Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders.

IMPORTANCE: Short transverse myelitis (STM; <3 vertebral segments) is considered noncharacteristic of neuromyelitis optica (NMO) spectrum disorders (NMOSDs). Nonappreciation of the potential for STM to occur in NMOSD may lead to increased disability from delay in diagnosis and appropriate treatment. OBJECTIVES: To determine the frequency of short lesions at the initial myelitis manifestation of NMOSD and to compare the demographic, clinical, and radiological characteristics of aquaporin-4-IgG (AQP4-IgG) seropositive and seronegative STM. DESIGN, SETTING, AND PARTICIPANTS: We reviewed the records and images of patients at the Mayo Clinic who were identified as AQP4-IgG positive from 1996 to 2014. Inclusion criteria were first STM episode, magnetic resonance imaging performed 90 days or less from symptom onset, spinal cord T2-hyperintense lesion less than 3 vertebral segments, AQP4-IgG seropositivity, and a final diagnosis of NMO or NMOSD. Patients with an initial longitudinally extensive transverse myelitis were excluded (n = 151). Patients with STM who were seronegative for AQP4-IgG among an Olmsted County population-based cohort of inflammatory demyelinating disorders of the central nervous system were used as a control group. MAIN OUTCOMES AND MEASURES: Delay to diagnosis in months, clinical and radiological characteristics, and disability measured by ambulatory status. RESULTS: Twenty-five patients who were AQP4-IgG seropositive with an initial STM represented 14% of initial myelitis episodes among patients with NMOSD. The STM episode was defined as the first manifestation of NMOSD in 10 patients (40%) preceded by optic neuritis in 13 patients (52%) and preceded by a nausea and vomiting episode in 2 patients (8%). In comparison with the excluded patients with NMOSD who had an initial longitudinally extensive transverse myelitis, delay to diagnosis/treatment was greater when initial lesions were short (P = .02). In AQP4-IgG-positive STM cases, subsequent myelitis episodes were longitudinally extensive in 92%. Attributes more common in patients with AQP4-IgG-positive STM than in 27 population-based patients with AQP4-IgG-negative STM included the following: nonwhite race/ethnicity; tonic spasms; coexisting autoimmunity; magnetic resonance imaging (central cord lesions, T1 hypointensity, and a brain inconsistent with multiple sclerosis); and cerebrospinal fluid (oligoclonal bands lacking). CONCLUSIONS AND RELEVANCE: Short transverse myelitis is not uncommon in NMOSD and, when it is present, delays diagnosis and treatment. Clinical and radiological characteristics identified in this study may help select patients with STM who are at the highest risk for an NMOSD. Short transverse myelitis does not exclude consideration of AQP4-IgG testing or NMOSD diagnosis.

Neural autoantibody clusters aid diagnosis of cancer.

PURPOSE: Clustering of neural autoantibodies in patients with paraneoplastic neurologic disorders may predict tumor type. A mathematical analysis of neural autoantibody clusters was performed in 78,889 patients undergoing evaluation for a suspected paraneoplastic autoimmune neurologic disorder. Tumor predictive autoantibody profiles were confirmed in sera from patients with histologically proven tonsillar cancer, thymoma, and lung cancer. PATIENTS AND METHODS: Of note, 78,889 patient sera were tested for 15 defined neural autoantibodies (1.2 million tests). The observed and hypothesized frequencies of autoantibody clusters were compared and their tumor associations defined. A tumor validation study comprised serum from 368 patients with a variety of tumors (thymoma, lung, or tonsil). RESULTS: Informative oncological associations included (i) thymoma in 85% of patients with muscle striational, acetylcholine receptor antibodies plus CRMP5 autoantibodies; (ii) lung carcinoma in 80% with both P/Q-type and N-type calcium channel antibodies plus SOX1-IgG; and (iii) in men, prostate carcinoma frequency more than doubled when striational and muscle AChR specificities were accompanied by ganglionic AChR antibody. In women, amphiphysin-IgG alone was associated commonly with breast carcinoma, but amphiphysin-IgG, coexisting with antineuronal nuclear autoantibody-type 1 or CRMP5-IgG, was associated with lung cancer (P < 0.0001). In the validation cohorts, many tumor-associated profiles were encountered that matched the clusters identified in the screening study (e.g., 15% of thymoma patients had striational, acetylcholine receptor antibodies plus collapsin response-mediator protein-5 autoantibodies). CONCLUSIONS: Neural autoantibodies commonly coexist in specific clusters that are identifiable by comprehensive screening. Signature autoantibody clusters may predict a patient's cancer risk and type.

Diagnostic utility of NMO/AQP4-IgG in evaluating CNS inflammatory disease in Thai patients.

Epidemiological studies in Thailand have reported that inflammatory demyelinating diseases (IDDs) commonly affect the optic nerve and spinal cord. We investigated the diagnostic utility of aquaporin (AQP)-4-IgG testing in 31 consecutive patients evaluated for CNS IDDs in 3 academic Thai hospital neurology clinics between February 2008 and January 2009. Patients were classified into 3 clinical diagnostic groups: Neuromyelitis optica (NMO, n=10) multiple sclerosis (MS, n=5) and unclassified IDD (n=16). All sera were tested blindly by cell binding (Euroimmun) assay (CBA). Sera were also tested by indirect immunofluorescence assay (IFA) and ELISA (RSR/Kronus). After initial screening by CBA, AQP4-IgG was detected in 6 NMO patients (60%); 3 of the 4 seronegative cases were receiving immunosuppressants. AQP4-IgG was detected in 13 unclassified IDD cases (81%), but in no MS cases. Cell binding assay and ELISA were more sensitive than IFA (p=0.0004). The 81% seropositivity rate in "unclassified" patients suggests that AQP4 autoimmunity accounts for a significant proportion of Thai CNS inflammatory demyelinating disease, especially those with optic neuritis or transverse myelitis, with or without abnormal brain MRI, in whom a specific diagnosis or clear-cut treatment approach is unclear.