Yoshiharu Taguchi

Chronic Kidney Disease and CHADS2 Score Independently Predict Cardiovascular Events and Mortality in Patients With Nonvalvular Atrial Fibrillation

Chronic kidney disease is a risk factor for cardiovascular events, but how it relates to the prognosis associated with clinical risk factors for thromboembolism in patients with nonvalvular atrial fibrillation (AF) is not well known. Estimated glomerular filtration rate (eGFR), score for congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke/transient ischemic attack (CHADS(2)), and clinical outcomes of cardiovascular events were determined in 387 patients with nonvalvular AF (mean age 66 years, 289 men, mean follow-up 5.6 ± 3.2 years). Decreased eGFR (<60 ml/min/1.73 m(2)) combined with CHADS(2) score ≥2 was associated with higher all-cause (12.9% vs 1.4% per year, hazard ratio [HR] 6.9, p <0.001) and cardiovascular (6.5% vs 0.2% per year, HR 29.7, p <0.001) mortalities compared to preserved eGFR (≥60 ml/min/1.73 m(2)) combined with CHADS(2) score <2. This was also true for rates of cardiac events (cardiac death, nonfatal myocardial infarction, or hospitalization for worsening of heart failure, 10.4% vs 1.3% per year, HR 8.9, p <0.001), ischemic stroke (3.6% vs 0.2% per year, HR 11.0, p <0.001), and cardiovascular events (cardiac events and ischemic stroke, 13.6% vs 1.5% per year, HR 8.3, p <0.001). On multivariate analysis, CHADS(2) score ≥2, decreased eGFR, and male gender independently predicted all-cause mortality. In conclusion, combined eGFR and CHADS(2) score could be an independent powerful predictor of cardiovascular events and mortality in patients with nonvalvular AF. Long-term mortality, cardiac events, and stroke risk were >8 times higher when decreased eGFR (<60 ml/min/1.73 m(2)) was present with higher CHADS(2) score (≥2).

Evaluation of SLC20A2 mutations that cause idiopathic basal ganglia calcification in Japan

Objective: To investigate the clinical, genetic, and neuroradiologic presentations of idiopathic basal ganglia calcification (IBGC) in a nationwide study in Japan. Methods: We documented clinical and neuroimaging data of a total of 69 subjects including 23 subjects from 10 families and 46 subjects in sporadic cases of IBGC in Japan. Mutational analysis of SLC20A2 was performed. Results: Six new mutations in SLC20A2 were found in patients with IBGC: 4 missense mutations, 1 nonsense mutation, and 1 frameshift mutation. Four of them were familial cases and 2 were sporadic cases in our survey. The frequency of families with mutations in SLC20A2 in Japan was 50%, which was as high as in a previous report on other regions. The clinical features varied widely among the patients with SLC20A2 mutations. However, 2 distinct families have the same mutation of S637R in SLC20A2 and they have similar characteristics in the clinical course, symptoms, neurologic findings, and neuroimaging. In our study, all the patients with SLC20A2 mutations showed calcification. In familial cases, there were symptomatic and asymptomatic patients in the same family. Conclusion: SLC20A2 mutations are a major cause of familial IBGC in Japan. The members in the families with the same mutation had similar patterns of calcification in the brain and the affected members showed similar clinical manifestations.

Creutzfeldt-Jakob disease with florid plaques after cadaveric dural graft in a Japanese woman

