Microvascular decompression is effective for oculomotor nerve palsy caused by posterior cerebral artery compression: A case report.

Background: Oculomotor nerve palsy is often associated with diabetes mellitus or caused by compression by a cerebral aneurysm. Here, we report a rare case of oculomotor nerve palsy caused by compression by the posterior cerebral artery (PCA). Case Description: A 66-year-old woman suddenly developed diplopia and right blepharoptosis. Her symptoms suggested incomplete right oculomotor nerve palsy. Magnetic resonance imaging showed that a sharp curve in the right PCA had compressed the right oculomotor nerve. Microvascular decompression surgery was performed. Intraoperative findings showed that the P2 portion of the PCA had caused an indentation in the oculomotor nerve in the prepontine cistern. The transposition of the PCA with a prosthesis released the pressure. After the operation, her right blepharoptosis gradually improved. She had fully recovered by 48 days after the operation. Conclusion: Neurovascular compression (NVC) is recognized as the cause of hemifacial spasms, trigeminal neuralgia, and glossopharyngeal neuralgia. This case report demonstrated that NVC can also cause oculomotor nerve palsy. A high index of clinical suspicion can detect vascular compression of the oculomotor nerve. Prompt diagnosis and appropriate surgical management can achieve clinical improvement.

Mu Rhythm Desynchronization while Observing Rubber Hand Movement in the Mirror: The Interaction of Body Representation with Visuo-Tactile Stimulation.

During rubber hand illusion (RHI), participants feel that a rubber (fake) hand is their own (i.e., embodiment of the rubber hand) if the unseen real hand and seen rubber hand are stroked synchronously (i.e., visuo-tactile stimuli). The RHI is also evoked if the real and rubber hands are placed in the same position (i.e., visual-proprioceptive congruency), which can be performed using a mirror setting. Using electroencephalography (EEG) and mirror settings, we compared µ rhythm (8-13 Hz) event-related desynchronization (ERD; an index of sensorimotor activation) while watching the movements of embodied or non-embodied rubber hands, which was preceded by an observation of the rubber hand with or without synchronous visuo-tactile stimuli. The illusory ownership of the fake hand was manipulated using visual continuity with (RHI) and without (non-RHI) a fake forearm. Resultantly, an ownership-dependent µ rhythm ERD was found when delivering visuo-tactile stimuli; a greater and more persistent µ rhythm ERD during the rubber hand movement was identified in the RHI in comparison to the non-RHI condition. However, no difference was observed between the two when observing the fake hand alone. These findings suggest the possibility that a self-related multisensory interaction between body representation (top-down processing) and visuo-tactile inputs (bottom-up processing) before a fake hand movement produces ownership-dependent sensorimotor activations during subsequent movement observations.

Tactile temporal order judgment during rubber hand illusion: Distinct modulation of the point of subjective simultaneity and temporal resolution.

During the rubber hand illusion (RHI), individuals feel a fake hand as their own (ownership) and a perceived position of their real hand shifts toward the fake hand (proprioceptive drift; PD), which represents updating of multisensory hand representations. Bimanual tactile temporal order judgment (TOJ) includes processes of localizing tactile stimuli in space, for which multisensory hand representations are essential. According to the common processes, we examined tactile TOJ performance during the RHI and non-RHI. Temporal resolution (TR) as TOJ accuracy worsened during the non-RHI compared to the RHI. Additionally, a significant correlation between TR and PD was observed only in the non-RHI condition. However, the point of subjective simultaneity (PSS), which offers relative weighting of tactile inputs from the right and left hands, was correlated with illusory hand ownership. These results suggest that PSS and TR from tactile TOJ during RHI relate to self-attribution and localization of the hand, respectively.

Predictability of Delayed Visual Feedback Under Rubber Hand Illusion Modulates Localization but Not Ownership of the Hand.

