Papers by Janja Pretnar-oblak
Cerebrovascular Diseases, 2003
Journal of Thrombosis and Thrombolysis
Moyamoya vascular pattern and dural arteriovenous fistula (dAVF) are rare vascular abnormalities ... more Moyamoya vascular pattern and dural arteriovenous fistula (dAVF) are rare vascular abnormalities and both can be secondary to head trauma. The role of dural angiogenesis in the pathophysiology of vascular malformation is rather unclear. We report a unique case of moyamoya vasculopathy simultaneously associated with dAVF after heavy head trauma. It seems that both moyamoya syndrome and dAVFs are associated with dural angiogenesis induced by head trauma. The interrelationship between vascular abnormalities is complex and unclear.Vaskularna struktura moyamoya i arteriovenska fistula dure (dAVF) su rijetke krvožilne nepravilnosti koje mogu nastati kao posljedica ozljede glave. Uloga duralne angiogeneze u patofiziologiji vaskularne malformacije prilično je nejasna. Opisujemo jedinstven slučaj moyamoya vaskulopatije istodobno udružene s dAVF nakon teške traume glave. Čini se da su i sindrom moyamoya i dAVF udruženi s duralnom angiogenezom izazvanom ozljedom glave. Međuodnos vaskularnih ne...
Clinical Neuroradiology
In the absence of an automated software analysis, the role of computed tomography perfusion (CTP)... more In the absence of an automated software analysis, the role of computed tomography perfusion (CTP) in a real time clinical practice is not well established. We evaluated the clinical significance of a widely accessible and simple visual grading scale of CTP in the anterior circulation of acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). The single center consecutive CT investigations of AIS patients treated with MT in the anterior circulation have been evaluated retrospectively. ASPECT score and collateral circulation evaluation based on the Maas score were determined. Time to peak parametric maps, derived from CTP, were graded into four categories, from least to most favorable. The primary endpoint was functional outcome evaluated as modified Rankin Scale (mRS) ≤ 2 at 90 days after MT. We included 318 patients in the analysis; 142 (45%) patients had mRS ≤ 2 after 90 days, mortality rate was 24%. Higher CTP and Maas score were significantly correlated with better clinical outcome (Pearson χ2 25.0 and 37.7, respectively; p < 0.01). Collateral circulation and CTP grades were strongly interrelated (Pearson χ2 78.6; p < 0.01). The CTP grade demonstrated statistically significant independent correlation with the clinical outcome irrespective of the collateral circulation grade, ASPECT score and age (OR 2.5; p = 0.011). The correlation was more pronounced in patients with normal collateral circulation (OR 3.27; p = 0.029). We demonstrated that both visually graded CTP and collateral circulation grade strongly correlated with the clinical outcome of MT in the anterior circulation of AIS patients. Importantly, CTP correlated with the clinical outcome independent of the collateral circulation.
which permits unrestricted use, distribution, and reproduction in any medium, provided the origin... more which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Endothelium forms the inner cellular lining of blood vessels and plays an important role in many physiological functions including the control of vasomotor tone. Cerebral endothelium is probably one of the most specific types but until recently it was impossible to determine its function. In this review, the role of cerebrovascular reactivity to L-arginine (CVR-L-Arg) for assessment of cerebral endothelial function is discussed. L-Arginine induces vasodilatation through enhanced production of nitric oxide (NO) in the cerebral endothelium. Transcranial Doppler sonography is used for evaluation of cerebral blood flow changes. The method is noninvasive, inexpensive, and enables reproducible measurements. CVR-L-Arg has been compared to flow-mediated dilatation as a gold standard for systemic endothelial function and intima-media thickness as a marker for morphologi...
Radiology and Oncology, 2016
Background The aim of the study was to investigate the sensitivity and specificity of non-contras... more Background The aim of the study was to investigate the sensitivity and specificity of non-contrast computed tomography (NCCT) in the diagnosis of cerebral venous sinus thrombosis (CVST). Methods. Screening our neurological department database, we identified 53 patients who were admitted to neurological emergency department with clinical signs of CVST. Two independent observers assessed the NCCT scans for the presence of CVST. CT venography and/or MR venography were used as a reference standard. Interobserver agreement between the two readers was assessed using Kappa statistic. Attenuation inside the cerebral venous sinuses was measured and compared between the patient and the control group. Results CVST was confirmed in 13 patients. Sensitivity and specificity of NCCT for overall presence of CVST were 100% and 83%, respectively, with Kappa value of 0.72 (a good agreement between observers). The attenuation values between CVST patients and control group were significantly different (...
