Neuromyelitis optica (Devic disease)The spectrum of Neuromyelitis optica (NMO) or Devic disease is wider than previously thought and includes recurrent myelitis, optic neuritis and may even occur with brain lesions. A lecture is followed by access to full article text relating to NMO"
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Access to fulltext of main articles relating to NMOAnti-aquaporin-4 antibody is involved in thepathogenesis of NMO: a study on antibody titre.
Anti-aquaporin-4 antibody is involved in thepathogenesis of NMO: a study on antibody titre. Brain. 2007 May;130(Pt 5):1235-43 Authors: Takahashi T, Fujihara K, Nakashima I, Misu T,Miyazawa I, Nakamura M, Watanabe S, Shiga Y, Kanaoka C, Fujimori J,Sato S, Itoyama Y NMO-IgG is a disease-specific autoantibody for neuromyelitisoptica (NMO) and its target antigen is aquaporin-4 (AQP4) waterchannel. Recently, we established a sensitive anti-AQP4 antibody assayusing human AQP4-transfected cells, which appeared more sensitive thanthe original NMO-IgG assay. So far, there has been no large-scale studyon anti-AQP4 antibody titre in NMO and related disorders. We tested 148sera of patients with NMO, high-risk syndrome of NMO, multiplesclerosis (MS), clinically isolated syndrome suggestive of MS andmiscellaneous diseases. We analysed the relation of anti-AQP4 antibodytitres and clinical and laboratory parameters. The sensitivity ofanti-AQP4 antibody assay was 91% (95% CI 79-100) for NMO and 85%(65-100) for high-risk syndrome, and the specificity was 100% (91-100)for NMO and high-risk syndrome, that is, none with the other disorderswas positive. Among 21 anti-AQP4 antibody-positive cases whose NMO-IgGwere tested, 15 were NMO-IgG-positive and 6 were NMO-IgG-negative.Higher anti-AQP4 antibody titres were associated with completeblindness and extensive or large cerebral lesions on MRI. The lengthsof spinal cord lesions on MRI were positively correlated with thetitres of anti-AQP4 antibody at the nadir of exacerbations. A fewpatients who had short (approx. one to two vertebral segments) spinalcord lesions on MRI were also seropositive with low anti-AQP4 antibodytitres, but did have other clinical and MRI features of NMO. Anti-AQP4antibody titres became lower after high-dose methylprednisolone, and afollow-up showed anti-AQP4 antibody titres remained low in relapse-freeperiods under immunosuppression. Cerebrospinal fluid (CSF)-anti-AQP4antibody was detected when the serum-antibody titres exceeded 512x, atthe ratio of 1 (CSF) to 500 (serum). Using a sensitive assay, theresults of the present study suggest that NMO and high-risk syndromemay be essentially anti-AQP4 antibody-associated disorders, and thatthe anti-AQP4 antibody titres have significant clinical andimmunological implications in NMO. PMID: 17449477 [PubMed - indexed for MEDLINE]
Neuromyelitis optica IgG status in acute partialtransverse myelitis. Arch Neurol. 2006 Oct;63(10):1398-400 Authors: Scott TF, Kassab SL, Pittock SJ BACKGROUND: Neuromyelitis optica (NMO) IgG is a specificmarker for NMO. Furthermore, a high proportion of patients withlongitudinally extensive transverse myelitis (characterized by spinalcord lesions extending 3 vertebral segments or more on magneticresonance imaging) are seropositive for NMO-IgG and are considered tohave a limited form of NMO. The NMO-IgG status in mild cases of acutepartial transverse myelitis asociated with minimal magnetic resonanceimaging abnormalities (spinal cord lesions <2 vertebral segmentson magnetic resonance imaging) is unknown. OBJECTIVE: To investigatethe NMO-IgG status of patients with acute partial transverse myelitisand a normal cerebral magnetic resonance image. DESIGN: Observational,retrospective consecutive case series with longitudinal follow-up.SETTING: Allegheny Multiple Sclerosis Treatment Center. PATIENTS: Threegroups of patients were tested for NMO-IgG. Group 1 consisted of 22patients with acute partial transverse myelitis, group 2 consisted of 4patients with definite