[3] As a demyelinating disease, MS disrupts the nervous system's ability to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems.

Intelligence, language, and semantic memory are usually preserved, and the level of cognitive impairment varies considerably between people with MS.[35][36][37] Uhthoff's phenomenon, a worsening of symptoms due to exposure to higher-than-usual temperatures, and Lhermitte's sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS, although may not always be present.

[1] Another presenting manifestation that is rare but highly suggestive of a demyelinating process such as MS is bilateral internuclear ophthalmoplegia, where the patient experiences double vision when attempting to move their gaze to the right & left.

[47][48] 85% of cases begin as a clinically isolated syndrome (CIS) over a number of days with 45% having motor or sensory problems, 20% having optic neuritis,[31] and 10% having symptoms related to brainstem dysfunction, while the remaining 25% have more than one of the aforementioned difficulties.

However, it is crucial to adhere to established diagnostic criteria when treating optic neuritis due to the broad range of alternative causes, such as neuromyelitis optica spectrum disorder (NMOSD), and other autoimmune or infectious conditions.

[2] A relationship between season of birth and MS lends support to this idea, with fewer people born in the Northern Hemisphere in November compared to May being affected later in life.

[73] Environmental risk factor reviews have correlated lower sun exposure with higher MS rates though the effect does not completely align with earth's solar irradiance latitude gradient.

High environmental risks were found from oil well fumes, pesticides and low-frequency magnetic fields, e.g., electric power transmission towers and passageways.

[15] The three main characteristics of MS are the formation of lesions in the central nervous system (also called plaques), inflammation, and the destruction of myelin sheaths of neurons.

[1] As briefly detailed in the causes section of this article, MS is currently thought to stem from a failure of the body's immune system to kill off autoreactive T-cells & B-cells.

[8] To be specific, MS involves the loss of oligodendrocytes, the cells responsible for creating and maintaining a fatty layer—known as the myelin sheath—which helps the neurons carry electrical signals (action potentials).

[8] A repair process, called remyelination, takes place in the early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell's myelin sheath.

Gadolinium can be administered intravenously as a contrast agent to highlight active plaques, and by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.

[120] Independently of the types published by the MS associations, regulatory agencies such as the FDA often consider special courses, trying to reflect some clinical trial results on their approval documents.

[162] Interferons may produce flu-like symptoms;[163] some people taking glatiramer experience a post-injection reaction with flushing, chest tightness, heart palpitations, and anxiety, which usually lasts less than thirty minutes.

[5][167] Fingolimod may give rise to hypertension and slowed heart rate, macular edema, elevated liver enzymes, or a reduction in lymphocyte levels.

[142][144] Tentative evidence supports the short-term safety of teriflunomide, with common side effects including headaches, fatigue, nausea, hair loss, and limb pain.

[197] Evidence suggests vitamin D supplementation, irrespective of the form and dose, provides no benefit for people with MS; this includes for measures such as relapse recurrence, disability, and MRI lesions while effects on health‐related quality of life and fatigue are unclear.

[25] The diagnosis was based on Charcot triad and clinical observation until Schumacher made the first attempt to standardize criteria in 1965 by introducing some fundamental requirements: Dissemination of the lesions in time (DIT) and space (DIS), and that "signs and symptoms cannot be explained better by another disease process".

Saint Lidwina of Schiedam (1380–1433), a Dutch nun, may be one of the first clearly identifiable people with MS. From the age of 16 until her death at 53, she had intermittent pain, weakness of the legs and vision loss: symptoms typical of MS.[222] Both cases have led to the proposal of a "Viking gene" hypothesis for the dissemination of the disease.

[224][225] Another early account of MS was kept by the British diarist W. N. P. Barbellion, pen name of Bruce Frederick Cummings (1889–1919), who maintained a detailed log of his diagnosis and struggle.

[226] Charles Dickens, a keen observer, described possible bilateral optic neuritis with reduced contrast vision and Uhthoff's phenomenon in the main female character of Bleak House (1852–1853), Esther Summerville.

[16] Even though a variety of studies showed the connection between an EBV infection and a later development of multiple sclerosis, the mechanisms behind this correlation are not completely clear, and several theories have been proposed to explain the relationship between the two diseases.

[229] This is supported by the fact that treatment against B-cells, e.g. ocrelizumab, reduces the symptoms of multiple sclerosis: annual relapses appear less frequently and the disability progression is slower.

[230] A 2022 Stanford University study has shown that during an EBV infection, molecular mimicry can occur, where the immune system will produce antibodies against the EBNA1 protein, which at the same time is able to bind to GlialCAM in the myelin.

Additionally, they observed a phenomenon which is uncommon in healthy individuals but often detected in multiple sclerosis patients – B-cells are trafficking to the brain and spinal cord, where they are producing oligoclonal antibody bands.

It is probable that B-cells, expressing IGHV 3–7 genes entered the CSF and underwent affinity maturation after facing GlialCAM, which led consequently to the production of high-affinity anti-GlialCAM antibodies.

[238] Since disease progression is the result of degeneration of neurons, the roles of proteins showing loss of nerve tissue such as neurofilaments, tau, and N-acetylaspartate are under investigation.

[252] It has also been proposed that certain bacteria found in the gut use molecular mimicry to infiltrate the brain via the gut–brain axis, initiating an inflammatory response and increasing blood-brain barrier permeability.

[256][better source needed] In 2024, scientists shared research on their findings of ancient migration to northern Europe from the Yamnaya area of culture,[257] tracing MS-risk gene variants dating back around 5,000 years.