Devic's Neuromyelitis Optica Research Articles

Devic?s neuromyelitis optica: clinical features and prognostic factors

Devic's neuromyelitis optica (NMO) onset is characterized by optic neuritis (ON) and transverse myelitis (TM), either simultaneously or in isolation. Thereafter, the course of the disease can be monophasic (no other attack) or relapsing (sequences of ON and TM, no other neurological system involved). The risk of having a relapsing course is related to gender, older age at onset, less severe motor impairment after the myelitic onset, interval length between first and second attack. The risk of an unfavourable evolution (severe disability or death) during a relapsing course is mainly related to high relapse rate during the first two years of the disease. In summary, relapsing NMO patients tend to have a poor prognosis, requiring more effective immunosuppressive treatments.

Devic?s neuromyelitis optica and mitochondrial DNA mutation: a case report

Cases are described with Leber's optic atrophy and neurological symptoms and/or MRI lesions suggestive of multiple sclerosis. We describe a case of a young woman with Devic's neuromyelitis optica and 3460 homoplasmic mitochondrial DNA mutation.

Oligoclonal bands in Devic's neuromyelitis optica and multiple sclerosis: differences in repeated cerebrospinal fluid examinations.

We studied repeated cerebrospinal fluids of patients with Devic's neuromyelitis optica (NMO) and multiple sclerosis (MS). Variations of oligoclonal bands (OBs) had opposite trends in the two groups. In MS, OBs were detected in 399 of 411 patients (97%) and never disappeared. In NMO, OBs were detected in three of 11 patients (27%) and always disappeared. The hypothesis that NMO and MS follow distinct pathogenetic pathways is supported by our findings, which can be useful for the differentiation of NMO from MS.

A functional MRI study of movement-associated cortical changes in patients with Devic's neuromyelitis optica

Movement-associated cortical changes have been shown in several neurological conditions and were found to be associated to the extent of brain and cord damage. Devic's neuromyelitis optica (DNO) is characterized by a severe involvement of the cord and optic nerve, with sparing of the brain. To assess the actual role of cord pathology on the pattern of movement-associated cortical recruitment, we obtained functional magnetic resonance imaging (fMRI) from patients with DNO and investigated whether the extent of brain activation is correlated with the extent of cervical cord damage. We studied 10 right-handed DNO patients and 15 sex- and age-matched healthy controls. The MRI assessment consisted of the following: (a) fMRI during repetitive flexion extension of the last four fingers of the right and left hand, (b) brain and cervical cord conventional MRI, and (c) cervical cord magnetization transfer (MT) MRI. Compared to controls and for both tasks, DNO patients had an increased recruitment of several regions of the sensorimotor network (primary sensorimotor cortex, postcentral gyrus, middle frontal gyrus, rolandic operculum, secondary sensorimotor cortex, precuneus, and cerebellum) and of several other regions mainly in the temporal and occipital lobes, such as MT/V5, the fusiform gyrus, the cuneus, and the parahippocampal gyrus. For both tasks, strong correlations ( r values ranging from −0.76 to −0.85) were found between relative activations of cortical sensorimotor areas and the severity of cervical cord damage. This study shows an abnormal pattern of movement-associated cortical activations in patients with DNO, which extends beyond the ‘classical’ sensorimotor network and also involves visual areas devoted to motion processing. The correlation found between fMRI changes and the extent of cord damage suggests that such functional cortical changes might have an adaptive role in limiting the clinical outcome of DNO structural pathology.

Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis

Devic's neuromyelitis optica (NMO) associates optic neuritis and myelopathy without other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS). However, there have been no previous studies comparing these two pathologies and it is still unclear if NMO is a separate entity or a subtype of MS. In the present study, we compared a series of NMO patients with a series of MS patients for whom optic neuritis or myelopathy was the presenting symptom, in order to determine the place of NMO in the spectrum of MS. We retrospectively studied 30 patients diagnosed with NMO and we compared these patients with 50 consecutive MS cases revealed by optic neuritis or acute myelopathy. MS patients were only included if a relapse occurred demonstrating time and space dissemination. We compared the two groups in terms of clinical presentation, laboratory findings (MRI and CSF) and clinical outcome. NMO patients were older and more frequently women than MS patients but the difference was not significant. CSF and MRI data were clearly different: oligoclonal bands (OCB) were found in 23% of NMO cases and 88% of MS (P < 0.001), abnormal brain MRI data were observed in 10% of NMO cases and 66% of MS (P < 0.001) and a large spinal cord lesion was observed in 67% of NMO cases and 7.4% of MS cases (P < 0.001). Clinical outcome was evaluated as more severe in the NMO group (P < 0.001). On the basis of clinical data, all NMO patients but three had dissemination in time and space. When we included MRI parameters, only two of the NMO patients met criteria for MS and one of the MS patients met criteria for NMO. Our study demonstrates that NMO and MS should be considered as two different entities. The respective criteria for NMO and MS were able to distinguish these two pathologies but only when MRI data were applied. This finding could have implications for future therapeutic trials.

