Autoimmune and demyelinating optic neuritis | Archivos de la Sociedad Española de Oftalmología (English Edition)

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"apellidos" => "Sanchez-Dalmau" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Oftalmología, Sección de Neuroftalmología y Estrabismos, Hospital Universitari Son Espases, Palma de Mallorca, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital Universitari de Bellvitge, Consultora de Neuroftalmología, L’Hospitalet de Llobregat, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Neurooftalmología, Institut Clínic d’Oftalmología (ICOF), Hospital Clínic, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neuritis ópticas desmielinizantes y autoinmunes" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 551 "Ancho" => 905 "Tamanyo" => 49893 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "MOGopathy with bilateral compromise ON and perineuritis." ] ] ] "textoCompleto" => "Definition<a class="elsevierStyleCrossRefs" href="#bib0005">1–3</a>The concept of optic neuritis (ON) encompasses the inflammatory processes of the optic nerve and is a clinical concept. It expresses as loss of vision, usually acute. When the intraocular portion (pre-laminar and/or laminar) is compromised, it is called papillitis because it occurs with papillary edema. If it involves only the retrolaminar portion it is called retrobulbar neuritis.Epidemiology<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a>The estimated annual incidence in our environment is five cases per 100,000 inhabitants,<a class="elsevierStyleCrossRef" href="#bib0020">4</a> although this figure varies according to different studies. The typical ON is unilateral and predominanlty affects females (75%) and young people between 15 and 45 years of age. ON is more prevalent in northern European countries and the USA (85%). Most are caused by multiple sclerosis (MS),<a class="elsevierStyleCrossRef" href="#bib0015">3</a> either in the context of established disease or as an isolated form of onset (isolated clinical syndrome).ON with atypical characteristics (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) is more prevalent in non-Caucasian populations. It has various causes and MS is not one of the main ones.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Physiopathology<a class="elsevierStyleCrossRefs" href="#bib0015">3,5</a>The optic nerve is formed by the axons of the retinal ganglion cells, which myelinize in the retrolaminar portion as they exit the lamina cribrosa. Myelin is provided by oligodendrocytes, which are affected in MS. In animal models it has been observed that the difference between papillitis and retrobulbar ON depends on the place of compromise, before or after the lamina cribrosa. In both cases there is an inflammatory infiltration of monocytes mediated by T-helper cells (Th). Although the response is mainly cellular, there may be a humoral component. This inflammation is accompanied by areas of demyelination (plaques) with associated axonal degeneration. Myelin is phagocytized by macrocytes and activated microglia, and a scar reaction appears. Astrocytes participate in the appearance of fibrous tissue in plaques that interrupt the nerve impulse. After the inflammatory episode, a usually incomplete remyelinization occurs.Natural history<a class="elsevierStyleCrossRef" href="#bib0030">6</a>The typical ON starts with vision loss that worsens in about 10–15 days. A rapid visual recovery appears after two to three weeks, and is usually almost complete after about five weeks. There may be improvement up to a year after the onset of the condition. Approximately 90% of patients with typical optic neuritis recover visual function after the first episode on the basis of natural, untreated evolution. The visual prognosis is generally good. However, very low initial visual acuity (no light perception) is a factor in poor long-term prognosis. Prolongation of the symptomatology or no improvement over time should alert to the possibility of another process.ClinicThe condition may be acute, subclinical (asymptomatic) or chronic. The acute form is the most common.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>SymptomsUnilateral compromise with progressive visual loss in hours or days, accompanied by ocular or orbital pain that precedes in a couple of days or coincides with visual loss in up to 92% of cases. The pain is retroocular, of mild intensity and worsens with globe adduction and elevation. Chromatic vision is significantly compromised. Positive visual phenomena (photopsies) have been described as flashes or spots such as snowflakes, and even frontal headaches.Other typical, but not specific, associated phenomena are<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Uhthoff’s Phenomenon: worsening or temporary visual blurring triggered by heat, stress, or exercise. It appears in the chronic phase of the disease.</li><li class="elsevierStyleListItem" id="lsti0010">•Pulfrich effect: abnormal stereoscopic perception of moving objects due to asymmetric conduction speed between the compromised and healthy optic nerve.</li></ul>Exploratory findings<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">•Relative Afferent Pupil Defect (RAPD) in the affected eye, which can be quantified with neutral density filters. In cases of bilateral neuritis it may not be very evident.</li><li class="elsevierStyleListItem" id="lsti0020">•Acquired dyschromatopsia. Color vision is usually very altered even in cases of relative preservation of visual acuity at the onset of neuritis.</li><li class="elsevierStyleListItem" id="lsti0025">•Altered contrast sensitivity (Pelli-Robson films).</li><li class="elsevierStyleListItem" id="lsti0030">•Highly variable visual field defects<a class="elsevierStyleCrossRef" href="#bib0035">7</a>:<ul class="elsevierStyleList" id="lis0011"><li class="elsevierStyleListItem" id="lsti0035">•Fuzzy defect: 48%</li><li class="elsevierStyleListItem" id="lsti0040">•Localised defect (altitudinal or archaic): 20%</li><li class="elsevierStyleListItem" id="lsti0045">•Central or centrocecal scotoma: 8%</li><li class="elsevierStyleListItem" id="lsti0050">•Other defects or scotomas: 24%.</li></ul></li><li class="elsevierStyleListItem" id="lsti0055">•Fundus: the optic disc is normal at the onset of retrobulbar neuritis or has diffuse effacement with or without bleeding in papillitis (20–40%). Papillary pallor indicates past permanent damage. This finding is not useful to establish the diagnosis of optic neuritis in case of a new acute visual loss.</li><li class="elsevierStyleListItem" id="lsti0060">•Increased thickness of the circumpapillary (CP) retinal nerve fiber layer (RNFL) in acute phase optical coherence tomography (OCT) in up to 50% of cases. Subsequently, a significant loss of nerve fibres is established during the first 6 months of follow-up.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> This mainly affects the upper and lower quadrants and is more prominent in the atypical ON.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Atrophy and thickness loss in RNFL-CP has been documented in demyelinating diseases even without episodes of symptomatic neuritis, and may respond to subclinical activity or transynaptic degeneration of the optic pathway.<a class="elsevierStyleCrossRef" href="#bib0045">9</a></li></ul>Diagnosis<a class="elsevierStyleCrossRefs" href="#bib0005">1,3</a>Diagnosis is based on the above described clinical presentation and exploratory findings. The typical pathocrony of ON of demyelinating etiology is highlighted: acute onset, progressive worsening between 7–10 days, a period of functional stability (of approximately the same duration as the previous one), followed by a period of recovery, of variable duration and amount. The possibility of non-demyelinating etiologies should be considered if there are atypical features such as simultaneous and bilateral involvement, if the patient is outside the age range, if the pathocronia does not follow a typical pattern, etc. The main clinical differences between typical and atypical typical ON are listed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Further studies<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Co-management between the ophthalmologist and the neurologist is recommended.Upon initial suspicion of typical or atypical neuritis, a complete physical examination by a neurologist and an analysis (hemogram, ionogram, biochemistry, proteinogram, globular sedimentation rate (ESR), C-reactive protein (CRP), as well as magnetic resonance imaging (MRI) are required.Examination of the cerebrospinal fluid (CSF) for IgG oligoclonal bands (OCB) may be helpful, although this should be postponed if the patient has been treated with steroids in the acute phase.<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0065">•The initial analysis has a low diagnostic yield in typical neuritis, while in atypical ones it is useful to direct the research according to the patient profile: serologies to rule out infectious causes (syphilis, Herpesviridae family, intracellular bacteria [Bartonella, Coxiella, Rickettsia, Toxoplasma], Borrelia, tuberculosis, hepatitis B and C, HIV and West Nile virus) and autoimmunity profile (ANA, ECA, p-ANCA and c-ANCA), as well as the determination of specific antibodies (IgG-AQP4, Anti-MOG, Anti-CRMP5, Anti-GFAP3).</li><li class="elsevierStyleListItem" id="lsti0070">•Brain and orbital MRI with gadolinium and fat suppression, preferably 1−2 mm thin sections. In the acute phase, (first 4 weeks) it is characteristic to enhance the optic nerve in T1 with contrast and increase the signal in STIR sequences. In the chronic phase, thinning of the nerve with hypersignal in T2 appears in relation to the degree of visual impairment. If neuritis is associated with MS, there can be lesions in the periventricular white matter, chiasm, brain stem and cerebellum. Active lesions capture gadolinium.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> The presence of demyelinating lesions on initial MRI is a risk marker for the development of MS.<a class="elsevierStyleCrossRef" href="#bib0050">10</a></li><li class="elsevierStyleListItem" id="lsti0075">•In atypical neuritis, more extensive, bilateral involvement may occur, predominantly in the posterior of the optic nerve. It may also involve the chiasm and optic bands, or even predominantly affect the sheath of the optic nerve as in perineuritis<a class="elsevierStyleCrossRefs" href="#bib0055">11,12</a> or in neuritis associated with anti-MOG.<a class="elsevierStyleCrossRef" href="#bib0065">13</a></li><li class="elsevierStyleListItem" id="lsti0080">•There is a reduction in the amplitude of the P100 wave and an increase in its latency in acute phase PEV. Normalisation of the P100 amplitude occurs in the visual recovery phase, although increased latency persists.</li><li class="elsevierStyleListItem" id="lsti0085">•The presence of OCB and the elevation of CSF immunoglobulin G suggest the presence of a demyelinating disease according to McDonald's criteria.<a class="elsevierStyleCrossRef" href="#bib0070">14</a></li></ul>Treatment<a class="elsevierStyleCrossRef" href="#bib0005">1</a>It is prescribed individually according to the depth of the initial visual loss and its evolution during the first week. Treatment with megadose steroids is ideally initiated after the imaging test, which should be obtained as soon as possible. The multicenter clinical trial ‘Optic Neuritis Treatment Trial’ (ONTT) demonstrated that the administration of high-dose intravenous steroids accelerated visual recovery in patients with typical ON, although it did not modify the final visual prognosis.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> The initial trend was to treat with intravenous methylprednisolone 250 mg/6 h for 3 days. It is currently accepted to administer 1 g/24 h E.V. for 3 days on an outpatient basis. The ONTT study also showed that the use of oral steroids could increase the rate of new episodes of ON.