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.
[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.
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 recent problems with artificial anti-TNF-α autoimmunity also point to the possibility of tumor necrosis factor alpha involvement in some multiple sclerosis variants.
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.
[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.
[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.
[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.
[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.
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.
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.
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.
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.
[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.
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.
[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.
[150] Pediatric MS patients tend to have active inflammatory disease course with a tendency to have brainstem / cerebellar presentations at onset.
[medical citation needed] Currently there is no single diagnosis test for MS that is 100% sensitive and specific.
[citation needed] The pathological definition based on proven dissemination in time and space has problems.