Safety of tooth extraction in patients receiving direct oral anticoagulant treatment versus warfarin: a prospective observation study.

The aim of this study was to compare the safety of tooth extraction in patients receiving direct oral anticoagulants (DOACs) or warfarin without cessation of their antithrombotic treatment. This prospective observational study included 367 patients undergoing tooth extraction (119 receiving DOACs and 248 receiving warfarin). All extractions in DOAC patients were performed 6-7h after taking DOACs in consideration of the half-life in blood under continued antithrombotic treatment. To examine the potential postoperative bleeding risk related to the time of extraction and the drug concentration of blood, activated partial thromboplastin time (APTT) in dabigatran and prothrombin time (PT) in rivaroxaban were measured three times after administration. A total of 390 tooth extractions were performed: 128 in the DOAC patients and 262 in warfarin patients. Postoperative bleeding occurred in four extractions (3.1%) in the DOAC group and in 23 (8.8%) in the warfarin group. There was no statistically significant difference between the two groups (odds ratio: 2.362, 95% confidence interval (CI) 0.819-6.815, p=0.112). APTT and PT prolongation in almost all cases decreased with time after taking the medicine. Our findings suggest that interruption of DOAC therapy is not necessary for tooth extraction if the procedure is performed at least 6h after the last dose.

Selective occipital artery sonography for dural arteriovenous fistulas. A case report.

Carotid duplex sonography is a useful method for evaluation of dural arteriovenous fistulas. The resistance index of the external carotid artery has been reported to correlate with the efficacy of treatment and recurrence or aggravation of dural arteriovenous fistulas. Herein, we describe a case of dural arteriovenous fistulas mainly supplied by the occipital artery and show that the resistance index of the occipital artery was more sensitive than that of the external carotid artery. To the best of our knowledge, this is the first report to describe the feasibility of occipital artery detection by carotid duplex sonography and clinical application of the resistance index of the occipital artery for dural arteriovenous fistulas.

Postoperative evaluation of changes in extracranial-intracranial bypass graft using superficial temporal artery duplex ultrasonography.

BACKGROUND AND PURPOSE: Extracranial-intracranial (ECIC) bypass grafts have been assessed postoperatively by various neuroradiologic techniques. The aim of this prospective study was to evaluate postoperative changes in ECIC bypass graft by using superficial temporal artery duplex ultrasonography (STDU). Furthermore, this study assessed the ability of STDU to predict cerebrovascular reserve capacity (CVR). MATERIALS AND METHODS: Forty-five consecutive patients who underwent ECIC bypass procedure for atherosclerotic internal carotid artery occlusion were enrolled in this prospective study. All patients underwent single-photon emission CT and STDU preoperatively, 14 days after, 3 months after, 1 year after, and 2 years after ECIC bypass. RESULTS: The diameter and flow velocities of the ipsilateral superficial temporal artery (STA), and regional cerebral blood flow (rCBF) showed increase during the first 2 weeks and then remained stable, whereas CVR showed a constant improvement up to 2 years after surgery. The STA diameter and mean STA flow velocity correlated significantly with CVR at 1 year after surgery (r2 = 0.1232 and r2 = 0.08716, respectively; P < .05). A cutoff value of 1.8 mm STA diameter was determined as the most reliable value to predict CVR greater than 10% at 1 year after surgery. The positive predictive value was calculated as 96.6%, the negative predictive value as 43.8%, the sensitivity as 75.7%, the specificity as 87.5%, and the likelihood ratio as 6.056. CONCLUSIONS: ECIC bypass grafts can be assessed postoperatively in a noninvasive fashion with STDU. This technique provides information regarding patency as well as quantitative assessment of bypass function. Moreover, STDU is useful to predict CVR improvement.

Eccentric stenosis of the carotid artery associated with ipsilateral cerebrovascular events.

