Diagnosis guide for clinicians

Neuromyelitis optica spectrum disorder (NMOSD): when to suspect it and what to test

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Neuromyelitis optica spectrum disorder is an inflammatory disease of the central nervous system, distinct from multiple sclerosis, that is classified by whether serum aquaporin-4 antibodies (AQP4-IgG) are found.Source 2015 IPND diagnostic criteria

The 2015 international criteria name optic neuritis, acute myelitis and area postrema syndrome, meaning intractable hiccups or nausea and vomiting, as its most common presentations.

Source 2015 IPND diagnostic criteria

In a 175-patient multicentre study, patients with both optic neuritis and myelitis waited a median of 37.5 months for the correct diagnosis. Of those with data, 42.5% were first told they had MS.

Source Jarius 2012 study of 175 patients

29.4%Patients first misdiagnosed with multiple sclerosis in a 187-patient cohort from 3 US academic centersMealy 2012 US multicenter cohort

12%AQP4-IgG positive Mayo Clinic patients whose first symptom was intractable vomiting; 75% were first evaluated for a GI causeApiwattanakul 2010 Mayo Clinic vomiting series

0.5% vs 0.1%False-positive AQP4-IgG results by ELISA versus fixed cell-based assay in sera from 1040 people in an MS cohortPittock 2014 MS cohort serology study

G36.0ICD-10-CM code, neuromyelitis optica [Devic]NLM ICD-10-CM lookup

Orphanet recordORPHA:71211 ↗

Inheritance

Multigenic/multifactorial

Age of onset

Childhood, Adolescent, Adult, Elderly

Prevalence

1 to 9 per 1,000,000 annual incidence, Worldwide
1 to 9 per 100,000 point prevalence, Worldwide
1 to 9 per 100,000 point prevalence, United States

Also called

Devic disease, NMOSD

Live from Orphanet (INSERM) via Orphadata, licensed CC BY 4.0, data version 2026-06-23.

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Patterns to test Red flags Often mistaken for What to test Family screening ICD-10 codes Once confirmed For the patient

Patterns that should prompt a test for Neuromyelitis optica spectrum disorder (NMOSD)

Each sign below is common on its own, which is why Neuromyelitis optica spectrum disorder (NMOSD) is missed. Published studies describe these combinations as the picture to act on. Rows are ordered from the highest published figure to the lowest, within each kind of measure.

Where testing finds it

Share of each screened or biopsied group found to have Neuromyelitis optica spectrum disorder (NMOSD), from the cited studies. A bar spans the lowest to the highest published figure.

1
AQP4-IgG ordered on clinical suspicion+Serum tested by live cell-based assay
1371 Mayo Clinic patients tested for serum AQP4-IgG in 2018 and 2019
Of 1371 tested, 41 (3%) were positive and all 41 fulfilled the 2015 criteria; 10 seronegative patients also met criteria (Redenbaugh 2021).Redenbaugh 2021 live assay study
3%
2
A multiple sclerosis diagnosis+Serum AQP4-IgG tested by ELISA and fixed cell-based assay
1040 people in a population-representative northern California MS cohort whose sera were tested for AQP4-IgG
Only 2 of 1040 (0.2%) had neuromyelitis optica instead, both with optic neuritis and a long cord lesion; 5 ELISA positives and 1 fixed cell-based positive were false (Pittock 2014).Pittock 2014 MS cohort serology study
0.2%
3
Idiopathic nausea or vomiting+Gastroparesis or normal gastric emptying
435 patients with idiopathic nausea or vomiting in a gastroparesis research repository, 318 with gastroparesis and 117 without
AQP4-IgG was not detected in any of the 435 control patients, while 14% of 70 seropositive NMOSD patients had begun with intractable vomiting (Iorio 2013).Iorio 2013 gastroenterology study
0%

How often diagnosed patients show it

Share of patients already diagnosed who had the finding, in the group named on each row. Groups differ by age and type, so read each row with its group.

