神经领域-神经系统自身免疫性疾病方向

METHODS:OBJECTIVES:Multiple sclerosis (MS) patients suffer from high levels of anxiety. However, it is unclear which factors are related to anxiety, since study results are inconsistent, and the associated factors have not been examined comprehensively. In this study, we investigated the demographic, disease-related and psychological factors associated with anxiety in MS patients. MATERIALS AND METHODS:Cross-sectional data of 119 MS patients were used. Anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), fatigue (Fatigue Severity Scale), cognitive complaints (Cognitive Failures Questionnaire) and cognitive functioning (Wisconsin Card Sorting Test, Controlled Oral Word Association Test, Letter Digit Substitution Test, Concept Shifting Test, Wechsler Memory Test Faces and the Dutch version of the California Verbal Learning Test) were measured. Bivariate and multivariable regression analyses were conducted to test the associations between anxiety and potential contributing factors. RESULTS:In this sample, 42% of the MS patients had clinically significant levels of anxiety, defined by a score ≥8 on the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS). A significant correlation was found between anxiety and depressive symptoms, fatigue, cognitive complaints and psychiatric history. In the multivariable analysis, only depressive symptoms and cognitive complaints remained significantly related to anxiety. CONCLUSIONS:Anxiety is common in MS patients and most strongly related to psychological factors. This knowledge can be taken into account when treating patients with MS. Further research is needed using longitudinal designs and incorporating other factors known to influence anxiety, such as coping, negative affectivity and social support.

METHODS:OBJECTIVE:To assess the risk of losing income from salaries and risk disability pension for multiple sclerosis patients with a clinically stable disease course 3 years after the start of disease-modifying therapy (DMT). METHODS:Data from the Danish Multiple Sclerosis Registry were linked to other Danish nationwide population-based databases. We included patients who started treatment with a DMT between 2001 and 2014. Patients were categorised into a clinically stable group (No Evidence of Disease Activity (NEDA-2)) and a clinically active group (relapse activity or 6-month confirmed Expanded Disability Status Scale worsening). Outcomes were: (1) loss of regular income from salaries and (2) a transfer payment labelled as disability pension. We used a Cox proportional hazards model to estimate confounder-adjusted HRs, and absolute risks were plotted using cumulative incidence curves accounting for competing risks. RESULTS:We included 2406 patients for the income analyses and 3123 patients for the disability pension analysis. Median follow-up from index date was ~5 years in both analyses. The NEDA-2 group had a 26% reduced rate of losing income (HR 0.74; 95% CI 0.60 to 0.92). HRs were calculated for 5-year intervals in the disability pension analysis: year 0-5: a 57% reduced rate of disability pension for the NEDA-2 group (HR 0.43; 95% CI 0.33 to 0.55) and year 5-10: a 36% reduced rate (HR 0.64; 95% CI 0.40 to 1.01). CONCLUSION:Clinically stable disease course (NEDA-2) is associated with a reduced risk of losing income from salaries and a reduced risk of disability pension.

