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2.
Mult Scler Relat Disord ; 85: 105526, 2024 May.
Article in English | MEDLINE | ID: mdl-38489945

ABSTRACT

BACKGROUND: Eosinophils in cerebrospinal fluid (CSF) are an uncommon finding most often associated with parasitic infections, but have also been described in some neuroinflammatory disorders. Eosinophilic infiltration is not thought to be a typical feature of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We aim to describe the rate of CSF eosinophil positivity in a cohort of pediatric MOGAD patients. METHODS: Single-center retrospective chart review of pediatric MOGAD patients. Clinical and laboratory data was collected from the electronic medical record and analyzed. RESULTS: Of 46 pediatric patients with positive serum myelin oligodendrocyte glycoprotein antibody (MOG-IgG) identified, 38 patients fulfilling internationally proposed MOGAD diagnostic criteria were included for analysis. 6 patients with MOGAD were excluded as no CSF data was available, and 2 patients with positive MOG-IgG but diagnosis more consistent with MS were excluded. Median age was 7.3 years, and 19/38 (50 %) were female. Acute disseminated encephalomyelitis (ADEM) was the most common presenting phenotype (23/38, 61 %), and other phenotypes included optic neuritis (10/38, 26 %), transverse myelitis (3/38, 8 %), and neuromyelitis optica spectrum disorder (NMOSD) (2/38, 5 %). 12 of 36 (33 %) patients with all lumbar puncture (LP) data available had CSF eosinophils present, with eosinophil mean of 3 % and range from 1 % to 18 % of CSF while blood cells. CONCLUSION: CSF eosinophils were present in one third of pediatric MOGAD patients, which is a higher rate than previously reported in either MOGAD or aquaporin-4 antibody positive NMOSD cohorts. Understanding the CSF composition of pediatric MOGAD patients helps to facilitate more prompt diagnosis and treatment and may shed light onto underlying pathologic mechanisms of disease with the goal to inform future therapeutic targets.


Subject(s)
Autoantibodies , Eosinophils , Myelin-Oligodendrocyte Glycoprotein , Humans , Myelin-Oligodendrocyte Glycoprotein/immunology , Female , Male , Child , Retrospective Studies , Eosinophils/immunology , Child, Preschool , Adolescent , Autoantibodies/cerebrospinal fluid , Autoantibodies/blood , Encephalomyelitis, Acute Disseminated/immunology , Encephalomyelitis, Acute Disseminated/cerebrospinal fluid , Encephalomyelitis, Acute Disseminated/blood , Encephalomyelitis, Acute Disseminated/diagnosis , Neuromyelitis Optica/cerebrospinal fluid , Neuromyelitis Optica/immunology , Neuromyelitis Optica/blood , Infant , Myelitis, Transverse/immunology , Myelitis, Transverse/cerebrospinal fluid , Myelitis, Transverse/blood , Optic Neuritis/immunology , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/blood , Demyelinating Autoimmune Diseases, CNS/cerebrospinal fluid , Demyelinating Autoimmune Diseases, CNS/immunology , Demyelinating Autoimmune Diseases, CNS/blood
3.
J Neurol ; 271(5): 2662-2671, 2024 May.
Article in English | MEDLINE | ID: mdl-38366070

ABSTRACT

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.


Subject(s)
Autoantibodies , Myelin-Oligodendrocyte Glycoprotein , Humans , Myelin-Oligodendrocyte Glycoprotein/immunology , Male , Female , Adult , Middle Aged , Autoantibodies/cerebrospinal fluid , Autoantibodies/blood , Aged , Adolescent , Young Adult , Child , Aged, 80 and over , Child, Preschool , Demyelinating Autoimmune Diseases, CNS/cerebrospinal fluid , Demyelinating Autoimmune Diseases, CNS/immunology , Demyelinating Autoimmune Diseases, CNS/diagnosis , Demyelinating Autoimmune Diseases, CNS/blood , Encephalomyelitis, Acute Disseminated/diagnosis , Encephalomyelitis, Acute Disseminated/cerebrospinal fluid , Encephalomyelitis, Acute Disseminated/immunology , Encephalomyelitis, Acute Disseminated/blood , Retrospective Studies , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/immunology , Optic Neuritis/diagnosis , Optic Neuritis/blood
6.
Clin Neurol Neurosurg ; 202: 106507, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33493883

ABSTRACT

INTRODUCTION: Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders. METHODS: We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019. RESULTS: Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels. CONCLUSION: EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF.


