Incidence and Prevalence of Neuromyelitis Optica Spectrum Disorders in the Background of International Consensus Diagnostic Criteria - A Systematic Review.

Introduction of international consensus criteria (2015 IPND criteria) for neuromyelitis optica spectrum disorders (NMOSDs) has improved diagnostic accuracy for aquaporin 4 (AQP4)-IgG-associated and seronegative NMOSDs. This study aimed to review relevant publications related to the incidence and prevalence of NMOSDs and provide an updated review of the global epidemiology of NMOSDs in the light of new diagnostic criteria. A comprehensive literature search was performed from January 2015 to June 2021 by using appropriate keywords in PubMed, Scopus, and Web of Science. Relevant papers that fulfilled inclusion criteria were shortlisted and reviewed. Twenty-one papers were selected for this review. Incidence of NMOSDs was 0.04-0.25/100,000 in predominantly white and 0.34-1.31/100,000 in nonwhite populations. Prevalence was 0.70-1.91/100,000 in white and 0.86-4.52/100,000 in nonwhite populations. The 2015 IPND criteria significantly improved the incidence and prevalence rates for NMOSDs when compared to the Wingerchuk 2006 criteria. Incidence of MOG-IgG-associated NMOSDs was 0.12-0.13/100,000, with prevalence in children 0.03-1.4/100,000 and in adults 0.65-2/100,000. In this systematic review, studies that used uniform diagnostic criteria and confirmed cases after testing for AQP4-IgG were included. The prevalence of NMOSDs was estimated to be <5/100,000 globally. A clear bias was seen in favor of nonwhite and indigenous populations. This review highlights the need for prospective population-based epidemiological studies and the importance of surveys in nonwhite populations around the globe.

Cases of neuromyelitis optica spectrum disorder from the East Africa region, highlighting challenges in diagnostics and healthcare access.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an auto-immune disease of the central nervous system (CNS) associated with the IgG-antibody against aquaporin-4 (AQP4-IgG). There is little published epidemiology of NMOSD from sub-Saharan Africa (SSA). METHODS: We retrospectively collated NMOSD cases admitted to our tertiary regional neurology centre. RESULTS: We identified 11 cases (10 female, average age 30 years). 64% (7/11) were seropositive for AQP4-IgG, measured using indirect immunofluorescence. The remaining cases could either not afford tests, or had pathognomonic radiological features. 57% (4/7) of seropositive cases had concurrent/recent CNS infection. All patients were treated with high-dose intravenous methylprednisolone (IVMP), and 36% (4/11) also had plasma exchange. Only 55% (6/11) of the patients were seen by a neurologist at presentation: they had less relapses (1.3 vs 2.4), less diagnostic delay (2.3 vs 7.4 months), and were less disabled at the end of our review period. 10 cases were immunosuppressed long-term: 60% on mycophenolate, 30% azathioprine, and one on rituximab. CONCLUSION: Our study is the largest case series of NMOSD from the East Africa region. Patients faced challenges of access to appropriate and affordable testing, and timely availability of a neurologist at onset, which had impacts on their functional outcomes. The majority of the seropositive cases had recent/concurrent CNS infections, suggesting triggered auto-immunity.

The 2015 IPND Criteria Increases the Yield in Diagnosis of Neuromyelitis Optica Spectrum Disorder in Thai Patients Compared to the 2006 Diagnostic Criteria.

