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OBJECTIVES: In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD. METHODS: CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured. RESULTS: CSF-C3a and CSF-C5a levels were significantly higher in MOGAD (mean ± SD, 5,629 ± 1,079 pg/mL and 2,930 ± 435.8 pg/mL) and AQP4+NMOSD (6,017 ± 3,937 pg/mL and 2,544 ± 1,231 pg/mL) than in MS (1,507 ± 1,286 pg/mL and 193.8 ± 0.53 pg/mL). CSF-C3a, CSF-C4a, and CSF-C5a did not differ between MOGAD and AQP4+NMOSD while CSF-C5b-9 (membrane attack complex, MAC) levels were significantly lower in MOGAD (17.4 ± 27.9 ng/mL) than in AQP4+NMOSD (62.5 ± 45.1 ng/mL, p = 0.0019). Patients with MOGAD with severer attacks (Expanded Disability Status Scale [EDSS] ≥ 3.5) had higher C5b-9 levels (34.0 ± 38.4 ng/m) than those with milder attacks (EDSS ≤3.0, 0.9 ± 0.7 ng/mL, p = 0.044). DISCUSSION: The complement pathway is activated in both MOGAD and AQP4+NMOSD, but MAC formation is lower in MOGAD, particularly in those with mild attacks, than in AQP4+NMOSD. These findings may have pathogenetic and therapeutic implications in MOGAD.
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Acuaporina 4 , Activación de Complemento , Inmunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/sangre , Acuaporina 4/inmunología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Glicoproteína Mielina-Oligodendrócito/inmunología , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Anciano , Complemento C5a/líquido cefalorraquídeo , Complemento C5a/metabolismo , Complemento C5a/inmunología , Adulto Joven , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Complemento C3a/metabolismo , Complemento C3a/líquido cefalorraquídeo , Complemento C3a/inmunología , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/líquido cefalorraquídeo , Complejo de Ataque a Membrana del Sistema Complemento/inmunologíaRESUMEN
Background: Recently, cases of overlapping encephalitis caused by anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been reported, and their clinical characteristics are gradually becoming clear. Acute-phase treatment typically involves the use of steroids, and although some studies have suggested that steroids can be effective, the extent of their efficacy has not yet been fully explored. Case presentation: We present the case of a 25-year-old man with anti-NMDAR and anti-MOG antibody overlapping encephalitis who showed considerable improvement after steroid treatment. To gain a deeper understanding of the efficacy of steroids in managing this condition, we conducted a literature review of cases of anti-NMDAR and anti-MOG antibody double-positive encephalitis that were treated with steroids during the acute phase. Thirteen cases were analyzed, including a new case diagnosed at our hospital. All patients showed improvement after receiving steroid treatment in the acute phase. Ten patients did not have any sequelae, and nine of them showed a rapid or major response during the acute phase. In contrast, three patients experienced sequelae (mild cognitive decline, visual impairment, and memory impairment, respectively), with their response to steroids in the acute phase being slow or limited. Relapses occurred in five patients, in one patient during steroid tapering, and in another two patients after cessation of steroids. Conclusion: Steroid therapy can be effective in the acute stage of anti-NMDAR and anti-MOG antibody overlapping encephalitis. A positive prognosis may be expected in patients who experience substantial improvement with steroid therapy during the acute phase.
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Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Esteroides , Humanos , Masculino , Adulto , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Esteroides/uso terapéutico , Resultado del Tratamiento , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis/tratamiento farmacológico , Encefalitis/inmunología , Encefalitis/diagnóstico , Receptores de N-Metil-D-Aspartato/inmunología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidoresRESUMEN
BACKGROUND: Nerve fibers related to pain and temperature sensation in the trigeminal nerve territory converge with the upper cervical spinal nerves from the level of the lower medulla oblongata to the upper cervical cord. This structure is called the trigemino-cervical complex and may cause referred pain in the territory of the trigeminal or upper cervical spinal nerves. CASE SERIES: Here, we report three cases of paroxysmal neuralgia in the occipital region with mild conjunctivitis or a few reddish spots in the ipsilateral trigeminal nerve territory. The patients exhibited gradual progression of these reddish spots evolving into vesicles over the course of several days, despite the absence of a rash in the occipital region. The patients were diagnosed with trigeminal herpes zoster and subsequently received antiherpetic therapy. Remarkably, the neuralgia in the occipital region showed gradual amelioration or complete resolution before the treatment, with no sequelae reported in the occipital region. DISCUSSION: The trigemino-cervical complex has the potential to cause neuralgia in the occipital region, as referred pain, caused by trigeminal herpes zoster. These cases suggest that, even if conjunctivitis or reddish spots appear to be trivial in the trigeminal nerve territory, trigeminal herpes zoster should be considered when neuralgia occurs in the ipsilateral occipital region.
