Identifying the course of demyelinating disease associated with myelin oligodendrocyte glycoprotein (MOG) autoantibodies is critical to guide appropriate treatment choices. OBJECTIVE To characterize serial anti-MOG antibody serologies and clinical and imaging features at presentation and during follow-up in an inception cohort of prospectively monitored children with acquired demyelination. DESIGN, SETTING, AND PARTICIPANTS In this prospective cohort study, study participants were recruited from July 2004 to February 2017 through the multicenter Canadian Pediatric Demyelinating Disease Study. Inclusion criteria included (1) incident central nervous system demyelination, (2) at least 1 serum sample obtained within 45 days from onset, and (3) complete clinical information. Of 430 participants with acquired demyelinating syndrome recruited, 274 were included in analyses. Of 156 excluded participants, 154 were excluded owing to missing baseline samples and 2 owing to incomplete clinical information. Data were analyzed from May to October 2018. MAIN OUTCOMES AND MEASURES Presence of anti-MOG antibodies was blindly assessed in serial samples collected over a median of 4 years. Clinical, magnetic resonance imaging, and cerebrospinal fluid features were characterized at presentation, and subsequent disease course was assessed by development of new brain magnetic resonance imaging lesions, total lesion volume at last evaluation, annualized relapse rates, Expanded Disability Status Scale score and visual functional score at 4 years, and any disease-modifying treatment exposure. RESULTS Of the 274 included participants, 140 (51.1%) were female, and the median (interquartile range) age of all participants was 10.8 (6.2-13.9) years. One-third of children were positive for anti-MOG antibodies at the time of incident demyelination. Clinical presentations included a combination of optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis for 81 of 84 anti-MOG antibody-positive children (96%). Brain lesions were present in 51 of 76 anti-MOG antibody-positive participants (67%), but magnetic resonance imaging characteristics differed with age at presentation. Complete resolution of baseline lesions was observed in 26 of 49 anti-MOG antibody-positive participants (53%). On serial serum analysis, 38 of 67 participants (57%) who were seropositive at onset became seronegative (median time to conversion, 1 year). Among all participants who were positive for anti-MOG antibodies at presentation, clinical relapses occurred in 9 of 24 children (38%) who remained persistently seropositive and in 5 of 38 children (13%) who converted to seronegative status. CONCLUSIONS AND RELEVANCE Myelin oligodendrocyte glycoprotein antibodies are common in children with acquired demyelinating syndrome and are transient in approximatively half of cases. Even when persistently positive, most anti-MOG antibody-positive children experience a monophasic disease. The presence of anti-MOG antibodies at the time of incident demyelination should...

We report the largest single-center experience with extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) and recurrent acute rejection (AR) after lung transplantation. Lung transplant recipients undergoing ECP for BOS and recurrent AR were included (1997-2007). The rate of forced expiratory volume in 1 second (FEV1) decline was used as the primary measure and graft survival post-ECP as the secondary measure of efficacy. Twenty-four transplant recipients were included (BOS, n=12; recurrent AR, n=12). In recipients with BOS, decline in FEV1 was 112 mL/month before the start of ECP and 12 mL/month after 12 ECP cycles (P=0.011), mean (95% CI) change in rate of decline was 100 (28-171). Median patient survival was 7.0 (range, 3.0-13.6) years, median patient survival post-ECP 4.9 (range, 0.5-8.4) years. No ECP-related complications occurred. Extracorporeal photopheresis reduces the rate of lung function decline in recipients with BOS and is well tolerated. Furthermore, recipients with recurrent AR experience clinical stabilization. However, the underlying mechanism of ECP remains subject to further research.

