Glossary | MS in depth

A

Absolute difference: The plain difference between two risks, for example 29 minus 17 per cent.
Action potential: The brief electrical pulse a nerve cell sends along its axon.
Aggressive MS: MS with frequent relapses, poor recovery and rapid build-up of disability in the first years. There is no agreed definition.
Ancient DNA: DNA recovered from human remains thousands of years old, used to trace how genes spread.
Annualised relapse rate: The number of relapses per person-year in a study group, estimated over the observation period.
Anti-CD20: Medicines that remove B cells by attaching to the CD20 protein on their surface, such as ocrelizumab and ofatumumab.
Antigen-specific tolerance: Switching off the immune response against one target, such as myelin, while leaving the rest of the immune system working.
Astrocyte: A star-shaped support cell of the brain and spinal cord. In AQP4-positive NMOSD, antibodies target a protein on astrocytes.
Axon (nerve fibre): The long extension of a nerve cell that carries its signal. Losing axons, rather than myelin alone, is thought to cause most lasting disability.

B

B cell: A white blood cell that can present targets to T cells, release inflammatory signals and mature into antibody-making cells. Some B-cell-targeting medicines are highly effective MS treatments.
Baló's concentric sclerosis: A rare form of demyelination in which a lesion forms alternating rings of lost and preserved myelin.
Benign MS: A disputed label for MS with little disability after many years, usually an EDSS of 3 or less after 10 years.
Biologic: A medicine made by living cells, usually a protein such as an antibody, given by injection or infusion.
Black hole: A lesion that stays dark on T1-weighted MRI, a sign of severe tissue and axon loss.
Blood-brain barrier: The tight lining of the small blood vessels of the brain and spinal cord, which keeps most immune cells and large molecules out.
Brain atrophy: Loss of brain volume over time. It happens with age in everyone and is often faster in MS, but measurements can also be affected by inflammation and treatment.
BTK inhibitor: A medicine that blocks Bruton’s tyrosine kinase, an enzyme involved in signalling in B cells and microglia. How well it enters the brain varies between medicines.

C

CD4 and CD8: Markers that divide T cells into helpers (CD4), which direct responses, and cytotoxic cells (CD8), which kill.
Central vein sign: A small vein running through the centre of a lesion on MRI. It can support an MS diagnosis in specified circumstances under the 2024 McDonald criteria.
Cerebrospinal fluid: The clear fluid around the brain and spinal cord, sampled by lumbar puncture.
CIS: Clinically isolated syndrome: a first episode suggestive of inflammatory demyelination. Depending on the other evidence, MS may already be diagnosable.
Clinico-radiological paradox: The poor match between lesions on standard MRI and a person's disability.
Clonal expansion: Many copies of one immune cell, made after it meets its target.
Compartmentalised inflammation: Inflammation that persists inside the brain and spinal cord behind a largely closed barrier.
Conduction block: Failure of a signal to pass along a stretch of axon that has lost its myelin.
Confirmed disability progression: A rise in EDSS meeting a stated threshold and still present at a check, often three or six months later. The threshold and confirmation rules vary by trial.
Cortical lesion: A lesion in the cortex, the outer grey matter of the brain. Often hard to see on standard MRI.
Cuprizone model: Mice fed cuprizone, a chemical that kills the cells that make myelin, used to study loss of myelin and repair without an immune attack.
Cytokine: A signalling protein that immune cells release to direct other cells.
Cytomegalovirus: A common herpesvirus related to EBV and spread in a similar way. Infection with it did not raise MS risk.

D

Dawson's fingers: Oval lesions pointing away from the ventricles along small veins, typical of MS.
Disease-modifying therapy (DMT): A medicine taken over months or years to change the course of MS, as opposed to treating a relapse or a symptom.
Dissemination in space and time: Evidence of MS-typical damage in different parts of the nervous system and at different times. The current diagnostic criteria allow some pathways without separate evidence of damage at different times.

E

EAE: Experimental autoimmune encephalomyelitis: an MS-like disease caused in animals, usually mice, by immunising them against a myelin protein. The most used animal model of MS.
EBNA1: A protein of the Epstein-Barr virus. Some antibodies against it also bind a brain protein, GlialCAM.
EDSS: Expanded Disability Status Scale, from 0 (normal examination) to 10, the main disability measure in trials. Its middle range depends heavily on walking.
Epstein-Barr virus (EBV): A common herpes virus that causes glandular fever. Infection appears to be almost necessary for MS, but most infected people never develop it.
Evoked potentials: Tests that measure how fast a nerve pathway carries a signal, for example from the eye to the brain. Slowing suggests lost myelin.

F

FLAIR: Fluid-attenuated inversion recovery: an MRI sequence that shows lesions as bright spots and darkens the fluid around them.
Functional neurological disorder: Real neurological symptoms caused by a problem in how the nervous system works rather than by damage to it.

