The damage in the second report fulfilled all pathological diagnostic criteria of MS and can therefore be classified as MS in its own right. The lesions were classified as pattern II in the Lucchinetti system. This case of human EAE also showed Dawson fingers.Using the confluent demyelination as barrier between MS and ADEM, some other reports about EAE in humans classify its effects as ADEM but not always. In Japanese patients exposed to rabies vaccine that contained neural tissue, the clinical presentation resembled ADEM more than MS but the lesions were like acute multiple sclerosis (Uchimura and Shiraki, 1957). Anti-TNF demyelination
Recent problems with monoclonal antibodies point to an involvement of tumor necrosis factor alpha in the multiple sclerosis onset. Specifically, a monoclonal antibody against TNF-α (adalimumab) has been reported to induce a MS-like diseaseAlso some experimental therapies for other diseases has produced MS artificially in patients. Specifically, monoclonal antibodies treating cancer like pembrolizumab and infliximab have been reported to produce MS artificially. Specific forms of EAE
Since the discovery of the four lucchinetti patterns, new EAE models have been published, specifically mimicking the patterns I and II. DTH-EAE for pattern I (T cell and macrophage-mediated delayed-type hypersensitivity) and fMOG-EAE for pattern II (antibody-mediated focal myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalitis)Also a model for pattern III lesions has been developed in which mitochondrial metabolism is impaired, resulting in a tissue energy deficiency, a mechanism later termed "virtual hypoxia". The demyelination, characterized by loss of myelin-associated glycoprotein, has been described as "hypoxia-like".
The archetypical first clinical symptom is weakness of tail tonus that progresses to paralysis of the tail, followed by a progression up the body to affect the hind limbs and finally the forelimbs.However, similar to MS, the disease symptoms reflect the anatomical location of the inflammatory lesions, and may also include emotional lability, sensory loss, optic neuritis, difficulties with coordination and balance (ataxia), and muscle weakness and spasms. Recovery from symptoms can be complete or partial and the time varies with symptoms and disease severity. Depending on the relapse-remission intervals, rats can have up to three bouts of disease within an experimental period. In mice
Demyelination is produced by injection of brain extracts, CNS proteins (such as myelin basic protein), or peptides from such protein emulsified in an adjuvant such as complete Freunds adjuvant. The presence of the adjuvant allows the generation of inflammatory responses to the protein/peptides. In many protocols, mice are coinjected with pertussis toxin to break down the blood-brain barrier and allow immune cells access to the CNS tissue. This immunisation leads to multiple small disseminated lesions of demyelination (as well as micro-necroses) in the brain and spinal cord and the onset of clinical symptoms.Although sharing some features, mostly demyelination, this model, first introduced in the 1930s, differs from human MS in several ways. EAE either kills animals or leaves them with permanent disabilities; animals with EAE also suffer severe nerve inflammation, and the time course of EAE is entirely different from MS, being the main antigen (MBP) in charge.