神经领域-神经系统自身免疫性疾病方向

METHODS:OBJECTIVES:PMR frequently co-occurs with GCA. So far, a simple biomarker for detecting concomitant arterial inflammation in PMR patients is lacking. Furthermore, biomarkers predicting disease course in PMR are awaited. We here investigated the diagnostic and prognostic value of acute-phase markers (ESR, CRP, IL-6, serum amyloid A) and angiogenesis markers (VEGF, soluble Tie2, angiopoietin-1, angiopoietin-2) in isolated PMR and PMR/GCA overlap patients. METHODS:We prospectively included 39 treatment-naïve PMR patients, of whom 10 patients also showed evidence of large vessel GCA by PET-CT. Age-matched healthy controls (n = 32) and infection controls (n = 13) were included for comparison. Serum marker levels were measured by an ELISA or Luminex assay. Receiver operating characteristic and Kaplan-Meier analyses were used to asses diagnostic and prognostic accuracy, respectively. RESULTS:All acute-phase and angiogenesis markers, except angiopoietin-1, were higher in isolated PMR patients than in healthy controls. Angiopoietin-2, ESR and soluble Tie-2 were significantly higher in patients with PMR/GCA overlap than in isolated PMR patients. Angiopoeietin-2, but not soluble Tie2, outperformed ESR and CRP in discriminating patients with and without overlapping GCA (area under the curve: 0.90; sensitivity: 100%; specificity: 76%). Moreover, high angiopoietin-2 levels were associated with long-term glucocorticoid requirement. CONCLUSION:Assessment of angiopoietin-2 at baseline may assist diagnosis of concomitant vasculitis in PMR. Moreover, high levels of angiopoietin-2 were associated with an unfavourable disease course in isolated PMR patients. These findings imply that angiopoietin-2 is an interesting diagnostic and prognostic biomarker in PMR.

METHODS::Objective: The purpose of this article is to review the literature for both 3,4-diaminopyridine (3,4-DAP) and amifampridine for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). Amifampridine (Firdapse) is the salt form of 3,4-DAP and was approved by the Food and Drug Administration for the treatment of LEMS. Data Sources: PubMed, TRIP database, and EMBASE searches were conducted without a back date (current to June 2019) utilizing the following search terms: amifampridine, 3,4-diaminopyridine, and Lambert-Eaton myasthenic syndrome. Completed trials were also reviewed at clinicaltrials.gov. Study Selection and Data Extraction: Criteria for article inclusion consisted of human subjects, age ≥18 years, phase II or III clinical trials, and English language for both drugs. Observational and pharmacokinetic studies for amifampridine were also included. Data Synthesis: Prior to the approval of amifampridine, 3,4-DAP was first-line for the management of LEMS symptoms. Two phase III trials have evaluated amifampridine to confirm efficacy, both showing superiority over placebo in the management of LEMS symptoms, with minimal adverse effects. A significant improvement in both quantitative myasthenia gravis scores and Subjective Global Impression scores was established at days 4 and 14. Relevance to Patient Care and Clinical Practice: With an improved stability profile and decreased dose variability, amifampridine will likely assume the role of first-line management of LEMS. Conclusions: Amifampridine has been shown to improve symptoms of LEMS and is generally well tolerated.

METHODS:OBJECTIVES:PMR and GCA are associated with increased risk of vascular disease. However, it remains unclear whether this relationship is causal or reflects a common underlying propensity. The aim of this study was to identify whether known cardiovascular risk factors increase the risk of PMR and GCA. METHODS:Clinical records were examined using key word searches to identify cases of PMR and GCA, applying current classification criteria in a population-based cohort. Associations between cardiovascular risk factors and incident PMR and GCA were analysed using Cox proportional hazards. RESULTS:In 315 022 person years of follow-up, there were 395 incident diagnoses of PMR and 118 incident diagnoses of GCA that met the clinical definition. Raised diastolic blood pressure (>90 mmHg) at baseline/recruitment was associated with subsequent incident PMR [hazard ratio=1.35 (95% CI 1.01, 1.80) P=0.045], and ever-smoking was associated with incident GCA [hazard ratio=2.01 (95% CI 1.26, 3.20) P=0.003]. Estimates were similar when the analysis was restricted to individuals whose diagnoses satisfied the current classification criteria sets. CONCLUSION:PMR and GCA shares common risk factors with vascular disease onset, suggesting a common underlying propensity. This may indicate a potential for disease prevention strategies through modifying cardiovascular risk.

