Isolated large demyelinated plaque with clinical and radiologic appearance suggestive of cervical intramedullary tumor diagnosed after surgery.

Isolated spinal demyelinating lesions are rare and often associated with multiple sclerosis. While initial radiological findings may suggest a tumor, a definitive diagnosis requires a histological diagnosis. A 45-year-old woman presented with progressive spastic tetraparesis for 1 week. She had no prior history of neurological or systemic illness. Brain and thoracic magnetic resonance imaging (MRI) were normal, but cervical MRI revealed an intramedullary tumor extending from C3 to C4. Surgery was performed. Histopathological examination revealed an inflammatory demyelinating plaque, not a tumor. The patient experienced significant improvement in her clinical condition postsurgery and remains under neurological follow-up. We discuss this case alongside a review of similar cases reported in the literature, focusing on clinical presentation, laboratory findings, MRI features, and follow-up of patients with tumor-like inflammatory demyelinating diseases of the spinal cord initially diagnosed as intramedullary tumors.

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.

Cortical plasticity in AQP4-positive NMOSD: a transcranial magnetic stimulation study.

Aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) is an autoimmune disease characterized by suboptimal recovery from attacks and long-term disability. Experimental data suggest that AQP4 antibodies can disrupt neuroplasticity, a fundamental driver of brain recovery. A well-established method to assess brain LTP is through intermittent theta-burst stimulation (iTBS). This study aimed to explore neuroplasticity in AQP4-NMOSD patients by examining long-term potentiation (LTP) through iTBS. We conducted a proof-of-principle study including 8 patients with AQP4-NMOSD, 8 patients with multiple sclerosis (MS), and 8 healthy controls (HC) in which iTBS was administered to induce LTP-like effects. iTBS-induced LTP exhibited significant differences among the 3 groups (p: 0.006). Notably, AQP4-NMOSD patients demonstrated impaired plasticity compared to both HC (p = 0.01) and pwMS (p = 0.02). This pilot study provides the first in vivo evidence supporting impaired neuroplasticity in AQP4-NMOSD patients. Impaired cortical plasticity may hinder recovery following attacks suggesting a need for targeted rehabilitation strategies.

Contactin -Associated protein1 Regulates Autophagy by Modulating the PI3K/AKT/mTOR Signaling Pathway and ATG4B Levels in Vitro and in Vivo.

Contactin-associated protein1 (Caspr1) plays an important role in the formation and stability of myelinated axons. In Caspr1 mutant mice, autophagy-related structures accumulate in neurons, causing axonal degeneration; however, the mechanism by which Caspr1 regulates autophagy remains unknown. To illustrate the mechanism of Caspr1 in autophagy process, we demonstrated that Caspr1 knockout in primary neurons from mice along with human cell lines, HEK-293 and HeLa, induced autophagy by downregulating the PI3K/AKT/mTOR signaling pathway to promote the conversion of microtubule-associated protein light chain 3 I (LC3-I) to LC3-II. In contrast, Caspr1 overexpression in cells contributed to the upregulation of this signaling pathway. We also demonstrated that Caspr1 knockout led to increased LC3-I protein expression in mice. In addition, Caspr1 could inhibit the expression of autophagy-related 4B cysteine peptidase (ATG4B) protein by directly binding to ATG4B in overexpressed Caspr1 cells. Intriguingly, we found an accumulation of ATG4B in the Golgi apparatuses of cells overexpressing Caspr1; therefore, we speculate that Caspr1 may restrict ATG4 secretion from the Golgi apparatus to the cytoplasm. Collectively, our results indicate that Caspr1 may regulate autophagy by modulating the PI3K/AKT/mTOR signaling pathway and the levels of ATG4 protein, both in vitro and in vivo. Thus, Caspr1 can be a potential therapeutic target in axonal damage and demyelinating diseases.

A pilot study of monocytes in relapsing remitting multiple sclerosis: Correlation with disease activity.