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Herpes Zóster , Humanos , Masculino , Femenino , Herpes Zóster/complicaciones , Persona de Mediana Edad , Anciano , Neuralgia/etiología , Nervio Trigémino/fisiopatología , Neuralgia del Trigémino/etiologíaRESUMEN
White blood cell (WBC) count profiles in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are still unknown. This study evaluated the total WBC count, differential WBC counts, monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) in patients with these diseases within three months from an attack before acute treatment or relapse prevention and compared the profiles with those in matched volunteers or in multiple sclerosis (MS) patients. AQP4-NMOSD patients (n = 13) had a higher neutrophil count (p = 0.0247), monocyte count (p = 0.0359), MLR (p = 0.0004), and NLR (p = 0.0037) and lower eosinophil (p = 0.0111) and basophil (p = 0.0283) counts than those of AQP4-NMOSD-matched volunteers (n = 65). Moreover, patients with MOGAD (n = 26) had a higher overall WBC count (p = 0.0001), neutrophil count (p < 0.0001), monocyte count (p = 0.0191), MLR (p = 0.0320), and NLR (p = 0.0002) than those of MOGAD-matched volunteers (n = 130). The three demyelinating diseases showed similar levels of the total and differential WBC counts; however, MOGAD and MS showed different structures in the hierarchical clustering and distributions on a two-dimensional canonical plot using differential WBC counts from the other three groups. WBC count profiles were similar in patients with MOGAD and MS but differed from profiles in matched volunteers or patients with AQP4-NMOSD.
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Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Acuaporina 4 , Autoanticuerpos , Recuento de Leucocitos , Glicoproteína Mielina-Oligodendrócito , OligodendroglíaAsunto(s)
COVID-19 , Enfermedad de Leigh , Humanos , COVID-19/complicaciones , Vasoconstricción , SARS-CoV-2 , Síndrome , VacunaciónRESUMEN
The spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF), and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial 2-fold dilutions to determine end point titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgGSERUM, MOG-IgGCSF and the phenotypes with multivariable regression. A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgGSERUM, but two with multiple sclerosis cases were MOG-IgGCSF-positive; the specificities of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% [95% confidence interval (CI) 99-100%] and 99% (95% CI 97-100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM was associated with ON and ADEM, whereas MOG-IgGCSF was associated with ADEM and CE. The number needed to test for MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others). In terms of MOG-IgGSERUM/CSF status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG.
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Encefalitis , Inmunoglobulina G , Esclerosis Múltiple , Glicoproteína Mielina-Oligodendrócito , Mielitis , Neuromielitis Óptica , Neuritis Óptica , Humanos , Acuaporina 4 , Autoanticuerpos , Estudios Transversales , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Esclerosis Múltiple/diagnóstico , Glicoproteína Mielina-Oligodendrócito/sangre , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeoRESUMEN
BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder that often manifests after infections or vaccinations. We report two patients who developed MOGAD out of eight patients with juvenile myelomonocytic leukemia (JMML) that has never been reported. METHODS: We investigated two patients with JMML who developed MOGAD among 127 patients with leukemia from 2012 to 2021. RESULTS: Patient 1 was treated for JMML and developed fever and impaired consciousness at two years and one month of age. Magnetic resonance imaging revealed high-intensity lesions in the left frontal and left occipital white matter. The serum anti-MOG antibody test was positive, while the test was negative in the stored serum 45 days before the onset of encephalopathy. He had relapse of MOGAD after steroid therapy and plasmapheresis. Patient 2, who was treated for JMML, became apathetic and mute at three years and seven months of age. Magnetic resonance imaging revealed left frontoparietal subcortical high-intensity lesions. Anti-MOG antibody at the onset of encephalopathy was positive, while it was negative in stored serum 57 days before and 47 days after the onset. CONCLUSION: We treated two patients who developed MOGAD out of eight patients with JMML and none with MOGAD out of 119 patients with acute lymphocytic leukemia, acute myelocytic leukemia, or chronic myelocytic leukemia. The activated autoimmune process via the RAS pathway abnormality may have led to the formation of the anti-MOG antibody and the onset of MOGAD. MOGAD can occur in children with JMML, and abnormalities of the RAS pathway possibly contribute to its onset.
