Neuromyelitis optica spectrum disorder

1770: 801: 1279: 493: 1621:. 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 411:(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 2129: 1314:). 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). 4983:

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

624:

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

4693:

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,

5491:

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

739:

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

3745:

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

2823:

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

3951:

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".

558:(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 625:

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.

5170:

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".

2481:

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.

3043:

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".

3285:

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".

319:, 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. 3479:

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.

3995:

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".

7435: 7420: 4387:

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).

5676:

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

3189:

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".

5792:

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".

3329:

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".

383:

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".

4131:

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).

3622:

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.

3726:

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,

2005:+ 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: 236:

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

1572:

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.

7331: 7326: 4862:

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".

7343: 7321: 1667:. 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. 6395: 2316:

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".

4743: 6494: 2674:

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".

6105: 395:

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.

4802: 1217:, 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 3775:

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).

6294: 754:, 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 4082:

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

6690: 6390: 6685: 2152: 2578:

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

496:

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

4773: 3873: 2505: 6487: 4832: 1679:. 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. 5954: 1486:

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

826:

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

5627:

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).

2519:

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).

7313: 6342: 4039:

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

3140:"The cerebrospinal fluid immunoglobulin transcriptome and proteome in neuromyelitis optica reveals central nervous system-specific B cell populations" 6446: 5979: 3824:

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).

7303: 6480: 2635:

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

1564: 7517: 7283: 6956: 6451: 5947: 1290:

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.

5535:

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".

7308: 6940: 6461: 6266: 5431: 4224:

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

3703: 2437: 972: 744: 672: 4339:"Interferon-β-related tumefactive brain lesion in a Caucasian patient with neuromyelitis optica and clinical stabilization with tocilizumab" 7146: 7134: 6596: 6426: 6352: 6312: 5078:"A comparison of pediatric and adult neuromyelitis optica spectrum disorders: A review of clinical manifestation, diagnosis, and treatment" 1875: 1240: 719: 617:, 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 232:). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients. 2433: 2024: 2002: 1675:

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

1244: 1125: 1089: 725: 447: 4561: 7365: 7298: 6853: 3908:

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?".

3376:

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

7068: 6871: 4810: 4084:"Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder" 1231:

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

6385: 2492: 2329: 4744:"FDA approves first treatment for neuromyelitis optica spectrum disorder, a rare autoimmune disease of the central nervous system" 4511:"Early disruption of glial communication via connexin gap junction in multiple sclerosis, Baló's disease and neuromyelitis optica" 6456: 6332: 6322: 6279: 6133: 6100: 6080: 6421: 1929:

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

761:

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

7187: 6053: 1957: 961: 5403:

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

6702: 6678: 6508: 6337: 6249: 1969: 1188: 461:

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

6894: 4650:

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

7381: 7266: 7182: 7124: 6673: 4134:"Metabolomics reveals distinct, antibody-independent, molecular signatures of MS, AQP4-antibody and MOG-antibody disease" 1936:

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

7512: 7350: 6724: 6416: 6380: 6075: 4838: 4779: 4749: 1311: 6860: 2259:

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.

1254:

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

743:

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

7338: 6888: 6560: 4404:

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

3884: 1723:) has been suggested to be identical to NMO (differences between OSMS and classic MS in Japanese patients). In the 1552: 1152: 789: 629: 621:. Loss of cells other than astrocytes is a consequence of collateral inflammatory damage or astrocyte dysfunction. 416: 185: 7230: 2451: 1738:

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

7522: 7288: 7256: 7208: 7057: 6636: 6317: 6202: 5992: 5679:"Identification of the flotillin-1/2 heterocomplex as a target of autoantibodies in bona fide multiple sclerosis" 1746: 729: 1940:. Six different patterns of damage have been reported in NMO, raising the possibility of six different types of 271:

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

7450: 7355: 7129: 6543: 1177:), it is still possible to consider NMO as part of the MS spectrum. Besides, some NMO-AQP4(−) variants are not 809: 633: 407:(MS) can be similar in clinical and radiological presentation, and MS may very rarely present with an NMO-like 7360: 555: 331:. Lesions in the brain stem or upper cervical spinal cord can cause respiratory insufficiency. Lesions in the 5629:"Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica" 7293: 7049: 6867: 6719: 6709: 6553: 6037: 1789: 1774: 1750: 1613:

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).

7527: 7490: 7225: 7217: 7172: 6848: 6820: 6668: 5971: 4337:

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

2722:"Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later" 2110: 1443: 1109: 128: 987:

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

7240: 7114: 6932: 6910: 6825: 6748: 6658: 6645: 6570: 3430:

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

2147: 1937: 1477: 1344: 918: 769:

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

680: 5939: 5842:

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

4406:"Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica" 3138:

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

2636: 299:

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

7177: 6994: 6883: 6360: 6284: 6017: 5746: 4417: 2733: 2591: 2580:"Association of subcortical structural shapes with fatigue in neuromyelitis optica spectrum disorder" 2532: 1805: 1719:. In fact, Asian optic-spinal multiple sclerosis (OSMS) (which constitutes 30% of the cases of MS in 1610: 1232: 1191:

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

1129: 609:(IgM), inflammatory cells, and complement deposits around blood vessels. AQP4-IgG is a member of the 137: 7439: 7106: 6753: 6608: 6548: 6188: 6110: 5848: 2521:"Fatigue in patients with neuromyelitis optica spectrum disorder and its impact on quality of life" 1961: 1915: 1660: 1614: 1199: 1144: 1140: 579: 288: 2452:"Neuromyelitis optica spectrum disorder | Radiology Reference Article | Radiopaedia.org" 1870:

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

1158:

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

450:

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

7276: 7261: 7249: 6999: 6950: 6787: 6650: 6538: 6289: 6173: 6168: 6163: 6153: 5560: 5517: 5473: 5385: 5196: 5152: 5108: 5009: 4965: 4922: 4675: 4540: 4488: 4064: 4021: 3977: 3933: 3849: 3505: 3461: 3378:"Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype" 3355: 3311: 3215: 3069: 2849: 2805: 2699: 2656: 2296: 2157: 2046: 1788:

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

1758: 1742: 1724: 1579: 1307: 688: 637: 404: 248: 165: 133: 75: 6472: 3755:

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

2637:"Factors Associated with Fatigue in Neuromyelitis Optica Spectrum Disorder in a Tunisian Cohort" 2493:

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

7461: 7039: 7005: 6977: 6968: 6900: 6876: 6743: 6591: 6365: 6148: 6058: 5925: 5896:"Classifying the antibody-negative NMO syndromes: Clinical, imaging, and metabolomic modeling" 5875: 5844:"Classifying the antibody-negative NMO syndromes, Clinical, imaging, and metabolomic modeling" 5824: 5795:"Antibody signatures in patients with histopathologically defined multiple sclerosis patterns" 5774: 5710: 5658: 5609: 5552: 5509: 5465: 5427: 5377: 5342: 5291: 5237: 5214:

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

5188: 5144: 5100: 5058: 5001: 4957: 4914: 4879: 4725: 4667: 4629: 4611: 4532: 4480: 4445: 4370: 4319: 4292: 4241: 4206: 4165: 4113: 4056: 4013: 3969: 3925: 3841: 3806: 3709: 3699: 3662: 3644: 3601: 3546: 3497: 3453: 3409: 3347: 3303: 3267: 3207: 3171: 3120: 3061: 3025: 2990: 2941: 2889: 2841: 2797: 2759: 2691: 2617: 2560: 2415: 2397: 2288: 2280: 2142: 2028: 1923: 1879: 1809: 1648: 1640: 1629: 1236: 1174: 1113: 751: 676: 614: 583: 559: 540: 506: 477: 443: 356: 352: 336: 118: 59: 7162: 7033: 7028: 6813: 6808: 6090: 5915: 5907: 5865: 5857: 5814: 5806: 5764: 5754: 5700: 5690: 5648: 5640: 5599: 5591: 5544: 5501: 5457: 5369: 5332: 5322: 5281: 5271: 5227: 5180: 5136: 5092: 5048: 5040: 4993: 4949: 4906: 4871: 4715: 4707: 4659: 4619: 4603: 4522: 4472: 4435: 4425: 4360: 4350: 4282: 4272: 4233: 4196: 4155: 4145: 4103: 4095: 4048: 4005: 3961: 3917: 3833: 3796: 3788: 3689: 3652: 3636: 3591: 3583: 3536: 3489: 3443: 3399: 3389: 3339: 3295: 3257: 3249: 3199: 3161: 3151: 3110: 3100: 3053: 3017: 2980: 2972: 2931: 2923: 2833: 2789: 2749: 2741: 2683: 2648: 2607: 2599: 2550: 2540: 2405: 2387: 2272: 2106: 1855: 1526: 1074: 984: 868:

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

823: 786: 782: 770: 703: 606: 571: 432: 372: 237: 189: 5216:"Role of return migration in the emergence of multiple sclerosis in the French West Indies" 7084: 6775: 6400: 6370: 5733:"Anti-aquaporin-1 autoantibodies in patients with neuromyelitis optica spectrum disorders" 5731:

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

2961:"The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica" 2134: 2102: 1846:

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

1824: 1820: 1356:

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

1192: 755: 618: 512: 284: 280: 3625:"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders" 3572:"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders" 2088: 1801: 1602:

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

804:

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

5750: 4940:

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

4421: 2737: 2595: 2536: 2468:

