Time Trends in Intracerebral Hemorrhage Associated with Oral Anticoagulation and Its Risks Factors in Spain from 2008 to 2015.

BACKGROUND: Intracerebral hemorrhage (ICH) is 7- to 10-fold higher in anticoagulated patients. Given the more extended use of oral anticoagulants, an increase in the prevalence of ICH associated with oral anticoagulation (ICH-OAC) could be expected. However, there is no previous study that assesses the time trends of ICH-OAC in Spain. METHODS: We conducted a combined data analysis after creating a joint database of the 3 most important epidemiological studies on ICH-OAC of our country: the EPICES study (2008-2009), the TAC Registry (TR) study (2012-2013) and the TAC Registry 2 (TR2) study (2015). We finally included 65, 235, and 366 patients from the EPICES, TR, and TR2 studies, respectively. RESULTS: We have observed a 3.73-fold increase in the crude annual incidence of ICH-OAC throughout the period of study, with proportion of ICH-OAC out of total ICH increasing from 8.4% in 2008 to 18.2% in 2015. Age, dyslipidemia, and prior antiplatelet treatment increased during the study, but we found no statistically significant differences in other risk factors for ICH-OAC. CONCLUSIONS: The incidence of ICH-OAC is increasing in our country. It might at least be partly explained by aging of the population, with mean age at presentation being higher in the last years.

Outcomes of Nonagenarians with Acute Ischemic Stroke Treated with Intravenous Thrombolytics.

BACKGROUND: Nonagenarians are under-represented in thrombolytic trials for acute ischemic stroke (AIS). The effectiveness of intravenous thrombolytics in nonagenarians in terms of safety and outcome is not well established. MATERIALS AND METHODS: We used a multinational registry to identify patients aged 90 years or older with good baseline functional status who presented with AIS. Differences in outcomes-disability level at 90 days, frequency of symptomatic intracerebral hemorrhage (sICH), and mortality-between patients who did and did not receive thrombolytics were assessed using multivariable logistic regression, adjusted for prespecified prognostic factors. Coarsened exact matching (CEM) was utilized before evaluating outcome by balancing both groups in the sensitivity analysis. RESULTS: We identified 227 previously independent nonagenarians with AIS; 122 received intravenous thrombolytics and 105 did not. In the unmatched cohort, ordinal analysis showed a significant treatment effect (adjusted common odds ratio [OR]: .61, 95% confidence interval [CI]: .39-.96). There was an absolute difference of 8.1% in the rate of excellent outcome in favor of thrombolysis (17.4% versus 9.3%; adjusted ratio: .30, 95% CI: .12-.77). Rates of sICH and in-hospital mortality were not different. Similarly, in the matched cohort, CEM analysis showed a shift in the primary outcome distribution in favor of thrombolysis (adjusted common OR: .45, 95% CI: .26-.76). CONCLUSIONS: Nonagenarians treated with thrombolytics showed lower stroke-related disability at 90 days than those not treated, without significant difference in sICH and in-hospital mortality rates. These observations cannot exclude a residual confounding effect, but provide evidence that thrombolytics should not be withheld from nonagenarians because of age alone.

Clinical Course and Outcomes of Small Supratentorial Intracerebral Hematomas.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) volume, particularly if ≥30 mL, is a major determinant of poor outcome. We used a multinational ICH data registry to study the characteristics, course, and outcomes of supratentorial hematomas with volumes <30 mL. METHODS: Basic characteristics, clinical and radiological course, and 30-day outcomes of these patients were recorded. Outcomes were categorized as early neurological deterioration (END), hematoma expansion, Glasgow Outcome Scale (GOS), and in-hospital death. Poor outcome was defined as composite of in-hospital death and severe disability (GOS ≤ 3). Comparison was conducted based on hemorrhage location. Logistic regression using dichotomized outcome scales was applied to determine predictors of poor outcome. RESULTS: Among 375 cases of supratentorial ICH with volumes <30 mL, expansion and END rates were 19.2% and 7.5%, respectively. Hemorrhage growth was independently associated with END (odds ratio: 28.7, 95% confidence interval [CI]: 8.51-96.5; P < .0001). Expansion rates did not differ according to ICH location. Overall, 13.9% (exact binomial 95% CI: 10.5-17.8) died in the hospital and 29.1% (CI: 24.5-34.0) had severe disability at 30 days; there was a cumulative poor outcome rate of 42.9% (CI: 37.9-48.1). Age, admission Glasgow Coma Scale, intraventricular extension, and END were independently associated with poor outcome. There was no difference in poor outcome rates between lobar and deep locations (40.2% versus 43.8%, P = .56). CONCLUSION: Patients with supratentorial ICH <30 mL have high rates of poor outcome at 30 days, regardless of location. Nearly 1 in 5 hematomas <30 mL expands, leading to END or death.

