Kiichi Unoda

Eicosapentaenoic acid (EPA) induces peroxisome proliferator-activated receptors and ameliorates experimental autoimmune encephalomyelitis

Eicosapentaenoic acid (EPA), one of the n-3 polyunsaturated fatty acids, is a neuroprotective lipid with anti-inflammatory properties. We investigated the possible therapeutic effect of EPA on experimental autoimmune encephalomyelitis (EAE). EAE mice were fed a diet with or without EPA. The clinical EAE scores of the EPA-fed mice were significantly lower than those of the non-EPA mice. In the EPA-treated mice, IFN-γ and IL-17 productions were remarkably inhibited and the expression levels of peroxisome proliferator-activated receptors were significantly enhanced in the CNS-infiltrating CD4T cells. Thus EPA shows promise as a potential new therapeutic agent against multiple sclerosis.

The Relation of Urinary 8-OHdG, A Marker of Oxidative Stress to DNA, and Clinical Outcomes for Ischemic Stroke

Background: Oxidative stress/free radical generation after ischemic stroke contributes to neuronal cell injury. We evaluated the utility of an oxidative stress marker, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), to demonstrate an association between the changes of 8-OHdG and outcomes after acute ischemic stroke. Methods: We enrolled 44 patients (26 males and 18 females) who visited our hospital due to acute ischemic stroke. Urine was collected on admission and on Days 7, and 8-OHdG was measured by ELISA. The relationships between 8-OHdG levels, stroke subtypes, and clinical outcomes based on the NIHSS and modified Rankin Scale (mRS) upon discharge was evaluated. Results: In the overall cohort, the mean urinary level of 8-OHdG on Day 7 was increased than that on Day 0. The 8-OHdG levels on Day 0 were not different between patients with poor and good outcomes. However, an increasing rate from Day 0 to 7 (Δ 8-OHdG) in stroke patients with a poor outcome(mRS ≥3) was significantly higher than those with a good outcome (mRS ≤2) (2.54 vs 39.44, p = 0.004). Conclusions: The biochemical changes related to 8-OHdG and oxidative stress may be considered a marker of ischemic brain injury and clinical outcome of ischemic stroke.

Postural Abnormality as a Risk Marker for Leg Deep Venous Thrombosis in Parkinson’s Disease

Background Pulmonary thromboembolism is a common cause of death in patients with autopsy-confirmed Parkinsonism. This study investigated the incidence of leg deep vein thrombosis in Parkinson’s disease and relationships between deep vein thrombosis and clinical/laboratory findings, including postural abnormalities as assessed by photographic measurements. Methods This cross-sectional study assessed the presence of deep vein thrombosis using bilateral leg Doppler ultrasonography in 114 asymptomatic outpatients with Parkinson’s disease. Results Deep vein thrombosis was detected in 23 patients (20%) with Parkinson’s disease. Deep vein thrombosis was located in the distal portion in 18 patients and in the proximal portion in 5 patients. No significant differences in age, sex, body mass index, disease duration, Hoehn-Yahr stage, anti-Parkinson’s drugs, or daily levodopa-equivalent dose were seen between deep vein thrombosis-positive and -negative groups. Univariate analysis for developing deep vein thrombosis in patients with Parkinson’s disease identified the following markers: long-term wheelchair use, bent knee, bent spine, and D-dimer elevation. Bending angles were significantly greater in the deep vein thrombosis-positive group at the knee and spine than in the deep vein thrombosis-negative group. Half of Parkinson’s disease patients with camptocormia had deep vein thrombosis. Among diabetes mellitus cases, long-term wheelchair use, bent knee over 15°, camptocormia, D-dimer elevation, the more risk markers were associated with a higher incidence of DVT. The presence of risk markers contributed to the development of deep vein thrombosis. On multivariate logistic regression analysis, a bent knee posture was strongly associated with an increased risk of deep vein thrombosis. Conclusion Presence of leg deep vein thrombosis correlated with postural abnormalities in Parkinson’s disease. We recommend non-invasive ultrasonographic screening for leg deep vein thrombosis in these high-risk patients with Parkinson’s disease.

Clinical characteristics of long-term survival with noninvasive ventilation and factors affecting the transition to invasive ventilation in amyotrophic lateral sclerosis: Transition from NIV to TIV

Introduction: We evaluated post–noninvasive ventilation survival and factors for the transition to tracheostomy in amyotrophic lateral sclerosis (ALS). Methods: We analyzed 197 patients using a prospectively collected database with 114 patients since 2000. Results: Among 114 patients, 59 patients underwent noninvasive ventilation (NIV), which prolonged the total median survival time to 43 months compared with 32 months without treatment. The best post‐NIV survival was associated with a lack of bulbar symptoms, higher measured pulmonary function, and a slower rate of progression at diagnosis. The transition rate from NIV to tracheostomy gradually decreased over the years. Patients using NIV for more than 6 months were more likely to refuse tracheostomy and to be women. Discussion: This study confirmed a positive survival effect with NIV, which was less effective in patients with bulbar dysfunction. Additional studies are required to determine the best timing for using NIV with ALS in patients with bulbar dysfunction. Muscle Nerve 58:770–776 2018

Preventive Effect of Cilostazol on Pneumonia in Patients with Acute Cerebral Infarction

BACKGROUND The antiplatelet drug cilostazol decreases the risk of ischemic stroke recurrence in patients with chronic cerebral infarction. Additionally, cilostazol reduces the occurrence of pneumonia in these patients. The purpose of this study was to investigate whether cilostazol is effective for preventing pneumonia in patients with acute cerebral infarction. MATERIALS AND METHODS A total of 199 consecutive Japanese patients with noncardioembolic acute cerebral infarction, who visited our hospital from January 2010 to April 2016, were retrospectively assessed by using medical records. We compared changes in the occurrence of pneumonia between cilostazol (n = 127) and noncilostazol (n = 72) groups. RESULTS A total of 76% of patients in the cilostazol group were not administered other antiplatelet drugs. The median duration until cilostazol administration was 5 days (interquartile range = 2-8 days) after the onset of cerebral infarction. A total of 8.0% of the cohort was accompanied by pneumonia. The incidence of pneumonia in the cilostazol group was significantly lower than that in the noncilostazol group (4.7% versus 13.9%, P = .02). Within 30 days after acute cerebral infarction, the presence of neurological deterioration in the cilostazol group tended to be lower compared with the noncilostazol group, but this difference was not significant (5.5% versus 12.5%, P = .08). CONCLUSIONS These findings suggest that cilostazol is effective for preventing pneumonia in patients with acute cerebral infarction.

Neurologic disorders associated with anti-glutamic acid decarboxylase antibodies: A comparison of anti-GAD antibody titers and time-dependent changes between neurologic disease and type I diabetes mellitus

To determine clinical features of neurologic disorders associated with anti-glutamic acid decarboxylase antibodies (anti-GAD-Ab), we examined titers and time-dependent changes of anti-GAD-Ab. Six patients, stiff person syndrome (2), cerebellar ataxia (1), limbic encephalitis (1), epilepsy (1), brainstem encephalitis (1), were compared with 87 type I diabetes mellitus (T1DM) patients without neurologic disorders. Anti-GAD-Ab titers and index were higher in neurologic disorders than in T1DM, suggesting intrathecal antibody synthesis. Anti-GAD-Ab titers in T1DM decreased over time, whereas they remained high in neurologic disorders. Immunotherapy improved neurological disorders and anti-GAD-Ab titers and index provide clinically meaningful information about their diagnostic accuracy.