Olfactory dysfunction, influenced by factors such as aging and environmental stress, is linked to various neurological disorders. The olfactory bulb\'s connections to brain areas like the hypothalamus, piriform cortex, entorhinal cortex, and limbic system make olfactory dysfunction a contributor to a range of neuropathological conditions. Recent research has underscored that olfactory deficits are prevalent in individuals with both metabolic syndrome and dementia. These systemic metabolic alterations correlate with olfactory impairments, potentially affecting brain regions associated with the olfactory bulb. In cases of metabolic syndrome, phenomena such as insulin resistance and disrupted glucose metabolism may result in compromised olfactory function, leading to multiple neurological issues. This review synthesizes key findings on the interplay between metabolic-induced olfactory dysfunction and neuropathology. It emphasizes the critical role of olfactory assessment in diagnosing and managing neurological diseases related to metabolic syndrome.

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Rosettes and pseudorosettes are morphologic cell arrangements found in many neuroepithelial neoplasms in human medicine, including embryonal nervous system tumors (neuroblastoma, medulloblastoma, pineoblastoma, and retinoblastoma), non-embryonal nervous system tumors (ependymoma, astrocytoma, oligodendroglioma, and choroid plexus tumors), and other extraneural neuroepithelial neoplasms. Although these structures are also described in neuroepithelial neoplasms of domestic animals, their frequency is still poorly characterized or inconsistently documented in veterinary medicine. Furthermore, rosettes and pseudorosettes need to be interpreted with caution and within a clinical and pathologic context and should not be solely relied upon for diagnostic confirmation of a particular neoplasm. Here, we review the morphologic features and frequency of the most common types of rosettes and pseudorosettes described in neuroepithelial neoplasms of domestic animals, focusing primarily on those occurring in the nervous system and closely associated tissues.

Background: The postmortem diagnostic of individuals having suffered presumptive neurodegenerative disease comprises exclusion of a prion disease, extensive brain sampling and histopathological evaluation, which are resource-intensive and time consuming. To exclude prion disease and to achieve prompt accurate preliminary diagnosis, we developed a fast-track procedure for the histopathological assessment of brains from patients with suspected neurodegenerative disease. Methods: Based on the screening of two brain regions (frontal cortex and cerebellum) with H&E and six immunohistochemical stainings in 133 brain donors, a main histopathological diagnosis was established and compared to the final diagnosis made after a full histopathological work-up according to our brain bank standard procedure. Results: In over 96 % of cases there was a concordance between the fast-track and the final main neuropathological diagnosis. A prion disease was identified in four cases without prior clinical suspicion of a prion infection. Conclusion: The fast-track screening approach relying on two defined, easily accessible brain regions is sufficient to obtain a reliable tentative main diagnosis in individuals with neurodegenerative disease and thus allows for a prompt feedback to the physicians. However, a more thorough histological work-up taking into account the clinical history and the working diagnosis from fast-track screening is necessary for accurate staging and for assessment of co-pathologies.

BACKGROUND: Research quality within the neurosurgical field remains suboptimal. Therefore, many studies published in the neurosurgical literature lack enough statistical power to establish the presence or absence of clinically important differences between treatment arms. The field of neurotrauma deals with additional challenges, with fewer financial incentives and restricted resources in low-income and middle-income countries with the highest burden of neurotrauma diseases. In this systematic review, we aim to estimate the prevalence of false claims of equivalence in the neurosurgical trauma literature and identify its predictive factors.
METHODS: The Preferred Reporting Items for Systematic Review and Meta-Analyses recommendations were followed. Randomised clinical trials that enrolled only traumatic brain injury patients and investigated any type of intervention (surgical or non-surgical) will be eligible for inclusion. The MEDLINE/PubMed database will be searched for articles in English published from January 1960 to July 2020 in 15 top-ranked journals. A false claim of equivalence will be identified by insufficient power to detect a clinically meaningful effect: for categorical outcomes, a difference of at least 25% and 50%, and for continuous outcomes, a Cohen\'s d of at least 0.5 and 0.8. Using the number of patients in each treatment arm and the minimum effect sizes to be detected, the power of each study will be calculated with the assumption of a two-tailed alpha that equals 0.05. Standardised differences between the groups with and without a false claim of equivalence will be calculated, and the variables with a standardised difference equal or above 0.2 and 0.5 will be considered weakly and strongly associated with false claims of equivalence, respectively. The data analysis will be blinded to the authors and institutions of the studies.
BACKGROUND: This study will not involve primary data collection. Therefore, formal ethical approval will not be required. The final systematic review will be published in a peer-reviewed journal and presented at appropriate conferences.

