Professor Michael Nilsson

© 2017, © 2017 World Stroke Organization. Stroke recovery research involves distinct biological and clinical targets compared to the study of acute stroke. Guidelines are proposed for the pre-clinical modeling of stroke recovery and for the alignment of pre-clinical studies to clinical trials in stroke recovery.

© 2017 The Authors Motor function may be enhanced if aerobic exercise is paired with motor training. One potential mechanism is that aerobic exercise increases levels of brain-derived neurotrophic factor (BDNF), which is important in neuroplasticity and involved in motor learning and motor memory consolidation. This study will examine the feasibility of a parallel-group assessor-blinded randomised controlled trial investigating whether task-specific training preceded by aerobic exercise improves upper limb function more than task-specific training alone, and determine the effect size of changes in primary outcome measures. People with upper limb motor dysfunction after stroke will be allocated to either task-specific training or aerobic exercise and consecutive task-specific training. Both groups will perform 60 hours of task-specific training over 10 weeks, comprised of 3 × 1 hour sessions per week with a therapist and 3 × 1 hours of home-based self-practice per week. The combined intervention group will also perform 30 minutes of aerobic exercise (70¿85%HR max ) immediately prior to the 1 hour of task-specific training with the therapist. Recruitment, adherence, retention, participant acceptability, and adverse events will be recorded. Clinical outcome measures will be performed pre-randomisation at baseline, at completion of the training program, and at 1 and 6 months follow-up. Primary clinical outcome measures will be the Action Research Arm Test (ARAT) and the Wolf Motor Function Test (WMFT). If aerobic exercise prior to task-specific training is acceptable, and a future phase 3 randomised controlled trial seems feasible, it should be pursued to determine the efficacy of this combined intervention for people after stroke.

© The Author(s) 2016. Focal hyperperfusion after acute ischaemic stroke could be of prognostic value depending upon its spatial localisation and temporal dynamics. Factors associated with late stage (12-24 h) perilesional hyperperfusion, identified using arterial spin labelling, are poorly defined. A prospective cohort of acute ischaemic stroke patients presenting within 4.5 h of symptom onset were assessed with multi-modal computed tomography acutely and magnetic resonance imaging at 24 ± 8 h. Multivariate logistic regression analysis and receiver operating characteristics curves were used. One hundred and nineteen hemispheric acute ischaemic stroke patients (mean age = 71 ± 12 years) with 24 h arterial spin labelling imaging were included. Forty-Two (35.3%) patients showed perilesional hyperperfusion on arterial spin labelling at 24 h. Several factors were independently associated with perilesional hyperperfusion: good collaterals (71% versus 29%, P < 0.0001; OR = 5, 95% CI = [1.6, 15.7], P = 0.005), major reperfusion (81% versus 48%, P = < 0.0001; OR = 7.5, 95% CI = [1.6, 35.1], P = 0.01), penumbral salvage (76.2% versus 47%, P = 0.002; OR = 6.6, 95% CI = [1.8, 24.5] , P = 0.004), infarction in striatocapsular (OR = 9.5, 95% CI = [2.6, 34], P = 0.001) and in cortical superior division middle cerebral artery (OR = 4.7, 95% CI = [1.4, 15.7] , P = 0.012) territory. The area under the receiver operating characteristic curve was 0.91. Our results demonstrate good arterial collaterals, major reperfusion, penumbral salvage, and infarct topographies involving cortical superior middle cerebral artery and striatocapsular are associated with perilesional hyperperfusion.