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> If there is a recurrence of visual loss on stopping or lowering the dose, the study needs to be expanded in collaboration with an internal medicine specialist.In contrast to the ONTT result, a Cochrane review established that steroid treatment did not improve visual acuity, contrast sensitivity or visual field in the long term.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Likewise, two studies studied the effect of intravenous megadose of methylprednisolone versus oral steroids at bioequivalent doses, 1000 mg<a class="elsevierStyleCrossRef" href="#bib0085">17</a> or 1250 mg.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Both studies yielded similar results; therefore, it was concluded that oral megadosis did not differ significantly from endovenous megadosis in the treatment of acute optic neuritis. The follow-up of 28 days and 6 months respectively, poses some limitations on the validity of the latter studies.Recently, a new study of the role of steroids has been proposed, taking into account the variables of time of evolution, dose and associated antibodies.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>If ON occurs in the context of MS defined by McDonald criteria, the CHAMPS or ETOMS studies<a class="elsevierStyleCrossRefs" href="#bib0100">20,21</a> have established the usefulness of immunomodulatory treatment.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Update on the classification of autoimmune ONBeyond the classification between typical or atypical neuritis by the clinical characteristics defined in the ONTT study, alternatives have been proposed. Petzold’s classification in 2014 was eminently clinical (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>) and only took into account the presence of IgG-AQP4 antibodies.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> The discovery of new antibodies has produced a revolution with new classification proposals.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Multiple sclerosis<a class="elsevierStyleCrossRefs" href="#bib0005">1,5,7</a>MS is a chronic and disabling disease that affects young adults. It is 3–4 times more common in women than in men. ON is a typical form of compromise, it may be the first manifestation and/or reappear throughout the course of the disease.MS etiology is multifactorial and not completely understood. There is a genetic predisposition, erroneous responses to unidentified environmental antigens and an autoimmune response mediated by collaborating T-lymphocytes (Lth). These access the central nervous system (CNS) and cause a cellular and humoral inflammatory reaction that destroys both myelin (focal lesions known as plaques) and the axonal tissue they cover.The diagnosis of MS is established through a combination of clinical, neuroimaging and laboratory criteria that have been unified and agreed upon. These are McDonald’s criteria and are not treatment guidelines. Their purpose is to agree on the procedures to be performed for the correct diagnosis of MS and they are applied primarily to patients with a clinical isolated syndrome (CIS). The International Advisory Committee on Clinical Trials in MS last reviewed and updated the criteria in 2017. It also discussed misdiagnosis, differential diagnosis and the appropriate application of these criteria with particular emphasis on diagnosis in various populations and in patients with atypical presentations.<a class="elsevierStyleCrossRef" href="#bib0070">14</a>Neuromyelitis optica (NMO)<a class="elsevierStyleCrossRefs" href="#bib0125">25,26</a>NMO (Devic’s disease) had been considered a more aggressive form of MS with preferential involvement of the optic nerve and spinal cord. The detection of antiaquaporin-4 antibodies (AQP4) in 2005 produced a new diagnostic approach. It is now accepted that NMO is a demyelinating disease different from MS. IgG-AQP4 are antibodies to the AQP4 membrane protein present in astrocytes, so NMO is proposed as an astrocytopathy.It is more frequent in Asian and African populations, and affects children and young people, especially women. Bilateral or simultaneous involvement is more indicative of NMO than MS. It can also affect the optic chiasm and bands and the Müller cells of the retina.<a class="elsevierStyleCrossRefs" href="#bib0135">27,28</a> It causes significant visual field defects, with high contrast vision less than 20/200. It is often accompanied by transverse myelitis with paraparesis. In 30% there are other autoimmune disorders, mainly systemic lupus erythematosus (SLE) and Sjögren's disease and, less frequently, a paraneoplastic disorder.<a class="elsevierStyleCrossRef" href="#bib0145">29</a>The diagnosis is based on the latest Wingerchuk criteria and depends on the presence of IgG-AQP4. If antibodies are detected, only neuritis or any other “nuclear” manifestation is required to establish the diagnosis of NMO. If the antibodies are negative, the criteria are stricter: the presence of two or more typical pictures with their characteristic lesions is required on brain and spinal cord MRI<a class="elsevierStyleCrossRef" href="#bib0130">26</a> (<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>The initial treatment is with corticosteroids and plasmapheresis, sometimes with the addition of immunosuppressants such as rituximab. In the maintenance phase azathioprine, mycophenolate or rituximab can be used. Immunomodulators prescribed in MS are contraindicated in NMO because they worsen its progression. Accordingly, it is vital to differentiate NMO from MS. Serum anti-AQP4 levels are monitored to control disease activity and the need for treatment, especially rituximab infusions. Anti-QP4+ neuritis often has a poorer prognosis because of its greater severity and poorer visual recovery compared to MS and other etiologies, even with an equal degree of damage to the ganglion cell layer in OCT.<a class="elsevierStyleCrossRef" href="#bib0150">30</a>Chronic recurrent optic neuritis (CRION)In 2003 a clinical series on recurrent ON of presumed autoimmune etiology without clinical or radiological criteria for MS was published under this acronym. CRION was more frequent in individuals of African descent and in women. It occurred with uni or bilateral neuritis associated with pain, in some cases accompanied by uveitis. Systemic study of these patients ruled out granulomatous diseases and revealed the presence of anti-nuclear antibodies (ANA) in one case. Acute phase treatment with intravenous steroids had to be maintained orally for a period of time due to recurrence or relapse, which was one of its diagnostic features.<a class="elsevierStyleCrossRefs" href="#bib0015">3,11</a> In the long term, if the maintenance dose of steroids was very high, an immunosuppressant was associated.Subsequently, the presence of myelin oligocendrocyte autoantibodies (anti-MOG) was detected in some patients with this clinical profile. It is now accepted that some CRION-type neuritis would be part of the spectrum of anti-MOG diseases.<a class="elsevierStyleCrossRef" href="#bib0155">31</a>Optic neuritis with anti-MOG or MOGopathy antibodies<a class="elsevierStyleCrossRefs" href="#bib0160">32–35</a>The detection of anti-MOG antibodies in several syndromes with CNS demyelination has produced a conceptual change. Patients with anti-MOG antibodies may develop monophasic (ADEM-acute disseminated encephalomyelitis, seronegative NMO, isolated neuritis) or multiphasic (CRION, seronegative optic neuromyelitis spectrum diseases) CNS demyelinating episodes. These would constitute the disorders with anti-MOG antibodies or mogopathies.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> The myelin glycoprotein of oligodendrocytes is a membrane protein that could be involved in the destruction or phagocytosis of myelin through macrophages.<a class="elsevierStyleCrossRef" href="#bib0170">34</a>There are two peak ages of presentation, although any age can be compromised. The first peak appears in childhood with a predominance of ADEM. The second appears between the third and fourth decade of life where isolated ON and other pictures of the NMO spectrum are more frequent.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> The clinical presentation may be indistinguishable between NMO and MS in some cases.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> The predominance of women over men is not demonstrated and there is conflicting data. It is estimated that it would be responsible for about 14% of NMO.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> For the moment, diagnostic criteria have not been agreed upon. It is speculated that anti-MOG disorders would be responsible for a large part of CRION-type neuritis, as well as a very frequent cause of ADEM and other demyelinating pathologies such as MS in children.The visual impairment may manifest itself as an episode of either isolated or recurrent ON, or recurrent after the completion of the initial steroid treatment. Neuritis is retrobulbar or papillitis.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> MRI shows frequent bilateral involvement of the optic nerve with more extensive lesions than in MS and BMN. They predominantly affect the orbital portion and rarely the chiasm and optic bands. Other frequently affected areas are the supratentorial deep white substance and the spinal cord. The patterns vary according to age of presentation and are different from MS and BMN<a class="elsevierStyleCrossRefs" href="#bib0165">33,38</a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>It is necessary to select the cases that are tributaries of anti-MOG serum antibody determinations to avoid misdiagnosis. In addition, is necessary to conduct a study in validated cell cultures.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> CSF determinations are not diagnostic, although according to some authors they may be sufficient.<a class="elsevierStyleCrossRef" href="#bib0195">39</a> Exceptionally, they can coexist with other antibodies such as anti-AQP4 and even OCB. If there are no new episodes, anti-MOG antibodies may become negative, reappearing with each recurrence.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>Treatment is based on high-dose steroids and plasmapheresis in the acute phase. Drugs with CD20 targets and immunosuppressants such as rituximab, ofatumumab, azathioprine, corticoids<a class="elsevierStyleCrossRef" href="#bib0165">33</a> or tocilizumab<a class="elsevierStyleCrossRef" href="#bib0200">40</a> have been proposed for the prevention of relapses. Between 50–80% of patients usually develop sequelae. Early treatment of myelitis, a predictor of the severity of sequelae, is important for prevention<a class="elsevierStyleCrossRef" href="#bib0165">33</a> (<a class="elsevierStyleCrossRefs" href="#tbl0035">Tables 7 and 8</a>).<elsevierMultimedia ident="tbl0035"></elsevierMultimedia><elsevierMultimedia ident="tbl0040"></elsevierMultimedia>Final considerationsCriteria for the diagnosis and treatment of MS and NMO require frequent and constant updates. In contrast, said criteria still need to be validated and agreed upon for MOGopathies. Clinical classifications are progressively replaced by those based on neuroimmunology and etiopathogenesis. The new antibodies (anti-MOG, anti-AQP4) are being defined with some clinical profiles associated with ON. In other cases such as GlyR (glycine receptor) their pathological significance is still unknown.