Case report: First treatment of acute ischaemic stroke in a patient on active rivaroxaban therapy using andexanet alfa and rtPA combined with early complete recovery.

Patients with non-large vessel occlusion acute ischemic stroke (NL-AIS) on oral anticoagulants (OAC) constitute the biggest portion among those who cannot receive any potential-reperfusion treatment even if they appear early in the hospital. We present the first case of therapy for NL-AIS in a patient with active anti-Xa anticoagulation, combining andexanet alfa and rtPA, who was recruited for STRoke On AntiCoagulants for Thrombolysis (acronym: STROACT), an ongoing therapeutic trial for non-LVO ischemic stroke on a DOAC. This is also the first report of the use of andexanet alfa-rtPA for AIS in a patient on rivaroxaban, which is the most frequently used non-vitamin K antagonist oral anticoagulant. The patient received the intravenous bolus of 800 mg of andexanet (contralateral arm), followed by a bolus of rtPA (10% of the calculated dose; ipsilateral arm), then a continuous infusion of andexanet at 8 mg/min for 120 min (contralateral arm), and rtPA (90% of the calculated dose; ipsilateral arm)-both stopped after completion of 38.9 and 74% of infusion dose, respectively, due to the severe adverse event related to the administration of rtPA. In this schema, both infusions are ongoing concurrently for approximately 60 min, and then andexanet is administered alone until the completion of the dose (altogether lasting approximately 3 h). The therapy was spectacularly effective, with early and complete improvement in NIHSS from 8 to 0 points in 70 min from the initiation of the therapy; mRS = 0. Obviously, a single case cannot drive any standard therapeutic decisions, but the experience we share in this article may help manage selected special clinical problems, especially when a patient's expected outcome is poor and there is no other way to help than experimentally. Additionally, it seems a valuable addition to recent meta-data on thrombolysis in anticoagulated patients. Trial registration: https://www.clinicaltrialsregister.eu. Identifier: 2020-004898-41. Date of registration: March 31, 2021.

Cerebral and skin microcirculatory dysfunction in type 1 diabetes.

INTRODUCTION: An increase in cerebral pulsatility index (PI), measured by transcranial Doppler, reflects the presence of cerebral microangiopathy. A decrease in distance between skin capillaries (DISTANCE) and an increase in the ratio between the area of capillaries and total area of examined skin (COVERAGE), revealed by capillaroscopy, reflects skin microangiopathy. However, little is known about the association between the cerebral and skin microvasculature function in patients at risk of microcirculatory dysfunction. AIM: To assess PI of the middle cerebral artery by transcranial Doppler and the DISTANCE and COVERAGE of the nailfold capillaries by quantitative capillaroscopy in patients with type 1 diabetes and control subjects without diabetes, and to investigate relationships between these parameters. MATERIAL AND METHODS: The study group consisted of 51 patients with type 1 diabetes (median age: 37.5 years) and 23 volunteers free from chronic diseases (median age: 37.9 years). RESULTS: Median PI was higher in patients than in control subjects (0.82 vs. 0.75; p < 0.01). Median DISTANCE was lower in patients than in control subjects (220.9 µm vs. 239.7 µm; p = 0.03), while median COVERAGE was higher in patients than in control subjects (20.4% vs. 18.3%; p = 0.01). No correlations between PI and DISTANCE or COVERAGE were found, but PI was correlated with patients' age and diabetes duration. CONCLUSIONS: In spite of simultaneous presence of cerebral and skin microangiopathy, we found no association between cerebral and skin microvasculature dysfunction. This seems to indicate independent progression of microcirculatory injury in cerebral and peripheral vascular beds.

The influence of propofol on middle cerebral artery flow velocity (VMCA) in patients with unruptured intracranial aneurysms during induction of general anaesthesia.

BACKGROUND: The estimated prevalence of unruptured intracranial aneurysms is 3%. Standard monitoring does not enable one to assess the influence of anaesthetics on the factors determining intracranial homeostasis. Thanks to transcranial Doppler ultrasonography, middle cerebral artery flow velocity (VMCA), reflecting cerebral blood flow, can be measured. The aim of the study was to assess the effects of propofol on intracranial homeostasis in patients with unruptured intracranial aneurysms during the induction of anaesthesia based on VMCA changes. METHODS: The study encompassed 21 patients (group II) anaesthetised for elective craniotomy due to unruptured intracranial aneurysms. The control group (group I) included 21 patients who underwent discoidectomy. VMCA, as well as HR, MAP, etCO2, and SpO2 were monitored at the following time points: T0 ­ onset of study; T1 ­ after 1 minute; T2 ­ onset of preoxygenation; T3 ­ after 1 minute of preoxygenation; T4 ­ administration of fentanyl; T5 ­ 1 minute after fentanyl; T6 ­ administration of propofol; T7 ­ 1 minute after propofol; T8 ­ intubation; T9 ­ 1 minute after intubation; T10 ­ 2 minutes after intubation. RESULTS: In both groups, no changes in mean HR, etCO2 and SpO2 were observed at the successive time points of observation. In groups I and II, an MAP decrease between T6 and T7 and an MAP increase between T7 and T9 were noted. There were no intergroup differences in mean values of MAP at the times of observation. In both groups and bilaterally, a VMCA decrease was recorded between T6 and T7 and an increase between T7 and T8. There were no intergroup differences in mean values of VMCA at the times of observation. In both groups, a weak correlation between VMCA and MAP changes was found bilaterally. CONCLUSIONS: Propofol depresses the cerebral circulation during the induction of anaesthesia. The presence of an unruptured aneurysm does not affect the reactivity of the cerebral vessels during the induction of anaesthesia with propofol.

