Myelin Oligodendrocyte Glycoprotein Research Articles

A rare presentation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) as acute hemorrhagic longitudinally extensive transverse myelitis

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated disease is usually associated with optic neuritis, acute disseminated encephalomyelitis or transverse myelitis. We are presenting a rare case report wherein myelin oligodendrocyte glycoprotein antibody seropositivity was associated with hemorrhagic longitudinally extensive transverse myelitis. To our knowledge, no such cases were found to be published.Case presentationA 15-year-old female came with complaints of sudden onset paraparesis. MRI was performed within 48 h from the episode of paraparesis, which revealed a long-segment, intramedullary, expansile and heterogeneously enhancing spinal cord lesion extending from T1 vertebral level up to conus medullaris. Few foci of blooming were also noted within the spinal cord on gradient sequences. Laboratory evaluation of cerebrospinal fluid analysis revealed no significant abnormality. Neuromyelitis optica antibodies were negative, and myelin oligodendrocyte glycoprotein antibodies (MOG) showed seropositivity. The patient was started on methylprednisolone and plasmapheresis for the same after which the patient gradually improved and regained her ability to walk. Follow-up MRI was performed after 4 weeks, which revealed significant reduction in the extent of the intramedullary lesion described earlier.ConclusionsHemorrhagic longitudinally extensive transverse myelitis without any involvement of optic nerves and brain may show MOG seropositivity, and it should be considered as one of the differential diagnosis in acute myelopathy.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Following Adenovirus Meningitis After First Delivery: Case Report and Literature Review

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Following Adenovirus Meningitis After First Delivery: Case Report and Literature Review

Beyond Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibodies: Alternative Causes of Optic Neuritis.

Optic neuritis (ON) is the most common cause of vision loss in young adults. It manifests as acute or subacute vision loss, often accompanied by retrobulbar discomfort or pain during eye movements. Typical ON is associated with Multiple Sclerosis (MS) and is generally mild and steroid-responsive. Atypical forms are characterized by unusual features, such as prominent optic disc edema, poor treatment response, and bilateral involvement, and they are often associated with autoantibodies against aquaporin-4 (AQP4) or Myelin Oligodendrocyte Glycoprotein (MOG). However, in some cases, AQP4 and MOG antibodies will return as negative, plunging the clinician into a diagnostic conundrum. AQP4- and MOG-seronegative ON warrants a broad differential diagnosis, including autoantibody-associated, granulomatous, and systemic disorders. These rare forms need to be identified promptly, as their management and prognosis are greatly different. The aim of this review is to describe the possible rarer etiologies of non-MS-related and AQP4- and MOG-IgG-seronegative inflammatory ON and discuss their diagnoses and treatments.

Invasive Multimodality Neuromonitoring to Manage Cerebral Edema in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory disorder of the CNS with a variety of clinical manifestations, including cerebral edema. Case Summary: A 7-year-old boy presented with headaches, nausea, and somnolence. He was found to have cerebral edema that progressed to brainstem herniation. Invasive multimodality neuromonitoring was initiated to guide management of intracranial hypertension and cerebral hypoxia while he received empiric therapies for neuroinflammation. Workup revealed serum myelin oligodendrocyte glycoprotein antibodies. He survived with a favorable neurologic outcome. Conclusion: We describe a child who presented with cerebral edema and was ultimately diagnosed with MOGAD. Much of his management was guided using data from invasive multimodality neuromonitoring. Invasive multimodality neuromonitoring may have utility in managing life-threatening cerebral edema due to neuroinflammation.

