2017-18Research/NMOSD

Complement biomarkers reflect the pathological status of neuromyelitis optica spectrum disorders.

We retrospectively analyzed 21 patients with NMOSD (19 females and 2 males) and 25 patients with GBS (14 females and 11 males) (Table 1). The mean age at the time of blood collection in the acute phase of NMOSD was 48.0 years, mean duration of illness was 5.1 years, and mean expanded disability status scale (EDSS) was 5.3. Mean EDSS during NMOSD remission was 4.5. The mean age at GBS onset was 50.8 years, and the mean severity of illness was Hughes functional grade scale 3.4. Mean Hughes functional grade scale during the remission phase of GBS (at discharge) was 1.7. Anti-AQP4 and anti-glycolipid autoantibodies were positive in 81% patients with NMOSD and 88% patients with GBS, respectively.

Overlapping Autoimmune Neurological Syndrome: A Case Report of Triple-Positive Antibody

In this case report, we present a middle-aged patient displaying the clinical manifestations of these three rare neurological disorders (NMOSD, MG, and anti-NMDAR encephalitis). By presenting this unusual case, we hope to help clinicians be more vigilant about the possibility of overlapping neurological syndromes that will help avoid delays in the diagnosis and treatment of these conditions.

Burden and cost of comorbidities in patients with neuromyelitis optica spectrum disorder

A total of 162 patients with NMOSD and 810 non-NMOSD controls were evaluated. A significantly higher proportion of NMOSD patients had comorbidities than non-NMOSD controls.

Results: A total of 162 patients with NMOSD and 810 non-NMOSD controls were evaluated. A significantly higher proportion of NMOSD patients had comorbidities than non-NMOSD controls (66.7% vs 41.5%; P < 0.001). Concomitant autoimmune disease occurred in 19.1% vs 4.9% (P < 0.001) of patients with NMOSD vs non-NMOSD controls. NMOSD patients incurred significantly higher total median (interquartile range) healthcare costs per patient ($68,386.48 [$23,373.54-$160,862.70]) than matched non-NMOSD controls with autoimmune disease ($17,215.13 [$6715.48-$31,441.93]; P < 0.001) or patients with NMOSD without autoimmune comorbidity ($23,905.42 [$8632.82-$67,251.54]; P = 0.022). Similarly, patients with NMOSD and non-autoimmune comorbidities incurred higher median healthcare costs than matched controls.

Impact of psychiatric distress and physical disability on quality of life in neuromyelitis optica spectrum disorder and chronic autoimmune demyelinating polyneuropathies

Highlights

Physical disability and psychiatric distress affected QoL in NMOSD and CADP.

NMOSD reported higher subjective well-being than CADP patients.

Possible cause: distinct therapy regimens/relapse-driven vs. chronic disease course.

Psychiatric distress in NMOSD and CADP should be addressed adequately.

Therapy Approved for Rare Neurological Autoimmune Disorder

Satralizumab-mwge, marketed as Enspryng, was approved for adults with NMOSD who have antibodies against the aquaporin 4 (AQP4) protein. Binding of the antibodies with AQP4 activates the immune system and results in elevated, inflammation-promoting levels of interleukin 6 in cerebrospinal fluid. Satralizumab-mwge blocks interleukin 6 signaling pathways.

Application of 2015 Seronegative Neuromyelitis Optica Spectrum Disorder Diagnostic Criteria for Patients With Myelin Oligodendrocyte Glycoprotein IgG–Associated Disorders

Among patients with MOGAD, 23% of adults and 31% of children fulfilled the seronegative NMOSD criteria. The proportion of cases meeting the seronegative NMOSD criteria increased slightly when subgroups restricted to more than 2-year follow-up or a relapsing course were analyzed.

Elevated serum interleukin-39 levels in patients with neuromyelitis optica spectrum disorders correlated with disease severity

Highlights

Serum IL-39 levels in patients with NMOSD were significantly higher than that in RRMS patients, NND patients and HCs.