METHODS:PURPOSE:To determine the age- and sex-specific prevalence and incidence of demyelinating optic neuritis and the risk of multiple sclerosis (MS) in pediatric and adult populations in South Korea. DESIGN:A nationwide, population-based, retrospective study using data from the Korean National Health Claims database from 2010 to 2016. PARTICIPANTS:The entire South Korean population aged 65 years of age or younger (n = 44 700 564). All patients with optic neuritis from the entire Korean population were included. METHODS:Patients aged 14 years of age or younger were classified as pediatric patients, and those aged 15 to 65 years were classified as adults. Each group was analyzed separately. Patients with optic neuritis had a subsequent diagnosis, including idiopathic, MS, neuromyelitis optica (NMO), and acute disseminated encephalomyelitis. Prevalence and incidence, conversion rate to MS, and treatment modalities (steroids, plasmapheresis, interferon-β, and immunosuppressants) were estimated. MAIN OUTCOME MEASURES:Prevalence and incidence of optic neuritis, and conversion rate to MS. RESULTS:Among 44 700 564 individuals, 531 pediatric patients (50.7% female) and 7183 adults (53.3% female) were identified as having optic neuritis. Annual incidence was 1.04 (95% confidence interval [CI], 1.01-1.07) per 100 000 pediatric individuals and 3.29 (95% CI, 3.28-3.30) per 100 000 adults. Peak incidence was observed at 10 to 14 years in the pediatric population and at 30 to 34 years and 50 to 54 years in the adult population. Conversion rate to MS was 13.8% in the pediatric population and 11.4% in the adult population. Fourteen percent of all patients were treated with chronic immunosuppressants, 38% of patients with NMO underwent plasmapheresis, and 50% of patients with MS were treated with interferon-β. CONCLUSIONS:This is a nationwide epidemiologic study of optic neuritis in individuals of all ages in South Korea. The incidence of optic neuritis and subsequent risk of MS in the pediatric population are comparable to those reported in western countries but are lower in the adult population than in western countries. The incidence rate in adults was 3.2-fold higher than in the pediatric population, and the overall MS conversion rate in the entire Korean population was estimated to be 10.6%.

METHODS::Cerebrospinal fluid (CSF) free light chains (FLC) may be an alternative biomarker to oligoclonal bands (OCB) in multiple sclerosis (MS). Herein, we compared the diagnostic accuracy of CSF OCB and FLC and we tested the prognostic value of FLC in a cohort of 64 MS patients and 106 controls. A κ-index >7.83 was more sensitive but less specific than OCB in discriminating MS patients from controls. Additionally, a κ-index >10.61 performed better than OCB in the discrimination between MS and controls with inflammatory neurological diseases (p < .001). In clinically isolated syndrome (CIS) patients, a κ-index >10.61 significantly predicted time to conversion to MS (p = .020). κ-index might be a valid alternative to OCB as a diagnostic biomarker for MS and might also be a prognostic marker in CIS.

METHODS:OBJECTIVES:People with cerebellar ataxia have few options to improve the standing stability they need for function. Strategic placement of light weights on the torso using the balance-based torso-weighting (BBTW) method has improved stability and reduced falls in people with multiple sclerosis, but has not been tested in cerebellar ataxia. We examined whether torso-weighting increased standing stability and/or functional movement in people with cerebellar ataxia. METHODS:Ten people with cerebellar ataxia and 10 matched controls participated in this single-session quasi-experimental pilot study. People with ataxia performed the Scale for the Assessment and Rating of Ataxia (SARA) prior to clinical testing. All participants donned inertial sensors that recorded postural sway; stopwatches recorded duration for standing and mobility tasks. All participants stood for up to 30 s on firm and foam surfaces with eyes open then eyes closed, and performed the Timed Up and Go (TUG) test. Light weights (0.57-1.25 kg) were strategically applied to a vest-like garment. Paired t tests compared within-group differences with and without BBTW weights. Independent t tests assessed differences from controls. All t tests were one-tailed with alpha set at .05. RESULTS:Duration of standing for people with ataxia was significantly longer with weighting (p = .004); all controls stood for the maximum time of 120 s with and without weights. More severe ataxia according to SARA was moderately correlated with greater improvement in standing duration with BBTW (Pearson r = .54). Tasks with more sensory challenges (eyes closed, standing on firm surface) showed less body sway with weighting. Duration for the TUG was unchanged by torso-weighting in people with ataxia. CONCLUSION:Strategic weighting improved standing stability but not movement speed in people with ataxia. BBTW has potential for improving stability and response to challenging sensory conditions in this population. Future studies should further examine gait stability measures along with movement speed.

