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1.	Longinetti, Elisa, et al. (författare) Neurodegenerative and psychiatric diseases among families with amyotrophic lateral sclerosis 2017 Ingår i: Neurology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0028-3878 .- 1526-632X. ; 89:6, s. 578-585 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Objective: To estimate risks of neurodegenerative and psychiatric diseases among patients with amyotrophic lateral sclerosis (ALS) and their families. Methods: We conducted a register-based nested case-control study during 1990-2013 in Sweden to assess whether ALS patients had higher risks of other neurodegenerative and psychiatric diseases before diagnosis. We included 3,648 ALS patients and 36,480 age-, sex-, and county-of-birth matched population controls. We further conducted a follow-up study of the cases and controls to assess the risks of other neurodegenerative and psychiatric diseases after ALS diagnosis. To assess the potential contribution of familial factors, we conducted similar studies for the relatives of ALS patients and their controls. Results: Individuals with previous neurodegenerative or psychiatric diseases had a 49% increased risk of ALS (odds ratio=1.49, 95% confidence interval=1.35-1.66), compared to individuals without these diseases. After diagnosis, ALS patients had increased risks of other neurodegenerative or psychiatric diseases (hazard ratio=2.90, 95% confidence interval=2.46-3.43), compared to individuals without ALS. The strongest associations were noted for frontotemporal dementia, Parkinson’s disease, other dementia, Alzheimer’s disease, neurotic disorders, depression, stress-related disorders, and drug abuse/dependence. First-degree relatives of ALS patients had higher risk of neurodegenerative diseases, whereas only children of ALS patients had higher risk of psychiatric disorders, compared to relatives of the controls. Conclusions: Familial aggregation of ALS and other neurodegenerative diseases implies a shared etiopathogenesis among all neurodegenerative diseases. The increased risk of psychiatric disorders among ALS patients and their children might be attributable to non-motor symptoms of ALS and severe stress response toward the diagnosis.
2.	Aarnio, K., et al. (författare) Cardiovascular events after ischemic stroke in young adults: A prospective follow-up study 2016 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 86:20, s. 1872-1879 Tidskriftsartikel (refereegranskat)abstract Objectives:To study the long-term risk of recurrent cardiac, arterial, and venous events in young stroke patients, and whether these risks differed between etiologic subgroups.Methods:The study population comprised 970 patients aged 15-49 years from the Helsinki Young Stroke Registry (HYSR) who had an ischemic stroke in 1994-2007. We obtained follow-up data until 2012 from the Finnish Care Register and Statistics Finland. Cumulative 15-year risks were analyzed with life tables, whereas relative risks and corresponding confidence intervals (CI) were based on hazard ratios (HR) from Cox regression analyses.Results:There were 283 (29.2%) patients with a cardiovascular event during the median follow-up of 10.1 years (range 0.1-18.0). Cumulative 15-year risk for venous events was 3.9%. Cumulative 15-year incidence rate for composite vascular events was 34.0 (95% CI 30.1-38.2) per 1,000 person-years. When adjusted for age and sex, patients with an index stroke caused by high-risk sources of cardioembolism had the highest HR for any subsequent cardiovascular events (3.7; 95% CI 2.6-5.4), whereas the large-artery atherosclerosis group had the highest HR (2.7; 95% CI 1.6-4.6) for recurrent stroke compared with patients with stroke of undetermined etiology.Conclusions:The risk for future cardiovascular events after ischemic stroke in young adults remains high for years after the index stroke, in particular when the index stroke is caused by high-risk sources of cardioembolism or large-artery atherosclerosis.
3.	af Edholm, Karolina, et al. (författare) Clinical Reasoning : Leg weakness and stiffness at the emergency room 2019 Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 92:6, s. E622-E625 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract A 48-year-old woman from the Maghreb came to the emergency department with insidious gait difficulties, urgency, and constipation starting 6 months prior to the visit. The patient's complaints consisted of weakness, stiffness, and pain in her legs. Her medical history consisted of Hashimoto thyroiditis and breast cancer, with the latter having motivated surgery 4 months prior to admission. Histopathologic examination had demonstrated ductal cancer sensitive to estrogen and mapping with sentinel node biopsy ruled out metastasis. For that reason, the patient was treated with local radiation given weekly over 1 month and treatment with tamoxifen was started. Physical examination upon admission demonstrated weakness and spasticity in both legs. Reflexes were brisk; bilateral nonsustained foot clonus and Babinski sign were also present. Bilateral dorsal flexion was reduced, but vibration and sensation to touch and pinprick were normal. Sphincter tonus was reduced; systemic manifestations such as myalgias, fever, skin rashes, uveitis, sicca, and arthritic joints were absent.
4.	Ajroud-Driss, Senda, et al. (författare) Impact of Patisiran on Overall Health Status in hATTR Amyloidosis : Results from the APOLLO Trial 2019 Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878 .- 1526-632X. ; 92:15 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
5.	Akram, Harith, et al. (författare) Optimal deep brain stimulation site and target connectivity for chronic cluster headache 2017 Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878 .- 1526-632X. ; 89:20, s. 2083-2091 Tidskriftsartikel (refereegranskat)abstract Objective: To investigate the mechanism of action of deep brain stimulation for refractory chronic cluster headache and the optimal target within the ventral tegmental area. Methods: Seven patients with refractory chronic cluster headache underwent high spatial and angular resolution diffusion MRI preoperatively. MRI-guided and MRI-verified electrode implantation was performed unilaterally in 5 patients and bilaterally in 2. Volumes of tissue activation were generated around active lead contacts with a finite-element model. Twelve months after surgery, voxel-based morphometry was used to identify voxels associated with higher reduction in headache load. Probabilistic tractography was used to identify the brain connectivity of the activation volumes in responders, defined as patients with a reduction of >= 30% in headache load. Results: There was no surgical morbidity. Average follow-up was 34 +/- 14 months. Patients showed reductions of 76 +/- 33% in headache load, 46 +/- 41% in attack severity, 58 +/- 41% in headache frequency, and 51 +/- 46% in attack duration at the last follow-up. Six patients responded to treatment. Greatest reduction in headache load was associated with activation in an area cantered at 6 mm lateral, 2 mm posterior, and 1 mm inferior to the midcommissural point of the third ventricle. Average responders' activation volume lay on the trigeminohypothalamic tract, connecting the trigeminal system and other brainstem nuclei associated with nociception and pain modulation with the hypothalamus, and the prefrontal and mesial temporal areas. Conclusions: We identify the optimal stimulation site and structural connectivity of the deep brain stimulation target for cluster headache, explicating possible mechanisms of action and disease pathophysiology.
6.	Alston, CL, et al. (författare) Late-onset respiratory failure due to TK2 mutations causing multiple mtDNA deletions 2013 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 81:23, s. 2051-2053 Tidskriftsartikel (refereegranskat)
7.	Alves, G., et al. (författare) CSF A beta(42) predicts early-onset dementia in Parkinson disease 2014 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 82:20, s. 1784-1790 Tidskriftsartikel (refereegranskat)abstract Objective:To test in vivo the proposal from clinicopathologic studies that -amyloid (A) pathology shortens the time to dementia in Parkinson disease (PD), and to explore the utility of CSF A and related measures as early prognostic biomarkers of dementia in an incident PD cohort.Methods:We assessed a population-based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis. We analyzed CSF concentrations of A42, A40, and A38 using a multiplexed immunoassay with electrochemiluminescence (ECL) detection and levels of A42, total tau, and phosphorylated tau using ELISA. Patients were followed prospectively for 5 years. Dementia was diagnosed according to published criteria.Results:CSF levels of A42 were significantly decreased in patients who developed dementia (n = 20, 19.2%) compared to those who did not (n = 84, 80.8%), as measured by ECL (-33%, p = 0.006) as well as ELISA (-36%, p < 0.001). No differences were observed for other markers. Low A42 values predicted a substantially increased risk for subsequent dementia at high sensitivity (85%), with hazard ratios of 9.9 (95% confidence interval 2.3-43.5, p = 0.002) for A42(ECL) <376 pg/mL and 7.6 (2.2-26.4, p = 0.001) for A42(ELISA) <443 pg/mL, after adjustment for baseline age and PD-mild cognitive impairment (MCI) status. A42 reductions tended to precede the onset of PD-MCI that progressed to dementia.Conclusions:These in vivo data support the role of A pathology in the etiology and highlight the potential utility of CSF A42 as an early prognostic biomarker of dementia associated with PD.
