An Overview of Primary Progressive Multiple Sclerosis (PPMS)

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Primary progressive multiple sclerosis (PPMS) affects around 10 percent of people living with multiple sclerosis (MS). Of the three types of the disease, PPMS is considered the rarest and, as with other forms of MS, the course of PPMS is highly variable, affecting each person differently. Some may become disabled within a few years, whereas others remain stable for decades.

Onset and Course

The most common form of MS, known as relapsing-remitting MS (RRMS), is characterized by acute attacks of symptoms followed by periods of remission where the MS doesn’t progress. When the disease does start progressing, it's called secondary progressive MS (SPMS). This progression is thought to occur within 20 years of disease onset in around 90 percent of untreated MS patients.

PPMS, by contrast, is progressive from the start. Disability gradually accumulates, becoming worse over time. As with SPMS, in some people, PPMS is accompanied down the road by occasional relapse or evidence of new MRI activity.

PPMS

  • Progressive disability from the start

  • May include occasional acute relapses or plateaus

  • Average age at onset is 40 years

  • Makes up around 10 percent of MS cases at onset

  • Occurs in males and females equally

RRMS

  • Acute attacks followed by periods of remission

  • May become progressive overtime

  • Average age at onset is 30 years

  • Accounts for 85 percent to 90 percent of MS cases at onset

  • Occurs two to three times more often in females than males

PPMS can be characterized even further at different stages into these categories:

  • Active with progression: This indicates a relapse and/or new magnetic resonance imaging (MRI) activity, along with evidence that disability is worsening.
  • Active without progression: There are relapses and/or new MRI activity, but no evidence that MS is worsening.
  • Not active with progression: There are no relapses or new MRI activity, but there's evidence that the disease is worsening.
  • Not active without progression: The disease is stable.

Symptoms

MS symptoms are different in every individual, and in PPMS, they tend to be associated with movement.

Spinal Cord Symptoms

People diagnosed with PPMS often have walking problems due to the progressive atrophy (wasting and degeneration) of the spinal cord.

Also known as progressive myelopathy, these symptoms may include:

  • Spastic paraparesis: An increasingly spastic gait in which your legs will begin to stiffen, causing a visible limp and/or rhythmic jerkiness
  • Spastic hemiparesis: A weakness or immobility on one side of your body, which may affect your legs, arms, or hands
  • Exercise intolerance: The decreased ability to exercise
  • Ataxia: Clumsiness and lack of muscle coordination

When your spinal cord is affected by the disease, it can interfere with more than just movement. It can also cause impairment of sexual, bowel, and bladder function. Fatigue is also common with this and all other forms of multiple sclerosis.

Cerebellar Symptoms

While the spinal cord is the main target of injury in PPMS, your brain may also be affected, primarily the part known as the cerebellum, which regulates balance and coordination.

This condition, known as progressive cerebellar syndrome (PCS), is seen less often than progressive myelopathy but can manifest with:

  • Tremor: Impairment of fine hand movement due to severe intention tremor
  • Hypotonia: Loss of muscle tone
  • Gait ataxia: Loss of balance
  • Dysmetria: Inability to coordinate movement in which your either overshoot or undershoot the intended position of your arm, leg, or hand
  • Dysdiadochokinesia: Inability to perform rapidly alternating movements such as screwing in a light bulb

Uncommon Symptoms

While far less common, PPMS can affect other parts of the central nervous system such as the brainstem, which is situated between the brain and spinal cord, and the cerebrum, the main body of the brain.

These symptoms are rare in PPMS but may include:

Causes

It's not clear exactly what causes any type of MS, though there seems to be a genetic component involved that raises your susceptibility to develop it when you're exposed to the right environmental factors such as:

Diagnosis

Diagnosing PPMS has special challenges since people with it have a slow gradual loss of function over months to years. Because the imaging tests can be similar between PPMS and RRMS, your doctor will use your symptom history to help make this diagnosis. It may take several years or more to definitively diagnose PPMS, especially if your symptoms have just started.