BACKGROUND: The 2015 International Panel for Neuromyelitis Optica (NMO) Diagnosis (IPND) criteria was revised using systematic literature reviews and consensus from the experts. It facilitates NMOSD diagnosis and is applicable in an Asian population. OBJECTIVE: To compare the utility of the 2015 IPND criteria and the 2006 NMO diagnostic criteria for the diagnosis of NMO/SD. METHODS: We retrospectively reviewed the electronic medical records 5 of patients with NMOSD who attended Multiple Sclerosis and Related Disorders Clinic between January 2010 and December 2016. Two independent investigators applied the 2006 revised diagnostic criteria for NMO in patients who fulfilled the 2015 IPND criteria. RESULTS: Of all 70 cases who had an NMOSD diagnosis according to 2015 criteria, 56 cases (80.0%) were positive for aquaporin-4 immunoglobulin (AQP4-IgG). Nineteen patients (27.1%) fulfilled the 2006 NMO diagnostic criteria. The 2015 IPND criteria identified 51 more NMOSD cases, increasing the diagnostic yield by 268%, compared to the 2006 criteria. The median time from onset to diagnosis by using the 2015 IPND criteria was shorter than those identified by the 2006 criteria (128 vs. 547 days, p=0.002). The 2015 IPND also provides for lesser attacks occurring before achieving diagnosis (1.7 vs. 2.7, p<0.001). In the absence of known AQP4-IgG serostatus, the 2015 criteria still indicated NMOSD patients by a 124% increase in detection rate (p<0.001); however, time to diagnosis was not statistically significant between the two criteria (258 vs. 604 days, p=0.081). CONCLUSIONS: Compared to the 2006 criteria, the 2015 IPND criteria increased diagnostic yield for NMOSD regardless of AQP4-IgG status and shortened the time from onset to diagnosis in patients with NMOSD with known AQP4-IgG serostatus.

A population-based epidemiological study of neuromyelitis optica spectrum disorder in Hungary.

BACKGROUND AND PURPOSE: The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO Diagnosis (IPND) criteria. METHODS: A retrospective population-based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016. Possible NMOSD patients were selected via multistage re-evaluation from multiple sources. Crude and sex- and serostatus-specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person-years) from 2006 to 2015 were estimated and age-adjusted rates were determined. RESULTS: Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 [95% confidence interval (CI) 1.52-2.28] per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person-years provided an incidence rate of 1.32 (95% CI 1.08-1.61) per 1 000 000 person-years. Age-adjusted prevalence was 1.87 (95% CI 1.56-2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98-1.46) per 1 000 000 person-years. CONCLUSIONS: In this first report of a large population-based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.

Validation of the 2015 diagnostic criteria for neuromyelitis optica spectrum disorders in a cohort of South Indian patients.

BACKGROUND: Neuromyelitis Optica spectrum disorders (NMOSD) are one of the most common CNS demyelinating disorders as they will present with disabling recurrent demyelinating attacks. Hence, it is of paramount importance to diagnose early, and early diagnoses and intervention will prevent further relapses associated with NMOSD. New international consensus criteria have been proposed and studies validating its application towards diagnoses of NMOSD in south Asian population are meagre. Hence we validated the proposed International Panel for NMO Diagnosis (IPND), 2015 criteria to study the clinical, demographic profile and sero-status of patients who are presenting with core clinical symptoms of NMOSD in South India and compare it with 2006 criteria. METHODS: A retrospective study was conducted in a tertiary hospital for a period of one year. Patients who had at least one core clinical feature of NMOSD were included. Demographics and clinical data were recorded and analysed. Cases were evaluated using 2015 IPND and 2006 criteria for all patients, data was analysed using SPSS. RESULTS: A total of 110 patients were included and 91(82.72%) patients fulfilled IPND 2015 criteria. Out of 91 patients, 70 patients were AQP4 antibody positive and 21 were negative. Out of 110, only 30 (27.2%) satisfied 2006 criteria (24 or 80% were seropositive). 2015 criteria were more sensitive in identifying 61 new NMOSD cases juxtaposed to 2006 criteria, this difference was statistically significant (P<0.05). CONCLUSION: The 2015 IPND criteria were more sensitive and specific than previous 2006 criteria as it covered diverse clinical manifestations of NMOSD. Applying this criteria, NMOSD could be diagnosed among patients with monophasic illness, isolated recurrent optic neuritis, isolated recurrent myelitis, cerebral syndrome, diencephalic syndrome, brainstem syndrome and area postrema syndrome, thus improving the diagnostic yield.

MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome.

