Clinical impact of 11C-Pittsburgh compound-B positron emission tomography in addition to magnetic resonance imaging and single-photon emission computed tomography on diagnosis of mild cognitive impairment to Alzheimer's disease.

ABSTRACT: This study aimed to evaluated the clinical impact of adding [11C] Pittsburgh compound-B (11C-PiB) PET for clinical diagnosis of mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia.Twenty six (mean age 78.5 ±â€Š5.18 years, 21 females) AD (n = 7), amnestic MCI (n = 12), non-amnestic MCI (n = 3), vascular dementia, progressive supranuclear palsy (PSP) with frontotemporal dementia (FTD), FTD (n = 1 each), and normal (n = 1) patients underwent 11C-PiB-PET, MRI, and SPECT scanning. 11C-PiB-PET was compared with MRI and SPECT for clinical impact.11C-PiB-PET showed positivity in 6, 9, and 0 of the AD, amnestic MCI, and non-amnestic MCI patients, respectively, and 0 of those with another disease. Parahippocampal atrophy at VSASD was observed in 5 AD patients, 6 amnestic and PiB-positive MCI patients, 1 amnestic and PiB-negative MCI patient, and 1 vascular dementia patient. Parietal lobe hypoperfusion in SPECT findings was observed in 6, 4, and 2 of those, respectively, as well as 1 each of non-amnestic MCI, vascular dementia, and normal cases. Sensitivity/specificity/accuracy for selecting PiB-positive patients among the 15 MCI patients for 11C-PiB-PET were 100% (9/9)/100% (6/6)/100% (15/15), for VSRAD were 66.7% (6/9)/83.3% (5/6)/73.3% (11/15), and for SPECT were 44.4% (4/9)/50.0% (3/6)/46.7% (7/15), while those were 88.9% (8/9)/33.3% (2/6)/66.7% (10/15)/for combined VSRAD and SPECT. 11C-PiB-PET accuracy was significantly higher than that of SPECT.11PiB-PET alone may be useful for selecting patients who will progress from MCI to AD in the future, although follow-up study is necessary to clarify the outcome of MCI patients.

Dentatorubrothalamic tract reduction using fixel-based analysis in corticobasal syndrome.

PURPOSE: The word "fixel" refers to the specific fiber population within each voxel, and fixel-based analysis (FBA) is a recently developed technique that facilitates fiber tract-specific statistical analysis. The aim of the paper is to apply FBA to detect impaired fibers for corticobasal syndrome (CBS) especially in regions that contain multiple crossed fibers. METHODS: FBA was performed in cohorts of participants clinically diagnosed with CBS (n = 10) and Parkinson's disease (n = 15) or in healthy controls (n = 9). The parameters of the diffusion weighted image were echo time, 83 ms; time, 8123.6 ms; flip angle, 90°; section thickness, 2 mm; b = 1000 s/mm2; and 32 axes. Diffusion tensor analysis was conducted using tract-based spatial statistics (TBSS), and white matter volume was estimated via voxel-based morphometry. RESULTS: A comparison of PD or HC to CBS revealed a significant difference in the dentatorubrothalamic tract of the brainstem in FBA in addition to the affected regions in voxel-based morphometry and TBSS (family-wise error-corrected p < 0.05). Reduction of the white matter fibers crossing the brainstem could not be detected via microstructural changes identified using TBSS, but it was detected using FBA. CONCLUSION: FBA has some advantages in determining the distribution of corticobasal syndrome lesions.

Cranial Autonomic Symptoms of Migraine in Japan: Prospective Study of 373 Migraine Patients at a Tertiary Headache Center.

