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.

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.

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.

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.

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.

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.

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.

Sulfatide accumulation in the dystrophic terminals of gracile axonal dystrophy mice: lipid analysis using matrix-assisted laser desorption/ionization imaging mass spectrometry.

The gracile axonal dystrophy (gad) mutation in Uch-l1, the gene encoding the ubiquitin carboxy-terminal hydrolase isozyme L1 (UCH-L1), causes selective dying back degeneration of dorsal root ganglion neuron in the medulla oblongata along with progressive sensory-motor ataxia. Axonal spheroids are observed within degenerating axons, and their contents may illuminate the pathogenic mechanisms leading to neurodegeneration in gad mice. To analyze changes in negatively charged lipid molecules in dystrophic axons of gad mice, we performed matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS), electron microscopy, and fluorescence immunohistochemistry on tissue sections from gad and wild-type mouse medulla. MALDI-IMS revealed that m/z 806.68 and 822.68 molecules, assigned to sulfatide (ST) C18:0 and ST C18:0(OH), respectively, were concentrated in the dorsomedial medulla. This spatial distribution overlapped significantly with that of axonal spheroids. Immunostaining revealed that spheroids accumulated myelin and lymphocyte protein, a known ST binding protein. Sulfatides with short-chain fatty acids (C16-C20) are generally localized in intracellular vesicles; therefore, ST C18:0 accumulation may reflect intracellular vesicle aggregation within spheroids. Ubiquitin system disruption apparently alters lipid metabolism, membrane organization, protein turnover, and axonal transport. Changes in membrane organization, particularly STs within lipid rafts, may disrupt cellular signaling pathways necessary for neuronal viability.

Bone marrow mononuclear cells promote proliferation of endogenous neural stem cells through vascular niches after cerebral infarction.

Increasing evidence shows that administration of bone marrow mononuclear cells (BMMCs) is a potential treatment for various ischemic diseases, such as ischemic stroke. Although angiogenesis has been considered primarily responsible for the effect of BMMCs, their direct contribution to endothelial cells (ECs) by being a functional elements of vascular niches for neural stem/progenitor cells (NSPCs) has not been considered. Herein, we examine whether BMMCs affected the properties of ECs and NSPCs, and whether they promoted neurogenesis and functional recovery after stroke. We compared i.v. transplantations 1 x 10(6) BMMCs and phosphate-buffered saline in mice 2 days after cortical infarction. Systemically administered BMMCs preferentially accumulated at the postischemic cortex and peri-infarct area in brains; cell proliferation of ECs (angiogenesis) at these regions was significantly increased in BMMCs-treated mice compared with controls. We also found that endogenous NSPCs developed in close proximity to ECs in and around the poststroke cortex and that ECs were essential for proliferation of these ischemia-induced NSPCs. Furthermore, BMMCs enhanced proliferation of NSPCs as well as ECs. Proliferation of NSPCs was suppressed by additional treatment with endostatin (known to inhibit proliferation of ECs) following BMMCs transplantation. Subsequently, neurogenesis and functional recovery were also promoted in BMMCs-treated mice compared with controls. These results suggest that BMMCs can contribute to the proliferation of endogenous ischemia-induced NSPCs through vascular niche regulation, which includes regulation of endothelial proliferation. In addition, these results suggest that BMMCs transplantation has potential as a novel therapeutic option in stroke treatment.

[A case of muscle sodium channelopathy with markedly high value of serum creatine kinase and mild eyelid myotonia].

We report on a Japanese 13-year-old male without a family history of muscle disease admitted to our hospital due to an elevated serum creatine kinase. From the age of 3 he was complaining of muscle stiffness during and after exercise. At the age of 7 he experienced muscle stiffness and weakness during long-distance running, which would continue till the next day, disappearing only after resting for a day. Upon examination, we noted that repeated eyelid contractions induced myotonia that increased in the cold. Electromyography revealed myotonic discharge in the tongue muscle. Genetic analysis revealed a mutation of Nav1.4, M1592V. Although this mutation had originally been reported in families with Hyperkalemic periodic paralysis (Hyper PP), we diagnosed as paramyotonia congenita due to the symptoms of exercise and cold-induced myotonia without an attack of generalized weakness. This case suggest that sodium channelopathy is very rare, but should be considered in the differential diagnosis of an elevation of serum creatine kinase even if coexisting myotonia is only mild.

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.

Mice lacking the schizophrenia-associated protein FEZ1 manifest hyperactivity and enhanced responsiveness to psychostimulants.

FEZ1 (fasciculation and elongation protein zeta 1), a mammalian ortholog of Caenorhabditis elegans UNC-76, interacts with DISC1 (disrupted in schizophrenia 1), a schizophrenia susceptibility gene product, and polymorphisms of human FEZ1 have been associated with schizophrenia. We have now investigated the role of FEZ1 in brain development and the pathogenesis of schizophrenia by generating mice that lack Fez1. Immunofluorescence staining revealed FEZ1 to be located predominantly in gamma-aminobutyric acid-containing interneurons. The Fez1(-/-) mice showed marked hyperactivity in a variety of behavioral tests as well as enhanced behavioral responses to the psychostimulants MK-801 and methamphetamine. In vivo microdialysis revealed that the methamphetamine-induced release of dopamine in the nucleus accumbens was exaggerated in the mutant mice, suggesting that enhanced mesolimbic dopaminergic transmission contributes to their hyperactivity phenotype. These observations implicate impairment of FEZ1 function in the pathogenesis of schizophrenia.

