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Types of Multiple Sclerosis
It all begins with..., one day you're walking at home or work and then your leg gives out and you fall. You may have these strange spots in your eyes that never seem to go away even when you clean your glasses. Your arm feels like it has fallen asleep again, or you seem to be tired all of the time and can't get your energy back. It could be that your speech is slurred and you haven't had anything to drink in a week or two, or it's the middle of summer and you thought you were going to get that yard work done, instead you feel wiped out and have to rest. Then your arms and hands shake or tremor uncontrollably, or one of another hundred things could be happening. It's time for you to go see a doctor.

Then you see a doctor, and then a neurologist, and have some wonderful tests done to rule out some conditions and then to verify one. A magnetic resonance imaging (MRI) will reveal if there is any scarring and then a lumbar puncture or spinal tap will provide you with confirmation. You are then presented with multiple sclerosis (MS) and it's the answer, the reason, and the cause. What is this horrible thing and what's it doing to you? What will become of you and your future? Where will this thing take you and how bad will it get?

The two MRI's below show lesions on the brain and on the spinal cord. There are three distinct lesions on the left image of the brain and three distinct lesions on the spinal cord around the 2nd and 3rd cervical vertebra. There is a great significance to the lesions on the spinal cord in that the location is prior to any branching off. Lesions at this location can have a profound impact on multiple locations and possibly with greater severity. This could be compared to damage on a high voltage electrical wire and when it has problems, all of the smaller wires have problems.

Benign Course

Natural history studies have demonstrated that a certain percentage of people with MS experience a benign course. However defining "benign MS" and determining the point at which a person can be classified as having a benign course, are the subject of some controversy.

Determining When the MS Disease Course is Benign

Natural history studies from Northern Ireland, Olmstead County, Minnesota, South Wales, and Gothenburg, Sweden, demonstrate conclusively that a certain percentage of people with MS experience a benign course, meaning no relapses and mild, stable disability over time. The estimate of 10% having benign disease after 20-30 years of illness seems realistic.

The challenge lies in determining what the term "benign" really means, and how long into the disease course one has to wait in order to determine that the course is, in fact, benign. Natural history studies have relied heavily on the Expanded Disability Status Scale (EDSS) measure disease progression; however even within the studies cited here, there is variation in the score (<2 - <3) used to define benign MS. In addition, the EDSS places heavy emphasis on ambulation status, with little attention paid to other functions, including cognition.

With increasing awareness of the potential for significant cognitive impairment in patients with CIS and in patients with little or no physical disability, defining benign MS, and determining the patients for whom early and ongoing treatment with a disease-modifying agent is appropriate, are the subject of some debate.

Progressive Course

MS is a chronic, progressive disease that leads to increasing disability in most individuals. Descriptions of the disease have always included two types of clinical processes, an acute process involving relapses and a chronically persistent progressive process, for which the underlying pathogenic mechanisms of onset are unknown. The vast majority of individuals present with the acute relapsing-remitting form of the disease, and the treatments that are currently available to treat MS are most effective for these individuals. For the majority of those patients who eventually transition to secondary-progressive MS (SPMSP) and for those whose disease course is progressive from onset, primary progressive MS (PPMS), treatment options at this time primarily involve symptomatic management and rehabilitation to mitigate the impact of the disease progression.

In spite of the apparent differences in clinical manifestation between the disease courses, the consensus is that these differences are more quantitative than qualitative and that the relapsing and progressive courses of MS fall along a disease spectrum, with genetic and environmental factors contributing to the variations. While continuing to examine the apparent similarities and differences between the MS disease courses, the international MS community has come together to expedite the development of effective disease-modifying and symptom management therapies for progressive forms of MS.

The International Progressive MS Collaborative has identified the following five research priorities: experimental models for progressive MS; identification and validation of treatment targets and repurposing opportunities; proof-of-concept clinical trial strategies; clinical outcome measures; and symptom management and rehabilitation strategies.

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Visible Lesions on MRI The 1st image (left or top) is in the public domain and falls under Image License A defined under the Image License section of the Disclaimer page.
The brain MRI shows 3 large lesions and several smaller throught the area.
image info These 2 images are Copyright © and fall under Image License F defined under the Image License section of the Disclaimer page.

The Four Main Types of MS
In 1996, four disease courses that were originally identified in MS were updated by the International Advisory Committee on Clinical Trials of MS in 2013. The changes include: the addition of clinically isolated syndrome and the elimination of progressive relapsing MS (PRMS). In addition, modifiers have been added to promote more effective conversations about disease activity and progression and shared decision-making about treatment options.