BACKGROUND AND PURPOSE: Eccentric stenosis of the coronary artery is associated with plaque disruption and acute coronary syndrome. The purpose of the present study was to determine whether eccentric stenosis of the carotid artery contributes to cerebrovascular events. MATERIALS AND METHODS: Of 6859 patients with vascular diseases who underwent duplex carotid ultrasonography, we studied 512 internal carotid arteries in 441 patients who had a maximum area stenosis at or more than 70%, which corresponds with approximately 50% or more by the NASCET method. The maximal (A) and minimal wall thicknesses (B) were measured on cross-sectional sonography images, and an eccentricity index was calculated using the following formula: (A - B)/A. Arteries in the lowest quartile of the eccentricity index (<0.69) were defined as having a concentric stenosis, whereas the others were defined as having eccentric stenosis. The underlying clinical characteristics and plaque morphologies, as well as the occurrence of ipsilateral ischemic stroke or transient ischemic attack in the preceding year, were compared between patients with eccentric and concentric stenosis. RESULTS: Patient characteristics and plaque morphology were similar between the 2 groups. Cerebrovascular events occurred more frequently ipsilaterally to the artery with eccentric stenosis (13.5%) than to the artery with concentric stenosis (5.5%; P = .013); the difference was more evident when cerebrovascular events of presumed carotid arterial origin were assessed (P = .005). After adjusting for risk factors and plaque morphology, eccentric stenosis was independently related to the presence of recent cerebrovascular events (odds ratio = 2.76; 95% confidence interval = 1.19-6.40). CONCLUSIONS: In patients with an area carotid stenosis of 70% or more, eccentric plaque was associated with a significantly increased incidence of ipsilateral cerebrovascular events compared with patients with concentric stenosis.

Population-based distribution of plasminogen activity and estimated prevalence and relevance to thrombotic diseases of plasminogen deficiency in the Japanese: the Suita Study.

Reduced plasminogen activity with a normal level of antigen is commonly observed in Japanese individuals. The first reported patient with plasminogen deficiency was accompanied with deep vein thrombosis. The present study examines whether heterozygous or homozygous deficiency of plasminogen is a risk factor for thrombotic disease. This study measures the plasminogen activity of 4517 individuals in the general population, determines the cut-off to define plasminogen deficiency, and identifies plasminogen deficiencies in the control groups and thrombotic disease groups. In another study, we examined the phenotypes of consecutive patients with homozygous plasminogen deficiency detected in our hospital. We found 173 and two of 4517 individuals to have heterozygous and homozygous deficiency with normal plasminogen antigen level, respectively, and 19 to have heterozygous deficiency with reduced antigen levels. The incidence of plasminogen deficiency in an age- and sex-matched control group (13/324, 4.01% for deep vein thrombosis or 13/330, 3.94% for stroke) selected from the 4517 individuals was not significantly different from those in patients with deep vein thrombosis (3/108, 2.78%) or cardioembolic stroke (6/110, 5.55%). Among 19 patients with homozygous plasminogen deficiency showing about 10% plasminogen activity, none had deep vein thrombosis. These findings indicate that neither heterozygous nor homozygous plasminogen deficiency constitutes a significant risk factor for thrombotic disease.

Effect of prothrombin complex concentrate on INR and blood coagulation system in emergency patients treated with warfarin overdose.

We investigated the effect of prothrombin complex concentrate (PCC) on the international normalized ratio (INR) and blood coagulation system in two emergent patients treated with warfarin for secondary prevention of cardioembolic stroke due to nonvalvular atrial fibrillation. An 80-year-old woman developed massive subcutaneous hemorrhage and swelling on her right upper extremity with weak pulsation of the right radial artery and had an INR above 10. An 83-year-old man had pleural effusion with an INR value of 6.69 and pleural puncture was immediately required. We administered 500 IU of PCC to the two patients (17.2 IU/kg and 12.5 IU/kg) with 10 mg of vitamin K. The INR decreased to 1.12 and 1.85, respectively, with an increase of plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa 10 min after administration. The plasma levels of the thrombin-antithrombin III complex increased (from 4.0 to 12.0 micro g/l and from 0.5 to 28.9 micro g/l, respectively, normal value <3.0), but prothrombin fragment 1+2 increased minimally 10 min after administration (from 0.4 to 1.1 nmol/ml and from 0.4 to 0.7 nmol/ml, respectively, normal value 0.4-1.4 nmol/ml). Plasma levels of D-dimer remained unchanged. The massive subcutaneous hemorrhage in the former patient improved in 14 days. Anticoagulation was restarted in the latter patient after 14 days of PCC administration. There were no embolic episodes during the month after PCC administration. In conclusion, a small amount of PCC may be effective in immediately correcting increased INR levels with increased plasma levels of protein C and coagulant factors IIa, VIIa, IXa, and Xa and may partially activate the coagulation system without any effects on plasma levels of D-dimer.