The Japanese National Committee for Creutzfeldt-Jakob disease (CJD) reported there are 43 patients with CJD in Japan after implantation of cadaveric dura mater, and that no case of new-variant CJD (nvCJD) has been detected. We report a case with similar features to nvCJD. At the age of 38 years, a Japanese woman received a cadaveric dural graft (Lyodura, B Braun Melsungen AG, Germany) after a clipping procedure of the right middle cerebral artery aneurysm in September, 1985. In November, 1994, 110 months after the procedure, she became unsteady and had blurred vision. She was admitted to hospital because of progressing ataxia. Examination disclosed dementia, visual disturbance, hyperreflexia, and cerebellar ataxia. Blood chemistry and cerebrospinal fluid were normal. Brain computed tomography (CT) showed no abnormal lesions. There was slow activities without periodic discharge on her electroencephalogram (EEG). gradually decreased and could not be detected after 40 months. In the second patient, the IgA antibody value remained low. None of the remaining eight patients developed detectable IgA antibodies. Thus far, a total of 1707 infusions have been given and only six (0·4%) mild systemic adverse reactions (headache, nausea, and/or light dizziness) have been noted. Our preliminary experience indicates that prophylactic IgG replacement therapy can safely be given to patients with selective IgA deficiency including those with IgA antibodies by subcutaneous administration. The treatment seems to be effective as the frequency of bacterial respiratory tract infections was reduced. One possible explanation why administration of IgG is effective in IgA deficiency could be that the patients are given additional specific antibodies that they themselves are unable to produce in sufficient amounts. According to the estimated prevalence, the number of IgA deficient individuals is 20 000 in Sweden, 120 000 in UK, and at least 250 000 in the USA. Given that 30% of these have an increased susceptibility to infections, further studies are needed to decide whether to broaden the indications for administration of subcutaneous IgG.

Study of Hemostatic Biomarkers in Acute Ischemic Stroke by Clinical Subtype

BACKGROUND We studied the usefulness of hemostatic biomarkers in assessing the pathology of thrombus formation, subtype diagnosis, prognosis in the acute phase of cerebral infarction, and differences between various hemostatic biomarkers. METHODS Our study included 69 patients with acute cerebral infarction who had been hospitalized within 2 days of stroke onset. Fibrin monomer complex (FMC), soluble fibrin (SF), D-dimer, thrombin-antithrombin III complex, fibrinogen, antithrombin III, and fibrin/fibrinogen degradation products (FDPs) were assayed as hemostatic biomarkers on days 1, 2, 3, and 7 of hospitalization. RESULTS In the cardioembolic (CE) stroke group, FMC and SF levels were significantly higher on days 1 and 2 of hospitalization, and D-dimer levels were significantly higher on day 1 of hospitalization, compared to the noncardioembolic (non-CE) stroke group. FDP levels were significantly higher at all times in the CE group compared to the non-CE group. Neither the National Institute of Health Stroke Scale (NIHSS) used during hospitalization nor the modified Rankin Scale (mRS) used at discharge found any significant correlations to hemostatic biomarkers, but the NIHSS score during hospitalization was significantly higher in the CE group than in the non-CE group. CONCLUSIONS Measurements of hemostatic biomarkers, such as FMC, SF, and D-dimer on the early stage of cerebral infarction are useful for distinguishing between CE and non-CE stroke.

Lipoprotein(a) is a risk factor for occurrence of acute myocardial infarction in patients with coronary vasospasm

OBJECTIVES The purpose of this study is to determine whether lipoprotein(a) (Lp[a]) is an independent risk factor for coronary spasm and occurrence of acute myocardial infarction (AMI) in patients with coronary spasm. BACKGROUND Although elevated serum Lp(a) levels are known to be associated with coronary atherosclerosis and AMI, the association between the elevated level of this lipoprotein and coronary spasm remains to be elucidated. METHODS Serum Lp(a) levels were measured using a latex immunoassay in 77 patients with coronary spasm but without a significant (>75%) fixed coronary stenosis, including 16 with prior myocardial infarction (MI), in 177 patients with a fixed stenosis but without rest angina, including 114 with prior MI and in 81 control subjects without coronary artery disease. RESULTS The serum Lp(a) level in patients with coronary spasm (median; 17 mg/dl) was higher (p < 0.01) than in control subjects (12 mg/dl) but lower (p < 0.01) than in patients with a fixed stenosis (23 mg/dl). The incidence of subjects with higher (>25 mg/dl) serum Lp(a) levels was higher in patients with a fixed stenosis (46%, p < 0.01) but not in patients with coronary spasm (27%), compared with control subjects (21%). Among the patients with coronary spasm, the incidence of higher Lp(a) levels was higher in patients with than in those without a history of prior MI (56% vs. 21%, p < 0.05). The patients with higher Lp(a) levels had a higher incidence of prior MI than those without (41% vs. 13%, p < 0.05). The multivariate analysis confirmed that higher serum Lp(a) level is an independent determinant for prior MI in these patients (odds ratio, 4.19; 95%, confidence interval, 1.03 to 17.00). CONCLUSIONS Elevated serum level of Lp(a) was found to be associated with a history of prior MI in patients with coronary spasm, suggesting that Lp(a) may play an important role in the genesis of thrombotic coronary occlusion and the occurrence of AMI subsequent to coronary spasm.