Prior to the mid-1990's, when someone was diagnosed with MS, it was generally felt that there was not much that could be done to keep it at bay. Once the current medications were approved and the results looked so good, doctors began to place patients on the medications as soon as they were diagnosed. As with any illness, early treatment is the key to slowing down the progression. Unfortunately, slowing it down is the best option at the current time. Every step, with every drug, brings us that much closer to a time when MS can be stopped, reversed, or even cured.

Clinically Isolated Syndrome (CIS)

Relapsing Remitting Multiple Sclerosis (RRMS)

Secondary Progressive Multiple Sclerosis (SPMS)

Primary Progressive Multiple Sclerosis (PPMS)
Clinically Isolated Syndrome (CIS)
Clinically isolated syndrome (CIS) is one of the MS disease courses. CIS refers to a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination (loss of the myelin that covers the nerve cells) in the central nervous system (CNS). CIS can be either monofocal or multifocal:

With CIS, an MRI may demonstrate damage only in the area responsible for the current symptoms; with MS, there may be multiple lesions on MRI in different areas of the brain. A person with CIS, by definition, is experiencing the first episode of symptoms caused by inflammation and demyelination in the CNS; a person with MS has experienced more than one episode.

Monofocal episode - The person experiences a single neurologic sign or symptom. For example, an attack of optic neuritis — that’s caused by a single lesion.

Multifocal episode - The person experiences more than one sign or symptom. For example, an attack of optic neuritis accompanied by weakness on one side — caused by lesions in more than one place.

The episode usually has no associated fever or infection and is followed by a complete or partial recovery.

CIS Progression To MS

Individuals who experience CIS may or may not go on to develop MS. In diagnosing CIS, the healthcare provider faces two challenges: first, to determine whether the person is experiencing a neurologic episode caused by damage in the CNS; and second, to determine the likelihood that a person experiencing this type of demyelinating event is going to go on to develop MS.

High risk of developing MS: - When CIS is accompanied by MRI-detected brain lesions that are similar to those seen in MS, the person has a 60 to 80% chance of a second neurologic event and diagnosis of MS within several years.

Low risk of developing MS: - When CIS is not accompanied by MRI-detected brain lesions, the person has about a 20% chance of developing MS over the same period of time.

According to the 2010 revisions to the diagnostic criteria for MS, the diagnosis of MS can be made when CIS is accompanied by MRI findings (old lesions or scars) that confirm that an earlier episode of damage occurred in a different location in the CNS. As MRI technology becomes more advanced, it's likely that the diagnosis of MS will be made more quickly and there will be fewer people diagnosed with CIS.

An accurate diagnosis at this time is important because people with a high risk of developing MS are encouraged to begin treatment with a disease-modifying therapy in order to delay or prevent a second neurologic episode and, therefore, the onset of MS. In addition, early treatment may minimize future disability caused by further inflammation and damage to nerve cells, which are sometimes silent (occurring without any noticeable symptoms). Several medications are now approved by the U.S. Food and Drug Administration (FDA) for CIS: Avonex®, Betaseron®, Copaxone®, Extavia®, Glatopa™.

Like MS, CIS is two to three times more common in women than men. 70% of people diagnosed with CIS are between the ages of 20 and 40 years (average 30 years) but people can develop CIS at older or younger ages. Based upon clinical symptoms alone, CIS and MS may appear the same. In both, damage to the myelin sheath (demyelination) interferes with the way nerve impulses are carried from the brain, resulting in neurologic symptoms.

According to the 2010 revisions to the diagnostic criteria for MS, when CIS is accompanied by specific findings on MRI that demonstrate that another episode has occurred in the past, the diagnosis of MS can be made.

Many episodes of CIS are mild and resolve without treatment. In other cases, treatment with high dose oral or intravenous methylprednisolone (a steroid) is typically recommended. An MS disease-modifying therapy is often recommended for people diagnosed with a CIS that is considered more likely to progress to clinically definite MS (CDMS), with the goal of delaying a second attack.

Several large-scale clinical trials have been conducted to determine whether early treatment following a CIS can delay the second clinical event, and therefore the diagnosis of CDMS. Based on the results of these studies, the U.S. Food & Drug Administration (FDA) has expanded the indication of several medications used to treat MS to include individuals who have experienced a first clinical episode and have MRI findings consistent with MS. The results of these trials, and the FDA's approval of expanded labeling for certain medications used to treat MS, support the earliest possible treatment for MS, which many believe may delay the development of permanent clinical disabilities.

