Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology.

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman's rho = 0.668 p < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13-3.54]% vs. 0.53 [0.14-3.07]%, p = 0.923) or in NT-proBNP expression (0.29 [0.11-0.58]% vs. 0.18 [0.05-0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process.

The capacity of neurological pupil index to predict the absence of somatosensory evoked potentials after cardiac arrest - An observational study.

Background: In neurologic prognostication of comatose survivors from cardiac arrest, two independent predictors of poor outcome are the loss of the Pupillary light reflex (PLR) and the loss of the N20 response from Somatosensory Evoked potentials (SSEP). The PLR can be quantitatively assessed by pupillometry. Both tests depend on the midbrain, in which a dysfunction reflects a severe hypoxic injury. We reasoned that a certain level of defective PLR would be predictive of a bilaterally absent SSEP N20 response. Method: Neurological Pupil index (NPi) from the pupillometry and the SSEP N20 response were registered >48 h after cardiac arrest in comatose survivors. Clinical data were retrospectively analyzed. A receiver operating characteristic curve was used to evaluate the capacity of NPi to predict bilaterally absent SSEP N20 response. An NPi threshold value resulting in <5% false positive rate (FPR) for bilaterally absent N20 response was identified. Results: From February 2020 to August 2022, we included 54 patients out of which 49 had conclusive pupillometry and SSEP examinations. The NPi threshold value with FPR < 5% was 3.4, yielding 36% sensitivity (95% CI 18-55) and significantly discriminated between respective groups with preserved and bilaterally absent N20 response to SSEP (p-value <0.01). Conclusion: In this limited cohort, NPi < 3.4 in patients remaining comatose >48 hours after cardiac arrest predicted bilateral loss of the SSEP N20 response with a FPR < 5%. If validated in a larger cohort, an NPi threshold may be clinically applied in settings where SSEP is unavailable.

Reduced long-term mortality after successful resective epilepsy surgery: a population-based study.

BACKGROUND: We investigated all-cause and epilepsy-related mortality in patients operated with resective epilepsy surgery and in non-operated patients with drug-resistant epilepsy. Our hypothesis was that patients who proceed to surgery have lower mortality over time compared with non-operated patients. METHOD: Data from 1329 adults and children from the Swedish National Epilepsy Surgery Register and 666 patients with drug-resistant epilepsy who had undergone presurgical work-up but not been operated were analysed. The operated patients had follow-ups between 2 and 20 years. We used the Swedish Cause of Death Register to identify deaths. Autopsy reports were collected for patients with suspected sudden unexpected death in epilepsy (SUDEP). Kaplan-Meier and Cox regression analyses were performed to identify predictors for mortality and SUDEP. RESULTS: SUDEP accounted for 30% of all deaths. Surgery was associated with lower all-cause mortality (HR 0.7, 95% CI 0.5 to 0.9), also when adjusted for age, sex and tonic-clonic seizures at inclusion. The benefit of surgery seemed to persist and possibly even increase after 15 years of follow-up. Risk factors of mortality for operated patients were persisting seizures and living alone. Of the operated patients, 37% had seizures, and these had a higher risk of mortality (HR 2.1, 95% CI 1.4 to 3.0) and SUDEP (HR 3.5, 95% CI 1.7 to 7.3) compared with patients with seizure freedom at last follow-up. CONCLUSIONS: In this large population-based epilepsy surgery cohort, operated patients had a lower all-cause mortality compared with non-operated patients with drug-resistant epilepsy. Seizure freedom was the most important beneficial factor for both all-cause mortality and SUDEP among operated patients.

White blood cell subtypes and neutrophil extracellular traps content as biomarkers for stroke etiology in acute ischemic stroke clots retrieved by mechanical thrombectomy.

BACKGROUND: Lymphocytes, macrophages, neutrophils, and neutrophil extracellular traps (NETs) associate with stroke risk factors and form a thrombus through different mechanisms. We investigated the total WBCs, WBC subtypes and NETs composition in acute ischemic stroke (AIS) clots to identify possible etiological differences that could help us further understand the process of thrombosis that leads to AIS. METHODS: AIS clots from 100 cases each of atherothrombotic (AT), cardioembolic (CE) and cryptogenic stroke etiology were collected per-pass as part of the CÚRAM RESTORE registry of AIS clots. Martius Scarlet Blue stain was used to identify the main histological components of the clots. Immunohistochemical staining was used to identify neutrophils, lymphocytes, macrophages, and NETs patterns. The cellular and histological components were quantified using Orbit Image Analysis software. RESULTS: AT clots were larger, with more red blood cells and fewer WBCs than CE clots. AT clots had more lymphocytes and cryptogenic clots had fewer macrophages than other etiologies. Most significantly, CE clots showed higher expression of neutrophils and extracellular web-like NETs compared to AT and cryptogenic clots. There was also a significantly higher distribution of web-like NETs around the periphery of the CE clots while a mixed distribution was observed in AT clots. CONCLUSION: The difference in neutrophil and NETs expression in clots from different etiologies may provide insight into the mechanism of clot formation.

