Central vein sign and other radiographic features distinguishing myelin oligodendrocyte glycoprotein antibody disease from multiple sclerosis and aquaporin-4 antibody-positive neuromyelitis optica.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) can radiographically mimic multiple sclerosis (MS) and aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Central vein sign (CVS) prevalence has not yet been well-established in MOGAD. OBJECTIVE: Characterize the magnetic resonance imaging (MRI) appearance and CVS prevalence of MOGAD patients in comparison to matched cohorts of MS and AQP4+ NMOSD. METHODS: Clinical MRIs from 26 MOGAD patients were compared to matched cohorts of MS and AQP4+ NMOSD. Brain MRIs were assessed for involvement within predefined regions of interest. CVS was assessed by overlaying fluid-attenuated inversion recovery (FLAIR) and susceptibility-weighted sequences. Topographic analyses were performed on spinal cord and orbital MRIs when available. RESULTS: MOGAD patients had fewer brain lesions and average CVS+ rate of 12.1%, compared to 44.4% in MS patients (p = 0.0008). MOGAD spinal cord and optic nerve involvement was lengthier than MS (5.8 vs 1.0 vertebral segments, p = 0.020; 3.0 vs 0.5 cm, p < 0.0001). MOGAD patients tended to have bilateral/anterior optic nerve pathology with perineural contrast enhancement, contrasting with posterior optic nerve involvement in NMOSD. CONCLUSION: CVS+ rate and longer segments of involvement in the spinal cord and optic nerve can differentiate MOGAD from MS, but do not discriminate as well between MOGAD and AQP4+ NMOSD.

Dysphagia in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease as a surrogate of brain involvement?

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are demyelinating disorders that typically affect the optic nerves and the spinal cord. However, recent studies have demonstrated various forms of brain involvement indicating encephalitic syndromes, which consequently are included in the diagnostic criteria for both. Swallowing is processed in a distributed brain network and is therefore disturbed in many neurological diseases. The aim of this study was to investigate the occurrence of oropharyngeal dysphagia in NMOSD and MOGAD using flexible endoscopic evaluation of swallowing (FEES) as a surrogate parameter of brain involvement. METHODS: Thirteen patients with NMOSD and MOGAD (mean age 54.2 ± 18.6 years, six men) who received FEES during clinical routine were retrospectively reviewed. Their extent of oropharyngeal dysphagia was rated using an ordinal dysphagia severity scale. FEES results were compared to a control group of healthy individuals. Dysphagia severity was correlated with the presence of clinical and radiological signs of brain involvement, the Expanded Disability Status Scale (EDSS) and the occurrence of pneumonia. RESULTS: Oropharyngeal dysphagia was present in 8/13 patients, including six patients without other clinical indication of brain involvement. Clinical or subclinical swallowing impairment was significantly more severe in patients with NMOSD and MOGAD compared to the healthy individuals (p = 0.009) and correlated with clinical signs of brain involvement (p = 0.038), higher EDSS (p = 0.006) and pneumonia (p = 0.038). CONCLUSION: Oropharyngeal dysphagia can occur in NMOSD and MOGAD and might be associated with pneumonia and disability. FEES may help to detect subclinical brain involvement.

Biomarkers in Rare Demyelinating Disease of the Central Nervous System.

Rare neurological diseases are a heterogeneous group corresponding approximately to 50% of all rare diseases. Neurologists are among the main specialists involved in their diagnostic investigation. At the moment, a consensus guideline on which neurologists may base clinical suspicion is not available. Moreover, neurologists need guidance with respect to screening investigations that may be performed. In this respect, biomarker research has emerged as a particularly active field due to its potential applications in clinical practice. With respect to autoimmune demyelinating diseases of the Central Nervous System (CNS), although these diseases occur in the frame of organ-specific autoimmunity, pathology of the disease itself is orchestrated among several anatomical and functional compartments. The differential diagnosis is broad and includes, but is not limited to, rare neurological diseases. Multiple Sclerosis (MS) needs to be differentially diagnosed from rare MS variants, Acute Disseminated Encephalomyelitis (ADEM), the range of Neuromyelitis Optica Spectrum Disorders (NMOSDs), Myelin Oligodendrocyte Glycoprotein (MOG) antibody disease and other systemic inflammatory diseases. Diagnostic biomarkers may facilitate timely diagnosis and proper disease management, preventing disease exacerbation due to misdiagnosis and false treatment. In this review, we will describe advances in biomarker research with respect to rare neuroinflammatory disease of the CNS.

Optical coherence tomography angiography measurements in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease: A systematic review and meta-analysis.

PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are immune-mediated disorders that can often manifest with optic neuritis (ON) among other symptoms. Optical coherence tomography angiography (OCTA) is an emerging diagnostic method that can quantify retinal capillary blood flow and vessel density (VD), which have been shown to be affected in NMOSD and MOGAD. Hence, we aimed to systematically review the studies addressing retinal microvasculature using OCTA in these diseases. DESIGN: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, and Web of Sciences were systematically searched to identify articles addressing OCTA measurements in patients with NMOSD or MOGAD. Following the data extraction, a meta-analysis was performed on the study population and OCTA types amongst at least two homogenous studies. RESULTS: Twenty-two studies on NMOSD, MOGAD, or both were included. Parafoveal superficial retinal capillary plexus (SRCP) VD and radial peripapillary capillary (RPC) VD were diminished in NMOSD ON+ and NMOSD ON- groups compared to healthy controls (HCs). In addition, both the SRCP VD and RPC VD were significantly reduced in NMOSD ON+ compared to NMOSD ON-. However, meta-analysis for deep retinal capillary plexus (DRCP) did not show a significant difference between NMOSD patients and HCs, or among ON+ and ON- patients. Furthermore, there was no significant difference in foveal avascular zone (FAZ) area size between NMOSD patients and HCs. Regarding MOGAD, the meta-analysis showed decreased parafoveal SRCP VD and RPC VD in MOGAD ON+ patients compared to HCs. Comparing NMOSD ON+ and MOGAD ON+, a meta-analysis was conducted for RPC VD, which showed no significant difference between the two groups. CONCLUSIONS: This systematic review and meta-analysis confirmed reduced VD in the macular and peripapillary areas in NMOSD and MOGAD eyes, particularly in the parafoveal SRCP and RPC, which is further impacted by prior ON.

Uncovering the Diagnostic Challenge of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Case Study of Acute Bilateral Vision Loss.

We discuss a perplexing case of a 51-year-old female with a history of asthma and morbid obesity, presenting with acute bilateral vision loss of unknown etiology. The patient's clinical course was marked by a constellation of symptoms, including blurry vision, eyeball pain, photophobia, headache, nausea, and dizziness, prompting a multidisciplinary approach for diagnostic evaluation. Despite a comprehensive workup and a temporal artery biopsy ruling out large vessel arteritis, the etiology of vision loss remained elusive until myelin oligodendrocyte glycoprotein (MOG) antibody testing returned positive, implicating myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). High-dose corticosteroid therapy was initiated. However, the patient had worsening visual symptoms and was started on plasmapheresis and subsequent administration of Rituximab to prevent relapses, along with a long-term steroid taper regimen. This case underscores the diagnostic challenge of optic neuritis, particularly in MOGAD. It emphasizes the importance of a thorough evaluation and multidisciplinary collaboration.

Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

For over two centuries, clinicians have been aware of various conditions affecting white matter which had come to be grouped under the umbrella term multiple sclerosis. Within the last 20 years, specific scientific advances have occurred leading to more accurate diagnosis and differentiation of several of these conditions including, neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody disease. This new understanding has been coupled with advances in disease-modifying therapies which must be accurately applied for maximum safety and efficacy.

Case of MOG-IgG-associated disease with ankylosing spondylitis: A rare coexistence.

Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) is an inflammatory neurological disease. It progresses with attacks by affecting the optic nerves and spinal cord. Bilateral or recurrent optic neuritis are the most common findings in adult patients. Its association with systemic autoimmune disorders such as Sjögren syndrome, antiphospholipid syndrome, autoimmune thyroiditis, and celiac disease is rare. The first and only case of MOGAD in a patient with ankylosing spondylitis with a history of anti-tumor necrosis factor-alpha (anti-TNF-α) use was reported. Herein, we present the coexistence of MOGAD in a patient with AS who did not have a history of anti-TNF-α therapy.

Paediatric MOG-antibody disease presenting with intracranial hypertension and unilateral vision loss without radiological evidence of optic neuritis.

Intracranial hypertension (IH) is poorly described in paediatric myelin oligodendrocyte glycoprotein antibody disease (MOGAD). We describe a unique case of seropositive MOGAD in an obese 13-year-old boy who presented with an isolated IH, bilateral optic disc swelling and sudden-onset complete vision loss in one eye without radiological evidence of optic nerve involvement. Treatment with intravenous methylprednisolone combined with an emergency shunt fully restored vision and resolved the optic disc swelling. This report adds to the growing body of evidence suggesting that obese children presenting with isolated IH should be investigated for MOGAD, and the importance of managing IH during MOGAD.

