Nobuhiro Dougu

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).

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.

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.

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.

Transesophageal echocardiographic findings are independent and relevant predictors of ischemic stroke in patients with nonvalvular atrial fibrillation.

Background and Purpose Not only clinical factors, including the CHADS2 score, but also echocardiographic findings have been reported to be useful for predicting the risk of ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF). However, it remains to be determined which of these factors might be more relevant for evaluation of the risk of stroke in each patient. Methods In 490 patients with NVAF who underwent transesophageal echocardiography (TEE), we examined the long-term incidence of ischemic stroke events (mean follow-up time, 5.7±3.3 years). For each patient, the predictive values of gender, the CHADS2 risk factors (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, history of cerebral ischemia), the CHADS2 score, and the findings on echocardiography, including TEE risk markers, were assessed. Results The ischemic stroke rate was significantly correlated with the CHADS2 score (p<0.05). According to the results of univariate analyses, age ≥75 years, history of cerebral ischemia, CHADS2 score ≥2, and presence of TEE risk were significantly correlated with the incidence of ischemic stroke. Cox proportional hazards regression analyses identified age ≥75 years and presence of TEE risk as significant predictors of subsequent ischemic stroke events in patients with NVAF. As compared with that in persons below 75 years of age without TEE risk, the ischemic stroke rate was significantly higher in persons who were ≥75 years of age with TEE risk (4.3 vs. 0.56%/year, adjusted hazard ratio=8.94, p<0.001). Conclusions TEE findings might be more relevant predictors of ischemic stroke than the CHADS2 score in patients with NVAF. The stroke risk was more than 8-fold higher in patients aged ≥75 years with TEE risk.

Alleviation of myoclonus after bilateral pallidal deep brain stimulation for Lance–Adams syndrome

Lance–Adams syndrome (LAS), which can occur after cardiorespiratory arrest (CPA), is characterized by rest-, action-, and stimulus-sensitive myoclonus with or without other neurological signs such as ataxia, cognitive impairment, epilepsy, and pyramidal signs [4–6, 15]. In 1963, Lance and Adams first described four patients with posthypoxic generalized myoclonic jerks [6]. Although case reports have been described sporadically, effective therapies have not been established [1, 2, 4, 5, 7, 8, 10, 13–15]. Deep brain stimulation (DBS) is widely used to treat movement disorders such as Parkinson’s disease [3], dystonia [12], and myoclonic diseases [9, 11]. Although functional neurosurgery, including intrathecal baclofen therapy (ITB) and DBS, has been performed to treat LAS, evidence for the success of these treatments is scarce [1, 14]. Here, we report a case of LAS treated successfully with bilateral globus pallidus interna (GPi) DBS. A 54-year-old man presented to the emergency department for respiratory distress, went into CPA, and was resuscitated. He was diagnosed with metabolic acidosis due to alcohol-related acute hepatic failure. CPA recurred following a tracheotomy due to obstruction of the tracheal tube by phlegm. Myoclonic movement emerged in the extremities after the patient regained consciousness. Neither valproic acid nor clonazepam provided effective treatment. The patient was referred to our hospital 1 year after the onset of myoclonus due to significant impairments in his gait and activities of daily living (Video). Surface electromyograms revealed a cortical myoclonus pattern (Fig. 1a). Giant somatosensory-evoked potentials were not observed. Magnetic resonance imaging (MRI) revealed no ischemic lesions, and he was diagnosed with LAS. The Unified Myoclonus Rating Scale (UMRS) results are shown in Table 1. A screening ITB test was performed, but was not effective. Next, we attempted to apply DBS to the posterior subthalamic area (PSA) and ventral intermediate nucleus (Vim) while the patient was awake. We informed the patient of the risk of hemorrhage during the operative procedure and the patient consented. We implanted the microelectrodes into the targets stereotactically (as determined by MRI) using microrecording, and stimulated the electrodes while the patient performed a writing task. The patient experienced numbness during low-amplitude stimulation of the left PSA, but his symptoms did not improve. Similarly, left Vim stimulation did not improve his symptoms. Subsequently, we inserted electrodes into the bilateral GPi. Microelectrode recordings confirmed multiunit activities in the GPi and identified the ventral border. The symptoms were unchanged during intraoperative stimulation. Because there were no associated side effects, we implanted leads (model 3387, Medtronic, Minneapolis, Electronic supplementary material The online version of this article (doi:10.1007/s00415-015-7748-x) contains supplementary material, which is available to authorized users.

Impact of Bilateral Subthalamic Stimulation on Motor/Cognitive Functions in Parkinson’s Disease

It is still unclear whether deep brain stimulation targeted to the bilateral subthalamic nucleus (STN-DBS) affects cognitive function in Parkinsons disease (PD). This prospective study was aimed to systemically evaluate the impact of bilateral STN-DBS on motor and cognitive functions in patients with PD. This study included totally 11 Japanese patients with medically intolerant PD. Neurological and cognitive status was precisely evaluated before and 1 year after bilateral STN-DBS, using unified Parkinsons disease rating scale (UPDRS), levodopa equivalent doses, mini-mental state examination (MMSE), Japanese adult reading test (JART), repeatable battery for the assessment of neuropsychological status (RBANS), and Wechsler adult intelligence scale-revised (WAIS-R). Preoperative RBANS and WAIS-R identified cognitive dysfunction that could not be detected by MMSE and JART. Before surgery, PD patients had significantly impaired immediate memory and attention. Motor function significantly improved 1 year after bilateral STN-DBS. Bilateral STN-DBS did not affect any score on cognitive examinations. However, postoperative improvements of total score on RBANS and performance intelligence quotient (PIQ) scores on WAIS-R were closely related to those of UPDRS part III off (R2 = 0.61, P < 0.01; R2 = 0.39, P < 0.05, respectively). These findings strongly suggest that bilateral STN-DBS may significantly improve cognitive function in a certain subgroup of patients whose therapeutic effects on motor function are prominent.

A case of neurolymphomatosis presented as cauda equine syndrome accompanied with M-proteinemia

A 63-year-old man developed a syndrome of cauda equine, with the numbness which is a left lower extremity from the left buttocks, weakness of left leg, and a dysfunction of bladder and bowel. Enhanced MRI revealed the enhancement of lower cauda equine, and a nerve conduction test revealed decreased F-wave persistency in the tibial nerve and increased F-wave latency in the peroneal nerve on the both sides. M-proteinemia was admitted and myeloma was suspected. By a biopsy of a vertebral arch, we diagnosed with diffuse large B-cell lymphoma. We treated with dexamethasone and R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone (prednisolone)), then the symptom was improved. In case of caude equine syndrome with M-proteinemia, a possibility of the malignant lymphoma should also be considered.