Subject(s)
DNA, Viral/cerebrospinal fluid , Epstein-Barr Virus Infections/physiopathology , Herpesvirus 4, Human/genetics , Immunocompetence , Infectious Encephalitis/physiopathology , Meningitis/physiopathology , Adult , Aged , Coinfection , Cytomegalovirus Infections/cerebrospinal fluid , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/physiopathology , Encephalitis, Herpes Simplex/cerebrospinal fluid , Encephalitis, Herpes Simplex/complications , Encephalitis, Herpes Simplex/physiopathology , Encephalitis, Viral/cerebrospinal fluid , Encephalitis, Viral/complications , Encephalitis, Viral/physiopathology , Enterococcus faecalis , Epstein-Barr Virus Infections/cerebrospinal fluid , Epstein-Barr Virus Infections/complications , Female , Gram-Positive Bacterial Infections/cerebrospinal fluid , Gram-Positive Bacterial Infections/complications , Gram-Positive Bacterial Infections/physiopathology , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/complications , Guillain-Barre Syndrome/physiopathology , Humans , Infectious Encephalitis/cerebrospinal fluid , Infectious Encephalitis/complications , Infectious Encephalitis/microbiology , Intensive Care Units , Intracranial Hypotension/cerebrospinal fluid , Intracranial Hypotension/complications , Intracranial Hypotension/physiopathology , Male , Meningitis/cerebrospinal fluid , Meningitis/complications , Meningitis/microbiology , Meningitis, Pneumococcal/cerebrospinal fluid , Meningitis, Pneumococcal/complications , Meningitis, Pneumococcal/physiopathology , Meningitis, Viral/cerebrospinal fluid , Meningitis, Viral/complications , Meningitis, Viral/physiopathology , Middle Aged , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/complications , Optic Neuritis/physiopathology , Streptococcal Infections/cerebrospinal fluid , Streptococcal Infections/complications , Streptococcal Infections/physiopathology , Streptococcus pneumoniae , Varicella Zoster Virus Infection/cerebrospinal fluid , Varicella Zoster Virus Infection/complications
7.
Mod Rheumatol Case Rep ; 4(1): 84-89, 2020 01.
Article in English | MEDLINE | ID: mdl-33086977

ABSTRACT

Optic perineuritis (OPN), which is an inflammatory disorder affecting the optic nerve sheath, is one of the rare complications in granulomatosis with polyangiitis (GPA). Although several groups have reported that immunosuppressive therapies are generally effective against GPA-associated OPN, so far, there is little information as to other options for refractory cases. Here we demonstrate a case of GPA-associated OPN, which is refractory to potent immunosuppressive therapy including high-dose glucocorticoid, intravenous cyclophosphamide and rituximab therapy, and effective application of therapeutic plasma exchange. We also report here that CSF IL-6 levels may serve as a new biomarker for GPA-associated OPN.


Subject(s)
Granulomatosis with Polyangiitis/complications , Immunosuppressive Agents/administration & dosage , Optic Neuritis/etiology , Optic Neuritis/therapy , Plasma Exchange , Biomarkers , Combined Modality Therapy , Granulomatosis with Polyangiitis/cerebrospinal fluid , Humans , Interleukin-6/cerebrospinal fluid , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/diagnosis , Plasma Exchange/methods , Recurrence , Treatment Outcome
8.
Mult Scler Relat Disord ; 41: 102005, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32114369

