| 11. |
- Haglund, Mattias, et al.
(författare)
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Locus ceruleus degeneration is ubiquitous in Alzheimer's disease: possible implications for diagnosis and treatment.
- 2006
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Ingår i: Neuropathology. - : Wiley. - 0919-6544 .- 1440-1789. ; 26:6, s. 528-532
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Tidskriftsartikel (refereegranskat)abstract
- Degeneration of the locus ceruleus (LC) and decreased cortical levels of norepinephrine are common findings in Alzheimer's disease (AD), but their significance is unknown. Because the noradrenergic system is accessible to pharmacological intervention, the role of LC degeneration and noradrenergic dysfunction in the pathogenesis and clinical manifestations of AD needs clarification. Hypothetically, loss of noradrenergic innervation could cause microvascular dysfunction and manifest as ischemia. The objectives of this study were to develop a scale for assessment of LC degeneration and to determine whether degeneration of the LC correlates quantitatively with either duration of clinical dementia, overall severity of AD pathology or with measures of ischemic non-focal white matter disease (WMD) in AD. This report is a pathological follow-up of a clinical longitudinal dementia study of 66 consecutive cases of AD without admixture of vascular dementia (VaD) from the Lund Longitudinal Dementia Study, neuropathologically diagnosed between 1990 and 1999. Ten cases of VaD were included for comparative purposes. No correlation between degree of LC degeneration and duration of dementia, AD or WMD severity was found. LC degeneration was significantly more severe in the AD group than in the VaD group. Even though LC degeneration was not associated with WMD or the severity of AD pathology in this AD material, we suggest that clinical studies on the consequences of noradrenergic dysfunction are warranted. Treatment augmenting noradrenergic signaling is available and safe. The marked difference in the level of LC degeneration between AD and VaD cases suggests that LC degeneration could be used as a diagnostic marker of AD.
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| 12. |
- Holm, Ida Elisabeth, et al.
(författare)
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A reassessment of the neuropathology of frontotemporal dementia linked to chromosome 3
- 2007
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Ingår i: Journal of Neuropathology and Experimental Neurology. - 1554-6578. ; 66:10, s. 884-891
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Tidskriftsartikel (refereegranskat)abstract
- A large Danish family has previously been reported in which autosomal dominant frontotemporal dementia (FTD) is genetically linked to chromosome 3 (FTD-3). A mutation was recently identified in the CHMP2B gene that is probably responsible for causing disease in this family. Because of its neuropathologic findings, FTD-3 was originally categorized as a subtype of frontotemporal lobar degeneration, termed "dementia lacking distinctive histopathology." We now report a reevaluation of the neuropathologic changes in this family. Postmortem material from 4 affected family members was available for examination. Gross examination revealed generalized cortical atrophy that was most severe in frontal and temporal cortices. Microscopy showed loss of cortical neurons. microvacuolation of layer 11, mild gliosis, and demyelination of the deep white matter. Results of immunohistochemical staining for alpha-synuclein, prion protein, neurofilament, and tau protein were unremarkable. Variable numbers of small, round, ubiquitin-positive cytoplasmic inclusions were present in the dentate granule layer of the hippocampus in all 4 cases. Rare ubiquitin-positive inclusions were also found in frontal and temporal cortical neurons. These inclusions were also positive for p62 but not for TDP-43. The finding of ubiquitin- and p62-positive, TDP-43-neaative cytoplasmic inclusions in the hippocampus and neocortex suggests reclassification of the neuropathology of FTD-3 as a unique subtype of frontotemporal lobar degeneration with ubiquitin-positive inclusions that are TDP-43 -negative.
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| 13. |
- Järnum, Hanna, et al.
(författare)
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Diffusion and perfusion MRI of the brain in comatose patients treated with mild hypothermia after cardiac arrest: A prospective observational study.
- 2009
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 80, s. 425-430
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Outcome for resuscitated cardiac arrest (CA) patients is poor. The 1-year survival rate with favourable neurological outcome (CPC 1-2) after out-of-hospital CA is reported to be 4%. Among resuscitated patients treated within an ICU, approximately 50% regain consciousness, whereas the other 50% remain comatose before they die. Induced hypothermia significantly improves the neurological outcome and survival in patients with primary CA who remain comatose after return of spontaneous circulation. AIM: To evaluate magnetic resonance imaging (MRI) changes in resuscitated CA patients remaining in coma after treatment with hypothermia. METHODS: This prospective, observational study comprised 20 resuscitated CA patients who remained in coma 3 days after being treated with mild hypothermia (32-34 degrees C during 24h). Diffusion and perfusion MRI of the entire brain was performed approximately 5 days after CA. Autopsy was done on two patients. RESULTS: The largest number of diffusion changes on MRI was found in the 16 patients who died. The parietal lobe showed the largest difference in number of acute ischaemic MRI lesions in deceased compared with surviving patients. Perfusion changes, >/=+/-2 SD compared with healthy volunteers from a previously published cerebral perfusion study, were found in seven out of eight patients. The autopsies showed lesions corresponding to the pathologic changes seen on MRI. CONCLUSION: Diffusion and perfusion MRI are potentially helpful tools for the evaluation of ischaemic brain damage in resuscitated comatose patients treated with hypothermia after CA.
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| 14. |
- Karlsson, Christine, et al.
(författare)
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Genetic intratumour heterogeneity in high-grade brain tumours is associated with telomere-dependent mitotic instability.
