桑原 聡

OBJECTIVE: To describe the heterogeneity of electrodiagnostic (EDx) studies in Guillain-Barré syndrome (GBS) patients collected as part of the International GBS Outcome Study (IGOS). METHODS: Prospectively collected clinical and EDx data were available in 957 IGOS patients from 115 centers. Only the first EDx study was included in the current analysis. RESULTS: Median timing of the EDx study was 7 days (interquartile range 4-11) from symptom onset. Methodology varied between centers, countries and regions. Reference values from the responding 103 centers were derived locally in 49%, from publications in 37% and from a combination of these in the remaining 15%. Amplitude measurement in the EDx studies (baseline-to-peak or peak-to-peak) differed from the way this was done in the reference values, in 22% of motor and 39% of sensory conduction. There was marked variability in both motor and sensory reference values, although only a few outliers accounted for this. CONCLUSIONS: Our study showed extensive variation in the clinical practice of EDx in GBS patients among IGOS centers across the regions. SIGNIFICANCE: Besides EDx variation in GBS patients participating in IGOS, this diversity is likely to be present in other neuromuscular disorders and centers. This underlines the need for standardization of EDx in future multinational GBS studies.

The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. To clarify the association between individual variations in behavioral inhibition system and brain 5-HT2A receptor availability and specify which brain networks were involved in healthy male subjects, using [18F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. Behavioral inhibition system score negatively correlated with 5-HT2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. Individuals with high behavioral inhibition system displays low 5-HT2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion.

BACKGROUND: Since June 2013, Japan has suspended proactive recommendation of human papillomavirus (HPV) vaccination due to self-reported diverse symptoms, including pain and motor dysfunction, as possible serious adverse events following immunization. Although these symptoms may be seen in adolescents without HPV vaccination, their frequency, taking into account disease severity, has not been examined. METHODS: A two-stage, descriptive, nationwide epidemiological survey was conducted in 2016, with a 6-month target period from July 1 to December 31, 2015, to estimate the prevalence and incidence of diverse symptoms among Japanese adolescents without HPV vaccination. Participants were 11,037 medical departments in hospitals selected nationwide by stratified random sampling. Eligible patients had to satisfy four criteria: (1) aged 12-18 years upon visiting hospital; (2) having at least one of four symptoms/disorders (pain or sensory dysfunction, motor dysfunction, autonomic dysfunction, or cognitive impairment); (3) symptoms/disorders persisting for at least 3 months; and (4) both criteria (2) and (3) influence attendance at school or work. We then extracted data of patients with diverse symptoms similar to those after HPV vaccination while considering opinions of doctors in charge. RESULTS: Estimated 6-month period prevalence of diverse symptoms among girls aged 12-18 years without HPV vaccination was 20.2 per 100,000. Annual incidence was estimated to be 7.3 per 100,000. CONCLUSION: Adolescent Japanese girls without HPV vaccination also visited hospitals with diverse symptoms similar to those following HPV vaccination. Our findings predict the medical demands for coincident diverse symptoms, which are temporally associated with but not caused by HPV vaccination of Japanese adolescents.

BACKGROUND: The Movement Disorders Society (MDS)-Unified Parkinson's Disease Rating Scale (UPDRS) is increasingly used to assess motor dysfunction before and after subthalamic nucleus deep brain stimulation (STN-DBS). OBJECTIVES: We, therefore, investigated whether the MDS-UPDRS can detect longitudinal changes in motor function after STN-DBS in the same way as UPDRS. METHODS: We examined 21 patients with Parkinson's disease (PD) (mean age 59.2 ± 10.6 years, mean disease duration 12.0 ± 3.0 years) who underwent STN-DBS and whose motor functions were assessed by the UPDRS and MDS-UPDRS before, 3 months after, and 1 year after STN-DBS. We then evaluated the consistency between the scores of Parts II and III of the UPDRS and MDS-UPDRS during the off phase using Lin's concordance coefficient (LCC) and a Bland-Altman plot. RESULTS: The scores of Parts II and III of both the UPDRS and MDS-UPDRS were significantly decreased 3 months and 1 year after STN-DBS during the off phase. Scores of the UPDRS and MDS-UPDRS showed significant positive correlations before and after STN-DBS. We calculated estimated MDS-UPDRS scores from the UPDRS scores using a regression line and calculated the LCC between the MDS-UPDRS and the estimated MDS-UPDRS scores. The LCC value was 0.59-0.91, which suggests a relatively high consistency between the UPDRS and MDS-UPDRS. The Bland-Altman plot showed that differences between both scores were basically within ±1.96 standard deviations of the difference. CONCLUSION: The present preliminary study indicated that the utility of the MDS-UPDRS in evaluating motor function before and after STN-DBS demonstrates its potential equivalency to the UPDRS.

Frontotemporal brain sagging syndrome (FBSS) is a progressive disorder characterized by symptoms similar to the behavioral variant of frontotemporal dementia (FTD), with a sagging appearance of the brain on imaging similar to that observed in spontaneous intracranial hypotension (SIH). The onset of behavioral and cognitive symptoms of FBSS is insidious and progressive, similar to those of FTD. Here, we report a case involving a 53-year-old man with progressive hypersomnolence, apathy, forgetfulness, and personality changes but without headache or auditory symptoms. The combination of frontotemporal dysfunction, hypersomnolence, and the appearance of a sagging brain on magnetic resonance imaging suggested a diagnosis of FBSS. Although a definite site of cerebrospinal fluid leakage could not be identified in our case, clinical symptoms and imaging findings were improved after an epidural blood patch. Considering FBSS as a differential diagnosis of FTD is important even in the absence of typical SIH symptoms, such as headache or auditory symptoms.

