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International Journal of Molecular... Apr 2024Resveratrol is a natural polyphenol which has a very low bioavailability but whose antioxidant, anti-inflammatory and anti-apoptotic properties may have therapeutic...
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.
Topics: Animals; Mice; Multiple Sclerosis; Resveratrol; Neuroprotection; Administration, Intranasal; Encephalomyelitis, Autoimmune, Experimental; Nanoparticles
PubMed: 38612856
DOI: 10.3390/ijms25074047 -
Journal of Clinical Medicine Apr 2024This study evaluated the plasma concentration of prolylcarboxypeptidase (PRCP) and its clinical relevance in patients with idiopathic acute optic neuritis (ON). We...
This study evaluated the plasma concentration of prolylcarboxypeptidase (PRCP) and its clinical relevance in patients with idiopathic acute optic neuritis (ON). We investigated the expression of PRCP in the optic nerves of experimental autoimmune optic neuritis (EAON)-induced mice. Peripheral blood samples were collected from ON patients (n = 20) and healthy controls (n = 20). ELISA was used to measure the plasma PRCP levels. We performed measurements of visual acuity and the mean thicknesses of the macular ganglion cell layer plus inner plexiform layer (GCL+IPL) at diagnosis and 6 months after diagnosis. The PRCP mRNA expression in EAON-induced mice was markedly higher than that in naïve mice. The mean plasma PRCP level was significantly higher in patients with ON than in controls. Plasma PRCP levels were negatively correlated with logMAR visual acuity at 6 months after diagnosis and differences in macular GCL+IPL thickness during an ON attack. A plasma PRCP level of 49.98 (pg/mL) predicted the recurrence of ON with a 75% sensitivity and 87.5% specificity. Patients with idiopathic acute ON had higher plasma PRCP levels, and this was positively correlated with final visual outcome and well-preserved macular GCL+IPL thickness during an ON attack. The increase in plasma PRCP level may reflect its compensatory secretion to counteract neuroinflammation in ON patients.
PubMed: 38610803
DOI: 10.3390/jcm13072038 -
Cells Mar 2024Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) featuring numerous neuropathologies, including optic neuritis (ON)...
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) featuring numerous neuropathologies, including optic neuritis (ON) in some patients. However, the molecular mechanisms of ON remain unknown. Galectins, β-galactoside-binding lectins, are involved in various pathophysiological processes. We previously showed that galectin-3 (gal-3) is associated with the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the current study, we investigated the expression of gal-3 in the visual pathway in EAE mice to clarify its role in the pathogenesis of ON. Immunohistochemical analysis revealed upregulation of gal-3 in the visual pathway of the EAE mice during the peak stage of the disease, compared with naïve and EAE mice during the chronic stage. Gal-3 was detected mainly in microglia/macrophages and astrocytes in the visual pathway in EAE mice. In addition, gal-3/Iba-1 cells, identified as phagocytic by immunostaining for cathepsin D, accumulated in demyelinating lesions in the visual pathway during the peak disease stage of EAE. Moreover, NLRP3 expression was detected in most gal-3/Iba-1 cells. These results strongly suggest that gal-3 regulates NLRP3 signaling in microglia/macrophages and neuroinflammatory demyelination in ON. In astrocytes, gal-3 was expressed from the peak to the chronic disease stages. Taken together, our findings suggest a critical role of gal-3 in the pathogenesis of ON. Thus, gal-3 in glial cells may serve as a potential therapeutic target for ON.
