Delhi Journal of Ophthalmology

Comparative Study of Spectrum of Neuromyelitis Optica and Multiple Sclerosis in Indian Population

Sonal Patil, Kalpana Jain, J.M. Manohar
Sardar Patel Medical College, Bikaner, Rajasthan, India

Corresponding Author:

Kalpna Jain 
Professor, Department of Ophthalmology
S.P. Medical College, Bikaner-334003,
Rajasthan, India
Email id:

Received: 27-DEC-2017

Accepted: 01-FEB-2018

Published Online: 27-FEB-2020


Purpose: The purpose of this study is to differentiate neuromyelitis optica and its related disorders.
Materials and Method: A retrospective single site study of 104 patients from July 2014 to October 2017 with optic neuritis and/or myelitis was done. After history taking and complete ocular examination, neurological examination, cerebrospinal fluid examination, magnetic resonance imaging and aquaporin 4 antibody testing, patients were categorised as neuromyelitis optica, multiple sclerosis and others. 
Results: Neuromyelitis optica was diagnosed in 38 patients, multiple sclerosis in 48 patients and 18 were others. Female predominance (76%) was noted in neuromyelitis optica patients. Seropositivity for aquaporin 4 autoantibodies was associated with higher relapse rate. In neuromyelitis optica 55% patients responded to steroid therapy, 30% referred for plasmapheresis, and 15% patients needed imunosuppressive therapy. 
Conclusion: Considerable overlap exists between neuromyelitis optica and multiple sclerosis, both have to be differentiated because both diseases have different treatment guidelines.

Keywords :Neuromyelitis optica, Multiple sclerosis, Transverse myelitis, Cerebrospinal fluid pleocytosis, Aquaporin 4 auto antibodies

Neuromyelitis optica (NMO) or Devic disease is a rare, inflammatory disorder of the central nervous system. The condition was defined by Dr Eugene Devic, in 1894.1 The definitive diagnosis of neuromyelitis optica requires the presence of optic neuritis and transverse myelitis. Limited forms of the disease associated with NMO-IgG seropositivity are termed neuromyelitis optica spectrum disorder (NMOSD). Early, accurate diagnosis of neuromyelitis optica or neuromyelitis optica spectrum disorders has major impact on patient treatment outcomes. The choice of therapy should be rationale. Several disease modifying agents used in multiple sclerosis patients should be avoided in neuromyelitis optica because of their apparent lack of efficacy or, in some cases, their potential to exacerbate the disease. Considering the importance of diagnosis of neuromyelitis optica and its treatment implications present study focuses on clinical features,blood investigations, radiological investigations and cerebrospinal fluid examination of neuromyelitis optica and various other features that differentiate it from multiple sclerosis.

Material and Methods
This study is the retrospective,single site study. Total 104 patients were enrolled in study presenting with optic neuritis and/or myelitis from July 2014 to October 2017. All the patient were informed about the design of study and informed consent was taken. Patients were categorised into various groups based on clinical and various diagnostic test. Each patient underwent detailed ophthalmic and neurological evaluation, fundus examination, magnetic resonance imaging scans, cerebrospinal fluid examination, aquaporin 4 antibody test.

Patients categorised into following three groups based on clinical and various diagnostic test
Group 1- Neuromyelitis optica [38 patients]
Group 2- Multiple sclerosis [48 patients]
Group 3- Others [18 patients] 

Neuromyelitis optica affects comparatively younger female population as compared to multiple sclerosis as shown in Table 1 and Graph 1 female preponderance of around 76% was found in neuromyelitis optica patients and 70% among multiple sclerosis patients as shown in Table 2 Graph 2.
Table 3 shows, visual recovery was poor in 24 patients out of 38 patients with neuromyelitis optica. Visual recovery was comparatively better in multiple sclerosis, out of 22 patients of multiple sclerosis having visual manifestations, 18 patients had good visual recovery as show in Graph 3. 9 patients having associated macular oedema in neuromyelitis optica while one patient had macular oedema in multiple sclerosis patients.
Table 4 and Graph 4 shows that statistically significant (p value =0.05) difference was present in overall average, between extensive longitudinal cord lesions of patients seropositive and seronegative for aquaporin 4. Relapse rate of 0.001 was also statistically significant (p value =0.05) difference present in overall average between patients who tested positive and negative on Aquaporin 4. Favourable response to steroids was present in 55% of patients ,30% of patients were treated by plasmapheresis,15% patients treated by immunosuppressive therapy (Table 5 and Graph 5). Patients with multiple sclerosis received steroids, relapsing forms of MS received interferon or glatiramer acetate as a first-line therapy.