Background: Numerous immune cells are involved in developing multiple sclerosis (MS). Monocytes are believed to be the first to enter the brain and initiate inflammation. The role of monocyte subtypes in MS needs to be better understood. Objective: The current study aims to investigate the presence of different subsets of monocytes in relapsing-remitting MS (RRMS) Egyptian patients and their correlation with disease activity. Methods: This study included 44 RRMS patients (22 patients in relapse, 22 patients in remission), diagnosed according to the 2017 MacDonalds criteria, and 44 matched healthy controls. Personal and medical histories were taken from the patients, and the Expanded Disability Status Scale (EDSS) was used to evaluate the degree of impairment. Characterization of peripheral blood monocyte subsets was done by flow cytometry for all participants. Results: The percentage of classical, intermediate, and non-classical monocyte subsets showed a significant increase in RRMS patients than controls with p-values of 0.029, 0.049, and 0.043, respectively. In the RRMS patients, there were no statistically significant correlations (p-values >0.05) between the EDSS scores, the duration of disease, and number of relapses in the past year and the percentages of the various monocyte subsets. Furthermore, there were no significant differences in the percentage of each monocyte subset between RRMS patients in remission and those experiencing a relapse (p-values >0.05). However, patients with evidence of activity in magnetic resonance imaging (MRI) had a significantly high percentage of non-classical monocytes with a p-value of 0.002. Conclusion: In RRMS patients, the three monocyte subsets (classical, non-classical and intermediate) increase significantly regardless of the disease activity. This increase denotes the vital role of monocytes and innate immunity in MS pathology, especially the non-classical monocyte subset. These findings suggest that monocytes might be a promising MS therapeutic target.

A rare presentation of acute-onset chronic inflammatory demyelinating polyneuropathy with the detection of anti-GM3 and anti-sulfatides antibodies: a case report.

Objectives: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated neuropathy defined by clinical progression for more than 2 months. 16-20% of CIDP patients may present with rapidly progressive weakness that resembles GBS, known as acute-onset CIDP (A-CIDP). However, it is challenging to distinguish from GBS-TRF because of their similar clinical symptom and features. In this case review, we report a patient with A-CIDP with the detection of anti-GM3 and anti-sulfatides antibodies, which rarely have been in A-CIDP and may account for her progressive and recurrent symptoms. Methods: We analyzed existing medical literature and described a clinical case of A-CIDP with antibodies positive. Results: We reported a 56-year-old female presented with bilateral lower extremity weakness and distal numbness. She experienced similar symptoms four times and responded well to the IVIg therapy. Lumbar puncture demonstrated albumin-cytologic dissociation and EDX examination revealed multiple peripheral nerve damage. After ruling out other demyelination diseases, a diagnosis of A-CIDP was made. Discussion: The antiganglioside and anti-sulfatide antibodies are involved in CIDP pathogenesis and can help to distinguish A-CIDP and other variants. To prevent secondary damage, it is important to monitor relapse and remission symptoms along the treatment line. A rare case of A-CIDP is discussed concerning the detection of anti-GM3 and anti-sulfatides antibodies, thus making a retrospective comparison of antibodies in some literature to understand A-CIDP better.

Fulminant demyelinating disease of the central nervous system effectively treated with a combination of decompressive craniectomy and immunotherapy: A case report and literature review.

Key Clinical Message: Accurately identifying fulminant demyelinating diseases is important for sudden onset of asymmetric cerebral white matter lesions with mass effect. Initially, immunotherapy should be administered; however, surgical intervention should be performed with poor response to medical management and evident signs of cerebral herniation. Abstract: A case of fulminant demyelinating disease of the central nervous system that required decompressive craniectomy 8 days after symptom onset is presented. The patient recovered without sequelae after a combination of neurosurgery and immunotherapy with steroids and has remained relapse-free for 4 years.

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.

Solitary Tumefactive Demyelinating Lesions in Children: Clinical and Magnetic Resonance Imaging Features, Pathologic Characteristics, and Outcomes.

BACKGROUND: Isolated tumefactive demyelinating lesions (≥2 cm) may be difficult to distinguish from contrast-enhancing brain tumors, central nervous system infections, and (rarely) tissue dysgenesis, which may all occur with increased signal on T2-weighted images. Establishing an accurate diagnosis is essential for management, and we delineate our single-center experience. METHODS: We performed a retrospective review of medical records, imaging, and biopsy specimens for patients under 18 years presenting with isolated tumefactive demyelination over a 10-year period. RESULTS: Ten children (eight female) met inclusion criteria, with a median age of 14.1 years. Lesions were most likely to involve the thalamus (six of 10), brainstem (five of 10), basal ganglia (four of 10), or corpus callosum (four of 10). Eighty percent had perilesional edema at presentation, and 60% had midline shift. Biopsies demonstrated demyelination with perivascular lymphocytic infiltration and axonal damage ranging from mild to severe. All patients were initially treated with high-dose corticosteroids, and eight of 10 required additional medical therapies such as intravenous immunoglobulin, plasmapheresis, cyclophosphamide, or rituximab. Increased intracranial pressure was managed aggressively with two of 10 patients requiring decompressive craniectomies. Clinical outcomes varied. CONCLUSIONS: Solitary tumefactive demyelinating lesions are rare, and aggressive management of inflammation and increased intracranial pressure is essential. Biopsy is helpful to evaluate for other diagnoses on the differential and maximize therapies. Treatment beyond initial therapy with corticosteroids is often required. Isolated tumefactive demyelinating lesions are uncommon; multicenter natural history studies are needed to better delineate differential diagnoses and optimal therapies.

