|
 |
|
ORIGINAL ARTICLE |
|
|
|
| Ahead of print
publication |
| |
Clinico-epidemiological profile and outcome of pediatric neuromyelitis optica spectrum disorder at an eastern Indian tertiary care center
Suman Das1, Gourango Prosad Mondal2, Ramesh Bhattacharya2, Kartik Chandra Ghosh2, Sarbajit Das2, Hemakrishna Pattem2
1 Department of Neurology, Bangur Institute of Neurology, Kolkata, India
2 Department of Neurology, Calcutta National Medical College, Kolkata, West Bengal, India
| Date of Submission | 16-Sep-2020 |
| Date of Decision | 10-Jan-2021 |
| Date of Acceptance | 24-Mar-2021 |
| Date of Web Publication | 07-Jan-2022 |
Correspondence Address:
Suman Das,
Department of Neurology, Bangur Institute of Neurology, Sambhunath Pandit St, Gokhel Road, Bhowanipore, Kolkata 700020, West Bengal.
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpn.JPN_238_20
 Abstract | | |
Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory central nervous system disorder. Patients either have antibodies to aquaporin 4 (AQ4)/myelin oligodendrocyte glycoprotein (MOG) or are double seronegatives (DSN). Aim: We aimed at comparing the clinico-epidemiological features and outcome of the subgroups of NMOSD. Design: Prospective longitudinal observational study. Materials and Methods: NMOSD was diagnosed by using the 2006 Wingerchuk criteria. Patients diagnosed between September 2016 and August 2018 were prospectively followed upto July 2020. Acute episodes were treated with steroids, and immunomodulators were started in patients with aquaporin 4 IgG (anti-AQ4+) and in relapsing cases of anti-MOG+ and DSN groups. Disability was assessed by using the Expanded Disability Status Scale (EDSS). Comparisons were made between patients who were anti-AQ4 and anti-MOG positive and those with DSN. Statistical analysis was done by SPSS 20.0 software. Results: Among 13 patients, the female:male ratio was 1.16:1, and the mean age of disease onset was 9.65 ± 3.25 years. Overall, 15.38% patients were anti-AQ4+, 30.67% were anti-MOG+, 53.86% were DSN, 69.2% had relapsing disease, and 30.8% had monophasic disease (P = 0.11). The mean to relapse was 13.16±3.5 months; 61.5% patients had long segment myelitis and 53.86% had optic neuritis on their first presentation (P = 0.99). Cerebral syndrome occurred among one patient with anti-MOG+ and in three patients with DSN. The EDSS scores were significantly lower among patients who were anti-MOG+. Conclusion: The female:male ratio was more equitable and the age of disease onset was lower in our cohort compared with western data. There was no significant difference in the clinico-demographic characteristics among the three groups; however, outcome was better in the anti-MOG+ group. Rituximab was effective for recurrent relapses.
Keywords: Aquaporin 4, double seronegative, myelin oligodendrocyte glycoprotein, neuromyelitis optica
How to cite this URL:
Das S, Mondal GP, Bhattacharya R, Ghosh KC, Das S, Pattem H. Clinico-epidemiological profile and outcome of pediatric neuromyelitis optica spectrum disorder at an eastern Indian tertiary care center. J Pediatr Neurosci [Epub ahead of print] [cited 2023 Mar 25]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=335193 |
| Introduction | |  |
NMOSD is a chronic relapsing inflammatory disorder of the central nervous system. Anti-AQ4 antibodies are sensitive and specific for NMOSD.[1] However, pediatric neuroinflammatory conditions associated with MOG antibodies also present with a similar clinical syndrome.[2] Recent years have exhibited an exponential rise in research in pediatric NMOSD, but publications from India are exceedingly rare. Pediatric NMOSD accounts for 3–5% of all NMOSD cases.[3] The incidence and prevalence rates of anti-AQ4 disease were 0.05–4/100,000/year and 0.52–4.7/100,000 population[4]. Further research is needed to ascertain the epidemiology of anti-MOG related pediatric NMOSD.[1]
| Materials and Methods | | |
This prospective, observational study was conducted at the Neurology department of Calcutta National Medical College. Institutional ethics committee approval was obtained, and the parents signed the consent forms.