Myelin Oligodendrocyte Glycoprotein Optic Neuritis Presenting With Orbital Apex Syndrome.

A 36-year-old man presented with an acute onset of a right eye monocular altitudinal defect associated with pain on eye movement upon waking up from sleep. His right eye subsequently developed outward deviation and a total loss of vision. Clinical examination of the right eye revealed a visual acuity of no light perception (NLP) with the presence of relative afferent pupillary defect (RAPD) and involvement of cranial nerves II, III, IV, and VI. A marked optic disc swelling and peripapillary hemorrhages were seen in the right fundus. Contrast-enhanced computed tomography of the brain and orbit showed a unilateral enlargement and enhancement of the right intraorbital and intracanalicular segments of the optic nerve with surrounding fat stranding and orbital apex crowding. Magnetic resonance imaging showed T2/fluid-attenuated inversion recovery hyperintensity and enhancement of the optic nerve and the myelin sheath. Serum anti-myelin oligodendrocyte glycoprotein antibodies were detected. He was treated with corticosteroids, plasma exchange, and intravenous immunoglobulin. His vision improved slowly after treatment. This case report shows the diverse manifestations of myelin oligodendrocyte glycoprotein antibody disease, which includes the orbital apex syndrome.

Retinal structural and microvascular changes in myelin oligodendrocyte glycoprotein antibody disease and neuromyelitis optica spectrum disorder: An OCT/OCTA study.

Purpose: To compare the optical coherence tomography (OCT)/OCT angiography (OCTA) measures in patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). Methods: Twenty-one MOG, 21 NMOSD, and 22 controls were enrolled in our study. The retinal structure [retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL)] was imaged and assessed with the OCT; OCTA was used to image the macula microvasculature [superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP)]. Clinical information such as disease duration, visual acuity, and frequency of optic neuritis and disability was recorded for all patients. Results: Compared with NMOSD patients, MOGAD patients showed significantly reduced SVP density (P = 0.023). No significant difference (P > 0.05) was seen in the microvasculature and structure when NMOSD-ON was compared with MOG-ON. In NMOSD patients, EDSS, disease duration, reduced visual acuity, and frequency of ON significantly correlated (P < 0.05) with SVP and ICP densities; in MOGAD patients, SVP correlated with EDSS, duration, reduced visual acuity, and frequency of ON (P < 0.05), while DCP density correlated with disease duration, visual acuity, and frequency of ON. Conclusions: Distinct structural and microvascular changes were identified in MOGAD patients compared with NMOSD patients suggesting that the pathological mechanisms are different in NMOSD and MOGAD. Retinal imaging via the SS-OCT/OCTA might have the potential to be used as a clinical tool to evaluate the clinical features associated with NMOSD and MOGAD.

Centrally-located transverse myelitis would facilitate the differentiation of NMOSD and MOG-AD from MS.

OBJECTIVES: Differentiating neuromyelitis optica spectrum disorder (NMOSD) and Myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) from multiple sclerosis (MS) is important since MS therapies might result in progression and relapse of the former diseases. Evidence of long extending transverse myelitis (LETM) in magnetic resonance imaging (MRI) is one of the requirements to make an NMOSD diagnosis. However, centrally located lesions on spinal MRI may bring higher sensitivity and specificity to the NMOSD and MOG-AD diagnosis. METHODS: We aimed to assess the association between NMOSD diagnosis and the presence of centrally located lesions at disease onset. We reviewed 102 medical records from the Isfahan MS clinic who presented with cervical cord lesions and 17 MS, 23 NMOSD, and 6 MOG-AD patients were selected. We collected demographic, clinical, and MRI data of patients who had clinical presentations of cervical cord lesion at disease onset, and the characteristics of the lesion were studied. RESULTS: There was an association between NMOSD diagnosis and presence of a centrally located lesion (CLTM) (P < 0.001), presence of an LETM (P < 0.001), and an intermediate to high axial cord expansion (P < 0.001). CLTM and LETM can also be found in MOG-AD patients. The presence of CLTM (sensitivity and specificity: 95.65% and 69.56%), possessed higher sensitivity and specificity for NMO diagnosis than LETM presence (sensitivity and specificity: 78.26% and 43.47%). CONCLUSION: A diagnostic criteria including the centrality, location, and expansion of the transverse myelitis lesions, in addition to LETM, may be more accurate in the diagnosis of NMOSD and MOG-AD and their distinction from MS.

MOG antibody associated disease (MOGAD) presenting with extensive brain stem encephalitis: A case report.