Acta neuropathologica, Oct 29, 2016
We recently reported a novel neurological syndrome characterized by a unique NREM and REM parasom... more We recently reported a novel neurological syndrome characterized by a unique NREM and REM parasomnia with sleep apnea and stridor, accompanied by bulbar dysfunction and specific association with antibodies against the neuronal cell-adhesion protein IgLON5. All patients had the HLA-DRB1*1001 and HLA-DQB1*0501 alleles. Neuropathological findings in two patients revealed a novel tauopathy restricted to neurons and predominantly involving the hypothalamus and tegmentum of the brainstem. The aim of the current study is to describe the neuropathological features of the anti-IgLON5 syndrome and to provide diagnostic levels of certainty based on the presence of associated clinical and immunological data. The brains of six patients were examined and the features required for the neuropathological diagnosis were established by consensus. Additional clinical and immunological criteria were used to define "definite", "probable" and "possible" diagnostic categories....
Journal of Stroke and Cerebrovascular Diseases, 2022
CAA is a heterogeneous group of diseases caused by Aβ deposition in the vascular walls, often lea... more CAA is a heterogeneous group of diseases caused by Aβ deposition in the vascular walls, often leading to lobar ICH and cognitive impairment. Although CAA is rare in younger patients, it has been associated with specific mutations as well as with other causes. We present four cases of patients with CAA and recurrent ICH who have a history of severe TBI in childhood. Our cases as well as review of the literature suggest that a history of TBI in patients with genetic predispositions such as male sex may be associated with CAA in young persons.
Frontiers in Neurology, 2021
Background and Purpose: Idarucizumab achieves instant reversal of anticoagulation and enables int... more Background and Purpose: Idarucizumab achieves instant reversal of anticoagulation and enables intravenous thrombolysis (IVT) in dabigatran-treated acute ischemic stroke (AIS) patients. AIS in dabigatran-treated patients is a rare event, therefore the experience is limited. A review of all published cases was performed to evaluate the safety and effectiveness of this therapeutic strategy.Methods: We searched PubMed and Scopus for all published cases of IVT after reversal with idarucizumab in dabigatran-treated AIS patients. The outcomes were safety assessed by hemorhagic transformation (HT), symptomatic intracranial hemorrhage (SICH) and death, and efficacy assessed by National Institutes of Health Stroke Scale (NIHSS) reduction.Results: We identified 251 AIS patients (39,9% females) with an average age of 74 years. HT, SICH, and death were reported in 19 (7.6%), 9 (3.6%), and 21 (8.4%) patients, respectively. Patients experiencing HT presented with more severe strokes (median NIHSS ...
CNS Drugs, 2021
Background Idarucizumab reverses the anticoagulant dabigatran; it is recommended during intraveno... more Background Idarucizumab reverses the anticoagulant dabigatran; it is recommended during intravenous thrombolysis treatment of dabigatran-treated patients with acute ischemic stroke (AIS) and in dabigatran-treated patients with intracranial hemorrhage (ICH). Methods Outcomes of consecutive idarucizumab/dabigatran-treated patients with intravenous thrombolysis-treated AIS ( n = 22) were compared with consecutive similar intravenous thrombolysis-treated patients with AIS who were not anticoagulated ( n = 182) [primary aim]; idarucizumab/dabigatran-treated patients with ICH ( n = 13) were compared with patients with ICH who received the anticoagulants rivaroxaban or apixaban ( n = 24) [secondary aim]. Efficacy was estimated by National Institutes of Health Stroke Scale score changes between admission and discharge and by the modified Rankin score after 3 months; safety was assessed by symptomatic ICH and mortality. Results Basal neurological impairment was similar in both idarucizumab/d...
Journal of Thrombosis and Thrombolysis, 2021
Prescribing anticoagulation therapy in very old (≥ 80-years) patients with atrial fibrillation (A... more Prescribing anticoagulation therapy in very old (≥ 80-years) patients with atrial fibrillation (AF) is an emerging clinical issue, but current knowledge and recommendations are insufficient. We aimed to determine the efficacy and safety of direct oral anticoagulants (DOACs) in secondary stroke prevention in very old patients and to explore the related geriatric functional status of these patients. Three hundred fifty-three consecutive ≥ 80-year-old patients treated for transient ischemic attack (TIA) or ischemic stroke (IS) at the neurological clinic at UMC Ljubljana, who were prescribed DOACs for AF between December 2012 and May 2020, were included. Data regarding recurrent TIA/IS, major bleeds, intracranial hemorrhage (ICH) and death were collected. Data were descriptively compared with data from RCTs- including younger patients. Patients prescribed DOACs between January 2018 and May 2020 were contacted in December 2020, and their functional status was assessed using the Barthel index (BI). The efficacy of secondary stroke prevention with DOACs was comparable to RCTs for significantly younger patients. Major bleeds occurred more often, but most incidences were gastrointestinal, and the rate of ICH was comparable. Importantly, most patients were highly independent determined by BI. Overall, our real world results suggest that DOACs are as effective at preventing IS in secondary prevention in very old patients than in younger patients and that geriatric functional assessment could be a useful tool in the decision-making process.
