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1.
J Neurol ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39249105

RESUMEN

BACKGROUND: Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS) and myelin-oligodendrocyte-glycoprotein IgG-associated disease (MOGAD). This study evaluated the applicability of optical coherence tomography (OCT) for differentiating between both diseases in two independent cohorts. METHODS: One hundred sixty two patients from seven sites underwent standard OCT and high-contrast visual acuity (HCVA) testing at least 6 months after first ON. Of these, 100 patients (32 MOGAD, 68 MS) comprised the primary investigational cohort, while 62 patients (31 MOGAD, 31 MS) formed a validation cohort. A composite score distinguishing between MOGAD and MS was developed using multivariate logistic regression. RESULTS: Bilateral simultaneous ON occurred more frequently in MOGAD compared to MS (46.9 vs. 11.8%, p < 0.001). OCT revealed more peripapillary retinal nerve fiber layer (pRNFL) atrophy in all segments in MOGAD compared to predominantly temporal pRNFL atrophy in MS (p < 0.001). HCVA was better preserved in MS (p = 0.007). pRNFL thickness in all except for temporal segments was suitable for differentiating MOGAD and MS. Simultaneous bilateral ON and critical atrophy in nasal (< 58.5 µm) and temporal superior (< 105.5 µm) segments were included into the composite score as three independent predictors for MOGAD. The composite score distinguished MOGAD from MS with 75% sensitivity and 90% specificity in the investigational cohort, and 68% sensitivity and 87% specificity in the validation cohort. CONCLUSION: Following a single ON-episode, MOGAD exhibits more pronounced global pRNFL atrophy and lower visual acuity after ON compared to MS. The introduced OCT-based composite score enabled differentiation between the two entities across both cohorts.

2.
Eur J Neurol ; 31(7): e16301, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38628041

RESUMEN

BACKGROUND AND PURPOSE: Cryopyrin-associated periodic syndrome is a rare autoinflammatory disease caused by gain-of-function mutations or variants in the NLRP3 gene. Clinically, patients suffer from a broad spectrum of both systemic and neurological symptoms. The aim of this study was to determine whether systemic inflammation demonstrated by serum amyloid A (SAA) elevation is associated with neuroinflammation assessed by optical coherence tomography (OCT). METHODS: Thirty eyes of 15 patients with NLRP3 low penetrance mutations (PwNLRP3) and 20 eyes of 10 age- and sex-matched healthy controls were examined by spectral-domain OCT as part of routine clinical care. All retinal layers and clinical features were evaluated. RESULTS: At baseline no significant retinal neuroaxonal inflammation or degeneration was observed in all measured retinal layers amongst PwNLRP3 compared with healthy controls. In a pooled analysis of all individual OCT time points a significant difference regarding the macular retinal nerve fibre layer was detected. Increased levels of SAA showed a positive association with averaged combined outer plexiform layer and outer nuclear layer volumes (ρ < 0.0001, r2 = 0.35). CONCLUSION: In cryopyrin-associated periodic syndrome increased combined outer plexiform layer and outer nuclear layer volumes are mirrored by SAA increase, an acute phase reactant indicating systemic inflammation. Our findings identify OCT as a candidate biomarker to monitor subclinical neuroinflammation and to assess disease activity in PwNLRP3.


Asunto(s)
Síndromes Periódicos Asociados a Criopirina , Proteína con Dominio Pirina 3 de la Familia NLR , Tomografía de Coherencia Óptica , Humanos , Masculino , Femenino , Síndromes Periódicos Asociados a Criopirina/diagnóstico por imagen , Síndromes Periódicos Asociados a Criopirina/genética , Adulto , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Adolescente , Adulto Joven , Niño , Persona de Mediana Edad , Proteína Amiloide A Sérica/metabolismo , Retina/diagnóstico por imagen , Retina/patología
3.
Mult Scler Relat Disord ; 67: 104175, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36126540