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

1769: 800: 291:, affecting an entire cross-section of the spinal cord, and showing bilateral symptoms. 7141: 7090: 6918: 6627: 6504: 6375: 6065: 6027: 5920: 5895: 5870: 5843: 5819: 5794: 5769: 5732: 5705: 5678: 5653: 5628: 5604: 5579: 5337: 5310: 5286: 5259: 5053: 5028: 4720: 4695: 4624: 4591: 4440: 4405: 4365: 4338: 4287: 4260: 4160: 4133: 4108: 4083: 3801: 3776: 3657: 3624: 3596: 3571: 3541: 3524: 3404: 3377: 3262: 3237: 3166: 3139: 3115: 3088: 2985: 2960: 2936: 2911: 2754: 2721: 2612: 2555: 2520: 2410: 2375: 1930: 1903: 1716: 1694: 1618: 1491: 1321: 1317: 1303: 1093: 1044: 1034: 999: 965: 851: 544: 462: 304: 221: 7444: 5595: 5461: 5311:"The history of neuromyelitis optica. Part 2: 'Spinal amaurosis', or how it all began" 4237: 2912:"IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel" 2072:-negative NMO can be classified into three groups, and that this classification has a 1990:, although, as of 2015, there are only initial reports about the involvement of these 1866:(enzyme-linked immunosorbent assay) kits were soon developed, However, serum AQP4-IgG 7506: 7167: 7119: 6989: 6758: 6714: 6565: 6223: 5521: 5156: 5013: 4679: 3937: 3837: 2703: 2660: 2579: 2300: 2013: 1797: 1259: 1166: 994:

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

873: 594: 575: 548: 524: 332: 308: 68: 5564: 5477: 5389: 5200: 4969: 4492: 4025: 3981: 3853: 3465: 3359: 3315: 2809: 740:

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

6663: 6533: 6516: 6183: 5112: 4926: 4544: 4068: 3509: 3238:"A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica" 3219: 3073: 2853: 2062: 2010: 1953: 1941: 1871: 1828: 1712: 1655:

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

1514: 1502: 1463: 1416: 1398: 1333: 1267: 1263: 1255: 1225: 1214: 1170: 1148: 1060: 926: 732: 692: 660: 435: 428: 412: 364: 316: 312: 300: 258:

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

240: 213: 181: 177: 169: 157: 153: 84: 1278: 7455: 5911: 5861: 5759: 4953: 4607: 4476: 4430: 3965: 3921: 3777:"Histopathology and clinical course of MOG-antibody-associated encephalomyelitis" 3694: 3640: 3587: 3523:

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

3493: 3448: 3431: 2959:

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

2545: 1578:

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

6622: 6583: 6525: 6198: 6193: 6138: 4711: 2687: 2652: 2392: 2317: 2162: 2040: 2017: 1998: 1987: 1983: 1891: 1843: 1835: 1785: 1781: 1687: 1656: 1591: 1587: 1320:

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

1300: 1222: 1218: 1211: 1105: 1078: 1016: 1005: 819: 664: 648: 587: 567: 563: 516: 439: 368: 244: 225: 217: 108: 80: 7466: 5810: 5029:"Autologous haematopoietic stem cell transplantation for neurological diseases" 4052: 3731: 3681: 2603: 492: 7429: 6733: 6603: 6242: 6178: 6158: 6143: 6117: 6002: 5695: 5644: 5548: 5373: 5327: 5184: 5096: 4997: 4875: 4774:"FDA Approves New Therapy for Rare Disease Affecting Optic Nerve, Spinal Cord" 4663: 4355: 4150: 4009: 3394: 3156: 3105: 3021: 2506:"NMOSD, Fatigue, and Thalamic Volume - Neuromyelitis Optica Spectrum Disorder" 2276: 2124: 1919: 1911: 1817: 1732: 1632: 1603: 1583: 1379: 1329: 1085: 1038: 914: 816: 566:-6 as culprits responsible for the BBB failure. There is broad consensus that 446:) are the cause, and in 10–40% of the remaining cases, IgG antibodies against 328: 149: 144: 5505: 5140: 5044: 4910: 4833:"FDA Approves Treatment for Rare Disease Affecting Optic Nerves, Spinal Cord" 4615: 4277: 4099: 3648: 3343: 3299: 3057: 2837: 2793: 2401: 2284: 736:

cerebral spinal fluid into lymph nodes causes autoimmune reaction formation.

6843: 6794: 6782: 6765: 6697: 6218: 6213: 6022: 6007: 4389: 3760: 3746:

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

3089:"Selective localization of IgG from cerebrospinal fluid to brain parenchyma" 2113: 1976: 1847: 1813: 1793: 1702: 1652: 1644: 1538: 1336:

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

1178: 1068: 900: 827: 766: 762: 707: 644: 602: 536: 532: 520: 408: 344: 252: 161: 64: 5929: 5879: 5828: 5778: 5714: 5662: 5613: 5556: 5513: 5469: 5381: 5346: 5295: 5276: 5241: 5232: 5215: 5192: 5148: 5104: 5062: 5005: 4961: 4918: 4883: 4729: 4671: 4633: 4536: 4484: 4449: 4374: 4323: 4296: 4245: 4210: 4169: 4117: 4060: 4017: 3973: 3929: 3845: 3810: 3713: 3666: 3605: 3550: 3501: 3457: 3432:"Relationship between NMO-antibody and anti-MOG antibody in optic neuritis" 3413: 3351: 3307: 3271: 3253: 3211: 3175: 3124: 3065: 3029: 2994: 2945: 2893: 2845: 2801: 2763: 2695: 2621: 2564: 2432:

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

2419: 2292: 2260: 4201: 4184: 307:, ON). ON may lead to varying degrees of visual impairment with decreased 7485: 7023: 7015: 6981: 6835: 6738: 6208: 5997: 5737: 3686:

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

2927: 2073: 2069: 2050: 1907: 1899: 1895: 1851: 1754: 1676: 1248: 1136: 1081: 1048: 1030: 995: 944: 941: 903: 884: 876: 863: 774: 656: 598: 528: 481: 340: 327:

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

229: 173: 1282:

Chemical structure of methylprednisolone, which is used to treat attacks

1139:

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

6012: 4527: 4510: 3688:. IDKD Springer Series. Cham, Switzerland: Springer. pp. 165–176. 2910:

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

2745: 1991: 1839: 1728: 1686:, with a MS:NMOSD ratio of 42:7. Among 13 NMOSD patients, 77% had long 1683: 1622: 778: 724:

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

392: 360: 268: 7412: 3203: 2976: 1088:

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

7424: 7062: 6803: 6770: 5987: 3792: 2096: 1705: 1690: 1594:—worsen NMO disease progression and should not be used to treat NMO. 1182: 1163: 1118: 1052: 1012: 948: 929: 888: 880: 684: 668: 652: 351:. Additional brain lesions are common but often asymptomatic (though 283:, paralysis in the limbs, lost or reduced sensation, spasms, loss of 17: 4590:

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

4088:

Multiple Sclerosis Journal: Experimental, Translational and Clinical

3087:

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

1735:, MS is rare; but when it appears, it often takes the form of OSMS. 1625:

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

1609:

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

1262:" for these diseases, while others prefer a more generic term "AQP4- 7318:

Spinal muscular atrophy with lower extremity predominance (SMALED)

1906:. A number of drugs are being studied: aquaporumab (non-pathogenic 628:

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

4261:"Autoantibodies to Potassium Channel KIR4.1 in Multiple Sclerosis" 1965: 1867: 1863: 1859: 1768: 1720: 1698: 1664: 1325: 1277: 1239:, plus other non-related but clinically similar syndromes such as 1056: 1009: 991:

Standard NMO, according to the diagnostic criteria described above

812:, which have undergone multiple revisions, most recently in 2015. 799: 491: 470: 466: 348: 1647:

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

1639:

Approximately 20% of patients with monophasic NMO have permanent

1021:

inflammatory demyelinating diseases of the central nervous system

6032: 2092: 2034: 1287: 964:

are consistent with NMO. Preliminary reports suggest that other

610: 287:

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

6476: 5943: 4696:"Treatment of neuromyelitis optica: Review and recommendations" 2376:"Neuromyelitis Optica Spectrum Disorder and Anti-MOG Syndromes" 574:

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

419:, cerebrospinal fluid findings, disease course, and prognosis. 212:) are a spectrum of autoimmune diseases characterized by acute 4562:"Neuromyelitis optica - Diagnosis and treatment - Mayo Clinic" 2079:

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

1979:. It has been found in seronegative NMO and some MS patients. 922: 27:

Acute inflammation diseases of the optic nerve and spinal cord

1898:

have focused on targeted treatment aimed at anti-aquaporin 4

3770: 3768: 1827:

control. They recognized these symptoms were the result of

1155:

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

103:

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

6396:

Megalencephalic leukoencephalopathy with subcortical cysts

1442:

the current standard treatment. Most of these medications

1235:. Therefore, it includes all the clinical variants due to 1128:-ab levels can be too low to be detected. Some additional 5027:

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

1808:

student Fernand Gault described 16 patients who had lost

1628:

It is possible that the relapsing form is related to the

593:

Within astrocytes, AQP4 is primarily found in astrocytic

431:

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

3730:, May 04, 2010; 74 (18) Clinical/Scientific Notes, DOI: 3684:. In Hodler J, Kubik-Huch RA, von Schulthess GK (eds.). 3682:"13 Demyelinating Diseases of the CNS (Brain and Spine)" 765:

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

469:

can produce NMO-IgG autoantibodies, leading to cases of

4645: 4643: 2043:

associated NMO which could be related to pattern III MS

1266:", which also includes deficiencies of AQP4 with a non- 1135:

NMO differs from MS in that it usually has more severe

551:, since the astrocytes are semi-selectively destroyed. 3525:"Revised diagnostic criteria for neuromyelitis optica" 1902:. The most established method for antibody removal is 597:

that abut blood vessels and the linings of the brain (

543:. Thus, NMOSD involving AQP4-IgG can be considered an 6106:

Lesional demyelinations of the central nervous system

3617: 3615: 2374:

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

1708:. Only 56% had clinically definite NMO at follow-up. 527:

that allows water to pass through the membrane. AQP4

7402: 1015:

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

971:

NMOSD with MOG-IgG is considered a manifestation of

846:

Additional MRI findings for absent/unknown AQP4-IgG

613:

immunoglobulin family, which is an activator of the

7476: 7406: 7239: 7216: 7207: 7200: 7155: 7105: 7077: 7048: 7014: 6976: 6965: 6931: 6909: 6834: 6644: 6635: 6621: 6581: 6524: 6515: 6439: 6409: 6351: 6303: 6265: 6258: 6232: 6126: 6046: 5978: 4312:

Nihon Rinsho. Japanese Journal of Clinical Medicine

706:-negative cases are less understood. It seems that 195: 143: 127: 117: 107: 99: 91: 74: 58: 40: 35: 5900:Neurology: Neuroimmunology & Neuroinflammation 5033:Journal of Neurology, Neurosurgery, and Psychiatry 2880:Wingerchuk DM (May 2006). "Neuromyelitis optica". 2312: 2310: 1831:of the optic nerve and spinal cord, respectively. 1547:The most commonly used treatment for NMOSD today. 960:Rarely, it has been reported that some courses of 6295:Chronic inflammatory demyelinating polyneuropathy 4556: 4554: 2065:. They constitute an overlap between NMO and MS. 1390:Monoclonal antibody against complement protein C5 1124:Another problem for diagnosis is that AQP4-ab in 1004:Asian optic-spinal multiple sclerosis (OSMS), or 773:involvement. Myelin-oligodendrocyte glycoprotein 4585: 4583: 4581: 2068:As of 2019 some statistical studies showed that 535:, and the tetramers aggregate. AQP4 is found in 6391:Leukoencephalopathy with vanishing white matter 5253: 5251: 4399: 4397: 3564: 3562: 3560: 3371: 3369: 3231: 3229: 2905: 2903: 1874:were found in NMO AQP4-negative cases, such as 95:Median: age 40 for AQP4-IgG, age 31 for MOG-IgG 3881:2006 Rare Neuroimmunologic Disorders Symposium 3781:Annals of Clinical and Translational Neurology 2715: 2713: 2153:Idiopathic inflammatory demyelinating diseases 1968:) and atypical NMO, leading to the concept of 1823:of the limbs, loss of sensation, and often of 1741:Rarely, NMO may occur in the context of other 695:is often quite distinct from that seen in MS. 6488: 5955: 4504: 4502: 2875: 2873: 2871: 2869: 2867: 2865: 2863: 2318:https://www.ncbi.nlm.nih.gov/books/NBK571350/ 1753:) or infectious diseases. In some cases, the 8: 5424:Multiple Sclerosis: The History of a Disease 4310:Kurosawa K, Fujihara K (November 2014). "". 3867: 3865: 3863: 3732:https://doi.org/10.1212/WNL.0b013e3181dc1a7f 2720:Pittock SJ, Lucchinetti CF (February 2016). 2330:"Neuromyelitis optica – Symptoms and causes" 2049:NMO, defined by the absence of all previous 1944:. As of 2019, only three of them are known. 1324:. This treatment involves the patient's own 747:are grouped within AQP4-IgG-negative NMOSD. 7403: 7213: 7204: 6973: 6641: 6632: 6521: 6495: 6481: 6473: 6262: 5962: 5948: 5940: 5726: 5724: 2726:Annals of the New York Academy of Sciences 1792:created sustained interest on the part of 1358: 998:, and bilateral simultaneous or recurrent 32: 6343:Experimental autoimmune encephalomyelitis 5919: 5869: 5818: 5768: 5758: 5704: 5694: 5652: 5603: 5578:Papadopoulos MC, Verkman AS (June 2012). 5336: 5326: 5285: 5275: 5231: 5052: 4719: 4623: 4526: 4439: 4429: 4390:https://doi.org/10.1016/j.jns.2017.10.036 4364: 4354: 4286: 4276: 4200: 4159: 4149: 4107: 3874:"Neuromyelitis Optica (Devic's Syndrome)" 3800: 3761:https://doi.org/10.1016/j.jns.2019.01.024 3693: 3656: 3595: 3540: 3447: 3425: 3423: 3403: 3393: 3261: 3165: 3155: 3114: 3104: 2984: 2935: 2753: 2611: 2554: 2544: 2409: 2391: 1882:-negative cases still remain idiopathic. 1409:Monoclonal antibody against CD19+ B cells 815:Diagnostic criteria are more relaxed for 651:. The damage can range from inflammatory 458:(HLA) alleles are associated with NMOSD. 6447:List of multiple sclerosis organizations 4700:Multiple Sclerosis and Related Disorders 2775: 2773: 2676:Multiple Sclerosis and Related Disorders 2641:Multiple Sclerosis and Related Disorders 2491:Mayo Clinic. Neuromyelitis optica 2020; 1982:Finally, other proteins under study are 1544:antibody against CD20 – B cell depletion 1448: 836: 691:distribution. Therefore, the pattern of 5309:Jarius S, Wildemann B (November 2018). 4592:"The Treatment of Neuromyelitis Optica" 3680:Barkhof F, Koeller KK (February 2020). 2174: 1975:Other autoantibody being researched is 1565:hematopoietic stem cell transplantation 1162:, and some MS cases are reported to be 1143:. In addition oligoclonal bands in the 1108:-Ab-negative NMO presents problems for 206:Neuromyelitis optica spectrum disorders 36:Neuromyelitis optica spectrum disorders 7284:Distal hereditary motor neuronopathies 6957:Template:Demyelinating diseases of CNS 6452:List of people with multiple sclerosis 6328:Neuromyelitis optica spectrum disorder 6275:Neuromyelitis optica spectrum disorder 5580:"Aquaporin 4 and neuromyelitis optica" 5426:. New York: Demos Medical Publishing. 5258:Jarius S, Wildemann B (January 2013). 2057:Antibody negative neuromyelitis optica 968:may play a role in rare cases of NMO. 683:), but they differ from MS pattern II 255:protein in the central nervous system. 5260:"The history of neuromyelitis optica" 3741: 3739: 2824:erythematosus: A preliminary study". 2369: 2254: 2252: 2250: 2248: 2246: 2244: 2242: 2240: 2238: 2236: 2234: 2232: 2230: 2228: 2226: 2224: 2222: 2220: 2218: 2216: 2214: 2212: 2210: 2208: 2206: 2204: 2202: 2200: 2198: 2020:-Ab+) – around 80% of total NMO cases 1393:Approved for AQP4-IgG-positive NMOSD 1241:anti-MOG associated encephalomyelitis 973:anti-MOG associated encephalomyelitis 894:dorsal medulla/area postrema lesions 830:, is sufficient for NMOSD diagnosis. 7: 7135:Idiopathic intracranial hypertension 6427:Mitochondrial DNA depletion syndrome 6313:Acute disseminated encephalomyelitis 5085:Journal of the Neurological Sciences 4986:Journal of the Neurological Sciences 4138:Acta Neuropathologica Communications 2916:The Journal of Experimental Medicine 2367: 2365: 2363: 2361: 2359: 2357: 2355: 2353: 2351: 2349: 2196: 2194: 2192: 2190: 2188: 2186: 2184: 2182: 2180: 2178: 1430:Approved forAQP4-IgG-positive NMOSD 720:antiMOG associated encephalomyelitis 636:(DTI), although less so compared to 123:Symptoms, blood antibody titers, MRI 4984:monitoring. A six-year follow-up". 