Examination of the prescription of antiepileptic drugs to prenatal and postpartum women in Japan from a health administrative database.

PURPOSE: To evaluate the prevalence and patterns of prescriptions of antiepileptic drugs (AEDs) to prenatal and postpartum women in Japan using a large administrative database. METHODS: The dates of pregnancy onset and delivery were estimated using published algorithms and infant birth months. The prevalence of prescribed AEDs, the maximum dose of some AEDs, and the frequency of potential combination therapy with AEDs were evaluated for the 180 days before pregnancy onset, during pregnancy, and at 180-day postpartum. RESULTS: In total, 33 941 pregnant women were eligible for analysis. At least one AED was prescribed to 225 women (66 per 10 000 deliveries) between 180 days before pregnancy and 180-day postpartum and for 135 women (40 per 10 000 deliveries) during pregnancy. The prevalence of AED prescription declined during the first and second trimesters and increased in the third trimester and postpartum. Valproate was the most frequently prescribed drug, followed by clonazepam, lamotrigine, and carbamazepine. Nine (18.4%) of the 49 women with at least one prescription record of valproate in the first trimester were prescribed more than 600 mg/day of valproate. Concerning potential combination therapy, 40 (12 per 10 000 deliveries) concurrently received two or more AEDs between 180 days before pregnancy and 180-day postpartum, respectively, 31 (9 per 10 000 deliveries) women received these drugs during pregnancy. CONCLUSIONS: Various AEDs were prescribed to pregnant Japanese women. Women of reproductive age should select the appropriate AED before becoming pregnant, depending on the risk benefit profile.

Effects With and Without Clopidogrel Loading Treatment for Acute Ischemic Cerebrovascular Disease Patients: A Retrospective Cohort Study.

OBJECTIVES: We investigated the effectiveness of clopidogrel loading (CL) treatment compared with usual clopidogrel non-loading (NL) treatment for acute ischemic cerebrovascular disease. METHODS: We screened consecutive 1072 patients with ischemic cerebrovascular disease within 48 hours of symptom onset admitted to our hospital. Eligible patients were divided into the CL group (300 mg on day 1, followed by 50-75 mg once daily) and NL group (50-75 mg once daily). The incidence proportion of neurologic deterioration during hospitalization was compared between the 2 groups using logistic regression analysis. RESULTS: A total of 224 patients, 39 in CL group and 185 in NL group, were enrolled. The frequency of neurologic deterioration did not significantly differ between the 2 groups (risk ratio [95% confidence interval]: 1.47 [.88-2.46]). On the preset subgroup analysis according to stroke subtype, the frequency of neurologic deterioration in CL group was significantly higher in branch atheromatous disease (risk ratio: 2.44 [1.67-3.55]) and was not different statistically in transient ischemic attack (risk ratio: 0). The analysis adjusted by several confounders showed that the incidence proportion of neurologic deterioration was not significantly different in large artery atherosclerosis (adjusted odds ratio: 1.06 [.23-4.84]) as crude analysis. The incidence proportion of adverse events was not significantly different between the 2 groups. CONCLUSIONS: The effect of CL therapy differed by stroke subtypes in preventing neurologic deterioration. CL therapy appeared to be ineffective in branch atheromatous disease. Therefore, the choice of CL therapy should carefully be made according to stroke subtypes.

Intravenous tissue plasminogen activator therapy for an acute ischemic stroke patient with later diagnosed unilateral moyamoya syndrome.

We report the use of intravenous tissue plasminogen activator (t-PA) therapy in a 38-year-old patient who was later diagnosed with unilateral moyamoya syndrome. The patient had a sudden onset of unconsciousness, vomiting, dysarthria, and tetraparesis. A neurologic examination revealed consciousness disturbance, right central facial nerve palsy, dysarthria, and tetraparesis with bilateral exotropia and horizontal gaze palsy. A magnetic resonance imaging scan on admission did not reveal fresh cerebral infarction or hemorrhage, but magnetic resonance angiography revealed severe stenosis at the terminal portion of left internal carotid artery, the anterior cerebral arteries, and the right vertebral artery. We suspected infarction of brain stem. The patient was treated with intravenous t-PA approximately 2.5 hours after onset, and the patient demonstrated a remarkable recovery 1 day after onset and had only a minimal deficit at discharge (12 days after onset). Cerebral angiography 7 days after onset confirmed the diagnosis of moyamoya disease. The present case suggests that therapeutic intravenous t-PA may be applicable for an acute ischemic stroke patient coexisting with moyamoya disease after careful evaluation and discussion with patient and family.

Scheie syndrome diagnosed after cerebral infarction.

