MS is a chronic disease affecting the central nervous system (brain and spinal cord). It involves the immune system mistakenly attacking the protective myelin sheath surrounding nerve fibers. While disease activity is traditionally tracked through clinical relapses (episodes of new or worsening symptoms), significant damage occurs “silently” beneath the threshold of noticeable symptoms—the “sleeper charge.” This underlying activity drives long-term disability through continuous inflammation and neurodegeneration.
Defining the Sleeper Charge
The sleeper charge is chronic, low-level inflammation trapped within the central nervous system, causing persistent damage without triggering a clinical relapse. This smoldering inflammation occurs primarily within existing MS lesions (areas of demyelination and nerve fiber loss). The process is driven by the sustained activation of resident immune cells called microglia.
These activated microglia gather at the edge of old lesions and slowly destroy myelin and axons. Unlike the acute inflammation of a relapse, which involves immune cells from outside the CNS, the sleeper charge is compartmentalized and non-symptomatic. It erodes neurological function without causing recognizable outward signs.
Detection Through Advanced Imaging
Specialized imaging techniques are necessary for identifying and monitoring the sleeper charge. Magnetic Resonance Imaging (MRI) is the primary tool used to visualize these areas, often called chronic active lesions (CALs) or slowly expanding lesions (SELs). These lesions differ from acute lesions, which are typically bright on post-contrast T1-weighted MRI scans due to a temporarily disrupted blood-brain barrier.
One method uses advanced MRI sequences to detect iron, which accumulates in activated microglia at the lesion’s periphery. These “iron-rim lesions” appear as a dark ring on susceptibility-based MRI scans and mark chronic inflammation. Another approach tracks the concentric enlargement of established lesions over time, identifying them as slowly expanding lesions. This monitoring reveals the lesion is growing at a gradual, persistent rate due to smoldering activity.
Long-Term Consequences of Silent Activity
The sleeper charge is linked to the progressive accumulation of neurological disability. This slow, persistent damage, often called “progression independent of relapse activity,” occurs even without clinical relapses. Chronic smoldering lesions are associated with brain tissue volume loss, known as brain atrophy.
Brain atrophy measures irreversible neurodegeneration and predicts long-term disability. This silent activity also impairs cognitive functions, such as processing speed and memory, impacting daily life. The destruction caused by the sleeper charge drives the long-term worsening characterizing progressive MS.
Therapeutic Goals for Hidden Disease
A primary goal of modern disease-modifying therapies (DMTs) is to suppress this underlying inflammation to prevent long-term neurological decline. Highly effective DMTs are increasingly used early to limit the formation of chronic active lesions. Studies indicate that some treatments can reduce the volume of slowly expanding lesions, offering a way to target the sleeper charge directly.
Treatment success is often measured by achieving No Evidence of Disease Activity (NEDA), which traditionally includes no relapses, no disability progression, and no new or active lesions on conventional MRI. Given the sleeper charge, NEDA is evolving to include metrics that address this chronic inflammation more directly. Future strategies may involve combination therapies, specifically including agents that target the microglial cells driving this chronic inflammation.