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
Background and Purpose
We aimed to evaluate factors associated with neurological worsening among patients with lacunar or non‐lacunar infarction admitted within 3 hours and between 3 and 24 hours ...after stroke onset.
Methods
All patients admitted to Haukeland university hospital between 2006 and 2016 with acute cerebral infarction on MRI and admission within 24 hours were included. Repeated National Institute of Health Stroke Scale (NIHSS) scoring was performed in all patients whenever possible. Neurological worsening during the hospital stay was defined as NIHSS score increase ≥3 compared to NIHSS score on admission.
Results
In patients with lacunar infarction admitted within 3 hours of onset, neurological worsening was associated with low NIHSS score on admission, low body temperature, and leukoaraiosis, whereas only internal carotid artery stenosis or occlusion was associated with neurological worsening in non‐lacunar infraction. For patients admitted 3‐24 hours after onset, neurological worsening was associated with low body temperature, high systolic blood pressure, and short time from onset to admission in patients with lacunar infarction, whereas high systolic blood pressure, high NIHSS score on admission, middle cerebral artery occlusion, and high blood glucose were associated with neurological worsening in patients with non‐lacunar infarction (all P < 0.05).
Conclusions
Lacunar infarctions with minor neurological deficits within 3 hours of stroke onset are at high risk of neurological worsening especially if concomitant low body temperature and leukoaraiosis.
Background and aim
We aimed to explore the relation between hemoglobin level and ischemic stroke severity and short‐term improvement in patients admitted to hospital within 3 hours of stroke onset.
...Methods
The relation between stroke severity and hemoglobin was explored by locally weighted scatterplot smoothing (lowess smoother) curves. The effect of hemoglobin on short‐term outcome was determined by means of linear regression analyses with NIHSS score day 7 as dependent variable after adjusting for confounders including NIHSS score on admission. Analyses were performed to disclose clinical factor associated with hemoglobin level.
Results
This study includes 905 ischemic stroke patients admitted within 3 hours of stroke onset. Lowess smoother curves showed a U‐shaped relation between NIHSS score on admission and mRS score day 7 and hemoglobin level. Regression analysis showed low hemoglobin to be independently associated with females, high age, severe stroke, low systolic blood pressure, prior cerebral infarction, not smoking, not atrial fibrillation, and unknown etiology (all P < 0.05). Another regression analysis showed that high NIHSS score day 7 was independently associated with low hemoglobin after adjusting for confounders including NIHSS score on admission.
Conclusions
We found a U‐shaped relationship between hemoglobin level on admission and stroke severity. There was no U‐shaped relationship between improvement and hemoglobin level. Poor short‐term improvement was associated with low hemoglobin levels.
Background and purpose
Sex differences in acute ischemic stroke is of increasing interest in the era of precision medicine. We aimed to explore sex disparities in baseline characteristics, management ...and outcomes in patients treated with intravenous thrombolysis included in the Norwegian Tenecteplase trial (NOR‐TEST).
Methods
NOR‐TEST was an open‐label, randomized, blinded endpoint trial, performed from 2012 to 2016, comparing treatment with tenecteplase to treatment with alteplase within 4.5 h after acute ischemic stroke symptom onset. Sex differences at baseline, treatment and outcomes were compared using multivariable logistic regression models. Heterogeneity in treatment was evaluated by including an interaction term in the model.
Results
Of 1100 patients enrolled, 40% were women, and in patients aged >80 years, the proportion of women was greater than men (19% vs. 14%; p = 0.02). Women had a lower burden of cardiovascular risk factors, such as diabetes mellitus (11% vs. 15%; p = 0.05) and a higher mean high‐density lipoprotein cholesterol level (1.7 ± 0.6 mmol/L vs. 1.3 ± 0.4 mmol/L; p < 0.001), and a higher proportion of women had never smoked (45% vs. 33%; p < 0.001) compared with men. While there was no sex difference in time from onset of symptoms to admission, door to needle time or in‐hospital workup, women were admitted with more severe stroke (National Institutes of Health Stroke Scale NIHSS score 6.2 ± 5.6 vs. 5.3 ± 5.1; p = 0.01). Stroke mimic diagnosis was more common in women (21% vs. 15%; p = 0.01). There were no significant sex differences in clinical outcome, measured by the NIHSS, the modified Rankin Scale, intracranial hemorrhage and mortality.
Conclusion
Women were underrepresented in number in NOR‐TEST. The included women had a lower cardiovascular risk factor burden and more severe strokes.