<a class="elsevierStyleCrossRef" href="#bib0245">49</a>High resolution 3 Tesla MRI and new generation OCT have allowed a more comprehensive characterization of lesions along the visual pathway, allowing the discovery of types of lesional mechanisms that remained unknown.Finally, new treatments are available for MS (ocrelizumab, alemtuzumab, siponimod…)<a class="elsevierStyleCrossRef" href="#bib0250">50</a> and for NMO (inebilizumab, satralizumab, eculizumab…),<a class="elsevierStyleCrossRef" href="#bib0255">51</a> as well as new specific guidelines for the new entities discovered. A new approach to neuroprotection and re-myelinization may change the current paradigm with drugs such as opicinumab, high-dose biotin, trophic factors such as EPO and antioxidants. Ophthalmologists handling this pathology must become familiar with these treatments and their specific possible side effects.Conflict of interestNo conflict of interests was declared by the authors." "textoCompletoSecciones" => array:1 [ "secciones" => array:20 [ 0 => array:3 [ "identificador" => "xres1371328" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1260314" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1371327" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1260315" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Definition" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Epidemiology" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Physiopathology" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Natural history" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Clinic" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Symptoms" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Exploratory findings" ] ] ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Diagnosis" ] 10 => array:2 [ "identificador" => "sec0045" "titulo" => "Further studies" ] 11 => array:2 [ "identificador" => "sec0050" "titulo" => "Treatment" ] 12 => array:2 [ "identificador" => "sec0055" "titulo" => "Update on the classification of autoimmune ON" ] 13 => array:2 [ "identificador" => "sec0060" "titulo" => "Multiple sclerosis" ] 14 => array:2 [ "identificador" => "sec0065" "titulo" => "Neuromyelitis optica (NMO)" ] 15 => array:2 [ "identificador" => "sec0070" "titulo" => "Chronic recurrent optic neuritis (CRION)" ] 16 => array:3 [ "identificador" => "sec0075" "titulo" => "Optic neuritis with anti-MOG or MOGopathy antibodies" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0080" "titulo" => "Final considerations" ] ] ] 17 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 18 => array:2 [ "identificador" => "xack476238" "titulo" => "Acknowledgements" ] 19 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-03-30" "fechaAceptado" => "2020-05-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1260314" "palabras" => array:6 [ 0 => "Optic neuritis" 1 => "Multiple sclerosis (MS)" 2 => "Neuromyelitis optica (NMO)" 3 => "MOG-opathy" 4 => "CRION" 5 => "Anti-MOG antibody" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1260315" "palabras" => array:6 [ 0 => "Neuritis ópticas" 1 => "Esclerosis múltiple (MS)" 2 => "Neuromielitis óptica (NMO)" 3 => "MOGopatía" 4 => "CRION" 5 => "Anticuerpos anti-MOG" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The knowledge on demyelinating and autoimmune optic neuropathies has experienced a revolution the last decade since the discovery of anti-aquaporin 4 antibody. Improvements in diagnostic techniques, and the finding of new targets, along with advances in neuroimmunology have led to the detection of antibodies related to demyelinating diseases. A review is presented on the classical and new concepts in optic neuritis. The debate on the classification of demyelinating and autoimmune optic neuritis is presented. Furthermore, the updated diagnostic criteria in multiple sclerosis and neuro-myelitis optics are described. Finally, the latest insights into Myelin Oligodendrocyte Glycoprotein (MOG) disorders and chronic-recurring optic neuropathies (CRION) are highlited." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El conocimiento sobre las neuropatías ópticas desmielinizantes y autoinmunes ha experimentado una revolución en la útima década tras el descubrimiento de los anticuerpos anti-acuaporina 4 (AQP4). Las mejoras en las técnicas diagnósticas, el descubrimiento de nuevas dianas y el avance de la neuro-inmunología ha permitido la detección de anticuerpos asociados a las enfermedades desmielinizantes. Se presenta una revisión de los conceptos clásicos y nuevos de las neuritis ópticas desmielinizantes y autoimmunes. Se describe el debate en las constantes reformulaciones de su clasificación. Asimismo se actualizan los criterios diagnósticos de la esclerosis múltiple y de la neuromielitis óptica. Finalmente, se presentan los nuevos conceptos sobre las MOG-opatías y las neuropatías opticas inflamatorias crónico-recurrentes (CRION)." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: García Ortega A, Montañez Campos FJ, Muñoz S, Sanchez-Dalmau B. Neuritis ópticas desmielinizantes y autoinmunes. Arch Soc Esp Oftalmol. 2020. https://doi.org/10.1016/j.oftal.2020.05.010" ] ] "multimedia" => array:13 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 736 "Ancho" => 905 "Tamanyo" => 68291 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Optic Neuromyelitis: Axial flair MRI with post-optic chiasm enhancement. The mark that indicated the lesion has been removed to facilitate its identification." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 551 "Ancho" => 905 "Tamanyo" => 49893 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "MOGopathy with bilateral compromise ON and perineuritis." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Optic neuritis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Typical \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Atypical \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Young adult, > female. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Under 12 and over 50 years old. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ancestry \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Northern Europe. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">African, Asian, Native American \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lateralism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unilateral. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Simultaneous bilateral or rapid sequential. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2354939.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary of differential epidemiological characteristics of typical and atypical ON.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Optic neuritis \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Typical \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Atypical \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lateralism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unilateral. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Simultaneous bilateral or rapid sequential. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Periocular, worsens with eye movements. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Periocular. Variable in intensity from severe to painless Persists beyond 2 weeks. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vision \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate unilateral loss followed by spontaneous recovery. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe loss (worse than 0.1) without improvement, progressive visual loss of more than 2 weeks evolution. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fundus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Normal, or mild papilla edema. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prominent papilla edema with over 1 month of evolution. It can be associated to neuroretinitis and hemorrhages. Vitritis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Previous episodes. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Family history. History of neoplasms. Erratic or relapsed response after withdrawal of steroids. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Good response to steroids. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2354940.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary of differential clinical characteristics of typical and atypical ON.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>" ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">After a typical ON episode, 38 per cent of patients will develop MS within 10 years. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First episode of typical ON without other demyelinating alterations in MRI, 22% will develop MS at 10 years. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">First episode of typical ON associated with demyelinating lesions on MRI, the risk of MS is 56% at 10 years. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In established MS, typical ON appears in 50% at some point in its evolution. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2354936.png" ] ] ] ] "descripcion" => array:1 [ "en" => "ON conversion risk in MS.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>" ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SION \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Simple isolated ON. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RION \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recurring ON. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CRION \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic recurrent ON. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NMO-ON \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neuromyelitis optica. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MSON \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ON associated with MS. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">UCON \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Unclassified ON. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2354938.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Petzold Classification Autoimmune Optical Neuropathies 2014.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>" ] ] 6 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0035" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple sclerosis: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative anti-AQP4 antibody \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative anti-MOG antibody \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Spectrum disorders of optical neuromyelitis: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive anti-QA4 antibody \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative anti-MOG antibody \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNS demyelination associated with anti-MOG (MOGopathies): \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative anti-AQP4 antibody \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive anti-Mog antibody. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2354937.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Neuroimmunological classification of demyelinating syndromes in the central nervous system." ] ] 7 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0040" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diagnosis of NMO with IgG-AQP4 + \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 + nuclear clinic. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IgG-AQP4+ with best available method. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Exclusion of other diagnoses<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a>. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diagnosis of NMO without IgG-AQP4 + or unknown status \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 + nuclear clinic resulting from one or more episodes fulfilling: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">At least one episode of ON, extensive longitudinal transverse myelitis, or post-traumatic area syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dissemination in space (2 + nuclear lesions) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IgG-AQP4- with best available method \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Exclusion of other diagnoses. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nuclear panels \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ON. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute myelitis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post-traumatic stress syndrome. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mesencephalic syndrome. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Symptomatic narcolepsy or acute diencephalic syndrome with characteristic MRI lesions. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Symptomatic brain syndrome with characteristic MRI lesions. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Additional MRI requirements for NMO diagnosis IgG-AQP4- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ON with normal MRI or non-specific white substance lesions. Hyperintensive lesions in T2 or enhancement with gadolinium in T1 extending over > 1/2 of the ON pathway or chiasmatic involvement \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myelitis: spinal cord MRI with lesions affecting 3 or more contiguous vertebral segments (extensive longitudinal transverse myelitis). OR 3 or + contiguous segments of focal spinal atrophy with a previous history of myelitis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post-traumatic area syndrome: Bulbar dorsal or post-traumatic area injury on brain MRI \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mesencephalic syndrome: With periependymal lesions. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2354933.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "Other diagnoses: Sarcoidosis, paraneoplastic neoplasm/syndrome, vascular pathology, infection." ] ] ] "descripcion" => array:1 [ "en" => "International diagnostic criteria for NMO 201526." ] ] 8 => array:8 [ "identificador" => "tbl0035" "etiqueta" => "Table 7" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0045" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ON as an isolated clinical syndrome</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinic \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MS \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NMO \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MOGopathies \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Very often. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Very frequent \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Visual impairment. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Variable. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Severe. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Papilla edema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absent or not evident. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Absent or not evident. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequent and marked. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bilateral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rare simultaneous compromise. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequent. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequent. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Simultaneous compromise \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rare \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myelitis, post-traumatic stress syndrome. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ADEM. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Progressive. More frequent over eye with previous ON<a class="elsevierStyleCrossRef" href="#bib0205">41</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recurring. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Single-phase or recurrent. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Laboratory</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequently Anti-AQP4 + \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-MOG + \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CSF: \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OCB+, mild-moderate pleocytosis. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Possibility OCB +, moderate-intense pleocytosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Possibility OCB +, variable pleocytosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Response to treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Corticosteroids only speed up recovery (controversial). \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Poor, requires immediate treatment. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Good, requires immediate treatment, often corticoid-dependent. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Visual forecast \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Good. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bad. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Good. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Image</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Temporal RNFL-CP and GLC/IPL compromise \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Widespread and severe alteration of RNFL-CP and GLC/IPL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Widespread involvement of RNFL-CP. Less severe CLM/IPL involvement comparable to MS. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Affecting outer layers by direct damage to Müller cells. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Brain (MRI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Periventricular lesions in white substance. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hemispheric lesions in white substance, dorsal periepidural bulb. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lesions deep white substance and midbrain. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Optic nerve (MR)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><elsevierMultimedia ident="202008070707449361"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MS: unilateral compromise, usually retrobulbar MRI shows enhancement at T2, and gadolinium capture at T1. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><elsevierMultimedia ident="202008070707449362"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NMO: may be more bilaterally affected. Chiasmatic and even ribbon involvement is very suggestive of NMO AQ4+. MRI at T1 with gadolinium shows uptake of posterior half of both optic nerves and chiasm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><elsevierMultimedia ident="202008070707449363"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MOGopathies: There may be uni or bilateral involvement, often involving the optic nerve sheath, and perineural tissue. This is quite characteristic. MRI in T1 with gadolinium shows enhancement of both nerves and their perineural tissue. In MOG+ cases, it usually affects a greater length of the nerve than in MS-associated neuritis. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2354935.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main clinical differential characteristics of ON by MS, NMO and MOGopathies.<a class="elsevierStyleCrossRefs" href="#bib0120">24,33,42,43</a>GLC ganglion cell layer IPL Internal plexiform layer." ] ] 9 => array:8 [ "identificador" => "tbl0040" "etiqueta" => "Table 8" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0050" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diffuse myeloclastic sclerosis (Schilder’s Disease)<a class="elsevierStyleCrossRef" href="#bib0220">44</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rare and aggressive of controversial etiology. Preferential compromise of children and young people. It produces progressive neurological deterioration with ON, chiasmitis, papillitis and involvement of cortical association areas. In MRI, large bihemispheric lesions with considerable inflammatory component. It is monophasic and partially responds to treatment with corticoids. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute Disseminated Encephalomyelitis (ADEM)<a class="elsevierStyleCrossRefs" href="#bib0195">39,45</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mostly affects children, slight preference for males. Appears after previous infectious episode or rarely a vaccination. Multifocal and monophasic clinic. Demyelinating lesions exceeding 2 mm in both optical nerves up to 15% of cases in ADEMON subtype. Important association to anti-MOG antibodies (33−66% cases). Without optic neuritis all published cases are MOG + \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post-vaccine optic neuritis<a class="elsevierStyleCrossRefs" href="#bib0005">1,46</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Isolated ON, starting between days and up to 3 months after exposure to viral and bacterial antigens, especially the flu vaccine. Bilateral (80%), painful (60%) and with papilla edema (80%). Good response to steroids (megadose). In some cases it is necessary to prolong the steroids orally if complete visual recovery is not achieved. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sarcoidosis-associated optic neuritis<a class="elsevierStyleCrossRef" href="#bib0235">47</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Favorite population: women of African descent with papillitis or retrobulbar neuritis. Inflammation is granulomatous. Intraocular inflammation (uveitis) may be accompanied by optic neuromyelitis-like (neuro-sarcoidosis). Excellent response to steroids. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post-infectious autoimmune optic neuritis<a class="elsevierStyleCrossRef" href="#bib0025">5</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Associated with viral and, to a lesser extent, bacterial infections, debuts between 1 and 3 weeks after infectious clinic. Acute, bilateral compromise with papilla edema, or neuroretinitis in children and young adults. Normal neuroimaging despite CSF pleocytosis. Excellent visual prognosis although visual defects and slight residual papillary pallor persist. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Secondary Optic Neuritis</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systemic lupus erythematosus, ANCA granulomatosis, Whipple’s disease, Sjögren’s disease and other systemic vasculopathies and inflammatory diseases can occur with ON. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Numerous studies link them to the presence of specific antibodies, especially IgG-AQP4.<a class="elsevierStyleCrossRef" href="#bib0240">48</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2354934.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Other diseases with optic neuritis in the context of autoimmune demyelination.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>" ] ] 10 => array:5 [ "identificador" => "202008070707449361" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 520 "Ancho" => 750 "Tamanyo" => 25865 ] ] ] 11 => array:5 [ "identificador" => "202008070707449362" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx2.jpeg" "Alto" => 579 "Ancho" => 750 "Tamanyo" => 29135 ] ] ] 12 => array:5 [ "identificador" => "202008070707449363" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx3.jpeg" "Alto" => 568 "Ancho" => 750 "Tamanyo" => 29183 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:51 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neuritis ópticas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.J. 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Review

Autoimmune and demyelinating optic neuritis

Neuritis ópticas desmielinizantes y autoinmunes

A. García Ortegaa,

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albertogarciaortega83@gmail.com

Corresponding author.

