Diagnosing NMOSD
AN AQP4-IgG ANTIBODY TEST IS RECOMMENDED FOR DIAGNOSING NMOSD1
Conducting proper antibody testing using a cell-based assay (CBA), and having a full diagnostic workup,* is important to diagnosing NMOSD and distinguishing it from other autoimmune diseases.
AQP4-IgG, aquaporin-4 immunoglobulin G.
This is a hypothetical patient.
*Diagnostic workup includes a complete medical history and physical exam, labs, electrophysiological analysis, and imaging studies.1
BECAUSE AQP4-IgG+ NMOSD IS THE MOST PREVALENT FORM
OF NMOSD, FOLLOW THESE DIAGNOSTIC CRITERIA2,3
At least 1 core clinical characteristic2:
- Optic neuritis
- Acute myelitis
- Area postrema syndrome
- Acute brain stem syndrome
- Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic magnetic resonance imaging (MRI) lesions
- Symptomatic cerebral syndrome with NMOSD-typical brain lesions
Positive test for AQP4-IgG antibodies2:
- 73% of NMOSD cases are AQP4-IgG+3
Exclusion of alternative diagnoses such as multiple sclerosis (MS), sarcoidosis, or neoplasm2:
SEVERAL TYPES OF TESTING CAN HELP DETERMINE IF A PATIENT HAS NMOSD1
Medical History and Physical Exam
Perform detailed medical history
Pay special attention to:
- Brain stem symptoms
- Neuropathic pain
- Painful tonic spasms
Laboratory Tests
Blood work
- Rule out infection and connective disorders
Cerebrospinal fluid (CSF) diagnostics
- Unlike in MS, most CSF Motor evoked potentials alterations in NMOSD present during acute events and disappear during remission
Serum AQP4-IgG testing
- Essential and most important test in the diagnosis of NMOSD
- Confirm with methodologically independent assay
Electrophysiology Analysis
Visual evoked potentials
Median and tibial somatosensory evoked potentials
Motor evoked potentials
Imaging Studies
MRI
- Image entire central nervous system (CNS)
- Central longitudinal spinal cord lesions are typical of NMOSD
Optical coherence tomography
- Useful for imaging unmyelinated CNS axons within the retina
LIVE CBA IS THE PREFERRED METHOD OF TESTING FOR AQP4-IgG+ NMOSD2,4
The likelihood of having a false-negative result with enzyme-linked immunosorbent assay (ELISA) methodology is between 1.5 and 15 times greater when compared to the CBA.
Live CBAs2
- Specifically, live CBAs are the preferred method of testing due to high sensitivity and specificity of results and a lower rate of false positives as compared to fixed CBAs and ELISA
- The International Panel for NMO Diagnosis (IPND) strongly recommends testing with CBAs whenever possible because they optimize autoantibody detection
FALSE NEGATIVES CAN HAPPEN; IF SIGNS POINT TO NMOSD, A RETEST IS RECOMMENDED4
A false negative is more likely to happen if:
- A patient is recovering from relapse
- A patient is currently on immunosuppressive therapies
- A less accurate method of testing was used
If clinical suspicion remains, you may retest 3 to 6 months after a negative result.4
References: 1. Trebst C, Jarius S, Berthele A, et al. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol. 2014;261(1):1-16. 2. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189. 3. Hamid SHM, Whittam D, Mutch K, et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J Neurol. 2017;264(10):2088-2094. 4. Waters PJ, Pittock SJ, Bennett JL, Jarius S, Weinshenker BG, Wingerchuk DM. Evaluation of aquaporin-4 antibody assays. Clin Exp Neuroimmunol. 2014;5(3):290-303. 5. Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14. 6. Kitley J, Leite MI, Nakashima I, et al. Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain. 2012;135(pt 6):1834-1849.