1
Intractable hiccups or nausea+Myelitis or optic neuritis soon after
35 AQP4 antibody positive patients in Sendai, Japan
Episodes occurred in 15 of 35 (43%) and preceded myelitis or optic neuritis in 54% of the 35 episodes (Takahashi 2008).Takahashi 2008 hiccup and nausea study
43%
2
An earlier diagnosis of multiple sclerosis+Severe optic neuritis or myelitis
People with NMOSD in a US cohort of 187, a 175-patient multicentre study and a Taiwanese cohort of 189
MS was the first diagnosis in 29.4% (Mealy 2012), 42.5% of those with data (Jarius 2012) and 55.0% (Hsu 2025, Chugai-funded).Mealy 2012 US multicenter cohort
29.4% to 55%
3
Acute myelitis or optic neuritis+CSF with more than 50 leukocytes/μL or with neutrophils+No oligoclonal bands
Patients with NMOSD in studies cited by the 2015 International Panel for NMO Diagnosis
CSF pleocytosis above 50 leukocytes/μL occurs in about 35%, and neutrophils in 44% of attack samples (Wingerchuk 2015).2015 IPND diagnostic criteria
35% to 44%
4
Protracted nausea, vomiting or hiccups+No accompanying neurological symptoms
199 people with NMOSD at one Dallas academic center, 71 first misdiagnosed and 128 diagnosed correctly
Protracted nausea, vomiting or hiccups alone had occurred in 32.4% of the misdiagnosed against 12.5% of the others (Smith 2023).Smith 2023 Dallas misdiagnosis study
12.5% to 32.4%
5
Intractable vomiting as the first symptom+An unrevealing GI evaluation
AQP4-IgG positive patients in 2 Mayo Clinic series
Vomiting came first in 12% (Apiwattanakul 2010) and 14% (Iorio 2013); the first evaluation was gastroenterologic in 75% of the 2010 series.Apiwattanakul 2010 Mayo Clinic vomiting series
12% to 14%
6
Intractable nausea, vomiting or hiccups for 48 hours or more+No other cause found+A dorsal medulla lesion on MRI, when present
430 AQP4-IgG positive patients in an international NMOSD database
Isolated area postrema attacks were the onset event in 7.1% to 10.3% and a later event in 9.4% to 14.5% (Shosha 2018).Shosha 2018 area postrema study
7.1% to 10.3%

Also described, without a comparable figure

Optic neuritis in both eyes at once or with acuity of 20/200 or worse + Chiasm involvement or an altitudinal field defect: The panel gives no frequency and notes that bilateral optic neuritis can occur in MS and altitudinal defects in ischemic optic neuropathy.2015 IPND diagnostic criteria
Acute myelitis with a lesion of 3 or more vertebral segments + A complete cord syndrome or paroxysmal tonic spasms: The panel calls LETM the most specific imaging feature and very uncommon in adult MS, without giving a frequency.2015 IPND diagnostic criteria

These figures describe published study groups. They are not the chance that any one patient has Neuromyelitis optica spectrum disorder (NMOSD), and bars whose ranges overlap are not in a settled order.

Red flags for Neuromyelitis optica spectrum disorder (NMOSD)

What the cited sources describe, grouped by life stage and organ. Each line links to its source.

Eye

Optic neuritis that is bilateral at once, involves the optic chiasm, causes an altitudinal field defect or leaves acuity of 20/200 or worse, which the 2015 panel calls particularly suggestive.2015 IPND diagnostic criteria
Orbital MRI showing bilateral optic nerve involvement, posterior predominance with extension into the chiasm, or a lesion over more than half the nerve length.2015 IPND diagnostic criteria
Acuity below 20/200 during an acute attack, which the German NEMOS group describes as frequent in AQP4-IgG positive NMOSD and MOGAD but rare in MS.NEMOS 2023 recommendations, part I
Optic neuritis in the second eye days or a few weeks after the first; NEMOS advises repeat eye examinations after a unilateral attack.NEMOS 2023 recommendations, part I

Spinal cord

A cord lesion spanning 3 or more vertebral segments (LETM) with acute myelitis, which the 2015 panel calls the most specific imaging feature and very uncommon in adult MS.2015 IPND diagnostic criteria
A complete rather than partial spinal cord syndrome, especially with paroxysmal tonic spasms.2015 IPND diagnostic criteria
Lesions centered on the cord gray matter with swelling, or a cervical lesion that extends up into the brainstem.2015 IPND diagnostic criteria
Short lesions do not exclude it; 7% to 14% of first myelitis attacks in AQP4-IgG positive patients did not meet the LETM definition.2015 IPND diagnostic criteria
Seropositive patients in a 175-patient study more often had cord lesions of 6 or more segments and severe weakness than seronegative patients.Jarius 2012 study of 175 patients

Gut and brainstem (area postrema syndrome)