A Rare and Challenging Presentation of Acute Hemorrhagic Leukoencephalitis With Tumefactive Demyelinating Lesions in a 41-Year-Old Male.

Acute hemorrhagic leukoencephalitis (AHLE) is a rare and severe inflammatory condition of the central nervous system (CNS), characterized by hemorrhagic lesions in the brain's white matter. Here, we present a case of AHLE with concurrent tumefactive demyelinating disease, highlighting the diagnostic and management challenges associated with this complex presentation. Tumefactive multiple sclerosis (MS) is a rare variant of MS characterized by large, space-occupying lesions in the CNS. Concurrently, hemorrhagic leukoencephalitis (HLE) represents a severe inflammatory disorder characterized by hemorrhagic lesions within the CNS white matter. The diagnosis of tumefactive MS with associated HLE posed significant diagnostic challenges due to overlapping clinical and radiological features. Management involved high-dose corticosteroid therapy and supportive care measures, with longitudinal follow-up to assess treatment response and prevent complications. The patient exhibited a favorable clinical response to treatment, with gradual improvement in symptoms and resolution of radiological abnormalities. The coexistence of tumefactive MS with HLE is exceptionally rare and presents diagnostic and therapeutic challenges. We report a 41-year-old male presenting with acute neurological symptoms, including severe headache, confusion, left-sided body weakness, slurred speech, and blurred vision. Neurological examination revealed dysarthric speech, right homonymous hemianopia, left upper motor neuron facial palsy, and motor deficits. MRI demonstrated multifocal areas of T2 hyperintensity with associated hemorrhage, suggestive of tumefactive MS with associated HLE. Diagnostic workup included neurological examination, MRI imaging, cerebrospinal fluid analysis, and serological testing. Management involved high-dose corticosteroid therapy and supportive care measures. The patient exhibited a favorable clinical response to treatment, with gradual improvement in symptoms and resolution of radiological abnormalities. Longitudinal follow-up confirmed sustained improvement. In conclusion, the coexistence of tumefactive MS with HLE poses diagnostic challenges due to overlapping features. This case underscores the importance of considering rare and atypical presentations of CNS demyelinating disease and the potential complications, including associated HLE. Comprehensive evaluation, multidisciplinary collaboration, and individualized management are essential for optimizing outcomes in patients with complex CNS inflammatory disorders.

Identifying high-risk neurological phenotypes in adult-onset classic monogenic autoinflammatory diseases: when should neurologists consider testing?

BACKGROUND: Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early detection for effective treatment, the neurological manifestations of these disorders remain inadequately recognized. METHODS: We conducted a systematic review searching Pubmed, Embase and Scopus for case reports and case series related to neurological manifestations in adult-onset monogenic autoinflammatory diseases. Selection criteria focused on the four most relevant adult-onset autoinflammatory diseases-deficiency of deaminase 2 (DADA2), tumor necrosis factor receptor associated periodic fever syndrome (TRAPS), cryopyrin associated periodic fever syndrome (CAPS), and familial mediterranean fever (FMF). We extracted clinical, laboratory and radiological features to propose the most common neurological phenotypes. RESULTS: From 276 records, 28 articles were included. The median patient age was 38, with neurological symptoms appearing after a median disease duration of 5 years. Headaches, cranial nerve dysfunction, seizures, and focal neurological deficits were prevalent. Predominant phenotypes included stroke for DADA2 patients, demyelinating lesions and meningitis for FMF, and meningitis for CAPS. TRAPS had insufficient data for adequate phenotype characterization. CONCLUSION: Neurologists should be proactive in diagnosing monogenic autoinflammatory diseases in young adults showcasing clinical and laboratory indications of inflammation, especially when symptoms align with recurrent or chronic meningitis, small vessel disease strokes, and demyelinating lesions.