Journal of Stroke and Cerebrovascular Diseases, 2021
BACKGROUND The prognosis for unilateral lateral medullary infarction (ULMI) is generally good but... more BACKGROUND The prognosis for unilateral lateral medullary infarction (ULMI) is generally good but may be aggravated by respiratory failure with fatal outcome. Respiratory failure has been reported in patients with severe bulbar dysfunction and large rostral medullary lesions, but its associated factors have not been systematically studied. We aimed to assess clinical and radiological characteristics associated with respiratory failure in patients with pure acute ULMI. MATERIALS AND METHODS Seventy-one patients (median age 55 years, 59 males) with MRI-confirmed acute pure ULMI were studied retrospectively. Clinical characteristics were assessed and bulbar symptoms were scored using a scale developed for this study. MRI lesions were classified into 4 groups based on their vertical extent (localized/extensive) and the involvement of the open and/or closed medulla. Clinical characteristics, bulbar scores and MRI lesion characteristics were compared between patients with and without respiratory failure. RESULTS Respiratory failure occurred in 8(11%) patients. All patients with respiratory failure were male (p = 0.336), had extensive lesions involving the open medulla (p = 0.061), progression of bulbar symptoms (p=0.002) and aspiration pneumonia (p < 0.001). Peak bulbar score (OR, 7.9 [95% CI, 2.3-160.0]; p < 0.001) and older age (OR, 1.2 [95%CI, 1.0-1.6]; p=0.006) were independently associated with respiratory failure. CONCLUSIONS Extensive damage involving the open/rostral medulla, clinically presenting with severe bulbar dysfunction, in conjunction with factors such as aspiration pneumonia and older age appears to be crucial for the development of respiratory failure in pure ULMI. Further prospective studies are needed to identify other potential risk factors, pathophysiology, and effective preventive measures for respiratory failure in these patients.
Respiratory Physiology & Neurobiology, 2021
Our aim was to perform an exploratory study of various irregular breathing patterns (IBPs) across... more Our aim was to perform an exploratory study of various irregular breathing patterns (IBPs) across different sleep stages in patients with acute unilateral lateral medullary infarction (ULMI) and compare them to apparently healthy individuals. Polysomnography (PSG) was analyzed for IBPs, such as periodic breathing, ataxic breathing and tachypnea. IBPs were found in 52% of healthy and 90% of ULMI subjects (p = 0.001) and occurred in long (≥ 10 min) episodes in 8% of healthy and 68% of ULMI (p < 0.001). In healthy subjects, short (< 10 min) episodes of mild to moderate ataxic breathing were observed in wakefulness and light sleep and short episodes of periodic breathing upon sleep onset. In ULMI, the most common IBPs were ataxic and periodic breathing (80% of patients), followed by shallow tachypnea (28%). Ataxic breathing predominated in wakefulness, ataxic or periodic breathing in light sleep, while breathing tended to normalize in deep and REM sleep. Considering the IBPs occurring in the healthy group as physiological, probably pathological breathing patterns (tachypnea, long episodes of moderate/severe ataxic or long episodes of periodic breathing) occurred in 67% of ULMI patients. Our findings suggest that ULMI might exacerbate physiological sleep-stage-dependent breathing pattern irregularities, such as ataxic and periodic breathing, in terms of intensity and duration or might even induce non-physiological IBP, such as shallow tachypnea with sustained hypoxia.
Clinical Drug Investigation, 2020
Background: The real-life benefits and risks of the direct oral anticoagulants (DOAC) for non-val... more Background: The real-life benefits and risks of the direct oral anticoagulants (DOAC) for non-valvular atrial fibrillation (NVAF) have been disputed. This study aimed to compare the 1-year risk of major events for new users of dabigatran (D) or rivaroxaban (R) vs. vitamin K antagonists (VKA) in NVAF. Methods: Cohorts of new users of D, R or VKA for NVAF in 2013 were identified and followed-up for one year in the 66 million persons nationwide French claims and hospitalization database (SNIIRAM). NVAF was defined from full coverage, hospitalization or procedure for atrial fibrillation without valvular disease using 3-year database history. For each comparison, patients were matched 1:1 on highdimensional propensity score, including major arterial thrombosis and bleeding risk factors; Hazard ratios (HR) [95% confidence interval] were determined over one year during first prescribed anticoagulant exposure, using the Cox proportional hazard risk model.