Topics: Animals; Humans; Mice; Encephalomyelitis, Autoimmune, Experimental; Galectin 3; Galectins; Multiple Sclerosis; Neuroinflammatory Diseases; NLR Family, Pyrin Domain-Containing 3 Protein; Optic Neuritis; Visual Pathways
PubMed: 38607051
DOI: 10.3390/cells13070612 -
Frontiers in Neurology 2024Growing evidence has demonstrated that peripapillary hyperreflective ovoid mass-like structures (PHOMS) are novel structures rather than a subtype of optic disc drusen.... (Review)
Review
Growing evidence has demonstrated that peripapillary hyperreflective ovoid mass-like structures (PHOMS) are novel structures rather than a subtype of optic disc drusen. They correspond to the laterally bulging herniation of optic nerve fibers and are believed to be the marker of axoplasmic stasis. PHOMS present in a broad spectrum of diseases, including optic disc drusen, tilted disc syndrome, papilloedema, multiple sclerosis, non-arteritic anterior ischemic optic neuropathy, optic neuritis, Leber hereditary optic neuropathy, and so on. We focus on the multimodal imaging features, pathophysiological mechanisms of PHOMS, and their association with multiple diseases and healthy people in this review to deepen the ophthalmologists' understanding of PHOMS. Additionally, we provide some new directions for future research.
PubMed: 38606274
DOI: 10.3389/fneur.2024.1379801 -
Medical Hypothesis, Discovery &... 2023Multiple sclerosis (MS) is a chronic neurodegenerative disease that damages myelinated fibers within the central nervous system. Data obtained using optical coherence...
BACKGROUND
Multiple sclerosis (MS) is a chronic neurodegenerative disease that damages myelinated fibers within the central nervous system. Data obtained using optical coherence tomography (OCT) have recently been identified as a potential biomarker for this disease. We aimed to measure circumpapillary retinal nerve fiber layer thickness (cpRNFLT) using OCT and to compare the results in healthy participants with those of individuals having clinically definitive MS with and without a history of optic neuritis.
METHODS
This cross-sectional study recruited patients with clinically confirmed MS, with and without optic neuritis, and healthy individuals as a control group. We documented demographic characteristics, duration of MS, and time elapsed since the episode of optic neuritis. All participants underwent a thorough ocular examination and measurement of total, superior, and inferior cpRNFLT using swept-source OCT.
RESULTS
In participants with MS, women outnumbered men in the subsets with (90%) and without (64%) optic neuritis. The control group comprised approximately similar numbers of men and women. There was a statistically significant difference in total, superior, and inferior cpRNFLT between study groups (all < 0.001). Pairwise comparisons revealed significantly thinner total, superior, and inferior cpRNFLTs in patients having MS with and without (all < 0.001) optic neuritis when compared with the controls. We found significantly higher total, superior, and inferior cpRNFLTs in women than in men (all < 0.05). However, we found no significant correlation between total, superior, or inferior cpRNFLT and patient age, duration of MS, or time elapsed since the optic neuritis episode (all > 0.05), except for a significant moderate inverse correlation between patient age and total cpRNFLT (r = - 0.41; < 0.05), indicating a loss of total cpRNFLT with age.
CONCLUSIONS
Patients with clinically confirmed MS, with or without optic neuritis, had a significantly decreased cpRNFLT compared to that of healthy individuals. There was a significant inverse correlation between age and total cpRNFLT and a difference in cpRNFLT between the sexes, indicating that age and sex may influence the measurement of cpRNFLT using OCT in patients with MS. As a screening tool, OCT should be used along with other existing diagnostic modalities for patients with definite or suspected MS. Further longitudinal studies including various classifications of MS with or without isolated episodes of optic neuritis, along with diagnostic accuracy studies, could provide more robust conclusions on the suitability of OCT as a biomarker of MS.
PubMed: 38601055
DOI: 10.51329/mehdiophthal1485 -
Brain & Spine 2024Patients with multiple sclerosis (MS) are more likely to develop trigeminal neuralgia (TN) compared to the regular population, due to scarring of the nerve and...
BACKGROUND
Patients with multiple sclerosis (MS) are more likely to develop trigeminal neuralgia (TN) compared to the regular population, due to scarring of the nerve and development of a demyelination plaque. Despite treatment, approximately 10% of MS patients treated for TN experience symptom recurrence, including the development of MS-like symptoms such as optic neuritis and bilateral facial pain.