Manifestations of Myelinating Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Rare Case of Suppurative Meningoencephalitis.

Myelinating oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system (CNS) mediated by MOG antibodies (MOG-IgG). It is associated with autoimmunity and encompasses various syndromes. However, manifestations presenting with symptoms of suppurative meningoencephalitis are rare. In this case, we admitted an 80-year-old male patient who presented with fever, headache, mental and behavioral abnormalities, and disturbance of consciousness. The cerebrospinal fluid (CSF) examination revealed elevated levels of leukocytes and protein, while magnetic resonance imaging (MRI) of the brain showed an abnormal signal in the parietal lobe surrounding the posterior horn of the right lateral ventricle. The patient tested positive for serum MOG-IgG, confirming the diagnosis of MOG-IgG-related meningoencephalitis. The treatment included intravenous immunoglobulin, glucocorticoids, third-generation cephalosporins, and immunosuppressants. Following the treatment, the patient experienced complete recovery.

Intranasal Resveratrol Nanoparticles Enhance Neuroprotection in a Model of Multiple Sclerosis.

PURPOSE: Resveratrol is a natural polyphenol which has a very low bioavailability but whose antioxidant, anti-inflammatory and anti-apoptotic properties may have therapeutic potential for the treatment of neurodegenerative diseases such as multiple sclerosis (MS). Previously, we reported the oral administration of resveratrol nanoparticles (RNs) elicited a neuroprotective effect in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, at significantly lower doses than unconjugated resveratrol (RSV) due to enhanced bioavailability. Furthermore, we demonstrated that the intranasal administration of a cell-derived secretome-based therapy at low concentrations leads to the selective neuroprotection of the optic nerve in EAE mice. The current study sought to assess the potential selective efficacy of lower concentrations of intranasal RNs for attenuating optic nerve damage in EAE mice. METHODS: EAE mice received either a daily intranasal vehicle, RNs or unconjugated resveratrol (RSV) for a period of thirty days beginning on the day of EAE induction. Mice were assessed daily for limb paralysis and weekly for visual function using the optokinetic response (OKR) by observers masked to treatment regimes. After sacrifice at day 30, spinal cords and optic nerves were stained to assess inflammation and demyelination, and retinas were immunostained to quantify retinal ganglion cell (RGC) survival. RESULTS: Intranasal RNs significantly increased RGC survival at half the dose previously shown to be required when given orally, reducing the risk of systemic side effects associated with prolonged use. Both intranasal RSV and RN therapies enhanced RGC survival trends, however, only the effects of intranasal RNs were significant. RGC loss was prevented even in the presence of inflammatory and demyelinating changes induced by EAE in optic nerves. CONCLUSIONS: The intranasal administration of RNs is able to reduce RGC loss independent of the inflammatory and demyelinating effects on the optic nerve and the spinal cord. The concentration of RNs needed to achieve neuroprotection is lower than previously demonstrated with oral administration, suggesting intranasal drug delivery combined with nanoparticle conjugation warrants further exploration as a potential neuroprotective strategy for the treatment of optic neuritis, alone as well as in combination with glucocorticoids.

Is Resistance Training an Option to Improve Functionality and Muscle Strength in Middle-Aged People with Multiple Sclerosis? A Systematic Review and Meta-Analysis.

Background: Currently, it is essential to adopt physical therapy strategies, such as resistance training, to enhance muscle strength and gait in middle-aged individuals (ages 45-65) suffering from Multiple Sclerosis. This is crucial in combating the typical symptoms of neurodegenerative diseases associated with functional loss. The objective of this study is to determine the effects of resistance training interventions on walking and muscle strength in middle-aged people with Multiple Sclerosis. Methods: A systematic review with meta-analysis was conducted by searching specific keywords in the PubMed, Scopus, Cochrane, and Web of Science databases. For inclusion, studies had to incorporate resistance training as a primary or significant component of the overall intervention for middle-aged patients with MS. Out of the 3675 articles identified, 12 randomized clinical trials met the criteria for inclusion in the review, with resistance training being a consistent feature in all of them. Results: Muscle strength and gait were evaluated as the main variables, with fatigue and the quality of life as secondary variables. This review reveals that resistance training significantly improves muscle strength. Resistance training achieves modest and non-significant improvements in gait. Notably, studies combining resistance training with motor control exercises achieve results of greater clinical significance in terms of gait. However, resistance training yields variable positive effects on perceived fatigue and the quality of life. Conclusion: Resistance training is useful for improving muscle strength; however, walking needs to be combined with motor control training.