Taq1A polymorphism is a DRD2 gene variant located in an exon of the ANKK1 gene and has an important role in the brain's dopaminergic functions. Some studies have indicated that A1 carriers have an increased risk of developing Parkinson's disease (PD) and show poorer clinical performance than A2 homo carriers. Previous studies have suggested that A1 carriers had fewer dopamine D2 receptors in the caudate and increased cortical activity as a compensatory mechanism. However, there is little information about morphological changes associated with this polymorphism in patients with PD. The study's aim was to investigate the relationship between brain volume and Taq1A polymorphism in PD using voxel-based morphometry (VBM). Based on Taq1A polymorphism, 103 patients with PD were divided into two groups: A1 carriers (A1/A1 and A1/A2) and A2 homo carriers (A2/A2). The volume of the left prefrontal cortex (PFC) was significantly decreased in A2 homo carriers compared to A1 carriers. This finding supports the association between Taq1A polymorphism and brain volume in PD and may explain the compensation of cortical function in A1 carriers with PD.

BACKGROUND: The standardized T1-weighted/T2-weighted (sT1w/T2w) ratio for the middle cerebellar peduncle (MCP) has been reported to be sensitive for detecting degenerative changes in the cerebellar subtype of multiple system atrophy (MSA-C), even in the early stages. We aimed to investigate the diagnostic value of the MCP sT1w/T2w ratio for differentiating between MSA-C and spinocerebellar ataxia (SCA). METHODS: We included 32 MSA-C, 8 SCA type 3 (SCA3), 16 SCA type 6 (SCA6) patients, and 17 controls, and the MCP sT1w/T2w ratio was analyzed using a region-of-interest approach. The diagnostic performance of the MCP sT1w/T2w ratio in discriminating among MSA-C, SCA3, and SCA6 was assessed and compared with diagnosis based on visual interpretation of MCP hyperintensities and the "hot cross bun" (HCB) sign. RESULTS: MCP sT1w/T2w ratio values were markedly lower in patients with MSA-C than in those with SCA3, those with SCA6, and controls (p < 0.001). The MCP sT1w/T2w ratio showed high diagnostic accuracy for distinguishing MSA-C from SCA3 (area under curve = 0.934), SCA6 (area under curve = 0.965), and controls (area under curve = 0.980). The diagnostic accuracy of the MCP sT1w/T2w ratio for differentiating MSA-C from SCA3 or SCA6 (90.0% for MSA-C vs. SCA3, and 91.7% for MSA-C vs. SCA6) was comparable to or superior than that of visual interpretation of MCP hyperintensities (80.0-87.5% in MSA-C vs. SCA3 and 87.6-97.9% in MSA-C vs. SCA6) or the HCB sign (72.5-80.0% in MSA-C vs. SCA3 and 77.1-93.8% in MSA-C vs. SCA6). CONCLUSIONS: The MCP sT1w/T2w ratio might be a sensitive imaging-based marker for detecting MSA-C-related changes and differentiating MSA-C from SCA3 or SCA6.

Objective Immunomodulatory drugs and proteasome inhibitors are therapeutic options for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. This study aimed to evaluate the efficacy and safety of the combination of ixazomib, lenalidomide, and dexamethasone (IRd) for POEMS syndrome. Methods Six consecutive patients with POEMS syndrome who were treated with the IRd regimen at Chiba University Hospital between April 2018 and August 2021 were included. Serum M-protein and serum vascular endothelial growth factor (sVEGF) levels, overall neuropathy limitation scales (ONLS), clinical symptoms, and adverse events were assessed. Results Of the six patients, five had received prior treatments. Patients received a median of 5 cycles (range, 3-28 cycles) of IRd. Following treatment, serum M-protein disappeared in two patients, sVEGF levels returned to normal in two patients, two patients showed a reduction in the ONLS of 1, and clinical symptoms improved in four patients. The median level of sVEGF decreased from 2,395 pg/mL (range, 802-6,120 pg/mL) to 1,428 pg/mL (range, 183-3,680 pg/mL) in three months. Adverse events, including rash, neutropenia, sensory peripheral neuropathy, and nausea, were observed in three patients, which necessitated dose reduction or discontinuation of treatment. Conclusion IRd can be a therapeutic option for POEMS syndrome, albeit with careful monitoring of adverse events.

Objective: Fatigue is a major disabling problem in patients with neuromuscular disorders. Both nerve demyelination and increased axonal branching associated with collateral sprouting reduce the safety factor for impulse transmission and could cause activity-dependent hyperpolarization and conduction block during voluntary contraction, and thus fatigue. This study aimed to investigate whether activity-dependent conduction block is associated with fatigue in demyelinating neuropathies and lower motor neuron disorders. Methods: This study included 31 patients (17 with chronic inflammatory demyelinating polyneuropathy [CIDP] and 14 with spinal and bulbar muscular atrophy [SBMA]). Sixteen healthy subjects served as normal controls. Fatigue was assessed using the Fatigue Scale for Motor and Cognitive Functions (FSMC). Compound muscle action potential (CMAP) recording and nerve excitability testing after median nerve stimulation in the wrist were performed before and after maximal voluntary contraction of the abductor pollicis brevis for 1 min. Results: Patients with CIDP/SBMA had prominent fatigue with higher FSMC motor scores (P < 0.0001) than normal controls. After voluntary contractions, CMAP amplitudes decreased significantly in four of the 17 patients with CIDP and one of the 14 patients with SBMA. The reduction in CMAP amplitude was associated with the fatigue score in the motor but not in the cognitive domain. After voluntary contraction, excitability testing showed axonal hyperpolarization in the normal and CIDP/SBMA groups. Conclusions: In CIDP or SBMA, fatigue is caused by voluntary contraction-induced membrane hyperpolarization and conduction block, presumably due to the critically lowered safety factor due to demyelination or increased axonal branching. Significance: Peripheral fatigue can be objectively assessed using CMAP amplitudes and nerve excitability testing.

