Types, courses and the spectrum

Where the names come from

Until the 1990s, neurologists used many different names for the course of MS. In 1996 an international survey of MS experts, led by Fred Lublin and Stephen Reingold, agreed on four: relapsing-remitting, secondary progressive, primary progressive and progressive-relapsing.[1] The definitions were revised in 2013. Progressive-relapsing MS was dropped, because people with that label are now described as having primary progressive MS with activity. Clinically isolated syndrome was added as the first presentation of the disease. Each course was also given two qualifiers, assessed at least once a year: whether the disease is active, meaning relapses or new MRI lesions, and whether it is progressing, meaning disability is worsening steadily.[2] A person might therefore be described as having "relapsing-remitting MS, active" or "secondary progressive MS, not active, with progression".

Relapsing-remitting MS

Most people with MS start with relapsing-remitting MS (RRMS). Relapses, episodes of new or worsening symptoms lasting at least 24 hours, are followed by partial or complete recovery, with stable periods in between (lesson 4.2). Recovery does not mean that all damage has reversed. Disability can still build up, both from relapses that leave something behind and from slow worsening between them, which is often hard to notice at first.[2][18]

Secondary progressive MS

Secondary progressive MS (SPMS) describes steady worsening that follows an initial relapsing course. The change is usually recognised only looking back, after a year or more of worsening, rather than at one clear moment. Relapses or new MRI activity can still occur, so progression does not mean that inflammation has stopped. Medicines are licensed for "active" SPMS in some regions, which is why the qualifier matters in practice.[2]

Primary progressive MS

Primary progressive MS (PPMS) describes worsening from the start, without an initial relapsing phase. It does not mean uninterrupted worsening every day. Plateaus, short periods of improvement and new MRI activity can occur. The 2024 diagnostic criteria use the same framework for PPMS as for relapsing MS, and require at least 12 months of progression (lesson 5.2).[2][6]

Primary progressive MS in more detail

In the ORATORIO trial, published in 2017, ocrelizumab reduced the risk of confirmed disability progression in primary progressive MS compared with placebo. It was the first time a medicine had done this in a phase 3 trial of PPMS.[3] The approved uses differ between regions. In the EU, ocrelizumab is approved for early PPMS with signs of inflammation on imaging, while the US approval has no such restriction.[4][5]

Many other approaches have been tried in PPMS and have not worked. The Research section keeps a running record of every one of them, and of the trials still under way.

Before the diagnosis: CIS and RIS

Clinically isolated syndrome (CIS) is a first episode of symptoms typical of inflammation in the brain, spinal cord or optic nerve, such as optic neuritis, in someone who does not yet meet the criteria for MS. Radiologically isolated syndrome (RIS) describes MRI lesions typical of MS in someone who has had no symptoms, usually found on a scan done for another reason. Neither is a type of MS in itself. Under the 2024 diagnostic criteria, many people with CIS, and some with RIS, can now be diagnosed with MS at the first assessment, when the scan and spinal fluid provide enough evidence.[6]

Age at onset

MS in children. Fewer than 5 per cent of people with MS have their first symptoms in childhood. In the largest natural history study, of 394 people with onset at 16 or younger, 98 per cent started with a relapsing course, against 84 per cent of those with adult onset. They took about 10 years longer to reach secondary progression and fixed disability, but reached them about 10 years younger, at a median age of 41 for secondary progression.[7] Children also have more relapses. In a US cohort, the relapse rate was 2.3 times that of adults over the first six years.[8] This points to more inflammation early in the disease, while the slower build-up of disability may reflect a young brain's greater ability to compensate.

MS that starts after 50. About 5 per cent of people with MS have their first symptoms at 50 or older. In a meta-analysis of these studies, about half started with a relapsing course, and in some studies progressive onset was more common. Weakness was the most common first symptom, and the spinal cord was often involved.[9] Diagnosis is harder at this age, because small white spots from other causes are common on MRI, which is why the 2024 criteria ask for extra evidence in people over 50 (lesson 5.2).

Labels for how severe the course is

Benign MS is used for people who have little disability after many years, usually an EDSS of 3 or less after 10 years or more. The label is controversial. Depending on the definition, between 30 and 80 per cent of people with RRMS meet it at 10 years, and it does not protect against worsening later.[11] The EDSS also misses much of what matters. In one cohort, 43 of 342 people met the definition, and over the following years nearly half of them developed cognitive impairment and three quarters had new lesions on MRI, without any change in their EDSS.[10]

Aggressive MS, sometimes called highly active MS, describes the opposite: frequent relapses with poor recovery and rapid build-up of disability in the first years. There is no agreed definition. A 2018 ECTRIMS workshop could not reach consensus, because data linking a severe course to imaging or blood markers were lacking.[12] The term matters in practice, because a course like this is a common reason to start the most effective treatments early.

