| 31. |
- Liljegren, Madeleine, et al.
(författare)
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Physical aggression among patients with dementia, neuropathologically confirmed post-mortem
- 2018
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 33:2, s. 242-248
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate the prevalence of physical aggression among patients with dementia of different types and to analyze potential differences in clinical traits, in terms of singular or repetitive behavior and occurrence in early or late stage of the disease. We also aimed at examining against whom the physical aggression was exerted.MethodsWe included 281 cases with a neuropathological dementia diagnosis from the brain bank at the Department of Pathology, Lund University, for this retrospective medical records review. The study covers cases with a post-mortem examination performed between 1967 and 2013.ResultsOf the 281 patients studied, 97 (35%) patients had a history of exerting physical aggression during the course of their disease. The patients with frontotemporal dementia exerted physical aggression earlier in the course of their disease than Alzheimer's disease patients. The most frequent victims of the patients' physical aggression were health staff and other patients. The aggression also affected family members as well as (to the demented patient) unknown people. The frequency of the physical aggression differed among the different diagnostic groups; frontotemporal dementia patients exhibiting a higher physical aggression frequency score than did Alzheimer's disease patients.ConclusionsThe patterns of manifested physical aggression thus differ between the frontotemporal dementia and Alzheimer's disease patient groups in this study. Knowledge about such differences may be of value in decision making in patient care.
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| 32. |
- Liljegren, Madeleine, et al.
(författare)
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Police Interactions Among Neuropathologically Confirmed Dementia Patients: Prevalence and Cause
- 2018
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Ingår i: Alzheimer Disease and Associated Disorders. - 1546-4156. ; 32:4, s. 346-350
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Tidskriftsartikel (refereegranskat)abstract
- Objective:The aim of this study was to investigate and compare the prevalence and recurrence of police interaction (PI) with patients diagnosed with dementia. We also aimed to study the reason behind the PI, the time of occurrence of PI, and potential consequences of the PI.Methods:For this retrospective medical records’ review, we included 281 cases with a neuropathologic dementia diagnosis from the Department of Pathology, Region Skane/Lund University, between 1967 and 2013. The diagnoses were Alzheimer disease, frontotemporal lobar degeneration, vascular dementia, and mixed dementia. A prerequisite was that extensive clinical investigation and follow-up had been conducted at the Department of Geriatric Psychiatry in Lund.Results:Of the 281 patients studied, 50 (18%) had a history of interacting with the police during the course of their disease. Frontotemporal dementia patients had a relatively higher prevalence of PI and more often due to criminal behavior. The recurrence of PIs differed among the groups; frontotemporal dementia patients exhibited a higher PI recurrence compared with the other groups.Conclusions:The patterns of PIs differ between the frontotemporal dementia and Alzheimer disease patients. Knowledge about such differences may be of value for the police, the judiciary system, and the society in general.
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| 33. |
- Meinert, Monika, et al.
(författare)
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Danon disease presenting with early onset of hypertrophic cardiomyopathy and peripheral pigmentary retinal dystrophy in a female with a de novo novel mosaic mutation in the LAMP2 gene
- 2019
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Ingår i: Ophthalmic Genetics. - : Informa UK Limited. - 1381-6810 .- 1744-5094. ; 40:3, s. 227-236
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the phenotype and genotype in a young woman with Danon disease. Methods: The patient underwent an ophthalmic examination including best corrected visual acuity (BCVA), fundus photography and fundus autofluorescence (FAF), full-field electroretinography (full-field ERG), multifocal ERG, optical coherence tomography (OCT) and SAP-Humphrey 30-2 at the ages of 20 and 25. Electrooculography, fluorescein angiography (FA), indocyanine angiography and OCT angiography were performed only once. Genetic testing using a Next-Generation Sequencing panel and immunohistochemical analysis of LAMP2 protein expression were performed in the patient's explanted heart, and the patient's cardiologic and ophthalmologic records were retrospectively reviewed. Results: A de novo, novel, mosaic mutation, c.135dupA; p.(Trp46Metfs*10) was identified in exon 2 of the LAMP2 gene. Immunohistochemical investigation of the myocardium in the explanted heart revealed pronounced deficiency of LAMP2 protein in cardiomyocytes. The color photographs, FAF images and FA revealed more extensive peripheral pigmentary retinal dystrophy (PPRD) at the 5-year follow-up examination. No changes were observed in BCVA, OCT, SAP-Humphrey 30-2 or multifocal ERG findings at follow-up. Full-field ERG showed an asymmetric interocular reduction in ERG response at follow-up: the b-wave amplitude of the rod response had decreased by 29% in the right eye, but by only 6 % in the left eye. The a-wave amplitude of single-flash response had decreased by 9 % in the left eye, while it had increased by 3% in the right eye. Conclusions: Although PPRD progressed slowly, it was an important clue in the diagnosis of the life-threatening condition of Danon disease.
