Long-term prognostic value of [15O]H2O PET imaging in patients suspected for cerebral hemodynamic insufficiency.

OBJECTIVES: Quantitative regional cerebral perfusion (rCBF) measurements using [15O]H2O PET with arterial cannulation and acetazolamide (ACZ) challenge have been reserved to identify high-risk patients that are candidates for by-pass operation. We aimed to assess the prognostic value of various parameters in quantitative [15O]H2O PET measurements in patients not subsequently undergoing surgery. METHODS: We identified 32 eligible patients who underwent [15O]H2O brain PET imaging for suspicion of hemodynamic insufficiency between 2009 and 2020. Cerebrovascular events were defined as new ischemic lesions on MRI, stroke, transient ischemic attack, vascular dementia. Follow-up period was 91 months (range: 26-146). rCBF before (rCBFbase) and after (rCBFacz) ACZ challenge and the relative increase (CVR), were examined in the anterior (ACA), middle (MCA), and posterior (PCA) cerebral artery territories of the affected hemisphere, and the most recent MRI scans were scored for infarcts and white matter lesions. RESULTS: Receiver operating characteristic (ROC) curve analysis showed higher prognostic accuracy for rCBFacz(AUC:0.82) compared to CVR (AUC:0.72) and rCBFbase (AUC:0.77). ROC AUC, optimal thresholds (and corresponding sensitivity/specificity/accuracy) for rCBFacz after ACZ in individual territories were 0.79 and 37.8 mL 100g-1 min-1 (0.81/0.63/0.72) for the ACA, 0.84 and 32 mL 100g-1 min-1 (0.81/0.75/0.78) for the MCA, and 0.70 and 43.9 ml/(mL 100g-1 min-1 (0.81/0.43/0,62) for the PCA. Kaplan Meier survival curve showed longer event-free survival in patients with rCBFacz below cut-off (p=0.007). In multivariate analysis rCBFacz remained a significant predictor when correcting for age. CONCLUSION: Quantitative rCBF measurements after ACZ challenge with [15O]H2O PET provided high prognostic value for future cerebrovascular events.

Computer-Based Cognitive Rehabilitation in Patients with Visuospatial Neglect or Homonymous Hemianopia after Stroke.

OBJECTIVES: The purpose of this pilot study was to investigate the feasibility and effects of computer-based cognitive rehabilitation (CBCR) in patients with symptoms of visuospatial neglect or homonymous hemianopia in the subacute phase following stroke. METHOD: A randomized, controlled, unblinded cross-over design was completed with early versus late CBCR including 7 patients in the early intervention group (EI) and 7 patients in the late intervention group (LI). EI received CBCR training immediately after inclusion (m = 19 days after stroke onset) for 3 weeks and LI waited for 3 weeks after inclusion before receiving CBCR training for 3 weeks (m = 44 days after stroke onset). RESULTS: CBCR improved visuospatial symptoms after stroke significantly when administered early in the subacute phase after stroke. The same significant effect was not found when CBCR was administered later in the rehabilitation. The difference in the development of the EI and LI groups during the first 3 weeks was not significant, which could be due to a lack of statistical power. CBCR did not impact mental well-being negatively in any of the groups. In the LI group, the anticipation of CBCR seemed to have a positive impact of mental well-being. CONCLUSION: CBCR is feasible and has a positive effect on symptoms in patients with visuospatial symptoms in the subacute phase after stroke. The study was small and confirmation in larger samples with blinded outcome assessors is needed.

Significance of arterial spin labeling perfusion and susceptibility weighted imaging changes in patients with transient ischemic attack: a prospective cohort study.

