Long-term outcome of a pragmatic trial of multifaceted intervention (STROKE-CARD care) to reduce cardiovascular risk and improve quality-of-life after ischaemic stroke and transient ischaemic attack: study protocol.

BACKGROUND: Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of incident cardiovascular events and recurrent stroke. Despite compelling evidence about the efficacy of secondary prevention, a substantial gap exists between risk factor management in real life and that recommended by international guidelines. We conducted the STROKE-CARD trial (NCT02156778), a multifaceted pragmatic disease management program between 2014 and 2018 with follow-up until 2019. This program successfully reduced cardiovascular risk and improved health-related quality of life and functional outcome in patients with acute ischaemic stroke or TIA within 12 months after the index event. To investigate potential long-term effects of STROKE-CARD care compared to standard care, an extension of follow-up is warranted. METHODS: We aim to include all patients from the STROKE-CARD trial (n = 2149) for long-term follow-up between 2019 and 2021 with the study visit scheduled 3-6 years after the stroke/TIA event. The co-primary endpoint is the composite of major recurrent cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, and vascular death) from hospital discharge until the long-term follow-up visit and health-related quality of life measured with the European Quality of Life-5 Dimensions (EQ-5D-3L) at the final visit. Secondary endpoints include overall mortality, long-term functional outcome, and target-level achievement in risk factor management. DISCUSSION: This long-term follow-up will provide evidence on whether the pragmatic post-stroke/TIA intervention program STROKE-CARD is capable of preventing recurrent cardiovascular events and improving quality-of-life in the long run. Trial registration clinicaltrials.gov: NCT04205006 on 19 December 2019.

Case report: Dissolving carotid plaque associated to Lorlatinib-related dyslipidemia.

We present a case with prolonged Lorlatinib-related dyslipidemia causing internal carotid artery stenosis, putting the patient at risk of cerebrovascular events. Through intensified lipid-lowering treatment and dose reduction of Lorlatinib, LDL-C levels decreased markedly. Surprisingly, the left sided internal carotid artery stenosis dissolved accordingly. Due to the high efficacy of the new selective tyrosine kinase inhibitors and resulting long-term treatment, it is essential to carefully follow-up and include drug specific side effect monitoring. This case emphasizes that Loraltinib-related dyslipidemia has to be taken seriously and treatment should be initiated as promptly as possible. We conclude that in cases were lipid dysregulation remains and Lorlatinib treatment has to be continued, cerebrovascular appraisal through ultrasound should be considered and, if stenosis is evident, intensified treatment regimen of dyslipidemia or dose reduction of Lorlatinib should be discussed in an interdisciplinary setting.

Substantia nigra hyperechogenicity as a marker for Parkinson's disease: a population-based study.

BACKGROUND: The clinical diagnosis of Parkinson's disease (PD) is currently anchored in its cardinal motor symptoms. According to hospital-based studies, an enlarged echogenicity in the area of the substantia nigra (SN) assessed with transcranial sonography (TCS) may represent a useful biomarker in the diagnosis of PD. OBJECTIVE: To evaluate SN hyperechogenicity as a marker for PD in the Bruneck Study cohort, which is representative of the general elderly community. METHODS: The diagnostic accuracy of TCS in distinguishing clinically diagnosed PD from nonparkinsonian subjects was assessed in 574 subjects from this cohort. RESULTS: There was a good diagnostic accuracy of TCS in distinguishing PD subjects from nonparkinsonian subjects with an area under the curve value of 0.82. At a receiver-operating characteristic curve analysis-based cutoff value for SN hyperechogenicity of 0.18 cm(2), TCS had a sensitivity of 88.2% (95% confidence interval, CI, 64.4-98.0), a specificity of 77.0% (95% CI 72.8-80.6), a positive predictive value of 12.7% (95% CI 7.8-20.0) and a negative predictive value of 99.4% (95% CI 97.8-100.0) for subjects with clinically definite PD at baseline. When analyzing the same population after 5 years with regard to the presence of known and newly diagnosed PD cases, baseline TCS yielded very similar diagnostic accuracy values. CONCLUSION: SN hyperechogenicity may represent a useful biomarker for PD not only in a hospital-based setting but also in the general community.

Prognostic relevance of limb shaking in symptomatic carotid artery occlusion.