, F.J. Montañez Camposa, S. Muñozb, B. Sanchez-Dalmauc

a Servicio de Oftalmología, Sección de Neuroftalmología y Estrabismos, Hospital Universitari Son Espases, Palma de Mallorca, Spain

b Hospital Universitari de Bellvitge, Consultora de Neuroftalmología, L’Hospitalet de Llobregat, Spain

c Unidad de Neurooftalmología, Institut Clínic d’Oftalmología (ICOF), Hospital Clínic, Barcelona, Spain

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which myelinize in the retrolaminar portion as they exit the <span class="elsevierStyleItalic">lamina cribrosa</span>&#46; Myelin is provided by oligodendrocytes&#44; which are affected in MS&#46; In animal models it has been observed that the difference between papillitis and retrobulbar ON depends on the place of compromise&#44; before or after the <span class="elsevierStyleItalic">lamina cribrosa</span>&#46; In both cases there is an inflammatory infiltration of monocytes mediated by T-helper cells &#40;Th&#41;&#46; Although the response is mainly cellular&#44; there may be a humoral component&#46; This inflammation is accompanied by areas of demyelination &#40;plaques&#41; with associated axonal degeneration&#46; Myelin is phagocytized by macrocytes and activated microglia&#44; and a scar reaction appears&#46; Astrocytes participate in the appearance of fibrous tissue in plaques that interrupt the nerve impulse&#46; After the inflammatory episode&#44; a usually incomplete remyelinization occurs&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Natural history<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></span><p id="par0025" class="elsevierStylePara elsevierViewall">The typical ON starts with vision loss that worsens in about 10&#8211;15 days&#46; A rapid visual recovery appears after two to three weeks&#44; and is usually almost complete after about five weeks&#46; There may be improvement up to a year after the onset of the condition&#46; Approximately 90&#37; of patients with typical optic neuritis recover visual function after the first episode on the basis of natural&#44; untreated evolution&#46; The visual prognosis is generally good&#46; However&#44; very low initial visual acuity &#40;no light perception&#41; is a factor in poor long-term prognosis&#46; Prolongation of the symptomatology or no improvement over time should alert to the possibility of another process&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Clinic</span><p id="par0030" class="elsevierStylePara elsevierViewall">The condition may be acute&#44; subclinical &#40;asymptomatic&#41; or chronic&#46; The acute form is the most common&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Symptoms</span><p id="par0035" class="elsevierStylePara elsevierViewall">Unilateral compromise with progressive <span class="elsevierStyleBold">visual loss</span> in hours or days&#44; accompanied by <span class="elsevierStyleBold">ocular or orbital pain</span> that precedes in a couple of days or coincides with visual loss in up to 92&#37; of cases&#46; The pain is retroocular&#44; of mild intensity and worsens with globe adduction and elevation&#46; Chromatic vision is significantly compromised&#46; Positive visual phenomena &#40;photopsies&#41; have been described as flashes or spots such as snowflakes&#44; and even frontal headaches&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Other typical&#44; but not specific&#44; associated phenomena are<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Uhthoff&#8217;s Phenomenon</span>&#58; worsening or temporary visual blurring triggered by heat&#44; stress&#44; or exercise&#46; It appears in the chronic phase of the disease&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleUnderline">Pulfrich effect</span>&#58; abnormal stereoscopic perception of moving objects due to asymmetric conduction speed between the compromised and healthy optic nerve&#46;</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Exploratory findings</span><p id="par0055" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Relative Afferent Pupil Defect &#40;RAPD&#41; in the affected eye&#44; which can be quantified with neutral density filters&#46; In cases of bilateral neuritis it may not be very evident&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Acquired dyschromatopsia&#46; Color vision is usually very altered even in cases of relative preservation of visual acuity at the onset of neuritis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Altered contrast sensitivity &#40;Pelli-Robson films&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Highly variable visual field defects<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#58;<ul class="elsevierStyleList" id="lis0011"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Fuzzy defect&#58; 48&#37;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Localised defect &#40;altitudinal or archaic&#41;&#58; 20&#37;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Central or centrocecal scotoma&#58; 8&#37;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Other defects or scotomas&#58; 24&#37;&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Fundus&#58; the optic disc is normal at the onset of retrobulbar neuritis or has diffuse effacement with or without bleeding in papillitis &#40;20&#8211;40&#37;&#41;&#46; Papillary pallor indicates past permanent damage&#46; This finding is not useful to establish the diagnosis of optic neuritis in case of a new acute visual loss&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Increased thickness of the circumpapillary &#40;CP&#41; retinal nerve fiber layer &#40;RNFL&#41; in acute phase optical coherence tomography &#40;OCT&#41; in up to 50&#37; of cases&#46; Subsequently&#44; a significant loss of nerve fibres is established during the first 6 months of follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> This mainly affects the upper and lower quadrants and is more prominent in the atypical ON&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Atrophy and thickness loss in RNFL-CP has been documented in demyelinating diseases even without episodes of symptomatic neuritis&#44; and may respond to subclinical activity or transynaptic degeneration of the optic pathway&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p></li></ul></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Diagnosis<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a></span><p id="par0110" class="elsevierStylePara elsevierViewall">Diagnosis is based on the above described clinical presentation and exploratory findings&#46; The typical pathocrony of ON of demyelinating etiology is highlighted&#58; acute onset&#44; progressive worsening between 7&#8211;10 days&#44; a period of functional stability &#40;of approximately the same duration as the previous one&#41;&#44; followed by a period of recovery&#44; of variable duration and amount&#46; The possibility of non-demyelinating etiologies should be considered if there are atypical features such as simultaneous and bilateral involvement&#44; if the patient is outside the age range&#44; if the pathocronia does not follow a typical pattern&#44; etc&#46; The main clinical differences between typical and atypical typical ON are listed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Further studies<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></span><p id="par0115" class="elsevierStylePara elsevierViewall">Co-management between the ophthalmologist and the neurologist is recommended&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Upon initial suspicion of typical or atypical neuritis&#44; a complete physical examination by a neurologist and an analysis &#40;hemogram&#44; ionogram&#44; biochemistry&#44; proteinogram&#44; globular sedimentation rate &#40;ESR&#41;&#44; C-reactive protein &#40;CRP&#41;&#44; as well as magnetic resonance imaging &#40;MRI&#41; are required&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Examination of the cerebrospinal fluid &#40;CSF&#41; for IgG oligoclonal bands &#40;OCB&#41; may be helpful&#44; although this should be postponed if the patient has been treated with steroids in the acute phase&#46;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">The initial analysis has a low diagnostic yield in typical neuritis&#44; while in atypical ones it is useful to direct the research according to the patient profile&#58; serologies to rule out infectious causes &#40;syphilis&#44; <span class="elsevierStyleItalic">Herpesviridae</span> family&#44; intracellular bacteria &#91;<span class="elsevierStyleItalic">Bartonella&#44; Coxiella&#44; Rickettsia&#44; Toxoplasma&#93;&#44; Borrelia&#44;</span> tuberculosis&#44; hepatitis B and C&#44; HIV and West Nile virus&#41; and autoimmunity profile &#40;ANA&#44; ECA&#44; p-ANCA and c-ANCA&#41;&#44; as well as the determination of specific antibodies &#40;IgG-AQP4&#44; Anti-MOG&#44; Anti-CRMP5&#44; Anti-GFAP3&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Brain and orbital MRI with gadolinium and fat suppression&#44; preferably 1&#8722;2&#8239;mm thin sections&#46; In the acute phase&#44; &#40;first 4 weeks&#41; it is characteristic to enhance the optic nerve in T1 with contrast and increase the signal in STIR sequences&#46; In the chronic phase&#44; thinning of the nerve with hypersignal in T2 appears in relation to the degree of visual impairment&#46; If neuritis is associated with MS&#44; there can be lesions in the periventricular white matter&#44; chiasm&#44; brain stem and cerebellum&#46; Active lesions capture gadolinium&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The presence of demyelinating lesions on initial MRI is a risk marker for the development of MS&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0140" class="elsevierStylePara elsevierViewall">In atypical neuritis&#44; more extensive&#44; bilateral involvement may occur&#44; predominantly in the posterior of the optic nerve&#46; It may also involve the chiasm and optic bands&#44; or even predominantly affect the sheath of the optic nerve as in perineuritis<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a> or in neuritis associated with anti-MOG&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0145" class="elsevierStylePara elsevierViewall">There is a reduction in the amplitude of the P100 wave and an increase in its latency in acute phase PEV&#46; Normalisation of the P100 amplitude occurs in the visual recovery phase&#44; although increased latency persists&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">The presence of OCB and the elevation of CSF immunoglobulin G suggest the presence of a demyelinating disease according to McDonald&#39;s criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p></li></ul></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Treatment<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></span><p id="par0155" class="elsevierStylePara elsevierViewall">It is prescribed individually according to the depth of the initial visual loss and its evolution during the first week&#46; Treatment with megadose steroids is ideally initiated after the imaging test&#44; which should be obtained as soon as possible&#46; The multicenter clinical trial &#8216;Optic Neuritis Treatment Trial&#8217; &#40;ONTT&#41; demonstrated that the administration of high-dose intravenous steroids accelerated visual recovery in patients with typical ON&#44; although it did not modify the final visual prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The initial trend was to treat with intravenous methylprednisolone 250&#8239;mg&#47;6&#8239;h for 3 days&#46; It is currently accepted to administer 1&#8239;g&#47;24&#8239;h E&#46;V&#46; for 3 days on an outpatient basis&#46; The ONTT study also showed that the use of oral steroids could increase the rate of new episodes of ON&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> If there is a recurrence of visual loss on stopping or lowering the