[Preventive treatment to avoid recurrence of stroke and TIA is effective]. / Förebyggande behandling efter ischemisk stroke/TIA har effekt.

Healthy living with physical activity, healthy eating habits, no smoking, and no alcohol overuse have an important role in primary and secondary stroke prevention. Further secondary prevention depends on type and cause of stroke or TIA. After intracerebral bleeding, ischemic stroke or TIA, preventive pharmacological therapies include antihypertensive drugs. After ischemic stroke or TIA, treatment with antithrombotics (oral anticoagulants or antiplatelets) and statins is recommended. In stroke due to unusual causes, the pharmacological preventive treatment described above may need modification. For symptomatic carotid stenosis, carotid surgery is recommended, preferably within the first 14 days after onset. A surgical preventive treatment is closure of patent foramen ovale in patients aged 18-60 years with ischemic stroke of unknown cause.

Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke-A Prospective Observational Study.

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4-8.5 and OR 5.7, 95% CI: 2.5-12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1-3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.

Risk of poststroke epilepsy after reperfusion therapies: A national cohort study.

BACKGROUND AND PURPOSE: The risk of poststroke epilepsy (PSE) after endovascular treatment (EVT) is not well characterized. In this nationwide study, we assessed the risk of PSE after EVT and identified associated predictors. METHODS: We included all individuals (n = 3319) treated with EVT (±intravenous thrombolysis [IVT]) between 2015 and 2019 in the Swedish National Quality Register for EVT. Two control groups were identified from the Swedish Stroke Register: the first treated with IVT alone (n = 3132) and the second with no treatment (n = 3184), both matched for age, sex, stroke severity, and time of stroke. RESULTS: PSE developed in 7.9% (n = 410). The survival-adjusted 2-year risk was 6.5% (95% confidence interval [CI] = 5.28-7.70) after EVT, 10.0% (95% CI = 8.25-11.75) after IVT, and 12.3% after no revascularization (95% CI = 10.33-14.25). The hazard ratio (HR) of PSE after EVT was almost half compared to no treatment (HR = 0.51, 95% CI = 0.41-0.64). The risk of PSE after EVT was lower compared to no treatment in a multivariable Cox model that adjusted for age, sex, hemicraniectomy, and stroke severity (HR = 0.76, 95% CI = 0.60-0.96). Multivariable predictors of PSE after EVT were large infarction on computed tomography Day 1, high posttreatment National Institutes of Health Stroke Scale score, and need of assistance 3 months after stroke. IVT before EVT was associated with a lower risk of PSE (HR = 0.66, 95% CI = 0.46-0.94). CONCLUSIONS: This nationwide study identified a reduced risk of PSE after EVT. Markers of severe infarction after EVT were associated with PSE, whereas IVT given before EVT was protective.

Cancer and stroke: commonly encountered by clinicians, but little evidence to guide clinical approach.

The association between stroke and cancer is well-established. Because of an aging population and longer survival rates, the frequency of synchronous stroke and cancer will become even more common. Different pathophysiologic mechanisms have been proposed how cancer or cancer treatment directly or via coagulation disturbances can mediate stroke. Increased serum levels of D-dimer, fibrin degradation products, and CRP are more often seen in stroke with concomitant cancer, and the clot retrieved during thrombectomy has a more fibrin- and platelet-rich constitution compared with that of atherosclerotic etiology. Multiple infarctions are more common in patients with active cancer compared with those without a cancer diagnosis. New MRI techniques may help in detecting typical patterns seen in the presence of a concomitant cancer. In ischemic stroke patients, a newly published cancer probability score can help clinicians in their decision-making when to suspect an underlying malignancy in a stroke patient and to start cancer-screening studies. Treating stroke patients with synchronous cancer can be a delicate matter. Limited evidence suggests that administration of intravenous thrombolysis appears safe in non-axial intracranial and non-metastatic cancer patients. Endovascular thrombectomy is probably rather safe in these patients, but probably futile in most patients placed on palliative care due to their advanced disease. In this topical review, we discuss the epidemiology, pathophysiology, and prognosis of ischemic and hemorrhagic strokes as well as cerebral venous thrombosis and concomitant cancer. We further summarize the current evidence on acute management and secondary preventive therapy.

