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Inflammatory demyelinating diseases of the central nervous system

March 04, 2023

Inflammatory demyelinating diseases (IDDs), sometimes called Idiopathic (IIDDs) due to the unknown etiology of some of them, are a heterogenous group of demyelinating diseases - conditions that cause damage to myelin, the protective sheath of nerve fibers - that occur against the background of an acute or chronic inflammatory process.[1][2][3] IDDs share characteristics with and are often grouped together under Multiple Sclerosis. They are sometimes considered different diseases from Multiple Sclerosis,[4][5] but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.[6][7]

Multiple sclerosis for some people is a syndrome more than a single disease.[8] As of 2019, three auto-antibodies have been found in atypical MS giving birth to separate diseases: Anti-AQP4 diseases, Anti-MOG and Anti-NF spectrums.[9] A LHON-associated MS[10] has also been reported, and in addition there have been inconclusive reports of TNF-α blockers inducing demyelinating disorders.[11]

The subject is under intense research and the list of MS autoantibodies is expected to grow in the near future.[12][13][14]

Separated variants

Several previous MS variants have been recently separated from MS after the discovery of a specific auto-antibody. Those autoantibodies are currently anti-AQP4, anti-MOG and some anti-Neurofascins.[15]

The pathogenic mechanism is usually not related to the clinical course. Therefore, one given pathogenic underlying condition can yield several clinical diseases, and one disease can be produced by several pathogenic conditions.[citation needed]

These conditions can appear as Neuromyelitis optica (NMO), and its associated "spectrum of disorders" (NMOSD), currently considered a common syndrome for several separated diseases[16] but with some still idiopathic subtypes. Some researchers think that there could exist an overlapping between Anti-NMDA receptor encephalitis cases and neuromyelitis optica or acute disseminated encephalomyelitis.[17]

Anti-AQP4 spectrum

See Anti-AQP4 diseases

Originally found in neuromyelitis optica, this autoantibody has been associated with other conditions. Its current spectrum is as following:

Anti-MOG spectrum

See Anti-MOG associated encephalomyelitis

Anti-MOG associated spectrum, often clinically presented as an anti-MOG autoimmune encephalomyelitis,[21][22] but can also appear as negative NMO or atypical multiple sclerosis.[23]

The presence of anti-MOG autoantibodies has been associated with the following conditions[24]

  • Some cases of aquaporin-4-seronegative neuromyelitis optica: NMO derived from an antiMOG associated encephalomyelitis,[22]
  • Some cases of acute disseminated encephalomyelitis, specially the recurrent ones (MDEM)[25]
  • Some cases of McDonalds-positive multiple sclerosis[24][26][23][27]
  • isolated optic neuritis or transverse myelitis[24]
  • Recurrent optic neuritis. The repetition of an idiopatic optic neuritis is considered a distinct clinical condition, and it has been found to be associated with anti-MOG autoantibodies[28]

The anti-mog spectrum in children is equally variated: Out of a sample of 41 children with MOG-antibodies 29 had clinical NMOSD (17 relapsing), 8 had ADEM (4 relapsing with ADEM-ON), 3 had a single clinical event CIS, and 1 had a relapsing tumefactive disorder. Longitudinal myelitis was evident on MRI in 76[percent]. It has also been noted that percentage of children with anti-mog antibodies respect a demyelinating sample is higher than for adults[32]

Some NMO patients present double positive for autoantibodies to AQP4 and MOG. These patients have MS-like brain lesions, multifocal spine lesions and retinal and optic nerves atrophy.[33]

Anti-neurofascin spectrum

See Anti-neurofascin demyelinating diseases

Some anti-neurofascin demyelinating diseases were previously considered a subtype of Multiple Sclerosis but now they are considered a separate entity, as it happened before to anti-MOG and anti-AQP4 cases. Around 10% of MS cases are now thought to be anti-Neurofascin disease in reality.[34]

Anti-neurofascin autoantibodies have been reported in atypical cases of MS and CIDP, and a whole spectrum of Anti-neurofascin demyelinating diseases has been proposed.[35]

Some cases of CIDP are reported to be produced by auto-antibodies against several neurofascin proteins. These proteins are present in the neurons and four of them have been reported to produce disease: NF186, NF180, NF166 and NF155.[35]

Antibodies against Neurofascins NF-155 can also appear in MS[36] and NF-186 could be involved in subtypes of MS[37] yielding an intersection between both conditions.

Summarising, autoantibodies against several neurofascins can produce MS: neurofascin186 (NF186), neurofascin155 (NF155), contactin 1 (CNTN1), contactin associated protein 1 (CASPR1) and gliomedin. All of them nodal and paranodal proteins.[35]

Demyelination associated with anti-TNF therapy

Main article: TNF inhibitor

Several anti-TNF drugs like adalimumab[38][39] are commonly prescribed by a number of autoimmune conditions. Some of them have been reported to produce a CNS-demyelination compatible with standard MS.[11][40][41] Several other monoclonal antibodies like pembrolizumab,[42] nivolumab[43] and infliximab[44] have been also reported to produce MS as an adverse event.[45][11] Nevertheless, it is not so similar as reported in the previous references.[46][improper synthesis?][clarification needed]

The reactions following Anti-TNF therapy have been diverse according to the source of the disease.[40][41][43][failed verification] Some of these cases can be classify as ADEM, using the confluent demyelination as barrier between both conditions.[47][non-primary source needed]

In most cases, the damage fulfills all pathological diagnostic criteria of MS and can therefore be classified as MS in its own right.[medical citation needed] The lesions were classified as pattern II in the Lassman/Lucchinetti system. Some lesions also showed Dawson fingers,[41][improper synthesis?] which is supposed to be a MS-only feature.

These recent problems with artificial anti-TNF-α autoimmunity also point to the possibility of tumor necrosis factor alpha involvement in some multiple sclerosis variants.[medical citation needed]

LHON-associated MS

Also a previous subtype of MS associated to LHON has been described (LHON-MS)[10] It is a presentation of LHON with MS-like CNS damage.

It used to satisfy McDonalds definition for MS, but after demonstration that LHON can produce this kind of lesions, the "no better explanation" requirement does not hold anymore. It is not due to auto-antibodies, but to defective mitochondria instead.[48]

The symptoms of this higher form of the disease include loss of the brain's ability to control the movement of muscles, tremors, and cardiac arrhythmia.[49] and the lack of muscular control.[50]

Relapsing anti-NMDAR encephalitis

Atypical Anti-NMDA receptor encephalitis (a kind of Autoimmune encephalitis) can appear in the form of relapsing optic neuritis.[51][failed verification][non-primary source needed]

Variants still idiopathic

Apart of the previously cited spectrums (Anti-AQP4 diseases, Anti-MOG, and Anti-NF) there is a long list of MS variants, with possibly different pathogenesis, which are still idiopathic and considered inside the MS-spectrum.

Pseudotumefactive variants

Most atypical variants appear as tumefactive or pseudotumefactive variants (lesions whose size is more than 2 cm (0.79 in), with mass effect, oedema and/or ring enhancement)[52][53] Some cases of the following have shown anti-MOG auto-antibodies and therefore they represent MS cases only partially.[citation needed]

  • Acute disseminated encephalomyelitis or ADEM, a closely related disorder in which a known virus or vaccine triggers autoimmunity against myelin. Around 40% of the ADEM cases are due to an "anti-MOG associated encephalomyelitis".[24] It includes Acute hemorrhagic leukoencephalitis, possibly a variant of Acute disseminated encephalomyelitis
  • Marburg multiple sclerosis, an aggressive form, also known as malignant, fulminant or acute MS, currently reported to be closer to anti-MOG associated ADEM than to standard MS.[54] and is sometimes considered a synonym for Tumefactive multiple sclerosis[55]
  • Balo concentric sclerosis, an unusual presentation of plaques forming concentrenic circles, which can sometimes get better spontaneously.
  • Schilder disease or diffuse myelinoclastic sclerosis: is a rare disease that presents clinically as a pseudotumoural demyelinating lesion; and is more common in children.[56][57]
  • Solitary sclerosis: This variant has been recently proposed (2012) by Mayo Clinic researchers.[58] though it was also reported by other groups more or less at the same time.[59][60] It is defined as isolated demyelinating lesions which produce a progressive myelopathy similar to primary progressive MS.

Atypical lesion location variants

Also the location of the lesions can be used to classify variants:

Myelocortical multiple sclerosis

Myelocortical multiple sclerosis (MCMS), proposed variant with demyelination of spinal cord and cerebral cortex but not of cerebral white matter [61] Several atypical cases could belong here. See the early reports of MCMS<[62][63]

AQP4-negative Optic-spinal MS

Real Optic-spinal MS (OSMS) without anti-AQP4 antibodies, has been consistently reported, and it is classified into the MS spectrum.[64][65]

OSMS has its own specific immunological biomarkers[66] The whole picture is under construction and several reports exists about overlapping conditions.

Pure spinal MS

Pure spinal multiple sclerosis: Patients with clinical and paraclinical features suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the McDonald criteria[67] Some inflammatory conditions are associated with the presence of scleroses in the CNS.[68] Optic neuritis (monophasic and recurrent) and Transverse myelitis (monophasic and recurrent)

LHON associated MS

LHON associated MS (LHON-MS), a presentation of LHON with MS-like CNS damage, and therefore a subtype of MS according to McDonalds definition.[10]

Atypical OCB variants

Also different classifications by body fluid biomarkers is possible:

  • Oligoclonal negative MS: Some reports point to the possibility of a different pathogenesis[69] They represent around 5% of the cases[70] which is suspected to be immunogenetically different.[71] Their evolution is better than standard MS patients,[72]
  • Oligoclonal IgM positive MS, with immunoglobulin-M Bands (IgM-Bands), which accounts for a 30-40% of the MS population and has been identified as a predictor of MS severity.[73] It has been reported to have a poor response to interferon-beta but a better response to glatimer acetate instead[74]
  • OCB's types: OCBs are made up of activated B-cells. It seems that the molecular targets for the OCB's are patient-specific.[75]

Radiologically atypical variants

Inside well defined MS (Lesions disseminated in time and space with no other explanation) there are atypical cases based in radiological or metabolic criteria. A four-groups classification has been proposed:[76]

Other radiological classification of atypical lesions proposes the following four subtypes:[78]

  • infiltrative
  • megacystic
  • Baló-like
  • ring-like lesions

Atypical clinical courses

In 1996, the US National Multiple Sclerosis Society (NMSS) Advisory Committee on Clinical Trials in Multiple Sclerosis (ACCTMS) standardized four clinical courses for MS (Remitent-Recidivant, Secondary Progressive, Progressive-Relapsing and Primary progressive). Later,[79] some reports state that those "types" were artificially made up trying to classify RRMS as a separate disease so that the number of patients was low enough to get the interferon approved by the FDA under the orphan drugs act.[79] Revisions in 2013 and 2017 removed the Progressive-Relapsing course and introduced CIS as a variety/course/status of MS, establishing the actual classification (CIS, RRMS, SPMS and PPMS). Nevertheless, these types are not enough to predict the responses to medications and several regulatory agencies use additional types in their recommendations lide Highly active MS, Malignant MS, Aggressive MS or Rapidly progressive MS.[80]

Highly Active MS

As of 2019, HAMS is defined as an RRMS phenotype with one or more of the following characteristics:[80]

  1. DSS scale of 4 points at 5 years of onset of the disease
  2. Multiple relapses (two or more) with incomplete recovery in the ongoing year
  3. More than 2 brain magnetic resonance imaging (MRI) studies demonstrating new lesions or increase in the size of the lesions in T2, or lesions that enhance with gadolinium despite treatment (Clinical case 1 and 2).
  4. No response to treatment with one or more DMTs for at least one year.

There is a group of patients who have defined clinical and radiological risk factors that predict a behavior of greater risk of conversion to HAMS, without having the diagnostic criteria of HAMS in a first clinical attack have predictors of high risk.

Some other previous authors have used other definitions like:

  • High activity according to 2017 definition of activity
  • Rapid accumulation of physical and cognitive deficit, despite treatment with DMT's.
  • Being eligible for immunoablative therapy followed by autologous haematopoietic stem cell transplantation (aHSCT) because of a) the failure of conventional treatment, b) frequent and severe (disabling) relapses, or c) MRI activity (new T2 or gadolinium-enhancing lesions).

Malignant MS

See malignant multiple sclerosis

Occasionally, the term ‘malignant’ MS (MMS) has been used to describe aggressive phenotypes of MS, but this is another ambiguous term that—despite wide usage—means different things to different people.

In 1996, the US National MS Society (NMSS) Advisory Committee on Clinical Trials in Multiple Sclerosis, “malignant MS” was also included, namely, “disease with a rapid progressive course, leading to significant disability in multiple neurologic systems or death in a relatively short time after disease onset.”[full citation needed]

Many authors[who?] reserve the term malignant for fulminant forms of MS that deteriorate so rapidly from the outset as to be almost monophasic, and result in death within months to a few years. One such example is the Marburg variant of MS, which is classically characterized by extensive necrotic and/or tumefactive lesions with mass effect.

Despite recent (and increasing) emphasis on early detection of patients with aggressive MS, the original definition of MMS was not modified by the NMSS Advisory Committee in its latest publication in 2013 (Lublin et al., 2014).[full citation needed]

Aggressive MS

Common to all definitions is the early, unexpected acquisition of disability followed by frequent relapses and highly active disease seen on MRI.

One definition can be based on EDSS score and the time to develop secondary progressive MS (SPMS) (Menon et al., 2013).[full citation needed]

No consensus exists on the speed of progression or degree of disability sufficient for aggressive MS, but some assume that reaching an EDSS score of 6 points probably represents an upper limit beyond which the risk-benefit ratio for an aggressive treatment is unfavourable.[citation needed]

Pragmatically, AMS has been defined as any type of MS that is associated with repeated severe attacks and accelerated accrual of disability—put more simply, "rapidly progressive" MS.

Rapidly progressive multiple sclerosis

This kind of MS was previously reported to behave different that the standard progressive course,[81] being linked to Connexin 43 autoantibodies with pattern III lesions (distal oligodendrogliopathy)[82] and being responsive to plasma exchange[83]

In very rapidly progressive multiple sclerosis the use of immunosuppressive therapy (mitoxantrone/cyclophosphamide), rituximab, autologous haematopoietic stem cell therapy or combination therapy should be considered carefully.[84]

Under research

Some auto-antibodies have been found consistently across different MS cases but there is still no agreement on their relevance:

  • HEPACAM: A cross-reactivity between HepaCam (GlialCam) and EBNA1 has been reported as of 2022 on 25% of MS cases[85]
  • Anti-kir4.1: A KIR4.1 multiple sclerosis variant was reported in 2012[86] and later reported again,[87] which could be considered a different disease (as Devic's disease did before), and can represent up to a 47% of the MS cases
  • Anoctamin 2: Auto-antibodies against anoctamin-2 (ANO-2), one of the ion-channel proteins, have been reported consistently since 2013[88]
    • This finding is not universal. Most of the MS patients do not show auto-antibodies against ANO-2. Therefore, this points toward an ANO2 autoimmune sub-phenotype in MS.[89]
    • Later reports point towards a mimicry between ANO-2 and EBV-EBNA-1 protein[90]
  • Anti-NMDAR autoantibodies: There is an overlap between cases of Anti-NMDA receptor encephalitis and MS, NMO and ADEM.[17] It also could be a confusion with Anti-NMDA receptor encephalitis in the early stages[91] but there are also anti-NMDAR reported cases that evolve to McDonalds MS[92]
  • Anti-Flotilin spectrum: The proteins Flotillin 1 and flotillin 2 have been recently identified as target antigens in some patients with multiple sclerosis. First 14 cases were reported together in the first report, and 3 new cases were reported later inside a cohort of 43 patients.[93]
  • Mutations in GJB1 coding for connexin 32, a gap junction protein expressed in Schwann cells and oligodendrocytes, that usually produce Charcot-Marie-Tooth disease. In some cases also MS (as defined by McDonalds criteria) can appear in these patients.[94]
  • Also an OPA1 variant [95] exists.
  • There exist some reports by Drs. Aristo Vojdani, Partha Sarathi Mukherjee, Joshua Berookhim, and Datis Kharrazian of an aquaporin-related multiple sclerosis, related to vegetal aquaporin proteins.[96]
  • Auto-antibodies against histones have been reported to be involved.[97]
  • Anti-AQP1 could be involved in atypical MS and NMO[98]
  • N-type calcium channel antibodies can produce cognitive relapses mimicking MS related cognitive decline, and may coexist with MS.[99]
  • MLKL-MS: Mixed lineage kinase domain like pseudokinase (MLKL) related MS - A preliminary report has pointed out evidence of a novel neurodegenerative spectrum disorder related to it.[100]

Other auto-antibodies can be used to stablish a differential diagnosis from very different diseases like Sjögren syndrome which can be separated by Anti–Calponin-3 autoantibodies.[101]

The correlation between this genetic mutation and MS was challenged but in 2018 has been replicated by an independent team.[102] Notice that this results do not refer to general MS.

In general, NMO-like spectrum without known auto-antibodies is considered MS. Principal component analysis of these cases show 3 different kinds of antibody-negative patients. The metabolite discriminators of RRMS and Ab-NMOSD suggest that these groupings have some pathogenic meaning.[103]

As MS is an active field for research, the list of auto-antibodies is not closed nor definitive. For example, some diseases like Autoimmune GFAP Astrocytopathy or variants of CIDP that affects the CNS (CIDP is the chronic counterpart of Guillain–Barré syndrome) could be included. Autoimmune variants peripheral neuropathies or progressive inflammatory neuropathy could be in the list assuming the autoimmune model for MS, together with a rare demyelinating lesional variant of trigeminal neuralgia[104][failed verification] and some NMDAR Anti-NMDA receptor encephalitis.[54]

Venous induced demyelination has also been proposed as a hypothetical MS variant produced by CCSVI, Susac's syndrome and Neuro-Behçet's disease (MS has an important vascular component[105]), myalgic encephalomyelitis (aka chronic fatigue syndrome).[106]

Also leukoaraiosis can produce lesions disseminated in time and space, condition usually sufficient in the MS definition. Maybe two sub-conditions of Leukodystrophy: Adrenoleukodystrophy and Adrenomyeloneuropathy could be in the list. Specially interesting is X-linked adrenoleukodystrophy (X-ALD or CALD).[107]

Genetic types

Different behaviour has been reported according to the presence of different HLA genes.

HLA DRB3*02:02 patients

In HLA DRB3 cases, autoimmune reactions against the enzyme GDP-L-fucose synthase has been reported[108][109] The same report points that the autoimmune problem could derive from the gut microbiota.

HLA-DRB1*15:01 has the strongest association with MS.[110]

HLA-DRB1*04:05, HLA-B*39:01, and HLA-B*15:01 are associated with independent MS susceptibility and HLA-DQβ1 position 9 with phenylalanine had the strongest effect on MS susceptibility.[110]

Another possible type is one with auto-antibodies against GDP-L-fucose synthase. In HLA-DRB3*02:02 patients, autoimmune reactions against the enzyme GDP-L-fucose synthase has been reported[108][109] The same report points that the autoimmune problem could derive from the gut microbiota.