BackgroundProadrenomedullin (ProADM) confers additional prognostic information to established clinical risk scores in lower respiratory tract infections (LRTI). We aimed to derive a practical algorithm combining the CURB65 score with ProADM-levels in patients with community-acquired pneumonia (CAP) and non-CAP-LRTI.MethodsWe used data of 1359 patients with LRTI enrolled in a multicenter study. We chose two ProADM cut-off values by assessing the association between ProADM levels and the risk of adverse events and mortality. A composite score (CURB65-A) was created combining CURB65 classes with ProADM cut-offs to further risk-stratify patients.ResultsCURB65 and ProADM predicted both adverse events and mortality similarly well in CAP and non-CAP-LRTI. The combined CURB65-A risk score provided better prediction of death and adverse events than the CURB65 score in the entire cohort and in CAP and non-CAP-LRTI patients. Within each CURB65 class, higher ProADM-levels were associated with an increased risk of adverse events and mortality. Overall, risk of adverse events (3.9%) and mortality (0.65%) was low for patients with CURB65 score 0-1 and ProADM ≤0.75 nmol/l (CURB65-A risk class I); intermediate (8.6% and 2.6%, respectively) for patients with CURB65 score of 2 and ProADM ≤1.5 nmol/l or CURB classes 0-1 and ProADM levels between 0.75-1.5 nmol/L (CURB65-A risk class II), and high (21.6% and 9.8%, respectively) for all other patients (CURB65-A risk class III). If outpatient treatment was recommended for CURB65-A risk class I and short hospitalization for CURB65-A risk class II, 17.9% and 40.8% of 1217 hospitalized patients could have received ambulatory treatment or a short hospitalization, respectively.ConclusionsThe new CURB65-A risk score combining CURB65 risk classes with ProADM cut-off values accurately predicts adverse events and mortality in patients with CAP and non-CAP-LRTI. Additional prospective cohort or intervention studies need to validate this score and demonstrate its safety and efficacy for the management of patients with LRTI.Trial RegistrationProcalcitonin-guided antibiotic therapy and hospitalisation in patients with lower respiratory tract infections: the prohosp study; isrctn.org Identifier: ISRCTN: ISRCTN95122877

ImportanceAutoimmune encephalitis misdiagnosis can lead to harm.ObjectiveTo determine the diseases misdiagnosed as autoimmune encephalitis and potential reasons for misdiagnosis.Design, Setting, and ParticipantsThis retrospective multicenter study took place from January 1, 2014, to December 31, 2020, at autoimmune encephalitis subspecialty outpatient clinics including Mayo Clinic (n = 44), University of Oxford (n = 18), University of Texas Southwestern (n = 18), University of California, San Francisco (n = 17), University of Washington in St Louis (n = 6), and University of Utah (n = 4). Inclusion criteria were adults (age ≥18 years) with a prior autoimmune encephalitis diagnosis at a participating center or other medical facility and a subsequent alternative diagnosis at a participating center. A total of 393 patients were referred with an autoimmune encephalitis diagnosis, and of those, 286 patients with true autoimmune encephalitis were excluded.Main Outcomes and MeasuresData were collected on clinical features, investigations, fulfillment of autoimmune encephalitis criteria, alternative diagnoses, potential contributors to misdiagnosis, and immunotherapy adverse reactions.ResultsA total of 107 patients were misdiagnosed with autoimmune encephalitis, and 77 (72%) did not fulfill diagnostic criteria for autoimmune encephalitis. The median (IQR) age was 48 (35.5-60.5) years and 65 (61%) were female. Correct diagnoses included functional neurologic disorder (27 [25%]), neurodegenerative disease (22 [20.5%]), primary psychiatric disease (19 [18%]), cognitive deficits from comorbidities (11 [10%]), cerebral neoplasm (10 [9.5%]), and other (18 [17%]). Onset was acute/subacute in 56 (52%) or insidious (>3 months) in 51 (48%). Magnetic resonance imaging of the brain was suggestive of encephalitis in 19 of 104 patients (18%) and cerebrospinal fluid (CSF) pleocytosis occurred in 16 of 84 patients (19%). Thyroid peroxidase antibodies were elevated in 24 of 62 patients (39%). Positive neural autoantibodies were more frequent in serum than CSF (48 of 105 [46%] vs 7 of 91 [8%]) and included 1 or more of GAD65 (n = 14), voltage-gated potassium channel complex (LGI1 and CASPR2 negative) (n = 10), N-methyl-d-aspartate receptor by cell-based assay only (n = 10; 6 negative in CSF), and other (n = 18). Adverse reactions from immunotherapies occurred in 17 of 84 patients (20%). Potential contributors to misdiagnosis included overinterpretation of positive serum antibodies (53 [50%]), misinterpretation of functional/psychiatric, or nonspecific cognitive dysfunction as encephalopathy (41 [38%]).Conclusions and RelevanceWhen evaluating for autoimmune encephalitis, a broad differential diagnosis should be considered and misdiagnosis occurs in many settings including at specialized centers. In this study, red flags suggesting alternative diagnoses included an insidious onset, positive nonspecific serum antibody, and failure to fulfill autoimmune encephalitis diagnostic criteria. Autoimmune encephalitis misdiagnosis leads to morbidity from unnecessary immunotherapies and delayed treatment of the correct diagnosis.