8.	Andersen, Peter M. (författare) Is all ALS genetic? 2017 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 89:3, s. 220-221 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
9.	Arnoldussen, Ilse A. C., et al. (författare) Adiposity is related to cerebrovascular and brain volumetry outcomes in the RUN DMC study 2019 Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 93:9, s. e864-e878 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Adiposity predictors, body mass index (BMI), waist circumference (WC), and blood leptin and total adiponectin levels were associated with components of cerebral small vessel disease (CSVD) and brain volumetry in 503 adults with CSVD who were ≥50 years of age and enrolled in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC).METHODS: RUN DMC participants were followed up for 9 years (2006-2015). BMI, WC, brain imaging, and dementia diagnoses were evaluated at baseline and follow-up. Adipokines were measured at baseline. Brain imaging outcomes included CSVD components, white matter hyperintensities, lacunes, microbleeds, gray and white matter, hippocampal, total brain, and intracranial volumes.RESULTS: Cross-sectionally among men at baseline, higher BMI, WC, and leptin were associated with lower gray matter and total brain volumes, and higher BMI and WC were associated with lower hippocampal volume. At follow-up 9 years later, higher BMI was cross-sectionally associated with lower gray matter volume, and an obese WC (>102 cm) was protective for ≥1 lacune or ≥1 microbleed in men. In women, increasing BMI and overweight or obesity (BMI ≥25 kg/m2 or WC >88 cm) were associated with ≥1 lacune. Longitudinally, over 9 years, a baseline obese WC was associated with decreasing hippocampal volume, particularly in men, and increasing white matter hyperintensity volume in women and men.CONCLUSIONS: Anthropometric and metabolic adiposity predictors were differentially associated with CSVD components and brain volumetry outcomes by sex. Higher adiposity is associated with a vascular-neurodegenerative spectrum among adults at risk for vascular forms of cognitive impairment and dementias.
10.	Aronsson, Mattias, et al. (författare) Cost-effectiveness of endovascular thrombectomy in patients with acute ischemic stroke. 2016 Ingår i: Neurology. - : American Academy of neurology. - 0028-3878 .- 1526-632X. ; 86:11, s. 1053-9 Tidskriftsartikel (refereegranskat)abstract Objective:To evaluate the cost-effectiveness of adding endovascular thrombectomy to standard care in patients with acute ischemic stroke.Methods:The cost-effectiveness analysis of endovascular thrombectomy in patients with acute ischemic stroke was based on a decision-analytic Markov model. Primary outcomes from ESCAPE, Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA), Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT), and Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) along with data from published studies and registries were used in this analysis. We used a health care payer perspective and a lifelong time horizon to estimate costs and effects.Results:The model showed that adding thrombectomy with stent retrievers to guideline-based care (including IV thrombolysis) resulted in a gain of 0.40 life-years and 0.99 quality-adjusted life-years along with a cost savings of approximately $221 per patient. The sensitivity analysis showed that the results were not sensitive to changes in uncertain parameters or assumptions.Conclusions:Adding endovascular treatment to standard care resulted in substantial clinical benefits at low costs. The results were consistent throughout irrespective of whether data from ESCAPE, EXTEND-IA, MR CLEAN, REVASCAT, or SWIFT PRIME were used in this model.
11.	Aziz, Tipu Z., et al. (författare) To sleep or not to sleep during deep brain stimulation surgery for Parkinson disease? 2017 Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 89:19, s. 1938-1939 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
12.	Benatar, Michael, et al. (författare) Presymptomatic ALS genetic counseling and testing : Experience and recommendations 2016 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 86:24, s. 2295-2302 Forskningsöversikt (refereegranskat)abstract Remarkable advances in our understanding of the genetic contributions to amyotrophic lateral sclerosis (ALS) have sparked discussion and debate about whether clinical genetic testing should routinely be offered to patients with ALS. A related, but distinct, question is whether presymptomatic genetic testing should be offered to family members who may be at risk for developing ALS. Existing guidelines for presymptomatic counseling and testing are mostly based on small number of individuals, clinical judgment, and experience from other neurodegenerative disorders. Over the course of the last 8 years, we have provided testing and 317 genetic counseling sessions (including predecision, pretest, posttest, and ad hoc counseling) to 161 first-degree family members participating in the Pre-Symptomatic Familial ALS Study (Pre-fALS), as well as testing and 75 posttest counseling sessions to 63 individuals with familial ALS. Based on this experience, and the real-world challenges we have had to overcome in the process, we recommend an updated set of guidelines for providing presymptomatic genetic counseling and testing to people at high genetic risk for developing ALS. These recommendations are especially timely and relevant given the growing interest in studying presymptomatic ALS.
13.	Benatar, Michael, et al. (författare) Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS 2018 Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 90:7, s. E565-E574 Tidskriftsartikel (refereegranskat)abstract ObjectiveTo examine the safety and tolerability as well as the preliminary efficacy of arimoclomol, a heat shock protein co-inducer that promotes nascent protein folding, in patients with rapidly progressive SOD1 amyotrophic lateral sclerosis (ALS).MethodsThis was a double-blind, placebo-controlled trial in which patients with rapidly progressive SOD1-mutant ALS were randomized 1:1 to receive arimoclomol 200 mg tid or matching placebo for up to 12 months. Study procedures were performed using a mix of in-person and remote assessments. Primary outcome was safety and tolerability. Secondary outcome was efficacy, with survival as the principal measure. Additional efficacy measures were the rates of decline of the Revised ALS Functional Rating Scale (ALSFRS-R) and percent predicted forced expiratory volume in 6 seconds (FEV6), and the Combined Assessment of Function and Survival (CAFS).ResultsThirty-eight participants were randomized. Thirty-six (19 placebo, 17 arimoclomol) were included in the prespecified intent-to-treat analysis. Apart from respiratory function, groups were generally well-balanced at baseline. Adverse events occurred infrequently, and were usually mild and deemed unlikely or not related to study drug. Adjusting for riluzole and baseline ALSFRS-R, survival favored arimoclomol with a hazard ratio of 0.77 (95% confidence interval [CI] 0.32-1.80). ALSFRS-R and FEV6 declined more slowly in the arimoclomol group, with treatment differences of 0.5 point/month (95% CI -0.63 to 1.63) and 1.24 percent predicted/month (95% CI -2.77 to 5.25), respectively, and the CAFS similarly favored arimoclomol.ConclusionsThis study provides Class II evidence that arimoclomol is safe and well-tolerated at a dosage of 200 mg tid for up to 12 months. Although not powered for therapeutic effect, the consistency of results across the range of prespecified efficacy outcome measures suggests a possible therapeutic benefit of arimoclomol.Clinicaltrials.gov identifierNCT00706147.Classification of evidenceThis study provides Class II evidence that arimoclomol is safe and well-tolerated at a dosage of 200 mg tid for up to 12 months. The study lacked the precision to conclude, or to exclude, an important therapeutic benefit of arimoclomol.
14.	Bergman, Joakim, et al. (författare) Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study 2018 Ingår i: Neurology. - : Wolters Kluwer. - 1526-632X .- 0028-3878. ; 91:20 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To perform a phase 1b assessment of the safety and feasibility of intrathecally delivered rituximab as a treatment for progressive multiple sclerosis (PMS) and to evaluate the effect of treatment on disability and CSF biomarkers during a 1-year follow-up period. METHODS: Three doses of rituximab (25 mg with a 1-week interval) were administered in 23 patients with PMS via a ventricular catheter inserted into the right frontal horn and connected to a subcutaneous Ommaya reservoir. Follow-ups were performed at 1, 3, 6, 9, and 12 months. RESULTS: Mild to moderate vertigo and nausea were common but temporary adverse events associated with intrathecal rituximab infusion, which was otherwise well tolerated. The only severe adverse event was a case of low-virulent bacterial meningitis that was treated effectively. Of 7 clinical assessments, only 1 showed statistically significant improvement 1 year after treatment. No treatment effect was observed during the follow-up period among 6 CSF biomarkers. CONCLUSIONS: Intrathecal administration of rituximab was well tolerated. However, it may involve a risk for injection-related infections. The lack of a control group precludes conclusions being drawn regarding treatment efficacy. CLINICALTRIALSGOV IDENTIFIER: NCT01719159. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that intrathecal rituximab treatment is well tolerated and feasible in PMS but involves a risk of severe infections. © 2018 American Academy of Neurology.
15.	Bosch, Jackie, et al. (författare) Effects of blood pressure and lipid lowering on cognition Results from the HOPE-3 study 2019 Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878 .- 1526-632X. ; 92:13, s. E1435-E1446 Tidskriftsartikel (refereegranskat)abstract Objective: To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk.Methods: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 x 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were >= 70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end.Results: Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD +/- 3.5 years); 59% were women; 45% had hypertension; and 24% had >= 12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures.Conclusions: Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people. ClinicalTrials.gov identifier: NCT00468923. Classification of evidence: This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.
