Video support for prehospital stroke consultation: implications for system design and clinical implementation from prehospital simulations.

BACKGROUND: Video consultations between hospital-based neurologists and Emergency Medical Services (EMS) have potential to increase precision of decisions regarding stroke patient assessment, management and transport. In this study we explored the use of real-time video streaming for neurologist-EMS consultation from the ambulance, using highly realistic full-scale prehospital simulations including role-play between on-scene EMS teams, simulated patients (actors), and neurologists specialized in stroke and reperfusion located at the remote regional stroke center. METHODS: Video streams from three angles were used for collaborative assessment of stroke using the National Institutes of Health Stroke Scale (NIHSS) to assess symptoms affecting patient's legs, arms, language, and facial expressions. The aim of the assessment was to determine appropriate management and transport destination based on the combination of geographical location and severity of stroke symptoms. Two realistic patient scenarios were created, with severe and moderate stroke symptoms, respectively. Each scenario was simulated using a neurologist acting as stroke patient and an ambulance team performing patient assessment. Four ambulance teams with two nurses each all performed both scenarios, for a total of eight cases. All scenarios were video recorded using handheld and fixed cameras. The audio from the video consultations was transcribed. Each team participated in a semi-structured interview, and neurologists and actors were also interviewed. Interviews were audio recorded and transcribed. RESULTS: Analysis of video-recordings and post-interviews (n = 7) show a more thorough prehospital patient assessment, but longer total on-scene time, compared to a baseline scenario not using video consultation. Both ambulance nurses and neurologists deem that video consultation has potential to provide improved precision of assessment of stroke patients. Interviews verify the system design effectiveness and suggest minor modifications. CONCLUSIONS: The results indicate potential patient benefit based on a more effective assessment of the patient's condition, which could lead to increased precision in decisions and more patients receiving optimal care. The findings outline requirements for pilot implementation and future clinical tests.

Difficulties in the prehospital assessment of patients with TIA/stroke.

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.

Acute symptomatic seizures and epilepsy after mechanical thrombectomy.

PURPOSE: The purpose of this study was to assess the incidence of acute symptomatic seizures and poststroke epilepsy (PSE) in a well-characterized cohort of patients treated with mechanical thrombectomy. In addition, we aimed to describe the dynamics of blood markers of brain injury in patients that developed PSE. METHODS: Participants of the prospective AnStroke Trial of anesthesia method during mechanical thrombectomy were included and acute symptomatic seizures and PSE ascertained by medical records review. Blood markers neurofilament light (NFL), tau, glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), and neuron-specific enolase (NSE) were assessed. RESULTS: A total of 90 patients with acute anterior ischemic stroke were included. Median National Institutes of Health Stroke Scale (NIHSS) at admission to hospital was 18 (IQR 15-22). Recanalization was achieved in 90%. No patients had epilepsy prior to the ischemic stroke. Four patients (4.4%) had acute symptomatic seizures and four patients (4.4%) developed PSE during the follow-up time (to death or last medical records review) of 0-4.5 years (median follow-up 1070 days IQR 777-1306), resulting in a two-year estimated PSE risk of 5.3% (95%CI: 0.2-10.4%). Blood markers of brain injury (NFL, tau, GFAP, S100B, and NSE) were generally above the cohort median in patients that developed PSE. CONCLUSIONS: The incidence of PSE after mechanical thrombectomy was low in our cohort. All blood biomarkers displayed interesting sensitivity and specificity. However, the number of PSE cases was small and more studies are needed on risk factors for PSE after mechanical thrombectomy. The potential of blood markers of brain injury markers to contribute to assessment of PSE risk should be explored further. This article is part of the Special Issue "Seizures & Stroke".

Cerebrospinal fluid neurofilament light and tau protein as mortality biomarkers in parkinsonism.

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.

Cerebrospinal fluid biomarkers in patients with neurological symptoms but without neurological diseases.

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.

Off-hour admission and impact on neurological outcome in endovascular treatment for acute ischemic stroke.

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.

Midlife Stress in Relation to Late-Life Cerebrospinal Fluid Biomarkers of Alzheimer's Disease: A 25-Year Follow-Up Study.

