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Frontiers in Immunology 2023Pure Neural Leprosy (PNL) is a form of this long time known disease that affects only the peripheral nervous system. Since it is a rare form of the disease, its...
INTRODUCTION
Pure Neural Leprosy (PNL) is a form of this long time known disease that affects only the peripheral nervous system. Since it is a rare form of the disease, its pathophisiology is still poorly understood.
OBJECTIVE
Describe the cytokines profile in patients with PNL.
METHODS
30 Patients diagnosed with PNL in the Souza Araujo Outpatient Clinic and with cytokines evaluated were selected. They were evaluated by neurologists and diagnosed after a nerve biopsy. Serum levels of IL-1 β, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-ϒ, CXCL-10/IP-10 and TGF-β were evaluates at the moment of the diagnosis.
RESULTS
Neural thickening was a common clinical finding in this groups of patients. Small and medium sensitive fibers signs and symptoms were present in 92% of the patients and motor involvement in 53%. 43% of patients presented neuropathic pain and no one had neuritis TGF-beta, IL-17, CCl-2 and IP-10. CCL-2 levels were associated with demyelinating patters and IP-10 and IL-1o were associated with axonal patterns at NCS.
DISCUSSION
PNL patients' cytokine profile appears to be different of other clinical forms of leprosy, with the presence of cytokines described in both tuberculoid and lepromatous leprosy. High levels of CCl-2 may be related to the presence of silent neuritis as well as the presence of IL-10. PNL is unique a form of leprosy, therefore, understanding its immunological profiles essential to better understand the disease itself.
Topics: Humans; Leprosy, Tuberculoid; Cytokines; Interleukin-10; Interleukin-17; Chemokine CXCL10; Leprosy; Transforming Growth Factor beta; Neuritis
PubMed: 38116016
DOI: 10.3389/fimmu.2023.1272471 -
Annals of Medicine Dec 2023To appraise whether plasma exchange (PLEX) effectively improves visual function for acute optic neuritis (ON) in neuromyelitis optica (NMO) or neuromyelitis optica... (Review)
Review
OBJECTIVES
To appraise whether plasma exchange (PLEX) effectively improves visual function for acute optic neuritis (ON) in neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD).
METHODS AND ANALYSIS
We searched Medline, Embase, Cochrane Library, ProQuest Central, and Web of Science to identify relevant articles published between 2006 and 2020.Eligible studies were in English and evaluated visual outcomes for people with acute ON in NMO or NMOSD treated with PLEX. They also had adequate pre- and posttreatment data. Excluded were studies with 1 or 2 case reports, or incomplete data.
RESULTS
Twelve studies were qualitatively synthesized (1 RCT; 1 controlled NRSI; 10 observational studies). Five before-and-after observational studies were used for quantitative synthesis. The PLEX in the 5 studies (3 to 7 cycles over 2 to 3 weeks) was performed as second-line or adjunctive therapy for acute ON in NMO/NMOSD.The qualitative synthesis revealed that visual-acuity recovery occurred between one day and 6 months after the first PLEX cycle completion. Thirty-two of 48 participants in the 5 quantitative-synthesis studies received PLEX. Relative to pre-PLEX values, visual-acuity improvements were nonsignificant at these post-PLEX time points: 1 day (SMD 0.611; 95% CI -0.620 to 1.842); 2 weeks (SMD 0.0214; 95% CI -1.250 to 1.293); 3 months (SMD 1.014; 95% CI -0.954 to 2.982); and 6 months (SMD 0.450; 95% CI -2.643 to 3.543).
CONCLUSIONS
There were inadequate data to determine whether PLEX effectively treats acute ON in NMO/NMOSD.
Topics: Humans; Plasma Exchange; Neuromyelitis Optica; Optic Neuritis; Outcome Assessment, Health Care
PubMed: 37387119
DOI: 10.1080/07853890.2023.2227422 -
Journal of Neurology Oct 2023Few studies documented the potential association between vaccination and the risk of central demyelination (CD). Specifically, anti-hepatitis B and anti-human...
BACKGROUND
Few studies documented the potential association between vaccination and the risk of central demyelination (CD). Specifically, anti-hepatitis B and anti-human papillomavirus (HPV) vaccines have been the subject of distrust with regard to their implication to trigger CD.
