Kinematic analysis of 24-hour recording of walking pattern in patients with vascular parkinsonism.

BACKGROUND: There is a need to define the basic characteristics of various kinematic parameters recorded during walking in patients with vascular parkinsonism (VP). The present study was designed to determine the kinematic features of walking in VP patients. For this purpose, gait acceleration and gait cycle were recorded continuously over 24-h period of daily living in VP patients, patients with Parkinson's disease (PD), and healthy subjects. METHODS: We used our newly developed 24-h monitoring device, the portable gait rhythmogram, which records gait during walking, and computes gait-induced accelerations with pattern matching algorithm. We studied nine VP patients with history of multiple lacunar infarcts (mean age ± standard deviation (SD): 72.6 ± 5.0 years, 7 men), 39 PD patients (mean age ± SD: 70.8 ± 5.8 years, 18 women), and 15 normal control subjects (mean age ± SD: 67.9 ± 4.7 years, 9 men). RESULTS: The "amount of overall movements per 24 h" was lower in VP and PD, compared with the control, with no significant differences between the two groups. Gait acceleration during walking was significantly lower (p < 0.01 in each case), while the gait cycle was the same in VP and PD patients compared with the control. CONCLUSIONS: The results suggest that deficit in force production and preservation of gait rhythm are common features of walking patterns in VP and PD patients.

Independent regulation of the cycle and acceleration in parkinsonian gait analyzed by a long-term daily monitoring system.

BACKGROUND: Few reports have objectively assessed gait patterns of Parkinson's disease (PD) patients in their daily lives. We investigated the mean gait cycle and mean gait acceleration using a portable gait rhythmogram (PGR). METHOD: We continuously recorded PGR measurements for 24 h in 64 PD patients with the ability to independently engage in activities of daily living. RESULTS: There was no significant difference in the mean gait cycle between PD patients and normal controls. However, the mean gait cycle was significantly faster in PD patients in the modified Hoehn and Yahr stage 1.5 than those in stages 2.5-3.0. The mean gait acceleration in PD patients was significantly less than in normal controls, but there were no significant differences among the stage groups. CONCLUSION: The results suggest that the cycle and acceleration of gait movements are controlled independently and that disturbances in these movements have different clinical courses in PD.

The MG-QOL15 Japanese version: validation and associations with clinical factors.

INTRODUCTION: Our study aim was to produce a Japanese translation of the 15-item Myasthenia Gravis Quality-of-Life Scale (MG-QOL15), assess its reliability and validity, and examine clinical factors affecting self-perceived QOL in MG. METHODS: We evaluated 327 consecutive patients with MG seen at six neurological centers. All patients completed the Japanese version of the MG-QOL15 (MG-QOL15-J), the Beck Depression Inventory-second edition (BDI-II), and a generic health-related QOL questionnaire, the SF-36. Disease severity was determined according to the Myasthenia Gravis Foundation of America (MGFA) quantitative MG score and the MG composite. RESULTS: The MG-QOL15-J exhibited adequate internal reliability, test-retest repeatability, and concurrent validity with SF-36, disease severity, and known-patient groups categorized by MGFA post-intervention status. Multivariate analysis revealed severity, dose of oral corticosteroids, and BDI-II as independent factors negatively affecting QOL. CONCLUSION: The MG-QOL15-J is anticipated to be a valuable clinical measure of QOL in Japanese patients with MG.

Relationship between NMO-antibody and anti-MOG antibody in optic neuritis.