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| 34. |
- Nilholm, Clara, et al.
(författare)
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Dietary intervention with an Okinawan-based Nordic diet in type 2 diabetes renders decreased interleukin-18 concentrations and increased neurofilament light concentrations in plasma
- 2018
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Ingår i: Nutrition Research. - : Elsevier BV. - 0271-5317. ; 60, s. 13-25
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Tidskriftsartikel (refereegranskat)abstract
- Food may induce inflammation and favor development of metabolic diseases, which have been associated with increased inflammation and potential risk of cognitive impairment. It is customary to know whether food or disease promote inflammation. Our hypothesis was that Okinawan-based Nordic (O-BN) diet leads to decreased circulating concentrations of inflammatory and neural biomarkers. The objectives of this study were to examine the effects of the O-BN diet on inflammatory and neural responses. First, 2 different breakfasts; one standard and another O-BN-based, were given in random order to 19 healthy volunteers. Second, a 12-week O-BN-dietary intervention was performed in type 2 diabetes mellitus (T2DM), where the participants were followed for another 16-weeks, with registration of anthropometry and metabolic parameters. Non-diabetic subjects served as controls at baseline. Plasma was analyzed for cytokines by a 10-plex Luminex assay and neurofilament light (NfL) by an ultrasensitive Single molecule assay. Cytokine levels decreased after a single breakfast intake, independent of diet composition. Cytokine levels were higher in T2DM than in controls. Anthropometric and metabolic parameters were improved by the dietary intervention. In parallel, cytokine levels were lowered, although only significantly for IL-18 (P =.001), with a tendency of significance for IL-12p70 (P =.07). Levels of IL-18 correlated with glucose, HbA1c and lipids, but not with body mass index, insulin or blood pressure. NfL levels increased during the intervention (P =.049). O-BN-based diet does not affect postprandial cytokine levels in health, whereas it renders decreased circulating IL-18 levels along with metabolic biomarkers in T2DM, with no beneficial effect on NfL.
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| 35. |
- Nilsson, Markus, et al.
(författare)
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Imaging brain tumour microstructure
- 2018
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119. ; 182, s. 232-250
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Forskningsöversikt (refereegranskat)abstract
- Imaging is an indispensable tool for brain tumour diagnosis, surgical planning, and follow-up. Definite diagnosis, however, often demands histopathological analysis of microscopic features of tissue samples, which have to be obtained by invasive means. A non-invasive alternative may be to probe corresponding microscopic tissue characteristics by MRI, or so called ‘microstructure imaging’. The promise of microstructure imaging is one of ‘virtual biopsy’ with the goal to offset the need for invasive procedures in favour of imaging that can guide pre-surgical planning and can be repeated longitudinally to monitor and predict treatment response. The exploration of such methods is motivated by the striking link between parameters from MRI and tumour histology, for example the correlation between the apparent diffusion coefficient and cellularity. Recent microstructure imaging techniques probe even more subtle and specific features, providing parameters associated to cell shape, size, permeability, and volume distributions. However, the range of scenarios in which these techniques provide reliable imaging biomarkers that can be used to test medical hypotheses or support clinical decisions is yet unknown. Accurate microstructure imaging may moreover require acquisitions that go beyond conventional data acquisition strategies. This review covers a wide range of candidate microstructure imaging methods based on diffusion MRI and relaxometry, and explores advantages, challenges, and potential pitfalls in brain tumour microstructure imaging.
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| 36. |
- Ohlsson, Bodil, et al.
(författare)
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Atrophic Myenteric and Submucosal Neurons Are Observed in Parkinson's Disease
- 2019
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Ingår i: Parkinson's Disease. - : Hindawi Limited. - 2042-0080 .- 2090-8083. ; 2019
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Tidskriftsartikel (refereegranskat)abstract
- Aim. Parkinson's disease is often accompanied by gastrointestinal symptoms, especially constipation. Microscopic studies of the enteric nervous system and enteric neuropathy have often been performed by immunostaining in the myenteric plexa. The aim of the present study was to examine whether pathologic changes could be identified by conventional hematoxylin and eosin (H&E) staining and could also be seen in the submucosal plexa. Materials and Methods. In 20 deceased cases (11 male/9 female) of Parkinson's disease, the intestinal tract was investigated for potential neuroganglionic disease. Ten cases (7 male/3 female) of non-Parkinson, intestinally asymptomatic individuals were used as controls. Specimens from the jejunum and colon were sampled. The material was treated with standard histopathological procedures, i.e., fixed in formaldehyde solution, dehydrated and embedded in paraffin, sectioned at 5 μm thickness, and stained with H&E and immunostaining for α-synuclein. Results. In 15 cases (7 male/8 female) of Parkinson's disease, atrophic/pycnotic nerve plexus cells were present, i.e., signs of ganglionic degeneration in the submucosal and/or myenteric plexa, mostly identified in both loci, by H&E staining. In some cases, the degenerative signs were mild, however, corroborated by findings of α-synuclein deposits in the ganglion cells. The remaining 5 cases showed no signs of degeneration in the H&E staining, but immunostaining revealed minimal α-synuclein deposits in 3 cases. None of the controls showed any ganglionic degeneration/α-synuclein deposits. Conclusion. It seems possible to identify a morphologic intestinal disease substrate in Parkinson's disease by H&E staining, showing ganglion cell pycnosis and degeneration in both plexa. This finding may indicate a potential to diagnose enteric neuropathy in highly accessible sites.