OBJECTIVE: To investigate longitudinal brain atrophy in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We investigated the longitudinal brain atrophy rate in patients with aquaporin-4 antibody-positive NMOSD (AQP4+NMOSD) and those with multiple sclerosis (MS) in a retrospective cohort study. Brain volume was calculated with statistical parametric mapping-12. RESULTS: We enrolled 36 patients with AQP4+NMOSD and 60 with MS. Patients with NMOSD were older and had a higher Kurtzke's expanded disability status scale score at baseline MRI compared with those with MS. Disease duration, annual relapse rate and intervals from the last attack and from disease-modifying drugs initiation were not significantly different between the two groups. Lower normalised lesion volume and higher normalised white matter volume were found in patients with NMOSD compared with those with MS at baseline MRI. However, the annualised atrophy rate of normalised brain volume was similar between the NMOSD (median 0.47; IQR 0.75; p=0.49) and MS (median 0.46; IQR 0.84) groups. After adjustment of age and the presence of clinical relapse, no differences of the annualised atrophy rate of normalised brain volume also were found for NMOSD and MS. Patients with AQP4+NMOSD with long cord lesion showed higher annualised atrophy rate of normalised grey matter volume compared with those without long cord lesion. CONCLUSIONS: Silent progression of brain atrophy was present in patients with AQP4+NMOSD, as shown in patients with MS, even in the clinically inactive age-matched cases. Subclinical dying back degeneration may explain the brain atrophy in patients with AQP4 +NMOSD.

DNAJC7 has recently been identified as an amyotrophic lateral sclerosis (ALS) gene via large-scale exome analysis, and its involvement in ALS is still unclear in various populations. This study aimed to determine the frequencies and characteristics of the DNAJC7 variants in a Japanese ALS cohort. A total of 807 unrelated Japanese patients with sporadic ALS were screened via exome analysis. In total, we detected six rare missense variants and one splice-site variant of the DNAJC7 gene, which are not reported in the Japanese public database. Furthermore, the missense variants are located around the TPR domain, which is important for the function of DNAJC7. The total frequency of the DNAJC7 variants in Japanese ALS patients was estimated at 0.87%. Collectively, these results suggest that variants of DNAJC7 are rare cause of Japanese patients with sporadic ALS.

OBJECTIVE: To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs). RESULTS: Statements were prepared according to the GRADE Evidence-to-Decision frameworks. Typical CIDP and CIDP variants were distinguished. The previous term "atypical CIDP" was replaced by "CIDP variants" because these are well characterized entities (multifocal, focal, distal, motor, or sensory CIDP). The levels of diagnostic certainty were reduced from three (definite, probable, possible CIDP) to only two (CIDP and possible CIDP), because the diagnostic accuracy of criteria for probable and definite CIDP did not significantly differ. Good Practice Points were formulated for supportive criteria and investigations to be considered to diagnose CIDP. The principal treatment recommendations were: (a) intravenous immunoglobulin (IVIg) or corticosteroids are strongly recommended as initial treatment in typical CIDP and CIDP variants; (b) plasma exchange is strongly recommended if IVIg and corticosteroids are ineffective; (c) IVIg should be considered as first-line treatment in motor CIDP (Good Practice Point); (d) for maintenance treatment, IVIg, subcutaneous immunoglobulin or corticosteroids are recommended; (e) if the maintenance dose of any of these is high, consider either combination treatments or adding an immunosuppressant or immunomodulatory drug (Good Practice Point); and (f) if pain is present, consider drugs against neuropathic pain and multidisciplinary management (Good Practice Point).

BACKGROUND AND OBJECTIVES: To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact. METHODS: Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19+B220high thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated. RESULTS: The frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19+B220high thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy. DISCUSSION: Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG.

OBJECTIVE: To compare the disease course in patients with mild Guillain-Barré syndrome (GBS) who were treated with intravenous immunoglobulin (IVIg) or supportive care only. METHODS: We selected patients from the prospective observational International GBS Outcome Study (IGOS) who were able to walk independently at study entry (mild GBS), treated with one IVIg course or supportive care. The primary endpoint was the GBS disability score four weeks after study entry, assessed by multivariable ordinal regression analysis. RESULTS: Of 188 eligible patients, 148 (79%) were treated with IVIg and 40 (21%) with supportive care. The IVIg group was more disabled at baseline. IVIg treatment was not associated with lower GBS disability scores at 4 weeks (adjusted OR (aOR) 1.62, 95% CI 0.63 to 4.13). Nearly all secondary endpoints showed no benefit from IVIg, although the time to regain full muscle strength was shorter (28 vs 56 days, p=0.03) and reported pain at 26 weeks was lower (n=26/121, 22% vs n=12/30, 40%, p=0.04) in the IVIg treated patients. In the subanalysis with persistent mild GBS in the first 2 weeks, the aOR for a lower GBS disability score at 4 weeks was 2.32 (95% CI 0.76 to 7.13). At 1 year, 40% of all patients had residual symptoms. CONCLUSION: In patients with mild GBS, one course of IVIg did not improve the overall disease course. The certainty of this conclusion is limited by confounding factors, selection bias and wide confidence limits. Residual symptoms were often present after one year, indicating the need for better treatments in mild GBS.

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; This study assessed the morphological changes and diffusion tensor imaging (DTI)-derived parameters of the brachial plexus using magnetic resonance neurography (MRN) in patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Eight patients with anti-MAG neuropathy underwent MRN of the brachial plexus with 3-dimensional (3D) short tau inversion recovery (STIR) and DTI sequences. Two neuroradiologists and a neurologist qualitatively assessed nerve hypertrophy on 3D STIR MRN. The cross-sectional area (CSA) of the nerve roots was measured. Quantitative analyses of fractional anisotropy (FA) and axial, radial, and mean diffusivity (AD, RD, and MD) were obtained after postprocessing on DTI and manual segmentation. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; There was nerve hypertrophy in 37.5% of the patients with anti-MAG neuropathy. All patients with anti-MAG neuropathy with nerve hypertrophy were refractory to rituximab therapy. The CSA of the nerve roots was inversely correlated with FA and positively correlated with MD and RD. FA decreased in the nerve roots and inversely correlated with disease duration. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Nerve hypertrophy appears in the proximal portion of peripheral nerves, such as the brachial plexus, in patients with anti-MAG neuropathy. Altered diffusion in the nerve roots might be associated with the loss of myelin integrity due to the demyelination process in anti-MAG neuropathy.

