Spatiotemporal Cofilin Signaling, Microglial Activation, Neuroinflammation, and Cognitive Impairment Following Hemorrhagic Brain Injury.

Intracerebral hemorrhage (ICH) is a significant health concern associated with high mortality. Cofilin plays a crucial role in stress conditions, but its signaling following ICH in a longitudinal study is yet to be ascertained. In the present study, we examined the cofilin expression in human ICH autopsy brains.

Misidentification of Infection as Aspergillosis in a Patient with Chronic Renal Failure.

Aspergillosis is a commonly diagnosed fungal infection. Histopathologic examination alone can have diagnostic pitfalls due to the overlapping of fungal morphology. We report a case of infection initially misdiagnosed as aspergillosis.

Interleukin-1β drives NEDD8 nuclear-to-cytoplasmic translocation, fostering parkin activation via NEDD8 binding to the P-ubiquitin activating site.

Background: Neuroinflammation, typified by elevated levels of interleukin-1 (IL-1) α and β, and deficits in proteostasis, characterized by accumulation of polyubiquitinated proteins and other aggregates, are associated with neurodegenerative disease independently and through interactions of the two phenomena. We investigated the influence of IL-1β on ubiquitination via its impact on activation of the E3 ligase parkin by either phosphorylated ubiquitin (P-Ub) or NEDD8.

Methods: Immunohistochemistry and Proximity Ligation Assay were used to assess colocalization of parkin with P-tau or NEDD8 in hippocampus from Alzheimer patients (AD) and controls.

Long-term Seizure Disorder Caused by a Dermoid Cyst with Catastrophic Developments.

Glioblastoma multiforme (GBM) is a World Health Organization (WHO) grade IV primary malignant astrocytoma. Aneurysms are devastating intracranial neurovascular pathologies. Intracranial dermoid cysts are common, benign lesions which can be clinically silent or associated with seizure disorder.

Benchmarking Subspecialty Practice in Academic Anatomic Pathology: The 2017 Association of Pathology Chairs Survey.

Assessment of physician workloads has become increasingly important in modern academic physician practice, where it is commonly used to allocate resources among departments, to determine staffing, and to set the compensation of individual physicians. The physician work relative value unit system is a frequently used metric in this regard. However, the application of this system to the practice of pathology has proven problematic.

Outsourcing of Academic Clinical Laboratories: Experiences and Lessons From the Association of Pathology Chairs Laboratory Outsourcing Survey.

American hospitals are increasingly turning to service outsourcing to reduce costs, including laboratory services. Studies of this practice have largely focused on nonacademic medical centers. In contrast, academic medical centers have unique practice environments and unique mission considerations.

A Case Report of in Utero Williams Syndrome Arterial Malformation.

Introduction: Williams syndrome (WS), an autosomal dominant condition linked to gene deletions on chromosome 7, can cause supravalvular aortic narrowing and death. WS-associated mutations are believed to disrupt arterial elastin fibers, causing smooth muscle malformation, endomysial fibrosis and severe hypertension. Previous studies demonstrated arterial ultrastructural anomalies in adult WS patients.

A Unique Case of Carotid Splaying by a Cervical Vagal Neurofibroma and the Role of Neuroradiology in Surgical Management.

Carotid splaying, also known as the Lyre sign, is a widening of the carotid bifurcation due to the displacement of the internal carotid artery and the external carotid artery just distal to the point of divergence. This phenomenon is classically exhibited by highly vascularized carotid body tumors and, in rare cases, by cervical sympathetic chain schwannomas. Demonstration of the Lyre sign by a cervical vagal neurofibroma, however, is a unique occurrence that has not been previously documented in the literature.

Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs.

Introduction: Alzheimer apolipoprotein E (APOE) ɛ4/ɛ4 carriers have earlier disease onset and more protein aggregates than patients with other APOE genotypes. Autophagy opposes aggregation, and important autophagy genes are coordinately regulated by transcription factor EB (TFEB) binding to "coordinated lysosomal expression and regulation" (CLEAR) DNA motifs.

Methods: Autophagic gene expression was assessed in brains of controls and Alzheimer's disease (AD) patients parsed by APOE genotype and in a glioblastoma cell line expressing either apoE3 or apoE4.

Multiple supratentorial subependymomas causing obstructive hydrocephalus.

Introduction: Subependymomas are benign intraventricular tumours that most often occur asymptomatically and are found incidentally on autopsy. Symptomatic examples requiring surgical intervention are exceedingly rare.

Case Presentation: A 55-year-old man with no history of neurological symptoms presented with multiple episodes of loss of consciousness and increasing headaches.

The Art of Mimicry: Anterior Clinoid Dural-Based Cavernous Hemangioma Mistaken for a Meningioma.

Background: Cavernous hemangiomas account for 5%-13% of central nervous system vascular lesions. They are usually found intra-axially but rarely involve extra-axial structures, most commonly the middle cranial fossa. A cavernous hemangioma manifesting as a clinoid meningioma is extremely rare.

Aging, Alzheimer's, and APOE genotype influence the expression and neuronal distribution patterns of microtubule motor protein dynactin-P50.

Reports from neural cell cultures and experimental animal studies provide evidence of age- and disease-related changes in retrograde transport of spent or misfolded proteins destined for degradation or recycling. However, few studies address these issues in human brain from those who either age without dementia and overt neuropathology, or succumb to Alzheimer's; especially as such propensity may be influenced by APOE genotype. We studied the expression and distribution of the dynein subunit dynactin-P50, the β amyloid precursor protein (βAPP), and hyperphosphorylated tau (P-tau) in tissues and tissue sections of brains from non-demented, neuropathology-free patients and from Alzheimer patients, with either APOE ε3,3 or APOE ε4,4.

Loss of angiotensin II receptor expression in dopamine neurons in Parkinson's disease correlates with pathological progression and is accompanied by increases in Nox4- and 8-OH guanosine-related nucleic acid oxidation and caspase-3 activation.

Background: In rodent models of Parkinson's disease (PD), dopamine neuron loss is accompanied by increased expression of angiotensin II (AngII), its type 1 receptor (AT1), and NADPH oxidase (Nox) in the nigral dopamine neurons and microglia. AT1 blockers (ARBs) stymie such oxidative damage and neuron loss. Whether changes in the AngII/AT1/Nox4 axis contribute to Parkinson neuropathogenesis is unknown.

Frontotemporal lobar degeneration FTLD-tau: preclinical lesions, vascular, and Alzheimer-related co-pathologies.

Frontotemporal lobar degeneration with τ pathology (FTLD-tau) is one of a group of neurodegenerative diseases that manifests with cognitive decline. Alzheimer (AD) and cerebrovascular lesions are commonly noted in the brains of most elderly individuals, begging the question as to whether (a) coexisting AD and vascular pathology or age contribute to the development of FTLD-tau disorders and vice versa and (b) FTLD-tau-like pathology can be found in non-diseased individuals. We studied brains of FTLD-tau cases exhibiting (a) argyrophilc grain disease (AGD), (b) progressive supranuclear palsy (PSP), (c) corticobasal degeneration (CBD), or (d) Pick's disease (PiD) for coexisting AD and vascular pathology for comparison with that of non-diseased individuals and AD patients.

Epilepsy: neuroinflammation, neurodegeneration, and APOE genotype.

Background: Precocious development of Alzheimer-type neuropathological changes in epilepsy patients, especially in APOE ϵ4,4 carriers is well known, but not the ways in which other APOE allelic combinations influence this outcome. Frozen and paraffin-embedded tissue samples resected from superior temporal lobes of 92 patients undergoing temporal lobectomies as a treatment for medication-resistant temporal lobe epilepsy were used in this study. To determine if epilepsy-related changes reflect those in another neurological condition, analogous tissue samples harvested from 10 autopsy-verified Alzheimer brains, and from 10 neurologically and neuropathologically normal control patients were analyzed using immunofluorescence histochemistry, western immunoblot, and real-time PCR to determine genotype effects on neuronal number and size, neuronal and glial expressions of amyloid β (Aβ) precursor protein (βAPP), Aβ, apolipoprotein E (ApoE), S100B, interleukin-1α and β, and α and β secretases; and on markers of neuronal stress, including DNA/RNA damage and caspase 3 expression.

Pathology of clinical and preclinical Alzheimer's disease.

Alzheimer's disease (AD) is characterized neuropathologically by the presence of amyloid plaques, neuritic plaques, and neurofibrillary tangles (NFTs). These lesions occur not only in demented individuals with AD but also in non-demented persons. In non-demented individuals, amyloid and neuritic plaques are usually accompanied with NFTs and are considered to represent asymptomatic or preclinical AD (pre-AD) pathology.

Ossification in an extra-intradural spinal meningioma-pathologic and surgical vistas.

Background Context: Intradural and intratumorous ossification in spinal meningiomas are rare compared to their cranial counterparts. Extradural extension of the spinal meningioma is not uncommon. To the best of our knowledge, the ossification in an extra-intradural spinal meningioma is not yet reported in the literature.

Microglia in Alzheimer brain: a neuropathological perspective.

Microglia have long been noted to be present and activated in Alzheimer brain. Demonstrations that these microglia are associated with the specific lesions of Alzheimer disease-Aβ plaques and neurofibrillary tangles-and that these microglia overexpress the potent proinflammatory cytokine interleukin-1 led to the recognition of a potential pathogenic role for these cells in initiation and progression of disease. Activated, cytokine-overexpressing microglia are near-universal components of Aβ plaques at early (diffuse) and mid (neuritic) stages of progression in Alzheimer brain, and only decline in end-stage, dense core plaques.

Apolipoprotein epsilon 3 alleles are associated with indicators of neuronal resilience.

Background: Epilepsy is associated with precocious development of Alzheimer-type neuropathological changes, including appearance of senile plaques, neuronal loss and glial activation. As inheritance of APOE ε4 allele(s) is reported to favor this outcome, we sought to investigate neuronal and glial responses that differ according to APOE genotype. With an eye toward defining ways in which APOE ε3 alleles may foster neuronal well-being in epilepsy and/or APOE ε4 alleles exacerbate neuronal decline, neuronal and glial characteristics were studied in temporal lobectomy specimens from epilepsy patients of either APOE ε4,4 or APOE ε3,3 genotype.

Apolipoprotein E expression is elevated by interleukin 1 and other interleukin 1-induced factors.

Background: We have previously outlined functional interactions, including feedback cycles, between several of the gene products implicated in the pathogenesis of Alzheimer's disease. A number of Alzheimer-related stressors induce neuronal expression of apolipoprotein E (ApoE), β-amyloid precursor protein (βAPP), and fragments of the latter such as amyloid β-peptide (Aβ) and secreted APP (sAPP). These stressors include interleukin-1 (IL-1)-mediated neuroinflammation and glutamate-mediated excitotoxicity.

Capillary cerebral amyloid angiopathy identifies a distinct APOE epsilon4-associated subtype of sporadic Alzheimer's disease.

The deposition of amyloid beta-protein (Abeta) in the vessel wall, i.e., cerebral amyloid angiopathy (CAA), is associated with Alzheimer's disease (AD).

Tripartite components of a hepatocellular carcinoma with distinct immunohistochemical and metastatic features.

We report an unusual case of hepatocellular carcinoma with three histologically and immunohistochemically distinct components, arising in a noncirrhotic liver, with a pulmonary tumor embolus from one of the three components. The histological patterns of the three components were fibrolamellar, well-differentiated nodular, and pleomorphic. The immunophenotypes were, respectively CK7- /CK20- /Hep Par1+, CK7+ /CK20- /Hep Par1+, and CK7+ /CK20+ /Hep Par1-.

Trafficking of glucose, lactate, and amyloid-beta from the inferior colliculus through perivascular routes.

Metabolic brain imaging is widely used to evaluate brain function and disease, and quantitative assays require local retention of compounds used to register changes in cellular activity. As labeled metabolites of [1- and 6-(14)C]glucose are rapidly released in large quantities during brain activation, this study evaluated release of metabolites and proteins through perivascular fluid flow, a pathway that carries solutes from brain to peripheral lymphatic drainage sites. Assays with [3,4-(14)C]glucose ruled out local oxidation of glucose-derived lactate as a major contributor of label loss.

Neuropathology and the neuroinflammation idea.

A role for innate immunity in neurodegenerative diseases is now widely accepted, although debate continues over the relative contributions of these processes to disease progression and/or to disease amelioration. The idea that microglia and cytokines are important in neurodegeneration arose from neuropathological observations, especially in Alzheimer's disease. Microglia are invariant components of the Abeta plaques of Alzheimer's disease, where they show a waxing and waning of numbers, activation state, and cytokine expression during plaque progression.

Pituitary adenoma with craniopharyngioma component.

Neoplasms consisting of pituitary adenoma and craniopharyngioma components are rare and are being increasingly recognized. Their histogenesis is not clear. Most represent collision tumors; others are difficult to assess.