Bilateral Subthalamic Deep Brain Stimulation for Camptocormia Associated with Parkinson’s Disease

Background: Few multiple case studies of the effects of deep brain stimulation for camptocormia associated with Parkinson’s disease have been reported. Although deep brain stimulation was in some cases not effective against camptocormia, it is unclear in which types of patients it was effective in treating camptocormia. Objective: We treated 4 Parkinson’s disease patients with camptocormia and evaluated their paraspinal muscle status by computed tomography to specify the characteristics of cases of effective treatment. Methods: The 2 female and 2 male patients in this study were 60–69 years old, with a disease duration from onset to surgery of 7–13 years and a follow-up period of 18–40 months. The electrodes were implanted bilaterally in the subthalamic nuclei. Results: Camptocormia was improved in 3 cases, and was unchanged in the remaining case although other parkinsonian symptoms improved. The computed tomography number of paraspinal muscle in the unimproved patient was much smaller than that in the improved patients. Conclusions: A relationship may exist between improvement of camptocormia and severity of paraspinal muscle degeneration.

Detection of autoantibody against extracellular epitopes of N-methyl-D-aspartate receptor by cell-based assay.

The concept of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, a severe, potentially lethal, treatment-responsive disorder, mediated by autoantibodies against NMDAR was proposed. Because paraneoplastic anti-NMDAR encephalitis has a better prognosis after tumor resection and immunotherapy, rapid quantitative systems for detecting functional autoantibodies against extracellular epitopes of NMDAR are necessary. To detect autoantibodies recognizing extracellular epitopes of NMDAR, we stably expressed mutant NMDAR that decreases Ca(2+) permeability on a heterologous cell surface without any antagonist. Serum and CSF samples from patients were analysed using the cells expressing mutant NMDAR subunits by immunocytochemistry and on-cell Western analysis using live cells stably expressing mutant NMDAR. Furthermore, we were able to express mutant GluRζ1(NR1, GluN1) subunit of NMDAR alone on the cell surface and obtained direct evidence of the presence of autoantibodies recognizing extracellular epitopes of GluRζ1 and the induction of internalization by autoantibodies in serum and CSF from patients. The specificity of on-cell Western analysis was improved at 37°C. The combination of this rapid quantitative assay using our on-cell western analysis, detailed analysis of extracellular epitopes of NMDAR, and internalization assay of NMDAR will be valuable for the diagnosis, evaluation of clinical treatments, and follow-up of anti-NMDAR encephalitis.

Differential diagnosis of cerebral infarction using an algorithm combining atrial fibrillation and D-dimer level