Rarer forms

Some people have lesions that look or behave very differently from typical MS. These forms are rare, and they matter because they can be mistaken for a brain tumour or an infection, and because some overlap with other diseases. They are known as atypical inflammatory demyelinating syndromes.[13]

Tumefactive MS. A tumefactive lesion is a demyelinating lesion larger than 2 cm, often with swelling around it, pressure on nearby tissue and a ring of contrast enhancement on MRI, so that it can look like a tumour or an abscess. In the largest series, of 168 people whose lesions were confirmed by biopsy, 61 per cent had their first neurological episode at the time, and 70 per cent went on to develop MS. Most had other, smaller lesions as well, and only 17 per cent still had a single lesion at follow-up. In those followed for more than 10 years, disability was lower than in people with typical MS of the same duration, with a median EDSS of 1.5 against 3.5.[14] Tumefactive lesions can also occur in NMOSD and MOGAD, so antibody tests are part of the work-up (lesson 10.1).

Baló's concentric sclerosis. Here a lesion forms alternating rings of lost and preserved myelin, which look like the rings of an onion or a tree on MRI and under the microscope.[13][15] Large Baló lesions can resemble a tumour. In many people the lesion appears as the first episode of MS or alongside typical MS lesions, and Baló-like lesions have also been described in NMOSD.

Marburg variant. This is the most severe form: a sudden onset with many large, active lesions and rapid worsening over weeks. A 2026 systematic review found only 23 reported cases with treatment and outcome described. Six of the 23 people died. Improvement was more frequent in those who received cyclophosphamide or mitoxantrone in addition to high-dose steroids, often with plasma exchange.[16]

Schilder's disease. Also called diffuse myelinoclastic sclerosis, it consists of one or two very large lesions in the white matter of the cerebral hemispheres, often in both, which can look like a tumour. It is mainly considered in children, and can be a single episode or relapse.[13][17]

Progressive solitary sclerosis. In 2016, researchers at the Mayo Clinic described 30 people with gradually worsening weakness for more than a year caused by a single demyelinating lesion, with no other lesions and no relapses elsewhere. The lesion was most often in the neck part of the spinal cord. Half had spinal fluid findings typical of MS. These people look like progressive MS clinically, but one lesion does not meet the diagnostic criteria, and the authors suggested that future criteria could include this presentation.[19]

Older textbooks also describe "opticospinal MS", affecting mainly the optic nerves and spinal cord, which was reported mostly in Asia. Many of those cases are now known to have been NMOSD (lesson 10.1).

From fixed types to a spectrum

The 2013 definitions already treated the course names as descriptions of how a person presents at a given time, not as separate diseases.[2] Fred Lublin, who led both panels, has since called them "clinical constructs based on what the patient presents with at the time."[22]

Large datasets support a more continuous view. In the two large ocrelizumab trials in relapsing MS, most confirmed disability worsening happened without a relapse, which the authors said challenges the distinction between relapsing and progressive forms.[18] An analysis of more than 27,000 people from trials and registries found that progression independent of relapse activity started early, occurred in every type of MS, and became the main driver of disability over time.[20]

In 2023 an international expert group proposed treating the course of MS as a spectrum, defined by how much each of several overlapping processes contributes in a given person at a given time: focal inflammation that causes relapses and new lesions, widespread smouldering inflammation and nerve damage, and the brain's capacity to repair and compensate. Ageing increases the brain's vulnerability and reduces its resilience. In this view, what looks like a change to a progressive course is a gradual shift in that balance, not the start of a different disease.[21] A related account argues that much of the difference between relapsing and progressive MS reflects neurological reserve, the brain's ability to compensate for damage. Early damage is hidden by reserve, and as reserve is used up by the disease and by ageing, the same slow processes become visible as progression.[23]

Lublin describes this as "viewing the disease as a spectrum", along which people "can move bidirectionally": a relapsing phase, a stable phase and a progressive phase can follow one another, and a person in a progressive phase can stabilise or have relapses again. In his words, "It's one disease along a spectrum."[22]

What replaces the labels

The aim is to describe each person by the processes active in their disease, measured with MRI, blood and spinal fluid markers, rather than by a course label alone. Some of these measures are already in use. Paramagnetic rim lesions and the central vein sign are part of the 2024 diagnostic criteria (lesson 6.2), and neurofilament light is used in trials (lesson 7.2).[6]

In 2026, members of the International Advisory Committee on Clinical Trials in MS, the group that wrote the 1996 and 2013 definitions, published a roadmap for moving from the current course descriptions to ones based on biology. They set out what is wrong with the current descriptions, what new ones would need, and the steps towards them.[24] Until such descriptions are agreed and validated, the course names remain in use for diagnosis, for the licences of medicines and for deciding who can join a trial.