METHODS
From a systematic national registry, patients with first signs of CD (cases) were identified and documented for their exposure to vaccination up to 24 months before the first signs occurred. This exposure was compared to that of a representative sample of general practice patients without a history of CD, randomly selected from a national registry (referents). CD cases were 2:1 matched on age, sex, index date (ID), and region of residence. Vaccines against influenza, HPV, hepatitis B and diphtheria-tetanus-pertussis-poliomyelitis-haemophilus (DTPPHae) were considered. Associations between vaccination and CD were assessed using multivariate conditional logistic regressions, controlled for confounding factors.
FINDINGS
564 CD cases were matched to 1,128 randomly selected referents (age range: 2-79 years old). Overall, 123 (22%) CD cases and 320 (28%) referents had received at least one vaccine within 24 months before ID. Adjusted odds ratios (ORs) for any vaccination were 0.69, 95% confidence interval (CI) [0.54-0.88] with respect to any CD first signs, 0.68 [0.51-0.90] for myelitis and 0.70 [0.42-1.17] for optic neuritis. Adjusted ORs for any CD first signs were 1.02 [0.71-1.47] for influenza vaccine (administered in 9.6% of cases and 10.4% of referents) and 0.72 [0.53-0.99] for DTPPHae vaccine (administered in 10.8% of cases and 14.5% of referents). Vaccines against hepatitis B and HPV were only administered in 1.1% and 1.2% of cases and in 2.9% and 3.2% of referents respectively, which statistically explained the point estimates < 1 (ORs of 0.39 [0.16-0.94] and of 0.32 [0.13-0.80]).
INTERPRETATION
No increased risk of CD incidence was observed amongst vaccinated patients. Lower rates of vaccination against hepatitis B and HPV observed in patients with CD compared to referents may be due to the reluctance of physicians to vaccinate patients considered at risk of CD.
Topics: Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Papillomavirus Infections; Vaccination; Vaccines; Case-Control Studies; Demyelinating Diseases; Hepatitis B Vaccines
PubMed: 37351662
DOI: 10.1007/s00415-023-11822-y -
Genes Dec 2023Optic neuritis (ON) is an inflammatory condition affecting the optic nerve, leading to vision impairment and potential vision loss. This manuscript aims to provide a... (Review)
Review
Optic neuritis (ON) is an inflammatory condition affecting the optic nerve, leading to vision impairment and potential vision loss. This manuscript aims to provide a comprehensive review of the current understanding of ON, including its definition, epidemiology, physiology, genetics, molecular pathways, therapy, ongoing clinical studies, and future perspectives. ON is characterized by inflammation of the optic nerve, often resulting from an autoimmune response. Epidemiological studies have shown a higher incidence in females and an association with certain genetic factors. The physiology of ON involves an immune-mediated attack on the myelin sheath surrounding the optic nerve, leading to demyelination and subsequent impairment of nerve signal transmission. This inflammatory process involves various molecular pathways, including the activation of immune cells and the release of pro-inflammatory cytokines. Genetic factors play a significant role in the susceptibility to ON. Several genes involved in immune regulation and myelin maintenance have been implicated in the disease pathogenesis. Understanding the genetic basis can provide insights into disease mechanisms and potential therapeutic targets. Therapy for ON focuses on reducing inflammation and promoting nerve regeneration. Future perspectives involve personalized medicine approaches based on genetic profiling, regenerative therapies to repair damaged myelin, and the development of neuroprotective strategies. Advancements in understanding molecular pathways, genetics, and diagnostic tools offer new opportunities for targeted therapies and improved patient outcomes in the future.
Topics: Animals; Female; Humans; Encephalomyelitis, Autoimmune, Experimental; Optic Neuritis; Optic Nerve; Inflammation; Cytokines
PubMed: 38137014
DOI: 10.3390/genes14122192 -
Antioxidants (Basel, Switzerland) Jul 2023Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve.... (Review)
Review
Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber's hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies.
PubMed: 37508003
DOI: 10.3390/antiox12071465 -
Neurotherapeutics : the Journal of the... Jul 2023Resveratrol is a natural polyphenol which may be useful for treating neurodegenerative diseases such as multiple sclerosis (MS). To date, current immunomodulatory...
