Multiple sclerosis (MS) is often categorized into four groups based on the disease course: 1) relapsing-remitting, 2) secondary progressive, 3) primary progressive, and 4) progressive relapsing1. The first two groups are also called relapsing-onset diseases while the other two groups fall under the category of progressive-onset diseases2.

In approximately 85% of patients, the initial course of the disease is relapsing-remitting. This type of MS is characterized by acute attacks (episodes) that are followed by full or partial recovery and a period of remission in between attacks. It is estimated that approximately half of the patients have some residual deficits six months after an attack. Patients with relapsing-remitting MS experience an average of one to two attacks per year. Over time, the frequency of acute attacks often decreases. MS episodes can manifest themselves through a wide variety of neurological symptoms including sensory-, motor-, cerebellum-, brain-stem-, and autonomic system–related symptoms. There is no way to predict the timing and location of the future attacks in an individual3. The first clinical episode of the disease (the first attack) is called clinically isolated syndrome. In every patient with relapsing-remitting MS, the clinical course of the disease starts—by definition—with clinically isolated syndrome (frequently involves a sensory pathway in the spinal cord or optic/retrobulbar neuritis); however, only some patients (30% to 70%) who experience clinically isolated syndrome progress to develop MS2,3,4.

About 65% of patients with an initial relapsing-remitting disease course develop secondary progressive MS5. In these patients a steady decline of neurological functioning happens with or without occasional attacks2,5. It has been suggested that the change in disease course is a result of a shift from a predominantly inflammatory phase to a predominantly degenerative one2. Based on available studies, it is estimated that the median time from the onset of relapsing-remitting disease until conversion to the secondary progressive course is about 19 years (some authors suggest 10 to 15 years)6,7. Studies have identified multiple predicting factors for time to conversion from relapsing-remitting to secondary progressive MS. Older age, male sex, spinal-cord-related symptoms right from the onset, residual disease after initial attack, short remission period between the first two attacks, and increased number of attacks in the first two to five years of onset are shown by some studies to be associated with a faster progression to secondary progressive course; however, the results of other studies are inconsistent in some cases6.

In the other two types of MS (primary progressive and progressive relapsing), the disease is predominantly degenerative right from the onset. Progressive-onset disease is seen in about 15% of patients with MS. These patients are more likely to be older and male when compared with patients who have relapsing-remitting disease. Initial motor or cerebellar symptoms are more common in progressive-onset disease, while relapsing-remitting disease often presents with optic neuritis or sensory symptoms. The two groups also differ in their MRI presentations, pointing to the predominance of the inflammatory process in relapsing-remitting MS. As the name suggests, primary-progressive MS is characterized by a steady progression of the disease from the onset without acute exacerbations. Similar to individuals with primary-progressive MS, patients with progressive-relapsing MS also show progression from the onset but also have clear superimposed acute attacks during the course of their disease1-3. It should be noted that except in exceptional circumstances, it is often not possible to diagnose the subtype of MS at the time of initial diagnosis, as it requires an observation of the disease behavior over a period of time or a well-documented relevant medical history3.

In another system of categorization, MS is divided into two groups: 1) benign MS, and 2) malignant MS. Benign MS is a term that is used for a subset of patients whose disease is deemed to have a good prognosis to the point that it may not require the same management as other patients. The entity of benign MS and its exact clinical definition are in fact matters of controversy. Some authors suggest that patients with minimal disability over a certain period of time after diagnosis (five to 15 years) are unlikely to end up with major disabilities; therefore the early use of disease-modifying agents in these patients is not justified. Others argue that although initial disability might be an indicator of long-term disability in MS, the evidence is not adequate to suggest a different course of action in this subgroup of patients; plus making the diagnosis of benign MS is not straightforward, especially in the initial stages of the disease. Thus, the clinical implications of the issue are controversial8. In contrast, the term “malignant MS” has also been used to show the other extreme of the disease spectrum. Patients with malignant MS are those who accumulate a considerable degree of disability over a relatively short period of time. Similarly to benign MS, there is no consensus on the exact clinical definition of malignant MS and its implications in clinical practice2.

The clinical course of pediatric MS has some overlap with that of adults; nevertheless, there are distinct clinical characteristics especially in younger children with MS. Children with MS commonly present with multiple symptoms, although monosymptomatic presentation is not uncommon. Seizures—a very rare manifestation of MS in adults—are seen in about 5% of children with MS. It takes children with MS more time to reach the secondary-progressive stage; however, their average age at the time of conversion is still lower than that of adults9.

A range of other neurological conditions are sometimes categorized as subtypes of MS or atypical forms of MS. These include Marburg’s acute MS, Balò’s concentric sclerosis, Devic’s disease (also known as neuromyelitis optica or NMO), Schilder’s diffuse sclerosis, and acute disseminated leucoencephalomyelitis. There is no consensus on whether these conditions represent part of the MS spectrum or if they are completely separate entities; however, most practice guidelines address these conditions as separate entities from MS10.

Patients who face the diagnosis of MS are often concerned with long-term prognosis of the disease. Younger age of onset, female sex, optic neuritis or sensory symptoms at onset, and relapsing-remitting subtype are associated with better prognosis8,11. The average life expectancy of MS patients is five to 10 years lower than that of the general population; nevertheless, about 40% of patients with MS reach their seventh decade of life. About 10% of MS patients are unable to walk 10 years after the initial diagnosis; this increases to 89% at the time of a patient’s death5,11. On average, it takes approximately eight years from MS diagnosis to develop limitations in ambulation, about 20 years to have to use a stick for walking, and around 30 years to become wheelchair-dependent. In their discussion with MS patients, physicians should consider the great variability of these prognosis data among different individuals. Although the significance of some prognostic factors has been identified statistically, their application to individual MS patients is of limited value12.