Fatigue 7 years post-stroke: Predictors and correlated features.

BACKGROUND: Post-stroke fatigue (PSF) is common with great impact on quality of life. We explored predictive and cross-sectionally correlated features in the long term after ischemic stroke. METHODS: This study comprises 430 participants of the prospective Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), aged 18-69 years at index stroke. Information on acute stroke severity and cardiovascular risk factors was collected at index stroke. After 7 years, PSF was assessed by the Daily Fatigue Impact Scale (D-FIS). Cognitive, neurological, and functional outcomes, and symptoms of depression and anxiety, pain, insomnia, and physical activity were also assessed. Associations between baseline variables and PSF were analyzed by ordinal regression. Correlations between PSF and cross-sectionally assessed variables, and between PSF and baseline variables, were analyzed with Spearman's or point-biserial correlation for the whole sample and in sex-stratified analyses. RESULTS: At 7 years post-stroke, 80% of the participants reported some impact of fatigue. Female sex and stroke severity were independently associated with PSF, whereas no associations were detected with baseline cardiovascular risk factors. In cross-sectional analyses at 7 years, we found correlations between PSF and poor functional, neurological, and cognitive outcomes, as well as depressive symptoms, anxiety, insomnia, pain, and low physical activity (p < .001 throughout). The correlation with insomnia was stronger in women than in men (two-way ANOVA interaction test, p = .03). CONCLUSIONS: Our findings confirm that PSF is common in the long term after ischemic stroke and show a complex interplay with sex and several other outcomes. Future studies should address causal relationships and interventions towards fatigue and coexisting features.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

Does prior administration of rtPA influence acute ischemic stroke clot composition? Findings from the analysis of clots retrieved with mechanical thrombectomy from the RESTORE registry.

BACKGROUND AND PURPOSE: There is still much debate whether bridging-therapy [intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT)] might be beneficial compared to MT alone. We investigated the effect of IVT on size and histological composition of the clots retrieved from patients undergoing bridging-therapy or MT alone. METHODS: We collected mechanically extracted thrombi from 1000 acute ischemic stroke (AIS) patients included in RESTORE registry. Patients were grouped according to the administration (or not) of IVT before thrombectomy. Gross photos of each clot were taken and Extracted Clot Area (ECA) was measured using ImageJ software. Martius Scarlett Blue stain was used to characterize the main histological clot components [red blood cells (RBCs), fibrin (FIB), platelets/other (PTL)] and Orbit Image Analysis was used for quantification. Additionally, we calculated the area of each main component by multiplying the component percent by ECA. Chi-squared and Kruskal-Wallis tests were used for statistical analysis. RESULTS: 451 patients (45%) were treated with bridging-therapy while 549 (55%) underwent MT alone. When considering only percent histological composition, we did not find any difference in RBC% (P = 0.895), FIB% (P = 0.458) and PTL% (P = 0.905). However, bridging-therapy clots were significantly smaller than MT-alone clots [32.7 (14.8-64.9) versus 36.8 (20.1-79.8) mm2, N = 1000, H1 = 7.679, P = 0.006*]. A further analysis expressing components per clot area showed that clots retrieved from bridging-therapy cases contained less RBCs [13.25 (4.29-32.06) versus 14.97 (4.93-39.80) mm2, H1 = 3.637, P = 0.056] and significantly less fibrin [9.10 (4.62-17.98) versus 10.54 (5.57-22.48) mm2, H1 = 7.920, P = 0.005*] and platelets/other [5.04 (2.26-11.32) versus 6.54 (2.94-13.79) mm2, H1 = 9.380, P = 0.002*] than MT-alone clots. CONCLUSIONS: Our results suggest that previous IVT administration significantly reduces thrombus size, proportionally releasing all the main histological components.

S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages.

Background and purpose: Post-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH. Methods: We analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis. Results: PTIH was associated with higher S100b levels in clots (0.33 [0.08-0.85] vs. 0.07 [0.02-0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0-23.0] vs. 14.0 [10.5-19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1-4] vs. 1 [1-2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots. Conclusions: Higher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation.