Resveratrol is a natural polyphenol which may be useful for treating neurodegenerative diseases such as multiple sclerosis (MS). To date, current immunomodulatory treatments for MS aim to reduce inflammation with limited effects on the neurodegenerative component of this disease. The purpose of the current study is to develop a novel nanoparticle formulation of resveratrol to increase its solubility, and to assess its ability to prevent optic nerve and spinal cord degeneration in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Resveratrol nanoparticles (RNs) were made using a thin rehydration technique. EAE mice received a daily oral administration of vehicle, RNs or unconjugated resveratrol for one month. They were assessed daily for clinical signs of paralysis and weekly for their visual acuity with optokinetic responses (OKR). After one month, their spinal cords and optic nerves were stained for inflammation and demyelination and retinal ganglion cells immunostained for Brn3a. RNs were stable for three months. The administration of RNs did not have any effect on clinical manifestation of EAE and did not preserve OKR scores but reduced the intensity of the disease. It did not reduce inflammation and demyelination in the spinal cord and the optic nerve. However, RNs were able to decrease RGC loss compared to the vehicle. Results demonstrate that resveratrol is neuroprotective by reducing RGC loss. Interestingly, neuroprotective effects and decreased disease severity occurred without reduction of inflammation or demyelination, suggesting this therapy may fill an unmet need to limit the neurodegenerative component of MS.
Topics: Mice; Animals; Resveratrol; Neuroprotective Agents; Optic Neuritis; Solubility; Mice, Inbred C57BL; Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; Inflammation; Disease Models, Animal
PubMed: 37160530
DOI: 10.1007/s13311-023-01378-0 -
Neurology(R) Neuroimmunology &... Nov 2023Optical coherence tomography angiography (OCTA) is a noninvasive high-resolution imaging technique for assessing the retinal vasculature and is increasingly used in... (Review)
Review
BACKGROUND AND OBJECTIVES
Optical coherence tomography angiography (OCTA) is a noninvasive high-resolution imaging technique for assessing the retinal vasculature and is increasingly used in various ophthalmologic, neuro-ophthalmologic, and neurologic diseases. To date, there are no validated consensus criteria for quality control (QC) of OCTA. Our study aimed to develop criteria for OCTA quality assessment.
METHODS
To establish criteria through (1) extensive literature review on OCTA artifacts and image quality to generate standardized and easy-to-apply OCTA QC criteria, (2) application of OCTA QC criteria to evaluate interrater agreement, (3) identification of reasons for interrater disagreement, revision of OCTA QC criteria, development of OCTA QC scoring guide and training set, and (4) validation of QC criteria in an international, interdisciplinary multicenter study.
RESULTS
We identified 7 major aspects that affect OCTA quality: (O) obvious problems, (S) signal strength, (C) centration, (A) algorithm failure, (R) retinal pathology, (M) motion artifacts, and (P) projection artifacts. Seven independent raters applied the OSCAR-MP criteria to a set of 40 OCTA scans from people with MS, Sjogren syndrome, and uveitis and healthy individuals. The interrater kappa was substantial (κ 0.67). Projection artifacts were the main reason for interrater disagreement. Because artifacts can affect only parts of OCTA images, we agreed that prior definition of a specific region of interest (ROI) is crucial for subsequent OCTA quality assessment. To enhance artifact recognition and interrater agreement on reduced image quality, we designed a scoring guide and OCTA training set. Using these educational tools, 23 raters from 14 different centers reached an almost perfect agreement (κ 0.92) for the rejection of poor-quality OCTA images using the OSCAR-MP criteria.
DISCUSSION
We propose a 3-step approach for standardized quality control: (1) To define a specific ROI, (2) to assess the occurrence of OCTA artifacts according to the OSCAR-MP criteria, and (3) to evaluate OCTA quality based on the occurrence of different artifacts within the ROI. OSCAR-MP OCTA QC criteria achieved high interrater agreement in an international multicenter study and is a promising QC protocol for application in the context of future clinical trials and studies.
Topics: Humans; Consensus; Fluorescein Angiography; Retina; Retinal Vessels; Tomography, Optical Coherence
PubMed: 37813596
DOI: 10.1212/NXI.0000000000200169 -
Skeletal Radiology Sep 2023Beginning in May 2022, monkeypox infection and vaccination rates dramatically increased due to a worldwide outbreak. This case highlights magnetic resonance (MR)...
Beginning in May 2022, monkeypox infection and vaccination rates dramatically increased due to a worldwide outbreak. This case highlights magnetic resonance (MR) neurography findings in an individual who developed Parsonage-Turner syndrome (PTS) 5 days after monkeypox symptom onset and 12 days after receiving the JYNNEOS vaccination. MR neurography of the patient's left suprascapular nerve demonstrated intrinsic hourglass-like constrictions, a characteristic finding of peripheral nerves involved in PTS. Other viral infections and vaccinations are well-documented triggers of PTS, an underrecognized peripheral neuropathy that is thought to be immune-mediated and results in severe upper extremity pain and weakness. The close temporal relationship between monkeypox infection and vaccination, and PTS onset, in this case, suggests a causal relationship and marks the first known report of peripheral neuropathy associated with monkeypox.