The rubber hand illusion (RHI) is a perceptual illusion, whereby a fake hand is recognized as one's own hand when a fake hand and felt real hand are stroked synchronously. RHI strength is mainly assessed using a questionnaire rating and proprioceptive drift (PD). PD is characterized by the proprioceptively sensed location of the participant's own hand shifting toward the location of the fake hand after RHI. However, the relationship between the two measures of hand ownership and location remains controversial due to mixed findings: some studies report correlations between them, while others show that they are independent. Here, we demonstrated significant PD without RHI using delayed visual feedback. In this RHI study, video images of the fake hand were delivered to the subjects, and four delay intervals of visual feedback (80, 280, 480, and 680ms) were introduced. In four of six conditions, the delay interval was fixed throughout the condition. In the other two conditions, four delays were delivered in a predetermined order (i.e., serial condition; higher predictability) or in a pseudo-random order (i.e., random condition; low predictability). For the four conditions with a fixed delay, the questionnaire ratings and PD declined significantly when the delay interval exceeded circa 300ms. In both the serial and random conditions, no illusory ownership of the fake hand was reported in the questionnaire. In contrast, greater PD was found in the random condition but not in the serial condition. Our findings suggest that hand ownership and localization are caused by distinct multisensory integration processes.

Reduced default mode network connectivity relative to white matter integrity is associated with poor cognitive outcomes in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: The aim of this study was to investigate whether default mode network (DMN) connectivity and brain white matter integrity at baseline were associated with severe cognitive impairments at baseline and poor cognitive outcomes after shunt placement in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Twenty consecutive patients with iNPH whose symptoms were followed for 6 months after shunt placement and 10 healthy controls (HCs) were enrolled. DMN connectivity and brain white matter integrity at baseline in the patients with iNPH and HCs were detected by using resting-state functional magnetic resonance imaging (MRI) with independent component analysis and diffusion tensor imaging, respectively, and these MRI indexes were compared between the patients with iNPH and HCs. Performance on neuropsychological tests for memory and executive function and on the gait test was assessed in the patients with iNPH at baseline and 6 months after shunt placement. We divided the patients with iNPH into the relatively preserved and reduced DMN connectivity groups using the MRI indexes for DMN connectivity and brain white matter integrity, and the clinical measures were compared between the relatively preserved and reduced DMN connectivity groups. RESULTS: Mean DMN connectivity in the iNPH group was significantly lower than that in the HC group and was significantly positively correlated with Rey auditory verbal learning test (RAVLT) immediate recall scores and frontal assessment battery (FAB) scores. Mean fractional anisotropy of the whole-brain white matter skeleton in the iNPH group was significantly lower than that in the HC group. The reduced DMN connectivity group showed significantly worse performance on the RAVLT at baseline and significantly worse improvement in the RAVLT immediate recall and recognition scores and the FAB scores than the preserved DMN connectivity group. Moreover, the RAVLT recognition score highly discriminated patients with relatively preserved DMN connectivity from those with relatively reduced DMN connectivity. CONCLUSIONS: Our findings indicated that iNPH patients with reduced DMN connectivity relative to the severity of brain white matter disruption have severe memory deficits at baseline and poorer cognitive outcomes after shunt placement. However, further larger-scale studies are needed to confirm these findings.

Distinct modulation of mu and beta rhythm desynchronization during observation of embodied fake hand rotation.

The rubber hand illusion (RHI) is a phenomenon whereby participants recognize a fake hand as their own. Studies have examined the effects of observing fake hand movements after the RHI on brain sensorimotor activity, although results remain controversial. To address these discrepancies, we investigated the effects of observation of fake hand rotation after the RHI on sensorimotor mu (µ: 8-13 Hz) and beta (ß: 15-25 Hz) rhythm event-related desynchronization (ERD) using electroencephalography (EEG). Questionnaire results and proprioceptive drift revealed that the RHI occurred in participants when their invisible hand and fake visible hand were stroked synchronously but not during asynchronous stroking. Independent component (IC) clustering from EEG data during movement observation identified three IC clusters, including the right sensorimotor, left sensorimotor, and left occipital cluster. In the right sensorimotor cluster, we observed distinct modulation of µ and ß ERD during fake hand rotation. Illusory ownership over the fake hand enhanced µ ERD but inversely attenuated ß ERD. Further, the extent of µ ERD correlated with proprioceptive drift, but not with questionnaire ratings, whereas the converse results were obtained for ß ERD. No ownership-dependent ERD modulation was detected in the left sensorimotor cluster. Alpha (α: 8-13 Hz) rhythm ERD of the left occipital cluster was smaller in the synchronous condition than in the asynchronous condition, but α ERD was not correlated with questionnaire rating or drift. These findings suggest that observing embodied fake hand rotation induces distinct cortical processing in sensorimotor brain areas.

