What is progressive MS?

Neurology

Multiple sclerosis (MS) is a disease that interferes with your brain’s ability to operate your body. It can be disabling. Evidence suggests that the disease happens when your immune system attacks a substance called myelin.

Myelin acts as a type of insulation on your nerve cells. This process can lead to damage in and around the nerves in your brain and spinal cord, as well as nerves involved in your vision.

There are 4 disease courses that have been identified in multiple sclerosis: relapsing-remitting MS (RRMS), primary-progressive MS (PPMS), secondary-progressive MS (SPMS), and progressive-relapsing MS. Each course might be mild, moderate, or severe. Therefore, MS affects people differently.

PPMS is identified by steadily worsening neurologic functions in the beginning without distinct relapses (attacks or exacerbations) or remission. The rate of progression may vary with occasional plateaus and temporary minor improvements, but declining neurologic progression is continuous.

Facts about primary progressive MS

People with PPMS tend to experience problems with walking. They may also have more trouble doing their jobs and their normal activities. Men and women are evenly affected by this type.

About 10% of people diagnosed with MS have this type. On average, people with the primary progressive form of MS start having symptoms between ages 35 and 39.

Symptoms

These are symptoms of MS:

  • Trouble walking

  • Vision problems

  • Muscle weakness

  • Difficulty staying balanced

  • Paralysis

  • Numbness

  • Prickling sensations

  • Dizziness

  • Shakiness

  • Difficulty thinking clearly

  • Mood changes

  • Depression

  • Sexual dysfunction

  • Trouble with bowel and bladder control

Diagnosis

If you have the primary progressive form of MS, it may take your healthcare provider longer to diagnose it. Methods that your healthcare provider may use to diagnose primary progressive MS include:

  • Discussing your symptoms with you

  • Performing a physical examination to see how your nerves and muscles are working

  • MRI scans of your brain and spinal cord; these create images so your healthcare provider can look for signs of damage that suggest MS

  • A spinal tap, which allows the healthcare provider to remove a sample of spinal fluid to check for signs of MS

  • A test called visual evoked potential testing to see how well your optic nerves are working

Treatment

Several drugs are available to treat relapsing forms of MS. But the FDA hasn’t approved any medicines to treat primary progressive MS. These drugs treat a process in the body that happens more in the relapsing form than the primary progressive form.

Your healthcare provider may still be able to use 1 of these medicines in your case. But more likely your healthcare provider will try to provide treatments that relieve symptoms and improve your quality of life. These may address problems like depression, sexual dysfunction, and fatigue.

Prevention

Experts don’t know of a way to prevent MS. But if your body temperature goes up, it may make your symptoms worse for a short time. As a result, you may want to avoid overheating.

Managing this condition

Physical and occupational therapy may be helpful. For example, therapists may teach you exercise strategies and how to manage new symptoms that develop. Your healthcare provider will also probably want to meet with you on a regular basis to monitor your disease.

Regular exercise and getting plenty of sleep may also help.

Primary Progressive Multiple Sclerosis

What is primary-progressive multiple sclerosis?

Multiple sclerosis (MS) is a neurodegenerative disease. It interferes with your brain’s ability to control your body. It can be disabling.

There are 4 main types of MS:

  • Relapsing-remitting MS (RRMS)

  • Primary-progressive MS (PPMS)

  • Secondary-progressive MS (SPMS)

  • Progressive-relapsing MS

Each type might be mild, moderate, or severe. MS affects people differently.

With PPMS, neurologic functions get steadily worse in the beginning. There are no symptom flare-ups (also called relapses or attacks). And there is no recovery (remission). How fast the disease progresses may vary. There can be times when things are stable. And there can be periods of short-term (temporary) minor improvements. But declining neurologic progression is constant.

Men and women are evenly affected by this type of MS. About 10% of people diagnosed with MS have PPMS. On average, people with primary-progressive MS start having symptoms between ages 35 and 39.

What causes primary-progressive MS?