Anti-aquaporin-4 antibody induces astrocytic cytotoxicity in the absence of CNS antigen-specific T cells.

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Anti-aquaporin-4 antibody (AQP4-Ab) is a highly specific serum autoantibody that is detected in patients with NMO. Several lines of evidence indicate that AQP4-Ab not only serves as a disease marker but also plays a pivotal role in the pathogenesis of NMO. Although the pathogenicity of AQP4-Ab in vivo has recently been demonstrated, the presence of CNS antigen-specific T cells is recognized as a prerequisite for the antibody to exert pathogenic effects. Thus, it remains unclear whether AQP4-Ab is the primary cause of the disease or a disease-modifying factor in NMO. Here we report that pre-treatment with complete Freund's adjuvant (CFA) alone is sufficient for AQP4-Ab to induce astrocytic damage in vivo. Our results show the primary pathogenic role of AQP4-Ab in the absence of CNS antigen-specific T cells, and suggest that danger signals provided by nonspecific inflammation can be a trigger for those who harbor the autoantibody to develop NMO.

Immunodeficiency reduces neural stem/progenitor cell apoptosis and enhances neurogenesis in the cerebral cortex after stroke.

Acute inflammation in the poststroke period exacerbates neuronal damage and stimulates reparative mechanisms, including neurogenesis. However, only a small fraction of neural stem/progenitor cells survives. In this report, by using a highly reproducible model of cortical infarction in SCID mice, we examined the effects of immunodeficiency on reduction of brain injury, survival of neural stem/progenitor cells, and functional recovery. Subsequently, the contribution of T lymphocytes to neurogenesis was evaluated in mice depleted for each subset of T lymphocyte. SCID mice revealed the reduced apoptosis and enhanced proliferation of neural stem/progenitor cells induced by cerebral cortex after stroke compared with the immunocompetent wild-type mice. Removal of T lymphocytes, especially the CD4(+) T-cell population, enhanced generation of neural stem/progenitor cells, followed by accelerated functional recovery. In contrast, removal of CD25(+) T cells, a cell population including regulatory T lymphocytes, impaired functional recovery through, at least in part, suppression of neurogenesis. Our findings demonstrate a key role of T lymphocytes in regulation of poststroke neurogenesis and indicate a potential novel strategy for cell therapy in repair of the central nervous system.

Endothelial cells support survival, proliferation, and neuronal differentiation of transplanted adult ischemia-induced neural stem/progenitor cells after cerebral infarction.

Transplantation of neural stem cells (NSCs) has been proposed as a therapy for a range of neurological disorders. To realize the potential of this approach, it is essential to control survival, proliferation, migration, and differentiation of NSCs after transplantation. NSCs are regulated in vivo, at least in part, by their specialized microenvironment or "niche." In the adult central nervous system, neurogenic regions, such as the subventricular and subgranular zones, include NSCs residing in a vascular niche with endothelial cells. Although there is accumulating evidence that endothelial cells promote proliferation of NSCs in vitro, there is no description of their impact on transplanted NSCs. In this study, we grafted cortex-derived stroke-induced neural stem/progenitor cells, obtained from adult mice, onto poststroke cortex in the presence or absence of endothelial cells, and compared survival, proliferation, and neuronal differentiation of the neural precursors in vivo. Cotransplantation of endothelial cells and neural stem/progenitor cells increased survival and proliferation of ischemia-induced neural stem/progenitor cells and also accelerated neuronal differentiation compared with transplantation of neural precursors alone. These data indicate that reconstitution of elements in the vascular niche enhances transplantation of adult neural progenitor cells.

[A woman with cerebellar ataxia and hypergonadotropic hypogonadism].

A 26-year-old woman with primary amenorrhea in association with hypergonadotropinism, and lacking a vagina and uterus, suffered from a gradually progressive gait disturbance in her adolescence. The patient has no family history of ataxia and a chromosome study showed a normal karyotype (46,XX). Using the revised Hasegawa Dementia Scale, her cognitive function was measured as that of a normal adult, however, neurological examination revealed symptoms of scanning speech, horizontal gaze-evoked nystagmus, and ataxia. Bulging eyes, high-arched palate, scoliosis and ventricular septal defect were also observed. A brain MRI showed atrophy of the cerebellum. A 123I-IMP brain SPECT study showed hypoperfusion in the cerebellum. Previous studies show that among patients with cerebellar ataxia and hypergonadotropic hypogonadism, some show an autosomal recessive inheritance, while others have no family history. As a cause, a chromosomal abnormality is unlikely because all reported karyotypes were normal. This case is different from other reported cases in that she is not mentally impaired or deaf. The present case indicates that there is a close relationship between cerebellar ataxia and hypogonadism, and that other symptoms such as deafness and mental impairment could be an additional variable in patients with cerebellar ataxia arid hypergonadotropic hypogonadism.

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.