G

Gadolinium: A contrast agent injected before an MRI scan. It leaks into lesions where the barrier is open.
Gadolinium-enhancing lesion: A lesion that lights up on MRI after a contrast injection, because the dye leaks through a damaged blood-brain barrier. A sign of recent inflammatory activity.
GCIPL: Ganglion cell and inner plexiform layer: the retinal layer containing the nerve cells whose axons form the optic nerve.
Genetic variant: A difference in the DNA sequence between people. Most risk variants for MS are common and have small effects.
Genome-wide association study: A study comparing the DNA of many people with and without a disease to find variants linked to it.
GFAP: Glial fibrillary acidic protein, released by astrocytes. Studied as a blood marker of slow progression.
Glandular fever (infectious mononucleosis): An illness caused by first infection with EBV in adolescence or adulthood, with fever, sore throat and tiredness. It doubles the risk of MS.
Glia limitans: The inner wall of the blood-brain barrier, formed by the feet of astrocytes.

H

Hazard ratio: A comparison of the event rate over time between groups. A hazard ratio of 0.76 means the estimated hazard was 24 per cent lower in one group during the study. It does not necessarily mean 24 per cent fewer people had the event.
HLA: Human leucocyte antigen: molecules that display protein fragments to T cells. Different versions change MS risk.
HLA-DRB1*15:01: A version of an immune gene that is the strongest single genetic risk factor for MS.

I

IgG index: A ratio comparing antibody levels in spinal fluid and blood, corrected for leakage. A raised index suggests antibody made in the nervous system.
Integrin: A grip molecule on immune cells that lets them stick to vessel walls. Natalizumab blocks α4 integrin.
Intrathecal synthesis: Production of antibodies inside the brain and spinal cord rather than in the blood.
Isoelectric focusing: A laboratory method that separates proteins by electrical charge on a gel, used to show oligoclonal bands.

K

Kappa free light chains: Fragments of antibodies measured in spinal fluid. Raised levels show antibody production inside the nervous system and can support a diagnosis of MS.
Kappa index: The level of kappa free light chains in spinal fluid relative to blood, corrected for leakage.

L

Late-onset MS: MS with first symptoms at the age of 50 or older.
Latent infection: A virus staying quietly inside cells without making new virus, often for life.
Lesion (plaque): An area of damage where myelin has been lost and the tissue scarred.
Lhermitte's sign: A brief electric sensation down the spine or limbs when bending the neck, from a lesion in the neck part of the spinal cord.
Lumbar puncture: A procedure that takes a small sample of spinal fluid through a needle in the lower back.
Lysolecithin model: A small injection of lysolecithin into the spinal cord or brain, which strips myelin in one place, used to study repair.

M

Macrophage: A large immune cell that swallows debris, including stripped myelin. In the brain it comes from blood monocytes.
Marburg variant: A very rare, sudden and severe form of MS with many large active lesions.
McDonald criteria: The international criteria for diagnosing MS, last revised in 2024 and published in 2025.
Meninges: The membranes that cover the brain and spinal cord.
Microglia: The resident immune cells of the brain and spinal cord. In MS they sustain slow inflammation at the edges of chronic lesions.
MOG: Myelin oligodendrocyte glycoprotein, a protein on the outer surface of myelin. An antibody against it causes MOGAD.
Molecular mimicry: When the immune response to a microbe also recognises a similar-looking protein of the body.
Monoclonal antibody: A laboratory-made antibody designed to attach to one target. Many names end in -mab, but newer naming conventions use other endings.
Myelin: The fatty sheath wrapped around many nerve fibres in the brain and spinal cord. It lets signals jump quickly along the fibre. MS damages it.

N

NEDA: No evidence of disease activity: no relapses, no new or enlarging MRI lesions and no confirmed disability worsening over a stated period. Some versions add brain atrophy or blood markers.
Neurodegenerative disease: A disease in which nerve cells are lost progressively over years, such as Alzheimer's, Parkinson's and ALS.
Neurofilament light (NfL): A protein released when nerve fibres are damaged. Blood levels can rise with new inflammation and fall on effective treatment. Other conditions can also affect its level.
Neurological reserve: The brain's ability to compensate for damage, so that it does not yet cause symptoms.
Node of Ranvier: A short bare gap between two segments of myelin, where the nerve signal is renewed.
Normal-appearing white matter: White matter that looks normal on standard MRI but shows diffuse damage under the microscope.
Number needed to treat: How many people must be treated for one of them to benefit.

O

OCT: Optical coherence tomography: a quick eye scan that measures the thickness of nerve layers in the retina, a window on nerve loss.
Oligoclonal bands: Distinct bands of antibodies found in spinal fluid but not matched in blood, showing antibody production inside the nervous system. They are common in MS but are not specific to it.
Oligodendrocyte: The cell in the brain and spinal cord that makes myelin. One oligodendrocyte can wrap many axons.
Oligodendrocyte precursor cell (OPC): An immature cell that can mature into an oligodendrocyte and make new myelin. Repair depends on it.
Optic neuritis: Inflammation of the optic nerve, causing blurred vision and pain on moving the eye. Often the first symptom of MS.
Organoid: A small three-dimensional cluster of human cells grown from stem cells that copies some features of an organ such as the brain.