ABSTRACT

BACKGROUND: Patients with anti-aquaporin-4 (AQP4) water channel antibody-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein (MOG) associated disease (MOGAD) often present with similar clinical symptoms, and some cases are hard to differentiate at the time of onset. In this study, we compared the clinical characteristics, cerebrospinal fluid (CSF) analysis parameters, and peripheral T/B lymphocyte subsets during the active and chronic phases in AQP4-NMOSD and MOGAD. METHODS: A total of 17 MOGAD cases and 24 AQP4-NMOSD cases were studied. The clinical characteristics in both groups were summarized, including disease duration, total number of attacks, lesions, prevention of relapse during remission, and CSF analysis results during the active phase. T/B lymphocyte subsets were further investigated in the active and chronic phases. RESULTS: In the comparative study on clinical symptoms, a large proportion of optic neuritis was unilateral in MOGAD. In the comparative study on CSF analysis, protein level was significantly lower in MOGAD compared with AQP4-NMOSD (p = 0.006); myelin basic protein was significantly lower in MOGAD compared with AQP4-NMOSD (p = 0.04); albumin quotient was significantly lower in MOGAD compared with AQP4-NMOSD (p = 0.02); and IgG Quotient was significantly lower in MOGAD compared with AQP4-NMOSD (p = 0.05). In the analysis of T/B lymphocyte subsets, plasmablasts of the B cell subset in the active phase were significantly lower in MOGAD (2.1 ± 2.4) compared to AQP4-NMOSD (7.8 ± 7.2) (p < 0.05). In the chronic phase, transitional B cells were significantly higher in MOGAD (2.1 ± 1.8) compared to AQP4-NMOSD (0.6 ± 0.4) (p < 0.01). CONCLUSION: Clinical characteristics of MOGAD were similar to those of AQP4-NMOSD, but increased blood brain barrier permeability was suggested to be less severe in MOGAD compared to AQP4-NMOSD from CSF analysis. Furthermore, the pathogenesis of the two diseases was clearly distinct as plasmablasts in the active phase were not elevated in MOGAD, but were increased in AQP4-NMOSD.


Subject(s)
Aquaporin 4/immunology , B-Lymphocyte Subsets , Blood-Brain Barrier/physiopathology , Demyelinating Autoimmune Diseases, CNS , Myelin-Oligodendrocyte Glycoprotein/immunology , Optic Neuritis , T-Lymphocyte Subsets , Adult , Demyelinating Autoimmune Diseases, CNS/blood , Demyelinating Autoimmune Diseases, CNS/cerebrospinal fluid , Demyelinating Autoimmune Diseases, CNS/immunology , Demyelinating Autoimmune Diseases, CNS/physiopathology , Female , Humans , Male , Middle Aged , Neuromyelitis Optica/blood , Neuromyelitis Optica/cerebrospinal fluid , Neuromyelitis Optica/immunology , Neuromyelitis Optica/physiopathology , Optic Neuritis/blood , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/immunology , Optic Neuritis/physiopathology
9.
Dis Markers ; 2019: 9320791, 2019.
Article in English | MEDLINE | ID: mdl-31583031

ABSTRACT

BACKGROUND: Multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the central nervous system, typically features immune-mediated focal demyelination and secondary axonal degeneration. Cerebral hypoperfusion of the normal-appearing white matter (NAWM) has been reported in MS patients and may be mediated by elevated levels of endothelin-1 (ET-1), a most potent vasoconstrictive peptide released from reactive astrocytes in MS focal lesions. Optic neuritis (ON) is one of the most frequent manifestations of MS and also shows peripapillary vascular hypoperfusion in combination with disc swelling. AIMS: We aimed to compare serum and cerebrospinal fluid (CSF) levels of ET-1 as a potential prognostic marker of MS-ON in two groups of patients differing for severity of MS-ON clinical presentation. MATERIALS AND METHODS: A cross-sectional study to compare serum and CSF levels of ET-1 between patients with clinically aggressive MS-ON (A-MS-ON) and nonaggressive MS-ON (NA-MS-ON) according to conventional ophthalmological criteria, including optical coherence tomography. CSF and serum concentrations of ET-1 were measured using a commercially available ELISA method. RESULTS: Sixteen patients consecutively referred to the Units of Neurology for visual disturbances attributable to MS were recruited, 11 (69%) patients with A-MS-ON and 5 (31%) with NA-MS-ON. Median CSF ET-1 levels and CSF/serum ET-1 quotient were significantly higher in patients with A-MS-ON (0.30 vs. 0.56 ng/ml) as compared to NA-MS-ON (0.16 vs. 0.16). CONCLUSIONS: Severity and failure in the recovery from ON in MS patients may depend from vascular hypoperfusion of the optic nerve induced by high intrathecally produced ET-1, a potential prognostic marker of ON recovery in MS. The detection of CSF ET-1 levels may allow identifying groups of ON patients potentially benefitting from treatment with ET-1 antagonists (e.g., bosentan).