METHODS
A computed tomography (CT) scan was performed preoperatively on two patients diagnosed with multiple sclerosis (MS) who experienced secondary trigeminal neuralgia (TN). A precise reference frame was strapped firmly to the patient's forehead during the intraoperative procedure. Preliminary CT images were registered using the navigation system and the bony landmarks were set.
CASE DESCRIPTION
Two patients diagnosed with multiple sclerosis (MS) who experienced refractory trigeminal neuralgia (TN) underwent percutaneous balloon compression. Initial conservative treatment and one dosage of Gamma Knife Radiosurgery (GKR) resulted in symptom control for a few weeks. Both patients had an acute recurrence of pain; thus, percutaneous retrogasserian balloon compression was performed. During follow-up, the patients reported a 70% decrease in pain after the procedure, with minimal recurrence of shooting episodes.
CONCLUSION
Management of trigeminal neuralgia secondary to drug-resistant multiple sclerosis presents a persistent challenge. The percutaneous technique for retrogasserian balloon compression may offer a solution for some patients, but it presents unique challenges for neurosurgeons. Given the complexity of the pathogenesis, target identification, and the potential absence of neurovascular conflict, microvascular decompression remains a debated approach for this patient population. While stereotactic radiosurgery may be a promising alternative.
PubMed: 38596449
DOI: 10.1016/j.bas.2024.102798 -
Cureus Mar 2024Concurrent tuberculous optic neuritis (ON) and optic perineuritis (OPN) in a patient with human immunodeficiency virus (HIV) is extremely rare. HIV-induced progressive...
Concurrent tuberculous optic neuritis (ON) and optic perineuritis (OPN) in a patient with human immunodeficiency virus (HIV) is extremely rare. HIV-induced progressive CD4 depletion is associated with an increased risk of tuberculosis (TB), disseminated TB, and death. Early detection and initiation of anti-TB therapy with corticosteroid commencement helps in achieving better visual outcomes. Interestingly, we report a case of concurrent ON and OPN in a patient with HIV-TB co-infection. A 29-year-old lady, a prisoner, with newly diagnosed treatment-naive HIV, presented with acute-onset reduced vision in the left eye for 10 days. It was associated with pain in eye movement and headache. The patient was known to be a drug abuser since the age of 19 years and was a sexual worker. Her CD4 count was 292 cells/mm.Visual acuity of the right eye was 6/12 with a pinhole of 6/9, and there was no perception of light (NPL) in all four quadrants of the left eye. Relative afferent pupillary defect (RAPD) was positive in the left eye. Both anterior segments were unremarkable. The right eye fundoscopy showed a normal optic disc, while the left eye showed a hyperemic disc. During subsequent follow-up, the patient had reduced right eye vision, and the vision dropped to 6/30 with a pinhole of 6/15. Her erythrocyte sedimentation rate (ESR) was raised to 88 mm/h. The Mantoux test was positive. Chest radiography was normal. MRI of the brain and orbit showed significant enhancement of the right optic nerve and left optic nerve sheath suggesting the diagnosis of right eye ON and left eye OPN secondary to TB. The patient was co-managed with an infectious disease team. She was started on highly active antiretroviral therapy (HAART) treatment (oral Tenvir-EM and efavirenz) upon presentation. Anti-TB therapy was commenced two months later. She was started on the intensive phase of the anti-TB regime followed by the maintenance phase. Oral dexamethasone was given concurrently according to the central nervous system (CNS) TB regime for six weeks. During follow-up, her right eye visual acuity was 6/9, and her left eye visual acuity improved to 6/12. Fundoscopy showed bilateral pale discs. To date, no episodes of recurrence have been seen.
PubMed: 38595896
DOI: 10.7759/cureus.55867 -
Clinical & Experimental Neuroimmunology Feb 2024We report a rare case of paraneoplastic neurological syndrome with dual seropositivity of anti-aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in a 40...
Anti-aquaporin-4 immunoglobulin G/anti-myelin oligodendrocyte glycoprotein immunoglobulin G double-positive paraneoplastic neurological syndrome in a patient with triple-negative breast cancer.
