Vascular risk factor control and adherence to secondary preventive medication after ischaemic stroke.

BACKGROUND: Studies regarding adequacy of secondary stroke prevention are limited. We report medication adherence, risk factor control and factors influencing vascular risk profile following ischaemic stroke. METHODS: A total of 664 home-dwelling participants in the Norwegian Cognitive Impairment After Stroke study, a multicenter observational study, were evaluated 3 and 18 months poststroke. We assessed medication adherence by self-reporting (4-item Morisky Medication Adherence Scale) and medication persistence (defined as continuation of medication(s) prescribed at discharge), achievement of guideline-defined targets of blood pressure (BP) (<140/90 mmHg), low-density lipoprotein cholesterol (LDL-C) (<2.0 mmol L-1 ) and haemoglobin A1c (HbA1c) (≤53 mmol mol-1 ) and determinants of risk factor control. RESULTS: At discharge, 97% were prescribed antithrombotics, 88% lipid-lowering drugs, 68% antihypertensives and 12% antidiabetic drugs. Persistence of users declined to 99%, 88%, 93% and 95%, respectively, at 18 months. After 3 and 18 months, 80% and 73% reported high adherence. After 3 and 18 months, 40.7% and 47.0% gained BP control, 48.4% and 44.6% achieved LDL-C control, and 69.2% and 69.5% of diabetic patients achieved HbA1c control. Advanced age was associated with increased LDL-C control (OR 1.03, 95% CI 1.01 to 1.06) and reduced BP control (OR 0.98, 0.96 to 0.99). Women had poorer LDL-C control (OR 0.60, 0.37 to 0.98). Polypharmacy was associated with increased LDL-C control (OR 1.29, 1.18 to 1.41) and reduced HbA1c control (OR 0.76, 0.60 to 0.98). CONCLUSION: Risk factor control is suboptimal despite high medication persistence and adherence. Improved understanding of this complex clinical setting is needed for optimization of secondary preventive strategies.

Atomically resolved phase transition of fullerene cations solvated in helium droplets.

Helium has a unique phase diagram and below 25 bar it does not form a solid even at the lowest temperatures. Electrostriction leads to the formation of a solid layer of helium around charged impurities at much lower pressures in liquid and superfluid helium. These so-called 'Atkins snowballs' have been investigated for several simple ions. Here we form HenC60+ complexes with n exceeding 100 via electron ionization of helium nanodroplets doped with C60. Photofragmentation of these complexes is measured by merging a tunable narrow-bandwidth laser beam with the ions. A switch from red- to blueshift of the absorption frequency of HenC60+ on addition of He atoms at n=32 is associated with a phase transition in the attached helium layer from solid to partly liquid (melting of the Atkins snowball). Elaborate molecular dynamics simulations using a realistic force field and including quantum effects support this interpretation.

Migraine in patients with systemic lupus erythematosus is associated with reduced cerebral grey matter volume but not with measures of glial activation or anti-NR2 or anti-P antibodies.

BACKGROUND AND PURPOSE: Migraine is frequent in patients with systemic lupus erythematosus (SLE), but the pathogenesis and pathophysiology are poorly understood. Migraine is assumed to be a consequence of abnormal neuronal excitability. Based on the hypothesis that the threshold for migraine is lower in SLE patients due to cerebral disturbances, whether structural abnormalities of the brain or relevant biomarkers are associated with headaches in SLE was investigated. METHODS: Sixty-seven SLE patients and age- and gender-matched healthy subjects participated. Volumes of grey matter (GM) and white matter (WM) were estimated from cerebral magnetic resonance images with SPM8 software. Anti-NR2 and anti-P antibodies and protein S100B were measured in cerebrospinal fluid. RESULTS: In regression analyses, larger GM volumes in SLE patients reduced the odds for headache in general [odds ratio (OR) 0.98, P = 0.048] and for migraine in particular (OR 0.95, P = 0.004). No localized loss of GM was observed. Larger WM volumes in patients increased the odds for migraine (OR 1.04, P = 0.007). These findings could not be confirmed in healthy subjects. Neither anti-NR2 and anti-P antibodies nor S100B were associated with headaches in SLE patients. CONCLUSIONS: Systemic lupus erythematosus patients with migraine have a diffuse reduction in GM compared to patients without migraine. This finding was not observed in healthy subjects with migraine, and selected biomarkers did not indicate specific pathophysiological processes in the brain. These findings indicate that unknown pathogenic processes are responsible for the increased frequency of migraine in SLE patients.

