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Background: In patients with TIA/stroke, early assessment is critical., Aim: To describe patients who were not directly transported to hospital by ambulance after prehospital assessment., Methods: Patients hospitalized with TIA/stroke in Gothenburg, Data were obtained from the EMS and hospital case record system., Results: There were 7,812 patients with TIA/stroke, of which 4,853 (62%) were candidates for EMS transport. Among them, 176 (3.6%) were not directly transported to hospital by ambulance. In 45% of them, delay from symptom onset to calling for EMS was ≤24 hours. On EMS arrival, common symptom was dizziness (28%), followed by weakness in arm or leg (21%), loss of sensibility (13%), speech disturbances (7%), and facial numbness (4%). The modified National Institute of Health Stroke Score (mNIHSS) was 0 in 80% and >1 in two per cent. The NIHSS at the emergency department was 1-4 in 39% and 5-15 in six per cent. The EMS clinician made the decision not to transport the patient to hospital by the EMS in 84%, the dispatcher in 12% and the patient or relatives in four per cent. Patients were involved in the decision in 51%. Final diagnosis was stroke in 74% and the proportion who were independent in normal daily activities at hospital discharge decreased by 15% compared with before event., Conclusion: About 3%-4% of patients with TIA/stroke were not directly transported to hospital by EMS after prehospital assessment. The most common symptom was dizziness. Decision-support tools for EMS to identify time-sensitive conditions are required., (© 2020 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Background: Elevated levels of the cerebrospinal fluid (CSF) neuronal injury markers (neurofilament light chain [NF-L] and total tau protein [t-tau]) and of the astroglial marker glial fibrillary acidic protein (GFAP) are found in etiologically different neurological disorders affecting the peripheral and the central nervous system., Aims: To explore the role of CSF biomarkers in the clinical management of patients admitted for alarming neurological symptoms, but in whom neurological disorders could be excluded., Methods: Study participants were patients seeking medical attention for neurological symptoms primarily considered to be caused by a neurological diagnosis and investigated according to clinical routine. Demographic, clinical, and CSF data were extracted retrospectively from medical records. Patients with a final neurological diagnosis were excluded., Results: Out of 990 patients, 900 with a neurological diagnosis were excluded leaving 90 patients without a final neurological diagnosis. Sixty-eight (75.6%) were females. Median (range) age at lumbar puncture was 34.7 (16.9-65.1) years. Age-adjusted CSF-NF-L, CSF-t-tau, and CSF-GFAP concentrations were normal in 89 (98.9%), 86 (95.6%), and 87 (96.7%) patients, respectively., Conclusion: In patients with significant neurological symptoms but in whom a neurological diagnosis could not be made, the CSF markers NF-L, t-tau, and GFAP did not indicate signs of neuronal or astroglial cell damage close to symptom onset. Consequently, increased levels of CSF markers are not expected in this patient group and, if present, should raise suspicion of underlying neurological disorders and motivate further investigations., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Mortality is increased in parkinsonian disorders, moderately in Parkinson's disease (PD) but markedly in atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Still, there are no reliable quantitative biomarkers for mortality. The cerebrospinal fluid (CSF) neurodegeneration biomarkers such as neurofilament light chain (NF-L), total tau (t-tau), and the tau pathology marker phosphorylated tau (p-tau) are related to mortality in other neurological disorders (eg, amyotrophic lateral sclerosis, Alzheimer's disease), but have not been investigated in this respect in parkinsonian disorders., Aims: To investigate the CSF biomarkers' (NF-L, t-tau, and p-tau) relationship to mortality in parkinsonian disorders., Methods: Demographic, mortality, and CSF data were collected from 68 PD and 83 APD patients. Survival analysis was conducted using Cox regression, with age at lumbar puncture, gender, diagnosis, and levels of CSF biomarkers as predictors., Results: NF-L in CSF was associated with increased mortality in synucleinopathies (PD, MSA; HR 3.698 [2.196-6.228, 95% confidence interval (CI)], P < 0.001), in PSP (HR 2.767 [1.126-6.802 95% CI], P = 0.027), and in the entire cohort (HR 1.661 [1.082-2.55, 95% CI], P = 0.02). t-Tau in CSF was associated with increased mortality in PSP (HR 9.587 [1.143-80.418], P = 0.037). p-Tau in CSF was associated with decreased mortality in synucleinopathies (HR 0.196 [0.041-0.929, 95% CI], P = 0.040). Atypical parkinsonian disorders and tauopathies were associated with higher mortality (HR 8.798 [4.516-17.14, 95% CI] and HR 3.040 [1.904-4.854], respectively, P < 0.001)., Conclusion: NF-L and tau protein in CSF might be useful for mortality prognosis in patients with parkinsonian disorders and should be investigated in larger studies., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: In the new era of endovascular treatment for acute ischemic stroke, one of the main predictors of good neurological outcome is a short time interval from stroke onset to recanalization of the occluded vessel. In this study, we examined the effect of on-hour vs off-hour admittance on the time intervals from stroke onset to recanalization in patients with acute ischemic stroke (AIS) undergoing endovascular treatment (EVT)., Methods: One-hundred-ninety-eight patients receiving EVT for anterior AIS between 2007 and 2016 were included. Time of day and weekday for stroke admittance were recorded as well as several time intervals. Age, sex, co-morbidities, admission National Institutes of Health Stroke Scale (NIHSS), intraprocedural blood pressure, blood glucose, modified Thrombolysis in Cerebral Ischemia score (mTICI) and neurological outcome at 3 months, measured as modified Rankin Scale (mRS), were registered. On-hour was defined as 8 am-4 pm weekdays, and off-hour as weekdays outside these hours and weekends., Results: The time interval from CT (computed tomography) to recanalization was longer during off-hours, while no difference was seen in the time interval from stroke onset to CT. No statistically significant difference was seen in neurological outcome between the on- and off-hour groups in a univariate analysis., Conclusions: Stroke admittance during off-hours is associated with longer time interval from CT examination to vessel recanalization. The study highlights the need of logistic improvement and probably more resources off-hour in order to deliver an effective stroke care around the clock., (© 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Time delay from stroke onset to arrival in hospital is an important obstacle to widespread reperfusion therapy. To increase knowledge about stroke, and potentially decrease this delay, a 27-month national public information campaign was carried out in Sweden., Aims: To assess the effects of a national stroke campaign in Sweden., Methods: The variables used to measure campaign effects were knowledge of the AKUT test [a Swedish equivalent of the FAST (Face-Arm-Speech-Time)] test and intent to call 112 (emergency telephone number) . Telephone interviews were carried out with 1500 randomly selected people in Sweden at eight points in time: before, three times during, immediately after, and nine, 13 and 21 months after the campaign., Results: Before the campaign, 4% could recall the meaning of some or all keywords in the AKUT test, compared with 23% during and directly after the campaign, and 14% 21 months later. Corresponding figures were 15%, 51%, and 50% for those remembering the term AKUT and 65%, 76%, and 73% for intent to call 112 when observing or experiencing stroke symptoms. During the course of the campaign, improvement of stroke knowledge was similar among men and women, but the absolute level of knowledge for both items was higher for women at all time points., Conclusion: The nationwide campaign substantially increased knowledge about the AKUT test and intention to call 112 when experiencing or observing stroke symptoms, but knowledge declined post-intervention. Repeated public information therefore appears essential to sustain knowledge gains., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The Satisfaction With Life Scale (SWLS) is a global measure of life satisfaction (LS). The objective of this study was to evaluate the psychometric properties (data completeness, scaling assumptions, targeting and reliability) of the SWLS in a sample of people with Parkinson's disease (PD)., Materials and Methods: A postal survey including a Swedish version of the SWLS and demographic information was administered to 174 persons with PD; 97 responded and received a second survey after 2 weeks., Results: The mean (SD) age and PD duration of the 97 responders were 73 (8) and 7 (6) years, respectively. Data completeness was 92% to 97% for the five items in the SWLS and 92% for the total score (5-35 points). The mean score of the SWLS was 24.2 points (7.7), indicating that this group had an average LS. The items' means and SDs were roughly parallel and the score distribution was even. The internal consistency reliability (Cronbach's alpha) was 0.90. The test-retest reliability, assessed by the intraclass correlation coefficient, was 0.78. The scale showed no systematic difference between the first and second response. The standard error of measurement was 3.6 points, and the smallest detectable difference was 10.0 points., Conclusions: This evaluation of the psychometric properties of the SWLS shows that the scale has good data completeness, scaling assumptions and targeting and that the internal consistency reliability and the test-retest reliability are acceptable. Thus, the SWLS is a psychometrically sound and suitable tool to asses LS in people with PD., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: Recognition of stroke symptoms and activation of emergency services are essential in minimizing delay for acute stroke treatments. In this study, we assessed public stroke awareness in Sweden., Methods: One thousand and five hundred residents aged 18-79 years participated in a telephone survey. Open-ended questions were used to assess knowledge of stroke symptoms, risk factors, and action if witnessing or experiencing a potential stroke., Results: Seventy-two percentage could report at least one stroke symptom and 86% at least one risk factor. Only 13% could report three or more stroke symptoms. Female sex (OR, 1.79; 95% CI, 1.30-2.45) and high education (OR, 2.30; 95% CI, 1.38-3.80) were associated with knowledge of stroke symptoms. Sixty-five percentage indicated they would call the emergency number 112 if witnessing or experiencing a potential stroke. Female sex (OR, 1.48; 95% CI, 1.18-1.85) and high education (OR, 1.40; 95% CI, 1.01-1.93) were positively associated, while increasing age (OR, 0.99; 95% CI, 0.98-0.99) was negatively associated with intent to call 112., Conclusion: We confirm a rather low public awareness of stroke in Sweden, poorer among males and those with low education. With increasing age, a lower proportion indicated intent to call 112 for stroke symptoms., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Cerebrospinal fluid (CSF) levels of neurofilament triplet protein (NFL), a non-specific marker of neuronal damage, are normal in Parkinson's disease (PD) but increased after brain trauma and in several neurological disorders. Using longitudinal CSF-NFL measurements as an indicator of neuronal damage, this study investigated the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the brain, directly following the surgical intervention and in chronically treated patients with PD., Materials and Methods: CSF-NFL levels were measured consecutively in eight patients with PD before and after STN-DBS treatment., Results: CSF-NFL levels were normal prior to STN-DBS and increased sharply during the first 2 weeks post-operatively, but normalized after 12 months or more., Conclusion: The STN-DBS procedure leads to an acute but limited neuronal damage, as expected. However, normal CSF-NFL levels at 12 months post-operatively and beyond suggest the absence of any long-term neuronal damage caused by long-term STN-DBS stimulation., (© 2010 John Wiley & Sons A/S.)

