Neuroimaging and clinical outcomes of oral anticoagulant-associated intracerebral hemorrhage.

OBJECTIVE: Whether intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. METHODS: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. RESULTS: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67-1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = -2.83, 95% CI = -5.28 to -0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30-0.84), and smaller baseline hematoma volume (linear regression coefficient = -0.24, 95% CI = -0.47 to -0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81-1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63-1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49-1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57-1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75-1.43). INTERPRETATION: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702-712.

Portuguese Observational Study of Ischaemic Stroke in Patients Medicated with Non-Vitamin K Antagonist Oral Anticoagulants.

INTRODUCTION: Clinical trials and subsequent meta-analyses showed advantages of non-vitamin K antagonists oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation. The impact of preadmission anticoagulation in acute ischaemic stroke (AIS) has not been established. OBJECTIVE: To compare functional outcome of patients with AIS with preadmission NOACs vs. VKAs. METHODS: A retrospective analysis was conducted on consecutive AIS patients under oral anticoagulation (VKAs or NOACs) admitted in 4 Portuguese hospitals within a period of 30 months. Two primary outcomes were defined and compared between VKA and NOAC groups: symptomatic intracerebral hemorrhage transformation (sICH) and modified Rankin Scale (mRS) at 3 months. RESULTS: Four hundred sixty-nine patients were included, of whom 332 (70.8%) were treated with VKA and 137 (29.2%) with NOAC. Patients' median age was 78.0 and 234 (49.9%) were male. NOAC-treated patients had a higher median CHA2DS2-VASc score than those under VKA (5.0 vs. 4.0, p = 0.023). The two primary outcomes showed no statistical differences between the VKAs' group and the NOACs' group (sICH: 5.4 vs. 5.4% [p = 0.911]; mRS at 3 months: 3.0 vs. 3.0 [p = 0.646], respectively). CONCLUSION: Preadmission anticoagulation with NOACs in AIS has a functional impact similar to that of VKAs.

Diagnostic yield of next-generation sequencing applied to neurological disorders.

The exponential knowledge on the genetic etiology and the trend towards genetically-specific therapies for previously untreatable disorders, requires neurologists to be familiar with the strengths and weaknesses of Next-Generation Sequencing (NGS). Our aim was to assess the diagnostic yield of NGS studies in clinical practice in our setting. We performed a retrospective, cross-sectional, 18 months long study, from a single Portuguese center, of consecutive neurological patients for whom a NGS study was requested. A diagnosis rate (DR) of 33.2% was achieved for a total of 190 patients (89 children). It was higher for muscle diseases (DR 61.1%). In 20%, an inconclusive molecular diagnosis was obtained. The rate of incidental findings (IF) was 5.3%. We found better DR for clinical exome (52.6%, p < 0.05) although only 14% of patients were characterized using this approach. The performance of gene panels for muscle diseases was better but not statistically significant (DR 56.3% vs. 31.7% overall, p > 0.05). The reduced number of patients in several phenotypic groups limits the interpretation of specific diagnostic yields. The better yield of gene panels for muscle diseases suggests that gene panels may be a more cost-effective first-line test in well-defined phenotypes. For heterogeneous phenotypes and overall, WES-based virtual panels or clinical exome should be favored. We present daily practice evidence that, with the constraints of our health system, for one third of the patients with neurological disorders of undetermined etiology a definitive diagnosis can be reached with NGS.

Behavior Changes and Gait Unsteadiness: The Value of Imaging and Prompt Neurosurgical Intervention.

Cavernous angiomas are central nervous system malformations. Most common manifestations are seizures and acute focal neurological deficits. We present a case report of a seventy-one year-old man with a two-month history of behavior changes, attention deficit and indifference followed by gait unsteadiness. Neuropsychological evaluation showed severe cognitive impairment and executive dysfunction. Head computed tomography depicted a supraventricular hydrocephaly. Magnetic resonance imaging revealed a small hemorrhage, contiguous to a mesencephalic cavernous angioma, obstructing the Sylvius aqueduct, causing secondary hydrocephalus. Four months after endoscopic ventriculocisternostomy, neuropsychological evaluation showed improvement and the patient regained autonomy. Parenchyma cavernous angiomas causing direct hemorrhage and subsequent obstruction of the Sylvian aqueduct are uncommon. Sub-acute behavior and mental state abnormalities are rare first manifestations of cavernous angioma and requires high clinical suspicion for its correct diagnosis. Magnetic resonance imaging evaluation is crucial in the detection of such patients as prompt neurosurgical intervention may substantially improve cognitive function.

Os angiomas cavernosos são malformações do sistema nervoso central cujas manifestações mais comuns são crises epiléticas e défices neurológicos agudos. Apresentamos o caso clínico de um doente de 71 anos com uma história com dois meses de evolução de alteração do comportamento, défice de atenção e apatia, sucedidas por marcada instabilidade da marcha. A avaliação neuropsicológica revelava alterações cognitivas e disfunção executiva marcadas. Na Tomografia Computorizada Cerebral observava-se hidrocefalia supraventricular enquanto na Ressonância Magnética cerebral era possível observar uma pequena hemorragia que obstruía o aqueduto de Sylvius localizada contiguamente a um angioma cavernoso mesencefálico. Quatro meses após o tratamento com ventriculocisternostomia endoscópica, o doente apresentava melhoria significativa na avaliação neuropsicológica tendo voltado a adquirir a autonomia prévia. A apresentação de um angioma cavernoso parenquimatoso como uma obstrução do aqueduto de Sylvius secundária a hemorragia é invulgar. Rara é também a sua apresentação como alterações do comportamento e do estado mental subagudas. Uma avaliação neuroimagiológica e uma intervenção neurocirúrgica precoces foram essenciais para a melhoria cognitiva observada.

POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants.

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA2DS2VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39-1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55-2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants- and vitamin K antagonists-associated intracranial hemorrhage, despite unavailability of non-vitamin K antagonist oral anticoagulants-specific reversal agents.