BACKGROUND: In a prospective cohort of patients with transient ischemic attack (TIA), we investigated usefulness and feasibility of arterial spin labeling (ASL) perfusion and susceptibility weighted imaging (SWI) alone and in combination with standard diffusion weighted (DWI) imaging in subacute diagnostic work-up. We investigated rates of ASL and SWI changes and their potential correlation to lasting infarction 8 weeks after ictus. METHODS: Patients with TIA underwent 3T-MRI including DWI, ASL and SWI within 72 h of symptom onset. We defined lasting infarction as presence of 8-week MRI T2-fluid attenuated inversion recovery (FLAIR) hyperintensity or atrophy in the area of initial DWI-lesion. RESULTS: We included 116 patients. Diffusion and perfusion together identified more patients with ischemia than either alone (59% vs. 40%, p < 0.0001). The presence of both diffusion and perfusion lesions had the highest rate of 8-week gliosis scars, 65% (p < 0.0001). In white matter, DWI-restriction was the determinant factor for scar development. However, in cortical gray matter half of lesions with perfusion deficit left a scar, while lesions without perfusion change rarely resulted in scars (56% versus 21%, p = 0.03). SWI lesions were rare (6%) and a subset of perfusion lesions. SWI-lesions with DWI-lesions were all located in cortical gray matter and showed high scar rate. CONCLUSIONS: ASL perfusion increased ischemia detection in patients with TIA, and was most useful in conjunction with DWI. ASL was fast, robust and useful in a subacute clinical diagnostic setting. SWI had few positive findings and did not add information. TRIAL REGISTRATION: http://www.clinicaltrials.gov . Unique Identifier NCT01531946 , prospectively registered February 9, 2012.

Arterial spin labeling: a technical overview.

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging perfusion method based on changes in net-magnetization of blood water. The absence of contrast use and ionizing radiation, renders ASL valuable in hyper-acute settings as a monitoring tool for repeated dynamical measurements during and after intervention, and for patients with known co-morbidities. This text provides a short methodological introduction to ASL and contrasts it with traditional contrast-enhanced perfusion imaging. The review focused on sequence usefulness in the clinical setting of acute cerebral ischemia investigation.

Does the Primary Imaging Modality-Computed Tomography or Magnetic Resonance Imaging-Influence Stroke Physicians' Certainty on Whether or Not to Give Thrombolysis to Randomized Acute Stroke Patients?

BACKGROUND: Door-to-needle time of 20 minutes to stroke patients with intravenous tissue plasminogen activator (iv-tPA) is feasible when computed tomography (CT) is used as first-line of brain imaging. Magnetic resonance imaging (MRI)-based assessment is more time-consuming but superior in detecting acute ischemia. The certainty with which stroke physicians prescribe or refrain from giving iv-tPA treatment to CT- versus MRI-examined patients has not previously been studied. The aim of the present study was to determine the effect of a primary imaging strategy of CT or MRI on clinicians' certainty to prescribe or refrain from giving iv-tPA to patients with suspected acute stroke. METHOD: Consecutive patients with suspected stroke were quasi-randomized to either CT- or MRI-based assessment before potential iv-tPA treatment. The influence of (1) the clinical findings and (2) the image findings, and (3) the certainty with which the stroke physician prescribed or refrained from giving iv-tPA treatment were assessed with visual analog scales (VAS). Predictors of treatment certainty were identified with a random-effect model. RESULTS: Four-hundred forty-four consecutive patients were quasi-randomized. MRI influenced the final treatment decision more than CT (P = .002). Compared with CT-examined patients (mean VAS score 8.6, SD ±1.6) stroke physicians were significantly more certain when prescribing or refraining from giving iv-tPA to MRI-examined patients (mean VAS score 9.0, SD ±1.2) (P = .014). No differences in modified Rankin scale or mortality were detected at 3 months in CT- versus MRI-examined iv-tPA-treated patients. CONCLUSIONS: Stroke physicians were significantly more certain when prescribing iv-tPA to MRI-examined stroke patients, and MRI influences the final treatment decision significantly more compared with CT, although no difference in mortality and functional outcome at 3 months was detected between CT- and MRI-examined patients treated with iv-tPA.

Computed Tomography--Verified Leukoaraiosis Is a Risk Factor for Post-thrombolytic Hemorrhage.