OBJECTIVE: To clarify the detailed clinical characteristics of cranial autonomic symptoms (CAS) of Japanese patients with migraine and to get insight into the pathophysiological implications. BACKGROUND: Recent studies reported that CAS in migraine is causing diagnostic confusion with cluster headache or sinus headache; however, most reports have concerned Caucasians, and Asian data are scarce. The regional differences in the clinical characteristics of primary headaches between Caucasians and Asians have also been revealed recently. METHOD: This was a cross-sectional study. We investigated 373 patients with migraine in a tertiary headache center with face-to-face interviews. RESULTS: According to our findings, 158/373 (42.4%) patients with migraine had CAS and were characterized by more frequent cutaneous allodynia than those without CAS, suggesting the contribution of central sensitization; however, there were no statistically significant differences in pulsating pain or motion sensitivity as signs of peripheral sensitization. In contrast to the previous study, osmophobia was found to be significantly related to CAS. CONCLUSION: CAS in patients with migraine is common not only in Caucasians but also in Asians. Central sensitization seems to contribute more than peripheral sensitization to CAS manifestation, and osmophobia might be noteworthy among Asian patients with migraine. To avoid a misdiagnosis, we emphasize the need for comments on CAS in the international classification of headache disorders migraine criteria.

Differences in splicing defects between the grey and white matter in myotonic dystrophy type 1 patients.

Myotonic dystrophy type 1 (DM1) is a multi-system disorder caused by CTG repeats in the myotonic dystrophy protein kinase (DMPK) gene. This leads to the sequestration of splicing factors such as muscleblind-like 1/2 (MBNL1/2) and aberrant splicing in the central nervous system. We investigated the splicing patterns of MBNL1/2 and genes controlled by MBNL2 in several regions of the brain and between the grey matter (GM) and white matter (WM) in DM1 patients using RT-PCR. Compared with amyotrophic lateral sclerosis (ALS, as disease controls), the percentage of spliced-in parameter (PSI) for most of the examined exons were significantly altered in most of the brain regions of DM1 patients, except for the cerebellum. The splicing of many genes was differently regulated between the GM and WM in both DM1 and ALS. In 7 out of the 15 examined splicing events, the level of PSI change between DM1 and ALS was significantly higher in the GM than in the WM. The differences in alternative splicing between the GM and WM may be related to the effect of DM1 on the WM of the brain.

Changes in clinical features of multiple system atrophy in Japan.

INTRODUCTION: Multiple system atrophy (MSA) is an adult-onset progressive neurodegenerative disease that causes parkinsonism, cerebellar ataxia, and/or autonomic failure. MSA is categorized as MSA with predominant cerebellar ataxia (MSA-C) or MSA with predominant parkinsonism (MSA-P) according to the cardinal symptom at diagnosis. MSA-C has been reported to be the predominant presentation in Japan to date. However, major epidemiological studies regarding MSA in Japan were carried out before 2006; thus, the recent advancement of various imaging studies remains unclear. This study aimed to investigate the clinical characteristics of the recent MSA patients in Japan. METHODS: In this retrospective study, we divided 80 probable MSA patients into group A and group B and examined them to reveal whether the clinical features of MSA were different depending on the time periods of diagnosis (1989-2003 and 2004-2018, respectively). RESULTS: The age at onset was significantly higher in MSA-P patients than in MSA-C patients (p = 0.0039) and was also higher in group B than in group A (p = 0.013). Although MSA-C was the predominant type in both groups, MSA-P was significantly more frequent in group B than in group A (p = 0.039). Although not statistically significant, the early heart/mediastinum ratio in [123I]-meta-iodo benzylguanidine (MIBG) myocardial scintigraphy tended to be lower in patients with MSA-P than in those with MSA-C. CONCLUSION: The proportion of MSA-P was likely larger than previously recorded due to the aging population in Japan and the improvement of differential diagnosis between PD and MSA-P.

The relation between emotion regulation and migraine: A cross-cultural study on the moderating effect of culture.