Progressive demyelinating polyneuropathy after hematopoietic cell transplantation in metachromatic leukodystrophy: a case series.

Metachromatic leukodystrophy (MLD) is a neuro-metabolic disorder due to arylsulfatase A deficiency, causing demyelination of the central and peripheral nervous system. Hematopoietic cell transplantation (HCT) can provide a symptomatic and survival benefit for pre-symptomatic and early symptomatic patients by stabilizing CNS disease. This case series, however, illustrates the occurrence of severely progressive polyneuropathy shortly after HCT in two patients with late-infantile, one with late-juvenile, and one with adult MLD, leading to the inability to walk or sit without support. The patients had demyelinating polyneuropathy before HCT, performed at the ages of 2 years in the first two patients and at 14 and 23 years in the other two patients. The myeloablative conditioning regimen consisted of busulfan, fludarabine and, in one case, rituximab, with anti-thymocyte globulin, cyclosporine, steroids, and/or mycophenolate mofetil for GvHD prophylaxis. Polyneuropathy after HCT progressed parallel with tapering immunosuppression and paralleled bouts of infection and graft-versus-host disease (GvHD). Differential diagnoses included MLD progression, neurological GvHD or another (auto)inflammatory cause. Laboratory, electroneurography and pathology investigations were inconclusive. In two patients, treatment with immunomodulatory drugs led to temporary improvement, but not sustained stabilization of polyneuropathy. One patient showed recovery to pre-HCT functioning, except for a Holmes-like tremor, for which a peripheral origin cannot be excluded. One patient showed marginal response to immunosuppressive treatment and died ten months after HCT due to respiratory failure. The extensive diagnostic and therapeutic attempts highlight the challenge of characterizing and treating progressive polyneuropathy in patients with MLD shortly after HCT. We advise to consider repeat electro-neurography and possibly peripheral nerve biopsy in such patients. Nerve conduction blocks, evidence of the presence of T lymphocytes and macrophages in the neuronal and surrounding nerve tissue, and beneficial effects of immunomodulatory drugs may indicate a partially (auto)immune-mediated pathology. Polyneuropathy may cause major residual disease burden after HCT. MLD patients with progressive polyneuropathy could potentially benefit from a more intensified immunomodulatory drug regime following HCT, especially at times of immune activation.

AIF translocation into nucleus caused by Aifm1 R450Q mutation: generation and characterization of a mouse model for AUNX1.

Mutations in AIFM1, encoding for apoptosis-inducing factor (AIF), cause AUNX1, an X-linked neurologic disorder with late-onset auditory neuropathy (AN) and peripheral neuropathy. Despite significant research on AIF, there are limited animal models with the disrupted AIFM1 representing the corresponding phenotype of human AUNX1, characterized by late-onset hearing loss and impaired auditory pathways. Here, we generated an Aifm1 p.R450Q knock-in mouse model (KI) based on the human AIFM1 p.R451Q mutation. Hemizygote KI male mice exhibited progressive hearing loss from P30 onward, with greater severity at P60 and stabilization until P210. Additionally, muscle atrophy was observed at P210. These phenotypic changes were accompanied by a gradual reduction in the number of spiral ganglion neuron cells (SGNs) at P30 and ribbons at P60, which coincided with the translocation of AIF into the nucleus starting from P21 and P30, respectively. The SGNs of KI mice at P210 displayed loss of cytomembrane integrity, abnormal nuclear morphology, and dendritic and axonal demyelination. Furthermore, the inner hair cells and myelin sheath displayed abnormal mitochondrial morphology, while fibroblasts from KI mice showed impaired mitochondrial function. In conclusion, we successfully generated a mouse model recapitulating AUNX1. Our findings indicate that disruption of Aifm1 induced the nuclear translocation of AIF, resulting in the impairment in the auditory pathway.

Brain-Derived Neurotrophic Factor in Multiple Sclerosis Disability: A Prospective Study.