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Enfermedades Autoinmunes , Encefalopatías , Leucemia Mielomonocítica Juvenil , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Masculino , Leucemia Mielomonocítica Juvenil/terapia , Glicoproteína Mielina-Oligodendrócito , Fiebre , AutoanticuerposRESUMEN
Background: The autoantibody to myelin oligodendrocyte glycoprotein (MOG), a component of the central nervous system myelin, has been identified in a subset of demyelinating diseases. However, there is no convincing evidence to support the direct pathogenic contribution of this autoantibody. Objective: To elucidate the role of anti-MOG autoantibodies in human demyelinating disorders, we assessed the effect of autoantibodies on MOG-expressing cells. Methods: Mammalian cells expressing the human MOG protein reacted with human anti-MOG autoantibodies in the presence or absence of complement. Sera from 86 patients and 11 healthy sera were used. We analyzed anti-MOG antibody titers, IgG subclass, and their cytotoxic ability in sera from patients with various neurological diseases. Membrane attack complex (MAC) formation was examined by detection of complement C9 or C9neo with western blot or flow cytometry. Results: Among 86 patients, 40 were determined to be MOG-IgG-positive and 46 were negative. Anti-MOG-positive sera, but not -negative sera, caused cell death in MOG-expressing cells. This cytotoxic effect was disappeared after heat inactivation of sera. Importantly, anti-MOG IgG and externally added complement were necessary for sufficient cytotoxic effects. Anti-MOG autoantibodies were histologically colocalized with complement and formed a membrane attack complex consisting of anti-MOG IgG and complement factors. Conclusion: The human MOG antibody specifically killed MOG-expressing cells in vitro in the presence of externally added complement. Membrane attack complexes were formed on the cells, indicating that this autoantibody activated complement-mediated cytotoxicity. Further studies in larger numbers of patients are needed to characterize the role of complement in MOGAD.
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A 26-year-old woman developed a sudden headache, ptosis, and diplopia. Magnetic resonance imaging and angiography demonstrated a symmetrical lesion from the midbrain to the brainstem, involving the solitary nucleus and multifocal cerebral artery narrowing. Reversible cerebral vasoconstriction syndrome (RCVS) was suspected, and the patient improved after vasodilatation. Leigh syndrome was suspected due to the elevated serum pyruvate level, so mitochondrial DNA was analyzed, and an m.9176T>C mutation was detected. The final diagnosis was adult-onset Leigh syndrome manifesting as RCVS. An uncontrolled baroreflex due to a solitary nuclear lesion or endothelial dysfunction may have contributed to her unique presentation.
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Trastornos Cerebrovasculares , Cefaleas Primarias , Enfermedad de Leigh , Vasoespasmo Intracraneal , Femenino , Humanos , Adulto , Angiografía por Resonancia Magnética/métodos , Enfermedad de Leigh/diagnóstico , Enfermedad de Leigh/genética , Vasoconstricción , MutaciónRESUMEN
PURPOSE: Myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs) are associated with various central nervous system demyelinating disorders. Recently, they were detected in cerebral cortical encephalitis (CCE), which often causes seizures. We performed a literature review to elucidate the electroclinical features of CCE. In addition to the published cases, we describe a new, illustrative case of MOG-Ab-associated CCE (MOG-CCE) with multifocal seizures documented by video electroencephalograph (EEG). METHODS: We searched PubMed with the keywords "[MOG] AND [encephalitis]" and reviewed relevant articles. The articles included reports of patients with CCE (as demonstrated by magnetic resonance imaging) and serum MOG Ab positivity. Cases were excluded if no epileptic seizures were reported or if details of the seizures were unavailable. RESULTS: Our literature review identified 34 patients with MOG-CCE. An analysis of these 34 cases and the new case showed that 20 patients were male (57.1%), and the median age at presentation was 23 years (range, 6 to 46 years). Focal to bilateral tonic-clonic seizure was the most common seizure type, followed by focal motor seizure in the face or an arm or leg. EEG findings were available for 26 patients. Interictal epileptiform discharges (IEDs) and ictal EEG patterns were seen in 10 (38.5%) and 5 (19.2%) patients, respectively. Focal EEG abnormalities, including slow waves and IEDs, were observed in the central, parietal, occipital, or posterior temporal region. CONCLUSION: MOG-CCE has distinctive electroclinical features that differ from those of other autoimmune encephalitides. Careful electroclinical analysis of seizures can be helpful for diagnosing MOG-CCE.