2434:myelin oligodendrocyte glycoprotein 1780:First reports on an association of 1090:myelin oligodendrocyte glycoprotein 726:myelin oligodendrocyte glycoprotein 549:autoimmune astrocytic channelopathy 7366:Infantile progressive bulbar palsy 3542:10.1212/01.wnl.0000216139.44259.74 1816:and within weeks developed severe 25: 7069:Template:Cerebrovascular diseases 6872:Frontotemporal lobar degeneration 2061:Some cases of NMO are not due to 1189:Tumefactive demyelinating lesions 1008:+ OSMS. This variant can present 983:After the development of the NMO- 7089:For more detailed coverage, see 7067:For more detailed coverage, see 7038:For more detailed coverage, see 7004:For more detailed coverage, see 6955:For more detailed coverage, see 6457:Multiple sclerosis drug pipeline 6333:Diffuse myelinoclastic sclerosis 6323:Marburg acute multiple sclerosis 6280:Diffuse myelinoclastic sclerosis 6134:Management of multiple sclerosis 6101:Radiologically isolated syndrome 6081:Expanded Disability Status Scale 4041:Journal of Clinical Neuroscience 3838:10.1111/j.1600-0404.2008.01012.x 3757:Journal of Neurological Sciences 2127: 1948:Research into new autoantibodies 1800:in this rare syndrome. In 1894, 1427:Monoclonal antibody against IL-6 1206:Evolution of diagnostic criteria 908:periependymal brainstem lesions 601:). NMOSD brain lesions, as seen 6054:Diagnosis of multiple sclerosis 2265:Nature Reviews. Disease Primers 1958:glial fibrillary acidic protein 363:). Lesions may also affect the 87:, weakness, bladder dysfunction 6338:Tumefactive multiple sclerosis 6250:Research in multiple sclerosis 5970:Demyelinating diseases of the 4596:Journal of Neuro-Ophthalmology 3436:Journal of Neuro-Ophthalmology 1970:autoimmune GFAP astrocytopathy 1910:blocker of AQP4-IgG binding), 1507:DNA synthesis/repair inhibitor 919:diencephalic clinical syndrome 539:, which are the basis for the 1: 7518:Demyelinating diseases of CNS 7382:Amyotrophic lateral sclerosis 7267:Hereditary spastic paraplegia 7125:Normal pressure hydrocephalus 5596:10.1016/S1474-4422(12)70133-3 5462:10.1016/S0140-6736(04)17551-X 4754:(Press release). 27 June 2019 4238:10.1016/s1471-4914(00)01909-2 3826:Acta Neurologica Scandinavica 3192:European Journal of Neurology 1960:(GFAP)—was found in 2016, in 673:classified as type II lesions 480:) has opened a new avenue of 7351:Progressive muscular atrophy 6417:Central pontine myelinolysis 6386:Pelizaeus–Merzbacher disease 6381:Metachromatic leukodystrophy 6076:Clinically isolated syndrome 6047:Investigations and diagnosis 5912:10.1212/NXI.0000000000000626 5862:10.1212/NXI.0000000000000626 5760:10.1371/journal.pone.0074773 5683:Journal of Neuroinflammation 5315:Journal of Neuroinflammation 5264:Journal of Neuroinflammation 4954:10.1097/WCO.0b013e32814f1c6b 4942:Current Opinion in Neurology 4839:Food and Drug Administration 4780:Food and Drug Administration 4750:Food and Drug Administration 4608:10.1097/WNO.0000000000000102 4477:10.1212/WNL.0b013e3182a6cc23 4431:10.1371/journal.pone.0072919 4226:Trends in Molecular Medicine 3966:10.1212/WNL.0b013e318296e917 3922:10.1212/WNL.0b013e318296ea22 3695:10.1007/978-3-030-38490-6_13 3641:10.1212/WNL.0000000000001729 3588:10.1212/WNL.0000000000001729 3494:10.1001/jamaneurol.2013.5857 3449:10.1097/WNO.0b013e31823c9b6c 3382:Journal of Neuroinflammation 3144:Journal of Neuroinflammation 3093:Journal of Neuroinflammation 2546:10.1371/journal.pone.0177230 1351:FDA-approved pharmaceuticals 554:The astrocytes surround the 347:, as well as pain and tonic 6861:Primary progressive aphasia 6422:Marchiafava–Bignami disease 4784:(Press release). 2020-06-11 4712:10.1016/j.msard.2012.06.002 4183:Pearce JM (November 2005). 2688:10.1016/j.msard.2020.102451 2653:10.1016/j.msard.2023.105245 2624:– via www.nature.com. 2393:10.3390/biomedicines7020042 2031:– around 10% of total cases 1747:connective tissue disorders 1210:Since the discovery of the 1023:spectrum, sometimes called 810:consensus clinical criteria 710:are spared in these cases. 578:, where there is access to 511:NMOSD is usually caused by 113:Female sex, genetic factors 7544: 7183:Hashimoto's encephalopathy 6889:Posterior cortical atrophy 6710:Striatonigral degeneration 6561:Cavernous sinus thrombosis 5811:10.1007/s00401-019-02120-x 5494:Multiple Sclerosis Journal 4053:10.1016/j.jocn.2017.03.022 2663:– via ScienceDirect. 2604:10.1038/s41598-022-05531-1 1850:of NMO by detection of an 1553:intravenous immunoglobulin 1519:Inhibits folate metabolism 1483:Inhibits purine metabolism 1469:Inhibits purine metabolism 838:NMOSD diagnostic criteria 790:magnetic resonance imaging 717: 667:matters. The inflammatory 647:of NMO has focused on the 630:magnetic resonance imaging 504: 476:The discovery of NMO-IgG ( 417:magnetic resonance imaging 186:intravenous immunoglobulin 45:Neuromyelitis optica (NMO) 7289:Spinal muscular atrophies 7257:Primary lateral sclerosis 7115:Intracranial hypertension 6895:Creutzfeldt–Jakob disease 6318:Balo concentric sclerosis 5696:10.1186/s12974-017-0900-z 5645:10.1007/s00401-013-1116-7 5549:10.1007/s11064-013-1009-0 5374:10.1007/s00415-012-6594-3 5328:10.1186/s12974-019-1594-1 5185:10.1007/s00415-009-5171-x 5097:10.1016/j.jns.2018.02.028 4998:10.1016/j.jns.2016.11.016 4876:10.1001/archneur.63.7.957 4803:"Enspryng (satralizumab)" 4664:10.1016/j.ncl.2020.09.003 4509:Masaki K (October 2015). 4356:10.1186/s12883-014-0247-3 4151:10.1186/s40478-017-0495-8 4010:10.1191/1352458504ms988oa 3872:Wingerchuk, Dean (2006). 3759:, January 16, 2019, DOI: 3395:10.1186/s12974-015-0256-1 3157:10.1186/s12974-015-0240-9 3106:10.1186/s12974-018-1159-8 3022:10.1001/archneur.63.7.964 2277:10.1038/s41572-020-0214-9 2023:NMO derived from an anti- 1862:. The first quantitative 1838:researchers identified a 1643:, and 30% have permanent 1457: 1037:associated with systemic 1029:Longitudinally extensive 947:with NMOSD-typical brain 808:NMOSD is diagnosed using 781:were more likely to have 632:(MRI) can show damage in 415:, clinical presentation, 7356:Progressive bulbar palsy 7147:Intracranial hypotension 7130:Choroid plexus papilloma 6544:Herpesviral encephalitis 5506:10.1177/1352458512443917 5141:10.1177/1352458511412995 5045:10.1136/jnnp-2017-316271 4911:10.1177/1352458507077189 4694:Dean M. (October 2012). 4278:10.3389/fneur.2013.00125 4100:10.1177/2055217317742425 3344:10.1177/1352458514566666 3300:10.1177/1352458514551455 3058:10.1177/1352458516672015 2882:International MS Journal 2838:10.1177/1352458515613165 2794:10.1177/1352458515572241 1751:paraneoplastic syndromes 1444:affect the immune system 634:diffusion tensor imaging 359:, may be underdiagnosed 6868:Frontotemporal dementia 6554:Encephalitis lethargica 5422:T. Jock Murray (2005). 4094:(4): 2055217317742425. 