RESUMEN

BACKGROUND: Clinical onset of multiple sclerosis (MSpostvacc) and myelin-oligodendrocyte-glycoprotein-antibody-associated disease (MOGADpostvacc) has been reported in association with SARS-CoV-2-vaccination. There is uncertainty as to whether this is causality (denovo disease) or temporal coincidence (manifestation of a preexisting, subclinical neuroinflammation). OBJECTIVES: Comparing the clinical characteristics of MSpostvacc-patients versus patients with MS (PwMS) whose clinical onset occurred independently of vaccination (MSreference). METHODS: Consecutive patients with clinical onset ≤30 days after SARS-CoV-2-vaccination were included. Clinical data, cerebrospinal fluid (CSF) parameters and magnetic resonance imaging (MRI) as well as optical coherence tomography (OCT) data were compared to an age- and sex-matched MSreference-cohort. RESULTS: We identified 5 MSpostvacc and 1 MOGADpostvacc patients who developed their clinical onset ≤ 30 days after SARS-CoV-2-vaccination. Clinical characteristics, CSF, MRI and OCT parameters from MSpostvacc patients were comparable to the MSreference cohort and showed evidence of preexisting subclinical CNS disease. The single case with MOGADpostvacc clearly differed from PwMS in higher CSF cell counts, remission of MRI lesions during follow-up, and absence of oligoclonal bands. CONCLUSIONS: Our case series indicates that MSpostvacc patients showed a rather typical initial manifestation in temporal association with SARS-CoV-2-vaccination and harbored preexisting subclinical neuroinflammation. This argues against the denovo development of MS in this cohort.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Enfermedades Desmielinizantes , Esclerosis Múltiple , Humanos , Autoanticuerpos , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Enfermedades Desmielinizantes/inducido químicamente , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/líquido cefalorraquídeo , SARS-CoV-2 , Vacunación/efectos adversos
4.
J Neurol ; 269(12): 6366-6376, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35869995

RESUMEN

BACKGROUND: Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MSped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGADped) in children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode. METHODS: Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls. RESULTS: Thirteen MOGADped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MSped (14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGADped compared to MSped (pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm, p < 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm3, p < 0.001). Neither other macular layers nor P100 latency differed. MOGADped developed global atrophy affecting all peripapillary segments, while MSped displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGADped). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%, p = 0.016). CONCLUSION: First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.


Asunto(s)
Esclerosis Múltiple , Neuritis Óptica , Degeneración Retiniana , Humanos , Estudios Retrospectivos , Neuritis Óptica/diagnóstico , Retina/diagnóstico por imagen , Retina/patología , Tomografía de Coherencia Óptica/métodos , Degeneración Retiniana/patología , Esclerosis Múltiple/complicaciones , Trastornos de la Visión , Atrofia/patología
5.
Eur J Neurol ; 27(11): 2217-2224, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32589804

RESUMEN

BACKGROUND AND PURPOSE: Individuals with radiologically isolated syndrome (RIS) are at increased risk of converting to multiple sclerosis (MS). Early identification of later converters is crucial for optimal treatment decisions. The purpose of this study was to assess the predictive potential of optical coherence tomography (OCT) measures in individuals with RIS regarding conversion to MS. METHODS: This prospective observational cohort study included 36 individuals with RIS and 36 healthy controls recruited from two German MS centers. All individuals received baseline OCT and clinical examination and were longitudinally followed over up to 6 years. The primary outcome measure was the conversion to MS. RESULTS: During clinical follow-up of 46 (26-58) months (median, 25%-75% interquartile range), eight individuals with RIS converted to MS. Individuals converting to MS showed a thinning of the peripapillary retinal nerve fiber layer (pRNFL) and the common ganglion cell and inner plexiform layer (GCIP) at baseline and during follow-up. Individuals with a pRNFL of 99 µm or lower or a GCIP of 1.99 mm3 or lower were at a 7.5- and 8.0-fold risk for MS conversion, respectively, compared to individuals with higher measures. After correction for other known risk factors, Cox proportional hazards regression revealed a hazard ratio of 1.08 for conversion to MS for each 1 µm decline in pRNFL. CONCLUSIONS: Reduction of the pRNFL might be a novel and independent risk factor for conversion to MS in individuals with RIS. OCT might be useful for risk stratification and therapeutic decision-making in individuals with RIS.


