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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.

Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon inflammatory disease of the central nervous system, manifesting clinically as optic neuritis, myelitis, and certain brain and brainstem syndromes. Cases clinically diagnosed as NMOSD may include aquaporin 4 (AQP4)-antibody-seropositive autoimmune astrocytopathic disease, myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive inflammatory demyelinating disease, and double-seronegative disease. AQP4-antibody disease has a high female-to-male ratio (up to 9:1), and its mean age at onset of ~40 years is later than that seen in multiple sclerosis. For MOG-antibody disease, its gender ratio is closer to 1:1, and it is more common in children than in adults. Its clinical phenotypes differ but overlap with those of AQP4-antibody disease and include acute disseminated encephalomyelitis, brainstem and cerebral cortical encephalitis, as well as optic neuritis and myelitis. Double-seronegative disease requires further research and clarification. Population-based studies over the past two decades report the prevalence and incidence of NMOSD in different populations worldwide. One relevant finding is the varying prevalence observed in different racial groups. Consistently, the prevalence of NMOSD among Whites is ~1/100,000 population, with an annual incidence of

Introduction: The ability to name pictures has been investigated widely in healthy people and clinical populations. The Object and Action Naming Battery (OANB) is widely used for psycholinguistic research, aphasia research, and clinical practice. Normative databases for pictorial stimuli have been conducted in language processing studies to control for various psycholinguistic variables known to affect the availability of picture names. The present study provides Moroccan Arabic norms for name agreement, familiarity, imageability, visual complexity, and age of acquisition for 100 line drawings of actions and 162 line drawings of objects taken from Druks and Masterson. Methods and procedures: 160 healthy Moroccan Arabic-speaking individuals participated in this study. Name agreement values for the OANB items were collected from forty subjects, followed by collecting data for the psycholinguistic variables: spoken-word frequency, imageability, visual complexity, and age of acquisition from 120 participants. Results: The Moroccan Arabic OANB (MA-OANB) comprises 70 objects and 60 action pictures. 77% of the nouns and 68% of the verbs obtained 100% target responses. A minimum of 93 percent name agreement was reached for the remaining items. Norms were also collected for the following psycholinguistic variables: spoken-word frequency, imageability, age of acquisition, and visual complexity. Conclusion: The stimuli can be used for various psycholinguistic investigations and also for assessment and therapeutic purposes in Morocco. [ABSTRACT FROM AUTHOR]

Over 80% of genetic studies in the Parkinson's disease (PD) field have been conducted on individuals of European descent. There is a social and scientific imperative to understand the genetic basis of PD across global populations for therapeutic development and deployment. PD etiology is impacted by genetic and environmental factors that are variable by ancestry and region, emphasising the need for worldwide programs to gather large numbers of patients to identify novel candidate genes and risk loci involved in disease. Only a handful of documented genetic assessments have investigated families with PD in AfrAbia, which comprises the member nations of the Arab League and the African Union, with very limited cohort and case-control studies reported. This review article summarises prior research on PD genetics in AfrAbia, highlighting gaps and challenges. We discuss the etiological risk spectrum in the context of historical interactions, highlighting allele frequencies, penetrance, and the clinical manifestations of known genetic variants in the AfrAbian PD patient community. [ABSTRACT FROM AUTHOR]

The Mini-Mental State Examination (MMSE) is widely used for dementia screening. The purpose of this study was twofold. First, to cross-culturally adapt the Moroccan Arabic version of MMSE (MA-MMSE) to screen dementia among literate and illiterate elderly Moroccans, and second to analyze its psychometric properties. The MA-MMSE was administered to 80 elderly patients, 28 were females and 52 were males. Among all the participants, 22 showed evidence of dementia. Receiver Operator Characteristic (ROC), internal consistency, and test–retest reliability were investigated. The test–retest reliability was assessed by Spearman correlation analysis. Cronbach's α coefficients for internal consistency between total scores and subscores of the test were calculated. Areas under the ROC curve in literate and illiterate elderly Moroccans participants corresponded to 0.932 and 0.936, respectively. The cutoff point of 21/22 on the MA-MMSE in literate elderly had the highest sensitivity (85.7%), specificity (94.7%), and a positive likelihood ratio of (16.29%), whereas the cutoff point of 18/19 of the screening test in illiterate elderly yielded the highest sensitivity (92.9%), specificity (95.0%), and a positive likelihood ratio of (18.57%). The Cronbach's α values of the MA-MMSE for literate and illiterate elderly Moroccans were higher than 0.7. Thirty subjects were randomly selected for participation in the test–retest protocol. Participants were retested after an interval of 4–6 weeks. The test–retest reliability for total scores was significant 0.78 (p < 0.01). The findings provide preliminary evidence that the MA-MMSE is a feasible instrument for dementia screening. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) and spectrum disorder (NMO/SD) represent a vexing process and its clinical variants appear to have at their pathogenic core the loss of immune tolerance to the aquaporin-4 water channel protein. This process results in a characteristic pattern of astrocyte dysfunction, loss, and demyelination that predominantly affects the spinal cord and optic nerves. Although several empirical therapies are currently used in the treatment of NMO/SD, none has been proven effective in prospective, adequately powered, randomized trials. Furthermore, most of the current therapies subject patients to long-term immunologic suppression that can cause serious infections and development of cancers. The following is the first of a 2-part description of several key immune mechanisms in NMO/SD that might be amenable to therapeutic restoration of immune tolerance. It is intended to provide a roadmap for how potential immune tolerance restorative techniques might be applied to patients with NMO/SD. This initial installment provides a background rationale underlying attempts at immune tolerization. It provides specific examples of innovative approaches that have emerged recently as a consequence of technical advances. In several autoimmune diseases, these strategies have been reduced to practice. Therefore, in theory, the identification of aquaporin-4 as the dominant autoantigen makes NMO/SD an ideal candidate for the development of tolerizing therapies or cures for this increasingly recognized disease.

Neuromyelitis optica spectrum disorder (NMO/SD) and its clinical variants have at their core the loss of immune tolerance to aquaporin-4 and perhaps other autoantigens. The characteristic phenotype is disruption of astrocyte function and demyelination of spinal cord, optic nerves, and particular brain regions. In this second of a 2-part article, we present further perspectives regarding the pathogenesis of NMO/SD and how this disease might be amenable to emerging technologies aimed at restoring immune tolerance to disease-implicated self-antigens. NMO/SD appears to be particularly well-suited for these strategies since aquaporin-4 has already been identified as the dominant autoantigen. The recent technical advances in reintroducing immune tolerance in experimental models of disease as well as in humans should encourage quantum leaps in this area that may prove productive for novel therapy. In this part of the article series, the potential for regulatory T and B cells is brought into focus, as are new approaches to oral tolerization. Finally, a roadmap is provided to help identify potential issues in clinical development and guide applications in tolerization therapy to solving NMO/SD through the use of emerging technologies. Each of these perspectives is intended to shine new light on potential cures for NMO/SD and other autoimmune diseases, while sparing normal host defense mechanisms.