BACKGROUND: Effects of emotion suppression on physical health might be contingent on culture. Existing research on emotion regulation has mainly included western participants. Herewith the question arises, whether this gained expertise is transferable to an Asian culture. OBJECTIVES: This cross-sectional study evaluated to what extent the regulation of emotions is related to migraine and if the relation between emotion regulation and migraine complaints differs between a Western and an Asian population. Therefore, the main characteristics and symptoms of patients with migraine from both Germany and Japan are compared. METHODS: 261 Japanese and 347 German headache patients participated in this online study and completed self-report measures of emotion regulation (suppression and reappraisal) and headache complaints. RESULTS: Cultural groups did not differ regarding their demographic data, intake of medication and number of days with headache. German participants showed significantly higher levels of anxiety and lower levels of emotion suppression compared to Japanese patients. Emotion regulation is not correlated with headache complaints either in the Japanese or in the German patient group. CONCLUSION: Although group differences were found with respect to anxiety and emotion suppression, subsequent regression analysis revealed these differences were unrelated to headache complaints. As our baseline analysis focused on group means, approaches that examine individual reaction patterns to stress and accompanying sensory stimulus processing may prove to be more fruitful and illuminating.

Potential of Adult Endogenous Neural Stem/Progenitor Cells in the Spinal Cord to Contribute to Remyelination in Experimental Autoimmune Encephalomyelitis.

Demyelination and remyelination play pivotal roles in the pathological process of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a well-established animal model of MS. Although increasing evidence shows that various stimuli can promote the activation/induction of endogenous neural stem/progenitor cells (NSPCs) in the central nervous system, the potential contributions of these cells to remyelination following inflammatory injury remain to be fully investigated. In the present study, using an adult mouse model of EAE induced by myelin oligodendrocyte glycoprotein (MOG) peptide, we investigated whether adult NSPCs in the spinal cord can lead to remyelination under inflammatory conditions. Immunohistochemistry showed that cells expressing the NSPC marker Nestin appeared after MOG peptide administration, predominantly at the sites of demyelination where abundant inflammatory cells had accumulated, whereas Nestin+ cells were rarely present in the spinal cord of PBS-treated control mice. In vitro, Nestin+ NSPCs obtained from EAE mice spinal cords could differentiate into multiple neural lineages, including neurons, astrocytes, and myelin-producing oligodendrocytes. Using the Cre-LoxP system, we established a mouse strain expressing yellow fluorescent protein (YFP) under the control of the Nestin promoter and investigated the expression patterns of YFP-expressing cells in the spinal cord after EAE induction. At the chronic phase of the disease, immunohistochemistry showed that YFP+ cells in the injured regions expressed markers for various neural lineages, including myelin-forming oligodendrocytes. These results show that adult endogenous NSPCs in the spinal cord can be subject to remyelination under inflammatory conditions, such as after EAE, suggesting that endogenous NSPCs represent a therapeutic target for MS treatment.

[A case of muscle sarcoidosis with hypercalcemia, lower limb muscle strength and without bilateral hilar lymphadenopathy].

A 73-year-old man was hospitalized with complaints of general malaise, limb muscle weakness and weight loss progressing in 6 months. Ca, ACE, lysozyme, sIL-2R, vitamin 1.25 D was high in the blood test. Bilateral hilar lymphadenopathy on CT were not recognized, and CD4/CD8 ratio increased by bronchoalveolar lavage. In the 67Ga-citrate scintigraphy, accumulation was observed on the thigh and shoulder to the upper arm bilaterally. A muscle biopsy was performed from the right femoris muscle where the gadolinium contrast effect in the T1 weighted image was observed. As muscle biopsy revealed non-toxic epithelial cell granulomas, he was diagnosed as muscle sarcoidosis. Even if bilateral hilar lymphadenopathy is not observed, muscle sarcoidosis should be considered in patients developed with hypercalcemia and limb muscle weakness.

Primary care doctor fostering and clinical research training in Sweden: Implications for Japan.

In 2018, a new training program for primary care physicians was launched in Japan. As physicians responsible for the training of new primary care physicians, we have faced many problems, particularly in rural areas. The influence of this new program on primary care physicians in rural areas of Japan has not been sufficiently investigated. The aim of this research was to improve training for primary care physicians in Japan by examining training programs in Sweden, where the population challenges are similar to those seen in Japan. In this paper, we will express our opinions and describe the differences in the primary care fostering systems and clinical research training for generalist in Japan and Sweden.

Tongue Pressure Measurement and Videofluoroscopic Study of Swallowing in Patients with Parkinson's Disease.