Increased Intracranial Pressure in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Elevated intracranial pressure (ICP) in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) has been largely unexplored. The objectives of this study were to determine the frequency of increased ICP in MOGAD and its association with disease course and outcomes and to highlight cases requiring medical and/or surgical management of increased ICP. In this retrospective, single-center cohort study, we examined the clinical and paraclinical data from the initial presentation and follow-up data of children diagnosed with MOGAD. In those with opening pressure (OP) measurements, univariate analyses were used to evaluate factors associated with increased ICP, which was defined as OP > 28 cm H2O. We also present a case series of patients with or without OP measurement who required medical and/or surgical management of increased ICP. Of 86 children with MOGAD, 43 (50.0%) had an OP recorded and 7 (8.1%) required ICP management. In those with OP recorded, the median (interquartile range) OP for the different MOGAD phenotypes were: 30.0 (22.8-41.6) (acute disseminated encephalomyelitis, ADEM), 20.5 (16.1-23.6) (optic neuritis), 17.0 (17.0-22.5) (myelitis), and 19.5 (16.5-29.3) (other) cm H20. Overall, 20.9% had increased ICP based on an OP > 28 cm H2O, of whom 77.8% presented with ADEM. In a subgroup analysis of those presenting with ADEM, those with an elevated ICP had longer hospital stay (p = 0.007) and neurologic disability (defined as modified Rankin Scale >1) (p = 0.049). In those with or without OP recorded, 7 (6 with ADEM, one with cerebral cortical encephalitis) required ICP-directed therapies. Findings on brain MRI in these 7 children revealed extensive disease burden with bilateral cerebral involvement and evidence of restricted diffusion. While neuropsychological data in this small subset revealed significant variability, all sustained identifiable deficits after discharge, including attention-deficit hyperactivity disorders and language and learning disorders. In pediatric MOGAD, increased OP and ADEM at initial presentation were associated with longer hospital stays and greater long-term morbidity. Although invasive ICP monitoring has not been specifically advocated in the management of MOGAD, it is important to recognize signs and symptoms of increased ICP in these patients and consider ICP monitoring and management strategies based on clinical and radiologic findings, especially in those presenting with ADEM and with OP > 28 cm H2O.

Clinical practice guidelines for myelin oligodendrocyte glycoprotein antibody-associated disease in children

Clinical practice guidelines for myelin oligodendrocyte glycoprotein antibody-associated disease in children

Abstract 087: Cocaine‐Induced Acute Spinal Cord Ischemia Syndrome

Introduction Acute spinal cord ischemia syndrome (ASCIS) is a rare disease that is thought to comprise roughly only 1.2% of all strokes [1, 2]. These strokes primarily occur in the anterior spinal cord artery (ASA) and/or the posterior spinal cord artery (PCA) territory and can have widely variable clinical presentation. The use of recreational cocaine in young adults is well known to be responsible for acute ischemic and hemorrhagic strokes in individuals who lack other vascular risk factors. What is significantly rarer with few reported cases, however, is cocaine‐related ASCIS as the etiology of non‐traumatic acute spinal cord myelopathy [3‐7]. Methods N/A Results A 40‐year‐old female with a history of type I Diabetes mellitus, bipolar disorder, and polysubstance abuse presented with acute‐onset bilateral lower limb weakness, sensory loss, neck pain, and bladder incontinence. On admission, she reported using intravenous crack cocaine in the evening before admission and experiencing a fall in the bathroom a few hours after. She was unable to move her lower limbs following this fall. On examination, there was flaccid weakness in both lower extremities with decreased pinprick sensation below the T4 level and absent sensation below the thighs on both sides. She had no trauma preceding her symptoms and denied any recent vaccinations or travel history. An urgent CT (computed tomography) scan of the cervical, thoracic, and lumbar spine ruled out any obvious traumatic injury. Her urine drug screen was positive for cocaine, opiate, cannabinoid, and benzodiazepine. MRI (Magnetic Resonance Imaging) of the brain without contrast was unremarkable. MRI of the spine with contrast demonstrated two areas of T2 hyperintensities from C5‐C6 and T4 to the conus with cord expansion. The lesion in the thoracic spinal cord showed contrast enhancement and spared the dorsal column. Lumbar puncture was traumatic and showed elevated protein (>300 mg/dl) as well as elevated glucose (186 mg/dl). CSF studies, including meningitis/encephalitis panel, gram stain and culture, flow cytometry, cytology, and oligoclonal bands were negative. Serum autoimmune myelopathy panel, serum Aquaporin‐4 antibodies and MOG (Myelin Oligodendrocyte Glycoprotein) antibodies were negative. The other etiologies of non‐traumatic myelopathy, including HIV, Treponema pallidum, and HTLV‐I/II antibodies, were negative. A diagnostic spinal angiogram was completed with no evidence of arteriovenous fistula or aortic dissection. She completed five days of plasma exchange without any improvement and was transferred to an acute rehabilitation facility. At four months follow‐up, she continues to be flaccid in her lower limbs and requires a urinary catheter leading to frequent urinary tract infections. Conclusion While cocaine‐related cerebrovascular events are well documented, very few cases of cocaine‐related ASCIS have been described. The mechanism is thought to be multifactorial due vasospasm, cerebral vasculitis, vascular thrombosis, cardioembolism from cocaine‐induced myocardial infarction or cardiomyopathy, and hypertensive surges [9]. Due to the scarcity of these events, the patient outcomes are unclear. Other studies on outcomes of spinal cord ischemia have shown that ASIA Impairment Scale (AIS) score, lesion level, and patient age were the strongest predictors of neurologic and functional outcomes, whereas etiology of the ischemia had no effect on outcomes [10].

