Neuromyelitis Optica IgG Research Articles

Optic neuritis and recurrent myelitis in a woman with systemic lupus erythematosus

A 38-year-old woman with systemic lupus erythematosus presented with headaches and bilateral hearing loss. Brain MRI was initially suggestive of small-vessel disease developing in the context of neuropsychiatric systemic lupus erythematosus. Several months later, the patient developed optic neuritis, followed by recurrent attacks of myelitis. MRI of the spine revealed multifocal regions of myelitis affecting the cervical spine. Serological evaluation revealed the presence of neuromyelitis optica-IgG antibodies. MRI of the brain was nondiagnostic for multiple sclerosis. Recurrent myelitis and optic neuritis, occurring in the context of neuromyelitis optica (also known as Devic's syndrome). The patient had recurrent attacks of myelitis despite treatment with pulse cyclophosphamide. After initiation of rituximab, the patient experienced symptomatic improvement and had no further attacks of opticospinal disease.

Aquaporin-4 Autoantibodies in a Paraneoplastic Context

The neuromyelitis optica IgG autoantibody (NMO-IgG) is a validated biomarker for NMO and an emerging spectrum of inflammatory central nervous system-demyelinating disorders. Its antigen is the astrocytic water channel aquaporin-4; NMO-IgG has not been described in a cancer context. To report (1) neurologic and oncologic correlates for patients incidentally identified as NMO-IgG seropositive in a blinded evaluation for paraneoplastic autoantibodies and (2) the frequency of cancer in NMO-IgG-seropositive patients. Observational, retrospective case series. Neuroimmunology Laboratory and Neurology Clinical Practice, Mayo Clinic College of Medicine. From 1998 to 2007, we detected NMO-IgG in 2 patient groups: (1) 31 patients (88% female) identified incidentally among 180 000 patients evaluated for paraneoplastic autoantibodies and (2) 141 patients identified through physician-requested serological evaluation for a suspected NMO-spectrum disorder. In the first group, clinical information was available for 28 patients (90%). An NMO-spectrum disorder was diagnosed in 26 patients (93%), of whom 6 had a neoplasm (5 carcinomas [2 breast, 1 lung, 1 thymic, and 1 uterine cervical] and 1 B-cell lymphoma) and 1 had monoclonal gammopathy. In 4 patients, NMO-related symptoms followed neoplasia detection (median, 14 [range 3-18] months), and in 2 patients, symptoms preceded neoplasia detection (by 5 and 3 months). Two patients had carcinoma (1 breast and 1 lung) without neurological evidence of an NMO-spectrum disorder. In the second group, neoplasms were recorded in 7 seropositive patients (5.0%) with a clinically diagnosed NMO-spectrum disorder: 3 carcinomas (all breast), 1 thyroid Hürthle cell, 1 carcinoid, 1 pituitary somatotropinoma, and 1 B-cell lymphoma. An eighth patient had monoclonal gammopathy. Aquaporin-4-specific IgG in some cases of NMO may reflect a paraneoplastic immune response. The clinical utility of this autoantibody as a cancer marker warrants prospective investigation.

Is Sjögren myelopathy Devic disease?

Central nervous system (CNS) involvement in Sjogren syndrome was first described as a condition resembling multiple sclerosis,1 though frequent spinal cord involvement has resulted in the term “Sjogren myelopathy” being...

Seroprevalence of Neuromyelitis Optica-IgG of Childhood Compared to Adults

The clinical and radiological characteristics and serostatus of neuromyelitis optica (NMO)-IgG in 87 children with inflammatory demyelinating CNS disorders were analyzed in a study at the Mayo Clinic, Rochester, MN, and other centers in the US, Canada, and Argentina.