Left Atrial Size and Ischemic Events after Ischemic Stroke or Transient Ischemic Attack in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. RESULTS: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9-2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02-3.00). CONCLUSION: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.

Discovery of a Novel Class of State-Dependent NaV1.7 Inhibitors for the Treatment of Neuropathic Pain.

The discovery of a novel class of state-dependent voltage-gated sodium channel (NaV)1.7 inhibitors is described. By the modification of amide or urethane bond in NaV1.7 blocker III, structure-activity relationship studies that led to the identification of novel NaV1.7 inhibitor 2i (DS01171986) were performed. Compound 2i exhibited state-dependent inhibition of NaV1.7 without NaV1.1, NaV1.5 or human ether-a-go-go related gene (hERG) liabilities at concentrations up to 100 µM. Further biological profiling successfully revealed that 2i possessed potent analgesic properties in a murine model of neuropathic pain (ED50: 3.4 mg/kg) with an excellent central nervous system (CNS) safety margin (> 600 fold).

Sensorimotor and Posterior Brain Activations During the Observation of Illusory Embodied Fake Hand Movement.

In the rubber hand illusion (RHI), the subject recognizes a fake hand as his or her own. We recently found that the observation of embodied fake hand movement elicited mu-rhythm (8-13 Hz) desynchronization on electroencephalography (EEG), suggesting brain activation in the sensorimotor regions. However, it is known that mu-rhythm desynchronization during action observation is confounded with occipital alpha-rhythm desynchronization, which is modulated by attention. This study examined the independence of brain activities in the sensorimotor and occipital regions relating to the movement observation under the RHI. The invisible participant's left and fake right hands were stroked simultaneously, which was interrupted by unexpected fake hand movements. A mirror-reversed image of the fake hand was shown on a monitor in front of the participant with a delay of 80, 280, or 480 ms. Illusion strength decreased as a function of the delay. EEG independent component analysis (ICA) and ICA clustering revealed six clusters with observation-induced desynchronization of 8-13 Hz frequency band. In the right sensorimotor cluster, mu-rhythm desynchronization was the greatest under the 80-ms delay, while alpha-rhythm desynchronization of the occipital clusters did not show delay-dependence. These results suggest that brain activation in the sensorimotor areas (i.e., mu-rhythm desynchronization) induced by embodied fake hand movement is independent of that in the occipital areas (alpha-rhythm desynchronization).

Prior Anticoagulation and Short- or Long-Term Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients With Nonvalvular Atrial Fibrillation.

Background We aimed to clarify associations between prior anticoagulation and short- or long-term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio ( INR ) <2 on admission, 28 (2.4%) received prior warfarin treatment with an INR ≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation ( INR <2: adjusted odds ratio: 0.58; 95% CI, 0.42-0.81; P=0.001; INR ≥2: adjusted odds ratio: 0.40; 95% CI, 0.16-0.97; P=0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20-6.15; P=0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01581502.

The Relationship Between the Virtual Hand Illusion and Motor Performance.