BACKGROUND: Damage to astrocytes by anti-aquaporin-4 antibody (AQP4-Ab), also known as NMO antibody, has been implicated as the cause of neuromyelitis optica. Myelin oligodendrocyte glycoprotein (MOG) is well known as the causative protein of multiple sclerosis (MS). MOG antigen is currently considered as a cause of optic neuritis (ON) associated with MS because immunization with MOG antigen derived from oligodendrocytes induces murine ON with myelitis. We investigated the relationship between NMO antibody (NMO-Ab) and anti-MOG antibody (MOG-Ab) and potential in patients with ON for recovery of vision. METHODS: Thirty-three eyes of 23 patients with ON were studied. At presentation, serum NMO-Ab was measured by immunofluorescence using HEK 293 cells transfected with AQP4-GFP, and anti-MOG1-125 antibody was measured by enzyme-linked immunosorbent assay. MOG-Ab seropositivity was defined by comparing with MOG-Ab level obtained from 8 healthy normal subjects. RESULTS: Eleven (47%) of 23 ON patients were NMO-Ab seropositive, while 8 (34%) of the 23 patients were MOG-Ab seropositive. Six (26%) of 23 patients were seropositive for both NMO-Ab and MOG-Ab. Ten (43%) of 23 patients were seronegative for both antibodies. Three (50%) of 6 eyes of patients seropositive for both antibodies did not respond to corticosteroid pulse therapy and plasmapheresis, and visual acuity remained unchanged. In the NMO-Ab/MOG-Ab group, visual acuity improved significantly (P < 0.0001). In the other 3 groups (NMO-Ab/MOG-Ab, NMO-Ab/MOG-Ab, and NMO-Ab/MOG-Ab), visual acuity did not change significantly (P = 0.53, 0.42, and 0.45, respectively). CONCLUSION: NMO-Ab and MOG-Ab could be potential biomarkers to determine visual prognosis in patients with ON.

Long-term effects of cabergoline and levodopa in Japanese patients with early Parkinson's disease: a 5-year prospective study.

Several international studies have suggested that treatment of early Parkinson's disease (PD) with a dopamine agonist instead of levodopa delays the occurrence of motor complications. This 5-year prospective, open, multicenter randomized study aimed to compare the effects of cabergoline on the onset of motor complications with those of levodopa in Japanese patients with early PD. Patients who had never been treated with dopamine agonists or levodopa were enrolled in this study. Four of 45 patients in the cabergoline group and 11 of 46 patients in the levodopa group developed motor complications. The estimated cumulative incidence of motor complications in the cabergoline and levodopa groups was 17% and 34% (hazard ratio, 0.57;95% confidence interval, 0.18-1.81; p = 0.347). Thirty-five adverse events (AEs) were reported in 24 patients in the cabergoline group, while 16 AEs were reported in 13 patients in the levodopa group. Patients in the cabergoline group showed fewer motor complications than did those in the levodopa group, although the difference was not statistically significant. However, the hazard ratio found in this study was similar to those in previous reports.

Quantitative assessment of gait bradykinesia in Parkinson's disease using a portable gait rhythmogram.

To quantify gait bradykinesia during daily activity in patients with Parkinson's disease (PD), we measured movement-induced accelerations over more than 24h in 50 patients with PD and 17 age-matched normal controls, using a new device, the portable gait rhythmogram. Acceleration values induced by various movements, averaged each 10 min, exhibited a gamma distribution. The mean value of the distribution curve was used as an index of the "amount of overall movement per 24h". Characteristic changes were observed in both the gait cycle and gait acceleration. During hypokinesia, the gait cycle became either faster or slower. A number of patients with marked akinesia/bradykinesia showed a reduced and narrow range of gait acceleration, i.e., a range of floor reaction forces. The results suggest that assessment of the combination of changes in gait cycle and gait acceleration can quantitatively define the severity of gait bradykinesia.

Regional cerebral blood flow patterns in patients with freezing of gait due to lacunar infarction: SPECT study using three-dimensional stereotactic surface projections.

BACKGROUND: Although freezing of gait (FOG) is reportedly caused by cerebrovascular disease, few studies have examined its pathology. We examined regional cerebral blood flow (rCBF) patterns in patients with FOG resulting from chronic lacunar infarction using single-photon emission computed tomography (SPECT). METHODS: Among patients with chronic lacunar infarction treated at our outpatient unit, we performed N-isopropyl-p-[(123)I]-iodoamphetamine SPECT in seven patients with FOG (FOG group) and in 20 patients without FOG (non-FOG group). We analyzed and compared the SPECT data using three-dimensional stereotactic surface projections of the two groups. RESULTS: On z-score maps, the FOG group showed a significant reduction in rCBF in the bilateral anterior cingulate cortices compared with the non-FOG group. The mean z-score for the bilateral cingulate gyri was significantly higher in the FOG group than in the non-FOG group (p < .01). When the cingulate gyrus data of the anterior and posterior subregions were analyzed on a region-by-region basis, the mean z-score for the left anterior cingulate gyrus was significantly higher than that for the right cingulate gyrus (p < .05). CONCLUSION: These results suggest that anterior cingulate cortex dysfunction may be involved in the pathology of FOG in patients with chronic lacunar infarction.