BACKGROUND: Is computed tomography (CT)-verified leukoaraiosis (LA) a risk factor for post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage? METHODS: (1) Retrospective analysis based on a prospectively planned single-center registry of consecutive tissue plasminogen activator (tPA)-treated patients within 4.5 hours from symptom onset. Standard work-up included baseline noncontrast CT and CT angiography and next day follow-up noncontrast CT. Baseline noncontrast CT LA was graded using Fazekas' score and dichotomized as the absence (Fazekas, 0) or the presence (Fazekas, 1-3). Hemorrhagic transformation was rated using European Cooperative Acute Stroke Study (ECASS) criteria. Symptomatic intracerebral hemorrhage was defined as hemorrhage and deterioration of National Institutes of Health Stroke Scale (NIHSS) of 4 or greater within 36 hours from symptom onset. Endovascularly treated patients were excluded. (2) Pooled analysis with 1312 tPA-treated patients from literature. RESULTS: In all, 311 tPA-treated patients were included between April 2009 and July 2012. LA was present in 113 (36%). Twenty-three (7%) showed hemorrhagic transformation. LA positive patients had significantly higher hemorrhagic transformation frequency (11.5%, P = .04). LA doubled hemorrhagic transformation risk (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.4-5.8). Only 4 patients developed symptomatic intracerebral hemorrhage, 3 with LA. LA was not an independent risk factor for hemorrhagic transformation (P = .2). Pooled analysis of 1623 patients in total, hereof 479 LA positive patients, showed significantly higher symptomatic intracerebral hemorrhage frequency in 35 (7.3%) LA positive than that in 44 (3.8%) LA negative patients, (P = .005) and doubled symptomatic intracerebral hemorrhage risk in LA positives (OR, 1.97; 95% CI 1.22-3.19). CONCLUSIONS: LA doubles the risk of post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage; this finding does not support withholding thrombolysis from patients with LA.

Frequency of new pulmonary neoplasm incidentally detected by computed tomography angiography in acute stroke patients-a single-center study.

BACKGROUND: Incidental findings of suspect lung opacities are common in computed tomography (CT)-based thorax examinations, especially in high-risk patients, such as stroke patients. Screening with CT of the thorax has detected lung cancer in approximately .31%-1.20% of high-risk populations. The aim of the present study was to report the frequency of suspect lung opacities on routine acute stroke imaging. METHODS: Seven hundred and fifty-seven consecutive stroke patients evaluated for intravenous thrombolysis treatment within 4.5 hours of symptom debut, from June 2009 to December 2011, were included in a prospective registry on which this analysis was based. On admission, CT angiography from the aortic arch to vertex was performed, including the lung apices, corresponding to 1/3 of the total lung volume. A senior neuroradiologist reviewed all scans registering suspect lung opacities, which subsequently were characterized as either malignant, presumed malignant, presumed benign or benign, based on radiologic parameters of malignancy, positron emission tomography scan, histology, and clinical features. RESULTS: Suspect lung opacities appeared on the CT angiography in 20 patients (2.6%). Five suspect lung opacities were categorized as malignant and 3 suspect lung opacities were categorized as presumed malignant. This corresponds to an incidence of 1.1% (8 of 750). CONCLUSIONS: Malignant lung opacities were found in approximately 1% of this high-risk population, whereas our findings do not support full CT of the thorax as routine on stroke patients.

Time course of early postadmission hematoma expansion in spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Early hematoma expansion (EHE) in patients with intracerebral hematoma is a promising treatment target. To date, the time course of EHE has remained poorly described. We prospectively investigated the time course of EHE. METHODS: We included consecutive patients presenting spontaneous intracerebral hematoma within 4.5 hours. On admission, patients underwent noncontrast computed tomography (CT) and CT angiography. Serial hematoma volume estimations by transcranial B-mode ultrasound were effected through the contralateral transtemporal bone window by obtaining sagittal, transversal, and coronal diameter and calculating the ABC/2-formula. National Institute of Health Stroke Scale and transcranial B-mode ultrasound were performed consecutively every 30 minutes during the first 6 hours and from 6 to 12 hours every 2 hours. Follow-up CT and ultrasound were performed after ≈24 hours. RESULTS: Twenty-five patients with intracerebral hematoma were included; mean (SD) time from onset to CT was 108.6 (45.7) minutes. Ten (40%) patients had EHE. In patients with a final clinically significant hematoma expansion >12.5 mL, all EHE occurred within 6 hours after admission scan. EHE in spot sign positive patients continued during the first 5 hours after CT angiography. In spot sign-negative patients, no significant EHE was observed (Friedman test, P=0.476). Neurological deterioration occurred in 5 (20%) patients and was well temporally correlated with EHE. Transcranial B-mode ultrasound demonstrated good volume estimation compared with the follow-up CT with a maximum absolute volume deviation within 7 mL and minimal systematic error (mean deviation, 1.3 [confidence interval, -0.1 to 2.6] mL). CONCLUSIONS: EHE was reliably reflected by transcranial B-mode ultrasound and mainly occurred within the first 7 to 8 hours after symptom onset. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472224.