Bodily self-consciousness consists of agency (i.e., the feeling of controlling one's actions and causing external events) and body ownership (i.e., the feeling that one's body belongs to one's self). If a visual presentation of a virtual (fake) hand matches the active movement of a real hand, both the agency and body ownership of the virtual hand are induced [i.e., the active virtual hand illusion (VHI)]. However, previous active VHI studies have rarely considered the effects of goal-related movement errors (i.e., motor performance) on the senses of agency and ownership. Hence, the current study aimed to clarify the relationship between the active VHI and motor performance. To induce the VHI, 18 healthy subjects (three men and 15 women; 20.7 ± 7.3 years) were required to continuously move a virtual hand around a circle at a predetermined speed (i.e., spatial and temporal goals) using their active hand movements. While moving the virtual hand actively, five visual feedback delays were introduced: 90, 210, 330, 450, and 570 ms. It was found that the subjective ratings of both the agency and body ownership of the virtual hand decreased as a function of the delay intervals, whereas most of the spatial and temporal movement errors linearly increased. Using multiple regression analyses, we examined whether the agency and ownership ratings could be explained effectively by both the delay and movement errors. The results demonstrated that the agency was determined not only by the delay but also by the movement variability, whereas the body ownership was mostly determined by the delay. These findings suggest a possibility that the goal-related motor performance of the active VHI influences the agency judgment more strongly, while its effect on the ownership judgment is weaker.

Hand Dexterity Impairment in Patients with Cervical Myelopathy: A New Quantitative Assessment Using a Natural Prehension Movement.

Cervical myelopathy (CM) caused by spinal cord compression can lead to reduced hand dexterity. However, except for the 10 sec grip-and-release test, there is no objective assessment system for hand dexterity in patients with CM. Therefore, we evaluated the hand dexterity impairment of patients with CM objectively by asking them to perform a natural prehension movement. Twenty-three patients with CM and 30 age-matched controls were asked to reach for and grasp a small object with their right thumb and index finger and to subsequently lift and hold it. To examine the effects of tactile afferents from the fingers, objects with surface materials of differing textures (silk, suede, and sandpaper) were used. All patients also underwent the Japanese Orthopedic Association (JOA) test. Preoperative patients showed significantly greater grip aperture during reach-to-grasp movements and weaker grip force than controls only while attempting to lift the most slippery object (silk). Patients, immediately after surgery, (n = 15) tended to show improvements in the JOA score and in reaction time and movement time with respect to reaching movements. Multiple regression analysis demonstrated that some parameters of the prehension task could successfully predict subjective evaluations of dexterous hand movements based on JOA scores. These results suggest that quantitative assessments using prehension movements could be useful to objectively evaluate hand dexterity impairment in patients with CM.

Two-Year Outcomes of Anticoagulation for Acute Ischemic Stroke With Nonvalvular Atrial Fibrillation　- SAMURAI-NVAF Study.

BACKGROUND: We determined the 2-year long-term risk-benefit profile in patients with stroke or transient ischemic attack (TIA) receiving warfarin or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry in Japan.Methods and Results:NVAF patients within 7 days after onset of ischemic stroke/TIA were enrolled in 18 stroke centers. Outcome measures included ischemic and bleeding events and death in the 2-year follow-up period. We enrolled 1,116 patients taking either warfarin (650 patients) or DOACs (466 patients) at acute hospital discharge. DOAC users were younger and had lower National Institutes of Health Stroke Scale, CHADS2and discharge modified Rankin Scale scores than warfarin users (P<0.0001 each). Incidences of stroke/systemic embolism (adjusted hazard ratio, 1.07; 95% CI, 0.66-1.72), all ischemic events (1.13; 0.72-1.75), and ischemic stroke/TIA (1.58; 0.95-2.62) were similar between groups. Risks of intracranial hemorrhage (0.32; 0.09-0.97) and death (0.41; 0.26-0.63) were significantly lower for DOAC users. Infection was the leading cause of death, accounting for 40% of deaths among warfarin users. CONCLUSIONS: Stroke/TIA patients receiving DOACs for secondary prevention were younger and had lower stroke severity and risk indices than those receiving warfarin. Estimated cumulative incidences of stroke and systemic embolism within 2 years were similar between warfarin and DOACs users, but those of death and intracranial hemorrhage were significantly lower among DOAC users.

