Curr Rheumatol Rep (2016) 18:54

DOI 10.1007/s11926-016-0599-3

VASCULITIS (LR ESPINOZA, SECTION EDITOR)

Neuromyelitis Optica (Devic’s Syndrome): an Appraisal

Teresa M. Crout 1 & Laura P. Parks 1 & Vikas Majithia 1

# Springer Science+Business Media New York 2016

Abstract Neuromyelitis optica (NMO) and neuromyelitis possible with high-dose intravenous methylprednisolone
optica spectrum disorders (NMOSD), previously known as −1 gram daily for three to five consecutive days and in some
Devic’s syndrome, are a group of inflammatory disorders of cases, plasma exchange should be used. It is recommended that
the central nervous system (CNS) characterized by severe, every patient with NMOSD be started on an immunosuppressive
immune-mediated demyelination and axonal damage, pre- agent, such as, azathioprine, methotrexate, or mycophenolate
dominantly targeting optic nerves and the spinal cord typically and in some cases, rituximab, soon after the acute attack and
associated with a disease-specific serum NMO-IgG antibody usually be treated for about 5 years after the attack. These
that selectively binds aquaporin-4 (AQP4). The classic and advances have helped improve the prognosis and outcome in
best-defined features of NMOSD include acute attacks of bi- these disorders.
lateral or rapidly sequential optic neuritis (leading to visual
loss) or transverse myelitis (often causing limb weakness
Keywords Neuromyelitis optica . Devic’s syndrome .
and bladder dysfunction) or both with a typically relapsing
Aquaporin-4 antibody . Optic neuritis . Longitudinally
course. The diagnosis of NMO/NMOSD requires a consistent
extensive transverse myelitis . Central nervous system
history and examination with typical clinical presentations,
demyelination . Diagnosis . Treatment
findings on spinal cord neuroimaging with MRI, cerebrospi-
nal fluid analysis along with determination of AQP4-IgG se-
rum autoantibody status, and exclusion of other disorders.
Two major advances in this field has been the development Introduction
of diagnostic criteria and treatment recommendations.
Consensus diagnostic criteria have been established and were Neuromyelitis optica (NMO) and neuromyelitis optica spec-
recently revised and published in 2015, enhancing the ability trum disorders (NMOSD) are a group of inflammatory disor-
to make a diagnosis and appropriately evaluate these disor- ders of the central nervous system (CNS) characterized by
ders. Expert recommendations and uncontrolled trials form severe, immune-mediated demyelination and axonal damage,
the basis of treatment guidelines. All patients with suspected predominantly targeting optic nerves and the spinal cord. The
NMOSD should be treated for acute attacks as soon as most appropriate nomenclature of these disorders is
BNMOSD^ instead of neuromyelitis optica or previously
known Devic’s syndrome/disease, as there are a number of
This article is part of the Topical Collection on Vasculitis slightly different variations of the clinical presentation of these
disorders typically associated with a disease-specific serum
* Teresa M. Crout NMO-immunoglobulin G (IgG) antibody that selectively
tcrout@umc.edu binds aquaporin-4 (AQP4). In the past, NMOSD were consid-
ered to be variants of multiple sclerosis due to similarity in
1
Division of Rheumatology, Department of Medicine, University of
manifestations. It is now clear that these disorders are a dis-
Mississippi Medical Center, 2500 N. State Street, tinct clinical entity presenting with neurological manifesta-
Jackson, MS 39216, USA tions associated with involvement of the spinal cord and optic
54 Page 2 of 9 Curr Rheumatol Rep (2016) 18:54

