What are the other Names for this Condition? (Also known as/Synonyms)

• PPMS (Primary-Progressive Multiple Sclerosis)

What is Primary-Progressive Multiple Sclerosis? (Definition/Background Information)

• Multiple sclerosis (MS) is a common and chronic autoimmune disorder affecting the central nervous system (brain and spinal cord). In this disorder, the myelin sheath, a protective layer surrounding the nerve cells is progressively destroyed (called demyelination), resulting in associated neurological signs and symptoms
• The following four main courses of multiple sclerosis is reported, but not all courses may be observed in each individual:
  • Clinically isolated syndrome (CIS)
  • Relapsing-remitting multiple sclerosis (RRMS)
  • Secondary-progressive multiple sclerosis (SPMS)
  • Primary-Progressive Multiple Sclerosis (PPMS)
• Primary-Progressive Multiple Sclerosis may be described as an advanced stage of multiple sclerosis that develops in middle-aged adults typically within 10 years of MS onset. It is an uncommon form of MS and only between 10-15% develop PPMS
• Unlike other MS forms, in individuals with Primary-Progressive Multiple Sclerosis, the neurologic function keeps deteriorating constantly, right from disease onset, almost in the absence of relapses and remissions; thus, the burden of disability increases progressively
• There are minimal inflammatory attacks on the nerve sheath resulting in fewer lesions in the central nervous system, especially in the brain (seen on MRI scans). However, nerve damage and nerve loss are evidently observed in Primary-Progressive Multiple Sclerosis causing a set of associated signs and symptoms
• The common signs and symptoms associated with Primary-Progressive Multiple Sclerosis include balance issues, memory problems, chronic fatigue, dizziness, muscle stiffness causing walking difficulties, and vision problems
• The condition is termed primary-progressive, since individuals start showing a progressive worsening of the neurologic symptoms right from the beginning of multiple sclerosis itself. In secondary-progressive MS, individuals show increased disability only after the relapsing and remitting period has ended (typically after decades)
• The rate of progression of Primary-Progressive Multiple Sclerosis may vary from one individual to another and is difficult to predict. Some individuals seem to show a temporary respite, mild improvements, or even stable disease, for short durations; although, overall, a vast majority of the individuals have trouble performing normal day-to-day activities and need continuous support and assistance

Who gets Primary-Progressive Multiple Sclerosis? (Age and Sex Distribution)

• Primary-Progressive Multiple Sclerosis is observed in middle-aged adults, most commonly in adults between 35-39 years of age (some studies indicate an age group of 40-50 years)
• Both males and females are affected, and no gender preference is noted
• The condition is observed worldwide, and individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Primary-Progressive Multiple Sclerosis? (Predisposing Factors)

The risk factors associated with Primary-Progressive Multiple Sclerosis are not well-established, but may include:

• Family history of multiple sclerosis
• People of Northern European descent
• Environmental triggers: People living in certain countries with temperate climate, such as Southern Canada, Northern United States, New Zealand, and Europe, report a greater number of MS cases; hence, certain environmental factors may be involved
• Presence of autoimmune diseases such as type 1 diabetes mellitus and thyroid disease
• Smoking
• Studies have also shown that a lack of vitamin D may lead to MS
• Epstein-Barr virus (EBV) infection
• Individuals with certain HLA gene types have an increased risk for MS

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Primary-Progressive Multiple Sclerosis? (Etiology)

The exact cause of multiple sclerosis is unknown, but it is considered an autoimmune disorder. In MS, the body’s own immune system attacks the central nervous system, resulting in a set of neurological symptoms.

• Primary-Progressive Multiple Sclerosis is marked by an absence of nerve sheath inflammation, or it is significantly mild, when compared to what occurs during periods of relapses
• However, the central nervous system is progressively damaged from the onset of MS and neurologic function is severely compromised. The exact cause of such a development is presently unknown
• MRI studies of such affected individuals seem to indicate more lesions on the spinal cord than the brain. During the course of PPMS, there may be brief periods of relative calm and stable disease, including minor improvements (no new MRI activity noted); in some, the progression may be rapid

What are the Signs and Symptoms of Primary-Progressive Multiple Sclerosis?

Primary-Progressive Multiple Sclerosis is characterized by an absence of (or rarity of) relapses and remissions, but with worsening neurologic function and increased disability in the affected individuals.

Based on how the condition progresses over time, it is described as:

• Active and progressive, showing new activity on MRI scans and disease worsening
• Active and non-progressive, showing new activity on MRI scans but without any worsening of the disease
• Inactive and progressive, which is marked by the absence of new activity on MRI scans, but showing worsening of the condition
• Inactive and non-progressive that is marked by the absence of new activity on MRI scans and no progression of the condition

Evaluation of the above immensely aids the healthcare provider in understanding the course of PPMS and in bringing about any treatment modifications and rehabilitation strategies that may be necessary.