Intractable hiccups or nausea and vomiting with no other explanation, reported in 16% to 43% of patients in studies cited by the 2015 panel.2015 IPND diagnostic criteria
Isolated area postrema attacks opened the illness in 7.1% to 10.3% of 430 AQP4-IgG positive patients in an international database.Shosha 2018 area postrema study
Across 157 episodes, nausea lasted a median of 14 days, vomiting occurred a median of 5 times a day and hiccups accompanied 65% of episodes.Shosha 2018 area postrema study
Antiemetics or IV fluids alone brought partial improvement in only 11% of 104 attacks treated that way, and 78% of patients made frequent emergency room visits.Shosha 2018 area postrema study
Intractable vomiting was the first symptom in 12% of seropositive Mayo Clinic patients, and optic neuritis or myelitis followed after a median of 11 weeks.Apiwattanakul 2010 Mayo Clinic vomiting series
Intractable hiccup and nausea occurred in 43% of 35 seropositive Japanese patients and preceded myelitis or optic neuritis in 54% of episodes.Takahashi 2008 hiccup and nausea study
Gastroscopy with biopsy, small bowel X-ray and abdominal ultrasound were noninformative in Mayo Clinic patients who presented with intractable vomiting.Iorio 2013 gastroenterology study

Who is affected

Women outnumber men by up to 10 to 1 among AQP4-IgG positive patients, and incidence peaked at about age 40 in a large European cohort.NEMOS 2023 recommendations, part I
NEMOS says the diagnosis must also be considered in children and older adults; onset after age 60 made up 20% to 28% of new cases in some cohorts.NEMOS 2023 recommendations, part I
NINDS lists women, Black Americans and people with other autoimmune disorders as more likely to be affected.NINDS disorder page
About one-quarter of patients have signs of another autoimmune disorder, such as myasthenia gravis, lupus or Sjögren's disease.MedlinePlus Genetics
NORD notes that so-called lupus myelitis is most often NMOSD coexisting with systemic lupus erythematosus.NORD rare disease report

Spinal fluid and MRI clues that point away from MS

CSF with more than 50 leukocytes/μL, seen in about 35% of patients, or with neutrophils, seen in 44% of attack samples.2015 IPND diagnostic criteria
Absent CSF-restricted oligoclonal bands; NEMOS reports bands in 20% or fewer NMO cases against more than 90% in MS.NEMOS 2023 recommendations, part I
A brain MRI without Dawson fingers, inferior temporal periventricular lesions or cortical lesions, patterns the 2015 panel says are rarely seen in NMOSD.2015 IPND diagnostic criteria

Neuromyelitis optica spectrum disorder (NMOSD) is often mistaken for

Diagnoses patients commonly carry first, and why the sources say they are confused.

First diagnosis	Why it is confused
Multiple sclerosis	Both cause optic neuritis and myelitis; 29.4% of 187 patients at 3 US centers were first misdiagnosed with MS.Mealy 2012 US multicenter cohort
Clinically isolated syndrome or stroke	Among 56 misdiagnosed Latin American patients, earlier labels were MS in 66.1%, clinically isolated syndrome in 17.9% and cerebrovascular disease in 3.6%.Carnero Contentti 2023 Latin American cohort
Gastroparesis, reflux, food poisoning or gallbladder disease	Among 44 patients who first saw a gastroenterologist for area postrema symptoms, none had the cause identified and 20% received an incorrect diagnosis.Shosha 2018 area postrema study
Unspecified viral illness	Unspecified viral illness was the diagnosis given to 4 Mayo Clinic patients whose intractable vomiting was later tied to AQP4-IgG, and gallbladder polyp to 1.Iorio 2013 gastroenterology study
Idiopathic transverse myelitis	NORD says the myelitis of NMOSD may be indistinguishable from other cases of idiopathic transverse myelitis.NORD rare disease report
Lupus or Sjögren myelitis	NEMOS lists lupus and Sjögren's syndrome as differential diagnoses and cautions that both may coexist with AQP4-IgG positive NMOSD.NEMOS 2023 recommendations, part I
ADEM, connective tissue disease or syringomyelia	These were among the first diagnoses suspected in 11 patients of a 175-patient multicentre study.Jarius 2012 study of 175 patients
MOG antibody-associated disease	NEMOS calls MOGAD the most important antibody-related differential and says some patients meet the criteria for both.NEMOS 2023 recommendations, part I
Ischemic optic neuropathy	The 2015 panel notes that altitudinal visual field defects may also result from ischemic optic neuropathy.2015 IPND diagnostic criteria

Codes patients often carry before this diagnosis

For spotting the pattern in a problem list or registry. Descriptions are checked daily against NLM's ICD-10-CM service; this is not coding advice.

