealed by cryo-electron microscopy. Cellular studies of the G14R variant revealed increased inclusion formation, enhanced membrane association, and impaired dynamic reversibility of serine-129 phosphorylation. The atypical neuropathological features observed, which are reminiscent of those observed for the G51D aSyn variant, suggest a causal role of the SNCA variant with a distinct clinical and pathological phenotype, which is further supported by the properties of the mutant aSyn, compatible with the strain hypothesis of proteinopathies.

How fiber bundle alterations differ in presumed LATE and amnestic Alzheimer's disease.

Typical Alzheimer's disease (AD) and limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) are two neurodegenerative diseases that present with a similar initial amnestic clinical phenotype but are associated with distinct proteinopathies. We investigated white matter (WM) fiber bundle alterations, using fixel-based analysis, a state-of-the-art diffusion magnetic resonance imaging model, in early AD, presumed LATE, and controls. We also investigated regional cortical atrophy. Both amnestic AD and presumed LATE patients exhibited WM alterations in tracts of the temporal and limbic lobes and in callosal fibers connecting superior frontal gyri. In addition, presumed LATE patients showed alterations in callosal fibers connecting the middle frontal gyri and in the cerebello-thalamo-cortical tract. Cortical thickness was reduced in regions connected by the most altered tracts. These findings, the first to describe WM fiber bundle alterations in presumed LATE, are consistent with results on cortical atrophy and with the staging system of tau or TDP-43 accumulation. Fixel-based analysis revealed white matter (WM) fiber bundle alterations in presumed limbic-predominant age-related TAR DNA-binding protein 43 encephalopathy (LATE) patients identified by isolated episodic/limbic amnesia, the absence of positive Alzheimer's disease (AD) biomarkers, and no other neurological diagnosis after 2 years of follow-up. Presumed LATE and amnestic AD shared similar patterns of WM alterations in fiber bundles of the limbic and temporal lobes, in congruence with their similar limbic cognitive phenotype. Presumed LATE differed from AD by the alteration of the callosal fibers connecting the middle frontal gyri and of the cerebello-thalamo-cortical tract. WM fiber bundle alterations were consistent with results on regional cortical atrophy. The different anatomical patterns of WM degeneration could provide information on the propagation pathways of distinct proteinopathies.

Histopathology of Idiopathic Condylar Resorption Differs From Temporomandibular Joint-Only Juvenile Idiopathic Arthritis

BackgroundIdiopathic condylar resorption (ICR) is a rare condition of unknown etiology characterized by progressive decrease in volume and pathologic remodeling of a previously normal mandibular condyle. Juvenile Idiopathic Arthritis (JIA) affecting only the temporomandibular joint (TMJ-only JIA) is characterized by synovitis and destruction of TMJ tissues without involvement of other joints. It is often difficult to differentiate the two conditions because they exhibit similar phenotypes. PurposeTo compare histology of resected condylar specimens from patients with ICR and TMJ-only JIA. Specific aims were: 1) To correlate longitudinal clinical data with histopathology of resected condyle specimens, 2) To compare resorption patterns between the two disease processes. Study design, setting, sampleThis was a retrospective cohort study of patients treated at Massachusetts General Hospital (MGH) from 1999 through 2023. Predictor/exposure/independent variablePrimary predictor variable was the diagnosis (ICR or JIA). Secondary predictor variables included age, gender, race, putative contributing factors, and laboratory studies. Main outcome variable(s)Primary outcome variable was presence or absence of inflammatory infiltrates in bone and synovial specimens. Secondary outcome variables were structural integrity and morphologic characteristics of the condylar cartilage and bone. AnalysesSpearman correlation was used to assess the relationship between histological scores and age, gender, and possible associated contributing factors. A p-value < 0.05 was considered statistically significant. ResultsThirty-five subjects (67 specimens) were included in Group 1 (ICR). Eight subjects (15 specimens) were included in Group 2 (TMJ-only JIA). The histopathologic findings in ICR consisted of severe and irregular cartilage surface disruption, fibrocartilage degeneration, and subchondral bone with no inflammatory infiltrate. Degeneration was observed to begin at the anterior pole of the condyle and progress eventually to total resorption to the sigmoid notch. TMJ-only JIA was notable for more severe condylar degeneration and inflammation in the bone and synovia. There was no specific pattern of degeneration. For both groups, the subject’s age, gender, or putative contributing factors did not correlate with the histopathologic scores. Conclusions and RelevanceThese results support the hypothesis that “ICR” and TMJ-only JIA are distinct clinical entities and can be distinguished by histopathologic findings in the mandibular condyles and synovia.

