Is measles Immunoglobulin G (IgG) normal in a patient with suspected or confirmed Subacute Sclerosing Panencephalitis (SSPE)?

Measles IgG is NOT Normal During Silent SSPE—It is Dramatically Elevated

In patients with subacute sclerosing panencephalitis (SSPE), including during any "silent" or latent phase, measles IgG is never normal—it is dramatically elevated in both serum and cerebrospinal fluid (CSF), with the hallmark finding being intrathecal synthesis demonstrated by a CSF/serum measles antibody index ≥1.5. 1

Understanding the Immunologic Profile in SSPE

The term "silent SSPE" is somewhat misleading because the immune response is never truly silent:

• Measles-specific IgG remains dramatically elevated in both serum and CSF throughout all stages of SSPE, regardless of whether clinical symptoms are apparent 1, 2
• The CSF/serum measles antibody index ≥1.5 confirms intrathecal synthesis, indicating local CNS antibody production rather than passive leakage from serum—this is the diagnostic cornerstone 1, 3
• Persistent measles-specific IgM is present in 100% of SSPE patients, which is highly abnormal since IgM normally disappears completely within 30-60 days after acute measles infection 1, 4

The Critical Distinction: SSPE vs. Normal Post-Measles Immunity

After natural measles infection or vaccination, a normal immune response shows:

• Measles IgG at protective levels that persist lifelong 1
• Complete absence of IgM after the 30-60 day window following acute infection 1
• Normal CSF/serum antibody ratio without intrathecal synthesis 1

In contrast, SSPE demonstrates:

• Extremely high measles IgG titers far exceeding normal protective levels 1, 3
• Persistent IgM in both serum and CSF, often higher in CSF than serum, indicating ongoing immune stimulation from continuous CNS viral replication 1, 4
• CSF/serum measles antibody index ≥1.5, with values ranging from 2.3 to 36.9 in confirmed cases 3

Why the Antibody Response Remains Elevated

The persistent elevation reflects ongoing pathophysiology:

• SSPE results from persistent mutant measles virus infection in the CNS, not from systemic viremia, with the virus establishing true persistent infection in neurons and spreading trans-synaptically 1, 2
• The continuing release of measles antigen from persistent CNS viral replication prevents the normal shut-off of antibody synthesis, maintaining both IgG and IgM production 4
• This occurs years after the initial measles infection (typically 5-10 years, but can range from 4 months to decades), during which time there is no systemic viremia—only localized CNS infection 1, 5

Diagnostic Algorithm for Suspected SSPE

When SSPE is suspected based on clinical features (progressive neurological deterioration, myoclonic jerks, behavioral changes):

1. Obtain simultaneous serum and CSF samples for measles-specific IgG measurement 1, 2
2. Calculate the CSF/serum measles antibody index (CSQrel)—values ≥1.5 confirm intrathecal synthesis 1, 3
3. Test for persistent measles IgM in both serum and CSF—presence is pathognomonic for SSPE 1, 4
4. Confirm with EEG showing periodic complexes with 1:1 relationship to myoclonic jerks 2, 6
5. MRI may show white matter lesions or discrete hippocampal high signal, though this is present in only ~60% of cases 7, 2

The combination of persistent measles IgM, elevated IgG, and CSF/serum measles antibody index ≥1.5 has 100% sensitivity and 93.3% specificity for SSPE diagnosis. 1, 2

Critical Pitfalls to Avoid

Do not confuse SSPE with:

• Acute measles reinfection: Shows high-avidity IgG with IgM positivity but a normal CSF/serum index, whereas SSPE shows extremely high titers with an elevated CSF/serum index ≥1.5 1
• Multiple sclerosis with MRZ reaction: Demonstrates intrathecal synthesis against at least 2 of 3 viral agents (measles, rubella, zoster), whereas SSPE shows an isolated, extremely strong measles-only response 1, 6
• False-positive IgM in low-prevalence settings: In areas where measles is rare, false-positive IgM results can occur; confirmatory testing using direct-capture IgM EIA method is recommended when IgM is detected without epidemiologic linkage to confirmed measles 1

Clinical Context and Timeline

The immunologic abnormalities in SSPE exist throughout the disease course:

• Initial measles infection occurs with viremia during acute illness, followed by normal IgM disappearance within 30-60 days 1
• Years of apparent latency (mean 9.6 years) follow, during which persistent CNS infection is established without systemic viremia 1, 5
• When SSPE becomes clinically apparent, the abnormal antibody pattern (elevated IgG, persistent IgM, elevated CSF/serum index) is already present and remains throughout all disease stages 1, 4

There is no truly "silent" phase from an immunologic standpoint—the dramatically elevated measles antibodies with intrathecal synthesis are present before, during, and after clinical symptom onset. 1, 4