We report a rare case of paraneoplastic neurological syndrome with dual seropositivity of anti-aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in a 40 year-old woman with metastatic triple-negative breast cancer. She received multiple lines of anti-neoplastic treatment, including immunotherapy with pembrolizumab, as well as cytotoxic chemotherapy. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis followed by left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid analysis during both episodes showed normal glucose and protein, and elevated white blood cell count. Cytology was negative for malignancy. Cerebrospinal fluid was positive for neuromyelitis optica immunoglobulin G antibody anti-aquaporin-4, and autoimmune myelopathy panel was positive for myelin oligodendrocyte glycoprotein antibody. The patient had significant clinical and radiographic improvement after completion of five cycles of plasmapheresis followed by intravenous immunoglobulin. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every 6 months and daily low-dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case shows that these antibodies can occur concurrently and cause clinical features, such as both neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease, in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or cerebrospinal fluid profile negative for leptomeningeal carcinomatosis.
PubMed: 38595690
DOI: 10.1111/cen3.12767 -
Journal of Pharmacy & Bioallied Sciences Feb 2024Although immunization against coronavirus disease 2019 (COVID-19) is ongoing, adverse reactions to these vaccinations have been observed in isolated cases. We aimed to...
BACKGROUND AND OBJECTIVES
Although immunization against coronavirus disease 2019 (COVID-19) is ongoing, adverse reactions to these vaccinations have been observed in isolated cases. We aimed to report different neurological complications developed after COVID-19 vaccination.
MATERIALS AND METHODS
In our case series study, we report all cases of CNS demyelination following COVID-19 immunization. Clinical evaluation, brain MRI, and CSF analysis for oligoclonal bands and IgG index were performed for all patients. Other investigations were performed for selected patients, including spine MRI, EEG, VEP, and aquaporin-4.
RESULTS
Eighteen patients (eight males and ten females) with no history of COVID-19 infection had neurological manifestations (vertigo, ataxia, recurrent attacks of loss of consciousness, optic neuritis, and myelitis) starting within 14 days after Pfizer ( = 12) and AstraZeneca ( = 6) vaccination. MRI was obtained during the acute stage of the disease. The most common presenting symptoms were optic neuritis and hemiparesis. Sixteen patients had altered signal intensity and multiple variable-sized, round to ill-defined oval lesions suggestive of MS. Two showed findings compatible with transverse myelitis.
CONCLUSION
This study identified CNS demyelination complications after COVID-19 vaccination. The COVID-19 vaccination could result in CNS complications, possibly connected to a post-vaccination inflammatory process. We recommend continuous post-marketing monitoring for adverse reactions in individuals who received the vaccines to establish a connection and guarantee the long-term safety of COVID-19 vaccines.
PubMed: 38595635
DOI: 10.4103/jpbs.jpbs_1084_23 -
Neural Regeneration Research Dec 2024Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis. Over the past 20 years, the search for...
Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis. Over the past 20 years, the search for biomarkers for neuromyelitis optica has been ongoing. Here, we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica. Research in this area is consistently increasing, with China and the United States leading the way on the number of studies conducted. The Mayo Clinic is a highly reputable institution in the United States, and was identified as the most authoritative institution in this field. Furthermore, Professor Wingerchuk from the Mayo Clinic was the most authoritative expert in this field. Keyword analysis revealed that the terms "neuromyelitis optica" (261 times), "multiple sclerosis" (220 times), "neuromyelitis optica spectrum disorder" (132 times), "aquaporin 4" (99 times), and "optical neuritis" (87 times) were the most frequently used keywords in literature related to this field. Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis. Furthermore, aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder. Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarker for myelin oligodendrocyte glycoprotein antibody-associated disease. Recent biomarkers for neuromyelitis optica include cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein, serum astrocyte damage biomarkers like FAM19A5, serum albumin, and gamma-aminobutyric acid. The latest prospective clinical trials are exploring the potential of these biomarkers. Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder. The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity, specificity, and safety for the accurate diagnosis of neuromyelitis optica.
PubMed: 38595291
DOI: 10.4103/NRR.NRR-D-24-00109