Table 1: Age distribution of patients

Graph 1: Age distribution of patients

Table 2: Sex distribution of patients

Graph 2: Sex distribution of patients

Table 3: Ocular and CNS manifestations of patients presenting with optic neuritis or myelitis or both

Graph 3: Visual Outcome of Patients

Table 4: Aquaporin 4 serology testing of NMO cases

Graph 4: Aquaporin 4 Serology of Neromyelitis Optica Patients

Table 5: Treatment outcome of neuromyelitis optica patients

Graph 5: Treatment response of neuromyelitis optica patients

Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) are inflammatory disorders of the central nervous system characterized by severe, immune-mediated demyelination and axonal damage predominantly targeting optic nerves and spinal cord. Traditionally considered a variant of multiple sclerosis, Now neuromyelitis optica is recognized as a distinct clinical entity based on unique immunologic features. The disease specific serum NMO-IgG antibody that selectively binds aquaporin-4 (AQP4) has led to increased understanding of a diverse spectrum of disorders. 
Optic neuritis (ON) is a disorder of the optic nerve, characterised by acute inflammation and presenting with sudden onset monocular visual loss and ocular pain in young adults, more commonly in women. It is a common initial manifestation of multiple sclerosis (MS).2 When optic neuritis occurs, brain magnetic resonance imaging (MRI) often demonstrates demyelination lesions.3
Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation, demyelination, gliosis scarring, and neuronal loss. Attacks of optic neuritis in neuromyelitis optica can be bilateral (rare in multiple sclerosis) or unilateral; myelitis can be severe and transverse (rare in multiple sclerosis) and is typically longitudinally extensive, involving three or more contiguous vertebral segments as shown in Figure 1. NMO was initially considered to be a monophasic disease but recently more than 80% of cases NMO is a relapsing disease.4,5

Figure 1: MRI spine showing longitudinally extensive increased signal intensity of spinal cord from C2 to C7 on T2-weighted imaging

Neuromyelitis optica spectrum disorders encompasses forms of NMO that do not satisfy the 2006 criteria of neuromyelitis optica. Isolated unilateral or simultaneous bilateral or recurrent optic neuritis (ON); isolated or recurrent transverse myelitis (TM); typical neuromyelitis optica brain lesions (corpus callosum, hypothalamus, brainstem, periventricular) with or without detectable anti AQP4-IgG autoantibody and seropositive patients with NMO Ig G having myelitis associated with collagen vascular disorders and many more are also loosely termed as neuromyelitis optica spectrum disorders(NMOSD).6
Neuromyelitis optica has variable prevalence. It had previously been suggested that neuromyelitis optica has ethnical predilection for nonwhites.7-12 About 15% to 57% of central demyelinating diseases in African–American, Japanese, and Indian populations were consistent with neuromyelitis optica while this disease comprised less than 2% of demyelinating diseases of the CNS in Caucasians.9-12 In Asian countries, however, neuromyelitis optica, often called optico-spinal MS (OSMS) constitutes 15–40% of all MS forms.13
Isolated optic neuritis (ON) is a common presenting sign in neuromyelitis optica and multiple sclerosis (MS) as shown in Figure 2. Multiple sclerosis patients recover significant visual acuity following optic neuritis, neuromyelitis optica patients often manifest severe visual loss. The mechanisms behind these distinct clinical outcomes was elucidated after the discovery of a highly specific serum immunoglobulin G autoantibody (AQP4-IgG) that targets AQP4, the major plasma membrane water channel on astrocytes, suggested AQP4 as a specific immunologic target in neuromyelitis optica optic neuritis.13,14