Rapidly progressive multiple sclerosis

See malignant multiple sclerosis

This is a specially aggressive clinical course of progressive MS[111] that has been found to be caused by a special genetic variant. It is due to a mutation inside the gene NR1H3, an arginine to glutamine mutation in the position p.Arg415Gln, in an area that codifies the protein LXRA.[112]

Primary progressive variants

Some researchers propose to separate primary progressive MS from other clinical courses. PPMS, after recent findings seem to point that it is pathologically a very different disease.[113][114][115][116][non-primary source needed]

Some authors think since long ago that primary progressive MS should be considered a disease different from standard MS,[117][118] and it was also proposed that PPMS could be heterogeneous[119]

Clinical variants have been described. For example, Late Onset MS.[120][111] It is due to a mutation inside the gene NR1H3, an arginine to glutamine mutation in the position p.Arg415Gln, in an area that codifies the protein LXRA.


For the rest of the progressive cases, it has been found that the lesions are diffuse instead of the normal focal ones,[121] and are different under MR spectroscopy.[122] RRMS and PPMS patients also show differences on the retinal layers yields examined under OCT.[123]

Some authors have proposed a dual classification of PPMS, according to the shape of edges of the scars, in MS-like and ADEM-like[124] Proteomic analysis have shown that two proteins, Secretogranin II and Protein 7B2, in CSF can be used to separate RRMS from PPMS[125]

Recently, the hypothesis of PPMS being apart from RRMS/SPMS is taken further credibility due that it was shown that CSF from PPMS patients can carry the disease to other animals, producing neurodegeneration in mice[113] and that Normal Appearing White Matter (NAWM) structure is also different[126][non-primary source needed]

The predominant lesions in PPMS are slowly expanding lesions with T cells, microglial, and macrophage-associated demyelination in close similar to pattern I demyelination[127]

As of 2019 it has been found that the profile of T-cells is different in PPMS and SPMS[128][non-primary source needed]

Clinical situations inside standard MS

MS can be considered among the acquired demyelinating syndromes with a multiphasic instead of monophasic behaviour.[129] Multiple sclerosis has a prodromal stage in which an unknown underlying condition, able to damage the brain, is present, but no lesion has still developed.

MS is usually classified in clinical types, though they are unrelated to the underlying pathology. Some critical reports say that the current "types" were artificially made up, just to treat RRMS as a separate disease. In this way the number of patients was low enough to enter the orphan drugs act, and get the interferon approved by the FDA under this schema.[79] Recent reviews state that all types are a mixture of inflammation and neurodegeneration, and that all types should be considered the same disease.[130]

Other possible clinical courses are:

Preclinical MS: CIS and CDMS

The first manifestation of MS is the so-called Clinically isolated syndrome, or CIS, which is the first isolated attack. The current diagnosis criteria for MS do not allow doctors to give an MS diagnosis until a second attack takes place. Therefore, the concept of "clinical MS", for an MS that can be diagnosed, has been developed. Until MS diagnosis has been established, nobody can tell whether the disease one is dealing with is MS.[citation needed]

Cases of MS before the CIS are sometimes found during other neurological inspections and are referred to as subclinical MS.[131] Preclinical MS refers to cases after the CIS but before the confirming second attack.[132] After the second confirming attack the situation is referred to as CDMS (clinically defined multiple sclerosis).[133]

CIS itself is sometimes considered itself as a disease entity, different from MS. Even if they share the same underlying condition CIS is not MS given that it lacks the presence of lesions.[134] Approximately 84% of the subjects with CIS experience a second clinical demyelinating event and are diagnosed with clinically definite MS (CDMS) within 20 years.

RIS, subclinical and silent MS

See also Radiologically isolated syndrome

Silent MS has been found in autopsies before the existence of MRI[135] showing that the so-called "clinical definitions" cannot be applied to around 25% of the MS cases.[136] Currently a distinction is made between "silent" and subclinical.

In absence of attacks, sometimes a radiological finding suggestive of demyelination (T2 hyperintensities[137]) can be used to establish a pre-diagnosis of MS. This is often named "Radiologically Isolated Syndrome" (RIS). Cases before the first attack or CIS are subclinical in the sense that they do not produce clinical situations.

If a second radiological event appears without clinical consequences, the clinical situation is named "Silent MS" (Okuda criteria).[138] Anyway, it is reported that all MS cases have an active subclinical phase before the CIS[139]

It has been noted that some aspects of the MS underlying condition are present in otherwise healthy MS patients' relatives,[140] suggesting a wider scope for the "silent MS" term.

In these cases Interleukin-8 is a risk for clinical conversion.[141] It has also been proposed that always exists a subclinical phase in the beginning of every MS case, during which the permeability of the BBB can be used for diagnosis[142]

It is also under investigation whether MS has a prodrome, i.e., a preliminary stage in which the disease exists with non-specific symptoms. Some reports point to a prodrome of several years for RRMS and decades for PPMS.[143]

Aggressive multiple sclerosis

Relapsing-Remitting MS is considered aggressive when the frequency of exacerbations is not less than 3 during 2 years. Special treatment is often considered for this subtype.[144] According to these definition aggressive MS would be a subtype of RRMS.

Other authors disagree and define aggressive MS by the accumulation of disability, considering it as a rapidly disabling disease course[145] and therefore inside PPMS.

The aggressive course is associated to grey matter damage and meningeal inflammation, and presents a special intrathecal (meninges and CSF) inflammatory profile.[146]

After the 2016 revision of the MS phenotypes, it is called Highly active multiple sclerosis[80]

Mitoxantrone was approved for this special clinical course. Some reports point to Alemtuzumal being beneficial.[147]

Pediatric and pubertal MS

MS cases are rare before puberty, but they can happen. Whether they constitute a separate disease is still an open subject. Anyway, even this pubertal MS could be more than one disease, because early-onset and late-onset have different demyelination patterns.[148]

Pediatric MS patients tend to have active inflammatory disease course with a tendency to have brainstem / cerebellar presentations at onset. Due to efficient repair mechanisms at early life, pediatric MS patients tend to have longer time to reach EDSS 6 but reach it at earlier age.[149]

An iron-responsive variant of MS has been reported in children.[150]

Controversy for the definition

Given that the etiology of MS is unknown, the current definitions of MS are all based on its appearance.[medical citation needed] The most commonly used definition, the McDonald criteria, requires just the presence of demyelinating lesions separated in space and time, together with the exclusion of every known demyelinating condition.[medical citation needed]

This unspecific definition has been criticized. For some people this has turned MS into a heterogeneous condition with several underlying problems.[151] Besides, the complementary problem also exists. Given that McDonalds-MS is based just in the distribution of the lesions, even twins with the same underlying condition can be classified different[152]

Finally, the "exclusion of every other known disease" condition also creates problems. Rightfully classified MS patients can be rightfully classified out of the spectrum when their particular underlying problem is discovered. For example, neuromyelitis optica was previously considered MS and currently is not, even if it appears that the MS definition has not changed.[medical citation needed]

Currently there is no single diagnosis test for MS that is 100% sensitive and specific.[153][154]

Pathological and clinical definitions

McDonald criteria propose a clinical diagnosis based on a pathological definition, saying that the focus for diagnosis "remains on the objective demonstration of dissemination of lesions in both time and space" (DIT and DIS). But given that other diseases produce similar lesions, it is also required that those lesions cannot be explained by any other known disease.[citation needed]

This open definition present problems.[155] For example, before the discovery of anti-AQP4 in 2006, most optic-spinal MS patients were classified rightfully as MS. Currently they are classified as NMO. Both diagnosis are correct even though the definition has not (apparently) changed.

According to some pathologists, a pathological definition is required because clinical definitions have problems with differential diagnosis[43] and they always use a pathological definition on articles about post-mortem retrospective diagnosis, but for practitioners that need a diagnosis as soon as possible MS is often regarded as a pure clinical entity, defined simply by a positive result in the standard clinical case definition being then named "clinically definite MS" (CDMS, Poser) or simply "MS" (McDonald).[156]

Both definitions lead to different results. For example, confluent subpial cortical lesions are the most specific finding for MS, being exclusively present in MS patients.[157] but can only be detected post-mortem by an autopsy[158] Therefore, any other diagnosis method will have false positives.

Other meanings of MS

There is no known etiology for MS and therefore no etiology-based definition is possible. Comparison to a post-mortem retrospective diagnosis is possible, but useless to practitioners and short-term researchers, and it is not usually done. Therefore, all meanings for the words "Multiple Sclerosis" are somehow diffuse.[citation needed]

The pathological definition based on proven dissemination in time and space has problems. For example, it leaves situations like RIS (radiologically isolated syndrome) outside the MS spectrum because the lack of proof, even in the case that this condition later could shown the same pathogenic conditions than MS cases.[159]

Besides, usually the term "multiple sclerosis" is used to refer to the presence of the unknown underlying condition that produces the MS lesions instead to the mere presence of the lesions. The term MS is also used to refers to the process of developing the lesions.[160]

Some authors instead speak about the biological disease vs. its clinical presentation.[161]

Anyway, the precise meaning in each case can be normally deduced from the context.

Handling several clinical definitions

Given that several definitions of MS coexist, some authors are referring to them using whether CDMS for Poser positives, or McDonalds-MS with a prefix for McDonalds positives, including the release year in the prefix.[162]

CIS and conversion to MS

The 2010 revision of the McDonald criteria[163] allows the diagnosis of MS with only one proved lesion (CIS). Consistently, the later revision for the MS phenotypes in 2013 was forced to consider CIS as one of the MS phenotypes.[164]

Therefore, the former concept of "Conversion from CIS to MS", that was declared when a patient had a second MS attack, does not apply anymore. More accurate is now to speak about conversions from the CIS phenotype to other MS phenotype.[165]

