Fumio Miyashita

Effect of Prothrombin Complex Concentrate on Hematoma Enlargement and Clinical Outcome in Patients with Anticoagulant-Associated Intracerebral Hemorrhage

Background: The present study was carried out to determine the effect of prothrombin complex concentrate (PCC) on hematoma enlargement (HE) and the early clinical outcome of intracerebral hemorrhage (ICH) patients on long-term warfarin treatment. Methods: Themedical records and computed tomography (CT) images of 50 consecutive ICH patients on long-term warfarin treatment (35 men, 15 women; 69 ± 12 years old) were reviewed. International normalized ratio (INR) values, frequency of HE and clinical outcome were compared between patients treated with and without PCC. Results: INR values on admission were above 2.0 in 37 patients, of whom 19 were given PCC (PCC group) and 18 were not given PCC (control group). In these 37 patients, the frequency of HE (p = 0.017), the number of patients with a poor clinical outcome (modified Rankin Scale score ≧3 at 30 days or at discharge; p = 0.045) and in-hospital mortality (p = 0.042) were significantly higher in the control than in the PCC group. On multivariate logistic regression analysis with adjustment, PCC administration was independently associated (odds ratio 0.03, 95% confidence interval 0.00–0.63; p = 0.023) with a reduction in poor clinical outcome in ICH patients whose INR values were >2.0 on admission. Conclusions: Immediate INR reversal with PCC may prevent HE and subsequent poor outcome.

Clinical phenotype in X-linked Charcot-Marie-Tooth disease with an entire deletion of the connexin 32 coding sequence.

To clarify the clinical phenotype and molecular mechanism in X-linked Charcot-Marie-Tooth disease (CMTX) patients with a deletion of the whole connexin 32 (Cx32) coding sequence, we studied a family with this deletion by electrophysiology, Southern blotting and quantitative PCR analyses. Two brothers with no copy of Cx32, 27 and 25 years old, showed steppage gait, moderate muscle atrophy and weakness, and mild sensory disturbance in the distal parts of the legs. The clinical phenotypes in these brothers were not different from those in patients with other types of severe Cx32 mutations. Their mother, with one copy of Cx32, showed very mild muscle weakness and sensory disturbance. An electrophysiological study showed a nonuniform demyelinating neuropathy with some aspects of an axonal-loss neuropathy. Sural nerve biopsy showed loss of myelinated fibers, many relatively thin myelin sheaths, clusters of small myelinated fibers, and some onion bulb formations. The present findings suggest that both a demyelinating process and an axonal involvement were present in the patients with total defect of Cx32 probably due to loss of the function mechanism of Cx32 as the underlying molecular mechanism, because a dominant negative effect theory is not applicable in these patients.

Enlargement of Acute Intracerebral Hematomas in Patients on Long-Term Warfarin Treatment

Background: The relationship between warfarin administration and the frequent development of enlarged hematomas in patients with acute intracerebral hemorrhage (ICH) is controversial. The present study was carried out to examine this issue. Methods: This study reviewed 41 patients with nontraumatic ICH within 24 h after stroke onset from 1999 to 2003 who received long-term warfarin treatment (29 men and 12 women, 70 ± 12 years old) and 323 patients who had not been on warfarin (177 men and 146 women, 66 ± 13 years old). The hematoma volume (HV) on admission, final HV, frequency of hematoma enlargement (HE) and other background characteristics were investigated. Results: Both the HV on admission (p = 0.031) and final HV (p = 0.001) were larger in patients on warfarin than in those not receiving warfarin. HE occurred more frequently (p < 0.001), and mortality at 30 days or at discharge was higher (p = 0.003) in the warfarin group than in the control group. A multivariate adjusted logistic regression analysis showed that warfarin treatment (OR = 5.75, 95% CI = 2.41–13.8, p < 0.001), liver disease (OR = 2.59, 95% CI = 1.12–5.99, p = 0.026), and the National Institutes of Health Stroke Scale score (OR = 1.10, 95% CI = 1.04–1.15, p < 0.001, per 1-score increase) on admission were independently related to HE. Conclusions: Acute ICH in patients on long-term warfarin treatment appears to be associated with HE.