Background: Psychiatric and neurological symptoms are common among soldiers exposed to blast without suffering a direct head injury. It is not known whether such symptoms are direct consequences of blast overpressure., Objective: To examine if repeated detonating explosions or firing if of heavy weapons is associated with neurochemical evidence of brain damage., Materials and Methods: Three controlled experimental studies. In the first, army officers were exposed to repeated firing of a FH77B howitzer or a bazooka. Cerebrospinal fluid (CSF) was taken post-exposure to measure biomarkers for brain damage. In the second, officers were exposed for up to 150 blasts by firing a bazooka, and in the third to 100 charges of detonating explosives of 180 dB. Serial serum samples were taken after exposure. Results were compared with a control group consisting of 19 unexposed age-matched healthy volunteers., Results: The CSF biomarkers for neuronal/axonal damage (tau and neurofilament protein), glial cell injury (GFAP and S-100b), blood-brain barrier damage (CSF/serum albumin ratio) and hemorrhages (hemoglobin and bilirubin) and the serum GFAP and S-100b showed normal and stable levels in all exposed officers., Discussion: Repeated exposure to high-impact blast does not result in any neurochemical evidence of brain damage. These findings are of importance for soldiers regularly exposed to high-impact blast when firing artillery shells or other types of heavy weapons., (© 2010 John Wiley & Sons A/S.)