Associations between Pre-Admission Risk Scores and Two-Year Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND: We aimed to clarify associations between pre-admission risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic stroke or transient ischemic attack (TIA) patients with non-valvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry. METHODS: From 18 Japanese stroke centers, ischemic stroke or TIA patients with NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were defined as death/disability (modified Rankin Scale score ≥3) at 2 years, 2-year mortality, and ischemic or hemorrhagic events within 2 years. RESULTS: A total of 1,192 patients with NVAF (527 women; mean age, 78 ± 10 years), including 1,141 ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality, and ischemic or hemorrhagic events increased significantly with increasing pre-admission CHADS2 (p for trend <0.001 for death/disability and mortality, p for trend = 0.024 for events), CHA2DS2-VASc (p for trend <0.001 for all), and HAS-BLED (p for trend = 0.004 for death/disability, p for trend <0.001 for mortality, p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point, 1.52; 95% CI 1.35-1.71; p <0.001 for death/disability; hazard ratio (HR) per 1 point, 1.23; 95% CI 1.12-1.35; p <0.001 for mortality; HR per 1 point, 1.14; 95% CI 1.02-1.26; p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41-1.72, p < 0.001; 1.21, 1.12-1.30, p < 0.001; 1.17, 1.07-1.27, p < 0.001; respectively), and HAS-BLED (1.33, 1.17-1.52, p < 0.001; 1.23, 1.10-1.38, p < 0.001; 1.18, 1.05-1.34, p = 0.008; respectively) scores were independently associated with all outcome measures. CONCLUSIONS: In ischemic stroke or TIA patients with NVAF, all pre-admission risk scores were independently associated with death/disability at 2 years and 2-year mortality, as well as ischemic or hemorrhagic events within 2 years.

Spontaneous imitative movements induced by an illusory embodied fake hand.

In the rubber hand illusion (RHI), individuals perceive a fake hand as their own when the hidden real hand and visible fake hand are synchronously stroked. Several RHI studies have reported that visual manipulation of the embodied fake hand inversely affects the perceptual processing of the observer's own hand (e.g., thermal or pain sensitivity). In this study, we examined whether motor manipulation of the fake hand similarly affects the observer's motor system. Our study employed a novel RHI paradigm wherein stroking was interrupted by unexpected movement of the fake hand (i.e., finger spreading) while measuring electroencephalography (EEG). We found that participants often spontaneously moved their hands in accordance with the movement of the fake hand only in the RHI (synchronous) sessions. EEG analyses revealed enhanced neural activation (mu-rhythm desynchronization) of the motor system during observation of the fake hand movement. Moreover, motor activation was greater in the synchronous than in the asynchronous condition and significantly correlated with the feeling of body ownership over the fake hand. These findings provide strong behavioral and neurophysiological evidence of 'motor back projection', in which the movement of an illusory embodied body part is inversely transferred to the sensorimotor system of the observer.

Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii.

Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and that these interneurons might be equivalent to those identified in animal experiments.

Body ownership and agency: task-dependent effects of the virtual hand illusion on proprioceptive drift.

Body ownership and agency are fundamental to self-consciousness. These bodily experiences have been intensively investigated using the rubber hand illusion, wherein participants perceive a fake hand as their own. After presentation of the illusion, the position of the participant's hand then shifts toward the location of the fake hand (proprioceptive drift). However, it remains controversial whether proprioceptive drift is able to provide an objective measurement of body ownership, and whether agency also affects drift. Using the virtual hand illusion (VHI), the current study examined the effects of body ownership and agency on proprioceptive drift, with three different visuo-motor tasks. Twenty healthy adults (29.6 ± 9.2 years old) completed VH manipulations using their right hand under a 2 × 2 factorial design (active vs. passive manipulation, and congruent vs. incongruent virtual hand). Prior to and after VH manipulation, three different tasks were performed to assess proprioceptive drift, in which participants were unable to see their real hands. The effects of the VHI on proprioceptive drift were task-dependent. When participants were required to judge the position of their right hand using a ruler, or by reaching toward a visual target, both body ownership and agency modulated proprioceptive drift. Comparatively, when participants aligned both hands, drift was influenced by ownership but not agency. These results suggest that body ownership and agency might differentially modulate various body representations in the brain.

Higher Risk of Ischemic Events in Secondary Prevention for Patients With Persistent Than Those With Paroxysmal Atrial Fibrillation.