Loss of cerebral white matter in primary Sjögren's syndrome: a controlled volumetric magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Although brain involvement is common in primary Sjögren's syndrome (pSS), results from cerebral imaging studies are inconsistent. This study aimed to perform both voxel-wise and global brain volume analyses in a nearly population-based pSS cohort to explore whether the patients displayed any focal or diffuse volume differences compared with healthy subjects. METHODS: Global grey matter (GM) and white matter (WM) volumes were measured and compared in 60 patients with pSS and 60 age- and gender-matched healthy subjects. Regression models were constructed with potential explanatory variables for GM and WM volumes. In the same groups, voxel-wise morphometric analyses were performed. RESULTS: In analyses of global GM and WM, the patients had lower WM volumes than healthy subjects (540 ± 63 cm(3) vs. 564 ± 56 cm(3), P = 0.02), but no differences in GM. Voxel-wise analyses displayed no localized areas of GM or WM volume differences between pSS patients and healthy subjects. CONCLUSION: Individuals with pSS have a diffuse reduction of cerebral WM but no localized loss of WM or GM. This indicates a general deleterious effect on WM due to pSS itself.

Headache in primary Sjøgren's syndrome: a population-based retrospective cohort study.

BACKGROUND: We investigated whether the prevalence of primary headaches was higher in patients with primary Sjøgren's syndrome (PSS) than in healthy individuals. METHODS: This retrospective cohort study included 71 patients with PSS (patients) based on the American European Consensus Classification criteria, and 71 age- and gender-matched healthy subjects (controls). Headaches were classified according to the International Classification of Headache Disorders. We measured depression with the Beck Depression Inventory, and fatigue with the Fatigue Severity Scale. RESULTS: Fifty-one patients and 42 controls had headaches in the previous 12 months (71.8% vs. 59.2%, P = 0.10). Thirty-eight patients and 28 controls had tension type headaches (TTHs) (53.5% vs. 39.4%, P = 0.12). Eight patients (11.3%) and one control had chronic TTHs (P = 0.05). Migraines and migraines with aura were equally prevalent in patients (26.8% and 11.3%, respectively) and controls (28.2% and 15.5%, respectively; P = 0.61). CONCLUSIONS: In general, patients did not have more migraines or headaches than controls. However, patients had more chronic TTHs than controls. Chronic TTHs were not associated with PSS-related autoantibodies, fatigue, depression, abnormalities on magnetic resonance imaging or abnormalities in the cerebrospinal fluid. Patients with PSS did, however, have higher depression and fatigue scores than controls.

Multivariate classification of patients with Alzheimer's and dementia with Lewy bodies using high-dimensional cortical thickness measurements: an MRI surface-based morphometric study.

CONTEXT: Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common neurodegenerative dementia types. It is important to differentiate between them because of the differences in prognosis and treatment approaches. OBJECTIVE: Investigate if sparse partial least squares (SPLS) classification of cortical thickness measurements could differentiate between AD and DLB. METHODS: Two independent cohorts without MR-protocol alignment in Norway and Slovenia with 97 AD and DLB subjects were enrolled. Cortical thickness measurements acquired with Freesurfer were used in subsequent SPLS classification runs. The cohorts were analyzed separately and afterwards combined. The models were trained with leave-one-out cross validation and test datasets where used when available. To study the impact of MR-protocol alignment, the classifiers were additionally tested on sets drawn exclusively from the independent cohorts. RESULTS: The obtained sensitivity/specificity/AUC values were 94.4/88.89/0.978 and 88.2/94.1/0.969 in the Norwegian and Slovenian cohorts, respectively. Both cohorts showed AD-associated pattern of thinning in mid-anterior temporal, occipital and subgenual cingulate cortex, whereas the pattern supportive for DLB included thinning in dorsal cingulate, posterior temporal and lateral orbitofrontal regions. When combining the cohorts, sensitivity/specificity/AUC were 82.1/85.7/0.948 for the training and 77.8/75/0.731 for the testing datasets with the same pattern-of-difference. The models tested on datasets drawn exclusively from the independent cohorts did not produce adequate accuracy. CONCLUSION: SPLS classification of cortical thickness is a good method for differentiating between AD and DLB, relatively stable even for mixed data, but not when tested on completely independent data drawn from different cohorts (without MR-protocol alignment).

White matter hyperintensities in mild lewy body dementia.

BACKGROUND: The objective of this study was to explore the load of white matter hyperintensities (WMH) in patients with Lewy body dementia (LBD) and compare to Alzheimer's disease (AD) and normal controls (NC). METHODS: Diagnosis of LBD and AD was made according to consensus criteria and cognitive tests were administered. MRI scans for 77 (61 AD and 16 LBD) patients and 37 healthy elderly control subjects were available for analysis. We segmented WMH from FLAIR images using an automatic thresholding technique and calculated the volume of WMH in several regions of the brain, using non-parametric tests to compare groups. Multivariate regression was applied. RESULTS: There were no significant differences in WMH between AD and LBD. We found a significant correlation between total and frontal WMH and Mini-Mental State Examination (MMSE) and verbal fluency scores in the AD group, but not in the LBD group. CONCLUSION: The WMH load in LBD was similar to that of AD. A correlation between WMH load and cognition was found in the AD group, but not in the LBD group, suggesting that vascular disease contributes to cognitive impairment in AD but not LBD.