Blood flow in the left atrial appendage and embolic stroke in nonvalvular atrial fibrillation.

It is unclear if low flow velocity in the left atrial appendage (LAA) is a predisposing factor to stroke in patients with nonvalvular atrial fibrillation (NVAF). We investigated flow velocity in the LAA in NVAF patients in relation to a past history of stroke and other potential embolic sources. We measured and analyzed peak flow velocities into (FV-in) and out of (FV-out) the LAA in a middle portion of the LAA in 35 NVAF patients by transesophageal echocardiography (TEE). We divided the NVAF patients into 3 groups: the Eaf group had a history of embolic stroke without any other potential embolic sources; the Emulti group had other potential embolic sources, and the control group had no embolic history. FV-in and FV-out in the Eaf group (12.3 +/- 6.7 and 10.2 +/- 7.3 cm/s) were significantly lower than those in the control group (24.3 +/- 11.3 and 19.9 +/- 8.8 cm/s; multicomparison Scheffé's test, p = 0.0123 and 0.0395, respectively). The Emulti group varied in those values from less than 5 to above 35. Low flow velocity in the LAA seems to be a predisposing factor for stroke in NVAF patients without any other sources of emboli.

Hypertension and neurovascular compression of the left lateral medulla oblongata in ischemic stroke.

Hypertension is a major risk factor for stroke. Neurovascular compression (NC) of the left ventrolateral medulla oblongata may cause arterial hypertension. We evaluated the relationship between the two ischemic stroke patients. We classified 69 patients under 50 years old (49 men and 20 women, aged 43.6 +/- 7.3 years) based on magnetic resonance imaging findings as follows: NC patients (n = 38; 10 with NC on the right side, 18 with NC on the left side, and 10 with NC on both sides) and non-NC patients (n = 31). We compared the following clinical characteristics between the two groups: (1) risk factors for stroke, including hypertension, diabetes mellitus, hypercholesterolemia, and smoking and (2) stroke subtype. Hypertension was more frequent in the NC group than in the non-NC group (58 vs. 19%, p = 0.001). Hypertension was more frequent in patients with left-side NC than in those with right-side NC (78 vs. 20%, p = 0.005). No other differences were observed between the two groups. Twelve patients presented with atherothrombotic stroke, 16 with cardioembolic stroke, 24 with lacunar stroke and 17 with stroke of miscellaneous etiology. NC was significantly more common in patients with lacunar stroke as compared with those affected by other stroke subtypes (p = 0.015). We found a significant relationship between hypertension and NC of the ventrolateral medulla oblongata on the left side in ischemic stroke patients younger than 50 years of age. Some patients with lacunar stroke may have hyptertension related to NC.

Secondary prevention of stroke in patients with nonvalvular atrial fibrillation: optimal intensity of anticoagulation.