Relapsing-remitting multiple sclerosis, or multiple sclerosis, unspecified G35.A, G35.D

In a US cohort, 29.4% of patients with NMOSD were first misdiagnosed with multiple sclerosis.Mealy 2012 US multicenter cohort

Unspecified optic neuritis, or retrobulbar neuritis, bilateral H46.9, H46.13

Optic neuritis that is bilateral at once or leaves acuity of 20/200 or worse is particularly suggestive, per the 2015 panel.2015 IPND diagnostic criteria

Acute transverse myelitis in demyelinating disease of central nervous system, or myelitis, unspecified G37.3, G04.91

A cord lesion of 3 or more vertebral segments is the most specific imaging feature of NMOSD in the 2015 criteria.2015 IPND diagnostic criteria

Nausea with vomiting, unspecified; vomiting, unspecified; or nausea R11.2, R11.10, R11.0

Intractable vomiting was the first symptom in 12% of seropositive Mayo Clinic patients.Apiwattanakul 2010 Mayo Clinic vomiting series

Hiccough R06.6

Hiccups accompanied 65% of area postrema episodes and lasted a median of 14 days.Shosha 2018 area postrema study

Gastroparesis K31.84

Gastroparesis was the most frequent incorrect diagnosis given by gastroenterologists for area postrema symptoms.Shosha 2018 area postrema study

Testing for Neuromyelitis optica spectrum disorder (NMOSD), step by step

The testing order the cited guidance describes, by who it applies to. It summarizes published guidance and is not a plan for any one patient.

Anyone with optic neuritis, acute myelitis, area postrema syndrome or another core characteristic

Serum AQP4-IgG
NEMOS recommends AQP4-IgG testing in all patients with 1 of the 6 core clinical characteristics, and names serum as the specimen of choice.NEMOS 2023 recommendations, part I

Every AQP4-IgG order

Ask for a cell-based assay
The 2015 panel recommends cell-based serum assays, read by microscopy or flow cytometry, whenever possible, and says they have the best current sensitivity and specificity.2015 IPND diagnostic criteria

Patients in an acute attack

Draw blood before treatment
NEMOS says steroids, plasma exchange, immunoadsorption, immunosuppressants and IV immunoglobulin may rarely cause false-negative or ambiguous results, so samples should ideally be taken first.NEMOS 2023 recommendations, part I

Unexplained intractable nausea, vomiting or hiccups

Apply the area postrema criteria
Shosha and colleagues require symptoms for at least 48 hours, or less if MRI shows a new area postrema lesion, and exclusion of other causes.Shosha 2018 area postrema study

Everyone with suspected NMOSD

MRI of brain and spinal cord
NEMOS calls cranial and spinal MRI mandatory in the initial workup and says orbital MRI may be required in selected patients.NEMOS 2023 recommendations, part I
Lumbar puncture
NEMOS highly recommends lumbar puncture for differential diagnosis, with oligoclonal bands, cell count and differential, protein, lactate and glucose.NEMOS 2023 recommendations, part I

AQP4-IgG negative patients who meet NMOSD criteria

MOG-IgG by cell-based assay
NEMOS says these patients are to be evaluated for MOGAD, and that those who meet MOGAD criteria should no longer be given an NMOSD diagnosis.NEMOS 2023 recommendations, part I
Read MOG-IgG against the 2023 criteria
The International MOGAD Panel makes MOG-IgG a core criterion, stresses cell-based assays and says not all patients with MS should be screened.2023 International MOGAD Panel criteria

Low-titer ELISA positives or atypical presentations

Confirm an unexpected positive
The 2015 panel recommends confirmatory testing, ideally with 1 or more different AQP4-IgG assay techniques, and notes samples may need referral to a specialized laboratory.2015 IPND diagnostic criteria

Seronegative patients with a typical picture

Retest a negative result
The 2015 panel says retesting should be considered before B-cell or antibody-targeted therapies and in seronegative patients who relapse.2015 IPND diagnostic criteria

AQP4-IgG positive patients

Apply the 2015 criteria with AQP4-IgG
NMOSD is diagnosed with at least 1 of 6 core clinical characteristics, a positive AQP4-IgG test and exclusion of alternative diagnoses.2015 IPND diagnostic criteria

Seronegative patients or testing unavailable

Apply the 2015 criteria without AQP4-IgG
The panel requires 2 or more different core characteristics, at least 1 being optic neuritis, myelitis with LETM or area postrema syndrome, plus supportive MRI findings.2015 IPND diagnostic criteria

Everyone before a final diagnosis

Check for warning signs of another disease
NEMOS lists a progressive course, attack nadir in under 4 hours, worsening beyond 4 weeks, and findings that suggest sarcoidosis, cancer or chronic infection.NEMOS 2023 recommendations, part I

