Seizures in inflammatory demyelinating disorders of the central nervous system.

BACKGROUND: Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may be associated with acute symptomatic seizures and chronic epilepsy as well. The clinical features of the seizures and/or accompanying epilepsy seen in each disease group may vary. In this study, we aimed to contribute to the existing literature by describing the clinical features of seizures and epilepsy in our demyelinating patient population. METHODS: We retrospectively analyzed patients who were followed up in our tertiary referral center neurology demyelinating diseases outpatient clinic between 2019 and 2024. Patients who had at least one seizure before, simultaneously, or after the diagnosis of demyelinating disease were included in the study. RESULTS: Among 1735 patients with MS, 40 had experienced at least one epileptic seizure (2.3 %). Thirty patients (1.7 %) had seizures that could not be explained by another factor than MS. When secondary progressive MS (SPMS) and relapsing-remitting MS (RRMS) were compared, the interval between MS-epilepsy diagnosis was longer and seizure recurrence was more in SPMS. However, the prognosis of epilepsy was good in both subtypes. There were 21 patients followed up with antibody-positive neuromyelitis optica spectrum disorder. No patient had a seizure during the follow-up. We identified 56 patients who fulfilled the criteria for MOGAD with high antibody titers. Seizures were observed in three of them (5.4 %). All of them had status epilepticus either at the onset or during the course of the disease. CONCLUSION: Even rare, seizures constitute one of the important clinical features of the inflammatory demyelinating disorders of the central nervous system. The pathophysiologic mechanism underlying seizures in MS is still not clear. Seizures may occur through different mechanisms in patients where seizures are the initial symptom or a sign of relapse and those that occur spontaneously during the progressive course of the disease. Prevalence of status epilepticus was common in MOGAD patients. Given the rarity of the seizures in CNS demyelinating disorders, it is difficult the define clinical and pathophysiological characteristics of accompanying seizures and epilepsy. Future studies conducted on large patient groups will contribute to the existing literature.

Patterns and utility of myelin oligodendrocyte glycoprotein (MOG) antibody testing in cerebrospinal fluid.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an idiopathic central nervous system (CNS) demyelinating disease gaining recognition with wider availability of cell-based assay (CBA) testing and recently published diagnostic criteria. However, uncertainty remains regarding the interpretation of antibody titers, particularly cerebrospinal fluid (CSF) MOG antibody titers. METHODS: All MOG IgG CBA results performed by the provincial MitogenDx laboratory in Alberta from July 2017 to July 2023 were retrieved. Chart review was performed in patients with both serum and CSF testing and ≥ 1 positive MOG antibody result. Demographics, antibody titers, clinical and imaging features, treatment, and diagnosis were analyzed based on serum/CSF status. RESULTS: Among 4494 MOG CBA assays, there were 413 CSF samples in 402 patients, and 268 patients had at least one associated serum sample. Mean time between CSF and serum testing was 20.9 days (range 0-870 days), most with testing within 30 days. Five of the 268 patients had serum positive/CSF positive MOG antibodies, 4 with acute disseminated encephalomyelitis and 1 with longitudinally extensive transverse myelitis. Twenty-three patients had serum positive/CSF negative MOG and 13/23 with optic neuritis. CSF MOG antibody positive patients were younger, and more likely to remain MOG seropositive versus CSF negative patients. No seronegative patient had MOG antibodies in CSF. CONCLUSIONS: In province-wide testing, CSF MOG antibodies were rare, only in MOG seropositive patients and none with optic neuritis. Our study does not support a clear role for CSF MOG antibody testing in the majority of patients, although further study is required.

Urine neopterin in childhood acute demyelinating diseases: Potential for differential diagnosis.