Cerebral white matter hyperintensities are not increased in patients with primary Sjögren's syndrome.

BACKGROUND AND PURPOSE: It is frequently thought that cerebral white matter hyperintensities (WMHs) on T-2 weighted MRI scans are increased in patients with autoimmune diseases. An increased frequency of WHMs has been described in primary Sjögren's syndrome (PSS), but no controlled studies exist. The aim of this study was therefore to compare WMHs in PSS patients and healthy subjects applying the new European-American criteria for PSS. METHODS: Cross-sectional controlled study of 68 unselected PSS patients and 68 healthy subjects was carried out. WMHs were rated using Scheltens method. RESULTS: There were no differences in total or any regional WMH scores between PSS patients and healthy subjects. CONCLUSIONS: Patients with PSS do not have increased WMH load or distribution when compared with healthy subjects.

Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjögren syndrome: a comparative population-based study.

OBJECTIVES: To compare the prevalence and pattern of neuropsychiatric (NP) syndromes observed in systemic lupus erythematosus (SLE) to patients with Primary Sjögren syndrome (PSS) using the American College of Rheumatology (ACR) criteria for the 19 NP syndromes seen in SLE. METHODS: A population-based study was conducted including 68 patients with SLE (mean (SD) age 43.8 (13.6) years) and 72 with PSS (age 57.8 (13.0) years). Specialists in internal medicine, neurology and neuropsychology performed standardised examinations. Cerebral MRI scans and neurophysiological studies were performed in all patients. RESULTS: Similar prevalences in SLE and PSS were observed for headaches (87% vs 78%, p = 0.165), cognitive dysfunction (46% vs 50%, p = 0.273), mood disorders (26% vs 33%, p = 0.376), anxiety disorders (12% vs 4%, p = 0.095), cranial neuropathy (1% vs 4%, p = 0.339) and seizure disorders (7% vs 3%, p = 0.208). Cerebrovascular disease was more common in SLE than PSS (12% vs 3%, p = 0.049); but mononeuropathy (0% vs 8%, p = 0.015) and polyneuropathy (18% vs 56%, p<0.001) were less common in SLE than PSS. Other syndromes were rare or absent in both patient groups. CONCLUSIONS: Headache, cognitive dysfunction and mood disorders are common in both diseases, but otherwise there are distinct differences in NP involvement, with cerebrovascular diseases more prevalent in SLE and neuropathies more common in PSS. This indicates that some NP disease mechanisms are shared while others differ between the two diseases.

Cerebellar leukoencephalopathy: most likely histiocytosis-related.

BACKGROUND: Histiocytosis, both Langerhans and non-Langerhans cell type, can be associated with cerebellar white matter abnormalities, thought to be paraneoplastic. The associated clinical picture consists of ataxia, spasticity, and cognitive decline. Hormonal dysfunction is frequent. MRI shows cerebellar white matter abnormalities, as well as brainstem and basal ganglia abnormalities. This so-called "neurodegenerative syndrome" may occur years before or during manifest histiocytosis and also years after cure. We discovered similar MRI abnormalities in 13 patients and wondered whether they could have the same syndrome. METHODS: We reviewed the clinical and laboratory information of these 13 patients and evaluated their brain MRIs. Seven patients underwent spinal cord MRI. RESULTS: All patients were isolated cases; 10 were male. They had signs of cerebellar and pyramidal dysfunction, behavioral problems, and cognitive decline. MRI showed abnormalities of the cerebellar white matter, brainstem, basal ganglia, and, to a lesser extent, cerebral white matter. Three patients had spinal cord lesions. Three patients had laboratory evidence of hormonal dysfunction. No evidence was found of an underlying metabolic defect. In two patients biopsy of nodular brain lesions revealed histiocytic infiltrates. CONCLUSIONS: Considering the striking clinical and MRI similarities between our patients and the patients with this neurodegenerative syndrome in the context of proven histiocytosis, it is likely that they share the same paraneoplastic syndrome, although we cannot exclude a genetic disorder with certainty. The fact that we found histiocytic lesions in two patients substantiates our conclusion. Patients with cerebellar white matter abnormalities should be monitored for histiocytosis.

Grey matter atrophy in early versus late dementia in Parkinson's disease.

There is considerable heterogeneity within patients with Parkinson's disease (PD) regarding time from onset of PD to dementia. We compared grey matter atrophy using magnetic resonance images (MRIs) of patients with PD who developed dementia early and late in the disease course. The group with early dementia had more atrophy than the group with late dementia in some areas, while the late dementia group had symmetrical reduction in concentration of grey matter in the insula bilaterally compared to the early dementia group. Our results indicate that the early development of dementia in PD is associated with more severe degeneration of cortical and sub-cortical structures.