See also

References

  1. ^ Höftberger R, Lassmann H (2018). "Inflammatory demyelinating diseases of the central nervous system". Handbook of Clinical Neurology. 145: 263–283. doi:10.1016/B978-0-12-802395-2.00019-5. ISBN 9780128023952. PMC 7149979. PMID 28987175.
  2. ^ "Find out more about demyelinating diseases, including multiple sclerosis". Mayo Clinic. Retrieved 2022-06-23.
  3. ^ Fontaine B (September 2001). "[Borderline forms of multiple sclerosis]". Revue Neurologique (in French). 157 (8-9 Pt 2): 929–934. PMID 11787357.
  4. ^ Wingerchuk DM, Lucchinetti CF (June 2007). "Comparative immunopathogenesis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis". Current Opinion in Neurology. 20 (3): 343–350. doi:10.1097/WCO.0b013e3280be58d8. PMID 17495631. S2CID 17386506.
  5. ^ Poser CM, Brinar VV (October 2007). "Disseminated encephalomyelitis and multiple sclerosis: two different diseases - a critical review". Acta Neurologica Scandinavica. 116 (4): 201–206. doi:10.1111/j.1600-0404.2007.00902.x. PMID 17824894. S2CID 44411472.
  6. ^ Weinshenke B, Miller D (1999-01-13). "Multiple sclerosis: one disease or many?". In Siva A, Kesselring J, Thompson AJ (eds.). Frontiers in Multiple Sclerosis, II. Taylor & Francis. pp. 37–46. ISBN 978-1-85317-506-0.
  7. ^ Hartung HP, Grossman RI (May 2001). "ADEM: distinct disease or part of the MS spectrum?". Neurology. 56 (10): 1257–1260. doi:10.1212/WNL.56.10.1257. PMID 11376169. S2CID 219199163.
  8. ^ Zabad RK, Stewart R, Healey KM (October 2017). "Pattern Recognition of the Multiple Sclerosis Syndrome". Brain Sciences. 7 (10): 138. doi:10.3390/brainsci7100138. PMC 5664065. PMID 29064441.
  9. ^ Fujihara K (June 2019). "Neuromyelitis optica spectrum disorders: still evolving and broadening". Current Opinion in Neurology. 32 (3): 385–394. doi:10.1097/WCO.0000000000000694. PMC 6522202. PMID 30893099.
  10. ^ a b c Bargiela D, Chinnery PF (September 2019). "Mitochondria in neuroinflammation - Multiple sclerosis (MS), leber hereditary optic neuropathy (LHON) and LHON-MS". Neuroscience Letters. 710: 132932. doi:10.1016/j.neulet.2017.06.051. PMID 28668384. S2CID 38817368.
  11. ^ a b c Kemanetzoglou, Elissavet; Andreadou, Elisabeth (2017). "CNS Demyelination with TNF-α Blockers". Current Neurology and Neuroscience Reports. 17 (4): 36. doi:10.1007/s11910-017-0742-1. ISSN 1528-4042. PMC 5364240. PMID 28337644.
  12. ^ Lang K, Prüss H (September 2017). "Frequencies of neuronal autoantibodies in healthy controls: Estimation of disease specificity". Neurology. 4 (5): e386. doi:10.1212/NXI.0000000000000386. PMC 5515597. PMID 28761905.
  13. ^ Kusunoki S (December 2013). "Autoantibodies in neuroimmunological diseases; relevance of fine specificity". Experimental Neurology. 250: 219–220. doi:10.1016/j.expneurol.2013.10.009. PMID 24120752. S2CID 45173537.
  14. ^ Seay M, Galetta S (September 2018). "Glial Fibrillary Acidic Protein Antibody: Another Antibody in the Multiple Sclerosis Diagnostic Mix". Journal of Neuro-Ophthalmology. 38 (3): 281–284. doi:10.1097/WNO.0000000000000689. PMID 29923872. S2CID 49310332.
  15. ^ Sato DK, Callegaro D, Lana-Peixoto MA, Waters PJ, de Haidar Jorge FM, Takahashi T, et al. (February 2014). "Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders". Neurology. 82 (6): 474–481. doi:10.1212/WNL.0000000000000101. PMC 3937859. PMID 24415568.
  16. ^ Weinshenker BG, Wingerchuk DM (February 2014). "The two faces of neuromyelitis optica". Neurology. 82 (6): 466–467. doi:10.1212/WNL.0000000000000114. PMID 24415570. S2CID 30860834.
  17. ^ a b Gahr M, Lauda F, Wigand ME, Connemann BJ, Rosenbohm A, Tumani H, et al. (April 2015). "Periventricular white matter lesion and incomplete MRZ reaction in a male patient with anti-N-methyl-D-aspartate receptor encephalitis presenting with dysphoric mania". BMJ Case Reports. 2015: bcr2014209075. doi:10.1136/bcr-2014-209075. PMC 4422915. PMID 25917068.
  18. ^ Li Y, Xie P, Lv F, Mu J, Li Q, Yang Q, et al. (October 2008). "Brain magnetic resonance imaging abnormalities in neuromyelitis optica". Acta Neurologica Scandinavica. 118 (4): 218–225. doi:10.1111/j.1600-0404.2008.01012.x. PMID 18384459. S2CID 22270592.
  19. ^ Wingerchuk D (2006). (PDF). 2006 Rare Neuroimmunologic Disorders Symposium. Archived from the original (PDF) on 2006-09-25. Retrieved 2007-01-05.
  20. ^ Ikeda K, Ito H, Hidaka T, Takazawa T, Sekine T, Yoshii Y, et al. (2011). "Repeated non-enhancing tumefactive lesions in a patient with a neuromyelitis optica spectrum disorder". Internal Medicine. 50 (9): 1061–1064. doi:10.2169/internalmedicine.50.4295. PMID 21532234.
  21. ^ Pröbstel AK, Rudolf G, Dornmair K, Collongues N, Chanson JB, Sanderson NS, et al. (March 2015). "Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype". Journal of Neuroinflammation. 12 (1): 46. doi:10.1186/s12974-015-0256-1. PMC 4359547. PMID 25889963.
  22. ^ a b Spadaro M, Gerdes LA, Mayer MC, Ertl-Wagner B, Laurent S, Krumbholz M, et al. (March 2015). "Histopathology and clinical course of MOG-antibody-associated encephalomyelitis". Annals of Clinical and Translational Neurology. 2 (3): 295–301. doi:10.1002/acn3.164. PMC 4369279. PMID 25815356.
  23. ^ a b Spadaro M, Gerdes LA, Krumbholz M, Ertl-Wagner B, Thaler FS, Schuh E, et al. (October 2016). "Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis". Neurology. 3 (5): e257. doi:10.1212/NXI.0000000000000257. PMC 4949775. PMID 27458601.
  24. ^ a b c d Reindl M, Di Pauli F, Rostásy K, Berger T (August 2013). "The spectrum of MOG autoantibody-associated demyelinating diseases". Nature Reviews. Neurology. 9 (8): 455–461. doi:10.1038/nrneurol.2013.118. PMID 23797245. S2CID 7219279.
  25. ^ Baumann M, Hennes EM, Schanda K, Karenfort M, Bajer-Kornek B, Diepold K, et al. (2015). "OP65 – 3006: Clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis and MOG antibodies". European Journal of Paediatric Neurology. 19: S21. doi:10.1016/S1090-3798(15)30066-0.
  26. ^ Jarius S, Metz I, König FB, Ruprecht K, Reindl M, Paul F, et al. (October 2016). "Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in 'pattern II multiple sclerosis' and brain biopsy findings in a MOG-IgG-positive case". Multiple Sclerosis. 22 (12): 1541–1549. doi:10.1177/1352458515622986. PMID 26869529. S2CID 1387384.
  27. ^ Kitagawa S, Osada T, Kaneko K, Takahashi T, Suzuki N, Nakahara J (December 2018). "[Clinical analysis of opticospinal multiple sclerosis (OSMS) presentation detecting anti-myelin oligodendrocyte glycoprotein (MOG) antibody]". Rinsho Shinkeigaku = Clinical Neurology. 58 (12): 737–744. doi:10.5692/clinicalneurol.cn-001184. PMID 30487359.
  28. ^ Chalmoukou K, Stathopoulos P, Alexopoulos H, Akrivou S, Dalakas M (2015). "Recurrent Optic Neuritis (rON) is characterised by Anti-MOG Antibodies: A follow-up study". Neurology. 84 (14 Suppl P5): 274.
  29. ^ Rossman I (2015). "An 8 Year Old Girl with Chronic Inflammatory Optic Neuritis (CRION): the Youngest Reported Case to Date". Neurology. 84 (14): Supplement P7.015.
  30. ^ Chalmoukou K, Alexopoulos H, Akrivou S, Stathopoulos P, Reindl M, Dalakas MC (August 2015). "Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis". Neurology. 2 (4): e131. doi:10.1212/NXI.0000000000000131. PMC 4496630. PMID 26185777.
  31. ^ Cantó LN, Boscá SC, Vicente CA, Gil-Perontín S, Pérez-Miralles F, Villalba JC, et al. (2019). "Brain Atrophy in Relapsing Optic Neuritis Is Associated With Crion Phenotype". Frontiers in Neurology. 10: 1157. doi:10.3389/fneur.2019.01157. PMC 6838209. PMID 31736862.
  32. ^ Tenembaum S, Waters P, Leite M, Woodhall M, Princich J, Segura M, et al. (2015-04-06). "Spectrum of MOG Autoantibody-Associated Inflammatory Diseases in Pediatric Patients (I4-3A)". Neurology. 84 (14 Supplement). ISSN 0028-3878.
  33. ^ Yan Y, Li Y, Fu Y, Yang L, Su L, Shi K, et al. (December 2016). "Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD". Science China Life Sciences. 59 (12): 1270–1281. doi:10.1007/s11427-015-4997-y. PMC 5101174. PMID 26920678.
  34. ^ Goncalves MV, Fragoso YD (April 2019). "The involvement of anti-neurofascin 155 antibodies in central and peripheral demyelinating diseases". Neuroimmunology and Neuroinflammation. 8: 6. doi:10.20517/2347-8659.2019.08. S2CID 146038130.
  35. ^ a b c Kira JI, Yamasaki R, Ogata H (November 2019). "Anti-neurofascin autoantibody and demyelination". Neurochemistry International. 130: 104360. doi:10.1016/j.neuint.2018.12.011. PMID 30582947.
  36. ^ Stich O, Perera S, Berger B, Jarius S, Wildemann B, Baumgartner A, Rauer S (May 2016). "Prevalence of neurofascin-155 antibodies in patients with multiple sclerosis". Journal of the Neurological Sciences. 364: 29–32. doi:10.1016/j.jns.2016.03.004. PMID 27084211. S2CID 29204735.
  37. ^ "Progressive MS: a new perspective | Multiple Sclerosis Society UK". www.mssociety.org.uk. Archived from the original on 2006-09-25.
  38. ^ Engel S, Luessi F, Mueller A, Schopf RE, Zipp F, Bittner S (2020). "PPMS onset upon adalimumab treatment extends the spectrum of anti-TNF-α therapy-associated demyelinating disorders". Therapeutic Advances in Neurological Disorders. 13: 1756286419895155. doi:10.1177/1756286419895155. PMC 6940603. PMID 31921355.
  39. ^ Alnasser Alsukhni R, Jriekh Z, Aboras Y (2016). "Adalimumab Induced or Provoked MS in Patient with Autoimmune Uveitis: A Case Report and Review of the Literature". Case Reports in Medicine. 2016: 1423131. doi:10.1155/2016/1423131. PMC 5093248. PMID 27840642.
  40. ^ a b Vicente LG, Viqueira BR, de las Peñas MJ, Cobos RG, Moreno JP, Gonzalez RA (2016). "Relapse in a paucisymptomatic form of multiple sclerosis in a patient treated with nivolumab". Neuro Oncol. 18: iv25. doi:10.1093/neuonc/now188.085.
  41. ^ a b c Höftberger R, Leisser M, Bauer J, Lassmann H (December 2015). "Autoimmune encephalitis in humans: how closely does it reflect multiple sclerosis ?". Acta Neuropathologica Communications. 3 (1): 80. doi:10.1186/s40478-015-0260-9. PMC 4670499. PMID 26637427.
  42. ^ Romeo MA, Garassino MC, Moiola L, Galli G, Comi G, Martinelli V, Filippi M (December 2019). "Multiple sclerosis associated with pembrolizumab in a patient with non-small cell lung cancer". Journal of Neurology. 266 (12): 3163–3166. doi:10.1007/s00415-019-09562-z. PMID 31586260. S2CID 203654410.
  43. ^ a b c Lassmann H (February 2010). "Acute disseminated encephalomyelitis and multiple sclerosis". Brain. 133 (Pt 2): 317–319. doi:10.1093/brain/awp342. PMID 20129937.
  44. ^ Kalinowska-Lyszczarz A, Fereidan-Esfahani M, Guo Y, Lucchinetti CF, Tobin WO (August 2020). "Pathological findings in central nervous system demyelination associated with infliximab". Multiple Sclerosis. 26 (9): 1124–1129. doi:10.1177/1352458519894710. PMC 7297659. PMID 31845616.
  45. ^ Garcia, Catherine R.; Jayswal, Rani; Adams, Val; Anthony, Lowell B; Villano, John L. (10 February 2019). "Multiple Sclerosis Outcomes after Cancer Immunotherapy". Clinical & Translational Oncology. 21 (10): 1336–1342. doi:10.1007/s12094-019-02060-8. ISSN 1699-048X. PMC 6702101. PMID 30788836.
  46. ^ Williams I, Uhlig HH (December 2020). "Demyelination After Anti-TNF Therapy: Who is at Risk?". Journal of Crohn's & Colitis. 14 (12): 1651–1652. doi:10.1093/ecco-jcc/jjaa144. PMID 33026456.
  47. ^ Young NP, Weinshenker BG, Parisi JE, Scheithauer B, Giannini C, Roemer SF, et al. (February 2010). "Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis". Brain. 133 (Pt 2): 333–348. doi:10.1093/brain/awp321. PMC 2822631. PMID 20129932.
  48. ^ Nikoskelainen EK, Marttila RJ, Huoponen K, Juvonen V, Lamminen T, Sonninen P, Savontaus ML (August 1995). "Leber's "plus": neurological abnormalities in patients with Leber's hereditary optic neuropathy". Journal of Neurology, Neurosurgery, and Psychiatry. 59 (2): 160–164. doi:10.1136/jnnp.59.2.160. PMC 485991. PMID 7629530.
  49. ^ . health-cares.net. Archived from the original on 6 May 2016.
  50. ^ "Multiple sclerosis - Symptoms and causes". Mayo Clinic. Retrieved 2022-06-24.
  51. ^ Ma C, Wang C, Zhang Q, Lian Y (2019). "Emerging role of prodromal headache in patients with anti-N-methyl-D-aspartate receptor encephalitis". Journal of Pain Research. 12: 519–526. doi:10.2147/JPR.S189301. PMC 6365221. PMID 30787630.
  52. ^ Lucchinetti CF, Gavrilova RH, Metz I, Parisi JE, Scheithauer BW, Weigand S, et al. (July 2008). "Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis". Brain. 131 (Pt 7): 1759–1775. doi:10.1093/brain/awn098. PMC 2442427. PMID 18535080.
  53. ^ Given CA, Stevens BS, Lee C (January 2004). "The MRI appearance of tumefactive demyelinating lesions". AJR. American Journal of Roentgenology. 182 (1): 195–199. doi:10.2214/ajr.182.1.1820195. PMID 14684539.
  54. ^ a b Hardy TA, Reddel SW, Barnett MH, Palace J, Lucchinetti CF, Weinshenker BG (August 2016). "Atypical inflammatory demyelinating syndromes of the CNS". The Lancet. Neurology. 15 (9): 967–981. doi:10.1016/S1474-4422(16)30043-6. PMID 27478954. S2CID 26341166.
  55. ^ Jiménez Arango JA, Uribe Uribe CS, Toro González G (March 2015). "Lesser-known myelin-related disorders: focal tumour-like demyelinating lesions". Neurologia. 30 (2): 97–105. doi:10.1016/j.nrl.2013.06.004. PMID 24094691.
  56. ^ Garrido C, Levy-Gomes A, Teixeira J, Temudo T (2004). "[Schilder's disease: two new cases and a review of the literature]" [Schilder's disease: two new cases and a review of the literature]. Revista de Neurología (in Spanish). 39 (8): 734–738. doi:10.33588/rn.3908.2003023. PMID 15514902.
  57. ^ Afifi AK, Bell WE, Menezes AH, Moore SA (October 1994). "Myelinoclastic diffuse sclerosis (Schilder's disease): report of a case and review of the literature". Journal of Child Neurology. 9 (4): 398–403. CiteSeerX 10.1.1.1007.559. doi:10.1177/088307389400900412. PMID 7822732. S2CID 38765870.
  58. ^ Schmalstieg WF, Keegan BM, Weinshenker BG (February 2012). "Solitary sclerosis: progressive myelopathy from solitary demyelinating lesion". Neurology. 78 (8): 540–544. doi:10.1212/WNL.0b013e318247cc8c. PMID 22323754. S2CID 52859541.
  59. ^ Lattanzi S (July 2012). "Solitary sclerosis: Progressive myelopathy from solitary demyelinating lesion". Neurology. 79 (4): 393, author reply 393. doi:10.1212/01.wnl.0000418061.10382.f7. PMID 22826546.
  60. ^ Ayrignac X, Carra-Dalliere C, Homeyer P, Labauge P (December 2013). "Solitary sclerosis: progressive myelopathy from solitary demyelinating lesion. A new entity?". Acta Neurologica Belgica. 113 (4): 533–534. doi:10.1007/s13760-013-0182-x. PMID 23358965. S2CID 17631796.
  61. ^ Trapp BD, Vignos M, Dudman J, Chang A, Fisher E, Staugaitis SM, et al. (October 2018). "Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study". The Lancet. Neurology. 17 (10): 870–884. doi:10.1016/S1474-4422(18)30245-X. PMC 6197820. PMID 30143361.
  62. ^ Vignos MC (2016). A histopathological and magnetic resonance imaging assessment of myelocortical multiple sclerosis: A new pathological variant (Ph.D. thesis). Kent State University.
  63. ^ Hendrickson M, Chang A, Fisher E (September 30, 2013). "ECTRIMS 2013: Posters: Myelocortical multiple sclerosis: a subgroup of multiple sclerosis patients with spinal cord and cortical demyelination". Multiple Sclerosis Journal. 19 (11_suppl): 74–558. doi:10.1177/1352458513502429. hdl:20.500.11940/2342. ISSN 1352-4585. S2CID 208628537.
  64. ^ Meneguette NS, Almeida KM, Figueiredo MT, de Araújo E, Araújo AC, Alvarenga MP, et al. (November 2021). "Optic neuritis in Asian type opticospinal multiple sclerosis (OSMS-ON) in a non-Asian population: A functional-structural paradox" (PDF). Multiple Sclerosis and Related Disorders. 56: 103260. doi:10.1016/j.msard.2021.103260. PMID 34562767. S2CID 237636213.
  65. ^ Matsushita T, Isobe N, Matsuoka T, Shi N, Kawano Y, Wu XM, et al. (July 2009). "Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese". Multiple Sclerosis. 15 (7): 834–847. doi:10.1177/1352458509104595. PMID 19465451. S2CID 19372571.
  66. ^ Mercan Ö, Ülger Z, Handan Mısırlı C, Türkoğlu R (2018). "Opticospinal Multiple Sclerosis Clinical Course and Immunological Parameters". Experimed. 8 (2): 47–51. doi:10.26650/experimed.2018.18002.
  67. ^ Schee JP, Viswanathan S (May 17, 2018). "Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum". Multiple Sclerosis Journal. 25 (8): 1189–1195. doi:10.1177/1352458518775912. ISSN 1352-4585. PMID 29771191. S2CID 21709554.
  68. ^ O'Connor P, Marriott J (2010). (PDF). In Hohlfeld R, Lucchinetti CF (eds.). Multiple sclerosis 3 (1st ed.). Philadelphia: Saunders Elsevier. ISBN 978-1-4160-6068-0. Archived from the original (PDF) on 2015-08-24. Retrieved 2015-01-14.
  69. ^ Mihalova T, Kwong JL, Alachkar H (2019-12-01). "214 Analysis of CSF IgG index, IgG synthesis and clinical presentation among CSF OCBs negative patients". Journal of Neurology, Neurosurgery & Psychiatry. 90 (12): e54. doi:10.1136/jnnp-2019-ABN-2.181 (inactive 31 December 2022). ISSN 0022-3050.{{cite journal}}: CS1 maint: DOI inactive as of December 2022 (link)
  70. ^ Link H, Huang YM (November 2006). "Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness". Journal of Neuroimmunology. 180 (1–2): 17–28. doi:10.1016/j.jneuroim.2006.07.006. PMID 16945427. S2CID 22724352.
  71. ^ Imrell K, Landtblom AM, Hillert J, Masterman T (September 2006). "Multiple sclerosis with and without CSF bands: clinically indistinguishable but immunogenetically distinct". Neurology. 67 (6): 1062–1064. doi:10.1212/01.wnl.0000237343.93389.35. PMID 17000979. S2CID 21855273.
  72. ^ Zeman AZ, Kidd D, McLean BN, Kelly MA, Francis DA, Miller DH, et al. (January 1996). "A study of oligoclonal band negative multiple sclerosis". Journal of Neurology, Neurosurgery, and Psychiatry. 60 (1): 27–30. doi:10.1136/jnnp.60.1.27. PMC 486185. PMID 8558146.
  73. ^ Li R, Patterson KR, Bar-Or A (July 2018). "Reassessing B cell contributions in multiple sclerosis". Nature Immunology. 19 (7): 696–707. doi:10.1038/s41590-018-0135-x. PMID 29925992. S2CID 49347759.
  74. ^ Casanova B, Lacruz L, Villar ML, Domínguez JA, Gadea MC, Gascón F, et al. (August 2018). "Different clinical response to interferon beta and glatiramer acetate related to the presence of oligoclonal IgM bands in CSF in multiple sclerosis patients". Neurological Sciences. 39 (8): 1423–1430. doi:10.1007/s10072-018-3442-y. PMID 29882169. S2CID 46954452.
  75. ^ Graner M, Pointon T, Manton S, Green M, Dennison K, Davis M, et al. (21 February 2020). "Oligoclonal IgG antibodies in multiple sclerosis target patient-specific peptides". PLOS ONE. 15 (2): e0228883. Bibcode:2020PLoSO..1528883G. doi:10.1371/journal.pone.0228883. PMC 7034880. PMID 32084151.
  76. ^ Codjia P, Ayrignac X, Carra-Dalliere C, Cohen M, Charif M, Lippi A, et al. (SFSEP OFSEP) (February 2019). "Multiple sclerosis with atypical MRI presentation: Results of a nationwide multicenter study in 57 consecutive cases". Multiple Sclerosis and Related Disorders. 28: 109–116. doi:10.1016/j.msard.2018.12.022. PMID 30592992. S2CID 58550590.
  77. ^ a b Ayrignac X, Menjot de Champfleur N, Menjot de Champfleur S, Carra-Dallière C, Deverdun J, Corlobe A, Labauge P (June 2016). "Brain magnetic resonance imaging helps to differentiate atypical multiple sclerosis with cavitary lesions and vanishing white matter disease". European Journal of Neurology. 23 (6): 995–1000. doi:10.1111/ene.12931. PMID 26727496. S2CID 3917307.
  78. ^ Wallner-Blazek M, Rovira A, Fillipp M, Rocca MA, Miller DH, Schmierer K, et al. (August 2013). "Atypical idiopathic inflammatory demyelinating lesions: prognostic implications and relation to multiple sclerosis". Journal of Neurology. 260 (8): 2016–2022. doi:10.1007/s00415-013-6918-y. PMID 23620065. S2CID 28377856.
  79. ^ a b c Dobson R, Giovannoni G (January 2019). "Multiple sclerosis - a review". European Journal of Neurology. 26 (1): 27–40. doi:10.1111/ene.13819. PMID 30300457.
  80. ^ a b c Díaz C, Zarco LA, Rivera DM (May 2019). "Highly active multiple sclerosis: An update". Multiple Sclerosis and Related Disorders. 30: 215–224. doi:10.1016/j.msard.2019.01.039. PMID 30822617. S2CID 73460639.
  81. ^ Morcos Y, Lee SM, Levin MC (August 2003). "A role for hypertrophic astrocytes and astrocyte precursors in a case of rapidly progressive multiple sclerosis". Multiple Sclerosis. 9 (4): 332–341. doi:10.1191/1352458503ms931oa. PMID 12926837. S2CID 43651011.
  82. ^ Masaki K, Suzuki SO, Matsushita T, Matsuoka T, Imamura S, Yamasaki R, et al. (2013). "Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica". PLOS ONE. 8 (8): e72919. Bibcode:2013PLoSO...872919M. doi:10.1371/journal.pone.0072919. PMC 3749992. PMID 23991165.
  83. ^ Seidi O (January 27, 2015). The Role of Therapeutic Plasma Exchange in Clinical Neurology (Report) – via khartoumspace.uofk.edu.
  84. ^ Broadley SA, Barnett MH, Boggild M, Brew BJ, Butzkueven H, Heard R, et al. (August 2015). "A new era in the treatment of multiple sclerosis". The Medical Journal of Australia. 203 (3): 139–41, 141e.1. doi:10.5694/mja14.01218. hdl:10536/DRO/DU:30080418. PMID 26224184. S2CID 10805065.
  85. ^ Wekerle H (March 2022). "Epstein-Barr virus sparks brain autoimmunity in multiple sclerosis". Nature. 603 (7900): 230–232. Bibcode:2022Natur.603..230W. doi:10.1038/d41586-022-00382-2. PMID 35169323. S2CID 246866517.