To diagnose any form of MS, your doctor will do a thorough medical and symptom history, a physical examination, and MRI of your brain and spinal cord. If your MRI doesn't show enough evidence to confirm a diagnosis of MS, your doctor may do a lumbar puncture and/or visual evoked potentials for additional evidence.

MRI

In order to diagnose PPMS, your symptoms must have worsened for at least one year and you should have typical MS lesions in your brain and/or spine.

However, using MRI to diagnose PPMS presents a bit of a challenge since the results of brain MRIs of people with PPMS may be more subtle than those of people with RRMS, with far fewer gadolinium-enhancing (active) lesions.

Lumbar Puncture

Also referred to as a spinal tap, lumbar punctures can be very helpful in making the diagnosis of PPMS and ruling out other conditions.

Having one of two findings from a spinal tap is important in confirming a diagnosis of PPMS, including:

  • Presence of oligoclonal bands: This means that "bands" of certain proteins (immunoglobulins) show up when the spinal fluid is analyzed. Oligoclonal bands in the cerebrospinal fluid can be seen in up to 95 percent of people with MS but can be found in other disorders, too.
  • Intrathecal IgG antibody production: This means that IgG is produced within the spinal fluid compartment—a sign that there is an immune system response.

Visual Evoked Potentials

Visual evoked potentials (VEPs) testing involves wearing electroencephalogram (EEG) sensors on your scalp while watching a black-and-white checkered pattern on a screen. The EEG measures slowed responses to visual events, which indicates neurological dysfunction.

VEPs have also been helpful in solidifying a diagnosis of PPMS, especially when other criteria are not met definitively.

Diagnostic Criteria

Definite PPMS can be diagnosed when you have at least one year of documented clinical progression, which means that your MS symptoms have steadily gotten worse, plus two of the following:

  • A brain lesion that's typical of MS
  • Two or more MS lesions in the spinal cord
  • A positive lumbar puncture, meaning that there's evidence of either oligoclonal bands or an elevated IgG antibody level

Differential Diagnoses

There are many neurological diseases that can mimic MS, so much of the burden of diagnosing any type of MS is eliminating the possibility that it could be something else. Some of these include:

Treatment

Treatment for PPMS may include medications and/or rehabilitation therapies. Note, however, that it is more difficult than for RRMS.

Medications

Typically, MS is treated with disease-modifying therapies (DMTs), which slow down the course of your disease. However, there's only one DMT that has been approved by the U.S. Food and Drug Administration (FDA) for PPMS; in contrast, there are numerous DMTs to treat RRMS.

Ocrevus (ocrelizumab) was approved to treat PPMS in 2017. The first dose is given intravenously in two 300-milligram (mg) doses two weeks apart. After that, it's given in 600 mg doses once every six months.

Other DMTs haven't been found to be effective for treating PPMS, so most doctors don't use them. There's more research being done on effective treatments for PPMS though, so there's hope that new medications will emerge in the future.

Beyond Ocrevus, your doctor can give you prescription medications to help you manage your MS symptoms, such as:

  • MS-related fatigue
  • Pain
  • Gait impairment
  • Bladder and/or bowel dysfunction
  • Depression
  • Cognitive impairment
  • Sexual dysfunction
  • Muscle spasms

Rehabilitation Therapies

Rehabilitation specialists can also help you deal with MS symptoms like fatigue, mobility difficulties, muscle pain and spasticity, swallowing difficulties, aspiration, and cognitive impairment. These rehabilitation therapies include:

  • Physical therapy
  • Occupational therapy
  • Speech-language therapy
  • Cognitive rehabilitation
  • Vocational rehabilitation
  • Multidisciplinary strategies

A Word From Verywell

A diagnosis of PPMS may take several years, and since there are a number of other neurological conditions that need to be ruled out, it's important to see a doctor for a proper diagnosis if you're experiencing neurological symptoms. While the diagnosis process may be tedious, try to be patient and keep being proactive in your care. Remember that a diagnosis of PPMS is not fatal, and if you work closely with your healthcare team, you can keep your quality of life at its fullest.

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