Tsuyoshi Torii

Lack of an association between cystatin C gene polymorphisms in Japanese patients with Alzheimer’s disease

Associations between polymorphisms of the cystatin C gene (CST3) at 5′ flanking region and exon 1 in Caucasian patients with late onset AD and exon 1 in a US study of late onset AD have been reported. Clinically diagnosed Japanese patients with AD and Japanese normal control subjects were assessed for the presence of polymorphisms of CST3. The authors could not confirm the previously reported association between CST3 polymorphisms and AD in Japan. Age had no effect on the CST3 genotype.

Dinucleotide repeat polymorphisms in the Neprilysin gene are not associated with sporadic Alzheimer's disease

In the pathological process of Alzheimers disease (AD), deposition of amyloid beta-peptide (A beta) in the brain parenchyma plays an important role. Neprilysin (NEP), a neutral endopeptidase, degrades A beta, and it is postulated that decreased NEP activity may contribute to the development of AD by promoting the accumulation of A beta. The human NEP gene possesses four dinucleotide repeat polymorphisms, and it is possible that these polymorphisms regulate the NEP expression levels and influence the pathological cascade of AD. Therefore, we investigated the association of these polymorphisms with AD. We performed genotyping of each polymorphism in 201 Japanese sporadic AD patients and 208 Japanese controls. There were no significant differences between the AD and control groups in allele frequencies of each polymorphism. We conclude that these polymorphisms in the NEP gene do not contribute to genetic risk factors for sporadic AD.

Effects of Meteorological Conditions on the Risk of Ischemic Stroke Events in Patients Treated with Alteplase—HEWS-tPA

BACKGROUND Predicting a day that presents a high risk for the occurrence of ischemic stroke events may enable health professionals to prepare for emergency stroke therapy more properly. We evaluated the association between meteorological conditions and the frequency of ischemic stroke events in Japanese patients. METHODS Ischemic stroke patients (n = 299) who were treated with alteplase at 9 stroke hospitals in 3 restricted areas were examined. The daily rates of ischemic stroke events were compared with the daily mean thermo-hydrological index (THI), the atmospheric pressure, and the daily changes of these variables for the 6 days preceding an ischemic stroke event using Poisson regression analysis. RESULTS We trisected onset days based on the THI (low-temperature, intermediate-temperature, and high-temperature), atmospheric pressure (low-pressure, intermediate-pressure, and high-pressure), changes in THI for preceding 6 days from the previous day (cooler, unchanged-temperature, and warmer), and changes in atmospheric pressure (decreased-pressure, unchanged-pressure, and increased-pressure). The frequency of ischemic stroke was significantly higher on low-temperature or high-pressure days (risk ratio, 1.398, P = .022; risk ratio, 1.374, P = .039), on warmer-temperature days, and when atmospheric pressure varied from the day before (P < .05). There were significantly lower risks for ischemic stroke events on cooler-temperature days, and higher risks were associated with a variation in atmospheric pressure 3 days before the onset from 4 days before (P < .05). CONCLUSIONS There were higher risks for ischemic stroke events associated with low ambient temperature, high atmospheric pressure, increased temperature, and varied atmospheric pressure. Also, atmospheric pressure variation 3 days before may be associated.

Dinucleotide repeat polymorphism in interferon-γ gene is not associated with sporadic Alzheimer's disease

Various factors have been suggested to participate in Alzheimers disease (AD) pathology, and some inflammatory cytokines may play an important role in the development of AD. Interferon‐γ (IFNG), an important pro‐inflammatory cytokine, is encoded by a single gene mapped to chromosome 12, one of the candidate locus of AD. The first intron in the IFNG gene represents a CA repeat polymorphism that is possible to affect the IFNG secretion dose. We speculate that the polymorphism may have some roles on the inflammatory process and the pathologic change in AD, so we analyzed the IFNG gene polymorphism in 199 Japanese AD patients and 225 Japanese controls. There were no significant differences in allele frequency between the AD and control groups. We conclude that IFNG gene polymorphism is not associated with development of AD.

Various meteorological conditions exhibit both immediate and delayed influences on the risk of stroke events: The HEWS–stroke study