16.	Braillon, A (författare) Healthy diet and lifestyle and risk of stroke in a prospective cohort of women 2015 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 84:22, s. 2293-2293 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
17.	Burkill, Sarah, et al. (författare) Mortality trends for multiple sclerosis patients in Sweden from 1968 to 2012 2017 Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 89:6, s. 555-562 Tidskriftsartikel (refereegranskat)abstract Objective: To assess trends in mortality and causes of death for patients with multiple sclerosis (MS) relative to those without MS in Sweden.Methods: Patients with an MS diagnosis in Sweden between 1964 and 2012 were identified with the Patient Register and the Multiple Sclerosis Register. For this cohort study, each patient with MS (n = 29,617) was matched with 10 individuals without MS (n = 296,164) on sex, year of birth, vital status, and region of residence at the time of MS diagnosis with the Total Population Register. The Causes of Death Register was used to identify causes of death. Cox proportional hazard models were constructed to assess whether risk of mortality was increased for patients with MS.Results: The hazard ratio (HR) for patients with MS was 2.92 (95% confidence interval [CI] 2.86-2.99) for all-cause mortality over the entire study period. The largest differences between the cohorts were death resulting from respiratory (HR 5.07, 95% CI 4.87-5.26) and infectious (HR 4.07, 95% CI 3.70-4.47) diseases. Overall and for each specific cause, there have been improvements for the MS group and a subsequent reduction in the HR. The HR decreased from 6.52 (95% CI 5.79-7.34) for the period of 1968 to 1980 to 2.08 (95% CI 1.95-2.22) for the time period of 2001 to 2012. An interaction between time period and MS exposure showed that the decrease in mortality over time was statistically significant, with a larger decrease for patients with MS than their matched comparators.Conclusions: There has been a substantial improvement in mortality overall and for each specified cause of death for patients with MS compared with individuals without MS; however, large differences still remain.
18.	Burman, Joachim, 1974-, et al. (författare) Autologous hematopoietic stem cell transplantation for MS : Safer than previously thought 2017 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 88:22, s. 2072-2073 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
19.	Burman, Joachim, 1974-, et al. (författare) Epilepsy in multiple sclerosis: A nationwide population-based register study. 2017 Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 89:24, s. 2462-2468 Tidskriftsartikel (refereegranskat)abstract To determine the cumulative incidence of epilepsy in a population-based cohort of patients with multiple sclerosis (MS) and to investigate the association between epilepsy and clinical features of MS.All available patients in the Swedish MS register (n = 14,545) and 3 age- and sex-matched controls per patient randomly selected from the population register (n = 43,635) were included. Data on clinical features of MS were retrieved from the Swedish MS register, and data on epilepsy and death were retrieved from comprehensive patient registers.The cumulative incidence of epilepsy was 3.5% (95% confidence interval [CI] 3.17-3.76) in patients with MS and 1.4% (95% CI 1.30-1.52) in controls (risk ratio 2.5, 95% CI 2.19-2.76). In a Cox proportional model, MS increased the risk of epilepsy (hazard ratio 3.2, 95% CI 2.64-3.94). Patients with relapsing-remitting MS had a cumulative incidence of epilepsy of 2.2% (95% CI 1.88-2.50), whereas patients with progressive disease had a cumulative incidence of 5.5% (95% CI 4.89-6.09). The cumulative incidence rose continuously with increasing disease duration to 5.9% (95% CI 4.90-7.20) in patients with disease duration ≥34 years. Patients with an Expanded Disability Status Scale (EDSS) score ≥7 had a cumulative incidence of epilepsy of 5.3% (95% CI 3.95-7.00). Disease duration and EDSS score were associated with epilepsy after multiple logistic regression (odds ratio [OR] 1.03, 95% CI 1.01-1.04 per year, p = 0.001; and OR 1.2, 95% CI 1.09-1.26 per EDSS step, p < 0.0001).Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy. Our data suggest a direct link between severity of MS and epilepsy.
20.	Burt, Richard K., et al. (författare) Non-myeloablative hematopoietic stem cell transplantation (HSCT) is superior to disease modifying drug (DMD) treatment in highly active Relapsing Remitting Multiple Sclerosis (RRMS) : interim results of the Multiple Sclerosis International Stem cell Transplant (MIST) Randomized Trial 2018 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 90 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
21.	Buyck, P. J., et al. (författare) Diagnostic accuracy of noncontrast CT imaging markers in cerebral venous thrombosis 2019 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:8 Tidskriftsartikel (refereegranskat)abstract Objective To assess the added diagnostic value of semiquantitative imaging markers on noncontrast CT scans in cerebral venous thrombosis (CVT). Methods In a retrospective, multicenter, blinded, case-control study of patients with recent onset (<2 weeks) CVT, 3 readers assessed (1) the accuracy of the visual impression of CVT based on a combination of direct and indirect signs, (2) the accuracy of attenuation values of the venous sinuses in Hounsfield units (with adjustment for hematocrit levels), and (3) the accuracy of attenuation ratios of affected vs unaffected sinuses in comparison with reference standard MRI or CT angiography. Controls were age-matched patients with (sub)acute neurologic presentations. Results We enrolled 285 patients with CVT and 303 controls from 10 international centers. Sensitivity of visual impression of thrombosis ranged from 41% to 73% and specificity ranged from 97% to 100%. Attenuation measurement had an area under the curve (AUC) of 0.78 (95% confidence interval [CI] 0.74-0.81). After adjustment for hematocrit, the AUC remained 0.78 (95% CI 0.74-0.81). The analysis of attenuation ratios of affected vs unaffected sinuses had AUC of 0.83 (95% CI 0.8-0.86). Adding this imaging marker significantly improved discrimination, but sensitivity when tolerating a false-positive rate of 20% was not higher than 76% (95% CI 0.70-0.81). Conclusion Semiquantitative analysis of attenuation values for diagnosis of CVT increased sensitivity but still failed to identify 1 out of 4 CVT. Classification of evidence This study provides Class II evidence that visual analysis of plain CT with or without attenuation measurements has high specificity but only moderate sensitivity for CVT.
22.	Bäckström, David, et al. (författare) Early predictors of mortality in parkinsonism and Parkinson disease: A population-based study 2018 Ingår i: Neurology. - : Wolters Kluwer. - 1526-632X .- 0028-3878. ; 91:22 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To examine mortality and associated risk factors, including possible effects of mild cognitive impairment, imaging, and CSF abnormalities, in a community-based population with incident parkinsonism and Parkinson disease. METHODS: One hundred eighty-two patients with new-onset, idiopathic parkinsonism were diagnosed from January 2004 through April 2009, in a catchment area of 142,000 inhabitants in Sweden. Patients were comprehensively investigated according to a multimodal research protocol and followed prospectively for up to 13.5 years. A total of 109 patients died. Mortality rates in the general Swedish population were used to calculate standardized mortality ratio and expected survival, and Cox proportional hazard models were used to investigate independent predictors of mortality. RESULTS: The standardized mortality ratio for all patients was 1.84 (95% confidence interval 1.50-2.22, p < 0.001). Patients with atypical parkinsonism (multiple system atrophy or progressive supranuclear palsy) had the highest mortality. In early Parkinson disease, a mild cognitive impairment diagnosis, freezing of gait, hyposmia, reduced dopamine transporter activity in the caudate, and elevated leukocytes in the CSF were significantly associated with shorter survival. CONCLUSION: Although patients presenting with idiopathic parkinsonism have reduced survival, the survival is highly dependent on the type and characteristics of the parkinsonian disorder. Patients with Parkinson disease presenting with normal cognitive function seem to have a largely normal life expectancy. The finding of a subtle CSF leukocytosis in patients with Parkinson disease with short survival may have clinical implications. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
23.	Carew, J. D., et al. (författare) Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS 2011 Ingår i: Neurology. - Minneapolis, Minn : Lancet Publications Inc.. - 0028-3878 .- 1526-632X. ; 77:14, s. 1370-1375 Tidskriftsartikel (refereegranskat)abstract Objectives: It has been speculated that amyotrophic lateral sclerosis (ALS) is characterized by a premanifest period during which neurodegeneration precedes the appearance of clinical manifestations. Magnetic resonance spectroscopy (MRS) was used to measure rations of neurometabolites in the cervical spine of asymptomatic individuals with a mutation in the SOD1 gene (SOD1+) and compare their neurometabolic ratios to patients with ALS and healthy controls.Methods: A cross-sectional study of (1)H-MRS of the cervical spine was performed on 24 presymptomatic SOD1+ volunteers, 29 healthy controls, and 23 patients with ALS. All presymptomatic subjects had no symptoms of disease, normal forced vital capacity, and normal electromyographic examination. Relative concentrations of choline (Cho), creatine (Cr), myo-inositol (Myo), and N-acetylasparate (NAA) were determined.Results: NAA/Cr and NAA/Myo rations are reduced in both SOD1+ subjects (39.7%, p = 0.001 and 18.0%, p = 0.02) and patients with ALS (41.2%, p < 0.001 and 24.0%, p = 0.01) compared to controls. Myo/Cr is reduced (10.3%, p = 0.02) in SOD1+ subjects compared to controls, but no difference was found between patients with ALS and controls. By contrast, NAA/Cho is reduced in patients with ALS (24.0%, p = 0.002), but not in presymptomatic SOD1+ subjects compared to controls.Conclusions: Changes in neurometabolite ratios in the cervical spinal cord are evident in presymptomatic SOD1+ individuals in advance of symptoms and clinical or electromyographic changes in this population resemble changes observed in patients with clinically apparent ALS. This suggest that neurometabolic changed occur early in the course of the disease process.
