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Background and objectivesNeuromyelitis optica spectrum disorder (NMOSD) is a rare debilitating autoimmune disease of the CNS. Three monoclonal antibodies were recently approved as maintenance therapies for aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD (eculizumab, inebilizumab, and satralizumab), prompting the need to consider best practice therapeutic decision-making for this indication. Our objective was to develop validated statements for the management of AQP4-IgG-seropositive NMOSD, through an evidence-based Delphi consensus process, with a focus on recommendations for eculizumab, inebilizumab, and satralizumab.MethodsWe recruited an international panel of clinical experts in NMOSD and asked them to complete a questionnaire on NMOSD management. Panel members received a summary of evidence identified through a targeted literature review and provided free-text responses to the questionnaire based on both the data provided and their clinical experience. Responses were used to generate draft statements on NMOSD-related themes. Statements were voted on over a maximum of 3 rounds; participation in at least 1 of the first 2 rounds was mandatory. Panel members anonymously provided their level of agreement (6-point Likert scale) on each statement. Statements that failed to reach a predefined consensus threshold (≥67%) were revised based on feedback and then voted on in the next round. Final statements were those that met the consensus threshold (≥67%).ResultsThe Delphi panel comprised 24 experts, who completed the Delphi process in November 2021 after 2 voting rounds. In round 1, 23/25 statements reached consensus and were accepted as final. The 2 statements that failed to reach consensus were revised. In round 2, both revised statements reached consensus. Twenty-five statements were agreed in total: 11 on initiation of or switching between eculizumab, inebilizumab, and satralizumab; 3 on monotherapy/combination therapy; 7 on safety and patient population considerations; 3 on biomarkers/patient-reported outcomes; and 1 on research gaps.DiscussionAn established consensus method was used to develop statements relevant to the management of AQP4-IgG-seropositive NMOSD. These international statements will be valuable for informing individualized therapeutic decision-making and could form the basis for standardized practice guidelines.

Background: It is unknown whether people with aquaporin-4 antibody positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) experience a prodrome, although a few cases report AQP4 + serology up to 16 years before the first attack. Objectives: To evaluate whether individuals with AQP4-IgG + NMOSD have prodromal neurologic symptoms preceding the first attack. Methods: We reviewed medical records of participants meeting the 2015 diagnostic criteria for AQP4-IgG + NMOSD from four demyelinating disease centres in the Canadian NMOSD cohort study CANOPTICS. We searched for neurologic symptoms occurring at least 30 days before the first attack. Results: Of 116 participants with NMOSD, 17 (14.7%) had prodromal neurologic symptoms. The median age was 48 years (range 25–83) at first attack; 16 (94.1%) were female. Participants presented with numbness/tingling (n = 9), neuropathic pain (n = 5), visual disturbance (n = 4), tonic spasms (n = 2), Lhermitte sign (n = 2), severe headache (n = 2), incoordination (n = 2), weakness (n = 1), psychosis (n = 1) or seizure (n = 1). Of eight who underwent magnetic resonance imaging (MRI) brain, orbits and/or spinal cord, five had T2 lesions. Within 1.5–245 months (median 14) from the onset of prodromal neurologic symptoms, participants experienced their first NMOSD attack. Conclusions: One in seven people with NMOSD experienced neurologic symptoms before their first attack. Further investigation of a possible NMOSD prodrome is warranted. [ABSTRACT FROM AUTHOR]

Background: Prodromal phases are well recognized in many inflammatory and neurodegenerative diseases, including multiple sclerosis. We evaluated the possibility of a prodrome in aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) using health administrative data. Methods: We investigated individuals with AQP4 + NMOSD and MOGAD, confirmed by medical chart review, in Ontario, Canada. Each NMOSD and MOGAD participant was matched 1:5 to general population controls by sex, birth year, immigrant status, and region. Total outpatient visits and hospitalizations were compared in the 5 years preceding the incident attack in multivariable negative binomial models. Results: We identified 96 people with AQP4 + NMOSD, matched to 479 controls, and 61 people with MOGAD, matched to 303 controls. In the 5 years preceding the incident attack, health care use was elevated for outpatient visits and hospitalizations for the NMOSD cohort (adjusted rate ratio (aRR): 1.47; 95% confidence interval (CI): 1.25–1.73; aRR: 1.67; 95% CI: 1.19–2.36, respectively) but not for MOGAD. Rate ratios steadily increased in NMOSD for outpatient visits in the 2 years preceding the incident attack. Conclusion: Our findings support a prodromal phase preceding clinical onset of AQP4 + NMOSD. Earlier recognition and management of NMOSD patients may be possible. [ABSTRACT FROM AUTHOR]

Recognizing neuromyelitis optica spectrum disorder (NMOSD) and differentiating NMOSD from multiple sclerosis (MS) and other disorders can be challenging yet it is extremely important to prevent misdiagnosis, defined in this review as the incorrect diagnosis of patients who truly have NMOSD, particularly in aquaporin-4-IgG (AQP4-IgG)-seronegative cases. The heterogeneity of clinical presentations and wide range of differential diagnoses often lead to missed diagnoses of NMOSD. Misapplication of the 2015 NMOSD criteria and misinterpretation of clinical and neuroradiological findings are relevant factors associated with misdiagnosis in clinical practice. Despite the presence of a specific biomarker for NMOSD (AQP4-IgG), misdiagnosis rates have been reported as high as 35%. Studies indicate that misdiagnosed patients often undergo unnecessary prolonged immunotherapy, leading to health risks and increased morbidity. Accurate definitive diagnosis is crucial as long-term outcomes and treatment approaches differ based on the correct diagnosis, and inappropriate immunotherapy can lead to disability in NMOSD patients. This review outlines factors linked to NMOSD misdiagnosis and briefly discusses strategies to reduce misdiagnosis. [ABSTRACT FROM AUTHOR]

Waiting for medical care is the by-product of system rationing, where demand exceeds supply. In this short report we expand on the conventional concept of the queue, by focusing on the regulation of demand and by incorporating a funnel and spout analogy. Real-world examples are used to illustrate the infancy of funnel or demand-side reform initiatives targeting the queue, and the suggestion is made that policy needs to address the concept of 'waiting' much earlier in the treatment cycle. Keywords: Waiting lists; Supply; Demand; Health systems; System rationing