Neuromyelitis optica spectrum disorder

1759: 790: 1268: 482: 1610:. In patients with the monophasic form, the transverse myelitis and optic neuritis occur simultaneously or within days of each other. On the other hand, patients with the relapsing form are more likely to have weeks or months between the initial attacks, and to have better motor recovery after the initial transverse myelitis event. Relapses usually occur early, with about 55% of 400:(e.g. in patients with long-standing MS resulting in confluent spinal cord lesions mimicking the longitudinally extensive spinal cord lesions typically seen in NMO). In consequence, NMO was in the past wrongly considered a clinical variant of MS. However, NMO is not related to MS in the vast majority of cases and differs from MS substantially in terms of 2118: 1303:). Early initiation of treatment with steroids has been shown to improve vision-related outcomes after acute attacks. However, there is no high-level evidence for steroids affecting long-term outcomes; this treatment strategy was borrowed from that for similar diseases (idiopathic optic neuritis and multiple sclerosis). 4972:

Evangelopoulos ME, Andreadou E, Koutsis G, Koutoulidis V, Anagnostouli M, Katsika P, Evangelopoulos DS, Evdokimidis I, Kilidireas C (January 2017). "Treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders with rituximab using a maintenance treatment regimen and close CD19 B cell

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Many treatments are used despite the lack of phase III clinical trials testing their efficacy. Neither inferiority nor superiority to the newer, FDA approved drugs has been clearly demonstrated; and, considering their being relatively inexpensive and being availability in pill format, these drugs are

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found on the surface of oligodendrocytes and the outermost surface of myelin sheaths. Its function is not entirely known. MOG-IgG is produced outside the central nervous system (CNS) despite MOG existing only in the CNS (with the BBB separating the two), leading to the hypothesis that MOG drained via

613:

NMOSD selectively affects the optic nerve, spinal cord, and brain stem. This selectivity can be explained by the increased amount of AQP4 in these structures, and, furthermore, by the increased amount of AQP4 aggregates in the optic nerve and spinal cord. The increased BBB permeability at the area

4682:

Kimbrough, Dorlan J.; Fujihara, Kazuo; Jacob, Anu; Lana-Peixoto, Marco A.; Isabel Leite, Maria; Levy, Michael; Marignier, Romain; Nakashima, Ichiro; Palace, Jacqueline; de Seze, Jérôme; Stuve, Olaf; Tenembaum, Silvia N.; Traboulsee, Anthony; Waubant, Emmanuelle; Weinshenker, Brian G.; Wingerchuk,

5480:

Isobe, Noriko; Yonekawa, Tomomi; Matsushita, Takuya; Kawano, Yuji; Masaki, Katsuhisa; Yoshimura, Satoshi; Fichna, Jakub; Chen, Shu; Furmaniak, Jadwiga; Smith, Bernard Rees; Kira, Jun-Ichi (2012). "Quantitative assays for anti-aquaporin-4 antibody with subclass analysis in neuromyelitis optica".

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can help to establish a more accurate diagnosis. Oligoclonal bands in NMO are rare and they tend to disappear after attacks, while in MS they are nearly always present and persistent. It is important to notice for differential diagnosis that, though uncommon, it is possible to have longitudinal

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MOG-IgG-positive NMOSD brain lesions, as seen under a microscopic, show demyelination with preservation of oligodendrocytes and axons, presence of inflammatory cells, and IgG and complement deposits. MOG-IgG levels coarsely correlate with disease severity, with levels being higher during active

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Glial Fibrillary Acid Protein Immunoglobulin G (GFAP-IgG) Related Myelitis: Characterization and Comparison with Aquaporin-4-IgG Myelitis, Elia Sechi, P. Pearse Morris, Andrew McKeon, Sean Pittock, Shannon Hinson, Brian Weinshenker, Allen J. Aksamit, Evan A. Jolliffe, Anastasia Zekeridou, Dean

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FDA-approved pharmaceuticals against AQP4-IgG-positive NMOSD, shown to be effective in phase III clinical trials, first became available in 2019. As of 2020, they are among the most expensive drugs worldwide. They are not available in pill form, which, along with their high price, limits their

2812:

Kovacs KT, Kalluri SR, Boza-Serrano A, Deierborg T, Csepany T, Simo M, Rokusz L, Miseta A, Alcaraz N, Czirjak L, Berki T, Molnar T, Hemmer B, Illes Z (August 2016). "Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus

3940:

Marignier R, Bernard-Valnet R, Giraudon P, Collongues N, Papeix C, Zéphir H, Cavillon G, Rogemond V, Casey R, Frangoulis B, De Sèze J, Vukusic S, Honnorat J, Confavreux C (June 2013). "Aquaporin-4 antibody-negative neuromyelitis optica: distinct assay sensitivity-dependent entity".

547:(BBB), a system responsible for preventing substances in the blood from entering the brain. For antibodies from the blood to reach astrocytes in the central nervous system (CNS), they must cross the BBB, the mechanism of which is not completely known. Some reports point to the 614:

postrema helps explain involvement there. AQP4 is present in tissues outside the central nervous system (e.g. the kidneys), but these tissues aren't affected in NMOSD, at least in part because of the presence of autoimmune downregulators outside of the central nervous system.

5159:

Bizzoco E, Lolli F, Repice AM, Hakiki B, Falcini M, Barilaro A, Taiuti R, Siracusa G, Amato MP, Biagioli T, Lori S, Moretti M, Vinattieri A, Nencini P, Massacesi L, Matà S (November 2009). "Prevalence of neuromyelitis optica spectrum disorder and phenotype distribution".

2470:

Huang W, Wang L, Zhang B, Zhou L, Zhang T, Quan C. Effectiveness and tolerability of immunosuppressants and monoclonal antibodies in preventive treatment of neuromyelitis optica spectrum disorders: a systematic review and network meta-analysis. Mult Scler Relat Disord.

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Uchida T, Mori M, Uzawa A, Masuda H, Muto M, Ohtani R, Kuwabara S (July 2017). "Increased cerebrospinal fluid metalloproteinase-2 and interleukin-6 are associated with albumin quotient in neuromyelitis optica: Their possible role on blood-brain barrier disruption".

3274:

Ikeda K, Kiyota N, Kuroda H, Sato DK, Nishiyama S, Takahashi T, Misu T, Nakashima I, Fujihara K, Aoki M (April 2015). "Severe demyelination but no astrocytopathy in clinically definite neuromyelitis optica with anti-myelin-oligodendrocyte glycoprotein antibody".

308:, may occur in isolation or prior to formal loss of visual acuity. Compared to idiopathic ON and ON due to multiple sclerosis (MS), ON due to NMOSD more often results in severe visual loss at onset, with bilateral involvement, and permanent visual deficits. 3468:

Kitley J, Waters P, Woodhall M, Leite MI, Murchison A, George J, Küker W, Chandratre S, Vincent A, Palace J (March 2014). "Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study".

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status and the monophasic form related to its absence. Unlike MS, NMO rarely has a secondary progressive phase in which patients have increasing neurologic decline between attacks without remission. Instead, disabilities arise from the acute attacks.

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Bergamaschi R, Tonietti S, Franciotta D, Candeloro E, Tavazzi E, Piccolo G, Romani A, Cosi V (February 2004). "Oligoclonal bands in Devic's neuromyelitis optica and multiple sclerosis: differences in repeated cerebrospinal fluid examinations".

7424: 7409: 4376:

Alexander B. Ramos et al., A case of NMO spectrum disorder presenting with undiagnosed Sjogren's syndrome and a single, atypical tumefactive lesion: A clinical conundrum, Neur. Sciences, December 15, 2017Volume 383, Pages 216–218, DOI:

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Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG (July 2015).

5665:

Hahn S, Trendelenburg G, Scharf M, Denno Y, Brakopp S, Teegen B, Probst C, Wandinger KP, Buttmann M, Haarmann A, Szabados F, Vom Dahl M, Kümpfel T, Eichhorn P, Gold H, Paul F, Jarius S, Melzer N, Stöcker W, Komorowski L (June 2017).

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Why autoimmunity develops is largely unknown. Multiple genetic and environmental factors are known to increase the risk of developing NMOSD. The strongest risk factor is being female, especially in AQP4-IgG-positive NMOSD. Multiple

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AQP4-IgG levels are coarsely correlated with NMOSD disease activity, those levels generally increasing before relapse and declining during remission, with higher levels being correlated to more severe disease manifestation.

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Either 1) brain MRI showing normal findings or only nonspecific white matter lesions, or 2) optic nerve MRI showing T2-hyperintensity, or T1 enhancing lesion, greater than 1/2 optic nerve length or involving optic chiasm

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Kim SH, Kwak K, Hyun JW, Joung A, Lee SH, Choi YH, Lee JM, Kim HJ (July 2017). "Diffusion tensor imaging of normal-appearing white matter in patients with neuromyelitis optica spectrum disorder and multiple sclerosis".

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Stork, Lidia; Ellenberger, David; Ruprecht, Klemens; Reindl, Markus; Beißbarth, Tim; Friede, Tim; Kümpfel, Tania; Gerdes, Lisa A.; Gloth, Mareike; Liman, Thomas; Paul, Friedemann; Brück, Wolfgang; Metz, Imke (2020).

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Yeo, Tianrong; Probert, Fay; Jurynczyk, Maciej; Sealey, Megan; Cavey, Ana; Claridge, Timothy D. W.; Woodhall, Mark; Waters, Patrick; Leite, Maria Isabel; Anthony, Daniel C.; Palace, Jacqueline (1 November 2019).

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Ketelslegers IA, Modderman PW, Vennegoor A, Killestein J, Hamann D, Hintzen RQ (December 2011). "Antibodies against aquaporin-4 in neuromyelitis optica: distinction between recurrent and monophasic patients".

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Ketelslegers IA, Van Pelt DE, Bryde S, Neuteboom RF, Catsman-Berrevoets CE, Hamann D, Hintzen RQ (October 2015). "Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort".

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Signs and symptoms usually follow a relapsing and remitting course, but occasionally can be progressive (monophasic). Deficits can be temporary or permanent, the latter especially in the absence of treatment.

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Long term neurologic deficits are the cumulative effects of acute attacks, emphasizing the importance of acute treatment. Traditionally, attacks have been treated with short courses (3–5 days) of high dosage

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Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004). "A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis".

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Jurynczyk M, Probert F, Yeo T, Tackley G, Claridge TD, Cavey A, Woodhall MR, Arora S, Winkler T, Schiffer E, Vincent A, DeLuca G, Sibson NR, Isabel Leite M, Waters P, Anthony DC, Palace J (December 2017).

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Wingerchuk, Dean M.; Banwell, Brenda; Bennett, Jeffrey L.; Cabre, Philippe; Carroll, William; Chitnis, Tanuja; de Seze, Jérôme; Fujihara, Kazuo; Greenberg, Benjamin; Jacob, Anu; Jarius, Sven (2015-07-14).

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If AQP4-IgG is undetected, or its status is unknown, two core clinical criteria, each with supportive MRI findings, along with the ruling out of alternative diagnoses, are needed for an NMOSD diagnosis.

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M.C. Kruer, T.K. Koch, D.N. Bourdette, D. Chabas, E. Waubant, S. Mueller, M.A. Moscarello, J. Dalmau, R.L. Woltjer, G. Adamus, NMDA Receptor Encephalitis Mimicking Seronegative Neuromyelitis Optica,

1994:+ is very small and it can be considered a coincidence of two completely separate diseases in the same person. Assuming these cases can be verified, five different kinds of NMO are being considered: 225:

Neuromyelitis optica (NMO) is a particular disease within the NMOSD spectrum. It is characterised by optic neuritis and longitudinally extensive myelitis. In more than 80% of NMO cases, the cause is

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can be used in severe cases of NMO. Available data suggests that this procedure can reduce inflammatory activity in the short term, but a clear majority of the patients will relapse within 5 years.

7320: 7315: 4851:

Weinstock-Guttman B, Ramanathan M, Lincoff N, Napoli SQ, Sharma J, Feichter J, Bakshi R (July 2006). "Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease)".

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Iorio R, Rindi G, Erra C, Damato V, Ferilli M, Sabatelli M (May 2015). "Neuromyelitis optica spectrum disorder as a paraneoplastic manifestation of lung adenocarcinoma expressing aquaporin-4".

7332: 7310: 1656:. However, the spectrum of NMO has widened, due to improved diagnostic criteria; and the options for treatment have improved. As a result, researchers believe these estimates will be lowered. 6384: 2305:

Banerjee S, Butcher R. Rituximab for the Treatment of Neuromyelitis Optica Spectrum Disorder . Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2021 Feb. Available from:

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Watanabe S, Misu T, Miyazawa I, Nakashima I, Shiga Y, Fujihara K, Itoyama Y (September 2007). "Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis".

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Nasralla, Salam; Abboud, Hesham (November 2020). "Is neuromyelitis optica without AQP4-IgG a T-cell mediated disease? insights from checkpoint inhibitor immune-related adverse events".

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Pittock SJ, Weinshenker BG, Lucchinetti CF, Wingerchuk DM, Corboy JR, Lennon VA (July 2006). "Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression".

6094: 384:

is a common symptom, with studies showing that as many as 77% of people with NMOSD have fatigue. Fatigue has been found to correlate with quality of life in people with NMOSD.

4791: 1206:, it has been found that it appears also in patients with NMO-like symptoms that do not fulfill the clinical requirements to be diagnosed with NMO (recurrent and simultaneous 3764:

Spadaro M, Gerdes LA, Mayer MC, Ertl-Wagner B, Laurent S, Krumbholz M, Breithaupt C, Högen T, Straube A, Giese A, Hohlfeld R, Lassmann H, Meinl E, Kümpfel T (March 2015).

6283: 743:, anti-MOG diseases form the wider part of the NMO spectrum. The NMO cases are classified in four classes, according to the presence or absence of any of these two main 4071:

Arru G, Sechi E, Mariotto S, Farinazzo A, Mancinelli C, Alberti D, Ferrari S, Gajofatto A, Capra R, Monaco S, Deiana GA, Caggiu E, Mameli G, Sechi LA, Sechi GP (2017).

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https://www.merckmanuals.com/en-ca/home/brain,-spinal-cord,-and-nerve-disorders/multiple-sclerosis-ms-and-related-disorders/neuromyelitis-optica-spectrum-disorder-nmosd

6679: 6379: 6674: 2141: 2567:

Seok, Jin Myoung; Cho, Wanzee; Son, Doo-Hwan; Shin, Jong Hwa; Cho, Eun Bin; Kim, Sung Tae; Kim, Byoung Joon; Seong, Joon-Kyung; Min, Ju-Hong (January 28, 2022).

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The most common initial manifestation of the disease is inflammation of the spinal cord (myelitis). Myelitis causes spinal cord dysfunction, which can result in

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Illustration of the four different types of glial cells found in the central nervous system: ependymal cells, astrocytes, microglial cells, and oligodendrocytes

4762: 3862: 2494: 6476: 4821: 1668:. NMO is more common in women than men, with women comprising over two-thirds of patients and more than 80% of those with the relapsing form of the disease. 5943: 1475:

Has partially replaced azathioprine due to proposed better efficacy and tolerability. Sometimes combined with steroids due to months-long onset of action.

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First reported effective in 1998 and was mainstay of treatment 10+ years thereafter. Sometimes combined with steroids due to months-long onset of action.

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mechanism, targeting a perivascular protein, as the culprit of NMO, and in 2004 an unknown specific autoantibody was found. In 2005 they identified the

815:

cases than they are for seronegative AQP4-IgG ones. If AQP4-IgG is detected, then one core clinical criterion, along with the ruling out of alternative

5616:

Misu T, Höftberger R, Fujihara K, Wimmer I, Takai Y, Nishiyama S, Nakashima I, Konno H, Bradl M, Garzuly F, Itoyama Y, Aoki M, Lassmann H (June 2013).

2508:

Seok, Jin Myoung; Choi, Misong; Cho, Eun Bin; Lee, Hye Lim; Kim, Byoung Joon; Lee, Kwang Ho; Song, Pamela; Joo, Eun Yeon; Min, Ju-Hong (May 23, 2017).

7302: 6331: 4028:

Komatsu J, Sakai K, Nakada M, Iwasa K, Yamada M (August 2017). "Long spinal cord lesions in a patient with pathologically proven multiple sclerosis".

3129:"The cerebrospinal fluid immunoglobulin transcriptome and proteome in neuromyelitis optica reveals central nervous system-specific B cell populations" 6435: 5968: 3813:

Li Y, Xie P, Lv F, Mu J, Li Q, Yang Q, Hu M, Tang H, Yi J (October 2008). "Brain magnetic resonance imaging abnormalities in neuromyelitis optica".

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Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM, Trebst C, Weinshenker B, Wingerchuk D, Parisi JE, Lassmann H (July 2002).

7292: 6469: 2624:

Adouania, Mahdi; Mohamed, Dina Ben; Chaibi, Azza; Zouari, Rania; Rachdi, Amine; Said, Zakaria; Nabli, Fatma; Sassi, Samia Ben (December 1, 2023).

1553: 7506: 7272: 6945: 6440: 5936: 1279:

for NMO, but it is treatable. Some patients recover, but many are left with impairment of vision and limbs, which can be severe in some cases.

5524:

Isobe N, Yonekawa T, Matsushita T, et al. (May 2013). "Clinical relevance of serum aquaporin-4 antibody levels in neuromyelitis optica".

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Jarius S, Wildemann B (January 2013). "On the contribution of Thomas Clifford Allbutt, F.R.S., to the early history of neuromyelitis optica".

7297: 6929: 6450: 6255: 5420: 4213:

Lassmann H, Brück W, Lucchinetti C (March 2001). "Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy".

3692: 2426: 961: 733: 661: 4328:"Interferon-β-related tumefactive brain lesion in a Caucasian patient with neuromyelitis optica and clinical stabilization with tocilizumab" 7135: 7123: 6585: 6415: 6341: 6301: 5067:"A comparison of pediatric and adult neuromyelitis optica spectrum disorders: A review of clinical manifestation, diagnosis, and treatment" 1864: 1229: 708: 606:, which seems to play an integral part in the autoimmune response. There is a loss of astrocytes, and sometimes also a loss of neurons and 221:). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients. 2422: 2013: 1991: 1664:

Prevalence varies by region, ranging from 0.5 to 10 cases per 100,000 people. Unlike MS, prevalence has not been found to be related to

1233: 1114: 1078: 714: 436: 4550: 7354: 7287: 6842: 3897:

Fujihara K, Leite MI (June 2013). "Seronegative NMO: a sensitive AQP4 antibody test clarifies clinical features and next challenges".

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A retrospective study found that prevalence of neuromyelitis optica spectrum disorders was 1.5% among a random sample of neurological

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Fujihara K, Sato DK (October 2013). "AQP4 antibody serostatus: Is its luster being lost in the management and pathogenesis of NMO?".

3365:

Pröbstel AK, Rudolf G, Dornmair K, Collongues N, Chanson JB, Sanderson NS, Lindberg RL, Kappos L, de Seze J, Derfuss T (March 2015).

7057: 6860: 4799: 4073:"Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder" 1220:

The term neuromyelitis optica spectrum disorders (NMOSD) has been designed to allow incorporation of cases associated with non-AQP4

6374: 2481: 2318: 4733:"FDA approves first treatment for neuromyelitis optica spectrum disorder, a rare autoimmune disease of the central nervous system" 4500:"Early disruption of glial communication via connexin gap junction in multiple sclerosis, Baló's disease and neuromyelitis optica" 6445: 6321: 6311: 6268: 6122: 6089: 6069: 6410: 1918:

There is little research into the primary causes of the anti-AQP4 auto-antibodies. It has been noticed that some cases could be

750:

The clinical course and the response to therapy is different for various diseases classed within these groups, showing a better

7176: 6042: 1946: 950: 5392:

Devic E (1894). "Myélite subaiguë compliquée de névrite optique" [Subacute myelitis complicated with optic neuritis].

6691: 6667: 6497: 6326: 6238: 1958: 1177: 450:

NMO was associated in the past with many systemic diseases. Some researchers have pointed out that some other cases could be

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Wallach, AI; Tremblay, M; Kister, I (February 2021). "Advances in the Treatment of Neuromyelitis Optica Spectrum Disorder".

7370: 7255: 7171: 7113: 6662: 4123:"Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease" 1925:

In addition, several NMO variants have been discovered with antibodies other than those against AQP4, turning NMO into a

7501: 7339: 6713: 6405: 6369: 6064: 4827: 4768: 4738: 1300: 6849: 2248:

Jarius, Sven; Paul, Friedemann; Weinshenker, Brian G.; Levy, Michael; Kim, Ho Jin; Wildemann, Brigitte (2020-10-22).

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treatment, to prevent relapses of NMO, is generally employed; but the exact duration of such treatment is debatable.

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These variants are expected to respond to the same treatments as standard NMO. Some authors propose to use the name "

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Antibodies against MOG are considered mostly absent in similar diseases, such as MS. Therefore, it can be said that

7327: 6877: 6549: 4393:

Masaki K, Suzuki SO, Matsushita T, Matsuoka T, Imamura S, Yamasaki R, Suzuki M, Suenaga T, Iwaki T, Kira J (2013).

3873: 1712:) has been suggested to be identical to NMO (differences between OSMS and classic MS in Japanese patients). In the 1541: 1141: 778: 618: 610:. Loss of cells other than astrocytes is a consequence of collateral inflammatory damage or astrocyte dysfunction. 405: 174: 7219: 2440: 1727:

The majority of NMO patients have no affected relatives, and it is generally regarded as a nonfamilial condition.

7511: 7277: 7245: 7197: 7046: 6625: 6306: 6191: 5981: 5668:"Identification of the flotillin-1/2 heterocomplex as a target of autoantibodies in bona fide multiple sclerosis" 1735: 718: 1929:. Six different patterns of damage have been reported in NMO, raising the possibility of six different types of 260:

of NMOSD depend on the neurologic structures the disease affects, and, to some extent, the antibodies involved.

7439: 7344: 7118: 6532: 1166:), it is still possible to consider NMO as part of the MS spectrum. Besides, some NMO-AQP4(−) variants are not 798: 622: 396:(MS) can be similar in clinical and radiological presentation, and MS may very rarely present with an NMO-like 7349: 544: 320:. Lesions in the brain stem or upper cervical spinal cord can cause respiratory insufficiency. Lesions in the 5618:"Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica" 7282: 7038: 6856: 6708: 6698: 6542: 6026: 1778: 1763: 1739: 1602:

afterwards. However, at least 85% of patients have a relapsing form of the disease with repeated attacks of

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Baghbanian, Seyed Mohammad; Asgari, Nasrin; Sahraian, Mohammad Ali; Moghadasi, Abdorreza Naser (May 2018).

7516: 7479: 7214: 7206: 7161: 6837: 6809: 6657: 5960: 4326:

Harmel J, Ringelstein M, Ingwersen J, Mathys C, Goebels N, Hartung HP, Jarius S, Aktas O (December 2014).

2711:"Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later" 2099: 1432: 1098: 117: 976:

test, the spectrum of disorders comprising NMO was expanded. The spectrum is now believed to consist of:

7229: 7103: 6921: 6899: 6814: 6737: 6647: 6634: 6559: 3419:

Kezuka T, Usui Y, Yamakawa N, Matsunaga Y, Matsuda R, Masuda M, Utsumi H, Tanaka K, Goto H (June 2012).

2136: 1926: 1466: 1333: 907: 758:

for those in the NMO-Ab(+)/MOG-Ab(+) group. The MOG-related NMO can be radiologically identified by the

669: 5928: 5831:

Tianrong Yeo; Fay Probert; Maciej Jurynczyk; Megan Sealey; Ana Cavey; et al. (October 28, 2019).

4395:"Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica" 3127:

Kowarik MC, Dzieciatkowska M, Wemlinger S, Ritchie AM, Hemmer B, Owens GP, Bennett JL (January 2015).

2625: 288:

The second most common initial manifestation of the disease is inflammation of the optic nerve and/or

7166: 6983: 6872: 6349: 6273: 6006: 5735: 4406: 2722: 2580: 2569:"Association of subcortical structural shapes with fatigue in neuromyelitis optica spectrum disorder" 2521: 1794: 1708:. In fact, Asian optic-spinal multiple sclerosis (OSMS) (which constitutes 30% of the cases of MS in 1599: 1221: 1180:

in NMO are not usual, but they have been reported to appear in several cases mistakenly treated with

1118: 598:(IgM), inflammatory cells, and complement deposits around blood vessels. AQP4-IgG is a member of the 126: 7428: 7095: 6742: 6597: 6537: 6177: 6099: 5837: 2510:"Fatigue in patients with neuromyelitis optica spectrum disorder and its impact on quality of life" 1950: 1904: 1649: 1603: 1188: 1133: 1129: 568: 277: 2441:"Neuromyelitis optica spectrum disorder | Radiology Reference Article | Radiopaedia.org" 1859:

only moderately reflects disease activity, severity, or neurological prognosis. Later, some other

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Recently, the presence of AQP4 has been found to distinguish standard MS from NMO; but as MS is a

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are the cause. The cause of the remaining cases is still unknown, and it is likely heterogeneous.

7265: 7250: 7238: 6988: 6939: 6776: 6639: 6527: 6278: 6162: 6157: 6152: 6142: 5549: 5506: 5462: 5374: 5185: 5141: 5097: 4998: 4954: 4911: 4664: 4529: 4477: 4053: 4010: 3966: 3922: 3838: 3494: 3450: 3367:"Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype" 3344: 3300: 3204: 3058: 2838: 2794: 2688: 2645: 2285: 2146: 2035: 1777:

disorders date back to the late 18th and early 19th century. However, only an 1870 report by Sir

1747: 1731: 1713: 1568: 1296: 677: 626: 393: 237: 154: 122: 64: 6461: 3744:

Kun Jia et al., Anti-neurofascin-155 antibody-positive neuromyelitis optica spectrum disorders,

2626:"Factors Associated with Fatigue in Neuromyelitis Optica Spectrum Disorder in a Tunisian Cohort" 2482:

https://www.mayoclinic.org/diseases-conditions/neuromyelitis-optica/symptoms-causes/syc-20375652

7450: 7028: 6994: 6966: 6957: 6889: 6865: 6732: 6580: 6354: 6137: 6047: 5914: 5885:"Classifying the antibody-negative NMO syndromes: Clinical, imaging, and metabolomic modeling" 5864: 5833:"Classifying the antibody-negative NMO syndromes, Clinical, imaging, and metabolomic modeling" 5813: 5784:"Antibody signatures in patients with histopathologically defined multiple sclerosis patterns" 5763: 5699: 5647: 5598: 5541: 5498: 5454: 5416: 5366: 5331: 5280: 5226: 5203:

Cabre P, Signate A, Olindo S, Merle H, Caparros-Lefebvre D, Béra O, Smadja D (December 2005).

5177: 5133: 5089: 5047: 4990: 4946: 4903: 4868: 4714: 4656: 4618: 4600: 4521: 4469: 4434: 4359: 4308: 4281: 4230: 4195: 4154: 4102: 4045: 4002: 3958: 3914: 3830: 3795: 3698: 3688: 3651: 3633: 3590: 3535: 3486: 3442: 3398: 3336: 3292: 3256: 3196: 3160: 3109: 3050: 3014: 2979: 2930: 2878: 2830: 2786: 2748: 2680: 2606: 2549: 2404: 2386: 2277: 2269: 2131: 2017: 1912: 1868: 1798: 1637: 1629: 1618: 1225: 1163: 1102: 740: 665: 603: 572: 548: 529: 495: 466: 432: 345: 341: 325: 107: 48: 7151: 7022: 7017: 6802: 6797: 6079: 5904: 5896: 5854: 5846: 5803: 5795: 5753: 5743: 5689: 5679: 5637: 5629: 5588: 5580: 5533: 5490: 5446: 5358: 5321: 5311: 5270: 5260: 5216: 5169: 5125: 5081: 5037: 5029: 4982: 4938: 4895: 4860: 4704: 4696: 4648: 4608: 4592: 4511: 4461: 4424: 4414: 4349: 4339: 4271: 4261: 4222: 4185: 4144: 4134: 4092: 4084: 4037: 3994: 3950: 3906: 3822: 3785: 3777: 3678: 3641: 3625: 3580: 3572: 3525: 3478: 3432: 3388: 3378: 3328: 3284: 3246: 3238: 3188: 3150: 3140: 3099: 3089: 3042: 3006: 2969: 2961: 2920: 2912: 2822: 2778: 2738: 2730: 2672: 2637: 2596: 2588: 2539: 2529: 2394: 2376: 2261: 2095: 1844: 1515: 1063: 973: 857:

intramedullary lesion > 3 contiguous segments, or spinal atrophy ≥ 3 contiguous segments

812: 775: 771: 759: 692: 595: 560: 421: 361: 226: 178: 5205:"Role of return migration in the emergence of multiple sclerosis in the French West Indies" 7073: 6764: 6389: 6359: 5722:"Anti-aquaporin-1 autoantibodies in patients with neuromyelitis optica spectrum disorders" 5720:

Tzartos JS; Stergiou C; Kilidireas, K; Zisimopoulou, P; Thomaidis, T; Tzartos, SJ (2013).

2950:"The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica" 2123: 2091: 1835:

protein as the target of the disease, and developed the first in-house test to aid in the

1813: 1809: 1345:

accessibility. These new drugs' effectiveness against AQP4-IgG-negative NMOSD is unknown.

1181: 744: 607: 501: 273: 269: 3614:"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders" 3561:"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders" 2077: 1790: 1591:

Normally, some improvement appears in a few weeks, but severe residual symptoms and even

793:

MRI image of a patient with transverse myelitis, one of the diagnostic criteria for NMOSD

5739: 4929:

Matiello M, Jacob A, Wingerchuk DM, Weinshenker BG (June 2007). "Neuromyelitis optica".

4410: 2726: 2584: 2525: 2457:

Levin MC. Neuromyelitis optica spectrum disorder. Kenilworth (NJ): Merck Manuals; 2020:

1758: 789: 280:, affecting an entire cross-section of the spinal cord, and showing bilateral symptoms. 7130: 7079: 6907: 6616: 6493: 6364: 6054: 6016: 5909: 5884: 5859: 5832: 5808: 5783: 5758: 5721: 5694: 5667: 5642: 5617: 5593: 5568: 5326: 5299: 5275: 5248: 5042: 5017: 4709: 4684: 4613: 4580: 4429: 4394: 4354: 4327: 4276: 4249: 4149: 4122: 4097: 4072: 3790: 3765: 3646: 3613: 3585: 3560: 3530: 3513: 3393: 3366: 3251: 3226: 3155: 3128: 3104: 3077: 2974: 2949: 2925: 2900: 2743: 2710: 2601: 2544: 2509: 2399: 2364: 1919: 1892: 1705: 1683: 1607: 1480: 1310: 1306: 1292: 1082: 1033: 1023: 988: 954: 840: 533: 451: 293: 210: 7433: 5584: 5450: 5300:"The history of neuromyelitis optica. Part 2: 'Spinal amaurosis', or how it all began" 4226: 2901:"IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel" 2061:-negative NMO can be classified into three groups, and that this classification has a 1979:, although, as of 2015, there are only initial reports about the involvement of these 1855:(enzyme-linked immunosorbent assay) kits were soon developed, However, serum AQP4-IgG 7495: 7156: 7108: 6978: 6747: 6703: 6554: 6212: 5510: 5145: 5002: 4668: 3926: 3826: 2692: 2649: 2568: 2289: 2002: 1786: 1248: 1155: 983:

Limited forms of NMO, such as single or recurrent events of longitudinally extensive

862: 583: 564: 537: 513: 321: 297: 57: 5553: 5466: 5378: 5189: 4958: 4481: 4014: 3970: 3842: 3454: 3348: 3304: 2798: 729:

disease, and higher levels being associated with more severe disease manifestation.

6652: 6522: 6505: 6172: 5101: 4915: 4533: 4057: 3498: 3227:"A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica" 3208: 3062: 2842: 2051: 1999: 1942: 1930: 1860: 1817: 1701: 1644:

within five years. In some patients (33% in one study), transverse myelitis in the

1503: 1491: 1452: 1405: 1387: 1322: 1256: 1252: 1244: 1214: 1203: 1159: 1137: 1049: 915: 721: 681: 649: 424: 417: 401: 353: 305: 301: 289: 247:

Less common diseases with other manifestations are also part of the NMOSD spectrum.

229: 202: 170: 166: 158: 146: 142: 73: 1267: 7444: 5900: 5850: 5748: 4942: 4596: 4465: 4419: 3954: 3910: 3766:"Histopathology and clinical course of MOG-antibody-associated encephalomyelitis" 3683: 3629: 3576: 3512:

Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG (May 2006).

3482: 3437: 3420: 2948:

Lucchinetti CF, Guo Y, Popescu BF, Fujihara K, Itoyama Y, Misu T (January 2014).

2534: 1567:

It is important to note that certain immunosuppressants used to treat MS—such as

6611: 6572: 6514: 6187: 6182: 6127: 4700: 2676: 2641: 2381: 2306: 2151: 2029: 2006: 1987: 1976: 1972: 1880: 1832: 1824: 1774: 1770: 1676: 1645: 1580: 1576: 1309:

can be an effective treatment when attacks progress after the administration of

1289: 1211: 1207: 1200: 1094: 1067: 1005: 994: 808: 653: 637: 576: 556: 552: 505: 428: 357: 233: 214: 206: 97: 69: 7455: 5799: 5018:"Autologous haematopoietic stem cell transplantation for neurological diseases" 4041: 3720: 3670: 2592: 481: 7418: 6722: 6592: 6231: 6167: 6147: 6132: 6106: 5991: 5684: 5633: 5537: 5362: 5316: 5173: 5085: 4986: 4864: 4763:"FDA Approves New Therapy for Rare Disease Affecting Optic Nerve, Spinal Cord" 4652: 4344: 4139: 3998: 3383: 3145: 3094: 3010: 2495:"NMOSD, Fatigue, and Thalamic Volume - Neuromyelitis Optica Spectrum Disorder" 2265: 2113: 1908: 1900: 1806: 1721: 1621: 1592: 1572: 1368: 1318: 1074: 1027: 903: 805: 555:-6 as culprits responsible for the BBB failure. There is broad consensus that 435:) are the cause, and in 10–40% of the remaining cases, IgG antibodies against 317: 138: 133: 5494: 5129: 5033: 4899: 4822:"FDA Approves Treatment for Rare Disease Affecting Optic Nerves, Spinal Cord" 4604: 4266: 4088: 3637: 3332: 3288: 3046: 2826: 2782: 2390: 2273: 725:

cerebral spinal fluid into lymph nodes causes autoimmune reaction formation.

6832: 6783: 6771: 6754: 6686: 6207: 6202: 6011: 5996: 4378: 3749: 3735:

Wingerchuk, Eoin P. Flanagan, Neurology Apr 2018, 90 (15 Supplement) S13.006

3078:"Selective localization of IgG from cerebrospinal fluid to brain parenchyma" 2102: 1965: 1836: 1802: 1782: 1691: 1641: 1633: 1527: 1325:

and mixed with a solution, then the new blood mixture being pumped back in.

1167: 1057: 889: 816: 755: 751: 696: 633: 591: 525: 521: 509: 397: 333: 241: 150: 53: 5918: 5868: 5817: 5767: 5703: 5651: 5602: 5545: 5502: 5458: 5370: 5335: 5284: 5265: 5230: 5221: 5204: 5181: 5137: 5093: 5051: 4994: 4950: 4907: 4872: 4718: 4660: 4622: 4525: 4473: 4438: 4363: 4312: 4285: 4234: 4199: 4158: 4106: 4049: 4006: 3962: 3918: 3834: 3799: 3702: 3655: 3594: 3539: 3490: 3446: 3421:"Relationship between NMO-antibody and anti-MOG antibody in optic neuritis" 3402: 3340: 3296: 3260: 3242: 3200: 3164: 3113: 3054: 3018: 2983: 2934: 2882: 2834: 2790: 2752: 2684: 2610: 2553: 2421:

A subset of anti-AQP4-negative cases is associated with antibodies against

2408: 2281: 2249: 4190: 4173: 296:, ON). ON may lead to varying degrees of visual impairment with decreased 7474: 7012: 7004: 6970: 6824: 6727: 6197: 5986: 5726: 3675:

Diseases of the Brain, Head and Neck, Spine 2020–2023: Diagnostic Imaging

2916: 2062: 2058: 2039: 1896: 1888: 1884: 1840: 1743: 1665: 1237: 1125: 1070: 1037: 1019: 984: 933: 930: 892: 873: 865: 852: 763: 645: 587: 517: 470: 329: 316:

Less commonly than the spinal cord and optic nerve, NMOSD can affect the

218: 162: 1271:

Chemical structure of methylprednisolone, which is used to treat attacks

1128:

after an acute episode than standard MS, which infrequently presents as

6001: 4516: 4499: 3677:. IDKD Springer Series. Cham, Switzerland: Springer. pp. 165–176. 2899:

Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (August 2005).

2734: 1980: 1828: 1717: 1675:, with a MS:NMOSD ratio of 42:7. Among 13 NMOSD patients, 77% had long 1672: 1611: 767: 713:

The second most frequent autoantibody in NMO is MOG-IgG, which targets

381: 349: 257: 7401: 3192: 2965: 1077:

NMO poses a diagnostic challenge. Some cases could be related to anti-

7413: 7051: 6792: 6759: 5976: 3781: 2085: 1694: 1679: 1583:—worsen NMO disease progression and should not be used to treat NMO. 1171: 1152: 1107: 1041: 1001: 937: 918: 877: 869: 673: 657: 641: 340:. Additional brain lesions are common but often asymptomatic (though 272:, paralysis in the limbs, lost or reduced sensation, spasms, loss of 4579:

Kowarik, Markus C.; Soltys, John; Bennett, Jeffrey L. (March 2014).

4077:

Multiple Sclerosis Journal: Experimental, Translational and Clinical

3076:

Mørch MT, Sørensen SF, Khorooshi R, Asgari N, Owens T (April 2018).

1724:, MS is rare; but when it appears, it often takes the form of OSMS. 1614:

having a relapse in the first year and 90% in the first five years.

1598:

The disease can be monophasic, i.e. a single episode with permanent

1251:" for these diseases, while others prefer a more generic term "AQP4- 7307:

Spinal muscular atrophy with lower extremity predominance (SMALED)

1895:. A number of drugs are being studied: aquaporumab (non-pathogenic 617:

In NMOSD, areas of brain tissue that appear normal in conventional

4250:"Autoantibodies to Potassium Channel KIR4.1 in Multiple Sclerosis" 1954: 1856: 1852: 1848: 1757: 1709: 1687: 1653: 1314: 1266: 1228:, plus other non-related but clinically similar syndromes such as 1045: 998: 980:

Standard NMO, according to the diagnostic criteria described above

801:, which have undergone multiple revisions, most recently in 2015. 788: 480: 459: 455: 337: 1636:

in one or both legs. Among patients with relapsing NMO, 50% have

1628:

Approximately 20% of patients with monophasic NMO have permanent

1010:

inflammatory demyelinating diseases of the central nervous system

6021: 2081: 2023: 1276: 953:

are consistent with NMO. Preliminary reports suggest that other

599: 276:

and bowel control, or erectile dysfunction. The myelitis can be

6465: 5932: 4685:"Treatment of neuromyelitis optica: Review and recommendations" 2365:"Neuromyelitis Optica Spectrum Disorder and Anti-MOG Syndromes" 563:

initially enters the brain via BBB-deficient sites such as the

408:, cerebrospinal fluid findings, disease course, and prognosis. 201:) are a spectrum of autoimmune diseases characterized by acute 4551:"Neuromyelitis optica - Diagnosis and treatment - Mayo Clinic" 2068:

Later studies have increased the number of groups up to four.

1968:. It has been found in seronegative NMO and some MS patients. 911: 16:

Acute inflammation diseases of the optic nerve and spinal cord

1887:

have focused on targeted treatment aimed at anti-aquaporin 4

3759: 3757: 1816:

control. They recognized these symptoms were the result of

1144:

are uncommon in NMO, but occur in over 90% of MS patients.

92:

AQP4-IgG-positive, MOG-IgG-positive (recurrent, monophasic)

6385:

Megalencephalic leukoencephalopathy with subcortical cysts

1431:

the current standard treatment. Most of these medications

1224:. Therefore, it includes all the clinical variants due to 1117:-ab levels can be too low to be detected. Some additional 5016:

Burman J, Tolf A, Hägglund H, Askmark H (February 2018).

1797:

student Fernand Gault described 16 patients who had lost

1617:

It is possible that the relapsing form is related to the

582:

Within astrocytes, AQP4 is primarily found in astrocytic

420:

attack on the nervous system. In more than 80% of cases,

3719:, May 04, 2010; 74 (18) Clinical/Scientific Notes, DOI: 3673:. In Hodler J, Kubik-Huch RA, von Schulthess GK (eds.). 3671:"13 Demyelinating Diseases of the CNS (Brain and Spine)" 754:

for those in the NMO-Ab(−)/MOG-Ab(−) group, and a worse

458:

can produce NMO-IgG autoantibodies, leading to cases of

4634: 4632: 2032:

associated NMO which could be related to pattern III MS

1255:", which also includes deficiencies of AQP4 with a non- 1124:

NMO differs from MS in that it usually has more severe

540:, since the astrocytes are semi-selectively destroyed. 3514:"Revised diagnostic criteria for neuromyelitis optica" 1891:. The most established method for antibody removal is 586:

that abut blood vessels and the linings of the brain (

532:. Thus, NMOSD involving AQP4-IgG can be considered an 6095:

Lesional demyelinations of the central nervous system

3606: 3604: 2363:

Lana-Peixoto, Marco A.; Talim, Natália (2019-06-12).

1697:. Only 56% had clinically definite NMO at follow-up. 516:

that allows water to pass through the membrane. AQP4

7391: 1004:

like MS does, but it should not be confused with an

960:

NMOSD with MOG-IgG is considered a manifestation of

835:

Additional MRI findings for absent/unknown AQP4-IgG

602:

immunoglobulin family, which is an activator of the

7465: 7395: 7228: 7205: 7196: 7189: 7144: 7094: 7066: 7037: 7003: 6965: 6954: 6920: 6898: 6823: 6633: 6624: 6610: 6570: 6513: 6504: 6428: 6398: 6340: 6292: 6254: 6247: 6221: 6115: 6035: 5967: 4301:

Nihon Rinsho. Japanese Journal of Clinical Medicine

695:-negative cases are less understood. It seems that 184: 132: 116: 106: 96: 88: 80: 63: 47: 29: 24: 5889:Neurology: Neuroimmunology & Neuroinflammation 5022:Journal of Neurology, Neurosurgery, and Psychiatry 2869:Wingerchuk DM (May 2006). "Neuromyelitis optica". 2301: 2299: 1820:of the optic nerve and spinal cord, respectively. 1536:The most commonly used treatment for NMOSD today. 949:Rarely, it has been reported that some courses of 6284:Chronic inflammatory demyelinating polyneuropathy 4545: 4543: 2054:. They constitute an overlap between NMO and MS. 1379:Monoclonal antibody against complement protein C5 1113:Another problem for diagnosis is that AQP4-ab in 993:Asian optic-spinal multiple sclerosis (OSMS), or 762:involvement. Myelin-oligodendrocyte glycoprotein 4574: 4572: 4570: 2057:As of 2019 some statistical studies showed that 524:, and the tetramers aggregate. AQP4 is found in 6380:Leukoencephalopathy with vanishing white matter 5242: 5240: 4388: 4386: 3553: 3551: 3549: 3360: 3358: 3220: 3218: 2894: 2892: 1863:were found in NMO AQP4-negative cases, such as 84:Median: age 40 for AQP4-IgG, age 31 for MOG-IgG 3870:2006 Rare Neuroimmunologic Disorders Symposium 3770:Annals of Clinical and Translational Neurology 2704: 2702: 2142:Idiopathic inflammatory demyelinating diseases 1957:) and atypical NMO, leading to the concept of 1812:of the limbs, loss of sensation, and often of 1730:Rarely, NMO may occur in the context of other 684:is often quite distinct from that seen in MS. 6477: 5944: 4493: 4491: 2864: 2862: 2860: 2858: 2856: 2854: 2852: 2307:https://www.ncbi.nlm.nih.gov/books/NBK571350/ 1742:) or infectious diseases. In some cases, the 8: 5413:Multiple Sclerosis: The History of a Disease 4299:Kurosawa K, Fujihara K (November 2014). "". 3856: 3854: 3852: 3721:https://doi.org/10.1212/WNL.0b013e3181dc1a7f 2709:Pittock SJ, Lucchinetti CF (February 2016). 2319:"Neuromyelitis optica – Symptoms and causes" 2038:NMO, defined by the absence of all previous 1933:. As of 2019, only three of them are known. 1313:. This treatment involves the patient's own 736:are grouped within AQP4-IgG-negative NMOSD. 7392: 7202: 7193: 6962: 6630: 6621: 6510: 6484: 6470: 6462: 6251: 5951: 5937: 5929: 5715: 5713: 2715:Annals of the New York Academy of Sciences 1781:created sustained interest on the part of 1347: 987:, and bilateral simultaneous or recurrent 21: 6332:Experimental autoimmune encephalomyelitis 5908: 5858: 5807: 5757: 5747: 5693: 5683: 5641: 5592: 5567:Papadopoulos MC, Verkman AS (June 2012). 5325: 5315: 5274: 5264: 5220: 5041: 4708: 4612: 4515: 4428: 4418: 4379:https://doi.org/10.1016/j.jns.2017.10.036 4353: 4343: 4275: 4265: 4189: 4148: 4138: 4096: 3863:"Neuromyelitis Optica (Devic's Syndrome)" 3789: 3750:https://doi.org/10.1016/j.jns.2019.01.024 3682: 3645: 3584: 3529: 3436: 3414: 3412: 3392: 3382: 3250: 3154: 3144: 3103: 3093: 2973: 2924: 2742: 2600: 2543: 2533: 2398: 2380: 1871:-negative cases still remain idiopathic. 1398:Monoclonal antibody against CD19+ B cells 804:Diagnostic criteria are more relaxed for 640:. The damage can range from inflammatory 447:(HLA) alleles are associated with NMOSD. 6436:List of multiple sclerosis organizations 4689:Multiple Sclerosis and Related Disorders 2764: 2762: 2665:Multiple Sclerosis and Related Disorders 2630:Multiple Sclerosis and Related Disorders 2480:Mayo Clinic. Neuromyelitis optica 2020; 1971:Finally, other proteins under study are 1533:antibody against CD20 – B cell depletion 1437: 825: 680:distribution. Therefore, the pattern of 5298:Jarius S, Wildemann B (November 2018). 4581:"The Treatment of Neuromyelitis Optica" 3669:Barkhof F, Koeller KK (February 2020). 2163: 1964:Other autoantibody being researched is 1554:hematopoietic stem cell transplantation 1151:, and some MS cases are reported to be 1132:. In addition oligoclonal bands in the 1097:-Ab-negative NMO presents problems for 195:Neuromyelitis optica spectrum disorders 25:Neuromyelitis optica spectrum disorders 7273:Distal hereditary motor neuronopathies 6946:Template:Demyelinating diseases of CNS 6441:List of people with multiple sclerosis 6317:Neuromyelitis optica spectrum disorder 6264:Neuromyelitis optica spectrum disorder 5569:"Aquaporin 4 and neuromyelitis optica" 5415:. New York: Demos Medical Publishing. 5247:Jarius S, Wildemann B (January 2013). 2046:Antibody negative neuromyelitis optica 957:may play a role in rare cases of NMO. 672:), but they differ from MS pattern II 244:protein in the central nervous system. 5249:"The history of neuromyelitis optica" 3730: 3728: 2813:erythematosus: A preliminary study". 2358: 2243: 2241: 2239: 2237: 2235: 2233: 2231: 2229: 2227: 2225: 2223: 2221: 2219: 2217: 2215: 2213: 2211: 2209: 2207: 2205: 2203: 2201: 2199: 2197: 2195: 2193: 2191: 2189: 2187: 2009:-Ab+) – around 80% of total NMO cases 1382:Approved for AQP4-IgG-positive NMOSD 1230:anti-MOG associated encephalomyelitis 962:anti-MOG associated encephalomyelitis 883:dorsal medulla/area postrema lesions 819:, is sufficient for NMOSD diagnosis. 7: 7124:Idiopathic intracranial hypertension 6416:Mitochondrial DNA depletion syndrome 6302:Acute disseminated encephalomyelitis 5074:Journal of the Neurological Sciences 4975:Journal of the Neurological Sciences 4127:Acta Neuropathologica Communications 2905:The Journal of Experimental Medicine 2356: 2354: 2352: 2350: 2348: 2346: 2344: 2342: 2340: 2338: 2185: 2183: 2181: 2179: 2177: 2175: 2173: 2171: 2169: 2167: 1419:Approved forAQP4-IgG-positive NMOSD 709:antiMOG associated encephalomyelitis 625:(DTI), although less so compared to 112:Symptoms, blood antibody titers, MRI 4973:monitoring. A six-year follow-up". 2423:myelin oligodendrocyte glycoprotein 1769:First reports on an association of 1079:myelin oligodendrocyte glycoprotein 715:myelin oligodendrocyte glycoprotein 538:autoimmune astrocytic channelopathy 7355:Infantile progressive bulbar palsy 3531:10.1212/01.wnl.0000216139.44259.74 1805:and within weeks developed severe 14: 7058:Template:Cerebrovascular diseases 6861:Frontotemporal lobar degeneration 2050:Some cases of NMO are not due to 1178:Tumefactive demyelinating lesions 997:+ OSMS. This variant can present 972:After the development of the NMO- 7078:For more detailed coverage, see 7056:For more detailed coverage, see 7027:For more detailed coverage, see 6993:For more detailed coverage, see 6944:For more detailed coverage, see 6446:Multiple sclerosis drug pipeline 6322:Diffuse myelinoclastic sclerosis 6312:Marburg acute multiple sclerosis 6269:Diffuse myelinoclastic sclerosis 6123:Management of multiple sclerosis 6090:Radiologically isolated syndrome 6070:Expanded Disability Status Scale 4030:Journal of Clinical Neuroscience 3827:10.1111/j.1600-0404.2008.01012.x 3746:Journal of Neurological Sciences 2116: 1937:Research into new autoantibodies 1789:in this rare syndrome. In 1894, 1416:Monoclonal antibody against IL-6 1195:Evolution of diagnostic criteria 897:periependymal brainstem lesions 590:). NMOSD brain lesions, as seen 6043:Diagnosis of multiple sclerosis 2254:Nature Reviews. Disease Primers 1947:glial fibrillary acidic protein 352:). Lesions may also affect the 76:, weakness, bladder dysfunction 6327:Tumefactive multiple sclerosis 6239:Research in multiple sclerosis 5959:Demyelinating diseases of the 4585:Journal of Neuro-Ophthalmology 3425:Journal of Neuro-Ophthalmology 1959:autoimmune GFAP astrocytopathy 1899:blocker of AQP4-IgG binding), 1496:DNA synthesis/repair inhibitor 908:diencephalic clinical syndrome 528:, which are the basis for the 1: 7507:Demyelinating diseases of CNS 7371:Amyotrophic lateral sclerosis 7256:Hereditary spastic paraplegia 7114:Normal pressure hydrocephalus 5585:10.1016/S1474-4422(12)70133-3 5451:10.1016/S0140-6736(04)17551-X 4743:(Press release). 27 June 2019 4227:10.1016/s1471-4914(00)01909-2 3815:Acta Neurologica Scandinavica 3181:European Journal of Neurology 1949:(GFAP)—was found in 2016, in 662:classified as type II lesions 469:) has opened a new avenue of 7340:Progressive muscular atrophy 6406:Central pontine myelinolysis 6375:Pelizaeus–Merzbacher disease 6370:Metachromatic leukodystrophy 6065:Clinically isolated syndrome 6036:Investigations and diagnosis 5901:10.1212/NXI.0000000000000626 5851:10.1212/NXI.0000000000000626 5749:10.1371/journal.pone.0074773 5672:Journal of Neuroinflammation 5304:Journal of Neuroinflammation 5253:Journal of Neuroinflammation 4943:10.1097/WCO.0b013e32814f1c6b 4931:Current Opinion in Neurology 4828:Food and Drug Administration 4769:Food and Drug Administration 4739:Food and Drug Administration 4597:10.1097/WNO.0000000000000102 4466:10.1212/WNL.0b013e3182a6cc23 4420:10.1371/journal.pone.0072919 4215:Trends in Molecular Medicine 3955:10.1212/WNL.0b013e318296e917 3911:10.1212/WNL.0b013e318296ea22 3684:10.1007/978-3-030-38490-6_13 3630:10.1212/WNL.0000000000001729 3577:10.1212/WNL.0000000000001729 3483:10.1001/jamaneurol.2013.5857 3438:10.1097/WNO.0b013e31823c9b6c 3371:Journal of Neuroinflammation 3133:Journal of Neuroinflammation 3082:Journal of Neuroinflammation 2535:10.1371/journal.pone.0177230 1340:FDA-approved pharmaceuticals 543:The astrocytes surround the 336:, as well as pain and tonic 6850:Primary progressive aphasia 6411:Marchiafava–Bignami disease 4773:(Press release). 2020-06-11 4701:10.1016/j.msard.2012.06.002 4172:Pearce JM (November 2005). 2677:10.1016/j.msard.2020.102451 2642:10.1016/j.msard.2023.105245 2613:– via www.nature.com. 2382:10.3390/biomedicines7020042 2020:– around 10% of total cases 1736:connective tissue disorders 1199:Since the discovery of the 1012:spectrum, sometimes called 799:consensus clinical criteria 699:are spared in these cases. 567:, where there is access to 500:NMOSD is usually caused by 102:Female sex, genetic factors 7533: 7172:Hashimoto's encephalopathy 6878:Posterior cortical atrophy 6699:Striatonigral degeneration 6550:Cavernous sinus thrombosis 5800:10.1007/s00401-019-02120-x 5483:Multiple Sclerosis Journal 4042:10.1016/j.jocn.2017.03.022 2652:– via ScienceDirect. 2593:10.1038/s41598-022-05531-1 1839:of NMO by detection of an 1542:intravenous immunoglobulin 1508:Inhibits folate metabolism 1472:Inhibits purine metabolism 1458:Inhibits purine metabolism 827:NMOSD diagnostic criteria 779:magnetic resonance imaging 706: 656:matters. The inflammatory 636:of NMO has focused on the 619:magnetic resonance imaging 493: 465:The discovery of NMO-IgG ( 406:magnetic resonance imaging 175:intravenous immunoglobulin 34:Neuromyelitis optica (NMO) 7278:Spinal muscular atrophies 7246:Primary lateral sclerosis 7104:Intracranial hypertension 6884:Creutzfeldt–Jakob disease 6307:Balo concentric sclerosis 5685:10.1186/s12974-017-0900-z 5634:10.1007/s00401-013-1116-7 5538:10.1007/s11064-013-1009-0 5363:10.1007/s00415-012-6594-3 5317:10.1186/s12974-019-1594-1 5174:10.1007/s00415-009-5171-x 5086:10.1016/j.jns.2018.02.028 4987:10.1016/j.jns.2016.11.016 4865:10.1001/archneur.63.7.957 4792:"Enspryng (satralizumab)" 4653:10.1016/j.ncl.2020.09.003 4498:Masaki K (October 2015). 4345:10.1186/s12883-014-0247-3 4140:10.1186/s40478-017-0495-8 3999:10.1191/1352458504ms988oa 3861:Wingerchuk, Dean (2006). 3748:, January 16, 2019, DOI: 3384:10.1186/s12974-015-0256-1 3146:10.1186/s12974-015-0240-9 3095:10.1186/s12974-018-1159-8 3011:10.1001/archneur.63.7.964 2266:10.1038/s41572-020-0214-9 2012:NMO derived from an anti- 1851:. The first quantitative 1827:researchers identified a 1632:, and 30% have permanent 1446: 1026:associated with systemic 1018:Longitudinally extensive 936:with NMOSD-typical brain 797:NMOSD is diagnosed using 770:were more likely to have 621:(MRI) can show damage in 404:, clinical presentation, 7345:Progressive bulbar palsy 7136:Intracranial hypotension 7119:Choroid plexus papilloma 6533:Herpesviral encephalitis 5495:10.1177/1352458512443917 5130:10.1177/1352458511412995 5034:10.1136/jnnp-2017-316271 4900:10.1177/1352458507077189 4683:Dean M. (October 2012). 4267:10.3389/fneur.2013.00125 4089:10.1177/2055217317742425 3333:10.1177/1352458514566666 3289:10.1177/1352458514551455 3047:10.1177/1352458516672015 2871:International MS Journal 2827:10.1177/1352458515613165 2783:10.1177/1352458515572241 1740:paraneoplastic syndromes 1433:affect the immune system 623:diffusion tensor imaging 348:, may be underdiagnosed 6857:Frontotemporal dementia 6543:Encephalitis lethargica 5411:T. Jock Murray (2005). 4083:(4): 2055217317742425. 1879:Since the discovery of 1779:Thomas Clifford Allbutt 1764:Thomas Clifford Allbutt 1321:being removed from the 1149:heterogeneous condition 1054:periventricular nucleus 868:(prolonged episodes of 632:Most research into the 445:human leukocyte antigen 7162:Hepatic encephalopathy 6248:Demyelinating diseases 5961:central nervous system 5526:Neurochemical Research 5266:10.1186/1742-2094-10-8 4254:Frontiers in Neurology 4174:"Neuromyelitis optica" 2484:. Accessed 2020 Nov 23 2461:. Accessed 2020 Nov 23 2250:"Neuromyelitis optica" 2100:biomedical engineering 1766: 1714:indigenous populations 1700:NMO is more common in 1272: 1187:Also, an overlap with 1101:. The behavior of the 1099:differential diagnosis 1090:Differential diagnosis 794: 486: 416:NMOSD is caused by an 118:Differential diagnosis 7220:Ataxia–telangiectasia 7177:Static encephalopathy 6900:Mitochondrial disease 6738:Spasmodic torticollis 6648:Basal ganglia disease 5788:Acta Neuropathologica 5622:Acta Neuropathologica 5573:The Lancet. Neurology 4853:Archives of Neurology 4191:10.1038/sj.sc.3101758 2999:Archives of Neurology 2137:Demyelinating disease 1927:heterogeneous disease 1761: 1467:mycophenolate mofetil 1270: 968:Spectrum constituents 792: 484: 240:), the most abundant 7167:Toxic encephalopathy 6873:Lewy bodies dementia 6350:Adrenoleukodystrophy 6274:MOG antibody disease 6076:Serological and CSF 6027:Uhthoff's phenomenon 5351:Journal of Neurology 5222:10.1093/brain/awh624 5162:Journal of Neurology 4802:on 23 September 2020 4248:Schneider R (2013). 3243:10.1093/brain/awf151 2917:10.1084/jem.20050304 1998:NMO derived from an 1646:cervical spinal cord 1426:Off-label treatments 1357:Date of FDA approval 1329:Secondary prevention 1121:have been proposed. 571:(CSF). In any case, 304:defects, or loss of 127:autoimmune disorders 7502:Autoimmune diseases 7215:Friedreich's ataxia 6598:Meningoencephalitis 6538:Limbic encephalitis 6178:Monomethyl fumarate 5740:2013PLoSO...874773T 5215:(Pt 12): 2899–910. 4411:2013PLoSO...872919M 2727:2016NYASA1366...20P 2585:2022NatSR..12.1579S 2526:2017PLoSO..1277230S 1951:transverse myelitis 1905:neutrophil elastase 1875:Research directions 1732:autoimmune diseases 1722:subtropical regions 1650:respiratory failure 1604:transverse myelitis 1444:Mechanism of action 1360:Mechanism of action 1191:has been reported. 1130:transverse myelitis 828: 676:in their prominent 575:is produced mainly 569:cerebrospinal fluid 545:blood–brain barrier 490:Anti-AQP4+ variants 264:Spinal cord effects 7466:External resources 7251:Pseudobulbar palsy 6989:Status epilepticus 6940:Multiple sclerosis 6777:Myoclonic epilepsy 6640:movement disorders 6586:Acute disseminated 6528:Viral encephalitis 6279:Multiple sclerosis 6163:Interferon beta-1b 6158:Interferon beta-1a 6153:Glatiramer acetate 6143:Diroximel fumarate 6116:Approved treatment 5969:Signs and symptoms 5118:Multiple Sclerosis 4888:Multiple Sclerosis 4641:Neurologic Clinics 4555:www.mayoclinic.org 4517:10.1111/neup.12211 3987:Multiple Sclerosis 3321:Multiple Sclerosis 3277:Multiple Sclerosis 3035:Multiple Sclerosis 2815:Multiple Sclerosis 2771:Multiple Sclerosis 2735:10.1111/nyas.12794 2573:Scientific Reports 2147:Multiple sclerosis 1883:involvement, some 1867:IgG, but some NMO 1767: 1317:being pumped out, 1297:methylprednisolone 1273: 1232:. Some cases with 1164:potassium channels 1048:areas such as the 1008:-negative form of 826: 795: 703:Anti-MOG+ variants 627:multiple sclerosis 592:under a microscope 487: 454:. It appears that 394:multiple sclerosis 388:Comparison with MS 364:(AQP4-IgG) NMOSD. 342:cognitive deficits 252:Signs and symptoms 155:methylprednisolone 123:Multiple sclerosis 7489: 7488: 7389: 7388: 7385: 7384: 7381: 7380: 7185: 7184: 7090: 7089: 7029:Template:Headache 6995:Template:Epilepsy 6916: 6915: 6890:Vascular dementia 6733:Status dystonicus 6606: 6605: 6581:Encephalomyelitis 6459: 6458: 6424: 6423: 6355:Alexander disease 6138:Dimethyl fumarate 6080:Oligoclonal bands 6048:McDonald criteria 5489:(11): 1541–1551. 5445:(9451): 2106–12. 5422:978-1-888799-80-4 3694:978-3-030-38489-0 3237:(Pt 7): 1450–61. 3193:10.1111/ene.13321 2966:10.1111/bpa.12099 2439:Gaillard, Frank. 2132:Anti-AQP4 disease 2018:encephalomyelitis 1746:remains unknown ( 1682:, 38% had severe 1565: 1564: 1435:in various ways. 1423: 1422: 1240:have been found. 1140:lesions on brain 1103:oligoclonal bands 947: 946: 741:anti-AQP4 disease 734:anti-MOG diseases 719:integral membrane 717:(MOG). MOG is an 660:in NMO have been 604:complement system 549:metalloproteinase 530:glymphatic system 496:Anti-AQP4 disease 473:into the causes. 326:medulla oblongata 192: 191: 188:Up to 1 in 10,000 108:Diagnostic method 19:Medical condition 7524: 7512:Myelin disorders 7393: 7203: 7194: 7152:Brain herniation 6963: 6803:Intention tremor 6798:Essential tremor 6663:Postencephalitic 6631: 6622: 6511: 6492:Diseases of the 6486: 6479: 6472: 6463: 6252: 6222:Other treatments 6100:Dawson's fingers 5953: 5946: 5939: 5930: 5923: 5922: 5912: 5879: 5873: 5872: 5862: 5828: 5822: 5821: 5811: 5778: 5772: 5771: 5761: 5751: 5717: 5708: 5707: 5697: 5687: 5662: 5656: 5655: 5645: 5613: 5607: 5606: 5596: 5564: 5558: 5557: 5521: 5515: 5514: 5477: 5471: 5470: 5433: 5427: 5426: 5408: 5402: 5401: 5389: 5383: 5382: 5346: 5340: 5339: 5329: 5319: 5295: 5289: 5288: 5278: 5268: 5244: 5235: 5234: 5224: 5200: 5194: 5193: 5156: 5150: 5149: 5112: 5106: 5105: 5071: 5062: 5056: 5055: 5045: 5013: 5007: 5006: 4969: 4963: 4962: 4926: 4920: 4919: 4883: 4877: 4876: 4848: 4842: 4841: 4839: 4837: 4832:. 17 August 2020 4818: 4812: 4811: 4809: 4807: 4798:. Archived from 4788: 4782: 4781: 4779: 4778: 4759: 4753: 4752: 4750: 4748: 4729: 4723: 4722: 4712: 4679: 4673: 4672: 4636: 4627: 4626: 4616: 4576: 4565: 4564: 4562: 4561: 4547: 4538: 4537: 4519: 4495: 4486: 4485: 4449: 4443: 4442: 4432: 4422: 4390: 4381: 4374: 4368: 4367: 4357: 4347: 4323: 4317: 4316: 4307:(11): 1897–902. 4296: 4290: 4289: 4279: 4269: 4245: 4239: 4238: 4210: 4204: 4203: 4193: 4169: 4163: 4162: 4152: 4142: 4117: 4111: 4110: 4100: 4068: 4062: 4061: 4025: 4019: 4018: 3981: 3975: 3974: 3949:(24): 2194–200. 3937: 3931: 3930: 3894: 3888: 3887: 3885: 3884: 3878: 3872:. Archived from 3867: 3858: 3847: 3846: 3810: 3804: 3803: 3793: 3782:10.1002/acn3.164 3761: 3752: 3742: 3736: 3732: 3723: 3713: 3707: 3706: 3686: 3666: 3660: 3659: 3649: 3608: 3599: 3598: 3588: 3555: 3544: 3543: 3533: 3509: 3503: 3502: 3465: 3459: 3458: 3440: 3416: 3407: 3406: 3396: 3386: 3362: 3353: 3352: 3315: 3309: 3308: 3271: 3265: 3264: 3254: 3222: 3213: 3212: 3175: 3169: 3168: 3158: 3148: 3124: 3118: 3117: 3107: 3097: 3073: 3067: 3066: 3041:(8): 1072–1084. 3029: 3023: 3022: 2994: 2988: 2987: 2977: 2945: 2939: 2938: 2928: 2896: 2887: 2886: 2866: 2847: 2846: 2809: 2803: 2802: 2766: 2757: 2756: 2746: 2706: 2697: 2696: 2660: 2654: 2653: 2621: 2615: 2614: 2604: 2564: 2558: 2557: 2547: 2537: 2505: 2499: 2498: 2491: 2485: 2478: 2472: 2468: 2462: 2455: 2449: 2448: 2436: 2430: 2419: 2413: 2412: 2402: 2384: 2360: 2333: 2332: 2330: 2329: 2315: 2309: 2303: 2294: 2293: 2245: 2126: 2121: 2120: 2119: 2072:Notable patients 1907:inhibitor), and 1885:research studies 1787:ophthalmologists 1516:cyclophosphamide 1455:(Imuran, Azasan) 1438: 1348: 1189:Sjögren syndrome 1040:associated with 943:None additional 924:None additional 829: 608:oligodendrocytes 596:Immunoglobulin M 362:Immunoglobulin-G 227:immunoglobulin G 179:cyclophosphamide 42:Devic's syndrome 22: 7532: 7531: 7527: 7526: 7525: 7523: 7522: 7521: 7492: 7491: 7490: 7485: 7484: 7461: 7460: 7404: 7390: 7377: 7303:Congenital DSMA 7224: 7181: 7140: 7086: 7074:Sleep disorders 7062: 7039:Cerebrovascular 7033: 6999: 6956: 6950: 6912: 6894: 6819: 6765:Choreoathetosis 6638: 6615: 6602: 6566: 6500: 6490: 6460: 6455: 6451:Pathophysiology 6420: 6394: 6390:CAMFAK syndrome 6360:Canavan disease 6336: 6288: 6243: 6217: 6111: 6031: 5963: 5957: 5927: 5926: 5881: 5880: 5876: 5830: 5829: 5825: 5780: 5779: 5775: 5719: 5718: 5711: 5664: 5663: 5659: 5615: 5614: 5610: 5566: 5565: 5561: 5532:(5): 997–1001. 5523: 5522: 5518: 5479: 5478: 5474: 5435: 5434: 5430: 5423: 5410: 5409: 5405: 5391: 5390: 5386: 5348: 5347: 5343: 5297: 5296: 5292: 5246: 5245: 5238: 5202: 5201: 5197: 5158: 5157: 5153: 5124:(12): 1527–30. 5114: 5113: 5109: 5069: 5064: 5063: 5059: 5015: 5014: 5010: 4971: 4970: 4966: 4928: 4927: 4923: 4885: 4884: 4880: 4850: 4849: 4845: 4835: 4833: 4820: 4819: 4815: 4805: 4803: 4790: 4789: 4785: 4776: 4774: 4761: 4760: 4756: 4746: 4744: 4731: 4730: 4726: 4681: 4680: 4676: 4638: 4637: 4630: 4578: 4577: 4568: 4559: 4557: 4549: 4548: 4541: 4497: 4496: 4489: 4451: 4450: 4446: 4392: 4391: 4384: 4375: 4371: 4325: 4324: 4320: 4298: 4297: 4293: 4247: 4246: 4242: 4212: 4211: 4207: 4171: 4170: 4166: 4119: 4118: 4114: 4070: 4069: 4065: 4027: 4026: 4022: 3983: 3982: 3978: 3939: 3938: 3934: 3896: 3895: 3891: 3882: 3880: 3876: 3865: 3860: 3859: 3850: 3812: 3811: 3807: 3763: 3762: 3755: 3743: 3739: 3733: 3726: 3714: 3710: 3695: 3668: 3667: 3663: 3610: 3609: 3602: 3557: 3556: 3547: 3511: 3510: 3506: 3467: 3466: 3462: 3418: 3417: 3410: 3364: 3363: 3356: 3327:(12): 1513–20. 3317: 3316: 3312: 3273: 3272: 3268: 3224: 3223: 3216: 3177: 3176: 3172: 3126: 3125: 3121: 3075: 3074: 3070: 3031: 3030: 3026: 2996: 2995: 2991: 2954:Brain Pathology 2947: 2946: 2942: 2898: 2897: 2890: 2868: 2867: 2850: 2821:(9): 1192–201. 2811: 2810: 2806: 2768: 2767: 2760: 2708: 2707: 2700: 2662: 2661: 2657: 2623: 2622: 2618: 2566: 2565: 2561: 2520:(5): e0177230. 2507: 2506: 2502: 2493: 2492: 2488: 2479: 2475: 2471:2019;35:246-252 2469: 2465: 2456: 2452: 2438: 2437: 2433: 2420: 2416: 2362: 2361: 2336: 2327: 2325: 2317: 2316: 2312: 2304: 2297: 2247: 2246: 2165: 2160: 2124:Medicine portal 2122: 2117: 2115: 2112: 2092:Cassie Mitchell 2074: 2048: 1939: 1931:auto-antibodies 1877: 1801:in one or both 1756: 1662: 1652:and subsequent 1589: 1520:DNA crosslinker 1428: 1342: 1331: 1311:corticosteroids 1293:corticosteroids 1285: 1265: 1197: 1182:interferon beta 1168:astrocytopathic 1156:channelopathies 1092: 1014:optic-spinal MS 970: 787: 774:involvement on 745:auto-antibodies 711: 705: 512:protein in the 498: 492: 479: 477:Pathophysiology 414: 390: 379: 370: 314: 286: 270:muscle weakness 266: 254: 38:Devic's disease 20: 17: 12: 11: 5: 7530: 7528: 7520: 7519: 7514: 7509: 7504: 7494: 7493: 7487: 7486: 7483: 7482: 7470: 7469: 7467: 7463: 7462: 7459: 7458: 7447: 7436: 7421: 7405: 7400: 7399: 7397: 7396:Classification 7387: 7386: 7383: 7382: 7379: 7378: 7376: 7375: 7374: 7373: 7362: 7361: 7360: 7359: 7358: 7357: 7352: 7342: 7337: 7336: 7335: 7330: 7325: 7324: 7323: 7318: 7313: 7305: 7300: 7295: 7290: 7285: 7275: 7261: 7260: 7259: 7258: 7253: 7248: 7234: 7232: 7226: 7225: 7223: 7222: 7217: 7211: 7209: 7200: 7191: 7187: 7186: 7183: 7182: 7180: 7179: 7174: 7169: 7164: 7159: 7154: 7148: 7146: 7142: 7141: 7139: 7138: 7133: 7131:Cerebral edema 7128: 7127: 7126: 7121: 7116: 7111: 7100: 7098: 7092: 7091: 7088: 7087: 7085: 7084: 7083: 7082: 7080:Template:Sleep 7070: 7068: 7064: 7063: 7061: 7060: 7054: 7049: 7043: 7041: 7035: 7034: 7032: 7031: 7025: 7020: 7015: 7009: 7007: 7001: 7000: 6998: 6997: 6991: 6986: 6981: 6975: 6973: 6960: 6952: 6951: 6949: 6948: 6942: 6937: 6932: 6926: 6924: 6918: 6917: 6914: 6913: 6911: 6910: 6908:Leigh syndrome 6904: 6902: 6896: 6895: 6893: 6892: 6881: 6880: 6875: 6870: 6869: 6868: 6854: 6853: 6852: 6847: 6846: 6845: 6829: 6827: 6821: 6820: 6818: 6817: 6812: 6807: 6806: 6805: 6800: 6789: 6788: 6787: 6786: 6781: 6780: 6779: 6769: 6768: 6767: 6757: 6752: 6751: 6750: 6745: 6740: 6735: 6719: 6718: 6717: 6716: 6711: 6706: 6701: 6696: 6695: 6694: 6684: 6683: 6682: 6672: 6671: 6670: 6665: 6660: 6644: 6642: 6635:Extrapyramidal 6628: 6619: 6617:encephalopathy 6608: 6607: 6604: 6603: 6601: 6600: 6595: 6590: 6589: 6588: 6577: 6575: 6568: 6567: 6565: 6564: 6563: 6562: 6552: 6547: 6546: 6545: 6540: 6535: 6530: 6519: 6517: 6508: 6502: 6501: 6494:nervous system 6491: 6489: 6488: 6481: 6474: 6466: 6457: 6456: 6454: 6453: 6448: 6443: 6438: 6432: 6430: 6426: 6425: 6422: 6421: 6419: 6418: 6413: 6408: 6402: 6400: 6396: 6395: 6393: 6392: 6387: 6382: 6377: 6372: 6367: 6365:Krabbe disease 6362: 6357: 6352: 6346: 6344: 6338: 6337: 6335: 6334: 6329: 6324: 6319: 6314: 6309: 6304: 6298: 6296: 6290: 6289: 6287: 6286: 6281: 6276: 6271: 6266: 6260: 6258: 6249: 6245: 6244: 6242: 6241: 6236: 6235: 6234: 6225: 6223: 6219: 6218: 6216: 6215: 6210: 6205: 6200: 6195: 6192:+hyaluronidase 6185: 6180: 6175: 6170: 6165: 6160: 6155: 6150: 6145: 6140: 6135: 6130: 6125: 6119: 6117: 6113: 6112: 6110: 6109: 6104: 6103: 6102: 6097: 6092: 6084: 6083: 6082: 6074: 6073: 6072: 6067: 6058: 6057: 6055:Poser criteria 6052: 6051: 6050: 6039: 6037: 6033: 6032: 6030: 6029: 6024: 6019: 6017:Optic neuritis 6014: 6009: 6004: 5999: 5994: 5989: 5984: 5979: 5973: 5971: 5965: 5964: 5958: 5956: 5955: 5948: 5941: 5933: 5925: 5924: 5874: 5823: 5794:(3): 547–564. 5773: 5709: 5657: 5608: 5559: 5516: 5472: 5428: 5421: 5403: 5384: 5341: 5290: 5236: 5195: 5168:(11): 1891–8. 5151: 5107: 5057: 5028:(2): 147–155. 5008: 4964: 4921: 4878: 4843: 4813: 4783: 4754: 4724: 4695:(4): 180–187. 4674: 4628: 4566: 4539: 4504:Neuropathology 4487: 4460:(14): 1186–8. 4444: 4382: 4369: 4318: 4291: 4240: 4205: 4164: 4112: 4063: 4020: 3976: 3932: 3905:(24): 2176–7. 3889: 3848: 3805: 3776:(3): 295–301. 3753: 3737: 3724: 3708: 3693: 3661: 3624:(2): 177–189. 3600: 3545: 3524:(10): 1485–9. 3504: 3471:JAMA Neurology 3460: 3408: 3354: 3310: 3266: 3214: 3187:(7): 966–973. 3170: 3119: 3068: 3024: 2989: 2940: 2888: 2848: 2804: 2758: 2698: 2655: 2616: 2559: 2500: 2486: 2473: 2463: 2450: 2431: 2414: 2334: 2310: 2295: 2162: 2161: 2159: 2156: 2155: 2154: 2149: 2144: 2139: 2134: 2128: 2127: 2111: 2108: 2107: 2106: 2089: 2073: 2070: 2052:autoantibodies 2047: 2044: 2043: 2042: 2033: 2027: 2021: 2010: 1938: 1935: 1920:paraneoplastic 1893:plasmapheresis 1876: 1873: 1861:autoantibodies 1755: 1752: 1686:, and 23% had 1684:optic neuritis 1661: 1658: 1608:optic neuritis 1588: 1585: 1563: 1562: 1559: 1557: 1550: 1549: 1547: 1545: 1538: 1537: 1534: 1531: 1524: 1523: 1521: 1518: 1512: 1511: 1509: 1506: 1500: 1499: 1497: 1494: 1488: 1487: 1485: 1483: 1481:corticosteroid 1477: 1476: 1473: 1470: 1463: 1462: 1459: 1456: 1449: 1448: 1445: 1442: 1427: 1424: 1421: 1420: 1417: 1414: 1411: 1408: 1402: 1401: 1399: 1396: 1393: 1390: 1384: 1383: 1380: 1377: 1374: 1371: 1365: 1364: 1361: 1358: 1355: 1352: 1341: 1338: 1330: 1327: 1307:Plasmapheresis 1284: 1281: 1264: 1261: 1253:astrocytopathy 1196: 1193: 1091: 1088: 1087: 1086: 1083:autoantibodies 1066:negative NMO: 1060: 1034:Optic neuritis 1031: 1024:optic neuritis 1016: 991: 989:optic neuritis 981: 969: 966: 955:autoantibodies 945: 944: 941: 926: 925: 922: 899: 898: 895: 885: 884: 881: 859: 858: 855: 848: 847: 843: 841:Optic neuritis 837: 836: 833: 786: 783: 739:Together with 707:Main article: 704: 701: 648:damage of the 584:foot processes 534:astrocytopathy 502:autoantibodies 494:Main article: 491: 488: 478: 475: 462:-derived NMO. 452:paraneoplastic 425:autoantibodies 413: 410: 389: 386: 378: 375: 369: 368:Disease course 366: 313: 310: 294:optic neuritis 285: 282: 265: 262: 256:The signs and 253: 250: 249: 248: 245: 230:autoantibodies 213:, ON) and the 211:optic neuritis 190: 189: 186: 182: 181: 136: 130: 129: 120: 114: 113: 110: 104: 103: 100: 94: 93: 90: 86: 85: 82: 78: 77: 67: 61: 60: 51: 45: 44: 31: 27: 26: 18: 15: 13: 10: 9: 6: 4: 3: 2: 7529: 7518: 7517:Rare diseases 7515: 7513: 7510: 7508: 7505: 7503: 7500: 7499: 7497: 7481: 7477: 7476: 7472: 7471: 7468: 7464: 7457: 7453: 7452: 7448: 7446: 7442: 7441: 7437: 7435: 7431: 7430: 7426: 7422: 7420: 7416: 7415: 7411: 7407: 7406: 7403: 7398: 7394: 7372: 7369: 7368: 7367: 7364: 7363: 7356: 7353: 7351: 7348: 7347: 7346: 7343: 7341: 7338: 7334: 7331: 7329: 7326: 7322: 7319: 7317: 7314: 7312: 7309: 7308: 7306: 7304: 7301: 7299: 7296: 7294: 7291: 7289: 7286: 7284: 7281: 7280: 7279: 7276: 7274: 7271: 7270: 7269: 7267: 7263: 7262: 7257: 7254: 7252: 7249: 7247: 7244: 7243: 7242: 7240: 7236: 7235: 7233: 7231: 7227: 7221: 7218: 7216: 7213: 7212: 7210: 7208: 7204: 7201: 7199: 7195: 7192: 7188: 7178: 7175: 7173: 7170: 7168: 7165: 7163: 7160: 7158: 7157:Reye syndrome 7155: 7153: 7150: 7149: 7147: 7143: 7137: 7134: 7132: 7129: 7125: 7122: 7120: 7117: 7115: 7112: 7110: 7109:Hydrocephalus 7107: 7106: 7105: 7102: 7101: 7099: 7097: 7093: 7081: 7077: 7076: 7075: 7072: 7071: 7069: 7065: 7059: 7055: 7053: 7050: 7048: 7045: 7044: 7042: 7040: 7036: 7030: 7026: 7024: 7021: 7019: 7016: 7014: 7011: 7010: 7008: 7006: 7002: 6996: 6992: 6990: 6987: 6985: 6982: 6980: 6977: 6976: 6974: 6972: 6968: 6964: 6961: 6959: 6953: 6947: 6943: 6941: 6938: 6936: 6933: 6931: 6928: 6927: 6925: 6923: 6922:Demyelinating 6919: 6909: 6906: 6905: 6903: 6901: 6897: 6891: 6888: 6887: 6886: 6885: 6879: 6876: 6874: 6871: 6867: 6864: 6863: 6862: 6858: 6855: 6851: 6848: 6844: 6841: 6840: 6839: 6836: 6835: 6834: 6831: 6830: 6828: 6826: 6822: 6816: 6813: 6811: 6810:Restless legs 6808: 6804: 6801: 6799: 6796: 6795: 6794: 6791: 6790: 6785: 6782: 6778: 6775: 6774: 6773: 6770: 6766: 6763: 6762: 6761: 6758: 6756: 6753: 6749: 6748:Blepharospasm 6746: 6744: 6741: 6739: 6736: 6734: 6731: 6730: 6729: 6726: 6725: 6724: 6721: 6720: 6715: 6712: 6710: 6707: 6705: 6704:Hemiballismus 6702: 6700: 6697: 6693: 6690: 6689: 6688: 6685: 6681: 6678: 6677: 6676: 6673: 6669: 6666: 6664: 6661: 6659: 6656: 6655: 6654: 6651: 6650: 6649: 6646: 6645: 6643: 6641: 6636: 6632: 6629: 6627: 6623: 6620: 6618: 6613: 6609: 6599: 6596: 6594: 6591: 6587: 6584: 6583: 6582: 6579: 6578: 6576: 6574: 6569: 6561: 6558: 6557: 6556: 6555:Brain abscess 6553: 6551: 6548: 6544: 6541: 6539: 6536: 6534: 6531: 6529: 6526: 6525: 6524: 6521: 6520: 6518: 6516: 6512: 6509: 6507: 6503: 6499: 6495: 6487: 6482: 6480: 6475: 6473: 6468: 6467: 6464: 6452: 6449: 6447: 6444: 6442: 6439: 6437: 6434: 6433: 6431: 6427: 6417: 6414: 6412: 6409: 6407: 6404: 6403: 6401: 6397: 6391: 6388: 6386: 6383: 6381: 6378: 6376: 6373: 6371: 6368: 6366: 6363: 6361: 6358: 6356: 6353: 6351: 6348: 6347: 6345: 6343: 6339: 6333: 6330: 6328: 6325: 6323: 6320: 6318: 6315: 6313: 6310: 6308: 6305: 6303: 6300: 6299: 6297: 6295: 6291: 6285: 6282: 6280: 6277: 6275: 6272: 6270: 6267: 6265: 6262: 6261: 6259: 6257: 6253: 6250: 6246: 6240: 6237: 6233: 6230: 6229: 6227: 6226: 6224: 6220: 6214: 6213:Teriflunomide 6211: 6209: 6206: 6204: 6201: 6199: 6196: 6193: 6189: 6186: 6184: 6181: 6179: 6176: 6174: 6171: 6169: 6166: 6164: 6161: 6159: 6156: 6154: 6151: 6149: 6146: 6144: 6141: 6139: 6136: 6134: 6131: 6129: 6126: 6124: 6121: 6120: 6118: 6114: 6108: 6105: 6101: 6098: 6096: 6093: 6091: 6088: 6087: 6086:Radiological 6085: 6081: 6078: 6077: 6075: 6071: 6068: 6066: 6063: 6062: 6060: 6059: 6056: 6053: 6049: 6046: 6045: 6044: 6041: 6040: 6038: 6034: 6028: 6025: 6023: 6020: 6018: 6015: 6013: 6010: 6008: 6005: 6003: 6000: 5998: 5995: 5993: 5990: 5988: 5985: 5983: 5980: 5978: 5975: 5974: 5972: 5970: 5966: 5962: 5954: 5949: 5947: 5942: 5940: 5935: 5934: 5931: 5920: 5916: 5911: 5906: 5902: 5898: 5894: 5890: 5886: 5878: 5875: 5870: 5866: 5861: 5856: 5852: 5848: 5844: 5840: 5839: 5834: 5827: 5824: 5819: 5815: 5810: 5805: 5801: 5797: 5793: 5789: 5785: 5777: 5774: 5769: 5765: 5760: 5755: 5750: 5745: 5741: 5737: 5734:(9): e74773. 5733: 5729: 5728: 5723: 5716: 5714: 5710: 5705: 5701: 5696: 5691: 5686: 5681: 5677: 5673: 5669: 5661: 5658: 5653: 5649: 5644: 5639: 5635: 5631: 5628:(6): 815–27. 5627: 5623: 5619: 5612: 5609: 5604: 5600: 5595: 5590: 5586: 5582: 5579:(6): 535–44. 5578: 5574: 5570: 5563: 5560: 5555: 5551: 5547: 5543: 5539: 5535: 5531: 5527: 5520: 5517: 5512: 5508: 5504: 5500: 5496: 5492: 5488: 5484: 5476: 5473: 5468: 5464: 5460: 5456: 5452: 5448: 5444: 5440: 5432: 5429: 5424: 5418: 5414: 5407: 5404: 5399: 5396:(in French). 5395: 5388: 5385: 5380: 5376: 5372: 5368: 5364: 5360: 5356: 5352: 5345: 5342: 5337: 5333: 5328: 5323: 5318: 5313: 5309: 5305: 5301: 5294: 5291: 5286: 5282: 5277: 5272: 5267: 5262: 5258: 5254: 5250: 5243: 5241: 5237: 5232: 5228: 5223: 5218: 5214: 5210: 5206: 5199: 5196: 5191: 5187: 5183: 5179: 5175: 5171: 5167: 5163: 5155: 5152: 5147: 5143: 5139: 5135: 5131: 5127: 5123: 5119: 5111: 5108: 5103: 5099: 5095: 5091: 5087: 5083: 5079: 5075: 5068: 5061: 5058: 5053: 5049: 5044: 5039: 5035: 5031: 5027: 5023: 5019: 5012: 5009: 5004: 5000: 4996: 4992: 4988: 4984: 4980: 4976: 4968: 4965: 4960: 4956: 4952: 4948: 4944: 4940: 4937:(3): 255–60. 4936: 4932: 4925: 4922: 4917: 4913: 4909: 4905: 4901: 4897: 4894:(8): 968–74. 4893: 4889: 4882: 4879: 4874: 4870: 4866: 4862: 4859:(7): 957–63. 4858: 4854: 4847: 4844: 4831: 4829: 4823: 4817: 4814: 4801: 4797: 4793: 4787: 4784: 4772: 4770: 4764: 4758: 4755: 4742: 4740: 4734: 4728: 4725: 4720: 4716: 4711: 4706: 4702: 4698: 4694: 4690: 4686: 4678: 4675: 4670: 4666: 4662: 4658: 4654: 4650: 4646: 4642: 4635: 4633: 4629: 4624: 4620: 4615: 4610: 4606: 4602: 4598: 4594: 4590: 4586: 4582: 4575: 4573: 4571: 4567: 4556: 4552: 4546: 4544: 4540: 4535: 4531: 4527: 4523: 4518: 4513: 4510:(5): 469–80. 4509: 4505: 4501: 4494: 4492: 4488: 4483: 4479: 4475: 4471: 4467: 4463: 4459: 4455: 4448: 4445: 4440: 4436: 4431: 4426: 4421: 4416: 4412: 4408: 4405:(8): e72919. 4404: 4400: 4396: 4389: 4387: 4383: 4380: 4373: 4370: 4365: 4361: 4356: 4351: 4346: 4341: 4337: 4333: 4332:BMC Neurology 4329: 4322: 4319: 4314: 4310: 4306: 4302: 4295: 4292: 4287: 4283: 4278: 4273: 4268: 4263: 4259: 4255: 4251: 4244: 4241: 4236: 4232: 4228: 4224: 4221:(3): 115–21. 4220: 4216: 4209: 4206: 4201: 4197: 4192: 4187: 4184:(11): 631–4. 4183: 4179: 4175: 4168: 4165: 4160: 4156: 4151: 4146: 4141: 4136: 4132: 4128: 4124: 4116: 4113: 4108: 4104: 4099: 4094: 4090: 4086: 4082: 4078: 4074: 4067: 4064: 4059: 4055: 4051: 4047: 4043: 4039: 4035: 4031: 4024: 4021: 4016: 4012: 4008: 4004: 4000: 3996: 3992: 3988: 3980: 3977: 3972: 3968: 3964: 3960: 3956: 3952: 3948: 3944: 3936: 3933: 3928: 3924: 3920: 3916: 3912: 3908: 3904: 3900: 3893: 3890: 3879:on 2006-09-25 3875: 3871: 3864: 3857: 3855: 3853: 3849: 3844: 3840: 3836: 3832: 3828: 3824: 3821:(4): 218–25. 3820: 3816: 3809: 3806: 3801: 3797: 3792: 3787: 3783: 3779: 3775: 3771: 3767: 3760: 3758: 3754: 3751: 3747: 3741: 3738: 3731: 3729: 3725: 3722: 3718: 3712: 3709: 3704: 3700: 3696: 3690: 3685: 3680: 3676: 3672: 3665: 3662: 3657: 3653: 3648: 3643: 3639: 3635: 3631: 3627: 3623: 3619: 3615: 3607: 3605: 3601: 3596: 3592: 3587: 3582: 3578: 3574: 3571:(2): 177–89. 3570: 3566: 3562: 3554: 3552: 3550: 3546: 3541: 3537: 3532: 3527: 3523: 3519: 3515: 3508: 3505: 3500: 3496: 3492: 3488: 3484: 3480: 3477:(3): 276–83. 3476: 3472: 3464: 3461: 3456: 3452: 3448: 3444: 3439: 3434: 3431:(2): 107–10. 3430: 3426: 3422: 3415: 3413: 3409: 3404: 3400: 3395: 3390: 3385: 3380: 3376: 3372: 3368: 3361: 3359: 3355: 3350: 3346: 3342: 3338: 3334: 3330: 3326: 3322: 3314: 3311: 3306: 3302: 3298: 3294: 3290: 3286: 3282: 3278: 3270: 3267: 3262: 3258: 3253: 3248: 3244: 3240: 3236: 3232: 3228: 3221: 3219: 3215: 3210: 3206: 3202: 3198: 3194: 3190: 3186: 3182: 3174: 3171: 3166: 3162: 3157: 3152: 3147: 3142: 3138: 3134: 3130: 3123: 3120: 3115: 3111: 3106: 3101: 3096: 3091: 3087: 3083: 3079: 3072: 3069: 3064: 3060: 3056: 3052: 3048: 3044: 3040: 3036: 3028: 3025: 3020: 3016: 3012: 3008: 3004: 3000: 2993: 2990: 2985: 2981: 2976: 2971: 2967: 2963: 2959: 2955: 2951: 2944: 2941: 2936: 2932: 2927: 2922: 2918: 2914: 2910: 2906: 2902: 2895: 2893: 2889: 2884: 2880: 2876: 2872: 2865: 2863: 2861: 2859: 2857: 2855: 2853: 2849: 2844: 2840: 2836: 2832: 2828: 2824: 2820: 2816: 2808: 2805: 2800: 2796: 2792: 2788: 2784: 2780: 2776: 2772: 2765: 2763: 2759: 2754: 2750: 2745: 2740: 2736: 2732: 2728: 2724: 2720: 2716: 2712: 2705: 2703: 2699: 2694: 2690: 2686: 2682: 2678: 2674: 2670: 2666: 2659: 2656: 2651: 2647: 2643: 2639: 2635: 2631: 2627: 2620: 2617: 2612: 2608: 2603: 2598: 2594: 2590: 2586: 2582: 2578: 2574: 2570: 2563: 2560: 2555: 2551: 2546: 2541: 2536: 2531: 2527: 2523: 2519: 2515: 2511: 2504: 2501: 2496: 2490: 2487: 2483: 2477: 2474: 2467: 2464: 2460: 2454: 2451: 2446: 2442: 2435: 2432: 2428: 2424: 2418: 2415: 2410: 2406: 2401: 2396: 2392: 2388: 2383: 2378: 2374: 2370: 2366: 2359: 2357: 2355: 2353: 2351: 2349: 2347: 2345: 2343: 2341: 2339: 2335: 2324: 2320: 2314: 2311: 2308: 2302: 2300: 2296: 2291: 2287: 2283: 2279: 2275: 2271: 2267: 2263: 2259: 2255: 2251: 2244: 2242: 2240: 2238: 2236: 2234: 2232: 2230: 2228: 2226: 2224: 2222: 2220: 2218: 2216: 2214: 2212: 2210: 2208: 2206: 2204: 2202: 2200: 2198: 2196: 2194: 2192: 2190: 2188: 2186: 2184: 2182: 2180: 2178: 2176: 2174: 2172: 2170: 2168: 2164: 2157: 2153: 2150: 2148: 2145: 2143: 2140: 2138: 2135: 2133: 2130: 2129: 2125: 2114: 2109: 2104: 2101: 2097: 2093: 2090: 2087: 2083: 2079: 2076: 2075: 2071: 2069: 2066: 2064: 2060: 2055: 2053: 2045: 2041: 2037: 2034: 2031: 2028: 2025: 2022: 2019: 2015: 2011: 2008: 2004: 2003:channelopathy 2001: 1997: 1996: 1995: 1993: 1989: 1984: 1982: 1978: 1974: 1969: 1967: 1962: 1960: 1956: 1952: 1948: 1944: 1936: 1934: 1932: 1928: 1923: 1921: 1916: 1914: 1910: 1906: 1902: 1898: 1894: 1890: 1886: 1882: 1874: 1872: 1870: 1866: 1862: 1858: 1854: 1850: 1846: 1842: 1838: 1834: 1830: 1826: 1821: 1819: 1815: 1811: 1808: 1804: 1800: 1796: 1792: 1788: 1784: 1780: 1776: 1772: 1765: 1760: 1753: 1751: 1749: 1745: 1741: 1737: 1733: 1728: 1725: 1723: 1719: 1715: 1711: 1707: 1703: 1698: 1696: 1693: 1689: 1685: 1681: 1678: 1674: 1669: 1667: 1659: 1657: 1655: 1651: 1647: 1643: 1639: 1635: 1631: 1626: 1623: 1620: 1615: 1613: 1609: 1605: 1601: 1596: 1595:may persist. 1594: 1586: 1584: 1582: 1578: 1574: 1570: 1560: 1558: 1555: 1552: 1551: 1548: 1546: 1543: 1540: 1539: 1535: 1532: 1529: 1526: 1525: 1522: 1519: 1517: 1514: 1513: 1510: 1507: 1505: 1502: 1501: 1498: 1495: 1493: 1490: 1489: 1486: 1484: 1482: 1479: 1478: 1474: 1471: 1468: 1465: 1464: 1460: 1457: 1454: 1451: 1450: 1443: 1440: 1439: 1436: 1434: 1425: 1418: 1415: 1412: 1409: 1407: 1404: 1403: 1400: 1397: 1394: 1391: 1389: 1386: 1385: 1381: 1378: 1375: 1372: 1370: 1367: 1366: 1362: 1359: 1356: 1353: 1350: 1349: 1346: 1339: 1337: 1335: 1328: 1326: 1324: 1320: 1316: 1312: 1308: 1304: 1302: 1298: 1294: 1291: 1282: 1280: 1278: 1269: 1262: 1260: 1258: 1254: 1250: 1249:channelopathy 1246: 1241: 1239: 1235: 1231: 1227: 1223: 1218: 1216: 1213: 1209: 1205: 1202: 1194: 1192: 1190: 1185: 1183: 1179: 1175: 1173: 1172:demyelinating 1169: 1165: 1161: 1157: 1154: 1150: 1145: 1143: 1139: 1135: 1131: 1127: 1122: 1120: 1116: 1111: 1109: 1104: 1100: 1096: 1089: 1084: 1080: 1076: 1072: 1069: 1065: 1061: 1059: 1055: 1051: 1047: 1043: 1039: 1035: 1032: 1029: 1025: 1021: 1017: 1015: 1011: 1007: 1003: 1000: 996: 992: 990: 986: 982: 979: 978: 977: 975: 967: 965: 963: 958: 956: 952: 942: 939: 935: 932: 928: 927: 923: 920: 917: 913: 909: 905: 901: 900: 896: 894: 891: 887: 886: 882: 879: 875: 871: 867: 864: 863:Area Postrema 861: 860: 856: 854: 850: 849: 844: 842: 839: 838: 834: 832:Core criteria 831: 830: 824: 820: 818: 814: 810: 807: 802: 800: 791: 784: 782: 780: 777: 773: 769: 765: 761: 757: 753: 748: 746: 742: 737: 735: 730: 726: 723: 720: 716: 710: 702: 700: 698: 694: 689: 685: 683: 679: 675: 671: 670:demyelination 667: 663: 659: 655: 651: 647: 643: 642:demyelination 639: 635: 630: 628: 624: 620: 615: 611: 609: 605: 601: 597: 593: 589: 585: 580: 578: 577:intrathecally 574: 570: 566: 565:area postrema 562: 558: 554: 550: 546: 541: 539: 535: 531: 527: 523: 519: 515: 514:cell membrane 511: 507: 503: 497: 489: 483: 476: 474: 472: 468: 463: 461: 457: 453: 448: 446: 440: 438: 434: 430: 426: 423: 419: 411: 409: 407: 403: 399: 395: 387: 385: 383: 376: 374: 367: 365: 363: 359: 355: 351: 347: 344:, as well as 343: 339: 335: 331: 327: 323: 322:area postrema 319: 312:Brain effects 311: 309: 307: 303: 299: 298:visual acuity 295: 291: 284:Optic effects 283: 281: 279: 275: 271: 263: 261: 259: 251: 246: 243: 242:water channel 239: 235: 231: 228: 224: 223: 222: 220: 216: 212: 208: 204: 200: 196: 187: 183: 180: 176: 172: 168: 164: 160: 156: 152: 148: 144: 140: 137: 135: 131: 128: 124: 121: 119: 115: 111: 109: 105: 101: 99: 95: 91: 87: 83: 79: 75: 71: 68: 66: 62: 59: 58:ophthalmology 55: 52: 50: 46: 43: 39: 35: 32: 28: 23: 7473: 7449: 7438: 7423: 7408: 7365: 7264: 7237: 7198:Degenerative 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