This study investigated the relationship between tongue pressure during swallowing and dysphagia in patients with Parkinson's disease (PD). A total of 24 patients with PD (12 men and 12 women, mean age 70.4 years) were studied. Their mean Hoehn and Yahr scale was 3.0 ± 1.3 (range 1-5). All participants underwent tongue pressure measurement and videofluorography during swallowing. Tongue pressure when swallowing 5 mL of barium on videofluorography was measured using a sensor sheet with five sensors. Based on the findings of videofluorography, the patients were divided into two groups: dysphagic PD group (n = 9) and non-dysphagic PD group (n = 15). The maximal magnitude (kPa), duration (s), time to peak pressure (s), and pressure gradient (kPa/s) of tongue pressure were analyzed for each part. For duration, time to peak pressure, and pressure gradient, similar values were calculated from the total waveform. There was no significant difference in maximal tongue pressure between the groups. The dysphagic PD group had prolonged duration of tongue pressure and time to peak pressure and a reduced pressure gradient compared with the non-dysphagic PD group. These results indicate that there is a clear difference in the temporal aspects of tongue pressure between the non-dysphagic and dysphagic PD patients. These differences provide the characteristics of tongue movement during swallowing in PD patients with dysphagia, which may be useful for the diagnosis and treatment of dysphagia.

Influence of Helicobacter pylori infection on periodontitis.

AIM: The relationship of Helicobacter pylori infection with periodontitis was examined. METHODS: The study subjects were 686 individuals (males 504, females 182; mean age 53.8 years) who underwent a screening test for periodontitis between April 2015 and March 2018 and whose H. pylori infection status could be determined. The periodontitis test was performed by examining saliva concentrations of lactate dehydrogenase and hemoglobin (Hb), with a lactate dehydrogenase level ≥ 350 U/L and/or hemoglobin level ≥ 2 µg/mL defined as positive for periodontitis. RESULTS: Among subjects found positive in screening for periodontitis, those classified as negative and positive for H. pylori infection, as well as post-eradicated were 81 (39.7%), 30 (14.7%), and 93 (45.6%), respectively, while those among subjects shown negative for periodontitis numbered 241 (50.0%), 52 (10.8%), and 189 (39.2%), respectively. Subjects noted as negative, positive, and post-eradicated for H. pylori infection comprised 25.2%, 36.6%, and 32.9%, respectively, of all shown positive for periodontitis. Multiple logistic regression analysis indicated that the risk for positive in the periodontitis test was higher among subjects with H. pylori infection as compared with those without, while post-eradicated status tended to reduce that risk. Repeated examinations performed following H. pylori eradication showed that the number of subjects positive for periodontitis was decreased among those who underwent successful eradication. CONCLUSION: Helicobacter pylori infection increases the risk for occurrence of periodontitis, which can be reduced by successful eradication.

Intravenous immunoglobulin for maintenance treatment of multifocal motor neuropathy: A multi-center, open-label, 52-week phase 3 trial.

Intravenous immunoglobulin (IVIg) therapy is currently the only established treatment in patients with multifocal motor neuropathy (MMN), and many patients have an IVIg-dependent fluctuation. We aimed to investigate the efficacy and safety of every 3 week IVIg (1.0 g/kg) for 52 weeks. This study was an open-label phase 3 clinical trial, enrolling 13 MMN patients. After an induction IVIg therapy (0.4 g/kg/d for 5 consecutive days), maintenance dose (1.0 g/kg) was given every 3 weeks for 52 weeks. The major outcome measures were the Medical Research Council (MRC) sum score and hand-grip strength at week 52. This trial is registered with ClinicalTrials.gov, number NCT01827072. At week 52, 11 of the 13 patients completed the study, and all 11 had a sustained improvement. The mean (SD) MRC sum score was 85.6 (8.7) at the baseline, and 90.6 (12.8) at week 52. The mean grip strength was 39.2 (30.0) kPa at the baseline and 45.2 (32.8) kPa at week 52. Two patients dropped out because of adverse event (dysphagia) and decision of an investigator, respectively. Three patients developed coronary spasm, dysphagia, or inguinal herniation, reported as the serious adverse events, but considered not related with the study drug. The other adverse effects were mild and resolved by the end of the study period. Our results show that maintenance treatment with 1.0 g/kg IVIg every 3 week is safe and efficacious for MMN patients up to 52 weeks. Further studies are required to investigate optimal dose and duration of maintenance IVIg for MMN.