The exact cause of MS is not known, but research suggests it develops when your immune system attacks a substance called myelin. Myelin acts as a type of insulation on your nerve cells. This process can lead to damage in and around the nerves in your brain and spinal cord. It can also damage nerves used for vision.

What are the symptoms of primary-progressive MS?

The occurrence and severity of PPMS symptoms vary with each person. Symptoms can include:

  • Pain (for example, headaches, pain in the legs and feet, back pain, and muscle spasms)

  • Electric-shock sensations that run down the back and limbs when the neck is bent (Lhermitte sign)

  • Trouble walking

  • Vision problems

  • Muscle weakness

  • Trouble staying balanced

  • Paralysis

  • Numbness

  • Prickling feelings

  • Dizziness

  • Shakiness

  • Trouble thinking clearly

  • Mood changes

  • Depression

  • Sexual problems

  • Trouble with bowel and bladder control

How is primary-progressive MS diagnosed?

Methods that your healthcare provider may use to diagnose MS include:

  • Discussion. Your healthcare provider will talk with you about your symptoms.

  • Physical exam. This is done to see how your nerves and muscles are working.

  • MRI scans of your brain and spinal cord. These images will help your healthcare provider look for signs of damage that suggest MS.

  • Optical coherence tomography (OCT). This test measures nerve fibers in the retina.

  • Spinal tap (lumbar puncture). Your healthcare provider removes a sample of spinal fluid to check for signs of MS.

  • Visual evoked potentials (VEP). This test is done to see how well your optic nerves are working.

After the general diagnosis of MS, the diagnosis of PPMS is based almost exclusively on the patient’s symptom history. Because of this, it may take time for the PPMS diagnosis to be made.

How is primary-progressive MS treated?

Several medicines are available to treat relapsing forms of MS. But the FDA hasn’t approved any medicines to treat primary-progressive MS. Your healthcare provider may still be able to use 1 of these medicines in your case. But more likely your healthcare provider will try to provide treatments that relieve symptoms and improve your quality of life. These may address problems such as depression, sexual problems, and extreme tiredness (fatigue).

How can I prevent primary-progressive MS?

Experts don’t know how to prevent MS or the PPMS type of MS. Some people limit MS relapses by avoiding specific triggers such as stress and overheating.

How do I manage primary-progressive MS?

Physical and occupational therapy may be helpful. For example, therapists may teach you exercise strategies and how to manage new symptoms that develop. Your healthcare provider will also probably want to meet with you on a regular basis to monitor your disease.

Regular exercise and getting plenty of sleep may also help. If your body temperature goes up, it may make your symptoms worse for a short time. So it’s best to not do things that could lead to overheating, such as extended periods of time in the sun or overexerting yourself.

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  • The 4 Types of MS
  • The Importance of Early Treatment
  • How Is MS Treated?

Patients usually experience a first neurologic event suggestive of MS known as Clinically Isolated Syndrome (CIS). It lasts for at least 24 hours, with symptoms and signs indicating either a single lesion (monofocal) or more than one lesion (multifocal) within the central nervous system.1

There are 4 types of MS. They’re named according to the way the disease acts on the body over time.2

The 4 Types of MS

  • Relapsing-Remitting MS (RRMS). This is the most common form of multiple sclerosis. About 85% of people with MS are initially diagnosed with RRMS. People with RRMS have temporary periods called relapses, flare-ups or exacerbations, when new symptoms appear2
  • Secondary-Progressive MS (SPMS). In SPMS, symptoms worsen more steadily over time, with or without the occurrence of relapses and remissions. Most people who are diagnosed with RRMS will transition to SPMS at some point3
  • Primary-Progressive MS (PPMS). This type of MS is not very common, occurring in about 10% of people with MS. PPMS is characterized by slowly worsening symptoms from the beginning, with no relapses or remissions2
  • Progressive-Relapsing MS (PRMS). A rare form of MS (5%), PRMS is characterized by a steadily worsening disease state from the beginning, with acute relapses but no remissions, with or without recovery2

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The Importance of Early Treatment

If you are diagnosed with MS or a first-time MS event, you should consider talking about starting treatment as soon as possible with your healthcare team. Researchers have found that MS often causes more damage in the first year than in later years.4

Learn more about the symptoms and diagnosis of MS.