Topical naphazoline in the treatment of myasthenic blepharoptosis.

INTRODUCTION: When treating ocular myasthenia gravis (MG), the risk/benefit profile of corticosteroids is unclear, and acetylcholinesterase inhibitors are not very effective. We examined the efficacy of topical naphazoline in the treatment of myasthenic blepharoptosis. METHODS: Sixty MG patients with blepharoptosis (32 with ocular symptoms only and 28 with mild generalized symptoms) were enrolled in a multicenter open trial of topical naphazoline. The effects were reported by patients via a questionnaire and were also confirmed for each patient at the clinic. RESULTS: Among 70 eyes of 60 patients, 20 eyes (28.6%) of 17 patients (28.3%) exhibited a marked response (full eye opening), and 24 eyes (34.3%) of 20 patients (33.3%) showed a good response (adequate but incomplete eye opening). Topical naphazoline was evaluated as useful in the treatment of myasthenic blepharoptosis by >70% of the patients. CONCLUSIONS: Topical naphazoline was found to be an effective supplementary symptomatic treatment for myasthenic blepharoptosis.

Fatigue in Japanese patients with Parkinson's disease: a study using Parkinson fatigue scale.

The objective of this multicenter cross-sectional study was to determine the prevalence of fatigue and factors contributing to it in a large sample of Japanese patients with Parkinson's disease (PD). We used the 16-item Parkinson Fatigue Scale (PFS-16), which was designed to assess fatigue exclusively associated with PD. We carried out this study using PFS-16, the Unified Parkinson's Disease Rating Scale, Zung's Self-Rating Depression Scale, Parkinson's Disease Sleep Scale (PDSS), and the PD quality of life (QOL) scale (PDQ-39) by interview using questionnaires and physical examination by neurologists in 361 nondemented PD patients. Fatigue (an average PFS score of 3.3 or greater) was revealed in 151 patients (41.8%). Multiple logistic regression analysis indicated that the significant independent variables related to the presence of fatigue were the scores of PDSS and PDQ-39. Depression score was not a significant contributing factor. Our study revealed that the prevalence of fatigue in Japanese PD patients is as high as that in Western countries, and that fatigue is a relatively independent symptom, although sleep disturbance may be associated with fatigue. Since fatigue is significantly related to QOL reduction, therapeutic interventions including treatment of sleep disturbance are important.

Correlation between depressive symptoms and nocturnal disturbances in Japanese patients with Parkinson's disease.

Depression and nocturnal disturbances are frequent in patients with Parkinson's disease (PD). The aim of this study was to determine the correlation between depressive symptoms and nocturnal disturbances in patients with PD in Japan. The subjects of this multi-center cross-sectional study were 188 patients with PD and 144 age-matched controls who were assessed for nocturnal disturbances by the Parkinson's disease sleep scale (PDSS) and for depressive symptoms by Zung Self-Rating Depression Scale (SDS). Depressive symptoms (SDS score of > or =40) were identified in 122 patients (64.9%). The SDS was significantly higher in PD patients than control subjects. The stepwise regression model identified PDSS (p<0.001) and Unified Parkinson's Disease Rating Scale I (mental state) (p=0.002) as significant determinants of SDS. Stepwise regression analysis identified item 15 (daytime sleepiness) (p=0.002), item 13 (early morning tremor) (p=0.008), item 12 (nocturnal dystonia) (p=0.015), and item 3 (sleep maintenance insomnia) (p=0.026) as significant predictors of SDS. Our results indicated that depressive symptoms in PD correlate significantly with nocturnal disturbances, and that daytime sleepiness, dystonia, tremor and sleep fragmentation are the most common nocturnal disturbances in depressed patients with PD.

Postural Abnormality in Parkinson's Disease: A Large Comparative Study With General Population.