28 Neurocognitive profile of pediatric acquired demyelinating syndrome with and without myelin oligodendrocyte glycoprotein antibody disease (MOGAD)

Objective:Pediatric acquired demyelinating syndromes (PADS) include a heterogeneous group of diagnoses, including acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), optic neuritis (ON) and transverse myelitis (TM). Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is often associated with demyelinating conditions, but may also present with encephalopathy without demyelinating lesions. Approximately 30% of patients diagnosed with MOGAD experience a relapse. Neurocognitive outcomes in PADS have reduced performance on tasks related to attention, processing speed, visual motor, and fine motor functioning. Psychosocial problems include anxiety, depression, and fatigue. Neurocognitive and psychosocial impacts of MOGAD events for the pediatric population are sparse. The current study sought to characterize neurocognitive sequelae from MOGAD (MAGAD+) compared to patients diagnosed with PADS without MOGAD (MOGAD-).Participants and Methods:Twenty children and adolescents (6–18 years) diagnosed with PADS were recruited using a clinic convenience sample of patients. Study participants completed a neurocognitive battery and parents completed questionnaires of behavioral and emotional functioning. Demographic and medical variables were collected via retrospective chart review. Chi square and t-test analyses were used to compare MOGAD+ and MOGAD- groups. Performance on neuropsychological and behavioral questionnaires were compared to established sex and age norms to assess the degree to which group means deviate from normative expectations.Results:MOGAD+ and MOGAD- groups did not significantly differ based on demographic, neurocognitive, or parent reported social and behavioral functioning. Neurocognitive testing documented mean scores that were in the average range between groups. Notable variability in performance was observed within both MOGAD+ and MOGAD- groups. Bilateral fine motor deficits, visual motor, visual perception attention, and executive functioning deficits were notable for the combined PADS group, with 30-50% performing >1.5 SD below the mean. The number of white matter lesions or hospital duration were not significantly associated with performance on neurocognitive measures. However, older age of onset of PADS was significantly correlated with lower performance on visual motor integration and visual perception tasks (r(18) = -.50 p = .026; r(18) = -.53 p = .016). Findings also revealed associations of shorter hospitalization stays with higher behavioral symptoms on a parent measure of social/behavioral functioning (r(18) = -.47 p = .037).Conclusions:Consistent with the PADS literature, relative to control norms, lower performance on tasks related to attention, executive functioning, visual motor, and fine motor skills, irrespective of MOGAD status, are observed in the current study. The variability of functioning and heterogeneity observed across PADS diagnoses warrants further study to better understand the impact of clinical course, treatment outcomes, and neuropsychological sequelae over time in this population. Higher behavioral distress with shorter hospital stays may indicate a potential opportunity for patient and family education preparing for return to home/community. The current study was limited by small sample size, variable time since hospitalization, and heterogeneous diagnoses within PADS that make it difficult to generalize findings. Future studies could prospectively follow patients over time to better understand the trajectory of recovery, identify predictors for relapse, and those at greatest risk of neurocognitive and behavioral deficits.

Clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease in Brazil: a single-center experience.

Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody-associated disease (MOGAD) is an immune-mediated neurological disorder with a broad spectrum of clinical presentation that is often difficult to distinguish from other demyelinating diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorder. To describe the clinical and paraclinical characteristics of MOGAD in a Brazilian tertiary center. We retrospectively reviewed the records of adult and pediatric patients who tested positive for anti-MOG antibodies and presented with clinical and radiological diseases compatible with MOGAD. Forty-one patients (10 children) were included: 56% female, 58% Caucasian, mean age at onset 31 years (range 6-64), with a mean disease duration of 59.6 months (range 1-264 months). The most frequent onset presentation was optic neuritis (68%), acute disseminated encephalomyelitis (ADEM, 12%), and myelitis (10%). A monophasic disease course was observed in 49%. EDSS median was 2.1 at the last visit. Most patients (83%) were under continuous immunosuppressive treatment. Azathioprine was the first-line treatment in 59%. In all ADEM cases, conus, and root involvement was radiologically observed on MRI. Brazilian MOGAD patients presented with a similar spectrum of previously reported MOGAD phenotypes. Conus and spinal root involvement seems to be frequently present in MOGAD-ADEM and could serve as radiologic characteristics of this clinical entity.

Serum neurofilament and glial fibrillary acidic protein in idiopathic and seropositive transverse myelitis.

Serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect the disease activity and disability in central nervous system (CNS) demyelinating diseases. However, the clinical significance of NfL and GFAP in idiopathic transverse myelitis (iTM), an inflammatory spinal cord disease with unknown underlying causes, remains unclear. This study aimed to investigate NfL and GFAP levels in iTM and their association with the clinical parameters compared with those in TM with disease-specific antibodies such as anti-aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies (sTM). We collected serum and clinical data of 365 patients with CNS inflammatory diseases from 12 hospitals. The serum NfL and GFAP levels were measured in patients with iTM (n=37) and sTM (n=39) using ultrasensitive single-molecule array assays. Regression analysis was performed to investigate the associations between serum levels of NfL and GFAP and the clinical parameters such as higher EDSS scores (EDSS ≥ 4.0). Mean NfL levels were not significantly different between iTM (50.29pg/ml) and sTM (63.18pg/ml) (p=0.824). GFAP levels were significantly lower in iTM (112.34pg/ml) than in sTM (3814.20pg/ml) (p=0.006). NfL levels correlated with expanded disability status scale (EDSS) scores in sTM (p=0.001) but not in iTM (p=0.824). Disease duration also correlated with higher EDSS scores in sTM (p=0.017). NfL levels and disease duration correlated with EDSS scores in sTM, and GFAP levels could be a promising biomarker to differentiate iTM from sTM.

Delayed oculomotor response associates with optic neuritis in youth with demyelinating disorders.

Impairment in visual and cognitive functions occur in youth with demyelinating disorders such as multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease. Quantitative behavioral assessment using eye-tracking and pupillometry can provide functional metrics for important prognostic and clinically relevant information at the bedside. Children and adolescents diagnosed with demyelinating disorders and healthy, age-matched controls completed an interleaved pro- and anti-saccade task using video-based eye-tracking and underwent spectral-domain optical coherence tomography examination for evaluation of retinal nerve fiber layer and ganglion cell inner plexiform layer thickness. Low-contrast visual acuity and Symbol Digit Modalities Test were performed for visual and cognitive functional assessments. We assessed saccade and pupil parameters including saccade reaction time, direction error rate, pupil response latency, peak constriction time, and peak constriction and dilation velocities. Generalized Estimating Equations were used to examine the association of eye-tracking parameters with optic neuritis history, structural metrics, and visual and cognitive scores. The study included 36 demyelinating disorders patients, aged 8-18 yrs. (75% F; median=15.22 yrs., SD=2.8) and 34 age-matched controls (65% F; median=15.26 yrs., SD=2.3). Surprisingly, pro- and anti-saccade performance was comparable between patients and controls, whereas pupil control was altered in patients. Oculomotor latency measures were strongly associated with the number of optic neuritis episodes, including saccade reaction time, pupil response latency, and peak constriction time. Peak constriction time was associated with both retinal nerve fiber layer and ganglion cell inner plexiform layer thickness. Pupil response latency and peak constriction time were associated with visual acuity. Pupil velocity for both constriction and dilation was associated with Symbol Digit Modalities Test scores. The strong associations between oculomotor measures with history of optic neuritis, structural, visual, and cognitive assessments in these cohorts demonstrates that quantitative eye-tracking can be useful for probing demyelinating injury of the brain and optic nerve. Future studies should evaluate their utility in discriminating between demyelinating disorders and tracking disease progression.