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MS Treatment Options5

There are various MS treatment options available today that have been shown to decrease the frequency of relapses and to delay disease progression. There are several ways that these treatment options can be taken. Some treatments use an injection—either subcutaneous (under the skin) or intramuscular (into the muscle)—while others are given intravenously (via an infusion) or orally (by mouth).

  • Beta interferons are injectable medications used for the treatment of relapsing-remitting MS. Certain beta interferon products also may be used for a first clinical episode with MRI findings consistent with MS. Depending on the medication, injections for beta interferons can be either subcutaneous or intramuscular and dosing can vary from every other day to once a week
  • Glatiramer acetate is given by subcutaneous injection every day for the treatment of relapsing-remitting MS. It is also used for patients who have experienced a first clinical episode and have MRI findings consistent with MS
  • Fingolimod is a once-daily oral capsule indicated for the treatment of relapsing forms of MS to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability
  • Teriflunomide is a once-daily oral tablet used for the treatment of patients with relapsing forms of multiple sclerosis
  • Dimethyl fumarate is an oral capsule taken twice a day that is used to treat people with relapsing forms of MS
  • Mitoxantrone is a chemotherapeutic agent for the treatment of worsening relapsing-remitting MS, progressive-relapsing MS or secondary-progressive MS, and is used to reduce neurologic disability and/or the frequency of clinical exacerbations. It is administered intravenously by an infusion once every three months
  • Natalizumab is an intravenous medication reserved for patients with rapidly progressing MS or with high disease activity despite the use of an alternate MS therapy. It is administered once every four weeks

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  1. Kappos L, Polman CH. Freedman MS, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology. 2006; 67: 1242-1249.
  2. Hooper K. Managing Progressive MS. New York, NY: National Multiple Sclerosis Society; 2011.
  3. Multiple Sclerosis: Just the Facts New York, NY; National Multiple Sclerosis Society;2011.
  4. Kuhlmann T, Lingfield G, Bitsch A, Schuchardt J, Bruck W. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain. 2002;125:2202-2212.
  5. National Multiple Sclerosis Society. The MS Disease – Modifying Medications. New York, NY: National Multiple Sclerosis Society; 2012.

10 Essential Facts About Primary-Progressive MS

For many people with multiple sclerosis (MS), treating the condition focuses on preventing and managing relapses — acute symptoms that are often absent for long stretches of time. Ultimately the disease can result in disability in walking, thinking, and working.

But in people with primary-progressive MS (PPMS) — a small subset of the overall MS population — there is no initial relapse that heralds the onset of the disease, just a gradual appearance of symptoms. This can make PPMS more difficult to identify than so-called relapsing-remitting MS. To make matters more difficult, out of the 15 disease-modifying treatments currently available for MS in the United States, only one is approved for PPMS.

But despite the challenges that PPMS often presents, great strides have been made in its treatment and management. Here are 10 things you should know about PPMS:

1. There’s often no easily identifiable pattern of symptoms in PPMS. While relapsing forms of MS tend to cause an acute neurological episode that’s hard to ignore, the onset of PPMS “is much more gradual and insidious,” according to Patricia K. Coyle, MD, neurologist and director of the Multiple Sclerosis Comprehensive Care Center at Stony Brook University School of Medicine in Stony Brook, New York.

Classic symptoms of PPMS, according to Coyle, include difficulty walking, leg weakness, and muscle spasticity. But because the onset of these symptoms is gradual, “People are more apt to write it off as, ‘I’m getting older, I’m getting clumsier,’” says Dr. Coyle. “I think it’s very easy to miss it for a period of time.”