  86. ^ Srivastava R, Aslam M, Kalluri SR, Schirmer L, Buck D, Tackenberg B, et al. (July 2012). "Potassium channel KIR4.1 as an immune target in multiple sclerosis". The New England Journal of Medicine. 367 (2): 115–123. doi:10.1056/NEJMoa1110740. PMC 5131800. PMID 22784115.
  87. ^ Schneider R (2013). "Autoantibodies to Potassium Channel KIR4.1 in Multiple Sclerosis". Frontiers in Neurology. 4: 125. doi:10.3389/fneur.2013.00125. PMC 3759297. PMID 24032025.
  88. ^ Ayoglu B, Häggmark A, Khademi M, Olsson T, Uhlén M, Schwenk JM, Nilsson P (September 2013). "Autoantibody profiling in multiple sclerosis using arrays of human protein fragments". Molecular & Cellular Proteomics. 12 (9): 2657–2672. doi:10.1074/mcp.M112.026757. PMC 3769337. PMID 23732997.
  89. ^ Ayoglu B, Mitsios N, Kockum I, Khademi M, Zandian A, Sjöberg R, et al. (February 2016). "Anoctamin 2 identified as an autoimmune target in multiple sclerosis". Proceedings of the National Academy of Sciences of the United States of America. 113 (8): 2188–2193. Bibcode:2016PNAS..113.2188A. doi:10.1073/pnas.1518553113. PMC 4776531. PMID 26862169.
  90. ^ Tengvall K, Huang J, Hellström C, Kammer P, Biström M, Ayoglu B, et al. (August 2019). "Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk". Proceedings of the National Academy of Sciences of the United States of America. 116 (34): 16955–16960. doi:10.1073/pnas.1902623116. PMC 6708327. PMID 31375628.
  91. ^ Belova AN, Grygorieva VN, Rasteryaeva MV, Ruina EA, Belova EM, Solovieva VS, Boyko AN (2019). "[Anti-NMDAR encephalitis associated with relapsing optic neuritis: a case report and differential diagnosis]". Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova. 119 (10. Vyp. 2): 137–146. doi:10.17116/jnevro201911910137. PMID 31934999. S2CID 210193928.
  92. ^ Baheerathan A, Brownlee WJ, Chard DT, Shields K, Gregory R, Trip SA (February 2017). "Antecedent anti-NMDA receptor encephalitis in two patients with multiple sclerosis". Multiple Sclerosis and Related Disorders. 12: 20–22. doi:10.1016/j.msard.2016.12.009. PMID 28283100.
  93. ^ Mariotto S, Gajofatto A, Alberti D, Lederer S, Monaco S, Ferrari S, Hoeftberger R (April 2019). "Flotillin-1/2 autoantibodies in patients with inflammatory disorders of the CNS". Neurology. 92 (15 Supplement): P2.2-072(P2. 2-072).
  94. ^ Koutsis G, Breza M, Velonakis G, Tzartos J, Kasselimis D, Kartanou C, et al. (February 2019). "X linked Charcot-Marie-Tooth disease and multiple sclerosis: emerging evidence for an association". Journal of Neurology, Neurosurgery, and Psychiatry. 90 (2): 187–194. doi:10.1136/jnnp-2018-319014. PMID 30196252. S2CID 52175657.
  95. ^ Yu-Wai-Man P, Spyropoulos A, Duncan HJ, Guadagno JV, Chinnery PF (September 2016). "A multiple sclerosis-like disorder in patients with OPA1 mutations". Annals of Clinical and Translational Neurology. 3 (9): 723–729. doi:10.1002/acn3.323. PMC 5018584. PMID 27656661.
  96. ^ Vojdani A, Mukherjee PS, Berookhim J, Kharrazian D (2015). "Detection of Antibodies against Human and Plant Aquaporins in Patients with Multiple Sclerosis". Autoimmune Diseases. 2015: 905208. doi:10.1155/2015/905208. PMC 4529886. PMID 26290755.
  97. ^ Baranova SV, Mikheeva EV, Buneva VN, Nevinsky GA (November 2019). "Antibodies from the Sera of Multiple Sclerosis Patients Efficiently Hydrolyze Five Histones". Biomolecules. 9 (11): 741. doi:10.3390/biom9110741. PMC 6920934. PMID 31731780.
  98. ^ Tzartos JS, Stergiou C, Kilidireas K, Zisimopoulou P, Thomaidis T, Tzartos SJ (2013). "Anti-aquaporin-1 autoantibodies in patients with neuromyelitis optica spectrum disorders". PLOS ONE. 8 (9): e74773. Bibcode:2013PLoSO...874773T. doi:10.1371/journal.pone.0074773. PMC 3781161. PMID 24086369.
  99. ^ Robers M, Tokhie H, Borazanci A (2018-04-10). "N-Type Calcium Channel Antibody Encephalitis Coexisting With Multiple Sclerosis (P5.397)". Neurology. 90 (15 Supplement). ISSN 0028-3878.
  100. ^ Faergeman SL, Evans H, Attfield KE, Desel C, Kuttikkatte SB, Sommerlund M, et al. (May 2020). "A novel neurodegenerative spectrum disorder in patients with MLKL deficiency". Cell Death & Disease. 11 (5): 303. doi:10.1038/s41419-020-2494-0. PMC 7195448. PMID 32358523.
  101. ^ Birnbaum J, Hoke A, Lalji A, Calabresi P, Bhargava P, Casciola-Rosen L (October 2018). "Brief Report: Anti-Calponin 3 Autoantibodies: A Newly Identified Specificity in Patients With Sjögren's Syndrome". Arthritis & Rheumatology. 70 (10): 1610–1616. doi:10.1002/art.40550. PMID 29749720.
  102. ^ Zhang Y, Wang L, Jia H, Liao M, Chen X, Xu J, et al. (July 2018). "Genetic variants regulate NR1H3 expression and contribute to multiple sclerosis risk". Journal of the Neurological Sciences. 390: 162–165. doi:10.1016/j.jns.2018.04.037. PMID 29801879. S2CID 44082278.
  103. ^ Yeo T, Probert F, Jurynczyk M, Sealey M, Cavey A, Claridge TD, et al. (November 2019). "Classifying the antibody-negative NMO syndromes: Clinical, imaging, and metabolomic modeling". Neurology. 6 (6): e626. doi:10.1212/NXI.0000000000000626. PMC 6865851. PMID 31659123.
  104. ^ Tohyama S, Hung PS, Cheng JC, Zhang JY, Halawani A, Mikulis DJ, et al. (May 2020). "Trigeminal neuralgia associated with a solitary pontine lesion: clinical and neuroimaging definition of a new syndrome". Pain. 161 (5): 916–925. doi:10.1097/j.pain.0000000000001777. PMC 7170433. PMID 31842151.
  105. ^ Minagar A, Jy W, Jimenez JJ, Alexander JS (April 2006). "Multiple sclerosis as a vascular disease". Neurological Research. 28 (3): 230–235. doi:10.1179/016164106X98080. PMID 16687046. S2CID 16896871.
  106. ^ "Chronic Fatigue Syndrome - Symptoms, Diagnosis, Treatment of Chronic Fatigue Syndrome". Health Information. New York Times. The following test results... are seen consistently...: Brain MRI showing swelling in the brain or destruction of part of the nerve cells (demyelination)
  107. ^ Bergner CG, Genc N, Hametner S, Franz J, van der Meer F, Mitkovski M, et al. (October 2021). "Concurrent axon and myelin destruction differentiates X-linked adrenoleukodystrophy from multiple sclerosis". Glia. 69 (10): 2362–2377. doi:10.1002/glia.24042. PMID 34137074.
  108. ^ a b "Link Between Gut Flora and Multiple Sclerosis Discovered". Neuroscience News. 2018-10-11. Retrieved 2022-06-29.
  109. ^ a b Planas R, Santos R, Tomas-Ojer P, Cruciani C, Lutterotti A, Faigle W, et al. (October 2018). "GDP-l-fucose synthase is a CD4+ T cell-specific autoantigen in DRB3*02:02 patients with multiple sclerosis". Science Translational Medicine. 10 (462): eaat4301. doi:10.1126/scitranslmed.aat4301. PMID 30305453. S2CID 52959112.
  110. ^ a b Ogawa K, Okuno T, Hosomichi K, Hosokawa A, Hirata J, Suzuki K, et al. (August 2019). "Next-generation sequencing identifies contribution of both class I and II HLA genes on susceptibility of multiple sclerosis in Japanese". Journal of Neuroinflammation. 16 (1): 162. doi:10.1186/s12974-019-1551-z. PMC 6683481. PMID 31382992.
  111. ^ a b Wang Z, Sadovnick AD, Traboulsee AL, Ross JP, Bernales CQ, Encarnacion M, et al. (June 2016). "Nuclear Receptor NR1H3 in Familial Multiple Sclerosis". Neuron. 90 (5): 948–954. doi:10.1016/j.neuron.2016.04.039. PMC 5092154. PMID 27253448.
  112. ^ Hain HS, Hakonarson H (June 2016). "The Added Value of Family Material in the Discovery of Multiple Sclerosis Genes". Neuron. 90 (5): 905–906. doi:10.1016/j.neuron.2016.05.027. PMID 27253441.
  113. ^ a b Cristofanilli M, Rosenthal H, Cymring B, Gratch D, Pagano B, Xie B, Sadiq SA (November 2014). "Progressive multiple sclerosis cerebrospinal fluid induces inflammatory demyelination, axonal loss, and astrogliosis in mice". Experimental Neurology. 261: 620–632. doi:10.1016/j.expneurol.2014.07.020. PMID 25111532. S2CID 21263405.
  114. ^ Ulloa B, Alahiri M, Liu Y, Sadiq S (2015). "Cerebrospinal Fluid Haptoglobin (Hp) Levels are elevated in MS patients with progressive disease". Neurology. 84 (14): 213.
  115. ^ Elkjaer ML, Nawrocki A, Kacprowski T, Lassen P, Simonsen AH, Marignier R, et al. (2020). "Molecular markers in the CSF proteome differentiate neuroinflammatory diseases". Research Square. doi:10.21203/rs.3.rs-19710/v1. S2CID 236819936.
  116. ^ Vernejoul J, Cali F, Lin J, Sadiq S (2020-04-14). "Single Cell Analysis of MS CSF B-Cells Show Significant Differences in Expansion Patterns and Gene Family Usage Between MS Subtypes (4673)". Neurology. 94 (15 Supplement). ISSN 0028-3878.
  117. ^ Vukusic S, Confavreux C (February 2003). "Primary and secondary progressive multiple sclerosis". Journal of the Neurological Sciences. 206 (2): 153–155. doi:10.1016/S0022-510X(02)00427-6. PMID 12559503. S2CID 19215860.
  118. ^ Dressel A, Kolb AK, Elitok E, Bitsch A, Bogumil T, Kitze B, et al. (December 2006). "Interferon-beta1b treatment modulates cytokines in patients with primary progressive multiple sclerosis". Acta Neurologica Scandinavica. 114 (6): 368–373. doi:10.1111/j.1600-0404.2006.00700.x. PMID 17083335. S2CID 71465403.
  119. ^ Villar LM, Casanova B, Ouamara N, Comabella M, Jalili F, Leppert D, et al. (August 2014). "Immunoglobulin M oligoclonal bands: biomarker of targetable inflammation in primary progressive multiple sclerosis". Annals of Neurology. 76 (2): 231–240. doi:10.1002/ana.24190. PMID 24909126. S2CID 16397501.
  120. ^ Curbelo M, Martinez A, Steinberg J, Carra A (April 2016). "LOMS vs. Other Diseases: The Consequence of "To Be or Not To Be"". Neurology. 86 (16 Supplement): P3.081.
  121. ^ Zwemmer JN, Bot JC, Jelles B, Barkhof F, Polman CH (April 2008). "At the heart of primary progressive multiple sclerosis: three cases with diffuse MRI abnormalities only". Multiple Sclerosis. 14 (3): 428–430. doi:10.1177/1352458507084591. PMID 18208890. S2CID 27178351.
  122. ^ Reinke SN, Broadhurst DL, Sykes BD, Baker GB, Catz I, Warren KG, Power C (September 2014). "Metabolomic profiling in multiple sclerosis: insights into biomarkers and pathogenesis". Multiple Sclerosis. 20 (10): 1396–1400. doi:10.1177/1352458513516528. PMID 24468817. S2CID 24226475.
  123. ^ Balk LJ, Tewarie P, Killestein J, Polman CH, Uitdehaag B, Petzold A (August 2014). "Disease course heterogeneity and OCT in multiple sclerosis". Multiple Sclerosis. 20 (9): 1198–1206. doi:10.1177/1352458513518626. PMID 24402036. S2CID 7737278.
  124. ^ Poser CM, Brinar VV (June 2004). "The nature of multiple sclerosis". Clinical Neurology and Neurosurgery. 106 (3): 159–171. doi:10.1016/j.clineuro.2004.02.005. PMID 15177764. S2CID 23522920.
  125. ^ Liguori M, Qualtieri A, Tortorella C, Direnzo V, Bagalà A, Mastrapasqua M, et al. (2014). "Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration". PLOS ONE. 9 (8): e103984. Bibcode:2014PLoSO...9j3984L. doi:10.1371/journal.pone.0103984. PMC 4123901. PMID 25098164.
  126. ^ Ramos I, Rehman IU, Sharrack B, Woodroofe N (2017-04-18). "Revealing underlying differences of NAWM from primary and secondary progressive MS (P4.404)". Neurology. 88 (16 Supplement). ISSN 0028-3878.
  127. ^ Abdelhak A, Weber MS, Tumani H (2017). "Primary Progressive Multiple Sclerosis: Putting Together the Puzzle". Frontiers in Neurology. 8: 234. doi:10.3389/fneur.2017.00234. PMC 5449443. PMID 28620346.
  128. ^ Acquaviva M, Bassani C, Sarno N, Dalla Costa G, Romeo M, Sangalli F, et al. (2019). "Loss of Circulating CD8+ CD161high T Cells in Primary Progressive Multiple Sclerosis". Frontiers in Immunology. 10: 1922. doi:10.3389/fimmu.2019.01922. PMC 6702304. PMID 31474991.
  129. ^ Quintana FJ, Patel B, Yeste A, Nyirenda M, Kenison J, Rahbari R, et al. (December 2014). "Epitope spreading as an early pathogenic event in pediatric multiple sclerosis". Neurology. 83 (24): 2219–2226. doi:10.1212/WNL.0000000000001066. PMC 4277672. PMID 25381299.
  130. ^ Lassmann H (2019). "Pathogenic Mechanisms Associated With Different Clinical Courses of Multiple Sclerosis". Frontiers in Immunology. 9: 3116. doi:10.3389/fimmu.2018.03116. PMC 6335289. PMID 30687321.
  131. ^ Hakiki B, Goretti B, Portaccio E, Zipoli V, Amato MP (August 2008). "'Subclinical MS': follow-up of four cases". European Journal of Neurology. 15 (8): 858–861. doi:10.1111/j.1468-1331.2008.02155.x. PMID 18507677. S2CID 27212599.
  132. ^ Lebrun C, Bensa C, Debouverie M, De Seze J, Wiertlievski S, Brochet B, et al. (February 2008). "Unexpected multiple sclerosis: follow-up of 30 patients with magnetic resonance imaging and clinical conversion profile". Journal of Neurology, Neurosurgery, and Psychiatry. 79 (2): 195–198. doi:10.1136/jnnp.2006.108274. PMID 18202208. S2CID 11750372.
  133. ^ Frisullo G, Nociti V, Iorio R, Patanella AK, Marti A, Mirabella M, et al. (December 2008). "The persistency of high levels of pSTAT3 expression in circulating CD4+ T cells from CIS patients favors the early conversion to clinically defined multiple sclerosis". Journal of Neuroimmunology. 205 (1–2): 126–134. doi:10.1016/j.jneuroim.2008.09.003. PMID 18926576. S2CID 27303451.
  134. ^ Hou Y, Jia Y, Hou J (July 2018). "Natural Course of Clinically Isolated Syndrome: A Longitudinal Analysis Using a Markov Model". Scientific Reports. 8 (1): 10857. Bibcode:2018NatSR...810857H. doi:10.1038/s41598-018-29206-y. PMC 6052069. PMID 30022111.
  135. ^ Mackay RP, Hirano A (December 1967). "Forms of benign multiple sclerosis. Report of two "clinically silent" cases discovered at autopsy". Archives of Neurology. 17 (6): 588–600. doi:10.1001/archneur.1967.00470300030007. PMID 6054893.
  136. ^ Engell T (May 1989). "A clinical patho-anatomical study of clinically silent multiple sclerosis". Acta Neurologica Scandinavica. 79 (5): 428–430. doi:10.1111/j.1600-0404.1989.tb03811.x. PMID 2741673. S2CID 21581253.
  137. ^ Lebrun C, Kantarci OH, Siva A, Pelletier D, Okuda DT (February 2018). "Anomalies Characteristic of Central Nervous System Demyelination: Radiologically Isolated Syndrome". Neurologic Clinics. 36 (1): 59–68. doi:10.1016/j.ncl.2017.08.004. PMID 29157404.
  138. ^ Gabelic T, Ramasamy DP, Weinstock-Guttman B, Hagemeier J, Kennedy C, Melia R, et al. (January 2014). "Prevalence of radiologically isolated syndrome and white matter signal abnormalities in healthy relatives of patients with multiple sclerosis". AJNR. American Journal of Neuroradiology. 35 (1): 106–112. doi:10.3174/ajnr.A3653. PMC 7966501. PMID 23886745.
  139. ^ Banwell B (June 2019). "Are children with multiple sclerosis really "old" adults". Multiple Sclerosis. 25 (7): 888–890. doi:10.1177/1352458519841505. PMID 30945591.
  140. ^ Gabelic T, Weinstock-Guttman B, Melia R, Lincoff N, Masud MW, Kennedy C, et al. (December 2013). "Retinal nerve fiber thickness and MRI white matter abnormalities in healthy relatives of multiple sclerosis patients". Clinical Neurology and Neurosurgery. 115 (Suppl 1): S49–S54. doi:10.1016/j.clineuro.2013.09.021. PMID 24321155. S2CID 41756033.
  141. ^ Rossi S, Motta C, Studer V, Macchiarulo G, Germani G, Finardi A, et al. (October 2015). "Subclinical central inflammation is risk for RIS and CIS conversion to MS". Multiple Sclerosis. 21 (11): 1443–1452. doi:10.1177/1352458514564482. PMID 25583841. S2CID 22377941.
  142. ^ Cramer SP, Modvig S, Simonsen HJ, Frederiksen JL, Larsson HB (September 2015). "Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis". Brain. 138 (Pt 9): 2571–2583. doi:10.1093/brain/awv203. PMC 4547053. PMID 26187333.
  143. ^ Cortese M (2017-12-18). Marianna, The timing of environmental risk factors and prodromal signs of multiple sclerosis (Ph.D. thesis).
  144. ^ Sazonov DV, Malkova NA, Bulatova EV, Riabukhina OV (2009). "[Combined therapy of aggressive remitted multiple sclerosis with mitoxantrone in combination with copaxone]". Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova. 109 (12): 76–79. PMID 20037526.
  145. ^ Rush CA, MacLean HJ, Freedman MS (July 2015). "Aggressive multiple sclerosis: proposed definition and treatment algorithm". Nature Reviews. Neurology. 11 (7): 379–389. doi:10.1038/nrneurol.2015.85. PMID 26032396. S2CID 205516534.
  146. ^ Magliozzi R, Howell OW, Nicholas R, Cruciani C, Castellaro M, Romualdi C, et al. (April 2018). "Inflammatory intrathecal profiles and cortical damage in multiple sclerosis" (PDF). Annals of Neurology. 83 (4): 739–755. doi:10.1002/ana.25197. PMID 29518260. S2CID 5042430.
  147. ^ Notas K, Papadaki E, Orologas A, Moschou M, Kimiskidis VK (February 2020). "Switching from fingolimod to alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis: Α case series". Multiple Sclerosis and Related Disorders. 38: 101517. doi:10.1016/j.msard.2019.101517. PMID 31751858. S2CID 208228516.
  148. ^ Chabas D, Castillo-Trivino T, Mowry EM, Strober JB, Glenn OA, Waubant E (September 2008). "Vanishing MS T2-bright lesions before puberty: a distinct MRI phenotype?". Neurology. 71 (14): 1090–1093. CiteSeerX 10.1.1.594.9445. doi:10.1212/01.wnl.0000326896.66714.ae. PMID 18824673. S2CID 24065442.
  149. ^ Alroughani R, Boyko A (March 2018). "Pediatric multiple sclerosis: a review". BMC Neurology. 18 (1): 27. doi:10.1186/s12883-018-1026-3. PMC 5845207. PMID 29523094.
  150. ^ van Rensburg SJ, Peeters AV, van Toorn R, Schoeman J, Moremi KE, van Heerden CJ, Kotze MJ (June 2019). "Identification of an iron-responsive subtype in two children diagnosed with relapsing-remitting multiple sclerosis using whole exome sequencing". Molecular Genetics and Metabolism Reports. 19: 100465. doi:10.1016/j.ymgmr.2019.100465. PMC 6434495. PMID 30963028.
  151. ^ Minagar A (2014). "Multiple Sclerosis: An Overview of Clinical Features, Pathophysiology, Neuroimaging, and Treatment Options". Colloquium Series on Integrated Systems Physiology: From Molecule to Function. 6 (4): 1–117. doi:10.4199/C00116ED1V01Y201408ISP055. S2CID 71379237.
  152. ^ Susman E (2016). "News from the ECTRIMS Congress". Neurology Today. 16 (21): 18–19. doi:10.1097/01.NT.0000508402.13786.97. S2CID 78597245.
  153. ^ Rovira À, Wattjes MP, Tintoré M, Tur C, Yousry TA, Sormani MP, et al. (August 2015). "Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-clinical implementation in the diagnostic process". Nature Reviews. Neurology. 11 (8): 471–482. doi:10.1038/nrneurol.2015.106. PMID 26149978.
  154. ^ Mistry N, Dixon J, Tallantyre E, Tench C, Abdel-Fahim R, Jaspan T, et al. (May 2013). "Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain". JAMA Neurology. 70 (5): 623–628. doi:10.1001/jamaneurol.2013.1405. PMID 23529352.
  155. ^ Schippling S (November 2017). "MRI for multiple sclerosis diagnosis and prognosis". Neurodegenerative Disease Management. 7 (6s): 27–29. doi:10.2217/nmt-2017-0038. PMID 29143579.
  156. ^ McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. (July 2001). "Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis". Annals of Neurology. 50 (1): 121–127. CiteSeerX 10.1.1.466.5368. doi:10.1002/ana.1032. PMID 11456302. S2CID 13870943.
  157. ^ Lassmann H (December 2014). "Multiple sclerosis: lessons from molecular neuropathology". Experimental Neurology. 262 (Pt A): 2–7. doi:10.1016/j.expneurol.2013.12.003. PMID 24342027. S2CID 25337149.
  158. ^ Kutzelnigg A, Faber-Rod JC, Bauer J, Lucchinetti CF, Sorensen PS, Laursen H, et al. (January 2007). "Widespread demyelination in the cerebellar cortex in multiple sclerosis". Brain Pathology. 17 (1): 38–44. doi:10.1111/j.1750-3639.2006.00041.x. PMC 8095596. PMID 17493036. S2CID 38379112.
  159. ^ Lebrun C, Kantarci OH, Siva A, Pelletier D, Okuda DT, et al. (RISConsortium) (February 2018). "Anomalies Characteristic of Central Nervous System Demyelination: Radiologically Isolated Syndrome". Neurologic Clinics. 36 (1): 59–68. doi:10.1016/j.ncl.2017.08.004. PMID 29157404.
  160. ^ Dutta R, Trapp BD (June 2006). "[Pathology and definition of multiple sclerosis]". La Revue du Praticien (in French). 56 (12): 1293–1298. PMID 16948216.
  161. ^ Quintana FJ, Patel B, Yeste A, Nyirenda M, Kenison J, Rahbari R, et al. (Canadian Pediatric Demyelinating Disease Network) (December 2014). "Epitope spreading as an early pathogenic event in pediatric multiple sclerosis". Neurology. 83 (24): 2219–2226. doi:10.1212/WNL.0000000000001066. PMC 4277672. PMID 25381299.
  162. ^ Dalla Costa G, Martinelli V, Sangalli F, Moiola L, Colombo B, Radaelli M, et al. (February 2019). "Prognostic value of serum neurofilaments in patients with clinically isolated syndromes". Neurology. 92 (7): e733–e741. doi:10.1212/WNL.0000000000006902. PMC 6382362. PMID 30635483.
  163. ^ Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. (February 2011). "Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria". Annals of Neurology. 69 (2): 292–302. doi:10.1002/ana.22366. PMC 3084507. PMID 21387374.
  164. ^ Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sørensen PS, Thompson AJ, et al. (July 2014). "Defining the clinical course of multiple sclerosis: the 2013 revisions". Neurology. 83 (3): 278–286. doi:10.1212/WNL.0000000000000560. PMC 4117366. PMID 24871874.
  165. ^ Dalton CM, Brex PA, Miszkiel KA, Hickman SJ, MacManus DG, Plant GT, et al. (July 2002). "Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis". Annals of Neurology. 52 (1): 47–53. doi:10.1002/ana.10240. PMID 12112046. S2CID 24039151.