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Encefalitis , Enfermedad de Hashimoto , Autoanticuerpos , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Encefalitis/complicaciones , Encefalitis/diagnóstico , Femenino , Enfermedad de Hashimoto/complicaciones , Humanos , Imagen por Resonancia Magnética , Masculino , Glicoproteína Mielina-Oligodendrócito , Convulsiones/complicacionesRESUMEN
BACKGROUND: Retinal atrophy in the chronic phase of optic neuritis (ON) in anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains unclear. METHODS: Patients with these diseases were repeatedly evaluated using optical coherence tomography (OCT) for the circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) in the ON-involved eyes during relapse-free period after the first ON episode before relapse. Optic MRI with short tau inversion recovery (STIR) sequences was further evaluated retrospectively. RESULTS: Twelve patients with MOGAD (20 eyes with ON-involvement) and 14 with AQP4-Ab-positive NMOSD (16 eyes with ON-involvement) were enrolled. The progression of retinal atrophy ≥12 months after onset was observed in AQP4-Ab-positive NMOSD, but was not apparent in MOGAD. A decrease in retinal thickness by the same amount results in more severe visual impairment in AQP4-Ab-positive NMOSD. On optic MRI, the residual STIR hyperintensity in the optic nerves remained in the chronic phase in almost all eyes with ON in both diseases. Optic nerve atrophy occurred in all evaluated ON-involved eyes in AQP4-Ab-positive NMOSD, while it was observed in half of ON-involved eyes in MOGAD. CONCLUSIONS: Progression of retinal atrophy in the chronic phase has been observed in patients with AQP4-Ab-positive NMOSD, while it remains uncertain in patients with MOGAD. The visual impairments upon similar levels of retinal atrophy would be worse in AQP4-Ab-positive NMOSD, possibly attributable in part to a higher incidence of optic nerve atrophy in this disease.
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Neuromielitis Óptica , Neuritis Óptica , Acuaporina 4 , Atrofia , Autoanticuerpos , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/diagnóstico por imagen , Neuritis Óptica/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) is a newly identified autoimmune demyelinating disorder that is often associated with acute disseminated encephalomyelitis and usually occurs postinfection or postvaccination. Here we report a case of MOGAD after mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. A previously healthy 68-year-old woman presented to our department with gradually worsening numbness on the right side of her face, which began 14 days after her second dose of an mRNA-1273 vaccination. The patient's brain MRI revealed a right cerebellar peduncle lesion with gadolinium enhancement, a typical finding of MOGAD. A neurological examination revealed paresthesia on her right V2 and V3 areas. Other neurological examinations were unremarkable. Laboratory workups were positive for serum MOG-IgG as assessed by live cell-based assays and the presence of oligoclonal bands in the cerebrospinal fluid (CSF). The patient's serum test results for cytoplasmic-antineutrophil cytoplasmic antibodies, perinuclear-cytoplasmic-antineutrophil cytoplasmic antibodies, GQ1b-antibodies, and aquaporin-4 antibodies (AQP4-IgG) were all negative. Tests for soluble interleukin (IL)-2 receptors in the serum, IL-6 in the CSF and skin pricks, and angiotensin converting enzyme tests were all unremarkable. The patient was diagnosed with MOGAD after receiving an mRNA SARS-CoV-2 vaccination. After two courses of intravenous methylprednisolone treatment, the patient's symptoms improved and her cerebellar peduncle lesion shrunk slightly without gadolinium enhancement. To date, there have only been two cases of monophasic MOGAD following SARS-CoV-2 vaccination, including both the ChAdOx1 nCOV-19 and mRNA-1273 vaccines, and the prognosis is generally similar to other typical MOGAD cases. Although the appearance of MOG antibodies is relatively rare in post-COVID-19-vaccine demyelinating diseases, MOGAD should be considered in patients with central nervous system (CNS) demyelinating diseases after receiving a SARS-CoV-2 vaccine.
