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1.
Neurol Neuroimmunol Neuroinflamm ; 11(1): e200188, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38134369

RESUMO

BACKGROUND AND OBJECTIVES: Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) serum levels are useful to define disease activity in different neurologic conditions. These biomarkers are increased in patients with aquaporin-4 antibody-positive NMOSD (AQP4+NMOSD) during clinical attacks suggesting a concomitant axonal and glial damage. However, there are contradictory results in double seronegative NMOSD (DS-NMOSD). The aim of this study was to characterize the neuronal, axonal, and glial damage of DS-NMOSD in comparison with AQP4+NMOSD. METHODS: Patients with DS-NMOSD (i.e., for AQP4 and myelin oligodendrocyte glycoprotein antibodies-MOG-Abs) and age-matched AQP4+NMOSD diagnosed according to the latest diagnostic criteria and with available serum samples obtained within 3 months from onset/relapse were retrospectively enrolled from 14 international centers. Clinical and radiologic data were collected. Serum NfL, GFAP, tau, and UCH-L1 levels were determined using an ultrasensitive paramagnetic bead-based ELISA (SIMOA). Statistical analysis was performed using nonparametric tests and receiver-operating characteristic (ROC) curve analysis. RESULTS: We included 25 patients with AQP4+NMOSD and 26 with DS-NMOSD. The median age at disease onset (p = 0.611) and female sex predominance (p = 0.072) were similar in the 2 groups. The most common syndromes at sampling in both AQP4+NMOSD and DS-NMOSD were myelitis (56% vs 38.5%) and optic neuritis (34.6% vs 32%), with no statistical differences (p = 0.716). Median EDSS at sampling was 3.2 (interquartile range [IQR] 2-7.7) in the AQP4+NMOSD group and 4 (IQR [3-6]) in the DS-NMOSD group (p = 0.974). Serum GFAP, tau, and UCH-L1 levels were higher in patients with AQP4+NMOSD compared with those with DS-NMOSD (median 308.3 vs 103.4 pg/mL p = 0.001; median 1.2 vs 0.5 pg/mL, p = 0.001; and median 61.4 vs 35 pg/mL, p = 0.006, respectively). The ROC curve analysis showed that GFAP, tau, and UCH-L1, but not NfL, values were able to discriminate between AQP4+ and DS-NMOSD (area under the curve (AUC) tau: 0.782, p = 0.001, AUC GFAP: 0.762, p = 0.001, AUC UCH-L1: 0.723, p = 0.006). NfL levels were associated with EDSS at nadir only in patients with AQP4+NMOSD. DISCUSSION: Serum GFAP, tau, and UCH-L1 levels discriminate between AQP4+NMOSD and DS-NMOSD. The different biomarker profile of AQP4+NMOSD vs DS-NMOSD suggests heterogeneity of diseases within the latter category and provides useful data to improve our understanding of this disease.


Assuntos
Neuromielite Óptica , Humanos , Feminino , Lactente , Neuromielite Óptica/diagnóstico , Aquaporina 4 , Estudos Retrospectivos , Glicoproteína Mielina-Oligodendrócito , Biomarcadores
2.
Ocul Immunol Inflamm ; 31(5): 1068-1072, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35522251

RESUMO

PURPOSE: To report an atypical case of MOG antibody-associated optic neuritis with Roth spots and widespread retinal hemorrhages. CASE REPORT: A 49-year-old woman complained of 1 week history painful visual loss in the left eye. Funduscopy exam showed a severe optic disc edema associated with multiple peripapillar hemorrhages, peripheral retinal hemorrhages and Roth spots in the left eye. Orbit MRI revealed an hyperintensity in the left optic nerve, enhanced with gadolinium. The serum Myelin Oligodendrocyte (MOG) antibodies was found positive. Early intravenous high dose of steroids rapidly improved visual acuity and fundus abnormalities rapidly resolved. CONCLUSION: Retinal hemorrhages can also be detected in case of optic disc edema associated with an optic neuritis, as seen in MOGAD.