Confirmed NMOSD

Record serostatus
The FDA labels for Soliris, Ultomiris, Uplizna and Enspryng limit the NMOSD indication to adults who are anti-AQP4 antibody positive.FDA labels for the 4 NMOSD drugs

Where testing goes wrong

For harm avoidance, the 2015 panel wrote that observational data suggest interferon beta, natalizumab and fingolimod may worsen NMO.2015 IPND diagnostic criteria
NEMOS says beta-interferons, glatirameroids, natalizumab, alemtuzumab, sphingosine 1-phosphate receptor modulators and fumarates should not be used in patients diagnosed with NMOSD.NEMOS 2024 recommendations, part II
NEMOS calls glatirameroids merely ineffective, and says interferon beta, natalizumab, fingolimod, alemtuzumab and dimethyl fumarate have been reported to trigger severe attacks.NEMOS 2024 recommendations, part II
Palace and colleagues described a patient first diagnosed with MS who had 3 relapses in 10 months on interferon beta-1a while AQP4 antibody titers rose.Palace 2010 interferon beta case report
Kleiter and colleagues reported 5 patients given natalizumab for presumed MS; 9 relapses occurred, 4 patients gained disability and 1 died 2 months after stopping.Kleiter 2012 natalizumab case series
Min and colleagues reported extensive brain lesions during fingolimod treatment in a trial participant whose diagnosis was later changed from MS to NMOSD.Min 2012 fingolimod case report
Azzopardi and colleagues described 3 patients with NMOSD who kept relapsing after alemtuzumab; 2 died, and the authors caution against its use in NMO.Azzopardi 2016 alemtuzumab case series
Javadian and colleagues reported a single patient with severe attacks of optic neuritis and myelitis after starting dimethyl fumarate.Javadian 2021 dimethyl fumarate case report
Misdiagnosis can lead to MS treatment; 71.5% of misdiagnosed patients in a Latin American cohort were prescribed disease-modifying drugs.Carnero Contentti 2023 Latin American cohort
Interferon beta had been given to 52.6% of patients first misdiagnosed with MS in a 175-patient study, against 12.5% of those diagnosed correctly.Jarius 2012 study of 175 patients
NEMOS says ELISA, tissue immunohistochemistry and immunoprecipitation assays are less sensitive or specific and should no longer be used for routine clinical testing.NEMOS 2023 recommendations, part I
ELISA can mislead; in sera from 1040 people in an MS cohort, 5 ELISA positives and 1 fixed cell-based positive were false.Pittock 2014 MS cohort serology study
The 2015 panel cites mean sensitivity of 63% to 64% for ELISA and tissue immunofluorescence, against 76.7% for cell-based assays.2015 IPND diagnostic criteria
In a comparison on coded sera at 2 centers, sensitivity was 77% by flow cytometry, 73% by visual cell-based assay and 60% by commercial ELISA.Waters 2012 assay comparison
Across 21 assays at 15 European centres, sensitivity ranged from 51.5% to 100% and specificity from 85.8% to 100%; cell-based assays did best overall.Waters 2016 European assay comparison
In Mayo Clinic service testing, 5 of 31 sera with suspected false-negative ELISA results were positive by a live cell-based flow cytometry assay.Fryer 2014 Mayo Clinic assay study
A live cell-based assay had no false positives among 1371 Mayo Clinic patients tested, yet 10 seronegative patients still met NMOSD criteria and 7 of those had MOG-IgG.Redenbaugh 2021 live assay study
A first negative test is not final; misdiagnosed patients waited a mean of 3.9 years between a negative and a later positive live cell-based result.Smith 2023 Dallas misdiagnosis study
Mayo Clinic Laboratories cautions that AQP4-IgG may drop below detectable levels after IV methylprednisolone, plasmapheresis or immunosuppressants.Mayo Clinic Laboratories test catalog
NEMOS discourages broad, unselected AQP4-IgG screening of patients with MS, because it may yield an unfavorable ratio of false-positive to true-positive results.NEMOS 2023 recommendations, part I
NEMOS treats AQP4-IgG found only in CSF, IgM or IgA without IgG, and double positivity with MOG-IgG as warning signs that call for repeat testing.NEMOS 2023 recommendations, part I
MS-like white matter lesions do not exclude NMOSD; the 2015 panel notes that as many as 16% of patients fulfil Barkhof MRI criteria for MS.2015 IPND diagnostic criteria
Overdiagnosis also occurs; in a review of 68 patients with mimics, 82% did not fulfil the 2015 criteria and 5 had false AQP4-IgG positivity.Zara 2023 review of NMOSD mimics
Delay carries a cost; among 182 seropositive patients with myelitis, delay in diagnosis and preventive treatment was associated with greater disability.Mealy 2019 disability study
In a Chugai-funded Taiwanese study, 104 of 189 seropositive patients (55.0%) were first classified as MS, and they had more relapses.Hsu 2025 Taiwan study
ARUP notes that a negative AQP4-IgG result does not rule out NMOSD, because false negatives may occur during immunosuppression.ARUP Consult
Orphanet records NMOSD as ORPHA:71211 and maps it to ICD-10 code G36.0 as an exact match.Orphanet cross-references