We report a 41-year-old woman with Scheie syndrome diagnosed after cerebral infarction. She presented with acute onset dysarthria and right upper limb weakness. The neurologic findings revealed dysarthria, right central facial paralysis, mild right hemiparesis, and mild sensory impairment in the right arm and leg. Diffusion-weighted magnetic resonance imaging (MRI) showed subtle high signal lesions in the left corona radiata and posterior limb of the internal capsule. The diagnosis was made by a coarse facial appearance, claw hands, pigmentary degeneration of the bilateral retinas, and a deficiency of the enzymatic activity of lysosomal α-L-iduronidase. The patient was successfully treated with intravenous recombinant tissue plasminogen activator (rtPA) followed by enzyme replacement therapy. The prognosis of this disease would improve with enzyme replacement therapy. It is necessary to be aware of cerebral infarction in patients with Scheie syndrome.

Effectiveness and safety of a program for appropriate urinary catheter use in stroke care: A multicenter prospective study.

OBJECTIVES: Since patients with stroke frequently develop bladder dysfunction, a careful approach is required to reduce unnecessary indwelling urinary catheter (IUC) for preventing catheter-associated urinary tract infection (CAUTI). This study aimed to assess the effectiveness and safety of a program to promote appropriate IUC use in stroke care. METHODS: We conducted a prospective interrupted time series study in three tertiary care hospitals in Japan. Adult patients with acute stroke were eligible. The study consisted of three phases: baseline, education and implementation. Our program included an assessment of IUC indications, educational meetings among healthcare professionals, reminders for removal of inappropriate IUC and a urinary retention protocol. The primary outcome was the proportion of inappropriate IUC use to assess effectiveness. The device utilization ratio and incidence of CAUTI were examined to assess effectiveness, and incidences of urinary retention and all symptomatic urinary tract infection (UTI) were examined to assess safety. RESULTS: Among 976 patients who met the inclusion criteria, 738 were analysed. Inappropriate IUC use decreased from 50.1% in the baseline phase to 22.5% in the implementation phase (absolute risk reduction in interrupted time series analysis 42.4% [95% confidence interval, 19.2%-65.6%]). The device utilization ratio decreased from 0.302 to 0.194 (p < 0.001), whereas CAUTI did not change significantly (from 8.81 to 8.28 per 1000 catheter-days; incidence rate ratio 0.95 [0.44-1.94]). All symptomatic UTI decreased from 9.5% to 4.9% (p = 0.015), with no increase in urinary retention. CONCLUSIONS: Our program improved the appropriateness of IUC use in stroke care while ensuring safety.

Analysis of triptan use during pregnancy in Japan: A case series.

To evaluate the safety of triptan use during pregnancy in a Japanese population, we descriptively analyzed the data on pregnancy and fetal outcomes from 128 pregnant women using triptans for migraine treatment at two Japanese facilities that provided counseling on drug exposure in pregnancy between 2001 and 2017. The risks of miscarriage, low birth weight, and preterm birth were similar to those reported in the demographic statistics in Japan. The incidence proportion of malformation was also within the baseline risk range. Accumulated data suggest that exposure to triptans during pregnancy does not clearly increase the risk of negative pregnancy and fetal outcomes. This finding can help reduce anxiety in pregnant women with migraines who are taking triptans.

Publisher Correction: Inadequate Folic Acid Intake Among Women Taking Antiepileptic Drugs During Pregnancy in Japan: A Cross-Sectional Study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Inadequate Folic Acid Intake Among Women Taking Antiepileptic Drugs During Pregnancy in Japan: A Cross-Sectional Study.

This study aimed to assess characteristics of pregnant women taking antiepileptic drugs with inadequate folic acid intake. This cross-sectional study examined pregnant women taking antiepileptic drugs who were registered in the Japanese Drug Information Institute in Pregnancy (JDIIP) database between October 2005 and December 2016. Participants were classified into two groups according to when they started folic acid supplementation (before pregnancy: 'adequate', after pregnancy or never: 'inadequate'). Logistic regression analysis was performed to investigate factors associated with inadequate folic acid intake. Of 12,794 registrants, 468 pregnant women were taking antiepileptics during the first trimester. Of these, we analysed data from 456 women who had no missing data. As a result, inadequate folic acid intake was noted among 83.3% of them, suggesting that the current level of folic acid intake is insufficient overall. Younger age, smoking, alcohol drinking, multiparity, unplanned pregnancy, and being prescribed AEDs by paediatric or psychiatric departments were independent factors associated with inadequate folic acid intake. As planned pregnancy was the strongest factor, healthcare professionals should ensure that childbearing women taking antiepileptics are informed of the importance of planned pregnancy. In addition, healthcare professionals must gain a better understanding of folic acid intake, as the prevalence of adequate intake differed according to which departments prescribed antiepileptic drugs.