Emerging Principles for Treating Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)

Emerging Principles for Treating Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)

A Canadian case control study investigating demographic and environmental factors associated with MOGAD.

Little is known about demographic and environmental factors associated with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). To investigate factors associated with MOGAD using a case-control design and validated questionnaire from the Environmental Risk Factors in Multiple Sclerosis Study (EnvIMS). We enrolled patients with positive MOG antibody serology and diagnosis of MOGAD at six Canadian centres. MOGAD participants completed the EnvIMS questionnaire, and were compared to unaffected controls from the Canadian arm of EnvIMS. We calculated crude and adjusted odds ratios (OR) using logistic regression models and Firth's procedure for rare events. We enrolled 39 MOGAD participants with mean (SD) age 45.0 (14.4) years, 28 (71.8%) women, 25 (64.1%) White, 26 (66.7%) residents of Ontario, and mean BMI 28.6 (7.1). They were compared to 956 controls. Using multivariable logistic regression, larger body size at age 10 years (OR: 3.57, 95% CI:1.23 - 10.33) and non-White ethnicity (OR:3.81, 95% CI:1.93-7.54) were associated with higher odds of MOGAD. Among Ontario residents, current BMI ≥30 was associated with higher odds of MOGAD (OR:2.79, 95% CI:1.03-7.53). Our findings are hypothesis-generating due to the sample size, but suggest that obesity and ethnicity should be explored as potential risk factors for MOGAD in other settings.

Classification of Myelin Oligodendrocyte Glycoprotein Antibody-Related Disease and Its Mimicking Acute Demyelinating Syndromes in Children Using MRI-Based Radiomics: From Lesion to Subject

To develop MRI-based radiomics models from the lesion level to the subject level and assess their value for differentiating myelin oligodendrocyte glycoprotein antibody-related disease (MOGAD) from non-MOGAD acute demyelinating syndromes in pediatrics. 66 MOGAD and 66 non-MOGAD children were assigned to the training set (36/35), internal test set (14/16), and external test set (16/15), respectively. At the lesion level, five single-sequence models were developed alongside a fusion model (combining these five sequences). The radiomics features of each lesion were quantified as the lesion-level radscore (LRS) using the best-performing model. Subsequently, a lesion-typing function was employed to classify lesions into two types (MOGAD-like or non-MOGAD-like), and the average LRS of the predominant type lesions in each subject was considered as the subject-level radscore (SRS). Based on SRS, a subject-level model was established and compared toboth clinical models and radiologists' assessments. At the lesion level, the fusion model outperformed the five single-sequence models in distinguishing MOGAD and non-MOGAD lesions (0.867 and 0.810 ofarea under the curve[AUC] in internal and external testing, respectively). At the subject level, the SRS model showed superior performance (0.844 and 0.846 of AUC in internal and external testing, respectively) compared to clinical models and radiologists' assessments for distinguishing MOGAD and non-MOGAD. MRI-based radiomics models have potential clinical value for identifying MOGAD from non-MOGAD. The fusion model and SRS model can distinguish between MOGAD and non-MOGAD at the lesion level and subject level, respectively, providing a differential diagnosis method for these two diseases.

Pro-inflammatory GPR75 and anti-apoptotic phospholipase signaling pathways contribute to the ameliorating effect of soluble epoxide hydrolase inhibition on chronic experimental autoimmune encephalomyelitis in mice.