dose&#44; the study needs to be expanded in collaboration with an internal medicine specialist&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">In contrast to the ONTT result&#44; a Cochrane review established that steroid treatment did not improve visual acuity&#44; contrast sensitivity or visual field in the long term&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Likewise&#44; two studies studied the effect of intravenous megadose of methylprednisolone versus oral steroids at bioequivalent doses&#44; 1000&#8239;mg<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> or 1250&#8239;mg&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Both studies yielded similar results&#59; therefore&#44; it was concluded that oral megadosis did not differ significantly from endovenous megadosis in the treatment of acute optic neuritis&#46; The follow-up of 28 days and 6 months respectively&#44; poses some limitations on the validity of the latter studies&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Recently&#44; a new study of the role of steroids has been proposed&#44; taking into account the variables of time of evolution&#44; dose and associated antibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">If ON occurs in the context of MS defined by McDonald criteria&#44; the CHAMPS or ETOMS studies<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> have established the usefulness of immunomodulatory treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Update on the classification of autoimmune ON</span><p id="par0175" class="elsevierStylePara elsevierViewall">Beyond the classification between typical or atypical neuritis by the clinical characteristics defined in the ONTT study&#44; alternatives have been proposed&#46; Petzold&#8217;s classification in 2014 was eminently clinical &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41; and only took into account the presence of IgG-AQP4 antibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> The discovery of new antibodies has produced a revolution with new classification proposals&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Multiple sclerosis<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;5&#44;7</span></a></span><p id="par0180" class="elsevierStylePara elsevierViewall">MS is a chronic and disabling disease that affects young adults&#46; It is 3&#8211;4 times more common in women than in men&#46; ON is a typical form of compromise&#44; it may be the first manifestation and&#47;or reappear throughout the course of the disease&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">MS etiology is multifactorial and not completely understood&#46; There is a genetic predisposition&#44; erroneous responses to unidentified environmental antigens and an autoimmune response mediated by collaborating T-lymphocytes &#40;Lth&#41;&#46; These access the central nervous system &#40;CNS&#41; and cause a cellular and humoral inflammatory reaction that destroys both myelin &#40;focal lesions known as plaques&#41; and the axonal tissue they cover&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The diagnosis of MS is established through a combination of clinical&#44; neuroimaging and laboratory criteria that have been unified and agreed upon&#46; These are McDonald&#8217;s criteria and are not treatment guidelines&#46; Their purpose is to agree on the procedures to be performed for the correct diagnosis of MS and they are applied primarily to patients with a clinical isolated syndrome &#40;CIS&#41;&#46; The International Advisory Committee on Clinical Trials in MS last reviewed and updated the criteria in 2017&#46; It also discussed misdiagnosis&#44; differential diagnosis and the appropriate application of these criteria with particular emphasis on diagnosis in various populations and in patients with atypical presentations&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Neuromyelitis optica &#40;NMO&#41;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;26</span></a></span><p id="par0195" class="elsevierStylePara elsevierViewall">NMO &#40;Devic&#8217;s disease&#41; had been considered a more aggressive form of MS with preferential involvement of the optic nerve and spinal cord&#46; The detection of antiaquaporin-4 antibodies &#40;AQP4&#41; in 2005 produced a new diagnostic approach&#46; It is now accepted that NMO is a demyelinating disease different from MS&#46; IgG-AQP4 are antibodies to the AQP4 membrane protein present in astrocytes&#44; so NMO is proposed as an astrocytopathy&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">It is more frequent in Asian and African populations&#44; and affects children and young people&#44; especially women&#46; Bilateral or simultaneous involvement is more indicative of NMO than MS&#46; It can also affect the optic chiasm and bands and the M&#252;ller cells of the retina&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a> It causes significant visual field defects&#44; with high contrast vision less than 20&#47;200&#46; It is often accompanied by transverse myelitis with paraparesis&#46; In 30&#37; there are other autoimmune disorders&#44; mainly systemic lupus erythematosus &#40;SLE&#41; and Sj&#246;gren&#39;s disease and&#44; less frequently&#44; a paraneoplastic disorder&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">The diagnosis is based on the latest Wingerchuk criteria and depends on the presence of IgG-AQP4&#46; If antibodies are detected&#44; only neuritis or any other &#8220;nuclear&#8221; manifestation is required to establish the diagnosis of NMO&#46; If the antibodies are negative&#44; the criteria are stricter&#58; the presence of two or more typical pictures with their characteristic lesions is required on brain and spinal cord MRI<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0210" class="elsevierStylePara elsevierViewall">The initial treatment is with corticosteroids and plasmapheresis&#44; sometimes with the addition of immunosuppressants such as rituximab&#46; In the maintenance phase azathioprine&#44; mycophenolate or rituximab can be used&#46; Immunomodulators prescribed in MS are contraindicated in NMO because they worsen its progression&#46; Accordingly&#44; it is vital to differentiate NMO from MS&#46; Serum anti-AQP4 levels are monitored to control disease activity and the need for treatment&#44; especially rituximab infusions&#46; Anti-QP4&#43; neuritis often has a poorer prognosis because of its greater severity and poorer visual recovery compared to MS and other etiologies&#44; even with an equal degree of damage to the ganglion cell layer in OCT&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Chronic recurrent optic neuritis &#40;CRION&#41;</span><p id="par0215" class="elsevierStylePara elsevierViewall">In 2003 a clinical series on recurrent ON of presumed autoimmune etiology without clinical or radiological criteria for MS was published under this acronym&#46; CRION was more frequent in individuals of African descent and in women&#46; It occurred with uni or bilateral neuritis associated with pain&#44; in some cases accompanied by uveitis&#46; Systemic study of these patients ruled out granulomatous diseases and revealed the presence of anti-nuclear antibodies &#40;ANA&#41; in one case&#46; Acute phase treatment with intravenous steroids had to be maintained orally for a period of time due to recurrence or relapse&#44; which was one of its diagnostic features&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;11</span></a> In the long term&#44; if the maintenance dose of steroids was very high&#44; an immunosuppressant was associated&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Subsequently&#44; the presence of myelin oligocendrocyte autoantibodies &#40;anti-MOG&#41; was detected in some patients with this clinical profile&#46; It is now accepted that some CRION-type neuritis would be part of the spectrum of anti-MOG diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Optic neuritis with anti-MOG or MOGopathy antibodies<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32&#8211;35</span></a></span><p id="par0225" class="elsevierStylePara elsevierViewall">The detection of anti-MOG antibodies in several syndromes with CNS demyelination has produced a conceptual change&#46; Patients with anti-MOG antibodies may develop monophasic &#40;ADEM-acute disseminated encephalomyelitis&#44; seronegative NMO&#44; isolated neuritis&#41; or multiphasic &#40;CRION&#44; seronegative optic neuromyelitis spectrum diseases&#41; CNS demyelinating episodes&#46; These would constitute the disorders with anti-MOG antibodies or mogopathies&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The myelin glycoprotein of oligodendrocytes is a membrane protein that could be involved in the destruction or phagocytosis of myelin through macrophages&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">There are two peak ages of presentation&#44; although any age can be compromised&#46; The first peak appears in childhood with a predominance of ADEM&#46; The second appears between the third and fourth decade of life where isolated ON and other pictures of the NMO spectrum are more frequent&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> The clinical presentation may be indistinguishable between NMO and MS in some cases&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> The predominance of women over men is not demonstrated and there is conflicting data&#46; It is estimated that it would be responsible for about 14&#37; of NMO&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> For the moment&#44; diagnostic criteria have not been agreed upon&#46; It is speculated that anti-MOG disorders would be responsible for a large part of CRION-type neuritis&#44; as well as a very frequent cause of ADEM and other demyelinating pathologies such as MS in children&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">The visual impairment may manifest itself as an episode of either isolated or recurrent ON&#44; or recurrent after the completion of the initial steroid treatment&#46; Neuritis is retrobulbar or papillitis&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> MRI shows frequent bilateral involvement of the optic nerve with more extensive lesions than in MS and BMN&#46; They predominantly affect the orbital portion and rarely the chiasm and optic bands&#46; Other frequently affected areas are the supratentorial deep white substance and the spinal cord&#46; The patterns vary according to age of presentation and are different from MS and BMN<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33&#44;38</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0240" class="elsevierStylePara elsevierViewall">It is necessary to select the cases that are tributaries of anti-MOG serum antibody determinations to avoid misdiagnosis&#46; In addition&#44; is necessary to conduct a study in validated cell cultures&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> CSF determinations are not diagnostic&#44; although according to some authors they may be sufficient&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> Exceptionally&#44; they can coexist with other antibodies such as anti-AQP4 and even OCB&#46; If there are no new episodes&#44; anti-MOG antibodies may become negative&#44; reappearing with each recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">Treatment is based on high-dose steroids and plasmapheresis in the acute phase&#46; Drugs with CD20 targets and immunosuppressants such as rituximab&#44; ofatumumab&#44; azathioprine&#44; corticoids<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> or tocilizumab<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> have been proposed for the prevention of relapses&#46; Between 50&#8211;80&#37; of patients usually develop sequelae&#46; Early treatment of myelitis&#44; a predictor of the severity of sequelae&#44; is important for