Neuromyelitis Optica Research Articles

Development and validation of a claims-based algorithm to identify patients with Neuromyelitis Optica Spectrum disorder

IntroductionNo validated algorithm exists to identify patients with neuromyelitis optica spectrum disorder (NMOSD) in healthcare claims data. We developed and tested the performance of a healthcare claims–based algorithm to identify patients with NMOSD. MethodsUsing medical record data of 101 adults with NMOSD, multiple sclerosis (MS), or myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD), we tested the sensitivity and specificity of claims-based algorithms developed through interviews with neurologists. We tested the best-performing algorithm's face validity using 2016–2019 data from IBM MarketScan Commercial and Medicare Supplemental databases. Demographics and clinical characteristics were reported. ResultsAlgorithm inclusion criteria were age ≥ 18 years and (≥1 NMO diagnosis [or ≥ 1 transverse myelitis (TM) and ≥ 1 optic neuritis (ON) diagnosis] and ≥ 1 NMOSD drug) or (≥2 NMO diagnoses ≥90 days apart). Exclusion criteria were MS diagnosis or use of MS-specific drug after last NMO diagnosis or NMOSD drug; sarcoidosis diagnosis after last NMO diagnosis; or use of ≥1 immune checkpoint inhibitor. In medical record billing data of 50 patients with NMOSD, 30 with MS, and 21 with MOGAD, the algorithm had 82.0% sensitivity and 70.6% specificity. When applied to healthcare claims data, demographic and clinical features of the identified cohort were similar to known demographics of NMOSD. ConclusionsThis clinically derived algorithm performed well in medical records. When tested in healthcare claims, demographics and clinical characteristics were consistent with previous clinical findings. This algorithm will enable a more accurate estimation of NMOSD disease burden using insurance claims datasets.

Human NMO-IgG Induced Different Pathological and Immunological Changes in the CNS and Peripheral Tissues of Mice.

The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica immunoglobulin G antibodies (NMO-IgG)]. Although NMO-IgG can induce pathological changes in the central nervous system (CNS), the immunological changes in the CNS and peripheral tissue remain largely unknown. We investigated whether NMO-IgG binds to tissue expressing AQP4 and induces immunological changes in the peripheral tissue and CNS. C57BL/6 female mice were assigned into an NMOSD or control group. Pathological and immunological changes in peripheral tissue and CNS were measured by immunostaining and flow cytometry, respectively. Motor impairment was measured by open-field test. We found that NMO-IgG did bind to astrocyte- and AQP4-expressing peripheral tissue, but induced glial fibrillary acidic protein and AQP4 loss only in the CNS. NMO-IgG induced the activation of microglia and modulated microglia polarization toward the classical (M1) phenotype, but did not affect innate or adaptive immune cells in the peripheral immune system, such as macrophages, neutrophils, Th17/Th1, or IL-10-producing B cells. In addition, NMOSD mice showed significantly less total distance traveled and higher immobility time in the open field. We found that injection of human NMO-IgG led to astrocytopathic lesions with microglial activation in the CNS. However, there were no significant pathological or immunological changes in the peripheral tissues.

Early clinical response and complications of therapeutic plasma exchange in central nervous system demyelinating diseases.