Serum IL-39 levels in patients with NMOSD were positively correlated with EDSS score.

These findings suggested that IL-39 may play a pro-inflammatory role in the pathogenesis of NMOSD and correlate with disease severity.

Epidemiology of Neuromyelitis Optica Spectrum Disorder and Its Prevalence and Incidence Worldwide

The prevalence range of NMOSD is ~0.5–4/100,000, and may be up to 10/100,000 in certain racial groups. There appears to be varying prevalence rates of NMOSD, most cases of which are AQP4-antibody-positive cases, among the different racial groups worldwide, with East Asians and Blacks having a higher prevalence than Whites. The data suggest that certain genetic and environmental factors associated with race may be involved in the pathogenesis of NMOSD. Among AQP4-antibody-negative NMOSD, some patients are MOG-antibody-positive, and unlike AQP4-antibody-positive NMOSD, males, and females are equally affected by MOG-antibody-associated disease and the prevalence may be higher in children than in adults.

Accessibility to AQP4-antibody and MOG-antibody testing, which is currently limited in many regions, is a challenge to overcome.

Altered Resting-State Functional Connectivity Density in Patients With Neuromyelitis Optica-Spectrum Disorders

Significantly decreased (corrected p < 0.05) long-range FCD was seen in the right superior parietal gyrus (SPG) in patients with NMOSD when compared to HCs. Increased long-range FCD was seen in the right fusiform gyrus (FFG), left orbital part of superior frontal orbital gyrus (ORBsup) and left anterior cingulum and paracingulate gyri (ACG) in NMOSD patients (corrected p < 0.05). The regions with reduced short-range FCD in NMOSD were the left angular gyrus (ANG) and right SPG (corrected p < 0.05).

Optic neuritis associated with anti-NMDA receptor antibody in the remission phase of anti-NMDA receptor encephalitis

We report a girl who was readmitted because of unilateral eye pain and vision impairment in the remission period of anti-NMDAR encephalitis. Based on the limited available literature on the treatment of optic neuritis associated with anti-NMDA receptor antibody, she was treated with a combination of corticosteroids and intravenous immunoglobulin with clinical improvement. Optic neuritis in the remission phase of anti-N-methyl-D-aspartate receptor encephalitis remains relatively uncommon.

Dramatic efficacy of ofatumumab in refractory pediatric-onset AQP4-IgG neuromyelitis optica spectrum disorder

Although emerging treatments have been proposed in AQP4-IgG NMOSD, this observation suggests that subcutaneous OFA may be a well-tolerated and effective alternative in refractory AQP4-IgG NMOSD or in case of intolerance of RTX. Further studies will be necessary to explore the safety and efficacy of OFA in NMOSD in a controlled clinical trial.

EC Clears Eculizumab (Soliris) for Neuromyelitis Optica

The European Commission (EC) has approved an expanded indication for the humanized monoclonal antibody eculizumab (Soliris, Alexion Pharmaceuticals) to include adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody

Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) – revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management

Recent insights into the pathogenesis of NMOSD have led to the development of novel targeted and highly effective therapies for patients with AQP4-IgG-positive NMOSD. These therapies provide a more personalized approach to treatment, considering factors, such as disease activity, age, comorbidities, family planning, side effects, route of administration, patient choice, availability, and costs. They also allow for switching between therapies in case of side effects or insufficient treatment response. Unmet needs in NMOSD therapy include understanding the long-term disease course, determining optimal immunotherapy durations, developing strategies for treatment cessation and de-escalation, and searching for biomarkers indicating attack risk.

New Treatment Perspectives for Acute Relapses in Neuromyelitis Optica Spectrum Disorder

Highlights

Available treatment options for acute NMOSD attacks include high-dose corticosteroids and TPE.

Despite these treatments, severe NMOSD attacks may result in permanent neurological disability.

The evolving pathogenic knowledge of NMOSD has identified new therapeutic targets for NMOSD relapses.