nerves in presence of serum NMO-IgG antibody. In this arti- with systemic autoimmune disorders and tend to have a num-
cle, NMO and NMOSD are used interchangeably. ber of other autoantibodies [17•, 18]. In one cohort of 78
patients with NMO, seropositivity for antinuclear antibodies
(ANA) and Sjögren’s syndrome A/Sjögren’s syndrome B
Background (SSA/SSB) was found in 53 and 17 %, respectively [18].
This is quite relevant to the rheumatologists involved in care
Devic and Gault, in 1894, first described a series of patients of these individuals and can make the diagnosis and treatment
with a monophasic course of bilateral (or rapidly sequential) quite challenging.
optic neuritis and myelitis [1–3]. Devic and Gault also coined
the term neuro-myélite optique aiguë [1, 3]. In 1907, the
Turkish physician Acchioté suggested naming the syndrome Epidemiology
after Devic [4••]. The description by Devic and Gault sug-
gested the disease to have a severe initial clinical manifesta- The prevalence of NMOSD in various studies ranges from 0.5
tion and significant disability in a monophasic pattern unlike to 4 per 100,000 population [19••, 20–22]. Recurrent NMO is
multiple sclerosis. Subsequently, it remained hard to distin- typically a disease of women and afflicts them up to ten times
guish from multiple sclerosis due to similar clinical presenta- more commonly than men [19••, 20, 23]. A similar difference
tion both at onset and over the course as well as lack of a clear in incidence or monophasic NMO has not been described.
distinguishing feature. It was felt that NMO and multiple scle- NMO can affect any age group but median age of the disease
rosis represented one disease entity, with variable phenotypes onset is in 30s [19••, 20, 22]. In contrast, multiple sclerosis has
and expression. This notion, however, was debunked with a median age in 20s and is about twice more likely in women.
discovery and description of a disease-specific serum NMO- NMO is usually sporadic, though a few familial cases have
IgG antibody that selectively binds AQP4 in 2004 [5]. Further been reported. Ethnic pattern of the NMO suggests a predilec-
evidence continues to suggest that NMO is distinct from clas- tion for minorities although the exact incidence here remains
sic relapsing-remitting multiple sclerosis with respect to path- debatable.
ogenesis, imaging features, biomarkers, neuropathology, and
response to treatment.
Clinical Presentation and Features

Pathogenesis The classic and best-defined features of NMO include acute

attacks of bilateral or rapidly sequential optic neuritis usually
No definite cause for NMO and NMO spectrum disorders has leading to visual loss or transverse myelitis, presenting with
been found. In genetically predisposed individuals, an un- limb weakness, bladder dysfunction, and sensory loss or si-
known trigger causes activation of an autoimmune inflamma- multaneous presentation of both optic neuritis and transverse
tory cascade directed against central nervous system, usually myelitis, with a typically relapsing course [1, 24, 25•, 26].
spinal cord and optic nerves, leading to demyelination and Other NMOSD typically present with a variation of these
axonal injury [6]. Both gray and white matters are targets of two major clinical features or some other less common pre-
the inflammatory process in NMO spectrum disorders and are sentation [26]. These are the patients who have neurological
involved during the disease process [7]. NMO is primarily an symptoms similar to the classic NMO but do not fit the typical
antibody-mediated disorder mediated mainly by humoral im- presentation. They are usually classified/diagnosed under the
mune system [8, 9]. In a vast majority of patients, NMO spec- heading of NMOSD. It remains unclear at this time, whether
trum disorders are mediated by NMO-IgG antibody, which is these disorders are a subset of NMO or entirely different set of
also referred to as the AQP4 autoantibody. Currently, avail- disorders with possibly a different underlying antibody or a
able evidence suggests that serum anti-AQP4 titers correlate different pathogenesis. These disorders are outlined in
with clinical disease activity, drop after immunosuppressive Table 1.
treatment, and remain low during remissions [10–13]. The As highlighted above, a progressive, relapsing disease is
inflammatory process in NMO primarily targets astrocytes seen in the majority of cases of NMO. A monophasic course
due to high prevalence of AQP4 in their foot processes at accounts for the remaining 10 % and is more often associated
the blood brain barrier [14, 15•]. Histopathologic examination with simultaneous optic neuritis (ON) and myelitis. Attacks of
of NMO lesions shows immunoglobulin and complement de- optic neuritis and myelitis are often more severe and, if un-
posits in a characteristic vasculocentric rim and rosette pattern treated, remission is poorer than in MS, which leads to a faster
around hyalinized blood vessels, suggesting its direct involve- accrual of irreversible neurological disability. Attacks most
ment in initiation and/or propagation of inflammatory process often occur over days, with variable degrees of recovery over
[9, 16]. NMO spectrum disorders are frequently associated weeks to months [27••]. A progressive course seems to be
Curr Rheumatol Rep (2016) 18:54 Page 3 of 9 54

Table 1 Neuromyelitis optica (NMO)/neuromyelitis optica spectrum disorders (NMOSD)

Classic NMO (meeting core diagnostic criteria)