Appropriate treatment reduces the severity and duration of relapses in demyelinating diseases of Central Nervous System (CNS). If high-dose corticosteroids treatment fails, therapeutic plasma exchange (TPE) is considered as a rescue treatment. This study aimed to investigate early clinical response and complications of TPE and prognostic factors in CNS demyelinating relapses. This prospective observational study was designed in a tertiary center during one year. All adult patients diagnosed corticosteroid-resistant Multiple Sclerosis (MS), NeuroMyelitis Optica Spectrum Disorder (NMOSD), idiotypic Transverse Myelitis or Clinical Isolated Syndrome relapses, were eligible. Clinical response is defined based on Expanded Disability Status Scale (EDSS) at discharge. Clinical and laboratory complications recorded. Seventy-two patients were analyzed which 58.3% patients were female. MS was diagnosed for 61.1% of cases. Thirty-five patients (48.6%) responded and the mean differences of EDSS significantly decreased 0.60 score (CI95%:0.44-.77). Electrolyte imbalances and thrombocytopenia occurred in 80.6% and 55.6% of cases respectively and 40.3% of patients had systemic reactions. However, 26.4% patients experienced moderate to severe complications. In patients with moderate to severe disability, responders were younger (MD: 8.42years, CI95%: 1.67-15.17) and had lower EDSS score at admission (median:6, IQR: 5.5-6 against 7.5 IQR: 6.5-8). The risk of failure was higher in active progressive MS patients compared with RRMS patients (OR: 6.06, CI 95%:1.37-26.76). Patients with thrombocytopenia were hospitalized more than others (MD: 1.5 days, CI 95%: 0-3). Females were more prone to hypokalemia and systemic reactions (OR: 3.11, CI 95%:1.17-8.24 and OR: 6.67, CI 95%:2.14-20.81 respectively). The most common indication of TPE was corticosteroid-resistant severe MS relapses. About half of the patients presented an early clinical response. Lower disability, younger age and RRMS diagnosis are prognostic factors of better response. One out of four patients experienced moderate to severe complications, mainly electrolyte imbalances and systemic reactions. Appropriate interventions against these complications should be considered during TPE, especially in females.

Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders.

To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD). A total of 33 patients with NMOSD treated with inebilizumab (Group INB, n=15) or rituximab (Group RTX, n=18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes. Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients (P<0.05), accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio (P<0.05). Moreover, inebilizumab treatment showed a partial effect in preventing optic nerve atrophy (P<0.05). However, there were no significant differences in other therapeutic effects compared to rituximab, which has previously demonstrated substantial therapeutic efficacy (P>0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections. The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

Preferences for neuromyelitis optica spectrum disorder treatments: A conjoint analysis with neurologists in Spain

BackgroundThe treatment landscape for neuromyelitis optica spectrum disorder (NMOSD) has changed in recent years with the approval of therapies with different efficacy, safety and administration profiles. ObjectiveThe aim of this study was to assess neurologists’ preferences for different NMOSD treatment attributes using conjoint analysis (CA). MethodsWe conducted an online, non-interventional, cross-sectional study in collaboration with the Spanish Society of Neurology. Our CA assessed five drugs’ attributes: prevention of relapse, prevention of disability accumulation, safety risk, management during pregnancy, and route and frequency of administration. Participants were presented with eight hypothetical treatment scenarios to rank based on their preferences from the most preferred to the least. An ordinary least squares method was selected to estimate weighted preferences. ResultsA total of 104 neurologists were included. Mean age (standard deviation-SD) was 37.7 (10.3) years, 52.9 % were male, and median time (interquartile range) of experience managing NMOSD was 5.0 (2.9, 10.8) years. Neurologists placed the greatest importance on efficacy attributes, time to relapse (44.1 %) being the most important, followed by preventing disability accumulation (36.8 %). In contrast, route and frequency of administration (4.6 %) was the least important characteristic. Participants who prioritised efficacy attributes felt more comfortable in decision-making, had fewer past experiences of care-related regret and a lower attitude to risk taking than their counterparts. ConclusionNeurologists’ treatment preferences in NMOSD were mainly driven by efficacy attributes. These results may be useful to design policy decisions and treatment guidelines for this condition.

Characterizing mortality in patients with AQP4-Ab+ neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder is an autoimmune disease, causing severe disability due to relapses, but recent mortality data are limited. Among 396 patients seropositive for anti-aquaporin-4 antibody from 2014 to 2020 in the United Kingdom, 39 deaths occurred: 19 (48.7%) were unrelated to disease; 14 (35.9%) were severe disability- or relapse-related; and 4 (10.3%) were attributed to malignancy/infection. Mean annual mortality was 1.92% versus 0.63% in the matched population. The standardized mortality ratio was 3.04 (95% confidence interval 1.67-5.30) with 1.29% excess mortality per year in patients. Median Expanded Disability Status Scale before death was 7.0. Results highlight the importance of preventing relapses that drive disability.