1890:Since the discovery of 1790:Thomas Clifford Allbutt 1775:Thomas Clifford Allbutt 1332:being removed from the 1160:heterogeneous condition 1065:periventricular nucleus 879:(prolonged episodes of 643:Most research into the 456:human leukocyte antigen 7173:Hepatic encephalopathy 6259:Demyelinating diseases 5972:central nervous system 5537:Neurochemical Research 5277:10.1186/1742-2094-10-8 4265:Frontiers in Neurology 4185:"Neuromyelitis optica" 2495:. Accessed 2020 Nov 23 2472:. Accessed 2020 Nov 23 2261:"Neuromyelitis optica" 2111:biomedical engineering 1777: 1725:indigenous populations 1711:NMO is more common in 1283: 1198:Also, an overlap with 1112:. The behavior of the 1110:differential diagnosis 1101:Differential diagnosis 805: 497: 427:NMOSD is caused by an 129:Differential diagnosis 7231:Ataxia–telangiectasia 7188:Static encephalopathy 6911:Mitochondrial disease 6749:Spasmodic torticollis 6659:Basal ganglia disease 5799:Acta Neuropathologica 5633:Acta Neuropathologica 5584:The Lancet. Neurology 4864:Archives of Neurology 4202:10.1038/sj.sc.3101758 3010:Archives of Neurology 2148:Demyelinating disease 1938:heterogeneous disease 1772: 1478:mycophenolate mofetil 1281: 979:Spectrum constituents 803: 495: 251:), the most abundant 7178:Toxic encephalopathy 6884:Lewy bodies dementia 6361:Adrenoleukodystrophy 6285:MOG antibody disease 6087:Serological and CSF 6038:Uhthoff's phenomenon 5362:Journal of Neurology 5233:10.1093/brain/awh624 5173:Journal of Neurology 4813:on 23 September 2020 4259:Schneider R (2013). 3254:10.1093/brain/awf151 2928:10.1084/jem.20050304 2009:NMO derived from an 1657:cervical spinal cord 1437:Off-label treatments 1368:Date of FDA approval 1340:Secondary prevention 1132:have been proposed. 582:(CSF). In any case, 315:defects, or loss of 138:autoimmune disorders 7513:Autoimmune diseases 7226:Friedreich's ataxia 6609:Meningoencephalitis 6549:Limbic encephalitis 6189:Monomethyl fumarate 5751:2013PLoSO...874773T 5226:(Pt 12): 2899–910. 4422:2013PLoSO...872919M 2738:2016NYASA1366...20P 2596:2022NatSR..12.1579S 2537:2017PLoSO..1277230S 1962:transverse myelitis 1916:neutrophil elastase 1886:Research directions 1743:autoimmune diseases 1733:subtropical regions 1661:respiratory failure 1615:transverse myelitis 1455:Mechanism of action 1371:Mechanism of action 1202:has been reported. 1141:transverse myelitis 839: 687:in their prominent 586:is produced mainly 580:cerebrospinal fluid 556:blood–brain barrier 501:Anti-AQP4+ variants 275:Spinal cord effects 7477:External resources 7262:Pseudobulbar palsy 7000:Status epilepticus 6951:Multiple sclerosis 6788:Myoclonic epilepsy 6651:movement disorders 6597:Acute disseminated 6539:Viral encephalitis 6290:Multiple sclerosis 6174:Interferon beta-1b 6169:Interferon beta-1a 6164:Glatiramer acetate 6154:Diroximel fumarate 6127:Approved treatment 5980:Signs and symptoms 5129:Multiple Sclerosis 4899:Multiple Sclerosis 4652:Neurologic Clinics 4566:www.mayoclinic.org 4528:10.1111/neup.12211 3998:Multiple Sclerosis 3332:Multiple Sclerosis 3288:Multiple Sclerosis 3046:Multiple Sclerosis 2826:Multiple Sclerosis 2782:Multiple Sclerosis 2746:10.1111/nyas.12794 2584:Scientific Reports 2158:Multiple sclerosis 1894:involvement, some 1878:IgG, but some NMO 1778: 1328:being pumped out, 1308:methylprednisolone 1284: 1243:. Some cases with 1175:potassium channels 1059:areas such as the 1019:-negative form of 837: 806: 714:Anti-MOG+ variants 638:multiple sclerosis 603:under a microscope 498: 465:. It appears that 405:multiple sclerosis 399:Comparison with MS 375:(AQP4-IgG) NMOSD. 353:cognitive deficits 263:Signs and symptoms 166:methylprednisolone 134:Multiple sclerosis 7500: 7499: 7400: 7399: 7396: 7395: 7392: 7391: 7196: 7195: 7101: 7100: 7040:Template:Headache 7006:Template:Epilepsy 6927: 6926: 6901:Vascular dementia 6744:Status dystonicus 6617: 6616: 6592:Encephalomyelitis 6470: 6469: 6435: 6434: 6366:Alexander disease 6149:Dimethyl fumarate 6091:Oligoclonal bands 6059:McDonald criteria 5500:(11): 1541–1551. 5456:(9451): 2106–12. 5433:978-1-888799-80-4 3705:978-3-030-38489-0 3248:(Pt 7): 1450–61. 3204:10.1111/ene.13321 2977:10.1111/bpa.12099 2450:Gaillard, Frank. 2143:Anti-AQP4 disease 2029:encephalomyelitis 1757:remains unknown ( 1693:, 38% had severe 1576: 1575: 1446:in various ways. 1434: 1433: 1251:have been found. 1151:lesions on brain 1114:oligoclonal bands 958: 957: 752:anti-AQP4 disease 745:anti-MOG diseases 730:integral membrane 728:(MOG). MOG is an 671:in NMO have been 615:complement system 560:metalloproteinase 541:glymphatic system 507:Anti-AQP4 disease 484:into the causes. 337:medulla oblongata 203: 202: 199:Up to 1 in 10,000 119:Diagnostic method 30:Medical condition 16:(Redirected from 7535: 7523:Myelin disorders 7404: 7214: 7205: 7163:Brain herniation 6974: 6814:Intention tremor 6809:Essential tremor 6674:Postencephalitic 6642: 6633: 6522: 6503:Diseases of the 6497: 6490: 6483: 6474: 6263: 6233:Other treatments 6111:Dawson's fingers 5964: 5957: 5950: 5941: 5934: 5933: 5923: 5890: 5884: 5883: 5873: 5839: 5833: 5832: 5822: 5789: 5783: 5782: 5772: 5762: 5728: 5719: 5718: 5708: 5698: 5673: 5667: 5666: 5656: 5624: 5618: 5617: 5607: 5575: 5569: 5568: 5532: 5526: 5525: 5488: 5482: 5481: 5444: 5438: 5437: 5419: 5413: 5412: 5400: 5394: 5393: 5357: 5351: 5350: 5340: 5330: 5306: 5300: 5299: 5289: 5279: 5255: 5246: 5245: 5235: 5211: 5205: 5204: 5167: 5161: 5160: 5123: 5117: 5116: 5082: 5073: 5067: 5066: 5056: 5024: 5018: 5017: 4980: 4974: 4973: 4937: 4931: 4930: 4894: 4888: 4887: 4859: 4853: 4852: 4850: 4848: 4843:. 17 August 2020 4829: 4823: 4822: 4820: 4818: 4809:. Archived from 4799: 4793: 4792: 4790: 4789: 4770: 4764: 4763: 4761: 4759: 4740: 4734: 4733: 4723: 4690: 4684: 4683: 4647: 4638: 4637: 4627: 4587: 4576: 4575: 4573: 4572: 4558: 4549: 4548: 4530: 4506: 4497: 4496: 4460: 4454: 4453: 4443: 4433: 4401: 4392: 4385: 4379: 4378: 4368: 4358: 4334: 4328: 4327: 4318:(11): 1897–902. 4307: 4301: 4300: 4290: 4280: 4256: 4250: 4249: 4221: 4215: 4214: 4204: 4180: 4174: 4173: 4163: 4153: 4128: 4122: 4121: 4111: 4079: 4073: 4072: 4036: 4030: 4029: 3992: 3986: 3985: 3960:(24): 2194–200. 3948: 3942: 3941: 3905: 3899: 3898: 3896: 3895: 3889: 3883:. Archived from 3878: 3869: 3858: 3857: 3821: 3815: 3814: 3804: 3793:10.1002/acn3.164 3772: 3763: 3753: 3747: 3743: 3734: 3724: 3718: 3717: 3697: 3677: 3671: 3670: 3660: 3619: 3610: 3609: 3599: 3566: 3555: 3554: 3544: 3520: 3514: 3513: 3476: 3470: 3469: 3451: 3427: 3418: 3417: 3407: 3397: 3373: 3364: 3363: 3326: 3320: 3319: 3282: 3276: 3275: 3265: 3233: 3224: 3223: 3186: 3180: 3179: 3169: 3159: 3135: 3129: 3128: 3118: 3108: 3084: 3078: 3077: 3052:(8): 1072–1084. 3040: 3034: 3033: 3005: 2999: 2998: 2988: 2956: 2950: 2949: 2939: 2907: 2898: 2897: 2877: 2858: 2857: 2820: 2814: 2813: 2777: 2768: 2767: 2757: 2717: 2708: 2707: 2671: 2665: 2664: 2632: 2626: 2625: 2615: 2575: 2569: 2568: 2558: 2548: 2516: 2510: 2509: 2502: 2496: 2489: 2483: 2479: 2473: 2466: 2460: 2459: 2447: 2441: 2430: 2424: 2423: 2413: 2395: 2371: 2344: 2343: 2341: 2340: 2326: 2320: 2314: 2305: 2304: 2256: 2137: 2132: 2131: 2130: 2083:Notable patients 1918:inhibitor), and 1896:research studies 1798:ophthalmologists 1527:cyclophosphamide 1466:(Imuran, Azasan) 1449: 1359: 1200:Sjögren syndrome 1051:associated with 954:None additional 935:None additional 840: 619:oligodendrocytes 607:Immunoglobulin M 373:Immunoglobulin-G 238:immunoglobulin G 190:cyclophosphamide 53:Devic's syndrome 33: 21: 7543: 7542: 7538: 7537: 7536: 7534: 7533: 7532: 7503: 7502: 7501: 7496: 7495: 7472: 7471: 7415: 7401: 7388: 7314:Congenital DSMA 7235: 7192: 7151: 7097: 7085:Sleep disorders 7073: 7050:Cerebrovascular 7044: 7010: 6967: 6961: 6923: 6905: 6830: 6776:Choreoathetosis 6649: 6626: 6613: 6577: 6511: 6501: 6471: 6466: 6462:Pathophysiology 6431: 6405: 6401:CAMFAK syndrome 6371:Canavan disease 6347: 6299: 6254: 6228: 6122: 6042: 5974: 5968: 5938: 5937: 5892: 5891: 5887: 5841: 5840: 5836: 5791: 5790: 5786: 5730: 5729: 5722: 5675: 5674: 5670: 5626: 5625: 5621: 5577: 5576: 5572: 5543:(5): 997–1001. 