Subject(s)
Endothelin-1/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Optic Nerve/metabolism , Optic Neuritis/cerebrospinal fluid , Adult , Astrocytes/metabolism , Astrocytes/pathology , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Cross-Sectional Studies , Endothelin-1/blood , Female , Humans , Male , Middle Aged , Multiple Sclerosis/blood , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/physiopathology , Optic Nerve/diagnostic imaging , Optic Neuritis/blood , Optic Neuritis/diagnostic imaging , Optic Neuritis/physiopathology , Severity of Illness Index , Tomography, Optical Coherence , White Matter/diagnostic imaging , White Matter/metabolism
10.
Mult Scler Relat Disord ; 34: 14-16, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31226544

ABSTRACT

A subset of patients with neuromyelitis optica spectrum disorders are positive for myelin-oligodendrocyte glycoprotein (MOG) antibodies. These patients present with distinct clinical demyelinating syndrome often confused for multiple sclerosis. We describe the case of a patient who initially presented with 10-day history of right-sided retro-orbital headache worse with lateral gaze, photophobia, and subjective decreased visual acuity. After successful treatment on a steroid regimen, this patient represented two weeks following discharge with seizure and was found to have unilateral meningeal T2-FLAIR MRI hyperintensity with associated cortical swelling, a rare finding. CSF studies showed negative anti-AQP4 antibodies and positive anti-MOG antibodies. This case demonstrates that patients presenting with symptoms concerning for NMOSD who are AQP4-Ab-negative should be tested for anti-MOG antibodies for optimized disease management and important prognostic implications.


Subject(s)
Encephalitis/diagnostic imaging , Encephalitis/immunology , Meninges/diagnostic imaging , Myelin-Oligodendrocyte Glycoprotein/antagonists & inhibitors , Optic Neuritis/diagnostic imaging , Optic Neuritis/immunology , Autoantibodies/cerebrospinal fluid , Encephalitis/cerebrospinal fluid , Encephalitis/drug therapy , Humans , Magnetic Resonance Imaging , Male , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/drug therapy , Prognosis , Steroids/therapeutic use , Young Adult
11.
Mult Scler ; 25(11): 1488-1495, 2019 10.
Article in English | MEDLINE | ID: mdl-30043667

ABSTRACT

OBJECTIVES: To evaluate the validity of the revised 2017 McDonald criteria for multiple sclerosis (MS) compared with the 2010 McDonald criteria to predict conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS). METHODS: A total of 163 patients from seven referral hospitals in Korea, who experienced a first clinical event suggestive of MS between 2006 and 2017, were enrolled. Patients were stratified into two groups according to outcome at the last visit: CDMS converters who experienced a second clinical event and non-converters. RESULTS: Of the 163 patients with a mean follow-up of 63 months, 60% converted to CDMS. The sensitivity, specificity, positive and negative predictive values and accuracy were, respectively, 88.8%, 43.1%, 70.2%, 71.8% and 70.6% for the 2017 McDonald criteria and 53.1%, 69.2%, 72.2%, 49.5% and 59.5% for the 2010 McDonald criteria. After exclusion of 82 patients who received disease-modifying agents before the second attack, the specificity of the 2017 and 2010 McDonald criteria increased to 85.0% and 95.0%, but sensitivity decreased to 83.6% and 47.5%, respectively. CONCLUSION: The 2017 McDonald criteria afforded higher sensitivity and accuracy but lower specificity compared with the 2010 McDonald criteria for prediction of conversion to CDMS in Korean CIS patients.


Subject(s)
Demyelinating Diseases/diagnostic imaging , Multiple Sclerosis/diagnosis , Adolescent , Adult , Crotonates/therapeutic use , Demyelinating Diseases/cerebrospinal fluid , Demyelinating Diseases/drug therapy , Disease Progression , Female , Fingolimod Hydrochloride/therapeutic use , Glatiramer Acetate/therapeutic use , Humans , Hydroxybutyrates , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Interferon-beta/therapeutic use , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/diagnostic imaging , Nitriles , Oligoclonal Bands/cerebrospinal fluid , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/diagnostic imaging , Quinolones/therapeutic use , Reproducibility of Results , Republic of Korea , Sensitivity and Specificity , Time Factors , Toluidines/therapeutic use , Young Adult
12.
BMJ Case Rep ; 11(1)2018 Dec 22.
Article in English | MEDLINE | ID: mdl-30580292

ABSTRACT

A 49-year-old Caucasian woman presented with subacute headache and right eye pain associated with scotoma, blurred vision and photophobia. MRI was suggestive of optic neuritis of the right optic nerve and she was treated with steroids. Due to persistent symptoms, a lumbar puncture was performed and cerebrospinal fluid analysis was positive for venereal disease research laboratory and rapid plasma reagin titres. On further history, she recalled experiencing an illness associated with diffuse rash, likely secondary syphilis, 1-2 months prior. She tested negative for HIV. She was treated with intravenous penicillin for 2 weeks following which she experienced improvement in symptoms.