March 04, 2023
inflammatory, demyelinating, diseases, central, nervous, system, this, article, needs, more, medical, references, verification, relies, heavily, primary, sources, specifically, relies, heavily, primary, sources, please, review, contents, article, appropriate, . This article needs more medical references for verification or relies too heavily on primary sources specifically It relies too heavily on primary sources Please review the contents of the article and add the appropriate references if you can Unsourced or poorly sourced material may be challenged and removed Find sources Inflammatory demyelinating diseases of the central nervous system news newspapers books scholar JSTOR June 2022 This article may be confusing or unclear to readers Please help clarify the article There might be a discussion about this on the talk page July 2022 Learn how and when to remove this template message Inflammatory demyelinating diseases IDDs sometimes called Idiopathic IIDDs due to the unknown etiology of some of them are a heterogenous group of demyelinating diseases conditions that cause damage to myelin the protective sheath of nerve fibers that occur against the background of an acute or chronic inflammatory process 1 2 3 IDDs share characteristics with and are often grouped together under Multiple Sclerosis They are sometimes considered different diseases from Multiple Sclerosis 4 5 but considered by others to form a spectrum differing only in terms of chronicity severity and clinical course 6 7 Multiple sclerosis for some people is a syndrome more than a single disease 8 As of 2019 three auto antibodies have been found in atypical MS giving birth to separate diseases Anti AQP4 diseases Anti MOG and Anti NF spectrums 9 A LHON associated MS 10 has also been reported and in addition there have been inconclusive reports of TNF a blockers inducing demyelinating disorders 11 The subject is under intense research and the list of MS autoantibodies is expected to grow in the near future 12 13 14 Contents 1 Separated variants 1 1 Anti AQP4 spectrum 1 2 Anti MOG spectrum 1 3 Anti neurofascin spectrum 1 4 Demyelination associated with anti TNF therapy 1 5 LHON associated MS 1 6 Relapsing anti NMDAR encephalitis 2 Variants still idiopathic 2 1 Pseudotumefactive variants 2 2 Atypical lesion location variants 2 2 1 Myelocortical multiple sclerosis 2 2 2 AQP4 negative Optic spinal MS 2 2 3 Pure spinal MS 2 2 4 LHON associated MS 2 3 Atypical OCB variants 2 4 Radiologically atypical variants 2 5 Atypical clinical courses 2 5 1 Highly Active MS 2 5 2 Malignant MS 2 5 3 Aggressive MS 2 5 4 Rapidly progressive multiple sclerosis 3 Under research 4 Genetic types 4 1 HLA DRB3 02 02 patients 4 2 Rapidly progressive multiple sclerosis 5 Primary progressive variants 6 Clinical situations inside standard MS 6 1 Preclinical MS CIS and CDMS 6 2 RIS subclinical and silent MS 6 3 Aggressive multiple sclerosis 6 4 Pediatric and pubertal MS 7 Controversy for the definition 7 1 Pathological and clinical definitions 7 2 Other meanings of MS 7 3 Handling several clinical definitions 7 4 CIS and conversion to MS 8 See also 9 ReferencesSeparated variants EditSeveral previous MS variants have been recently separated from MS after the discovery of a specific auto antibody Those autoantibodies are currently anti AQP4 anti MOG and some anti Neurofascins 15 The pathogenic mechanism is usually not related to the clinical course Therefore one given pathogenic underlying condition can yield several clinical diseases and one disease can be produced by several pathogenic conditions citation needed These conditions can appear as Neuromyelitis optica NMO and its associated spectrum of disorders NMOSD currently considered a common syndrome for several separated diseases 16 but with some still idiopathic subtypes Some researchers think that there could exist an overlapping between Anti NMDA receptor encephalitis cases and neuromyelitis optica or acute disseminated encephalomyelitis 17 Anti AQP4 spectrum Edit See Anti AQP4 diseasesOriginally found in neuromyelitis optica this autoantibody has been associated with other conditions Its current spectrum is as following Seropositive Devic s disease according to the diagnostic criteria described above Limited forms of Devic s disease such as single or recurrent events of longitudinally extensive myelitis and bilateral simultaneous or recurrent optic neuritis Asian optic spinal MS this variant can present brain lesions like MS 18 Longitudinally extensive myelitis or optic neuritis associated with systemic autoimmune disease Optic neuritis or myelitis associated with lesions in specific brain areas such as the hypothalamus periventricular nucleus and brainstem 19 Some cases of tumefactive multiple sclerosis 20 Anti MOG spectrum Edit See Anti MOG associated encephalomyelitisAnti MOG associated spectrum often clinically presented as an anti MOG autoimmune encephalomyelitis 21 22 but can also appear as negative NMO or atypical multiple sclerosis 23 The presence of anti MOG autoantibodies has been associated with the following conditions 24 Some cases of aquaporin 4 seronegative neuromyelitis optica NMO derived from an antiMOG associated encephalomyelitis 22 Some cases of acute disseminated encephalomyelitis specially the recurrent ones MDEM 25 Some cases of McDonalds positive multiple sclerosis 24 26 23 27 isolated optic neuritis or transverse myelitis 24 Recurrent optic neuritis The repetition of an idiopatic optic neuritis is considered a distinct clinical condition and it has been found to be associated with anti MOG autoantibodies 28 CRION Chronic relapsing inflammatory optic neuritis A distinct clinical entity from other inflammatory demyelinating diseases 29 Some reports consider it a form of Anti MOG encephalomyelitis 30 and the most recent ones consider it the main phenotype of the anti MOG spectrum 31 The anti mog spectrum in children is equally variated Out of a sample of 41 children with MOG antibodies 29 had clinical NMOSD 17 relapsing 8 had ADEM 4 relapsing with ADEM ON 3 had a single clinical event CIS and 1 had a relapsing tumefactive disorder Longitudinal myelitis was evident on MRI in 76 percent It has also been noted that percentage of children with anti mog antibodies respect a demyelinating sample is higher than for adults 32 Some NMO patients present double positive for autoantibodies to AQP4 and MOG These patients have MS like brain lesions multifocal spine lesions and retinal and optic nerves atrophy 33 Anti neurofascin spectrum Edit See Anti neurofascin demyelinating diseasesSome anti neurofascin demyelinating diseases were previously considered a subtype of Multiple Sclerosis but now they are considered a separate entity as it happened before to anti MOG and anti AQP4 cases Around 10 of MS cases are now thought to be anti Neurofascin disease in reality 34 Anti neurofascin autoantibodies have been reported in atypical cases of MS and CIDP and a whole spectrum of Anti neurofascin demyelinating diseases has been proposed 35 Some cases of CIDP are reported to be produced by auto antibodies against several neurofascin proteins These proteins are present in the neurons and four of them have been reported to produce disease NF186 NF180 NF166 and NF155 35 Antibodies against Neurofascins NF 155 can also appear in MS 36 and NF 186 could be involved in subtypes of MS 37 yielding an intersection between both conditions Summarising autoantibodies against several neurofascins can produce MS neurofascin186 NF186 neurofascin155 NF155 contactin 1 CNTN1 contactin associated protein 1 CASPR1 and gliomedin All of them nodal and paranodal proteins 35 Demyelination associated with anti TNF therapy Edit Main article TNF inhibitor Several anti TNF drugs like adalimumab 38 39 are commonly prescribed by a number of autoimmune conditions Some of them have been reported to produce a CNS demyelination compatible with standard MS 11 40 41 Several other monoclonal antibodies like pembrolizumab 42 nivolumab 43 and infliximab 44 have been also reported to produce MS as an adverse event 45 11 Nevertheless it is not so similar as reported in the previous references 46 improper synthesis clarification needed The reactions following Anti TNF therapy have been diverse according to the source of the disease 40 41 43 failed verification Some of these cases can be classify as ADEM using the confluent demyelination as barrier between both conditions 47 non primary source needed In most cases the damage fulfills all pathological diagnostic criteria of MS and can therefore be classified as MS in its own right medical citation needed The lesions were classified as pattern II in the Lassman Lucchinetti system Some lesions also showed Dawson fingers 41 improper synthesis which is supposed to be a MS only feature These recent problems with artificial anti TNF a autoimmunity also point to the possibility of tumor necrosis factor alpha involvement in some multiple sclerosis variants medical citation needed LHON associated MS Edit Also a previous subtype of MS associated to LHON has been described LHON MS 10 It is a presentation of LHON with MS like CNS damage It used to satisfy McDonalds definition for MS but after demonstration that LHON can produce this kind of lesions the no better explanation requirement does not hold anymore It is not due to auto antibodies but to defective mitochondria instead 48 The symptoms of this higher form of the disease include loss of the brain s ability to control the movement of muscles tremors and cardiac arrhythmia 49 and the lack of muscular control 50 Relapsing anti NMDAR encephalitis Edit Atypical Anti NMDA receptor encephalitis a kind of Autoimmune encephalitis can appear in the form of relapsing optic neuritis 51 failed verification non primary source needed Variants still idiopathic EditApart of the previously cited spectrums Anti AQP4 diseases Anti MOG and Anti NF there is a long list of MS variants with possibly different pathogenesis which are still idiopathic and considered inside the MS spectrum Pseudotumefactive variants Edit Most atypical variants appear as tumefactive or pseudotumefactive variants lesions whose size is more than 2 cm 0 79 in with mass effect oedema and or ring enhancement 52 53 Some cases of the following have shown anti MOG auto antibodies and therefore they represent MS cases only partially citation needed Acute disseminated encephalomyelitis or ADEM a closely related disorder in which a known virus or vaccine triggers autoimmunity against myelin Around 40 of the ADEM cases are due to an anti MOG associated encephalomyelitis 24 It includes Acute hemorrhagic leukoencephalitis possibly a variant of Acute disseminated encephalomyelitis Marburg multiple sclerosis an aggressive form also known as malignant fulminant or acute MS currently reported to be closer to anti MOG associated ADEM than to standard MS 54 and is sometimes considered a synonym for Tumefactive multiple sclerosis 55 Balo concentric sclerosis an unusual presentation of plaques forming concentrenic circles which can sometimes get better spontaneously Schilder disease or diffuse myelinoclastic sclerosis is a rare disease that presents clinically as a pseudotumoural demyelinating lesion and is more common in children 56 57 Solitary sclerosis This variant has been recently proposed 2012 by Mayo Clinic researchers 58 though it was also reported by other groups more or less at the same time 59 60 It is defined as isolated demyelinating lesions which produce a progressive myelopathy similar to primary progressive MS Atypical lesion location variants Edit Also the location of the lesions can be used to classify variants Myelocortical multiple sclerosis Edit Myelocortical multiple sclerosis MCMS proposed variant with demyelination of spinal cord and cerebral cortex but not of cerebral white matter 61 Several atypical cases could belong here See the early reports of MCMS lt 62 63 AQP4 negative Optic spinal MS Edit Real Optic spinal MS OSMS without anti AQP4 antibodies has been consistently reported and it is classified into the MS spectrum 64 65 OSMS has its own specific immunological biomarkers 66 The whole picture is under construction and several reports exists about overlapping conditions Pure spinal MS Edit Pure spinal multiple sclerosis Patients with clinical and paraclinical features suggestive of cord involvement of multiple sclerosis MS type albeit not rigidly fulfilling the McDonald criteria 67 Some inflammatory conditions are associated with the presence of scleroses in the CNS 68 Optic neuritis monophasic and recurrent and Transverse myelitis monophasic and recurrent LHON associated MS Edit LHON associated MS LHON MS a presentation of LHON with MS like CNS damage and therefore a subtype of MS according to McDonalds definition 10 Atypical OCB variants Edit Also different classifications by body fluid biomarkers is possible Oligoclonal negative MS Some reports point to the possibility of a different pathogenesis 69 They represent around 5 of the cases 70 which is suspected to be immunogenetically different 71 Their evolution is better than standard MS patients 72 Oligoclonal IgM positive MS with immunoglobulin M Bands IgM Bands which accounts for a 30 40 of the MS population and has been identified as a predictor of MS severity 73 It has been reported to have a poor response to interferon beta but a better response to glatimer acetate instead 74 OCB s types OCBs are made up of activated B cells It seems that the molecular targets for the OCB s are patient specific 75 Radiologically atypical variants Edit Inside well defined MS Lesions disseminated in time and space with no other explanation there are atypical cases based in radiological or metabolic criteria A four groups classification has been proposed 76 Tumefactive demyelinating lesion TDL onset MS Acute disseminated encephalomyelitis ADEM like MS Multiple sclerosis with cavitary lesions Atypical multiple sclerosis cases similar to vanishing white matter disease but etiologically different from both 77 Lesions similar to vanishing white matter disease 77 Leukodystrophy like MS Other radiological classification of atypical lesions proposes the following four subtypes 78 infiltrative megacystic Balo like ring like lesionsAtypical clinical courses Edit In 1996 the US National Multiple Sclerosis Society NMSS Advisory Committee on Clinical Trials in Multiple Sclerosis ACCTMS standardized four clinical courses for MS Remitent Recidivant Secondary Progressive Progressive Relapsing and Primary progressive Later 79 some reports state that those types were artificially made up trying to classify RRMS as a separate disease so that the number of patients was low enough to get the interferon approved by the FDA under the orphan drugs act 79 Revisions in 2013 and 2017 removed the Progressive Relapsing course and introduced CIS as a variety course status of MS establishing the actual classification CIS RRMS SPMS and PPMS Nevertheless these types are not enough to predict the responses to medications and several regulatory agencies use additional types in their recommendations lide Highly active MS Malignant MS Aggressive MS or Rapidly progressive MS 80 Highly Active MS Edit As of 2019 HAMS is defined as an RRMS phenotype with one or more of the following characteristics 80 DSS scale of 4 points at 5 years of onset of the disease Multiple relapses two or more with incomplete recovery in the ongoing year More than 2 brain magnetic resonance imaging MRI studies demonstrating new lesions or increase in the size of the lesions in T2 or lesions that enhance with gadolinium despite treatment Clinical case 1 and 2 No response to treatment with one or more DMTs for at least one year There is a group of patients who have defined clinical and radiological risk factors that predict a behavior of greater risk of conversion to HAMS without having the diagnostic criteria of HAMS in a first clinical attack have predictors of high risk Some other previous authors have used other definitions like High activity according to 2017 definition of activity Rapid accumulation of physical and cognitive deficit despite treatment with DMT s Being eligible for immunoablative therapy followed by autologous haematopoietic stem cell transplantation aHSCT because of a the failure of conventional treatment b frequent and severe disabling relapses or c MRI activity new T2 or gadolinium enhancing lesions Malignant MS Edit See malignant multiple sclerosisOccasionally the term malignant MS MMS has been used to describe aggressive phenotypes of MS but this is another ambiguous term that despite wide usage means different things to different people In 1996 the US National MS Society NMSS Advisory Committee on Clinical Trials in Multiple Sclerosis malignant MS was also included namely disease with a rapid progressive course leading to significant disability in multiple neurologic systems or death in a relatively short time after disease onset full citation needed Many authors who reserve the term malignant for fulminant forms of MS that deteriorate so rapidly from the outset as to be almost monophasic and result in death within months to a few years One such example is the Marburg variant of MS which is classically characterized by extensive necrotic and or tumefactive lesions with mass effect Despite recent and increasing emphasis on early detection of patients with aggressive MS the original definition of MMS was not modified by the NMSS Advisory Committee in its latest publication in 2013 Lublin et al 2014 full citation needed Aggressive MS Edit Common to all definitions is the early unexpected acquisition of disability followed by frequent relapses and highly active disease seen on MRI One definition can be based on EDSS score and the time to develop secondary progressive MS SPMS Menon et al 2013 full citation needed No consensus exists on the speed of progression or degree of disability sufficient for aggressive MS but some assume that reaching an EDSS score of 6 points probably represents an upper limit beyond which the risk benefit ratio for an aggressive treatment is unfavourable citation needed Pragmatically AMS has been defined as any type of MS that is associated with repeated severe attacks and accelerated accrual of disability put more simply rapidly progressive MS Rapidly progressive multiple sclerosis Edit This kind of MS was previously reported to behave different that the standard progressive course 81 being linked to Connexin 43 autoantibodies with pattern III lesions distal