© The Author(s) 2016. Evaluation of the venous system may be useful in stroke prognostication and patient selection for acute intervention strategies. We report a novel phenomenon, delayed-late venous phase cortical vein filling, observed on dynamic computed tomography angiography obtained using multidetector computed tomography scanner, in acute ischemic stroke patients. The aim of this study was to examine the frequency of delayed-late venous phase cortical vein filling and assess its association to baseline collateral status. Dynamic computed tomography angiography images of acute ischemic stroke patients, being assessed for reperfusion therapy, were prospectively studied. Delayed-late venous phase cortical vein filling was defined by late venous phase opacification of cortical veins despite contrast clearance from contralateral cortical veins on dynamic computed tomography angiography. Time to peak of maximum arterial enhancement was recorded. A total of 117 patients (mean age = 70.6 ± 13.3 years; males = 48%) with hemispheric ischemic stroke who underwent acute dynamic computed tomography angiography were included in the study. Overall, 56 (48%) demonstrated delayed-late venous phase cortical vein filling. Poor collateralization (OR = 13.50; 95% CI = (4.2, 43); p = 0.0001) and longer time to peak of maximum arterial enhancement (OR = 3.2; 95% CI = (1.96, 5.3); p= 0.0001) were positively associated with delayed-late venous phase cortical vein filling. Delayed-late venous phase cortical vein filling was independently associated with poor baseline collateral status (75% vs. 15%, p = 0.0001; OR = 14.38; 95% CI = (4.33, 47.8); p = 0.0001). Delayed-late venous phase cortical vein filling is frequently seen in patients with acute ischemic stroke and is associated with poor baseline collateralization.

© 2015 Informa Healthcare. Conclusion: The new mattress and pillow for prone positioning (MPP) is efficient in reducing the apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) in most patients with obstructive sleep apnoea (OSA), with satisfactory compliance. Objective: The aim of the present study was to evaluate the effect of the prone body and head sleep position on severity of disease in patients with OSA after 4 weeks of adaptation to a mattress and pillow facilitating prone positioning. Methods: Fourteen patients with mild to severe OSA, 11 men and 3 women with a mean AHI of 26 (min, 6; max, 53) and mean ODI of 21 (min, 6; max, 51) were evaluated. Two polysomnographic (PSG) studies were performed. The first PSG study was without any treatment and the second was after 4 weeks of adaptation to the MPP for prone positioning of the body and the head. Results: Mean AHI and ODI decreased from 26 and 21 to 8 and 7, respectively (p < 0.001) with treatment. The mean time spent in the supine position was reduced from 128 to 10 min (p = 0.02) and the prone time increased from 42 to 174 min (p = 0.02) with the MPP. The mean total sleep time was 390 min during the first PSG study night without treatment and 370 min during the second night with the MPP (p = 0.7). Ten patients (71%) reduced their AHI by at least 50% and reached a value < 10 during treatment. All patients managed to sleep on the MPP for > 4 h per night during the 4-week study.

© 2015 IBRO. Sickness behaviors have become the focus of great interest in recent years as they represent a clear case of how peripheral disturbances in immune signaling can disrupt quite complex behaviors. In the current study, we were interested in examining whether we could identify any significant morphological disturbances in microglia associated with these sickness-like behaviors in adult male Sprague-Dawley rats. We chose lipopolysaccharide (LPS 100 µg/kg/i.p.), to induce sickness-like behaviors as it is the most well-validated approach to do so in rodents and humans. We were particularly interested in examining changes in microglia within the prefrontal cortex (PFC) as several recent neuroimaging studies have highlighted significant functional changes in this region following peripheral LPS administration. Paraformaldehyde-fixed tissue was collected from animals 24 h post LPS administration and labeled immunohistochemically with an antibody directed to bind to Iba-1, a protein known to be involved in the structural remodeling of microglia. To analyze changes, we have made use of two recently described image analysis procedures. The first is known as cumulative threshold spectra (CTS) analysis. The second involves the unsupervised digital reconstruction of microglia. We undertook these complementary analysis of microglial cells in the both the pre- and infralimbic divisions of the PFC. Our results indicated that microglial soma size was significantly enlarged, while cell processes had contracted slightly following LPS administration. To our knowledge this study is to first to definitely demonstrate substantial microglial disturbances within the PFC following LPS delivered at a dose that was sufficient to induce significant sickness-like behavior.