Treatment of acute basilar artery occlusion: Systematic review and meta-analysis.

INTRODUCTION: Acute basilar artery occlusion (BAO) results in strokes characterized by poor outcome. Intravenous and intraarterial thrombolysis with rt-PA (IV rt-PA and IA rt-PA, respectively) and mechanical thrombectomy (MT) are the most commonly used techniques to treat BAO, but their efficacy remains unclear. Unlike in previous papers, we compared all three methods of the treatment in a single work, including an update of meta-analysis regarding each of the three therapeutic approaches with recent trials. METHODS: We systematically reviewed all original studies testing the efficacy of any of the three basic methods of BAO treatment dated up to the end of Jan 2017. RESULTS: The final analysis included 31 studies that summarized 1358 patients. These subjects were organized into three therapeutic groups: IV rt-PA, IA rt-PA±IV rt-PA, MT±IV rt-PA±IA rt-PA. The weighted pooled estimates of a favorable outcome (mRS 0-2) were 32.57% (95% CI 16.44-51.03%/I2=67.5%, p=0.0795) in the first group, 22.56% (95% CI 16.85-28.79%/I2=52.1%, p=0.027) in the second group, and 37.04% (95% CI 32.27-41.92%/I2=32%, p=0.0895) in the third group. The Q-test subgroup analysis revealed the statistical superiority of MT±IV rt-PA±IA rt-PA over IA rt-PA±IV rt-PA (mRS 0-2: p=0.0003, mRS 6: p=0.0010) and over any rt-PA administration (either IV rt-PA or IA rt-PA±IV rt-PA) (mRS 0-2: p=0.0006, mRS 6: p=0.0056). CONCLUSIONS: Current data on the effects of the three basic approaches of the treatment of BAO are insufficient to generate high-class EBM guidelines. MT seems to be the most effective method of the treatment of acute BAO. The efficacy of IV or IA thrombolytic therapy in this indication remains unclear.

Diabetic symmetric polyneuropathy is associated with increased aortal stiffening but not cerebral angiopathy in type 1 diabetes.

INTRODUCTION: Diabetic symmetric polyneuropathy (DSP) and cerebral microangiopathy are common complications of type 1 diabetes (T1DM). However, little is known about associations between DSP, cerebral microcirculation and macrovascular injury in T1DM. We aimed to assess relationships between those complications. MATERIAL AND METHODS: We examined 42 patients (25 females; mean age 37.1±5.6years) with T1DM (mean disease duration 20.6±6.1years). DSP was diagnosed with the use of quantitative vibration sensory testing (QVST) and Michigan Neuropathy Screening Instrument (MNSI). Cerebral microvasculature was evaluated with measurements of vasomotor reactivity reserve (VMR) and pulsatility index (PI) of middle cerebral artery, macroangiopathic injury by measuring intima-media complex thickness (IMT) in the common carotid artery and carotid-femoral pulse-wave velocity (PWV). RESULTS: Patients with DSP (33.3%) showed higher PWV than those without DPS (10.5 vs 9.1m/s; P=0.03); no differences concerning VMR, PI or IMT existed. There were correlations between PWV and vibration perception thresholds (VPT) (r=0.44; P=0.004) and MNSI score (r=0.43; P=0.003); VPT showed impact on PWV (beta 0.34; P<0.03). CONCLUSIONS: DSP is associated with systemic macroangiopathy, reflected by increased carotid-femoral PWV, but not with the cerebral macro- and microangiopathy.

Decreased reactivity of skin microcirculation in response to L-arginine in later-onset type 1 diabetes.