Where to test

AQP4-IgG by flow cytometry (FACS), serum, Mayo Clinic Laboratories test NMOFS: Mayo Clinic Laboratories lists this assay for diagnosing NMOSD and distinguishing it from MS early in the course, and reports sensitivity above 80% and specificity above 99%. It is a laboratory-developed test that the FDA has not cleared or approved. AQP4-IgG is an antibody test, not a genetic test.Mayo Clinic Laboratories test catalog
AQP4-IgG and MOG-IgG by cell-based immunofluorescence, ARUP Laboratories: ARUP lists serum AQP4-IgG and MOG-IgG tests by cell-based indirect fluorescent antibody assay with reflex to titer, and a reflexive panel for autoimmune CNS demyelinating disease. ARUP calls serum the optimal specimen and says CSF testing adds little if any sensitivity.ARUP Consult

Family screening and referral

Who else in the family

NMOSD is usually not inherited, and no genes associated with it have been identified, according to MedlinePlus Genetics.MedlinePlus Genetics
Familial occurrence was estimated at about 3% of patients in a report of 12 families, and familial disease was indistinguishable from sporadic disease.Matiello 2010 familial NMO series
NORD reports a personal or family history of autoimmunity in 50% of cases, while more than 95% of patients have no affected relative.NORD rare disease report
The 2015 panel requires at least 1 clinical attack for diagnosis and says the natural history of asymptomatic AQP4-IgG seropositivity is poorly understood.2015 IPND diagnostic criteria

Who to refer to

Misdiagnosed patients in a Dallas cohort waited a median of 4.2 years to see a neuroimmunology specialist, against 0.5 years for those diagnosed correctly.Smith 2023 Dallas misdiagnosis study
The same study found a median delay to MRI of 4.7 years in misdiagnosed patients against 0.3 years.Smith 2023 Dallas misdiagnosis study
Shosha and colleagues note that area postrema syndrome is frequently evaluated by gastroenterologists and that symptoms led to hospital admission in 59 of 100 patients.Shosha 2018 area postrema study
Iorio and colleagues, writing for gastroenterologists, say AQP4-IgG testing should be considered in unexplained intractable vomiting, before optic neuritis or myelitis develops.Iorio 2013 gastroenterology study
NEMOS reports complete remission in up to 40% of patients when apheresis began within 2 days of attack onset, against 3.7% when it began at 7 days or later.NEMOS 2024 recommendations, part II
NINDS points patients to the Guthy-Jackson Charitable Foundation and The Sumaira Foundation for information.NINDS disorder page

Find a specialist by state

From the CMS NPI Registry, a public directory of US clinicians by registered specialty. A listing is not an endorsement and says nothing about experience with Neuromyelitis optica spectrum disorder (NMOSD); patient organizations and academic centers can often name experienced clinicians.

ICD-10-CM codes for Neuromyelitis optica spectrum disorder (NMOSD)

For orders, referrals and prior authorization. Each code is checked daily against NLM's ICD-10-CM service.

G36.0Neuromyelitis optica [Devic]Current in NLM's ICD-10-CM listNLM ICD-10-CM lookup

Once the diagnosis is confirmed

Neuromyelitis optica spectrum disorder (NMOSD) drugs for prescribers2 prescribing guides, side by side: Enspryng, Uplizna. The page also lists 2 other FDA-approved medicines without a guide yet.Open trials: 61Screen a de-identified patient against every recruiting Neuromyelitis optica spectrum disorder (NMOSD) study on ClinicalTrials.gov.Patient and family pageThe plain-language Neuromyelitis optica spectrum disorder (NMOSD) page, with trials, treatments and help paying.

For the patient: why your doctor ordered this test

Plain language a patient can read or take home.

Your doctor ordered these tests because your symptoms can be a sign of neuromyelitis optica spectrum disorder, often called NMOSD. It is a rare illness in which the immune system attacks the nerves of the eyes, the spinal cord and sometimes the brain.