24.	Caroli, A., et al. (författare) Mild cognitive impairment with suspected nonamyloid pathology (SNAP) Prediction of progression 2015 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 84:5, s. 508-515 Tidskriftsartikel (refereegranskat)abstract Objectives:The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI).Methods:We measured markers of amyloid pathology (CSF -amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [F-18]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A- and N+/N- based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A-N+ cases.Results:The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+, respectively; the proportion of APOE epsilon 4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N- and A+N+ groups (p 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A-N-, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N- patients did not (hazard ratio = 1.13, p = 0.771). In A+N- and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073).Conclusions:Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.
25.	Caroli, Anna, et al. (författare) Mild cognitive impairment with suspected nonamyloid pathology (SNAP) Prediction of progression 2015 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 84:5, s. 508-515 Tidskriftsartikel (refereegranskat)abstract Objectives:The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI).Methods:We measured markers of amyloid pathology (CSF -amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [F-18]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A- and N+/N- based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A-N+ cases.Results:The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+, respectively; the proportion of APOE epsilon 4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N- and A+N+ groups (p 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A-N-, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N- patients did not (hazard ratio = 1.13, p = 0.771). In A+N- and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073).Conclusions:Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.
26.	Chauhan, G., et al. (författare) Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting 2019 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:5 Tidskriftsartikel (refereegranskat)abstract ObjectiveTo explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts.MethodsWe performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI.ResultsThe mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 x 10(-8); and LINC00539/ZDHHC20, p = 5.82 x 10(-9). Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p([BI]) = 9.38 x 10(-25); p([SSBI]) = 5.23 x 10(-14) for hypertension), smoking (p([BI]) = 4.4 x 10(-10); p([SSBI]) = 1.2 x 10(-4)), diabetes (p([BI]) = 1.7 x 10(-8); p([SSBI]) = 2.8 x 10(-3)), previous cardiovascular disease (p([BI]) = 1.0 x 10(-18); p([SSBI]) = 2.3 x 10(-7)), stroke (p([BI]) = 3.9 x 10(-69); p([SSBI]) = 3.2 x 10(-24)), and MRI-defined white matter hyperintensity burden (p([BI]) = 1.43 x 10(-157); p([SSBI]) = 3.16 x 10(-106)), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p 0.0022), without indication of directional pleiotropy.ConclusionIn this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
27.	Chen, J., et al. (författare) Genome-wide association study identifies MAPT locus influencing human plasma tau levels 2017 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 88:7, s. 669-676 Tidskriftsartikel (refereegranskat)abstract Objective: To identify genetic loci associated with plasma tau concentrations in healthy elders and individuals with Alzheimer disease. Methods: Four hundred sixty-three non-Hispanic white individuals exceeding quality control criteria were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1) cohort. Association of plasma tau with genetic polymorphisms was performed with a linear regression model. Significant associations were validated in an independent replication cohort consisting of 431 healthy elders or individuals with mild cognitive impairment recruited from the University of California, San Francisco Memory and Aging Center. Results: The minor allele (A) of rs242557 in the microtubule-associated protein tau gene (MAPT) was associated with higher plasma tau levels at genome-wide significance (p = 4.85 x 10(-9), empiric family-wise error corrected p = 0.0024) in a dose-dependent fashion. This association was also observed in the replication cohort (p = 1.0 x 10(-5); joint analysis p = 1.2 x 10(-12)). Single nucleotide polymorphisms near PARK2 (rs2187213) (p = 6.15 x 10(-6)), IL2RA (rs7072793, rs7073236) (p = 7.89 x 10(-6)), and an intergenic locus on 9p21.3 (rs7047280) (p = 8.13 x 10(-6)) were identified as suggestive loci associated with plasma tau levels. Conclusions: MAPT H1c haplotype (rs242557) has previously been identified as a genetic risk factor for progressive supranuclear palsy and corticobasal degeneration. The current findings suggest that plasma tau concentration could be an endophenotype for identifying risk for 4-repeat tauopathies in older individuals.
28.	Coelho, Teresa, et al. (författare) Tafamidis for transthyretin familial amyloid polyneuropathy : A randomized, controlled trial 2012 Ingår i: Neurology. - Philadelphia : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 79:8, s. 785-792 Tidskriftsartikel (refereegranskat)abstract Objectives: To evaluate the efficacy and safety of 18 months of tafamidis treatment in patients with early-stage V30M transthyretin familial amyloid polyneuropathy (TTR-FAP). Methods: In this randomized, double-blind trial, patients received tafamidis 20 mg QD or placebo. Coprimary endpoints were the Neuropathy Impairment Score-Lower Limbs (NIS-LL) responder analysis (<2-point worsening) and treatment-group difference in the mean change from baseline in Norfolk Quality of Life-Diabetic Neuropathy total score (TQOL) in the intent-to-treat (ITT) population (n = 125). These endpoints were also evaluated in the efficacy-evaluable (EE; n = 87) population. Secondary endpoints, including changes in neurologic function, nutritional status, and TTR stabilization, were analyzed in the ITT population. Results: There was a higher-than-anticipated liver transplantation dropout rate. No differences were observed between the tafamidis and placebo groups for the coprimary endpoints, NIS-LL responder analysis (45.3% vs 29.5% responders; p = 0.068) and change in TQOL (2.0 vs 7.2; p = 0.116) in the ITT population. In the EE population, significantly more tafamidis patients than placebo patients were NIS-LL responders (60.0% vs 38.1%; p = 0.041), and tafamidis patients had better-preserved TQOL (0.1 vs 8.9; p = 0.045). Significant differences in most secondary endpoints favored tafamidis. TTR was stabilized in 98% of tafamidis and 0% of placebo patients (p < 0.0001). Adverse events were similar between groups. Conclusions: Although the coprimary endpoints were not met in the ITT population, tafamidis was associated with no trend toward more NIS-LL responders and a significant reduction in worsening of most neurologic variables, supporting the hypothesis that preventing TTR dissociation can delay peripheral neurologic impairment. Classification of evidence: This study provides Class II evidence that 20 mg tafamidis QD was associated with no difference in clinical progression in patients with TTR-FAP, as measured by the NIS-LL and the Norfolk QOL-DN score. Secondary outcomes demonstrated a significant delay in peripheral neurologic impairment with tafamidis, which was well tolerated over 18 months. Neurology (R) 2012;79:785-792
29.	Cousyn, Louis, et al. (författare) Brain MRI features and scoring of leukodystrophy in adult-onset Krabbe disease 2019 Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 93:7, s. E647-E652 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To perform a systematic analysis and scoring of brain MRI white matter hyperintensities (WMH) in adult-onset Krabbe disease.METHODS: We retrospectively collected basic clinical data and the first available brain MRI from patients with confirmed Krabbe disease with first clinical manifestations beyond 10 years of age. Data were obtained from our reference center for lysosomal diseases (n = 6) and from contacted authors of published articles describing patients with adult-onset Krabbe disease (n = 15). T2-weighted fluid-attenuated inversion recovery images of each patient were analyzed and scored using a radiologic score of WMH in a single center.RESULTS: The corticospinal tract was always affected by WMH (100% of patients), however, with some distinctions along the tract: the precentral gyrus (100%), corona radiata (95%), and posterior internal capsule (81%) were highly abnormal, whereas the mesencephalon (57%), pons (52%), and medulla oblongata (5%) were less affected. WMH were also frequently present in the posterior lateral periventricular white matter (95%), optic radiations (86%), postcentral gyrus (71%), medial lemniscus (62%), and corpus callosum, especially in the isthmus (71%), whereas the genu was always normal. A few patients did not have the classical MRI pattern but extensive hyperintensities (n = 3), or patchy distribution of hyperintensities mimicking an acquired etiology (n = 2), or very subtle hyperintensities of the corticospinal tract (n = 1).CONCLUSIONS: We specified the main locations of WMH, which were observed in the earliest stages of the disease and were also present in patients with atypical MRI pattern, highlighting the importance of radiologic features to guide the diagnosis.