Limited or partial forms of NMO:
• Single or recurrent episodes of myelitis, usually, but not always, involving longitudinally extensive spinal cord lesions (i.e., a spinal cord lesion on MRI
involving >3 vertebral segments)
• Single or recurrent unilateral or simultaneous bilateral optic neuritis
• Optic neuritis or transverse myelitis in isolation
Asian optic-spinal multiple sclerosis
Optic neuritis or longitudinally extensive spinal cord lesions associated with systemic autoimmune disease
Optic neuritis or myelitis associated with distinct brain MRI lesions typical of NMO
AQP4 antibody positivity with single or recurrent attacks of optic neuritis, myelitis, brainstem syndromes, or brain syndromes

extremely uncommon [27••]. No single clinical feature is disorders include encephalopathy and posterior reversible
disease-specific but some are highly characteristic. Central leukoencephalopathy, which are bilateral hypothalamic le-
nervous system involvement outside of the optic nerves and sions leading to symptomatic narcolepsy or excessive daytime
spinal cord can also occur in patients with NMO and NMOSD sleepiness, obesity, and various autonomic manifestations
but is relatively rare. such as hypotension, bradycardia, and hypothermia [28•,
Optic neuritis is inflammation of the optic nerve and pre- 30]. Another common symptom in patients with NMOSD is
sents with vision loss and eye pain that worsens with move- truncal and lower extremity pain [31].
ment of the eye. Individual optic neuritis attacks in NMO are Children with NMO frequently present with clinical fea-
indistinguishable from isolated syndromes of optic neuritis or tures of encephalopathy and/or seizures. They may also have
multiple sclerosis, though visual loss is generally more severe lesions on brain MRI resembling those typically seen with
in NMO [26, 28•]. Optic neuritis attacks in NMO are most multiple sclerosis or acute disseminated encephalomyelitis
commonly unilateral, but a sequential optic neuritis or bilater- [32].
al simultaneous optic neuritis is highly suggestive of NMO
[28•].
Transverse myelitis is inflammatory spinal cord dysfunc- Evaluation and Diagnosis
tion, presenting in a rapid fashion over hours or days in the
absence of a structural spinal cord abnormality. NMO and The diagnosis of NMO and NMOSD requires a typical history
NMOSD are associated with severe and extensive spinal cord and examination with typical clinical presentations, findings
involvement with transverse myelitis causing clinical findings on spinal cord neuroimaging with MRI, cerebrospinal fluid
of paraplegia/quadriplegia, bladder dysfunction, and a spinal analysis along with determination of AQP4-IgG serum auto-
cord sensory level below the level of the lesion [26, 28•]. In antibody status, and exclusion of other disorders.
contrast, myelitis in multiple sclerosis tends to be incomplete The detection of AQP4-IgG antibodies is very helpful and
and asymmetric [26, 28•]. The transverse myelitis in NMOSD somewhat specific for confirming the diagnosis in appropriate
typically involves three or more contiguous vertebral seg- clinical settings. Consensus diagnostic criteria for adults have
ments on MRI, a condition termed longitudinally extensive been established and were recently revised and published in
transverse myelitis (LETM), in contrast to multiple sclerosis 2015 [29••].
[24, 26]. Spinal involvement in the form of LETM is seen in a
majority of patients with NMOSD, but involvement of shorter Diagnostic Criteria
segment of spinal cord, seen in a minority of patients, has also
been described. These recently updated international consensus diagnostic
Other common clinical findings seen in patients with criteria for adult patients represent a significant advance in
NMOSD include brainstem symptoms due to medullary in- understanding of NMO and NMOSD. An 18-member inter-
volvement, which is the area postrema clinical syndrome of national panel for NMO diagnosis was convened to develop
nausea and vomiting or hiccups, associated with medullary these evidence-based criteria using systematic literature re-
lesions [26, 29••]. Brainstem involvement may lead to acute views of all available evidence to date [29••]. There were six
neurogenic respiratory failure and death [26]. different working groups, and multiple separate electronic sur-
In addition to the central nervous system involvement char- veys were used to facilitate and achieve consensus, endorsed
acteristic of NMOSD, muscle may also be involved, present- by 2/3 panel majority. The criteria unify the concepts of NMO
ing with elevated muscle enzymes or weakness. Other mani- and NMOSD and stratify it further by serologic testing
festations that can develop with NMO and NMO spectrum (NMOSD with or without AQP4-IgG) [29••]. The criteria
54 Page 4 of 9 Curr Rheumatol Rep (2016) 18:54