METHODS:OBJECTIVES:Cerebrospinal fluid (CSF) and blood neurofilaments (NFLs) are markers of axonal damage and are being investigated, mostly in relapsing-remitting (RR) MS, as a marker of disease activity and of response to treatment, while there are less data in progressive MS patients. Primary aim was to measure NFL in plasma samples of untreated patients with primary (PP) and secondary (SP) progressive MS and to correlate them with disability, disease severity, and prior/subsequent disability progression. MATERIALS AND METHODS:Neurofilament concentrations were measured using SIMOA (Single Molecule Array, Simoa HD-1 Analyzer; Quanterix). RESULTS:Neurofilament concentrations were measured on plasma samples of 70 progressive (27 PP and 43 SP), 21 RRMS patients, and 10 HCs. Longitudinal plasma NFL (pNFL) concentrations (median interval between sampling: 25 months) were available for nine PP/SP patients. PNFL concentrations were significantly higher in PP/SP compared to RRMS patients. They correlated with EDSS and MS Severity Score values. There was no difference in pNFL levels between PP/SP patients with EDSS progression in the preceding year (14% of patients) or during a median follow-up of 27 months (41%). In the longitudinal sub-study, pNFL levels increased in all patients between sampling by a mean value of 23% while EDSS mostly remained stable (77% of cases). CONCLUSION:In PP/SP progressive MS patients, pNFL levels correlate with disability and increase over time, but are not associated with prior/subsequent disability progression, as measured by EDSS, which may not be a sufficiently sensitive tool in this context.

METHODS:OBJECTIVE:Few data are available on the epidemiology and management of GCA in real life. We aimed to address this situation by using health insurance claims data for France. METHODS:This retrospective study used the Echantillon Généraliste de Bénéficiaires (EGB) database, a 1% representative sample of the French national health insurance system. The EGB contains anonymous data on long-term disease status, hospitalizations and reimbursement claims for 752 717 people. Data were collected between 2007 and 2015. The index date was defined as the date of the first occurrence of a GCA code. Demographics, comorbidities, diagnostic tests and therapies were analysed. Annual incidence rates were calculated, and incident and overall GCA cases were studied. RESULTS:We identified 241 patients with GCA. The annual incidence was 7-10/100 000 people ⩾50 years old. Among the 117 patients with incident GCA, 74.4% were females, with mean age 77.6 years and mean follow-up 2.2 years. After the index date, 51.3% underwent temporal artery biopsy and 29.1% high-resolution Doppler ultrasonography. Among the whole cohort, 84.3% used only glucocorticoids. The most-prescribed glucocorticoid-sparing agent was methotrexate (12.0%). CONCLUSION:The incidence of GCA in France is 7-10/100 000 people ⩾ 50 years old. Adjunct agents, mainly methotrexate, are given to only a few patients. The use of temporal artery biopsy in only half of the patients might reflect a shift toward the use of imaging techniques to diagnose GCA.

METHODS::Large artery stenosis of the arm or leg arteries or the cervical arteries has been described in giant cell arteritis (GCA); aortic involvement, nevertheless, is less frequent, even if imaging tools such as positron emission tomography (PET) computed tomography have increased the frequency in the observation of aortic involvement. A 56-year-old female with a medical history of GCA presented to our emergency department with an unruptured voluminous thoracoabdominal aortic aneurysm (TAAA). The fluorodeoxyglucose PET demonstrated the presence of high inflammatory activity. The patient underwent endovascular correction using a "sandwich technique." The 3-month control CT scan shows complete aneurysm exclusion. In high risk for surgery patients with GCA, the endovascular treatment with parallel stent graft of TAAA is safe and feasible.

METHODS:BACKGROUND:Individuals with multiple sclerosis (MS) tend to exhibit high levels of sedentary behavior which contributes to increased disability and comorbidity. Understanding what factors underlie the motivation to be physically active in this group is therefore important. OBJECTIVE:This theory-informed qualitative study explored spousal support and behavior in fostering self-determined physical activity engagement of adults with MS. METHODS:Eight couples were interviewed using a semi-structured interview guide derived from Self-Determination Theory. RESULTS:Analysis of transcribed audio recordings revealed that supportive and empathetic spousal communication, encouragement and expectations regarding physical activity, and bonding through co-participation increased feelings of relatedness. In addition, co-planning and problem-solving around physical activity and serving as a behavioral model facilitated perceptions of competency, while spouses who valued their partners' independence and offered choice enhanced autonomous motivation for physical activity. CONCLUSIONS:Insight into the marital context that supports self-determined physical activity decisions of individuals with MS may better inform family-oriented health promotion approaches in this group.