Background: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a relatively new entity of demyelinating diseases, clinically presenting with optic neuritis, transverse myelitis, or encephalic symptoms. Typical radiological features include demyelinating cerebral and spinal lesions, cortical involvement, leptomeningeal enhancement, or tumefactive lesions. Here we present a rare case of a young patient with extensive brain stem lesion on the MRI while exhibiting nystagmus, singultus and somnolence. Case presentation: A 30-year-old male patient presented initially with fever and impaired consciousness, but furthermore developed nystagmus, singultus and tetraparesis during the following week. Repeated MRI examinations revealed extensive brain stem edema with notable bilateral affection of the cerebellar peduncles and the pons. Antiviral and antibiotic treatment was changed to intravenous corticosteroids and immunoglobulins as soon as the diagnosis of MOGAD was established by testing serum and cerebrospinal fluid positive for MOG specific antibodies. MRI alterations vanished completely over time with a delayed, nearly complete clinical recovery of our patient. Conclusion: Brain stem affection in MOGAD is rare. However, in patients presenting with an unclear brain stem encephalitis the possibility of MOGAD should be considered and tested using MOG antibodies. In case of a positive testing treatment with steroids and immunoglobulins seems recommendable.

Clinical and Radiological Characteristics of Children and Adults With First-Attack Myelin Oligodendrocyte Glycoprotein Antibody Disease and Analysis of Risk Factors for Predicting the Severity at Disease Onset in Central China.

Objective: To analyze and compare different clinical, laboratory, and magnetic resonance imaging characteristics between pediatric and adult patients with first-attack myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and to explore predictive factors for severity at disease onset. Methods: Patients diagnosed with MOGAD at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2021 were enrolled in this retrospective study. Age at disease onset, sex, comorbidities, laboratory tests, magnetic resonance imaging (MRI) characteristics, and Expanded Disability Status Scale (EDSS) scores were collected and analyzed. The association between risk factors and initial EDSS scores at disease onset was analyzed using logistic regression models and Spearman correlation analyses. A receiver-operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of the uric acid and homocysteine (Hcy) levels for the severity of neurological dysfunction at the onset of MOGAD. Results: Sixty-seven patients (female, n=34; male, n=33) with first-attack MOGAD were included in this study. The mean age at onset was 26.43 ± 18.22 years (range: 3-79 years). Among patients <18 years of age, the most common presenting symptoms were loss of vision (36.0%), and nausea and vomiting (24.0%), and the most common disease spectrum was acute disseminated encephalomyelitis (ADEM) (40.0%). Among patients aged ≥18 years, the most common presenting symptoms were loss of vision (35.7%), paresthesia (33.3%), and paralysis (26.2%), and the most common disease spectrum was optic neuritis (35.7%). The most common lesions were cortical gray matter/paracortical white matter lesions in both pediatric and adult patients. Uric acid [odds ratio (OR)=1.014; 95% confidence interval (CI)=1.006-1.022; P=0.000] and serum Hcy (OR=1.125; 95% CI=1.017-1.246; P=0.023) levels were significantly associated with the severity of neurological dysfunction at disease onset. Uric acid levels (r=0.2583; P=0.035) and Hcy levels (r=0.3971; P=0.0009) were positively correlated with initial EDSS scores. The areas under the ROC curve were 0.7775 (95% CI= 0.6617‒0.8933; P<0.001) and 0.6767 (95% CI=0.5433‒0.8102, P=0.014) for uric acid and Hcy levels, respectively. Conclusion: The clinical phenotype of MOGAD varies in patients of different ages. The most common disease spectrum was ADEM in patients aged<18 years, while optic neuritis was commonly found in patients aged ≥18 years. The uric acid and Hcy levels are risk factors for the severity of neurological dysfunction at disease onset in patients with first-attack MOGAD.

Efficacy and safety of long-term immunotherapy in adult patients with MOG antibody disease: a systematic analysis.

OBJECTIVE: To summarise the evidence of the efficacy and safety of current long-term immunotherapies in patients with myelin oligodendrocyte glycoprotein antibody disease (MOG-AD). METHODS: We performed a sensitive literature search in MEDLINE and EMBASE for selected studies or case series discussing the long-term treatments and outcomes in adult patients with MOG-AD and conducted a qualitative analysis of each therapy. RESULTS: A total of 33 articles, including 712 patients with MOG-AD, matched our inclusion criteria, and seven kinds of drugs were analysed accordingly. Efficacy was mainly reflected by the change in the annual relapse rate before and after treatment. First, maintenance steroids, azathioprine, mycophenolate mofetil, and rituximab were demonstrated to be effective in multiple studies. However, relapses could still happen after therapy especially under specific circumstances. Second, regular intravenous immunoglobulin G (IVIG) and tocilizumab might be effective. IVIG reduced annual relapse rate and expanded disability status scale in five adult patients, and tocilizumab succeeded in preventing relapse in four refractory patients, though with scant evidence. Finally, multiple sclerosis-disease-modifying therapy seemed ineffective for patients with MOG-AD. As for safety, six patients experienced severe neutropenia during rituximab therapy. No other serious adverse events were reported for these treatments. CONCLUSIONS: Several preventive immunotherapies have been demonstrated to be effective and safe for adult patients with MOG-AD; however, large controlled studies for subgroups with specific manifestations are still needed in the future.