NMOSD can cause sudden loss of vision with eye pain, weakness or numbness in the arms and legs, or trouble with the bladder. In some people it starts with hiccups, nausea or vomiting that will not stop and that stomach tests cannot explain.

The main test is a blood test for an antibody called aquaporin-4, or AQP4. Your doctor may also order MRI scans, a test of spinal fluid and a second antibody test called MOG. If you have already had steroids or other treatment, tell your doctor, because treatment can change the result.

NMOSD can look like multiple sclerosis, but it is a different disease and is treated differently, so getting the right name for it is important. It usually does not run in families. A negative blood test does not always rule it out, and doctors or health care professionals may repeat it.

Questions clinicians ask about Neuromyelitis optica spectrum disorder (NMOSD) testing

Which combinations of findings should prompt testing for neuromyelitis optica spectrum disorder (NMOSD)?

In published screening and biopsy studies, the highest yields came from AQP4-IgG ordered on clinical suspicion plus serum tested by live cell-based assay (3% of 1371 Mayo Clinic patients tested for serum AQP4-IgG in 2018 and 2019), and from a multiple sclerosis diagnosis plus serum AQP4-IgG tested by ELISA and fixed cell-based assay (0.2% of 1040 people in a population-representative northern California MS cohort whose sera were tested for AQP4-IgG). Among patients already diagnosed, the most common combination began with intractable hiccups or nausea, seen in 43% of 35 AQP4 antibody positive patients in Sendai, Japan. These figures describe study groups, not any one patient's chance of having neuromyelitis optica spectrum disorder (NMOSD).

How often is NMOSD misdiagnosed as multiple sclerosis?

Published cohorts report an initial wrong diagnosis in 12% to 55.0% of patients, most often MS. MS was the first label in 29.4% of 187 US patients, 42.5% of patients with data in a 175-patient multicentre study and 55.0% of 189 Taiwanese patients. In a Latin American cohort, 12% were misdiagnosed, and 66.1% of those had been called MS.

Which AQP4-IgG assay is preferred, cell-based or ELISA?

Cell-based assays are preferred, with a pooled mean sensitivity of 76.7% against 63% to 64% for ELISA in the 2015 international criteria paper. In an MS cohort of 1040 sera, false positives ran 0.5% by ELISA and 0.1% by fixed cell-based assay. NEMOS says ELISA should no longer be used for routine clinical testing.

What are the 2015 diagnostic criteria for NMOSD?

With a positive AQP4-IgG test, 1 of 6 core clinical characteristics is enough once other diagnoses are excluded. The 6 are optic neuritis, acute myelitis, area postrema syndrome, acute brainstem syndrome, a diencephalic syndrome such as symptomatic narcolepsy, and a cerebral syndrome with typical lesions. Without AQP4-IgG, the panel requires 2 different core characteristics plus supportive MRI findings.

When do intractable hiccups or vomiting suggest NMOSD?

Proposed criteria ask for symptoms lasting at least 48 hours with other causes excluded, or less with a new area postrema lesion on MRI. Intractable vomiting was the first symptom in 12% to 14% of AQP4-IgG positive Mayo Clinic patients. AQP4-IgG was not found in any of 435 patients with idiopathic nausea or vomiting tested as controls.

Which MS drugs have been reported to worsen NMOSD?

NEMOS names 5 that have been reported to trigger severe attacks: interferon beta, natalizumab, fingolimod, alemtuzumab and dimethyl fumarate. The evidence is case reports and small case series. The reports cited here cover 1 patient on interferon beta-1a, 5 on natalizumab with 9 relapses, 1 on fingolimod, 3 on alemtuzumab and 1 on dimethyl fumarate. The 2015 international panel cited observational data on interferon beta, natalizumab and fingolimod.