Subject(s)
Eye Pain/microbiology , Headache/microbiology , Optic Neuritis/microbiology , Scotoma/microbiology , Syphilis/complications , Acute Disease , Cerebrospinal Fluid/microbiology , Eye Pain/cerebrospinal fluid , Eye Pain/diagnosis , Female , Headache/cerebrospinal fluid , Headache/diagnosis , Humans , Middle Aged , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/diagnosis , Scotoma/cerebrospinal fluid , Scotoma/diagnosis , Spinal Puncture , Syphilis/cerebrospinal fluid
13.
PLoS One ; 13(11): e0207726, 2018.
Article in English | MEDLINE | ID: mdl-30475854

ABSTRACT

Glucocorticoid (GC) refractory relapses in patients with multiple sclerosis (MS) or clinically isolated syndrome (CIS), who are in potential need of treatment escalation, are a key challenge in routine clinical practice. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) has been shown to be an endogenous counter-regulator of GC, and potentiates autoimmune-mediated neuroinflammation. In order to evaluate whether MIF levels are elevated in the cerebrospinal fluid (CSF) of MS patients (CSF-MIF), and whether they are higher still during a GC refractory relapse, we compared CSF-MIF concentrations of CIS/MS patients with acute optic neuritis as their first inflammatory episode (ON, n = 20), CIS/MS patients with a stable disease progression/without relapse (CIS/MS w/o, n = 18), and healthy controls (HC, n = 20) using ANOVA. Mean CSF-MIF concentrations in CIS/MS w/o patients were significantly higher than in ON patients and HCs, whereas ON patients and HCs did not differ. A subgroup analysis of the ON group revealed 10 patients to be responsive to GC-treatment (GC-ON) and 10 patients refractory under GC-treatment (rGC-ON). However, mean CSF-MIF concentrations did not differ between GC-ON and rGC-ON cases. We therefore conclude that MIF is not suitable for distinguishing GC responders from non-responders in a group of patients with acute optic neuritis, but it rather mirrors the ongoing inflammation in long-term MS disease progression.


Subject(s)
Glucocorticoids/therapeutic use , Macrophage Migration-Inhibitory Factors/cerebrospinal fluid , Multiple Sclerosis/complications , Optic Neuritis/complications , Optic Neuritis/drug therapy , Adolescent , Adult , Aged , Biomarkers/cerebrospinal fluid , Female , Humans , Male , Middle Aged , Optic Neuritis/cerebrospinal fluid , Treatment Outcome , Young Adult
14.
J Neuroimmunol ; 320: 98-100, 2018 07 15.
Article in English | MEDLINE | ID: mdl-29572032

ABSTRACT

Chloride imbalance between the serum and the cerebrospinal fluid (CSF) has been recently shown to exist in the acute phase of neuromyelitis optica (NMO). In this report, we studied the relation between the quotient of chloride (QCl) and the severity of optic neuritis (ON) in NMO patients. There was a positive correlation (R = 0.67; p < 0.05) between QCl and the length of ON-lesion. The visual prognosis also showed a positive correlation with QCl in the acute phase (R = 0.58; p < 0.05). These results support the theory that chloride imbalance between serum and CSF may trigger the ON in NMO spectrum disorders.


Subject(s)
Chlorides/blood , Chlorides/cerebrospinal fluid , Neuromyelitis Optica/blood , Neuromyelitis Optica/cerebrospinal fluid , Optic Neuritis/blood , Optic Neuritis/cerebrospinal fluid , Humans , Neuromyelitis Optica/complications , Optic Neuritis/etiology , Recurrence
15.
Eur J Neurol ; 25(4): 614-618, 2018 04.
Article in English | MEDLINE | ID: mdl-29272057