At this time, it is difficult to predict the future course a person who is diagnosed with a CIS will experience.
Relapsing Remitting Multiple Sclerosis (RRMS)
RRMS is the most common disease course and is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks, also called relapses or exacerbations, are followed by periods of partial or complete recovery (remissions). During remissions, all symptoms may disappear, or some symptoms may continue and become permanent. However, there is no apparent progression of the disease during the periods of remission.

At different points in time, RRMS can be further characterized as either active (with relapses and/or evidence of new MRI activity) or not active, as well as worsening (a confirmed increase in disability over a specified period of time following a relapse) or not worsening. An increase in disability is confirmed when the person exhibits the same level of disability at the next scheduled neurological evaluation, typically 6 to 12 months later. Approximately 85% of people with MS are initially diagnosed with RRMS.

Following a relapse, the new symptoms may disappear without causing any increase in level of disability, or the new symptoms may only partially disappear, resulting in an increase in disability. New lesions on MRI, as shown by the arrows, often occur as part of a relapse. However, new MRI lesions indicating MS activity may also occur without symptoms of which the person is aware.

RRMS is defined by inflammatory attacks on myelin (the layers of insulating membranes surrounding nerve fibers in the CNS), as well as the nerve fibers themselves. During these inflammatory attacks, activated immune cells cause small, localized areas of damage which produce the symptoms of MS. Because the location of the damage is so variable, no two people have exactly the same symptoms.

Why are modifiers used to characterize RRMS?

Disease activity and progression should be evaluated at regular intervals by neurologic examination and MRI. Being able to characterize the course of your disease at different points in time helps you and your MS care provider discuss your treatment options and expected outcomes. For example:
If you have RRMS that is active and worsening, you and your MS care provider will likely want to consider a more aggressive treatment approach than if there were no evidence of activity or worsening. Together, you can weigh the potential risks and benefits of other treatment options.
If your symptoms have not worsened on the treatment you are currently taking, but you have evidence of new disease activity on your MRI, you and your healthcare provider may discuss switching to another treatment with a different mechanism of action in order to control the disease activity more effectively and help prevent worsening.
If your RRMS is stable without evidence of MRI activity or worsening, you and your doctor can feel confident that the current treatment regimen is working effectively.

How does RRMS differ from progressive types of MS?

While RRMS is defined by attacks of inflammation (relapses) in the CNS, progressive forms of MS involve much less of this type of inflammation.
People with RRMS tend to have more brain lesions, also called plaques or scars, on MRI scans, and these lesions contain more inflammatory cells.
People with primary progressive MS (PPMS) tend to have more spinal cord lesions, which contain fewer inflammatory cells.

In RRMS, women are affected two to three times as often as men; in PPMS, the number of women and men are approximately equal.

RRMS is diagnosed earlier than the progressive disease courses:
Most people with RRMS are diagnosed in their 20s and 30s (although it can occur in childhood or later adulthood), while the onset of PPMS tends to be in ones 40s or 50s.
The transition to SPMS generally occurs in people who have been living with RRMS for at least 10 years.

The most common symptoms reported in RRMS include episodic bouts of fatigue, numbness, vision problems, spasticity or stiffness, bowel and bladder problems, and problems with cognition (learning and memory or information processing). People with progressive forms of MS are more likely to experience gradually worsening problems with walking and mobility, along with whatever other symptoms they may have.
Secondary Progressive Multiple Sclerosis (SPMS)
SPMS follows an initial relapsing-remitting course. Most people who are diagnosed with RRMS will eventually transition to a secondary progressive course in which there is a progressive worsening of neurologic function (accumulation of disability) over time. SPMS can be further characterized at different points in time as either active (with relapses and/or evidence of new MRI activity) or not active, as well as with progression (evidence of disease worsening on an objective measure of change over time, with or without relapses) or without progression.

This graphic shows the kinds of disease activity that can occur in SPMS; however each person's experience with SPMS will be unique. Following a period of relapsing-remitting disease, disability gradually increases over time, with or without evidence of disease activity (relapses or changes on MRI). In SPMS, occasional relapses may occur, as well as periods of stability.

Why are modifiers used to characterize SPMS?

Disease activity and progression should be evaluated at least yearly by neurologic examination and MRI. Being able to characterize the course of your disease at different points in time helps you and your MS care provider discuss your treatment options and expected outcomes. For example:
If you have SPMS that is active, you and your MS care provider will want to talk about treatment with a disease-modifying therapy to reduce the risk of a relapse.
If you have SPMS that is active and progressing in spite of the medication you are taking, the conversation with your MS care provider might be about the potential benefits and risks associated with switching to a more aggressive treatment strategy.
If your SPMS is not active but there is evidence of progression and accumulation of disability, you and your MS care provider will want to focus on rehabilitation strategies to help improve your function and mobility, and promote safety and independence.
If your SPMS is stable without activity or progression, the conversation with your MS care could focus on rehabilitation and other symptom management strategies to help you maintain function.