Longitudinally Extensive Transverse Myelitis in Highly Active Relapsing-remitting Multiple Sclerosis.

Transverse myelitis in multiple sclerosis is typically a short cord lesion with patchy distribution. Rarely, longitudinally extensive transverse myelitis can be seen in those with highly active disease or frequent relapses. The recognition of this uncommon phenotype in multiple sclerosis is important as the treatment is largely different from other demyelinating diseases. We describe a patient with highly active relapsing-remitting multiple sclerosis on interferon beta-1a who developed LETM after multiple relapses.

Isolated Double-Positive Optic Neuritis: A Case of Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibody Seropositivity.

Optic neuritis (ON) causes acute vision loss with typical and atypical profiles, serological markers, imaging findings, and clinical outcomes depending on the associated underlying pathophysiology. Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are the usual causes of acute severe sequential or simultaneous bilateral optic neuritis. These conditions are usually accompanied by multi-level spinal cord demyelination, and notably, they are typically positive for either NMO or Myelin oligodendrocyte glycoprotein (MOG) autoantibodies, but rarely both. We present a case of isolated sequential bilateral optic neuritis that was seropositive for both NMO and MOG antibodies.

The use of OCT in good visual acuity MOGAD and AQP4-NMOSD patients; with and without optic neuritis.

Myelin oligodendrocyte-antibody-associated disease (MOGAD) often presents with severe optic neuritis (ON) but tends to recover better than in aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD). We measured OCT and VEP in MOGAD and AQP4-NMOSD eyes with good visual function, with or without previous ON episodes. Surprisingly, OCT and/or VEPs were abnormal in 84% MOGAD-ON versus 38% AQP4-NMOSD-ON eyes (p = 0.009) with good vision, compared with 18% and 17% respectively of eyes with no previous ON. A sub-group with macular OCT performed as part of a research study confirmed both retinal and macular defects in visually-recovered MOGAD eyes. These findings have implications for investigation and management of MOGAD patients.

MRI Characteristics of NMO, MOG and MS Related Optic Neuritis.

Acute isolated optic neuritis can be the initial presentation of demyelinating inflammatory central nervous system disease related to multiple sclerosis (MS), neuromyelitis optica (NMO) or myelin oligodendrocyte glycoprotein antibody disease (MOG-AD). In addition to the well-characterized brain and spinal cord imaging features, important and characteristic differences in the radiologic appearance of the optic nerves in these disorders are being described, and magnetic resonance imaging (MRI) of the optic nerves is becoming an essential tool in the differential diagnosis of optic neuritis. Whereas typical demyelinating optic neuritis is a relatively mild and self-limited disease, atypical optic neuritis in NMO and MOG-AD is potentially much more vision-threatening and merits a different treatment approach. Thus, differentiation based on MRI features may be particularly important during the first attack of optic neuritis, when antibody status is not yet known. This review discusses the optic nerve imaging in the major demyelinating disorders with an emphasis on clinically relevant differences that can help clinicians assess and manage these important neuro-ophthalmic disorders. It also reviews the utility of optic nerve MRI as a prognostic indicator in acute optic neuritis.

Dimethyl Fumarate Was Ineffective but Not Harmful for a Patient with Myelin Oligodendrocyte Glycoprotein Antibody Disease.

We treated a myelin oligodendrocyte glycoprotein (MOG) antibody disease patient who had been prescribed dimethyl fumarate because she was thought to have been suffering from multiple sclerosis (MS). Mild optic neuritis relapsed at one year and four months after the administration of dimethyl fumarate. Therefore, dimethyl fumarate was ineffective for preventing relapse of MOG antibody disease. However, dimethyl fumarate for MOG antibody disease was not harmful compared with when disease-modifying drugs (DMDs) of MS were used for anti-aquaporin-4 antibody-positive neuromyelitis optica. If MS patients repeat relapses even after the start of DMDs, a differential diagnosis including MOG antibody disease should be made.