Neuromyelitis Optica (NMO) Antibody Positivity in Patients with Transverse Myelitis and No Visual Manifestations

Background and Purpose: To describe a subgroup of patients with IgG antibody to Aquaporin 4 Protein (AQP4) specific to neuromyelitis optica (NMO), who did not have clinical manifestations of optic nerve involvement at the time of diagnosis. Methods: Assessment of five patients (four African Americans and one Latino) with myelitis, who were NMO IgG antibody positive, who had no detected optic nerve involvement, over a span of one to eighteen years. Results: Cerebrospinal fluid (CSF) studies showed lymphocytic pleocytosis, elevated interleukin (IL6), oligoclonal bands (OCB), myelin basic protein (MBP), and elevated albumin and IgG index. Serology showed an association with antinuclear antibody (ANA) positivity and antithyroid peroxidase (TPO) antibody. Our patients responded well to acute treatment with intravenous corticosteroids and long-term treatment with oral prednisone and azathioprine. Conclusions: The aquaporin protein autoimmune disease previously identified as neuromyelitis optica (NMO) may more correctly be identified as neuromyelitis (NM), and future diagnostic criteria should take into account the population of patients with antibody to aquaporin 4 protein, without clinically evident optic nerve pathology. Future research may indicate that the entity of NMO is a subcategory of the NM population.

The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28-May 5, 2007

The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28-May 5, 2007

Revised diagnostic criteria for neuromyelitis optica (NMO)

We analyzed neuromyelitis optica (NMO) IgG in the serum or CSF samples from 46 patients with suspected NMO (28) and limited forms of NMO (18). One hundred and fifteen samples from multiple sclerosis (MS) patients were included as controls. The final clinical diagnosis after follow-up was 16 NMO, 12 MS, 11 transverse myelitis (TM) and seven recurrent optic neuritis (RON). NMO-IgG was detected in 62.5% of NMO, 50% of the recurrent longitudinally extensive TM, 14.3% of the RON but in none of the MS patients. The authors then compared the newly revised diagnostic criteria for NMO with the criteria published in 1999, in the 28 patients with suspected NMO. The revised criteria had higher specificity, and positive and negative predictive value (83.3% vs. 25%; 87.5% vs. 62.5; 83.3% vs. 75%), but slightly lower sensitivity (87.5% vs. 93.7%). Our study confirms NMO-IgG as a highly specific marker of NMO, and the usefulness of the revised diagnostic criteria in predicting a diagnosis of NMO.

Devic's syndrome in a woman with systemic lupus erythematosus: Diagnostic and therapeutic implications of testing for the neuromyelitis optica IgG autoantibody

Devic's syndrome in a woman with systemic lupus erythematosus: Diagnostic and therapeutic implications of testing for the neuromyelitis optica IgG autoantibody

Neuromyelitis Optica IgG Status in Acute Partial Transverse Myelitis

Neuromyelitis optica (NMO) IgG is a specific marker for NMO. Furthermore, a high proportion of patients with longitudinally extensive transverse myelitis (characterized by spinal cord lesions extending 3 vertebral segments or more on magnetic resonance imaging) are seropositive for NMO-IgG and are considered to have a limited form of NMO. The NMO-IgG status in mild cases of acute partial transverse myelitis asociated with minimal magnetic resonance imaging abnormalities (spinal cord lesions <2 vertebral segments on magnetic resonance imaging) is unknown. To investigate the NMO-IgG status of patients with acute partial transverse myelitis and a normal cerebral magnetic resonance image. Observational, retrospective consecutive case series with longitudinal follow-up. Allegheny Multiple Sclerosis Treatment Center. Three groups of patients were tested for NMO-IgG. Group 1 consisted of 22 patients with acute partial transverse myelitis, group 2 consisted of 4 patients with definite NMO (by 1999 criteria of Wingerchuk et al), and group 3 consisted of 6 patients with definite multiple sclerosis. NMO-IgG status. A commercially available assay for NMO antibodies was performed at the Mayo Clinic. Testing was performed during the convalescent stage of the illness. Of the 22 patients with acute partial transverse myelitis, only 1 was seropositive for NMO-IgG at presentation. This patient subsequently developed recurrent episodes of longitudinally extensive transverse myelitis that are typicaly seen in association with NMO-IgG. Three of the 4 patients meeting criteria for NMO were seropositive. None of the patients with multiple sclerosis had NMO-IgG detected. NMO-IgG is rarely encountered in patients with acute partial transverse myelitis, which is in sharp contrast to the high frequency of this antibody in patients with NMO and longitudinally extensive transverse myelitis.