30.	de Flon, Pierre, et al. (författare) Reduced inflammation in relapsing-remitting multiple sclerosis after therapy switch to rituximab 2016 Ingår i: Neurology. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 87:2, s. 141-147 Tidskriftsartikel (refereegranskat)abstract Objective: To describe the effects of switching treatment from ongoing first-line injectable therapies to rituximab on inflammatory activity measured by MRI and levels of CSF neurofilament light chain (CSF-NFL) in a cohort of patients with clinically stable relapsing-remitting multiple sclerosis (RRMS).Method: Seventy-five patients with clinically stable RRMS treated with the first-line injectables interferon-β (IFN-β) and glatiramer acetate (GA) at 3 Swedish centers were switched to rituximab in this open-label phase II multicenter study. After a run-in period of 3 months, 2 IV doses of 1,000 mg rituximab were given 2 weeks apart followed by repeated clinical assessment, MRI, and CSF-NFL for 24 months.Results: The mean cumulated number of gadolinium-enhancing lesions per patient at months 3 and 6 after treatment shift to rituximab was reduced compared to the run-in period (0.028 vs 0.36, p = 0.029). During the first year after treatment shift, the mean number of new or enlarged T2 lesions per patient was reduced (0.01 vs 0.28, p = 0.004) and mean CSF-NFL levels were reduced by 21% (p = 0.01).Conclusions: For patients with RRMS, a treatment switch from IFN or GA to rituximab is associated with reduced inflammatory activity measured by MRI and CSF-NFL.Classification of evidence: This study provides Class IV evidence that rituximab has an equal or superior effect in reducing inflammatory activity in RRMS measured by MRI and CSF-NFL compared to first-line injectables during the first year after treatment shift.
31.	Ding, Mozhu, et al. (författare) Atrial fibrillation, antithrombotic treatment, and cognitive aging : A population-based study 2018 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 91:19, s. e1732-e1740 Tidskriftsartikel (refereegranskat)abstract ObjectiveTo examine the association of atrial fibrillation (AF) with cognitive decline and dementia in old age, and to explore the cognitive benefit of antithrombotic treatment in patients with AF.MethodsThis population-based cohort study included 2,685 dementia-free participants from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001-2004 to 2010-2013. AF was ascertained from clinical examination, ECG, and patient registry. Global cognitive function was assessed using the Mini-Mental State Examination. We followed the DSM-IV criteria for the diagnosis of dementia, the NINDS-AIREN (National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences) criteria for vascular dementia, and the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer disease. Data were analyzed using multiple linear mixed-effects and Cox regression models.ResultsWe identified 243 participants (9.1%) with AF at baseline. During the 9-year follow-up period, 279 participants (11.4%) developed AF and 399 (14.9%) developed dementia. As a time-varying variable, AF was significantly associated with a faster annual Mini-Mental State Examination decline (beta coefficient = -0.24, 95% confidence interval [ CI]: -0.31 to -0.16) and an increased hazard ratio (HR) of all-cause dementia (HR = 1.40, 95% CI: 1.11-1.77) and vascular and mixed dementia (HR = 1.88, 95% CI: 1.09-3.23), but not Alzheimer disease (HR = 1.33, 95% CI: 0.92-1.94). Among people with either prevalent or incident AF, use of anticoagulant drugs, but not antiplatelet treatment, was associated with a 60% decreased risk of dementia (HR = 0.40, 95% CI: 0.18-0.92).Conclusion AF is associated with a faster global cognitive decline and an increased risk of dementia in older people. Use of anticoagulant drugs may reduce dementia risk in patients with AF.
32.	Dintica, Christina S., et al. (författare) Impaired olfaction is associated with cognitive decline and neurodegeneration in the brain 2019 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 92:7, s. e700-e709 Tidskriftsartikel (refereegranskat)abstract ObjectiveWe aimed to examine whether impaired olfaction is associated with cognitive decline and indicators of neurodegeneration in the brain of dementia-free older adults.MethodsWithin the Rush Memory and Aging Project, 380 dementia-free participants (mean age = 78 years) were followed for up to 15 years, and underwent MRI scans. Olfactory function was assessed using the Brief Smell Identification Test (B-SIT) at baseline, and categorized as anosmia (B-SIT <6), hyposmia (B-SIT 6-10 in men and 6-10.25 in women), and normal (B-SIT 10.25-12 in men and 10.5-12 in women). Cognitive function was annually assessed with a battery of 21 tests, from which composite scores were derived. Structural total and regional brain volumes were estimated. Data were analyzed using linear regression and mixed-effects models.ResultsAt study entry, 138 (36.3%) had normal olfactory function, 213 (56.1%) had hyposmia, and 29 (7.6%) had anosmia. In multiadjusted mixed-effects models, hyposmia (beta = -0.03, 95% confidence interval [CI] -0.05 to -0.02) and anosmia (beta = -0.13, 95% CI -0.16 to -0.09) were associated with faster rate of cognitive decline compared to normal olfaction. On MRI, impaired olfaction (hyposmia or anosmia) was related to smaller volumes of the hippocampus (beta = -0.19, 95% CI -0.33 to -0.05), and in the entorhinal (beta = -0.16, 95% CI -0.24 to -0.08), fusiform (beta = -0.45, 95% CI -0.78 to -0.14), and middle temporal (beta = -0.38, 95% CI -0.72 to -0.01) cortices.ConclusionImpaired olfaction predicts faster cognitive decline and might indicate neurodegeneration in the brain among dementia-free older adults.
33.	Edelvik, Anna, et al. (författare) Long-term outcomes of epilepsy surgery in Sweden A national prospective and longitudinal study 2013 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 81:14, s. 1244-1251 Tidskriftsartikel (refereegranskat)abstract Objective: To investigate prospective, population-based long-term outcomes concerning seizures and antiepileptic drug (AED) treatment after resective epilepsy surgery in Sweden. Methods: Ten-and 5-year follow-ups were performed in 2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to 1997 and 2000 to 2002, respectively. All patients had been prospectively followed in the Swedish National Epilepsy Surgery Register. Ninety-three patients, who were presurgically evaluated but not operated, served as controls. Results: In the long term (mean 7.6 years), 62% of operated adults and 50% of operated children were seizure-free, compared to 14% of nonoperated adults (p < 0.001) and 38% of nonoperated children (not significant). Forty-one percent of operated adults and 44% of operated children had sustained seizure freedom since surgery, compared to none of the controls (p < 0.0005). Multivariate analysis identified >= 30 seizures/month at baseline and long epilepsy duration as negative predictors and positive MRI to be a positive predictor of long-term seizure-free outcome. Ten years after surgery, 86% of seizure-free children and 43% of seizure-free adults had stopped AEDs in the surgery groups compared to none of the controls (p < 0.0005). Conclusions: This population-based, prospective study shows good long-term seizure outcomes after resective epilepsy surgery. The majority of the patients who are seizure-free after 5 and 10 years have sustained seizure freedom since surgery. Many patients who gain seizure freedom can successfully discontinue AEDs, more often children than adults. Classification of evidence: This study provides Class III evidence that more patients are seizure-free and have stopped AED treatment in the long term after resective epilepsy surgery than nonoperated epilepsy patients.
34.	Edelvik, Anna, 1971, et al. (författare) Prospective and longitudinal long-term employment outcomes after resective epilepsy surgery 2015 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 85:17, s. 1482-1490 Tidskriftsartikel (refereegranskat)abstract Objective:To investigate long-term employment outcomes after resective epilepsy surgery in a national population-based cohort of adults.Methods:In the Swedish National Epilepsy Surgery Register, all adults who were operated with resective epilepsy surgery from 1995 to 2010 were identified. Two-year follow-up was available for 473/496, 5-year follow-up for 220/240, 10-year follow-up for 240/278, and 15-year follow-up for 85/109 patients.Results:There were no significant changes in employment outcome over time at group level, but for those with full-time employment at baseline, 79%, 79%, 57%, and 47% of seizure-free patients were in full-time work at 2-, 5-, 10-, and 15-year follow-up, compared to patients with benefits at baseline, where 16%, 27%, 31%, and 33% of seizure-free patients worked full time at these time points (p = 0.018 at 10 years). More patients with full-time work had ability to drive, a family of their own, and higher educational status than patients in part-time work or on benefits. Univariate predictors for employment at long term were having employment preoperatively, higher education, favorable seizure outcome, male sex, and younger age at surgery. Multivariate predictors were having employment preoperatively, favorable seizure outcome, and younger age.Conclusions:The best vocational outcomes occurred in seizure-free patients who were employed or students at baseline, which may reflect a higher general psychosocial level of function. Younger age also predicted better employment outcomes and it therefore seems plausible that early referral for surgery could contribute to better vocational outcomes.