BACKGROUND/AIMS: Psychological stress has previously been associated with higher risk of developing late-life dementia, especially Alzheimer's disease (AD). This study tested whether longstanding midlife stress is related to cerebrospinal fluid (CSF) biomarkers of late-life AD, such as tau protein and amyloid beta (Aß). METHODS: The study included 79 nondemented females from the Prospective Population Study of Women in Gothenburg, Sweden, who responded to a standardized stress question at baseline (mean age 49 years) and underwent a lumbar puncture at follow-up 25 years later. Multiple linear regression models analyzed the relationships between midlife psychological stress and late-life CSF measures of total tau (t-tau), phosphorylated tau (p-tau), Aß40, and Aß42. RESULTS: Longstanding stress in midlife was associated with higher levels of CSF t-tau (ß = 0.64, p = 0.01) and Aß40 (ß = 0.60, p = 0.02) in late life. No associations were found between midlife stress and levels of p-tau or Aß42. CONCLUSION: The findings suggest that longstanding stress stimulates unspecific neurodegenerative processes, but not the core processes of AD, at least not in the early phase of the disease. The association with higher concentration of CSF t-tau may reflect neural degeneration and the association with higher Aß40 may be an early sign of Aß overproduction or cerebrovascular processes in the brain.

Transient increase in CSF GAP-43 concentration after ischemic stroke.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers reflect ongoing processes in the brain. Growth-associated protein 43 (GAP-43) is highly upregulated in brain tissue shortly after experimental ischemia suggesting the CSF GAP-43 concentration may be altered in ischemic brain disorders. CSF GAP-43 concentration is elevated in Alzheimer's disease patients; however, patients suffering from stroke have not been studied previously. METHODS: The concentration of GAP-43 was measured in longitudinal CSF samples from 28 stroke patients prospectively collected on days 0-1, 2-4, 7-9, 3 weeks, and 3-5 months after ischemia and cross-sectionally in 19 controls. The stroke patients were clinically evaluated using a stroke severity score system. The extent of the brain lesion, including injury size and degrees of white matter lesions and atrophy were evaluated by CT and magnetic resonance imaging. RESULTS: Increased GAP-43 concentration was detected from day 7-9 to 3 weeks after stroke, compared to day 1-4 and to levels in the control group (P = 0.02 and P = 0.007). At 3-5 months after stroke GAP-43 returned to admission levels. The initial increase in GAP-43 during the nine first days was associated to stroke severity, the degree of white matter lesions and atrophy and correlated positively with infarct size (rs = 0.65, P = 0.001). CONCLUSIONS: The transient increase of CSF GAP-43 is important to take into account when used as a biomarker for other neurodegenerative diseases such as Alzheimer's disease. Furthermore, GAP-43 may be a marker of neuronal responses after stroke and additional studies confirming the potential of CSF GAP-43 to reflect severity and outcome of stroke in larger cohorts are warranted.

General Anesthesia Versus Conscious Sedation for Endovascular Treatment of Acute Ischemic Stroke: The AnStroke Trial (Anesthesia During Stroke).

BACKGROUND AND PURPOSE: Retrospective studies have found that patients receiving general anesthesia for endovascular treatment in acute ischemic stroke have worse neurological outcome compared with patients receiving conscious sedation. In this prospective randomized single-center study, we investigated the impact of anesthesia technique on neurological outcome in acute ischemic stroke patients. METHODS: Ninety patients receiving endovascular treatment for acute ischemic stroke in 2013 to 2016 were included and randomized to general anesthesia or conscious sedation. Difference in neurological outcome at 3 months, measured as modified Rankin Scale score, was analyzed (primary outcome) and early neurological improvement of National Institutes of Health Stroke Scale and cerebral infarction volume. Age, sex, comorbidities, admission National Institutes of Health Stroke Scale score, intraprocedural blood pressure, blood glucose, Paco2 and Pco2 modified Thrombolysis in Cerebral Ischemia score, and relevant time intervals were recorded. RESULTS: In the general anesthesia group 19 of 45 patients (42.2%) and in the conscious sedation group 18 of 45 patients (40.0%) achieved a modified Rankin Scale score ≤2 (P=1.00) at 3 months, with no differences in intraoperative blood pressure decline from baseline (P=0.57); blood glucose (P=0.94); PaCO2 (P=0.68); time intervals (P=0.78); degree of successful recanalization, 91.1% versus 88.9% (P=1.00); National Institutes of Health Stroke Scale score at 24 hours 8 (3-5) versus 9 (2-15; P=0.60); infarction volume, 20 (10-100) versus 20(10-54) mL (P=0.53); and hospital mortality (13.3% in both groups; P=1.00). CONCLUSIONS: In endovascular treatment for acute ischemic stroke, no difference was found between general anesthesia and conscious sedation in neurological outcome 3 months after stroke. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01872884.