Several targeted therapeutic agents for NMOSD relapses have been tested in early-phase clinical trials.

This review summarizes the available data and discusses future perspectives of NMOSD relapse treatment.

Targeting B Cells to Modify MS, NMOSD, and MOGAD Part 1

This review more closely examines the clinical development of CD20 depletion and the pioneering contribution of rituximab. Phase 3 and the recently published postmarketing studies will be highlighted to better understand the relevant efficacy data and safety aspects of long-term B-cell depletion.

Connexins in neuromyelitis optica: a link between astrocytopathy and demyelination

Overall, our results suggest that dysregulation of connexins would play a pathogenetic role in neuromyelitis optica. The further identification of mechanisms leading to connexin dysfunction and soluble factors implicated, would provide interesting therapeutic strategies for demyelinating disorders.

Isolated opsoclonus heralding neuromyelitis optica spectrum disorder

Case Study. Opsoclonus is an ocular motility disorder characterized by spontaneous, arrhythmic conjugate saccades of varying amplitude occurring in all directions of gaze without normal intersaccadic interval. Etiological spectrum of opsoclonus encompasses paraneoplastic and neoplastic conditions, infectious and para-infectious encephalitis, autoimmune, metabolic and toxic encephalopathies, drugs, motor neuron diseases, multiple sclerosis and rarely neuromyelitis optica spectrum disorder (NMOSD). Opsoclonus has never been reported as a presenting manifestation heralding NMOSD.

High-throughput investigation of molecular and cellular biomarkers in NMOSD

Results NMOSD samples had a lower frequency of CD16⁺CD56⁺ NK cells. Both serum cohorts and multivariable logistic regression revealed increased levels of B-cell activating factor associated with NMOSD. Interleukin 6, CCL22, and CCL3 were also elevated in 1 NMOSD cohort of the 2 analyzed. Multivariable linear regression of serum analyte levels revealed a correlation between CX3CL1 (fractalkine) levels and the number of days since most recent disease relapse.

Conclusions Integrative analyses of cytokines, chemokines, and immune cells in participants with NMOSD and HCs provide congruence with previously identified biomarkers of NMOSD and highlight CD16⁺CD56⁺ NK cells and CX3CL1 as potential novel biomarker candidates.

Overlapping Demyelinating Syndrome (Neuromyelitis Optica Spectrum Disorders NMOSD With anti-NMDA Receptor Encephalitis); A Case Report

We report here an unusual and rare overlapping autoimmune syndrome in a young Omani female who first presented in 2011 with the clinical and radiological presentations of neuromyelitis optica spectrum disorder (NMOSD) and had a complete recovery. Five years later, she was admitted with the diagnosis of anti-NMDAR encephalitis and was found to have positive serum as well as CSF analyses results for AQP4 and anti-NMDAR antibodies. The patient showed significant improvement, for both clinical syndromes with good response to steroid and immunomodulating therapy.

Seronegative Neuromyelitis Optica Spectrum Disorder: An Unusual Presentation of Acute Brainstem Syndrome

Case Report. BACKGROUND Neuromyelitis optica (NMO) is an autoimmune, demyelinating, inflammatory disorder affecting the central nervous system, mostly targeting optic nerves and the spinal cord. NMO spectrum disorder (NMOSD) is a newly revised nomenclature in which new diagnostic criteria have been developed, including serological testing of serum aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies. Results of a negative antibody will group the patient in a seronegative subgroup.

Phosphodiesterase 10A IgG A novel biomarker of paraneoplastic neurologic autoimmunity

Mayo Clinic has identified a new novel (rare) antibody biomarker of neurologic paraneoplastic autoimmunity. PDE10A IgG defines a novel rare neurologic autoimmune syndrome and expands the spectrum of diagnosable paraneoplastic CNS disorders. The intracellular location of PDE10A suggests a T-cell-mediated pathology targeting cells displaying MHC1-bound PDE10A peptides.