Figure 2: Fundus photographs showing optic neuritis

Neuromyelitis optica spectrum disorders optic neuritis and multiple sclerosis optic neuritis is different; bilateral involvement is more common, and recurrent optic neuritis and severe residual visual dysfunction more likely in former.15-20 Common MRI imaging features include lesions extending over one-half the length of the optic nerve, posterior nerve involvement, and chiasmal inflammation.21,22
Merle et al in 2008 showed that there was more substantial peripapillary retinal nerve fiber layer loss in on optical coherence tomography in neuromyelitis optica than multiple sclerosis optic neuritis.23
Raz et al in 2010 showed that bitemporal or homonymous visual field defect occurred in neuromyelitis optica optic neuritis due to potential to involve the optic chiasm and tracts.24 
Fernandes et al in 2012 showed that neuromyelitis optica optic neuritis generally causes more severe visual field defects than multiple sclerosis optic neuritis. They also found that there was significant thickening of inner nuclear layer in neuromyelitis optica optic neuritis compared to multiple sclerosis.25
Gelfand et al in 2012 recognised microcystic changes in inner retinal layer in 25% of neuromyelitis optica patients.26
Relapsing–remitting form constitutes 80-90% of cases and thus more frequent than the monophasic.5,27-28 Prognostic factors for a relapsing course are female gender, older age at onset, a benign first myelitis attack, longer interval between the first two episodes (more than six months).29 Monophasic neuromyelitis optica has less predilection for females, has a less significant respiratory involvement and has a lower mortality rate than the relapsing form.30 Relapsing–remitting neuromyelitis optica has been considered initially as a aggressive form of multiple sclerosis. Even though the clinical appearance of the two diseases are similar, in particular at onset when patient may have optic neuritis or myelitis, the neuroradiologic and pathological features are considerably different.31 Furthermore, a progressive course rarely occurs in neuromyelitis optica, while it is the natural course in most multiple sclerosis patients, indicating a different pathogenic mechanism of CNS damage.6 The presence of antibodies directed against AQP4 in sera of patients affected by neuromyelitis optica disease has greatly contributed to differentiate neuromyelitis optica from multiple sclerosis. Neuromyelitis optica is similar to multiple sclerosis in that the body’s immune system attacks the myelin surrounding nerve cells. Unlike multiple sclerosis the attacks are not believed to be mediated by the immune system’s Tcells, but rather by antibodies called NMO-IgG. These antibodies target the protein aquaporin 4 in the cell membrane of astrocytes which acts as a channel for the transport of water across the cell membrane.32
Thus, we now consider neuromyelitis optica as a syndrome with a wide spectrum of clinical manifestations, from classical defined neuromyelitis optica to isolated longitudinally extensive transverse myelitis, isolated recurrent optic neuritis, or optic neuritis and longitudinally extensive transverse myelitis associated with systemic autoimmune diseases such as Systemic Lupus Erythematosus.6
A revised set of diagnostic criteria for neuromyelitis optica was proposed in 2006 by Mayo clinic. These new guidelines require two absolute criteria plus at least two of three supportive criteria.33
In 2015 a new review was published by an international panel refining the previous clinical case definition but leaving the main criteria unmodified.34

Absolute criteria:
1. acute myelitis
2. optic neuritis

Supportive criteria:
1. Spinal cord MRI with continuous T2-weighted signal abnormality extending over three or more vetebral segments, indicating a relatively large lesion in the spinal cord
2. Brain MRI not meeting criteria for multiple sclerosis at disease onset
3. NMO-IgG seropositive status

Neuromyelitis optic common in Africans and Asians while multiple sclerosis is common in white races. Simultaneous or successive and severe involvement of optic nerves and spinal cord present in neuromyelitis optica while confluent involvement is absent in multiple sclerosis. Longitudinal extension involving =3 spinal cord segments and CSF WBCs >50 cells/mm3 is is an important feature of neuromyelitis optica while in multiple sclerosis longitudinal involvement is always <3 segments and CSF WBCs <50 cells/mm3. Oligoclonal bands in CSF seen in 85% patients of multiple sclerosis patients.
Patients who fulfill neuromyelitis optica criteria but do not have detectable AQP4-IgG pose a diagnostic challenge.35 A major proportion of patients with neuromyelitis optica who have monophasic disease appear to be AQP4-IgG- seronegative compared to those with established relapsing disease.36 Few patients with clinical characteristics of neuromyelitis optica and AQP4- IgG-seronegative have detectable serum myelin oligodendrocyte glycoprotein (MOG) antibodies and might have different characteristics from those with AQP4-IgG.37,38 These findings might suggest that some AQP4-IgG seronegative patients with clinical and neuroimaging features of neuromyelitis optica spectrum disorders have a different pathogenesis. The role of MOG or other antibodies in disease pathogenesis remains to be elucidated.36
First line therapy of neuromyelitis optica consists of intravenous methylprednisolone 1 gm daily for 5 days followed by oral steroids. For steroid unresponsive attacks treatment given is plasma exchange. For prevention of relapses immunosuppressant medications like azathioprine, mycophenolate, and rituximab. Recent studies suggest first line monotherapy for neuromyelitis optica with azathioprine or mycophenolate or rituximab or prednisolone.
Methylprednisolone, plasmapheresis and immunosuppressants play role in management of neuromyelitis optica while management of multiple sclerosis consists of methylprednisolone and immunoglobulins. Interferon can worsen neuromyelitis optica, but comparatively helpful in multiple sclerosis.6
Natalizumab it is an integrin inhibitor worsens neuromyelitis optica while it is beneficial as escalation therapy in multiple sclerosis35 Fingolimod worsens neuromyelitis optica39 and has beneficial role in the treatment of relapsing-remitting multiple sclerosis by its unique immunoregulatory properties.39 Thus subtle differences exist between treatment of both disease.