Showing no spot sign is a strong predictor of independent living after intracerebral haemorrhage.

BACKGROUND: A spot sign on computed tomography angiography (CTA) is a potentially strong predictor of poor outcome on ultra-early radiological imaging. The aim of this study was to assess the spot sign as a predictor of functional outcome at 3 months as well as long-term mortality, with a focus on the ability to identify patients with a spontaneous, acceptable outcome. METHODS: In a prospective, consecutive single-centre registry of acute stroke patients, we investigated patients with spontaneous intracerebral haemorrhage (ICH) admitted within 4.5 h after symptom onset from April 2009 to January 2013. The standard work-up in our centre included CTA for spot sign status, unless a contraindication was present. Modified Rankin Scale (mRS) scores were assessed at 3 months in the outpatient clinic or by telephone interviews. Long-term mortality was assessed by electronic chart follow-up for up to 1,500 days. RESULTS: Of the 128 patients, 37 (28.9%) had a spot sign on admission CTA. The presence of a spot sign was associated with larger median admission haematoma volume [38.0 ml (IQR 18.0-78.0) vs. 12.0 ml (5.0-24.0); p<0.0001] and higher median National Institutes of Health Stroke Scale score [19 (IQR 12-23) vs. 12 (6-16); p<0.0001]. Three months after stroke, the median functional outcome was considerably better in patients without spot sign [mRS score 3 (IQR 2-4) vs. 6 (4-6); p<0.0001]. The absence of a spot sign showed a sensitivity and specificity for good outcome (mRS scores 0-2) of 0.91 and 0.36, respectively. The presence of a spot sign was, in multivariate models, an independent inverse predictor of good 3-month outcome (OR 0.17; 95% CI: 0.03-0.88) as well as a prominent independent predictor of poor 3-month outcome (mRS scores 5-6; OR 3.40; 95% CI: 1.10-10.5) and death during follow-up (HR 3.04; 95% CI: 1.45-6.34). Patients with a spot sign surviving the acute phase had long-term survival comparable to patients with no spot sign. CONCLUSION: The absence or presence of a spot sign is a reliable ultra-early predictor of long-term mortality and functional outcome in patients with spontaneous ICH.

Symptoms of arteria spinalis anterior syndrome in a patient with ischaemic stroke and Takayasu arteritis.

In Denmark, around 4,500 people are diagnosed with colorectal cancer (CRC) annually. This review investigates that while the efficacy of immunotherapy in CRC is still being studied, immunotherapy is currently only indicated in the treatment of mismatch-repair deficient (dMMR) metastatic CRC, which accounts for 10-15% of patients. Recent studies indicate high rates of pathologic response in dMMR CRC treated with pre-operative immunotherapy while large-scale studies on novel immunotherapy combinations are ongoing.

Left atrial late gadolinium enhancement in patients with ischaemic stroke.

AIMS: To evaluate the extent of left atrial (LA) fibrosis in patients with a recent stroke without atrial fibrillation and controls without established cardiovascular disease. METHODS AND RESULTS: This prospectively designed study used cardiac magnetic resonance to detect LA late gadolinium enhancement as a proxy for LA fibrosis. Between 2019 and 2021, we consecutively included 100 patients free of atrial fibrillation with recent ischaemic stroke (<30 days) and 50 age- and sex-matched controls. LA fibrosis assessment was achieved in 78 patients and 45 controls. Blinded to the cardiac magnetic resonance results, strokes were adjudicated according to modified Trial of Org 10172 in Acute Stroke Treatment classification as undetermined aetiology (n = 42) or as attributable to large- or small-vessel disease (n = 36). Patients with stroke had a larger extent of LA fibrosis [6.9%, interquartile range (IQR) 3.6-15.4%] than matched controls (4.2%, IQR 2.3-7.5%; P = 0.007). No differences in LA fibrosis were observed between patients with stroke of undetermined aetiology and those with large- or small-vessel disease (6.6%, IQR 3.8-16.0% vs. 6.9%, IQR 3.4-14.6%; P = 0.73). CONCLUSION: LA fibrosis was more extensive in patients with stroke than in age- and sex-matched controls. A similar extent of LA fibrosis was observed in patients with stroke of undetermined aetiology and stroke classified as attributable to large- or small-vessel disease. Our findings suggest that LA structural abnormality is more frequent in patients with stroke than in controls independent of aetiological classification.