Hypotension During Endovascular Treatment of Ischemic Stroke Is a Risk Factor for Poor Neurological Outcome.

BACKGROUND AND PURPOSE: In retrospective studies, patients receiving general anesthesia for endovascular treatment for acute ischemic stroke have worse neurological outcome compared with patients receiving conscious sedation. It has been suggested that this is caused by general anesthesia-associated hypotension. We investigated the effect of intraprocedural hypotension on neurological outcome. METHODS: One hundred eight patients with acute ischemic stroke, who underwent endovascular treatment in general anesthesia between 2007 and 2012, were included. Analyzed predictors of neurological outcome were age, sex, comorbidities, baseline National Institutes of Health Stroke Scale, intraprocedural relative changes in mean arterial blood pressure from baseline, blood glucose, modified Thrombolysis in Cerebral Infarction score, and elapsed time from stroke to computed tomography, groin puncture, and recanalization/end of procedure. RESULTS: A fall in mean arterial blood pressure of >40% was an independent predictor for poor neurological outcome (P=0.032), as were higher admission National Institutes of Health Stroke Scale score (P=0.008) and lack of recanalization (P=0.003). CONCLUSIONS: Profound intraprocedural hypotension is an independent predictor for poor neurological outcome in patients with acute ischemic stroke undergoing endovascular therapy in general anesthesia.

Higher CSF interleukin-6 and CSF interleukin-8 in current depression in older women. Results from a population-based sample.

OBJECTIVE: The literature regarding cerebrospinal fluid (CSF) cytokines in geriatric depression is sparse. The aim of this study was to examine associations between CSF interleukin-6 (IL-6), interleukin-8 (IL-8) and depression in a population-based sample of older women who were followed for 17 years. METHODS: 86 dementia-free women aged 70-84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992-3. CSF IL-6 and CSF IL-8 were measured. Psychiatric symptoms were rated with the Comprehensive Psychopathological Rating Scale at baseline and at three subsequent face-to-face examinations. Depression (major or minor) was diagnosed in accordance with DSM-IV/DSM-IV research criteria. RESULTS: At baseline, women with ongoing major (n=10) or minor depression (n=9) had higher levels of CSF IL-6 (p=0.008) and CSF IL-8 (p=0.007) compared with those without depression (n=67). Higher CSF IL-8 was related to higher MADRS score (p=0.003). New cases of depression were observed in 9 women during follow-ups. No associations between CSF cytokine levels and future depression could be shown in women without depression at baseline. CONCLUSION: Higher levels of CSF IL-6 and IL-8 were associated with current depression in this population-based sample. CSF IL-6 and CSF IL-8 may play a role in depression in late life.

Lower CSF interleukin-6 predicts future depression in a population-based sample of older women followed for 17 years.

OBJECTIVE: The literature regarding cerebrospinal fluid (CSF) cytokines in geriatric depression is sparse. The aim of this study was to examine associations between CSF interleukin-6 (IL-6) and related proinflammatory cytokines and current and future depression in a population-based sample of older women who were followed for 17 years. METHODS: 83 non-demented women aged 70-84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992-3. CSF- IL-6, interleukin-1ß (IL-1ß), interleukin- 8 (IL-8) and tumor necrosis factor-α (TNF-α) were measured. Psychiatric symptoms were rated with the Comprehensive Psychopathological Rating Scale at baseline and at three subsequent face-to-face examinations. Depression (major or minor) was diagnosed in accordance with DSM-IV/DSM-IV research criteria. RESULTS: At baseline, women with ongoing depression had lower levels of IL-6 (p<0.04), IL-8 (p<0.05) and TNF-α (p<0.05) compared with those without depression. In women without depression at baseline, lower CSF IL-6 levels predicted depression at one or more follow-up examination (p<0.03). Results from the generalized linear mixed logistic model using all baseline and follow-up data on depression status and Mini Mental State Examination score showed a significant relationship between IL-6 and depression (p=0.005 OR 0.370 CI [0.184-0.744]). CONCLUSION: Lower levels of CSF IL-6 were associated with current depression and with future depression during a follow-up of almost two decades. Our findings suggest that lower levels of CSF IL-6 may be related to depression vulnerability in later life.

Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia.