Inflammatory demyelinating diseases of the central nervous system (CNS) in childhood include clinically and radiologically defined diseases such as acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Differentiation between these phenotypes can be difficult and cases not meeting established diagnostic criteria may remain without any specific diagnosis for months. Laboratory markers can assist in the diagnosis and management of these diseases. Previous studies suggest serum kynurenine-tryptophan pathway products and serum neopterin as biomarkers for CNS autoimmune diseases. Because urine is a reliable and repeatable source for analysis of these products with the additional advantage of easy sampling, we measured neopterin concentrations in serum and urine samples, urinary biopterin and serum kynurenine-tryptophan levels in autoimmune demyelinating diseases of CNS: pediatric multiple sclerosis (pMS, n = 27), MOGAD (n = 10), NMOSD (n = 5) patients and a control group consisting of healthy children or children with non-inflammatory diseases (n = 13), total 55 children. Methods were high performance liquid chromatography (HPLC) for neopterin, biopterin and creatinine in urine and kynurenine and tryptophan in serum; ELISA was used for serum neopterin. Comparison for biomarkers between all diagnostic groups showed urinary neopterin values were significantly higher in the pMS group (p = 0.002). The cut-off point determined by ROC analysis indicated urinary neopterin >167.75 µmol/mol creatinine could distinguish the patients from the controls with a sensitivity of 71% and specificity of 90%. The most significant difference was between the pMS and control groups (p = 0.002) while no difference was observed between pMS patients who were in relapse or stable state. Therefore, urinary neopterin appeared as a potential marker that could differentiate pMS from other demyelinating patient groups MOGAD and NMOSD as well as from controls. The fact that pteridine pathway products had not been studied in urine and serum in children with demyelinating disease before highlights the novelty of this study. If further research in larger samples confirm the present results, these molecules might assist the differential diagnosis of pMS from other demyelinating CNS diseases.

Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G in the CSF: Clinical Implication of Testing and Association With Disability.

BACKGROUND AND OBJECTIVE: To investigate the clinical relevance of CSF myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) testing in a large multicenter cohort. METHODS: In this multicenter cohort study, paired serum-CSF samples from 474 patients with suspected inflammatory demyelinating disease (IDD) from 11 referral hospitals were included. After serum screening, patients were grouped into seropositive myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD, 31), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD, 60), other IDDs (217), multiple sclerosis (MS, 45), and non-IDDs (121). We then screened CSF for MOG-IgG and compared the clinical and serologic characteristics of patients uniquely positive for MOG-IgG in the CSF to seropositive patients with MOGAD. RESULTS: Nineteen patients with seropositive MOGAD (61.3%), 9 with other IDDs (CSF MOG + IDD, 4.1%), 4 with MS (8.9%), but none with AQP4-IgG + NMOSD nor with non-IDDs tested positive in the CSF for MOG-IgG. The clinical, pathologic, and prognostic features of patients uniquely positive for CSF MOG-IgG, with a non-MS phenotype, were comparable with those of seropositive MOGAD. Intrathecal MOG-IgG synthesis, observed from the onset of disease, was shown in 12 patients: 4 of 28 who were seropositive and 8 who were uniquely CSF positive, all of whom had involvement of either brain or spinal cord. Both CSF MOG-IgG titer and corrected CSF/serum MOG-IgG index, but not serum MOG-IgG titer, were associated with disability, CSF pleocytosis, and level of CSF proteins. DISCUSSION: CSF MOG-IgG is found in IDD other than MS and also in MS. In IDD other than MS, the CSF MOG-IgG positivity can support the diagnosis of MOGAD. The synthesis of MOG-IgG in the CNS of patients with MOGAD can be detected from the onset of the disease and is associated with the severity of the disease. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the presence of CSF MOG-IgG can improve the diagnosis of MOGAD in the absence of an MS phenotype, and intrathecal synthesis of MOG-IgG was associated with increased disability.

Leveraging Visual Outcome Measures to Advance Therapy Development in Neuroimmunologic Disorders.

The visual system offers unparalleled precision in the assessment of neuroaxonal damage. With the majority of patients with multiple sclerosis (MS) experiencing afferent and efferent visual dysfunction, outcome measures capturing these deficits provide insight into neuroaxonal injury, even in those with minimal disability. Ideal for use in clinical trials, visual measures are generally inexpensive, accessible, and reproducible. Quantification of visual acuity, visual fields, visual quality of life, and electrophysiologic parameters allows assessment of function, whereas optical coherence tomography (OCT) provides reliable measures of the structural integrity of the anterior afferent visual pathway. The technology of oculomotor biometrics continues to advance, and discrete measures of fixation, smooth pursuit, and saccadic eye movement abnormalities are ready for inclusion in future trials of MS progression. Visual outcomes allow tracking of neuroaxonal injury and aid in distinguishing MS from diseases such as neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD). OCT has also provided unique insights into pathophysiology, including the identification of foveal pitting in NMOSD, possibly from damage to Müller cells, which carry an abundance of aquaporin-4 channels. For some study designs, the cost-benefit ratio favors visual outcomes over more expensive MRI outcomes. With the next frontier of therapeutics focused on remyelination and neuroprotection, visual outcomes are likely to take center stage. As an international community of collaborative, committed, vision scientists, this review by the International MS Visual System Consortium (IMSVISUAL) outlines the quality standards, informatics, and framework needed to routinely incorporate vision outcomes into MS and NMOSD trials.

