Multiple sclerosis (MS) is a chronic disease of the central nervous system (brain and spinal cord) where the immune system attacks the protective myelin sheath surrounding nerve fibers. This attack disrupts communication between the brain and the body, causing various neurological symptoms. The way the disease develops is highly variable among individuals, defining the different courses of MS progression. These patterns help clinicians predict the disease trajectory and determine treatment strategies.
Clinically Isolated Syndrome
Clinically Isolated Syndrome (CIS) represents the first episode of neurological symptoms caused by inflammation and demyelination in the central nervous system. This initial episode must last at least 24 hours and cannot be attributed to fever or infection. CIS symptoms are similar to a full MS relapse, often involving the optic nerve, brainstem, or spinal cord, but a diagnosis of MS is not yet met.
A person who experiences CIS may or may not go on to develop definite multiple sclerosis. The likelihood of progression is determined by findings on a magnetic resonance imaging (MRI) scan taken at the time of the initial event. If the MRI shows multiple areas of damage (lesions) similar to those seen in MS, the risk of a second attack and a formal MS diagnosis is significantly higher. CIS is now considered a clinical phenotype in the spectrum of MS, and early treatment may be considered to delay conversion.
Relapsing-Remitting Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis (RRMS) is the most common initial form, accounting for approximately 85% of all MS diagnoses. This course is characterized by clearly defined periods of new or worsening neurological symptoms, known as relapses, followed by periods of remission. A relapse involves new symptoms or the worsening of old ones, lasting a minimum of 24 hours.
During remission, symptoms partially or completely resolve, and the person experiences a period of stability without disease progression. Not all symptoms may disappear completely after a relapse, meaning subtle disability accumulation can still occur over time. The frequency of relapses can vary greatly, but generally decreases as a person ages and the disease advances.
Secondary Progressive Multiple Sclerosis
Secondary Progressive Multiple Sclerosis (SPMS) develops after an initial period of RRMS. The transition is marked by a shift where the disease begins to steadily worsen, leading to a continuous, gradual accumulation of disability. This decline in function occurs independently of distinct relapses, although some people may still experience occasional attacks.
This change reflects a decrease in inflammatory activity (which causes relapses) and an increase in neurodegeneration, or the slow loss of nerve cells. The transition typically occurs 10 to 25 years after the initial RRMS diagnosis, though the timeline is highly variable. Disease-modifying therapies used during the RRMS phase are believed to have slowed the rate at which people transition to SPMS.
Primary Progressive Multiple Sclerosis
Primary Progressive Multiple Sclerosis (PPMS) is a distinct course characterized by neurological function steadily worsening from the onset, without the early relapse and remission cycles seen in RRMS. This form of MS is less common, affecting about 10% to 15% of people diagnosed with the disease, and disability gradually increases without periods of recovery.
The pathology of PPMS often involves more significant damage in the spinal cord compared to the brain lesions common in RRMS. This can lead to mobility issues and trouble walking being a prominent early symptom. Diagnosis requires a minimum of one year of documented progression and evidence of MS lesions in the central nervous system.
Tracking Disability and Disease Progression
Clinicians monitor the severity and rate of MS progression using standardized measures to assess neurological function and disability. The Expanded Disability Status Scale (EDSS) is the primary tool used, providing a score from 0 (no disability) to 10 (death from MS). Scores increase in half-point increments, with the scale heavily focused on walking ability, particularly from a score of 5.0 onward.
Magnetic resonance imaging (MRI) provides objective evidence of disease activity that may not be apparent through physical symptoms alone. MRI scans track the number and size of lesions (lesion load) and the degree of brain atrophy (loss of brain tissue). While new lesions correlate with relapses, brain atrophy and T1 black holes are considered markers of long-term neurodegeneration and disability accumulation.