Low Serum Calcium Levels Contribute to Larger Hematoma Volume in Acute Intracerebral Hemorrhage

Background and Purpose— We investigate whether admission serum calcium levels are associated with hematoma volume, stroke severity, and outcomes in patients with acute intracerebral hemorrhage. Methods— A total of 273 patients admitted within 24 hours after intracerebral hemorrhage onset was divided into quartiles based on admission serum calcium levels (Q1 [⩽9.0], Q2 [9.1–9.3], Q3 [9.4–9.7], Q4 [≥9.8] mg/dL). Results— Median hematoma volumes for each quartile (Q1 to Q4) were 18, 9, 10, and 9 mL (P=0.005), and median National Institutes of Health Stroke Scale scores were 16, 11, 11, and 9 (P=0.010), respectively. On multivariate analysis, Q1 had larger hematoma volume (P=0.025) and higher National Institutes of Health Stroke Scale score (P=0.020) than Q4. There were fewer patients with modified Rankin Scale scores 0 to 2 in Q1 than Q4 after adjustment for risk factors and comorbidities (odds ratio, 0.31; 95% confidence interval, 0.11–0.84) but not after additional adjustment for hematoma volume and National Institutes of Health Stroke Scale score. There were more patients with modified Rankin Scale scores 5 to 6 (P=0.016) and with fatal outcomes (P=0.048) in Q1 than Q4 as crude values, but not after adjustment. Conclusions— Low admission serum calcium levels were associated with larger hematoma volume and higher National Institutes of Health Stroke Scale score among patients with acute intracerebral hemorrhage.

Spontaneous heparin-induced thrombocytopenia syndrome without any proximate heparin exposure, infection, or inflammatory condition: Atypical clinical features with heparin-dependent platelet activating antibodies

Abstract Recent studies suggest that a thromboembolic disorder resembling heparin-induced thrombocytopenia (HIT), so-called spontaneous HIT syndrome, can occur in patients without any history of heparin exposure. It is likely due to anti-platelet factor 4 (PF4)/polyanion antibodies induced by other polyanions, such as bacterial surfaces and nucleic acids. We describe an atypical case of spontaneous HIT syndrome. A 70-year-old man suddenly presented with acute cerebral sinus thrombosis (CST). Soon after the initiation of unfractionated heparin (UFH) for the treatment of CST, his platelet count fell precipitously and he developed deep vein thrombosis, a clinical picture consistent with rapid-onset HIT but without any proximate episodes of heparin exposure, infection, trauma, surgery, or other acute illness. Antigen assays and a washed platelet activation assay indicated that the patient already possessed anti-PF4/heparin IgG antibodies with heparin-dependent platelet activation properties on admission. Cessation of UFH and initiation of argatroban resulted in prompt recovery of his platelet count without further thromboembolic events. We identified two similar cases in the literature. However, these patients do not meet the recently proposed criteria for spontaneous HIT syndrome. Even in atypical cases, however, inappropriate or delayed diagnosis of HIT appears to be associated with worse outcomes. We propose that these atypical cases should be included in the category of spontaneous HIT syndrome.

Location of acute brain hemorrhage in patients undergoing antithrombotic therapy

INTRODUCTION The relationship between antithrombotic therapy and the anatomical location of acute brain hematoma remains disputed. The current study was therefore designed to address this issue. METHODS The medical records and CT images were retrospectively reviewed in 484 consecutive patients with an acute brain hemorrhage (291 men, 193 women; mean age, 67.2+/-12.3 years) who were admitted to the hospital within 7 days of stroke onset from January 1999 through October 2003. Antithrombotic therapy had been performed in 116 patients (AT Group): warfarin (n=38), antiplatelet therapy (n=70), or both (n=8). The other 368 patients had not received antithrombotic therapy (non-AT Group). The hematoma location was compared among the groups. RESULTS The location of the hematoma was significantly different between the two groups (p<0.0001). The following locations were seen more frequently in the AT Group than in the non-AT Group: thalamic hemorrhage (44.8% vs. 30.7%), cerebellar hemorrhage (7.8% vs. 2.7%), and lobar hemorrhage (18.1% vs. 11.4%). The clinical characteristics in patients with thalamic, cerebellar, or lobar hemorrhage were compared with those with putaminal hemorrhage. A multivariate analysis using the logistic regression model showed that antithrombotic therapy was an independent factor for cerebellar hemorrhage (OR 3.66, 95%CI 1.31-10.18), lobar hemorrhage (OR 2.27, 95%CI 1.12-4.57), and thalamic hemorrhage (OR 2.20, 95%CI 1.06-4.54) in comparison to putaminal hemorrhage. CONCLUSIONS It therefore appears that antithrombotic therapy is independently associated with thalamic, cerebellar, and lobar hemorrhage.