oligodendrogliopathy 82 and being responsive to plasma exchange 83 In very rapidly progressive multiple sclerosis the use of immunosuppressive therapy mitoxantrone cyclophosphamide rituximab autologous haematopoietic stem cell therapy or combination therapy should be considered carefully 84 Under research EditSome auto antibodies have been found consistently across different MS cases but there is still no agreement on their relevance HEPACAM A cross reactivity between HepaCam GlialCam and EBNA1 has been reported as of 2022 on 25 of MS cases 85 Anti kir4 1 A KIR4 1 multiple sclerosis variant was reported in 2012 86 and later reported again 87 which could be considered a different disease as Devic s disease did before and can represent up to a 47 of the MS cases Anoctamin 2 Auto antibodies against anoctamin 2 ANO 2 one of the ion channel proteins have been reported consistently since 2013 88 This finding is not universal Most of the MS patients do not show auto antibodies against ANO 2 Therefore this points toward an ANO2 autoimmune sub phenotype in MS 89 Later reports point towards a mimicry between ANO 2 and EBV EBNA 1 protein 90 Anti NMDAR autoantibodies There is an overlap between cases of Anti NMDA receptor encephalitis and MS NMO and ADEM 17 It also could be a confusion with Anti NMDA receptor encephalitis in the early stages 91 but there are also anti NMDAR reported cases that evolve to McDonalds MS 92 Anti Flotilin spectrum The proteins Flotillin 1 and flotillin 2 have been recently identified as target antigens in some patients with multiple sclerosis First 14 cases were reported together in the first report and 3 new cases were reported later inside a cohort of 43 patients 93 Mutations in GJB1 coding for connexin 32 a gap junction protein expressed in Schwann cells and oligodendrocytes that usually produce Charcot Marie Tooth disease In some cases also MS as defined by McDonalds criteria can appear in these patients 94 Also an OPA1 variant 95 exists There exist some reports by Drs Aristo Vojdani Partha Sarathi Mukherjee Joshua Berookhim and Datis Kharrazian of an aquaporin related multiple sclerosis related to vegetal aquaporin proteins 96 Auto antibodies against histones have been reported to be involved 97 Anti AQP1 could be involved in atypical MS and NMO 98 N type calcium channel antibodies can produce cognitive relapses mimicking MS related cognitive decline and may coexist with MS 99 MLKL MS Mixed lineage kinase domain like pseudokinase MLKL related MS A preliminary report has pointed out evidence of a novel neurodegenerative spectrum disorder related to it 100 Other auto antibodies can be used to stablish a differential diagnosis from very different diseases like Sjogren syndrome which can be separated by Anti Calponin 3 autoantibodies 101 The correlation between this genetic mutation and MS was challenged but in 2018 has been replicated by an independent team 102 Notice that this results do not refer to general MS In general NMO like spectrum without known auto antibodies is considered MS Principal component analysis of these cases show 3 different kinds of antibody negative patients The metabolite discriminators of RRMS and Ab NMOSD suggest that these groupings have some pathogenic meaning 103 As MS is an active field for research the list of auto antibodies is not closed nor definitive For example some diseases like Autoimmune GFAP Astrocytopathy or variants of CIDP that affects the CNS CIDP is the chronic counterpart of Guillain Barre syndrome could be included Autoimmune variants peripheral neuropathies or progressive inflammatory neuropathy could be in the list assuming the autoimmune model for MS together with a rare demyelinating lesional variant of trigeminal neuralgia 104 failed verification and some NMDAR Anti NMDA receptor encephalitis 54 Venous induced demyelination has also been proposed as a hypothetical MS variant produced by CCSVI Susac s syndrome and Neuro Behcet s disease MS has an important vascular component 105 myalgic encephalomyelitis aka chronic fatigue syndrome 106 Also leukoaraiosis can produce lesions disseminated in time and space condition usually sufficient in the MS definition Maybe two sub conditions of Leukodystrophy Adrenoleukodystrophy and Adrenomyeloneuropathy could be in the list Specially interesting is X linked adrenoleukodystrophy X ALD or CALD 107 Genetic types EditDifferent behaviour has been reported according to the presence of different HLA genes HLA DRB3 02 02 patients Edit In HLA DRB3 cases autoimmune reactions against the enzyme GDP L fucose synthase has been reported 108 109 The same report points that the autoimmune problem could derive from the gut microbiota HLA DRB1 15 01 has the strongest association with MS 110 HLA DRB1 04 05 HLA B 39 01 and HLA B 15 01 are associated with independent MS susceptibility and HLA DQb1 position 9 with phenylalanine had the strongest effect on MS susceptibility 110 Another possible type is one with auto antibodies against GDP L fucose synthase In HLA DRB3 02 02 patients autoimmune reactions against the enzyme GDP L fucose synthase has been reported 108 109 The same report points that the autoimmune problem could derive from the gut microbiota Rapidly progressive multiple sclerosis Edit See malignant multiple sclerosisThis is a specially aggressive clinical course of progressive MS 111 that has been found to be caused by a special genetic variant It is due to a mutation inside the gene NR1H3 an arginine to glutamine mutation in the position p Arg415Gln in an area that codifies the protein LXRA 112 Primary progressive variants EditSome researchers propose to separate primary progressive MS from other clinical courses PPMS after recent findings seem to point that it is pathologically a very different disease 113 114 115 116 non primary source needed Some authors think since long ago that primary progressive MS should be considered a disease different from standard MS 117 118 and it was also proposed that PPMS could be heterogeneous 119 Clinical variants have been described For example Late Onset MS 120 111 It is due to a mutation inside the gene NR1H3 an arginine to glutamine mutation in the position p Arg415Gln in an area that codifies the protein LXRA For the rest of the progressive cases it has been found that the lesions are diffuse instead of the normal focal ones 121 and are different under MR spectroscopy 122 RRMS and PPMS patients also show differences on the retinal layers yields examined under OCT 123 Some authors have proposed a dual classification of PPMS according to the shape of edges of the scars in MS like and ADEM like 124 Proteomic analysis have shown that two proteins Secretogranin II and Protein 7B2 in CSF can be used to separate RRMS from PPMS 125 Recently the hypothesis of PPMS being apart from RRMS SPMS is taken further credibility due that it was shown that CSF from PPMS patients can carry the disease to other animals producing neurodegeneration in mice 113 and that Normal Appearing White Matter NAWM structure is also different 126 non primary source needed The predominant lesions in PPMS are slowly expanding lesions with T cells microglial and macrophage associated demyelination in close similar to pattern I demyelination 127 As of 2019 it has been found that the profile of T cells is different in PPMS and SPMS 128 non primary source needed Clinical situations inside standard MS EditMS can be considered among the acquired demyelinating syndromes with a multiphasic instead of monophasic behaviour 129 Multiple sclerosis has a prodromal stage in which an unknown underlying condition able to damage the brain is present but no lesion has still developed MS is usually classified in clinical types though they are unrelated to the underlying pathology Some critical reports say that the current types were artificially made up just to treat RRMS as a separate disease In this way the number of patients was low enough to enter the orphan drugs act and get the interferon approved by the FDA under this schema 79 Recent reviews state that all types are a mixture of inflammation and neurodegeneration and that all types should be considered the same disease 130 Other possible clinical courses are Preclinical MS CIS and CDMS Edit The first manifestation of MS is the so called Clinically isolated syndrome or CIS which is the first isolated attack The current diagnosis criteria for MS do not allow doctors to give an MS diagnosis until a second attack takes place Therefore the concept of clinical MS for an MS that can be diagnosed has been developed Until MS diagnosis has been established nobody can tell whether the disease one is dealing with is MS citation needed Cases of MS before the CIS are sometimes found during other neurological inspections and are referred to as subclinical MS 131 Preclinical MS refers to cases after the CIS but before the confirming second attack 132 After the second confirming attack the situation is referred to as CDMS clinically defined multiple sclerosis 133 CIS itself is sometimes considered itself as a disease entity different from MS Even if they share the same underlying condition CIS is not MS given that it lacks the presence of lesions 134 Approximately 84 of the subjects with CIS experience a second clinical demyelinating event and are diagnosed with clinically definite MS CDMS within 20 years RIS subclinical and silent MS Edit See also Radiologically isolated syndromeSilent MS has been found in autopsies before the existence of MRI 135 showing that the so called clinical definitions cannot be applied to around 25 of the MS cases 136 Currently a distinction is made between silent and subclinical In absence of attacks sometimes a radiological finding suggestive of demyelination T2 hyperintensities 137 can be used to establish a pre diagnosis of MS This is often named Radiologically Isolated Syndrome RIS Cases before the first attack or CIS are subclinical in the sense that they do not produce clinical situations If a second radiological event appears without clinical consequences the clinical situation is named Silent MS Okuda criteria 138 Anyway it is reported that all MS cases have an active subclinical phase before the CIS 139 It has been noted that some aspects of the MS underlying condition are present in otherwise healthy MS patients relatives 140 suggesting a wider scope for the silent MS term In these cases Interleukin 8 is a risk for clinical conversion 141 It has also been proposed that always exists a subclinical phase in the beginning of every MS case during which the permeability of the BBB can be used for diagnosis 142 It is also under investigation whether MS has a prodrome i e a preliminary stage in which the disease exists with non specific symptoms Some reports point to a prodrome of several years for RRMS and decades for PPMS 143 Aggressive multiple sclerosis Edit Relapsing Remitting MS is considered aggressive when the frequency of exacerbations is not less than 3 during 2 years Special treatment is often considered for this subtype 144 According to these definition aggressive MS would be a subtype of RRMS Other authors disagree and define aggressive MS by the accumulation of disability considering it as a rapidly disabling disease course 145 and therefore inside PPMS The aggressive course is associated to grey matter damage and meningeal inflammation and presents a special intrathecal meninges and CSF inflammatory profile 146 After the 2016 revision of the MS phenotypes it is called Highly active multiple sclerosis 80 Mitoxantrone was approved for this special clinical course Some reports point to Alemtuzumal being beneficial 147 Pediatric and pubertal MS Edit MS cases are rare before puberty but they can happen Whether they constitute a separate disease is still an open subject Anyway even this pubertal MS could be more than one disease because early onset and late onset have different demyelination patterns 148 Pediatric MS patients tend to have active inflammatory disease course with a tendency to have brainstem cerebellar presentations at onset Due to efficient repair mechanisms at early life pediatric MS patients tend to have longer time to reach EDSS 6 but reach it at earlier age 149 An iron responsive variant of MS has been reported in children 150 Controversy for the definition EditGiven that the etiology of MS is unknown the current definitions of MS are all based on its appearance medical citation needed The most commonly used definition the McDonald criteria requires just the presence of demyelinating lesions separated in space and time together with the exclusion of every known demyelinating condition medical citation needed This unspecific definition has been criticized For some people this has turned MS into a heterogeneous condition with several underlying problems 151 Besides the complementary problem also exists Given that McDonalds MS is based just in the distribution of the lesions even twins with the same underlying condition can be classified different 152 Finally the exclusion of every other known disease condition also creates problems Rightfully classified MS patients can be rightfully classified out of the spectrum when their particular underlying problem is discovered For example neuromyelitis optica was previously considered MS and currently is not even if it appears that the MS definition has not changed medical citation needed Currently there is no single diagnosis test for MS that is 100 sensitive and specific 153 154 Pathological and clinical definitions Edit McDonald criteria propose a clinical diagnosis based on a pathological definition saying that the focus for diagnosis remains on the objective demonstration of dissemination of lesions in both time and space DIT and DIS But given that other diseases produce similar lesions it is also required that those lesions cannot be explained by any other known disease citation needed This open definition present problems 155 For example before the discovery of anti AQP4 in 2006 most optic spinal MS patients were classified rightfully as MS Currently they are classified as NMO Both diagnosis are correct even though the definition has not apparently changed According to some pathologists a pathological definition is required because clinical definitions have problems with differential diagnosis 43 and they always use a pathological definition on articles about post mortem retrospective diagnosis but for practitioners that need a diagnosis as soon as possible MS is often regarded as a pure clinical entity defined simply by a positive result in the standard clinical case definition being then named clinically definite MS CDMS Poser or simply MS McDonald 156 Both definitions lead to different results For example confluent subpial cortical lesions are the most specific finding for MS being exclusively present in MS patients 157 but can only be detected post mortem by an autopsy 158 Therefore any other diagnosis method will have false positives Other meanings of MS Edit There is no known etiology for MS and therefore no etiology based definition is possible Comparison to a post mortem retrospective diagnosis is possible but useless to practitioners and short term researchers and it is not usually done Therefore all meanings for the words Multiple Sclerosis are somehow diffuse citation needed The pathological definition based on proven dissemination in time and space has problems For example it leaves situations like RIS radiologically isolated syndrome outside the MS spectrum because the lack of proof even in the case that this condition later could shown the same pathogenic conditions than MS cases 159 Besides usually the term multiple sclerosis is used to refer to the presence of the unknown underlying condition that produces the MS lesions instead to the mere presence of the lesions The term MS is also used to refers to the process of developing the lesions 160 Some authors instead speak about the biological disease vs its clinical presentation 161 Anyway the precise meaning in each case can be normally deduced from the context Handling several clinical definitions Edit Given that several definitions of MS coexist some authors are referring to them using whether CDMS for Poser positives or McDonalds MS with a prefix for McDonalds positives including the release year in the prefix 162 CIS and conversion to MS Edit The 2010 revision of the McDonald criteria 163 allows the diagnosis of MS with only one proved lesion CIS Consistently the later revision for the MS phenotypes in 2013 was forced to consider CIS as one of the MS phenotypes 164 Therefore the former concept of Conversion from CIS to MS that was declared when a patient had a second MS attack does not apply anymore More accurate is now to speak about conversions from the CIS phenotype to other MS phenotype 165 See also EditDemyelinating disease Pathophysiology of multiple sclerosis The Myelin ProjectReferences Edit Hoftberger R Lassmann H 2018 Inflammatory demyelinating diseases of the central nervous system Handbook of Clinical Neurology 145 263 283 doi 10 1016 B978 0 12 802395 2 00019 5 ISBN 9780128023952 PMC 7149979 PMID 28987175 Find out more about demyelinating diseases including multiple sclerosis Mayo Clinic Retrieved 2022 06 23 Fontaine B September 2001 Borderline forms of multiple sclerosis Revue Neurologique in French 157 8 9 Pt 2 929 934 PMID 11787357 Wingerchuk DM Lucchinetti CF June 2007 Comparative immunopathogenesis of acute disseminated encephalomyelitis neuromyelitis optica and multiple sclerosis Current Opinion in Neurology 20 3 343 350 doi 10 1097 WCO 0b013e3280be58d8 PMID 17495631 S2CID 17386506 Poser CM Brinar VV October 2007 Disseminated encephalomyelitis and multiple sclerosis two different diseases a critical review Acta Neurologica Scandinavica 116 4 201 206 doi 10 1111 j 1600 0404 2007 00902 x PMID 17824894 S2CID 44411472 Weinshenke B Miller D 1999 01 13 Multiple sclerosis one disease or many In Siva A Kesselring J Thompson AJ eds Frontiers in Multiple Sclerosis II Taylor amp Francis pp 37 46 ISBN 978 1 85317 506 0 Hartung HP Grossman RI May 2001 ADEM distinct disease or part of the MS spectrum Neurology 56 10 1257 1260 doi 10 1212 WNL 56 10 1257 PMID 11376169 S2CID 219199163 Zabad RK Stewart R Healey KM October 2017 Pattern Recognition of the Multiple Sclerosis Syndrome Brain Sciences 7 10 138 doi 10 3390 brainsci7100138 PMC 5664065 PMID 29064441 Fujihara K June 2019 Neuromyelitis optica spectrum disorders still evolving and broadening Current Opinion in Neurology 32 3 385 394 doi 10 1097 WCO 