OBJECTIVE: The aim of our study was to evaluate the vasodilatory effect of l-arginine infusion on the skin microcirculation and to assess the relationship between this effect and the presence of microangiopathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Capillaroscopy was performed before and after l-arginine infusion in 48 diabetic patients (26 women and 22 men; age, 39.8 ± 6.3 years) and 24 volunteers free of any chronic disease (13 women and 11 men; age, 38.0 ± 6.7 years). The skin microcirculation reactivity, as expressed by the percentage of area covered by capillaries (coverage) and the distance between capillaries (distance), and the relationship between microcirculation reactivity and the presence of microangiopathic complications were assessed. RESULTS: The distance before l-arginine infusion was significantly lower in patients than in controls (221 [153-311] vs. 240 [185-356] µm; P = 0.02) and did not differ after l-arginine infusion (223.5 [127-318] vs. 242.5 [181-341] µm; P = 0.27). The difference between the coverage values obtained before and after l-arginine infusion (Δcoverage) was significantly different from zero in the control group but not in the diabetes group. Patients with later onset of diabetes were characterized by decreased skin microcirculation reactivity when compared with patients with earlier onset of diabetes (-1.18 [-5.07 to 11.60] vs. 1.36 [-6.00 to 8.06]; P = 0.02) despite the higher prevalence of retinopathy in patients with earlier onset of diabetes (64% vs. 26%; P = 0.02). CONCLUSIONS: Skin microvascular reactivity is impaired in patients with later onset of type 1 diabetes. Capillaroscopy with l-arginine infusion is useful for the identification of skin microangiopathy in type 1 diabetes.

Angiogenin in middle-aged type 1 diabetes patients.

BACKGROUND: Angiogenin levels are increased in children and adolescent patients with type 1 diabetes, regardless of the extent of diabetic microangiopathy. However, little is known about the angiogenin concentrations in adults with type 1 diabetes. Thus we studied its level in middle aged subjects with the presence of diabetic nephro-, retino and neuropathy. METHODS: We investigated the data of 57 (age 39±6.6 years, 45.6% of males) patients with type 1 diabetes and 38 age-matched control subjects without diabetes (age 37.1±5.9 years, 42.1% of males), including medical histories, evidences of microangiopathy and serum angiogenin concentrations. RESULTS: Serum angiogenin level was lower in patients with type 1 diabetes [384.2(190.4-999.8) ng/ml] compared to controls [460.4(230.6-708.2) ng/ml], p=0.04. In patients with overt diabetic nephropathy the angiogenin level was higher when compared to patients without nephropathy [568.2(269.6-999.8) vs 369.4(190.4-999.8) ng/ml, p=0.01]. There were no differences between angiogenin levels in subgroups of patients distinguished by the presence of other microvascular complications or other concomitant vascular risk factors despite cigarette smoking [smokers: 516.2(294.4-999.8) vs. non-smokers: 372.1(190.4-924.8) ng/ml, p=0.01]. CONCLUSIONS: Regardless of the presence of diabetic microangiopathy, angiogenin level in middle-aged type 1 diabetes patients is lower than in controls. The presence of overt nephropathy and smoking habit in middle-aged patients with type 1 diabetes are associated with higher angiogenin level.

Cerebrovascular reactivity, intima-media thickness, and nephropathy presence in patients with type 1 diabetes.

OBJECTIVE: Cerebrovascular reactivity impairment was reported as a marker of cerebral microangiopathy in long-term type 1 diabetes. Intima-media complex thickening reflects early stages of macroangiopathy in type 1 diabetes. The analysis of the relationship between these variables and other microangiopathic complications might serve as a beneficial indicator for early prophylaxis in these patients. RESEARCH DESIGN AND METHODS: Vasomotor reactivity reserve (VMRr) and breath-holding index (BHI) of the middle cerebral artery were measured with transcranial Doppler in 59 patients (median age 32.0 years, range 20-51, 36 females) with type 1 diabetes, without history of cerebrovascular events, and 30 healthy control subjects (median age 31.5 years, range 25-39, 15 females). The relationships between the presence of selected vascular complications of type 1 diabetes and biochemical parameters, intima-media thickness (IMT), and VMRr and BHI in patients were analyzed. RESULTS: VMRr and BHI were lower in patients with type 1 diabetes when compared with healthy subjects (81.5 vs. 100%, P < 0.01, and 1.6 vs. 2.2, P = 0.04, respectively), whereas IMT was significantly higher in patients then in healthy control subjects (0.36 vs. 0.30 mm, P = 0.001). However, no association of IMT with VMRr was found. We found a significant reduction of VMRr and BHI in patients with diabetic nephropathy. CONCLUSIONS: The presence of diabetic nephropathy, but not IMT, can be regarded as an indicator of cerebral microangiopathy severity in patients with type 1 diabetes.

High magnesium or potassium hair accumulation is not associated with ischemic stroke risk reduction: a pilot study.

OBJECTIVES: Various studies suggest that deficiency of magnesium and potassium may be associated with increased risk of ischemic stroke. However, single time-point serum measurements may not be suitable for assessing long-term tissue levels. PATIENTS AND METHODS: We investigated Mg and K levels in hair of patients with acute ischemic stroke. The elements hair accumulation analysis might provide historical information on their concentrations over a longer period of time and probably reflects the corresponding nutritional condition. The concentrations of Mg and K in hair of 48 men with acute ischemic stroke and a control group were measured using spectroscopic methods. RESULTS: The mean Mg and K concentrations in hair of patients were significantly higher than in the controls. CONCLUSIONS: This analysis does not seem to confirm the results of the previous studies suggesting that Mg or K high levels (or their diet supplementation) might protect humans against ischemic stroke.