5534: 5533: 5529: 5490: 5489: 5485: 5446: 5445: 5441: 5434: 5421: 5420: 5416: 5402: 5401: 5397: 5359: 5358: 5354: 5308: 5307: 5303: 5257: 5256: 5249: 5213: 5212: 5208: 5169: 5168: 5164: 5135:(12): 1527–30. 5125: 5124: 5120: 5080: 5075: 5074: 5070: 5026: 5025: 5021: 4982: 4981: 4977: 4939: 4938: 4934: 4896: 4895: 4891: 4861: 4860: 4856: 4846: 4844: 4831: 4830: 4826: 4816: 4814: 4801: 4800: 4796: 4787: 4785: 4772: 4771: 4767: 4757: 4755: 4742: 4741: 4737: 4692: 4691: 4687: 4649: 4648: 4641: 4589: 4588: 4579: 4570: 4568: 4560: 4559: 4552: 4508: 4507: 4500: 4462: 4461: 4457: 4403: 4402: 4395: 4386: 4382: 4336: 4335: 4331: 4309: 4308: 4304: 4258: 4257: 4253: 4223: 4222: 4218: 4182: 4181: 4177: 4130: 4129: 4125: 4081: 4080: 4076: 4038: 4037: 4033: 3994: 3993: 3989: 3950: 3949: 3945: 3907: 3906: 3902: 3893: 3891: 3887: 3876: 3871: 3870: 3861: 3823: 3822: 3818: 3774: 3773: 3766: 3754: 3750: 3744: 3737: 3725: 3721: 3706: 3679: 3678: 3674: 3621: 3620: 3613: 3568: 3567: 3558: 3522: 3521: 3517: 3478: 3477: 3473: 3429: 3428: 3421: 3375: 3374: 3367: 3338:(12): 1513–20. 3328: 3327: 3323: 3284: 3283: 3279: 3235: 3234: 3227: 3188: 3187: 3183: 3137: 3136: 3132: 3086: 3085: 3081: 3042: 3041: 3037: 3007: 3006: 3002: 2965:Brain Pathology 2958: 2957: 2953: 2909: 2908: 2901: 2879: 2878: 2861: 2832:(9): 1192–201. 2822: 2821: 2817: 2779: 2778: 2771: 2719: 2718: 2711: 2673: 2672: 2668: 2634: 2633: 2629: 2577: 2576: 2572: 2531:(5): e0177230. 2518: 2517: 2513: 2504: 2503: 2499: 2490: 2486: 2482:2019;35:246-252 2480: 2476: 2467: 2463: 2449: 2448: 2444: 2431: 2427: 2373: 2372: 2347: 2338: 2336: 2328: 2327: 2323: 2315: 2308: 2258: 2257: 2176: 2171: 2135:Medicine portal 2133: 2128: 2126: 2123: 2103:Cassie Mitchell 2085: 2059: 1950: 1942:auto-antibodies 1888: 1812:in one or both 1767: 1673: 1663:and subsequent 1600: 1531:DNA crosslinker 1439: 1353: 1342: 1322:corticosteroids 1304:corticosteroids 1296: 1276: 1208: 1193:interferon beta 1179:astrocytopathic 1167:channelopathies 1103: 1025:optic-spinal MS 981: 798: 785:involvement on 756:auto-antibodies 722: 716: 523:protein in the 509: 503: 490: 488:Pathophysiology 425: 401: 390: 381: 325: 297: 281:muscle weakness 277: 265: 49:Devic's disease 31: 28: 23: 22: 15: 12: 11: 5: 7541: 7539: 7531: 7530: 7525: 7520: 7515: 7505: 7504: 7498: 7497: 7494: 7493: 7481: 7480: 7478: 7474: 7473: 7470: 7469: 7458: 7447: 7432: 7416: 7411: 7410: 7408: 7407:Classification 7398: 7397: 7394: 7393: 7390: 7389: 7387: 7386: 7385: 7384: 7373: 7372: 7371: 7370: 7369: 7368: 7363: 7353: 7348: 7347: 7346: 7341: 7336: 7335: 7334: 7329: 7324: 7316: 7311: 7306: 7301: 7296: 7286: 7272: 7271: 7270: 7269: 7264: 7259: 7245: 7243: 7237: 7236: 7234: 7233: 7228: 7222: 7220: 7211: 7202: 7198: 7197: 7194: 7193: 7191: 7190: 7185: 7180: 7175: 7170: 7165: 7159: 7157: 7153: 7152: 7150: 7149: 7144: 7142:Cerebral edema 7139: 7138: 7137: 7132: 7127: 7122: 7111: 7109: 7103: 7102: 7099: 7098: 7096: 7095: 7094: 7093: 7091:Template:Sleep 7081: 7079: 7075: 7074: 7072: 7071: 7065: 7060: 7054: 7052: 7046: 7045: 7043: 7042: 7036: 7031: 7026: 7020: 7018: 7012: 7011: 7009: 7008: 7002: 6997: 6992: 6986: 6984: 6971: 6963: 6962: 6960: 6959: 6953: 6948: 6943: 6937: 6935: 6929: 6928: 6925: 6924: 6922: 6921: 6919:Leigh syndrome 6915: 6913: 6907: 6906: 6904: 6903: 6892: 6891: 6886: 6881: 6880: 6879: 6865: 6864: 6863: 6858: 6857: 6856: 6840: 6838: 6832: 6831: 6829: 6828: 6823: 6818: 6817: 6816: 6811: 6800: 6799: 6798: 6797: 6792: 6791: 6790: 6780: 6779: 6778: 6768: 6763: 6762: 6761: 6756: 6751: 6746: 6730: 6729: 6728: 6727: 6722: 6717: 6712: 6707: 6706: 6705: 6695: 6694: 6693: 6683: 6682: 6681: 6676: 6671: 6655: 6653: 6646:Extrapyramidal 6639: 6630: 6628:encephalopathy 6619: 6618: 6615: 6614: 6612: 6611: 6606: 6601: 6600: 6599: 6588: 6586: 6579: 6578: 6576: 6575: 6574: 6573: 6563: 6558: 6557: 6556: 6551: 6546: 6541: 6530: 6528: 6519: 6513: 6512: 6505:nervous system 6502: 6500: 6499: 6492: 6485: 6477: 6468: 6467: 6465: 6464: 6459: 6454: 6449: 6443: 6441: 6437: 6436: 6433: 6432: 6430: 6429: 6424: 6419: 6413: 6411: 6407: 6406: 6404: 6403: 6398: 6393: 6388: 6383: 6378: 6376:Krabbe disease 6373: 6368: 6363: 6357: 6355: 6349: 6348: 6346: 6345: 6340: 6335: 6330: 6325: 6320: 6315: 6309: 6307: 6301: 6300: 6298: 6297: 6292: 6287: 6282: 6277: 6271: 6269: 6260: 6256: 6255: 6253: 6252: 6247: 6246: 6245: 6236: 6234: 6230: 6229: 6227: 6226: 6221: 6216: 6211: 6206: 6203:+hyaluronidase 6196: 6191: 6186: 6181: 6176: 6171: 6166: 6161: 6156: 6151: 6146: 6141: 6136: 6130: 6128: 6124: 6123: 6121: 6120: 6115: 6114: 6113: 6108: 6103: 6095: 6094: 6093: 6085: 6084: 6083: 6078: 6069: 6068: 6066:Poser criteria 6063: 6062: 6061: 6050: 6048: 6044: 6043: 6041: 6040: 6035: 6030: 6028:Optic neuritis 6025: 6020: 6015: 6010: 6005: 6000: 5995: 5990: 5984: 5982: 5976: 5975: 5969: 5967: 5966: 5959: 5952: 5944: 5936: 5935: 5885: 5834: 5805:(3): 547–564. 5784: 5720: 5668: 5619: 5570: 5527: 5483: 5439: 5432: 5414: 5395: 5352: 5301: 5247: 5206: 5179:(11): 1891–8. 5162: 5118: 5068: 5039:(2): 147–155. 5019: 4975: 4932: 4889: 4854: 4824: 4794: 4765: 4735: 4706:(4): 180–187. 4685: 4639: 4577: 4550: 4515:Neuropathology 4498: 4471:(14): 1186–8. 4455: 4393: 4380: 4329: 4302: 4251: 4216: 4175: 4123: 4074: 4031: 3987: 3943: 3916:(24): 2176–7. 3900: 3859: 3816: 3787:(3): 295–301. 3764: 3748: 3735: 3719: 3704: 3672: 3635:(2): 177–189. 3611: 3556: 3535:(10): 1485–9. 3515: 3482:JAMA Neurology 3471: 3419: 3365: 3321: 3277: 3225: 3198:(7): 966–973. 