Neuromyelitis Optica Spectrum Disorder In Patients Research Articles

A novel association of osmotic demyelination in Sjögren's syndrome prompts revisiting role of aquaporins in CNS demyelinating diseases: A literature review.

Primary Sjögren's syndrome (SS) is a chronic systemic autoimmune disease with varied neurological manifestations. SS is associated with anti-aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD), a demyelinating autoimmune disorder of the central nervous system (CNS). Intriguingly, there are reports of osmotic demyelinating syndrome (ODS), a supposedly non-inflammatory disorder, in the context of SS and renal tubular acidosis (RTA), both of which are not yet established risk factors for ODS. A literature search was undertaken to identify case reports of ODS in patients with SS. Details of the clinical and laboratory features of these patients were compiled. Additionally, we searched for NMOSD in patients with SS. We looked for co-existing RTA in patients with SS-ODS as well as SS-NMOSD. We also screened for reports of ODS in RTA without underlying SS. We identified 15 patients (all women, median age 40 years) with ODS in SS, and all of these patients had comorbid RTA. There were only three reported cases of ODS in RTA without underlying SS. We identified a total of 67 patients with SS-NMOSD, of whom only 3 (4.5%) had RTA. Hence, unlike NMOSD, the development of ODS in SS requires a prolonged osmotic or electrolyte abnormality caused by the comorbid RTA. The 15 patients with ODS and SS -RTA, showed heterogeneous clinical manifestations and outcomes. The most common symptom was quadriparesis, seen in 14 of the 15 patients. Eleven of the 15 patients had one of the following features, either alone or in combination: worsening of the sensorium, extensor plantar response, dysphagia/dysarthria, and facial palsy. The latter four manifestations were present at the onset in 7 patients and later in the course of the illness in the remaining 4 patients. Ocular palsy was seen in only four of the 15 patients and was a late manifestation. One patient who had extensive long-segment myelitis and subsequent ODS died, but most patients recovered without significant sequelae. None had hyponatremia, while all patients had hypokalemia and/or hypernatremia. Hypokalemia causing nephrogenic diabetes insipidus (NDI) followed by rapid rise in sodium and the resultant osmotic stress could potentially explain the occurrence of ODS in SS-RTA. Aquaporin (AQP) in astrocytes is implicated in ODS, and renal AQP is downregulated in NDI. Antibodies against AQPs are present in some patients with SS. Defective AQP is therefore a common link underlying all the connected diseases, namely SS, NDI, and ODS, raising the possibility of immune-mediated AQP dysfunction in the pathogenesis. The hitherto unreported association between SS-RTA and ODS may implicate SS and/or RTA in the development of ODS. In the setting of SS-RTA, ODS must be suspected when a patient with flaccid quadriparesis does not respond to the correction of potassium or develops additional neurological features along with a rise in sodium. Defective functions of AQPs may be a possible mechanism linking demyelinating CNS lesions, SS, and RTA. Studies evaluating AQP functions and serum antibodies against AQPs in these conditions are warranted.

Clinical and epidemiological aspects of neuromyelitis optic spectrum diseases in the russian population

To present clinical and epidemiological aspects of neuromyelitis optica spectrum disorders (NMOSD) in the Russian Federation. We studied 142 patients who met diagnostic criteria of 2015 for NMOSD. Sex, age at disease onset, presence or absence of aquaporin-4 immunoglobulin G antibodies (AQP4-IgG), mail clinical symptoms, oligoclonal IgG, therapy for the treatment of exacerbations and prevention of exacerbations, compliance with 2006 diagnostic criteria were assessed. The prevalence of women is 4.26:1, the most frequent age at disease onset is 18-29 years (36% of cases). The laboratory aspects of the disease are characterized and approaches to the treatment and prevention of exacerbations of NMOSD in patients of the Russian population are evaluated. Approaches to diagnostics are compared depending on the applied diagnostic criteria (34% of patients do not meet neuromyelitis optica 2006 diagnostic criteria). A prognosis for the prevalence of NMOSD in the Russian population has been proposed: 0.45-4.21/100000. This is the first published data on clinical and epidemiological characteristics of NMOSD in the Russian Federation.

HLA association in MOG-IgG- and AQP4-IgG-related disorders of the CNS in the Dutch population.

ObjectiveTo investigate the possible human leukocyte antigen (HLA) association of both myelin oligodendrocyte glycoprotein (MOG-IgG)-associated diseases (MOGAD) and aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) in the Dutch population with European ancestry to clarify similarities or differences in the immunogenetic background of both diseases.MethodsBlood samples from patients in the Dutch national MS/NMOSD expert clinic were tested for MOG-IgG and AQP4-IgG using a cell-based assay. HLA Class I and II genotyping was performed in 43 MOG-IgG–seropositive and 42 AQP4-IgG–seropositive Dutch patients with European ancestry and compared with those of 5,604 Dutch healthy blood donors.ResultsNo significant HLA association was found in MOG-IgG–seropositive patients. The AQP4-IgG–seropositive patients had a significant higher frequency of HLA-A*01 (61.9% vs 33.7%, OR 3.16, 95% CI, 1.707–5.863, p after correction [pc] = 0.0045), HLA-B*08 (61.9% vs 25.6%, OR 4.66, 95% CI, 2.513–8.643, pc < 0.0001), and HLA-DRB1*03 (51.2% vs 27.6%, OR 2.75, 95% CI, 1.495–5.042, pc = 0.0199) compared with controls.ConclusionsThe present study demonstrates differences in the immunogenetic background of MOGAD and AQP4-IgG–positive NMOSD. The strong positive association with HLA-A*01, -B*08, and -DRB1*03 is suggestive of a role of this haplotype in the etiology of AQP4-IgG–positive NMOSD in patients with European ancestry, whereas in MOGAD no evidence was found for any HLA association in these disorders.