Interobserver agreement in fusion status assessment after instrumental desis of the lower lumbar spine using 64-slice multidetector computed tomography: impact of observer experience.

PURPOSE: Persistent lower back pain after instrumental posterolateral desis may arise from incomplete fusion. We investigate the impact of experience on interobserver agreement in fusion estimation. METHODS: Four independent observers, two residents and two musculoskeletal radiologists, reviewed dedicated lumbar 64-MDCT scans and scored vertebral levels 1-5 after Glassman's grades, 1: solid bilateral fusion, 2: solid unilateral fusion, 3: partial bilateral fusion, 4: partial unilateral fusion, 5: non-fusion. We investigated two simplifying dichotomizations, solid bilateral fusion (Glassman 1) versus all others and uni- or bilateral fusion (Glassman 1-2) versus partial or non-fusion. RESULTS: Thirty-six patients with 61 operated lumbar levels were included. Interobserver agreement rates for four observers using Glassman's system were fair (kappa 0.32), either dichotomization showed moderate agreement (kappa 0.53 and 0.59). Observer pairs had comparable prevalence adjusted interobserver agreement rates (residents: PABAK 0.67 and 0.54; consultants: PABAK 0.57 and 0.71). CONCLUSIONS: Difference in observer experience seems of minor impact.

E-learn computed tomographic angiography: a proposed educational tool for computed tomographic angiography in acute stroke.

BACKGROUND: Computed tomographic angiography (CTA) is widely available in emergency rooms to assess acute stroke patients. To standardize readings and educate new readers, we developed a 3-step e-learning tool based on the test-teach-retest methodology in 2 acute stroke scenarios: vascular occlusion and "spot sign" in acute intracerebral hemorrhage. We hypothesized that an e-learning program enhances reading skills in physicians of varying experience. METHODS: We developed an HTML-based program with a teaching segment and 2 matching test segments. Tests were taken before and after the teaching segment; the test size was 40% of the teaching segment size. We assessed diagnostic accuracy and readers' confidence. Results were compared using the Wilcoxon rank sum test. RESULTS: Four neurologic consultants and four radiologic residents completed the program. The vascular occlusion teaching segment increased diagnostic accuracy from 42% to 68% (P = .005). The neurologic consultants showed significant progress, with average scores of 50% versus 75% (P = .027). The radiologic residents showed trend with progress, with average scores of 33% versus 60% (P = .081). The entire group detected spot sign correctly 69% before versus 92% after teaching (P = .009) and reported a median self-perceived diagnostic certainty of 50% versus 75% (P = .030). Self-perceived diagnostic certainty revealed no significant increase for vascular occlusion. CONCLUSIONS: The e-learning program is a useful educational tool for users of varying experience, and it enhances diagnostic confidence.

Atrial cardiomyopathy in patients with ischaemic stroke: a cross-sectional and prospective cohort study-the COAST study.