3181: 3130: 3079: 3035: 3000: 2951: 2899: 2859: 2815: 2769: 2709: 2666: 2627: 2570: 2511: 2497: 2484: 2474: 2461: 2442: 2425: 2345: 2321: 2306: 2173: 2172: 2170: 2167: 2166: 2165: 2160: 2155: 2150: 2145: 2139: 2138: 2122: 2119: 2118: 2117: 2100: 2084: 2081: 2063:autoantibodies 2058: 2055: 2054: 2053: 2044: 2038: 2032: 2021: 1949: 1946: 1931:paraneoplastic 1904:plasmapheresis 1887: 1884: 1872:autoantibodies 1766: 1763: 1697:, and 23% had 1695:optic neuritis 1672: 1669: 1619:optic neuritis 1599: 1596: 1574: 1573: 1570: 1568: 1561: 1560: 1558: 1556: 1549: 1548: 1545: 1542: 1535: 1534: 1532: 1529: 1523: 1522: 1520: 1517: 1511: 1510: 1508: 1505: 1499: 1498: 1496: 1494: 1492:corticosteroid 1488: 1487: 1484: 1481: 1474: 1473: 1470: 1467: 1460: 1459: 1456: 1453: 1438: 1435: 1432: 1431: 1428: 1425: 1422: 1419: 1413: 1412: 1410: 1407: 1404: 1401: 1395: 1394: 1391: 1388: 1385: 1382: 1376: 1375: 1372: 1369: 1366: 1363: 1352: 1349: 1341: 1338: 1318:Plasmapheresis 1295: 1292: 1275: 1272: 1264:astrocytopathy 1207: 1204: 1102: 1099: 1098: 1097: 1094:autoantibodies 1077:negative NMO: 1071: 1045:Optic neuritis 1042: 1035:optic neuritis 1027: 1002: 1000:optic neuritis 992: 980: 977: 966:autoantibodies 956: 955: 952: 937: 936: 933: 910: 909: 906: 896: 895: 892: 870: 869: 866: 859: 858: 854: 852:Optic neuritis 848: 847: 844: 797: 794: 750:Together with 718:Main article: 715: 712: 659:damage of the 595:foot processes 545:astrocytopathy 513:autoantibodies 505:Main article: 502: 499: 489: 486: 473:-derived NMO. 463:paraneoplastic 436:autoantibodies 424: 421: 400: 397: 389: 386: 380: 379:Disease course 377: 324: 321: 305:optic neuritis 296: 293: 276: 273: 267:The signs and 264: 261: 260: 259: 256: 241:autoantibodies 224:, ON) and the 222:optic neuritis 201: 200: 197: 193: 192: 147: 141: 140: 131: 125: 124: 121: 115: 114: 111: 105: 104: 101: 97: 96: 93: 89: 88: 78: 72: 71: 62: 56: 55: 42: 38: 37: 29: 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 7540: 7529: 7528:Rare diseases 7526: 7524: 7521: 7519: 7516: 7514: 7511: 7510: 7508: 7492: 7488: 7487: 7483: 7482: 7479: 7475: 7468: 7464: 7463: 7459: 7457: 7453: 7452: 7448: 7446: 7442: 7441: 7437: 7433: 7431: 7427: 7426: 7422: 7418: 7417: 7414: 7409: 7405: 7383: 7380: 7379: 7378: 7375: 7374: 7367: 7364: 7362: 7359: 7358: 7357: 7354: 7352: 7349: 7345: 7342: 7340: 7337: 7333: 7330: 7328: 7325: 7323: 7320: 7319: 7317: 7315: 7312: 7310: 7307: 7305: 7302: 7300: 7297: 7295: 7292: 7291: 7290: 7287: 7285: 7282: 7281: 7280: 7278: 7274: 7273: 7268: 7265: 7263: 7260: 7258: 7255: 7254: 7253: 7251: 7247: 7246: 7244: 7242: 7238: 7232: 7229: 7227: 7224: 7223: 7221: 7219: 7215: 7212: 7210: 7206: 7203: 7199: 7189: 7186: 7184: 7181: 7179: 7176: 7174: 7171: 7169: 7168:Reye syndrome 7166: 7164: 7161: 7160: 7158: 7154: 7148: 7145: 7143: 7140: 7136: 7133: 7131: 7128: 7126: 7123: 7121: 7120:Hydrocephalus 7118: 7117: 7116: 7113: 7112: 7110: 7108: 7104: 7092: 7088: 7087: 7086: 7083: 7082: 7080: 7076: 7070: 7066: 7064: 7061: 7059: 7056: 7055: 7053: 7051: 7047: 7041: 7037: 7035: 7032: 7030: 7027: 7025: 7022: 7021: 7019: 7017: 7013: 7007: 7003: 7001: 6998: 6996: 6993: 6991: 6988: 6987: 6985: 6983: 6979: 6975: 6972: 6970: 6964: 6958: 6954: 6952: 6949: 6947: 6944: 6942: 6939: 6938: 6936: 6934: 6933:Demyelinating 6930: 6920: 6917: 6916: 6914: 6912: 6908: 6902: 6899: 6898: 6897: 6896: 6890: 6887: 6885: 6882: 6878: 6875: 6874: 6873: 6869: 6866: 6862: 6859: 6855: 6852: 6851: 6850: 6847: 6846: 6845: 6842: 6841: 6839: 6837: 6833: 6827: 6824: 6822: 6821:Restless legs 6819: 6815: 6812: 6810: 6807: 6806: 6805: 6802: 6801: 6796: 6793: 6789: 6786: 6785: 6784: 6781: 6777: 6774: 6773: 6772: 6769: 6767: 6764: 6760: 6759:Blepharospasm 6757: 6755: 6752: 6750: 6747: 6745: 6742: 6741: 6740: 6737: 6736: 6735: 6732: 6731: 6726: 6723: 6721: 6718: 6716: 6715:Hemiballismus 6713: 6711: 6708: 6704: 6701: 6700: 6699: 6696: 6692: 6689: 6688: 6687: 6684: 6680: 6677: 6675: 6672: 6670: 6667: 6666: 6665: 6662: 6661: 6660: 6657: 6656: 6654: 6652: 6647: 6643: 6640: 6638: 6634: 6631: 6629: 6624: 6620: 6610: 6607: 6605: 6602: 6598: 6595: 6594: 6593: 6590: 6589: 6587: 6585: 6580: 6572: 6569: 6568: 6567: 6566:Brain abscess 6564: 6562: 6559: 6555: 6552: 6550: 6547: 6545: 6542: 6540: 6537: 6536: 6535: 6532: 6531: 6529: 6527: 6523: 6520: 6518: 6514: 6510: 6506: 6498: 6493: 6491: 6486: 6484: 6479: 6478: 6475: 6463: 6460: 6458: 6455: 6453: 6450: 6448: 6445: 6444: 6442: 6438: 6428: 6425: 6423: 6420: 6418: 6415: 6414: 6412: 6408: 6402: 6399: 6397: 6394: 6392: 6389: 6387: 6384: 6382: 6379: 6377: 6374: 6372: 6369: 6367: 6364: 6362: 6359: 6358: 6356: 6354: 6350: 6344: 6341: 6339: 6336: 6334: 6331: 6329: 6326: 6324: 6321: 6319: 6316: 6314: 6311: 6310: 6308: 6306: 6302: 6296: 6293: 6291: 6288: 6286: 6283: 6281: 6278: 6276: 6273: 6272: 6270: 6268: 6264: 6261: 6257: 6251: 6248: 6244: 6241: 6240: 6238: 6237: 6235: 6231: 6225: 6224:Teriflunomide 6222: 6220: 6217: 6215: 6212: 6210: 6207: 6204: 6200: 6197: 6195: 6192: 6190: 6187: 6185: 6182: 6180: 6177: 6175: 6172: 6170: 6167: 6165: 6162: 6160: 6157: 6155: 6152: 6150: 6147: 6145: 6142: 6140: 6137: 6135: 6132: 6131: 6129: 6125: 6119: 6116: 6112: 6109: 6107: 6104: 6102: 6099: 6098: 6097:Radiological 6096: 6092: 6089: 6088: 6086: 6082: 6079: 6077: 6074: 6073: 6071: 6070: 6067: 6064: 6060: 6057: 6056: 6055: 6052: 6051: 6049: 6045: 6039: 6036: 6034: 6031: 6029: 6026: 6024: 6021: 6019: 6016: 6014: 6011: 6009: 6006: 6004: 6001: 5999: 5996: 5994: 5991: 5989: 5986: 5985: 5983: 5981: 5977: 5973: 5965: 5960: 5958: 5953: 5951: 5946: 5945: 5942: 5931: 5927: 5922: 5917: 5913: 5909: 5905: 5901: 5897: 5889: 5886: 5881: 5877: 5872: 5867: 5863: 5859: 5855: 5851: 5850: 5845: 5838: 5835: 5830: 5826: 5821: 5816: 5812: 5808: 5804: 5800: 5796: 5788: 5785: 5780: 5776: 5771: 5766: 5761: 5756: 5752: 5748: 5745:(9): e74773. 5744: 5740: 5739: 5734: 5727: 5725: 5721: 5716: 5712: 5707: 5702: 5697: 5692: 5688: 5684: 5680: 5672: 5669: 5664: 5660: 5655: 5650: 5646: 5642: 5639:(6): 815–27. 5638: 5634: 5630: 5623: 5620: 5615: 5611: 5606: 5601: 5597: 5593: 5590:(6): 535–44. 5589: 5585: 5581: 5574: 5571: 5566: 5562: 5558: 5554: 5550: 5546: 5542: 5538: 5531: 5528: 5523: 5519: 5515: 5511: 5507: 5503: 5499: 5495: 5487: 5484: 5479: 5475: 5471: 5467: 5463: 5459: 5455: 5451: 5443: 5440: 5435: 5429: 5425: 5418: 5415: 5410: 5407:(in French). 5406: 5399: 5396: 5391: 5387: 5383: 5379: 5375: 5371: 5367: 5363: 5356: 5353: 5348: 5344: 5339: 5334: 5329: 5324: 5320: 5316: 5312: 5305: 5302: 5297: 5293: 5288: 5283: 5278: 5273: 5269: 5265: 5261: 5254: 5252: 5248: 5243: 5239: 5234: 5229: 5225: 5221: 5217: 5210: 5207: 5202: 5198: 5194: 5190: 5186: 5182: 5178: 5174: 5166: 5163: 5158: 5154: 5150: 5146: 5142: 5138: 5134: 5130: 5122: 5119: 5114: 5110: 5106: 5102: 5098: 5094: 5090: 5086: 5079: 5072: 5069: 5064: 5060: 5055: 5050: 5046: 5042: 5038: 5034: 5030: 5023: 5020: 5015: 5011: 5007: 5003: 4999: 4995: 4991: 4987: 4979: 4976: 4971: 4967: 4963: 4959: 4955: 4951: 4948:(3): 255–60. 4947: 4943: 4936: 4933: 4928: 4924: 4920: 4916: 4912: 4908: 4905:(8): 968–74. 4904: 4900: 4893: 4890: 4885: 4881: 4877: 4873: 4870:(7): 957–63. 4869: 4865: 4858: 4855: 4842: 4840: 4834: 4828: 4825: 4812: 4808: 4804: 4798: 4795: 4783: 4781: 4775: 4769: 4766: 4753: 4751: 4745: 4739: 4736: 4731: 4727: 4722: 4717: 4713: 4709: 4705: 4701: 4697: 4689: 4686: 4681: 4677: 4673: 4669: 4665: 4661: 4657: 4653: 4646: 4644: 4640: 4635: 4631: 4626: 4621: 4617: 4613: 4609: 4605: 4601: 4597: 4593: 4586: 4584: 4582: 4578: 4567: 4563: 4557: 4555: 4551: 4546: 4542: 4538: 4534: 4529: 4524: 4521:(5): 469–80. 4520: 4516: 4512: 4505: 4503: 4499: 4494: 4490: 4486: 4482: 4478: 4474: 4470: 4466: 4459: 4456: 4451: 4447: 4442: 4437: 4432: 4427: 4423: 4419: 4416:(8): e72919. 