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A rare cause of inherited frontotemporal dementia (FTD) is a mutation in the CHMP2B gene on chromosome 3 leading to the autosomal dominantly inherited FTD (CHMP2B -FTD). Since CHMP2B -FTD is clinically well-characterized, and patients show a distinct pattern of executive dysfunction, the condition offers possible insight in the early electroencephalographic (EEG) changes in the cortical networks. Specifically, EEG microstate analysis parses the EEG signals into topographies believed to represent discrete network activations. We investigated the EEG dynamics in patients with symptomatic CHMP2B -FTD (n = 5) as well as pre-symptomatic mutation carriers (n = 5) compared to non-carrier family members (n = 6). The data was parsed into four archetypal microstates and global power was calculated. A trend was found for lower occurrence in microstate D in CHMP2B -FTD (p- value = 0.177, F- value = 2.036). Patients with recent symptom onset (<1 year) showed an increased duration of microstate D, whereas patients who had been symptomatic for longer periods (>2 years) showed decreased duration. Patients with CHMP2B -FTD present with executive dysfunction, and microstate D has previously been shown to be associated with the fronto-parietal network. The biphasic pattern may represent the pathophysiological changes in brain dynamics during neurodegeneration, which may apply to other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background and purpose: Dementia disorders predispose for lethal complications and decrease life expectancy. A more profound knowledge regarding end‐stage conditions in dementia could therefore ameliorate treatment and care of these patients. Methods: Autopsy reports on 207 deceased individuals with clinically diagnosed neurocognitive disorder/dementia and on 200 neurocognitively healthy individuals of the same age range were studied. Autopsy results, especially cause of death, were compared between the dementia and the control groups. Results: The two most frequent causes of death in the dementia population were pneumonia (34.3%) and acute myocardial infarction (30.4%). This result differed from that of the control group, in which acute myocardial infarction (42.5%) accounted for most events of deaths, followed by circulatory failure (12.5%). The leading cause of death varied amongst dementia subtypes. Further, in Alzheimer's disease pneumonia was more frequent in severe/advanced cases whilst acute myocardial infarction was more common in milder cases. Conclusions: Cause of death differed between the demented and the general population of the same age and between subtypes of dementia. Alzheimer's disease severity was reflected in different final conditions. The findings have relevance for the final stage care and treatment in dementia disorders. [ABSTRACT FROM AUTHOR]

Aims: We observed a microvascular structure in the cerebral cortex that has not, to our knowledge, been previously described. We have termed the structure a 'raspberry', referring to its appearance under a bright‐field microscope. We hypothesized that raspberries form through angiogenesis due to some form of brain ischaemia or hypoperfusion. The aims of this study were to quantify raspberry frequency within the cerebral cortex according to diagnosis (vascular dementia, Alzheimer's disease, frontotemporal lobar degeneration and nondemented controls) and brain regions (frontal, temporal, parietal and occipital cortices, regardless of diagnosis). Materials and methods: In each of 10 age‐matched subjects per group, a 20‐mm section of the cerebral cortex was examined in haematoxylin‐and‐eosin‐stained sections of the frontal, temporal and parietal, and/or occipital lobes. Tests were performed to validate the haematoxylin‐and‐eosin‐based identification of relative differences between the groups, and to investigate inter‐rater variability. Results: Raspberry frequency was highest in subjects with vascular dementia, followed by those with frontotemporal lobar degeneration, Alzheimer's disease and last, nondemented controls. The frequency of raspberries in subjects with vascular dementia differed from that of all other groups at a statistically significant level. In the cerebral lobes, there was a statistically significant difference between the frontal and occipital cortices. Conclusions: We believe the results support the hypothesis that raspberries are a sign of angiogenesis in the adult brain. It is pertinent to discuss possible proangiogenic stimuli, including brain ischaemia (such as mild hypoperfusion due to a combination of small vessel disease and transient hypotension), neuroinflammation and protein pathology. [ABSTRACT FROM AUTHOR]