Women tend to be underrepresented in large clinical trials, and there is limited information on sex disaggregated analysis from clinical trials. In a sex disaggregated analysis of the Norwegian Tenecteplase Trial, a randomized trial comparing treatment with tenecteplase versus alteplase in 1100 patients with acute ischemic stroke, we found that there was underrepresentation of women in the trial and that women differed from men in risk profile, symptoms, and stroke mimic occurrence. There was no difference in outcomes or treatment.
The impact of age and 24‐h ambulatory blood pressure (ABPM) on arterial stiffness and carotid intima‐media thickness (cIMT) in ischemic stroke patients younger than 60 years of age is poorly ...explored. A total of 385 acute ischemic stroke patients (aged 49.6±9.7 years, 68% men) were prospectively included and grouped in younger (15–44 years, n = 93) and middle‐aged (45–60 years, n = 292). Arterial stiffness was measured by carotid‐femoral pulse wave velocity (PWV), and cIMT by carotid ultrasound. 24‐h ABPM was recorded. The middle‐aged stroke patients had higher prevalence of smoking, hypertension, diabetes mellitus, metabolic syndrome and hypercholesterolemia, and had higher PWV and cIMT (all p < .05). In multivariable linear regression analyses adjusted for sex, BMI, smoking, diabetes mellitus, total cholesterol, high‐density lipoprotein cholesterol, triglycerides, eGFR, systolic BP and concomitant antihypertensive treatment, 1SD (4.4 years) higher age was associated with higher PWV (β = 0.44,R2 = 0.46, p < .001) in the younger group, and with higher mean cIMT (β = 0.16, R2 = 0.21, p = .01) in the middle‐aged group. In the middle‐aged group, 24‐h pulse pressure had a significant association with PWV (β = 0.18, R2 = 0.19, p = .009), while the association with cIMT was attenuated (β = 0.13, R2 = 0.16, p = .065). 24‐h diastolic BP was associated with higher cIMT in the middle‐aged group (β = 0.24, p < .001, R2 = 0.23), but not with PWV in either age groups. Among ischemic stroke patients < 60 years, higher age was associated with increased arterial stiffness for patients up to age 44 years, and with cIMT in middle‐aged patients. 24‐h pulse pressure was associated with arterial stiffness, and 24‐h diastolic BP was associated with cIMT only in middle‐aged patients.
Progressive arterial stiffening may increase the risk of recurrent cardiovascular events in ischemic stroke survivors. Information about factors associated with progressive arterial stiffening during ...the follow-up of young patients with ischemic stroke is lacking.
Arterial stiffness by carotid-femoral pulse wave velocity (cf-PWV) and ambulatory 24-hour blood pressure (24hBP) were assessed in 81 women and 190 men ≤60 years of age included in the Norwegian Stroke in the Young (NOR-SYS) study 3 months and 5.5 years after the incident ischemic stroke, representing baseline and follow-up. Covariables of change in cf-PWV were identified using linear regression analysis.
At baseline, women had less prevalent hypertension (53% vs. 69%, p < 0.05), and lower clinic and 24hBP than men, whereas age, obesity, and prevalence of smoking and antihypertensive drug treatment did not differ. During follow-up, systolic 24hBP remained unchanged, while diastolic 24hBP fell significantly (p < 0.01). Cf-PWV was lower in women both at baseline (7.3 m/s vs. 8.1 m/s) and at follow-up (7.3 m/s vs. 8.0 m/s, both p < 0.001), but the average change during follow-up did not differ between genders. In linear regression analysis, an increase in cf-PWV at the 5-year follow-up was associated with the presence of hypertension and lower cf-PWV at baseline, and higher systolic 24hBP and lack of use of antihypertensive treatment at follow-up (all p < 0.05).
In ischemic stroke survivors participating in the NOR-SYS study, the 5-year increase in cf-PWV did not differ between genders and was associated with higher systolic 24hBP and lack of antihypertensive treatment.
Objectives
We aimed to assess frequencies and radiological aspects of single‐ and multiterritory clinical manifestation among patients with acute cerebral infarcts in multiple arterial territories ...(MACI).
Materials & methods
We retrospectively reviewed admission records and diffusion‐weighted magnetic resonance imaging of patients with MACI admitted to our stroke unit between 2006 and 2017. MACI was defined as acute cerebral ischemic lesions in at least two out of three arterial cerebral territories, that is, the left anterior, right anterior and the bilateral posterior territory. Patients with single‐ and multiterritory clinical manifestation were then compared for topographical distribution of the ischemic lesions, the number of ischemic lesions, and The Oxfordshire Community Stroke Project classification.