Inflammatory transverse myelitis: evolving concepts

Acute transverse myelitis is a pathogenetically heterogeneous inflammatory disorder of the spinal cord. Here we describe recent advances in inflammatory non-infectious transverse myelitis. Particular attention will be paid to the serum autoantibody marker NMO-IgG and its application to acute transverse myelitis. The recent identification of neuromyelitis optica-IgG, a novel marker of neuromyelitis optica spectrum disorders (including longitudinally extensive transverse myelitis), contributes to an evolving understanding of acute transverse myelitis. Other serological markers, such as collapsin response-mediator protein-5 -IgG and amphiphysin-IgG, predict specific cancers in the setting of a paraneoplastic acute transverse myelitis. Furthermore, novel inflammatory markers such as interleukin-6 or other proteins in their signaling pathways may represent markers of disease severity and potential therapeutic targets. Additional cerebrospinal fluid biomarkers, such as protein 14-3-3 and neuron-specific enolase, may be useful prognostic indicators in transverse myelitis. Acute transverse myelitis in children, in contrast to adults, is more likely to be longitudinally extensive, and has a better prognosis and lower likelihood of recurrence. Prognostic factors in pediatric transverse myelitis are reviewed. The recent identification of novel biomarkers associated with acute transverse myelitis has led to a better understanding of the spectrum of disorders associated with inflammatory transverse myelitis, as well as a greater appreciation of its diverse and complex pathogenetic basis.

Brain Abnormalities in Neuromyelitis Optica

Neuromyelitis optica (NMO) is a severe demyelinating disease defined principally by its tendency to selectively affect optic nerves and the spinal cord causing recurrent attacks of blindness and paralysis. Contemporary diagnostic criteria require absence of clinical disease outside the optic nerve or spinal cord. We have, however, frequently encountered patients with a well-established diagnosis of NMO in whom either asymptomatic or symptomatic brain lesions develop suggesting that the diagnostic criteria for NMO should be revised. To describe the magnetic resonance image (MRI) brain findings in NMO. Observational, retrospective case series. Patients We ascertained patients through a clinical biospecimens database of individuals with definite or suspected NMO. We included patients who (1) satisfied the 1999 criteria of Wingerchuk et al for NMO except for the absolute criterion of lacking symptoms beyond the optic nerve and spinal cord and the supportive criterion of having a normal brain MRI at onset; (2) had MRI evidence of a spinal cord lesion extending 3 vertebral segments or more (the most specific nonserological feature to differentiate NMO from MS); and (3) were evaluated neurologically and by brain MRI at the Mayo Clinic. Magnetic resonance images were classified as normal or as abnormal with either nonspecific, multiple sclerosis-like or atypical abnormalities. We evaluated whether brain lesions were symptomatic and analyzed the neuropathologic features of a single brain biopsy specimen. Sixty patients (53 women [88%]) fulfilled these inclusion criteria. The mean +/- SD age at onset was 37.2 +/- 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 were nonspecific, but 6 patients (10%) had multiple sclerosis-like lesions, usually asymptomatic. Another 5 patients (8%), mostly children, had diencephalic, brainstem or cerebral lesions, atypical for multiple sclerosis. When present, symptoms of brain involvement were subtle, except in 1 patient who was comatose and had large cerebral lesions. Asymptomatic brain lesions are common in NMO, and symptomatic brain lesions do not exclude the diagnosis of NMO. These observations justify revision of diagnostic criteria for NMO to allow for brain involvement.

Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis

We investigated whether neuromyelitis optica (NMO) IgG seropositivity at the initial presentation of longitudinally extensive transverse myelitis (LETM) predicts relapse of myelitis or development of optic neuritis. Prospective study of patients with initial LETM who were tested for the presence of NMO-IgG. Eleven of 29 patients (37.9%) were seropositive after a first attack of LETM spanning three or more vertebral segments on magnetic resonance imaging. Of 23 patients followed up for 1 year, none of 14 who were seronegative experienced a relapse or developed optic neuritis. Of 9 seropositive patients, 5 developed a second event: 4 of 9 (44%) developed recurrent transverse myelitis and 1 of 9 (11%) developed optic neuritis (p = 0.004). LETM represents an inaugural or limited form of NMO in a high proportion of patients. The 40% of patients who are seropositive for NMO-IgG are at high risk for relapse.