Orbital Metastasis of Undifferentiated/Anaplastic Thyroid Carcinoma.

A 52-year-old woman presented with decreased vision, diplopia, esotropia, proptosis, and right orbital pain. Clinical examination was suspicious for an orbital mass and additionally revealed a thyroid gland mass. Imaging studies showed an enhancing mass within the right lateral rectus muscle and a heterogeneous mass in the left lobe of the thyroid gland.

Different mechanisms of apolipoprotein E isoform-dependent modulation of prostaglandin E2 production and triggering receptor expressed on myeloid cells 2 (TREM2) expression after innate immune activation of microglia.

Several lines of evidence support immune response in brain as a mechanism of injury in Alzheimer disease (AD). Moreover, immune activation is heightened in apolipoprotein E (APOE) ε4 carriers; inhibitors of prostaglandin (PG) synthesis show a partially protective effect on AD risk from APOE ε4; and genetic variants in triggering receptor expressed on myeloid cells 2 (TREM2) are a rare but potent risk for AD. We tested the hypothesis that APOE ε4 inheritance modulates both the PGE2 pathway and TREM2 expression using primary murine microglia from targeted replacement (TR) APOE3/3 and APOE4/4 mice.

Prostaglandin E2 receptor subtype 2 regulation of scavenger receptor CD36 modulates microglial Aβ42 phagocytosis.

Recent studies underline the potential relevance of microglial innate immune activation in Alzheimer disease. Primary mouse microglia that lack prostaglandin E2 receptor subtype 2 (EP2) show decreased innate immune-mediated neurotoxicity and increased amyloid β (Aβ) peptide phagocytosis, features that were replicated in vivo. Here, we tested the hypothesis that scavenger receptor CD36 is an effector of EP2-regulated Aβ phagocytosis.

Hemorrhagic collision metastasis in a cerebral arteriovenous malformation.

A 26-year-old patient with recurrent choriocarcinoma of the testis presented with headache and progressive left homonymous hemianopsia. On initial MRI a grade 4 arteriovenous malformation (AVM) was identified in the right occipital lobe, which was further characterized by catheter angiography. Continued worsening of the headache in the following days prompted a follow-up MRI, which revealed a new T2 hypointense nodule and adjacent vasogenic edema in the periphery of the AVM.

Hemorrhagic collision metastasis in a cerebral arteriovenous malformation.

A 26-year-old patient with recurrent choriocarcinoma of the testis presented with headache and progressive left homonymous hemianopsia. On initial MRI a grade 4 arteriovenous malformation (AVM) was identified in the right occipital lobe, which was further characterized by catheter angiography. Continued worsening of the headache in the following days prompted a follow-up MRI, which revealed a new T2 hypointense nodule and adjacent vasogenic edema in the periphery of the AVM.

Autoimmune lymphocytic hypophysitis in association with autoimmune eye disease and sequential treatment with infliximab and rituximab.

Introduction: Autoimmune lymphocytic hypophysitis associates predominantly with other autoimmune endocrinopathies and is most commonly treated with glucocorticoids and/or decompressive pituitary surgery. Here we report a new association and treatment modality for lymphocytic hypophysitis.

Methods: A 52-year-old woman presented with scleritis, uveitis, facial palsy, and central diabetes insipidus, accompanied by thickened pituitary stalk and enlarged pituitary on cranial MRI.

Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice.

Frontotemporal dementia (FTD) is a neurodegenerative disease with devastating changes in behavioral performance and social function. Mutations in the progranulin gene (GRN) are one of the most common causes of inherited FTD due to reduced progranulin expression or activity, including in brain where it is expressed primarily by neurons and microglia. Thus, efforts aimed at enhancing progranulin levels might be a promising therapeutic strategy.

APOE genotype-dependent modulation of astrocyte chemokine CCL3 production.

Apolipoprotein E (apoE) is well known as a regulator of cholesterol homeostasis, and is increasingly recognized to play a prominent role in the modulation of innate immune response, including cell-to-cell communication and migration. Alzheimer's disease (AD) is a slowly progressive neurodegenerative disorder characterized by neuroinflammation that appears to be an important component of the pathophysiology of the disease. Astrocytes are the majority cell type in brain, exerting significant influence over a range of central nervous system activities, including microglial-mediated neuroinflammatory responses.

Flow cytometry analysis of synaptosomes from post-mortem human brain reveals changes specific to Lewy body and Alzheimer's disease.

Synaptic dysfunction is thought to have an important role in the pathophysiology of neurodegenerative diseases, such as Alzheimer's disease (AD) and Lewy body disease (LBD). To improve our understanding of synaptic alterations in health and disease, we investigated synaptosomes prepared from post-mortem human cerebral cortex, putamen (PT), and two regions of the caudate nucleus, dorso-lateral (DL) and ventro-medial (VM), regions commonly affected in AD and LBD. We observed that the fraction of synaptosomal particles with reactivity for dopamine transporter (DAT) was significantly reduced in the PT and VM caudate of patients with neuropathological diagnosis of LBD.

The co-occurrence of Alzheimer's disease and Huntington's disease: a neuropathological study of 15 elderly Huntington's disease subjects.

Background: Dementia is a common feature in both Huntington's disease (HD) and Alzheimer's disease (AD), as well as in the general elderly population. Few studies have examined elderly HD patients with dementia for neuropathologic evidence of both HD and AD.