In our study it was found that there is more significant positive relation between longitudinally extensive transverse myelitis and relapse rate with Aquaporin 4 positivity. There was female predominance in neuromyelitis optica patients. Considerable overlap exists between neuromyelitis optica and multiple sclerosis, both have to be differentiated because both diseases have different treatment guidelines.

  1. Gault F. Neuromyelitis optica Thesis. Lyon 1894 
  2. Ebers GC. Optic neuritis and multiple sclerosis. Arch Neurol 1985; 42:702–704. 
  3. Beck RW, Arrington J, Murtagh FR, Cleary PA, Kaufman DI. Optic Neuritis Study Group. Brain magnetic resonance imaging in acute optic neuritis: experience of the Optic Neuritis Study Group. Arch Neurol 1993; 50:841–84.
  4. Collongues N, Marignier R, Zephir H, Papeix C, Blanc F, Ritleng C, et al. Neuromyelitis optica in France: A multicenter study of 125 patients. Neurology 2010; 74:736-742.
  5. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 1999; 53:1107-14.
  6. Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol 2007; 6:805-15.
  7. Cabrera-Gómez JA, Kurtzke JF, González-Quevedo A, Lara-Rodríguez R. An epidemiological study of neuromyelitis optica in Cuba. J Neurol 2009; 256:35-44.
  8. Rivera JF, Kurtzke JF, Booth VJ, Corona VT 5th. Characteristics of Devic’s disease (neuromyelitis optica) in Mexico. J Neurol 2008; 255:710-5.
  9. Kira J. Multiple sclerosis in the Japanese population. Lancet Neurol 2003 Feb; 2:117-27.
  10. Cabre P, Heinzlef O, Merle H, Buisson GG, Bera O, Bellance R, et al. MS and neuromyelitis optica in Martinique (French West Indies). Neurology 2001; 56:507-14.
  11. Lau KK, Wong LK, Li LS, Chan YW, Li HL, Wong V. Epidemiological study of multiple sclerosis in Hong Kong Chinese: questionnaire survey. Hong Kong Med J 2002; 8:77-80.
  12. Wu JS, Zhang MN, Carroll WM, Kermode AG. Characterisation of the spectrum of demyelinating disease in Western Australia. J Neurol Neurosurg Psychiatry 2008; 79:1022-6.
  13. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker for neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004; 364:2106–2112.
  14. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005; 202:473–477.
  15. Kitley J, Leite MI, Nakashima I, Waters P, McNeillis B, Brown R, et al. Prognostic factors and disease course in aquaporin-4 antibodypositive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain 2012; 135: 1834–1849. 
  16. Merle H, Olindo S, Bonnan M, Donnio A, Richer R, Smadja D, et al. Natural history of the visual impairment of relapsing neuromyelitis optica. Ophthalmology 2007; 114:810–815. 
  17. Kitley JL, Leite MI, Matthews LA, Palace J. Use of mitoxantrone in neuromyelitis optica. Arch Neurol 2011; 68:1086–1087. 
  18. Fernandes DB, Ramos Rde I, Falcochio C, Apóstolos-Pereira S, Callegaro D, Monteiro ML. Comparison of visual acuity and automated perimetry findings in patients with neuromyelitis optica or multiple sclerosis after single or multiple attacks of optic neuritis. J Neuroophthalmol 2012; 32:102-106. 
  19. Merle H, Olindo S, Jeannin S, Hage R, Donnio A, Richer R, et al. Visual field characteristics in neuromyelitis optica in absence of and after one episode of optic neuritis. Clin Ophthalmol 2013; 7:1145–1153. 
  20. Pfueller CF, Paul F. Imaging the visual pathway in neuromyelitis optica. Mult Scler Int 2011; 2011:869814.
  21. Khanna S, Sharma A, Huecker J, Gordon M, Naismith RT, Van Stavern GP. Magnetic resonance imaging of optic neuritis in patients with neuromyelitis optica versus multiple sclerosis. J Neuroophthalmol 2012; 32:216-20.