BACKGROUND: Postural abnormalities in Parkinson's disease (PD) patients and unimpaired elderly are not well differentiated. Factors related to postural abnormality associated with PD are controversial. OBJECTIVE: We assessed differences in postural change between PD patients and unimpaired elderly and elucidated factors related to abnormal posture in PD patients. METHODS: We measured the dropped head angle (DHA), anterior flexion angle (AFA), and lateral flexion angle (LFA) of the thoracolumbar spine of an unprecedented 1,117 PD patients and 2,732 general population participants (GPPs) using digital photographs. Two statistical analyses were used for elucidating factors related to these angles. RESULTS: In GPPs, age was correlated with DHA, AFA, and LFA. DHAs, AFAs, and LFAs of PD patients and age-matched GPPs were 21.70° ± 14.40° and 13.13° ± 10.79°, 5.98° ± 12.67,°and - 3.82° ± 4.04°, and 0.86° ± 4.25° and 1.33° ± 2.16°, respectively. In PD patients, factors related to DHA were age, male sex, and H & Y stage during ON time. Factors related to AFA were age, duration of disease, H & Y stage during ON and OFF times, pain, vertebral disease, and bending to the right. A factor related to LFA was AFA. CONCLUSIONS: DHA and AFA of GGPs correlated with age and were larger in PD patients than those with in GPPs. Some PD patients showed angles far beyond the normal distribution. Thus, factors associated with disease aggravation affected postural abnormality in PD patients.

Excessive daytime sleepiness and sleep episodes in Japanese patients with Parkinson's disease.

In Parkinson's disease (PD), sudden unexpected sleep episodes and excessive daytime sleepiness (EDS) while driving and engaging in social activities are important problems. We conducted a multi-center study to clarify the prevalence and contributing factor of EDS and sleep episodes in Japanese patients with PD. We evaluated 188 patients with PD (85 men, 103 women) and 144 age-matched controls for sleepiness. EDS was defined as an Epworth sleepiness scale (ESS) score of >or=10. ESS score was significantly higher (6.6+/-4.2 vs. 5.6+/-3.8) and prevalence of sleep episodes was higher in PD than in controls (6.4% vs. 0.7%). PD patients with EDS were more likely to have sleep episodes (22.5% vs. 2.0%), higher score for disease severity and depressive symptoms, and on higher dose of dopaminergic agents than those without EDS. However, there were no differences in nocturnal disturbances between the two groups. ESS score was not different between patients taking ergot and non-ergot dopamine agonists. Logistic regression analysis demonstrated that mental state, total dose of dopaminergic agents, and ESS score were significant predictors of sleep episodes. ESS score of >or=10 had 75% sensitivity and 82.4% specificity for sleep episodes. These results suggest that sleepiness in PD is dependent on disease itself and dopaminergic treatment rather than nocturnal disturbances.

Treatment of Myasthenia Gravis With High-Dose Cholinesterase Inhibitors and Calcineurin Inhibitors Caused Spontaneous Muscle Cramps in Patients.

OBJECTIVES: The objective of this study was to investigate the influence of treatment with cholinesterase inhibitors (ChEIs) and calcineurin inhibitors (CNIs) on the occurrence of cramps in myasthenia gravis (MG) patients. METHODS: The frequency and duration of cramp and serum electrolytes were evaluated in 81 patients with MG. The patients were classified using Myasthenia Gravis Foundation of America postintervention status scores based on the treatment and the responsiveness to the treatment. Quantitative MG score, MG activities of daily living score, MG composite score, or MG quality of life 15 score was used to assess the health-related quality of life (QOL). RESULTS: Muscle cramps developed in 44 (54.3%) of 81 MG patients. The scores of MG activities of daily living, MG composite, or MG-QOL 15-item questionnaire in patients with cramp were significantly higher than those in patients without cramps (P = 0.002, P = 0.01, or P = 0.0022, respectively). The serum magnesium concentrations were lower in patients treated with CNI (n = 16) than in those not treated with CNI (n = 65) (P = 0.002). The probability of cramps was significantly higher in patients treated with ChEIs (≥180 mg/d) in addition to CNI than in patients who were treated with a low dose of ChEIs (≤60 mg/d) without concomitant CNI treatment (P = 0.017). CONCLUSIONS: Our data suggested that treatment with a high dose of ChEI and CNI accelerated the probability of cramps and reduced the QOL in MG patients.

Characteristics of sleep disturbances in Japanese patients with Parkinson's disease. A study using Parkinson's disease sleep scale.