Soluble epoxide hydrolase (sEH) inhibition has currently emerged as a therapeutic target in the treatment of various neuroinflammatory neurodegenerative diseases, including multiple sclerosis. Previously, we reported that treatment of mice with a sEH-selective inhibitor, 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea; TPPU), ameliorated chronic experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein 35-55 peptide immunization followed by injection of pertussis toxin to mice via regulating pro-inflammatory and anti-inflammatory pathways in the central nervous system. This study tested the hypothesis that the pro-inflammatory G protein-coupled receptor (GPR) 75 and anti-apoptotic phospholipase C (PLC) signaling pathways also contribute to the ameliorating effect of TPPU on chronic EAE. Brains and spinal cords of phosphate-buffered saline-, dimethyl sulfoxide-, or TPPU (3 mg/kg)-treated mice were used for the measurement of sEH, GPR75, Gaq/11, activator protein (AP)-1, PLC β4, phosphoinositide 3-kinase (PI3K) p85a, Akt1, mitogen-activated protein kinase kinase (MEK) 1/2, extracellular signal-regulated kinase (ERK) 1/2, cyclic adenosine monophosphate-response element-binding protein (CREB) 1, B-cell lymphoma (Bcl)-2, semaphorin (SEMA) 3A, and myelin proteolipid protein (PLP) expression and/or activity by using the immunoblotting method. Expression of sEH, GPR75, Gaq/11, c-jun, phosphorylated c-Jun, and SEMA3A was lower, while PLCβ4, phosphorylated PI3K p85a, phosphorylated Akt1, phosphorylated MEK1/2, phosphorylated ERK1/2, phosphorylated CREB1, Bcl-2, and myelin PLP expression was higher in the tissues of TPPU (3 mg/kg)-treated mice as compared with the EAE and vehicle control groups. Inhibition of sEH by TPPU ameliorates chronic EAE through suppressing pro-inflammatory GPR75/Gaq/11/AP-1 pathway and reducing expression of the remyelination inhibitor, SEMA3A, as well as increasing anti-apoptotic PLC/PI3K/Akt1/MEK1/2/ERK1/2/CREB1/Bcl-2 pathway activity and myelin PLP expression.

Longitudinal in vivo evaluation of retinal ganglion cell complex layer and dendrites in mice with experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE), induced by the immunization of myelin oligodendrocyte glycoprotein (MOG), is related to human MOG antibody-associated disease (MOGAD). Neuroinflammation and demyelination of the optic nerve can lead to retinal ganglion cell (RGC) death and axonal damage in MOGAD. Here, we aimed to evaluate the structural changes in RGCs longitudinally by in vivo imaging in mice with RGCs expressing yellow fluorescent protein along the course of EAE. Successful induction of EAE was confirmed by the neurological function scores and histology analyses. The changes in the thickness of ganglion cell complex (GCC) layer and RGC survival and dendrites were monitored longitudinally along the course of EAE. Before the onset of EAE, there were no significant changes in the number and morphology of RGCs and the thickness of the GCC layer as compared to the mice without EAE induction. After the onset of EAE, the thickness of the GCC layer and the RGC number and dendritic network all gradually decreased along the course of EAE. Notably, dendritic shrinkage could be detected earlier than the thinning of the GCC layer. In summary, this study delineated the longitudinal profile of RGC structural changes in EAE mice, providing an assessment platform for monitoring outcomes of RGC treatments.

Susceptibility-based imaging aids accurate distinction of pediatric-onset MS from myelin oligodendrocyte glycoprotein antibody-associated disease

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) and pediatric-onset multiple sclerosis (POMS) share clinical and magnetic resonance imaging (MRI) features but differ in prognosis and management. Early POMS diagnosis is essential to avoid disability accumulation. Central vein sign (CVS), paramagnetic rim lesions (PRLs), and central core lesions (CCLs) are susceptibility-based imaging (SbI)-related signs understudied in pediatric populations that may help discerning POMS from MOGAD. Methods: T2-FLAIR and SbI (three-dimensional echoplanar imaging (3D-EPI)/susceptibility-weighted imaging (SWI) or similar) were acquired on 1.5T/3T scanners. Two readers assessed CVS-positive rate (%CVS+), and their average score was used to build a receiver operator curve (ROC) assessing the ability to discriminate disease type. PRLs and CCLs were identified using a consensual approach. Results: The %CVS+ distinguished 26 POMS cases (mean age 13.7 years, 63% females, median EDSS 1.5) from 14 MOGAD cases (10.8 years, 35% females, EDSS 1.0) with ROC = 1, p < 0.0001, (cutoff 41%). PRLs were only detectable in POMS participants (mean 2.1±2.3, range 1–10), discriminating the two conditions with a sensitivity of 69% and a specificity of 100%. CCLs were more sensitive (81%) but less specific (71.43%). Conclusion: The %CVS+ and PRLs are highly specific markers of POMS. After proper validation on larger multicenter cohorts, consideration should be given to including such imaging markers for diagnosing POMS at disease onset.

