Therapeutic efficacy of heparin and direct factor Xa inhibitors in cancer-associated cryptogenic ischemic stroke with venous thromboembolism.

BACKGROUND: Anticoagulation therapy, especially using heparin or recently developed oral direct factor Xa inhibitors (DiXals), is recommended as first-line treatment for cancer-related venous thromboembolism (VTE). However, the preventive efficacy of these anticoagulants for cancer-associated ischemic stroke is still unknown. We retrospectively investigated the efficacy of subcutaneous unfractionated heparin (UFH) and DiXals for preventing the recurrence of cancer-associated cryptogenic ischemic stroke with VTE. METHODS: We retrospectively studied consecutive patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE who received subcutaneous UFH or oral DiXaIs at 9 hospitals. RESULT: Fifty-three patients (24 treated with UFH and 29 treated with DiXaIs) were enrolled. Of these, 47 demonstrated systemic metastasis (cancer stage IV). During 30-day follow-up after initiation of anticoagulation therapy, recurrent ischemic stroke was observed in only 1 patient (4%) in the UFH group and in 9 patients (31%) in the DiXal group. The incidence of major bleeding complications was similar between the 2 groups (4% and 10%, respectively). The cumulative risk of ischemic stroke recurrence within 30 days was lower with UFH than with DiXals (competing risk analysis, p = 0.008). In the DiXal group, patients who experienced recurrence showed significantly higher D-dimer levels than those without recurrence. CONCLUSION: In patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE, UFH demonstrated a lower rate of recurrent ischemic stroke than DiXaIs, and there were no differences in bleeding risk between the 2 treatments. D-dimer levels at stroke onset increased the risk of recurrence in the DiXal group but not in the UFH group.

A Case of Cerebral Venous Thrombosis and Deep Venous Thrombosis Due to Hyperthyroidism with Increased Factor VIII Activity.

A 48-year-old woman was admitted to our hospital because of headache and fever. She was diagnosed with aseptic meningitis. Five days later, she had a seizure and developed left hemiparesis. Magnetic resonance imaging showed hyperintensity in the right parietal area on fluid attenuated inversion recovery imaging. She was diagnosed as having cerebral venous thrombosis (CVT) because the suprasagittal sinus was invisible on the venographic studies. Moreover, deep venous thrombosis (DVT) was detected in her left lower extremity. Laboratory findings showed hyperthyroidism and markedly increased factor VIII activity. This is a rare case of concomitant CVT and DVT induced by high factor VIII activity due to hyperthyroidism under the presence of meningitis, an additional risk factor for thrombosis.

Effectiveness of Nonvitamin K Antagonist Oral Anticoagulants and Warfarin for Preventing Further Cerebral Microbleeds in Acute Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation and At Least One Microbleed: CMB-NOW Multisite Pilot Trial.

BACKGROUND: Nonvitamin K antagonist oral anticoagulants (NOACs) are considered superior, or at least noninferior, to warfarin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Here, we recruited acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one cerebral microbleed (CMB), and evaluated the proportion of patients who had an increased number of CMBs (%) after receiving anticoagulant therapy with NOACs or with warfarin for 12 months. METHODS: This was a multicenter, prospective, observational cohort study at 20 centers, conducted between 2015 and 2017, in which we recruited 85 patients with at least one CMB detected by 1.5T magnetic resonance imaging (T2*WI) at baseline, who received NOACs or warfarin for at least 12 months. We compared the proportions of patients with increased numbers of CMBs in the NOACs and warfarin treatment groups. RESULTS: The proportions of patients with increased numbers of CMBs at month 12 of treatment were 28.6% and 66.7% in the NOACs and warfarin groups, respectively. The new CMBs showed no specific regional localization in either group. In the NOACs and warfarin groups, physicians prescribed lower-than-standard dosing in 13.3% and 50% of the cases, respectively. The administration of reduced doses at physicians' discretion did not appear to alter the incidence of new CMBs. DISCUSSION: This is the first evidence to suggest efficacy of NOACs for preventing further CMBs in patients with at least one CMB, although no statistical evaluation was carried out.

YAMATO Study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy).

BACKGROUND AND PURPOSE: We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. METHODS: The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). RESULTS: One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69-85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group (P=1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P=0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group (P=0.443). The favorable outcome (modified Rankin Scale score of 0-2) at 3 months was also similar between the groups (53% versus 57%; P=0.738). CONCLUSIONS: The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index-j.htm. Unique identifier: UMIN000006330.

Relationship between cortex and pulvinar abnormalities on diffusion-weighted imaging in status epilepticus.

The aim of this study was to analyze the pattern of magnetic resonance diffusion-weighted imaging (DWI) findings in status epilepticus in terms of clinical characteristics. Participants comprised 106 patients with status epilepticus who were admitted to our hospital and underwent DWI. Forty-five patients (42.5 %) showed abnormal findings on DWI and were divided into two groups, comprising 26 patients (24.5 %) with cortex lesions alone and 19 patients (17.9 %) with cortex and pulvinar lesions in the same hemisphere. A long duration of status epilepticus (>120 min) tended to be more prevalent among patients with cortex and pulvinar lesions (57.9 %) than among patients with cortex lesions alone (30.8 %) by univariate and multivariate analyses. Todd's palsy tended to be more frequent in patients with abnormalities on DWI (24/45, 53.3 %) than in patients with normal DWI (21/61, 34.4 %). Six of the 26 patients with cortex lesions alone (23.1 %) had taken anti-epileptic drugs before the attack compared to none of the 19 patients with both cortex and pulvinar lesions. The trend toward a longer duration of status epilepticus in patients with both cortex and pulvinar lesions favors a spreading pattern of seizure discharge from cortex to pulvinar via cortico-pulvinar pathways, and anti-epileptic drugs might, to some extent, prevent spreading of seizure discharge from cortex to pulvinar. In addition, existence of high-intensity areas on DWI at the onset of epilepsy may be a predictive factor for the occurrence of Todd's palsy.

Arterial spin-labeling magnetic resonance imaging for diagnosis of late seizure after stroke.

BACKGROUND AND PURPOSE: Arterial spin labeling (ASL) is a non-invasive modality of magnetic resonance imaging (MRI) used to evaluate cerebral perfusion without a contrast agent. The usefulness of ASL for diagnosis in the acute phase of late seizure after stroke was evaluated. METHODS: Twelve consecutive patients diagnosed with late seizure after stroke were enrolled in this study. MRI including ASL was performed for each patient at the time of the emergency department visit. Eight of the patients underwent electroencephalography (EEG). RESULTS: All patients showed hyperperfusion around the stroke lesion on ASL. Only 6 patients showed high signal intensity along the cerebral cortex around the stroke lesion on diffusion-weighted imaging. The patients who underwent EEG showed slow activity, but paroxysmal discharges such as spikes or sharp waves were not observed. CONCLUSIONS: ASL was able to reveal hyperperfusion and was of great diagnostic value in the peri-ictal phase of late seizure after stroke.