ABSTRACT

BACKGROUND AND PURPOSE: Different biological and radiological biomarkers predict clinical conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS). The aim was to explore their role in predicting the outcome of patients with optic neuritis (ON), a CIS considered to have a benign prognosis. METHODS: Sixty-eight consecutive ON patients were followed prospectively. Magnetic resonance imaging (MRI) and cerebrospinal fluid studies including oligoclonal immunoglobulin G (IgG) bands (OCGBs), lipid-specific oligoclonal IgM bands (LS-OCMBs) and neurofilament light chain quantification were performed at disease onset. Conversion to clinically definite MS (CDMS) was monitored. RESULTS: The mean time of follow-up of our series was 46.4 months. Twenty-five patients (36.7%) developed CDMS during follow-up. Neurofilament light chain levels did not predict clinical conversion. By contrast, an abnormal MRI increased the risk of CDMS [hazard ratio (HR) 12.5, P = 0.013]. The clearest association was found in patients with more than three T2 lesions. OCGBs also predicted the onset of CDMS (HR 21.3, P = 0.003) and LS-OCMBs were associated with a shorter time to CDMS (HR = 116.6, P < 0.001). CONCLUSIONS: Magnetic resonance imaging and OCGBs predicted conversion to CDMS after an ON episode. In addition, LS-OCMBs identified the ON patients more likely to develop MS early. These results, applicable to the everyday clinical setting, may be of interest for therapeutic decisions.


Subject(s)
Optic Neuritis/diagnosis , Adult , Biomarkers , Cohort Studies , Disease Progression , Female , Follow-Up Studies , Humans , Immunoglobulin G/cerebrospinal fluid , Immunoglobulin M/cerebrospinal fluid , Magnetic Resonance Imaging , Male , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/diagnosis , Multiple Sclerosis/diagnostic imaging , Neurofilament Proteins/cerebrospinal fluid , Oligoclonal Bands , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/diagnostic imaging , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment , Treatment Outcome
16.
J Craniofac Surg ; 28(6): 1563-1564, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28749847

ABSTRACT

Optic neuritis is a common inflammatory disease of the optic nerve. And the cerebral spinal fluid (CSF) in the subarachnoid space of optic nerve is thought to be homogeneous as in spine. We report a case of optic neuritis, some unexpected opaque fluid observed to flow out from the optic canal during the optic canal decompression surgery when the CSF in spine is normal. One day after the surgery, the visual acuity of the patient improved dramatically to 0.4 from 0.05. This report highlights the possible restrictive pathological changes of the CSF in the optic nerve of acute optic neuritis, which may be the reason of the dysfunction of the optic nerve.


Subject(s)
Decompression, Surgical , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/surgery , Subarachnoid Space/surgery , Visual Acuity/physiology , Humans
17.
Brain Behav ; 7(1): e00584, 2017 01.
Article in English | MEDLINE | ID: mdl-28127508

ABSTRACT

INTRODUCTION: Previous studies have shown that serum uric acid (UA) modulates outcomes of neurological diseases, although little is known about cerebrospinal fluid (CSF) UA levels in neuromyelitis optica spectrum disorders (NMOSDs). METHODS: Cerebrospinal fluid and serum UA levels were measured in samples from 68 patients, including NMOSDs during relapse (n = 38) and controls with noninflammatory and non-neurodegenerative diseases (CTLs, n = 30). Correlation analysis was performed between CSF UA and clinical characteristics, serum UA, and blood-brain barrier integrity in NMOSDs. RESULTS: Cerebrospinal fluid UA levels in NMOSDs were significantly higher than in CTLs (p = .002), while serum UA differences between NMOSDs and CTLs were not statistically significant. In NMOSDs, CSF UA levels were significantly higher in patients with an impaired blood-brain barrier than in patients with an intact one (p < .001), and significantly higher in longer disease duration than in shorter disease duration patients (p = .002). CSF UA levels were also significantly higher in active patients upon MRI than in inactive patients (p < .001), and significantly higher in patients with brain lesions than without brain lesions (p = .024). CSF UA was significantly associated with the serum UA levels (r = .454, p = .002), disease duration (r = .383, p = .018), and blood-brain barrier index (r = .805, p < .001), but did not correlate with age, gender, annualized relapse rate, duration, or severity of NMOSD. Multiple regression analysis demonstrated that CSF UA was independent of the blood-brain barrier index (ß = .765, p < .001) and serum UA levels (ß = .01, p = .019) in NMOSDs. CONCLUSIONS: Cerebrospinal fluid UA levels were elevated in NMOSD patients during relapse, and were likely modified by serum UA levels and blood-brain barrier integrity.