Novel Mutations of the GNE Gene in Distal Myopathy with Rimmed Vacuoles Presenting with Very Slow Progression.

We report novel compound heterozygous mutations of the UDP-N-acetylglucosamine-2-epimerase and N-acetylmannosamine kinase (GNE) gene, c.302G>A (p.R101H) and c.617-4A>G, in a Japanese family with distal myopathy with rimmed vacuoles (DMRV) presenting with slow progression. The three patients could stand and walk even 36, 34, and 39 years after onset, respectively, although affected individuals become wheelchair bound on average 12 years after onset of the disease. The clinical spectrum of DMRV seems to be wider than previously thought in terms of both the clinical course and the severity of the disease.

Two cases of possible neuro-Sweet disease with meningoencephalitis as the initial manifestation.

We report 2 cases that were considered to be neuro-Sweet disease. They initially manifested with meningoencephalitis and no skin lesions, and rapidly improved with corticosteroid therapy. In both cases, patients complained of meningitic symptoms such as fever and headache, and HLA-B54 and -Cw1 turned out to be positive over the clinical course. Cerebrospinal fluid analysis showed increased levels of lymphocytes and protein. In case #1, fluid-attenuated inversion recovery (FLAIR), magnetic resonance imaging (MRI) and diffusion-weighted images (DWI) showed high-intensity signals in the right dorsal medulla oblongata, bilateral dorsal midbrain, and left thalamus. In case #2, FLAIR and DWI showed high-intensity signals in the bilateral cerebellar cortex and left caudate nucleus. Symptoms and MRI images were markedly improved in both cases after corticosteroid pulse therapy. According to published diagnostic criteria, these 2 cases were considered possible neuro-Sweet disease. These cases suggest that the combination of meningoencephalitis and HLA specificity is important to consider the possibility of neuro-Sweet disease, even without skin lesions.

Systemic blood pressure profile correlates with cardiac 123I-MIBG uptake in patients with Parkinson's disease.

To examine the correlation between the systemic blood pressure profile and cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's disease (PD), we monitored circadian blood pressure patterns of 37 PD patients of 49 to 85 years of age (mean, 71.8±8.4 years) using a portable blood pressure monitoring device. The duration of PD was 0.5 to 15 years, and the disability level (modified Hoehn and Yahr stage) ranged from 1.0 to 4.0 (mean, 2.7±0.7). There were 37 age- and sex-matched control subjects. Cardiac MIBG scintigraphy was performed for the 37 PD patients. Based on the nocturnal fall in mean arterial blood pressure (MABP), we classified patients into extreme dippers (nocturnal reduction of MABP >20%), dippers (>10% but <20%), nondippers (<10% but >0%), and inverted dippers (<0%). Average 24-hour MABP values revealed reduced BP variability in PD patients. The percentage nocturnal fall in MABP was significantly different between PD patients and control subjects (p<0.05). Significant correlations were found between % MABP reduction and the heart-to-mediastinum (H/M) ratio on early and delayed images (p<0.01). The UPDR motor score, early and delay H/M ratios were also significantly different between patients who were and were not dippers (p<0.05). The present results reported for the first time a significant correlation between the systemic blood pressure profile and cardiac (123)I-MIBG uptake in patients with PD. The degeneration between the brainstem and the postganglionic neurons of myocardial sympathetic nerves may progress in parallel in patients with PD.

Serial diffusion-weighted MRI and SPECT findings in a Creutzfeldt-Jakob disease patient with V180I mutation.

We report serial changes of diffusion-weighted imaging (DWI) and single photon emission computed tomography (SPECT) in a patient with Creutzfeldt-Jakob disease with V180I mutation (CJD180). DWI abnormalities in our patient were more predominantly observed in the left cerebral cortex than left basal ganglia. Hemilateral abnormalities progressed over 5 months to involve the contralateral side with increasing DWI signals. At 6 months, SPECT showed hypoperfusion in the left parietal and frontal lobes and the hypoperfusion region spread to the bilateral basal ganglia, right parietal and frontal lobes. SPECT imaging revealed marked cerebral blood flow reduction, predominantly in the cerebral cortex corresponding to brain areas with high-intensity DWI signals. During the follow-up period of CJD180, DWI was more sensitive than conventional FLAIR and T2-weighted images (T2WI) to detect and monitor the progression of abnormal hyperintense lesions. We suggest that serial DWI and SPECT findings are useful for not only early diagnosis of CJD but also for monitoring disease progression.