Myasthenia gravis (MG), a neuromuscular junction disorder, is caused by pathogenic autoantibodies. Interleukin-6 (IL-6) plays important roles in T helper 17 (Th17), T follicular helper (Tfh), and B cell activations as well as in antibody production. This study aimed to evaluate the clinical significance of serum IL-6 level as a biomarker of disease activity in patients with anti-acetylcholine receptor (AChR) antibody-positive MG. In the present study, serum IL-6 levels were measured in 93 treatment-naïve patients with anti-AChR antibody-positive MG and compared with those in 101 controls. Moreover, correlations between serum IL-6 levels and clinical characteristics were analyzed. Serum IL-6 levels were significantly higher in patients with anti-AChR antibody-positive MG than in controls (median [interquartile range], 2.5 [1.5-8.3] pg/mL vs. 1.5 [1.5-3.2] pg/mL, P < 0.001). The serum levels were correlated with the MG Foundation of America clinical classification (Spearman's ρ = 0.27; P < 0.01) and decreased following immunosuppressive treatment in parallel with disease activity (P = 0.01). In conclusion, IL-6 is involved in the pathogenesis of anti-AChR antibody-positive MG and could be a therapeutic target in MG.

To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs). Statements were prepared according to the GRADE Evidence-to-Decision frameworks. Typical CIDP and CIDP variants were distinguished. The previous term "atypical CIDP" was replaced by "CIDP variants" because these are well characterized entities (multifocal, focal, distal, motor, or sensory CIDP). The levels of diagnostic certainty were reduced from three (definite, probable, possible CIDP) to only two (CIDP and possible CIDP), because the diagnostic accuracy of criteria for probable and definite CIDP did not significantly differ. Good Practice Points were formulated for supportive criteria and investigations to be considered to diagnose CIDP. The principal treatment recommendations were: (a) intravenous immunoglobulin (IVIg) or corticosteroids are strongly recommended as initial treatment in typical CIDP and CIDP variants; (b) plasma exchange is strongly recommended if IVIg and corticosteroids are ineffective; (c) IVIg should be considered as first-line treatment in motor CIDP (Good Practice Point); (d) for maintenance treatment, IVIg, subcutaneous immunoglobulin or corticosteroids are recommended; (e) if the maintenance dose of any of these is high, consider either combination treatments or adding an immunosuppressant or immunomodulatory drug (Good Practice Point); and (f) if pain is present, consider drugs against neuropathic pain and multidisciplinary management (Good Practice Point).

A previous study using traditional paired-pulse TMS methods (amplitude-tracking) has reported differences in resting motor threshold (RMT) and short-interval intracortical inhibition (SICI) between healthy subjects of Caucasian and Han Chinese backgrounds, probably due to differences in the skull shape. The amplitude-tracking method delivers stimuli with constant intensity, and causes substantial variabilities in MEP amplitudes. To overcome this variability, threshold tracking transcranial magnetic stimulation (TT-TMS) has been developed. The present study aimed to investigate whether racial differences in motor cortical function exist, using TT-TMS. A total of 83 healthy volunteers (30 Caucasians, 25 Han Chinese and 28 Japanese) were included in the present series. In TT-TMS and nerve conduction studies, electrodes were placed on the dominant limb, with measures recorded from the abductor pollicis brevis muscle. Stimulations were delivered with a circular coil, directly above primary motor cortex. There were no significant differences at all the SICI intervals between races. Similarly, there were no significant differences in other measures of excitability including mean RMT, intracortical facilitation, and cortical silent period. Contrary to traditional amplitude-tracking TMS, motor cortical excitability and thereby motor cortical function is minimally influenced by racial differences when measured by TT-TMS. Recent studies have disclosed that SICI measured by TT-TMS differentiates amyotrophic lateral sclerosis (ALS) from ALS mimic disorders, with high sensitivity and specificity, in Caucasians. This study suggested that TT-TMS can be applied for the ALS diagnosis in Asian patients, as well as Caucasians.

OBJECTIVE: To investigate the association between changes in anti-acetylcholine receptor antibody (AChR Ab) levels induced by immunosuppressive treatment and myasthenia gravis (MG) prognosis at 1-year post-treatment in patients with MG. METHODS: We included 53 consecutive AChR Ab-positive patients with MG whose AChR Ab levels were remeasured within 100 days of initiating immunosuppressive treatment (median remeasuring time post-treatment: 71 (55-84) days). The AChR Ab level reduction rate (RR-AChRAb, %/day) adjusted for the time between treatment initiation, and AChR Ab level remeasurement was calculated as follows: (pretreatment-post-treatment AChR Ab level)/pretreatment AChR Ab level/days between therapy initiation and AChR Ab level remeasurement ×100. Participants were divided into two groups based on the cut-off value of RR-AChR Ab, determined using receiver operating characteristic analyses for achieving minimal manifestation (MM) or better status at 1-year postimmunosuppressive treatment. The Myasthenia Gravis Foundation of America postintervention status and MG activity of daily living (MG-ADL) score at 1-year post-treatment were compared between the two groups. RESULTS: The RR-AChRAb cut-off value was 0.64%/day. The high RR-AChRAb group had a higher ratio of MM or better status (90% vs 65%, p=0.03) and lower MG-ADL score (median; 1 vs 2, p=0.04) than the low RR-AChRAb group. Kaplan-Meier analyses showed the early MM achievement in the high RR-AChRAb group (p=0.002, log-rank test). CONCLUSIONS: High RR-AChRAb is associated with a favourable outcome at 1-year post-treatment. AChR Ab remeasurement within 100 days of therapy may be useful for predicting AChR Ab-positive MG outcomes at 1-year post-treatment.