0000000000000694 PMC 6522202 PMID 30893099 a b c Bargiela D Chinnery PF September 2019 Mitochondria in neuroinflammation Multiple sclerosis MS leber hereditary optic neuropathy LHON and LHON MS Neuroscience Letters 710 132932 doi 10 1016 j neulet 2017 06 051 PMID 28668384 S2CID 38817368 a b c Kemanetzoglou Elissavet Andreadou Elisabeth 2017 CNS Demyelination with TNF a Blockers Current Neurology and Neuroscience Reports 17 4 36 doi 10 1007 s11910 017 0742 1 ISSN 1528 4042 PMC 5364240 PMID 28337644 Lang K Pruss H September 2017 Frequencies of neuronal autoantibodies in healthy controls Estimation of disease specificity Neurology 4 5 e386 doi 10 1212 NXI 0000000000000386 PMC 5515597 PMID 28761905 Kusunoki S December 2013 Autoantibodies in neuroimmunological diseases relevance of fine specificity Experimental Neurology 250 219 220 doi 10 1016 j expneurol 2013 10 009 PMID 24120752 S2CID 45173537 Seay M Galetta S September 2018 Glial Fibrillary Acidic Protein Antibody Another Antibody in the Multiple Sclerosis Diagnostic Mix Journal of Neuro Ophthalmology 38 3 281 284 doi 10 1097 WNO 0000000000000689 PMID 29923872 S2CID 49310332 Sato DK Callegaro D Lana Peixoto MA Waters PJ de Haidar Jorge FM Takahashi T et al February 2014 Distinction between MOG antibody positive and AQP4 antibody positive NMO spectrum disorders Neurology 82 6 474 481 doi 10 1212 WNL 0000000000000101 PMC 3937859 PMID 24415568 Weinshenker BG Wingerchuk DM February 2014 The two faces of neuromyelitis optica Neurology 82 6 466 467 doi 10 1212 WNL 0000000000000114 PMID 24415570 S2CID 30860834 a b Gahr M Lauda F Wigand ME Connemann BJ Rosenbohm A Tumani H et al April 2015 Periventricular white matter lesion and incomplete MRZ reaction in a male patient with anti N methyl D aspartate receptor encephalitis presenting with dysphoric mania BMJ Case Reports 2015 bcr2014209075 doi 10 1136 bcr 2014 209075 PMC 4422915 PMID 25917068 Li Y Xie P Lv F Mu J Li Q Yang Q et al October 2008 Brain magnetic resonance imaging abnormalities in neuromyelitis optica Acta Neurologica Scandinavica 118 4 218 225 doi 10 1111 j 1600 0404 2008 01012 x PMID 18384459 S2CID 22270592 Wingerchuk D 2006 Neuromyelitis Optica Devic s Syndrome PDF 2006 Rare Neuroimmunologic Disorders Symposium Archived from the original PDF on 2006 09 25 Retrieved 2007 01 05 Ikeda K Ito H Hidaka T Takazawa T Sekine T Yoshii Y et al 2011 Repeated non enhancing tumefactive lesions in a patient with a neuromyelitis optica spectrum disorder Internal Medicine 50 9 1061 1064 doi 10 2169 internalmedicine 50 4295 PMID 21532234 Probstel AK Rudolf G Dornmair K Collongues N Chanson JB Sanderson NS et al March 2015 Anti MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype Journal of Neuroinflammation 12 1 46 doi 10 1186 s12974 015 0256 1 PMC 4359547 PMID 25889963 a b Spadaro M Gerdes LA Mayer MC Ertl Wagner B Laurent S Krumbholz M et al March 2015 Histopathology and clinical course of MOG antibody associated encephalomyelitis Annals of Clinical and Translational Neurology 2 3 295 301 doi 10 1002 acn3 164 PMC 4369279 PMID 25815356 a b Spadaro M Gerdes LA Krumbholz M Ertl Wagner B Thaler FS Schuh E et al October 2016 Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis Neurology 3 5 e257 doi 10 1212 NXI 0000000000000257 PMC 4949775 PMID 27458601 a b c d Reindl M Di Pauli F Rostasy K Berger T August 2013 The spectrum of MOG autoantibody associated demyelinating diseases Nature Reviews Neurology 9 8 455 461 doi 10 1038 nrneurol 2013 118 PMID 23797245 S2CID 7219279 Baumann M Hennes EM Schanda K Karenfort M Bajer Kornek B Diepold K et al 2015 OP65 3006 Clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis and MOG antibodies European Journal of Paediatric Neurology 19 S21 doi 10 1016 S1090 3798 15 30066 0 Jarius S Metz I Konig FB Ruprecht K Reindl M Paul F et al October 2016 Screening for MOG IgG and 27 other anti glial and anti neuronal autoantibodies in pattern II multiple sclerosis and brain biopsy findings in a MOG IgG positive case Multiple Sclerosis 22 12 1541 1549 doi 10 1177 1352458515622986 PMID 26869529 S2CID 1387384 Kitagawa S Osada T Kaneko K Takahashi T Suzuki N Nakahara J December 2018 Clinical analysis of opticospinal multiple sclerosis OSMS presentation detecting anti myelin oligodendrocyte glycoprotein MOG antibody Rinsho Shinkeigaku Clinical Neurology 58 12 737 744 doi 10 5692 clinicalneurol cn 001184 PMID 30487359 Chalmoukou K Stathopoulos P Alexopoulos H Akrivou S Dalakas M 2015 Recurrent Optic Neuritis rON is characterised by Anti MOG Antibodies A follow up study Neurology 84 14 Suppl P5 274 Rossman I 2015 An 8 Year Old Girl with Chronic Inflammatory Optic Neuritis CRION the Youngest Reported Case to Date Neurology 84 14 Supplement P7 015 Chalmoukou K Alexopoulos H Akrivou S Stathopoulos P Reindl M Dalakas MC August 2015 Anti MOG antibodies are frequently associated with steroid sensitive recurrent optic neuritis Neurology 2 4 e131 doi 10 1212 NXI 0000000000000131 PMC 4496630 PMID 26185777 Canto LN Bosca SC Vicente CA Gil Perontin S Perez Miralles F Villalba JC et al 2019 Brain Atrophy in Relapsing Optic Neuritis Is Associated With Crion Phenotype Frontiers in Neurology 10 1157 doi 10 3389 fneur 2019 01157 PMC 6838209 PMID 31736862 Tenembaum S Waters P Leite M Woodhall M Princich J Segura M et al 2015 04 06 Spectrum of MOG Autoantibody Associated Inflammatory Diseases in Pediatric Patients I4 3A Neurology 84 14 Supplement ISSN 0028 3878 Yan Y Li Y Fu Y Yang L Su L Shi K et al December 2016 Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD Science China Life Sciences 59 12 1270 1281 doi 10 1007 s11427 015 4997 y PMC 5101174 PMID 26920678 Goncalves MV Fragoso YD April 2019 The involvement of anti neurofascin 155 antibodies in central and peripheral demyelinating diseases Neuroimmunology and Neuroinflammation 8 6 doi 10 20517 2347 8659 2019 08 S2CID 146038130 a b c Kira JI Yamasaki R Ogata H November 2019 Anti neurofascin autoantibody and demyelination Neurochemistry International 130 104360 doi 10 1016 j neuint 2018 12 011 PMID 30582947 Stich O Perera S Berger B Jarius S Wildemann B Baumgartner A Rauer S May 2016 Prevalence of neurofascin 155 antibodies in patients with multiple sclerosis Journal of the Neurological Sciences 364 29 32 doi 10 1016 j jns 2016 03 004 PMID 27084211 S2CID 29204735 Progressive MS a new perspective Multiple Sclerosis Society UK www mssociety org uk Archived from the original on 2006 09 25 Engel S Luessi F Mueller A Schopf RE Zipp F Bittner S 2020 PPMS onset upon adalimumab treatment extends the spectrum of anti TNF a therapy associated demyelinating disorders Therapeutic Advances in Neurological Disorders 13 1756286419895155 doi 10 1177 1756286419895155 PMC 6940603 PMID 31921355 Alnasser Alsukhni R Jriekh Z Aboras Y 2016 Adalimumab Induced or Provoked MS in Patient with Autoimmune Uveitis A Case Report and Review of the Literature Case Reports in Medicine 2016 1423131 doi 10 1155 2016 1423131 PMC 5093248 PMID 27840642 a b Vicente LG Viqueira BR de las Penas MJ Cobos RG Moreno JP Gonzalez RA 2016 Relapse in a paucisymptomatic form of multiple sclerosis in a patient treated with nivolumab Neuro Oncol 18 iv25 doi 10 1093 neuonc now188 085 a b c Hoftberger R Leisser M Bauer J Lassmann H December 2015 Autoimmune encephalitis in humans how closely does it reflect multiple sclerosis Acta Neuropathologica Communications 3 1 80 doi 10 1186 s40478 015 0260 9 PMC 4670499 PMID 26637427 Romeo MA Garassino MC Moiola L Galli G Comi G Martinelli V Filippi M December 2019 Multiple sclerosis associated with pembrolizumab in a patient with non small cell lung cancer Journal of Neurology 266 12 3163 3166 doi 10 1007 s00415 019 09562 z PMID 31586260 S2CID 203654410 a b c Lassmann H February 2010 Acute disseminated encephalomyelitis and multiple sclerosis Brain 133 Pt 2 317 319 doi 10 1093 brain awp342 PMID 20129937 Kalinowska Lyszczarz A Fereidan Esfahani M Guo Y Lucchinetti CF Tobin WO August 2020 Pathological findings in central nervous system demyelination associated with infliximab Multiple Sclerosis 26 9 1124 1129 doi 10 1177 1352458519894710 PMC 7297659 PMID 31845616 Garcia Catherine R Jayswal Rani Adams Val Anthony Lowell B Villano John L 10 February 2019 Multiple Sclerosis Outcomes after Cancer Immunotherapy Clinical amp Translational Oncology 21 10 1336 1342 doi 10 1007 s12094 019 02060 8 ISSN 1699 048X PMC 6702101 PMID 30788836 Williams I Uhlig HH December 2020 Demyelination After Anti TNF Therapy Who is at Risk Journal of Crohn s amp Colitis 14 12 1651 1652 doi 10 1093 ecco jcc jjaa144 PMID 33026456 Young NP Weinshenker BG Parisi JE Scheithauer B Giannini C Roemer SF et al February 2010 Perivenous demyelination association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis Brain 133 Pt 2 333 348 doi 10 1093 brain awp321 PMC 2822631 PMID 20129932 Nikoskelainen EK Marttila RJ Huoponen K Juvonen V Lamminen T Sonninen P Savontaus ML August 1995 Leber s plus neurological abnormalities in patients with Leber s hereditary optic neuropathy Journal of Neurology Neurosurgery and Psychiatry 59 2 160 164 doi 10 1136 jnnp 59 2 160 PMC 485991 PMID 7629530 Cardiac arrythmia health cares net Archived from the original on 6 May 2016 Multiple sclerosis Symptoms and causes Mayo Clinic Retrieved 2022 06 24 Ma C Wang C Zhang Q Lian Y 2019 Emerging role of prodromal headache in patients with anti N methyl D aspartate receptor encephalitis Journal of Pain Research 12 519 526 doi 10 2147 JPR S189301 PMC 6365221 PMID 30787630 Lucchinetti CF Gavrilova RH Metz I Parisi JE Scheithauer BW Weigand S et al July 2008 Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis Brain 131 Pt 7 1759 1775 doi 10 1093 brain awn098 PMC 2442427 PMID 18535080 Given CA Stevens BS Lee C January 2004 The MRI appearance of tumefactive demyelinating lesions AJR American Journal of Roentgenology 182 1 195 199 doi 10 2214 ajr 182 1 1820195 PMID 14684539 a b Hardy TA Reddel SW Barnett MH Palace J Lucchinetti CF Weinshenker BG August 2016 Atypical inflammatory demyelinating syndromes of the CNS The Lancet Neurology 15 9 967 981 doi 10 1016 S1474 4422 16 30043 6 PMID 27478954 S2CID 26341166 Jimenez Arango JA Uribe Uribe CS Toro Gonzalez G March 2015 Lesser known myelin related disorders focal tumour like demyelinating lesions Neurologia 30 2 97 105 doi 10 1016 j nrl 2013 06 004 PMID 24094691 Garrido C Levy Gomes A Teixeira J Temudo T 2004 Schilder s disease two new cases and a review of the literature Schilder s disease two new cases and a review of the literature Revista de Neurologia in Spanish 39 8 734 738 doi 10 33588 rn 3908 2003023 PMID 15514902 Afifi AK Bell WE Menezes AH Moore SA October 1994 Myelinoclastic diffuse sclerosis Schilder s disease report of a case and review of the literature Journal of Child Neurology 9 4 398 403 CiteSeerX 10 1 1 1007 559 doi 10 1177 088307389400900412 PMID 7822732 S2CID 38765870 Schmalstieg WF Keegan BM Weinshenker BG February 2012 Solitary sclerosis progressive myelopathy from solitary demyelinating lesion Neurology 78 8 540 544 doi 10 1212 WNL 0b013e318247cc8c PMID 22323754 S2CID 52859541 Lattanzi S July 2012 Solitary sclerosis Progressive myelopathy from solitary demyelinating lesion Neurology 79 4 393 author reply 393 doi 10 1212 01 wnl 0000418061 10382 f7 PMID 22826546 Ayrignac X Carra Dalliere C Homeyer P Labauge P December 2013 Solitary sclerosis progressive myelopathy from solitary demyelinating lesion A new entity Acta Neurologica Belgica 113 4 533 534 doi 10 1007 s13760 013 0182 x PMID 23358965 S2CID 17631796 Trapp BD Vignos M Dudman J Chang A Fisher E Staugaitis SM et al October 2018 Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis a retrospective study The Lancet Neurology 17 10 870 884 doi 10 1016 S1474 4422 18 30245 X PMC 6197820 PMID 30143361 Vignos MC 2016 A histopathological and magnetic resonance imaging assessment of myelocortical multiple sclerosis A new pathological variant Ph D thesis Kent State University Hendrickson M Chang A Fisher E September 30 2013 ECTRIMS 2013 Posters Myelocortical multiple sclerosis a subgroup of multiple sclerosis patients with spinal cord and cortical demyelination Multiple Sclerosis Journal 19 11 suppl 74 558 doi 10 1177 1352458513502429 hdl 20 500 11940 2342 ISSN 1352 4585 S2CID 208628537 Meneguette NS Almeida KM Figueiredo MT de Araujo E Araujo AC Alvarenga MP et al November 2021 Optic neuritis in Asian type opticospinal multiple sclerosis OSMS ON in a non Asian population A functional structural paradox PDF Multiple Sclerosis and Related Disorders 56 103260 doi 10 1016 j msard 2021 103260 PMID 34562767 S2CID 237636213 Matsushita T Isobe N Matsuoka T Shi N Kawano Y Wu XM et al July 2009 Aquaporin 4 autoimmune syndrome and anti aquaporin 4 antibody negative opticospinal multiple sclerosis in Japanese Multiple Sclerosis 15 7 834 847 doi 10 1177 1352458509104595 PMID 19465451 S2CID 19372571 Mercan O Ulger Z Handan Misirli C Turkoglu R 2018 Opticospinal Multiple Sclerosis Clinical Course and Immunological Parameters Experimed 8 2 47 51 doi 10 26650 experimed 2018 18002 Schee JP Viswanathan S May 17 2018 Pure spinal multiple sclerosis A possible novel entity within the multiple sclerosis disease spectrum Multiple Sclerosis Journal 25 8 1189 1195 doi 10 1177 1352458518775912 ISSN 1352 4585 PMID 29771191 S2CID 21709554 O Connor P Marriott J 2010 Differential Diagnosis and Diagnostic Criteria for Multiple Sclerosis Application and Pitfalls PDF In Hohlfeld R Lucchinetti CF eds Multiple sclerosis 3 1st ed Philadelphia Saunders Elsevier ISBN 978 1 4160 6068 0 Archived from the original PDF on 2015 08 24 Retrieved 2015 01 14 Mihalova T Kwong JL Alachkar H 2019 12 01 214 Analysis of CSF IgG index IgG synthesis and clinical presentation among CSF OCBs negative patients Journal of Neurology Neurosurgery amp Psychiatry 90 12 e54 doi 10 1136 jnnp 2019 ABN 2 181 inactive 31 December 2022 ISSN 0022 3050 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint DOI inactive as of December 2022 link Link H Huang YM November 2006 Oligoclonal bands in multiple sclerosis cerebrospinal fluid an update on methodology and clinical usefulness Journal of Neuroimmunology 180 1 2 17 28 doi 10 1016 j jneuroim 2006 07 006 PMID 16945427 S2CID 22724352 Imrell K Landtblom AM Hillert J Masterman T September 2006 Multiple sclerosis with and without CSF bands clinically indistinguishable but immunogenetically distinct Neurology 67 6 1062 1064 doi 10 1212 01 wnl 0000237343 93389 35 PMID 17000979 S2CID 21855273 Zeman AZ Kidd D McLean BN Kelly MA Francis DA Miller DH et al January 1996 A study of oligoclonal band negative multiple sclerosis Journal of Neurology Neurosurgery and Psychiatry 60 1 27 30 doi 10 1136 jnnp 60 1 27 PMC 486185 PMID 8558146 Li R Patterson KR Bar Or A July 2018 Reassessing B cell contributions in multiple sclerosis Nature Immunology 19 7 696 707 doi 10 1038 s41590 018 0135 x PMID 29925992 S2CID 49347759 Casanova B Lacruz L Villar ML Dominguez JA Gadea MC Gascon F et al August 2018 Different clinical response to interferon beta and glatiramer acetate related to the presence of oligoclonal IgM bands in CSF in multiple sclerosis patients Neurological Sciences 39 8 1423 1430 doi 10 1007 s10072 018 3442 y PMID 29882169 S2CID 46954452 Graner M Pointon T Manton S Green M Dennison K Davis M et al 21 February 2020 Oligoclonal IgG antibodies in multiple sclerosis target patient specific peptides PLOS ONE 15 2 e0228883 Bibcode 2020PLoSO 1528883G doi 10 1371 journal pone 0228883 PMC 7034880 PMID 32084151 Codjia P Ayrignac X Carra Dalliere C Cohen M Charif M Lippi A et al SFSEP OFSEP February 2019 Multiple sclerosis with atypical MRI presentation Results of a nationwide multicenter study in 57 consecutive cases Multiple Sclerosis and Related Disorders 28 109 116 doi 10 1016 j msard 2018 12 022 PMID 30592992 S2CID 58550590 a b Ayrignac X Menjot de Champfleur N Menjot de Champfleur S Carra Dalliere C Deverdun J Corlobe A Labauge P June 2016 Brain magnetic resonance imaging helps to differentiate atypical multiple sclerosis with cavitary lesions and vanishing white matter disease European Journal of Neurology 23 6 995 1000 doi 10 1111 ene 12931 PMID 26727496 S2CID 3917307 Wallner Blazek M Rovira A Fillipp M Rocca MA Miller DH Schmierer K et al August 2013 Atypical idiopathic inflammatory demyelinating lesions prognostic implications and relation to multiple sclerosis Journal of Neurology 260 8 2016 2022 doi 10 1007 s00415 013 6918 y PMID 23620065 S2CID 28377856 a b c Dobson R Giovannoni G January 2019 Multiple sclerosis a review European Journal of Neurology 26 1 27 40 doi 10 1111 ene 13819 PMID 30300457 a b c Diaz C Zarco LA Rivera DM May 2019 Highly active multiple sclerosis An update Multiple Sclerosis and Related Disorders 30 215 224 doi 10 1016 j msard 2019 01 039 PMID 30822617 S2CID 73460639 Morcos Y Lee SM Levin MC August 2003 A role for hypertrophic astrocytes and astrocyte precursors in a case of rapidly progressive multiple sclerosis Multiple Sclerosis 9 4 332 341 doi 10 1191 1352458503ms931oa PMID 12926837 S2CID 43651011 Masaki K Suzuki SO Matsushita T Matsuoka T Imamura S Yamasaki R et al 2013 Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica PLOS ONE 8 8 e72919 Bibcode 2013PLoSO 872919M doi 10 1371 journal pone 0072919 PMC 3749992 PMID 23991165 Seidi O January 27 2015 The Role of Therapeutic Plasma Exchange in Clinical Neurology Report via khartoumspace uofk edu Broadley SA Barnett MH Boggild M Brew BJ Butzkueven H Heard R et al August 2015 A new era in the treatment of multiple sclerosis The Medical Journal of Australia 203 3 139 41 141e 1 doi 10 5694 mja14 01218 hdl 10536 DRO DU 30080418 PMID 26224184 S2CID 10805065 Wekerle H March 2022 Epstein Barr virus sparks brain autoimmunity in multiple sclerosis Nature 603 7900 230 232 Bibcode 2022Natur 603 230W doi 10 1038 d41586 022 00382 2 PMID 35169323 S2CID 246866517 Srivastava R Aslam M Kalluri SR Schirmer L Buck D Tackenberg B et al July 2012 Potassium channel KIR4 1 as an immune target in multiple sclerosis The New England Journal of Medicine 367 2 115 123 doi 10 1056 NEJMoa1110740 PMC 5131800 PMID 22784115 Schneider R 2013 Autoantibodies to Potassium Channel KIR4 1 in Multiple Sclerosis Frontiers in Neurology 4 125 doi 10 3389 fneur 2013 00125 PMC 3759297 PMID 24032025 Ayoglu B Haggmark A Khademi M Olsson T Uhlen M Schwenk JM Nilsson P September 2013 Autoantibody profiling in multiple sclerosis using arrays of human protein fragments Molecular amp Cellular Proteomics 12 9 2657 2672 doi 10 1074 mcp M112 026757 PMC 3769337 PMID 23732997 Ayoglu B Mitsios N Kockum I Khademi M