Microscopical anatomy of the peripheral nervous system: An essential notion for understanding the pathophysiology of very early classic Guillain-Barré syndrome.

The aim of this paper is to analyze the pathophysiological mechanisms acting in very early classic Guillain-Barré syndrome (GBS) (≤4 days of symptomatic onset). In this inaugural period, both in GBS and its animal model, experimental autoimmune neuritis, the outstanding pathological feature is inflammatory edema predominating in proximal nerve trunks, particularly spinal nerves, and possibly in preterminal nerve segments. Nerve trunks external to the subarachnoid angle possess epi- perineurium that is relatively inelastic and of low compliance. Here such edema can increase endoneurial fluid pressure that, when sufficiently critical, may stretch the perineurium and constrict transperineurial microcirculation, compromising blood flow and producing the potential for ischemic nerve injury, whose consequence is rapid partial or complete loss of nerve excitability. These histopathological features correlate well with electrophysiological and imaging findings reported in early GBS stages. Spinal nerve edema and ischemia help to understand the pattern of Wallerian-like degeneration observed in the axonal form of GBS, predominating in motor spinal roots at their exit from the dura matter (spinal nerves) with centrifugal distribution in more distant motor nerve trunks, and centripetal extension to the distal portion of intrathecal roots. The similarity of initial pathogenic mechanisms between demyelinating and axonal forms of GBS explains why an early increase of serum biomarkers of axonal damage is detected in both forms. In conclusion, knowledge of the microscopic anatomy of the peripheral nervous system is an essential step for a reliable understanding of pathophysiological mechanisms operating in the early phase of any classic GBS subtype.

Different Degeneration Patterns of Paraspinal Muscles Between Double-Level and Single-Level Lumbar Spondylolisthesis: An Magnetic Resonance Imaging Analysis of 140 Patients.

To evaluate the degeneration patterns of paraspinal muscles in double-level degenerative lumbar spondylolisthesis (dl-DLS) versus single-level degenerative lumbar spondylolisthesis (sl-DLS). A total of 67 dl-DLS and 73 sl-DLS patients were included. Multifidus (MF), erector spinae (ES), and psoas major (PM)'s fatty infiltration (FI) and relative cross-sectional area (rCSA) were measured. Sagittal parameters such as lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) were also assessed. Comparisons and correlation analysis were performed between the 2 groups. MF atrophy is worse in dl-DLS patients from L3-4 to L5-S1, with higher FI from L1-2 to L5-S1 compared to sl-DLS patients. ES atrophy and FI are more pronounced in dl-DLS patients from L1-2 to L5-S1. PM atrophy is more significant in dl-DLS patients at L2-3 to L5-S1, with heavier FI from L1-2 to L3-4, though no difference in FI from L4-5 to L5-S1. The rCSA and FI of MF and ES show significant differences between adjacent segments in both groups, except for MF rCSA between L3-4 and L4-5 in dl-DLS. In dl-DLS, PM rCSA negatively correlates with PT from L4-5 to L2-3, while FI of MF and ES in L5-S1 positively correlates with LL. In sl-DLS, PM FI in L4-5 and L5-S1 negatively correlates with LL. Degeneration of MF, ES, and PM is more severe in dl-DLS patients, particularly at the spondylolisthesis level. Severe paraspinal muscle degeneration can lead to spinal force imbalance and progression from sl-DLS to dl-DLS. The degradation of PM and ES correlates negatively with PT and SVA, indicating a link to pelvic decompensation and SVA abnormalities, potentially causing disproportionate degenerative changes in dl-DLS patients.

Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes.

In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes. Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary specialization and provide intriguing potential leads regarding the transcriptomic basis for selective vulnerability in distinct FTLD molecular-anatomical subtypes.

Integrative Proteomics-Metabolomics of In Vitro Degeneration of Cardiovascular Cell Lines.