prevention<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> &#40;<a class="elsevierStyleCrossRefs" href="#tbl0035">Tables 7 and 8</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0035"></elsevierMultimedia><elsevierMultimedia ident="tbl0040"></elsevierMultimedia><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Final considerations</span><p id="par0250" class="elsevierStylePara elsevierViewall">Criteria for the diagnosis and treatment of MS and NMO require frequent and constant updates&#46; In contrast&#44; said criteria still need to be validated and agreed upon for MOGopathies&#46; Clinical classifications are progressively replaced by those based on neuroimmunology and etiopathogenesis&#46; The new antibodies &#40;anti-MOG&#44; anti-AQP4&#41; are being defined with some clinical profiles associated with ON&#46; In other cases such as GlyR &#40;glycine receptor&#41; their pathological significance is still unknown&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">High resolution 3&#8239;Tesla MRI and new generation OCT have allowed a more comprehensive characterization of lesions along the visual pathway&#44; allowing the discovery of types of lesional mechanisms that remained unknown&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Finally&#44; new treatments are available for MS &#40;ocrelizumab&#44; alemtuzumab&#44; siponimod&#8230;&#41;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> and for NMO &#40;inebilizumab&#44; satralizumab&#44; eculizumab&#8230;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> as well as new specific guidelines for the new entities discovered&#46; A new approach to neuroprotection and re-myelinization may change the current paradigm with drugs such as opicinumab&#44; high-dose biotin&#44; trophic factors such as EPO and antioxidants&#46; Ophthalmologists handling this pathology must become familiar with these treatments and their specific possible side effects&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0265" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors&#46;</p></span></span>"
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          "titulo" => "Definition"
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          "titulo" => "Epidemiology"
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          "titulo" => "Physiopathology"
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              "identificador" => "sec0035"
              "titulo" => "Exploratory findings"
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          "identificador" => "sec0040"
          "titulo" => "Diagnosis"
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          "titulo" => "Further studies"
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          "identificador" => "sec0055"
          "titulo" => "Update on the classification of autoimmune ON"
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        13 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Multiple sclerosis"
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        14 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Neuromyelitis optica &#40;NMO&#41;"
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        15 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Chronic recurrent optic neuritis &#40;CRION&#41;"
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        16 => array:3 [
          "identificador" => "sec0075"
          "titulo" => "Optic neuritis with anti-MOG or MOGopathy antibodies"
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              "identificador" => "sec0080"
              "titulo" => "Final considerations"
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          "titulo" => "Conflict of interest"
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        18 => array:2 [
          "identificador" => "xack476238"
          "titulo" => "Acknowledgements"
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        19 => array:1 [
          "titulo" => "References"
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      ]
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    "fechaRecibido" => "2020-03-30"
    "fechaAceptado" => "2020-05-04"
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            0 => "Optic neuritis"
            1 => "Multiple sclerosis &#40;MS&#41;"
            2 => "Neuromyelitis optica &#40;NMO&#41;"
            3 => "MOG-opathy"
            4 => "CRION"
            5 => "Anti-MOG antibody"
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            0 => "Neuritis &#243;pticas"
            1 => "Esclerosis m&#250;ltiple &#40;MS&#41;"
            2 => "Neuromielitis &#243;ptica &#40;NMO&#41;"
            3 => "MOGopat&#237;a"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The knowledge on demyelinating and autoimmune optic neuropathies has experienced a revolution the last decade since the discovery of anti-aquaporin 4 antibody&#46; Improvements in diagnostic techniques&#44; and the finding of new targets&#44; along with advances in neuroimmunology have led to the detection of antibodies related to demyelinating diseases&#46; A review is presented on the classical and new concepts in optic neuritis&#46; The debate on the classification of demyelinating and autoimmune optic neuritis is presented&#46; Furthermore&#44; the updated diagnostic criteria in multiple sclerosis and neuro-myelitis optics are described&#46; Finally&#44; the latest insights into Myelin Oligodendrocyte Glycoprotein &#40;MOG&#41; disorders and chronic-recurring optic neuropathies &#40;CRION&#41; are highlited&#46;</p></span>"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">El conocimiento sobre las neuropat&#237;as &#243;pticas desmielinizantes y autoinmunes ha experimentado una revoluci&#243;n en la &#250;tima d&#233;cada tras el descubrimiento de los anticuerpos anti-acuaporina 4 &#40;AQP4&#41;&#46; Las mejoras en las t&#233;cnicas diagn&#243;sticas&#44; el descubrimiento de nuevas dianas y el avance de la neuro-inmunolog&#237;a ha permitido la detecci&#243;n de anticuerpos asociados a las enfermedades desmielinizantes&#46; Se presenta una revisi&#243;n de los conceptos cl&#225;sicos y nuevos de las neuritis &#243;pticas desmielinizantes y autoimmunes&#46; Se describe el debate en las constantes reformulaciones de su clasificaci&#243;n&#46; Asimismo se actualizan los criterios diagn&#243;sticos de la esclerosis m&#250;ltiple y de la neuromielitis &#243;ptica&#46; Finalmente&#44; se presentan los nuevos conceptos sobre las MOG-opat&#237;as y las neuropat&#237;as opticas inflamatorias cr&#243;nico-recurrentes &#40;CRION&#41;&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Garc&#237;a Ortega A&#44; Monta&#241;ez Campos FJ&#44; Mu&#241;oz S&#44; Sanchez-Dalmau B&#46; Neuritis &#243;pticas desmielinizantes y autoinmunes&#46; Arch Soc Esp Oftalmol&#46; 2020&#46; <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.oftal.2020.05.010">https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;j&#46;oftal&#46;2020&#46;05&#46;010</span></p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Optic Neuromyelitis&#58; Axial flair MRI with post-optic chiasm enhancement&#46; The mark that indicated the lesion has been removed to facilitate its identification&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Optic neuritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Typical&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Atypical&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Young adult&#44; &#62; female&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Under 12 and over 50 years old&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ancestry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Northern Europe&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">African&#44; Asian&#44; Native American&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lateralism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unilateral&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Simultaneous bilateral or rapid sequential&#46;&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Summary of differential epidemiological characteristics of typical and atypical ON&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Optic neuritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lateralism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Unilateral&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Simultaneous bilateral or rapid sequential&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Periocular&#44; worsens with eye movements&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Periocular&#46; Variable in intensity from severe to painless Persists beyond 2 weeks&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vision&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate unilateral loss followed by spontaneous recovery&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe loss &#40;worse than 0&#46;1&#41; without improvement&#44; progressive visual loss of more than 2 weeks evolution&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fundus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal&#44; or mild papilla edema&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prominent papilla edema with over 1 month of evolution&#46; It can be associated to neuroretinitis and hemorrhages&#46; Vitritis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Others&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Previous episodes&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Family history&#46; History of neoplasms&#46; Erratic or relapsed response after withdrawal of steroids&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Good response to steroids&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2354940.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Summary of differential clinical characteristics of typical and atypical ON&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">After a typical ON episode&#44; 38 per cent of patients will develop MS within 10 years&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">First episode of typical ON without other demyelinating alterations in MRI&#44; 22&#37; will develop MS at 10 years&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">First episode of typical ON associated with demyelinating lesions on MRI&#44; the risk of MS is 56&#37; at 10 years&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">In established MS&#44; typical ON appears in 50&#37; at some point in its evolution&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2354936.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">ON conversion risk in MS&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0030"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SION&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Simple isolated ON&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RION&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recurring ON&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CRION&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chronic recurrent ON&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NMO-ON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neuromyelitis optica&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MSON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ON associated with MS&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UCON&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Unclassified ON&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2354938.