Zandian A Sjoberg R et al February 2016 Anoctamin 2 identified as an autoimmune target in multiple sclerosis Proceedings of the National Academy of Sciences of the United States of America 113 8 2188 2193 Bibcode 2016PNAS 113 2188A doi 10 1073 pnas 1518553113 PMC 4776531 PMID 26862169 Tengvall K Huang J Hellstrom C Kammer P Bistrom M Ayoglu B et al August 2019 Molecular mimicry between Anoctamin 2 and Epstein Barr virus nuclear antigen 1 associates with multiple sclerosis risk Proceedings of the National Academy of Sciences of the United States of America 116 34 16955 16960 doi 10 1073 pnas 1902623116 PMC 6708327 PMID 31375628 Belova AN Grygorieva VN Rasteryaeva MV Ruina EA Belova EM Solovieva VS Boyko AN 2019 Anti NMDAR encephalitis associated with relapsing optic neuritis a case report and differential diagnosis Zhurnal Nevrologii I Psikhiatrii Imeni S S Korsakova 119 10 Vyp 2 137 146 doi 10 17116 jnevro201911910137 PMID 31934999 S2CID 210193928 Baheerathan A Brownlee WJ Chard DT Shields K Gregory R Trip SA February 2017 Antecedent anti NMDA receptor encephalitis in two patients with multiple sclerosis Multiple Sclerosis and Related Disorders 12 20 22 doi 10 1016 j msard 2016 12 009 PMID 28283100 Mariotto S Gajofatto A Alberti D Lederer S Monaco S Ferrari S Hoeftberger R April 2019 Flotillin 1 2 autoantibodies in patients with inflammatory disorders of the CNS Neurology 92 15 Supplement P2 2 072 P2 2 072 Koutsis G Breza M Velonakis G Tzartos J Kasselimis D Kartanou C et al February 2019 X linked Charcot Marie Tooth disease and multiple sclerosis emerging evidence for an association Journal of Neurology Neurosurgery and Psychiatry 90 2 187 194 doi 10 1136 jnnp 2018 319014 PMID 30196252 S2CID 52175657 Yu Wai Man P Spyropoulos A Duncan HJ Guadagno JV Chinnery PF September 2016 A multiple sclerosis like disorder in patients with OPA1 mutations Annals of Clinical and Translational Neurology 3 9 723 729 doi 10 1002 acn3 323 PMC 5018584 PMID 27656661 Vojdani A Mukherjee PS Berookhim J Kharrazian D 2015 Detection of Antibodies against Human and Plant Aquaporins in Patients with Multiple Sclerosis Autoimmune Diseases 2015 905208 doi 10 1155 2015 905208 PMC 4529886 PMID 26290755 Baranova SV Mikheeva EV Buneva VN Nevinsky GA November 2019 Antibodies from the Sera of Multiple Sclerosis Patients Efficiently Hydrolyze Five Histones Biomolecules 9 11 741 doi 10 3390 biom9110741 PMC 6920934 PMID 31731780 Tzartos JS Stergiou C Kilidireas K Zisimopoulou P Thomaidis T Tzartos SJ 2013 Anti aquaporin 1 autoantibodies in patients with neuromyelitis optica spectrum disorders PLOS ONE 8 9 e74773 Bibcode 2013PLoSO 874773T doi 10 1371 journal pone 0074773 PMC 3781161 PMID 24086369 Robers M Tokhie H Borazanci A 2018 04 10 N Type Calcium Channel Antibody Encephalitis Coexisting With Multiple Sclerosis P5 397 Neurology 90 15 Supplement ISSN 0028 3878 Faergeman SL Evans H Attfield KE Desel C Kuttikkatte SB Sommerlund M et al May 2020 A novel neurodegenerative spectrum disorder in patients with MLKL deficiency Cell Death amp Disease 11 5 303 doi 10 1038 s41419 020 2494 0 PMC 7195448 PMID 32358523 Birnbaum J Hoke A Lalji A Calabresi P Bhargava P Casciola Rosen L October 2018 Brief Report Anti Calponin 3 Autoantibodies A Newly Identified Specificity in Patients With Sjogren s Syndrome Arthritis amp Rheumatology 70 10 1610 1616 doi 10 1002 art 40550 PMID 29749720 Zhang Y Wang L Jia H Liao M Chen X Xu J et al July 2018 Genetic variants regulate NR1H3 expression and contribute to multiple sclerosis risk Journal of the Neurological Sciences 390 162 165 doi 10 1016 j jns 2018 04 037 PMID 29801879 S2CID 44082278 Yeo T Probert F Jurynczyk M Sealey M Cavey A Claridge TD et al November 2019 Classifying the antibody negative NMO syndromes Clinical imaging and metabolomic modeling Neurology 6 6 e626 doi 10 1212 NXI 0000000000000626 PMC 6865851 PMID 31659123 Tohyama S Hung PS Cheng JC Zhang JY Halawani A Mikulis DJ et al May 2020 Trigeminal neuralgia associated with a solitary pontine lesion clinical and neuroimaging definition of a new syndrome Pain 161 5 916 925 doi 10 1097 j pain 0000000000001777 PMC 7170433 PMID 31842151 Minagar A Jy W Jimenez JJ Alexander JS April 2006 Multiple sclerosis as a vascular disease Neurological Research 28 3 230 235 doi 10 1179 016164106X98080 PMID 16687046 S2CID 16896871 Chronic Fatigue Syndrome Symptoms Diagnosis Treatment of Chronic Fatigue Syndrome Health Information New York Times The following test results are seen consistently Brain MRI showing swelling in the brain or destruction of part of the nerve cells demyelination Bergner CG Genc N Hametner S Franz J van der Meer F Mitkovski M et al October 2021 Concurrent axon and myelin destruction differentiates X linked adrenoleukodystrophy from multiple sclerosis Glia 69 10 2362 2377 doi 10 1002 glia 24042 PMID 34137074 a b Link Between Gut Flora and Multiple Sclerosis Discovered Neuroscience News 2018 10 11 Retrieved 2022 06 29 a b Planas R Santos R Tomas Ojer P Cruciani C Lutterotti A Faigle W et al October 2018 GDP l fucose synthase is a CD4 T cell specific autoantigen in DRB3 02 02 patients with multiple sclerosis Science Translational Medicine 10 462 eaat4301 doi 10 1126 scitranslmed aat4301 PMID 30305453 S2CID 52959112 a b Ogawa K Okuno T Hosomichi K Hosokawa A Hirata J Suzuki K et al August 2019 Next generation sequencing identifies contribution of both class I and II HLA genes on susceptibility of multiple sclerosis in Japanese Journal of Neuroinflammation 16 1 162 doi 10 1186 s12974 019 1551 z PMC 6683481 PMID 31382992 a b Wang Z Sadovnick AD Traboulsee AL Ross JP Bernales CQ Encarnacion M et al June 2016 Nuclear Receptor NR1H3 in Familial Multiple Sclerosis Neuron 90 5 948 954 doi 10 1016 j neuron 2016 04 039 PMC 5092154 PMID 27253448 Hain HS Hakonarson H June 2016 The Added Value of Family Material in the Discovery of Multiple Sclerosis Genes Neuron 90 5 905 906 doi 10 1016 j neuron 2016 05 027 PMID 27253441 a b Cristofanilli M Rosenthal H Cymring B Gratch D Pagano B Xie B Sadiq SA November 2014 Progressive multiple sclerosis cerebrospinal fluid induces inflammatory demyelination axonal loss and astrogliosis in mice Experimental Neurology 261 620 632 doi 10 1016 j expneurol 2014 07 020 PMID 25111532 S2CID 21263405 Ulloa B Alahiri M Liu Y Sadiq S 2015 Cerebrospinal Fluid Haptoglobin Hp Levels are elevated in MS patients with progressive disease Neurology 84 14 213 Elkjaer ML Nawrocki A Kacprowski T Lassen P Simonsen AH Marignier R et al 2020 Molecular markers in the CSF proteome differentiate neuroinflammatory diseases Research Square doi 10 21203 rs 3 rs 19710 v1 S2CID 236819936 Vernejoul J Cali F Lin J Sadiq S 2020 04 14 Single Cell Analysis of MS CSF B Cells Show Significant Differences in Expansion Patterns and Gene Family Usage Between MS Subtypes 4673 Neurology 94 15 Supplement ISSN 0028 3878 Vukusic S Confavreux C February 2003 Primary and secondary progressive multiple sclerosis Journal of the Neurological Sciences 206 2 153 155 doi 10 1016 S0022 510X 02 00427 6 PMID 12559503 S2CID 19215860 Dressel A Kolb AK Elitok E Bitsch A Bogumil T Kitze B et al December 2006 Interferon beta1b treatment modulates cytokines in patients with primary progressive multiple sclerosis Acta Neurologica Scandinavica 114 6 368 373 doi 10 1111 j 1600 0404 2006 00700 x PMID 17083335 S2CID 71465403 Villar LM Casanova B Ouamara N Comabella M Jalili F Leppert D et al August 2014 Immunoglobulin M oligoclonal bands biomarker of targetable inflammation in primary progressive multiple sclerosis Annals of Neurology 76 2 231 240 doi 10 1002 ana 24190 PMID 24909126 S2CID 16397501 Curbelo M Martinez A Steinberg J Carra A April 2016 LOMS vs Other Diseases The Consequence of To Be or Not To Be Neurology 86 16 Supplement P3 081 Zwemmer JN Bot JC Jelles B Barkhof F Polman CH April 2008 At the heart of primary progressive multiple sclerosis three cases with diffuse MRI abnormalities only Multiple Sclerosis 14 3 428 430 doi 10 1177 1352458507084591 PMID 18208890 S2CID 27178351 Reinke SN Broadhurst DL Sykes BD Baker GB Catz I Warren KG Power C September 2014 Metabolomic profiling in multiple sclerosis insights into biomarkers and pathogenesis Multiple Sclerosis 20 10 1396 1400 doi 10 1177 1352458513516528 PMID 24468817 S2CID 24226475 Balk LJ Tewarie P Killestein J Polman CH Uitdehaag B Petzold A August 2014 Disease course heterogeneity and OCT in multiple sclerosis Multiple Sclerosis 20 9 1198 1206 doi 10 1177 1352458513518626 PMID 24402036 S2CID 7737278 Poser CM Brinar VV June 2004 The nature of multiple sclerosis Clinical Neurology and Neurosurgery 106 3 159 171 doi 10 1016 j clineuro 2004 02 005 PMID 15177764 S2CID 23522920 Liguori M Qualtieri A Tortorella C Direnzo V Bagala A Mastrapasqua M et al 2014 Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration PLOS ONE 9 8 e103984 Bibcode 2014PLoSO 9j3984L doi 10 1371 journal pone 0103984 PMC 4123901 PMID 25098164 Ramos I Rehman IU Sharrack B Woodroofe N 2017 04 18 Revealing underlying differences of NAWM from primary and secondary progressive MS P4 404 Neurology 88 16 Supplement ISSN 0028 3878 Abdelhak A Weber MS Tumani H 2017 Primary Progressive Multiple Sclerosis Putting Together the Puzzle Frontiers in Neurology 8 234 doi 10 3389 fneur 2017 00234 PMC 5449443 PMID 28620346 Acquaviva M Bassani C Sarno N Dalla Costa G Romeo M Sangalli F et al 2019 Loss of Circulating CD8 CD161high T Cells in Primary Progressive Multiple Sclerosis Frontiers in Immunology 10 1922 doi 10 3389 fimmu 2019 01922 PMC 6702304 PMID 31474991 Quintana FJ Patel B Yeste A Nyirenda M Kenison J Rahbari R et al December 2014 Epitope spreading as an early pathogenic event in pediatric multiple sclerosis Neurology 83 24 2219 2226 doi 10 1212 WNL 0000000000001066 PMC 4277672 PMID 25381299 Lassmann H 2019 Pathogenic Mechanisms Associated With Different Clinical Courses of Multiple Sclerosis Frontiers in Immunology 9 3116 doi 10 3389 fimmu 2018 03116 PMC 6335289 PMID 30687321 Hakiki B Goretti B Portaccio E Zipoli V Amato MP August 2008 Subclinical MS follow up of four cases European Journal of Neurology 15 8 858 861 doi 10 1111 j 1468 1331 2008 02155 x PMID 18507677 S2CID 27212599 Lebrun C Bensa C Debouverie M De Seze J Wiertlievski S Brochet B et al February 2008 Unexpected multiple sclerosis follow up of 30 patients with magnetic resonance imaging and clinical conversion profile Journal of Neurology Neurosurgery and Psychiatry 79 2 195 198 doi 10 1136 jnnp 2006 108274 PMID 18202208 S2CID 11750372 Frisullo G Nociti V Iorio R Patanella AK Marti A Mirabella M et al December 2008 The persistency of high levels of pSTAT3 expression in circulating CD4 T cells from CIS patients favors the early conversion to clinically defined multiple sclerosis Journal of Neuroimmunology 205 1 2 126 134 doi 10 1016 j jneuroim 2008 09 003 PMID 18926576 S2CID 27303451 Hou Y Jia Y Hou J July 2018 Natural Course of Clinically Isolated Syndrome A Longitudinal Analysis Using a Markov Model Scientific Reports 8 1 10857 Bibcode 2018NatSR 810857H doi 10 1038 s41598 018 29206 y PMC 6052069 PMID 30022111 Mackay RP Hirano A December 1967 Forms of benign multiple sclerosis Report of two clinically silent cases discovered at autopsy Archives of Neurology 17 6 588 600 doi 10 1001 archneur 1967 00470300030007 PMID 6054893 Engell T May 1989 A clinical patho anatomical study of clinically silent multiple sclerosis Acta Neurologica Scandinavica 79 5 428 430 doi 10 1111 j 1600 0404 1989 tb03811 x PMID 2741673 S2CID 21581253 Lebrun C Kantarci OH Siva A Pelletier D Okuda DT February 2018 Anomalies Characteristic of Central Nervous System Demyelination Radiologically Isolated Syndrome Neurologic Clinics 36 1 59 68 doi 10 1016 j ncl 2017 08 004 PMID 29157404 Gabelic T Ramasamy DP Weinstock Guttman B Hagemeier J Kennedy C Melia R et al January 2014 Prevalence of radiologically isolated syndrome and white matter signal abnormalities in healthy relatives of patients with multiple sclerosis AJNR American Journal of Neuroradiology 35 1 106 112 doi 10 3174 ajnr A3653 PMC 7966501 PMID 23886745 Banwell B June 2019 Are children with multiple sclerosis really old adults Multiple Sclerosis 25 7 888 890 doi 10 1177 1352458519841505 PMID 30945591 Gabelic T Weinstock Guttman B Melia R Lincoff N Masud MW Kennedy C et al December 2013 Retinal nerve fiber thickness and MRI white matter abnormalities in healthy relatives of multiple sclerosis patients Clinical Neurology and Neurosurgery 115 Suppl 1 S49 S54 doi 10 1016 j clineuro 2013 09 021 PMID 24321155 S2CID 41756033 Rossi S Motta C Studer V Macchiarulo G Germani G Finardi A et al October 2015 Subclinical central inflammation is risk for RIS and CIS conversion to MS Multiple Sclerosis 21 11 1443 1452 doi 10 1177 1352458514564482 PMID 25583841 S2CID 22377941 Cramer SP Modvig S Simonsen HJ Frederiksen JL Larsson HB September 2015 Permeability of the blood brain barrier predicts conversion from optic neuritis to multiple sclerosis Brain 138 Pt 9 2571 2583 doi 10 1093 brain awv203 PMC 4547053 PMID 26187333 Cortese M 2017 12 18 Marianna The timing of environmental risk factors and prodromal signs of multiple sclerosis Ph D thesis Sazonov DV Malkova NA Bulatova EV Riabukhina OV 2009 Combined therapy of aggressive remitted multiple sclerosis with mitoxantrone in combination with copaxone Zhurnal Nevrologii I Psikhiatrii Imeni S S Korsakova 109 12 76 79 PMID 20037526 Rush CA MacLean HJ Freedman MS July 2015 Aggressive multiple sclerosis proposed definition and treatment algorithm Nature Reviews Neurology 11 7 379 389 doi 10 1038 nrneurol 2015 85 PMID 26032396 S2CID 205516534 Magliozzi R Howell OW Nicholas R Cruciani C Castellaro M Romualdi C et al April 2018 Inflammatory intrathecal profiles and cortical damage in multiple sclerosis PDF Annals of Neurology 83 4 739 755 doi 10 1002 ana 25197 PMID 29518260 S2CID 5042430 Notas K Papadaki E Orologas A Moschou M Kimiskidis VK February 2020 Switching from fingolimod to alemtuzumab in patients with highly active relapsing remitting multiple sclerosis A case series Multiple Sclerosis and Related Disorders 38 101517 doi 10 1016 j msard 2019 101517 PMID 31751858 S2CID 208228516 Chabas D Castillo Trivino T Mowry EM Strober JB Glenn OA Waubant E September 2008 Vanishing MS T2 bright lesions before puberty a distinct MRI phenotype Neurology 71 14 1090 1093 CiteSeerX 10 1 1 594 9445 doi 10 1212 01 wnl 0000326896 66714 ae PMID 18824673 S2CID 24065442 Alroughani R Boyko A March 2018 Pediatric multiple sclerosis a review BMC Neurology 18 1 27 doi 10 1186 s12883 018 1026 3 PMC 5845207 PMID 29523094 van Rensburg SJ Peeters AV van Toorn R Schoeman J Moremi KE van Heerden CJ Kotze MJ June 2019 Identification of an iron responsive subtype in two children diagnosed with relapsing remitting multiple sclerosis using whole exome sequencing Molecular Genetics and Metabolism Reports 19 100465 doi 10 1016 j ymgmr 2019 100465 PMC 6434495 PMID 30963028 Minagar A 2014 Multiple Sclerosis An Overview of Clinical Features Pathophysiology Neuroimaging and Treatment Options Colloquium Series on Integrated Systems Physiology From Molecule to Function 6 4 1 117 doi 10 4199 C00116ED1V01Y201408ISP055 S2CID 71379237 Susman E 2016 News from the ECTRIMS Congress Neurology Today 16 21 18 19 doi 10 1097 01 NT 0000508402 13786 97 S2CID 78597245 Rovira A Wattjes MP Tintore M Tur C Yousry TA Sormani MP et al August 2015 Evidence based guidelines MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis clinical implementation in the diagnostic process Nature Reviews Neurology 11 8 471 482 doi 10 1038 nrneurol 2015 106 PMID 26149978 Mistry N Dixon J Tallantyre E Tench C Abdel Fahim R Jaspan T et al May 2013 Central veins in brain lesions visualized with high field magnetic resonance imaging a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain JAMA Neurology 70 5 623 628 doi 10 1001 jamaneurol 2013 1405 PMID 23529352 Schippling S November 2017 MRI for multiple sclerosis diagnosis and prognosis Neurodegenerative Disease Management 7 6s 27 29 doi 10 2217 nmt 2017 0038 PMID 29143579 McDonald WI Compston A Edan G Goodkin D Hartung HP Lublin FD et al July 2001 Recommended diagnostic criteria for multiple sclerosis guidelines from the International Panel on the diagnosis of multiple sclerosis Annals of Neurology 50 1 121 127 CiteSeerX 10 1 1 466 5368 doi 10 1002 ana 1032 PMID 11456302 S2CID 13870943 Lassmann H December 2014 Multiple sclerosis lessons from molecular neuropathology Experimental Neurology 262 Pt A 2 7 doi 10 1016 j expneurol 2013 12 003 PMID 24342027 S2CID 25337149 Kutzelnigg A Faber Rod JC Bauer J Lucchinetti CF Sorensen PS Laursen H et al January 2007 Widespread demyelination in the cerebellar cortex in multiple sclerosis Brain Pathology 17 1 38 44 doi 10 1111 j 1750 3639 2006 00041 x PMC 8095596 PMID 17493036 S2CID 38379112 Lebrun C Kantarci OH Siva A Pelletier D Okuda DT et al RISConsortium February 2018 Anomalies Characteristic of Central Nervous System Demyelination Radiologically Isolated Syndrome Neurologic Clinics 36 1 59 68 doi 10 1016 j ncl 2017 08 004 PMID 29157404 Dutta R Trapp BD June 2006 Pathology and definition of multiple sclerosis La Revue du Praticien in French 56 12 1293 1298 PMID 16948216 Quintana FJ Patel B Yeste A Nyirenda M Kenison J Rahbari R et al Canadian Pediatric Demyelinating Disease Network December 2014 Epitope spreading as an early pathogenic event in pediatric multiple sclerosis Neurology 83 24 2219 2226 doi 10 1212 WNL 0000000000001066 PMC 4277672 PMID 25381299 Dalla Costa G Martinelli V Sangalli F Moiola L Colombo B Radaelli M et al February 2019 Prognostic value of serum neurofilaments in patients with clinically isolated syndromes Neurology 92 7 e733 e741 doi 10 1212 WNL 0000000000006902 PMC 6382362 PMID 30635483 Polman CH Reingold SC Banwell B Clanet M Cohen JA Filippi M et al February 2011 Diagnostic criteria for multiple sclerosis 2010 revisions to the McDonald criteria Annals of Neurology 69 2 292 302 doi 10 1002 ana 22366 PMC 3084507 PMID 21387374 Lublin FD Reingold SC Cohen JA Cutter GR Sorensen PS Thompson AJ et al July 2014 Defining the clinical course of multiple sclerosis the 2013 revisions Neurology 83 3 278 286 doi 10 1212 WNL 0000000000000560 PMC 4117366 PMID 24871874 Dalton CM Brex PA Miszkiel KA Hickman SJ MacManus DG Plant GT et al July 2002 Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis Annals of Neurology 52 1 47 53 doi 10 1002 ana 10240 PMID 12112046 S2CID 24039151 Retrieved from https en wikipedia org w index php title Inflammatory demyelinating 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