Long-term cell culture is an important biological approach but is also characterized by degeneration in cellular morphology, proliferation rate, and function. To explore this phenomenon in a systematic way, we conducted an integrative proteomics-metabolomics measurement of two cardiovascular cell lines of AC16 and HUVECs. The 18th culturing passages, i.e., G18, showed as the turning points by cell metabolism profiles, in which the metabolomic changes demonstrated the dysfunction of energy, amino acid, and ribonucleotide metabolism metabolic pathways. Although active protein networks showed mitochondria abundance AC16 and oxidative/nitrative sensitive HUVECs indicated the different degeneration patterns, the G18 and G30 proteomics evidenced the senescence by processes of signal transduction, signaling by interleukins, programmed cell death, cellular responses to stimuli, cell cycle, mRNA splicing, and translation. Some crucial proteins (RPS8, HNRNPR, SOD2, LMNB1, PSMA1, DECR1, GOT2, OGDH, PNP, CBS, ATIC, and IMPDH2) and metabolites (L-glutamic acid, guanine, citric acid, guanosine, guanosine diphosphate, glucose 6-phosphate, and adenosine) that contributed to the dysregulation of cellular homeostasis are identified by using the integrative proteomic-metabolomic analysis, which highlighted the increased cellular instability. These findings illuminate some vital molecular processes when culturing serial passages, which contribute holistic viewpoints of in vitro biology with emphasis on the replicative senescence of cardiovascular cells.

Nanoscale volumetric fluorescence imaging via photochemical sectioning.

Optical nanoscopy of intact biological specimens has been transformed by recent advancements in hydrogel-based tissue clearing and expansion, enabling the imaging of cellular and subcellular structures with molecular contrast. However, existing high-resolution fluorescence microscopes have limited imaging depth, which prevents the study of whole-mount specimens without physical sectioning. To address this challenge, we developed "photochemical sectioning," a spatially precise, light-based sample sectioning process. By combining photochemical sectioning with volumetric lattice light-sheet imaging and petabyte-scale computation, we imaged and reconstructed axons and myelination sheaths across entire mouse olfactory bulbs at nanoscale resolution. An olfactory-bulb-wide analysis of myelinated and unmyelinated axons revealed distinctive patterns of axon degeneration and de-/dysmyelination in the neurodegenerative mouse, highlighting the potential for peta- to exabyte-scale super-resolution studies using this approach.

Uncovering patterns of white-matter degeneration in normal aging: links between morphometry and microstructure

Abstract While tract-wise differences in volume and microstructure are common targets of investigation in age-related changes in the white matter (WM), there has been relatively little exploration into other attributes of tract morphometry or its relation to microstructure in vivo, and limited understanding on how they jointly inform the understanding of the WM aging trajectory. This study examines ten WM tracts for tract-wise differences in morphometry (i.e. volume, length, and volume-to-length ratio) and microstructural integrity (i.e. fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) using diffusion MRI data from the Human Connectome Project in Aging (HCP-A) with the goal of laying the foundation for a more comprehensive model of age-related WM microstructure-morphometry trajectories with a special focus on age-shifted correlations and sex differences. Results indicated that degeneration in microstructure was detectable at younger ages than changes in morphometry, with widely heterogeneous patterns of interrelation and morphometry-microstructural associations in aging both across tracts and between sexes. Multi-parametric signatures of decline suggest differing stages or mechanisms of degeneration across tracts, with female subjects exhibiting a higher proportion of tracts in later stages of decline than males. This work highlights the value of integrating microstructural and morphometric measures of WM health, and encourages the integration of yet more modalities in improving our mechanistic understanding of WM aging.

Distinct biological property of tau in tau-first cognitive proteinopathy: Evidence by longitudinal clinical neuroimaging profiles and compared with late-onset Alzheimer disease.