BACKGROUND: A subset of patients with neuromyelitis optica spectrum disorders (NMOSD) has been shown to be seropositive for myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). OBJECTIVE: To describe the epidemiological, clinical, radiological, cerebrospinal fluid (CSF), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n = 50) as well as attack and long-term treatment outcomes. METHODS: Retrospective multicenter study. RESULTS: The sex ratio was 1:2.8 (m:f). Median age at onset was 31 years (range 6-70). The disease followed a multiphasic course in 80 % (median time-to-first-relapse 5 months; annualized relapse rate 0.92) and resulted in significant disability in 40 % (mean follow-up 75 ± 46.5 months), with severe visual impairment or functional blindness (36 %) and markedly impaired ambulation due to paresis or ataxia (25 %) as the most common long-term sequelae. Functional blindess in one or both eyes was noted during at least one ON attack in around 70 %. Perioptic enhancement was present in several patients. Besides acute tetra-/paraparesis, dysesthesia and pain were common in acute myelitis (70 %). Longitudinally extensive spinal cord lesions were frequent, but short lesions occurred at least once in 44 %. Fourty-one percent had a history of simultaneous ON and myelitis. Clinical or radiological involvement of the brain, brainstem, or cerebellum was present in 50 %; extra-opticospinal symptoms included intractable nausea and vomiting and respiratory insufficiency (fatal in one). CSF pleocytosis (partly neutrophilic) was present in 70 %, oligoclonal bands in only 13 %, and blood-CSF-barrier dysfunction in 32 %. Intravenous methylprednisolone (IVMP) and long-term immunosuppression were often effective; however, treatment failure leading to rapid accumulation of disability was noted in many patients as well as flare-ups after steroid withdrawal. Full recovery was achieved by plasma exchange in some cases, including after IVMP failure. Breakthrough attacks under azathioprine were linked to the drug-specific latency period and a lack of cotreatment with oral steroids. Methotrexate was effective in 5/6 patients. Interferon-beta was associated with ongoing or increasing disease activity. Rituximab and ofatumumab were effective in some patients. However, treatment with rituximab was followed by early relapses in several cases; end-of-dose relapses occurred 9-12 months after the first infusion. Coexisting autoimmunity was rare (9 %). Wingerchuk's 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald criteria for multiple sclerosis (MS) were met by 28 %, 32 %, 15 %, 33 %, respectively; MS had been suspected in 36 %. Disease onset or relapses were preceded by infection, vaccination, or pregnancy/delivery in several cases. CONCLUSION: Our findings from a predominantly Caucasian cohort strongly argue against the concept of MOG-IgG denoting a mild and usually monophasic variant of NMOSD. The predominantly relapsing and often severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis.

Neuromyelitis optica spectrum disorders in Algeria: A preliminary study in the region of Tizi Ouzou.

BACKGROUND: Neuromyelitis optica (NMO) is a disabling inflammatory condition that targets astrocytes in the optic nerves and spinal cord. Recent advances led to the individualization of a set of conditions now referred as NMO spectrum disorder (NMOSD). OBJECTIVE: To describe the prevalence and characteristics of NMO SD in north Algeria. PATIENTS AND METHODS: The present study is a retrospective and descriptive work which took place in Nedir Mohamed teaching hospital, Tizi-Ouzou, Algeria. 938 Medical files of patients with CNS inflammatory demyelinating diseases were reviewed then patients with optic neuritis and/or myelitis were preselected. Patients who met the 2015 neuromyelitis optica spectrum disorders criteria were selected and analyzed RESULTS: 08 Patients (3.4%) met the 2015 criteria for neuromyelitis optica spectrum disorders, 3/8 (37.5%) were positive to AQ4-IgG and 5/8 (62.5%) were negative. Mean age of onset was 29 years, female to male ratio was 3:1, cerebral MRI was normal in 75% of cases and longitudinally extensive transverse myelitis was present in 75% of cases. 37/232 Patients (15.9%) were considered at high risk of neuromyelitis optica spectrum disorders CONCLUSION: The present study suggests that the spectrum of NMO disorders is a rare entity among patients with optic nerve and spinal cord demyelinating lesions in north Algeria. However, the lack of accurate AQ4-IgG test certainly underestimates its real prevalence.