  22. Storoni M, Davagnanam I, Radon M, Siddiqui A, Plant GT. Distinguishing optic neuritis in neuromyelitis optica spectrum disease from multiple sclerosis: a novel magnetic resonance imaging scoring system. J Neuroophthalmol 2013; 33: 123–127.
  23. Merle H, Olindo S, Donnio A, Richer R, Smadja D, Cabre P. Retinal peripapillary nerve fiber layer thickness in neuromyelitis optica. Invest Ophthalmol Vis Sci 2008; 49:4412–4417.
  24. Raz N, Vaknin A, Chokron S, Ben-Hur T, Levin N. Functional MRI as a tool for assessing chiasmal visual defect in a patient with neuromyelitis optica. J Neurol Neurosurg Psychiatry 2010; 81:1174–117.
  25. Fernandes DB, Raza AS, Nogueira RG, Wang D, Callegaro D, Hood DC, et al. Evaluation of inner retinal layers in patients with multiple sclerosis or neuromyelitis optica using optical coherence tomography. Ophthalmology 2103; 120:387-94
  26. Gelfand JM, Cree BA, Calabresi P, Frohman E, Balcer L, Nolan R, et al. Microcytic macular oedema in neuromyelitis optica. Nmultiple Sclerosis Journal 2012; 18:260-260.
  27. O’Riordan JI, Gallagher HL, Thompson AJ, Howard RS, Kingsley DP, Thompson EJ, et al. Clinical, CSF, and MRI findings in Devic’s neuromyelitis optica. J Neurol Neurosurg Psychiatry 1996; 60:382–387.
  28. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology 2003; 60:848–853.
  29. Hazin R, Khan F, Bhatti MT. Neuromyelitis optica: current concepts and prospects for future management. Curr Opin Ophthalmol 2009; 20:434–439.
  30. Adoni T, Lino AM, da Gama PD, Apostolos-Pereira SL, Marchiori PE, Kok F, et al. Recurrent neuromyelitis optica in Brazilian patients: clinical,immunological, and neuroimaging characteristics. Mult Scler 2010; 16:81–86.
  31. Cabrera-Gomez JA, Bonnan M, Gonzalez-Quevedo A, Saiz-Hinarejos A, Marignier R, Olindo S, et al. Neuromyelitis optica positive antibodies confer a worse course in relapsing neuromyelitis optica in Cuba and French West Indies. Mult Scler 2009; 15:828–833.
  32. Wingerchuk DM. Neuromyelitis optica. The International MS Journal 2006; 13:42–50. 
  33. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006; 66:1485–1489. 
  34. Kowarik MC, Dzieciatkowska M, Wemlinger S, Ritchie AM, Hemmer B, Owens GP, et al. The cerebrospinal fluid immunoglobulin transcriptome and proteome in neuromyelitis optica reveals central nervous system-specific B cell populations. J Neuroinflammation 2015; 28:12:19.
  35. Marignier R, Bernard-Valnet R, Giraudon P, Collongues N, Papeix C, Zéphir H, et al. NOMADMUS Study Group: Aquaporin-4 antibody-negative neuromyelitis optica: distinct assay sensitivity-dependent entity. Neurology 2013; 80:2194–2200.
  36. Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J Neuroinflammation 2012; 9:14.
  37. Kitley J, Woodhall M, Waters P, Leite MI, Devenney E, Craig J, et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology 2012; 79:1273–1277. 
  38. Sato DK, Callegaro D, Lana-Peixoto MA, Waters PJ, de Haidar Jorge FM, Takahashi T, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 2014;82:474–481.
  39. Pittock SJ, Lucchinetti CF. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later. Ann N Y Acad Sci 2016; 1366:20–39.

Search PubMed for


Patil S, Jain K, Manohar JMComparative Study of Spectrum of Neuromyelitis Optica and Multiple Sclerosis in Indian Population.DJO 2019;30:25-30


Patil S, Jain K, Manohar JMComparative Study of Spectrum of Neuromyelitis Optica and Multiple Sclerosis in Indian Population.DJO [serial online] 2019[cited 2020 Apr 7];30:25-30. Available from: