神经领域-神经系统自身免疫性疾病方向

METHODS:OBJECTIVE:To determine which factors are associated with suboptimal disease-modifying therapy (DMT) adherence and to develop an explanatory model that could be used to identify individuals at risk and potentially inform interventions. DESIGN:Cross-sectional cohort study using electronic health records. SETTING:Veterans Health Administration (VA). PARTICIPANTS:Veterans with multiple sclerosis (MS) (N=2939; 79.69% men) who received care through the VA and were included in the VA MS Center of Excellence Data Repository. INTERVENTIONS:Not applicable. MAIN OUTCOME MEASURES:Suboptimal DMT adherence (<80%), demographics, co-occurring conditions, and health care use. RESULTS:Nearly 31% of participants had suboptimal adherence. Flags for suboptimal adherence included >20% missed appointments (odds ratio [OR], 3.78; 95% CI, 2.45-2.82), traumatic brain injuries (OR, 1.55; 95% CI, 1.12-2.14), age younger than 59 years (OR, 1.47; 95% CI, 1.23-1.74), ≥1 emergency department visits (OR, 1.40; 95% CI, 1.18-1.67), mood disorders (ie, depressive and bipolar disorders) (OR, 1.40; 95% CI, 1.18-1.66), and service connection (OR, 1.22; 95% CI, 1.01-1.47). Hyperlipidemia (OR, 0.77; 95% CI, 0.65-0.92) and being issued a wheelchair (OR, 0.83; 95% CI, 0.70-1.00) were associated with lower risk. CONCLUSIONS:Suboptimal adherence to DMTs continues to be an issue. Interventions that focus on person-level barriers should be urgently explored to increase adherence and improve self-management abilities.

METHODS:OBJECTIVE:To assess and compare the diagnostic performance of qualitative and (semi-)quantitative MRI and ultrasound for distinguishing chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) from segmental spinal muscular atrophy (sSMA). METHODS:Patients with CIDP (n = 13), MMN (n = 10), or sSMA (n = 12) and healthy volunteers (n = 30) were included. MRI of the brachial plexus, using short tau inversion recovery (STIR), nerve-specific T2-weighted (magnetic resonance neurography [MRN]), and diffusion tensor imaging (DTI) sequences, was evaluated. Furthermore, with ultrasound, cross-sectional areas of the nerves were evaluated. Three radiologists blinded for diagnosis qualitatively scored hypertrophy and increased signal intensity (STIR and MRN), and intraobserver and interobserver agreement was assessed. For the (semi-)quantitative modalities, group differences and receiver operator characteristics were calculated. RESULTS:Hypertrophy and increased signal intensity were found in all groups including healthy controls. Intraobserver and interobserver agreements varied considerably (intraclass correlation coefficients 0.00-0.811 and 0.101-0.491, respectively). DTI showed significant differences (p < 0.05) among CIDP, MMN, sSMA, and controls for fractional anisotropy, axial diffusivity, and radial diffusivity in the brachial plexus. Ultrasound showed significant differences in cross-sectional area (p < 0.05) among CIDP, MMN, and sSMA in upper arm and brachial plexus. For distinguishing immune-mediated neuropathies (CIDP and MMN) from sSMA, ultrasound yielded the highest area under the curve (0.870). CONCLUSION:Qualitative assessment of hypertrophy and signal hyperintensity on STIR or MRN is of limited value. DTI measures may discriminate among CIDP, MMN, and sSMA. Currently, ultrasound may be the most appropriate diagnostic imaging aid in the clinical setting.

METHODS::Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system that commonly manifests as a complex neuropsychiatric syndrome. Antibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with a range of clinical presentations including acute disseminated encephalomyelitis (ADEM), optic neuritis, and transverse myelitis. The concurrence of NMDAR encephalitis and demyelinating syndromes is rare. We describe the case of a 29-year-old male with NMDAR encephalitis and overlapping MOG antibody disease. The aim of this report is to add to the growing knowledge of phenotypic characteristics of overlap syndromes as their clinical and prognostic features may differ from those of single antibody disease.

METHODS::The K free light chains index (K-FLC index) has been proposed as an alternative test for intrathecal immunoglobulin synthesis in MS diagnosis. Aim of the study was to assess the accuracy of the K-FLC index in differentiating MS from other immune-mediated CNS disorders and NMOSD. Data were available from a cohort of 371 patients. K-FLC index was significantly higher in MS: MS mean K-FLC index 90.897 ± 134.198; NMOSD 17.992 ± 15.103; other immune-mediated CNS disorders 12.568 ± 24.440. The overall diagnostic accuracy of the K-FLC index was similar to intrathecal oligoclonal bands detection. However, as a quantitative variable, K-FLC index allowed easier discrimination of MS from other immune-mediated CNS disorders: highest K-FLC index values (> 100) were observed almost only in MS and are therefore strongly predictive of MS, in patients with the appropriate clinical presentation.

METHODS:BACKGROUND AND OBJECTIVE:Drug-induced myopathy is among the most common causes of muscle disease. An association has recently been described between programmed death-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors and immune-related adverse events (irAE) affecting the muscle. Here, we report the clinical and pathological findings of nine unrelated patients with PD-1 and PD-L1 inhibitors-associated myopathy. METHODS:We retrospectively analyzed 317 muscle biopsies performed for diagnostic purposes from January 2017 to June 2019. Patients were attended in two tertiary centers and muscle biopsies were performed and analyzed by two myology experts. Muscle biopsies were frozen in cooled isopenthane, cryostat sectioned and stained. Immunohistochemistry studies were also performed as a routine procedure in our lab. RESULTS:We identified 9 patients receiving anti-PD-1 or PD-L1 inhibitors consulting for either muscle weakness, asthenia, myasthenic-like syndrome or other muscle related-symptoms, along with biopsy-proven inflammatory myopathy. One had concomitant myocarditis. In most of the cases muscle biopsy showed a marked phenomenon of necrosis, macrophagy and muscle regeneration with perivascular inflammatory infiltrates with a large component of macrophagic cells. A tendency to perifascicular atrophy was also noticed. The expression of MHC class I antigens predominated in the perifascicular zones. Raised muscle enzymes were detected in 7 patients. CONCLUSION:A characteristic clinic-pathological pattern, including a myasthenia gravis-like syndrome plus myositis was found in patients receiving PD-1 and PD-1 L inhibitors. A large component of macrophages resembling granulomas seems to be the pathological hallmark of the syndrome. Further information is required to understand the wide spectrum of immune-related adverse events involving the muscle during or after treatment with anti-PD-1 inhibitors, but the pathological picture seems to be characteristic.

METHODS:INTRODUCTION:Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) can be associated with giant cell arteritis (GCA). In this nationwide study by the "French Network of dysimmune disorders associated with hemopathies" (MINHEMON) the objective was to evaluate characteristics, treatment and outcome of GCA MDS-MDS/MPN. PATIENTS AND METHODS:Retrospective analysis of patients that presented a MDS or MDS/MPN associated with GCA. Treatment efficiency, relapse-free and overall survival of GCA MDS-MDS/MPN were compared to GCA alone. RESULTS:Twenty-one patients with GCA MDS-MDS/MPN were included with median age 76 [42-92], M/F ratio 2.5, 8 MDS with multilineage dysplasia (38%), 4 chronic myelomonocytic leukemia (19%), at low or intermediate risk according to IPPS and IPSS-R. The prevalence of headaches, jaw claudication and anterior ischemic optic neuropathy was significantly lower in patients with GCA MDS-MDS/MPN compared to idiopathic GCA (14.3%, 0% and 0% versus 30%, 25%, and 25%, respectively; p < .05). Other clinical and histology findings were similar. All GCA patients received steroid therapy as first-line treatment. Complete or partial response was observed in 14 GCA MDS-MDS/MPN patients (66.7%), of whom 6 (28.6%) received combined immunosuppressive therapies (versus 10% of idiopathic GCA; p = .07). Relapse incidence was similar in the two groups. Steroid dependence was more frequent among GCA MDS-MDS/MPN patients (12 (57%) versus 18 (22.5%); p < .05). Relapse-free and steroid-free survivals were significantly decreased in GCA MDS-MDS/MPN patients (log rank 0.002 and 0.049 respectively), but not overall survival. CONCLUSION:Characteristics of GCA MDS-MDS/MPN seem different than idiopathic GCA, with a distinct clinical phenotype and poorer outcome with a higher risk of steroid dependence and relapse.

METHODS::Our objective was to evaluate whether IV immunoglobulin (IVIg) increases the risk of thromboembolic events in neurology outpatients with inflammatory neuropathies, as there is conflicting evidence supporting this hypothesis, mainly from non-neurologic cohorts. We investigated this question over 30 months in our cohort of patients with inflammatory neuropathies receiving regular IVIg and found a greater incidence of arterial and venous thromboembolic events than population-based rates determined by hospital admissions data. Vascular risk factors were more common in the event group but there were no IVIg administration factors that contributed to the risk. This study suggests that IVIg may have a small but contributory role in determining thromboembolic risk in the inflammatory neuropathy cohort and more evidence is required before it is clear whether the current primary prevention guidelines are appropriate in this group of patients.

