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Background and Objectives: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology., Methods and Results: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex., Conclusions: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry., (© The Author(s), 2015.)

Corticobasal syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS) are two of the atypical Parkinsonism syndromes, in that patients exhibit rigidity, occasional tremor and postural instability, but do not symptomatically respond to dopamine replacement. CBS and PSPS can often present with complex cognitive difficulties and neuropsychiatric disturbances. Symptoms of depression, apathy, or agitation can be subtle and are often overlooked as reactions to learning a new diagnosis of Parkinsonism. These symptoms may be the earliest presenting evidence of CBS or PSPS, and these syndromes can be misdiagnosed with a primary psychiatric disorder rather than a neurodegenerative condition. Patients may be inappropriately treated with antipsychotic medications that exacerbate the extra-pyramidal motor features of the syndromes. When symptoms are considered to comprise a neurodegenerative syndrome, it may be an inaccurate diagnosis as many features of CBS and PSPS not only overlap with each other, but also with other dementia syndromes. This review discusses similarities and differences between the syndromes of CBS and PSPS in terms of neuropsychiatric features. Improved characterization of the clinical syndromes is necessary to better predict underlying pathology. Improved education about these diseases would help patients, caregivers and clinicians to anticipate symptom progression and avoid premature nursing home placement.

Ethanol exposure profoundly affects learning and memory and neural plasticity. Key players underlying these functions are neurotrophins. The present study explored the effects of ethanol on the distribution of neurotrophins in the cerebral cortex of the adult rat. Age- and weight-matched pairs of adult male, Long-Evans rats were fed a liquid, ethanol-containing (6.7% v/v) diet or pair-fed an isocaloric control diet three consecutive days per week for 6, 12, 18, or 24 weeks. Brains were processed immunohistochemically for nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression and for the expression of three neurotrophin receptors, p75, trkA, and trkB. Total numbers of immunolabeled neurons in specific layers of somatosensory cortex of ethanol- and control-fed animals were determined stereologically. Ethanol exposure induced an increase in the numbers of NGF- or BDNF-expressing neurons and in neurotrophin content per somata. These changes were (a) time and (b) laminar dependent. In contrast, the number of receptor-expressing neurons did not change due to ethanol exposure or to length of time on the ethanol diet. Thus, ethanol induces the recruitment of cortical neurons to express neurotrophins and an increase in the amount of neurotrophin expression per neuron.

The hypothesis tested is that cortical neurotrophins communicate through an inducible autocrine/paracrine mechanism. As ethanol (Et) can induce cortical nerve growth factor (NGF) expression, adult rats were challenged with Et on three consecutive days per week for 6 weeks. The focus of the study was layer V, the chief repository of receptor-expressing neuronal cell bodies. Brains were collected immediately after the sixth Et exposure or 72 h later [i.e., following withdrawal (WD)]. Double-label in situ hybridization-immunohistochemistry studies showed that many neuronal somata co-expressed NGF mRNA with NGF, trkA, or phosphorylated trk (p-trk), essential components of an inducible autocrine system. The frequencies of co-labeling were affected by neither Et nor WD. On the contrary, Et increased the number of NGF mRNA-expressing neurons and the amount of NGF mRNA expressed per cell. Et also increased total cortical concentration of NGF protein, the number of layer V neurons expressing trkA transcript, the amount of trkA mRNA expressed per neuron, and trkA phosphorylation. Following WD, the frequency of NGF-mRNA-expressing cells increased, although transcript and protein content fell. WD induced an increase in trkA mRNA and protein expression, however, p-trk expression was unaffected. Thus, Et treatment reveals that layer V has inducible autocrine/paracrine and anterograde neurotrophin systems. WD unveils the dynamism and recruitability of these systems.

A high-performance liquid chromatographic method has been defined for the determination of eclanamine (free base of eclanamine maleate) and two of its metabolites, N-desmethyleclanamine and N,N-didesmethyleclanamine in urine. The method employs 10-ml urine samples, has a linear range from 5 to 500 ng/ml for the three compounds, and has a detection limit of 0.5 ng/ml for each compound. Sample preparation uses a cyanopropylsilane extraction column with washes of water, acetonitrile-water (30:70, v/v), and acetonitrile, and elution with 2% trifluoroacetic acid in acetonitrile. The eluate is evaporated to dryness, the residue dissolved in 1.0 ml acetonitrile-water (10:90, v/v) and 100 microliter are injected onto a Supelcosil LC-CN column. Eclanamine and its metabolites are eluted with an acetonitrile-water (35:65, v/v) eluent containing 0.01 M triethylamine and adjusted to pH 7.0 with phosphoric acid. The method has been validated by preparing and analyzing a series of fortified urines (range 2-500 ng/ml for each compound) on four separate days. Good linearity, precision, reproducibility, and specificity were obtained. Certification of the analytical method was accomplished by analyzing urine specimens collected from one volunteer administered a single oral dose of 45 mg eclanamine maleate. The data suggest that the metabolites of eclanamine have long elimination half-lives with levels still quantifiable in the 72-96 h collection interval.