Subject(s)
Blood-Brain Barrier , Multiple Sclerosis/cerebrospinal fluid , Neuromyelitis Optica/cerebrospinal fluid , Optic Neuritis/cerebrospinal fluid , Uric Acid/cerebrospinal fluid , Adolescent , Adult , Aged , Humans , Middle Aged , Multiple Sclerosis/blood , Neuromyelitis Optica/blood , Optic Neuritis/blood , Recurrence , Uric Acid/blood , Young Adult
18.
Zhonghua Yan Ke Za Zhi ; 52(12): 898-904, 2016 Dec 11.
Article in Chinese | MEDLINE | ID: mdl-27998453

ABSTRACT

Objective: To study the characteristics of neurosyphilis with optic neuritis as an initial finding. Methods: Retrospective analysis of clinical data and laboratory testing results of 16 cases (27 eyes) with optic neuritis as an initial finding of neurosyphilis from October 2010 to March 2015 in General Hospital of People's Liberation Army was made. Results: Six-teen patients (12 males, 4 females) were collected, the median age of patients was 47 (range 33 to 65) years ,the mean age was (49.63±9.05) years. Treponema pallidum particle agglutination assay (TPPA) analysis was positive in all of the patients and rapid plasma reagin (RPR) test was positive in 14 patients (2 patients did not test). Lumbar puncture was requested and performed for all patients. Cerebrospinal fluid (CSF) TPPA analysis was positive in 16 patients and RPR test was positive in 12 patients. The CSF white blood cell counting increased in 9 (56.3%) patients and 10(62.5%)patients presented with increased CSF protein level. Both eyes were involved in 11 patients (68.8%). Relative afferent papillary defect was positive in 11 patients. Twenty-seven eyes were affected in 16 patients, and among them 7 eyes' pupil diameter were 2.5 mm or less. Incipient visual acuity was less than 0.1 in 22 eyes. The slit lamp examination showed vitreous opacity in 12 eyes and visible cells in 6 eyes among 27 eyes. Fundus examination found that 6 eyes had papillary edema and 15 eyes had pallordisc among 27eyes. Electro-retinogram (ERG) was tested in 24 eyes, and 18 eyes were abnormal. Visual evoked potential (VEP) were performed in 26 eyes (flash VEP in 22 eyes, pattern VEP in 4 eyes), and all were abnormal. Fourteen eyes were tested by 30-2 perimetry, and 6 eyes had diffuse visual field defect, 2 eyes had peripheral visual field defect, 4 eyes had quadrant defect and 2 eyes had center scotoma. Fundus fluorescence angiography was done in 16 eyes and choroidal hyper-fluorescent dots were found in posterior pole in 4 eyes. All patients were treated with antibiotic medicines, among them 10 cases in the General Hospital, and 6 cases in the other hospitals. During 15 months follow-up after discharge, visual acuity of 17 eyes recovered to 0.5 and above. Conclusion: Syphilitic optic neuritis is a condition that manifests with severe visual loss and tends to involve both eyes, Some patients have a smaller pupil diameter. Due to the particular infective routes of the disease, patients often conceal their sexual history. The manifestations of ocular syphilis are complicated and easy to misdiagnose or undiagnose. Clinical manifestations combining with the detailed history taking, serum and cerebrospinal fluid examination can guide to an accurate diagnosis and prevent from permanent vision loss. (Chin J Ophthalmol, 2016, 52: 898-904).


Subject(s)
Eye Infections, Bacterial/diagnosis , Neurosyphilis/diagnosis , Optic Neuritis/diagnostic imaging , Treponema pallidum/isolation & purification , Adult , Aged , Diagnostic Errors , Evoked Potentials, Visual/physiology , Eye Infections, Bacterial/microbiology , Female , Fluorescein Angiography , Fluorescent Treponemal Antibody-Absorption Test , Fundus Oculi , Humans , Male , Middle Aged , Neurosyphilis/complications , Optic Neuritis/cerebrospinal fluid , Retrospective Studies , Scotoma , Treponema pallidum/immunology , Visual Acuity
19.
Eur J Neurol ; 23(5): 898-905, 2016 May.
Article in English | MEDLINE | ID: mdl-26872061