Background: Traumatic brain injury (TBI) is one of the most common causes of death and dismal outcome among children and young adults. The morbidity and mortality differ but more aggressive monitoring and more designated neuro intensive care units have improved the results. Studies have demonstrated a connection between apolipoprotein E (APOE) genotype and outcome after TBI, but few are prospective and none is from northern Europe. APOE has three alleles: epsilon2, epsilon3 and epsilon4., Methods: A total of 96 patients with Glasgow coma score (GCS) < or =8 were prospectively and consecutively included. APOE genotypes were all analyzed at the same laboratory from blood samples by polymerase chain reaction-restriction fragment length polymorphism., Results: All patients were assessed at 1 year with Glasgow outcome scale extended (GOSE), National Institute of Health Stroke Scale (NIHSS) and the Barthel daily living index. The genotype was available in all patients. Twenty-six patients expressed APOE epsilon4 while 70 patients did not. Outcome demonstrated that patients with APOE epsilon4 had worse outcome vs. those lacking this allele. When subdividing patients into gender, males with APOE epsilon4 did worse, a difference not detected among female patients., Conclusions: APOE epsilon4 correlated to worse outcome in TBI patients. We also found that males with APOE epsilon4 had poor outcome while females did not. Thus, the results indicate that genetic polymorphism may influence outcome after TBI.