Asunto(s)
Enfermedades Desmielinizantes , Esclerosis Múltiple , Enfermedades Desmielinizantes/diagnóstico por imagen , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Estudios Prospectivos , Retina/diagnóstico por imagen , Tomografía de Coherencia Óptica
6.
Clin Neuroradiol ; 30(2): 229-236, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30627749

RESUMEN

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare hereditary disease presenting with distinct imaging features in middle-aged adults. This article describes the typical imaging features focusing on the longitudinal course of RVCL-S lesions. METHODS: In this study six subjects (five male, five related) with RVCL-S were retrospectively included from two university hospitals. The median age of symptom onset was 40 ± 6 years. Magnetic resonance imaging (MRI) covering baseline and a median follow-up period of 33 months was reviewed in a structured way focusing on morphology, contrast enhancement and diffusion restriction of brain lesions. RESULTS: All patients showed patchy, T2 hyperintense white matter lesions (mean number 7.7 ± 1.8) with a periventricular predominance at the frontal lobes (59%). In all subjects, rim-enhancing white matter lesions with temporary diffusion restriction were present for a mean of 5.0 ± 3.9 months. Median duration of blood brain barrier disruption was 20 months. CONCLUSION: Periventricular patchy white matter lesions in the frontal lobes as well as rim-enhancing lesions with prolonged diffusion restriction and long-lasting contrast enhancement are characteristic imaging findings in RCVL-S and can be helpful in the differential diagnosis.


Asunto(s)
Leucoencefalopatías/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Arteria Retiniana/diagnóstico por imagen , Vena Retiniana/diagnóstico por imagen , Enfermedades Vasculares/diagnóstico por imagen , Adulto , Femenino , Humanos , Leucoencefalopatías/complicaciones , Leucoencefalopatías/patología , Masculino , Persona de Mediana Edad , Arteria Retiniana/patología , Vena Retiniana/patología , Estudios Retrospectivos , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/patología
8.
Clin Immunol ; 203: 45-52, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30974290

RESUMEN

OBJECTIVE: To determine the role of the NLRP3 inflammasome by using the selective NLRP3 inhibitor MCC950 in patients with NLRP3 low penetrance variants and clinical symptoms suggestive for an autoinflammatory syndrome including central nervous system (CNS) involvement. METHODS: Nineteen symptomatic patients with low penetrance NLRP3 variants (Q703K n = 17, V198M n = 2) recruited between 2011 and 2017 were included in this monocentric study. A functional inflammasome activation assay was performed in patients in comparison to healthy controls (HC), including the determination of interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor-necrosis factor alpha (TNF-α) secretion in the presence of the NLRP3 selective small-molecule inhibitor MCC950. Detailed clinical features were assessed and anti-IL-1 treatment response was determined. RESULTS: Peripheral blood mononuclear cells (PBMC) from patients with low penetrance NLRP3 variants displayed enhanced IL-1ß levels following inflammasome activation compared to HC. Furthermore, IL-1ß release was NLRP3-dependent as it was blocked by MCC950. The production of IL-6 and TNF-α was also increased in patients with low penetrance NLRP3 variants. Clinically, they presented with a heterogenous spectrum of neurological manifestations, while cranial nerve inflammation was the most common feature. Overall inflammasome activation did not correlate with disease severity. Eight of ten treated patients responded to anti IL-1 treatment, however a complete response was only documented in four patients. CONCLUSION: PBMC of several patients with NLRP3 low penetrance variants and CNS manifestation showed increased NLRP3-specific IL-1ß release upon stimulation and elevated NLRP3-independent IL-6 and TNF-α levels as those were not suppressed by MCC950. Our data suggest that beside the possible causal involvement of the NLRP3 inflammasome additional, yet unidentified genetic or environmental factors may contribute to the multi-organ inflammation in our patients and explain the partial response to IL-1 targeting therapies.


Asunto(s)
Nervios Craneales/inmunología , Enfermedades Autoinflamatorias Hereditarias/inmunología , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Leucocitos Mononucleares/fisiología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Enfermedades del Sistema Nervioso/inmunología , Adulto , Células Cultivadas , Femenino , Estudios de Seguimiento , Furanos/farmacología , Enfermedades Autoinflamatorias Hereditarias/genética , Compuestos Heterocíclicos de 4 o más Anillos , Humanos , Indenos , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Mutación/genética , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Enfermedades del Sistema Nervioso/genética , Penetrancia , Sulfonamidas/farmacología , Sulfonas , Factor de Necrosis Tumoral alfa/metabolismo
9.
Nervenarzt ; 89(10): 1095-1105, 2018 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-30215132

