Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system, including the brain, spinal cord, and optic nerves. In MS, the immune system mistakenly attacks myelin, the protective sheath around nerve fibers, disrupting signal transmission. This damage can lead to physical, mental, and sometimes psychiatric symptoms. The way MS changes and potentially worsens over time is known as disease progression.
The Four Main Patterns of MS
MS manifests in distinct patterns, describing how symptoms and disability unfold over time. These patterns help healthcare providers predict the disease’s course and determine appropriate management strategies. The four main clinical courses are Clinically Isolated Syndrome, Relapsing-Remitting MS, Secondary Progressive MS, and Primary Progressive MS.
Clinically Isolated Syndrome (CIS)
Clinically Isolated Syndrome (CIS) is a first episode of neurological symptoms lasting at least 24 hours, caused by inflammation and demyelination in the central nervous system. This initial event suggests MS but does not yet meet full diagnostic criteria. An MRI scan might show damage only in the area responsible for current symptoms. While some individuals may not experience further episodes, CIS can be the first indication of what may later become multiple sclerosis.
Relapsing-Remitting MS (RRMS)
Relapsing-Remitting MS (RRMS) is the most frequently diagnosed form, affecting approximately 85% of individuals at onset. This pattern is characterized by clearly defined attacks (relapses), where new symptoms appear or existing ones worsen significantly. These relapses are followed by periods of partial or complete recovery (remissions), during which symptoms may improve or even disappear. The timing and severity of these relapses and remissions can be unpredictable, though the disease does not worsen between attacks. Over time, RRMS can transition into a progressive phase.
Secondary Progressive MS (SPMS)
Secondary Progressive MS (SPMS) often develops in individuals who initially had RRMS, occurring 10 to 20 years after initial diagnosis. In SPMS, the disease transitions from distinct relapses and remissions to a steady, gradual worsening of neurological function. While some individuals with SPMS may still experience occasional relapses, these are less common, and recovery is often incomplete, leading to continuous disability accumulation. This phase involves less acute inflammation and more neurodegeneration, or nerve cell breakdown.
Primary Progressive MS (PPMS)
Primary Progressive MS (PPMS) is the least common form, affecting about 10% to 15% of people with MS. Unlike other forms, PPMS is characterized by a gradual worsening of neurological function from symptom onset, without distinct relapses or remissions. Symptoms slowly but steadily increase in severity. Individuals with PPMS are often diagnosed at a slightly older age, with a median onset around 40 years, and it affects men and women in roughly equal numbers, contrasting with the higher prevalence in women seen in relapsing forms.
Distinguishing Relapses from Progression
Understanding the difference between an MS relapse and disease progression is important, as they represent distinct aspects of disease activity. A relapse, or attack, involves new neurological symptoms or a significant worsening of existing ones lasting more than 24 hours. These episodes are caused by acute inflammation and demyelination within the central nervous system. Following a relapse, individuals may experience partial or complete recovery of symptoms.
In contrast, progression refers to the gradual, continuous accumulation of disability and worsening of neurological function. This decline often occurs independently of acute relapses and is driven by neurodegeneration, the slow loss of nerve cells. Progression Independent of Relapse Activity (PIRA) highlights that disability can worsen even without acute attacks or new inflammatory lesions on MRI, contributing significantly to long-term disability.
Monitoring Disease Activity and Progression
Healthcare professionals utilize tools and methods to track MS progression. These assessments provide insights into disease activity and disability accumulation, guiding treatment decisions.
Neurological examinations are a primary method, where doctors assess functions such as strength, coordination, balance, reflexes, and sensation. These examinations help identify changes in neurological function, indicating disease activity or worsening disability. Regular assessments allow clinicians to compare current function against previous evaluations, noting declines.
Magnetic Resonance Imaging (MRI) scans visualize areas of damage (lesions) in the brain and spinal cord. MRIs detect new or enlarging lesions, indicating inflammatory disease activity, even without new symptoms. MRI also helps monitor brain atrophy (tissue loss), which can correlate with long-term disability progression. Most individuals undergo at least one MRI every 6 months to 2 years to track these changes.
The Expanded Disability Status Scale (EDSS) is a widely used tool to quantify MS disability and monitor changes over time. This scale ranges from 0 (normal neurological examination) to 10 (death due to MS), with scores increasing in half-point increments as disability worsens. The EDSS heavily emphasizes walking ability but also assesses other functional systems like vision, coordination, sensation, and bladder control. While it provides a standardized measure of disability, its scoring can be subjective and may not capture all aspects of an individual’s experience.
Factors That Can Influence Progression
The rate and pattern of MS progression vary significantly among individuals, influenced by a combination of factors. The age at which symptoms first appear can play a role, with older age at onset correlating with a more rapid accumulation of disability. For instance, people diagnosed with Primary Progressive MS experience symptoms later in life, around age 40, compared to those with relapsing forms.
Initial symptoms can also indicate a different progression rate; for example, bilateral motor onset symptoms have been associated with quicker disease progression in PPMS. Gender also appears to be a factor, as men tend to have a higher risk of disease progression compared to women. Genetic predispositions and various lifestyle factors also influence the disease course. These include smoking, linked to an increased risk of disability progression, and vitamin D levels and obesity. Higher relapse activity in early MS has also been associated with an elevated risk of reaching disability milestones.
The Role of Treatment in Managing Progression
Disease-Modifying Therapies (DMTs) play a significant role in managing multiple sclerosis by altering the underlying disease course. While DMTs do not offer a cure for MS, their primary goal is to reduce the frequency and severity of relapses and to slow disability accumulation. These therapies work by targeting the immune system to reduce inflammatory attacks that damage myelin and nerve fibers in the central nervous system.
DMTs can also help prevent new lesion formation and limit new inflammatory activity visible on MRI scans. Research indicates that early and consistent treatment with approved DMTs is recommended to have the greatest impact on long-term progression. This proactive approach aims to delay irreversible central nervous system damage and associated disability accumulation. While some DMTs are approved for relapsing forms of MS, and a few for progressive forms, ongoing research continues to explore new treatments that can further slow or halt progression.