ABSTRACT

BACKGROUND AND PURPOSE: The role of chitinases and chitinase-like proteins in multiple sclerosis (MS) is currently unknown; however, cerebrospinal fluid (CSF) levels of chitinase 3-like 1 (CHI3L1) predict prognosis in early MS. Whether this applies to other chitinases and chitinase-like proteins is yet to be established. Our objective was to investigate the potential of chitinase 3-like 2 (CHI3L2) and chitotriosidase as prognostic biomarkers in optic neuritis (ON) as the first demyelinating episode and to evaluate the ability of CHI3L2 to predict long-term MS risk and disability. METHODS: In a prospective cohort of 73 patients with ON as a first demyelinating episode and 26 age-matched healthy controls levels of CHI3L2 and chitotriosidase in CSF were explored by enzyme-linked immunosorbent assay. Associations with magnetic resonance imaging white matter lesions, CSF oligoclonal bands, immunoglobulin G index and leukocyte count were investigated. Long-term MS risk and disability (Expanded Disability Status Scale, Multiple Sclerosis Functional Composite components) were examined in a retrospective cohort of 78 patients with ON as the first demyelinating episode (mean follow-up 14 years). The predictive ability of CHI3L2 was compared with CHI3L1. RESULTS: Cerebrospinal fluid levels of CHI3L2 and chitotriosidase were significantly elevated in patients with ON and were associated with MS risk measures. CHI3L2 levels predicted MS development after ON (hazard ratio 1.95, P = 0.00039, Cox regression) and cognitive impairment by the Paced Auditory Serial Addition Test (P = 0.0357, linear regression) at follow-up. In a multivariate analysis of MS risk, CHI3L2 performed better than CHI3L1. CONCLUSIONS: CHI3L2 and chitotriosidase are promising biomarkers in patients with a first demyelinating episode. Our findings thus support a role for these proteins as biomarkers in early MS.


Subject(s)
Brain/diagnostic imaging , Chitinases/cerebrospinal fluid , Hexosaminidases/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Optic Neuritis/cerebrospinal fluid , Adolescent , Adult , Biomarkers/cerebrospinal fluid , Disabled Persons , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis/diagnostic imaging , Optic Neuritis/diagnostic imaging , Prognosis , Prospective Studies , Retrospective Studies , Young Adult
20.
Mult Scler ; 22(5): 590-8, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26283696

ABSTRACT

BACKGROUND: Optic neuritis is a good model for multiple sclerosis relapse, but currently no tests can accurately predict visual outcome. OBJECTIVE: The purpose of this study was to examine whether cerebrospinal fluid (CSF) biomarkers of tissue damage and remodelling (neurofilament light chain (NF-L), myelin basic protein, osteopontin and chitinase-3-like-1) predict visual outcome after optic neuritis. METHODS: We included 47 patients with optic neuritis as a first demyelinating episode. Patients underwent visual tests, optical coherence tomography (OCT), magnetic resonance imaging (MRI) and lumbar puncture. Biomarkers were measured in CSF by enzyme-linked immunosorbent assay (ELISA). Patients were followed up six months after onset and this included visual tests and OCT. Outcome measures were inter-ocular differences in low contrast visual acuity (LCVA), retinal nerve fibre layer (RNFL) and ganglion cell layer+inner plexiform layer (GC-IPL) thicknesses. RESULTS: CSF NF-L levels at onset predicted inter-ocular differences in follow-up LCVA (ß=13.8, p=0.0008), RNFL (ß=5.6, p=0.0004) and GC-IPL (ß=4.0, p=0.0008). The acute-phase GC-IPL thickness also predicted follow-up LCVA (ß=12.9, p=0.0021 for NF-L, ß=-1.1, p=0.0150 for GC-IPL). Complete/incomplete remission was determined based on LCVA from 30 healthy controls. NF-L had a positive predictive value of 91% and an area under the curve (AUC) of 0.79 for incomplete remission. CONCLUSION: CSF NF-L is a promising biomarker of visual outcome after optic neuritis. This could aid neuroprotective/regenerative medical advancements.


Subject(s)
Intermediate Filaments/metabolism , Multiple Sclerosis/cerebrospinal fluid , Nerve Fibers/metabolism , Optic Neuritis/cerebrospinal fluid , Optic Neuritis/pathology , Retina/pathology , Adult , Axons/pathology , Female , Humans , Male , Middle Aged , Multiple Sclerosis/pathology , Nerve Fibers/pathology , Retinal Ganglion Cells/cytology , Tomography, Optical Coherence/methods , Visual Acuity/physiology
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