Multiple sclerosis (MS) is a demyelinating central nervous system disease that leads to neurological disability. Brain-derived neurotrophic factors (BDNFs) are neurotrophins involved in neurodegenerative disorders. This study analysed the relationship between serum BDNF, neurological disability and different MS treatments. We included 63 people with MS (PwMS), with relapsing-remitting MS or clinically isolated syndrome, and 16 healthy controls (HCs). We analysed the serum levels of BDNF and MS specific disability tests (Expanded Disability Status Scale, timed 25-foot walk test, nine-hole peg test), at baseline (V0) and after one year of interferon beta1a or teriflunomide treatment (V1). Baseline BDNF values were not different between the PwMS and HCs (p = 0.85). The BDNF levels were higher in PwMS vs. HCs after treatment (p = 0.003). BDNF was not related to last-year relapses or by the disease duration (all p > 0.05). The overall values for the PwMS decreased after one year (p < 0.001). Both treatments implied a similar reduction. BDNF was not related to neurological disability (p > 0.05). BDNF values were not influenced by the lesion burden, active lesions, or new lesions on MRI (p > 0.05). In our cohort, the PwMS had higher BDNF levels compared to the HCs after one year of treatment. BDNF was not related to clinical or paraclinical disease severity signs.

Myelin oligodendrocyte glycoprotein antibody titers by fixed cell-based assay: positive predictive value and impact of sample collection timing.

Introduction: In January 2023, our laboratory began performing serum myelin oligodendrocyte glycoprotein antibody (anti-MOG) titers by fixed cell-based assay (CBA). As a quality assurance (QA) assessment, we evaluated titer positive predictive value (PPV) as well as impact of sample collection timing on titers. Methods: Among patients who underwent antibody titers to distinguish between low-positive (<1:100) and clear-positive (≥1:100) anti-MOG, records were reviewed to classify results as true-positive (TP) or false-positive (FP) and facilitate PPV calculation. Timing of sample collection relative to administration of immunotherapy and symptom onset was determined for TP results. Results: Overall PPV of anti-MOG was 70/85 (82%). The PPV of low-positive anti-MOG was significantly lower than clear-positive anti-MOG (72% vs. 95%, p = 0.009). The difference in PPV between low-positive and clear-positive anti-MOG was significant among adults tested, but not children. Among patients with TP anti-MOG, the proportion who received immunotherapy prior to sample collection was significantly higher and median time from symptom onset to sample collection was significantly longer for low-positive compared to clear-positive results. Conclusion: Overall PPV of anti-MOG testing by fixed CBA was reasonably high. The PPV of low-positive anti-MOG was significantly lower than clear-positive anti-MOG. This was driven by the significantly lower PPV of low-positive anti-MOG in adults, possibly reflecting the lower prevalence of MOG antibody-associated disease among adults tested. Timing of sample collection relative to administration of immunotherapy and symptom onset may substantially impact titers, indicating that testing should ideally be performed prior to immunotherapy and close to time of attack.

Multiple Sclerosis Part 1: Essentials and the McDonald Criteria.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterized by relapsing-remitting or progressive neurologic symptoms and focal white matter lesions. The hallmark of the disease is the dissemination of CNS lesions in space and time, which is defined by the McDonald criteria. MRI is an essential diagnostic and prognostic biomarker for MS which can evaluate the entire CNS. MS mimics must be excluded before a diagnosis of MS is made.

Myelin oligodendrocyte glycoprotein antibody-associated disease with clinical presentation as multiple episodes of isolated meningeal involvement: a case report.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) constitutes a group of autoimmune neuroinflammatory conditions that are characterized by positive serum MOG-immunoglobulin G antibodies. The relationship between MOGAD and immune factors remains unclear. Herein, we report a man in his early 30s who initially presented symptoms of headache and low-grade fever persisting for 20 days. The patient experienced isolated meningitis onset and had recurrent meningitis as the primary clinical feature, which manifested as low-grade fever, headache, and neck rigidity. Although cranial magnetic resonance imaging showed no abnormalities, immunotherapy was promptly administered upon diagnosing MOGAD through positive MOG-specific antibody testing of cerebrospinal and serum fluids. Notably, the patient's symptoms exhibited rapid improvement following treatment. Although meningitis is traditionally associated with infectious diseases, it can also occur in antibody-related autoimmune diseases that affect the central nervous system. Consequently, MOGAD should be considered in cases of aseptic meningitis with an unknown etiology, to facilitate definitive diagnosis and enhance patient prognosis.