P

P100: The main peak of the visual evoked response, normally at about 100 milliseconds. A delay suggests loss of myelin.
Paediatric-onset MS: MS with first symptoms before the age of 18.
Paramagnetic rim lesion: A chronic lesion with a rim of iron-laden immune cells at its edge, visible on special MRI. A marker of smouldering inflammation.
Peptide: A short chain of amino acids, a fragment of a protein. T cells recognise peptides.
Perivascular space: The narrow sleeve around a blood vessel in the brain, between the vessel wall and the brain tissue.
Phase 1, 2 and 3: The stages of testing in people: safety and dose, then an early sign of effect, then a large test of benefit.
PIRA: Progression independent of relapse activity: disability that worsens without a relapse to explain it.
Placebo: A dummy treatment that looks like the real one, used so that trial results reflect the medicine itself.
Plasma cell: An antibody-making cell derived from a B cell. Most plasma cells do not carry CD20, so anti-CD20 medicines do not directly target them.
PML: Progressive multifocal leukoencephalopathy: a rare, serious brain infection by the JC virus, linked to some MS medicines.
Preclinical: Research done before testing in people, in cells or animals.
Prodrome: A phase before a disease is recognised, when changes are already happening. MS may have one lasting years.
Progressive solitary sclerosis: Slowly worsening weakness caused by a single demyelinating lesion.
Pseudo-atrophy: A faster fall in brain volume soon after starting an effective treatment, as swelling from inflammation resolves.
Pseudo-relapse: A temporary return of old symptoms during fever, infection or heat. It settles when the cause does and is not a relapse.

R

RAW: Relapse-associated worsening: disability left behind by incomplete recovery from a relapse.
Regulatory T cell: A T cell that holds other immune cells in check and helps prevent autoimmunity.
Relapse (attack): New or worsening symptoms lasting at least 24 hours, without fever or infection to explain them.
Relative reduction: How much smaller a risk becomes, as a share of the original risk.
Remyelination: The brain's own repair of lost myelin, by new oligodendrocytes. It happens in MS but often falls short.
Retinal nerve fibre layer: The layer of axons on the inner surface of the retina that forms the optic nerve. Measured by OCT.
RIS: Radiologically isolated syndrome: MRI changes typical of MS in someone without symptoms.

S

S1P modulator: A medicine that keeps immune cells in the lymph nodes by blocking the S1P signal they follow to leave, such as fingolimod.
Saltatory conduction: The way a signal travels along a myelinated axon, renewed at each gap in the myelin so it seems to jump.
Schilder's disease: A rare form of demyelination with one or two very large lesions in the cerebral white matter, mainly in children.
Schwann cell: The cell that makes myelin for nerves outside the brain and spinal cord. MS spares it.
Shadow plaque: A lesion that has been repaired with new, thinner myelin, so it looks paler than normal tissue.
Sibling recurrence risk: How much more likely a brother or sister of someone with a disease is to develop it than a member of the population.
Simoa: Single-molecule array, an ultra-sensitive laboratory method that made NfL measurable in blood.
Slowly expanding lesion: A lesion that grows slowly between MRI scans, a marker of smouldering inflammation.
Small molecule: A relatively small, chemically made drug molecule. Many are taken as tablets, but some are given by other routes.
Small vessel disease: Damage to the brain's small blood vessels with age, high blood pressure or diabetes. It causes white spots on MRI that can be mistaken for MS.
Smouldering lesion: A chronic lesion with a burnt-out centre and an active edge that slowly expands. Also called a chronic active or mixed active and inactive lesion.
Susceptibility-weighted imaging: An MRI technique sensitive to iron and veins, used to see rim lesions and the central vein sign.

T

T cell: A white blood cell that recognises a specific target and directs or carries out an immune attack.
T1 and T2: Two ways MRI can weight its pictures, based on how quickly hydrogen nuclei relax. Lesions look bright on T2 and grey or dark on T1.
T2 lesion: A lesion visible as a bright spot on a T2-weighted MRI sequence. New or enlarging T2 lesions, compared with an earlier scan, can show activity since that scan.
Tolerogenic dendritic cell: A dendritic cell grown in the laboratory to calm, rather than start, an immune response to the peptides it carries.
Tumefactive lesion: A demyelinating lesion larger than 2 cm, often with swelling, that can look like a tumour on MRI.

U

Uhthoff's phenomenon: A temporary return or worsening of symptoms with heat or exercise, caused by slower conduction in demyelinated fibres. It is not a relapse.

Z

Z score: How far a result is from the average of healthy people of the same age, in standard units. Zero is average, above 1.5 is high.