Introduction: Choroidal neovascularization (CNV) is a debilitating complication of age-related macular degeneration (AMD) and a leading cause of vision loss. Along with other angiogenic factors like vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1) and its receptor, IGF-1R, have been implicated in CNV., Purpose: We have previously shown that the cyclolignan picropodophyllin (PPP) efficiently blocks the insulin-like growth factor-1 receptor (IGF-1R) activity and causes cell death in uveal melanoma cell lines and in an in-vivo model. In this study we investigated the effect of PPP on VEGF expression both in vitro and in vivo and whether this effect has anti-angiogenic consequences in a murine CNV model., Materials and Methods: C57BL/6J mice with laser-induced CNVs were treated with PPP. Effects on CNV area were assayed by image analysis. VEGF levels in choroids and retinal pigment epithelial cells (APRE-19) were measured by Western blot or ELISA. Transcriptional activation of the VEGF promoter was determined by luciferase reporter gene assay., Results: Mice treated with PPP, administered intraperitoneally or orally, showed 22-32% (p = 0.002) decrease in CNV area. Furthermore, VEGF levels in the choroids were significantly reduced. In cultured APRE-19 cells, IGF-1 was shown to increase VEGF secretion. This increase was completely blocked by PPP. We could confirm that PPP reduced the level of transcriptional activity of VEGF promoter., Conclusions: PPP reduces IGF-1 dependent VEGF expression and CNV in vivo. Accordingly, IGF-1R inhibitors may be useful tools in the therapy of conditions associated with CNV including neovascular AMD.

Objectives: To investigate serum levels of glial fibrillary acidic protein (GFAP) and S-100B in patients with newly diagnosed high-grade gliomas., Materials and Methods: GFAP and S-100B were measured by enzyme-linked immunosorbent assay techniques in preoperative serum from 31 patients with high-grade gliomas. A database with clinical, radiological and histological variables was created for statistical analyses., Results: Mean serum levels of 239 ng/l (range 30-1210 ng/l) for GFAP and 58.3 ng/l (range 22-128 ng/l) for S-100B were found. Of the 31 patients, 16 had elevated levels of GFAP while only two showed increased S-100B concentrations. Tumour size was the only variable significantly associated with serum levels of GFAP (P < 0.0001) with a linear correlation coefficient of 0.67., Conclusions: Serum levels of GFAP demonstrated a linear correlation to tumour volume in patients with high-grade gliomas. GFAP seems to be a more reliable biomarker in patients with high-grade gliomas than the commercially available S-100B.

BACKGROUND - To evaluate cerebrospinal fluid (CSF) markers for neuronal degeneration and demyelination in idiopathic normal pressure hydrocephalus (INPH), subcortical arteriosclerotic encephalopathy (SAE), and neurologically healthy subjects. METHODS - Lumbar CSF concentrations of sulfatide, neurofilament protein light (NFL), total-tau (T-tau), hyperphosphorylated tau (P-tau), and beta-amyloid(1-42) (Abeta42) were analyzed in 62 INPH patients, 26 SAE patients, and 23 neurologically healthy controls. In INPH patients, samples before and after shunt surgery were analysed. RESULTS - The CSF concentration of NFL was elevated in INPH and SAE compared with the controls, and levels of T-tau, P-tau, and Abeta42 were lower in INPH compared with SAE and controls. No difference was seen for sulfatide. All markers except Abeta42 were significantly elevated after shunt surgery. CONCLUSIONS - The most striking finding was the power of the combined pattern of NFL, P-tau, and Abeta42 in distinguishing between the clinical diagnoses of INPH, SAE, and neurologically healthy elderly.