Devic’s disease: A devil’s trap for the Anesthesiologist: A case report

Neuromyelitis optica spectrum of disorder (NMOSD) is a rare autoimmune inflammatory relapsing astrocytopathy due to immunoglobulin against aquaporin 4 (AQP4) receptor. It is characterized by demyelination of the spinal cord and optic nerve. The vulnerability of demyelinated neurons to local anesthetics and increased response to neuromuscular blocking agents make the choice of anesthesia challenging. The rarity of the disease has made the literature scarce, especially when it comes to those undergoing surgeries and their anesthetic implications. We report the case of a 54-year-old patient with NMOSD who underwent modified radical mastectomy for carcinoma breast under general anesthesia. The use of multimodal analgesia for pain management and the avoidance of muscle relaxants resulted in an uneventful perioperative period in this patient.

Retinal structural thicknesses reflect clinically relevant microstructural white matter abnormalities in neuromyelitis optica spectrum disorders

BackgroundThinning of retinal thickness seen on optical coherence tomography (OCT) is frequent in patients with neuromyelitis optica spectrum disorder (NMOSD). We explored the association between OCT metrics, MRI measurements and clinical outcomes in NMOSD. Methods44 NMOSD and 60 controls underwent OCT and MR imaging. Mean peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell complex (GCC) thicknesses were measured. Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was used to measure the white matter microstructural integrity. In NMOSD patients, Expanded Disability Status Scale (EDSS) was used to quantify disability. Visual acuity (VA) was also performed for all participants. ResultspRNFL thickness was positively associated with mean diffusivity in left posterior thalamic radiation (pp = 0.010) and axial kurtosis in inferior cerebellar peduncle (p = 0.023). Similarly, GCC thickness in NMOSD patients was positively associated with fractional anisotropy in right superior longitudinal fascicules (p = 0. 041) and axial kurtosis of left cerebellar peduncle (p = 0.011). ConclusionsIn NMOSD, pRNFL and GCC reflect integrity of clinically relevant white matter structures underlying the value of OCT metrics as markers of neuronaxonal loss and disability.

Migraine Risk in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: A Nationwide Cohort Study in South Korea.

Although the relationship between migraine and multiple sclerosis (MS) has been reported, the risk of migraine in MS and neuromyelitis optica spectrum disorder (NMOSD) is unclear. Therefore, this study investigated the risk of migraine in the Korean MS and NMOSD populations. This study analyzed claims data from 1,492 patients with MS and 1,551 patients with NMOSD based on diagnostic codes in the Korean National Health Insurance Service. Migraine risk was compared with a control group (matched 1:5 for age, sex, and comorbidities) using Cox proportional hazards analysis. Patients aged &lt;20 years and with previous migraine were excluded. Migraine risk was higher in patients with MS (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI]: 1.15-1.62) but did not differ significantly in patients with NMOSD (aHR 1.05; 95% CI: 0.87-1.27) compared to controls. No significant sex-based differences in migraine risk were observed. Patients with NMOSD showed decreasing risk with age (p for interaction = 0.040). Comorbidities like hypertension, diabetes, or dyslipidemia did not significantly alter migraine risk in either group. The study results revealed an increased risk of migraines in patients with MS but not in patients with NMSOD compared with matched controls.

Treatment strategies and responses for attacks of neuromyelitis optica spectrum disorder: A real-world retrospective cohort study