RESUMEN

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are chronic inflammatory diseases of the central nervous system (CNS). They may cause inflammation in the brain, spinal cord and optic nerve. Both conditions must be differentiated from CNS manifestations of other systemic autoimmune diseases such as systemic lupus erythematosus (SLE), Sjögren's syndrome, autoinflammtory diseases and sarcoidosis, since amongst others myelitis and optic nerve inflammation may also occur in these conditions. Nevertheless, coexistence of MS or NMOSD with rheumatic disorders such as SLE or Sjögren's syndrome has also been reported especially in NMOSD. Since the therapeutic approach is different it is important to determine a clear diagnosis. In addition some drugs used in rheumatic disease such as anti-tumor necrosis factor biologics may induce inflammatory disease of the CNS and should be avoided in MS. An interdisciplinary approach between neuroimmunology and rheumatology is important for optimal care and treatment in such patients.


Asunto(s)
Alergia e Inmunología , Neurología , Reumatología , Diagnóstico Diferencial , Humanos , Enfermedades del Sistema Inmune/diagnóstico , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades Reumáticas/diagnóstico
10.
Nervenarzt ; 89(12): 1388-1399, 2018 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-30264269

RESUMEN

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation, and propose for the first time diagnostic criteria for MOG-EM.


Asunto(s)
Autoanticuerpos , Encefalomielitis , Neuromielitis Óptica , Neuritis Óptica , Acuaporina 4 , Autoanticuerpos/sangre , Encefalomielitis/sangre , Encefalomielitis/diagnóstico , Testimonio de Experto , Humanos , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuromielitis Óptica/sangre , Neuromielitis Óptica/diagnóstico
11.
J Neuroinflammation ; 15(1): 134, 2018 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-29724224

RESUMEN

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation.


Asunto(s)
Autoanticuerpos/sangre , Encefalomielitis/sangre , Encefalomielitis/diagnóstico , Inmunoglobulina G/sangre , Internacionalidad , Glicoproteína Mielina-Oligodendrócito/sangre , Animales , Biomarcadores/sangre , Humanos , Técnicas para Inmunoenzimas/métodos , Técnicas para Inmunoenzimas/tendencias
12.
Eur J Nucl Med Mol Imaging ; 45(8): 1423-1431, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29523925

RESUMEN

PURPOSE: Expression of the translocator protein (TSPO) is upregulated in activated macrophages/microglia and is considered to be a marker of neuroinflammation. We investigated the novel TSPO ligand [18F]GE-180 in patients with relapsing-remitting multiple sclerosis (RRMS) to determine the feasibility of [18F]GE-180 PET imaging in RRMS patients and to assess its ability to detect active inflammatory lesions in comparison with the current gold standard, contrast-enhanced magnetic resonance imaging (MRI). METHODS: Nineteen RRMS patients were prospectively included in this study. All patients underwent TSPO genotyping and were classified as high-affinity, medium-affinity or low-affinity binders (HAB/MAB/LAB). PET scans were performed after administration of 189 ± 12 MBq [18F]GE-180, and 60-90 min summation images were used for visual analysis and assessment of standardized uptake values (SUV). The frontal nonaffected cortex served as a pseudoreference region (PRR) for evaluation of SUV ratios (SUVR). PET data were correlated with MRI signal abnormalities, i.e. T2 hyperintensity or contrast enhancement (CE). When available, previous MRI data were used to follow the temporal evolution of individual lesions. RESULTS: Focal lesions were identified as hot spots by visual inspection. Such lesions were detected in 17 of the 19 patients and overall 89 [18F]GE-180-positive lesions were found. TSPO genotyping revealed 11 patients with HAB status, 5 with MAB status and 3 with LAB status. There were no associations between underlying binding status (HAB, MAB and LAB) and the signal intensity in either lesions (SUVR 1.87 ± 0.43, 1.95 ± 0.48 and 1.86 ± 0.80, respectively; p = 0.280) or the PRR (SUV 0.36 ± 0.03, 0.40 ± 0.06 and 0.37 ± 0.03, respectively; p = 0.990). Of the 89 [18F]GE-180-positive lesions, 70 showed CE on MRI, while the remainder presented as T2 lesions without CE. SUVR were significantly higher in lesions with CE than in those without (2.00 ± 0.53 vs. 1.60 ± 0.15; p = 0.001). Notably, of 19 [18F]GE-180-positive lesions without CE, 8 previously showed CE, indicating that [18F]GE-180 imaging may be able to detect lesional activity that is sustained beyond the blood-brain barrier breakdown. CONCLUSION: [18F]GE-180 PET can detect areas of focal macrophage/microglia activation in patients with RRMS in lesions with and without CE on MRI. Therefore, [18F]GE-180 PET imaging is a sensitive and quantitative approach to the detection of active MS lesions. It may provide information beyond contrast-enhanced MRI and is readily applicable to all patients. [18F]GE-180 PET imaging is therefore a promising new tool for the assessment of focal inflammatory activity in MS.