Journal of Thrombosis and Thrombolysis, 2020
Successful revascularization therapy is of paramount importance in patients suffering acute ische... more Successful revascularization therapy is of paramount importance in patients suffering acute ischemic stroke (AIS). However, there is currently only limited evidence on revascularization outcomes for patients suffering AIS while treated with direct oral anticoagulants (DOACs). The aim of our study was to determine the efficacy and safety of intravenous thrombolysis (IVT) and mechanical reperfusion (MeR) in AIS patients taking DOACs, and compare them to randomized clinical trials (RCTs), which included patients without DOAC treatment. In an observational cohort study, we analyzed clinical and radiological outcomes following AIS for all consecutive patients on DOAC therapy treated by IVT or MeR, between 2013 and 2019, at the University Medical Center Ljubljana. Patients in the IVT group were on dabigatran treatment and have received idarucizumab as a reversal agent prior to IVT. Patients in the MeR group had a large vessel occlusion. The primary outcome of the study was efficiency, defined as significant improvement after recanalization (National Institutes of Health Stroke Scale (NIHSS) score improvement of ≥8 points after 24 h and modified Rankin Scale (mRS) ≤2 after 3 months) and safety, defined as occurrence of symptomatic intracerebral hemorrhage (SICH) and mortality. Fifty-one DOAC-treated patients with AIS were included. Nineteen dabigatran-treated patients received IVT after reversal by idarucizumab. Thirty-two patients with a large vessel occlusion (12 on dabigatran, 12 on rivaroxaban, and 8 on apixaban) received MeR. Median NIHSS at admission was 9 in the IVT group and 17 in the MeR group. A significant clinical improvement, 24 h after revascularization (median improvement of NIHSS ≥8), occurred in 84% of patients treated with IVT and 25% of patients treated with MeR. A favorable functional outcome after 3 months (modified Rankin Scale (mRS) ≤2) occurred in 84 % of patients treated with IVT and 44% of patients treated with MeR. SICH occurred in one patient (5%) in the IVT group, and in two patients (6%) in the MeR group. In summary, in our observational study of DOAC-treated AIS patients, the level of IVT efficiency was substantially better than in the RCTs. At the same time, the results of MeR treatment were on the same level as in non-DOAC AIS patients included in the RCTs. The observed safety of IVT and MeR treatment was similar to the RCTs. We propose that thrombi in patients on dabigatran may have increased susceptibility to IVT, thereby allowing for better clinical results.
Journal of Stroke and Cerebrovascular Diseases, 2018
Background: Rapid inactivation of dabigatran by its specific inhibitor idarucizamab allows intrav... more Background: Rapid inactivation of dabigatran by its specific inhibitor idarucizamab allows intravenous thrombolysis (IVT) in patients suffering ischemic stroke while being treated with dabigatran. Only limited data of this approach is available and numerous questions regarding efficacy/safety remain to be answered. Herein, we present the findings from the Slovenian national cohort study. Methods: Retrospective analysis of all stroke patients treated with idarucizumab and IVT (n = 11) in the period from July 2016 to February 2018 from Slovenian region were analyzed. Results: The indication for dabigatran treatment in all 11 cases was nonvalvular atrial fibrillation. Importantly, 6 out of 11 cases were classified as severe ischemic strokes (National Institutes of Health Stroke Scale; NIHSS 10) with a median NIHSS 13. At admission, prolonged activated partial thromboplastin time was present in 9 patients indicating therapeutic anticoagulation activity. The average door-to-needle time was 156 minutes. After 3 months, 9 patients had a modified Rankin Score of less than or equal to 2 and 7 patients had mRS less than 1 whereas, 2 patients died due to symptomatic intracranial hemorrhage (sICH); 1 due to spontaneous sICH, and the other due to a large ischemic stroke with hemorrhagic transformation. No thrombotic complications were observed. Conclusions: Our data show that IVT after idarucizumab administration is a safe and effective method of treatment in ischemic stroke patients on dabigatran. We recorded a higher proportion of patients with favorable outcome as well as with sICH compared to the randomized controlled studies which could suggest a higher sensitivity of thrombi to IVT in dabigatran treated patients.
Stroke, 2006
Background and Purpose— In our study we hypothesized that statins improve endothelial function in... more Background and Purpose— In our study we hypothesized that statins improve endothelial function in patients with lacunar infarctions (LI). Cerebral and systemic endothelial function was determined before and after 3-months treatment with atorvastatin. Methods— Cerebral endothelial function was determined by l -arginine reactivity and systemic endothelial function by flow-mediated dilatation (FMD) in patients with LI (18 patients, aged 61.1±7.6 years), 20 age- and gender-matched patients with similar risk factors (SR) and 19 age- and gender-matched healthy controls. The mean arterial velocity (v m ) in both middle cerebral arteries was measured by transcranial Doppler sonography before, during and after a 30-minute intravenous infusion of l -arginine. FMD of the brachial artery after hyperaemia was determined. The measurements were repeated after 3-months treatment with 40 mg of atorvastatin per day. Results— l -arginine reactivity was decreased in LI patients (13.1±8.4%) and in patie...
American Journal of Hypertension, 2008
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Papers by Janja Pretnar-oblak