NMO (by 1999 criteria of Wingerchuk et al), andgroup 3 consisted of 6 patients with definite multiple sclerosis. MAINOUTCOME MEASURE: NMO-IgG status. A commercially available assay for NMOantibodies was performed at the Mayo Clinic. Testing was performedduring the convalescent stage of the illness. RESULTS: Of the 22patients with acute partial transverse myelitis, only 1 wasseropositive for NMO-IgG at presentation. This patient subsequentlydeveloped recurrent episodes of longitudinally extensive transversemyelitis that are typicaly seen in association with NMO-IgG. Three ofthe 4 patients meeting criteria for NMO were seropositive. None of thepatients with multiple sclerosis had NMO-IgG detected. CONCLUSION:NMO-IgG is rarely encountered in patients with acute partial transversemyelitis, which is in sharp contrast to the high frequency of thisantibody in patients with NMO and longitudinally extensive transversemyelitis. PMID: 17030654 [PubMed - indexed for MEDLINE]
Spontaneous opticospinal encephalomyelitis in adouble-transgenic mouse model of autoimmune T cell/B cell cooperation. J Clin Invest. 2006 Sep;116(9):2385-92 Authors: Krishnamoorthy G, Lassmann H, Wekerle H, Holz A We describe a double-transgenic mouse strain (opticospinalEAE [OSE] mouse) that spontaneously develops an EAE-like neurologicalsyndrome closely resembling a human variant of multiple sclerosis,Devic disease (also called neuromyelitis optica). Like in Devicdisease, the inflammatory, demyelinating lesions were located in theoptic nerve and spinal cord, sparing brain and cerebellum, and themurine lesions showed histological similarity with their humancorrelates. OSE mice have recombination-competent immune cellsexpressing a TCR-alphabeta specific for myelin oligodendrocyteglycoprotein (MOG) aa 35-55 peptide in the context of I-Ab along withan Ig J region replaced by the recombined heavy chain of a monoclonalantibody binding to a conformational epitope on MOG. OSE mouse B cellsbound even high dilutions of recombinant MOG, but not MOG peptide, andprocessed and presented it to autologous T cells. In addition, in OSEmice, but not in single-transgenic parental mice, anti-MOG antibodieswere switched from IgM to IgG1. PMID: 16955140 [PubMed - indexed for MEDLINE]
Neuromyelitis optica brain lesions localized atsites of high aquaporin 4 expression. Arch Neurol. 2006 Jul;63(7):964-8 Authors: Pittock SJ, Weinshenker BG, Lucchinetti CF,Wingerchuk DM, Corboy JR, Lennon VA BACKGROUND: Neuromyelitis optica (NMO)-IgG is a specificautoantibody marker for NMO. It binds selectively to aquaporin 4(AQP4), which is highly concentrated in astrocytic foot processes atthe blood-brain barrier and is not restricted to optic nerve and spinalcord. Although it is conventionally believed that the brain is spared,brain imaging abnormalities are not uncommon in patients with NMO.OBJECTIVE: To investigate the location of brain lesions that aredistinctive for NMO with respect to the localization of AQP4 inmammalian brain. DESIGN: Observational, retrospective case series.SETTING: Clinical serologic cohort of patients tested for NMO-IgG forwhom brain MRI images were available. PATIENTS: We identified 120patients seropositive for NMO-IgG for whom brain magnetic resonanceimages were available. MAIN OUTCOME MEASURE: Magnetic resonance imagingabnormalities. RESULTS: In 8 patients we observed recurring anddistinctive magnetic resonance imaging abnormalities in thehypothalamic and periventricular areas that corresponded to brainregions of high AQP4 expression. CONCLUSION: The distribution ofNMO-characteristic brain lesions corresponds to sites of high AQP4expression. PMID: 16831965 [PubMed - indexed for MEDLINE]