base the diagnosis on the presence of six core clinical charac- & Brain MRI is often normal in patients with NMO,
teristics, AQP4 antibody status, and MRI neuroimaging fea- particularly at onset, and spinal cord MRI typically
tures [29••]. The criteria also provide additional MRI require- exhibits extensive lesions spanning three or more ver-
ments as determined by the clinical presentation for NMOSD tebral segments. In MS, brain MRI usually has an
in seronegative cases or those with unknown AQP4-IgG an- abnormality, and following findings on a T2-
tibody status [29••]. The pediatric working group also con- weighted lesion are quite helpful in differentiating
cluded that the proposed diagnostic criteria for NMOSD are these following disorders: lesion adjacent to lateral
appropriate for pediatric patients with additional consideration ventricle, inferior temporal lobe white matter lesion,
of the caveats. ovoid (i.e., BDawson finger^) periventricular lesion,
These criteria are highlighted in Table 2. and U fiber juxtacortical lesion [33•]. However, these
neuroimaging findings do not necessarily exclude the
diagnosis of NMO, as they can occur in patients with
NMO who are seropositive for AQP4 antibodies [33•].
Differential Diagnosis In addition, the brain MRI may show abnormalities in
brainstem area in NMO [34, 35].
NMO spectrum disorders have to be distinguished from a & During acute attacks of NMO, the cerebrospinal fluid
number of other diseases, which can cause central nervous (CSF) may exhibit a neutrophilic pleocytosis, but it is
system demyelination. usually (70 to 85 % of cases) negative for oligoclonal
The most important disease to differentiate is multiple scle- bands.
rosis, which is the most common disorder likely to cause de- & The detection of AQP4 antibody positivity is specific for
myelination. The distinguishing features are as follows: NMO and NMO spectrum disorders.

Table 2 Neuromyelitis optica spectrum disorders (NMOSD) diagnostic criteria for adult patients. Reprinted from [29••] by permission of Wolters
Kluwer Health, Inc./Neurology

Diagnostic criteria for NMOSD with AQP4-IgG

1. At least one core clinical characteristic
2. Positive test for AQP4-IgG using best available detection method (cell-based assay strongly recommended)
3. Exclusion of alternative diagnoses
Diagnostic criteria for NMOSD without AQP4-IgG or NMOSD with unknown AQP4-IgG status
1. At least two core clinical characteristics occurring as a result of one or more clinical attacks and meeting all of the following requirements:
a. At least one core clinical characteristic must be optic neuritis, acute myelitis with LETM, or area postrema syndrome
b. Dissemination in space (two or more different core clinical characteristics)
c. Fulfillment of additional MRI requirements, as applicable
2. Negative tests for AQP4-IgG using best available detection method or testing unavailable
3. Exclusion of alternative diagnoses
Core clinical characteristics
1. Optic neuritis
2. Acute myelitis
3. Area postrema syndrome: episode of otherwise unexplained hiccups or nausea and vomiting
4. Acute brainstem syndrome
5. Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions
6. Symptomatic cerebral syndrome with NMOSD-typical brain lesions
Additional MRI requirements for NMOSD without AQP4-IgG and NMOSD with unknown AQP4-IgG status
1. Acute optic neuritis requires brain MRI showing (a) normal findings or only nonspecific white matter lesions or (b) optic nerve MRI with T2-
hyperintense lesion or T1-weighted gadolinium-enhancing lesion extending over >1/2 optic nerve length or involving optic chiasm
2. Acute myelitis requires associated intramedullary MRI lesion extending over ≥3 contiguous segments (LETM) or ≥3 contiguous segments of focal
spinal cord atrophy in patients with history compatible with acute myelitis
3. Area postrema syndrome requires associated dorsal medulla/area postrema lesions
4. Acute brainstem syndrome requires associated periependymal brainstem lesions

AQP4 aquaporin-4, IgG immunoglobulin G, LETM longitudinally extensive transverse myelitis lesions, NMOSD neuromyelitis optica spectrum
disorders
Curr Rheumatol Rep (2016) 18:54 Page 5 of 9 54