The present multicenter cross-sectional study was performed using semistructured questionnaires to determine the contributing factors of sleep disturbances in Japanese patients with Parkinson's disease (PD). We used the Parkinson's disease sleep scale (PDSS, Japanese version). All data were obtained by means of interviewed questionnaire and physical examination by neurologists. The study was carried out between April 2005 and December 2005 at eight university hospitals and affiliated facilities in the Kanto area of Japan. A total of 188 (85 men and 103 women) PD patients and 144 controls (64 men and 80 women) were included. Stepwise regression analysis identified complications of treatment, depression, age, and disease duration as significant risk factors of sleep disturbances in PD. Significant differences in total PDSS score were observed between Hoehn & Yahr (H&Y) Stages 1 and 4, between H&Y Stages 2 and 4, and between H&Y stages 3 and 4 (Bonferroni test). The results of this survey suggested that complications due to treatment (dyskinesia, wearing off, on-off), depressive state, and disease stage are significant determinants of sleep disorders in Japanese patients with PD. We speculate that the reduction of neurotransmitters involved in the sleep-wakefulness mechanism and degeneration of neurons progress together in parallel with deterioration of motor function.

New semiquantitative assessment of 123I-FP-CIT by an anatomical standardization method.

UNLABELLED: We evaluated a new semiquantitative procedure to more easily and objectively estimate the striatal uptake of 123I-FP-CIT in patients with Parkinsonian syndrome (PS) and essential tremor (ET), using an anatomical standardization method, the Neurostat. METHODS: Eleven patients with PS and 8 with ET were examined by clinical assessment and 123I-FP-CIT SPECT imaging. The modified Hoehn and Yahr Staging Scale and Unified Parkinson's Disease Rating Scale (UPDRS) were used to assess the stage and severity of the disease. The co-registered MR and SPECT images were created with fusion software included in Neurostat. On the cross section, which shows the largest area of striate, irregular shaped regions of interest corresponding to the striate and occipital cortex were drawn. Then the ratio of specific striatal uptake to non-specific occipital cortex, V3"(F), was calculated. Another calculation was done by VOIClassic, which is a software included in Neurostat to estimate the counts per voxel of anatomically defined regions such as caudate nucleus, putamen, occipital cortex, and total cortex. Using these count data, the ratio of specific striatal uptake to non-specific occipital cortex, V3"(OC), and total cortex, V3"(TC), was calculated. RESULTS: A fair linear correlation was observed between V3"(OC) and V3"(F) (y = 1.53x + 1.40; r = 0.756; p < 0.01), as well as between V3"(TC) and V3"(F) (y = 1.24x + 1.43; r = 0.713; p < 0.01). Both V3"(OC) and V3"(TC) yielded similar tendencies. Concerning discrimination between ET and PS, there was a significant difference between the mean V3" of PS and ET (p < 0.01). Concerning the correlation between V3" value and the severity of PS, the UPDRS motor score significantly correlated with the V3"(F) value (rs = -0.816). However, V3"(OC) and V3"(TC) correlated less with UPDRS (rs = -0.667 and -0.645, respectively). CONCLUSIONS: Semiquantitative parameters, V3"(OC) and V3"(TC), calculated by VOIClassic including the Neurostat system are useful and easily calculable parameters as well as V3"(F) for the differential diagnosis of PS from ET.

Transthyretin Val 107 in a Japanese patient with familial amyloid polyneuropathy.

A 70-year-old Japanese man with amyloid polyneuropathy associated with a Val 107 transthyretin (TTR) mutation is reported. The patient presented with carpal tunnel syndrome, cardiomyopathy, bulbar palsy, dysphonia and polyneuropathy. DNA analysis of the TTR gene revealed a point mutation responsible for substitution of valine for isoleucine at position 107 of the TTR molecule. Taken together with reports of patients with the same TTR variant, Val 107 TTR mutation is probably associated with a clinical phenotype characterized by carpal tunnel syndrome, cardiomyopathy, bulbar palsy and dysphonia. This case implies a worldwide distribution of the Val 107 TTR mutation with a common clinical phenotype, despite different ethnic background.

[A case of migrainous infarction accompanying idiopathic thrombocytopenic purpura].