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| 37. |
- Puschmann, Andreas, et al.
(författare)
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CHCHD2 and Parkinson's disease
- 2015
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Ingår i: Lancet Neurology. - 1474-4465. ; 14:7, s. 679-679
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Tidskriftsartikel (refereegranskat)
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| 38. |
- Quattromani, Miriana Jlenia, et al.
(författare)
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Extracellular Matrix Modulation Is Driven by Experience-Dependent Plasticity During Stroke Recovery
- 2018
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Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 55:3, s. 2196-2213
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Tidskriftsartikel (refereegranskat)abstract
- Following stroke, complete cellular death in the ischemic brain area may ensue, with remaining brain areas undergoing tissue remodelling to various degrees. Experience-dependent brain plasticity exerted through an enriched environment (EE) promotes remodelling after central nervous system injury, such as stroke. Post-stroke tissue reorganization is modulated by growth inhibitory molecules differentially expressed within the ischemic hemisphere, like chondroitin sulfate proteoglycans found in perineuronal nets (PNNs). PNNs in the neocortex predominantly enwrap parvalbumin-containing GABAergic (PV/GABA) neurons, important in sensori-information processing. Here, we investigate how extracellular matrix (ECM) proteases and their inhibitors may participate in the regulation of PNN integrity during stroke recovery. Rats were subjected to photothrombotic stroke in the motor cortex, and functional deficits were assessed at 7 days of recovery. Sham and stroked rats were housed in either standard or EE conditions for 5 days, and infarct volumes were calculated. PNNs were visualized by immunohistochemistry and counted in the somatosensory cortex of both hemispheres. mRNA expression levels of ECM proteases and protease inhibitors were assessed by RT-qPCR and their activity analyzed by gel zymography. PNNs and protease activity were also studied in brains from stroke patients where similar results were observed. EE starting 2 days after stroke and continuing for 5 days stimulated behavioral recovery of limb-placement ability without affecting infarct size. EE promoted a decrease of PNNs around PV/GABA neurons and a concomitant modulation of the proteolytic activity and mRNA expression of ECM proteases and protease inhibitors in the somatosensory cortex. This study provides molecular targets for novel therapies that could support rehabilitation of stroke patients.
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| 39. |
- Respondek, Gesine, et al.
(författare)
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Which ante mortem clinical features predict progressive supranuclear palsy pathology?
- 2017
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 32:7, s. 995-1005
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Forskningsöversikt (refereegranskat)abstract
- Background: Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. Objective: To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. Methods: We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Results: Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Conclusions: Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP.
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| 40. |
- Rodhe, Johanna, et al.
(författare)
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Spatio-temporal activation of caspase-8 in myeloid cells upon ischemic stroke
- 2016
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 4, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Ischemic stroke (caused by thrombosis, embolism or vasoconstriction) lead to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral macrophages, which contribute to an inflammatory response involved in regulation of the neuronal damage. We showed earlier that upon pro-inflammatory stimuli, the orderly activation of caspase-8 and caspase-3/7 regulates microglia activation through a protein kinase C-δ dependent pathway. Here, we present in vivo evidence for the activation of caspase-8 and caspase-3 in microglia/macrophages in post-mortem tissue from human ischemic stroke subjects. Indeed, CD68-positive microglia/macrophages in the ischemic peri-infarct area exhibited significant expression of the cleaved and active form of caspase-8 and caspase-3. The temporal and spatial activation of caspase-8 was further investigated in a permanent middle cerebral artery occlusion mouse model of ischemic stroke. Increasing levels of active caspase-8 was found in Iba1-positive cells over time in the peri-infarct area, at 6, 24 and 48 h after artery occlusion. Analysis of post-mortem brain tissue from human subject who suffered two stroke events, referred as recent and old stroke, revealed that expression of cleaved caspase-8 and -3 in CD68-positive cells could only be found in the recent stroke area. Analysis of cleaved caspase-8 and -3 expressions in a panel of human stroke cases arranged upon days-after stroke and age-matched controls suggested that the expression of these caspases correlated with the time of onset of stroke. Collectively, these data illustrate the temporal and spatial activation of caspase-8 and -3 in microglia/macrophages occurring upon ischemic stroke and suggest that the expression of these caspases could be used in neuropathological diagnostic work.
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