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OBJECTIVE: The patterns of relapse and relapse-prevention strategies for anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not completely investigated. We compared the patterns of relapse in later stages of MOGAD with those of anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD). METHODS: In this observational, comparative cohort study, 66 patients with MOGAD and 90 with AQP4-Ab-positive NMOSD were enrolled. We compared the patterns of relapse and annualized relapse rates (ARRs) in the first 10 years from disease onset, stratified by relapse-prevention treatments. RESULTS: Approximately 50% of the patients with MOGAD experienced relapses in the first 10 years. Among those not undergoing relapse-prevention treatments, ARRs in the first 5 years were slightly lower in MOGAD patients than in AQP4-Ab-positive NMOSD patients (MOGAD vs. AQP4-Ab NMOSD: 0.19 vs. 0.30; p = 0.0753). After 5 years, the ARR decreased in MOGAD patients (MOGAD vs. AQP4-Ab NMOSD: 0.05 vs. 0.34; p = 0.0001), with a 72% reduction from the first 5 years (p = 0.0090). Eight (61.5%) of the 13 MOGAD patients with more than 10-year follow-up from disease onset showed relapse 10 years after onset. Clustering in the timing and phenotype of attacks was observed in both disease patients. The effectiveness of long-term low-dose oral PSL for relapse prevention in patients with MOGAD has not been determined. CONCLUSIONS: The relapse risk in patients with MOGAD is generally lower than that in patients with AQP4-Ab-positive NMOSD, especially 5 years after onset. Meanwhile, relapses later than 10 years from onset are not rare in both diseases.
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Acuaporina 4 , Neuromielitis Óptica , Autoanticuerpos , Enfermedad Crónica , Estudios de Cohortes , Humanos , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica/tratamiento farmacológico , RecurrenciaRESUMEN
Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system; however, its exact mechanism is unknown. This study aimed to elucidate the profile of white blood cells (WBCs) in the acute phase of an MS attack. Sixty-four patients with MS at the time of diagnosis and 2492 age- and sex-adjusted healthy controls (HCs) were enrolled. Data regarding the blood cell counts were compared between the groups. The total WBC (p < 0.0001), monocyte (p < 0.0001), basophil (p = 0.0027), and neutrophil (p < 0.0001) counts were higher in the MS group than in the HC group, whereas the lymphocyte and eosinophil counts did not differ. Adjustments for the smoking status and body mass index yielded the same results. The total and differential WBC counts of the patients with MS did not correlate with the counts of T2 hyperintense brain lesions or the levels of neurological disturbance. In summary, patients with MS showed elevated counts of total WBCs, monocytes, basophils, and neutrophils at the time of diagnosis. However, the clinical relevance of these biomarkers in the context of the development and progression of MS remains unclear.
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Esclerosis Múltiple/sangre , Esclerosis Múltiple/terapia , Adulto , Biomarcadores/sangre , Femenino , Humanos , Recuento de Leucocitos , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: To elucidate the differences in the source and in the level of intrathecal synthesis between anti-aquaporin-4 antibodies (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). METHODS: Thirty-eight patients with MOG-IgG-associated disease and 36 with AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD) were studied for the antibody titers in the sera and CSF simultaneously collected in the acute attacks. The quotients between CSF and serum levels of albumin, total immunoglobulin G, and each disease-specific antibody were calculated. Intrathecal production level in each disease-specific antibody was evaluated by calculating the antibody index from these quotients. RESULTS: Eleven of the 38 patients with MOG-IgG were positive for the antibody only in the CSF, while no patient with AQP4-IgG showed CSF-restricted AQP4-IgG. Blood-brain barrier compromise as shown by raised albumin quotients was seen in 75.0% of MOG-IgG-positive cases and 43.8% of AQP4-IgG-positive cases. Moreover, MOG-IgG quotients were >10 times higher than AQP4-IgG quotients (effect size r = 0.659, p < 0.0001). Elevated antibody index (>4.0) was confirmed in 12 of 21 with MOG-IgG, whereas it was seen only in 1 of 16 with AQP4-IgG (φ = 0.528, p < 0.0001). The CSF MOG-IgG titers (ρ = 0.519, p = 0.001) and antibody indexes for MOG-IgG (ρ = 0.472, p = 0.036) correlated with the CSF cell counts but not with clinical disability. CONCLUSIONS: Intrathecal production of MOG-IgG may occur more frequently than that of AQP4-IgG. This finding implies the different properties of B-cell trafficking and antibody production between MOG-IgG-associated disease and AQP4-IgG-positive NMOSD.