BACKGROUND AND PURPOSE: The discrimination between paroxysmal and sustained (persistent or permanent) atrial fibrillation (AF) has not been considered in the approach to secondary stroke prevention. We aimed to assess the differences in clinical outcomes between mostly anticoagulated patients with sustained and paroxysmal AF who had previous ischemic stroke or transient ischemic attack. METHODS: Using data from 1192 nonvalvular AF patients with acute ischemic stroke or transient ischemic attack who were registered in the SAMURAI-NVAF study (Stroke Management With Urgent Risk-Factor Assessment and Improvement-Nonvalvular AF; a prospective, multicenter, observational study), we divided patients into those with paroxysmal AF and those with sustained AF. We compared clinical outcomes between the 2 groups. RESULTS: The median follow-up period was 1.8 (interquartile range, 0.93-2.0) years. Of the 1192 patients, 758 (336 women; 77.9±9.9 years old) and 434 (191 women; 77.3±10.0 years old) were assigned to the sustained AF group and paroxysmal AF groups, respectively. After adjusting for sex, age, previous anticoagulation, and initial National Institutes of Health Stroke Scale score, sustained AF was negatively associated with 3-month independence (multivariable-adjusted odds ratio, 0.61; 95% confidence interval, 0.43-0.87; P=0.006). The annual rate of stroke or systemic embolism was 8.3 and 4.6 per 100 person-years, respectively (multivariable-adjusted hazard ratio, 1.95; 95% confidence interval, 1.26-3.14) and that of major bleeding events was 3.4 and 3.1, respectively (hazard ratio, 1.13; 95% confidence interval, 0.63-2.08). CONCLUSIONS: Among patients with previous ischemic stroke or transient ischemic attack, those with sustained AF had a higher risk of stroke or systemic embolism compared with those with paroxysmal AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01581502.

Three-month risk-benefit profile of anticoagulation after stroke with atrial fibrillation: The SAMURAI-Nonvalvular Atrial Fibrillation (NVAF) study.

AIMS: This study was performed to determine the short-term risk-benefit profiles of patients treated with oral anticoagulation for acute ischemic stroke or transient ischemic attack using a multicenter, prospective registry. METHODS: A total of 1137 patients (645 men, 77 ± 10 years old) with acute ischemic stroke/transient ischemic attack taking warfarin (662 patients) or non-vitamin K antagonist oral anticoagulants (dabigatran in 205, rivaroxaban in 245, apixaban in 25 patients) for nonvalvular atrial fibrillation who completed a three-month follow-up survey were studied. Choice of anticoagulants was not randomized. Primary outcome measures were stroke/systemic embolism and major bleeding. RESULTS: Both warfarin and non-vitamin K antagonist oral anticoagulants were initiated within four days after stroke/transient ischemic attack onset in the majority of cases. Non-vitamin K antagonist oral anticoagulant users had lower ischemia- and bleeding-risk indices (CHADS2, CHA2DS2-VASc, HAS-BLED) and milder strokes than warfarin users. The three-month cumulative rate of stroke/systemic embolism was 3.06% (95% CI 1.96%-4.74%) in warfarin users and 2.84% (1.65%-4.83%) in non-vitamin K antagonist oral anticoagulant users (adjusted HR 0.96, 95% CI 0.44-2.04). The rate of major bleeding was 2.61% (1.60%-4.22%) and 1.11% (0.14%-1.08%), respectively (HR 0.63, 0.19-1.78); that for intracranial hemorrhage was marginally significantly lower in non-vitamin K antagonist oral anticoagulant users (HR 0.17, 0.01-1.15). Major bleeding did not occur in non-vitamin K antagonist oral anticoagulant users with a CHADS2 score <4 or those with a discharge modified Rankin Scale score ≤2. CONCLUSIONS: Stroke or systemic embolism during the initial three-month anticoagulation period after stroke/transient ischemic attack was not frequent as compared to previous findings regardless of warfarin or non-vitamin K antagonist oral anticoagulants were used. Intracranial hemorrhage was relatively uncommon in non-vitamin K antagonist oral anticoagulant users, although treatment assignment was not randomized. Early initiation of non-vitamin K antagonist oral anticoagulants during the acute stage of stroke/transient ischemic attack in real-world clinical settings seems safe in bleeding-susceptible Japanese population.