Neuromyelitis optica spectrum disorders in Arabian Gulf (NMOAG); establishment and initial characterization of a patient registry

ObjectiveTo describe the clinical and radiological characteristics of neuromyelitis optica spectrum disorders (NMOSD) patients from the Arabian Gulf relative to anti-aquaporin 4 antibody serostatus. MethodsRetrospective multicentre study of hospital records of patients diagnosed with NMOSD based on 2015 International Panel on NMOSD Diagnosis (IPND) consensus criteria. ResultsOne hundred forty four patients were evaluated, 64.3% were anti-AQP4 antibody positive. Mean age at onset and disease duration were 31±12 and 7 ± 6 years respectively. Patients were predominantly female (4.7:1). Overall; relapsing course (80%) was more common than monophasic (20%). Optic neuritis was the most frequent presentation (48.6%), regardless of serostatus. The proportion of patients (54.3%) with visual acuity of ≤ 0.1 was higher in the seropositive group (p = 0.018). Primary presenting symptoms of transverse myelitis (TM) were observed in 29% of patients, and were the most significant correlate of hospitalization (p<0.001). Relative to anti-APQ4 serostatus, there were no significant differences in terms of age of onset, course, relapse rates or efficacy outcomes except for oligoclonal bands (OCB), which were more often present in seronegative patients (40% vs.22.5%; p = 0.054). Irrespective of serostatus, several disease modifying therapies were instituted including steroids or immunosuppressives, mostly, rituximab and azathioprine in the cohort irrespective of serostatus. The use of rituximab resulted in reduction in disease activity. ConclusionThis is the first descriptive NMOSD cohort in the Arabian Gulf region. Seropositive patients were more prevalent with female predominance. Relapsing course was more common than monophasic. However, anti-AQP4 serostatus did not impact disease duration, relapse rate or therapeutic effectiveness. These findings offer new insights into natural history of NMOSD in patients of the Arabian Gulf and allow comparison with patient populations in different World regions.

Probable neuromyelitis optica spectrum disorder presenting with recurrent cranial neuropathy

AbstractBackgroundHypertrophic pachymeningitis has been recognized in neuromyelitis optica spectrum disorder (NMOSD). However, cranial nerve involvement as a result of pachymeningitis in NMOSD is not well known.Case presentationA 49‐year‐old woman, during an 8‐year period, suffered from recurrent, multiple cranial nerve palsies; that is, palsy of the right third (4 times) and right sixth (twice) cranial nerves, due most probably to a right cavernous sinus lesion from NMOSD. Sarcoidosis, Sjögren's syndrome or other collagen diseases were negative. Magnetic resonance imaging was negative for the first to fifth episode. Aquaporin‐4 immunoglobulin G was negative at the first episode; and not measured for the subsequent second to fifth episodes. Therefore, first to fifth episodes could be irrelevant to pachymeningitis or NMOSD. In contrast, at the sixth episode, gadolinium‐enhanced T1‐weighted coronal magnetic resonance imaging showed a pachymeningeal lesion adjacent to the right cavernous sinus. Parallel with this, aquaporin‐4 immunoglobulin G became positive. The patient was finally diagnosed with probable NMOSD and started on steroid pulse therapy, and her symptoms soon disappeared completely. After this, 5 mg/day oral prednisolone was started. In the subsequent 2 years, she has had no recurrence of diplopia.ConclusionsThis case report will help physicians suspect probable NMOSD in patients having recurrent, multiple cranial neuropathies, and provide them appropriate management and care.

Methotrexate is effective for the treatment of neuromyelitis optica spectrum disorders in Asian patients

AbstractBackgroundImmunosuppression is effective in the secondary prevention of neuromyelitis optica spectrum disorder (NMOSD) relapse. However, some of the newer immunosuppressive agents are costly or unavailable in resource‐poor countries; older immunosuppressive agents might be just as effective. We aimed to evaluate the efficacy and tolerability of methotrexate in treating NMOSD in an Asian cohort.MethodsWe retrospectively reviewed all patients with NMOSD treated with methotrexate at the National Neuroscience Institute, Singapore, between 1992 and September 2012. We compared the annualized relapse rates and disability as measured by the Expanded Disability Status Scale before and after methotrexate treatment.ResultsEight of 180 patients with central nervous system demyelinating diseases fulfilled the inclusion criteria. At median follow up of 53 months (range 42–70 months), the median post‐treatment annualized relapse rate was significantly lower than the pretreatment rate (0.00 [range 0.00–3.09] vs 0.97 [range 0.08–10.14] relapses). The median Expanded Disability Status Scale remained stable (pretreatment 6.5 [range 3.0–8.0] vs post‐treatment 6.0 [range 2.0–8.0], P = 0.238); 75% of our cohort remained relapse‐free on treatment. None of our patients were intolerant of methotrexate.ConclusionsMethotrexate is well‐tolerated in our NMOSD patients, and appears to be effective in decreasing relapse rates and preventing disability progression. It is widely available and less costly than newer immunomodulatory agents. As such, it can be recommended as a therapeutic option for NMOSD in patients who fail first‐line therapy.