We aimed to assess the treatment strategies utilized in patients with neuromyelitis optica spectrum disorder (NMOSD) experiencing relapses, including their frequency, types, and response after 6 months based on the Expanded Disability Status Scale (EDSS) score. MethodsWe conducted a retrospective study involving NMOSD patients from the Argentinean MS and NMOSD registry (RelevarEM, NCT 03375177). Treatment response at 6 months was categorized as “good” if the EDSS score decreased by ≥1 point after a nadir EDSS score ≤ 3, or by ≥2 points after a nadir EDSS score > 3, “poor” if the EDSS score decrease was slighter, and as “absent” if the EDSS score remained unchanged or worsened. ResultsWe included 120 NMOSD patients (seropositive N = 75), who experienced 250 NMOSD-related relapses and received 248 treatments. At 6 months, complete recovery was achieved in 70/98 (71.4%) and 15/19 (79%) patients, respectively. Predictors of a “good” response in our regression model were a younger age at disease onset (OR:3.54, CI95% 2.45–5.01, p < 0.0001) and a short delay from onset of relapse to treatment initiation (OR:1.56, CI95% 1.22–2.13, p = 0.004). ConclusionsApproximately two-thirds of patients experienced complete recovery, and younger age and a short delay to start treatment were independent predictors of a “good” response.

Clinical, outcome and aetiological chacteristics of inflammatory optic neuropathies. A series of Algerian patients

Introduction. Inflammatory optic neuropathies (ION) are frequent neuro ophthalmological emergencies. They often pose an etiological problem. Objectives. To study the clinical, radiological, etiological and evolutionary particularities of ION in Algerian patients. Patients and methods. Retrospective study of 23 patients, followed over a period of 6 years (from January 2016 to January 2022). All non-inflammatory causes were excluded, as well as any patient whose etiology was multiple sclerosis. Results. The etiologies identified were seropositive neuromyelitis optica (10 patients), seronegative forms (6 patients), idiopathic forms (4 patients), Mogopathies (2 patients) and one form related to an optic nerve glioma. Radiologically, optic nerve lesions with contrast were found in 9 patients whose causes varied between neuromyelitis optica, mogopathy and idiopathic forms. Discussion. Neuromyelitis optica seems to be the most frequent etiology, which is consistent with the literature. The response to the various immunological treatments is variable and depends on the proposed treatment and the earliness of its initiation. Nevertheless, a few cases of blindness have been reported despite optimal management. Conclusion. The management and prognosis of these conditions depend on the aetiology and the early initiation of treatment. Neuromyelitis optica dominates the causes in our series. The lesions observed on MRI centred on the optic nerve and their extent constitute an additional argument, helping the etiological research.

Longitudinally extensive transverse myelitis with trident sign and positive AQP4 antibody: a case report

BackgroundLongitudinally extensive transverse myelitis (LETM) is characterized by spinal cord lesions that affect at least three spinal cord segments. It can be associated with various inflammatory conditions. While imaging characteristics can aid in diagnosis, relying solely on them may lead to misinterpretation.Case presentationWe describe a 35-year-old woman who presented with subacute myelitis. Her cervical MRI (magnetic resonance imaging) revealed an extensive lesion from the area postrema down to the second thoracic level, with a trident sign observed in axial T1-weighted post-gadolinium imaging. The presence of a trident sign in MRI of patients with myelopathy is more commonly associated with sarcoidosis than other conditions. But our patient had positive (rechecked) AQP4 antibody and negative FDG-PET (fluorodeoxyglucose positron emission tomography) scan that shows trident sign could be seen in other inflammatory disorders such as NMO (neuromyelitis optica).ConclusionTrident sign is not pathognomonic for sarcoidosis, additional investigations are necessary to identify the diagnoses related to the trident sign.

Abnormal brain spontaneous neural activity in neuromyelitis optica spectrum disorder with neuropathic pain