How does SPMS differ from the other disease courses?

SPMS occurs in people who initially had a relapsing-remitting disease course. In other words, SPMS occurs as a second phase of the disease for many individuals. Primary progressive MS (PPMS) is the first — and only — phase of the illness for approximately 15 % of people with MS.

In SPMS, people may or may not continue to experience relapses caused by inflammation; the disease gradually changes from the inflammatory process seen in RRMS to a more steadily progressive phase characterized by nerve damage or loss.

The disease-modifying therapies may be effective for people with SPMS who experience relapses.
Primary Progressive Multiple Sclerosis (PPMS)
PPMS is characterized by worsening neurologic function (accumulation of disability) from the onset of symptoms, without early relapses or remissions. PPMS can be further characterized at different points in time as either active (with an occasional relapse and/or evidence of new MRI activity) or not active, as well as with progression (evidence of disease worsening on an objective measure of change over time, with or without relapse or new MRI activity) or without progression. Approximately 15 percent of people with MS are diagnosed with PPMS.

This graphic shows the kinds of disease activity that can occur in PPMS; however each person's experience with PPMS will be unique. PPMS can have brief periods when the disease is stable, with or without a relapse or new MRI activity, as well as periods when increasing disability occurs with or without new relapses or lesions on MRI.

Why are modifiers used to characterize PPMS?

Disease activity and progression should be evaluated at least yearly by neurologic examination and MRI. Being able to characterize the course of your disease course at different points in time helps you and your MS care provider have important conversations about your treatment options and prognosis. For example:
If you have PPMS that is active, with new MRI activity or relapses, your conversation with your MS care provider could be about starting treatment with a disease-modifying therapy to reduce the risk of a relapse, as well as rehabilitation to help improve function and mobility.
If you have PPMS that is stable without activity or progression, the conversation with your MS care provider should include the role of rehabilitation to help you maintain function, as well as other symptom management strategies that you may need.
If you have PPMS that is not active (no new MRI activity or relapses) but is progressing with increasing accumulation of disability, the conversation with your MS provider needs to focus on the rehabilitation strategies that can help you maintain function and keep you safe and independently mobile.

How does PPMS differ from the other disease courses?

Although there is a lot of variability among people with PPMS, we know that as a group, they differ in several ways from people with relapsing forms of MS:
Relapsing forms of MS (including relapsing-remitting MS, and secondary progressive in those individuals who continue to experience relapses) are defined by inflammatory attacks on myelin. PPMS involves much less inflammation of the type seen in relapsing MS. As a result, people with PPMS tend to have fewer brain lesions (also called plaques) than people with relapsing MS and the lesions tend to contain fewer inflammatory cells. People with PPMS also tend to have more lesions in the spinal cord than in the brain. Together, these differences make PPMS more difficult to diagnose and treat than relapsing forms of MS.
In the relapsing forms, women are affected two to three times as often as men; in PPMS, the numbers of women and men are approximately equal.
The average age of onset is approximately 10 years later in PPMS than in relapsing MS.
People with PPMS tend to experience more problems with walking and more difficulty remaining in the workforce.
In general, people with PPMS may also require more assistance with their everyday activities.

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Multiple Sclerosis Types of Prior to 2013

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In General

Each type is a worsening of the disease and when it reaches the next course, there is no turning back. That's why early detection and diagnosis is so important. When a doctor suspects that the symptoms could possibly be MS, they try to rule out anything else but it can only confirmed through an MRI and spinal tap. An MRI of the brain and spinal cord will show any lesions or scars existing or in an active state. A spinal tap will give them further confirmation of the disease when the spinal fluid is tested. Now they can proceed to the next step.

Since MS is a chronic disease, progression will most likely occur. On the bright side, around 80% of those with MS have relapsing-remitting MS (RRMS). You can also have progression while staying within your current clinical course. When progression increases in frequency, duration, severity, etc..., your clinical course may change.

You can have an impact on how strong or rapid your progression is by just remembering all those bits of advise from your doctors and even your parents - exercise daily, proper nutrition, don't stay up too late, get plenty of sleep, and the list goes on and on. It all boils down to taking care of yourself, your body and your mind. The other benefit of this bit of advice would possibly be a lowering of your cholesterol, a healthier heart, greater strength, and possibly an improvement of your symptoms.

Each of the four clinical courses can range from mild, moderate, or severe. It's all, however, just a degree of the same thing, you have MS. It's kind of like being pregnant, either you are or you aren't, how far along is the only variable.