© 2015, American School Health Association. BACKGROUND: Physical activity and structural differences in the hippocampus have been linked to educational outcome. We investigated whether a curriculum-based physical activity intervention correlates positively with children's academic achievement, psychological well-being, health-related quality of life (HRQoL), fitness, and structural development of the brain. METHODS: The study had a quasi-experimental design and a control group. National test results were gathered from 545 students, 122 in the intervention school, and 423 in 3 control schools. HRQoL and socioemotional data were collected with child and proxy versions of KIDSCREEN and the Strength and Difficulties Questionnaire. Overall, 79 students in grades 5 and 6 were recruited for an in-depth study, consisting of a submaximal oxygen consumption test and magnetic resonance imaging of the brain. HRQoL and socioemotional data were collected from 349 students (65%), 182 (52%) in the intervention school, and 167 (48%) in one of the control schools. RESULTS: Girls attending the intervention school were more likely to pass national tests in Swedish (odds ratio 5.7) and Mathematics (odds ratio 3.2). The fourth to sixth graders in the intervention school reported lower levels of conduct problems (p < .05), and the girls were also less likely to report hyperactivity (p < .05). Girls reported higher levels of emotional problems (p < .05) than boys. Boys in the intervention group had significantly higher levels of estimated maximal oxygen uptake (p < .05) than controls. No difference in hippocampal structure was seen. CONCLUSIONS: Curriculum-based physical activity in school may improve the academic achievement and psychological health of children, particularly for girls.

© 2014 Elsevier B.V. There are currently few approaches to transiently manipulate the expression of specific proteins in microglia of the brain. An antibody directed against an extracellular epitope of scavenger receptor class B, type I (SR-BI) was found to be selectively taken up by these cells in the brain. Other antibodies tested were not internalised by microglia. A vector was produced by linking the SR-BI antibody to polyethyleneimine and binding a DNA plasmid encoding green fluorescent protein. Infusions of this vector into the hippocampus produced a widespread transfection of cells, more than 80% of which were immunoreactive for microglial/macrophage markers. Transfection was not detected in cells expressing markers for astrocytes or neurons. Reporter gene expression was most prominent near the infusion site but was seen in tissue up to 4 mm away. DNA bound to polyethyleneimine alone or to a vector containing a different antibody did not produce transfection in the brain. Single injections of the vector containing the SR-BI antibody into the brain also resulted in transfection of microglia, albeit with lower efficiency. Vector modifications to promote lysis of endosomes or entry of DNA into the nucleus did not increase efficiency. The findings clearly demonstrate the capacity of the SR-BI antibody to selectively target brain microglia. This approach offers considerable potential to deliver DNA and other molecules capable of modifying the function of these cells in vivo.

Patients with early-onset dementia are a significantly under-recognized subgroup of patients with an increasing prevalence. Epidemiological studies are limited and studies of modifiable risk factors, such as physical fitness, are lacking. We aimed to investigate the associations between cardiovascular fitness individually and in combination with cognitive performance at age 18 and risk of early-onset dementia and mild cognitive impairment later in life. We performed a population-based cohort study of over 1.1 million Swedish, 18-year-old, male conscripts, who underwent conscription exams between 1968 and 2005. These males were then followed for up to 42 years. Objective data on cardiovascular fitness and cognitive performance were collected during conscription exams and were subsequently linked with hospital registries to calculate later risk of early-onset dementia and mild cognitive impairment using Cox proportional hazards models controlling for several confounders. The scores from the exams were divided into tertiles (low, medium, high) for the analyses. The mean follow-up time for the analyses was 25.7 years (standard deviation: 9.3) and the median was 27 years. In total, 30 195 315 person-years of follow-up were included in the study. In fully adjusted models, both low cardiovascular fitness and cognitive performance (compared to high) at age 18 were associated with increased risk for future early-onset dementia (cardiovascular fitness, n = 662 events: hazard ratio 2.49, 95%, confidence int erval 1.87-3.32; cognitive performance, n = 657 events: hazard ratio 4.11, 95%, confidence interval 3.19-5.29) and mild cognitive impairment (cardiovascular fitness, n = 213 events: hazard ratio 3.57, 95%, confidence interval 2.23-5.74; cognitive performance, n = 212 events: hazard ratio 3.23, 95%, confidence interval 2.12-4.95). Poor performance on both cardiovascular fitness and cognitive tests was associated with a > 7-fold (hazard ratio 7.34, 95%, confidence interval 5.08-10.58) and a > 8-fold (hazard ratio 8.44, 95%, confidence interval 4.64-15.37) increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively. In conclusion, lower cardiovascular fitness and cognitive performance in early adulthood were associated with an increased risk of early-onset dementia and mild cognitive impairment later in life, and the greatest risks were observed for individuals with a combination of low cardiovascular fitness and low cognitive performance. © 2014 The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