Topics: Humans; Brachial Plexus Neuritis; Mpox (monkeypox); Magnetic Resonance Imaging; Peripheral Nervous System Diseases; Vaccination
PubMed: 36752829
DOI: 10.1007/s00256-023-04298-4 -
Cureus Jul 2023Lyme disease (LD) is the most common vector-borne disease in the United States. The early localized disease presents with erythema migrans and nonspecific...
Lyme disease (LD) is the most common vector-borne disease in the United States. The early localized disease presents with erythema migrans and nonspecific constitutional symptoms. A neurological manifestation of LD (neuroborreliosis) is only seen in 10-15% of LD cases, and it typically presents as cranial neuritis or painful radiculitis. We report a case of a 33-year-old male who presented with progressive ascending bilateral lower extremities weakness with paresthesia in hands and feet following an upper respiratory tract infection and an abdominal rash. Cerebrospinal fluid (CSF) analysis revealed albuminocytologic dissociation. An electrodiagnostic study showed prolonged distal motor latency, conduction block, and absent F-wave response. Magnetic resonance imaging of the lumbar spine revealed enhancement of the cauda equina nerve roots. After a lack of improvement with intravenous immunoglobulin for presumed Guillain-Barré syndrome (GBS), Lyme serologies were sent and showed positive Lyme antibodies in serum and CSF as well as positive western blot IgM followed by IgG seroconversion a week later. The patient was started on IV ceftriaxone and doxycycline for four weeks with significant improvement in his symptoms. This is a rare case of LD presenting as GBS. Lyme can have diverse neurologic manifestations and should be considered in the differential diagnosis of GBS in the appropriate settings.
PubMed: 37614265
DOI: 10.7759/cureus.42322 -
Neurology(R) Neuroimmunology &... May 2024Optic neuritis is the most common optic neuropathy in young adults and a frequent manifestation of multiple sclerosis. Its clinical course is pertinent to the design of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Optic neuritis is the most common optic neuropathy in young adults and a frequent manifestation of multiple sclerosis. Its clinical course is pertinent to the design of visual pathway neuroprotection trials.
METHODS
This is a secondary analysis of longitudinal data from the TONE trial, which included 103 patients from 12 German academic tertiary centers with acute unilateral optic neuritis as a clinically isolated syndrome and baseline high-contrast visual acuity <0.5 decimal. Patients were randomized to 1,000 mg methylprednisolone i.v./d plus either erythropoietin (33,000 IU/d) or placebo (saline solution) for 3 days. They were followed up at standardized intervals with a battery of tests including high-contrast visual acuity, low-contrast letter acuity, contrast sensitivity, visual fields, visual evoked potentials, and retinal optical coherence tomography. At 6 months, participants answered a standardized questionnaire on vision-related quality of life (NEI-VFQ 25). We describe the disease course with mixed-effects piecewise linear models and calculate structure-function correlations using Pearson r. Because erythropoietin had no effect on the visual system, we use pooled (treatment-agnostic) data.
RESULTS
Patients experienced initial rapid and then decelerating improvements of visual function with thinning of inner and thickening of outer retinal layers. At 6 months, visual parameters were positively correlated with inner and negatively correlated with outer retinal thickness changes. Peripapillary retinal nerve fiber layer thinning predominantly occurred in sectors without previous swelling. At 6 months, macular ganglion cell and inner plexiform layer thinning was weakly correlated with the P100 peak time (r = -0.11) and moderately correlated with the amplitude of visual evoked potentials (r = 0.35). Only functional outcomes were at least moderately correlated with vision-related quality of life.
DISCUSSION
The longitudinal data from this large study cohort may serve as a reference for the clinical course of acute optic neuritis. The pattern of correlation between visual evoked potentials and inner retinal thinning may argue that the latter is mostly due to ganglion cell loss, rather than dysfunction. Visual pathway neuroprotection trials with functional outcomes are needed to confirm that candidate drugs will benefit patients' vision-related quality of life.
TRIAL REGISTRATION INFORMATION
ClinicalTrials.gov, NCT01962571.
Topics: Humans; Young Adult; Disease Progression; Erythropoietin; Evoked Potentials, Visual; Optic Neuritis; Quality of Life
PubMed: 38588480
DOI: 10.1212/NXI.0000000000200223