BackgroundNeuropathic pain is one of the most common symptoms in neuromyelitis optica spectrum disorder (NMOSD). Notwithstanding, its underlying mechanism remains obscure.MethodsThe amplitude of low-frequency fluctuations (ALFF) metric was employed to investigate spontaneous neural activity alterations via resting-state functional magnetic resonance imaging (rs-MRI) data from a 3.0 T MRI scanner, in a sample of 26 patients diagnosed with NMOSD with neuropathic pain (NMOSD-WNP), 20 patients with NMOSD but without neuropathic pain (NMOSD-WoNP), and 38 healthy control (HC) subjects matched for age and sex without the comorbidity of depressive or anxious symptoms.ResultsIt was observed that patients with NMOSD-WNP displayed a significant ALFF decrease in the left amygdala and right anterior insula, relative to both patients with NMOSD-WoNP and HC subjects. Furthermore, ALFF values in the left amygdala were negatively correlated with the scores of the Douleur Neuropathique en 4 Questions and McGill Pain Questionnaire (both sensory and affective descriptors) in patients with NMOSD-WNP. Additionally, there were negative correlations between the ALFF values in the right anterior insula and the duration of pain and the number of relapses in patients with NMOSD-WNP.ConclusionThe present study characterizes spontaneous neural activity changes in brain regions associated with sensory and affective processing of pain and its modulation, which underscore the central aspects in patients with NMOSD-WNP. These findings might contribute to a better understanding of the pathophysiologic basis of neuropathic pain in NMOSD.

Rituximab Therapy for Immune-Mediated Neurological Diseases: Our Experience at a Tertiary Care Centre.

Rituximab (RTX) is a monoclonal anti-CD20 chimeric antibody that inhibits B cell activity. However, it is an appealing substitute for traditional immunomodulatory drugs as a swiftly acting, targeted therapy with mounting evidence of efficacy and tolerance in numerous neuroinflammatory conditions. We discuss the scientific evidence for the use of RTX in neurological illnesses, as well as the dose, safety, and other practical elements of prescription. This study aims to assess and correlate the effects of RTX on immune-mediated neurological disorders. The primary objective of this study is to determine the outcomes in patients treated with RTX for the following conditions: myasthenia gravis (MG), autoimmune encephalitis, multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), immune-mediated peripheral neuropathy, and inflammatory muscle disease. The secondary objective is to assess adverse drug reactions in patients treated with RTX. This is a prospective observational study conducted at a tertiary care centre. The data were analyzed for the period from May 2022 to May 2024. Approval was obtained from the institutional ethics committee before commencing the study, andwritten informed consent was obtained from all patients. A total of 56 patients were included in the study. The distribution of patients according to diseases is as follows: MG (17), MS (11), NMOSD (10), MOGAD (7), immune-mediated peripheral neuropathy (6), autoimmune encephalitis (3), and inflammatory muscle disease (2). However, one patient was lost to follow-up in the autoimmune encephalitis group. All patients experienced improvements in symptoms, and no relapse episodes have been reported except for one patient who had a relapse in the inflammatory muscle disease group. During the infusion process, some adverse drug reactions, such as chills and rigors, were observed, and two patients experienced major side effects, such as Pott's disease and cryptogenic organizing pneumonia. Nevertheless, overall, rituximab shows promise as an off-labelimmunosuppressive treatment for the aforementioned neurological immune-mediated diseases.

A comparative study of hypothalamic involvement in patients with myelin oligodendrocyte glycoprotein antibody-associated disease, neuromyelitis optica spectrum disorder, and multiple sclerosis.

We aimed to characterize hypothalamic involvement in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare it with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). A retrospective study was performed to identify hypothalamic lesions in patients diagnosed with MOGAD, NMOSD, or MS from January 2013 to May 2020. The demographic, clinical, and radiological features were recorded. Hypothalamic dysfunction and prognosis were assessed through physical examination, biochemical testing, sleep monitoring, and magnetic resonance imaging. Hypothalamic lesions were observed in seven of 96 patients (7.3%) with MOGAD, 34 of 536 (6.3%) with NMOSD, and 16 of 356 (4.5%) with MS (p = 0.407). The time from disease onset to development of hypothalamic lesions was shortest in MOGAD (12 months). The frequency of bilateral hypothalamic lesions was the lowest in MOGAD (p = 0.008). The rate of hypothalamic dysfunction in MOGAD was 28.6%, which was lower than that in NMOSD (70.6%) but greater than that in MS patients (18.8%; p = 0.095 and p = 0.349, respectively). Hypothalamic dysfunction in MOGAD manifests as hypothalamic-pituitary-adrenal axis dysfunction and hypersomnia. The proportion of complete regression of hypothalamic lesions in MOGAD (100%) was much greater than that in NMOSD (41.7%) and MS patients (18.2%; p = 0.007 and p = 0.001, respectively). An improvement in hypothalamic dysfunction was observed in all MOGAD patients after immunotherapy. MOGAD patients have a relatively high incidence of asymptomatic hypothalamic lesions. The overall prognosis of patients with hypothalamic involvement is good in MOGAD, as the lesions completely resolve, and dysfunction improves after immunotherapy.