Correlation between acute ischaemic stroke clot length before mechanical thrombectomy and extracted clot area: Impact of thrombus size on number of passes for clot removal and final recanalization.

INTRODUCTION: We assessed the correlation between thrombus size before and after mechanical thrombectomy, measured as length by Computed Tomography Angiography/Non-Contrast Computed Tomography (CTA/NCCT) and Extracted Clot Area, ECA, respectively. We also assessed the influence of thrombus size on the number of passes required for clot removal and final recanalization outcome. MATERIALS AND METHODS: Acute ischaemic stroke (AIS) thrombi retrieved by mechanical thrombectomy from 500 patients and data of clot length by CTA/NCCT were collected from three hospitals in Europe. ECA was obtained by measuring the area of the extracted clot. Non-parametric tests were used for data analysis. RESULTS: A strong positive correlation was found between clot length on CTA/NCCT and ECA (rho = 0.619,N = 500,P < 0.0001*). Vessel size influences clot length on CTA/NCCT (H2 = 98.6, P < 0.0001*) and ECA (H2 = 105.6,P < 0.0001*), but the significant correlation between CTA/NCCT length and ECA was evident in all vessels. Poorer revascularisation outcome was associated with more passes (H5 = 73.1, P < 0.0001*). More passes were required to remove longer clots (CTA/NCCT; H4 = 31.4, P < 0.0001*; ECA; H4 = 50.2, P < 0.0001*). There was no significant main association between recanalization outcome and length on CTA/NCCT or ECA, but medium sized clots (ECA 20-40 mm2) were associated with least passes and highest revascularisation outcome (N = 500, X2 = 16.2, P < 0.0001*). CONCLUSION: Clot length on CTA/NCCT strongly correlates with ECA. Occlusion location influences clot size. More passes are associated with poorer revascularisation outcome and bigger clots. The relationship between size and revascularisation outcome is more complex. Clots of medium ECA take less passes to remove and are associated with better recanalization outcome than both smaller and larger clots.

Characterization of the 'White' Appearing Clots that Cause Acute Ischemic Stroke.

OBJECTIVES: Most clots retrieved from patients with acute ischemic stroke are 'red' in color. 'White' clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of 'white' clots retrieved by mechanical thrombectomy. MATERIALS AND METHODS: Seventy five 'white' thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. RESULTS: Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in 'white' clots' (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). 'White' clots contained significantly more platelets/other (p<0.001*) and collagen/calcification (p<0.001*) and less red blood cells (p<0.001*) and white blood cells (p=0.018*) than 'red' clots. The mean platelet and von Willebrand Factor expression was 43% and 24%, respectively. Adipocytes were found in four cases. 'White' clots were significantly smaller (p=0.016*), less hyperdense (p=0.005*) on computed tomography angiography/non-contrast CT and were associated with a smaller extracted clot area (p<0.001*) than 'red' clots. They primarily caused the occlusion of middle cerebral artery, were less likely to be removed by aspiration and more likely to require rescue-therapy for retrieval. CONCLUSIONS: 'White' clots represented 14% of our cohort and were platelet, von Willebrand Factor and collagen/calcification-rich. 'White' clots were smaller, less hyperdense, were associated with significantly more distal occlusions and were less successfully removed by aspiration alone than 'red' clots.

Cognitive function is an important determinant of employment amongst young ischaemic stroke survivors with good physical recovery.

BACKGROUND AND PURPOSE: This cross-sectional cohort study aims at investigating young ischaemic stroke survivors with good physical recovery 7 years post-stroke in order to analyze the relation between late cognitive ability and employment. METHODS: Consecutive ischaemic stroke survivors participating in the Sahlgrenska Academy Study on Ischemic Stroke, <55 years of age at stroke onset, and with no or minimal persisting neurological deficits corresponding to a score ≤2 on the National Institutes of Health Stroke Scale at long-term follow-up 7 years post-stroke were included. At this follow-up, the participants were assessed with respect to general cognitive function, processing speed, executive functions, cardiovascular risk factors, self-reported employment, cognitive difficulties, fatigue, depressive symptoms, anxiety and physical function. RESULTS: Seven years post-stroke 112/142 (79%) had part-time or full-time work and 30/142 (21%) had full-time disability pension or sick leave. Compared to those with full-time disability pension or sick leave, participants with current employment demonstrated significantly better performance with respect to general cognitive function and processing speed, and significantly lower self-ratings for cognitive difficulties, physical limitations, fatigue and depressed mood. Multivariable logistic regression selected self-rated memory (odds ratio [OR] 2.61, 95% confidence interval [CI] 1.61-4.21), processing speed (OR 3.50, 95% CI 1.67-7.33) and self-rated communication skills (OR 3.46, 95% CI 1.75-6.85) as most important correlates (area under the curve 0.83-0.87) of having current employment. CONCLUSION: This study indicates that cognitive dysfunction is an important contributor to long-term work disability amongst young stroke survivors with good physical recovery.