Nonvalvular atrial fibrillation (NVAF) is frequently seen in elderly people and has become a main cause of cardioembolic stroke. The efficacy of anticoagulation for primary prevention of stroke or transient ischaemic attacks (TIAs) in patients with NVAF has been established by prospective, randomised and controlled trials. Warfarin decreased the frequency of all strokes by 68% and the rate of the combined outcome of stroke, systemic embolism or death by 48%. Anticoagulation with warfarin using international normalised ratios (INRs) ranging from 2.0 to 3.0 is recommended for patients with NVAF, who have any of the risk factors identified by the Atrial Fibrillation Investigators (AFI) [previous stroke or TIA, history of hypertension, diabetes mellitus, advanced age (> or = 65 years old), congestive heart failure and coronary artery disease], the American College of Chest Physicians (ACCP) [increased age (> 75 years old), prior stroke, hypertension and heart failure], or the Stroke Prevention in Atrial Fibrillation (SPAF) investigators [women > 75 years old, prior stroke, systolic blood pressure > 160mm Hg, recent heart failure, and fractional shortening < 25% on echocardiography]. For the secondary prevention of stroke, the efficacy of adjusted-dose warfarin therapy has been demonstrated by 2 major randomised trials. SPAF III (INR 2.0 to 3.0) demonstrated a lower incidence of ischaemic stroke or systemic embolism (3.4 %/year) compared with low fixed-dose warfarin plus aspirin (acetylsalicylic acid) [11.9%]. The European Atrial Fibrillation Trial [EAFT] (INR 2.5 to 4.0) showed a lower incidence of all stroke (4.0 %/year) with adjusted-dose warfarin compared with placebo (12.0 %/year). The incidence of major bleeding in the adjusted-dose warfarin group in SPAF III and EAFT was 2.4 and 2.8 %/year, respectively. EAFT incidence rates for the occurrence of a first ischaemic or haemorrhagic complication analysed by INR range indicated that the rate was lowest at INRs of 2.0 to 2.9, and higher with INRs of 3.0 to 3.9. Therefore, the optimal intensity of anticoagulation for prevention of recurrent stroke seems to be an INR of between 2.0 and 3.0, as for primary prevention. Retrospective and prospective studies from Japan reported that in the elderly, haemorrhagic complications occur frequently with INRs above 2.6 and major ischaemic events cannot be prevented at INRs below 1.6. Therefore, an INR target between 1.6 and 2.6 may be an alternative for secondary prevention of stroke in elderly patients with NVAF who have a potential risk of bleeding, to avoid both major ischaemic and haemorrhagic events. Antiplatelets may be administered in patients who are unable to manage taking warfarin properly or who have a high risk of falling and subsequently sustaining a head injury, although the efficacy of antiplatelets for secondary prevention of stroke in NVAF has not yet been established.

Massive pontine hemorrhagic infarction associated with embolic basilar artery occlusion.

We report here an autopsy case of massive pontine hemorrhagic infarction secondary to embolic basilar artery occlusion. A large embolus appeared to have traversed the vertebral artery into the basilar artery as a result of basilarization of the vertebral artery due to severe stenosis of the contralateral vertebral artery. Extensive ischemia due to embolic occlusion of the entire length of the basilar artery, and migration of the embolus are assumed to have resulted in a massive pontine hemorrhagic infarction.

Microembolic signals and diffusion-weighted MR imaging abnormalities in acute ischemic stroke.

BACKGROUND AND PURPOSE: The clinical significance of microembolic signals (MESs) detected by transcranial Doppler sonography (TCD) in acute ischemic stroke remains unclear. The purpose of the present study was to assess the findings of diffusion-weighted MR imaging (DWI) and other clinical characteristics in patients with acute ischemic stroke and MESs. METHODS: We performed TCD and DWI within 48 hours and 7 days, respectively, after stroke onset in 28 patients with acute brain infarction. The relationship between the number of MESs and DWI findings, risk factors for stroke, National Institutes of Health Stroke Scale (NIHSS) score on admission, and arterial disease was examined. RESULTS: Ten patients had MESs detected by TCD (MES group) and 18 had no MESs (control group). The frequency of hypertension, diabetes mellitus, hyperlipidemia, and smoking; NIHSS score; blood-coagulation parameters; and interval between stroke onset and DWI study did not differ between the two groups. However, arterial disease was more frequent in the MES group than in the control group. Small, multifocal ischemic lesions (<10 mm in diameter) on DWI were more frequent in the MES group than in the control group. Conventional CT and MR imaging often failed to show these lesions. CONCLUSION: Small, often asymptomatic DWI abnormalities were more frequent in patients with MESs detected by TCD and with large-vessel occlusive diseases than in stroke patients without MESs. TCD and DWI may provide early clues to the mechanism of stroke in the acute phase.

Prediction of the final infarct volume within 6 h of stroke using single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime.

BACKGROUND: A simple method to predict the final infarct volume within 6 h of onset of hemispheric ischemic stroke based on the measurement of cerebral blood flow (CBF) using single photon emission computed tomography (SPECT) with techneticum-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) was investigated in a clinical model involving patients without definite early reperfusion or clinical recovery. METHODS: A group of 16 patients (group 1) was used to establish the methodology, which was then validated in a second group of 14 patients (group 2). The final infarct volume was defined using computed tomography (CT) performed at least 7 days after stroke. The relative CBF threshold value, expressed as a percentage of the mean contralateral hemispheric value, which most closely estimated the final infarct size on coregistered CT was established for each patient. RESULTS: The mean threshold CBF value for group 1 was 63.7%. When this value was used to predict infarct size in group 2, a close correlation was observed between the actual and the estimated sizes (r = 0.973, p < 0.0001). This value was not time dependent. CONCLUSIONS: If no significant early reperfusion or clinical recovery occurs, a CBF threshold value of 63.7% on (99m)Tc-HMPAO SPECT performed within 6 h of stroke onset will reliably predict the final infarct size.