& The myelopathy with NMO tends to be more severe than Glucocorticoids and plasmapheresis remain the two main-
with multiple sclerosis, with less likelihood of recovery. stays of therapy in the acute setting. Treatment with glucocor-
ticoids and immunosuppressive therapy is required for main-
Other disorders which need to be differentiated from tenance of remission and prevention of relapses and biologic
NMOSD include acute disseminated encephalomyelitis and response modifiers, such as rituximab hold promise in this
autoimmune diseases such as systemic lupus erythematosus, setting.
Behcet’s disease, Sjögren’s syndrome, intrathecal tumors, vas-
cular causes (e.g., spinal dural arteriovenous fistula), metabol-
Acute attacks All patients with suspected NMOSD should be
ic conditions (e.g., vitamin B12 deficiency causing subacute
treated for acute attacks, both initial and recurrent as soon as
combined degeneration of the spinal cord), and radiation ther-
possible. Initial treatment with high-dose intravenous methyl-
apy [36, 37]. The differential diagnosis is highlighted in
prednisolone −1 gram daily for three to five consecutive days
Table 3.
is usually needed [38••, 39••]. For patients with severe symp-
toms, unresponsive to glucocorticoids, plasma exchange
should be used [38••, 39••]. An initial treatment with intrave-
nous glucocorticoids plus plasma exchange may be associated
Treatment
with improved outcomes compared with glucocorticoid treat-
ment alone based on limited data [40]. Exchanges are usually
It is important to note that there are no controlled trials eval-
carried out every other day up to a total of seven exchanges.
uating the treatment of NMOSD, and treatment recommenda-
tions in this section are based upon data from observational
studies and by the consensus from clinical experience of experts Maintenance therapy There is no well-established or optimal
[38••, 39••]. therapy for the maintenance of remission and prevention of
General principles of treatment are as follows: relapse. It is however, recommended that every patient with
NMOSD be started on an immunosuppressive agent soon after
1. Humoral autoimmunity plays a major role in the pathogen- the acute attack and usually be treated for about 5 years after
esis of NMOSD, and immunosuppressive therapy targeting the the attack [38••, 39••].
humoral immunity may be beneficial. Data on the efficacy of preventive therapies is based upon
2. There is a high attack-related disability and early diagnosis, observational studies of systemic immunosuppressive agents
and intervention may offer the best chance to avoid loss of such as oral glucocorticoids, azathioprine, mycophenolate
neurological function and attain control. mofetil, methotrexate, mitoxantrone, and rituximab [38••,
3. The disease is relapsing, carries a poor prognosis, and over- 39••, 41••, 42–44, 45•, 46, 47•, 48, 49, 50•, 51•, 52•, 53].
all high risk of mortality in untreated patients and treatment Among these, oral glucocorticoids combined with azathio-
needs to be of long duration in these patients. prine, mycophenolate mofetil, and rituximab seem to have
better data than the other two agents do [38••, 39••, 41••,
42–44, 45•, 46, 47•, 48, 49, 50•, 51•, 52•, 53]. Comparative
Table 3 Differential diagnosis of NMO and NMOSD
data is not available, and all three oral agents can be used in
Multiple sclerosis treatment as initial treatment. They can reduce the relapses
Other CNS demyelinating conditions about 70–80 %, but failure rate remains high between 33
• Acute disseminated encephalomyelitis and 53 % [54••]. Initial and maintenance treatment of
Autoimmune diseases with CNS involvement seronegative disease is similar to the seropositive disease
• Systemic lupus erythematosus [38••, 39••].
• Behçet disease Other agents holding promise include tocilizumab and
• Sjögren’s syndrome eculizumab, which have been associated with improvement
• Sarcoidosis in a small number of patients with refractory NMO who failed
Infiltrative conditions one or more of the Bstandard^ treatments [55, 56•, 57•, 58•].
• Intrathecal tumors Limited observational evidence also suggests that use of
Vascular causes
intravenous immunoglobulin (IVIG) is not beneficial in treat-
• Spinal dural arteriovenous fistula
ment of acute attacks and for maintenance therapy [38••,
Metabolic conditions
39••]. In addition, treatment of NMO with interferon beta or
natalizumab has not been found to be effective and may be
• Vitamin B12 deficiency causing subacute combined degeneration of
the spinal cord harmful [59–62].
Radiation therapy Figure 1 illustrates treatment algorithm suggested by the
authors based on the currently available data.
54 Page 6 of 9 Curr Rheumatol Rep (2016) 18:54