Risk factors for idiopathic myelitis at admission and predictors for late diagnostic change.

Immune-mediated myelopathy (IMM) diagnosis is challenging, and its etiology may remain unclear despite extensive investigation. We evaluated diagnostic changes in IMM patients during follow-up. We included 80 patients, 61.3% female, with median follow-up time 62.5 months. Diagnoses at discharge were: 48.8% Multiple Sclerosis-IMM (MS-IMM), 32.5% I-IMM, 11.3% Neuromyelitis Optica Spectrum Disorders-IMM (NMOSD-IMM), 1.3% MOG encephalomyelitis (MOGAD), and 6.2% Others IMM (O-IMM). Twenty-two  patients (27.5%) changed diagnosis (median 15.5  months): 68.8% MS-IMM, 12.5%  NMOSD-IMM, 3.8% MOGAD, 10.0% I-IMM, and 5.0% O-IMM. Most patients that changed diagnosis were I-IMM. Predictive factors for diagnostic change in I-IMM were: autonomous gait (p = 0.029), lesions suggestive of MS (p = 0.039), higher number of lesions (p = 0.043), lesions length < 3 vertebral bodies (p = 0.033), cervical involvement (p = 0.038), and lower EDSS at admission (p = 0.013). Etiologic reclassifications in IMM are common, therefore patients require an appropriate follow-up time to increase diagnostic accuracy.

Anti-MAG neuropathy: From biology to clinical management.

The acquired chronic demyelinating neuropathies include a growing number of disease entities that have characteristic, often overlapping, clinical presentations, mediated by distinct immune mechanisms, and responding to different therapies. After the discovery in the early 1980s, that the myelin associated glycoprotein (MAG) is a target antigen in an autoimmune demyelinating neuropathy, assays to measure the presence of anti-MAG antibodies were used as the basis to diagnose the anti-MAG neuropathy. The route was open for describing the clinical characteristics of this new entity as a chronic distal large fiber sensorimotor neuropathy, for studying its pathogenesis and devising specific treatment strategies. The initial use of chemotherapeutic agents was replaced by the introduction in the late 1990s of rituximab, a monoclonal antibody against CD20+ B-cells. Since then, other anti-B cells agents have been introduced. Recently a novel antigen-specific immunotherapy neutralizing the anti-MAG antibodies with a carbohydrate-based ligand mimicking the natural HNK-1 glycoepitope has been described.

Myelin-oligodendrocyte glycoprotein antibody-associated disease.

Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Patients should not be diagnosed with multiple sclerosis or NMOSD if they have anti-MOG antibodies in their serum. However, many questions related to the clinical characterisation of MOGAD and pathogenetic role of MOG antibodies are still unanswered. Furthermore, therapy is mainly based on standard protocols for aquaporin-4 antibody-associated NMOSD and multiple sclerosis, and more evidence is needed regarding how and when to treat patients with MOGAD.

Prolonged Fever: An Atypical Presentation in MOG Antibody-Associated Disorders.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelinating disorders (MOGAD) are increasingly being recognized in the pediatric age group. Over time, unusual presentations have expanded the clinical presentation. We report 12 cases of MOGAD where prolonged fever (PF) was an important part of the symptom complex during the course of the illness. METHODS: After initial recognition of this atypical clinical presentation, more patients were recruited over 2 years and followed up prospectively. RESULTS: Eight of twelve patients had no clinical/imaging evidence of demyelination until much later in the course. Three clinical presentations recognized were fever of unknown origin (4 of 12), aseptic meningitis (4 of 12), and PF seen concurrently with established acute demyelination syndrome (4 of 12). Leukocytosis, raised inflammatory markers, and cerebrospinal fluid pleocytosis were almost universal. The first two presentations frequently caused diagnostic confusion, as MOGAD was not considered until several weeks after disease onset. The third group was more a therapeutic conundrum on how to manage the PF. Early seizures without encephalopathy were not uncommon and were probably independent of the later-appearing demyelination. CONCLUSIONS: This case series highlights PF as an important component of the pediatric MOGAD symptom complex. MOGAD could be considered in the differential diagnosis of these clinical presentations.

Pediatric onset multiple sclerosis: Future challenge for early diagnosis and treatment.

Multiple sclerosis is a major socio-economical burden as it represents the most common cause of non-traumatic neurological disability in young adults [1]. It affects also children with a lower prevalence and incidence but remains a major concern as disability may occur later during their adulthood. Therefore, there is an absolute need for earlier diagnosis and treatment. In this review, we would focus on how these objectives can be achieved.

Case Report: Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder Masquerading as Multiple Sclerosis: An Under-Recognized Entity?

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) covers a wide spectrum of manifestations and is defined by the presence of MOG seropositivity. However, in a proportion of patients, there may be an overlap in some of the clinical and radiological manifestations between MOGAD and multiple sclerosis (MS). Being wary of this entity is critical to ensure appropriate therapy. Herein, we present a case with recurrent episodes of short-segment myelitis typical for multiple sclerosis, but later diagnosed as MOGAD by MOG antibody seropositivity. This case, along with previous reports, highlights an increasingly recognized subgroup in MOGAD with initial clinical phenotypes suggestive of MS, but later showing a disease course and therapeutic response compatible with MOGAD. Given the potential overlap of some clinical phenotypes in patients with MS and those with MOGAD, we recommend MOG antibody testing in all patients with recurrent short-segment myelitis, conus medullaris involvement, and those who demonstrated steroid dependence.

Multiple Sclerosis Is Rare in Epstein-Barr Virus-Seronegative Children with Central Nervous System Inflammatory Demyelination.

Although Epstein-Barr virus (EBV) is hypothesized to be a prerequisite for multiple sclerosis (MS), up to 15% of children with a diagnosis of MS were reported to be EBV-seronegative. When re-evaluating 25 EBV-seronegative children out of 189 pediatric patients with a diagnosis of clinically isolated syndrome/MS, we found anti-myelin oligodendrocyte glycoprotein (MOG) antibody in 11 of 25 (44%) EBV-seronegative but only 9 of 164 (5.5%, p < 0.001) EBV-seropositive patients. After critical review, MS remained a plausible diagnosis in only 4 of 14 EBV-seronegative/MOG antibody-negative patients. In children with an MS-like presentation, EBV seronegativity should alert clinicians to consider diagnoses other than MS, especially MOG-antibody disease. ANN NEUROL 2021;89:1234-1239.

Clinical analysis of a patient simultaneously positive for antibodies of myelin oligodendrocyte glycoprotein and anti-N-methyl-D-aspartate receptor: A case report.

RATIONALE: Myelin oligodendrocyte glycoprotein (MOG) antibody (MOG-Ab) disease (MOG-AD) is a type of demyelinating disease of the central nervous system characterized by a high frequency of optic neuritis (ON) attacks. anti-Nmethyl-D-aspartate receptor (NMDAR) encephalitis (anti-NMDARe) is an autoimmune disorder characterized by memory deficits, conscious disturbance, and seizures. Cases of simultaneous occurrence of MOG-Ab and anti-NMDARe antibody (anti-NMDARe-Ab) are rarely reported and could be mistaken for overlapping MOG-antibody disease (MOG-AD) and NMDARe. The diagnosis of such patients is challenging. PATIENT CONCERNS: We report the case of a 37-year-old man who presented with recurrent headaches for 3 months and worsening symptoms over 2 weeks. He had a history of ON. He had a generalized seizure after 7 days in the hospital. DIAGNOSIS: Brain magnetic resonance imaging (MRI) and cerebrospinal fluid tests showed no apparent abnormalities. Repeat MRI showed slight lesions 7 days later, and cerebrospinal fluid tests showed the simultaneous occurrence of MOG-Ab and anti-NMDARe-Ab. INTERVENTIONS: He completely recovered after treatment with low doses of oral corticosteroids. OUTCOMES: Two months and 2 years follow-up showed that his condition was stable. LESSONS: The co-occurrence of MOG-Ab and anti-NMDAR-Ab does not indicate the co-occurrence of MOG-AD and anti-NMDARe. Laboratory findings should be combined with the clinical features to achieve an accurate and suitable diagnosis.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Current Insights into the Disease Pathophysiology, Diagnosis and Management.