Insulin-Like Growth Factor-II and Ischemic Stroke-A Prospective Observational Study.

Insulin-like growth factor-II (IGF-II) regulates prenatal brain development, but the role in adult brain function and injury is unclear. Here, we determined whether serum levels of IGF-II (s-IGF-II) are associated with mortality and functional outcome after ischemic stroke (IS). The study population comprised ischemic stroke cases (n = 492) and controls (n = 514) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months and 2 years using the modified Rankin Scale (mRS), and additionally, survival was followed at a minimum of 7 years or until death. S-IGF-II levels were higher in IS cases both in the acute phase and at 3-month follow-up compared to controls (p < 0.05 and p < 0.01, respectively). The lowest quintile of acute s-IGF-II was, compared to the four higher quintiles, associated with an increased risk of post-stroke mortality (median follow-up 10.6 years, crude hazard ratio (HR) 2.34, 95% confidence interval (CI) 1.56-3.49, and fully adjusted HR 1.64, 95% CI 1.02-2.61). In contrast, crude associations with poor functional outcome (mRS 3-6) lost significance after full adjustment for covariates. In conclusion, s-IGF-II was higher in IS cases than in controls, and low acute s-IGF-II was an independent risk marker of increased mortality.

The capacity of neurological pupil index to predict absence of somatosensory evoked potentials after cardiac arrest-A study protocol.

BACKGROUND: Anoxic-ischemic brain injury is the most common cause of death after cardiac arrest (CA). Robust methods to detect severe injury with a low false positive rate (FPR) for poor neurological outcome include the pupillary light reflex (PLR) and somatosensory evoked potentials (SSEP). The PLR can be assessed manually or with automated pupillometry which provides the neurological pupil index (NPi). We aim to describe the interrelation between NPi values and the absence of SSEP cortical response and to evaluate the capacity of NPi to predict the absence of cortical SSEP response in comatose patients after CA. METHODS: A total of 50 patients will be included in an explorative, prospective, observational study of adult (>18 years) comatose survivors of CA admitted to intensive care in a university hospital. NPi assessed with a hand-held pupillometer will be compared to SSEP signals recorded >48 hours after CA. Primary outcomes are sensitivity, specificity, and odds ratio for NPi to predict bilateral absence of the SSEP N20 signal, with NPi values corresponding to <5% FPRs of SSEP absence. Secondary outcomes are the PLR and SSEP sensitivity, specificity, and odds ratio for poor neurological outcome at hospital discharge and death at 30 days. DISCUSSION: The PLR and SSEP may have a systematic interrelation, and a certain NPi threshold could potentially predict the absence of cortical SSEP response. If this can be concluded from the present study, SSEP testing could be excluded in certain patients to save resources in the multimodal prognostication after CA. Editorial comment The interrelation between loss of the pupillary light reflex (PLR) and the loss of cortical response to a somatosensory evoked potential (SSEP) in comatose cardiac arrest patients is not known. This exploratory prospective study is designed to evaluate whether a specific degree of attenuated PLR, as measured by semiautomated pupillometry, can predict the bilateral loss of cortical SSEP response in severe anoxic/ischemic brain injury. Such an interrelation between the two methods would enable the use of pupillometry rather than the more resource demanding SSEP for neurologic prognostication in post cardiac arrest patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04720482, Registered 21 January 2021, retrospectively registered.

Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVE: To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). METHODS: We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age- and sex-matched (±5 years) stroke-free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist-to-hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. RESULTS: The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63-3.76) and MA (OR = 3.50, 95% CI = 2.19-5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61-5.47; OR = 4.32 for MA, 95% CI = 2.16-8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32-4.61; OR = 3.61 for MA, 95% CI = 1.75-7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right-to-left shunt in patients with PFO. INTERPRETATION: MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242-253.

The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome.

Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal-Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H1 = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.