METHODS:OBJECTIVE:We aimed to develop a model that can predict the probabilities of acute inflammatory demyelinating polyneuropathy (AIDP) based on nerve conduction studies (NCS) done within eight weeks. METHODS:The derivation cohort included 90 Malaysian GBS patients with two sets of NCS performed early (1-20days) and late (3-8 weeks). Potential predictors of AIDP were considered in univariate and multivariate logistic regression models to develop a predictive model. The model was externally validated in 102 Japanese GBS patients. RESULTS:Median motor conduction velocity (MCV), ulnar distal motor latency (DML) and abnormal ulnar/normal sural pattern were independently associated with AIDP at both timepoints (median MCV: p = 0.038, p = 0.014; ulnar DML: p = 0.002, p = 0.003; sural sparing: p = 0.033, p = 0.009). There was good discrimination of AIDP (area under the curve (AUC) 0.86-0.89) and this was valid in the validation cohort (AUC 0.74-0.94). Scores ranged from 0 to 6, and corresponded to AIDP probabilities of 15-98% at early NCS and 6-100% at late NCS. CONCLUSION:The probabilities of AIDP could be reliably predicted based on median MCV, ulnar DML and ulnar/sural sparing pattern that were determined at early and late stages of GBS. SIGNIFICANCE:A simple and valid model was developed which can accurately predict the probability of AIDP.

METHODS:OBJECTIVE:Driving ability can be compromised in individuals with multiple sclerosis (MS); however, the progressive nature of multiple sclerosis makes it difficult for clinicians to assess when performance on functional tasks, such as driving, has started to decline. The aim of the study was to evaluate the relationship between two measures of multiple sclerosis severity, the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite, and minor driving errors in a virtual reality driving simulator. DESIGN:Symptom severity was measured in 31 active drivers with multiple sclerosis using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite. Driving performance was measured using a standardized virtual reality driving simulator route. Executive functioning, a cognitive function commonly related to driving, was evaluated using the Trail Making Test B. RESULTS:Greater impairment on the Multiple Sclerosis Functional Composite was related to increased difficulty maintaining lane positioning (r = -0.49, P = 0.01) and poorer executive functioning (r = -0.52, P < 0.01). In contrast, the Expanded Disability Status Scale was not related to either measure. CONCLUSIONS:These findings suggest that poorer performance on the Multiple Sclerosis Functional Composite, and not the Expanded Disability Status Scale, may indicate vulnerability to minor driving errors as an early sign of driving compromise. The use of screening tools, such as the Multiple Sclerosis Functional Composite, could help clinicians identify increased driving risk and consider comprehensive driving evaluations earlier, before a major driving violation or accident occurs. TO CLAIM CME CREDITS:Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Describe the relationship between symptom severity and driving performance in a virtual reality driving simulator, and how the relationship may vary based on which symptom severity measure is used; (2) Identify nuanced differences between two commonly used multiple sclerosis (MS) symptom severity measures when assessing functional abilities such as driving; and (3) Utilize symptom severity screeners that can assist in monitoring symptom progression and assessing whether further driving evaluation is needed. LEVEL:Advanced. ACCREDITATION:The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

METHODS:OBJECTIVE:To investigate if patients with neuromyelitis optica spectrum disorder (NMOSD) develop subclinical visual pathway impairment independent of acute attacks. METHODS:A total of 548 longitudinally assessed full-field visual evoked potentials (VEP) of 167 patients with NMOSD from 16 centers were retrospectively evaluated for changes of P100 latencies and P100-N140 amplitudes. Rates of change in latencies (RCL) and amplitudes (RCA) over time were analyzed for each individual eye using linear regression and compared using generalized estimating equation models. RESULTS:The rates of change in the absence of optic neuritis (ON) for minimal VEP intervals of ≥3 months between baseline and last follow-up were +1.951 ms/y (n = 101 eyes; SD = 6.274; p = 0.012) for the P100 latencies and -2.149 µV/y (n = 64 eyes; SD = 5.013; p = 0.005) for the P100-N140 amplitudes. For minimal VEP intervals of ≥12 months, the RCL was +1.768 ms/y (n = 59 eyes; SD = 4.558; p = 0.024) and the RCA was -0.527 µV/y (n = 44 eyes; SD = 2.123; p = 0.111). The history of a previous ON >6 months before baseline VEP had no influence on RCL and RCA. ONs during the observational period led to mean RCL and RCA of +11.689 ms/y (n = 16 eyes; SD = 17.593; p = 0.003) and -1.238 µV/y (n = 11 eyes; SD = 3.708; p = 0.308), respectively. CONCLUSION:This first longitudinal VEP study of patients with NMOSD provides evidence of progressive VEP latency delay occurring independently of acute ON. Prospective longitudinal studies are needed to corroborate these findings and help to interpret the clinical relevance.