BACKGROUND: Frontotemporal dementia (FTD) is recognised as a clinically and morphologically heterogeneous group of interrelated neurodegenerative conditions. One of the subtypes within this disease spectrum is the behavioural variant FTD (bvFTD). This is known to be a varied disorder with a mixture of tau-positive and tau-negative underlying pathologies. The other subtypes include semantic dementia (SD), which generally exhibits tau-negative pathology, and progressive non-fluent aphasia (PNFA), which is usually tau-positive. As the clinical presentation of these subtypes may overlap, a specific diagnosis can be difficult to attain and today no specific biomarker can predict the underlying pathology. Neurofilament light chain protein (NFL), a cytoskeletal constituent of intermediate filaments, is thought to reflect neuronal and axonal death when appearing in the cerebrospinal fluid (CSF). NFL has been shown to be elevated in CSF in patients with FTD compared with AD and controls. Our hypothesis was that the levels of NFL also differ between the subtypes of FTD and may indicate the underlying pathological subtype. METHODS: We retrospectively analysed data from previous CSF analyses in 34 FTD cases (23 bvFTD, seven SD, four PNFA), 20 AD cases, and 26 healthy controls. A separate group of 10 neuropathologically verified and subtyped FTD cases (seven tau-negative, three tau-positive) were also analysed. RESULT: NFL levels were significantly higher in FTD compared with both AD (p<0.001) and controls (p<0.001). The NFL levels of SD and bvFTD were significantly higher (p<0.001) compared with AD. The biomarker profiles of PNFA and AD were similar. In the neuropathologically verified FTD cases, NFL was higher in the tau-negative than in the tau-positive cases (exact p=0.017). CONCLUSIONS: The marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies. The highest NFL values found in the SD group as well as in the neuropathologically verified tau-negative cases may be of subtype diagnostic value, if corroborated in larger patient cohorts. In bvFTD, a mixture of tau-positive and tau-negative underlying pathologies could possibly explain the intermediate NFL values.

Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab.

OBJECTIVE: The impact of present disease-modifying treatments (DMTs) in multiple sclerosis (MS) on nerve injury and reactive astrogliosis is still unclear. Therefore, we studied the effect of natalizumab treatment on the release of 2 brain-specific tissue damage markers into cerebrospinal fluid (CSF) in MS patients. METHODS: CSF samples from 92 patients with relapsing forms of MS were collected in a prospective manner prior to natalizumab treatment and after 6 or 12 months. In 86 cases, natalizumab was used as second-line DMT due to breakthrough of disease activity. The levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) were determined using highly sensitive in-house developed enzyme-linked immunosorbent assays. RESULTS: Natalizumab treatment led to a 3-fold reduction of NFL levels, from a mean value of 1,300 (standard deviation [SD], 2,200) to 400 (SD, 270) ng/l (p < 0.001). The later value was not significantly different from that found in healthy control subjects (350 ng/l; SD, 170; n = 28). Subgroup analysis revealed a consistent effect on NFL release, regardless of previous DMT or whether patients had relapses or were in remission within 3 months prior to natalizumab treatment. No differences between pre- and post-treatment levels of GFAP were detected. INTERPRETATION: Our data demonstrate that natalizumab treatment reduces the accumulation of nerve injury in relapsing forms of MS. It is anticipated that highly effective anti-inflammatory treatment can reduce axonal loss, thereby preventing development of permanent neurological disability.

Prediction of Outcome After Endovascular Embolectomy in Anterior Circulation Stroke Using Biomarkers.

Stroke is a major public health problem that can cause a long-term disability or death due to brain damage. Serious stroke is frequently caused by a large vessel occlusion in the anterior circulation, which should be treated by endovascular embolectomy if possible. In this study, we investigated the use of the brain damage biomarkers tau, NFL, NSE, GFAp, and S100B to understand the progression of nervous tissue damage and their relationship to outcome in such stroke after endovascular treatment. Blood samples were taken from 90 patients pre-treatment and 2 h, 24 h, 48 h, 72 h and 3 months after endovascular treatment. Stroke-related neurological deficit was estimated using the National Institute of Health Stroke Scale (NIHSS) at admission and at 24 h. Neurological outcome was evaluated at 3 months. After stroke, tau, NFL, GFAp and S100B increased in a time dependent manner, while NSE remained constant over time. At 3 months, tau and GFAp levels were back to normal whereas NFL was still high. Tau, NFL and GFAp correlated well to outcome, as well as to infarct volume and NIHSS at 24 h. The best time for prediction of poor outcome was different for each biomarker. However, the combination of NIHSS at 24 h with either tau, NFL or GFAp at 48 h gave the best prediction. The use of biomarkers in the early setting after endovascular treatment of stroke will lead to a simplified and standardized way to estimate the nervous tissue damage and possibly complement the clinical judgement in foreseeing the need of rehabilitation measures.