4415: 4411: 4407: 4400: 4398: 4394: 4391: 4384: 4381: 4376: 4372: 4367: 4362: 4357: 4352: 4348: 4344: 4343:BMC Neurology 4340: 4333: 4330: 4325: 4321: 4317: 4313: 4306: 4303: 4298: 4294: 4289: 4284: 4279: 4274: 4270: 4266: 4262: 4255: 4252: 4247: 4243: 4239: 4235: 4232:(3): 115–21. 4231: 4227: 4220: 4217: 4212: 4208: 4203: 4198: 4195:(11): 631–4. 4194: 4190: 4186: 4179: 4176: 4171: 4167: 4162: 4157: 4152: 4147: 4143: 4139: 4135: 4127: 4124: 4119: 4115: 4110: 4105: 4101: 4097: 4093: 4089: 4085: 4078: 4075: 4070: 4066: 4062: 4058: 4054: 4050: 4046: 4042: 4035: 4032: 4027: 4023: 4019: 4015: 4011: 4007: 4003: 3999: 3991: 3988: 3983: 3979: 3975: 3971: 3967: 3963: 3959: 3955: 3947: 3944: 3939: 3935: 3931: 3927: 3923: 3919: 3915: 3911: 3904: 3901: 3890:on 2006-09-25 3886: 3882: 3875: 3868: 3866: 3864: 3860: 3855: 3851: 3847: 3843: 3839: 3835: 3832:(4): 218–25. 3831: 3827: 3820: 3817: 3812: 3808: 3803: 3798: 3794: 3790: 3786: 3782: 3778: 3771: 3769: 3765: 3762: 3758: 3752: 3749: 3742: 3740: 3736: 3733: 3729: 3723: 3720: 3715: 3711: 3707: 3701: 3696: 3691: 3687: 3683: 3676: 3673: 3668: 3664: 3659: 3654: 3650: 3646: 3642: 3638: 3634: 3630: 3626: 3618: 3616: 3612: 3607: 3603: 3598: 3593: 3589: 3585: 3582:(2): 177–89. 3581: 3577: 3573: 3565: 3563: 3561: 3557: 3552: 3548: 3543: 3538: 3534: 3530: 3526: 3519: 3516: 3511: 3507: 3503: 3499: 3495: 3491: 3488:(3): 276–83. 3487: 3483: 3475: 3472: 3467: 3463: 3459: 3455: 3450: 3445: 3442:(2): 107–10. 3441: 3437: 3433: 3426: 3424: 3420: 3415: 3411: 3406: 3401: 3396: 3391: 3387: 3383: 3379: 3372: 3370: 3366: 3361: 3357: 3353: 3349: 3345: 3341: 3337: 3333: 3325: 3322: 3317: 3313: 3309: 3305: 3301: 3297: 3293: 3289: 3281: 3278: 3273: 3269: 3264: 3259: 3255: 3251: 3247: 3243: 3239: 3232: 3230: 3226: 3221: 3217: 3213: 3209: 3205: 3201: 3197: 3193: 3185: 3182: 3177: 3173: 3168: 3163: 3158: 3153: 3149: 3145: 3141: 3134: 3131: 3126: 3122: 3117: 3112: 3107: 3102: 3098: 3094: 3090: 3083: 3080: 3075: 3071: 3067: 3063: 3059: 3055: 3051: 3047: 3039: 3036: 3031: 3027: 3023: 3019: 3015: 3011: 3004: 3001: 2996: 2992: 2987: 2982: 2978: 2974: 2970: 2966: 2962: 2955: 2952: 2947: 2943: 2938: 2933: 2929: 2925: 2921: 2917: 2913: 2906: 2904: 2900: 2895: 2891: 2887: 2883: 2876: 2874: 2872: 2870: 2868: 2866: 2864: 2860: 2855: 2851: 2847: 2843: 2839: 2835: 2831: 2827: 2819: 2816: 2811: 2807: 2803: 2799: 2795: 2791: 2787: 2783: 2776: 2774: 2770: 2765: 2761: 2756: 2751: 2747: 2743: 2739: 2735: 2731: 2727: 2723: 2716: 2714: 2710: 2705: 2701: 2697: 2693: 2689: 2685: 2681: 2677: 2670: 2667: 2662: 2658: 2654: 2650: 2646: 2642: 2638: 2631: 2628: 2623: 2619: 2614: 2609: 2605: 2601: 2597: 2593: 2589: 2585: 2581: 2574: 2571: 2566: 2562: 2557: 2552: 2547: 2542: 2538: 2534: 2530: 2526: 2522: 2515: 2512: 2507: 2501: 2498: 2494: 2488: 2485: 2478: 2475: 2471: 2465: 2462: 2457: 2453: 2446: 2443: 2439: 2435: 2429: 2426: 2421: 2417: 2412: 2407: 2403: 2399: 2394: 2389: 2385: 2381: 2377: 2370: 2368: 2366: 2364: 2362: 2360: 2358: 2356: 2354: 2352: 2350: 2346: 2335: 2331: 2325: 2322: 2319: 2313: 2311: 2307: 2302: 2298: 2294: 2290: 2286: 2282: 2278: 2274: 2270: 2266: 2262: 2255: 2253: 2251: 2249: 2247: 2245: 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: 2185: 2183: 2181: 2179: 2175: 2168: 2164: 2161: 2159: 2156: 2154: 2151: 2149: 2146: 2144: 2141: 2140: 2136: 2125: 2120: 2115: 2112: 2108: 2104: 2101: 2098: 2094: 2090: 2087: 2086: 2082: 2080: 2077: 2075: 2071: 2066: 2064: 2056: 2052: 2048: 2045: 2042: 2039: 2036: 2033: 2030: 2026: 2022: 2019: 2015: 2014:channelopathy 2012: 2008: 2007: 2006: 2004: 2000: 1995: 1993: 1989: 1985: 1980: 1978: 1973: 1971: 1967: 1963: 1959: 1955: 1947: 1945: 1943: 1939: 1934: 1932: 1927: 1925: 1921: 1917: 1913: 1909: 1905: 1901: 1897: 1893: 1885: 1883: 1881: 1877: 1873: 1869: 1865: 1861: 1857: 1853: 1849: 1845: 1841: 1837: 1832: 1830: 1826: 1822: 1819: 1815: 1811: 1807: 1803: 1799: 1795: 1791: 1787: 1783: 1776: 1771: 1764: 1762: 1760: 1756: 1752: 1748: 1744: 1739: 1736: 1734: 1730: 1726: 1722: 1718: 1714: 1709: 1707: 1704: 1700: 1696: 1692: 1689: 1685: 1680: 1678: 1670: 1668: 1666: 1662: 1658: 1654: 1650: 1646: 1642: 1637: 1634: 1631: 1626: 1624: 1620: 1616: 1612: 1607: 1606:may persist. 1605: 1597: 1595: 1593: 1589: 1585: 1581: 1571: 1569: 1566: 1563: 1562: 1559: 1557: 1554: 1551: 1550: 1546: 1543: 1540: 1537: 1536: 1533: 1530: 1528: 1525: 1524: 1521: 1518: 1516: 1513: 1512: 1509: 1506: 1504: 1501: 1500: 1497: 1495: 1493: 1490: 1489: 1485: 1482: 1479: 1476: 1475: 1471: 1468: 1465: 1462: 1461: 1454: 1451: 1450: 1447: 1445: 1436: 1429: 1426: 1423: 1420: 1418: 1415: 1414: 1411: 1408: 1405: 1402: 1400: 1397: 1396: 1392: 1389: 1386: 1383: 1381: 1378: 1377: 1373: 1370: 1367: 1364: 1361: 1360: 1357: 1350: 1348: 1346: 1339: 1337: 1335: 1331: 1327: 1323: 1319: 1315: 1313: 1309: 1305: 1302: 1293: 1291: 1289: 1280: 1273: 1271: 1269: 1265: 1261: 1260:channelopathy 1257: 1252: 1250: 1246: 1242: 1238: 1234: 1229: 1227: 1224: 1220: 1216: 1213: 1205: 1203: 1201: 1196: 1194: 1190: 1186: 1184: 1183:demyelinating 1180: 1176: 1172: 1168: 1165: 1161: 1156: 1154: 1150: 1146: 1142: 1138: 1133: 1131: 1127: 1122: 1120: 1115: 1111: 1107: 1100: 1095: 1091: 1087: 1083: 1080: 1076: 1072: 1070: 1066: 1062: 1058: 1054: 1050: 1046: 1043: 1040: 1036: 1032: 1028: 1026: 1022: 1018: 1014: 1011: 1007: 1003: 1001: 997: 993: 990: 989: 988: 986: 978: 976: 974: 969: 967: 963: 953: 950: 946: 943: 939: 938: 934: 931: 928: 924: 920: 916: 912: 911: 907: 905: 902: 898: 897: 893: 890: 886: 882: 878: 875: 874:Area Postrema 872: 871: 867: 865: 861: 860: 855: 853: 850: 849: 845: 843:Core criteria 842: 841: 835: 831: 829: 825: 821: 818: 813: 811: 802: 795: 793: 791: 788: 784: 780: 776: 772: 768: 764: 759: 757: 753: 748: 746: 741: 737: 734: 731: 727: 721: 713: 711: 709: 705: 700: 696: 694: 690: 686: 682: 681:demyelination 678: 674: 670: 666: 662: 658: 654: 653:demyelination 650: 646: 641: 639: 635: 631: 626: 622: 620: 616: 612: 608: 604: 600: 596: 591: 589: 588:intrathecally 585: 581: 577: 576:area postrema 573: 569: 565: 561: 557: 552: 550: 546: 542: 538: 534: 530: 526: 525:cell membrane 522: 518: 514: 508: 500: 494: 487: 485: 483: 479: 474: 472: 468: 464: 459: 457: 451: 449: 445: 441: 437: 434: 430: 422: 420: 418: 414: 410: 406: 398: 396: 394: 387: 385: 378: 376: 374: 370: 366: 362: 358: 355:, as well as 354: 350: 346: 342: 338: 334: 333:area postrema 330: 323:Brain effects 322: 320: 318: 314: 310: 309:visual acuity 306: 302: 295:Optic effects 294: 292: 290: 286: 282: 274: 272: 270: 262: 257: 254: 253:water channel 250: 246: 242: 239: 235: 234: 233: 231: 227: 223: 219: 215: 211: 207: 198: 194: 191: 187: 183: 179: 175: 171: 167: 163: 159: 155: 151: 148: 146: 142: 139: 135: 132: 130: 126: 122: 120: 116: 112: 110: 106: 102: 98: 94: 90: 86: 82: 79: 77: 73: 70: 69:ophthalmology 66: 63: 61: 57: 54: 50: 46: 43: 39: 34: 19: 7484: 7460: 7449: 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