The speed of progression of PPMS and the signs and symptoms may be significantly different from one individual to another (and in the same individual). However, in many, a steady decline of physical activity and functional ability is noted.

The commonly observed signs and symptoms include:

• Chronic pain
• Longstanding fatigue/exhaustion
• Cognitive issues including poor memory
• Poor bowel and bladder function
• Poor eyesight
• Poor hand-eye-body coordination
• Sexual-related problems; decreased sex drive
• Numbness and tingling sensation
• Dizziness
• Loss of balance
• Unable to stand or walk due to weakened and/or stiffened leg muscles; muscle spasticity
• Depression and mood swings

How is Primary-Progressive Multiple Sclerosis Diagnosed?

A diagnosis of Primary-Progressive Multiple Sclerosis is difficult and challenging; according to some study reports, it may take several years to properly diagnose the condition. The diagnosis may involve the following tests and exams:

• Complete evaluation of medical history and family history, along with a thorough physical exam
• Evaluation of the presenting signs and symptoms and their progression over time following the onset of MS. The healthcare provider may use the expanded disability status scale (EDSS) to measure progression of multiple sclerosis
• Neurological examination that involves the central nervous system (brain and spinal cord)
• Magnetic resonance imaging (MRI) scan of the brain and spinal cord; a vast majority of the individuals show abnormal MRI scan results
• Spinal tap: Cerebrospinal fluid is examined for the presence of oligoclonal bands (these are antibodies present in the spinal fluid of individuals with multiple sclerosis)
• Visual evoked potential (VEP) test: The test measures the electrical activity in the scalp region in response to a light stimulus. Individuals with MS may have an abnormal VEP test
• Nerve function test
• Specialized blood tests to rule out other disorders or conditions with signs and symptoms similar to multiple sclerosis
• A diagnosis generally involves ruling out other conditions of the central nervous system that may cause similar neurological symptoms

According to the National Multiple Sclerosis Society, the diagnostic criteria for Primary-Progressive Multiple Sclerosis include:

• Disease progression that is observed for a minimum period of 12 months, and
• The satisfaction of any two conditions from among the following:
  • Presence of an MS-associated lesion in the brain
  • Presence of at least two MS-associated lesions in the spinal cord
  • Spinal fluid test results showing abnormal immune system activity in the central nervous system (CNS), through elevated IgG index or the presence of oligoclonal bands

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Primary-Progressive Multiple Sclerosis?

The complications associated with Primary-Progressive Multiple Sclerosis may include:

• Arms and legs shake due to seizure-like muscle spasms
• Paralysis
• Use of assistive devices, such as walkers or walking sticks, including motorized wheelchairs for mobility
• Migraine headaches
• Severe emotional distress
• Sudden sensation of electric shocks down the spinal cord
• Difficulty eating, swallowing, and performing simple daily tasks due to poor coordination
• Vision loss
• Adverse effects from the long-term use of medication

How is Primary-Progressive Multiple Sclerosis Treated?

Following a diagnosis of multiple sclerosis, the healthcare provider in consultation with the patient decides on the treatment plan and the use of prescription medications. The treatment of Primary-Progressive Multiple Sclerosis may include the following measures:

• Use of FDA-approved monoclonal antibody medications are currently available to suppress the immune system function, towards treating PPMS
• Acute attacks of the disorder are treated with corticosteroids and plasma exchange therapy (plasmapheresis)
• Pain medications may be administered, when required
• Use of other drugs such as baclofen (to reduce muscle spasm) or benzodiazepine
• Physical therapy is also helpful in treating the symptoms of the disorder
• Cholinergic drugs can be used to decrease urinary-related signs and symptoms
• Stem cell treatment (HSCT): It is an investigative therapy for consideration in clinical trials for patients with progressive MS
• Anti-depressants may be used for mood or behavior associated conditions
• Medications for sexual dysfunction (including erectile dysfunction)
• Physical therapy including occupational therapy and rehabilitation
• Healthy living including a well-balanced diet and exercising, including adequate sleep
• Support from family members and friends

How can Primary-Progressive Multiple Sclerosis be Prevented?

Currently, there are no effective preventative methods available for multiple sclerosis including Primary-Progressive Multiple Sclerosis.

What is the Prognosis of Primary-Progressive Multiple Sclerosis? (Outcomes/Resolutions)

Presently, multiple sclerosis is an incurable condition and its prognosis is difficult to predict. Nevertheless, in many, the life expectancy can be normal or near-normal. Most individuals with MS are able to continue with their life and work with minimal disabilities.

• Primary-Progressive Multiple Sclerosis may be described as an advanced stage of MS; the prognosis depends on its severity and long-term course
• Regular medical evaluation is essential to assess how the disease is progressing and if any changes are necessary to be brought into the treatment plans
• Many individuals with PPMS would need help and assistance for performing their normal day-to-day activities, due to moderate to severe disability as the disease progresses

Additional and Relevant Useful Information for Primary-Progressive Multiple Sclerosis:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/health-topics/neurological-institute/