Differences in lesion severity and cellular composition between in vivo assessed upstream and downstream sides of human symptomatic carotid atherosclerotic plaques.

BACKGROUND: The heterogeneous structure of carotid atherosclerotic plaques may be better understood if it is related to blood flow variations, influencing gene expression and cellular functions. Upstream of the maximum stenosis there is laminar blood flow and high shear stress, downstream there is turbulence and low shear stress. We studied if these variations were associated with differences in plaque morphology and composition between sites located up- and downstream of the maximum stenosis in symptomatic carotid plaques. METHODS: Patients with symptomatic carotid stenosis were examined with magnetic resonance angiography to localize the maximum stenosis in-vivo, prior to endarterectomy. In 41 endarterectomized specimens, transverse tissue sections prepared up- and downstream of the maximum stenosis were compared using histopathology and immunohistochemistry. RESULTS: The location of maximum stenosis relative the carotid bifurcation varied considerably between plaques. Compared with the downstream side, the upstream side of the stenosis had higher incidence of severe lesions with cap rupture and intraplaque hemorrhage, more macrophages, less smooth muscle cells and more collagen. CONCLUSIONS: The up- and downstream sides of symptomatic carotid plaques differed in plaque morphology and composition. This implies that the intraplaque location of sampling sites may be a confounding factor in studies of atherosclerotic plaques.

Effects of cerebrovascular disease on amyloid precursor protein metabolites in cerebrospinal fluid.

BACKGROUND: Alzheimer's disease (AD) and cerebrovascular disease (CVD) including chronic small vessel disease of the brain (SVD) are the most frequent causes of dementia. AD is associated with metabolism of amyloid precursor protein (APP) and low levels of amyloid-beta peptide (Abeta) X-42 in the cerebrospinal fluid (CSF). CVD and SVD are established risk factors for AD, brain white matter lesions (WML) are established surrogate markers for SVD and are also associated with reduced CSF AbetaX-42.A cohort survey was performed to examine whether SVD or acute CVD affects APP metabolism and to explore a potential association between WML and APP metabolism in two groups; cognitively impaired patients, subjective and mild (SCI and MCI) and stroke patients. Through measurements of CSF APP metabolite levels in patients with a wide range of WML volumes, this study aimed to determine how SVD influences APP metabolism. METHODS: Sixty-three patients were included: 37 with subjective cognitive impairment (SCI) or mild cognitive impairment (MCI) without stroke, and 26 after acute stroke. Chronic and acute WML volume and infarct volume were determined by magnetic resonance imaging (MRI) post-scan processing, and CSF levels of alpha- and beta-cleaved soluble APP (sAPP-alpha and sAPP-beta, AbetaX-38, AbetaX-40 and AbetaX-42) were determined. The Mann-Whitney test was used to compare the patient groups. Chronic and acute WML volumes, infarct volume, age, and sex were used as predictors for CSF biomarker levels in linear regression analysis. RESULTS: CSF levels of sAPP-alpha and sAPP-beta were strongly correlated (r = 0.95, p < 0.001) and lower levels of these biomarkers were found in the stroke group than in the SCI/MCI group; median sAPP-alpha 499.5 vs. 698.0 ng/mL (p < 0.001), sAPP-beta 258.0 vs. 329.0 ng/mL (p < 0.005). CSF levels of sAPP-alpha, sAPP-beta, AbetaX-38, AbetaX-40 and AbetaX-42 were inversely correlated with chronic WML volume (p

Is there a CSF biomarker profile related to depression in elderly women?