Assuntos
Neurite Óptica , Papiledema , Humanos , Autoanticorpos , Fundo de Olho , Glicoproteína Mielina-Oligodendrócito/uso terapêutico , Neurite Óptica/diagnóstico , Neurite Óptica/tratamento farmacológico , Papiledema/diagnóstico , Papiledema/tratamento farmacológico , Papiledema/etiologia , Hemorragia Retiniana , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade
3.
Insights Imaging ; 12(1): 151, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674050

RESUMO

OBJECTIVE: To evaluate the 3D Fast Gray Acquisition T1 Inversion Recovery (FGATIR) sequence for MRI identification of brainstem tracts and nuclei damage in multiple sclerosis (MS) patients. METHODS: From april to december 2020, 10 healthy volunteers and 50 patients with remitted-relapsing MS (58% female, mean age 36) underwent MR imaging in the Neuro-imaging department of the C.H.N.O. des Quinze-Vingts, Paris, France. MRI was achieved on a 3 T system (MAGNETOM Skyra) using a 64-channel coil. 3D FGATIR sequence was first performed on healthy volunteers to classify macroscopically identifiable brainstem structures. Then, FGATIR was assessed in MS patients to locate brainstem lesions detected with Proton Density/T2w (PD/T2w) sequence. RESULTS: In healthy volunteers, FGATIR allowed a precise visualization of tracts and nuclei according to their myelin density. Including FGATIR in MR follow-up of MS patients helped to identify structures frequently involved in the inflammatory process. Most damaged tracts were the superior cerebellar peduncle and the transverse fibers of the pons. Most frequently affected nuclei were the vestibular nuclei, the trigeminal tract, the facial nerve and the solitary tract. CONCLUSION: Combination of FGATIR and PD/T2w sequences opened prospects to define MS elective injury in brainstem tracts and nuclei, with particular lesion features suggesting variations of the inflammatory process within brainstem structures. In a further study, hypersignal quantification and microstructure information should be evaluated using relaxometry and diffusion tractography. Technical improvements would bring novel parameters to train an artificial neural network for accurate automated labeling of MS lesions within the brainstem.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33975914

RESUMO

OBJECTIVE: Based on animal models and human studies, there is now strong suspicion that host/microbiota mutualism in the context of gut microbial dysbiosis could influence immunity and multiple sclerosis (MS) evolution. Our goal was to seek evidence of deregulated microbiota-induced systemic immune responses in patients with MS. METHODS: We investigated gut and systemic commensal-specific antibody responses in healthy controls (n = 32), patients with relapsing-remitting MS (n = 30), and individuals with clinically isolated syndromes (CISs) (n = 15). Gut microbiota composition and diversity were compared between controls and patients by analysis of 16S ribosomal ribonucleic acid (rRNA) sequencing. Autologous microbiota and cultivable bacterial strains were used in bacterial flow cytometry assays to quantify autologous serum IgG and secretory IgA responses to microbiota. IgG-bound bacteria were sorted by flow cytometry and identified using 16S rRNA sequencing. RESULTS: We show that commensal-specific gut IgA responses are drastically reduced in patients with severe MS, disease severity being correlated with the IgA-coated fecal microbiota fraction (r = -0.647, p < 0.0001). At the same time, IgA-unbound bacteria elicit qualitatively broad and quantitatively increased serum IgG responses in patients with MS and CIS compared with controls (4.1% and 2.5% vs 1.9%, respectively, p < 0.001). CONCLUSIONS: Gut and systemic microbiota/immune homeostasis are perturbed in MS. Our results argue that defective IgA responses in MS are linked to a breakdown of systemic tolerance to gut microbiota leading to an enhanced triggering of systemic IgG immunity against gut commensals occurring early in MS.