BACKGROUND: Internal carotid artery (ICA) occlusion, present in up to 15% of stroke patients, may cause low-flow transient ischemic attacks (TIAs) like limb shaking (LS) or retinal claudication (RC). Reliable data on the frequency of these phenomena and their potential prognostic relevance are still sparse. AIMS: To provide more data about the frequency of low-flow TIA and investigate their influence on outcome. MATERIAL AND METHODS: Medical records of 260 consecutive patients with symptomatic ICA occlusion were carefully reviewed (survey period: January 2000 to December 2006). Baseline stroke severity and outcome at 90 days and in the long term were assessed. All patients were specifically questioned about symptoms of LS and RC, were exposed to bright light (pupillary testing) and carefully watched during testing of posture/gait and early mobilization. RESULTS: LS, RC or both occurred in 28.6, 9.5 and 2.7%, respectively, of patients eligible for a thorough assessment of low-flow TIAs (n = 147). An adverse outcome was more likely in patients with LS than in those without at day 90 (modified Ranking Scale ≥4, 45.2 vs. 21.9%, p = 0.005) and in the long term (median, 37 months) (52.7 vs. 23.1%, p < 0.001). In a multivariable analysis, prognostic relevance was found to be independent of baseline stroke severity (National Institutes of Health Stroke Scale). There was also a tendency towards higher rates of recurrent stroke and TIA in limb shakers. RC had no prognostic relevance regarding functional outcome and recurrent events. CONCLUSION: In patients with ICA occlusion, RC and LS are more common than previously assumed. The presence of LS is associated with a worse outcome independent of initial stroke severity and patient characteristics.

Cardiovascular risk factors and atherosclerosis in young women: atherosclerosis risk factors in female youngsters (ARFY study).

BACKGROUND AND PURPOSE: Little research has been conducted into risk factors of atherosclerosis development in young women. METHODS: This cross-sectional study enrolled 205 18- to 22-year-old female students from the Educational Centre for Allied Health Professions. A broad array of risk conditions and lifestyle behaviors was carefully assessed. Intima media thickness (IMT) was used as a well-established surrogate for atherosclerosis and a predictor of vascular risk. High IMT was defined as levels exceeding the 90th percentile in the common and/or internal carotid arteries. RESULTS: In multivariable logistic regression analysis, systolic blood pressure, family history for hypertension, lipoprotein(a), homocysteine, T-cell immune reaction against human heat shock protein 60, and exposure to environmental tobacco smoke and exhaust gases emerged as independent predictors of high IMT. Obesity, metabolic syndrome, and classical risk factors other than high blood pressure were rare and unrelated to IMT. Findings were similar once focusing on IMT as a continuous variable. CONCLUSIONS: In female youngsters displaying initiating stages of vascular pathology, blood pressure level and numerous nontraditional risk conditions showed a significant relation to high IMT. Our study indicates that (auto)immune processes, high lipoprotein(a), and environmental exposure to tobacco smoke and traffic exhaust may play a role in early atherogenesis.

Lack of association of soluble CD40 ligand with the presence of acute myocardial infarction or ischemic stroke in the emergency department.

BACKGROUND: Soluble CD40 ligand (sCD40L) has been proposed as a new risk marker for cardiovascular diseases; however, its possible role as a diagnostic marker in the emergency department (ED) has not yet been investigated. METHODS: We investigated sCD40L for the diagnosis of acute myocardial infarction or ischemic stroke in 1089 consecutive patients (525 males, 564 females; age, 17-98 years; median, 56 years) in an ED treating mainly adults with medical or neurologic emergencies. We used a research assay from Roche Diagnostics to measure sCD40L in heparinized plasma prepared from routinely drawn blood samples. RESULTS: Intraassay and interassay CVs in our laboratory ranged from 1.6%-4.2% and from 4.4%-4.9%, respectively. A multiple linear regression analysis revealed sCD40L concentration to be significantly associated with C-reactive protein concentration (P = 0.012) and platelet count (P < 0.001). In addition, a subgroup analysis revealed a significant association between smoking and sCD40L concentration (P = 0.006). All other tested variables, including discharge diagnosis, age, sex, and other laboratory variables, showed no significant associations. CONCLUSIONS: In adults presenting to the ED, sCD40L is not useful as a diagnostic marker for acute cardiac, cerebrovascular ischemic, or thromboembolic events.

American Society of Anesthesiology and Rankin as predictive parameters for the outcome of carotid endarterectomy within 28 days after an ischemic stroke.