Asunto(s)
Anticuerpos Bloqueadores/líquido cefalorraquídeo , Acuaporina 4/inmunología , Inmunoglobulina G/líquido cefalorraquídeo , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/inmunología , Adolescente , Adulto , Albúminas/análisis , Algoritmos , Anticuerpos Antiidiotipos , Especificidad de Anticuerpos , Acuaporina 4/líquido cefalorraquídeo , Barrera Hematoencefálica/patología , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/líquido cefalorraquídeo , Médula Espinal/inmunología , Médula Espinal/metabolismo , Adulto JovenRESUMEN
Aquaporin 4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) is an autoimmune astrocytopathic disease pathologically characterized by the massive destruction and regeneration of astrocytes with diverse types of tissue injury with or without complement deposition. However, it is unknown whether this diversity is derived from differences in pathological processes or temporal changes. Furthermore, unlike for the demyelinating lesions in multiple sclerosis, there has been no staging of astrocytopathy in AQP4-IgG+NMOSD based on astrocyte morphology. Therefore, we classified astrocytopathy of the disease by comparing the characteristic features, such as AQP4 loss, inflammatory cell infiltration, complement deposition and demyelination activity, with the clinical phase. We performed histopathological analyses in eight autopsied cases of AQP4-IgG+NMOSD. Cases comprised six females and two males, with a median age of 56.5 years (range, 46-71 years) and a median disease duration of 62.5 months (range, 0.6-252 months). Astrocytopathy in AQP4-IgG+NMOSD was classified into the following four stages defined by the astrocyte morphology and immunoreactivity for GFAP: (i) astrocyte lysis: extensive loss of astrocytes with fragmented and/or dust-like particles; (ii) progenitor recruitment: loss of astrocytes except small nucleated cells with GFAP-positive fibre-forming foot processes; (iii) protoplasmic gliosis: presence of star-shaped astrocytes with abundant GFAP-reactive cytoplasm; and (iv) fibrous gliosis: lesions composed of densely packed mature astrocytes. The astrocyte lysis and progenitor recruitment stages dominated in clinically acute cases (within 2 months after the last recurrence). Findings common to both stages were the loss of AQP4, a decreased number of oligodendrocytes, the selective loss of myelin-associated glycoprotein and active demyelination with phagocytic macrophages. The infiltration of polymorphonuclear cells and T cells (CD4-dominant) and the deposition of activated complement (C9neo), which reflects the membrane attack complex, a hallmark of acute NMOSD lesions, were selectively observed in the astrocyte lysis stage (98.4% in astrocyte lysis, 1.6% in progenitor recruitment, and 0% in protoplasmic gliosis and fibrous gliosis). Although most of the protoplasmic gliosis and fibrous gliosis lesions were accompanied by inactive demyelinated lesions with a low amount of inflammatory cell infiltration, the deposition of complement degradation product (C3d) was observed in all four stages, even in fibrous gliosis lesions, suggesting the past or chronic occurrence of complement activation, which is a useful finding to distinguish chronic lesions in NMOSD from those in multiple sclerosis. Our staging of astrocytopathy is expected to be useful for understanding the unique temporal pathology of AQP4-IgG+NMOSD.