We hypothesized that meteorological conditions on the onset day and conditions on the former days may play important roles in the modulation of physical conditions. Associations of meteorological factors and their changes in former days with stroke onset are of interest. We conducted a multicenter retrospective study to evaluate the frequency of stroke events and their interaction with meteorological conditions and their daily changes. Acute stroke patients (n = 3935, 73.5±12.4 years, 1610 females) who were admitted to 7 stroke hospitals in three restricted areas were enrolled in this study. Poisson regression models involving time-lag variables was used to compare daily rates of stroke events with mean thermo-hydrological index (THI), atmospheric pressure, and their daily changes. We divided onset days into quintiles based on the THI, atmospheric pressure, and their daily changes for the last 7 days. The frequencies of ischemic stroke significantly increased when THI varied either cooler or warmer from a previous day (extremely cooler, risk ratio (RR) 1.19, 95% confidence interval (CI) 1.05 to 1.34; extremely warmer, RR 1.16, 95% CI 1.03 to 1.31; r2 = 0.001 for the best regression, p = 0.001). Intracerebral hemorrhage frequencies significantly decreased on high-THI days (extremely high, RR 0.72, 95% CI 0.54 to 0.95; r2 = 0.013 for the best regression, p<0.001) and increased in high atmospheric pressure days (high, RR 1.31, 95% CI 1.04 to 1.65; r2 = 0.009 for the best regression, p<0.001). Additionally, even after adjusting for the THI on the onset day and its changes for the other days, intracerebral hemorrhage increased when THI got extremely cooler in 4 days prior (RR 1.33, 95% CI 1.03 to 1.71, r2 = 0.006 for the best regression, p<0.001). Various meteorological conditions may exhibit influences on stroke onset. And, when temperature cooled, there may be a possibility to show delayed influence on the frequency of intracerebral hemorrhage 4 days later.

Screening for Fabry Disease in Japanese Patients with Young-Onset Stroke by Measuring α-Galactosidase A and Globotriaosylsphingosine

BACKGROUND Fabry disease is an X-linked lysosomal storage disorder caused by mutations in GLA, which encodes the enzyme α-galactosidase A (α-Gal A). Although the prevalence of Fabry disease in patients with stroke has been reported to range from 0% to 4%, few cohort studies have examined Japanese stroke patients. We aimed to clarify the prevalence of Fabry disease and the frequency of GLA mutations among patients with young-onset stroke in Japan. METHODS From April 2015 to December 2016, we enrolled patients with young-onset (≤60 years old) ischemic stroke or intracerebral hemorrhage. We measured α-Gal A activity and the concentration of globotriaosylsphingosine in plasma. Genetic evaluations were performed in patients with low α-Gal A activity or high concentrations of globotriaosylsphingosine. RESULTS Overall, 516 patients (median age of onset, 52 years old; 120 women) were consecutively enrolled in this study. Five patients (4 men and 1 woman) had low α-Gal A activity, and no patients were detected with the screen for plasma globotriaosylsphingosine levels. The genetic analysis did not identify a causative mutation responsible for classic Fabry disease in any of the patients, but 2 patients (.4%) carried the p.E66Q in GLA. CONCLUSIONS No patient with Fabry disease was detected in our young-onset stroke cohort.

Multijoint Pain and Pulmonary Calcification with Long-term Hemodialysis

A 66-year-old man who had been on hemodialysis for 35 years was admitted to our hospital due to severe multi-joint pain and contractures. He had been taking alfacalcidol (0.25 μg/day) and calcium carbonate (3 g/day) and had a history of bilateral carpal tunnel syndrome. A laboratory examination showed hypercalcemia (12.3 mg/dL), hyperphosphotemia (5.6 mg/dL), and hyperbeta2-microglobulinemia (34.8 mg/L). Computed tomography revealed diffuse bilateral lung centrilobular ground glass opacity (Picture 1) and a mass near the coxae and glenohumeral joints (Picture 2). Metastatic pulmonary calcification (MPC) and dialysis-related amyloidosis (DRA) were diagnosed based on the history and imaging findings. MPC can progress to respiratory failure that leads to death. In this case, we considered the cause of MPC to be alfacalcidol, calcium carbonate, and long-term hemodialysis. The adequate control of electrolytes and highflux biocompatible membranes may provide expeditious treatment for patients with DRA and MPC (1).

Auditory agnosia caused by bilateral putamen haemorrhage

A 55-year-old right-handed man with a history of hypertension suddenly fell and developed right hemiparesis. Neurological examination revealed that he was alert, but did not appropriately respond to verbal questions and commands. Detailed examination revealed that he could correctly respond to written commands. His speech was almost fluent, showing no paraphasia and normal articulation. His written sentences were legible. Pure tone audiometry showed that his auditory acuity was relatively preserved. His brainstem auditory evoked potential components from I to V were recorded bilaterally with normal latency. Cerebral CT demonstrated fresh bleeding in the left putamen and an old haemorrhage on the opposite side. He was treated by antihypertensive therapy and rehabilitation. Although there remained mild sensory deficit on his right extremities and he felt a slight noise during conversation, he had little difficulty with verbal communication when he was transferred to another hospital on day 38.

A Case Report of Visual Disturbance Caused by Thrombosis of the Superior Sagittal Sinus

Superior sagittal sinus thrombosis is a rare condition caused by several diseases including malignancy. Major symptoms include headache, seizure, and motor weakness. Ocular sign is a minor symptom. The present case had visual disturbance caused by thrombosis of the superior sagittal sinus, which is an extremely rare case that was treated successfully by our team