35.	Edelvik, Anna, et al. (författare) Prospective and longitudinal long-term employment outcomes after resective epilepsy surgery 2015 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 85:17, s. 1482-1490 Tidskriftsartikel (refereegranskat)abstract Objective:To investigate long-term employment outcomes after resective epilepsy surgery in a national population-based cohort of adults.Methods:In the Swedish National Epilepsy Surgery Register, all adults who were operated with resective epilepsy surgery from 1995 to 2010 were identified. Two-year follow-up was available for 473/496, 5-year follow-up for 220/240, 10-year follow-up for 240/278, and 15-year follow-up for 85/109 patients.Results:There were no significant changes in employment outcome over time at group level, but for those with full-time employment at baseline, 79%, 79%, 57%, and 47% of seizure-free patients were in full-time work at 2-, 5-, 10-, and 15-year follow-up, compared to patients with benefits at baseline, where 16%, 27%, 31%, and 33% of seizure-free patients worked full time at these time points (p = 0.018 at 10 years). More patients with full-time work had ability to drive, a family of their own, and higher educational status than patients in part-time work or on benefits. Univariate predictors for employment at long term were having employment preoperatively, higher education, favorable seizure outcome, male sex, and younger age at surgery. Multivariate predictors were having employment preoperatively, favorable seizure outcome, and younger age.Conclusions:The best vocational outcomes occurred in seizure-free patients who were employed or students at baseline, which may reflect a higher general psychosocial level of function. Younger age also predicted better employment outcomes and it therefore seems plausible that early referral for surgery could contribute to better vocational outcomes.
36.	Ekblad, Laura L., et al. (författare) Midlife insulin resistance, APOE genotype, and late-life brain amyloid accumulation 2018 Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 90:13, s. e1150-e1157 Tidskriftsartikel (refereegranskat)abstract Objective To examine whether midlife insulin resistance is an independent risk factor for brain amyloid accumulation in vivo after 15 years, and whether this risk is modulated by APOE epsilon 4 genotype. Methods This observational study examined 60 elderly volunteers without dementia (mean age at baseline 55.4 and at follow-up 70.9 years, 55.5% women) from the Finnish population-based, nationwide Health2000 study with [C-11]Pittsburgh compound B-PET imaging in 2014-2016. The participants were recruited according to their homeostatic model assessment of insulin resistance (HOMA-IR) values in the year 2000, and their APOE epsilon 4 genotype. The exposure group (IR+, n = 30) consisted of individuals with HOMA-IR > 2.17 at baseline (highest tertile of the Health2000 study population), and the control group (IR-, n = 30) consisted of individuals with HOMA-IR < 1.25 at baseline (lowest tertile). The groups were enriched for APOE epsilon 4 carriers, resulting in 50% (n = 15) APOE epsilon 4 carriers in both groups. Analyses were performed with multivariate logistic and linear regression. Results An amyloid-positive PET scan was found in 33.3% of the IR-group and 60.0% of the IR+ group (odds ratio 3.0, 95% confidence interval 1.1-8.9, p = 0.04). The increased risk was seen in carriers and noncarriers of APOE epsilon 4 genotype. Higher midlife, but not late-life continuous HOMA-IR was associated with a greater brain amyloid burden at follow-up after multivariate adjustments for other cognitive and metabolic risk factors (ss = 0.11, 95% confidence interval 0.002-0.22, p = 0.04). Conclusions These results indicate that midlife insulin resistance is an independent risk factor for brain amyloid accumulation in elderly individuals without dementia.
37.	Erickson, C. M., et al. (författare) KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD 2019 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:16 Tidskriftsartikel (refereegranskat)abstract Objective To examine whether the KLOTHO gene variant KL-VS attenuates APOE4-associated beta-amyloid (A beta) accumulation in a late-middle-aged cohort enriched with Alzheimer disease (AD) risk factors. Three hundred nine late-middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center were genotyped to determine KL-VS and APOE4 status and underwent CSF sampling (n = 238) and/or 11C-Pittsburgh compound B (PiB)-PET imaging (n = 183). Covariate-adjusted regression analyses were used to investigate whether APOE4 exerted expected effects on A beta burden. Follow-up regression analyses stratified by KL-VS genotype (i.e., noncarrier vs heterozygous; there were no homozygous individuals) evaluated whether the influence of APOE4 on A beta was different among KL-VS heterozygotes compared to noncarriers. APOE4 carriers exhibited greater A beta burden than APOE4-negative participants. This effect was stronger in CSF (t = -5.12, p < 0.001) compared with PiB-PET (t = 3.93, p < 0.001). In the stratified analyses, this APOE4 effect on A beta load was recapitulated among KL-VS noncarriers (CSF: t = -5.09, p < 0.001; PiB-PET: t = 3.77, p < 0.001). In contrast, among KL-VS heterozygotes, APOE4-positive individuals did not exhibit higher A beta burden than APOE4-negative individuals (CSF: t = -1.03, p = 0.308; PiB-PET: t = 0.92, p = 0.363). These differential APOE4 effects remained after KL-VS heterozygotes and noncarriers were matched on age and sex. In a cohort of at-risk late-middle-aged adults, KL-VS heterozygosity was associated with an abatement of APOE4-associated A beta aggregation, suggesting KL-VS heterozygosity confers protections against APOE4-linked pathways to disease onset in AD.
38.	Eriksson, Hanna, et al. (författare) Family history increases the risk of late seizures after stroke 2019 Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1526-632X .- 0028-3878. ; 93:21 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To assess the association between a family history of epilepsy and risk of late poststroke seizures (LPS). METHODS: This register-based cohort study was based on adult patients from the Swedish Stroke Register (Riksstroke) with stroke from 2001 to 2012 and no prior epilepsy. LPS (>7 days after stroke) and epilepsy were ascertained in cases and in their first-degree biological relatives by cross-referencing Riksstroke, the Multi-Generation Register, and the National Patient Register. RESULTS: Of 86,550 patients with stroke, a family history of epilepsy was detected in 7,433 (8.6%), and LPS (>7 days after stroke) occurred in 7,307 (8.4%). The survival-adjusted risk of LPS was higher in patients with compared to those without a family history of epilepsy: 6.8% (95% confidence interval [CI] 6.2%-7.4%) vs 5.9% (95% CI 5.7%-6.1%) at 2 years and 9.5% (95% CI 8.7%-10.3%) vs 8.2% (95% CI 8.0%-8.4%) at 5 years. In a Cox model adjusted for age, sex, and stroke type, the hazard ratio (HR) for LPS in patients with stroke with ≥1 relative with epilepsy was 1.18 (95% CI 1.09-1.28). The increased HR remained significant with adjustments for stroke severity and in multiple sensitivity analyses. A higher risk for patients with stroke with >1 relative with epilepsy was also seen but was not significant in all Cox models. CONCLUSIONS: Although stroke characteristics remain the most important risk factors for LPS, having a first-degree relative with epilepsy also increases the risk in a multivariate analysis. The findings highlight the need for family history assessment in patients with stroke and the need for future studies on genetic vulnerability and environmental factors that may aid in the identification of at-risk individuals. © 2019 American Academy of Neurology.
39.	Eriksson, Marie, et al. (författare) Poststroke suicide attempts and completed suicides : a socioeconomic and nationwide perspective 2015 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 84:17, s. 1732-1738 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: We examined attempted and completed suicides after stroke to determine whether they were associated with socioeconomic status, other patient characteristics, or time after stroke.METHODS: This nationwide cohort study included stroke patients from Riksstroke (the Swedish Stroke Register) from 2001 to 2012. We used personal identification numbers to link the Riksstroke data with other national registers. Suicide attempts were identified by a record of hospital admission for intentional self-harm (ICD-10: X60-X84), and completed suicides were identified in the national Cause of Death Register. We used multiple Cox regression to analyze time from stroke onset to first suicide attempt.RESULTS: We observed 220,336 stroke patients with a total follow-up time of 860,713 person-years. During follow-up, there were 1,217 suicide attempts, of which 260 were fatal. This was approximately double the rate of the general Swedish population. Patients with lower education or income (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.11-1.68) for primary vs university and patients living alone (HR 1.73, 95% CI 1.52-1.97) had an increased risk of attempted suicide, and patients born outside of Europe had a lower risk compared to patients of European origin. Male sex, young age, severe stroke, and poststroke depression were other factors associated with an increased risk of attempted suicide after stroke. The risk was highest during the first 2 years after stroke.CONCLUSIONS: Both clinical and socioeconomic factors increase the risk of poststroke suicide attempts. This suggests a need for psychosocial support and suicide preventive interventions in high-risk groups of stroke patients.