OBJECTIVE: Recent studies suggest that carotid endarterectomy (CEA) is more effective when performed closer to an ischemic event than after an arbitrary 4- to 6-week delay. Factors need to be identified to evaluate potential perioperative complications after early CEA. METHODS: We investigated the influence of several clinical and morphological variables on the perioperative combined stroke and mortality rate and their influence on the modified Rankin-scale (mRS). In order to increase the statistical power, we combined data from three clinical studies (one multicenter and two single center trials) concerning the CEA after a waiting period of no more than 28 days. A perioperative stroke was defined as an important of at least 1 score in the mRS. Statistical analysis included univariate and multivariate analysis. RESULTS: A total of 226 patients (167 male), aged between 30 and 87 years (median 65.05 years) underwent CEA following an ischemic stroke within a period of no more than 28 days (median 12 days). The majority (>90%) showed severe stenosis of the internal carotid artery (>/=70%), 149 patients (66%) were ranked Rankin 2, P = .0245) for a deterioration of the postoperative neurological status of at least 1 Rankin grade. There was also a trend concerning the Rankin scale at admission (Rankin >2, P = .0658). The logistic regression analysis showed that patients with an ASA classification >2 and a preoperative Rankin >2 that were treated within 12 days after the initial ischemic event had the greatest risk for a perioperative deterioration of their neurological symptoms (odds ratio: 4.4, 1.48-13.0; P = .01). CONCLUSION: The ASA classification and the neurological status measured by the Rankin scale are predictive variables for the clinical perioperative outcome in patients treated within 28 days after an ischemic stroke. Patients ranked ASA

Recanalization of extracranial internal carotid artery occlusion after i.v. thrombolysis for acute ischemic stroke.

BACKGROUND: Although extracranial internal carotid artery (e-ICA) occlusion is a common pathology in patients undergoing intravenous thrombolysis for treatment of acute ischemic stroke, no data on e-ICA recanalization rate or potential effects on outcome are yet available. METHODS AND RESULTS: This study included 52 consecutive patients with e-ICA occlusion and ischemic stroke undergoing standard intravenous thrombolysis. The rate of e-ICA recanalization was 30.8% [95%CI, 18.2-43.3], documented at 3.5 [2.0-11.8] (median [IQR]) days after stroke, as compared to 8.6% [95%CI, 3.5-13.7] in a series of 116 consecutive patients with symptomatic e-ICA occlusion not undergoing thrombolysis (P<0.001 for difference). Functional outcome three months after stroke did not significantly differ for those with or without e-ICA recanalization following intravenous thrombolysis (modified Rankin scale ≤2: 31.3% vs. 22.2%, odds ratio 1.6 [95%CI, 0.4-5.9], P = 0.506). In patients with e-ICA occlusion of atherothrombotic origin, recanalization resulted in most instances in residual high-grade stenosis (13 of 14). CONCLUSIONS: Recanalization of e-ICA occlusion after stroke thrombolysis occurred in about one third of patients. Although e-ICA recanalization had no significant effect on patient outcome, control sonography in the early days after thrombolysis is recommended for the detection of potential residual e-ICA stenosis.

Phenotypical variability of post-partum reversible cerebral vasoconstriction syndrome.

Reversible cerebral vasoconstriction syndrome is recognized increasingly as a complication of the postpartum period. Our series of four cases illustrates its phenotypical variability, summarizes the diagnostic work-up, and outlines potential treatment strategies for this usually benign but sometimes disabling and life-threatening disease.

Cerebral vasoreactivity decreases overnight in severe obstructive sleep apnea syndrome: a study of cerebral hemodynamics.