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Petzold Classification Autoimmune Optical Neuropathies 2014&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0035"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple sclerosis&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative anti-AQP4 antibody&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative anti-MOG antibody&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Spectrum disorders of optical neuromyelitis&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive anti-QA4 antibody&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative anti-MOG antibody&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CNS demyelination associated with anti-MOG &#40;MOGopathies&#41;&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative anti-AQP4 antibody&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive anti-Mog antibody&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2354937.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Neuroimmunological classification of demyelinating syndromes in the central nervous system&#46;</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0040"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis of NMO with IgG-AQP4 &#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 &#43; nuclear clinic&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IgG-AQP4&#43; with best available method&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Exclusion of other diagnoses<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis of NMO without IgG-AQP4&#8239;&#43;&#8239;or unknown status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2 &#43; nuclear clinic resulting from one or more episodes fulfilling&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>At least one episode of ON&#44; extensive longitudinal transverse myelitis&#44; or post-traumatic area syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dissemination in space &#40;2&#8239;&#43;&#8239;nuclear lesions&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IgG-AQP4- with best available method&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Exclusion of other diagnoses&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Nuclear panels</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ON&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acute myelitis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Post-traumatic stress syndrome&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mesencephalic syndrome&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Symptomatic narcolepsy or acute diencephalic syndrome with characteristic MRI lesions&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Symptomatic brain syndrome with characteristic MRI lesions&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Additional MRI requirements for NMO diagnosis IgG-AQP4-</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ON with normal MRI or non-specific white substance lesions&#46; Hyperintensive lesions in T2 or enhancement with gadolinium in T1 extending over&#8239;&#62;&#8239;1&#47;2 of the ON pathway or chiasmatic involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Myelitis&#58; spinal cord MRI with lesions affecting 3 or more contiguous vertebral segments &#40;extensive longitudinal transverse myelitis&#41;&#46; OR 3 or&#8239;&#43;&#8239;contiguous segments of focal spinal atrophy with a previous history of myelitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Post-traumatic area syndrome&#58; Bulbar dorsal or post-traumatic area injury on brain MRI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mesencephalic syndrome&#58; With periependymal lesions&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ON as an isolated clinical syndrome</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NMO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MOGopathies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Very often&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frequent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Very frequent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Visual impairment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Variable&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Severe&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Papilla edema&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Absent or not evident&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Absent or not evident&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frequent and marked&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bilateral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rare simultaneous compromise&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frequent&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frequent&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Simultaneous compromise&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rare&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Myelitis&#44; post-traumatic stress syndrome&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ADEM&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recurrence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Progressive&#46; More frequent over eye with previous ON<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Recurring&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Single-phase or recurrent&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Laboratory</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frequently Anti-AQP4 &#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-MOG &#43;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CSF&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OCB&#43;&#44; mild-moderate pleocytosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Possibility OCB &#43;&#44; moderate-intense pleocytosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Possibility OCB &#43;&#44; variable pleocytosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Response to treatment</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Corticosteroids only speed up recovery &#40;controversial&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Poor&#44; requires immediate treatment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Good&#44; requires immediate treatment&#44; often corticoid-dependent&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Visual forecast</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Good&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bad&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Good&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Image</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OCT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Temporal RNFL-CP and GLC&#47;IPL compromise&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Widespread and severe alteration of RNFL-CP and GLC&#47;IPL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Widespread involvement of RNFL-CP&#46; Less severe CLM&#47;IPL involvement comparable to MS&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Affecting outer layers by direct damage to M&#252;ller cells&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brain &#40;MRI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Periventricular lesions in white substance&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Hemispheric lesions in white substance&#44; dorsal periepidural bulb&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Lesions deep white substance and midbrain&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Optic nerve &#40;MR&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">MS&#58; unilateral compromise&#44; usually retrobulbar MRI shows enhancement at T2&#44; and gadolinium capture at T1&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">NMO&#58; may be more bilaterally affected&#46; Chiasmatic and even ribbon involvement is very suggestive of NMO AQ4&#43;&#46; MRI at T1 with gadolinium shows uptake of posterior half of both optic nerves and chiasm&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">MOGopathies&#58; There may be uni or bilateral involvement&#44; often involving the optic nerve sheath&#44; and perineural tissue&#46; This is quite characteristic&#46; MRI in T1 with gadolinium shows enhancement of both nerves and their perineural tissue&#46; In MOG&#43; cases&#44; it usually affects a greater length of the nerve than in MS-associated neuritis&#46;&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Main clinical differential characteristics of ON by MS&#44; NMO and MOGopathies&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;33&#44;42&#44;43</span></a><span class="elsevierStyleItalic">GLC</span> ganglion cell layer IPL Internal plexiform layer&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Diffuse myeloclastic sclerosis &#40;Schilder&#8217;s Disease&#41;</span><a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Rare and aggressive of controversial etiology&#46; Preferential compromise of children and young people&#46; It produces progressive neurological deterioration with ON&#44; chiasmitis&#44; papillitis and involvement of cortical association areas&#46; In MRI&#44; large bihemispheric lesions with considerable inflammatory component&#46; It is monophasic and partially responds to treatment with corticoids&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Acute Disseminated Encephalomyelitis &#40;ADEM&#41;</span><a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">39&#44;45</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Mostly affects children&#44; slight preference for males&#46; Appears after previous infectious episode or rarely a vaccination&#46; Multifocal and monophasic clinic&#46; Demyelinating lesions exceeding 2&#8239;mm in both optical nerves up to 15&#37; of cases in ADEMON subtype&#46; Important association to anti-MOG antibodies &#40;33&#8722;66&#37; cases&#41;&#46; Without optic neuritis all published cases are MOG &#43;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Post-vaccine optic neuritis</span><a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;46</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Isolated ON&#44; starting between days and up to 3 months after exposure to viral and bacterial antigens&#44; especially the flu vaccine&#46; Bilateral &#40;80&#37;&#41;&#44; painful &#40;60&#37;&#41; and with papilla edema &#40;80&#37;&#41;&#46; Good response to steroids &#40;megadose&#41;&#46; In some cases it is necessary to prolong the steroids orally if complete visual recovery is not achieved&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Sarcoidosis-associated optic neuritis</span><a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Favorite population&#58; women of African descent with papillitis or retrobulbar neuritis&#46; Inflammation is granulomatous&#46; Intraocular inflammation &#40;uveitis&#41; may be accompanied by optic neuromyelitis-like &#40;neuro-sarcoidosis&#41;&#46; Excellent response to steroids&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Post-infectious autoimmune optic neuritis</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Associated with viral and&#44; to a lesser extent&#44; bacterial infections&#44; debuts between 1 and 3 weeks after infectious clinic&#46; Acute&#44; bilateral compromise with papilla edema&#44; or neuroretinitis in children and young adults&#46; Normal neuroimaging despite CSF pleocytosis&#46; Excellent visual prognosis although visual defects and slight residual papillary pallor persist&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Systemic lupus erythematosus&#44; ANCA granulomatosis&#44; Whipple&#8217;s disease&#44; Sj&#246;gren&#8217;s disease and other systemic vasculopathies and inflammatory diseases can occur with ON&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Numerous studies link them to the presence of specific antibodies&#44; especially IgG-AQP4&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a>&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 21735794
Original language: English

DOI:10.1016/j.oftale.2020.05.011

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