BACKGROUND: This study investigates primary lateral sclerosis (PLS) as a rare manifestation of the presenilin 1 (PSEN1) NM_000021 c.851C > T p.Pro284Leu variant in three siblings of a Colombian family, outlining its clinical and neuropathological features and their relationship to Alzheimer\'s disease (AD).
METHODS: Data were gathered using clinical evaluations, next-generation genetic sequencing, magnetic resonance imaging, biomarker analysis, and neuropathological examination.
RESULTS: Carriers of the PSEN1 Pro284Leu variant exhibited classic PLS symptoms, including unilateral onset and bulbar syndromes, along with cognitive decline. Neuropathology showed corticospinal tract degeneration without amyloid beta deposition in spinal white matter.
CONCLUSIONS: Our findings suggest an overlap between PLS and AD pathology in PSEN1 variant carriers. Results support considering PLS when diagnosing AD-related motor syndromes and including PSEN1 evaluation when performing genetic testing for PLS. The study highlights the need for further research to clarify the PLS-AD relationship, informing future treatments and clinical trials.
CONCLUSIONS: Pathogenic variants in presenilin 1 (PSEN1) can manifest as hereditary primary lateral sclerosis PSEN1 Pro284Leu carriers present motor, cognitive, and behavioral alterations  Cases had corticospinal tract microgliosis and severe Aβ pathology in motor cortex  There was no evidence of amyloid deposition in the spinal cord white matter  All the neuropathology images are available for online visualization  Myelin pallor in the spinal cord is confined to the lateral corticospinal tracts.

UNASSIGNED: Down syndrome (DS) is strongly associated with Alzheimer\'s disease (AD), attributable to APP overexpression. DS exhibits Amyloid-β (Aβ) and Tau pathology similar to early-onset AD (EOAD) and late-onset AD (LOAD). The study aimed to evaluate the Aβ plaque proteome of DS, EOAD and LOAD.
UNASSIGNED: Using unbiased localized proteomics, we analyzed amyloid plaques and adjacent plaque-devoid tissue (\'non-plaque\') from post-mortem paraffin-embedded tissues in four cohorts (n = 20/group): DS (59.8 ± 4.99 y/o), EOAD (63 ± 4.07 y/o), LOAD (82.1 ± 6.37 y/o) and controls (66.4 ± 13.04). We assessed functional associations using Gene Ontology (GO) enrichment and protein interaction networks.
UNASSIGNED: We identified differentially abundant Aβ plaque proteins vs. non-plaques (FDR < 5%, fold-change > 1.5) in DS (n = 132), EOAD (n = 192) and in LOAD (n = 128); there were 43 plaque-associated proteins shared between all groups. Positive correlations (p < 0.0001) were observed between plaque-associated proteins in DS and EOAD (R2 = 0.77), DS and LOAD (R2 = 0.73), and EOAD vs. LOAD (R2 = 0.67). Top Biological process (BP) GO terms (p < 0.0001) included lysosomal transport for DS, immune system regulation for EOAD, and lysosome organization for LOAD. Protein networks revealed a plaque enriched signature across all cohorts involving APP metabolism, immune response, and lysosomal functions. In DS, EOAD and LOAD non-plaque vs. control tissue, we identified 263, 269, and 301 differentially abundant proteins, including 65 altered non-plaque proteins across all cohorts. Differentially abundant non-plaque proteins in DS showed a significant (p < 0.0001) but weaker positive correlation with EOAD (R2 = 0.59) and LOAD (R2 = 0.33) compared to the stronger correlation between EOAD and LOAD (R2 = 0.79). The top BP GO term for all groups was chromatin remodeling (DS p = 0.0013, EOAD p = 5.79×10- 9, and LOAD p = 1.69×10- 10). Additional GO terms for DS included extracellular matrix (p = 0.0068), while EOAD and LOAD were associated with protein-DNA complexes and gene expression regulation (p < 0.0001).
UNASSIGNED: We found strong similarities among the Aβ plaque proteomes in individuals with DS, EOAD and LOAD, and a robust association between the plaque proteomes and lysosomal and immune-related pathways. Further, non-plaque proteomes highlighted altered pathways related to chromatin structure and extracellular matrix (ECM), the latter particularly associated with DS. We identified novel Aβ plaque proteins, which may serve as biomarkers or therapeutic targets.