Devic's neuromyelitis optica: study of nine cases.

Multiple sclerosis (MS) is by far the most popular diagnosis for patients with multifocal neurological disease. Owing to demyelinating inflammatory non-necrotic plaques of the white matter, MS can give remitting symptoms of virtually every part of the central nervous system. Corticosteroids are usually helpful. Devic's neuromyelitis optica (DNMO) is a neurological disease involving only the optic nerves and the spinal cord, where demyelination evolves towards necrosis and atrophy; the prognosis is poor and no satisfactory treatment is known. The objectives of this study are to describe clinical, biological, pathological and radiological data of patients with DNMO and to differentiate DNMO from MS. We studied the files of 14 patients diagnosed with possible DNMO in three French hospitals between 1980 and 1999 and reviewed the literature. Nine patients were included as definite DNMO. Five were excluded because they did not fulfil the diagnostic criteria. For the nine patients with definite DNMO, DNMO was either monophasic or multiphasic. The prognosis was generally poor: two patients died and five others developed severe disability such as blindness, para or quadriplegia or both. Cerebrospinal fluid study and neuroimaging were essential to confirm the diagnosis of DNMO. Various immunosuppressive treatments generally failed to benefit the patients. In the literature (as well as our 14 initial patients) only a few cases of patients described as suffering from DNMO fulfilled the diagnostic criteria. The others showed evidence that another disease like MS was involved. We stress that inclusion and exclusion criteria have to be kept in mind to differentiate clearly DNMO from MS and other central nervous system white matter diseases.

Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica.

Lucchinetti CF, Mandler RN, McGavern D, et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica.

A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica.

Devic's disease [neuromyelitis optica (NMO)] is an idiopathic inflammatory demyelinating disease of the CNS, characterized by attacks of optic neuritis and myelitis. The mechanisms that result in selective localization of inflammatory demyelinating lesions to the optic nerves and spinal cord are unknown. Serological and clinical evidence of B cell autoimmunity has been observed in a high proportion of patients with NMO. The purpose of this study was to investigate the importance of humoral mechanisms, including complement activation, in producing the necrotizing demyelination seen in the spinal cord and optic nerves. Eighty-two lesions were examined from nine autopsy cases of clinically confirmed Devic's disease. Demyelinating activity in the lesions was immunocytochemically classified as early active (21 lesions), late active (18 lesions), inactive (35 lesions) or remyelinating (eight lesions) by examining the antigenic profile of myelin degradation products within macrophages. The pathology of the lesions was analysed using a broad spectrum of immunological and neurobiological markers, and lesions were defined on the basis of myelin protein loss, the geography and extension of plaques, the patterns of oligodendrocyte destruction and the immunopathological evidence of complement activation. The pathology was identical in all nine patients. Extensive demyelination was present across multiple spinal cord levels, associated with cavitation, necrosis and acute axonal pathology (spheroids), in both grey and white matter. There was a pronounced loss of oligodendrocytes within the lesions. The inflammatory infiltrates in active lesions were characterized by extensive macrophage infiltration associated with large numbers of perivascular granulocytes and eosinophils and rare CD3(+) and CD8(+) T cells. There was a pronounced perivascular deposition of immunoglobulins (mainly IgM) and complement C9neo antigen in active lesions associated with prominent vascular fibrosis and hyalinization in both active and inactive lesions. The extent of complement activation, eosinophilic infiltration and vascular fibrosis observed in the Devic NMO cases is more prominent compared with that in prototypic multiple sclerosis, and supports a role for humoral immunity in the pathogenesis of NMO. Based on this study, future therapeutic strategies designed to limit the deleterious effects of complement activation, eosinophil degranulation and neutrophil/macrophage/microglial activation are worthy of further investigation.

Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile

Devic's neuromyelitis optica (NMO) associates optic neuritis and myelitis without any other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS), optic neuritis and myelitis being the inaugural symptom in 20% and 5% of MS cases, respectively. The aim of our study was to compare a new NMO cohort with recent studies and to try to determine the place of NMO in the spectrum of MS. We retrospectively studied 13 patients with a complete diagnostic workup for NMO. We compared our data with the most recent studies on NMO and with the criteria proposed by Wingerchuck et al. [Neurology 53 (1999) 1107]. We also determined whether these patients fulfilled the diagnostic criteria for MS. Thirteen patients (10 women and three men, with a mean age of 37.4 years) were included in the study. We found similar results to previously published data, except for an association with vasculitis in 38% of our cases. All but three of the patients fulfilled the clinical criteria for MS and two patients fulfilled both clinical and MRI criteria for MS. However, if we applied more restrictive criteria concerning spinal cord and brain MRI and CSF, none of our NMO patients fulfilled the MS diagnostic criteria. NMO might therefore be differentiated from MS by the application of more stringent criteria. Furthermore, all NMO patients should be investigated for vasculitis, even those with no history of systemic disease.