A strategy for the determination of enzyme kinetics using electrospray ionization with an ion trap mass spectrometer.

A simple and rapid means of enzyme kinetic analysis was achieved using electrospray ionization mass spectrometry and a one-point normalization factor. The model system used, glutathione S-transferase from porcine liver, is a two-substrate enzyme catalyzing the conjugation of glutathione with a variety of compounds containing an electrophilic center. An internal standard that is structurally similar to the product was added to the reaction quench solution, and a single-point normalization factor was used to determine the product concentration without the need of a calibration curve. Kinetic parameters, such as Km, Vmax and Ki (for thyroxine), obtained by electrospray mass spectrometry agreed with those obtained from traditional UV-vis spectroscopy, and competitive vs noncompetitive inhibition reactions could be delineated via mass spectrometry. These results suggest that our method can be applied to enzymatic processes in which spectrophotometric or spectrofluorometric assays are not feasible or when the relevant substrates do not incorporate chromophores or fluorophores. This new method is competitive with traditional UV assays in that it is facile and it involves very little analysis time.

Hypoiodous acid as guest molecule in protonated water clusters: a combined FT-ICR/DFT study of I(H2O)n+.

Cationic water clusters containing iodine, of the composition I(H2O)n+, n = 0-25, are generated in a laser vaporization source and investigated by FT-ICR mass spectrometry. An investigation of blackbody radiation-induced fragmentation of size-selected clusters I(H2O)n+, n = 3-15, under collision-free conditions revealed an overall linear increase of the unimolecular rate constant with cluster size, similar to what has been observed previously for other hydrated ions. Above a certain critical size, I(H2O)n+, n greater than or approx. 13, reacts with HCl by formation of the interhalide ICl and a protonated water cluster, which is the reverse of a known solution-phase reaction. Accompanying density functional calculations illustrate the conceptual differences between cationic and anionic iodine-water clusters I(H2O)n+/-. While I-(H2O)n is genuinely a hydrated iodide ion, the cationic closed-shell species I(H2O)n+ may be best viewed as a protonated water cluster, in which one water molecule is replaced by hypoiodous acid. In the strongly acidic environment, HOI is protonated because of its high proton affinity. However, similar to the well-known H3O+/H5O2+ controversy in protonated water clusters, a smooth transition between H2IO+ and H4IO2+ as core ions is observed for different cluster sizes.

Molecular orbital considerations in probing the stereoselective dissociations of cobalt-coordinated hexosamine monosaccharides.

The mechanisms for the stereoselective dissociation pathways of isomeric [CoIII(diaminopropane)2(hexosamine-2H)]+ complexes are studied by ion trap and Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). The exact masses of product ions were measured in order to determine the composition of each loss, and isotopic labeling experiments were used to determine which atoms were lost during dissociation. MS3 studies were used to probe the structures of the product ions from MS2 experiments. Based on the experimental evidence obtained, mechanisms explaining the dissociations are postulated. In deciphering the mechanisms, careful attention was paid to the molecular orbital alignment of the reacting bonds, and based on the molecular orbitals, transition state conformations were postulated. These transition states suggest how the observed stereoselectivity occurs. In each case, the carbohydrate/metal interaction was crucial in the dissociation processes.

Causes of death in a community-based study of Parkinson's disease.

INTRODUCTION: The aim of this community-based study of Parkinson's disease (PD) was to investigate the causes of death among PD patients over a 4-year period and to examine the quality of death certificates with regard to PD. PATIENTS AND METHODS: A total of 245 patients were diagnosed with PD on Jan 1st 1993 in a defined geographical area in Norway. This patient cohort was followed from 1993 until Dec 31st 1996. Some 84 patients died in the 4-year period of follow-up. Their death certificates were collected, and causes of death were registered. A control group with the same age and sex distribution as the decedents, from the same geographical area, were also examined for causes of death. RESULTS: We found that the deceased PD patients at baseline were older, had a higher Unified Parkinson's Disease Rating Scale (UPDRS) score and Hoehn and Yahr staging than those patients who did not die during the observation period. Twice as many PD patients (20%) as controls (9%) died from pneumonia, whereas more controls than patients died from ischemic heart disease. There was a trend towards more deaths from malignant neoplasms in the control group than among PD patients. Only 56% of the death certificates of the deceased patients had PD registered as either underlying or contributing cause of death. CONCLUSION: We found that in an unselected group of PD patients there is a significant increase in deaths from pneumonia. The low frequency of PD on deceased patients' death certificates show that research based on these certificates should be evaluated with caution.