Multiple sclerosis takes on many forms and every MS diagnosis is different. There is no way with certainty to predict how an individual’s disease will progress. However, there are four types of MS that define its clinical course. These currently accepted sub-categories were defined in 2013. New research and increased understanding of MS modified the prior classifications. One type was dropped while another added. (We will explore the four types below). These four standardized definitions capture the disease activity, based on relapse rate and MRI findings, and disease progression.
Let’s first review the disease itself. MS is caused by an abnormal autoimmune response that causes the immune system to attack the healthy tissue in the central nervous system, affecting the brain, spinal cord, and optic nerves. The resulting damage to myelin, the protective sheath that covers nerve fibers, causes communication problems between the brain and the rest of the body.
Changes in MS Treatment
The course of multiple sclerosis has improved over the past two decades. Today, MS patients fare better than 20 years ago: showing slower progression, fewer flares-ups, and decreased disability. Certainly, improved drug therapies are the most significant driver of the change. But earlier detection also has played a role. As MRI technology and laboratory techniques have improved, the diagnosis of MS can be made more quickly and easily.
In fact, the recommendations have changed over the past couple of decades to begin treatment as early as possible. Historically, diagnosing MS required a high burden of proof. MRI scans and spinal fluid analyses were not available to facilitate diagnosis. Instead, to be diagnosed with MS, three lesions, separated by time and space, needed to be observed. That meant that the patient had three clinical flares that affected different parts of the nervous system, and that there was at least six months between flares. Today, with improved technology, diagnosis of MS — or probable MS — can be made on radiologic findings and laboratory findings alone.
With the improved diagnosis of MS, there are currently four accepted types of multiple sclerosis, and one other designation that is gaining traction in the field.
Radiologic Isolated Syndrome (RIS)
To understand the types of MS, we start with Radiologic Isolated Syndrome (RIS). While RIS is not yet considered an official subgroup of MS, from a medical perspective, RIS detection warrants close surveillance.
Patients with RIS show abnormalities on an MRI of the brain or spinal cord that’s consistent with lesions of MS. (Lesions are increased white matter signals on an MRI). However, these individuals have not manifested clinical symptoms of MS. Often, a brain MRI was ordered for these patients after complaining of symptoms, such as headaches, that are not suggestive of MS. A global study published in 2020 which followed 457 people with the rare phenomenon of RIS revealed that over half went on to develop MS within ten years.
Clinically Isolated Syndrome (CIS)
Clinically Isolated Syndrome (CIS) refers to the very first episode of neurologic symptoms caused by inflammation or demyelination (loss of the myelin) in the central nervous system. The episode, which must last for at least 24 hours, is characteristic of MS but does not yet meet the criteria for a diagnosis of MS.
CIS can be either monofocal or multifocal. The difference between the two is implied by the name prefix: “mono” versus “multi.” During a monofocal episode, the patient suffers from a single neurologic sign or symptom that is caused by a single lesion. In a multifocal episode, the patient suffers from more than one sign or symptom caused by lesions in more than one part of the brain.
Those who experience CIS may or may not go on to develop MS. In fact, patients with their first clinical symptoms and with MRI findings consistent with MS have a 60 to 80 percent chance of developing MS in several years. If there are no associated MRI-detected brain lesions, the patient is at lower risk for developing MS, Only 20% of CIS patients develop MS in several years.
New diagnostic criteria for MS (updated in 2017) offer revised guidelines for a MS diagnosis of CIS patients. When CIS is accompanied by MRI evidence of a previous episode, made evident by old lesions or scars, the diagnosis of MS can be made. The presence of oligoclonal bands in a person’s cerebrospinal fluid can also help make the diagnosis.
Several Disease Modifying Drugs (DMD) for MS have been FDA approved for use in CIS. It is important to consider starting a DMD as it may delay or prevent progression to full-blown MS. These medications can reduce further damage from inflammation in the brain — therefore reducing long-term disability that can accompany MS.
Relapsing-Remitting MS (RRMS)
The most common type of MS is relapsing-remitting MS (RRMS). This disease course makes up 85 to 90 percent of the MS population.
Patients with relapsing-remitting MS have intermittent “relapses,” defined as new or worsening symptoms that last 48 hours or more. Relapses are followed by periods of partial or complete recovery, or remissions. Neurologic symptoms between relapses are stable or absent.
Whether a patient has a full resolution of the symptoms during remission periods depends on a several factors. Those factors include: the location of the white matter lesion in the brain (some areas are more sensitive than others); how much myelin repair has been done; and if the new lesion is in the same location or adjacent to a previous lesion. The most common symptoms of a relapse include worsened fatigue, visual blurring or loss, numbness, muscle stiffness, bowel and bladder dysfunction, and cognitive issues.
Treatment options include ongoing DMD to slow the disease progression and/or reduce the number of relapses. In addition, flares are often treated with short courses of oral or intravenous steroids.
Secondary Progressive MS (SPMS)
Some patients with RRMS progress to secondary progressive MS (SPMS). In SPMS, the progression is more of a steady decline without defined relapses and without periods of neurologic stability. Prior to the development of effective DMD, as many as 90% of patients with RRMS progressed to SPMS over 25 years. Currently, with the use of these medicines, closer to only 10% of RRMS patients develop SPMS over three decades.
Risk factors for developing SPMS include male sex, frequent flares early on, a higher MRI “burden” of white matter disease, spinal cord involvement, and a smaller brain volume (which suggests degeneration of the nerve cells in the brain).
Primary Progressive MS (PPMS)
PPMS is characterized by a steady decline in neurologic function and increasing disability, without early relapses or remissions. Neurological functioning decreases with consistent symptoms. There is little to no improvement or change.
In closing, here is some advice from BeCare Link’s Chief Medical Officer Charisse Litchman for those dealing with these different stages of MS.
If you don’t have the diagnosis of MS, seek treatment with your healthcare provider if you show symptoms, such as difficulty walking, visual loss or numbness. If you have been diagnosed with MS, make sure that your doctor empowers you as a partner in pursuing the most effective treatment. BeCare MS Link can help you and your doctor monitor any change in your neurologic exam that would warrant consideration of your treatment therapy.