We reported a 31 year-old man with repeated episodes of migraine at a frequency of about once a week on and after January, 2000. In January 2001, scintillating scotoma and pulsating headache appeared followed by left hemianopsia. His platelet count decreased to 80,000/microliter and high intensity areas were observed in the right occipital lobe and hippocampal gyrus on the FLAIR image of brain MRI. Subsequently performed brain MRA and vertebral angiography revealed segmental stenosis and obstruction in the right posterior cerebral artery. Under the diagnosis of migrainous infarction, sodium ozagrel and lomerizine hydrochloride were administered. Idiopathic thrombocytopenic purpura was additionally diagnosed based on the decreased platelet count which was then treated with predonisolone. After these treatment, his migraine attack disappeared. In this patient, platelet destruction due to idiopathic thrombocytopinic purpura and subsequent release of serotonin seemed to have involved in the occurrence of migrainous infarction.

[A case presenting vertical one-and-a-half syndrome and seesaw nystagmus due to thalamomesencephalic infarction].

A 58-year-old woman presented, conjugate upgaze palsy and monocular paresis of downward gaze in the ipsilateral eye (vertical one-and-a-half syndrome; VOHS) as well as seesaw nystagmus (SSN). Vertical oculocephalic response and conjugate horizontal gaze were preserved. Magnetic resonance imaging revealed a right thalamo-mesencephalic infarction including the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal. On the 22nd hospital day SSN was disappeared, and then on the 32nd day VOHS was improved. The lesions of VOHS may have affected the efferent tracts of riMLF and the descending fibres to the ipsilateral subnucleus of the inferior rectus and contralateral subnucleus of the superior oblique. Furthermore, it was assumed that SSN was caused simultaneously by a lesion in the interstitial nucleus of Cajal existing in the adjacent area of riMLF.

Human turnover dynamics during sleep: statistical behavior and its modeling.

Turnover is a typical intermittent body movement while asleep. Exploring its behavior may provide insights into the mechanisms and management of sleep. However, little is understood about the dynamic nature of turnover in healthy humans and how it can be modified in disease. Here we present a detailed analysis of turnover signals that are collected by accelerometry from healthy elderly subjects and age-matched patients with neurodegenerative disorders such as Parkinson's disease. In healthy subjects, the time intervals between consecutive turnover events exhibit a well-separated bimodal distribution with one mode at ⩽10 s and the other at ⩾100 s, whereas such bimodality tends to disappear in neurodegenerative patients. The discovery of bimodality and fine temporal structures (⩽10 s) is a contribution that is not revealed by conventional sleep recordings with less time resolution (≈30 s). Moreover, we estimate the scaling exponent of the interval fluctuations, which also shows a clear difference between healthy subjects and patients. We incorporate these experimental results into a computational model of human decision making. A decision is to be made at each simulation step between two choices: to keep on sleeping or to make a turnover, the selection of which is determined dynamically by comparing a pair of random numbers assigned to each choice. This decision is weighted by a single parameter that reflects the depth of sleep. The resulting simulated behavior accurately replicates many aspects of observed turnover patterns, including the appearance or disappearance of bimodality and leads to several predictions, suggesting that the depth parameter may be useful as a quantitative measure for differentiating between normal and pathological sleep. These findings have significant clinical implications and may pave the way for the development of practical sleep assessment technologies.

Japanese cases of neuromyelitis optica spectrum disorder associated with myasthenia gravis and a review of the literature.

BACKGROUND: The incidence of concurrent myasthenia gravis (MG) and neuromyelitis optica spectrum disorder (NMOSD) is higher than what chance predicts, yet it remains unclear why MG and NMOSD appear concurrently. OBJECTIVE: The purpose of the present study was to examine the clinical features of the concurrence of these diseases. METHODS: Clinical details were analyzed retrospectively. RESULTS: Three (0.5%) out of 631 MG patients had confirmed (n=2) or suspected (n=1) NMOSD. Two of these patients were women. All showed early-onset MG (EOMG) that preceded NMOSD and were positive for acetylcholine receptor antibody (AChR-Ab). Two patients were tested for aquaporin 4 antibody (AQP4-Ab) and were positive. Two patients were treated with a thymectomy that preceded NMOSD. Two patients had decreased frequency of regulatory T (Treg) cells. We identified in the literature 46 patients with both MG and NMOSD. Our results of female predominance, EOMG, MG preceding NMOSD, and positive AChR-Ab are consistent with previous descriptions. CONCLUSIONS: This is the first report to examine the frequency of NMOSD in Japanese patients with MG. The reduction and/or dysfunction of Treg cells may be one cause of NMOSD development in MG.