OBJECTIVE: To investigate the difference in clinical course after the first optic neuritis (ON) between aquaporin-4 IgG-associated disorder (AQPAD) and myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) METHODS: In this study, 31 eyes in 24 patients with AQPAD and 26 eyes in 18 patients with MOGAD were included. The clinical course for the first 6 months after the first ON was monitored by a retrospective cohort study. Best-corrected visual acuity (BCVA) was observed before the onset and at nadir, 2 weeks (2 W), 1 month (1 M), 2 months (2 M), 3 months (3 M) and 6 months (6 M). The decimal BCVA was converted to the logarithm of the minimal angle of resolution (logMAR) for statistical analyses. RESULTS: MOGAD eyes showed longer median number of days from ON onset to nadir (6.0 vs. 11.5, P = 0.012) and to treatment (7.0 vs. 11.0, P = 0.020) than AQPAD eyes. The median logMAR was higher in AQPAD eyes than in MOGAD eyes at nadir (2.00 vs. 1.77, P = 0.050), 2 W (1.85 vs. 0.40, P = 0.001), 2 M (0.023 vs. - 0.079, P = 0.032) and 3 M (0.046 vs. - 0.079, P = 0.002). The median time to recovery of BCVA to 0.7 was longer in AQPAD eyes than in MOGAD eyes (44.0 vs. 21.0 days, P = 0.024), but that to BCVA 1.0 was not different between the two disorders (168.0 vs. 40.0 days, respectively, P = 0.056). CONCLUSION: Compared with MOGAD eyes, AQPAD eyes tended to show worse visual outcome even during the first ON episode.

Autoantibodies have been identified as key players in several neuroimmunological disorders such as autoimmune encephalitis, CNS demyelinating diseases, neuropathies, and neuromuscular junction disorders. Recent advances of proteomic technologies enable scientists to determine the target protein of autoantibodies. These methods are divided into three categories, namely, (1) mass spectrometry (MS)-based method, (2) gene expression library screening, and (3) protein microarray. MS-based methods can analyze posttranslationally modified proteins or conformational proteins, while gene expression library screening cannot. However, in MS-based methods, protein-abundant bias could prevent the identification of the target protein, and DNA sequencing could be more easily performed than MS-based methods. Therefore, a sound knowledge of the advantages and limitations of each technique is required for selection of the optimal methodology for antigen identification in neuroimmunological disorders.

To identify novel biomarkers using the serological analysis of recombinant cDNA expression libraries (SEREX) method and to evaluate their clinical significance in amyotrophic lateral sclerosis (ALS). Serum of ALS patients were screened for autoantibodies using the SEREX method. The identified autoantibodies were validated by measuring their serum levels in 70 ALS patients, 60 normal controls (NC), and 62 Parkinson disease (PD) patients using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). The clinical relevance of these autoantibodies was investigated in ALS patients. SEREX identified 16 candidate antigens including β-actin (ACTB) in addition to proteasome subunit alpha type 7 (PSMA7) that we previously reported, and serum levels of antibodies against ACTB, were significantly higher in ALS patients than in NC (p < 0.001) and PD patients (p = 0.001). Moreover, serum levels of anti-ACTB antibody were higher in advanced stage ALS patients (Stage 4 on the King's ALS clinical staging) and in those with more severe disability (ALS Functional Rating Scale revised [ALSFRS-R] score < 40.5) compared to early stage (Stage 2 [2nd region involved)]) patients and those with less severe disability (ALSFRS-R score ≥ 40.5) (p = 0.003, p = 0.014). Anti-ACTB antibody levels were also negatively correlated with ALSFRS-R score (ρ = -0.409, p = 0.001), but positively correlated with clinical disease stage (ρ = 0.355, p = 0.003), and showed a weak positive correlation with disease duration (ρ = 0.294, p = 0.014). Anti-ACTB antibodies may be a potential biomarker of ALS could indicate disease severity.

<title>Abstract</title><italic>Rationale</italic> The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. <italic>Objectives</italic> To clarify the association between individual variations in behavioral inhibition system and brain 5-HT_2A receptor availability and specify which brain networks were involved in healthy male subjects, using [¹⁸F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. <italic>Result</italic>s Behavioral inhibition system score negatively correlated with 5-HT_2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT_2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. <italic>Conclusions</italic> Individuals with high behavioral inhibition system displays low 5-HT_2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS. CASE PRESENTATION: A 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient. CONCLUSIONS: We describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes.

BACKGROUND: This study aimed to investigate the frequency and risk factors for cerebral artery stenosis and occlusion in patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome. METHODS: We reviewed results of magnetic resonance angiography (MRA) or computed tomography angiography (CTA) in 61 patients with POEMS syndrome seen between 2010 and 2017. Stenosis or occlusion was assessed in the initial MRA/CTA. Multivariate analysis was used to identify risk factors for artery stenosis/occlusion. In an autopsy case, pathologic examination was conducted of the occluded middle cerebral arteries. RESULTS: Stenosis (> 50 %) or occlusion of the major cerebral arteries was found in 29 (47.5 %) patients on the initial MRA/CTA. The internal carotid artery was involved most frequently (32.8 %), followed by the anterior (21.3 %) and middle (16.4 %) cerebral arteries. The basilar (1.3 %) and vertebral (3.6 %) arteries were rarely affected. Cerebral infarction developed in eight (13.1 %) patients. The serum vascular endothelial growth factor (VEGF) level was an independent predictor for stenosis/occlusion (odds ratio, 1.228; 95 % confidence interval, 1.042-1.447; P = 0.014). An autopsy study showed occluded middle cerebral arteries by fibrous and myxomatous thickening of intima with splitting of the internal elastic lamina. Follow-up MRA in 23 patients showed improved, worsened, and unchanged stenosis in 20.7 %, 8.7 %, and 69.6 %, respectively. CONCLUSIONS: Cerebral large-vessel stenosis or occlusion is frequently seen in approximately half of patients with POEMS syndrome. Vasculopathy was related to serum VEGF levels and thereby disease activity. Assessment of cerebral vessels is recommended in these patients to improve management.