METHODS:OBJECTIVE:To determine demographic characteristics, clinical features, treatment regimens, and outcome of myasthenic crisis (MC) requiring mechanical ventilation (MV). METHODS:Analysis of patients who presented with MC between 2006 and 2015 in a German multicenter retrospective study. RESULTS:We identified 250 cases in 12 participating centers. Median age at crisis was 72 years. Median duration of MV was 12 days. Prolonged ventilation (>15 days) depended on age (p = 0.0001), late-onset myasthenia gravis (MG), a high Myasthenia Gravis Foundation of America Class before crisis (p = 0.0001 for IVb, odds ratio [OR] = infinite), number of comorbidities (>3 comorbidities: p = 0.002, OR 2.99), pneumonia (p = 0.0001, OR 3.13), and resuscitation (p = 0.0008, OR 9.15). MV at discharge from hospital was necessary in 20.5% of survivors. Patients with early-onset MG (p = 0.0001, OR 0.21), thymus hyperplasia (p = 0.002, OR 0), and successful noninvasive ventilation trial were more likely to be ventilated for less than 15 days. Noninvasive ventilation in 92 cases was sufficient in 38%, which was accompanied by a significantly shorter duration of ventilation (p = 0.001) and intensive care unit (ICU) stay (p = 0.01). IV immunoglobulins, plasma exchange, and immunoadsorption were more likely to be combined sequentially if the duration of MV and the stay in an ICU extended (p = 0.0503, OR 2.05). Patients who received plasma exchange or immunoadsorption as first-line therapy needed invasive ventilation significantly less often (p = 0.003). In-hospital mortality was 12%, which was significantly associated with the number of comorbidities (>3) and complications such as acute respiratory distress syndrome and resuscitation. Main cause of death was multiorgan failure, mostly due to sepsis. CONCLUSION:Mortality and duration of MC remained comparable to previous reports despite higher age and a high disease burden in our study. Prevention and treatment of complications and specialized neurointensive care are the cornerstones in order to improve outcome.

METHODS:OBJECTIVE:To investigate the immunological characteristics and their clinical relevance in anti-myelin oligodendrocyte glycoprotein (MOG)-IgG-associated and anti-aquaporin-4 (AQP4)-IgG-associated disorders (MOGAD and AQPAD) and multiple sclerosis (MS). METHODS:We measured peripheral blood helper T cell subsets (Th1, Th2, Th17 and regulatory T cell (Treg)) in patients with MOGAD (n=26), AQPAD (n=32) and MS (n=28) in the attack and remission phases by flow cytometry with intracellular cytokine staining. We also studied their correlation with clinical parameters. Ten normal subjects served as healthy controls. RESULTS:In all the three disorders, Th17 significantly increased at attack, and downregulated in the remission phases, although still elevated compare with healthy controls. MOGAD and AQPAD patients shared the common T cell profiles, while the extent of Th17 shift was more prominent in AQPAD. Patients with MS showed decreased Th2 than ones with MOGAD and AQPAD at attack. In terms of clinical correlation, MS patients showed that higher Th1 and Th17 proportion was associated with more frequent relapse and more severe clinical disability, whereas in MOGAD, higher Treg was associated with milder clinical severity. In AQPAD, no obvious correlation of Th profiles with clinical manifestation was found. CONCLUSIONS:The present study first investigated intracellular cytokine levels among MOGAD, AQPAD and MS. The different patterns and extent of helper T cell profiles could reflect the pathogenesis of each disorders, and may affect disease severity and activity.