Asunto(s)
Carbazoles , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Tomografía de Emisión de Positrones , Receptores de GABA/metabolismo , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple , Estudios Prospectivos , Adulto Joven
13.
Nervenarzt ; 88(12): 1377-1384, 2017 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-29038883

RESUMEN

Pediatric multiple sclerosis (MS) is one of the most important acquired neurological disorders in childhood and adolescence. A timely recognition, diagnosis and treatment are of utmost importance. This article highlights the current state of knowledge on the etiology, pathogenesis, diagnosis, clinical presentation and treatment in childhood. Although the rate of progression of disability in the early years is slower in younger patients compared to adults, a disease-modifying therapy should be started once MS is diagnosed.


Asunto(s)
Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/patología , Corteza Cerebral/patología , Diagnóstico Diferencial , Predisposición Genética a la Enfermedad/genética , Cadenas HLA-DRB1/genética , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/genética , Esclerosis Múltiple/terapia , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Esclerosis Múltiple Crónica Progresiva/etiología , Esclerosis Múltiple Crónica Progresiva/genética , Examen Neurológico , Médula Espinal/patología
14.
J Neuroinflammation ; 14(1): 123, 2017 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-28645295

RESUMEN

BACKGROUND: Autoantibodies, in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (MOG), aid as biomarkers in the differential diagnosis of demyelination. Here, we report on discovery of autoantibodies against flotillin in patients with multiple sclerosis (MS). METHODS: The target antigen was identified by histo-immunoprecipitation using the patients' sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis. Correct identification was ascertained by indirect immunofluorescence and neutralization tests using the target antigens recombinantly expressed in HEK293 cells. RESULTS: Serum and CSF of the index patient produced a fine-granular IgG indirect immunofluorescence staining of the hippocampal and cerebellar molecular layers. Flotillin-1 and flotillin-2 were identified as target autoantigens. They also reacted with recombinant human flotillin-1/2 co-expressed in HEK293 cells, but not with the individual flotillins in fixed- and live-cell assays. Moreover, neutralization using flotillin-1/2, but not the single flotillins, abolished the tissue reactivity of patient serum. Screening of 521 patients, for whom anti-aquaporin-4 testing was requested and negative, revealed 8 additional patients with anti-flotillin-1/2 autoantibodies. All eight were negative for anti-MOG. Six patients ex post fulfilled the revised McDonald criteria for MS. Vice versa, screening of 538 MS sera revealed anti-flotillin-1/2 autoantibodies in eight patients. The autoantibodies were not found in a cohort of 67 patients with other neural autoantibody-associated syndromes and in 444 healthy blood donors. CONCLUSIONS: Autoantibodies against the flotillin-1/2 heterocomplex, a peripheral membrane protein that is involved in axon outgrowth and regeneration of the optic nerve, are present in 1-2% of patients with bona fide MS.


Asunto(s)
Autoanticuerpos/metabolismo , Microdominios de Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Esclerosis Múltiple/metabolismo , Adulto , Animales , Autoanticuerpos/inmunología , Femenino , Células HEK293 , Humanos , Masculino , Microdominios de Membrana/inmunología , Proteínas de la Membrana/inmunología , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Ratas , Porcinos
15.
Mult Scler Relat Disord ; 11: 43-44, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28104255

RESUMEN

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an immune-mediated disease of the central nervous system with the presence of aquaporin 4-antibodies (AQP4-abs) in most cases. We describe a patient who developed NMOSD after a yellow fever vaccination. He presented to us with an unusual painful erythema Th7-9 triggered by touch in the respective skin area due to a cervical spinal cord lesion affecting the dorsolateral parts of C6/7. To our knowledge, this is the first case of NMOSD with such a clinical presentation expanding the clinical spectrum of NMOSD. It is important to be aware of that a yellow fever vaccination can trigger NMOSD.