Tau-first cognitive proteinopathy (TCP) denotes a clinical phenotype of Alzheimer disease (AD) showing Florzolotau(18F) positron emission tomography (PET) positivity but a negative amyloid status. We explored the biological property of tau using longitudinal cognitive and neuroimaging data in TCP and compared with late-onset AD (LOAD). We enrolled 56 patients with LOAD, 34 patients with TCP, and 26 cognitive unimpaired controls. All of the participants had historical data of 2 to 4 three-dimensional T1 images and 2 to 6 annual cognitive evaluations over a follow-up period of 7 years. Tau topography was measured using Florzolotau(18F) PET. In the LOAD and TCP groups, we constructed tau or gray matter clusters covarying with the cognitive measurements. We used mediator analysis to explore the regional tau load as predictor, gray matter partitions as mediators, and significant cognitive test scores as outcomes. Longitudinal cognitive decline and cortical thickness degeneration pattern were analyzed using a linear mixed-effects model. The TCP group had longitudinal declines in nonexecutive domains. The deterministic factor predicting the short-term memory score in TCP was the hippocampal volume and not directly via the medial and lateral temporal tau load. These features formed the conceptual differences with LOAD. The biological properties of tau and the longitudinal cognitive-imaging trajectory support the conceptual distinction between TCP and LOAD. TCP represents one specific entity featuring salient short-term memory impairment, declines in nonexecutive domains, a slower gray matter degenerative pattern, and a restricted impact of tau.

Symmetric and Profound Monoaminergic Degeneration in Parkinson's Disease with Premotor REM Sleep Behavior Disorder.

Rapid eye movement sleep behavior disorder (RBD) may precede or follow motor symptoms in Parkinson's disease (PD). While over 70% of idiopathic RBD cases phenoconvert within a decade, a small subset develops PD after a more extended period or remains nonconverted. These heterogeneous manifestations of RBD in PD prompt subtype investigations. Premotor RBD may signify "body-first" PD with bottom-up, symmetric synucleinopathy propagation. Explore brainstem and nigrostriatal monoaminergic degeneration pattern differences based on premotor RBD presence and duration in de novo PD patients. In a cross-sectional analysis of de novo PD patients (n = 150) undergoing FP-CIT PET and RBD Single-Question Screen, the cohort was categorized into groups with and without premotor RBD (PDRBD+/-), with further classification of PDRBD+ based on a 10-year duration of premotor RBD. Analysis of FP-CIT binding in the striatum and pons, striatal asymmetry, and striatum-to-pons ratios compared patterns of nigrostriatal and brainstem monoaminergic degeneration. PDRBD+ exhibited more severe and symmetrical striatal dopaminergic denervation compared to PDRBD-, with the difference in severity accentuated in the least-affected hemisphere. The PDRBD+<10Y subgroup displayed the most prominent striatal symmetry, supporting a more homogeneous "body-first" subtype. Pontine uptakes remained lower in PDRBD+ even after adjusting for striatal uptake, suggesting early degeneration of pontine monoaminergic nuclei. Premotor RBD in PD is associated with severe, symmetrical nigrostriatal and brainstem monoaminergic degeneration, especially in cases with PD onset within 10 years of RBD. This supports the concept of a "widespread, bottom-up" pathophysiological mechanism associated with premotor RBD in PD.

Maculopapillary Bundle Degeneration in Optic Neuropathies.

Degeneration of the maculopapillary bundle (MPB) is a prominent feature in a spectrum of optic neuropathies. MPB-selective degeneration is seen in specific conditions, such as nutritional and toxic optic neuropathies, Leber hereditary optic neuropathy (LHON), and dominant optic atrophy (DOA). Despite their distinct etiologies and clinical presentations, which encompass variations in age of incidence and monocular or binocular onset, these disorders share a core molecular mechanism: compromised mitochondrial homeostasis. This disruption is characterized by dysfunctions in mitochondrial metabolism, biogenesis, and protein synthesis. This article provides a comprehensive understanding of the MPB's role in optic neuropathies, emphasizing the importance of mitochondrial mechanisms in the pathogenesis of these conditions. Optical coherence tomography studies have characterized the retinal nerve fiber layer changes accompanying mitochondrial-affiliated optic neuropathies. Selective thinning of the temporal optic nerve head is preceded by thickening in early stages of these disorders which correlates with reductions in macular ganglion cell layer thinning and vascular atrophy. A recently proposed mechanism underpinning the selective atrophy of the MPB involves the positive feedback of reactive oxygen species generation as a common consequence of mitochondrial dysfunction. Additionally, new research has revealed that the MPB can undergo degeneration in the early stages of glaucoma, challenging the historically held belief that this area was not involved in this common optic neuropathy. A variety of anatomical risk factors influence the propensity of glaucomatous MPB degeneration, and cases present distinct patterns of ganglion cell degeneration that are distinct from those observed in mitochondria-associated diseases. This review synthesizes clinical and molecular research on primary MPB disorders, highlighting the commonalities and differences in their pathogenesis. 1.Temporal degeneration of optic nerve fibers accompanied by cecocentral scotoma is a hallmark of maculopapillary bundle (MPB) degeneration. 2.Mechanisms of MPB degeneration commonly implicate mitochondrial dysfunction. 3.Recent research challenges the traditional belief that the MPB is uninvolved in glaucoma by showing degeneration in the early stages of this common optic neuropathy, yet with features distinct from other MPB-selective neuropathies. 4.Reactive oxygen species generation is a mechanism linking mitochondrial mechanisms of MPB-selective optic neuropathies, but in-vivo and in-vitro studies are needed to validate this hypothesis.