Macroscopic and microscopic diversity of missplicing in the central nervous system of patients with myotonic dystrophy type 1.

Myotonic dystrophy type I (DM1) is a multiorgan disease caused by CTG-repeat expansion in the DMPK gene. Sequestration of the splicing factor MBNL1 results in aberrant splicing in many genes in DM1 skeletal muscle, whereas MBNL2 plays a leading role in missplicing in the central nervous system (CNS) of patients with DM1. Splicing misregulation of most MBNL2-regulated genes occurs in the temporal cortex but not in the cerebellum of autopsied patients with DM1. To understand the diversity at macroscopic and microscopic levels in CNS of patients with DM1. Using autopsied brain tissues, we examined alternative splicing ratios of MBNL2-regulated genes and expression levels of potential splicing factors. We found differences in splicing abnormalities among tested regions of the CNS from patients with DM1. In the frontal and temporal cortices and the hippocampus, many genes were aberrantly spliced, but severity differed among the brain regions. By contrast, there were no significant differences in the ratio of splicing variants for most of the genes in the cerebellar cortex and spinal cord between DM1 and control samples. We failed to find any change in the amount of potential factors (MBNL and CUGBP proteins and DMPK mRNA) which explain the modest missplicing in the cerebellum. LASER capture microdissection demonstrated splicing misregulation in the molecular layer of the cerebellum but not in the granular layer. This is the first study to reveal missplicing in a functional cell layer of DM1 and to compare splicing misregulation in a wide region of the CNS using statistical analysis.

Intravenous immunoglobulin for maintenance treatment of chronic inflammatory demyelinating polyneuropathy: a multicentre, open-label, 52-week phase III trial.

OBJECTIVE: Short-term efficacy of induction therapy with intravenous immunoglobulin (Ig) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is well established. However, data of previous studies on maintenance therapy were limited up to 24-week treatment period. We aimed to investigate the efficacy and safety of longer-term intravenous Ig therapy for 52 weeks. METHODS: This study was an open-label phase 3 clinical trial conducted in 49 Japanese tertiary centres. 49 patients with CIDP who fulfilled diagnostic criteria were included. After an induction intravenous Ig therapy (0.4 g/kg/day for five consecutive days), maintenance dose intravenous Ig (1.0 g/kg) was given every 3 weeks for up to 52 weeks. The primary outcome measures were the responder rate at week 28 and relapse rate at week 52. The response and relapse were defined with the adjusted Inflammatory Neuropathy Cause and Treatment scale. RESULTS: At week 28, the responder rate was 77.6% (38/49 patients; 95% CI 63% to 88%), and the 38 responders continued the maintenance therapy. At week 52, 4 of the 38 (10.5%) had a relapse (95% CI 3% to 25%). During 52 weeks, 34 (69.4%) of the 49 enrolled patients had a maintained improvement. Adverse events were reported in 94% of the patients; two patients (66-year-old and 76-year-old men with hypertension or diabetes) developed cerebral infarction (lacunar infarct with good recovery), and the other adverse effects were mild and resolved by the end of the study period. CONCLUSIONS: Maintenance treatment with 1.0 g/kg intravenous Ig every 3 weeks is an efficacious therapy for patients with CIDP, and approximately 70% of them had a sustained remission for 52 weeks. Thrombotic complications should be carefully monitored, particularly in elderly patients with vascular risk factors. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT01824251).

Oral soft tissue disorders are associated with gastroesophageal reflux disease: retrospective study.