In silico analysis of RPS4X (X-linked ribosomal protein) with active components from black seed (Nigella sativa) for potential treatment of multiple sclerosis

Multiple sclerosis is a complex disorder that is caused by demyelination and loss of axonal parts in the central nervous system. It is caused by many environmental and genetic factors. Various genetic markers such as HLA-DRB1, myelin basic protein, oligodendrocytic glycoprotein, caspase 1, interleukin-1, CD-20, Gap-43 protein, RPS4X (X-linked ribosomal protein), and fibrinogen are some of the factors involved in multiple sclerosis. The ribosomal protein S4 is upregulated in the MS brain. This disease is treated with several synthetic medicines and stem cell therapies which are associated with various side effects. Nigella sativa possesses neuroprotective, antioxidant, and anti-inflammatory properties with no potential side effects which make this plant a potential candidate for the treatment of multiple sclerosis in animal models as well as humans. However, its implications in MS are mainly limited to thymoquinone application. Thus, the present study is an attempt to investigate the role of bioactive molecules other than thymoquinone. Using Auto Dock vina, we investigated the interaction between the RPS4X gene protein of both quail and mouse with the herbal components. Although thymoquinone is the main active component of this herb, it was excluded due to its higher binding energy (-5.0 kcal/mol mouse, -5.3 kcal/mol quail) for the RPS4X gene. Out of 56 components quercetin (-7.0 kcal/mol mouse, -6.9 kcal/mol quail), and kaempferol (-6.7 kcal/mol mouse, -6.5 quail) were identified as the most potent components antioxidant based on their affinity values. Both of them have low toxicity and based on Density Functional Theory (DFT) Calculation kaempferol was the more reactive while quercetin was more stable. The molecular dynamic simulations showed stable binding interaction and flexibility of docked complexes confirming kaempferol and quercetin as potential binders for the proteins. Our data support the interaction between gene and active components of Nigella sativa and suggest their potential involvement in multiple sclerosis treatment.

Evaluation of different phytochemicals from Cannabis sativa against Myelin oligodendrocyte glycoprotein receptor

Evaluation of different phytochemicals from Cannabis sativa against Myelin oligodendrocyte glycoprotein receptor

Monoclonal antibody therapies for aquaporin-4-immunoglobulin G-positive neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease.

Monoclonal antibody therapies mark the new era of targeted treatment for relapse prevention in aquaporin-4 (AQP4)-immunoglobulin G (IgG)-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD). For over a decade, rituximab, an anti-CD20 B-cell-depleting agent, had been the most effectiveness treatment for AQP4-IgG+NMOSD. Tocilizumab, an anti-interleukin-6 receptor, was also observed to be effective. In 2019, several randomized, placebo-controlled trials were completed that demonstrated the remarkable efficacy of eculizumab (anti-C5 complement inhibitor), inebilizumab (anti-CD19 B-cell-depleting agent), and satralizumab (anti-interleukin-6 receptor), leading to the Food and Drug Administration (FDA) approval of specific treatments for AQP4-IgG+NMOSD for the first time. Most recently, ravulizumab (anti-C5 complement inhibitor) was also shown to be highly efficacious in an open-label, external-controlled trial. Although only some patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) warrant immunotherapy, there is currently no FDA-approved treatment for relapse prevention in MOGAD. Observational studies showed that tocilizumab was associated with a decrease in relapses, whereas rituximab seemed to have less robust effectiveness in MOGAD compared to AQP4-IgG+NMOSD. Herein, we review the evidence on the efficacy and safety of each monoclonal antibody therapy used in AQP4-IgG+NMOSD and MOGAD, including special considerations in children and women of childbearing potential.