Now either you have MS and you must take it very seriously or you don't. Just because you might have a mild case of RRMS doesn't mean that you don't have to treat it. No matter which severity of the clinical courses you may have, they all must be taken very seriously, for if you don't, it may just cost you a price that is more than you wish to pay.

It's important to know that you can no longer afford to burn the candle at both ends. It's important that you make that candle last as long as you can, because it's your only one and can't be replaced. You don't have to stop what you do, but rather become careful with your choices and mindful of the consequences. Just like when you are in your 40's or 50's, you can't and probably shouldn't act as if you are 18 again, whether or not you have MS. You can, however, still have a good time and enjoy life.
Not So Common Course of MS
Malignant Multiple Sclerosis (Malignant MS) is an aggressive and rare form of MS. It's characterized by rapidly progressive inflammation and destruction of myelin (protective covering surrounding the nerves) and increased formation of lesions and plaque in the brain and spine. The loss of myelin affects the brain's ability to transmit electrochemical impulses between the nerve cells of the brain, and the spinal cord, resulting in diminished or loss of neurological functioning.

People with this form of MS experience weakness in their extremities, difficulties with coordination and balance, spasticity, and paresthesias (abnormal sensory feelings of numbness and prickling sensations). Speech impediments, tremors, dizziness, hearing loss, changes in vision, bowel and bladder difficulties, falls, and cognitive impairments are other frequent complaints. As the disease progresses lesions develop in the areas of the brain responsible for information processing, resulting in cognitive impairments such as difficulties with concentration, attention, memory, language, and judgment.

People with malignant MS can have damage to regions of the brain responsible for behavior and emotions resulting in psychotic disorders such as manic depression and paranoia.

People with malignant MS experience a rapid decline in functioning. They require assistance with ambulation within five years from symptom onset due to the loss of the ability of the nerve cell (neurons) to transmit impulses to muscles that control motor functioning. Assistance with ADL’s is required.

Pediatric MS
Although MS occurs most commonly in adults, it’s also diagnosed in children and adolescents. Estimates suggest that 8,000 to 10,000 children (those 18 years of age or less) in the U.S. have MS, and another 10,000 to 15,000 have experienced at least one symptom suggestive of MS.

MS historically has been viewed as an adult-onset disease and the majority of research and support programs have targeted adults. Since 1980, however, over 400 cases of childhood MS have been recorded in over 25 medical publications. Initial symptoms have been seen as early as 13 months old, with diagnosis as young as 2 years of age. Largely because of new technology, the numbers of children and adolescents diagnosed with MS are steadily growing.

Studies have shown that 2 to 5% of all people with MS have a history of symptoms onset prior to the age 18. Diagnosis in children is more challenging than in adults due to the frequency of other childhood disorders with similar symptoms and characteristics.

For children, the first signs of the disease are typically different. A child may have a nerve disorder called acute disseminated encephalomyelitis (ADEM). The typical symptoms of ADEM may include headache, confusion, coma, seizures, stiff neck, fever, and major lack of energy. After a few weeks, the symptoms of ADEM will usally lessen or go away. Some children, however, will keep having problems that are the same as MS.

Most symptoms of MS seen in children are similar to those seen in adults. There are, however, symptoms experienced by children that are not typical in adults, such as seizures and mental status changes.

Increasing evidence suggests a slower disease course in children with MS, but significant disability can accumulate at an earlier age compared to individuals with adult onset MS. Psychosocial consequences of MS in children and adolescents may affect academic performance, family relations, and specific adolescent issues including self-image and relationships with peers. An evaluation by a trained professional can help determine appropriate interventions. Pediatricians may not be familiar with MS because they are not expecting to see it in children.

As the leading private funder of MS research, and because of the critical need to better understand childhood MS, the National MS Society established the first-of-its kind network of Pediatric MS Centers of Excellence. The centers were established in geographically diverse areas so that they can serve as regional centers for as many children and families living with MS as possible. They are staffed by teams of pediatric and adult MS experts who lead the field in MS diagnosis and treatment. The Center locations are:
Center for Pediatric-Onset Demyelinating Disease at the Children's Hospital of Alabama, University of Alabama at Birmingham
Pediatric MS Center of the Jacobs Neurological Institute, State University of New York at Buffalo
Mayo Clinic T. Denny Sanford Pediatric Outpatient Center, Rochester, MN
National Pediatric MS Center at Stony Brook University Hospital, Long Island
Partners Pediatric MS Center at the Massachusetts General Hospital for Children in Boston
University of California, San Francisco Regional Pediatric MS Center