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Cortical Pathology (cortical + pathology)
Selected AbstractsSelective chronic stress-induced in vivo ERK1/2 hyperphosphorylation in medial prefrontocortical dendrites: implications for stress-related cortical pathology?EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2002A. Trentani Abstract Stress has been shown to affect brain structural plasticity, promote long-term changes in multiple neurotransmitter systems and cause neuronal atrophy. However, the mechanisms involved in these stress-related neural alterations are still poorly understood. Mitogen-activated protein kinase (MAPK) cascades play a crucial role in the transduction of neurotrophic signal from the cell surface to the nucleus and are implicated in the modulation of synaptic plasticity and neuronal survival. An intriguing possibility is that stress might influence brain plasticity through its effects on selective members of such intracellular signalling cascades responsible for the transduction of neurotrophin signals. Here, we have investigated the effects of stress on the expression of three members of the MAPK/extracellular-regulated kinase (ERK) pathway such as phospho-ERK1, phospho-ERK2 and phospho-cAMP/calcium-responsive element-binding protein (CREB) in the adult rat brain. Male rats were subjected to mild footshocks and the patterns of protein expression were analysed after 21 consecutive days of stress. We found that chronic stress induced a pronounced and persistent ERK1/2 hyperphosphorylation in dendrites of the higher prefrontocortical layers (II and III) and a reduction of phospho-CREB expression in several cortical and subcortical regions. We hypothesized that defects in ERK signalling regulation combined with a reduced phospho-CREB activity may be a crucial mechanism by which sustained stress may induce atrophy of selective subpopulations of vulnerable cortical neurons and/or distal dendrites. Thus, ERK-mediated cortical abnormalities may represent a specific path by which chronic stress affects the functioning of cortical structures and causes selective neural network defects. [source] In Vivo Visualization of Senile-Plaque-Like Pathology in Alzheimer's Disease Patients by MR Microscopy on a 7T SystemJOURNAL OF NEUROIMAGING, Issue 2 2008Tsutomu Nakada MD ABSTRACT BACKGROUND Microscopic application of magnetic resonance imaging (MRI) has entered the era of clinical application. One of the most important targets is the visualization of pathological findings such as senile plaques (SP), in vivo, in patients with Alzheimer's disease (AD). Such an application provides not only the most accurate diagnostic tool for clinicians but also a solid basis for scientists for developing effective treatment and preventive strategies for AD. METHODS Focused microscopic studies were performed on parietal association cortex at the level of the centrum semiovale identified on conventional axial slices using a system constructed based on General Electric Signa LX (Waukesha, WI) equipped with a 900-mm clear bore superconducting magnet operating at 7.0 T in 10 patients (67-83-year old, five males, five females) who fulfilled the NINCD and the SADRDA criteria for probable AD, 10 age-matched controls (71-85-year old, five males, five females), and 20 young adults (22-35-year old, 10 males, 10 females) using a susceptibility weighted imaging (SWI) algorithm. RESULTS SWI microscopy consistently provided images with SP-like pathology extending within the entire parietal cortex in all cases of AD and 2 out of 10 age-matched volunteers. CONCLUSIONS Although the precise mechanisms leading to the higher susceptibility rendering SP-like pathology observable within the cortical mantle are not totally understood, the study unambiguously demonstrated that MR microscopy is capable of directly visualizing cortical pathology in AD patients in vivo. [source] Neuronal gene expression correlates of Parkinson's disease with dementia,MOVEMENT DISORDERS, Issue 11 2008Chelsea Stamper BS Abstract Dementia is a common disabling complication in patients with Parkinson's disease (PD). The underlying molecular causes of Parkinson's disease with dementia (PDD) are poorly understood. To identify candidate genes and molecular pathways involved in PDD, we have performed whole genome expression profiling of susceptible cortical neuronal populations. Results show significant differences in expression of 162 genes (P < 0.01) between PD patients who are cognitively normal (PD-CogNL) and controls. In contrast, there were 556 genes (P < 0.01) significantly altered in PDD compared to either healthy controls or to PD-CogNL cases. These results are consistent with increased cortical pathology in PDD relative to PD-CogNL and identify underlying molecular changes associated with the increased pathology of PDD. Lastly, we have identified expression differences in 69 genes in PD cortical neurons that occur before the onset of dementia and that are exacerbated upon the development of dementia, suggesting that they may be relevant presymptomatic contributors to the onset of dementia in PD. These results provide new insights into the cortical molecular changes associated with PDD and provide a highly useful reference database for researchers interested in PDD. © 2008 Movement Disorder Society [source] Parkinson's disease-cognitive rating scale: A new cognitive scale specific for Parkinson's diseaseMOVEMENT DISORDERS, Issue 7 2008Javier Pagonabarraga MD Abstract Cognitive defects associated with cortical pathology may be a marker of dementia in Parkinson's disease (PD). There is a need to improve the diagnostic criteria of PD dementia (PDD) and to clarify the cognitive impairment patterns associated with PD. Current neuropsychological batteries designed for PD are focused on fronto-subcortical deficits but are not sensitive for cortical dysfunction. We developed a new scale, the Parkinson's Disease-Cognitive Rating Scale (PD-CRS), that was designed to cover the full spectrum of cognitive defects associated with PD. We prospectively studied 92 PD patients [30 cognitively intact (CogInt), 30 mild cognitive impairment (MCI), 32 PDD] and 61 matched controls who completed the PD-CRS and neuropsychological tests assessing