Myelin oligodendrocyte glycoprotein (MOG)-associated disease (MOGAD) is a rare, antibody-mediated inflammatory demyelinating disorder of the central nervous system (CNS) with various phenotypes starting from optic neuritis, via transverse myelitis to acute demyelinating encephalomyelitis (ADEM) and cortical encephalitis. Even though sometimes the clinical picture of this condition is similar to the presentation of neuromyelitis optica spectrum disorder (NMOSD), most experts consider MOGAD as a distinct entity with different immune system pathology. MOG is a molecule detected on the outer membrane of myelin sheaths and expressed primarily within the brain, spinal cord and also the optic nerves. Its function is not fully understood but this glycoprotein may act as a cell surface receptor or cell adhesion molecule. The specific outmost location of myelin makes it a potential target for autoimmune antibodies and cell-mediated responses in demyelinating processes. Optic neuritis seems to be the most frequent presenting phenotype in adults and ADEM in children. In adults, the disease course is multiphasic and subsequent relapses increase disability. In children ADEM usually presents as a one-time incident. Luckily, acute immunotherapy is very effective and severe disability (ambulatory and visual) is less frequent than in NMOSD. A critical element of reliable diagnosis is detection of pathogenic serum antibodies MOG with accurate, specific and sensitive methods, preferably with optimized cell-based assay (CBA). MRI imaging can also help in differentiating MOGAD from other neuro-inflammatory disorders. Reports on randomised control trials are limited, but observational open-label experience suggests a role for high-dose steroids and plasma exchange in the treatment of acute attacks, and for immunosuppressive therapies, such as steroids, oral immunosuppressants and rituximab as maintenance treatment. In this review, we present up-to-date clinical, immunological, radiographic, histopathological data concerning MOGAD and summarize the practical aspects of diagnosing and managing patients with this disease.

E.U. paediatric MOG consortium consensus: Part 1 - Classification of clinical phenotypes of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

Over the past few years, increasing interest in the role of autoantibodies against myelin oligodendrocyte glycoprotein (MOG-abs) as a new candidate biomarker in demyelinating central nervous system diseases has arisen. MOG-abs have now consistently been identified in a variety of demyelinating syndromes, with a predominance in paediatric patients. The clinical spectrum of these MOG-ab-associated disorders (MOGAD) is still expanding and differs between paediatric and adult patients. This first part of the Paediatric European Collaborative Consensus emphasises the diversity in clinical phenotypes associated with MOG-abs in paediatric patients and discusses these associated clinical phenotypes in detail. Typical MOGAD presentations consist of demyelinating syndromes, including acute disseminated encephalomyelitis (ADEM) in younger, and optic neuritis (ON) and/or transverse myelitis (TM) in older children. A proportion of patients experience a relapsing disease course, presenting as ADEM followed by one or multiple episode(s) of ON (ADEM-ON), multiphasic disseminated encephalomyelitis (MDEM), relapsing ON (RON) or relapsing neuromyelitis optica spectrum disorders (NMOSD)-like syndromes. More recently, the disease spectrum has been expanded with clinical and radiological phenotypes including encephalitis-like, leukodystrophy-like, and other non-classifiable presentations. This review concludes with recommendations following expert consensus on serologic testing for MOG-abs in paediatric patients, the presence of which has consequences for long-term monitoring, relapse risk, treatments, and for counselling of patient and families. Furthermore, we propose a clinical classification of paediatric MOGAD with clinical definitions and key features. These are operational and need to be tested, however essential for future paediatric MOGAD studies.

E.U. paediatric MOG consortium consensus: Part 4 - Outcome of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

There is increasing knowledge on the role of antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) in acquired demyelinating syndromes and autoimmune encephalitis in children. Better understanding and prediction of outcome is essential to guide treatment protocol decisions. Therefore, this part of the Paediatric European Collaborative Consensus provides an oversight of existing knowledge of clinical outcome assessment in paediatric MOG-ab-associated disorders (MOGAD). The large heterogeneity in disease phenotype, disease course, treatment and follow-up protocols is a major obstacle for reliable prediction of outcome. However, the clinical phenotype of MOGAD appears to be the main determinant of outcome. Patients with a transverse myelitis phenotype in particular are at high risk of accruing neurological disability (motor and autonomic), which is frequently severe. In contrast, having a single episode of optic neuritis any time during disease course is broadly associated with a lower risk of persistent disability. Furthermore, MOG-ab-associated optic neuritis often results in good functional visual recovery, although retinal axonal loss may be severe. The field of cognitive and behavioural outcome and epilepsy following demyelinating episodes has not been extensively explored, but in recent studies acute disseminated encephalomyelitis (-like) phenotype in the young children was associated with cognitive problems and epilepsy in long-term follow-up. In conclusion, main domains of importance in determining clinical outcome in paediatric MOGAD are visual, motor, autonomic and cognitive function. A standardised evaluation of these outcome domains in all children is of importance to allow adequate rehabilitation and follow-up.