40.	Fazekas, Franz, et al. (författare) MRI in acute cerebral ischemia of the young: The Stroke in Young Fabry Patients (sifap1) Study. 2013 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 81:22, s. 1914-1921 Tidskriftsartikel (refereegranskat)abstract We focused on cerebral imaging findings in a large cohort of young patients with a symptomatic ischemic cerebrovascular event (CVE) to extract relevant pathophysiologic and clinical information.
41.	Feldman, H H, et al. (författare) Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease : LEADe 2010 Ingår i: Neurology. - Minneapolis ; New York : Lancet ; Ovid. - 0028-3878 .- 1526-632X. ; 74:12, s. 956-964 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: There is some evidence that statins may have a protective and symptomatic benefit in Alzheimer disease (AD). The LEADe study is a randomized controlled trial (RCT) evaluating the efficacy and safety of atorvastatin in patients with mild to moderate AD.METHODS: This was an international, multicenter, double-blind, randomized, parallel-group study. Subjects had mild to moderate probable AD (Mini-Mental State Examination score 13-25), were aged 50-90 years, and were taking donepezil 10 mg daily for > or 3 months prior to screening. Entry low-density lipoprotein cholesterol levels (LDL-C) were > 95 and < 195 mg/dL. Patients were randomized to atorvastatin 80 mg/day or placebo for 72 weeks followed by a double-blind, 8-week atorvastatin withdrawal phase. Coprimary endpoints were changes in cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog]) and global function (Alzheimer's Disease Cooperative Study Clinical Global Impression of Change [ADCS-CGIC]) at 72 weeks.RESULTS: A total of 640 patients were randomized in the study. There were no significant differences in the coprimary endpoints of ADAS-cog or ADCS-CGIC or the secondary endpoints. Atorvastatin was generally well-tolerated.CONCLUSIONS: In this large-scale randomized controlled trial evaluating statin therapy as a treatment for mild to moderate Alzheimer disease, atorvastatin was not associated with significant clinical benefit over 72 weeks. This treatment was generally well-tolerated without unexpected adverse events. Classification of evidence: This study provides Class II evidence that intensive lipid lowering with atorvastatin 80 mg/day in patients with mild to moderate probable Alzheimer disease (aged 50-90), taking donepezil, with low-density lipoprotein cholesterol levels between 95 and 195 mg/dL over 72 weeks does not benefit cognition (as measured by Alzheimer's Disease Assessment Scale-Cognitive Subscale) (p = 0.26) or global function (as measured by Alzheimer's Disease Cooperative Study Clinical Global Impression of Change) (p = 0.73) compared with placebo.
42.	Flam, B, et al. (författare) Authors' Response 2015 Ingår i: Journal of intensive care medicine. - : SAGE Publications. - 1525-1489 .- 0885-0666. ; 52:1, s. 493-4 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
43.	Gallo, Valentina, et al. (författare) Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: The EPIC cohort. 2013 Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 1526-632X .- 0028-3878. ; 80:9, s. 829-838 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: The aim of this study was to investigate for the first time the association between body fat and risk of amyotrophic lateral sclerosis (ALS) with an appropriate prospective study design. METHODS: The EPIC (European Prospective Investigation into Cancer and Nutrition) study included 518,108 individuals recruited from the general population across 10 Western European countries. At recruitment, information on lifestyle was collected and anthropometric characteristics were measured. Cox hazard models were fitted to investigate the associations between anthropometric measures and ALS mortality. RESULTS: Two hundred twenty-two ALS deaths (79 men and 143 women) occurred during the follow-up period (mean follow-up = 13 years). There was a statistically significant interaction between categories of body mass index and sex regarding ALS risk (p = 0.009): in men, a significant linear decrease of risk per unit of body mass index was observed (hazard ratio = 0.93, 95% confidence interval 0.86-0.99 per kg/m(2)); among women, the risk was more than 3-fold increased for underweight compared with normal-weight women. Among women, a significant risk reduction increasing the waist/hip ratio was also evident: women in the top quartile had less than half the risk of ALS compared with those in the bottom quartile (hazard ratio = 0.48, 95% confidence interval 0.25-0.93) with a borderline significant p value for trend across quartiles (p = 0.056). CONCLUSION: Increased prediagnostic body fat is associated with a decreased risk of ALS mortality.
44.	Gensicke, H., et al. (författare) Intravenous thrombolysis and platelet count 2018 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 90:8 Tidskriftsartikel (refereegranskat)abstract ObjectiveTo study the effect of platelet count (PC) on bleeding risk and outcome in stroke patients treated with IV thrombolysis (IVT) and to explore whether withholding IVT in PC < 100 x 10(9)/L is supported.MethodsIn this prospective multicenter, IVT register-based study, we compared PC with symptomatic intracranial hemorrhage (sICH; Second European-Australasian Acute Stroke Study [ECASS II] criteria), poor outcome (modified Rankin Scale score 3-6), and mortality at 3 months. PC was used as a continuous and categorical variable distinguishing thrombocytopenia (<150 x 10(9)/L), thrombocytosis (>450 x 10(9)/L), and normal PC (150-450 x 10(9)/L [reference group]). Moreover, PC < 100 x 10(9)/L was compared to PC 100 x 10(9)/L. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) from the logistic regression models were calculated.ResultsAmong 7,533 IVT-treated stroke patients, 6,830 (90.7%) had normal PC, 595 (7.9%) had thrombocytopenia, and 108 (1.4%) had thrombocytosis. Decreasing PC (every 10 x 10(9)/L) was associated with increasing risk of sICH (ORadjusted 1.03, 95% CI 1.02-1.05) but decreasing risk of poor outcome (ORadjusted 0.99, 95% CI 0.98-0.99) and mortality (ORadjusted 0.98, 95% CI 0.98-0.99). The risk of sICH was higher in patients with thrombocytopenic than in patients with normal PC (ORadjusted 1.73, 95% CI 1.24-2.43). However, the risk of poor outcome (ORadjusted 0.89, 95% CI 0.39-1.97) and mortality (ORadjusted 1.09, 95% CI 0.83-1.44) did not differ significantly. Thrombocytosis was associated with mortality (ORadjusted 2.02, 95% CI 1.21-3.37). Forty-four (0.3%) patients had PC < 100 x 10(9)/L. Their risks of sICH (ORunadjusted 1.56, 95% CI 0.48-5.07), poor outcome (ORadjusted 1.63, 95% CI 0.82-3.24), and mortality (ORadjusted 1.38, 95% CI 0.64-2.98) did not differ significantly from those of patients with PC 100 x 10(9)/L.ConclusionLower PC was associated with increased risk of sICH, while higher PC indicated increased mortality. Our data suggest that PC modifies outcome and complications in individual patients, while withholding IVT in all patients with PC < 100 x 10(9)/L is challenged.
45.	Gonzalez-Perez, Antonio, et al. (författare) Mortality after hemorrhagic stroke Data from general practice (The Health Improvement Network) 2013 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 81:6, s. 559-565 Tidskriftsartikel (refereegranskat)abstract Objective: To investigate short-term case fatality and long-term mortality after intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) using data from The Health Improvement Network database. Methods: Thirty-day case fatality was stratified by age, sex, and calendar year after ICH and SAH using logistic regression. Cox proportional hazards regression analyses were used to estimate the risk of death during the first year of follow-up and survivors at 1 year. Results: Case fatality after ICH was 42.0%, compared with 28.7% after SAH. It increased with age (ICH: 29.7% for 20-49 years, 54.6% for 80-89 years; SAH: 20.3% for 20-49 years, 56.7% for 80-89 years; both p-trend < 0.001), and decreased over the period 2000-2001 to 2006-2008 (ICH: from 53.1% to 35.8%, p-trend < 0.001; SAH: from 33.3% to 24.7%, p-trend = 0.02). Risk of death was significantly higher among stroke patients during the first year of follow-up compared with controls (ICH: hazard ratio [HR] 2.60, 95% confidence interval [CI] 2.09-3.24, p < 0.01; SAH: HR 2.87,95% CI 2.07-3.97, p < 0.01) and remained elevated among survivors at 1 year (ICH: HR 2.02, 95% CI 1.75-2.32, p < 0.01; SAH: HR 1.32, 95% CI 1.02-1.69, p = 0.03). Conclusions: More than one-third of individuals die in the first month after hemorrhagic stroke, and patients younger than 50 years are more likely to die after ICH than SAH. Short-term case fatality has decreased over time. Patients who survive hemorrhagic stroke have a continuing elevated risk of death compared with matched individuals from the general population.