Features and associations of optic neuritis in the Middle East: A cross-sectional study

BackgroundDifferences exist in the clinical profile of optic neuritis (ON) among various populations. The present study outlines the features of optic neuritis and its associations in Middle Eastern population. MethodsIn a single tertiary care neuro-ophthalmology clinic, we reviewed charts between 2016 and 2021, to identify patients with optic neuritis. Patients with at least one single episode of ON, and a follow up for at least 6 months were only included. Patients from countries outside the Middle East were not eligible. We performed a sub-analysis using data from the clinic, laboratory, and radiological findings to classify patients with optic neuritis into 4 groups: idiopathic ON, multiple sclerosis associated optic neuritis (MS-ON), neuromyelitis optica spectrum disorder associated optic neuritis (NMOSD-ON), and myelin oligodendrocyte glycoprotein associated disease optic neuritis (MOGAD-ON). Results77 patients met the criteria for inclusion in the study. Approximately, two thirds of the patients (64%, 95% CI [0.52–0.74]) had MS-ON, 17 patients had idiopathic ON (22.6%, 95% CI [0.13–0.33]), 6 patients were diagnosed with NMOSD-ON (8%, 95% CI [0.02–0.16]), and 4 patients had MOG-ON (5.3%, 95% CI [0.01–0.13]). More than half of patients with idiopathic ON were found to have clinically isolated syndrome (CIS) and thus to be at high risk of developing MS. Among all patients enrolled in the study, the mean age was 29.8 ± 9.53 years. Patients with MS-ON and MOG-ON were relatively younger compared to patients from other groups (P = 0.0005). There was a female preponderance among all groups except MOG-ON, where 80% were males (P = 0.11). The pre- and post-treatment logMAR visual acuity (VA) tended to be worse in NMOSD-ON than other categories (P = 0.062). Optic disc swelling was more common among patients with MOGAD-ON, and least common in patients with NMOSD (100% vs 0%, P = 0.001). 5 patients presented with simultaneous bilateral involvement, and all but one had NMOSD-ON. 29% of patients had recurrence during the time of the study with significant difference in prevalence across groups. There was no difference in the involvement of the chiasm, or the retro-chiasmal pathways across groups. ConclusionsOur study demonstrates that multiple sclerosis (MS) is the predominant CNS demyelinating disease associated with optic neuritis (ON) in the Middle Eastern population, mirroring trends observed in Western populations. The clinical and radiological features of each subtype showed no significant divergence compared to findings from studies conducted in other regions globally. These insights contribute to a deeper understanding of ON's clinical spectrum and aid in refining diagnostic and management strategies in the Middle Eastern population.

CSF sphingolipids are correlated with neuroinflammatory cytokines and differentiate neuromyelitis optica spectrum disorder from multiple sclerosis

BackgroundThere is a need for biomarkers of disease progression and therapeutic response in multiple sclerosis (MS). This study aimed to identify cerebrospinal fluid (CSF) lipids that differentiate MS from other...