INTRODUCTION: Despite workup for the aetiology of ischaemic stroke, about 25% of cases remain unexplained. Paroxysmal atrial fibrillation is typically suspected but often not detected. Even if atrial fibrillation (AF) is detected, the quantitative threshold of clinically relevant AF remains unclear. Emerging evidence suggests that left atrial (LA) functional and structural abnormalities may convey a risk of ischaemic stroke in which AF is only one of several features. These abnormalities have been termed 'atrial cardiomyopathy'. This study uses cardiac magnetic resonance (CMR) to evaluate atrial cardiomyopathy among patients with stroke of undetermined aetiology compared with those with an attributable mechanism and controls without established cardiovascular disease. METHODS AND ANALYSIS: This cross-sectional and prospective cohort study included 100 patients with recent ischaemic stroke and 50 controls with no established cardiovascular disease. The study will assess LA structural and functional abnormalities with CMR. Inclusion began in March 2019, and follow-up is planned to be complete in January 2023. There are two scheduled follow-ups: (1) 18 months after individual inclusion, counting from the index diagnostic MRI of the brain, (2) end of study follow-up at 18 months after inclusion of the last patient, assessing the incidence of recurrent ischaemic stroke, AF and cardiovascular death. The primary endpoint is the extent of CMR-assessed atrial fibrosis in the LA at baseline. The study is powered to detect a difference of 6% fibrosis between stroke of undetermined aetiology and stroke of known mechanism with a SD of 9%, a significance level of 0.05, and power of 80%. ETHICS AND DISSEMINATION: This study has been approved by the Danish National Committee on Health Research Ethics (H-18055313). All participants in the study signed informed consent. Results from the study will be published in peer-reviewed journals regardless of the outcome. TRIAL REGISTRATION NUMBER: NCT03830983.

Sex-Differences in Oral Anticoagulant-Related Intracerebral Hemorrhage.

Introduction and Aim: Data remain limited on sex-differences in patients with oral anticoagulant (OAC)-related intracerebral hemorrhage (ICH). We aim to explore similarities and differences in risk factors, acute presentation, treatments, and outcome in men and women admitted with OAC-related ICH. Method: This study was a retrospective observational study based on 401 consecutive patients with OAC-related ICH admitted within 24 h of symptom onset. The study was registered on osf.io. We performed logarithmic regression and cox-regression adjusting for age, hematoma volume, Charlson Comorbidity Index (CCI), and pre-stroke modified Ranking Scale (mRS). Gender and age were excluded from CHA2DS2-VASc and CCI was not adjusted for age. Results: A total of 226 men and 175 women were identified. More men were pre-treated with vitamin K-antagonists (73.5% men vs. 60.6% women) and more women with non-vitamin K-antagonist oral anticoagulants (26.5% men vs. 39.4% women), p = 0.009. Women were older (mean age 81.9 vs. 76.9 years, p < 0.001). CHA2DS2-VASc and CCI were similar in men and women.Hematoma volumes (22.1 ml in men and 19.1 ml in women) and National Institute of Health Stroke Scale (NIHSS) scores (13 vs. 13) were not statistically different, while median Glasgow Coma Scale (GCS) was lower in women, (14 [8;15] vs. 14 [10;15] p = 0.003).Women's probability of receiving reversal agents was significantly lower (adjusted odds ratio [aOR] = 0.52, p = 0.007) but not for surgical clot removal (aOR = 0.56, p = 0.25). Women had higher odds of receiving do-not-resuscitate (DNR) orders within a week (aOR = 1.67, p = 0.04). There were no sex-differences in neurological deterioration (aOR = 1.48, p = 0.10), ability to walk at 3 months (aOR = 0.69, p = 0.21) or 1-year mortality (adjusted hazard ratio = 1.18, p = 0.27). Conclusion: Significant sex-differences were observed in age, risk factors, access to treatment, and DNRs while no significant differences were observed in comorbidity burden, stroke severity, or hematoma volume. Outcomes, such as adjusted mortality, ability to walk, and neurological deterioration, were comparable. This study supports the presence of sex-differences in risk factors and care but not in presentation and outcomes.

Corrigendum: Sex-differences in oral anticoagulant-related intracerebral hemorrhage.

[This corrects the article DOI: 10.3389/fneur.2022.832903.].

[Todd's paralysis].

Todd's paralysis is a clinical entity consisting of acute focal neurological deficits following an epileptic seizure. It occurs after 6-13% of seizures, and the symptoms may last from minutes to 36 hours. Stroke with seizure at symptom onset is difficult to differentiate clinically from Todd's paralysis. The use of advanced imaging such as cerebral CT and MRI with angiography is recommended. This is a review of the current knowledge on pathogenesis, clinical presentation and differential diagnoses, and we propose an investigation plan for patients presenting with symptoms of Todd's paralysis.

Trends in incidence of oral anticoagulant-related intracerebral hemorrhage and sales of oral anticoagulants in Capital Region of Denmark 2010-2017.