BACKGROUND: Despite the emerging body of research on the potential of physical activity to improve learning and academic achievement, conclusive evidence regarding the effects of physical activity on academic achievement is lacking. The objective of this study was to determine the impact of a physical activity intervention program on academic performance. METHODS: A controlled cross-sectional design was used to investigate the hypothesis that the intervention program would increase the proportion of students in grade 5 who achieved the national learning goals in Swedish, mathematics, and English compared with 3 reference schools. Academic results from the years prior to and during the intervention program were analyzed. Logistic regression analyses assessed the odds of achieving the national learning goals when the intervention program was integrated into the elementary curricula. RESULTS: Higher proportions of students in the intervention school achieved the national goals in all 3 subjects compared with the reference schools after initiation of the intervention program. The odds for achieving the national learning goals in the intervention school increased 2-fold (p < .05), whereas these odds either did not change or decreased in the reference schools. CONCLUSION: Promoting physical activity in school by means of a curriculum-based intervention program may improve children's educational outcome. © 2014, American School Health Association.

Objective: To determine physical, cognitive and social activity levels of stroke patients undergoing rehabilitation, and whether these changed over time. Design: Observational study using behavioural mapping techniques to record patient activity over 12 hours on one weekday and one weekend day at baseline (week 1) and again two weeks later (week 2). Setting: A 20-bed mixed rehabilitation unit. Subjects: Fourteen stroke patients. Interventions: None. Main measures: Percentage of day spent in any activity or physical, cognitive and social activities. Level of independence using the Functional Independence Measure (FIM) and mood using the Patient Health Questionniare-9 (PHQ-9). Results: The stroke patients performed any activity for 49%, social activity for 32%, physical activity for 23% and cognitive activity for 4% of the day. Two weeks later, physical activity levels had increased by 4% (95% confidence interval (CI) 1 to 8), but levels of any activity or social and cognitive activities had not changed significantly. There was a significant: (i) positive correlation between change in physical activity and change in FIM score (r = 0.80), and (ii) negative correlation between change in social activity and change in PHQ-9 score (r = -0.72). The majority of activity was performed by the bedside (37%), and most physical (47%) and cognitive (54%) activities performed when alone. Patients undertook 5% (95% CI 2 to 9) less physical activity on the weekends compared with the weekdays. Conclusions: Levels of physical, cognitive and social activity of stroke patients were low and remained so even though level of independence and mood improved. These findings suggest the need to explore strategies to stimulate activity within rehabilitation environments. © The Author(s) 2013.

In recent years, the role and physiological regulation of the serine protease tissue-type plasminogen activator (t-PA and its inhibitors, including plasminogen activator inhibitor type-1 (PAI-1, in the brain have received much attention. However, as studies focusing these issues are difficult to perform in humans, a great majority of the studies conducted to date have utilized rodent in vivo and/or in vitro models. In view of the species-specific structural differences present in both the t-PA and the PAI-1 promoters, we have compared the response of these genes in astrocytes of rat and human origin. We reveal marked quantitative and qualitative species-specific differences in gene induction following treatment with various physiological and pathological stimuli. Thus, our findings are of importance for the interpretation of previous and future results related to t-PA and PAI-1 expression. © the authors, publisher and licensee Libertas Academica Limited.