We created an algorithm for diagnosing subtypes of cerebral infarction (CI) during the acute stage by combining atrial fibrillation (AF) and D‐dimer levels. One‐hundred and eight patients hospitalized for acute CI were retrospectively analyzed. CI was classified into cardioembolic, atherothrombotic, lacunar infarction or others. Patients were classified in AF group if they had AF on admission or a prior history of AF. This group was diagnosed to suffer cardioembolic infarction. In non‐AF group, cardioembolic infarction was diagnosed when D‐dimer level exceeded the cutoff point determined using a receiver operating curve. Then, usefulness of the algorithm was validated prospectively in 259 consecutive patients with acute CI. For the retrospective group, cardioembolic infarction was found in 82% of the AF group. In non‐AF group, cardioembolic infarction was found in only 2%, when D‐dimer level was <1.6 μg/ml. However, 41% of non‐AF group with atherothrombotic infarction had elevated D‐dimer level (≥1.6 μg/ml). Results for the validation group were similar to those for the retrospective group (sensitivity, 89%; specificity, 66%; positive predictive value, 50%; and negative predictive value, 94%). D‐dimer level in combination with AF can be useful for distinguishing CI subtypes during the acute stage.

Impact of persistent smoking on long-term outcomes in patients with nonvalvular atrial fibrillation

BACKGROUND Although smoking is a risk factor for cardiovascular diseases, little is known about the impact of smoking on long-term outcomes in patients with atrial fibrillation (AF). METHODS In 426 consecutive patients with nonvalvular AF (mean age, 66 years; 307 men; mean follow-up, 5.8±3.2 years), clinical variables including smoking status, CHADS2, and CHA2DS2-VASc score, incidences of cardiovascular events (stroke, myocardial infarction, or admission for heart failure), bleeding, and mortality were determined. RESULTS Incidences of intracranial bleeding (0.7% vs 0.1%/year, p<0.01), all-cause mortality (4.9% vs 2.6%/year, p<0.01), and death from stroke (0.8% vs 0.2%/year, p<0.05) were higher in patients with history of smoking than in those without it. Incidence of intracranial bleeding was significantly higher in persistent smokers than in non-persistent smokers (1.2% vs 0.2%/year, p<0.01). History of smoking predicted all-cause mortality [hazard ratio (HR), 2.7; 95% confidence interval (CI), 1.7-4.5; p<0.01] and death from stroke (HR 4.7; 95% CI 1.0-22.3; p<0.05) independent of age, antithrombotic treatment, CHADS2, and CHA2DS2-VASc score. Persistent smoking predicted intracranial bleeding (HR 4.4; 95% CI 1.1-17.6; p<0.05) independent of age and antithrombotic treatment. CONCLUSIONS Smoking status, independent of age, antithrombotic treatment, and clinical risk factors, predicted long-term adverse outcomes including bleeding events in patients with nonvalvular AF. There might be an obvious impact of persistent smoking on intracranial bleeding.

Predictors of Poor Outcome in Patients with Acute Cerebral Infarction

Background and Purpose Plasma D-dimer levels are elevated during the acute phase of cerebral infarction (CI). We investigated whether the D-dimer level on admission and other clinical characteristics could be used to predict the poor outcome of patients with acute CI. Methods The clinical characteristics and plasma D-dimer levels measured within 3 days of onset were compared according to outcome among patients with acute CI. Results In total, 359 consecutive patients (mean age, 71.8 years) were examined, of which 174 had a poor outcome [score on the modified Rankin scale (mRS) ≥3] at 30 days after hospitalization. The mean mRS score was higher and a poor outcome was observed more frequently among women than among men (p<0.001 for each). The proportions of women, cardioembolism, atrial fibrillation, advanced age (≥75 years), prior history of CI or transient ischemic attack, and elevated D-dimer level (≥1.0 µg/mL) were significantly higher among patients with a poor outcome than among those with a good outcome. A multivariate analysis showed that elevated D-dimer level [≥1.0 µg/mL; odds ratio (OR), 2.45; 95% confidence interval (95% CI), 1.52-3.89; p<0.01], advanced age (OR, 1.93; 95% CI, 1.21-3.07; p<0.01), and female gender (OR, 1.75; 95% CI, 1.08-2.83; p=0.02) were independent predictors of a poor outcome. Conclusions Certain clinical characteristics (gender and advanced age) and an elevated D-dimer level upon admission can be used to predict the outcome of patients with acute CI at 30 days after hospitalization.