MIAMI BEACH—Neuromyelitis optica can be differentiated from multiple sclerosis (MS) by revised diagnostic criteria that include the serum autoantibody marker NMO-IgG, Dean M. Wingerchuk, MD, reported at the 57th Annual Meeting of the American Academy of Neurology. “Our results support revised clinical neuromyelitis optica diagnostic criteria. We suggest that absolute criteria include only the presence of optic neuritis and acute myelitis, removing the requirement for no clinical evidence of neurologic disease outside the optic nerves and spinal cord. Major supportive criteria should include MRI evidence of a contiguous spinal cord lesion extending over three or more vertebral segments, or NMO-IgG seropositivity. At disease onset, the combination of a brain MRI that is either normal or does not meet radiologic criteria for MS (ie, nonspecific white matter lesions) together with the extensive spinal cord lesion is the most powerful diagnostic combination, with sensitivity of 91% and specificity of 97%. The presence of T2-weighted brain MRI lesions that meet imaging criteria for MS occurs in less than 10% of patients with neuromyelitis optica. Therefore, brain MRI results are best evaluated in the context of other criteria,” Dr. Wingerchuk said. NMO-IgG is specific for neuromyelitis optica and related conditions but is consistently negative in patients with clinically confirmed MS, he noted.

DIAGNOSTIC REVISION

Dr. Wingerchuk, an Associate Professor of Neurology at the Mayo Clinic in Scottsdale, Arizona, and colleagues had previously proposed diagnostic criteria to differentiate neuromyelitis optica from MS but later decided to revise the criteria after noting that some patients with a disease course most compatible with neuromyelitis optica also had neurologic manifestations originating outside the optic nerves and spinal cord or had MS-like brain lesions on MRI. The group also found that some patients with typical MS fulfilled the original neuromyelitis optica diagnostic criteria. After the discovery of the serum marker NMO- IgG, which appears highly specific for neuromyelitis optica, they began work on the revised set of criteria.

CLINICAL CRITERIA

The investigators calculated sensitivity, specificity, and likelihood ratios for each component of the 1999 neuromyelitis optica diagnostic criteria using an independent 118-patient sample from the Mayo Clinics. The reference gold standard was the clinical diagnosis without knowledge of the NMO-IgG result. Clinical diagnosis was neuromyelitis optica (using Wingerchuk criteria except allowing nonopticospinal symptoms) versus MS. The investigators then tested combinations of individual criteria to determine which were the most accurate.

Based on clinical diagnosis, 84 patients had neuromyelitis optica and 34 had MS, Dr. Wingerchuk reported. Twenty percent of patients with neuromyelitis optica had neurologic symptoms outside the optic nerves and spinal cord. “Combinations of clinical, MRI, and NMO-IgG status have greater diagnostic utility than individual components,” he said. “The best single rule-in criterion is positive NMO-IgG (93% specific). The best single rule-out criterion is absence of long (three-segment or more) cord lesions (97% sensitive). Combinations are more powerful. Negative or non-MS brain MRI findings plus a longitudinally extensive cord lesion indicates a high likelihood of neuromyelitis optica.”

NMO-IgG PREDICTS RELAPSE IN IDIOPATHIC TRANSVERSE MYELITIS

In related work, Dr. Wingerchuk’s group also reported that the presence of NMO-IgG predicts relapse in patients with longitudinally extensive idiopathic transverse myelitis. “Nearly two thirds of the patients with neuromyelitis optica relapsed and got transverse myelitis or optic neuritis within a year. The key point is that every patient who relapsed was NMO-IgG–positive. Because of this, we would suggest that in patients with what is presumed to be an idiopathic longitudinal transverse myelitis, you consider testing for NMO-IgG, and that seropositive patients with prophylactic treatments may be candidates for prophylactic immunosuppressive treatment,” said lead author Brian G. Weinshenker, MD.

Dr. Weinshenker, Professor of Neurology at the Mayo Clinic College of Medicine in Rochester, Minnesota, reported clinical follow-up on patients with a first episode of longitudinally extensive transverse myelitis (more than three vertebral segments) who were tested for NMO-IgG and who had no evidence of subsequent relevant neurologic events prior to serologic testing. Eleven of 29 (38%) eligible patients tested seropositive for NMO-IgG. Serologic status was not influenced by age at onset, interval from disease onset until serologic testing, or length of T2-weighted spinal cord lesion. At a mean follow-up of 21.2 months in seropositive cases and 24.9 months in seronegative cases, four seropositive cases developed recurrent transverse myelitis and one developed optic neuritis. None of the seronegative patients experienced either subsequent transverse myelitis or optic neuritis.

“Longitudinally extensive transverse myelitis is an initial manifestation or limited form of neuromyelitis optica in a subset of patients. In patients with single longitudinally extensive transverse myelitis, positive tests for NMO-IgG may predict high risk for developing recurrent transverse myelitis or optic neuritis,” Dr. Weinshenker said.

The prevalence of NMO-IgG seropositivity for patients in this series who have recently experienced a single episode of longitudinally extensive idiopathic transverse myelitis was approximately 40%. The investigators suspect that nearly half of idiopathic transverse myelitis cases may represent a limited form or initial episode of neuromyelitis optica, Dr. Weinshenker noted.

NR

—Janis Kelly

Suggested Reading
Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364:2106-2112.
Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53:1107-1114.
Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol. 2005; 7:173-182.
Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of relapsing course and survival. Neurology. 2003;60:848-853.
Chan KH, Tsang KL, Fong GC, et al. Idiopathic severe recurrent transverse myelitis: a restricted variant of neuromyelitis optica. Clin Neurol Neurosurg. 2005;107:132-135.

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