Sources

International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85(2):177-189 (Wingerchuk DM, Banwell B, Bennett JL et al for the International Panel for NMO Diagnosis; panel supported by the Guthy-Jackson Charitable Foundation, and several authors report ties to Alexion, MedImmune, Chugai and other drugmakers), via PubMed Central, 2015-06-19.
Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis. Journal of Neurology 2023;270(7):3341-3368 (Jarius S, Aktas O, Ayzenberg I et al; no specific funding, and several authors report fees from Alexion, Roche, Horizon and other drugmakers), via PubMed Central, 2023-04-06.
Update on the diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part II: Attack therapy and long-term management. Journal of Neurology 2024;271(1):141-176 (Kümpfel T, Giglhuber K, Aktas O et al; no specific funding, and several authors report fees from Roche, Alexion, Horizon and other drugmakers), via PubMed Central, 2023-09-07.
Area postrema syndrome: Frequency, criteria, and severity in AQP4-IgG-positive NMOSD. Neurology 2018;91(17):e1642-e1651 (Shosha E, Dubey D, Palace J et al; funded in part by the NIH, the Guthy-Jackson Charitable Foundation, Mayo Clinic and Alexion Pharmaceuticals), via PubMed Central, 2018-09-26.
Intractable vomiting as the initial presentation of neuromyelitis optica. Annals of Neurology 2010;68(5):757-761 (Apiwattanakul M, Popescu BF, Matiello M et al), via PubMed abstract; funding and disclosures not seen, 2010-11.
Intractable nausea and vomiting from autoantibodies against a brain water channel. Clinical Gastroenterology and Hepatology 2013;11(3):240-245 (Iorio R, Lucchinetti CF, Lennon VA et al; supported by the Guthy-Jackson Charitable Foundation, the NIH and Mayo Clinic, and some authors may accrue revenue from AQP4 antibody patents), via PubMed Central, 2012-12-01.
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Factors associated with the misdiagnosis of neuromyelitis optica spectrum disorder. Multiple Sclerosis and Related Disorders 2023;70:104498 (Smith AD, Moog TM, Burgess KW, McCreary M, Okuda DT; senior author reports consulting for Alexion, Genentech, Viela Bio and other drugmakers), via PubMed abstract, 2023-01-02.
Frequency of NMOSD misdiagnosis in a cohort from Latin America: Impact and evaluation of different contributors. Multiple Sclerosis Journal 2023;29(2):277-286 (Carnero Contentti E, López PA, Criniti J et al), via PubMed abstract; funding and disclosures not seen, 2022-12-01.
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Long-term disability in neuromyelitis optica spectrum disorder with a history of myelitis is associated with age at onset, delay in diagnosis/preventive treatment, MRI lesion length and presence of symptomatic brain lesions. Multiple Sclerosis and Related Disorders 2019;28:64-68 (Mealy MA, Mossburg SE, Kim SH et al; supported by the NIH, and some authors report fees from drugmakers), via PubMed abstract and PubMed Central PMC6397677, 2018-12-09.
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Development of extensive brain lesions following fingolimod (FTY720) treatment in a patient with neuromyelitis optica spectrum disorder. Multiple Sclerosis Journal 2012;18(1):113-115 (Min JH, Kim BJ, Lee KH), via PubMed abstract; funding and disclosures not seen, 2011-12-06.
Alemtuzumab use in neuromyelitis optica spectrum disorders: a brief case series. Journal of Neurology 2016;263(1):25-29 (Azzopardi L, Cox AL, McCarthy CL, Jones JL, Coles AJ), via PubMed abstract; funding and disclosures not seen, 2016-01.
Severe Relapses of Neuromyelitis Optica Spectrum Disorder During Treatment With Dimethyl Fumarate. Clinical Neuropharmacology 2021;44(1):21-22 (Javadian N, Magrouni H, Ghaffarpour M, Ranji-Burachaloo S; no conflicts of interest declared), via PubMed abstract, 2021-01.
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AQP4 autoantibody assay performance in clinical laboratory service. Neurology Neuroimmunology and Neuroinflammation 2014;1(1):e11 (Fryer JP, Lennon VA, Pittock SJ et al; supported by the NIH and the Guthy-Jackson Foundation, and some authors hold AQP4 antibody patents), via PubMed abstract, 2014-05-22.
Seroprevalence of aquaporin-4-IgG in a northern California population representative cohort of multiple sclerosis. JAMA Neurology 2014;71(11):1433-1436 (Pittock SJ, Lennon VA, Bakshi N et al), via PubMed abstract; funding and disclosures not seen, 2014-11.
Diagnostic value of aquaporin-4-IgG live cell based assay in neuromyelitis optica spectrum disorders. Multiple Sclerosis Journal Experimental, Translational and Clinical 2021;7(4):20552173211052656 (Redenbaugh V, Montalvo M, Sechi E et al; no funding received, and some authors report Alexion research funding), via PubMed abstract, 2021-11-26.
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Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. Lancet Neurology 2023;22(3):268-282 (Banwell B, Bennett JL, Marignier R et al), via PubMed abstract; funding and disclosures not seen, 2023-01-24.
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A reference for licensed professionals, checked against its sources on November 11, 2026. It summarizes what the cited guidance says and does not tell anyone how to diagnose or treat a specific patient. Guidelines change; the current guideline and the treating clinician's judgment govern. Trial Friend is an independent information service, not a medical provider.