Does Latent SSPE Involve Continuous Viral Replication?
Yes, latent SSPE involves continuous viral replication in the CNS—this is not true latency but rather persistent, ongoing viral activity that drives the disease process.
Understanding SSPE Pathophysiology
The term "latent" is actually a misnomer when applied to SSPE. The disease involves continuous, active viral replication in the central nervous system, not dormant virus that occasionally reactivates. 1, 2
Evidence of Ongoing Viral Replication
Persistent measles-specific IgM remains elevated for years—even decades—in both serum and CSF, which directly reflects ongoing CNS viral replication and continuous immune stimulation, not systemic viremia. 1, 2
The presence of measles-specific IgM is pathognomonic for active viral persistence in SSPE, as IgM normally disappears completely within 30-60 days after acute measles infection. 2
In SSPE, IgM detection indicates ongoing immune stimulation from continuous CNS viral replication, where the mutant measles virus establishes true persistent infection in neurons and spreads trans-synaptically. 2
The Clinical Timeline Clarifies the Mechanism
Initial measles infection occurs with systemic viremia during acute illness, followed by years of apparent clinical silence (2-10 years, sometimes as short as 4 months), and then SSPE emerges with progressive neurological symptoms. 2
During this "silent" period, there is no systemic viremia, but the virus persists and replicates continuously within the CNS at low levels—this is why it's not true latency. 2
The mutant measles virus accumulates envelope protein mutations that allow it to evade immune surveillance while maintaining the ability to replicate and spread between neurons. 2
Diagnostic Confirmation of Ongoing Replication
The combination of persistent measles IgM in both serum and CSF (often higher in CSF than serum), elevated IgG, and a CSF/serum measles antibody index ≥1.5 has 100% sensitivity and 93.3% specificity for SSPE diagnosis. 1, 2
The CSF/serum measles antibody index ≥1.5 confirms intrathecal antibody synthesis, proving local CNS production rather than passive leakage from serum—direct evidence of ongoing CNS infection. 1, 2
This persistent IgM reflects active viral persistence in the CNS, not acute infection, reinfection, or residual antibodies from resolved infection. 1
Critical Distinction from True Latency
Unlike truly latent viruses (e.g., herpes simplex virus or varicella-zoster virus that can remain dormant for years without replication), SSPE involves defective viral clearance with continuous low-level replication that eventually causes progressive neurodegeneration. 3, 4
The virus is able to infect neurons and survive in a persistent replicating form for years due to factors that favor humoral over cellular immune response, allowing immune evasion. 3
Clinical Implications
SSPE is progressive and almost always results in a vegetative state followed by death, with no effective cure—treatment focuses on maximizing quality of life, controlling seizures and myoclonus, and providing supportive care. 1
The only effective prevention strategy is measles vaccination with two doses of MMR vaccine, which has essentially eliminated SSPE in highly vaccinated populations. 1, 5
The persistent viral replication explains why SSPE is relentlessly progressive, with only 5% of patients experiencing spontaneous remission and 95% dying within 5 years of diagnosis. 3