Successive intramolecular transiminations in an iron (II) complex with chiral tridentate ligands.

Two molecules of S-2-pyridylmethylidene-1-(2-pyridyl)ethylamine coordinated to an iron(II) undergo successive transiminations yielding bis[1-(2-pyridyl)ethylidene-2-pyridylmethylamine]iron(II) in acetonitrile.

Optimal intensity of international normalized ratio in warfarin therapy for secondary prevention of stroke in patients with non-valvular atrial fibrillation.

OBJECTIVE: To determine optimal intensity of international normalized ratio (INR) of warfarin therapy for the prevention of ischemic events in patients with non-valvular atrial fibrillation (NVAF), we evaluated the risk of severe recurrent stroke, systemic embolism and major hemorrhagic complications according to INR and age. METHODS: We carried out the National Cardiovascular Center (NCVC) NVAF Secondary Prevention Study and analyzed data with those of Japanese Nonvaluvular Atrial Fibrillation-embolism Secondary Prevention Cooperative Study to elucidate relationships of major stroke and hemorrhage with INR and age. In both studies, all patients with cardioembolic stroke were given warfarin, monitored with INR every month, and followed up for primary endpoints of stroke and embolism to other parts of the body, and for secondary endpoints of major hemorrhagic complications requiring blood transfusion or hospitalization. We regarded ischemic stroke with NIH stroke scale (NIHSS) score > or = 10 or systemic embolism as a major ischemic event and ischemic stroke with NIHSS score <10 as a minor ischemic event. There were 203 patients enrolled in total (152 men and 51 women). We investigated the relationship of occurrence of the events with INR and age, and calculated the incidence rates of major and minor ischemic events and major hemorrhagic events. RESULTS: During the mean follow-up of 653 days, major ischemic stroke and systemic embolism occurred in only 4 patients with INR <1.6, minor ischemic stroke in 10 patients with INR 1.50-2.66, and major hemorrhage in 9 patients with INR 2.30-3.56. Patients with major ischemic or hemorrhagic events were significantly older than those without any events (75+/-4 years vs. 67+/-7 years, p<0.001 unpaired t test). Incidence rates of any events at INR < or = 1.59, 1.60-1.99, 2.00-2.59 and > or = 2.60 were 8.6%, 3.8%, 4.9%, and 25.7%/year, respectively. CONCLUSIONS: Major ischemic or hemorrhagic events occur often in the elderly NVAF patients, in whom an INR value of between 1.6 and 2.6 seems optimal to prevent such events.

Transoral carotid ultrasonographic findings in internal carotid artery dissection--a case report.

Transoral carotid ultrasonography (TOCU) is a new method to evaluate the far distal segment of the extracranial internal carotid artery (ICA) and may be superior to conventional carotid ultrasonography in evaluating ICA dissection. The authors report on the use of TOCU in detecting early stage ICA dissection.

Evaluation of posterior cerebral artery flow velocity by transcranial color-coded real-time sonography.

Using transcranial color-coded real-time sonography (TCCS), we measured peak-systolic flow velocities (PSVs) in segment P2 of 102 posterior cerebral arteries (PCAs) in 61 patients, with angiography. We divided 102 PCAs into four groups: control group (n = 70) with no significant stenotic lesions; PCS group (n = 7) with stenosis >/= 50% of P2 segment; Col (+) group (n = 13) and Col (-) group (n = 12) had occlusive lesions in the carotid system with or without collateral flow from PCA to the middle cerebral artery through the leptomeningeal anastomosis. In the PCS group, PSV (255.7 +/- 67.2 cm/s) was higher than in the other three groups (p < 0.0001). PSV was higher in the Col (+) group (127.6 +/- 31.2) than in the Col (-) (86.6 +/- 20.1) and control (83.8 +/- 24.8) groups (p < 0.001). The measurement of PSV in the P2 segment of PCA using TCCS may help to identify a significant stenosis in PCA.