BACKGROUND: OSAS has been associated with surrogate markers of atherosclerosis and is a known risk factor for stroke. However, there is limited data on the effects of recurring apneas in severe OSAS on cerebral circulation and their consequences on cerebrovascular reactivity and compliance. OBJECTIVE: To evaluate cerebral blood flow velocity (CBFV) changes and vascular compliance in patients with severe obstructive sleep apnea syndrome (OSAS) using transcranial Doppler sonography (TCD) and cerebral pulse transit time (PTT). METHODS: Seven patients (1 woman, 6 men, mean age 57.4 years) with severe OSAS underwent polysomnography at the sleep laboratory of the Neurology Department of Innsbruck Medical University. TCD was performed continuously during the whole night using a pulsed wave probe and was co-registered with routine polysomnography. Cerebrovascular reactivity was assessed by calculation of apnea and hypopnea-related CBFV changes. Arterial compliance was characterized by PTT derived from phase difference analysis between ECG and TCD signals. Sleep time was dichotomized into periods with high density of consecutive respiratory events (CRE) vs. periods with low density of consecutive respiratory events (non-CRE). TCD measurements of CBFV showed a regular, undulating pattern with flow minima immediately before apneas or hypopneas and maxima closely after their termination, reciprocally to peripheral O(2) saturation. CBFV reactivity was significantly diminished in CRE compared to non-CRE periods. PTT phase differences were reduced in non-CRE, and even more so in CRE periods, compared to initial wake phases. CONCLUSION: We found severe disturbances of cerebrovascular reactivity in OSAS patients. Our data demonstrate loss of vasoreactivity and increase of arterial stiffness, indicated by CBF hyporeactivity and PTT reduction, especially during CRE periods. These changes are likely to impair cerebral circulation and may be detrimental to the endothelium.

[Implementation of thrombolysis in acute stroke--10-year results of the Innsbruck stroke registry]. / Einsatz der Thrombolyse beim akut ischämischen Schlaganfall : 10-Jahres-Ergebnisse an der Stroke Unit Innsbruck.

BACKGROUND: Randomized controlled trials have yielded evidence for the efficacy and safety of intravenous alteplase in the therapy of acute ischemic stroke. A large patient registry has recently confirmed the safe implementation of this therapy in the clinical routine setting. METHODS: Between January 1998 and December 2007 302 stroke patients were treated with 0.9 mg/kg rt-PA at the stroke unit of the Innsbruck University Hospital. Severity and circumstances of the stroke event, indicators of pre- and intrahospital management as well as safety and outcome at three months were prospectively assessed in the local thrombolysis database. RESULTS: The number of patients receiving intravenous thrombolysis increased continuously from 2 patients in 1998 to 67 in 2007 and 87 patients in 2008. 43% of our patients were females. The median age and NIHSS-score on admission was 67 and 16, respectively. The mean onset-to-needle time decreased from 171 min to 110 min--mainly due to a substantial shortening of the door-to-needle time from 105 min to 45 min. A proportion of 41% of our patients were treated in the main working time while 59% received rt-PA during night and weekend service. A total of 38% of our patients were functionally independent at three months (mRS 0-2). Once considering the high initial stroke severity in our patient series and correcting the NIHSS scores to levels usually seen in randomized control trials and patient registries, 56% of our patients would reach a good outcome (mRS 0-2). The rate of symptomatic intracranial bleedings was low at 6.3%. CONCLUSION: Our data reinforce that intravenous thrombolysis is safe in the treatment of acute ischemic stroke in clinical routine setting. Establishment of modern stroke services and the implementation of structural operating procedures have contributed to an increase in the number of treated patients and a parallel decrease in door-to-needle time at our hospital. Widespread educational programs in the general community, introduction of optimized pre-hospital triage algorithms as well as the potential extension of the 3-hour window to 4.5 hours all are suitable measures to further extend the benefit of i.v. thrombolysis to large proportion of stroke patients.

Midbrain sonography in patients with essential tremor.

Several studies have reported an increased risk to develop Parkinson's disease (PD) in essential tremor (ET) populations. Hyperechogenicity of the substantia nigra (SN) is a common transcranial sonography (TCS) finding in PD and has been suggested as a PD risk-marker in nonparkinsonian subjects. This study compared SN areas of 44 ET patients with 100 controls and 100 PD patients. Sixteen percent of ET patients had SN hyperechogenicity as compared with 3% of controls and 75% of PD patients. These findings might correspond to an increased risk of ET patients to develop PD. Long-term follow-up will show if those with hyperechogenic SN develop PD, while these without will not.

Transcranial ultrasound shows nigral hypoechogenicity in restless legs syndrome.

In patients with Parkinson's disease, hyperechogenicity of the substantia nigra using transcranial ultrasound has been related to increased tissue concentrations of iron. Recently, deficient iron transport mechanisms in substantia nigra neurons have been described in postmortem tissue of patients with restless legs syndrome (RLS). This study was performed to study substantia nigra echogenicity in RLS patients compared with normal control subjects and Parkinson's disease patients. RLS patients had significantly reduced midbrain areas of hyperechogenicity compared with control subjects, and even more markedly reduced hyperechogenicity compared with Parkinson's disease patients. These findings lend further support to nigral iron deficiency as a pathogenetic factor in RLS.