Objective: To analyze the associations between cardiovascular fitness at age 18 years and future risk of epilepsy. Methods: Population-based cohort study of Swedish male conscripts (n = 1,173,079) born in 1950-1987, who were followed for up to 40 years. Data on cardiovascular fitness were collected during conscription exams and linked with hospital registers to calculate later risk of epilepsy using Cox proportional hazard models controlling for several confounders, including familial factors. Results: Epilepsy was recorded in 6,796 individuals during the follow-up time. In fully adjusted models, low and medium cardiovascular fitness (compared with high) at age 18 years was associated with increased risk of future epilepsy (hazard ratio 1.79, 95% confidence interval 1.57-2.03; and hazard ratio 1.36, 95% confidence interval 1.27-1.45, respectively). The associations changed only marginally after adjustment for familial influences and prior severe traumatic brain injury, cerebrovascular disease, or diabetes. Conclusions: Low cardiovascular fitness early in life is associated with an increased risk of epilepsy later in adulthood. These results agree with previous results from animal models. We propose that behaviors that increase cardiovascular fitness may act as positive disease-modifiers for the development of epilepsy. © 2013 American Academy of Neurology.

OBJECTIVE: To investigate the rate of and risk factors for head and neck injury in male soccer. DESIGN: Prospective cohort study. SETTING: Professional soccer. PARTICIPANTS: Twenty-six European teams between 2001/2002 and 2009/2010. ASSESSMENT OF RISK FACTORS: Simple and multiple risk factor analyses were evaluated using Cox regression for player-related variables and logistic regression for match-related variables. MAIN OUTCOME MEASURES: Injury rate (number of time loss injuries per 1000 hours). RESULTS: A total of 136 head and neck injuries were recorded (2.2% of all injuries). The head and neck injury rate was 0.17 (0.06 concussions) per 1000 hours. There was a 20-fold higher rate of head and neck injury during match play compared with training (rate ratio [RR], 20.2; 95% confidence interval [CI] , 13.3-30.6) and a 78-fold higher rate of concussions (RR, 78.5; 95% CI, 24.4-252.5). Mean layoff for concussion was 10.5 days, but 27% of the concussed players returned to play within 5 days. Defender was the only significant player-related risk factor for head and neck injuries in the multiple analysis (RR, 1.8; 95% CI, 1.0-3.1), whereas no significant variables were identified for concussions. CONCLUSIONS: Head and neck injuries were relatively uncommon in professional soccer. Defender was the playing position most at risk. More than one-quarter of the concussed players returned to play before what is recommended in the consensus statements by the major sports governing bodies. Copyright © 2013 by Lippincott Williams & Wilkins.

Post-traumatic hypopituitarism (PTHP) has been linked to disability and decreased quality of life. However, no studies have addressed the long-term consequences of PTHP in adults with severe traumatic brain injury (TBI) only. In this study, we evaluated the relationship between pituitary function, quality of life, and functioning in 51 patients (16-65 years of age) with severe TBI who were admitted to Sahlgrenska University Hospital, Gothenburg from 1999 to 2002. The patients were assessed once, 2-10 years after trauma. Data from the time of injury were collected retrospectively to adjust for injury severity. Outcome measures included hormonal testing, the Short Form-36 Health Survey, the Glasgow Outcome Scale-Extended, and a self-report questionnaire specifically designed for this study and based on the International Classification of Functioning, Disability and Health. Of 51 patients, 14 (27.5%) presented with PTHP, and 11 (21.6%) had isolated growth hormone deficiency. Patients with PTHP were more often overweight at follow-up (p=0.01); the higher body mass index was partially explained by PTHP (R 2 change=0.07, p=0.001). Otherwise no significant correlation was found among PTHP, functioning, or patient-reported quality of life. This study - which is unique in the homogeneity of the patients, the long follow-up time, and the use of injury severity as an outcome predictor - did not confirm results from previous studies linking PTHP to a worse outcome. Therefore, screening for PTHP might be restricted to specific subgroups such as overweight patients, indicating growth hormone deficiency. © 2013, Mary Ann Liebert, Inc.

© 2015 IEEE. Intrinsic Optical Signal imaging is a technique which allows the visualisation and mapping of activity related changes within the brain with excellent spatial and temporal resolution. We analysed a variety of signal and image processing techniques applied to real mouse imaging data. The results were compared in an attempt to overcome the unique issues faced when performing the technique on mice and improve the understanding of post processing options available.