Tomoaki Kameda

Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: The SAMURAI-NVAF Study

Background Large clinical trials are lack of data on non-vitamin K antagonist oral anticoagulants for acute stroke patients. Aim To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-NVAF registry (ClinicalTrials.gov NCT01581502). Method The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23-day stay) was assessed. Results Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10-month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS2, CHA2DS2-VASc, and HAS-BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four-days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20-day or shorter hospitalization (OR 2·46, 95% CI 1·87–3·24). Conclusions Warfarin use at acute hospital discharge was still common in the initial years after approval of nonvitamin K antagonist oral anticoagulants, although nonvitamin K antagonist oral anticoagulant users increased gradually. The index stroke was milder and ischemia-risk indices were lower in nonvitamin K antagonist oral anticoagulant users than in warfarin users. Early initiation of nonvitamin K antagonist oral anticoagulants seemed safe.

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.

Unique combination of hyperintense vessel sign on initial FLAIR and delayed vasoconstriction on MRA in reversible cerebral vasoconstriction syndrome: A case report

Background Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and reversible cerebral vasoconstriction on angiographic findings. It can be difficult to diagnose when initial angiography is normal. Case results A 30-year-old woman was admitted because of sudden-onset thunderclap headache and seizure on postpartum day 7. Brain MRI on fluid-attenuated inversion recovery (FLAIR) showed hyperintense vessel sign (HVS), which usually means slow flow due to severe proximal arterial stenosis. However, magnetic resonance angiography (MRA) indicated that proximal arteries was normal. After nicardipine treatment, her symptoms improved dramatically. Follow-up FLAIR on day 7 showed complete resolution of HVS, while a series of MRAs revealed reversible multifocal segmental vasoconstriction. Conclusions HVS on initial FLAIR is useful for an early diagnosis of reversible cerebral vasoconstriction syndrome. As the delayed vasoconstriction on MRA can be observed, reversible cerebral vasoconstriction syndrome may progress from distal small to proximal larger arteries.

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.

Diffusion-weighted imaging changes in a case of severe hypoglycemic encephalopathy.

A 75-year-old man with a history of diabetes mellitus on treatment with three oral hypoglycemic drugs was admitted to our hospital after being found unresponsive at home. Upon arrival, his blood glucose level was 11 mg/dL. The initial brain diffusion-weighted image (DWI), obtained between two and 19 hours after onset, revealed the presence of symmetric hyperintense lesions in the bilateral deep white matter (Picture 1). Five days later, new cerebral cortex lesions were found on DWI, while the previous lesions had disappeared (Picture 2). The patient died 14 days later due to pneumonia without regaining consciousness. Hypoglycemic encephalopathy often produces abnormal signals on brain DWI, especially in the cerebral cortex, hippocampus, basal ganglia and deep white matter (1). However, reports of serial DWI changes, such as that observed in the present case, are uncommon (2). Although the exact mechanisms underlying serial DWI changes are unknown, the observations in this case may provide a basis for predicting a poor prognosis due to hypoglycemic injury.

Mandibuloptosis as a cause of supine choking in a patient with amyotrophic lateral sclerosis

Orthopnea is a preference for breathing in an upright rather than a supine position, usually associated with congestive heart failure and/or pulmonary edema, lung diseases, neurological disorders, and other conditions. In patients with ALS, orthopnea in the supine position, which is predictive of poor prognosis [1], is mainly caused by upward displacement of the paretic diaphragms by abdominal organs, preventing adequate air intake [2, 3]. We present here an ALS patient who developed marked dyspnea in the supine position, presumably due to different mechanism. A 67-year-old ex-carpenter first noticed weakness in his right arm 2 years prior. The weakness extended to the right hand within 6 months. Neurological examination at that time revealed right spastic hemiplegia with intact sensation, atrophy of the right upper limb, and bilaterally increased tendon reflexes with positive Babinski signs. Both brain and cervical MRIs were unremarkable. A needle electromyography showed active neurogenic changes in all the examined muscles of the four limbs, confirming the diagnosis of ALS. The symptoms gradually worsened, and 16 months after onset, dysphagia and shortness of breath at night required him to avoid the supine position when sleeping. A neurological examination, 20 months after onset, revealed bilateral flail-arms and slight tongue atrophy with fasciculation. His speech was slurred and he had dysphagia, but was still able to walk without aid. All tendon reflexes were increased, with bilateral positive Babinski signs. His breathing was normal when sitting or lying on the right or left side, but he choked so severely when supine that he could not remain in that position for even a second; neither protrusion of the tongue nor respiratory support with a non-invasive ventilator prevented suffocation. The choking stopped immediately, however, with his head tilted and his jaw thrust forward. Blood gas analysis revealed no hypercapnia or hypoxia, although spirometry showed a slight reduction of his vital capacity (2.73 l; 79% of the predicted value). No organic lesions were found by laryngoscopy when sitting. X-ray examination (Fig. 1) showed the oropharyngeal airway to be normal when the patient was upright (Fig. 1a) but when supine with choking, the mandible slipped down, occluding the airway at the base of the tongue (Fig. 1b). Tilting the head and thrusting the jaw forward, in the supine position, restored the upper airway (Fig. 1c). The respiratory distress observed in this patient is a form of orthopnea, although it was not caused by weakness of the diaphragm. It seems rather to be caused by a dynamic collapse of the upper airway, presumably due to gravitational pull on the mandible. Mandibuloptosis, a term unfamiliar to neurologists, is a drop of the mandible caused by gravity. It is occasionally encountered in ALS patients, who keep their mouths open, with sialorrhea, because of weakness of the jaw-closure muscles (temporal and masseter muscles); this is mandibuloptosis in the upright position. Mandibuloptosis can also occur in the supine position, causing a collapse of the upper airway accompanied by glossoptosis, due to weakness of the lateral pterygoid muscle, responsible for jaw protraction. Indeed, our patient could not place his lower teeth in front of his upper teeth even when upright. The failure of M. Namekawa (&) T. Kameda I. Nakano Department of Neurology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan e-mail: mnamekaw@jichi.ac.jp