A case of familial amyloid polyneuropathy due to Phe33Val TTR with vitreous involvement as the initial manifestation.

We report a 61-year-old Japanese woman with transthyretin (TTR) Val33-related familial amyloid polyneuropathy (FAP). She presented with late-onset, vitreous involvement as the initial manifestation, slow development of polyneuropathy, cardiomyopathy, and severe autonomic failure without carpal tunnel syndrome. Liver transplantation was performed and her postoperative course was stable. Taken together with previous reports, vitreous opacities seem to be common to Val33 FAP. Vitreous amyloidosis is usually seen in combination with the involvement of other visceral organs. The findings in the present case emphasize that vitreous opacities could be the first manifestation of FAP.

A Case of Fahr's Disease Presenting as Chorea Successfully Treated by the Use of Quetiapine.

We report a case of 30-year-old man presenting chorea in his legs. A brain computed tomography (CT) scan showed bilateral symmetric calcifications in the basal ganglia, thalamus, cerebellum and subcortical white matter. Laboratory studies showed no abnormalities of serum calcium, phosphate, PTH, lactic acid, pyruvic acid and cerebrospinal fluid. Under the diagnosis of Fahr's disease (FD), we treated with quetiapine (75 mg/day), which completely abolished his symptoms and he showed no other side effect. Our experience suggests that quetiapine is well tolerated in FD patients and effectively treats chorea without extrapyramidal movement.

Evaluation of the effects of a health education program on the improvement of hypercholesterolemia.

This study examined the effects of a health education program based on the self- reliance and self-action philosophy and the use of group work methodology on hypercholesterolemia during and after the intervention period. Thirty-two people participated in the study. Measurement values were obtained at the commencement of the intervention (Baseline), during the 6-month intervention period, at the end of the 6-month intervention period (Middle Point) and 6 months after Middle Point (End Point). The average number of steps per day significantly increased during the 6-month intervention period. The energy intake and fat intake levels significantly decreased during the 6-month intervention period. Total cholesterol, triglyceride, and atherosclerosis-index levels significantly decreased between Baseline and End Point. The HDL cholesterol levels significantly increased between Baseline and End Point. Statistically significant decrease was also observed in total cholesterol and atherosclerosis-index levels between Baseline and Middle Point, and between Middle Point and End Point. It is concluded that the health education program based on self-reliance and self-action philosophy using a group work methodology is effective for improving hypercholesterolemia. Especially, the improvement in the serum total cholesterol and atherosclerosis-index levels was sustained even after the intervention period.

Effects of elevated carbon dioxide and ozone on foliar proanthocyanidins in Betula platyphylla, Betula ermanii, and Fagus crenata seedlings.

Proanthocyanidins (PAs) or condensed tannins are a major group of phenolic compounds in the leaves of birch trees and many other woody and herbaceous plants. These compounds constitute a significant allocation of carbon in leaves and are involved in plant responses to environmental stress factors, such as pathogens or herbivores. In some plants, PA concentrations are affected by atmospheric carbon dioxide (CO(2)) and ozone (O(3)) levels that may influence, for example, species fitness, community structure, or ecosystem nutrient cycling. Therefore, a study on the quantitative response of PAs to elevated concentrations of carbon dioxide (CO(2)) and ozone (O(3)) was undertaken in seedlings of Betula platyphylla, Betula ermanii, and Fagus crenata. Seedlings were exposed to ambient or elevated O(3) and CO(2) levels during two growing seasons in the Kanto district in Japan. Ten open-top chambers were used for five different treatments with two replicates: filtered air (FA), ambient air (ambient O(3), 43 ppb; ambient CO(2), 377 ppm), elevated O(3) (1.5 x ambient O(3), 66 ppb), elevated CO(2) (1.5 x ambient CO(2), 544 ppm), and elevated O(3) and CO(2) combined. In addition, seedlings growing in natural conditions outside of chambers were studied. Leaf samples were analyzed for total PA concentrations by butanol-HCl assay and for polymeric PA concentrations by normal-phase high-performance liquid chromatography. Total PA concentrations in leaves of all species were similarly affected by different treatments. They were significantly higher in seedlings treated with elevated CO(2) and O(3) combined, and in seedlings growing outside chambers compared with the FA controls. F. crenata contained only traces of polymeric PAs, but significant species x treatment interaction was observed in the polymeric PA concentrations in B. ermanii and B. platyphylla. In B. platyphylla, leaves treated with elevated CO(2) + O(3) differed significantly from all other treatments. It was suggested that the strongest effect of elevated CO(2) and O(3) combined on leaf PA contents resulted from the additive effect of these environmental factors on phenolic biosynthesis.