INDUCTION

ACUTE ATTACK

PULSE STEROIDS - IV PLASMA

Methylprednisolone 1 Poor Response EXCHANGE for 7
gram for 3-5 days treatments

Good Response

Consider RITUXIMAB in non-

responders
MAINTENANCE Consider CYCLOPHOSPHAMIDE in
PREDNISONE - 60 mg/day
connective tissue disease
Taper down to lowest effective
dose

METHOTREXATE AZATHIOPRINE MYCOPHENOLATE

Target dose 15-25 mg/week or Target dose 2 mg/kg/day or Target dose 2-3 gm/day

Can consider RITUXIMAB

RELAPSE

INDUCTION THERAPY
Pulse Steroids and/or Plasma Exchange

Consider MITOXANTRONE or
CYCLOPHOSPHAMIDE for
RITUXIMAB RITUXIMAB failure
1 gm 15 days apart every 6
months

Fig. 1 NMOSD management algorithm

Prognosis and paraplegia, within 5 years and with each attack, visual,
motor, sensory, or bladder deficits accumulate [24, 65, 66].
NMOSD tend to have a poor prognosis with a number of The overall 10-year mortality is 20–25 % with median
neurological sequelae especially in relapsing disease. survival of 8 years after the diagnosis [66, 67]. The cause of
Relapses are common and may be seen in up to 90 % of death is most commonly reported to be neurogenic respiratory
patients [24, 63•, 64]. Most studies show that NMOSD have failure likely as a result of the extension of cervical lesions into
an overall poor prognosis, especially with relapsing disease the brainstem or from primary brainstem lesions [24, 67].
which is quite commonly seen in as many as 90 % of the cases Certain parameters are linked to a worse prognosis, in-
[24, 63•, 64]. Relapse tends to happen early in the disease cluding the number of relapses within the first 2 years, se-
course occurring in about 50 % of patients within the first year verity of the first attack, older age at disease onset, and
of the initial event and within 2 to 3 years in 75 % [63•]. Each possibly an association with other autoimmune disorders
attack usually causes a significant disability, such as blindness and autoantibodies [24, 64–69]. Some studies have found a
Curr Rheumatol Rep (2016) 18:54 Page 7 of 9 54

link between NMO-IgG (AQP4 autoantibody) and disease Conclusions

course/prognosis [69–71]. In one study, patients with sero-
positivity for NMO-IgG had worse final visual outcomes Previously known as Devic’s syndrome/disease, neuromyelitis
than seronegative patients had and similarly, in another optica spectrum disorders (NMOSD) is a group of inflammatory
study, 29 patients who presented with longitudinally exten- disorders of the central nervous system (CNS) characterized by
sive transverse myelitis, 55 % of the NMO-IgG seropositive severe, immune-mediated demyelination and axonal damage,
patients developed a second event as compared to none in predominantly targeting optic nerves and spinal cord typically
the seronegative patients [69, 71]. Yet another study had associated with a disease-specific serum NMO-IgG antibody
conflicting results and found similar relapse rates and dis- that selectively binds aquaporin-4 (AQP4). Recently published
ability outcomes in NMO patients who were seronegative vs. diagnostic criteria have clarified the evaluation of the disorders.
seropositive [72•]. Although controlled trials are lacking, treatment with high dose
steroids and immunosuppressives based on expert recommen-
dations has been shown to improve outcome in these disorders.

Discussion and Future Direction Compliance with Ethical Standards

Conflict of Interest The authors declare that they have no conflict of

Significant progress has been made in the field of NMO and interest.
NMOSD especially in evaluation and diagnosis with the dis-
covery of AQP4 antibody in 2004, but a number of issues Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
remain unclear. A number of disorders are classified in the
of the authors.
NMOSD, but it is not well understood whether these disorders
are a subset of NMO or entirely different set of disorders. As
the progress occurs in understanding of these disorders, we
might know further about these conditions. While it is quite
easy to make the diagnosis in patients with a classic neurolog- References
ical presentation, it may be difficult to do the same when
neurological symptoms are similar to NMO but do not fit
Papers of particular interest, published recently, have been
the classic presentation. There is no established and accepted
highlighted as:
gold standard for the diagnosis. Recently published revised
• Of importance
consensus classification criteria establish guidelines in the un-
•• Of major importance
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validated in various populations. We, at this time, do not know [French]. Congr Fr Med. 1895;1:434–9.
3. Gault F. De la neuromyelite optique aigue [thesis]. Lyon; 1894.
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