Asunto(s)
Eritema/etiología , Neuromielitis Óptica/etiología , Vacuna contra la Fiebre Amarilla/efectos adversos , Fiebre Amarilla/prevención & control , Tronco Encefálico/diagnóstico por imagen , Eritema/líquido cefalorraquídeo , Eritema/diagnóstico por imagen , Eritema/patología , Humanos , Masculino , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/patología , Dolor/etiología , Piel/patología , Médula Espinal/diagnóstico por imagen , Vacunación/efectos adversos , Adulto Joven
16.
J Neurol ; 264(1): 139-151, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27844165

RESUMEN

Antibodies against conformation-dependent epitopes of myelin-oligodendrocyte-glycoprotein (MOG-abs) are present in subgroups of neuromyelitis optica spectrum disorder (NMOSD), recurrent optic neuritis (rON), multiple sclerosis (MS), and anti-NMDAR encephalitis. Using optical coherence tomography (OCT) we assessed whether MOG-abs might serve as potential marker of retinal axonal degeneration. We investigated a clinically heterogeneous cohort of 13 MOG-abs-positive patients (4 MOG-abs-positive rON, 4 MOG-abs-positive adult MS, 3 MOG-abs-positive relapsing encephalomyelitis, 2 MOG-abs-positive aquaporin-4-abs-negative NMOSD). As controls, we studied 13 age, sex and ON episode(s)-matched MOG-abs and aquaporin-4-abs-negative (AQP4-abs-negative) MS patients and 13 healthy controls (HC). In addition, we investigated 19 unmatched AQP4-abs-positive MOG-abs-negative NMOSD subjects. Considering all eyes, global pRNFL [in µm, mean (SD)] was significantly reduced in MOG-abs-positive patients [72.56 (22.71)] compared to MOG-abs-negative MS [80.81 (13.55), p = 0.0128], HCs [103.54 (8.529), p = 0.0014] and NMOSD [88.32 (18.43), p = 0.0353]. Non ON eyes from MOG-abs-positive subjects showed significant subclinical atrophy of temporal pRNFL quadrants. Microcystic macular edema (MME) was observed only in eyes of MOG-abs-positive (24%) and AQP4-abs-positive NMOSD (5.6%), but not in MOG-abs-negative MS or HC (p < 0.01). MOG-abs may serve as potential marker of retinal degeneration. Specifically, MOG-abs-related OCT features predominate in temporal pRNFL quadrants (resembling the MS retinal pattern), might be more severe than AQP4-abs-positive NMOSD, indicate subclinical pathology, and may be associated with MME.


Asunto(s)
Autoanticuerpos/sangre , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuritis Óptica/diagnóstico por imagen , Neuritis Óptica/inmunología , Retina/diagnóstico por imagen , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico por imagen , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Acuaporina 4/inmunología , Biomarcadores/metabolismo , Encefalomielitis/diagnóstico por imagen , Encefalomielitis/inmunología , Femenino , Estudios de Seguimiento , Humanos , Edema Macular/diagnóstico por imagen , Edema Macular/inmunología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/inmunología , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/inmunología , Nervio Óptico/diagnóstico por imagen , Tomografía de Coherencia Óptica
17.
Nervenarzt ; 87(6): 645-59, 2016 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-26927677

RESUMEN

With the approval of various substances for the immunotherapy of multiple sclerosis (MS), treatment possibilities have improved significantly over the last few years. Indeed, the choice of individually tailored preparations and treatment monitoring for the treating doctor is becoming increasingly more complex. This is particularly applicable for monitoring for a treatment-induced compromise of the immune system. The following article by members of the German Multiple Sclerosis Skills Network (KKNMS) and the task force "Provision Structures and Therapeutics" summarizes the practical recommendations for approved immunotherapy for mild to moderate and for (highly) active courses of MS. The focus is on elucidating the substance-specific relevance of particular laboratory parameters with regard to the mechanism of action and the side effects profile. To enable appropriate action to be taken in clinical practice, any blood work changes that can be expected, in addition to any undesirable laboratory findings and their causes and relevance, should be elucidated.