BACKGROUND: Dental erosion (DE), one of oral hard tissue diseases, is one of the extraoesophageal symptoms defined as the Montreal Definition and Classification of gastroesophageal reflux disease (GERD). However, no study evaluated the relationship between GERD and oral soft tissues. We hypothesized that oral soft tissue disorders (OSTDs) would be related to GERD. The study aimed to investigate the association OSTDs and GERD. METHODS: GERD patients (105 cases), older and younger controls (25 cases each) were retrospectively examined for oral symptoms, salivary flow volume (Saxon test), swallowing function (repetitive saliva swallowing test [RSST]), teeth (decayed, missing, and filled [DMF] indices), and soft tissues (as evaluation of OSTDs, gingivitis; papillary, marginal, and attached [PMA] gingival indexes, simplified oral hygiene indices [OHI-S], and inflammatory oral mucosal regions). Clinical histories, which included body mass index [BMI], the existence of alcohol and tobacco use, and bruxism, were also investigated. A P value of <0.05 was defined as statistically significant. RESULTS: GERD patients, older and younger controls participated and aged 66.4 ± 13.0, 68.3 ± 8.2 and 28.7 ± 2.6 years old, respectively. The most common oral symptom in the GERD patients was oral dryness. Salivary flow volume and swallowing function in the GERD patients were significantly lower than in either of the controls (all P < 0.05). Inflammatory oral mucosal regions were found only in the GERD patients. The DMF indices, as a measure of dental caries, in the GERD patients were higher than in the younger controls (P < 0.001), but lower than in the older controls (P = 0.033). The PMA gingival indexes, as a measurement for gingival inflammation, and OHI-S, as a measure for oral hygiene, in the GERD patients were significantly higher than in either of the controls (all P < 0.05). Though no significant differences in BMI, the existence of alcohol and tobacco use were found, bruxism, as an exacerbation factor of periodontal disease, in the GERD patients was significantly more frequent than in either control group (P = 0.041). CONCLUSIONS: OSTDs were associated with GERD, which was similar to the association between DE and GERD.

A Study on the Relationship between Reflux Esophagitis and Periodontitis.

Objective Metabolic syndrome and dental erosion have been demonstrated to correlate with gastroesophageal acid reflux disease (GERD), while periodontitis has been reported to have a positive relationship with metabolic syndrome. However, no correlation between periodontitis and GERD has yet been reported. We therefore investigated the relationship between periodontitis and GERD. Methods The subjects consisted of 280 individuals who visited the Health Center for a detailed medical checkup examination. Each underwent upper endoscopy and periodontitis examinations, with the latter performed by measuring the concentrations of lactate dehydrogenase and hemoglobin in saliva. The subjects were divided into those with positive and negative periodontitis findings, and the prevalence rates of endoscopically proven reflux esophagitis, dyslipidemia, hypertension, and hyperglycemia were compared. Results The number of subjects positive for periodontitis was 93, while 187 had negative findings. The prevalence of reflux esophagitis was not different between the positive and negative groups (8.6% vs. 8.0%). In addition, a multiple logistic regression analysis did not identify a positive relationship between the presence of periodontitis and reflux esophagitis. On the other hand, dyslipidemia and hypertension were more frequently observed in the subjects that were positive for periodontitis. Conclusion We did not find an association between periodontitis and reflux esophagitis in the present study. On the other hand, the presence of periodontitis was found to correlate with hypertension and dyslipidemia.

[Epidemiology of Guillain-Barré Syndrome].

The epidemiologic features of the Guillain-Barré syndrome (GBS) have been reported from North America, England, Iceland, and Norway before 1979. The population incidence rates of GBS fulfilling the NINCDS (National Institute of Neurological and Communicative Disorders and Stroke) criteria in USA, Canada, Italy, Spain, and Sweden ranged from 0.62 cases to 2.66 cases per 100,000 person-years across all age groups, with a relative risk of 1.78 for males. GBS incidence increased by 20% for every 10-year increase in age. In Japan, the incidence of GBS was 1.15 per 100,000 person-years. Males were affected 1.5 times more frequently than females. The average age of patients with GBS was 39.1 ± 20.0 years, which is lesser than that in North America and Europe. The relative ratio of the occurrence of Fisher syndrome among patients with GBS was higher than that in other Asian countries.