Alterations of Ca-responsive proteins within cholinergic neurons in aging and Alzheimer's disease

The molecular basis of selective neuronal vulnerability in Alzheimer's disease (AD) remains poorly understood. Using basal forebrain cholinergic neurons (BFCNs) as a model and immunohistochemistry, we have demonstrated significant age-related loss of the calcium-binding protein calbindin-D_28K (CB) from BFCN, which was associated with tangle formation and degeneration in AD. Here, we determined alterations in RNA and protein for CB and the Ca²⁺-responsive proteins Ca²⁺/calmodulin-dependent protein kinase I (CaMKI), growth-associated protein-43 (GAP43), and calpain in the BF. We observed progressive downregulation of CB and CaMKI RNA in laser-captured BFCN in the normal-aged-AD continuum. We also detected progressive loss of CB, CaMKIδ, and GAP43 proteins in BF homogenates in aging and AD. Activated μ-calpain, a calcium-sensitive protease that degrades CaMKI and GAP43, was significantly increased in the normal aged BF and was 10 times higher in AD BF. Overactivation of μ-calpain was confirmed using proteolytic fragments of its substrate spectrin. Substantial age- and AD-related alterations in Ca²⁺-sensing proteins most likely contribute to selective vulnerability of BFCN to degeneration in AD.     

Predictors and Outcomes of Frequent Emergency Department Users

OBJECTIVE: To identify predictors and outcomes associated with frequent emergency department (ED) users. METHODS: Cross-sectional intake surveys, medical chart reviews, and telephone follow-up interviews of patients presenting with selected chief complaints were performed at five urban EDs during a one-month study period in 1995. Frequent use was defined by four or more self-reported, prior ED visits. Multivariate logistic regression identified predictors of frequent ED visitors from five domains (demographics, health status, health access, health care preference, and severity of acute illness). Associations between high use and selected outcomes were assessed with logistic regression models. RESULTS: All study components were completed by 2,333 of 3,455 eligible patients (67.5%). Demographics predicting frequent use included being a single parent, single or divorced marital status, high school education or less, and income of less than $10,000 (1995). Health status predictors included hospitalization in the preceding three months, high ratings of psychological distress, and asthma. Health access predictors included identifying an ED or a hospital clinic as the primary care site, having a primary care physician (PCP), and visiting a PCP in the past month. Choosing the ED for free care was the only health preference predictive of heavy use. Illness severity measures were higher in frequent visitors, although these were not independently predictive in the multivariate model. Outcomes correlated with heavy use include increased hospital admissions, higher rates of ED return visits, and lower patient satisfaction, but not willingness to return to the ED or follow-up with a doctor. CONCLUSIONS: Frequent ED visits are associated with socioeconomic distress, chronic illness, and high use of other health resources. Efforts to reduce ED visits require addressing the unique needs of these patients in the emergency and primary care settings.     

Progressive supranuclear palsy with dementia: cortical pathology

Patients with progressive supranuclear palsy (PSP) often develop dementia, and cortical pathology has been documented in PSP. However, there are no reports correlating dementia in PSP with cortical pathology. We hypothesized that cases of PSP presenting with cognitive impairment would have more severe cortical tau pathology than those without. We compared 7 cases of PSP presenting with cognitive deficits (group 1) with 4 cases of PSP that did not (group 2). The subcortical tau pathology was almost identical in both groups. The cortical tau pathology was strikingly different in group 1, in which it was on average moderate, compared with group 2, in which it was minimal. The accumulation of cortical neuronoglial tau in PSP cases with dementia suggests that neurofibrillary pathology is central to the cause of dementia in PSP.     

Pineal chordoid meningioma complicated by repetitive hemorrhage during pregnancy: Case report and literature review

Chordoid meningioma is an uncommon variant of meningioma, and is very rarely found in the pineal region. We report a case of pineal region chordoid meningioma occurring in a young woman complicated by repetitive hemorrhages in the setting of pregnancy. A 23‐year‐old woman, 28 weeks pregnant, was transferred to our hospital for further management of a multi‐septated, hemorrhagic pineal region mass and hydrocephalus. MRI revealed a heterogeneous T2‐hyperintense lesion measuring 1.7 × 1.7 cm in the pineal gland. Resection of the tumor through an occipital transtentorial approach was performed. Histopathologic examination of the lesion confirmed the diagnosis of chordoid meningioma demonstrating cords and clusters of eosinophilic cells with rare cytoplasmic vacuolation arranged in a mucinous stroma. Additionally, there was abundant lymphoplasmacytic infiltration within the tumor. The details of this case are presented with a review of the literature.     

Inclusion body myositis with abundant ring fibers

Summary A 37-year-old male presenting with a 7-year history of leg weakness was found to have moderate weakness confined to the quadriceps and myopathic changes on electromyography. Serum creatine phosphokinase was 2130 units/liter. Biopsy of the quadriceps muscle revealed an inflammatory myopathy with cytoplasmic and nuclear filamentous inclusions characteristic of inclusion body myositis. An unusual finding was the large proportion of ring fibers along with severe atrophy and fibrosis. The pathogenesis of the ring fibers in this setting is discussed.