BACKGROUND: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. METHODS: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. RESULTS: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. CONCLUSIONS: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

Myasthenia gravis (MG) is an autoimmune disease with autoantibodies against the mainly nicotinic acetylcholine receptor (AChR). High mobility group box1 (HMGB1) acts as a danger signal and drives the pathogenesis of autoimmune-mediated diseases. However, the role of HMGB1 in the pathogenesis of MG is not fully understood. Therefore, in this study, we analyzed serum levels of HMGB1 and immunohistochemical HMGB1 staining of muscle tissues in the passive transfer MG model to investigate the role of HMGB1 in MG. As a result, serum HMGB1 levels tended to be higher and the quantitative score of muscle pathology showed greater HMGB1 deposition (P = 0.02) along with sparser AChR staining and more severe inflammation in the passive transfer MG rats (n = 6) than those in control rats (n = 6). These findings indicate that HMGB1 is an important mediator and biomarker for inflammation in the pathogenesis of MG and can be a therapeutic target in MG.

Hiccups, nausea and vomiting are known as the clinical manifestations of neuromyelitis optica spectrum disorder (NMOSD) linked to lesions of the area postraema in the medullary tegmentum. Here, we describe a 74-year-old male patient with NMOSD who presented with recurrent syncope due to severe orthostatic hypotension (OH) following symptoms of hiccups, nausea and vomiting. Brain magnetic resonance imaging revealed the lesion of the area postraema and it could be responsible for the symptom of OH. Considering the numerous related reports, we suspect that the prevalence of OH is underreported in the patients with NMOSD. OH may transition into more serious conditions, so it should be evaluated carefully in all patients with NMOSD, particularly when there is a lesion of the area postraema.

OBJECTIVE: We aimed to investigate the use of a myelin-sensitive MRI contrast, the standardized T1-weighted/T2-weighted (sT1w/T2w) ratio, for detecting early changes in the middle cerebellar peduncle (MCP) in cerebellar subtype multiple system atrophy (MSA-C) patients. METHODS: We included 28 MSA-C patients, including a subset of 17 MSA-C patients within 2 years of disease onset (early MSA-C), and 28 matched healthy controls. T1w and T2w scans were acquired using a 3-T MR system. The sT1w/T2w ratio in MCP was analyzed using SPM12 by utilizing a region-of-interest approach in normalized space. The diagnostic performance of the MCP sT1w/T2w ratio in discriminating MSA-C and the subgroup of early MSA-C from the matched controls was assessed. Correlation analyses were performed to evaluate the relationship between the MCP sT1w/T2w ratio and other clinical parameters including the International Cooperative Ataxia Scale (ICARS) score for quantifying cerebellar ataxia. RESULTS: Compared to controls, the sT1w/T2w ratio in the MCP was markedly lower in all (p < 0.001) MSA-C patients and 17 early (p < 0.001) MSA-C patients. The MCP sT1w/T2w ratio had high sensitivity (96%) and specificity (100%) to distinguish MSA-C from controls (area under the curve = 0.99), even for the early MSA-C group (area under the curve = 0.99; sensitivity = 94%, specificity = 100%). The MCP sT1w/T2w ratio correlated with the ICARS score in early MSA-C. CONCLUSIONS: The sT1w/T2w ratio can detect MSA-C-related changes in the MCP, even in the early stages of the disorder, and could be a sensitive biomarker for MSA-C. KEY POINTS: • The sT1w/T2w ratio can detect MSA-C-related changes in the middle cerebellar peduncle, even in the early stages of the disorder. • The middle cerebellar peduncle sT1w/T2w ratio correlated with a cerebellar ataxia score in early MSA-C patients.

INTRODUCTION: In this study we aimed to investigate the dispersion of mean consecutive difference (MCD) of concentric needle jitter studies of patients with myasthenia gravis (MG) and its effect on diagnostic sensitivity for MG. METHODS: One hundred fifty-three patients, including 76 patients with MG and 77 controls with possible MG who later received another diagnosis, underwent stimulated concentric needle jitter studies of the frontalis muscle. MCD mean, standard deviation (SD), and coefficient of variation (CV) were calculated. Diagnostic sensitivity and specificity were determined using receiver operating characteristic (ROC) analyses. RESULTS: MG patients showed a significantly greater MCD mean (MG: control, 26.3 μs; 13.5 μs [median]; P < .0001), MCD SD (MG: control, 12.8 μs; 5.1 μs [median]; P < .0001), and MCD CV (MG: control, 46.1; 37.5 [median]; P < .001) than those without MG. An ROC curve of SD showed a large area under the curve (0.88), and a cut-off value of 7.2 μs, which was calculated by maximum Youden index, exhibited high diagnostic sensitivity (86%) for MG. Combined MCD mean, outliers, and SD criteria showed higher sensitivity (88%) than conventional criteria alone (82%), at the expense of lower specificity. Five MG patients with normal MCD mean and abnormal MCD SD had only ocular symptoms. DISCUSSION: The dispersion of MCD as measured by MCD SD greater than 7.2 μs is significantly increased in patients with MG and may be a useful measure of abnormal jitter in the diagnosis of MG, especially for identifying patients with mild disease.