Long COVID: From olfactory dysfunctions to viral Parkinsonism.

Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019 (COVID-19). This varies from olfactory dysfunctions such as parosmia to cognitive and emotional challenges. Historically, the surge of neurological disorders followed the viral pandemics, for example, the emergence of Encephalitis Lethargica after the outbreak of Spanish Influenza. During and after COVID-19 infection, the problems associated with the sense of smell and the reports of affected olfactory and limbic brain areas are leading to a growing concern about the similarity with the symptoms and the pattern of degeneration observed at the onset of Parkinson's disease and Alzheimer's disease. These reports reveal the essentiality of long-term studies of olfactory and cognitive functions in the post-COVID era and the experiments using animal models to dissect the neural basis of these complications. In this manuscript, we summarize the research reporting the potential correlation between neurological disorders and viral pandemic outbreaks with a historical perspective. Further, we discuss the studies providing evidence of neurodegeneration due to severe acute respiratory syndrome coronavirus 2 infection by focusing on viral Parkinsonism.

Magnetic resonance imaging assessment of the patterns and distributions of spinal disc degeneration in patients residing in Lagos State

Background: Degenerative disc disease is a condition in which intervertebral discs losses its structure thereby resulting in loss of cushioning, fragmentation and herniation most times related to ageing. Structural defects and failure are common causes of degenerative disc disease. In some cases, the spine loses flexibility and bone spurs may pinch a nerve root, causing pain or weakness. The aim of this study was to assess the prevalence and distribution of disc degeneration over the spines in patients residing in Lagos state using magnetic resonance imaging. Materials and methods: This was a cross-sectional prospective study conducted among 163 patients presented for spinal magnetic resonance imaging (MRI) scan due to disc degeneration in some selected radio-diagnostic centres in Lagos State, Nigeria. The spine structural appearance, intervertebral disc structural appearance, signal intensity, pathologies, gender, age, height, weight and BMI of the patients will be recorded. Both descriptive (mean, percentage, charts and frequency) and inferential statistics (Chi-square) statistics were used for statistical analysis with p-value set at 0.05. Results: Out of 163, 96(58.9%) were female while males were 67(41.1%). The age of the study population ranges from 20 years to 90 years with a mean age of 57.17 ± 12.35. Grade V was highest 64 (39.3%) followed by 32 (25.8%) grade IV and least 10 (6.1%) were grade II. The study found the most common affected on L4/L5 disc with 35 (21.5%) adults demonstrating disc degeneration, while 17 (10.4%) adults demonstrated no disc degeneration. There is no statistically significant association between gender and pattern of disc degeneration (χ2 = 5.943, p =0.203). Conclusion: The majority of the patients had the grade V patterns of degenerated discs based Pffirman grading system. The most affected disc was the L4/L5 disc followed by the L3/L4 disc. There were negative correlations but not statistically significant between weight and BMI respectively and patterns of the disc degeneration diseases. There exist positive correlations but not statistically significant between age and height respectively, and patterns of the disc degeneration diseases. There is no statistically significant association between gender and pattern of disc degeneration.