PPMS can also affect cognitive function. In a study published in April 2013 in the journal Neurology, researchers found that participants with PPMS and those with relapsing-remitting MS both scored worse on cognitive and alertness tests than a control group without MS, but that those with PPMS had impaired cognition in more areas and were more impaired than those with relapsing-remitting MS.

Adding to the list of symptoms that may go unnoticed is a reduced sense of smell. According to a study published in June 2017 in the journal Neurology: Neuroimmunology & Neuroinflammation, 84 percent of participants with PPMS were found to have an impaired sense of smell, compared with just 31 percent of those with relapsing-remitting MS.

2. It’s unclear exactly what causes PPMS. According to Coyle, PPMS is believed to be the result of injury to the myelin that surrounds axons in the brain and spinal cord, as well as to the axons themselves. This neurodegeneration tends to affect all people with MS over time, but it’s unknown why people with PPMS rarely experience the focal inflammation that causes acute symptoms typical of people with relapsing forms of MS.

“Whether there’s a fundamental difference between primary-progressive MS and relapsing MS is not clear,” says Coyle.

According to the National Multiple Sclerosis Society (NMSS), people with PPMS tend to have fewer brain lesions, with fewer inflammatory cells, than people with relapsing MS — which may account for the differences in symptoms. But people with PPMS also tend to have more spinal lesions than brain lesions.

As noted in an article published in May 2017 in the journal Frontiers in Neurology, there are certain genetic factors associated with the risk of MS, but none of them have been shown to predict the type of MS someone develops.

3. PPMS affects only about 15 percent of people with MS. Estimates of the prevalence of PPMS among all people with MS range from about 10 to 15 percent, according to Coyle. The NMSS says that the number is close to 15 percent.

Unlike relapsing forms of MS, which are two to three times more likely to affect women, PPMS affects the two sexes about equally, according to the NMSS.

4. The onset of PPMS tends to occur later than relapsing forms of MS. People with PPMS tend to be older than those with relapsing MS, since the average age of diagnosis is about 10 years later, according to the NMSS.

While the reason for this later onset isn’t fully understood, Coyle says that it may reflect neurodegeneration (degeneration of the nervous system) that shows up clinically at midlife, when there has been a certain amount of loss of central nervous system function.

5. People with PPMS can stabilize for up to several years. In some people with PPMS, Coyle says, the gradual worsening of symptoms that characterizes this form of the disease will abate for up to a few years, for unknown reasons. Sometimes, she says, “You can even see little blips of improvement,” but inevitably this improvement is reversed, and a person’s neurological deficit worsens.

Even when a person with PPMS appears to be clinically stable in terms of symptoms, Coyle says, MRI scans typically show continuing damage to their central nervous system.

6. There is now an FDA-approved drug to treat PPMS. In March 2017, the Food and Drug Administration (FDA) approved Ocrevus (ocrelizumab) as the first disease-modifying drug for PPMS.

Ocrelizumab is given as an intravenous (IV) infusion, typically about every six months. It’s also approved for relapsing forms of MS.

According to a study published in January 2017 in The New England Journal of Medicine, ocrelizumab was found to reduce disability progression in people with PPMS compared with a placebo (inactive treatment). For example, by week 120 of the study, performance on a timed 25-foot walking test had worsened in 39 percent of participants receiving ocrelizumab, compared with 55 percent of those receiving the placebo.

The total volume of brain lesions after 120 weeks was also shown to shrink by an average of 3.4 percent in participants receiving ocrelizumab, compared with an increase of 7.4 percent in those receiving the placebo.

7. The approved drug may not work well in everyone with PPMS. While the overall effectiveness of ocrelizumab for PPMS has been demonstrated, the January 2017 study focused on younger people (age 55 or younger) with more inflammatory disease activity.

Additionally, according to Coyle, a later analysis requested by the FDA showed that ocrelizumab tended to work better in men than in women.