- 2007
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Ingår i: Neuropathology & Applied Neurobiology. - : Wiley. - 1365-2990 .- 0305-1846. ; 33:4, s. 440-454
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) and other high-grade brain tumours are typically characterized by complex chromosome abnormalities and extensive intratumour cytogenetic heterogeneity. The mechanisms behind this diversity have been little explored. In this study, we analysed the pattern of chromosome segregation at mitosis in 20 brain tumours. We found an abnormal segregation of chromatids at mitosis through anaphase bridging (10-25% of anaphase cells) in all 10 GBMs. Anaphase bridging was also found in two medulloblastomas (7-15%), one anaplastic astrocytoma (17%) and one oligodendroglioma (6%). These tumours showed a relatively high degree of cytogenetic complexity and heterogeneity. In contrast, cell division abnormalities were not found in low-grade brain tumours with less complex karyotypes, including two pilocytic astrocytomas and two ependymomas. Further analysis of two GBMs by fluorescence in situ hybridization with telomeric repeat probes revealed excessive shortening of TTAGGG repeats, indicating dysfunctional protection of chromosome ends. In xenografts established from these GBMs, there was a gradual reduction in cytogenetic heterogeneity through successive passages as the proportion of abnormally short telomeres was reduced and the frequency of anaphase bridges decreased from >25% to 0. However, bridging could be reintroduced in late-passage xenograft cells by pharmacological induction of telomere shortening, using a small-molecule telomerase inhibitor. Telomere-dependent abnormal segregation of chromosomes at mitosis is thus a common phenomenon in high-grade brain tumours and may be one important factor behind cytogenetic intratumour diversity in GBM.
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| 15. |
- Kongstad, Poul, et al.
(författare)
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Mechanical compressions and autopsy findings
- 2005
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - 1757-7241. ; 13:2, s. 87-88
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Tidskriftsartikel (refereegranskat)
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| 16. |
- Li, Jia-Yi, et al.
(författare)
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Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation.
- 2008
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 14, s. 501-503
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Tidskriftsartikel (refereegranskat)abstract
- Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-synuclein-positive Lewy bodies in grafted neurons. Our observation has key implications for understanding Parkinson's pathogenesis by providing the first evidence, to our knowledge, that the disease can propagate from host to graft cells. However, available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief.
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| 17. |
- Lindberg, Eva, et al.
(författare)
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Concurrent gain of 17q and the MYC oncogene in a medullomyoblastoma
- 2007
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Ingår i: Neuropathology. - : Wiley. - 0919-6544 .- 1440-1789. ; 27:6, s. 556-560
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Tidskriftsartikel (refereegranskat)abstract
- Medullomyoblastoma (MMB) is a rare cerebellar childhood tumor containing both myoblastic and primitive neuroectodermal components. Similar to the scenario in classical medulloblastoma, which contains the primitive neuroectodermal component only, gain of sequences from the long arm of chromosome 17 (17q) and gain of the MYC gene in 8q have been implicated in the pathogenesis of MMB. Because karyotypic analysis has not previously been performed for MMB, the mechanisms behind genomic imbalances in this tumor have remained unknown. Several other central aspects of this tumor, such as histocytogenetic origin, clinical characteristics, tumor behavior and prognosis, also remain unknown. We here report neuropathological and cytogenetic features of an MMB in a 3-year-old boy. Chromosome banding analysis and multicolor karyotyping revealed a hyperdiploid karyotype including an unbalanced 1; 17 translocation and isochromosome 17q formation, both leading to gain of 17q. There were also two extra copies of chromosome 8, leading to gain of the MYC oncogene, trisomies 5 and 13, and monosomy 9. Clonal chromosome changes were present in both the myoblastic and neuroectodermal components. Our findings support the notion that MMB and classical medulloblastoma arise through similar genetic mechanisms and that the two main tissue components in MMB are clonally related.
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| 18. |
- Malmborg, Carin, et al.
(författare)
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Mapping the intracellular fraction of water by varying the gradient pulse length in q-space diffusion MRI
- 2006
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Ingår i: Journal of Magnetic Resonance. - : Elsevier BV. - 1096-0856 .- 1090-7807. ; 180:2, s. 280-285
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Tidskriftsartikel (refereegranskat)abstract
- Finite gradient pulse lengths are traditionally considered a nuisance in q-space diffusion NMR and MRI, since the simple Fourier relation between the acquired signal and the displacement probability is invalidated. Increasing the value of the pulse length leads to an apparently smaller value of the estimated compartment size. We propose that q-space data at different gradient pulse lengths, but with the same effective diffusion time, can be used to identify and quantify components with free or restricted diffusion from multi-exponential echo decay curves obtained on cellular systems. The method is demonstrated with experiments on excised human brain white matter and a series of model systems with well-defined free, restricted, and combined free and restricted diffusion behavior. Time-resolved diffusion MRI experiments are used to map the spatial distribution of the intracellular fraction in a yeast cell suspension during sedimentation, and observe the disappearance of this fraction after a heat treatment. (c) 2006 Elsevier Inc. All rights reserved.
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| 19. |
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| 20. |
- Passant, Ulla, et al.
(författare)
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Psychiatric Symptoms and Their Psychosocial Consequences in Frontotemporal Dementia.
- 2005
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Ingår i: Alzheimer Disease and Associated Disorders. - 0893-0341. ; 19 Suppl 1, s. 15-18
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Tidskriftsartikel (refereegranskat)abstract
- Based on a retrospective study of 19 neuropathologically verified cases with frontotemporal dementia (FTD), neuropsychiatric symptoms related to behavioral disturbances and their psychosocial consequences were studied. The results indicate that frontotemporal dementia is often misdiagnosed early in the clinical course. Behavioural features with impaired social interactions, impaired personal regulation, and loss of insight were seen in all patients. The psychosocial consequences reported in this paper challenge future research in frontotemporal dementia.
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