Primary Progressive Multiple Sclerosis

Primary progressive multiple sclerosis is a type of multiple sclerosis where symptoms gradually worsen from the beginning, without the typical periods of symptom flare-ups and recovery seen in other forms of the disease. Unlike the more common relapsing-remitting MS, this progressive form affects about 10% of people diagnosed with MS and typically appears later in life.

Table of contents

• What is Primary Progressive Multiple Sclerosis?
• How Common is PPMS?
• Symptoms of PPMS
• Causes and Risk Factors
• How PPMS is Diagnosed
• Complications of PPMS
• Treatment Options
• Outlook and Life Expectancy

What is Primary Progressive Multiple Sclerosis?

Primary progressive multiple sclerosis (PPMS) is a type of multiple sclerosis, which is a disease where your immune system mistakenly attacks healthy parts of your central nervous system (your brain and spinal cord). Multiple sclerosis affects the protective covering around nerve cells called myelin, which works like insulation on an electrical wire. When this covering is damaged, it exposes the nerve fiber underneath, which can slow or block the signals being transmitted through it.^[1][2]

What makes PPMS different from other forms of MS is how symptoms appear and progress over time. Most people diagnosed with MS have what’s called relapsing-remitting multiple sclerosis (RRMS), which means they have periods when symptoms flare up, followed by periods when symptoms improve or go away. With PPMS, symptoms get worse over time from the very beginning. This happens slowly and gradually, with less frequent relapses or flare-ups.^[1][6]

The progressive worsening of symptoms happens because of neurodegeneration, which is when nerve cells in your brain and nervous system lose function. PPMS causes some inflammation along with this nerve damage. The disease affects people differently, and how fast symptoms worsen can vary from person to person. There can be times when things are stable, and there can be periods of short-term minor improvements, but nervous system problems steadily get worse.^[1][4]

Many people who have relapsing-remitting MS later develop another type called secondary progressive multiple sclerosis (SPMS), where symptoms begin to worsen steadily after an initial period of relapses and remissions. PPMS and SPMS are sometimes grouped together as progressive MS because they share similar symptoms. The main difference is that with PPMS, the progressive form is the first kind of MS you have, not something that develops after years of relapsing-remitting disease.^[1][7]

How Common is PPMS?

Approximately 1 million people are living with MS in the United States. About 10% of people diagnosed with MS have PPMS. In the UK, it is estimated that 10,000 to 15,000 people have primary progressive MS.^[1][6]

Most people receive a PPMS diagnosis in their 40s to 50s, though the condition can be present at any age. On average, people with PPMS start having symptoms between ages 35 and 39. This is typically later than relapsing-remitting MS, which is usually diagnosed under the age of 40.^[1][4][6]

About equal numbers of men and women are diagnosed with primary progressive MS. This is different from relapsing-remitting MS and secondary progressive MS, which are more common in women than men.^[4][6]

Symptoms of PPMS

The main symptom of PPMS is the gradual worsening of MS symptoms over time. Symptoms of PPMS aren’t entirely obvious at first but increase in severity over time. You may or may not have any symptom relapses or attacks with PPMS.^[1]

Common symptoms include:

• Vision changes such as blurred vision, double vision, eye pain, or trouble seeing^[1][7]
• Tingling or numbness in your body, arms, or legs^[1]
• A squeezing feeling around your chest or abdomen, sometimes called the “MS hug”^[1][7]
• Feeling tired or fatigue^[1]
• Difficulty trying to pee or a feeling of urgency when you need to pee, or trouble controlling your bladder or bowels^[1][7]
• An electrical shock sensation down your back, arms or legs when you bend your neck forward^[1][7]
• Trouble walking, difficulty with coordination, or loss of balance^[1][7]
• Muscle stiffness or weakness, including spastic movement^[1][7]
• Brain fog or difficulty with memory, concentration, learning new information, or information processing^[1][7]
• Dizziness or shakiness^[1]
• Mood changes or depression^[1]
• Sexual dysfunction^[1]

Causes and Risk Factors

The exact cause of MS is unknown. Medical science doesn’t have a good understanding of what causes MS. Your symptoms result from your immune system attacking your nervous system, but doctors don’t know exactly why that happens.^[1][7]

Research suggests it could be related to changes in your DNA (genetic predisposition) that make you more likely to have an autoimmune condition, which is when your immune system attacks healthy cells in your body by mistake. However, genetics only play a small part in MS, so your risk of passing the condition onto your future children is low.^[1][7]

Environmental factors can also play a role in developing MS. Examples include exposure to bacteria or viruses. MS rates vary considerably in different parts of the country, suggesting that environmental factors may be important.^[1][7]

How PPMS is Diagnosed

There isn’t one test to confirm or rule out a diagnosis of PPMS. PPMS takes time to diagnose. At first, your symptoms may be subtle, so it isn’t always clear that you have a condition. Your healthcare provider will make a diagnosis after collecting information from a variety of sources.^[1][7]

A diagnosis of primary progressive MS is often a clinical diagnosis, based on your medical history and the symptoms you’re experiencing, rather than on diagnostic tests alone. A neurologist will be looking for a pattern of worsening symptoms due to the slow and progressive loss of nerve cells. Diagnosing PPMS requires symptoms of PPMS for at least a year in combination with either brain scans or spinal tap results consistent with MS.^[6][7]

After a physical exam and taking your medical history, your healthcare provider may offer several tests:

• A general physical exam and a neurological exam^[7]
• An MRI (magnetic resonance imaging) to look for damage on your brain and spinal cord and to look for lesions^[1][7]
• A lumbar puncture (spinal tap) to find characteristics of MS, like oligoclonal bands commonly found in MS, but which can also be seen in other conditions. They can represent evidence of inflammation involving the brain and/or spinal cord^[1][7]
• Blood tests to rule out other conditions that have similar symptoms^[1][7]
• An optical coherence tomography (OCT), which is a painless test that scans the nerves in the back of your eye (retina) to detect damage, possibly caused by MS^[1][7]

Complications of PPMS

Symptoms of PPMS can lead to several complications that affect daily life:

• Muscle tightness (spasticity)^[1]
• Vision loss^[1]
• Difficulty controlling your bladder^[1]
• Sexual dysfunction^[1]
• Difficulty with memory^[1]
• Changes to your mood^[1]

Treatment Options

While there isn’t a cure for MS, treatment is available to help minimize ongoing damage and help you manage symptoms. Unfortunately, there aren’t many primary progressive multiple sclerosis treatments that address the underlying cause of the disease, so your options are limited compared to treatment for relapsing-remitting MS. Instead, many treatments for primary progressive MS focus on reducing symptoms and improving or maintaining quality of life.^[7]

Only one drug is currently approved by the U.S. Food and Drug Administration (FDA) to treat PPMS. It’s called ocrelizumab (Ocrevus) and works by destroying certain cells in your immune system. This medication has been proven to delay disability progression of PPMS. In September 2024, the FDA approved a subcutaneous version of ocrelizumab called Ocrevus Zunovo, which offers a twice-a-year, under-the-skin dosing option.^[7][13]

Apart from ocrelizumab, the best medications for primary progressive MS are specific drugs to treat symptoms such as depression, fatigue, or problems with urination.^[7]

Outlook and Life Expectancy

Like other forms of MS, primary progressive multiple sclerosis has no cure. However, it’s not considered fatal. People with MS live to be almost as old as the general population.^[7]

The rate at which symptoms become more severe varies from person to person, but typically the changes are slow and gradual over a number of years, though for some it can be more rapid. There can also be periods of minor improvement or times when symptoms stay the same.^[6]