46.	Gorram, Farida, et al. (författare) Variation of Penetrance estimates in a wide spectrum of TTR-FAP families : implication for management of carriers 2018 Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 90 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Objective: Refine estimation of penetrance in TTR-FAP families, unravelling the role of covariates. Background: TTR-FAP is an autosomal dominant neuropathy caused by mutations in the TTR gene. Recently, therapeutic advances including gene modifying approaches proved effective to halt disease progression. Val30Met, the most common variant in Portugal and Latin America is associated to age at onset (AO) below 50 y-o. In Western Europe, US, Japan, heterogeneity of TTR variants is associated to AO above 50 y-o, a mixed polyneuropathy and cardiomyopathy. Determining the risk of being affected (penetrance) is essential to guide gene carrier management.Design/Methods: NPSE is a non-parametric method developed to estimate penetrance, taking into account covariates. Genealogical data from 227 kindreds were collected. There were 92 Val30Met families from Sweden, 64 Val30Met from Portugal and 73 from France including 37 Val30Met and 36 families carrying other TTR variants frequently identified: Ser77Tyr (15), Ile107Val (12), Ser77Phe (9).Results: We found highly significant differences of penetrance between Val30Met families from various origins. Risk estimates also differed between the TTR variants (French Val30Met, Ser77Tyr, Ile107Val, Ser77Phe) (p < 0.004). In the French and Swedish Val30Met families, the disease risk remained below 10% until age 40 years then increased to 72% and 63% at 80 years, respectively. In Portuguese families, the risk was above 20% from age 30 years then up to 92% at 80 y-o. In Ile107Val, Ser77Tyr and Ser77Phe families the risk was virtually null until 50 years of age and raised to 54%, 70%, and 86% at age 80 years, respectively. A higher risk is observed when the disease is maternally inherited in Portuguese and Swedish kindreds (p <0.001).Conclusions: Important variation of penetrance is observed in TTR-FAP families according covariates. Such data will help for management of gene carriers, allowing early diagnosis and therapeutic initiation timely.
47.	Gustafsson, Helena, et al. (författare) Depression and subsequent risk of Parkinson disease : A nationwide cohort study 2015 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 84:24, s. 2422-2429 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To investigate the long-term risk of Parkinson disease (PD) after depression and evaluate potential confounding by shared susceptibility to the 2 diagnoses.METHODS: The nationwide study cohort included 140,688 cases of depression, matched 1:3 using a nested case-control design to evaluate temporal aspects of study parameters (total, n = 562,631). Potential familial coaggregation of the 2 diagnoses was investigated in a subcohort of 540,811 sibling pairs. Associations were investigated using multivariable adjusted statistical models.RESULTS: During a median follow-up period of 6.8 (range, 0-26.0) years, 3,260 individuals in the cohort were diagnosed with PD. The multivariable adjusted odds ratio (OR) for PD was 3.2 (95% confidence interval [CI], 2.5-4.1) within the first year of depression, decreasing to 1.5 (95% CI, 1.1-2.0) after 15 to 25 years. Among participants with depression, recurrent hospitalization was an independent risk factor for PD (OR, 1.4; 95% CI, 1.1-1.9 for ≥5 vs 1 hospitalization). In family analyses, siblings' depression was not significantly associated with PD risk in index persons (OR, 1.1; 95% CI, 0.9-1.4).CONCLUSIONS: The time-dependent effect, dose-response pattern for recurrent depression, and lack of evidence for coaggregation among siblings all indicate a direct association between depression and subsequent PD. Given that the association was significant for a follow-up period of more than 2 decades, depression may be a very early prodromal symptom of PD, or a causal risk factor.
48.	Gustafsson, Helena, et al. (författare) Low muscle strength in late adolescence and Parkinson disease later in life 2015 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 84:18, s. 1862-1869 Tidskriftsartikel (refereegranskat)abstract Objective:To evaluate maximal isometric muscle force at 18 years of age in relation to Parkinson disease (PD) later in life.Methods:The cohort consisted of 1,317,713 men who had their muscle strength measured during conscription (1969-1996). Associations between participants' muscle strength at conscription and PD diagnoses, also in their parents, were examined using multivariate statistical models.Results:After adjustment for confounders, the lowest compared to the highest fifth of handgrip strength (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.06-1.79), elbow flexion strength (HR 1.34, 95% CI 1.02-1.76), but not knee extension strength (HR 1.24, 95% CI 0.94-1.62) was associated with an increased risk of PD during follow-up. Furthermore, men whose parents were diagnosed with PD had reduced handgrip (fathers: mean difference [MD] -5.7 N [95% CI -7.3 to -4.0]; mothers: MD -5.0 N [95% CI -7.0 to -2.9]) and elbow flexion (fathers: MD -4.3 N [95% CI -5.7 to -2.9]; mothers: MD -3.9 N [95% CI -5.7 to -2.2]) strength, but not knee extension strength (fathers: MD -1.1 N [95% CI -2.9 to 0.8]; mothers: MD -0.7 N [95% CI -3.1 to 1.6]), than those with no such familial history.Conclusions:Maximal upper extremity voluntary muscle force was reduced in late adolescence in men diagnosed with PD 30 years later. The findings suggest the presence of subclinical motor deficits 3 decades before the clinical onset of PD.
49.	Hansson, Oskar, et al. (författare) Blood-based NfL : A biomarker for differential diagnosis of parkinsonian disorder 2017 Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 88:10, s. 930-937 Tidskriftsartikel (refereegranskat)abstract Objective: To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders. Methods: The study included 3 independent prospective cohorts: the Lund (n = 278) and London (n = 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n = 109) of patients with PD, PSP, MSA, or CBS with disease duration ≤3 years. Blood NfL concentration was measured using an ultrasensitive single molecule array (Simoa) method, and the diagnostic accuracy to distinguish PD from APD was investigated. Results: We found strong correlations between blood and CSF concentrations of NfL (ρ ≥ 0.73-0.84, p ≤ 0.001). Blood NfL was increased in patients with MSA, PSP, and CBS (i.e., all APD groups) when compared to patients with PD as well as healthy controls in all cohorts (p < 0.001). Furthermore, in the Lund cohort, blood NfL could accurately distinguish PD from APD (area under the curve [AUC] 0.91) with similar results in both the London cohort (AUC 0.85) and the early disease cohort (AUC 0.81). Conclusions: Quantification of blood NfL concentration can be used to distinguish PD from APD. Blood-based NfL might consequently be included in the diagnostic workup of patients with parkinsonian symptoms in both primary care and specialized clinics. Classification of evidence: This study provides Class III evidence that blood NfL levels discriminate between PD and APD.
50.	Hedström, Anna Karin, et al. (författare) Organic solvents and MS susceptibility Interaction with MS risk HLA genes 2018 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 91:5, s. E455-E462 Tidskriftsartikel (refereegranskat)abstract Objective We hypothesize that different sources of lung irritation may contribute to elicit an immune reaction in the lungs and subsequently lead to multiple sclerosis (MS) in people with a genetic susceptibility to the disease. We aimed to investigate the influence of exposure to organic solvents on MS risk, and a potential interaction between organic solvents and MS risk human leukocyte antigen (HLA) genes. Methods Using a Swedish population-based case-control study (2,042 incident cases of MS and 2,947 controls), participants with different genotypes, smoking habits, and exposures to organic solvents were compared regarding occurrence of MS, by calculating odds ratios with 95% confidence intervals using logistic regression. A potential interaction between exposure to organic solvents and MS risk HLA genes was evaluated by calculating the attributable proportion due to interaction. Results Overall, exposure to organic solvents increased the risk of MS (odds ratio 1.5, 95% confidence interval 1.2-1.8, p = 0.0004). Among both ever and never smokers, an interaction between organic solvents, carriage of HLA-DRB115, and absence of HLA-A02 was observed with regard to MS risk, similar to the previously reported gene-environment interaction involving the same MS risk HLA genes and smoke exposure. Conclusion The mechanism linking both smoking and exposure to organic solvents to MS risk may involve lung inflammation with a proinflammatory profile. Their interaction with MS risk HLA genes argues for an action of these environmental factors on adaptive immunity, perhaps through activation of autoaggressive cells resident in the lungs subsequently attacking the CNS.

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