UNASSIGNED: This is Part II of a four-part opinion review on traditional neuropsychological assessment methods and findings associated with mild traumatic brain injury (mTBI). This Part II review focuses on historical, psychometric and statistical issues involving traditional neuropsychological methods that have been used in neuropsychological outcome studies of mTBI, but demonstrates the critical limitations of traditional methods.
UNASSIGNED: This is an opinion review.
UNASSIGNED: Traditional neuropsychological tests are dated and lack specificity in evaluating such a heterogenous and complex injury as occurs with mTBI.
UNASSIGNED: In this review, we demonstrate traditional neuropsychological methods were never developed as standalone measures for detecting subtle changes in neurocognitive or neurobehavioral functioning and likewise, never designed to address the multifaceted issues related to underlying mTBI neuropathology symptom burden from having sustained a concussive brain injury.
UNASSIGNED: For neuropsychological assessment to continue to contribute to clinical practice and outcome literature involving mTBI, major innovative changes are needed that will likely require technological advances of novel assessment techniques more specifically directed to evaluating the mTBI patient. These will be discussed in Part IV.

Wilson\'s disease (WD) is inherited in an autosomal recessive manner and is caused by pathogenic variants of the ATP7B gene, which are responsible for impaired copper transport in the cell, inhibition of copper binding to apoceruloplasmin, and biliary excretion. This leads to the accumulation of copper in the tissues. Copper accumulation in the CNS leads to the neurological and psychiatric symptoms of WD. Abnormalities of copper metabolism in WD are associated with impaired iron metabolism. Both of these elements are redox active and may contribute to neuropathology. It has long been assumed that among parenchymal cells, astrocytes have the greatest impact on copper and iron homeostasis in the brain. Capillary endothelial cells are separated from the neuropil by astrocyte terminal legs, putting astrocytes in an ideal position to regulate the transport of iron and copper to other brain cells and protect them if metals breach the blood-brain barrier. Astrocytes are responsible for, among other things, maintaining extracellular ion homeostasis, modulating synaptic transmission and plasticity, obtaining metabolites, and protecting the brain against oxidative stress and toxins. However, excess copper and/or iron causes an increase in the number of astrocytes and their morphological changes observed in neuropathological studies, as well as a loss of the copper/iron storage function leading to macromolecule peroxidation and neuronal loss through apoptosis, autophagy, or cuproptosis/ferroptosis. The molecular mechanisms explaining the possible role of glia in copper- and iron-induced neurodegeneration in WD are largely understood from studies of neuropathology in Parkinson\'s disease and Alzheimer\'s disease. Understanding the mechanisms of glial involvement in neuroprotection/neurotoxicity is important for explaining the pathomechanisms of neuronal death in WD and, in the future, perhaps for developing more effective diagnostic/treatment methods.

Traumatic brain injury (TBI) and long bone fractures are a common injury pattern in polytrauma patients and modulate each other\'s healing process. As only a limited number of studies have investigated both traumatic sites, we tested the hypothesis that brain-bone polytrauma mutually impacts neuro- and osteopathological outcomes. Adult female C57BL/6N mice were subjected to controlled cortical impact (CCI), and/or osteosynthetic stabilized femoral fracture (FF), or sham surgery. Neuromotor and behavioral impairments were assessed by neurological severity score, open field test, rotarod test, and elevated plus maze test. Brain and bone tissues were processed 42 days after trauma. CCI+FF polytrauma mice had increased bone formation as compared to FF mice and increased mRNA expression of bone sialoprotein (BSP). Bone fractures did not aggravate neuropathology or neuroinflammation assessed by cerebral lesion size, hippocampal integrity, astrocyte and microglia activation, and gene expression. Behavioral assessments demonstrated an overall impaired recovery of neuromotor function and persistent abnormalities in anxiety-related behavior in polytrauma mice. This study shows enhanced bone healing, impaired neuromotor recovery and anxiety-like behavior in a brain-bone polytrauma model. However, bone fractures did not aggravate TBI-evoked neuropathology, suggesting the existence of outcome-relevant mechanisms independent of the extent of brain structural damage and neuroinflammation.