METHODS::The role of vaccination in the development of Guillain-Barré syndrome (GBS) is controversial, although cases of GBS have been reported following a wide range of vaccines. A nested case-control study was conducted between January 2011 and December 2015 in three Chinese cities. Four controls were matched to a case by gender, age, address and index date. An independent expert committee validated the diagnoses of cases and controls according to the Brighton Collaboration GBS case definition. Data on vaccinations were obtained from computerized vaccination records. Causal relations were assessed by conditional logistic regression. 1056 cases of GBS and 4312 controls were included in the analyses. Among paediatric and adult population, adjusted ORs for GBS occurrence within 180 days following vaccination were 0.94 (95% CI 0.54-1.62) and 1.09 (95% CI 0.88-1.32), respectively. No increased risk of GBS was detected for vaccination against hepatitis B, influenza, hepatitis A, varicella, rabies, polio(live), diphtheria, pertuss(acellular), tetanusis, measles, mumps, rubella, Japanese Encephalitis, and meningitis vaccines. Adjusted ORs for the recurrence of GBS after vaccination among paediatric and adult population were 0.85 (95% CI 0.07-9.50) and 1.18 (95% CI 0.49-2.65), respectively. In this large retrospective study, we did not find evidence of an increased risk of GBS and its recurrence among either paediatric (≤ 18 years) or adult (> 18 years) individuals within the 180 days following vaccinations of any kind, including influenza vaccination.

METHODS:BACKGROUND:Microvascular decompression (MVD) is highly effective in managing the neuropathic facial pain of trigeminal neuralgia (TN). Its utility in patients with TN and concurrent multiple sclerosis (MS) has been a subject of debate. The goal of this study was to identify demographic and perioperative variables associated with favorable outcome after MVD over the past 20 years in patients from our institution. METHODS:A retrospective analysis of our cohort of 33 patients diagnosed with MS and TN who underwent MVD between 1997 and 2017 to treat neuropathic facial pain was performed. Perioperative variables included MS disease burden, findings on preoperative magnetic resonance imaging (MRI), TN pain severity, and the presence of intraoperative neurovascular compression. MS disease burden was quantified using the Expanded Disability Status Scale. Preoperative and postoperative pain severity was quantified using the Barrow Neurological Institute (BNI) pain severity scale. RESULTS:A total of 33 patients with TN and MS were treated with MVD at our institution (out of the 632 total MVDs performed) between 1997 and 2017. Twenty-two patients (67%) maintained a reduction in pain at a mean follow-up of 53.5 months. Higher preoperative BNI pain intensity score was associated with unfavorable outcome after MVD (P = 0.006). No associations were identified between MS disease burden, presence of neurovascular compression or pontine demyelinating plaques on MRI, or intraoperative findings of neurovascular compression and treatment outcomes. CONCLUSIONS:MVD is a reasonable treatment option for patients with TN and MS, although the rate of freedom from pain is lower than that for the general TN population. Preoperative pain severity may be a predictor of treatment success.

METHODS:BACKGROUND:The purpose of the study was to determine the risk factors of post-surgery myasthenia crisis (PMC) among myasthenia gravis (MG) patients. METHODS:A meta-analysis to synthesize all eligible literatures was conducted to analyze PMC predictors among MG patients. RESULTS:A total of 15 trials with 2626 patients were included for the meta-analysis. As a result, patients with history of MC (RR = 3.36, 95%CI: 2.46-4.59, P < .001), generalized MG (RR = 0.39, 95%CI: 0.26-0.59, P < .001), bulbar symptom (RR = 3.59,95%CI:2.53-5.09, P < .001), thymoma (RR = 2.10, 95%CI:1.37-3.21, P = .001), post-surgery morbidity presence(RR = 2.59, 95%CI:1.90-3.54, P < .001), high-dose pyridostigmine usage (SMD = 0.480, 95%CI: 0.35-0.61 P < .001) tended to develop PMC. Large dose of steroid may reduce the incidence of PMC (RR = 0.41 95%CI: 0.18-0.94, P = .036). Regular steroid use (P = .066), immunosuppressive therapy (P = .179), gender (P = .774), and age at thymectomy (P = .212) had no impact upon PMC development. CONCLUSION:History of PMC, thymoma, generalized MG, bulbar symptom, and concomitant complication are the risk factors of PMC.