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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]
As of 2014 several previous MS variants had been separated from MS after the discovery of a specific auto-antibody. Those autoantibodies were 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]
Originally found in neuromyelitis optica, this autoantibody has been associated with other conditions. Its current spectrum is as following:
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]
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]
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]
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 ]
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]
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 ]
Apart from 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.
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 ]
Also the location of the lesions can be used to classify variants:
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]
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 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-MS), a presentation of LHON with MS-like CNS damage, and therefore a subtype of MS according to McDonalds definition. [10]
Also different classifications by body fluid biomarkers is possible:
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]
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]
As of 2019, HAMS is defined as an RRMS phenotype with one or more of the following characteristics: [80]
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:
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 ]
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.
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]
Some auto-antibodies have been found consistently across different MS cases but there is still no agreement on their relevance:
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]
Different behaviour has been reported according to the presence of different HLA genes.
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.
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]
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 ]
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:
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.
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] [144] [145]
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. [146] 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 [147] 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. [148]
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. [149]
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. [150]
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. [151]
An iron-responsive variant of MS has been reported in children. [152]
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 ] However as of 2023 most current MRI machines only pick up 60% of MS lesions, and even 7T machines only pick up 85%. The MS of MS people not discovered by MRI is found only in autopsy. [153]
This unspecific definition has been criticized. For some people this has turned MS into a heterogeneous condition with several underlying problems. [154] 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 [155]
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. [156] [157]
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. [158] 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). [159]
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. [160] but can only be detected post-mortem by an autopsy [161] Therefore, any other diagnosis method will have false positives.
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. [162]
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. [163]
Some authors instead speak about the biological disease vs. its clinical presentation. [164]
Anyway, the precise meaning in each case can be normally deduced from the context.
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. [165]
The 2010 revision of the McDonald criteria [166] 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. [167]
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. [168]
Acute disseminated encephalomyelitis (ADEM), or acute demyelinating encephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord to become inflamed, ADEM also attacks the nerves of the central nervous system and damages their myelin insulation, which, as a result, destroys the white matter. The cause is often a trigger such as from viral infection or vaccinations.
Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes.
Multiple sclerosis (MS) is an autoimmune disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, vision loss, eye pain, muscle weakness, and loss of sensation or coordination. MS takes several forms, with new symptoms either occurring in isolated attacks or building up over time. In the relapsing forms of MS, between attacks, symptoms may disappear completely, although some permanent neurological problems often remain, especially as the disease advances. In the progressive forms of MS, bodily function slowly deteriorates and disability worsens once symptoms manifest and will steadily continue to do so if the disease is left untreated.
Encephalomyelitis is inflammation of the brain and spinal cord. Various types of encephalomyelitis include:
Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of autoimmune diseases characterized by acute inflammation of the optic nerve and the spinal cord (myelitis). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients.
Myelin oligodendrocyte glycoprotein (MOG) is a glycoprotein believed to be important in the myelination of nerves in the central nervous system (CNS). In humans this protein is encoded by the MOG gene. It is speculated to serve as a necessary "adhesion molecule" to provide structural integrity to the myelin sheath and is known to develop late on the oligodendrocyte.
Experimental autoimmune encephalomyelitis, sometimes experimental allergic encephalomyelitis (EAE), is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases, including multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general.
Multiple sclerosis is an inflammatory demyelinating disease of the CNS in which activated immune cells invade the central nervous system and cause inflammation, neurodegeneration, and tissue damage. The underlying cause is currently unknown. Current research in neuropathology, neuroimmunology, neurobiology, and neuroimaging, together with clinical neurology, provide support for the notion that MS is not a single disease but rather a spectrum.
Multiple sclerosis and other demyelinating diseases of the central nervous system (CNS) produce lesions and glial scars or scleroses. They present different shapes and histological findings according to the underlying condition that produces them.
Baló's concentric sclerosis is a disease in which the white matter of the brain appears damaged in concentric layers, leaving the axis cylinder intact. It was described by József Mátyás Baló who initially named it "leuko-encephalitis periaxialis concentrica" from the previous definition, and it is currently considered one of the borderline forms of multiple sclerosis.
Marburg acute multiple sclerosis, also known as Marburg multiple sclerosis or acute fulminant multiple sclerosis, is considered one of the multiple sclerosis borderline diseases, which is a collection of diseases classified by some as MS variants and by others as different diseases. Other diseases in this group are neuromyelitis optica (NMO), Balo concentric sclerosis, and Schilder's disease. The graver course is one form of malignant multiple sclerosis, with patients reaching a significant level of disability in less than five years from their first symptoms, often in a matter of months.
Research in multiple sclerosis may find new pathways to interact with the disease, improve function, curtail attacks, or limit the progression of the underlying disease. Many treatments already in clinical trials involve drugs that are used in other diseases or medications that have not been designed specifically for multiple sclerosis. There are also trials involving the combination of drugs that are already in use for multiple sclerosis. Finally, there are also many basic investigations that try to understand better the disease and in the future may help to find new treatments.
Tumefactive multiple sclerosis is a condition in which the central nervous system of a person has multiple demyelinating lesions with atypical characteristics for those of standard multiple sclerosis (MS). It is called tumefactive as the lesions are "tumor-like" and they mimic tumors clinically, radiologically and sometimes pathologically.
Malignant multiple sclerosis is used to describe MS patients who reach significant level of disability in a short period of time. Malignant MS cases are not common, less than 5% of patients with MS experience this type of progression.
Current standards for diagnosing multiple sclerosis (MS) are based on the 2018 revision of McDonald criteria. They rely on MRI detection of demyelinating lesions in the CNS, which are distributed in space (DIS) and in time (DIT). It is also a requirement that any possible known disease that produces demyelinating lesions is ruled out before applying McDonald's criteria.
Multiple sclerosis (MS) can be pathologically defined as the presence of distributed glial scars (scleroses) in the central nervous system that must show dissemination in time (DIT) and in space (DIS) to be considered MS lesions.
MOG antibody disease (MOGAD) or MOG antibody-associated encephalomyelitis (MOG-EM) is an inflammatory demyelinating disease of the central nervous system. Serum anti-myelin oligodendrocyte glycoprotein antibodies are present in up to half of patients with an acquired demyelinating syndrome and have been described in association with a range of phenotypic presentations, including acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, and neuromyelitis optica.
Anti-neurofascin demyelinating diseases refers to health conditions engendered by auto-antibodies against neurofascins, which can produce both central and peripheral demyelination. Some cases of combined central and peripheral demyelination (CCPD) could be produced by them.
Anti-AQP4 diseases, are a group of diseases characterized by auto-antibodies against aquaporin 4.
Brenda Banwell is Chief of the Division of Neurology and Co-Director of the Neuroscience Center, and Professor of Neurology at Children's Hospital of Philadelphia and holder of the Grace R. Loeb Endowed Chair in Neurosciences. She also holds the title of Professor of Pediatrics and Neurology at the Perelman School of Medicine at the University of Pennsylvania.
The following test results... are seen consistently...: Brain MRI showing swelling in the brain or destruction of part of the nerve cells (demyelination)