Value of advanced interatrial block in the diagnosis of the ischemic stroke's aetiology: A cohort study.

INTRODUCTION AND OBJECTIVES: Advanced interatrial block has been linked with atrial fibrillation (AF) (Bayes syndrome). On the other hand, the aetiology of the stroke remains unknown in approximately 20-25% of patients admitted due to ischaemic stroke. The aim of this study was to evaluate whether advanced interatrial block and CHADS2-VASC scale is linked to AF in patients admitted due to ischaemic stroke without previous AF history. METHODS: A prospective analysis of consecutive in-hospital patients admitted with ischemic stroke between January/2018 and April/2019 in a stroke hospital was performed. Patients had to be in sinus rhythm at admission and without previous history of AF/atrial flutter. During follow up patients receive the usual care. RESULTS: A total of 236 patients were included. The median follow-up was 540 days (407-695). 19 patients (8.1%) had advanced interatrial block at admission. Advanced interatrial block was associated with the diagnosis of AF during follow up (5 (26.3%) Vs 21 (9.7%) p=0.027). A CHADS2-VASC score>4 at admission was also associated with AF diagnosis during follow up (23(14.6%) vs 3(3.9%) p=0.009). CONCLUSION: This study confirms the association of advanced interatrial block and CHADS2-VASC>4 at admission with the diagnosis of AF during follow up in patients with ischemic stroke. This association could have important implications in patients with ischemic stroke who present advanced interatrial block and without previous history of AF.

Low serum neurofilament light chain values identify optimal responders to dimethyl fumarate in multiple sclerosis treatment.

Serum neurofilament light chains (sNfL) are biomarkers of disease activity in multiple sclerosis (MS), but their value to predict response to treatment, and their association with patient immunological profile, need to be further explored. We studied 80 relapsing-remitting MS patients initiating dimethyl fumarate (DMF) treatment. sNfL levels were explored at baseline and at 3, 6 and 12 months by single molecule array. Blood lymphocyte subsets were measured at baseline and at 6 months by flow cytometry. Patients were followed a year and classified as NEDA (no evidence of disease activity) or ODA (ongoing disease activity). NEDA patients had lower sNfL levels at baseline (p = 0.0001), and after three (p = 0.004) and six (p = 0.03) months of DMF treatment. Consequently, low baseline sNfL values (≤ 12 pg/ml) increased the probability of NEDA (OR 5.8; CI 1.82-15.6; p = 0.002, after correcting by disease activity in the previous year), and associated with significant reductions of central memory CD4+ T lymphocytes, interferon-gamma+ CD8+ T lymphocytes, Natural Killer T cells, and memory B cells upon DMF treatment, being the highest differences in memory B cells (p < 0.0001). This shows that low baseline sNfL values identify MS patients with higher probability of optimal response to DMF and of a reduction in effector immune cells.

Prehospital selection of thrombectomy candidates beyond large vessel occlusion: M-DIRECT scale.

OBJECTIVE: Current prehospital scales used to detect large vessel occlusion reveal very low endovascular thrombectomy (EVT) rates among selected patients. We developed a novel prehospital scale, the Madrid-Direct Referral to Endovascular Center (M-DIRECT), to identify EVT candidates for direct transfer to EVT-capable centers (EVT-Cs). The scale evaluated clinical examination, systolic blood pressure, and age. Since March 2017, patients closer to a stroke unit without EVT capabilities and an M-DIRECT positive score have been transferred to the nearest EVT-C. To test the performance of the scale-based routing protocol, we compared its outcomes with those of a simultaneous cohort of patients directly transferred to an EVT-C. METHODS: In this prospective observational study of consecutive patients with stroke code seen by emergency medical services, we compared diagnoses, treatments, and outcomes of patients who were closer to an EVT-C (mothership cohort) with those transferred according to the M-DIRECT score (M-DIRECT cohort). RESULTS: The M-DIRECT cohort included 327 patients and the mothership cohort 214 patients. In the M-DIRECT cohort, 227 patients were negative and 100 were positive. Twenty-four (10.6%) patients required secondary transfer, leaving 124 (38%) patients from the M-DIRECT cohort admitted to an EVT-C. EVT rates were similar for patients with ischemic stroke in both cohorts (30.9% vs 31.5%). The M-DIRECT scale had 79% sensitivity, 82% specificity, and 53% positive predictive value for EVT. Recanalization and independence rates at 3 months did not differ between the cohorts. CONCLUSIONS: The M-DIRECT scale was highly accurate for EVT, with treatment rates and outcomes similar to those of a mothership paradigm, thereby avoiding EVT-C overload with a low rate of secondary transfers.