METHODS:BACKGROUND:Venous percutaneous transluminal angioplasty (vPTA) in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI) have shown contradictory results. The aim of the study is to evaluate the efficacy of the procedure in a randomized wait list control study. METHODS:66 adults with neurologist-confirmed diagnosis of MS and sonographic diagnosis of CCSVI were allocated into vPTA-yes group (n = 31) or vPTA-not group (n = 35, control group). vPTA was performed immediately 15 days after randomization in the PTA-yes group and 6 months later in the control group. Evoked potentials (EPs), clinical-functional measures (CFMs), and upper limb kinematic measures (ULKMs) were measured at baseline (T0) and six months after in both groups, just before the venous angioplasty in the vPTA-not group (T1). RESULTS:Comparing the vPTA-yes and vPTA-not group, the CFM-derived composite functional outcome showed 11 (37%) versus 7 (20%) improved, 1 (3%) versus 3 (8%) stable, 0 versus 7 (20%) worsened, and 19 (61%) versus 18 (51%) mixed patients (χ2 = 8.71, df = 3, P = 0.03). Unadjusted and adjusted (for baseline confounding variables) odds ratio at 95% confidence interval were, respectively, 1.93 (1.3-2.8), P value 0.0007, and 1.85 (1.2-1.7), P value 0.002. EP- and ULKM-derived composite functional outcome showed no significant difference between the two groups. CONCLUSIONS:Venous angioplasty can positively impact a few CFMs especially for the quality of life but achieving disability improvement is unlikely.

METHODS::Objective. Electroencephalogram (EEG) is a sensitive method for evaluation of anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. The aim was to investigate the EEG and clinical features and correlations in patients with anti-NMDAR encephalitis. Methods. Anti-NMDAR encephalitis patients (n = 98) with at least 1 EEG recording in our hospital were recruited between January 2012 and October 2017. We reviewed and analyzed the EEG and clinical data. Results. In our cohorts, 79 patients underwent EEG in the disease acute stage, and 39 in the recovery stage. Of the 79 patients, 70 (88.6%) EEG recordings in acute period were abnormal. Symptoms, including consciousness, movement disorder, coma, were correlated to the degree of EEG abnormalities (P < .05). The patients with more severe EEG abnormalities also had longer hospitalized and intensive care unit stay time (P < .05). We found that the EEG pattern of abnormal occipital alpha rhythm had a correlation with the clinical severity, and the Spearman coefficient was 0.448 (P = .000). Neither delta activities distribution nor prevalence showed correlations with clinical severity in acute stage. However, delta activities significantly decreased in the disease recovery stage. The other findings of EEG records were extreme delta brush (7cases, 8.9%), excess delta activities (diffuse slowing 30 cases, 38.0%), and epileptiform discharge (10 cases, 14.3%). Conclusion. This is the largest study of EEG recording in patients with anti-NMDAR encephalitis patients in China. EEG abnormalities, particularly occipital alpha rhythm, are correlated with clinical severity. EEG is useful for diagnosis and monitoring of treatment response in conjunction with clinical improvement.

METHODS:BACKGROUND:In PARADIGMS, a double-blind phase III trial in 215 paediatric patients with multiple sclerosis (MS) (10 to <18 years), fingolimod administered for up to 2 years significantly reduced the annualised relapse rate (ARR) and rate of new/newly enlarged T2 (n/neT2) lesions compared with interferon (IFN) β-1a. OBJECTIVES:To investigate (1) differences between treatment groups across subpopulations (treatment-naïve, younger/prepubertal patients); (2) disability progression. METHODS:ARRs at 10, 11 and 12 years were estimated based on predefined modelling extrapolations. Changes in Expanded Disability Status Scale (EDSS), and in 3 month (3M) and 6 month (6M) confirmed disability progression (CDP) were evaluated post hoc. RESULTS:In the treatment-naïve subpopulation, fingolimod reduced ARR and n/neT2 lesions by 85.8% and 53.4%, respectively versus INF β-1a (both p<0.001), compared with 81.9% and 52.6% in the overall population. Model-based ARR reductions in younger patients (≤12 years) were 91.9%-94.6%. Twice as many IFN β-1a-treated than fingolimod-treated patients had worse EDSS scores at study end (20.6% vs 10.5%, p=0.043). Risk reductions in 3M-CDP and 6M-CDP were 77.2% (p=0.007) and 80.2% (p=0.040), respectively. CONCLUSIONS:Fingolimod in paediatric MS was associated with consistent control of disease activity versus IFN β-1a (including treatment-naïve and younger patients) and resulted in less disability progression for up to 2 years. TRIAL REGISTRATION NUMBER:NCT01892722.