the cognitive domains included in the PD-CRS. Acceptability, construct validity, reliability, and the discriminative properties of the PD-CRS were examined. The PD-CRS included items assessing fronto-subcortical defects and items assessing cortical dysfunction. Construct validity, test-retest and inter-rater reliability of PD-CRS total scores showed an intraclass correlation coefficient >0.70. The PD-CRS showed an excellent test accuracy to diagnose PDD (sensitivity 94%, specificity 94%). The PD-CRS total scores and confrontation naming item scores-assessing "cortical" dysfunction,independently differentiated PDD from non-demented PD. Alternating verbal fluency and delayed verbal memory independently differentiated the MCI group from both controls and CogInt. The PD-CRS appeared to be a reliable and valid PD-specific battery that accurately diagnosed PDD and detected subtle fronto-subcortical deficits. Performance on the PD-CRS showed that PDD is characterized by the addition of cortical dysfunction upon a predominant and progressive fronto-subcortical impairment. © 2008 Movement Disorder Society [source] Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndromeMOVEMENT DISORDERS, Issue 8 2005Yoshio Tsuboi MD Abstract The objective of this study is to better define the pathological characteristics of pathologically proven progressive supranuclear palsy (PSP) presenting with the corticobasal syndrome (CBS). PSP is characterized by early falls, vertical supranuclear ophthalmoplegia, and axial rigidity, whereas asymmetric limb features, including rigidity, bradykinesia, apraxia, alien limb phenomena, and cortical sensory loss are characteristic of CBS. We investigated clinicopathological characteristics of 5 cases of PSP that presented with CBS (CBS-PSP). Comprehensive pathological analysis was undertaken to determine the presence of concomitant pathological processes as well as quantitative tau burden in cortical regions of CBS-PSP, compared with 8 typical PSP cases (Typ-PSP). The clinical features in the CBS-PSP cases included asymmetrical features, apraxia, alien limb phenomena, and progressive aphasia. All cases had Parkinsonism, and vertical supranuclear ophthalmoplegia was noted in all but 1 case of CBS-PSP. Secondary neuropathological diagnoses included argyrophilic grain disease (AGD) in 1 of the 8 cases of Typ-PSP, whereas Alzheimer's disease (AD), Lewy body disease, AGD, and vascular disease was found in 3 cases of CBS-PSP. Image analysis of cortical tau burden performed in 8 Typ-PSP and 3 CBS-PSP cases revealed a significant increased tau burden in mid-frontal and inferior-parietal cortices in the CBS-PSP cases. This study demonstrates that when PSP presents as CBS, it is most likely due to either a concurrent cortical pathology from a secondary process such as AD or from the primary pathology of PSP extending into cortical areas that are primarily and commonly affected in CBD. © 2005 Movement Disorder Society [source] MM2-cortical-type sporadic Creutzfeldt-Jakob disease with early stage cerebral cortical pathology presenting with a rapidly progressive clinical courseNEUROPATHOLOGY, Issue 6 2008Yoshiki Niimi We report the case of a 67-year-old man with MM2-cortical-type sporadic Creutzfeldt-Jakob disease (sCJD) with a rapidly progressive clinical course of 5 months. Initial symptoms were progressive memory disturbance and dementia. MRI revealed high signal-intensity lesions on diffusion-weighted images in the bilateral frontal and occipital cortices. Myoclonus and periodic sharp-wave complexes on the electroencephalogram were observed in the early disease stage. The clinical diagnosis was typical sCJD. Neuropathologic examination at autopsy showed widespread, characteristic cerebral neocortical involvement with large confluent vacuole-type spongiform change. Spongiform degeneration was also evident in the striatum and medial thalamus. In the cerebellar cortex, slight depletion of Purkinje neurons was evident without spongiform change in the molecular layer or apparent neuron loss in the granule cell layer. The inferior olivary nucleus showed slight hypertrophic astrocytosis without neuron loss. Prion protein (PrP) immunostaining showed widespread, characteristic perivacuolar-type PrP deposits with irregular plaque-like PrP deposits in the cerebral neocortex, striatum and medial thalamus. We believe this patient showed early-stage cerebral cortical pathology of MM2-cortical-type sCJD, which may provide clues regarding the pathologic progression of this rare sCJD subtype. Although MM2-cortical-type sCJD generally shows slow progression without myoclonus or periodic sharp-wave complexes, the present patient showed a rapidly progressive clinical course similar to that of MM1-type sCJD. [source] Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging studyBIPOLAR DISORDERS, Issue 3 2004Caleb M Adler Objectives:, Prefrontal white matter has been hypothesized to be integral to the pathophysiology of bipolar disorder. Recent morphometric studies however, have not observed changes in white matter in bipolar patients. We hypothesized that changes in prefrontal function in bipolar disorder, widely reported in the literature, may be related to a loss of white matter tract integrity with a resultant dysconnectivity syndrome. In this study we utilized diffusion tensor imaging (DTI) to examine prefrontal white matter in patients with bipolar disorder. Methods:, Nine patients with bipolar disorder and nine healthy controls were recruited. DTI and localizing anatomic data were acquired, and regions of interest (ROIs) identified in the prefrontal white matter at 15, 20, 25, and 30 mm superior to the anterior commissure (AC). Fractional anisotropy (FA) and trace apparent diffusion coefficient (TADC) were compared by ROI between study groups. Results:, The FA of ROIs 25 and 30 mm above the AC was significantly reduced in patients with bipolar disorder; FA of all ROIs showed high-medium to large effect sizes. No significant group differences were identified in TADC. Conclusions:, Our findings suggest that a loss of bundle coherence is present in prefrontal white matter. This loss of coherence may contribute to prefrontal cortical pathology in patients with bipolar disorder. [source] | ||||||||||