NMOSD was diagnosed using the 2006 Wingerchuk criteria. Patients diagnosed between September 2016 and August 2018 were prospectively followed upto July 2020. The core clinical criteria were optic neuritis (ON) involving >1/2 of the length of optic nerves or involving the chiasma, longitudinally extensive transverse myelitis (LETM) involving less than three spinal segments, area postrema syndrome (APS) with dorsal medulla lesions, acute brain stem syndrome with periependymal lesions, and acute diencephalic and symptomatic cerebral syndromes. For seropositive patients, the presence of one core criterion and for patients with DSN, the presence of at least two core criteria (one of which must be optic neuritis, myelitis, or area postrema syndrome) was needed for the diagnosis of NMOSD. The core features occurred either simultaneously or sequentially during further attacks. The initial brain magnetic resonance imaging (MRI) was either normal or not fulfilling the diagnostic criteria for multiple sclerosis.[5] The lesions were T2 hyperintense and T1 hypointense with gadolinium enhancements. Fat-suppressed images were taken for optic nerves.
Based on their clinical and radiological features, suspected cases of NMOSD were followed up longitudinally to determine the dissemination in time aspect of their disease course (relapsing versus monophasic NMOSD). Meticulous history was taken; complete hemograms with ESR, liver, renal and thyroid function tests, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI) of the brain, orbits, and spinal cord with contrast, tests for anti-AQ4 and MOG antibodies by immunofluorescence technique (fixed cell-based assay using transfected EU90 cells with screening dilution of 1:10), the full antinuclear antibody profiles, antineutrophilic cytoplasmic antibodies, anti-thyroid peroxidase assay, infection screen (hepatitis B, C, HIV, tuberculin skin test, and chest radiography), angiotensinogen-converting enzyme level, and vitamin B12 levels were tested for each patient.
The acute episodes were treated with intravenous methylprednisolone 30 mg/kg for five days followed by an oral prednisolone 1 mg/kg for three months and then tapered over the next four to eight weeks, depending on the severity of the attack.
For patients who were anti-AQ4 positive, preventive immunomodulator therapy was initiated promptly from the first attack since AQ4-IgG predicts relapses with cumulative neurodeficits.[6] However, for patients who were anti-MOG positive and patients with DSN, the preventive therapy was initiated after the first relapse.[7] The choice of immunomodulator was dictated by the financial status of the parents. Azathioprine (2.5–3 mg/kg) was the cheapest option. However, for affordable parents, we opted for mycophenolate mofetil (MMF) (2–3 mg/kg), because of its faster action and lower annualized relapse rates (ARR) compared with azathioprine[8],[9]. When immunomodulators were started, concomitant steroids were initially overlapped for six months before tapering, to enable the immunomodulators to become effective. For recurrent (>1) relapses, we used rituximab (375 mg/m2) at four weekly intervals, followed by scheduled infusions at six monthly intervals since the patients could not afford periodic CD19/20 counts.
Every patient was followed at the outpatient department, admitted at each relapse, and reinvestigated in the manner mentioned earlier. Repeat MRI scans were done during these visits to evaluate for the resolution of the lesions or their sequelae such as cord atrophy after LETM. Their disabilities were evaluated by using the EDSS and the Kurtzke’s Functional System Score (FSS) at the end of the two years’ follow-up. The FSS scores the pyramidal, visual, sensory, cerebellar, cerebral, and brain stem disabilities.
Statistical analysis was done by using the Statistical Package for Social Sciences (SPSS) 20.0 software. Continuous variables were analyzed by using the Student t-test, and categorical variables were analyzed with Fischer exact test. P < 0.05 was considered significant.
| Results | | |
Our study included 13 patients diagnosed within the study period. Overall, seven patients were females (F:M = 1.16:1), two had anti-AQ4 IgG (15.38%), four had anti-MOG IgG (30.67%), seven (53.86%) had DSN, nine (69.2%) cases had a relapsing course, and four (30.8%) had a monophasic course (P = 0.11). Relapsing disease occurred in 100%, 50%, and 71.4% of anti-AQ4+, anti-MOG+, and DSN groups, respectively. Simultaneous presentation of two core features occurred in four (30.7%) patients, whereas sequential presentation occurred in nine patients (P = 0.11). LETM was the initial presentation in eight patients (61.54%), followed by ON in seven (53.86%) patients (P = 0.99).
Intergroup comparisons were made. Patients with anti-MOG antibodies had significantly lower EDSS scores compared with the anti-AQP4+ (P = 0.02) and DSN groups (P = 0.03). Patients with anti-AQ4 antibodies had higher EDSS scores than patients with DSN, but this was not statistically significant (P = 0.1). Comparisons of other parameters in [Table 1] were also not significant. The two cases of preceding events were mild cough and cold one month before their development of neurodeficits. None had a history of recent vaccination.
[Table 2] shows that the anti-AQ4+ group had two cases of LETM and one case of ON. Brain stem affection was unique to this group. The anti MOG+ group had three cases of LETM, two cases of ON, and one case of cerebral syndrome. The DSN group had six cases of LETM, five cases of ON, and three cases of cerebral syndrome. All patients with LETM had cervicodorsal lesions, except two patients who had anti-MOG+, who had dorsolumbar lesions [Figure 1] and one patient with DSN who had only a dorsal spine lesion. All patients with ON had less than half of optic nerve involvement. Chiasmal involvement occurred in two cases of B/L ON, one each in the anti-AQ4+ and DSN groups. The patient with brain stem syndrome had lesions in the dorsal medulla [Figure 2], dorsal pons [Figure 3], and midbrain [Figure 4]. She had intractable vomiting due to area postrema involvement, dysarthria and dysphagia due to bulbar weakness, B/L lower motor neuron type facial palsy, and B/L inter-nuclear ophthalmoplegia. The patients with cerebral syndrome had headache and hemiparesis. One seronegative patient with LETM and cerebral syndrome had left homonymous hemianopia [Figure 5]. None had encephalopathy.  | Figure 1: MRI of spine (sagittal section) showing T2 hyperintensities (marked by arrows) in the thoracic spine and conus medullaris suggestive of long segment myelitis
Click here to view |
 | Figure 2: MRI of brain (axial section) showing T2 hyperintensities in bilateral medulla, involving the dorsal aspect on the right side
Click here to view |
 | Figure 3: MRI of brain (axial section) showing T2 hyperintensities in bilateral dorsal pons
Click here to view |
 | Figure 4: MRI of brain (axial section) showing confluent T2 hyperintensities in left midbrain and patchy involvement of the right side
Click here to view |
 | Figure 5: MRI of brain (axial section) showing T2 hyperintensities in bilateral occipital cortex, marked with arrows
Click here to view |
Oligoclonal band was negative in all patients with CSF, and none had an elevated IgG index. The VEP showed U/L or B/L prolonged P100 latencies in patients with ON. The VEP tests were also done in patients with isolated myelitis to identify subclinical optic neuropathy, but they were negative in all such cases. None had positive autoimmune markers.
It is evident from [Table 3] that lower age of disease onset, higher number of relapses, female sex, presence of a previous infectious event, lower time to relapse, and use of azathioprine as the immunomodulator were associated with worse outcomes.
| Discussion | | |
Discussion on demographics
From [Table 4], it is evident that our study cohort had a lower mean age of disease onset, but it was not significantly different from the previous Indian report (P = 0.58). The female:male ratio was similar to the multinational study,[10] and it was much lower than the western studies. Another U.S. study[17] had noted variations in the female:male ratio in different age groups, being 3.5:1 with children >11 years and 1.5:1 in those <11 years. Also, according to the Pediatric Working Group members of the International Panel on NMOSD (INPD), the female preponderance is of a lower magnitude in children (3:1 compared with 9:1 in adults)[5]. A lower frequency of anti-AQP4 IgG and a higher frequency of anti-MOG IgG were also noted in the multinational[10] and the previous Indian study.[16] | Table 4: Comparison of demographic features between different pediatric NMOSD studies
Click here to view |
Discussion on mono/polyphasic NMOSD
According to the INPD, a greater proportion of pediatric NMOSD (5–10%) may be monophasic.[5] A much higher proportion (30.8%) of cases were monophasic NMOSD in our study (50% in anti-MOG+ and 28.57% in seronegative groups). The relapse rate in patients who were anti-MOG+ in our study was comparable with that of a few other studies (48% and 50% reported by Duignan[18] and Narayan[2]). However, in coherence with the INPD data,[5] the female:male ratio in monophasic NMOSD in our study was equitable (1:1). According to INPD,[5] the pediatric monophasic LETM rarely ever have anti-AQ4 antibodies, and they may accompany monophasic acute disseminated encephalomyelitis (ADEM). In our study, two cases of monophasic LETM were anti-MOG+. In some reports, B/L ON with myelitis was the most common presentation of monophasic NMOSD.[19] Among the DSN monophasic cases in our study, one had B/L ON+LETM whereas one had U/L ON+LETM. Although the risk of early relapse within one year is high (60%) among patients who were anti-AQ4+, the interval between the index event and the first relapse has not been well defined among DSN.[20] According to the INPD,[5] a minimum five years of relapse-free period is needed after the index event to confidently diagnose the monophasic course. A Chinese retrospective study on 241 children found that 59.3% relapsed within one year, 27.4% during one to five years, and 13.3% beyond five years. The presentation with ON, non-LETM, and non-APS attacks predicted a low risk of early relapse. Hence, the existence of the monophasic course exhibits a novel long-term relapse-free form of NMOSD[21]. Since all our monophasic cases had LETM, we need to keep these cases on continuous follow-up to diagnose any possible relapses.
Discussion on subtype comparison
The age of presentation, female:male ratio, occurrence of preceding events, CSF parameters, numbers and mean times to relapses, resolution of MRI lesions on follow-up, and the number of patients needing immunomodulators were not significantly different in the three groups. However, patients who were anti-MOG + had significantly lowered morbidity compared with both patients who were anti-AQ4+ and those with DSN. Lechner[10] also found no differences in the age at presentation, sex ratio, frequency of oligoclonal bands, or median EDSS at the last follow-up between the three groups. However, in Lechner’s study,[10] children with anti-MOG IgG+ more frequently had a monophasic course after one year, presented with simultaneous ON and LETM, were less likely to receive immunosuppressive therapies, less frequently demonstrated periependymal lesions, and their lesions resolved more frequently. Kitley[22] also described the greater occurrence of simultaneous or sequential ON with myelitis in the anti-MOG+ group compared with the anti-AQ4+ group. In our study, the occurrence of the monophasic course and the chance of lesion resolution were higher among anti-MOGIgG+ children. However, the sequential ON with LETM occurred only in one case (25%). Because of these distinct features, and the relative lack of anti-MOG antibodies among adult patients with NMOSD, dilemma exists among several authors about whether to keep patients with anti-MOG+ under the umbrella of NMOSD or consider it as a separate entity.
Distinct features have also been described for patients with DSN: Caucasian race, lower female: male ratio, shorter disease duration, frequent monophasic course, lesser autoimmunity, and predominant ON+LETM presentation.[23] These findings were also established in a South Korean study, where the ARR and EDSS were comparable among patients with anti-AQ4+ and those with DSN. When compared with patients with anti-MOG+, patients with DSN had a similar female:male ratio and ARR, but higher EDSS levels.[24] In our DSN group, two (28.5%) had sequential ON and LETM, three (42.85%) had simultaneous ON and LETM, and interestingly three (42.85%) also had cerebral lesions. Although cerebral hemispheric involvement occurs in 16–32% of children with anti-AQ4+, its occurrence in the DSN group is rarer.[12],[17],[25] In a publication of 88 children with anti-AQ4+, brain abnormalities were observed in 68% cases, and these were predominantly located within periventricular regions of the third (diencephalic) and fourth ventricles (brain stem), supratentorial and infratentorial white matter, midbrain, and cerebellum. This correlated with the finding that 45% to 55% of children present with altered consciousness, behavioral changes, seizures, narcolepsy, ophthalmoparesis, intractable vomiting and hiccups, and ataxia[26]. However, confluent hemispheric lesions may cause hemiparesis, encephalopathy, and visual field defects depending on the area involved.[26] Although they are rarely described in patients with DSN,[26] three of our patients with DSN had confluent hemispheric lesions. Brain stem syndrome occurs in 40% children and 33–39% adults with anti-AQ4+.[27] Presentation with an isolated APS is more specific for patients with anti-AQP4+, than LETM extending to this area.[28] However, in our study, the patient with anti-AQ4+ had cervicodorsal LETM extending to the brain stem, rather than isolated APS.
Discussion on outcome
In our study, younger onset age, higher and faster relapses, female sex, and the use of azathioprine rather than MMF were associated with worse outcomes. The multivariable analyses in Zhou’s[8] study showed that sustained disability was independently associated with the presence of LETM, brain/brain stem symptoms, higher ARR, and the age of onset. In his study on outcome prediction models of patients with anti-AQ4+, Palace[29] found significant effects of onset age (younger patients had higher optic neuritis relapses with subsequent blindness), onset phenotype (higher relapses and hence, higher disabilities for brain stem and cerebral phenotypes), and ethnicity (higher relapses with disabilities for Caucasians and Africans, and lower relapses for Japanese) on NMOSD outcomes. Zhou[8] also described that azathioprine reduced ARR and disability more prominently in adults (79%) than in children (48%) and MMF and rituximab reduced the relapse frequency in children by 94% and 100%. In our study, rituximab stopped further relapses in both patients with anti-AQ4+ and those with DSN, but it was not needed in the anti-MOG+ group. Durozard[30] described that in patients with anti-AQ4+ treated with rituximab, relapses occurred only when the biological effect of rituximab decreased. However, in patients with anti-MOG+, one‐third relapsed despite a significant biological effect of rituximab. In this subgroup of NMOSD having a probable role of different immunological mechanisms, memory B‐cell depletion was unable to prevent relapse. A large retrospective multicenter study of patients with anti-MOG+ NMOSD suggested that maintenance immunotherapy reduced the recurrence of demyelinating episodes, with maintenance IVIG being associated with the lowest ARR. The relapse rates of patients on different immunomodulators were as follows: MMF (ARR=0.67), rituximab (ARR=0.59), azathioprine (ARR=0.2), and IV immunoglobulin (IVIG) (ARR=0).[31]
Thus, in conclusion, it needs to be emphasized that our study adds the following fresh data to the evolving literature on pediatric NMOSD: (1) The female:male ratio is far more equitable in the Indian cohort compared with western or even with other Asian (Chinese) data; (2) cerebral syndrome can occur in the DSN group more commonly than previously believed; (3) monophasic NMOSD can present with a single core feature among seropositive patients, rather than the most frequently reported simultaneous ON+LETM presentation; (4) patients with anti-MOG+ have better prognosis compared not only with patients who are anti-AQ4+, but also with patients with DSN; and (5) rituximab effectively stops relapses among both anti-AQ4+ and DSN groups, and it should be tried earlier in pediatric NMOSD.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Silvia, Tenembaum, E. Ann, Yeh, The Guthy-Jackson Foundation International Clinical Consortium (GJCF-ICC). Pediatric NMOSD: A review and position statement on approach to work-up and diagnosis. Front Pediatr2020;8:339.  |
| 2. | Narayan R, Simpson A, Fritsche K, Salama S, Pardo S, Mealy M, et al. MOG antibody disease: A review of MOG antibody seropositive neuromyelitis optica spectrum disorder. Mult Scler Relat Disord 2018;25:66-72. |
| 3. | Tenembaum S, Chitnis T, Nakashima I, Collongues N, McKeon A, Levy M, et al. Neuromyelitis optica spectrum disorders in children and adolescents. Neurology 2016;87:S59-66. |
| 4. | Pandit L, Asgari N, Apiwattanakul M, Palace J, Paul F, Leite MI, et al; GJCF International Clinical Consortium & Biorepository for Neuromyelitis Optica. Demographic and clinical features of neuromyelitis optica: A review. Mult Scler 2015;21:845-53. |
| 5. | Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al; International Panel for NMO Diagnosis. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015;85:177-89. |
| 6. | Dale RC, Brilot F, Duffy LV, Twilt M, Waldman AT, Narula S, et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology 2014;83:142-50. |
| 7. | Hacohen Y, Wong YY, Lechner C, Jurynczyk M, Wright S, Konuskan B, et al. Disease course and treatment responses in children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease. JAMA Neurol 2018;75:478-87. |
| 8. | Zhou Y, Zhong X, Shu Y, Cui C, Wang J, Wang Y, et al. Clinical course, treatment responses and outcomes in chinese paediatric neuromyelitis optica spectrum disorder. Mult Scler Relat Disord 2019;28:213-20. |
| 9. | Huh SY, Kim SH, Hyun JW, Joung AR, Park MS, Kim BJ, et al. Mycophenolate mofetil in the treatment of neuromyelitis optica spectrum disorder. JAMA Neurol 2014;71:1372-8. |
| 10. | Lechner C, Baumann M, Hennes EM, Schanda K, Marquard K, Karenfort M, et al. Antibodies to MOG and AQP4 in children with neuromyelitis optica and limited forms of the disease. J Neurol Neurosurg Psychiatry 2016;87:897-905. |
| 11. | Gmuca S, Hardy DI, Narula S, Stoll S, Harris J, Zhao Y, et al. Validation of claims-based diagnoses of adult and pediatric neuromyelitis optica spectrum disorder and variations in diagnostic evaluation and treatment initiation. Mult Scler Relat Disord 2020;37:101488. |
| 12. | Absoud M, Lim MJ, Appleton R, Jacob A, Kitley J, Leite MI, et al. Paediatric neuromyelitis optica: Clinical, MRI of the brain and prognostic features. J Neurol Neurosurg Psychiatry 2015;86:470-2. |
| 13. | Sepulveda M, Aldea M, Escudero D, Llufriu S, Arrambide G, Otero-Romero S, et al. Epidemiology of NMOSD in Catalonia: Influence of the new 2015 criteria in incidence and prevalence estimates. Mult Scler 2018;24:1843-51. doi: 10.1177/1352458517735191 |
| 14. | Fragoso YD, Ferreira ML, Oliveira EM, Domingues RB, Ribeiro TA, Brooks JB, et al. Neuromyelitis optica with onset in childhood and adolescence. Pediatr Neurol 2014;50:66-8. |
| 15. | Huppke P, Blüthner M, Bauer O, Stark W, Reinhardt K, Huppke B, et al. Neuromyelitis optica and NMO-igg in european pediatric patients. Neurology 2010;75:1740-4. |
| 16. | Pandit L, Sato DK, Mustafa S, Takahashi T, D’Cunha A, Malli C, et al. Serological markers associated with neuromyelitis optica spectrum disorder in South India. Ann Acad Neurol 2016;19:505-9. |
| 17. | Chitnis T, Ness J, Krupp L, Waubant E, Hunt T, Olsen CS, et al. Clinical features of neuromyelitis optica in children: US network of pediatric MS centers report. Neurology 2016;86:245-52. |
| 18. | Duignan S, Wright S, Rossor T, Cazabon J, Gilmour K, Ciccarelli O, et al. Myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies are highly specific in children with acquired demyelinating syndromes. Dev Med Child Neurol 2018;60:958-62. doi: 10.1111/dmcn.13703 |
| 19. | Jarius S, Wildemann B. The history of neuromyelitis optica. J Neuroinflammation 2013;10:8. |
| 20. | Weinshenker BG, Wingerchuk DM, Vukusic S, Linbo L, Pittock SJ, Lucchinetti CF, et al. Neuromyelitis optica igg predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol 2006;59:566-9. |
| 21. | Zhang W, Cui L, Zhang Y, Wang W, Wang R, Liu Z, et al. Questioning the existence of monophasic neuromyelitis optica spectrum disorder by defining a novel long-term relapse-free form from a large chinese population. J Neurol 2020;267:1197-205. |
| 22. | Kitley J, Waters P, Vincent A, Palace J. Features of neuromyelitis optica spectrum disorders and aquaporin-4 with myelin-oligodendrocyte glycoprotein antibodies-reply. JAMA Neurol 2014;71:924. |
| 23. | Siritho S, Prayoonwiwat N. Features of anti-aquaporin 4 antibody negative Thai patient with neuromyelitis optica spectrum disorder: A comparison with seropositive cases. J Neuro Sci 2014;1-2:17-21. |
| 24. | Kim HW, Lee EJ, Lee S, Kim H, Kim SK, Kim S, et al. Distinction of Double Seronegative Neuromyelitis Optica Spectrum Disease From AQP4-IgG Seropositive and MOG-IgG Seropositive Cases in Asian Patients. Stockholm, Sweden: ECTRIMS Online Library; 2019:278294; P1092. |
| 25. | Matsushita T, Isobe N, Piao H, Matsuoka T, Ishizu T, Doi H, et al. Reappraisal of brain MRI features in patients with multiple sclerosis and neuromyelitis optica according to anti-aquaporin-4 antibody status. J Neurol Sci 2010; 291:37-43. |
| 26. | Kim HJ, Paul F, Lana-Peixoto MA, Tenembaum S, Asgari N, Palace J, et al; Guthy-Jackson Charitable Foundation NMO International Clinical Consortium & Biorepository. MRI characteristics of neuromyelitis optica spectrum disorder: an international update. Neurology 2015;84:1165-73. |
| 27. | Kremer L, Mealy M, Jacob A, Nakashima I, Cabre P, Bigi S, et al. Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients. Mult Scler 2014;20:843-7. |
| 28. | Dubey D, Pittock SJ, Krecke KN, Flanagan EP. Association of extension of cervical cord lesion and area postrema syndrome with neuromyelitis optica spectrum disorder. JAMA Neurology 2017;74:359-61. doi: 10.1001/jamaneurol.2016.5441 |
| 29. | Palace J, Lin DY, Zeng D, Majed M, Elsone L, Hamid S, et al. Outcome prediction models in AQP4-igg positive neuromyelitis optica spectrum disorders. Brain 2019;142:1310-23. |
| 30. | Durozard P, Rico A, Boutiere C, Maarouf A, Lacroix R, Cointe S, et al. Comparison of the response to rituximab between myelin oligodendrocyte glycoprotein and aquaporin-4 antibody diseases. Ann Neurol 2020;87:256-66. |
| 31. | Chen JJ, Flanagan EP, Bhatti MT, Jitprapaikulsan J, Dubey D, Chiriboga ASSL, et al. Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder. Neurology 2020;95:e111-20. doi: 10.1212/WNL.0000000000009758 |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4]
|