Study of mitoxantrone for the treatment ofrecurrent neuromyelitis optica (Devic disease). Arch Neurol. 2006 Jul;63(7):957-63 Authors: Weinstock-Guttman B, Ramanathan M, Lincoff N,Napoli SQ, Sharma J, Feichter J, Bakshi R BACKGROUND: Neuromyelitis optica is a severe demyelinatingdisease that selectively involves the optic nerves and the spinal cordbut usually spares the brain. It is considered to have a B-cell-inducedpathogenesis. Mitoxantrone hydrochloride, a synthetic anthracenedioneapproved for worsening relapsing-remitting multiple sclerosis andsecondary progressive multiple sclerosis, has been shown to primarilysuppress the humoral response. OBJECTIVE: To evaluate the benefit ofmitoxantrone treatment in patients with relapsing neuromyelitis optica.DESIGN: Prospective 2-year study. SETTING: Academic multiple sclerosiscenter. PATIENTS: Five patients (3 women and 2 men) with an age rangeof 20 to 51 years and an Expanded Disability Status Scale score of 2.5to 6.5 (mean +/- SD, 4.40 +/- 1.88). INTERVENTIONS: Monthly intravenousinfusions of mitoxantrone hydrochloride, 12 mg/m2, for 6 monthsfollowed by 3 additional treatments every 3 months. MAIN OUTCOMEMEASURES: Expanded Disability Status Scale score measured every 3months and during relapses; findings on orbital, brain, and spinal cordmagnetic resonance images performed at baseline and at 3, 6, 12, 18,and 24 months; and visual evoked potentials and results ofophthalmologic evaluations performed at baseline and annually. RESULTS:During the 2 years of treatment, 2 patients each had a relapse oncewithin the initial 5 months of treatment (1 severe and 1 moderate).Improvement was seen clinically and on magnetic resonance images in 4patients. Patients generally tolerated the treatment well, although 1patient had a reversible decrease in cardiac ejection fraction.CONCLUSION: Our results suggest a beneficial effect of mitoxantronetreatment for relapsing neuromyelitis optica. PMID: 16831964 [PubMed - indexed for MEDLINE]
Neuromyelitis optica in patients with myastheniagravis who underwent thymectomy. Arch Neurol. 2006 Jun;63(6):851-6 Authors: Kister I, Gulati S, Boz C, Bergamaschi R, PiccoloG, Piccolo G, Oger J, Swerdlow ML BACKGROUND: Myasthenia gravis (MG) and neuromyelitis optica(NMO, also known as Devic disease) are rare autoimmune disorders, withupper-limit prevalence estimates in the general population of 15 per100,000 and 5 per 100,000, respectively. To our knowledge, anassociation between these diseases has not been previously reported.OBJECTIVES: To describe 4 patients with MG who developed NMO afterthymectomy and to analyze possible causes of apparent increasedprevalence of NMO among patients with MG. DESIGN: Case series.PATIENTS: Four patients with MG who underwent thymectomy.INTERVENTIONS: None. RESULTS: The prevalence of MG within the publishedcohort of patients with NMO is more than 150 times higher than that inthe general population. CONCLUSION: Dysregulation of B-cellautoimmunity in myasthenia, possibly exacerbated by loss of controlover autoreactive cells as a result of thymectomy, may predisposepatients to the development of NMO. PMID: 16769866 [PubMed - indexed for MEDLINE]
Devic disease with brainstem lesions. Arch Neurol. 2006 Apr;63(4):591-3 Authors: Chalumeau-Lemoine L, Chretien F, Gaëlle SiLarbi A, Brugieres P, Gray F, Brun-Buisson C, Creange A We describe a patient who suffered from an unusually severeform of neuromyelitis optica with a hyperacute time-course evolutionrequiring mechanical ventilation within 3 days. The patient died after72 days and autopsy showed major spinal cord, optic nerve, andbrainstem necrosis, and multifocal necrotic lesions on the cerebellumand cerebral white matter. PMID: 16606774 [PubMed - indexed for MEDLINE]
Brain abnormalities in neuromyelitis optica. Arch Neurol. 2006 Mar;63(3):390-6 Authors: Pittock SJ, Lennon VA, Krecke K, Wingerchuk DM,Lucchinetti CF, Weinshenker BG BACKGROUND: Neuromyelitis optica (NMO) is a severedemyelinating disease defined principally by its tendency toselectively affect optic nerves and the spinal cord causing recurrentattacks of blindness and paralysis. Contemporary diagnostic criteriarequire absence of clinical disease outside the optic nerve or spinalcord. We have, however, frequently encountered patients with awell-established diagnosis of NMO in whom either asymptomatic orsymptomatic brain lesions develop suggesting that the diagnosticcriteria for NMO should be revised. OBJECTIVE: To describe the magneticresonance image (MRI) brain findings in NMO. DESIGN: Observational,retrospective case series.Patients We ascertained patients through aclinical biospecimens database of individuals with definite orsuspected NMO. We included patients who (1) satisfied the 1999 criteriaof Wingerchuk et al for NMO except for the absolute criterion oflacking symptoms beyond the optic nerve and spinal cord and thesupportive criterion of having a normal brain MRI at onset; (2) had MRIevidence of a spinal cord lesion extending 3 vertebral segments or more(the most specific nonserological feature to differentiate NMO fromMS); and (3) were evaluated neurologically and by brain MRI at the MayoClinic. MAIN OUTCOME MEASURES: Magnetic resonance images wereclassified as normal or as abnormal with either nonspecific, multiplesclerosis-like or atypical abnormalities. We evaluated whether brainlesions were symptomatic and analyzed the neuropathologic features of asingle brain biopsy specimen. RESULTS: Sixty patients (53 women [88%])fulfilled these inclusion criteria. The mean +/- SD age at onset was37.2 +/- 18.4 years and the mean +/- SD duration of follow-up was 6.0+/- 5.6 years. Neuromyelitis optica-IgG was detected in 41 patients(68%). Brain MRI lesions were detected in 36 patients (60%). Most werenonspecific, but 6 patients (10%) had multiple sclerosis-like lesions,usually asymptomatic. Another 5 patients (8%), mostly children, haddiencephalic, brainstem or cerebral lesions, atypical for multiplesclerosis. When present, symptoms of brain involvement were subtle,except in 1 patient who was comatose and had large cerebral lesions.CONCLUSIONS: Asymptomatic brain lesions are common in NMO, andsymptomatic brain lesions do not exclude the diagnosis of NMO. Theseobservations justify revision of diagnostic criteria for NMO to allowfor brain involvement. PMID: 16533966 [PubMed - indexed for MEDLINE]
Role of return migration in the emergence ofmultiple sclerosis in the French West Indies. Brain. 2005 Dec;128(Pt 12):2899-910 Authors: Cabre P, Signate A, Olindo S, Merle H,Caparros-Lefebvre D, Béra O, Smadja D The emergence of multiple sclerosis in island societies hasbeen investigated only in a few Caucasian populations living intemperate regions. The effect of human migration on the risk ofdeveloping this disease is still an open question because of possiblegenetic selection. We conducted an epidemiological study of themultiple sclerosis population in the French West Indies (Martinique andGuadeloupe), a population which includes large numbers of West Indianswho have returned after emigrating to metropolitan France. Standardizedincidence ratios (SIRs) for multiple sclerosis among migrants werecalculated and their genetic characteristics were compared to those ofnon-migrants. The crude prevalence of multiple sclerosis was 14.8/10(5)on December 31, 1999 (95% CI: 11.9-17.7); and its crude mean annualincidence for the period July 1, 1999 to June 30, 2002 was 1.4/10(5)(95% CI: 1.0-1.8), confirming its emergence in the French West Indies.Recurrent neuromyelitis optica, which is virtually the only form ofmultiple sclerosis in black African populations in tropical regions,represented not >17.8% of these cases. During the 1,440,000person-years of follow-up, 33 incidence cases were identified inmigrants. Since the number of expected cases was 19.3, the overall SIRwas 1.71 (95% CI: 1.19-2.38; P < 0.01) among migrants. Theincrease in the SIR was more marked if the stay was made before the ageof 15 years (4.05, 95% CI: 2.17-6.83; P < 0.0001). Europeanancestry in the two migrating and non-migrating populations wassimilar. Martinique, which has a higher rate of return migration, has ahigher prevalence of multiple sclerosis (21.0/10(5) versus 8.5/10(5))and a higher incidence (2.0/10(5) versus 0.7/10(5)) than Guadeloupe.The emergence of the disease in the French West Indies is ofenvironmental rather than genetic origin. It may be explained eitherthrough the introduction by migrants of precipitating environmentalfactors that operate in a critical way before the age of 15 years,and/or by the recent disappearance from the French West Indies ofprotective environmental factors acting before this age. PMID: 16183661 [PubMed - indexed for MEDLINE]
The natural history of recurrent optic neuritis. Arch Neurol. 2004 Sep;61(9):1401-5 Authors: Pirko I, Blauwet LK, Lesnick TG, Weinshenker BG BACKGROUND: Optic neuritis (ON) may occur in isolation ormay herald multiple sclerosis (MS) or neuromyelitis optica (NMO).Occasionally, ON may recur many times without intervening evidence ofdissemination in space. OBJECTIVE: To define the clinical course andprognosis of patients with recurrent ON. DESIGN: Retrospective medicalrecord review and telephone follow-up survey. SETTING: Clinic-basedpractice in a large tertiary referral institution. MAIN OUTCOMEMEASURES: Survival analysis of conversion to MS and NMO and finalvisual impairment. We studied the association of clinical anddemographic factors, the presence of brain lesions on magneticresonance images, and the use of corticosteroid treatment at the timeof the first ON occurrence with conversion to MS and NMO. RESULTS: Weidentified 1274 patients with ON between 1994 and 2000 and selected 72(5.7%) with recurrent ON without intervening symptoms of a disseminateddemyelinating condition for further analysis. The 5-year conversionrate to NMO was 12.5% and to MS, 14.4%. Among 5 patients with 2 or morelesions consistent with MS on brain magnetic resonance images, 2(40.0%) converted to MS and none to NMO, while among 11 patientswithout such lesions, none converted to MS and 2 (18.2%) converted toNMO (P =.16). Conversion to MS occurred in 7 (19.4%) of 36 individualstreated for their first ON episode with corticosteroids vs 4 (44.4%) of9 untreated individuals (P =.19). There was no difference in theconversion rate to MS between those treated with intravenous steroids(4 [16.7%] of 24) vs oral steroids (3 [25.0%] of 12) (P =.33).Conversion to NMO occurred earlier than conversion to MS (2.3 +/- 1.6vs 5.3 +/- 4.3 years, respectively; P =.01). Women tended to convert toNMO more frequently than men (female-male ratio for NMO converters,7:1; MS converters, 2:1; nonconverters, 2:1; P =.56), as did those witha higher annual frequency of ON episodes (NMO converters, 2.0 +/- 1.3;MS converters, 1.0 +/- 1.0; nonconverters, 0.6 +/- 0.5; P =.04). Thenumber of ON events in the first 2 years following the first ON episodewas higher in the NMO group (NMO converters, 2.4 +/- 0.9; MSconverters, 1.9 +/- 1.1; nonconverters, 1.7 +/- 0.7; P =.04). The finalvisual impairment was greatest in the NMO group (P =.02). CONCLUSIONS:Patients with rapid succession of severe ON events are more likely todevelop a generalized demyelinating disease. Patients with NMO had aworse visual outcome. PMID: 15364686 [PubMed - indexed for MEDLINE]
Clinicopathological study of a myelinoligodendrocyte glycoprotein-induced demyelinating disease in LEW.1AV1rats. Brain. 2004 Oct;127(Pt 10):2201-13 Authors: Sakuma H, Kohyama K, Park IK, Miyakoshi A, TanumaN, Matsumoto Y Although multiple sclerosis is considered to be anautoimmune disease in the CNS, the immune responses that take place inthe CNS and lymphoid organs remain to be elucidated. Here, we havesuccessfully induced various subtypes of experimental autoimmuneencephalitis (EAE) in LEW.1AV1 rats carrying RT1(av1) on the Lewisbackground genes by immunization with recombinant rat myelinoligodendrocyte glycoprotein (MOG) in various solutions with adjuvants.The purpose of the present study was to analyse in more detail theclinical and immunopathological features of MOG-induced EAE in LEW.1AV1rats. Immunization with high doses of soluble MOG with pertussis toxininduced acute, frequently fatal EAE, whereas medium doses of partiallyaggregated MOG without pertussis toxin produced relapsing and remittingEAE. Secondary progressive EAE was induced in some rats by immunizationwith the immunization protocol having an intermediate nature betweenthe above two. The optic nerve (approximately 60% of the immunizedrats) and spinal cord (100%) were frequently involved and detectableboth clinically and pathologically, while there was no lesion in thecerebrum. Histological examination revealed that, despite variety inthe clinical subtypes, progression of the pathological processes wasstrikingly uniform, i.e. initial inflammation with minimaldemyelination followed by predominant demyelination with minimallymphocyte infiltration. These findings suggest that the lesion duringthe later stage is maintained by humoral factors. Taken together, thisexperimental system can serve as a model of neuromyelitis optica.Further analysis will provide useful information to elucidate thepathogenesis and to develop immunotherapy for neuromyelitis optica andmultiple sclerosis. PMID: 15282218 [PubMed - indexed for MEDLINE]
Neuromyelitis optica. Arch Neurol. 2003 Sep;60(9):1336-8 Authors: de Seze J PMID: 12975307 [PubMed - indexed for MEDLINE]
Glatiramer acetate treatment in Devic'sneuromyelitis optica. Brain. 2003 Jun;126(Pt 6):1E; author reply 1E-a Authors: Bergamaschi R PMID: 12764069 [PubMed - indexed for MEDLINE]
A role for humoral mechanisms in the pathogenesisof Devic's neuromyelitis optica. Brain. 2002 Jul;125(Pt 7):1450-61 Authors: Lucchinetti CF, Mandler RN, McGavern D, Bruck W,Gleich G, Ransohoff RM, Trebst C, Weinshenker B, Wingerchuk D, ParisiJE, Lassmann H Devic's disease [neuromyelitis optica (NMO)] is anidiopathic inflammatory demyelinating disease of the CNS, characterizedby attacks of optic neuritis and myelitis. The mechanisms that resultin selective localization of inflammatory demyelinating lesions to theoptic nerves and spinal cord are unknown. Serological and clinicalevidence of B cell autoimmunity has been observed in a high proportionof patients with NMO. The purpose of this study was to investigate theimportance of humoral mechanisms, including complement activation, inproducing the necrotizing demyelination seen in the spinal cord andoptic nerves. Eighty-two lesions were examined from nine autopsy casesof clinically confirmed Devic's disease. Demyelinating activity in thelesions was immunocytochemically classified as early active (21lesions), late active (18 lesions), inactive (35 lesions) orremyelinating (eight lesions) by examining the antigenic profile ofmyelin degradation products within macrophages. The pathology of thelesions was analysed using a broad spectrum of immunological andneurobiological markers, and lesions were defined on the basis ofmyelin protein loss, the geography and extension of plaques, thepatterns of oligodendrocyte destruction and the immunopathologicalevidence of complement activation. The pathology was identical in allnine patients. Extensive demyelination was present across multiplespinal cord levels, associated with cavitation, necrosis and acuteaxonal pathology (spheroids), in both grey and white matter. There wasa pronounced loss of oligodendrocytes within the lesions. Theinflammatory infiltrates in active lesions were characterized byextensive macrophage infiltration associated with large numbers ofperivascular granulocytes and eosinophils and rare CD3(+) and CD8(+) Tcells. There was a pronounced perivascular deposition ofimmunoglobulins (mainly IgM) and complement C9neo antigen in activelesions associated with prominent vascular fibrosis and hyalinizationin both active and inactive lesions. The extent of complementactivation, eosinophilic infiltration and vascular fibrosis observed inthe Devic NMO cases is more prominent compared with that in prototypicmultiple sclerosis, and supports a role for humoral immunity in thepathogenesis of NMO. Based on this study, future therapeutic strategiesdesigned to limit the deleterious effects of complement activation,eosinophil degranulation and neutrophil/macrophage/microglialactivation are worthy of further investigation. PMID: 12076996 [PubMed - indexed for MEDLINE]
Neuromyelitis optica (Devic's syndrome) in systemiclupus erythematosus: a case report. Rheumatology (Oxford). 2002 Apr;41(4):470-1 Authors: Gibbs AN, Moroney J, Foley-Nolan D, O'Connell PG PMID: 11961183 [PubMed - indexed for MEDLINE]
Matrix metalloproteinases and tissue inhibitors ofmetalloproteinases in cerebrospinal fluid differ in multiple sclerosisand Devic's neuromyelitis optica. Brain. 2001 Mar;124(Pt 3):493-8 Authors: Mandler RN, Dencoff JD, Midani F, Ford CC, Ahmed W,Rosenberg GA Matrix metalloproteinases (MMPs) are increased in the CSF ofpatients with multiple sclerosis. Devic's neuromyelitis optica (DNO) isa demyelinating syndrome that involves the optic nerve and cervicalcord but differs pathologically from multiple sclerosis. Therefore, wehypothesized that the type of inflammatory reaction that causes MMPs tobe elevated in multiple sclerosis would be absent in patients with DNO.CSF was collected from 23 patients with relapsing-remitting orsecondary progressive multiple sclerosis, all of whom were experiencingacute symptoms, from seven patients with DNO, and from seven normalvolunteers. Diagnoses were made according to current criteria on thebasis of clinical manifestations, imaging results and CSF studies. IgGsynthesis was increased in the CSF of multiple sclerosis patients butnot in that of DNO patients. Zymography, reverse zymography and ELISA(enzyme-linked immunosorbent assay) were used to measure gelatinase A(MMP-2), gelatinase B (MMP-9) and tissue inhibitors ofmetalloproteinases (TIMPs). Zymograms showed that multiple sclerosispatients had elevated MMP-9 compared with DNO patients and controls (P:< 0.05). TIMP-1 and TIMP-2 levels were similar in all threegroups. We conclude that multiple sclerosis patients have higher MMP-9levels in the CSF than patients with DNO, which supports the differentpathological mechanisms of these diseases. PMID: 11222449 [PubMed - indexed for MEDLINE]
Devic's neuromyelitis optica: a primary autoimmunedisease? Rheumatology (Oxford). 2000 Feb;39(2):215-7 Authors: Hutchinson D, Solomon T, Moots RJ PMID: 10725078 [PubMed - indexed for MEDLINE]
Optic neuritis in African Americans. Arch Neurol. 1998 Feb;55(2):186-92 Authors: Phillips PH, Newman NJ, Lynn MJ OBJECTIVE: To describe the clinical profile of demyelinatingoptic neuritis in African Americans. METHODS: The medical records ofall patients with a diagnosis of optic neuritis examined at theNeuro-Ophthalmology Unit at the Emory University Eye Center (Emory) andat the Grady Memorial Hospital Eye Clinic (Grady), Atlanta, Ga, between1989 and 1996 were retrospectively reviewed. PATIENTS: African Americanand white patients, aged 15 through 55 years, with a single initialepisode of acute optic neuritis of unknown or demyelinative origin wereincluded in the study. Study patients included 23 African Americanpatients and 56 white patients examined at Emory as well as 10 AfricanAmerican patients examined at Grady. RESULTS: There were no significantdifferences among the African American study patients, the white studypatients, and patients from the Optic Neuritis Treatment Trial (ONTT)regarding sex (P=.36), age (P=.73), or the presence of disc edema(P=.40), lesions found on magnetic resonance imaging (P=.43), ormultiple sclerosis (P=.54) at the onset of an initial episode of opticneuritis. The Emory African American patients presented with morefrequent severe visual loss (13 [93%] of 14 patients with a visualacuity < or =20/200) compared with Emory white patients (12[39%] of 31 patients; P=.002) and with ONTT patients (161 [36%] of 448patients; P<.001). At follow-up examination of at least 1 year,Emory African American patients had worse vision (9 [39%] of 23patients <20/40, and 4 [17%] of 23 patients < or =20/200)compared with Emory white patients (5 [8%] of 63 patients<20/40, P=.001; 3 [5%] of 63 patients < or =20/200,P=.08), and with ONTT patients (29 [7%] of 409 patients <20/ 40,P=.0001; 12 [3%] of 409 patients < or =20/200, P=.01). Comparedwith ONTT patients, the Emory African American patients combined withthe Grady African American patients had more frequent severe visualloss (visual acuity < or =20/200) at presentation (18 [90%] of20 patients vs 161 [36%] of 448 patients; P<.001) and atfollow-up examination of at least 1 year (6 [18%] of 33 patients vs 12[3%] of 409 patients; P=.002). Seven (58%) of 12 African Americanpatients with multiple sclerosis had a "neuromyelitis optica"presentation defined by the presence of neurological deficits limitedto the optic nerves and spinal cord. CONCLUSIONS: The African Americanstudy patients with a single episode of demyelinating optic neuritishad visual acuities more severely affected at onset and after 1 year offollow-up compared with the white study patients and with patients inthe ONTT. In the African American patients, multiple sclerosis occurredmost frequently in a "neuromyelitis optica" form. PMID: 9482360 [PubMed - indexed for MEDLINE]
Multiple sclerosis: comparison of the human T-cellresponse to S100 beta and myelin basic protein reveals parallels to ratexperimental autoimmune panencephalitis. Brain. 1997 Aug;120 ( Pt 8):1437-45 Authors: Schmidt S, Linington C, Zipp F, Sotgiu S, de WaalMalefyt R, Wekerle H, Hohlfeld R The adoptive transfer of autoreactive S100 beta-specific Tcells induces experimental autoimmune panencephalomyelitis anduveoretinitis in the Lewis rat, mimicking the distribution of lesionsseen in a subset of patients with multiple sclerosis. We studied thefrequency and functional properties of the human T-cell response toS100 beta in eight patients (two relapsing-remitting multiplesclerosis, one chronic-progressive multiple sclerosis, two withmultiple sclerosis and uveitis, two neuromyelitis optica, onepanuveitis) and in seven healthy individuals, using bovine S100 betafor T-cell stimulation. Both in patients and controls, the frequency ofS100 beta-specific T-cell responses was half of that obtained formyelin basic protein (MBP), and only 10% of that obtained usingpurified protein derivative (PPD). The stimulation indices obtained inresponse to S100 beta were also less than half those obtained witheither MBP or PPD. However, four long-term S100 beta-specific T-celllines were established and studied in more detail. The four T-celllines all exhibited a CD4+, CD8-, T-cell receptor alpha beta + surfacephenotype and secreted tumour necrosis factor-alpha, interferon-gamma,interleukin-10 and interleukin-4 upon antigenic stimulation, but theywere heterogenous with respect to T-cell receptor usage; two T-celllines expressed V beta 2, one V beta 6.7 and one V beta 13.Antigen-specificity was confirmed using bovine S100 beta beta and alphabeta-isoforms, as well as a recombinant rat S100 beta preparation. Theresponse to S100 beta was shown to the HLA-(human leukocyte antigen-)DR-restricted for two of the S100 beta-specific T-cell lines. HumanS100 beta-specific T-cell lines were cytotoxic, although to a lesserextent than MBP-specific T-cell lines derived from the same donors. Thephenotypic and functional properties of human S100 beta-specific T-celllines raise the possibility that these T cells are pathogenic, as theyare in the rat. The low frequency and proliferative index of S100beta-specific, as opposed to MBP-specific T-cell responses suggeststhat the T-cell response to this widely expressed calcium-bindingprotein is under more efficient regulatory control. PMID: 9278633 [PubMed - indexed for MEDLINE]
Disseminated cholesterol embolism presenting asneuromyelitis optica. Br Med J (Clin Res Ed). 1987 Oct 31;295(6606):1139 Authors: Harney B PMID: 3120915 [PubMed - indexed for MEDLINE]
Disseminated cholesterol embolism presenting asneuromyelitis optica. Br Med J (Clin Res Ed). 1987 Sep 19;295(6600):697 Authors: Goldman M, Rickaert F, Voordecker P, Goldman S,Flament-Durand J
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