Results
Out of 311 patients with MACI, 222 (71.4%) presented with single‐territory clinical manifestation. Involvement of the left hemisphere (OR = 0.37, 95% CI 0.16–0.82), less than five ischemic lesions (OR = 0.58, 95% CI 0.35–0.97), and partial anterior circulation infarct clinical stroke syndrome (OR = 0.57, 95% CI 0.34–0.97) were associated with single‐territory clinical manifestation. Involvement of all three territories (OR = 2.58, 95% = 1.48–4.50), more than 10 ischemic lesions (OR = 2.30, 95% CI 1.32–4.01) and total anterior circulation infarct clinical stroke syndrome (OR = 3.31, 95% CI 1.39–7.86) were associated with multiterritory clinical manifestation.
Conclusion
Most patients with MACI present with single‐territory clinical manifestation on admission. Diffusion‐weighted magnetic resonance imaging is therefore necessary for a definite diagnosis.
We aimed to assess frequencies and radiological aspects of single‐ and multi‐territory clinical manifestation among patients with acute cerebral infarcts in multiple arterial territories (MACI). The results show that most patients with MACI present with single‐territory clinical manifestation on admission. Diffusion‐weighted magnetic resonance imaging is therefore necessary for definite diagnosis.
We conducted a systematic review and individual participant data meta‐analysis to explore the role of C‐reactive protein (CRP) in early detection or prediction of post‐stroke infections. CRP, an ...acute‐phase reactant binds to the phosphocholine expressed on the surface of dead or dying cells and some bacteria, thereby activating complement and promoting phagocytosis by macrophages. We searched PubMed up to May‐2015 for studies measuring CRP in stroke and evaluating post‐stroke infections. Individual participants’ data were merged into a single database. CRP levels were standardized and divided into quartiles. Factors independently associated with post‐stroke infections were determined by logistic regression analysis and the additional predictive value of CRP was assessed by comparing areas under receiver operating characteristic curves and integrated discrimination improvement index. Data from seven studies including 699 patients were obtained. Standardized CRP levels were higher in patients with post‐stroke infections beyond 24 h. Standardized CRP levels in the fourth quartile were independently associated with infection in two different logistic regression models, model 1 stroke severity and dysphagia, odds ratio = 9.70 (3.10–30.41) and model 2 age, sex, and stroke severity, odds ratio = 3.21 (1.93–5.32). Addition of CRP improved discrimination in both models integrated discrimination improvement = 9.83% (0.89–18.77) and 5.31% (2.83–7.79), respectively, but accuracy was only improved for model 1 (area under the curve 0.806–0.874, p = 0.036). In this study, CRP was independently associated with development of post‐stroke infections, with the optimal time‐window for measurement at 24–48 h. However, its additional predictive value is moderate over clinical information. Combination with other biomarkers in a panel seems a promising strategy for future studies.
C‐reactive protein (CRP), an acute‐phase reactant binds to the phosphocholine expressed on the surface of dead or dying cells and some bacteria, thereby activating complement and promoting phagocytosis by macrophages. We evaluated the role of CRP in prediction or early detection of stroke‐associated infections through a systematic review and individual participant data meta‐analysis. As shown in the figure, CRP levels were higher in patients with post‐stroke infections beyond 24–48 h, but lacking additional predictive value over clinical predictors of infections. Incorporation of CRP in a future biomarker panel might aid in the clinical management of stroke‐associated infections.
Positive family history (FH+) of cardiovascular disease (CVD) is a risk factor for own CVD. We aimed to analyze the effect of different types of FH (stroke, coronary heart disease (CHD), peripheral ...artery disease (PAD) on carotid intima-media thickness (cIMT) in young and middle-aged ischemic stroke patients.
First-degree FH of CVD was assessed in ischemic stroke patients ≤ 60y using a standardized interview. Carotid ultrasound was performed and far wall cIMT in three carotid artery segments was registered, representing the common carotid (CCA-IMT), carotid bifurcation (BIF-IMT) and the internal carotid artery (ICA-IMT). Measurements were compared between FH+ and FH negative groups and stepwise backward regression analyses were performed to identify factors associated with increased cIMT.
During the study period 382 patients were enrolled, of which 262 (68%) were males and 233 (61%) reported FH of CVD. Regression analyses adjusting for risk factors revealed age as the most important predictor of cIMT in all segments. The association between FH+ and cIMT was modified by age (p = 0.014) and was significant only regarding ICA-IMT. FH+ was associated with increased ICA-IMT in patients aged < 45y (p = 0.001), but not in patients ≥ 45y (p = 0.083). The association with ICA-IMT was present for a FH of stroke (p = 0.034), but not a FH+ of CHD or PAD.
FH of stroke is associated with higher ICA-IMT in young ischemic stroke patients. Subtyping of cardiovascular FH is important to investigate heredity in young ischemic stroke patients.
ClinicalTrials.gov NCT01597453.
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