Pregnancy largely affects disease activity and clinical course in women with immune-mediated neurological disorders. Chronic inflammatory demyelinating polyneuropathy (CIDP) is rare but the most common chronic immune-mediated neuropathy; however, the effects of pregnancy on CIDP have never been investigated except case reports or series. We here provide a systematic review of the literature from 1 January 1969 to 30 June 2020 that revealed 24 women with CIDP, who had onset or relapse during pregnancy. Of these, 17 (71%) developed CIDP during the first pregnancy, and 8 (47%) had a relapse during subsequent pregnancies. Of the 17 patients, in whom the CIDP subtypes were determined, all of them had typical CIDP. First-line treatments for CIDP, such as corticosteroids, immunoglobulin and plasma exchange were efficacious and safe. We suggest that pregnancy can trigger typical CIDP in some women, and women with CIDP have a higher risk of relapse during pregnancy. The onset or relapse of CIDP during pregnancy is a rare but challenging constellation for physicians.

We herein report a case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis concurrent with NH2-terminal of α-enolase (NAE) antibodies. A 36-year-old Japanese woman presented with Gerstmann's syndrome followed by jerky involuntary movements, seizure, autonomic instability, and consciousness disturbance. NAE antibodies were detected in the serum; however, NMDAR antibodies were identified in the cerebrospinal fluid with a cell-based assay, confirming the diagnosis of anti-NMDAR encephalitis. This case highlights the fact that Gerstmann's syndrome can be a manifestation of anti-NMDAR encephalitis and that NAE may be identified concurrently with NMDAR antibodies, suggesting that the diagnosis of Hashimoto encephalopathy requires the reasonable exclusion of alternative diagnoses, including anti-NMDAR encephalitis.

INTRODUCTION: Patients with Parkinson's disease (PD) often present with gastric symptoms. Electrogastrography (EGG) can noninvasively assess gastric electric activity and may be useful for early PD diagnosis. The present study aimed to compare the efficacy of EGG in early PD diagnosis with those of 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and odor stick identification test -Japanese version (OSIT-J). METHODS: Thirty-seven untreated PD patients (mean age ± SD, 66 ± 8years; disease duration < 3 years) and 20 healthy control subjects (68 ± 6.9 years) were recruited. EGG and OSIT-J were performed in both groups, and MIBG scintigraphy in the PD group. EGG parameters were assessed in the preprandial and early and late postprandial segments using power spectrum analysis. RESULTS: Irregular EGG waves were observed in PD patients. The preprandial instability coefficient of dominant frequency (ICDF), an index of EGG irregularity, in PD patients (9.5% [6.3%]) was higher than that in controls (3.9% [3.9%], p = 0.00005). The OSIT-J score was also lower in PD patients (4.6 [3.3]) than in controls (7.7 [3.3], p = 0.006). In receiver operating characteristics analyses, the areas under the curves of preprandial ICDF and OSIT-J were 0.83 and 0.72, respectively. The sensitivities of preprandial ICDF and MIBG (delayed-phase) scintigraphy were 73% and 70%, respectively. CONCLUSIONS: Early and untreated PD patients showed irregular EGG waves and high ICDF. EGG showed better accuracy than the olfactory test for early PD diagnosis and similar sensitivity to MIBG scintigraphy.

High-dose intravenous immunoglobulin (IVIg) therapy has pharmacological suppressive actions against phagocytosis, complement system, pathogenic autoantibodies, and inflammatory cytokines, making it an effective treatment for autoimmune diseases. Unfortunately, there is no established evidence of the efficacy of IVIg therapy for autoimmune diseases of the central nervous system. Patients who are resistant to steroids and other immunosuppressive therapies or have complications that preclude the use of strong immunosuppressive therapies are considered eligible for IVIg therapy. The advantages of IVIg therapy include safety and ease of use. However, further evidence of the efficacy of IVIg treatment for autoimmune diseases of the central nervous system is warranted.

Background: Language dysfunction is a feature of cognitive impairment in amyotrophic lateral sclerosis (ALS) that may compromise communication. Objective: To elucidate language dysfunction in patients with ALS and its relationship with other neuropsychological tests and to identify the brain regions associated with this dysfunction using perfusion image. Methods: Overall, 37 patients with ALS were included in this study. Their neuropsychological function was investigated using the Western Aphasia Battery (WAB), Frontal Assessment Battery and Behavioral Assessment of the Dysexecutive Syndrome. N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography was used to examine regional cerebral blood flow and its relationship with WAB scores was investigated using multiple regression analyses, controlled for age, sex and years of education. Results: Frequency of language abnormality in ALS was 8.5% for spontaneous speech, 25.7% for auditory verbal comprehension, 8.8% for repetition, 14.7% for naming, 17.6% for reading and 51.4% for writing. The writing error was mainly omission and substitution of kana letters. Executive tests were correlated with naming (r > 0.5, p < 0.001) and reading (r > 0.4, p < 0.01) scores. With respect to the writing sub-test, positive perfusional relationship was only detected in the left angular gyrus. Conclusions: The left angular gyrus is the region associated with the writing errors observed in ALS.

Brain lesions in neuromyelitis optica spectrum disorders (NMOSD) are generally located at sites of high anti-aquaporin 4 (AQP4) expression. Clinical features of NMOSD associated with basal ganglia damage in sites not enriched with AQP4 remain unknown. Here we describe the case of an 82-year-old woman who developed dementia and bradykinesia for 5 weeks. Brain magnetic resonance imaging revealed obvious basal ganglia abnormalities. Test for serum anti-AQP4 antibody was positive, and she was diagnosed with NMOSD. Our case showed that NMOSD associated with dementia and/or Parkinson-like syndrome with basal ganglia lesions could be another clinical presentation in NMOSD.