E.U. paediatric MOG consortium consensus: Part 3 - Biomarkers of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

A first episode of acquired demyelinating disorder (ADS) in children is a diagnostic challenge as different diseases can express similar clinical features. Recently, antibodies against myelin oligodendrocyte glycoprotein (MOG) have emerged as a new ADS biomarker, which clearly allow the identification of monophasic and relapsing ADS forms different from MS predominantly in children. Due to the novelty of this antibody there are still challenges and controversies about its pathogenicity and best technique to detect it. In this manuscript we will discuss the recommendations and caveats on MOG antibody assays, role in the pathogenesis, and additionally discuss the usefulness of other potential new biomarkers in MOG-antibody associated disorders (MOGAD).

Anti-inflammatory and immune-modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation.

Autoreactive inflammatory CD4+ T cells, such as T helper (Th)1 and Th17 subtypes, have been found to associate with the pathogenesis of autoimmune disorders. On the other hand, CD4+ Foxp3+ T regulatory (Treg) cells are crucial for the immune tolerance and have a critical role in the suppression of the excessive immune and inflammatory response promoted by these Th cells. In contrast, dendritic cells (DCs) and macrophages are immune cells that through their inflammatory functions promote autoreactive T-cell responses in autoimmune conditions. In recent years, there has been increasing attention to exploring effective immunomodulatory or anti-inflammatory agents from the herbal collection of traditional medicine. Berberine, an isoquinoline alkaloid, is one of the main active ingredients extracted from medicinal herbs and has been shown to exert various biological and pharmacological effects that are suggested to be mainly attributed to its anti-inflammatory and immunomodulatory properties. Several lines of experimental study have recently investigated the therapeutic potential of berberine for treating autoimmune conditions in animal models of human autoimmune diseases. Here, we aimed to seek mechanisms underlying immunomodulatory and anti-inflammatory effects of berberine on autoreactive inflammatory responses in autoimmune conditions. Reported data reveal that berberine can directly suppress functions and differentiation of pro-inflammatory Th1 and Th17 cells, and indirectly decrease Th cell-mediated inflammation through modulating or suppressing other cells assisting autoreactive inflammation, such as Tregs, DCs and macrophages.

Free light chains kappa can differentiate between myelitis and noninflammatory myelopathy.

OBJECTIVE: To test the hypothesis that the intrathecal synthesis of free light chain kappa (FLC-k) can be used as a CSF biomarker to differentiate patients with myelitis due to multiple sclerosis (MS), myelitis due to neuromyelitis optica spectrum disease (NMOSD), and noninflammatory myelopathy, we analyzed FLC-k in 26 patients with MS myelitis, 9 patients with NMOSD myelitis, and 14 patients with myelopathy. METHODS: This is a retrospective monocentric cohort study. FLC-k were analyzed using the nephelometric Siemens FLC-k kit in paired samples of CSF and sera. Intrathecal fraction (IF) of FLC-k was plotted in a FLC-k quotient diagram. RESULTS: Ninety-six percent of patients with MS myelitis had an intrathecal synthesis of FLC-k in comparison with 55.6% for NMOSD and 14.3% of patients with noninflammatory myelopathy. The locally synthesized absolute amount of FLC-k was significantly higher in patients with myelitis due to MS than in patients with NMOSD (p = 0.038) or noninflammatory myelopathy (p < 0.0001). The sensitivity of FLC-k synthesis to detect inflammation in patients with myelitis is 85.7%. Using a receiver operating characteristic analysis, FLC-k IF >78% can discriminate patients with myelitis due to MS and NMOSD with a sensitivity of 88.5% and a specificity of 88.9% CONCLUSIONS: With the hyperbolic reference range in quotient diagrams for FLC-k, it is possible to distinguish inflammatory myelitis from noninflammatory myelopathies. An FLC-k IF >78% can be a hint to suspect myelitis due to MS rather than NMOSD.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Presenting with Slowly Progressive Myelitis and Longitudinally Extensive Spinal Cord Lesions.

We report a 65-year-old man with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) who presented with gait disturbance that he had experienced for approximately half a year. On neurological examination, he displayed spastic paraplegia and autonomic dysfunctions including dysuria and constipation. Spinal cord magnetic resonance imaging showed longitudinally extensive spinal cord lesions (LESCLs) extending from the cervical to the thoracic cords. The patient was negative for anti-myelin oligodendrocyte glycoprotein and anti-aquaporin 4 antibodies. Treatment with corticosteroids and intravenous immunoglobulin resulted in a clinical improvement. It is important to distinguish GFAP-A from slowly progressive myelitis with LESCLs.