Intradiscal vacuum phenomenon matches lumbar spine degeneration patterns in an ageing population

PurposeIntra-Discal Vacuum phenomenon (IDVP) is well-recognised, yet poorly visualised and poorly understood radiological finding in disc degeneration, particularly with regard to its role in spinal alignment. CT analysis of the lumbar spine in an aging population aims to identify patterns associated with IDVP including lumbopelvic morphology and associated spinal diagnoses.MethodsAn analysis was performed of an over-60s population sample of 2020 unrelated abdominal CT scans, without acute spinal presentations. Spinal analysis included sagittal lumbopelvic reconstructions to assess for IDVP and pelvic incidence (PI). Subjects with degenerative pathologies, including previous vertebral fractures, auto-fusion, transitional vertebrae, and listhesis, were also selected out and analysed separately.ResultsThe prevalence of lumbar spine IDVP was 50.3% (955/1898) and increased with age (125 exclusions). This increased in severity towards the lumbosacral junction (L1L2 8.3%, L2L3 10.9%, L3L4 11.5%, L4L5 23.9%, and L5S1 46.3%). A lower PI yielded a higher incidence of IDVP, particularly at L5S1 (p < 0.01). A total of 292 patients had IDVP with additional degenerative pathologies, which were more likely to occur at the level of isthmic spondylolisthesis, adjacent to a previous fracture or suprajacent to a lumbosacral transitional vertebra (p < 0.05).ConclusionsThis study identified the prevalence and severity of IDVP in an aging population. Sagittal patterns that influence the pattern of IVDP, such as pelvic incidence and degenerative pathologies, provide novel insights into the function of aging spines.

Prediction model based on MRI morphological features for distinguishing benign and malignant thyroid nodules

BackgroundThe low specificity of Thyroid Imaging Reporting and Data System (TI-RADS) for preoperative benign-malignant diagnosis leads to a large number of unnecessary biopsies. This study developed and validated a predictive model based on MRI morphological features to improve the specificity.MethodsA retrospective analysis was conducted on 825 thyroid nodules pathologically confirmed postoperatively. Univariate and multivariate logistic regression were used to obtain β coefficients, construct predictive models and nomogram incorporating MRI morphological features in the training cohort, and validated in the validation cohort. The discrimination, calibration, and decision curve analysis of the nomogram were performed. The diagnosis efficacy, area under the curve (AUC) and net reclassification index (NRI) were calculated and compared with TI-RADS.Results572 thyroid nodules were included (training cohort: n = 397, validation cohort: n = 175). Age, low signal intensity on T2WI, restricted diffusion, reversed halo sign in delay phase, cystic degeneration and wash-out pattern were independent predictors of malignancy. The nomogram demonstrated good discrimination and calibration both in the training cohort (AUC = 0.972) and the validation cohort (AUC = 0.968). The accuracy, sensitivity, specificity, PPV, NPV and AUC of MRI-based prediction were 94.4%, 96.0%, 93.4%, 89.9%, 96.5% and 0.947, respectively. The MRI-based prediction model exhibited enhanced accuracy (NRI>0) in comparison to TI-RADSs.ConclusionsThe prediction model for diagnosis of benign and malignant thyroid nodules demonstrated a more notable diagnostic efficacy than TI-RADS. Compared with the TI-RADSs, predictive model had better specificity along with a high sensitivity and can reduce overdiagnosis and unnecessary biopsies.

Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype.

Introduction: TULP1 exemplifies the remarkable clinical and genetic heterogeneity observed in inherited retinal dystrophies. Our research describes the clinical and molecular characteristics of a patient manifesting an atypical retinal dystrophy pattern, marked by the identification of both a previously unreported and a rarely encountered TULP1 variant. Methods: Whole-exome sequencing was performed to identify potential causative variants. The pathogenicity of the identified TULP1 variants was evaluated through in silico predictors and a minigene splice assay, specifically designed to assess the effect of the unreported TULP1 variant. Results: We identified two TULP1 gene variants in a patient exhibiting unusual and symmetrical alterations in both retinas, characterized by an increase in autofluorescence along the distribution of retinal vessels. These variants included a known rare missense variant, c.1376T>C, and a novel splice site variant, c.822G>T. For the latter variant (c.822G>T), we conducted a minigene splice assay that demonstrated the incorporation of a premature stop codon. This finding suggests a likely activation of the nonsense-mediated mRNA decay mechanism, ultimately resulting in the absence of protein production from this allele. Segregation analysis confirmed that these variants were in trans. Discussion: Our data support that individuals with biallelic TULP1 variants may present with a unique pattern of macular degeneration and periarteriolar vascular pigmentation. This study highlights the importance of further clinical and molecular characterization of TULP1 variants to elucidate genotype-phenotype correlations in the context of inherited retinal dystrophies.