8. Even with treatment, PPMS leads to gradual loss of neurological function. Progressive forms of MS, including PPMS, are considered more severe than relapsing-remitting MS because they inevitably lead to disability, according to Coyle. “Once a patient enters or is in a progressive stage,” she says, “there is going to be gradual deterioration.”

In a study published in April 2017 in Multiple Sclerosis Journal, researchers found that out of a group of 853 participants with PPMS from 24 countries, 17 percent had mild disability, 44 percent had moderate disability, and 39 percent had severe disability. Disability in each group tended to progress significantly over 10 years.

9. It’s important to treat symptoms of PPMS, not just the disease process. While there’s only one disease-modifying treatment with a modest benefit for PPMS, Coyle emphasizes that neurologists can still do a lot to help people with the condition manage their symptoms and improve their quality of life.

This means, according to Coyle, treating any spasticity, cramps, or pain, and talking about adaptive devices and behaviors to make daily tasks less arduous.

10. Attention to overall wellness may help slow the progression of PPMS. Coyle notes that in recent years it’s become increasingly clear how important a general wellness program is for people with PPMS. She emphasizes how important it is not to smoke, to maintain a healthy body weight, to do regular exercise, and to make sure you’re not deficient in vitamin D.

Primary-Progressive MS

Primary-progressive MS (PPMS) is a form of MS characterized by a gradual, but continuous, worsening of symptoms and disease progression from the beginning, or disease onset. PPMS affects a small percentage (about 10%) of patients diagnosed with MS.

There are usually no exacerbations (relapses, flare-ups, or attacks) with PPMS, but there may be periods of time when the disease appears to be stable. The rate of progression with PPMS (how quickly the patient gets worse) differs from patient to patient, and may fluctuate for the same patient over time.

How is PPMS different from disease courses that involve relapses?

There are a number of ways that patients with PPMS differ from those with relapsing forms of MS including relapsing-remitting MS (RRMS) and progressive-relapsing MS (PRMS).

Less inflammation and fewer lesions. In relapsing forms of MS, exacerbations generally involve inflammation attacking myelin. With PPMS, there tends to be less inflammation and fewer lesions (plaques) that form within the brain. Although lesions can occur anywhere along the CNS, in patients with PPMS, lesions tend to be located more in the spinal cord, rather than the brain. Additionally, with PPMS, there tend to be fewer inflammatory cells present in the lesions that do form.

Different rates of diagnosis by gender. Another way that PPMS differs from relapsing MS is how likely it is to be diagnosed in males versus females. PPMS affects males and females in equal numbers, while relapsing MS affects females 2 to 3 times as often as it does males.

Diagnosed later in life. PPMS tends to be diagnosed much later in life than relapsing MS. RRMS is most commonly diagnosed in persons aged 20-50. The average age when patients are diagnosed with PPMS is about 10 years older than with relapsing MS.

Associated with greater disability. Patients who have PPMS typically have greater difficulties with motor function, including walking, and are more likely to require help with daily activities. Patients with PPMS, therefore, are more likely to be unable to continue working than those with relapsing MS.

How is PPMS diagnosed?

For types of relapsing MS, diagnostic criteria (the evidence that must be present to make a diagnosis) require evidence of two or more areas of CNS damage that have occurred at different points in time, without any other explanation.

Due to the fact that CNS inflammation and inflammatory attacks (exacerbations, relapses, or flare-ups) are less likely with PPMS, diagnosis must be made using other criteria. The diagnosis of PPMS can be a slow process as gathering evidence of disease requires more time and effort.

Diagnostic criteria for PPMS include:

1. One or more year in which neurologic symptoms typical of MS get progressively worse; and

2. Two out of three of the following:

  • At least nine MS-like brain lesions visible using magnetic resonance imaging (MRI), or four or more MS-like brain lesions and positive results on visual evoked potential (VEP) testing showing impairment of transmission of signals in the optic nerve
  • MS-like lesions present on the spinal cord visible using MRI
  • Analysis of cerebrospinal fluid (taken by lumbar puncture) showing an abnormal immune response in the CNS typical of MS

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