Effective Education Materials to Advance Stroke Awareness Without Teacher Participation in Junior High School Students.

BACKGROUND Youth stroke education is promising for the spread of stroke awareness. The aim of this study was to examine whether our stroke awareness teaching materials without teachers participation can increase student awareness to act fast on suspected stroke signs. METHODS We used the face, arm, speech, and time (FAST) mnemonic derived from the Cincinnati Prehospital Stroke Scale. Seventy-three students of the second grade and 72 students of the third grade (age range, 13-15 years) in a junior high school were enrolled in the study. The students were divided into 2 groups: students who received a teachers lesson (group I) and those who did not receive a teachers lesson (group II). Students in group II watched an animated cartoon and read a Manga comic in class. All students took the educational aids home, including the Manga comic and magnetic posters printed with the FAST message. Questionnaires on stroke knowledge were examined at baseline and immediately and 3 months after receiving the intervention. RESULTS At 3 months after the intervention, a significant improvement in understanding the FAST message was confirmed in both the groups (group I, 85%; group II, 94%). Significant increases in the knowledge of risk factors were not observed in each group. CONCLUSIONS Our education materials include a Manga comic, an animated cartoon, and a magnetic poster, without an accompanying teachers lesson can increase stroke awareness, including the FAST message, in junior high school students.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy without Anterior Temporal Pole Involvement: A Case Report

The location of white matter lesions, especially in the anterior temporal poles (ATP), is helpful in the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We report a 49-year-old man with CADASIL who developed migraine with atypical aura, silent lacunar infarcts, and leukoencephalopathy without involvement of the ATP. The prevalence of migraine with aura in subjects with CADASIL is several times greater than that in the general population. Particularly in patients with CADASIL, the aura is often atypical (hemiplegic, basilar, or prolonged). A diagnosis of CADASIL should be considered in patients with lacunar infarcts, leukoencephalopathy, and migraine with atypical aura, even in the absence of white matter lesion in the ATPs.

Pituitary apoplexy during treatment with dabigatran

Pituitary apoplexy is known as an uncommon complication of pituitary adenoma, and anticoagulant therapy has been reported as one of the precipitating factors. We report an 85‐year‐old man who developed pituitary apoplexy during treatment with dabigatran. His medical history included a non‐functioning pituitary adenoma and non‐valvular atrial fibrillation. Headache occurred 4 days after changing the anticoagulant from warfarin to dabigatran; and other neurological symptoms, such as ptosis and ophthalmoplegia, subsequently developed. On admission, laboratory examination showed a prolonged activated partial thromboplastin time and moderately decreased kidney dysfunction. Emergency magnetic resonance imaging (MRI) showed pituitary hemorrhage in the tumor. Although dabigatran was reported to cause intracranial hemorrhage less commonly than warfarin, it could cause uncommon bleeding like in the present case.

Effects of Pretreatment Cerebral Blood Volume and Time to Recanalization on Clinical Outcomes in Endovascular Thrombectomy for Acute Ischemic Stroke

BACKGROUND Faster time to recanalization leads to better clinical outcomes in patients treated with endovascular thrombectomy. Whether the association between time to recanalization and clinical outcomes depends on cerebral blood volume (CBV) obtained from pretreatment computed tomography (CT) perfusion (CTP) imaging was investigated. METHODS In consecutive patients with acute ischemic stroke who achieved recanalization by endovascular thrombectomy for intracranial internal carotid artery or M1 occlusion, the effects on clinical outcome of time to recanalization and the relative CBV value (rCBV) assessed by pretreatment CTP were evaluated. The patient population was divided into 2 groups according to rCBV: normal rCBV group (rCBV ≥ .9) and low rCBV group (rCBV < .9). In each group, time to recanalization was compared between the good and the poor clinical outcome groups. RESULTS Sixty-four patients were eligible for this study. Twenty-six patients (40.6%) achieved good clinical outcomes. In the normal rCBV group, no association was found between clinical outcome and time to recanalization. In the low rCBV group, time to recanalization from CTP (101 minutes versus 136 minutes, P = .040) was significantly shorter in the good clinical outcome group. On binary logistic regression modeling, CTP to recanalization time (odds ratio 1.035 [1.004-1.067], P = .025) was an independent predictor of good clinical outcome only in the low rCBV group. CONCLUSIONS The association between time to recanalization and clinical outcomes depends on rCBV obtained from pretreatment CTP. Time to recanalization is more important for good clinical outcomes in patients with low rCBV than in patients with normal rCBV.