Lesions visualized by contrast-enhanced magnetic resonance imaging in transient ischemic attacks.

In patients with transient ischemic attacks (TIAs), contrast-enhanced magnetic resonance imaging (MRI) is more sensitive to visualize the recent ischemic lesions than conventional MRI. We examined the clinical characteristics of TIA patients presenting with enhanced lesions visualized by contrast-enhanced MRI. We retrospectively evaluated 64 patients with carotid TIAs. We evaluated the frequency and topography of TIA associated infarcts on contrast-enhanced MRI and compared the clinical background of patients with and without such lesions. Twenty-three patients underwent plain MRI only, while the remaining 41 patients underwent contrast-enhanced MRI. Of the latter 41 patients, 16 had abnormal enhanced lesions (39%: group L), while 25 had no lesions (61%: group NL). In group L, all lesions were spotty, and they were located in the cerebral cortex in 13 patients (81%), the subcortex in two (12%), and the perforator territory in one (6%). Aphasia or confusional state, hypertension, and emboligenic cardiac or arterial disease (stenosis > or =50%) were more frequently observed in group L than in group NL (38 vs. 8%, 81 vs. 48%, and 93 vs. 60%, respectively, P<0. 05). The TIA patients with enhanced lesions on MRI may be associated with an emboligenic cardiac or arterial disease, severe neurologic symptom compared to those without them.

Transcranial Doppler of a paradoxical brain embolism associated with a pulmonary arteriovenous fistula.

We herein report the case of a patient who had paradoxical brain embolism owing to a pulmonary arteriovenous fistula (PAVF) who was diagnosed as having a right-to-left shunt by transcranial Doppler (TCD) with saline contrast medium. TCD with saline contrast medium failed to detect any high-intensity transient signals immediately after catheter embolization of the PAVF. Thus, TCD with saline contrast medium was useful for identifying the presence of a right-to-left shunt and for confirming that the shunt had been obliterated after endovascular treatment.

[Homolateral ataxia and crural paresis following anterior cerebral artery territory infarction].

Homolateral ataxia and crural paresis (HACP) is defined as predominantly crural paresis with ipsilateral ataxia, a variant of ataxic hemiparesis (AH), by Fisher and his colleagues. HACP usually resulted from lacunar infarction in the basis pontis at the junction of the upper one-third and inferior two-third of the pons, or in the posterior limb of the internal capsule. We reported a patient with HACP which was caused by an infarct in the paracentral gyrus irrigated by the anterior cerebral artery (ACA). He had had no cerebellar signs before the onset of HACP, although he had old small infarcts in the right pons, right thalamus and left cerebellar hemisphere. Neuroimaging and other clinical studies suggested that the mechanism of the present infarction was the most-likely embolic, but not lacunar. As far as we know, there has been only one abstract presentation of a patient with HACP due to ACA territory infarction in Japan, although five such cases were recently reported by Bogousslavsky and others.

[A case with frequent episodes of transient ischemic attack presenting the Wallenberg syndrome before and after the onset of brain infarction].

A 52-year-old man with diabetes mellitus, hyperlipidemia and smoking habit, experienced transient ischemic attacks (TIAs) with symptoms of left orbital pain, left blepharoptosis and hoarseness lasting for five minutes on March 10, 1997. Subsequently, the same symptoms repeated once or twice daily. On March 28, he had dysphagia, numbness and disturbance of pain and temperature sensation (segmental dissociated sensory disturbance) on the right side of the body above the level of the Th10, the right upper limb and face. The deficits persisted for more than 24 hours. Angiographic studies revealed an occlusion of the left vertebral artery immediately after branching of the posterior inferior cerebellar artery. MRI demonstrated a hyperintense lesion on MRI T2 weighted image in the left lateral medulla. About three months after the completed stroke, he had six episodes of TIAs of left Horner's sign and hoarseness. To our knowledge, this is the rare case that had frequent TIAs presenting the Wallenberg syndrome before and after the onset of lateral medullary infarction. We speculate that the TIAs resulted from microembolism from the proximal end of occluted left vertebral artery and failure of the microcirculation in and around the lateral portion of the medulla oblongata.