Asunto(s)
Astrocitos/patología , Encéfalo/patología , Activación de Complemento/fisiología , Neuromielitis Óptica/patología , Anciano , Acuaporina 4/inmunología , Astrocitos/inmunología , Autoanticuerpos , Encéfalo/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/inmunologíaRESUMEN
OBJECTIVE: To elucidate the clinical characteristics of Japanese pediatric patients with acquired demyelinating diseases (ADS), positive for myelin oligodendrocyte glycoprotein antibody (MOG-IgG), we conducted a nation-wide survey. METHODS: Information about pediatric patients under 18 years old with ADS was solicited with surveys sent to 323 facilities. In an initial survey, we asked whether the center had any patients with ADS, and the MOG-IgG serostatus of the patients. In a follow-up survey, we requested more precise information on patients with ADS. RESULTS: Initial survey: 263 replies providing information on 175 patients were received. MOG-IgG were examined in 78 patients and 54 of those (69%) were positive for MOG-IgG. Follow-up survey: The characteristic involvement was optic neuritis, with visual disturbance and optic pain as characteristic symptoms. The relapse rate was 44% in patients positive for MOG-IgG, which was higher than that in seronegative patients (38%). For acute phase treatments, corticosteroid (CS), plasma exchange, and intravenous immunoglobulin (IVIG) were useful. To prevent relapse, CS, intermittent IVIG, immunosuppressants, and monoclonal antibodies were useful, but the efficacies of disease modifying drugs were uncertain. Sequelae such as visual disturbance, cognitive impairment, motor dysfunction, and epilepsy were observed in 11% of patients with MOG-IgG. CONCLUSIONS: MOG antibody-associated diseases were found to be common among pediatric ADS patients. Since a variety of sequelae were observed in these patients, it is important to identify the appropriate treatment to ensure the best outcome. The presence of the MOG autoantibody should be taken into consideration as part of the diagnostic criteria for pediatric ADS.
Asunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes Desmielinizantes SNC , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuritis Óptica , Adolescente , Acuaporina 4/inmunología , Niño , Preescolar , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Enfermedades Autoinmunes Desmielinizantes SNC/sangre , Enfermedades Autoinmunes Desmielinizantes SNC/complicaciones , Enfermedades Autoinmunes Desmielinizantes SNC/epidemiología , Enfermedades Autoinmunes Desmielinizantes SNC/inmunología , Epilepsia/epidemiología , Epilepsia/etiología , Femenino , Encuestas Epidemiológicas , Humanos , Japón/epidemiología , Masculino , Trastornos del Movimiento/epidemiología , Trastornos del Movimiento/etiología , Neuritis Óptica/sangre , Neuritis Óptica/complicaciones , Neuritis Óptica/epidemiología , Neuritis Óptica/inmunología , Recurrencia , Trastornos de la Visión/epidemiología , Trastornos de la Visión/etiologíaRESUMEN
Myelin oligodendrocyte glycoprotein (MOG)-IgG detected by the cell-based assay is associated with demyelinating diseases of the central nervous system, such as optic neuritis, myelitis, and acute disseminated encephalomyelitis, but rarely with peripheral neuropathy. Here, we describe the case of a 32-year-old MOG-IgG+ woman who developed central and peripheral demyelinating lesions. In contrast to previous similar cases, she uniquely presented with repeated subsequent relapses in the peripheral nerve, mimicking chronic inflammatory demyelinating polyneuropathy. Possible pathogenic implications of MOG-IgG in combined central and peripheral nervous system diseases are considered.
Asunto(s)
Enfermedades Desmielinizantes , Enfermedades del Sistema Nervioso Periférico , Adulto , Autoanticuerpos , Enfermedades Desmielinizantes/tratamiento farmacológico , Femenino , Humanos , Inmunoglobulina G , Glicoproteína Mielina-Oligodendrócito , EsteroidesRESUMEN
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis may develop concurrently with or separate from episodes of demyelinating disorders. Previously, we reported a patient with relapsing anti-NMDAR encephalitis who had presented with bilateral medial frontal cerebral cortical lesions at onset. Recently, we assessed CSF anti-myelin oligodendrocyte glycoprotein (MOG) antibody for the first time in this case and found that the patient had been double positive for anti-NMDAR and anti-MOG antibodies from onset. The two antibody titres, CSF cells, IL-6 and CXCL13 were all elevated at onset. Anti-NMDAR encephalitis may develop concurrently with anti-MOG antibody-associated cortical encephalitis and relapse with elevated levels of CSF cytokines.