In a previous study we found that nine of 47 siblings to multiple sclerosis (MS) patients with a normal neurological examination carry an intrathecal oligoclonal immunopathy with limited specificity, a condition we termed MS immunopathic trait. The purpose of this study is to further characterize the MS immunopathic trait phenotype. We found that the neurofilament light protein (NFL) and glial fibrillary acidic protein (GFAp) concentrations were increased in the group of patients with clinically definite MS (n = 47) in latent or slowly progressive phases. There was no increase in GFAp and NFL in cerebrospinal fluid in the healthy siblings of MS patients (n = 47), nor in the subgroup of these siblings with MS immunopathic trait (n = 9) compared with a group of healthy control subjects (n = 50). Thus, there was no indication of presymptomatic CNS parenchymal involvement in MS immunopathic trait.

Unlabelled: The diving response involves reflex bradycardia, apnoea and peripheral vasoconstriction and is known to exist in human infants. The response diminishes with increasing age and has been reported to disappear by the age of 6 mo. This study was performed to analyse the physiological events during natural diving of full-term healthy infants and describe how these events alter with maturation. Thirty-six infants were studied during diving exercises in infant swimming. All of the infants who participated showed an immediate decrease in heart rate when submerged. On average, the heart rate decreased by 25% (range -5.0% to -50.7%, p <0.0001). The bradycardia was sustained during the dive and for some seconds afterwards. The response was often followed by a tachycardia as the bradycardia ceased. A decline of reflex bradycardia was observed with increasing age (p = 0.03), but the response was still clearly evident in infants over the age of 6 mo., Conclusion: This study demonstrates the existence of a diving response in infants, which includes an immediate bradycardic response, suggesting vagal mediation. Although the bradycardic response gradually decreases, the study shows that a clear-cut response exists in children older than has previously been reported.

Unlabelled: Upcoming trials of neuroprotective strategies in severely asphyxiated newborn infants emphasize the need for early and objective markers of both good and bad long-term prognosis. Traditional markers such as neurological depression and seizures are not specific., Aim: To study whether measurement in the cerebrospinal fluid of some proteins known to be specific to the central nervous system was in covariance with the clinical course and long-term prognosis., Methods: Twenty-two asphyxiated infants were included in the study and compared with a control group of 8 infants without signs of perinatal asphyxia. Cerebrospinal fluid (CSF) was collected during the first 4 d of life and analysed for neurofilament protein (NFp), glial fibrillary acidic protein (GFAp), protein S-100 and neuron-specific enolase (NSE)., Results: The concentrations of all four proteins were significantly increased in the CSF of asphyxiated infants. The concentrations correlated significantly with other indicators of long-term prognosis and to neurological impairment at I y of age, or death before that time. Specifically, concentrations were excessively high in the five infants who died., Conclusions: High concentrations of brain-specific proteins are released into the CSF of asphyxiated infants. It might therefore be useful to measure these concentrations when excluding patients with the gravest prognosis from neuroprotective trials.

Glial fibrillary acidic protein (GFAP) is the structural protein of the intermediate filament of astroglia. The aims of the present study were to examine GFAP in the cerebrospinal fluid (CSF) of preterm infants at different postmenstrual ages and to evaluate the potential of GFAP to predict abnormal neurodevelopmental outcome. GFAP increased in correlation with postmenstrual age in preterm infants (n = 17) and full-term infants (n = 9). The levels were five times higher in preterm infants (n = 10) with an abnormal neonatal course and/or an abnormal neurological outcome than in healthy preterm infants. The positive predictive value of a GFAP higher than the 98th percentile of normal infants was 69%, while a GFAP level below this limit invariable predicted a good outcome. Simultaneously analysed noradrenaline, hypoxanthine and glutamate did not differ between the groups. We conclude that CSF GFAP increases with maturity and that CSF GFAP appears to be a promising marker for perinatal brain damage.

Control and ethanol-intoxicated rats were injured with a small cerebral stab wound and the extravasation of Evans blue-labelled albumin (EBA) was studied. Control rats displayed an extravasation of EBA in the immediate peri-traumatic area with subsequent uptake of EBA in neurons and glia. Ethanol-intoxicated rats showed a greater leakage of EBA as well as a wider area of leaking blood vessels around the stab wound, both in the peri-traumatic and in the early post-traumatic period. Neuronal uptake of EBA was enhanced and observed in a wider area in intoxicated than control rats. The difference in distribution of EBA among neurons and glia between intoxicated and control rats was partly a consequence of the difference in leakage of EBA in the experimental groups. However, part of the increased neuronal uptake of EBA might be explained by an effect of ethanol on nueronal plasmalemma. The results obtained indicated a more pronounced injury to endothelial and neuronal cells after small cerebral stab wounds in ethanol-intoxicated compared to control rats.