Asunto(s)
Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Monitorización Inmunológica/métodos , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/terapia , Humanos , Inmunocompetencia/efectos de los fármacos , Inmunocompetencia/inmunología , Esclerosis Múltiple/clasificación
18.
Cephalalgia ; 36(14): 1392-1396, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26848126

RESUMEN

BACKGROUND: Tolosa-Hunt syndrome (THS) is characterized by unilateral orbital pain, ipsilateral oculomotor paresis and a prompt response to treatment with corticosteroids. Several reports have demonstrated that the clinical features of THS are not specific to one causal aetiology and can lead to misdiagnosis. CASE REPORT: We report the case of a patient diagnosed with THS after an episode of unilateral orbital pain and diplopia with demonstration of granulomatous inflammation of both cavernous sinus on cerebral magnetic resonance imaging and an immediate response to treatment with corticosteroids. Progression of the disease over the following years, accompanied by increasing signs of inflammation on cerebral magnetic resonance imaging and cerebrospinal fluid pleocytosis, led to further diagnostic tests. Genetic analyses revealed a heterozygote low-penetrance mutation (Q703K) of the cryopyrin/NLRP3 gene compatible with a cryopyrin-associated periodic fever syndrome. DISCUSSION: This case report demonstrates that THS can be a central nervous system manifestation of cryopyrin-associated periodic fever syndrome, which therefore represents a differential diagnosis of THS, even in elderly patients.


Asunto(s)
Síndromes Periódicos Asociados a Criopirina/complicaciones , Síndromes Periódicos Asociados a Criopirina/diagnóstico por imagen , Fiebre/complicaciones , Fiebre/diagnóstico por imagen , Síndrome de Tolosa-Hunt/complicaciones , Síndrome de Tolosa-Hunt/diagnóstico por imagen , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana Edad , Oftalmoplejía/complicaciones , Oftalmoplejía/diagnóstico por imagen
19.
J Neuroimmune Pharmacol ; 11(1): 1-8, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26589235

RESUMEN

INTRODUCTION: Multiple sclerosis (MS) is an immune-mediated disease. Over the last decades therapeutic options have broadened tremendously. Nevertheless, various therapeutic agents, e.g., rituximab, are currently used in the treatment of MS off label. Disease or health registries are useful methods to collect information about off-label treatments. The German registry for autoimmune disease (GRAID) is a multicenter, retrospective, non-interventional database of patients with various autoimmune diseases. AIM/METHODS: The aim of this observational analysis is to present safety data of rituximab in the treatment of MS and neuromyelitis optica (NMO) in a real life clinical setting based on the available registry data. RESULTS: Data were collected nationwide in patients who received rituximab. 56 patients were treated with rituximab for MS or NMO. Average observation period was 9.6 months (SD 7.6, ranging from 6 to 29.7 months). Interval between treatments cycles differed tremendously (ranging from 0 to 21 months, median 10 months). Number of infusions ranged from 1 up to more than 8. The analysis provides experience on almost 50 patient years. Infusion related reactions were most common and reported in four patients; infections were seen in three patients (two of them were hospitalized for urinary tract infection and urosepsis). All patients recovered from infection. Full treatment response was attested in a quarter of the patients; two thirds benefited partially from treatment. DISCUSSION: Safety data of almost 50 patient years of treatment with rituximab show that rituximab is tolerated well in MS/NMO patients. Infections and infusion reactions are the most common adverse events. Our data may help the individual physician to balance efficacy of rituximab against the risk. • Data on rituximab in MS and NMO are provided for almost 50 patientyears • Rituximab was tolerated well • No unexpected side effects were seen • Almost 80% of the patients benefited at least partially from treatment.


Asunto(s)
Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Neuromielitis Óptica/tratamiento farmacológico , Rituximab/uso terapéutico , Adulto , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Resultado del Tratamiento
20.
Mult Scler ; 22(4): 533-43, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26362898

RESUMEN

OBJECTIVES: To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). METHODS: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. RESULTS: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R(2): 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited (R(2): 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. CONCLUSIONS: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.


Asunto(s)
Factores Inmunológicos/uso terapéutico , Interferon beta-1b/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Adulto , Evaluación de la Discapacidad , Progresión de la Enfermedad , Método Doble Ciego , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Factores Inmunológicos/efectos adversos , Interferon beta-1b/efectos adversos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Esclerosis Múltiple Crónica Progresiva/mortalidad , Análisis Multivariante , Factores de Tiempo , Resultado del Tratamiento
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