In light of our previous observation of higher levels of cerebrospinal fluid (CSF) amyloid beta-42 (Abeta42) and CSF/serum albumin ratio in major depressive disorder (MDD), we analyzed two additional CSF biomarkers reflecting neurodegeneration-neurofilament protein light (NFL) and glial fibrillary acidic protein (GFAp)-in relationship to prevalent geriatric depression. Neuropsychiatric, physical, and lumbar puncture examinations, with DSM-III-R-based depression diagnoses and measurement of CSF levels of NFL and GFAp, were evaluated among a population-based sample of 78 elderly women (mean age, 73.9+/-3.2 years) without dementia for at least 10 years after CSF collection. Eleven (13.1%) women had MDD, and higher levels of NFL compared with women without depression. A multivariate model including age, NFL, Abeta42 and the CSF/serum albumin ratio showed that each biomarker was independently and positively associated with MDD, and that this biomarker profile explained more variation in the model compared with single or combined biomarkers. A CSF profile with higher levels of NFL, Abeta42, and CSF/serum albumin ratio may indicate neuropathological and vascular events in depression etiology. This contrasts with the well-characterized pattern of low Abeta42, higher CSF/serum albumin ratio, and higher NFL in Alzheimer's disease.

Do patients with large vessel occlusion ischemic stroke harboring prestroke disability benefit from thrombectomy?

OBJECTIVES: Evidence of endovascular treatment (EVT) for acute large vessel occlusion (LVO) ischemic stroke in patients harboring substantial prestroke disability is lacking due to their exclusion from randomized trials. Here, we used routine care observational data to compare outcomes in patients with and without prestroke disability receiving EVT for LVO ischemic stroke. METHODS: Consecutive patients undergoing EVT for acute LVO ischemic stroke at the Sahlgrenska University Hospital from January 1st, 2015 to March 31st, 2018 were registered in the Sahlgrenska Stroke Recanalization Registry. Pre- and poststroke functional levels were assessed by the modified Rankin Scale (mRS). Outcomes were recanalization rate (mTICI = 2b/3), symptomatic intracranial hemorrhage [sICH], complications during hospital stay, and return to prestroke functional level and mortality at 3 months. RESULTS: Among 591 patients, 90 had prestroke disability (mRS ≥ 3). The latter group were older, more often female, had more comorbidities and higher NIHSS scores before intervention compared to patients without prestroke disability. Recanalization rates (80.0% vs 85.0%, p = 0.211), sICH (2.2% vs 6.3% p = 0.086) and the proportion of patients returning to prestroke functional level (22.7% vs 14.8% p = 0.062) did not significantly differ between those with and without prestroke disability. Patients with prestroke disability had higher complication rates during hospital stay (55.2% vs 40.1% p < 0.01) and mortality at 3 months (48.9% vs 24.3% p < 0.001). CONCLUSION: One of five with prestroke disability treated with thrombectomy for a LVO ischemic stroke returned to their prestroke functional level. However, compared to patients without prestroke disability, mortality at 3 months was higher.

Biomarkers in the cerebrospinal fluid and neurodegeneration in Langerhans cell histiocytosis.

BACKGROUND: Progressive neurodegeneration may result in potentially severe cognitive and motor dysfunctions as a complication of Langerhans cell histiocytosis (LCH), a suggested IL-17A-associated inflammatory condition. To detect this complication (CNS-LCH) early and to evaluate the potential efficacy of therapeutic interventions, biomarkers detecting and measuring ongoing neurodegeneration would be valuable. We evaluated cerebrospinal fluid (CSF) biomarkers of ongoing neurodegeneration in CNS-LCH patients. PROCEDURE: Nine patients with endocrine, neuromotor, cognitive or/and behavioral abnormalities as well as neuroradiological evidence of CNS-LCH were evaluated 4-12 years after LCH diagnosis for CSF levels of neurofilament protein light chain (NF-L), glial fibrillary acid protein (GFAp), and total tau protein (TAU). Two patients were analyzed longitudinally. One hundred ten children with newly diagnosed acute lymphoblastic leukemia (ALL) served as controls. RESULTS: NF-L, TAU, and GFAp levels were elevated in four, six, and eight of nine patients studied, respectively. NF-L (P < 0.001) and GFAp (P < 0.001) were higher in patients than in controls (TAU not analyzed in controls). The patient with most severe clinical and neuroradiological CNS-LCH displayed the highest levels of NF-L and GFAp whereas three patients without signs of systemic disease had low TAU levels and normal/slightly elevated NF-L. NF-L tended to be higher at radiological progression of neurodegeneration than at status quo (P = 0.07). Notably, we experienced frequent lumbar puncture complications in these patients. CONCLUSIONS: CSF levels of NF-L, TAU, and GFAp appear to be elevated in CNS-LCH. It would be valuable if these markers were validated in order to serve as markers for early CNS-LCH, to monitor disease progression and to evaluate various treatment attempts for CNS-LCH.