INTRODUCTION: Non-vitamin K-antagonist oral anticoagulants (NOAC) have become first choice oral anticoagulant (OAC) with decreasing use of vitamin K antagonists (VKA), partly due to lower risk of intracerebral hemorrhage (ICH). Aim: to identify trends in sale of OACs and relate them to trends in OAC-related ICH (OAC-ICH). PATIENTS AND METHODS: Study was based on the population in the Capital Region of Denmark (1.8 million inhabitants). We identified all patients admitted with a non-traumatic OAC-ICH in 2010-2017 and ascertained diagnosis and drug use through medical charts. We used information available in the public domain on sale of defined daily doses (DDD) of OAC in the Capital Region of Denmark. RESULTS: 453 patients with OAC-ICH out of a total of 2877 ICH-events were identified. From 2010 to 2017 sale of NOAC rose from 0.1 to 11.8 DDD/1000 inhabitants/day (p < 0.001); while VKA sale decreased from 7.6 to 5.2 DDD/1000 inhabitants/day (p < 0.001). The total number of ICH events was stable between 2010 and 2017, but the proportion of OAC-ICH events increased from 13% in 2010 to 22% in 2017 (p < 0.001). The proportion of ICH events related to NOAC had a significant increasing trend (p < 0.001), whereas a decreasing trend was observed for VKA (p = 0.04). DISCUSSION: In Denmark, the population on OACs has increased; resulting from increased use of NOACs. Parallel to this development, the proportion of OAC-ICH overall has increased based on an increasing trend in NOAC-related ICH. CONCLUSION: Our findings document a need for further research on prevention and treatment of this complication.

Dural tear from diagnostic lumbar puncture followed by long-term morbidity: a case report.

BACKGROUND: Lumbar punctures are performed in different medical settings and are a key procedure in the diagnosis of several neurological conditions. Complications are rare and generally self-limiting. There are no reports of symptomatic accumulation of fluid in the epidural space after lumbar puncture in adults and there are no studies on long-term outcome after post dural puncture headache (PDPH). CASE: A lumbar puncture was performed in a 29 y.o. slender woman with unspecific symptoms to rule out neuro-infection. Next day MRI showed substantial accumulation of CSF in the epidural space from C2 to the sacrum dislocating the spinal chord in the spinal canal. The condition was ameliorated by epidural blood-patching. At 5 months she was still impaired by severe orthostatic headache. CONCLUSIONS: The only plausible explanation for the massive CSF leak was a dural tear occurring during multiple attempts of lumbar puncture. Anterior dislocation of the spinal chord due to CSF leak is not a recognised complication to lumbar puncture. This complication was followed by long-term disability in our case. The diagnosis can be made by MRI. A difficult procedure with several attempts and use of traumatic technique may increase risk of this complication.

Brain resting-state connectivity in the development of secondary hyperalgesia in healthy men.

Central sensitization is a condition in which there is an abnormal responsiveness to nociceptive stimuli. As such, the process may contribute to the development and maintenance of pain. Factors influencing the propensity for development of central sensitization have been a subject of intense debate and remain elusive. Injury-induced secondary hyperalgesia can be elicited by experimental pain models in humans, and is believed to be a result of central sensitization. Secondary hyperalgesia may thus reflect the individual level of central sensitization. The objective of this study was to investigate possible associations between increasing size of secondary hyperalgesia area and brain connectivity in known resting-state networks. We recruited 121 healthy participants (male, age 22, SD 3.35) who underwent resting-state functional magnetic resonance imaging. Prior to the scan session, areas of secondary hyperalgesia following brief thermal sensitization (3 min. 45 °C heat stimulation) were evaluated in all participants. 115 participants were included in the final analysis. We found a positive correlation (increasing connectivity) with increasing area of secondary hyperalgesia in the sensorimotor- and default mode networks. We also observed a negative correlation (decreasing connectivity) with increasing secondary hyperalgesia area in the sensorimotor-, fronto-parietal-, and default mode networks. Our findings indicate that increasing area of secondary hyperalgesia is associated with increasing and decreasing connectivity in multiple networks, suggesting that differences in the propensity for central sensitization, assessed as secondary hyperalgesia areas, may be expressed as differences in the resting-state central neuronal activity.