[Ulcerative colitis associated with Vogt-Koyanagi-Harada disease]. / Colitis ulcerosa asociada a enfermedad de Vogt-Koyanagi-Harada.

We report the case of a female patient who was diagnosed with Vogt-Koyanagi-Harada disease at the age of 14 years and who developed myelopathy, resulting in paraparesis. A cerebral magnetic resonance imaging scan revealed the presence of T2-hyperintense lesions in the periventricular white matter, suggesting demyelinization. Twelve years later, ulcerative colitis was diagnosed during workup for abdominal pain associated with bloody diarrhea. The association of these two diseases has previously been reported anecdotically. The management of the ulcerative colitis was complicated by the patient's neurological manifestations. Even though recent reports support the use of anti-TNF drugs in the management of Vogt-Koyanagi-Harada-associated uveitis, because of the lack of experience in patients with neurological symptoms, and the presence of apparently demyelinating lesions in our patient, we did not use these drugs in this case.

Epidemiology of Intracranial Hemorrhage Associated with Oral Anticoagulants in Spain: Trends in Anticoagulation Complications Registry - The TAC 2 Study.

OBJECTIVE: Patients receiving treatment with oral anticoagulants (OACs) are at risk of intracranial hemorrhage (ICH). In this study, we describe the epidemiological and clinical characteristics of patients receiving OACs who experience ICH and compare those receiving vitamin K antagonists (ICH-VKAs) with those receiving direct OACs (ICH-DOACs). METHODS: We performed a national, multicenter, descriptive, observational, retrospective study of all adult patients receiving OACs who were admitted to the neurology department with ICH over a 1-year period. The study population was divided into 2 groups (ICH-VKAs and ICH-DOACs). Epidemiological, clinical, radiological, and therapy-related variables, as well as functional outcome, were compared at 3 months. A total of 366 cases were included (331 ICH-VKAs, 35 ICH- DOACs). RESULTS: The crude annual incidence of OAC-induced ICH was 3.8 (95% CI, 2.78-3.41) per 100,000 inhabitants/year. The mean (± SD) age was greater for ICH-DOACs (81.5 ± 8.3 vs. 77.7 ± 8.3 years; p = 0.012). The median (IQR) volume of the hemorrhage was lower for ICH-DOACs (11 [30.8] vs. 25 [50.7] mL; p = 0.03). The functional independence rate at 3 months (modified Rankin Scale, mRS < 3) was similar in both groups, although stroke-related mortality was greater in ICH-VKAs (40 vs. 72.7%; p = 0.02). The most frequently indicated poststroke antithrombotic therapy was DOACs (38.7%). CONCLUSION: We found that the incidence of OAC-induced ICH was greater than in previous studies. Hemorrhage volume and mortality were lower in ICH-DOACs than in ICH-VKAs. After stroke, DOACs were the most frequently indicated antithrombotic treatment.

Quality of Chronic Anticoagulation Control in Patients with Intracranial Haemorrhage due to Vitamin K Antagonists.

INTRODUCTION: Patients treated with vitamin K antagonists (VKA) are at increased risk of intracranial haemorrhage (ICH). The purpose of our study was to determine the quality of previous anticoagulation control in patients with VKA-associated ICH. MATERIALS AND METHODS: We prospectively assessed every consecutive patient admitted to our stroke unit with VKA-associated ICH between 2013 and 2016. Demographic, clinical, and radiological variables, as well as consecutive international normalized ratios (INR) during 7 previous months, were extracted. Time in therapeutic range (TTR), time over range (TOR), time below range (TBR), and percentage of INR within range (PINRR) were calculated. RESULTS AND DISCUSSION: The study population comprised 53 patients. Mean age was 79 years; 42% were women. Forty-eight patients had atrial fibrillation (AF) and 5 mechanical prosthetic valves. Therapeutic or infratherapeutic INR on arrival was detected in 64.4% of patients (95% CI 2.7 to 3.2). TTR was 67.8% (95% CI: 60.2 to 75.6 %) and PINRR was 75% (95% CI: 49.9-100). TOR was 17.2% (95% CI: 10.4 to 23.9% ) and TBR was 17% (95% CI: 10.6 to 23.9%). CONCLUSION: VKA-associated ICH happens usually in the context of good chronic anticoagulation control. Newer risk assessment methods are required.