Aims: Metabolic dysfunction is involved in modulating the disease process in Huntington disease (HD) but the underlying mechanisms are not known. The aim of this study was to investigate if the metabolic regulators sirtuins are affected in HD. Methods: Quantitative real‐time polymerase chain reactions were used to assess levels of SIRT1‐3 and downstream targets in post mortem brain tissue from HD patients and control cases as well as after selective hypothalamic expression of mutant huntingtin (HTT) using recombinant adeno‐associated viral vectors in mice. Results: We show that mRNA levels of the metabolic regulator SIRT1 are increased in the striatum and the cerebral cortex but not in the less affected cerebellum in post mortem HD brains. Levels of SIRT2 are only increased in the striatum and SIRT3 is not affected in HD. Interestingly, mRNA levels of SIRT1 are selectively increased in the lateral hypothalamic area (LHA) and ventromedial hypothalamus (VMH) in HD. Further analyses of the LHA and VMH confirmed pathological changes in these regions including effects on SIRT1 downstream targets and reduced mRNA levels of orexin (hypocretin), prodynorphin and melanin‐concentrating hormone (MCH) in the LHA and of brain‐derived neurotrophic factor (BDNF) in the VMH. Analyses after selective hypothalamic expression of mutant HTT suggest that effects on BDNF, orexin, dynorphin and MCH are early and direct, whereas changes in SIRT1 require more widespread expression of mutant HTT. Conclusions: We show that SIRT1 expression is increased in HD‐affected brain regions and that metabolic pathways are altered in the HD hypothalamus. [ABSTRACT FROM AUTHOR]

Late displacement of distal radius fractures, still in acceptable radiological position after 1–2 weeks, occurs in approximately one-third of cases. The aim of this study was to investigate the influence of late displacement on the functional outcome and quality of life at 1 year in non-operatively treated distal radius fractures. One hundred and seventy five unilateral conservatively treated distal radius fractures with minimal displacement after 10–14 days were finally evaluated in the study. Follow-up included radiographs at 3 months and clinical examination 1 year after the fracture. Final radiographic parameters, grip strength, range of motion, QuickDASH, EQ-5D and pain visual analogue scale were evaluated with multivariate analysis. Late displacement occurred in 28% of the cases and was associated with loss of grip strength and range of motion. No significant differences were seen in the outcome questionnaires.Level of evidence: II [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the validity, interobserver reliability, and intraobserver reproducibility of a digital templating system, the Mdesk™ in preoperative templating in cemented and reverse hybrid total hip arthroplasty (THA).Materials and Methods: Validity was evaluated by comparing the planned cup size, stem size, CCD angles, and neck length with the components used in 129 patients operated with cemented and reverse hybrid THA. The reliability was measured by comparing the templating results of two surgeons with each other (interobserver) and the results of two templatings carried out by first surgeon (intraobserver). The leg length discrepancy was measured before and after the operation to assess the templating ability to correct it.Results: The Mdesk™ system showed good validity (kappa value ranged from 0.64 to 0.96), especially when one size over and under the planned size were included. No difference between cemented and cementless stems was found. The interobserver reliability ranged from fair (kappa 0.23) to substantial (kappa 0.61) while the intraobserver reproducibility ranged from substantial (kappa 0.70) to excellent (kappa 0.82). Templating and intraoperative measures succeeded to restore the leg length.Conclusions: The Mdesk™ system has comparable validity and reliability with other templating systems used in clinical practice. We recommend that the same surgeon who does the preoperative radiographic templating to also perform the operation. Further studies are required to evaluate the results of succeeded templating in the long run. [ABSTRACT FROM AUTHOR]

The c.4309A>C mutation in the LRRK2 gene (LRRK2 p.N1437H) has recently been reported as the seventh pathogenic LRRK2 mutation causing monogenic Parkinson's disease (PD). So far, only two families worldwide have been identified with this mutation. By screening DNA from seven brains of PD patients, we found one individual with seemingly sporadic PD and LRRK2 p.N1437H mutation. Clinically, the patient had levodopa-responsive PD with tremor, and developed severe motor fluctuations during a disease duration of 19 years. There was severe and painful ON-dystonia, and severe depression with suicidal thoughts during OFF. In the advanced stage, cognition was slow during motor OFF, but there was no noticeable cognitive decline. There were no signs of autonomic nervous system dysfunction. Bilateral deep brain stimulation of the subthalamic nucleus had unsatisfactory results on motor symptoms. The patient committed suicide. Neuropathological examination revealed marked cell loss and moderate alpha-synuclein positive Lewy body pathology in the brainstem. There was sparse Lewy pathology in the cortex. A striking finding was very pronounced ubiquitin-positive pathology in the brainstem, temporolimbic regions and neocortex. Ubiquitin positivity was most pronounced in the white matter, and was out of proportion to the comparatively weaker alpha-synuclein immunoreactivity. Immunostaining for tau was mildly positive, revealing non-specific changes, but staining for TDP-43 and FUS was entirely negative. The distribution and shape of ubiquitin-positive lesions in this patient differed from the few previously described patients with LRRK2 mutations and ubiquitin pathology, and the ubiquitinated protein substrate remains undefined. [ABSTRACT FROM AUTHOR]