Non-demyelinating optic neuropathy: clinical entities.

Alternative causes of optic neuritis (ON), other than primary demyelination or non-demyelinating optic neuropathies which can mimic acute ON, should be rigorously considered if a patient with presumed ON does not follow the typical clinical course or has a normally appearing brain on magnetic resonance imaging. A thorough differential diagnosis includes viral and bacterial optic neuropathies, ischemic optic neuropathies, Devic's neuromyelitis optica, compressive or infiltrative optic neuropathies, Leber's hereditary optic neuropathy and toxic and deficiency optic neuropathies. All patients should undergo a complete neuroophthalmological examination to help exclude other diseases mimicking ON. Atypical clinical cases of optic neuropathy require further specific laboratory, neurophysiological and imaging tests to make a correct and early diagnosis.

Detection of brain-specific autoantibodies to myelin oligodendrocyte glycoprotein, S100β and myelin basic protein in patients with Devic's neuromyelitis optica

Neuromyelitis optica (NMO) is a rare syndrome characterized by the combination of acute optic neuritis and transverse myelitis, usually not seen in Multiple Sclerosis (MS) and other demyelinating syndromes of the central nervous system (CNS). A high prevalence of various autoantibodies has been described in patients with NMO suggesting a polyclonal activation of the humoral immune system. We examined autoantibody responses to myelin (MBP, MOG with isotypes and epitopes) and astroglial (S100β) antigens in four patients with NMO by ELISA and Immunoblot. All patients showed a positive anti-MOG response, with one showing reaction to the MOG epitope corresponding to amino acid sequence 63–87. MBP-autoantibodies were only detected in two and S100β-autoantibodies in one patient. Despite the limited number of samples, these findings suggest a predominant anti-MOG rather than anti-MBP or anti-S100β autoantibody response in NMO, though no NMO-specific antibody pattern was found, which is in keeping with a widespread acute immune activation, including a strong B-cell response.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in cerebrospinal fluid differ in multiple sclerosis and Devic's neuromyelitis optica.

Matrix metalloproteinases (MMPs) are increased in the CSF of patients with multiple sclerosis. Devic's neuromyelitis optica (DNO) is a demyelinating syndrome that involves the optic nerve and cervical cord but differs pathologically from multiple sclerosis. Therefore, we hypothesized that the type of inflammatory reaction that causes MMPs to be elevated in multiple sclerosis would be absent in patients with DNO. CSF was collected from 23 patients with relapsing-remitting or secondary progressive multiple sclerosis, all of whom were experiencing acute symptoms, from seven patients with DNO, and from seven normal volunteers. Diagnoses were made according to current criteria on the basis of clinical manifestations, imaging results and CSF studies. IgG synthesis was increased in the CSF of multiple sclerosis patients but not 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 of metalloproteinases (TIMPs). Zymograms showed that multiple sclerosis patients had elevated MMP-9 compared with DNO patients and controls (P: < 0.05). TIMP-1 and TIMP-2 levels were similar in all three groups. We conclude that multiple sclerosis patients have higher MMP-9 levels in the CSF than patients with DNO, which supports the different pathological mechanisms of these diseases.

Devic's neuromyelitis optica. Pathogenic characteristics and favorable response to immunotherapy in six acute patients

Devic's neuromyelitis optica. Pathogenic characteristics and favorable response to immunotherapy in six acute patients

Neuromyelitis optica (Devic's syndrome): no association with the primary mitochondrial DNA mutations found in Leber hereditary optic neuropathy.

Devic's neuromyelitis optica is a rare syndrome characterised by the combination of acute or subacute optic neuritis and transverse myelitis, in some cases considered to be a variant of multiple...

Devic's neuromyelitis optica associated with herpes-simplex infection and predominant gray rather than white matter involvement

Devic's neuromyelitis optica associated with herpes-simplex infection and predominant gray rather than white matter involvement

Devic's neuromyelitis optica: long-term follow-up and serial CSF findings in two cases

Sixteen cerebrospinal fluid (CSF) specimens serially obtained during long-term follow-up of two patients with Devic's neuromyelitis optica (DNO) were compared with 65 CSF samples from patients with multiple sclerosis (MS). By statistical analysis, the CSF profile in DNO was found to differ from that observed in MS, mainly showing pleocytosis, blood-brain barrier damage, and absence of persistent immunoglobulin G synthesis within the central nervous system. Oligoclonal bands, detected with isoelectric focusing, were present in CSF of 92% of the patients with MS, and in three CSF specimens from one patient with DNO during the first 6 months after disease onset. The bands disappeared in two subsequent samples. This finding has never been described in MS. One patient with DNO had an apparent chronic-relapsing course probably due to steroid dependence. The clinical and CSF features of our cases favour the nosographic independence of DNO and MS.