<sec><title>Background</title> Clinical outcomes in neuromyelitis optica spectrum disorders (NMOSD) vary across different regions. </sec><sec><title>Objective</title> To describe clinical profiles in Japanese and German NMOSD patients. </sec><sec><title>Methods</title> Medical records of aquaporin-4-immunoglobulin G (AQP4-IgG) positive NMOSD patients from Japan (n = 54) and Germany (n = 38) were retrospectively analyzed. </sec><sec><title>Results</title> The disability status was similar between both cohorts, although Japanese patients had a longer disease duration (13.3 ± 11.1 vs. 8.1 ± 6.9 years, p = 0.018) but similar relapse rates. Optic neuritis and myelitis were the most frequent attacks in both cohorts. Brain attacks occurred more frequently in Japanese patients (40.7% vs. 15.8%, p = 0.020). The time from disease onset (median [interquartile range] 2.3 [0.3-10.1] vs. 0.6 [0.2-1.9] years, p = 0.009) and the number of attacks (2.5 [1-7] vs. 2 [1-3], p = 0.047) until start of the first immunotherapy were higher in the Japanese cohort. Rituximab was the most common drug in the German cohort (52.6%) and not given in the Japanese cohort (p &lt; 0.001), where oral prednisolone was the most common drug (92.6% vs. 15.8%, p &lt; 0.001). The frequency of autoimmune comorbidities was higher in the German cohort (39.5% vs. 18.5%, p = 0.047). </sec><sec><title>Conclusion</title> Compared with Japanese NMOSD patients, German patients presented with similar disability despite shorter disease duration and earlier and more frequent immunosuppressive therapy. </sec>

Guillain-Barré syndrome is the most common cause of acute flaccid paralysis worldwide. Most patients present with an antecedent illness, most commonly upper respiratory tract infection, before the onset of progressive motor weakness. Several microorganisms have been associated with Guillain-Barré syndrome, most notably Campylobacter jejuni, Zika virus, and in 2020, the severe acute respiratory syndrome coronavirus 2. In C jejuni-related Guillain-Barré syndrome, there is good evidence to support an autoantibody-mediated immune process that is triggered by molecular mimicry between structural components of peripheral nerves and the microorganism. Making a diagnosis of so-called classical Guillain-Barré syndrome is straightforward; however, the existing diagnostic criteria have limitations and can result in some variants of the syndrome being missed. Most patients with Guillain-Barré syndrome do well with immunotherapy, but a substantial proportion are left with disability, and death can occur. Results from the International Guillain-Barré Syndrome Outcome Study suggest that geographical variations exist in Guillain-Barré syndrome, including insufficient access to immunotherapy in low-income countries. There is a need to provide improved access to treatment for all patients with Guillain-Barré syndrome, and to develop effective disease-modifying therapies that can limit the extent of nerve injury. Clinical trials are currently underway to investigate some of the potential therapeutic candidates, including complement inhibitors, which, together with emerging data from large international collaborative studies on the syndrome, will contribute substantially to understanding the many facets of this disease.

OBJECTIVE: This study aimed to investigate the timing of meeting the criteria for a status of "minimal manifestation (MM) or better" and the factors that influenced whether "MM or better status" or "MM or better status with an oral prednisolone (PSL) dose of 5 mg/day or less (5-mg MM)" was met in patients with acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG). METHODS: We performed a retrospective study in 93 patients with AChR antibody-positive generalized MG who were followed for 3 years after the start of immunotherapy. We reviewed clinical data, such as MG-related symptoms, the MG activities of daily living profile (MGADL) score, immunotherapy including the dose of PSL, and achievement of the status of MM or better at baseline and 3, 6, 12, 24, and 36 months after treatment. RESULTS: An MM or better status was achieved in 60% of the patients 3 months and in 90% of the patients 2 years after initiating immunotherapy. At 2 years, 60% of the patients had achieved the treatment goal, which was an "5-mg MM". More frequent plasmapheresis and higher dose of PSL within 3 months after immunotherapy initiation were associated with difficulty in achieving the 5-mg MM status at 2 years. CONCLUSION: Approximately 60% of the MG patients achieved the treatment goal within 2 years after treatment. PSL dose and the cumulative number of plasmapheresis procedures at 3 months after immunotherapy initiation may help identify treatment-resistant patients with MG.

BACKGROUND: Quantification of motor performance has a promising role in personalized medicine by diagnosing and monitoring, e.g. neurodegenerative diseases or health problems related to aging. New motion assessment technologies can evolve into patient-centered eHealth applications on a global scale to support personalized healthcare as well as treatment of disease. However, uncertainty remains on the limits of generalizability of such data, which is relevant specifically for preventive or predictive applications, using normative datasets to screen for incipient disease manifestations or indicators of individual risks. OBJECTIVE: This study explored differences between healthy German and Japanese adults in the performance of a short set of six motor tests. METHODS: Six motor tasks related to gait and balance were recorded with a validated 3D camera system. Twenty-five healthy adults from Chiba, Japan, participated in this study and were matched for age, sex, and BMI to a sample of 25 healthy adults from Berlin, Germany. Recordings used the same technical setup and standard instructions and were supervised by the same experienced operator. Differences in motor performance were analyzed using multiple linear regressions models, adjusted for differences in body stature. RESULTS: From 23 presented parameters, five showed group-related differences after adjustment for height and weight (R 2 between .19 and .46, p<.05). Japanese adults transitioned faster between sitting and standing and used a smaller range of hand motion. In stepping-in-place, cadence was similar in both groups, but Japanese adults showed higher knee movement amplitudes. Body height was identified as relevant confounder (standardized beta >.5) for performance of short comfortable and maximum speed walks. For results of posturography, regression models did not reveal effects of group or body stature. CONCLUSIONS: Our results support the existence of a population-specific bias in motor function patterns in young healthy adults. This needs to be considered when motor function is assessed and used for clinical decisions, especially for personalized predictive and preventive medical purposes. The bias affected only the performance of specific items and parameters and is not fully explained by population-specific ethnic differences in body stature. It may be partially explained as cultural bias related to motor habits. Observed effects were small but are expected to be larger in a non-controlled cross-cultural application of motion assessment technologies with relevance for related algorithms that are being developed and used for data processing. In sum, the interpretation of individual data should be related to appropriate population-specific or even better personalized normative values to yield its full potential and avoid misinterpretation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-021-00236-3.