Objective: We present neuropathological findings in a retrospective case series of 15 elderly HD patients (ages 60-91 years), 11 of whom had prominent clinical dementia.

Therapeutic implications of the prostaglandin pathway in Alzheimer's disease.

An important pathologic hallmark of Alzheimer's disease (AD) is neuroinflammation, a process characterized in AD by disproportionate activation of cells (microglia and astrocytes, primarily) of the non-specific innate immune system within the CNS. While inflammation itself is not intrinsically detrimental, a delicate balance of pro- and anti-inflammatory signals must be maintained to ensure that long-term exaggerated responses do not damage the brain over time. Non-steroidal anti-inflammatory drugs (NSAIDs) represent a broad class of powerful therapeutics that temper inflammation by inhibiting cyclooxygenase-mediated signaling pathways including prostaglandins, which are the principal mediators of CNS neuroinflammation.

Orbital neoplasms in adults: clinical, radiologic, and pathologic review.

Orbital neoplasms in adults may be categorized on the basis of location and histologic type. Imaging features of these lesions often reflect their tissue composition. Cavernous malformations (also known as cavernous hemangiomas), although not true neoplasms, are the most common benign adult orbital tumor.

A case of nodular fasciitis causing compressive optic neuropathy.

A 16-year-old girl with worsening vision, new OD visual field deficits, and tumor in right orbital apex underwent biopsy and surgical excision. Orbital imaging revealed an apical tumor causing bony erosion. Histopathology confirmed the diagnosis of nodular fasciitis.

Epigenetic signature and enhancer activity of the human APOE gene.

The human apolipoprotein E (APOE) gene plays an important role in lipid metabolism. It has three common genetic variants, alleles ε2/ε3/ε4, which translate into three protein isoforms of apoE2, E3 and E4. These isoforms can differentially influence total serum cholesterol levels; therefore, APOE has been linked with cardiovascular disease.

APOE3, but not APOE4, bone marrow transplantation mitigates behavioral and pathological changes in a mouse model of Alzheimer disease.

Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein-expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice.

Suppressed retinal degeneration in aged wild type and APPswe/PS1ΔE9 mice by bone marrow transplantation.

Alzheimer's disease (AD) is an age-related condition characterized by accumulation of neurotoxic amyloid β peptides (Aβ) in brain and retina. Because bone marrow transplantation (BMT) results in decreased cerebral Aβ in experimental AD, we hypothesized that BMT would mitigate retinal neurotoxicity through decreased retinal Aβ. To test this, we performed BMT in APPswe/PS1ΔE9 double transgenic mice using green fluorescent protein expressing wild type (wt) mice as marrow donors.

Perivascular, but not parenchymal, cerebral engraftment of donor cells after non-myeloablative bone marrow transplantation.

Myeloablative (MyA) bone marrow transplantation (BMT) results in robust engraftment of BMT-derived cells in the central nervous system (CNS) and is neuroprotective in diverse experimental models of neurodegenerative diseases of the brain and retina. However, MyA irradiation is associated with significant morbidity and mortality and does not represent a viable therapeutic option for the elderly. Non-myeloablative (NMyA) BMT is less toxic, but it is not known if the therapeutic efficacy observed with MyA BMT is preserved.

A diagnostic dilemma: infectious versus noninfectious multifocal choroiditis with panuveitis.

Background: The objective of this study was to report a diagnostic dilemma in a patient with multifocal choroiditis. This is a case report study.

Findings: A 68-year-old female presented with new onset of floaters in both eyes and diagnosed with bilateral panuveitis.

Ablation of the microglial protein DOCK2 reduces amyloid burden in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) neuropathology is characterized by innate immune activation primarily through prostaglandin E2 (PGE2) signaling. Dedicator of cytokinesis 2 (DOCK2) is a guanyl nucleotide exchange factor expressed exclusively in microglia in the brain and is regulated by PGE2 receptor EP2. DOCK2 modulates microglia cytokine secretion, phagocytosis, and paracrine neurotoxicity.

Downregulation of cannabinoid receptor 1 from neuropeptide Y interneurons in the basal ganglia of patients with Huntington's disease and mouse models.

Cannabinoid receptor 1 (CB(1) receptor) controls several neuronal functions, including neurotransmitter release, synaptic plasticity, gene expression and neuronal viability. Downregulation of CB(1) expression in the basal ganglia of patients with Huntington's disease (HD) and animal models represents one of the earliest molecular events induced by mutant huntingtin (mHtt). This early disruption of neuronal CB(1) signaling is thought to contribute to HD symptoms and neurodegeneration.

Gravin is a transitory effector of polo-like kinase 1 during cell division.

The mitogenic and second-messenger signals that promote cell proliferation often proceed through multienzyme complexes. The kinase-anchoring protein Gravin integrates cAMP and calcium/phospholipid signals at the plasma membrane by sequestering protein kinases A and C with G protein-coupled receptors. In this report we define a role for Gravin as a temporal organizer of phosphorylation-dependent protein-protein interactions during mitosis.

Massive intractable hemoptysis due to idiopathic granulomatous pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease is a rare condition with limited treatment options. The pathological hallmark of the disease is occlusion of pulmonary venules and small veins in the lobular septa. The etiology of the disease remains obscure.