Abstract: Fallout of anthropogenic 129I at northern Europe has been occurring since the early 1950. Nevertheless, it is still unclear where and how this radioactive iodine is incorporated in the surface environment. In order to elucidate part of this problem, we here present an investigation of the occurrence modes of 129I in varved lake sediments, collected in central Sweden and cover the period 1941–2007. Using a sequential extraction method, the results of 129I and 127I indicate that the partitioning of the two isotopes were more or less similar, despite the large gradient of 129I within the sediment. Organic bound iodine was the dominant form over other fractions, while iodine bound to metal oxides was negligible. The leachable part constituted 5–6% of the iodine. Diagenetic influence seems to exert a limited effect on distribution of iodine in the examined sediment section. [Copyright &y& Elsevier]

Objective: Accurate distinction between dementia subtypes is important for patient care and pharmacological treatment. Continuing systematic comparisons of clinical and neuropathological dementia diagnoses may provide a basis for further improvement of the diagnostic procedure. The purpose of this study was to investigate concordance between clinical dementia diagnosis and neuropathological findings in the specialized dementia care.Methods: Inclusion required 1) a clinical dementia disorder diagnosed at a hospital-based memory clinic and 2) a neuropathological examination within the Department of Pathology at the University Hospital in Lund, Sweden, during the years 1996-2006. A total of 176 consecutive patients fulfilled the criteria and were thus included. Clinical dementia diagnoses were obtained from the medical records and compared with the neuropathological findings.Results: The clinical and pathological dementia diagnoses were in full accordance in 86 (49%) of the patients (kappa 0.37). In an additional 24 (14%) cases, the clinical diagnosis corresponded with some but not all pathological components judged to contribute to the dementia disorder. Of the patients with clinical Alzheimer disease, 84% (46/55) had a significant Alzheimer component with or without other significant pathology at neuropathological examination. The corresponding figure for vascular dementia (VaD) was 59% (24/41), for frontotemporal dementia 74% (20/27), for combined Alzheimer and VaD 25% (4/16), and for dementia with Lewy bodies 67% (6/9).Conclusions: This study shows that clinical dementia diagnoses do not always correspond with neuropathological changes. It stresses the importance of neuropathological examination in research and in daily clinical practice. [ABSTRACT FROM AUTHOR]

Background: Investigations on cause of death may provide valuable information about life expectancy and on conditions of terminal dementia care, which perhaps can be ameliorated. Methods: The autopsy reports were studied on all patients ( n = 524; 55.3% females; median age 80 years) with a clinically and neuropathologically diagnosed dementia disorder who underwent a complete autopsy at the University Hospital in Lund, Sweden, during 1974–2004. Results: The two most common causes of death were bronchopneumonia (38.4%) and ischaemic heart disease (23.1%), whilst neoplastic diseases were uncommon (3.8%). In a general population of elderly studied for comparison, bronchopneumonia accounted for 2.8%, ischaemic heart disease for 22.0%, and neoplasm for 21.3% of the deaths. Amongst the demented patients, circulatory and respiratory system diseases were the causes of death in 23.2% and 55.5% of the Alzheimer patients, respectively, whilst the corresponding figures were 54.8% and 33.1% for the patients with vascular dementia. Conclusions: In patients with dementia, pneumonia as the immediate cause of death may reflect a terminal stage in which patient care and feeding is difficult to manage well. Knowledge about what actually causes death is of value in the terminal care of patients with dementia disorders. [ABSTRACT FROM AUTHOR]