Multimodal imaging analyses in neuromyelitis optica spectrum disorder with or without visual disturbance

Background and purposeNeuromyelitis optica spectrum disorder is a demyelinating and inflammatory affliction that often leads to visual disturbance. Various imaging techniques, including free-water imaging, have been used to determine neuroinflammation and degeneration. Therefore, this study aimed at determining multimodal imaging differences between patients with neuromyelitis optica spectrum disorder, especially those with visual disturbance, and healthy controls. Materials and methodsEighty-five neuromyelitis optica spectrum disorder patients and 89 age- and sex-matched healthy controls underwent 3-T magnetic resonance imaging (MRI). We analyzed adjusted brain-predicted age difference, voxel-based morphometry, and free-water–corrected diffusion tensor imaging (DTI) by tract-based spatial statistics in each patient group (MRI-positive/negative neuromyelitis optica spectrum disorder patients with or without a history of visual disturbance) compared with the healthy control group. ResultsMRI-positive neuromyelitis optica spectrum disorder patients exhibited reduced volumes of the bilateral thalamus. Tract-based spatial statistics showed diffuse white matter abnormalities in all DTI metrics in MRI-positive neuromyelitis optica spectrum disorder patients with a history of visual disturbance. In MRI-negative neuromyelitis optica spectrum disorder patients with a history of visual disturbance, voxel-based morphometry showed volume reduction of bilateral thalami and optic radiations, and tract-based spatial statistics revealed significantly lower free-water–corrected fractional anisotropy and higher mean diffusivity in the posterior dominant distributions, including the optic nerve radiation. ConclusionFree-water–corrected DTI and voxel-based morphometry analyses may reflect symptoms of visual disturbance in neuromyelitis optica spectrum disorder.

Glial Fibrillary Acidic Protein Astrocytopathy: Review of Pathogenesis, Imaging Features, and Radiographic Mimics.

Glial fibrillary acidic protein (GFAP) astrocytopathy is a recently described autoimmune inflammatory disorder of the CNS characterized by the presence of specific antibodies targeting the intracellular filament protein in mature astrocytes. The pathogenesis is heterogeneous and poorly understood, with around 20%-34% of cases occurring as a paraneoplastic syndrome, most frequently associated with ovarian teratomas. It presents clinically as acute or subacute encephalomyelitis, and the diagnosis relies on imaging and detection of GFAP-Immunoglobulin (GFAP-IgG) in the CSF. Characteristic imaging findings include linear perivascular enhancement in the white matter extending in a radial pattern. Other imaging findings include periependymal enhancement, longitudinally extensive cord signal changes, intramedullary enhancement, optic neuritis, and papillitis. There is significant imaging overlap with other neuroinflammatory diseases like neuromyelitis optica spectrum disorder and lymphoproliferative conditions. GFAP astrocytopathy is characteristically responsive to steroids with, however, a significant rate of relapse. Currently, literature on this novel entity is limited with no established diagnostic criteria or standard treatment regimen. This comprehensive review explores the clinical, radiographic, and histopathologic aspects of GFAP astrocytopathy, shedding light on its complex nature and potential diagnostic challenges. The paper highlights the neuroimaging findings with a focus on differentiating GFAP astrocytopathy from other neuroinflammatory disorders.

Development Perspectives for Curative Technologies in Primary Demyelinating Disorders of the Central Nervous System with Neuromyelitis Optica Spectrum Disorder (NMOSD) and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) at the Forefront.

Primary demyelinating disorders of the central nervous system (CNS) include multiple sclerosis and the orphan conditions neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD). Curative technologies under development aim to selectively block autoimmune reactions against specific autoantigens while preserving the responsiveness of the immune system to other antigens. Our analysis focused on target patient selection for such developments, carefully considering the relevant clinical, regulatory, and market-related aspects. We found that the selection of patients with orphan conditions as target populations offers several advantages. Treatments for orphan conditions are associated with limited production capacity, qualify for regulatory incentives, and may require significantly shorter and lower-scale clinical programs. Furthermore, they may meet a higher acceptable cost-effectiveness threshold in order to compensate for the low numbers of patients to be treated. Finally, curative technologies targeting orphan indications could enter less competitive markets with lower risk of generic price erosion and would benefit from additional market protection measures available only for orphan products. These advantages position orphan conditions and subgroups as the most attractive target indications among primary demyelinating disorders of the CNS. The authors believe that after successful proof-of-principle demonstrations in orphan conditions, broader autoimmune patient populations may also benefit from the success of these pioneering developments.