Substantia Nigra Echogenicity Predicts Response to Drug Withdrawal in Suspected Drug-Induced Parkinsonism.

INTRODUCTION: Response to drug withdrawal in patients with suspected drug-induced parkinsonism (DIP) is of prognostic and therapeutic importance, but cannot be predicted solely on clinical information. The aim of this study was to validate SN hyperechogenicity (SN+) assessed by transcranial sonography as a predictor of response to drug withdrawal in this group of patients. METHODS: Patients were diagnosed according to previously published criteria and prospectively included in the study. All patients were followed until complete recovery of parkinsonian symptoms or at least for 6 months after discontinuation of the offending drug and then diagnosed as DIP or parkinsonism following neuroleptic exposure (PFNE). Transcranial sonography (TCS) findings were compared with the clinical diagnosis. RESULTS: Sixty patients comprised the group for the final analysis. Sixteen patients were classified as PFNE and 44 as DIP. The area of SN echogenicity was significantly increased in the PFNE group (0.23 cm2; standard deviation [SD]: 0.04), compared to the DIP group (0.14 cm2; SD, 0.05; one-way analysis of variance; P < 0.001). Normal SN was significantly associated with complete recovery after withdrawal of the parkinsonism-inducing drug (P < 0.0005). Accuracy of SN+ to distinguish PFNE from DIP was: sensitivity 81.2%; specificity 84.1%; positive predictive value 47.4%; and negative predictive value 96.2%. CONCLUSIONS: We believe that SN+ assessed with TCS is a valid prognostic marker in the setting of suspected DIP. It is a nonexpensive, feasible technique that can be implemented for proper counseling and guidance of treatment decisions.

Epidemiology of Intracranial Haemorrhages Associated with Vitamin K Antagonist Oral Anticoagulants in Spain: TAC Registry.

BACKGROUND: Vitamin K antagonist oral anticoagulants (VKA-OACs) are effective for primary and secondary prevention of embolic events. The rate of haemorrhagic neurological complications in patients admitted to neurology departments in Spain is not yet known. AIMS: We aimed to determine the clinical and epidemiological characteristics of patients with intracranial haemorrhage secondary to VKA-OACs as well as the incidence of this severe complication. METHODS: We conducted a retrospective, descriptive, multi-centre study using information from the medical records of all patients admitted to neurology departments, diagnosed with spontaneous intracranial haemorrhage, and treated with VKA-OACs within a 1-year period. We collected demographic and care data from centres, patients' medical records [demographic data, medical history, haemorrhage origin, vascular risk factors, concomitant treatment, and National Institutes of Health Stroke Scale (NIHSS) scores], and patients' outcome at 3 months [independence (modified Rankin Scale score <3) and mortality rate]. RESULTS: Twenty-one hospitals serving a population of 8,155,628 inhabitants participated in the study. The total number of cases was 235, the mean age was 78.2 (SD 9.4) years, and the baseline NIHSS score was 11.6 (SD 9.5; median 9; interquartile range 14). The VKA-OACs used were acenocoumarol in 95.3% (224 patients) and warfarin in 4.7% (11 patients). The haemorrhage origin was deep in 29.8%, lobar in 25.5%, intraventricular in 11.5%, extensive in 17.4% (>100 ml), cerebellar in 12.3%, and in the brainstem in 3.4%. The international normalised ratio was within therapeutic ranges at admission (according to indication) in 29.4% (69 patients). The global incidence (cases per 100,000 inhabitants per year) is 2.88. The in-hospital mortality rate was 40%, and 24.3% of the patients were independent at 3 months, while the mortality at 3 months was 42.6%. CONCLUSION: VKA-OAC treatment is associated with a large percentage of all cases of spontaneous intracranial haemorrhage, an event leading to high dependence and mortality rates.