Assuntos
Microbioma Gastrointestinal/imunologia , Homeostase/imunologia , Microbiota/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/microbiologia , Adolescente , Adulto , Feminino , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/microbiologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Gravidade do Paciente , RNA Ribossômico 16S , Adulto Jovem
5.
Eur J Neurol ; 28(5): 1659-1664, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33528851

RESUMO

BACKGROUND AND OBJECTIVE: The prognosis in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a matter of debate. Our aim was to assess the long-term outcomes of patients with MOGAD. METHODS: We retrospectively analysed the clinical and paraclinical data of patients from the French nationwide observatory study NOMADMUS who tested positive for MOG antibodies (MOG-IgG) and who had clinical follow-up of at least 8 years from their first episode. RESULTS: Sixty-one patients (median [range] age at onset 27 [3-69] years), with a median (mean; range) follow-up of 177 (212.8; 98-657) months, were included. Among 58 patients with a relapsing course, 26.3% relapsed in the first year after onset. Of the 61 patients, 90.2% experienced at least one episode of optic neuritis. At last visit, the median (mean; range) Expanded Disability Status Scale (EDSS) score was 1 (2.12; 0-7.5), 12.5% had an EDSS score ≥6 and 37.5% had an EDSS score ≥3. Of 51 patients with final visual acuity (VA) data available, 15.7% had VA ≤0.1 in at least one eye and 25.5% had VA ≤0.5 in at least one eye. Bilateral blindness (VA ≤0.1) was present in 5.9% of patients. Finally, 12.5% of patients presented bladder dysfunction requiring long-term urinary catheterization. No factor associated significantly with a final EDSS score ≥3 or with final VA ≤0.1 was found. CONCLUSION: Overall long-term favourable outcomes were achieved in a majority of our patients, but severe impairment, in particular visual damage, was not uncommon.


Assuntos
Aquaporina 4 , Neurite Óptica , Autoanticorpos , Estudos de Coortes , Humanos , Glicoproteína Mielina-Oligodendrócito , Estudos Retrospectivos
6.
Pract Neurol ; 18(2): 159-161, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29208730

RESUMO

IgG4-related disease is now recognised as an important cause of intracranial and spinal hypertrophic pachymeningitis. Treatment with corticosteroids generally leads to significant clinical improvement. We present two cases of IgG4 pachymeningitis unresponsive to corticosteroids who improved with rituximab.


Assuntos
Imunoglobulina G , Fatores Imunológicos/uso terapêutico , Meningite/tratamento farmacológico , Rituximab/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Meningite/imunologia , Pessoa de Meia-Idade , Recidiva
8.
J Neurol ; 263(5): 883-887, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26964539

RESUMO

Optic neuritis could lead to severe visual impairment despite corticosteroids. Our aim was to evaluate the rate of visual improvement in patients treated with plasma exchange (PLEX) for severe steroid unresponsive optic neuritis and to identify predictive factors of outcome. Thirty-four patients (41 optic nerves damaged) with remaining visual acuity of 0.1 or less despite steroid pulse therapy were treated with PLEX from September 2010 to May 2015. Demographic and clinical neuro-ophthalmic findings, and spectral domain-optical coherence tomography data before PLEX treatment were analyzed. The mean symptom duration before PLEX was 34.6 days (median 28 days; range 6-92 days). After PLEX, the median final visual acuity was 0.8 and in 56 % of cases, final acuity was 0.5 or better. Past history of ipsilateral optic neuritis was associated significantly with poor outcome defined as final acuity less than 0.5. No significant difference in the visual outcome after PLEX was found between multiple sclerosis and neuromyelitis optica. In conclusion, this observational study showed that PLEX as second-line therapy led to a functionally important visual recovery in more than half patients with severe optic neuritis.


Assuntos
Neurite Óptica/terapia , Troca Plasmática , Adolescente , Adulto , Resistência a Medicamentos , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Neurite Óptica/diagnóstico , Neurite Óptica/fisiopatologia , Prognóstico , Estudos Retrospectivos , Esteroides/uso terapêutico , Resultado do Tratamento , Acuidade Visual , Adulto Jovem
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