What are the symptoms and treatment options if measles virus (MV) infects neurons?

Neurological Symptoms from Measles Virus Infection of Neurons

Yes, if measles virus (wild-type or vaccine strain) infects neurons, there would absolutely be symptoms—ranging from acute encephalitis to fatal progressive neurological disease—though vaccine-strain neurological complications are extraordinarily rare compared to wild-type measles.

Wild-Type Measles Neurological Manifestations

Acute Encephalitis

• Wild-type measles causes encephalitis in approximately 1 per 1,000 infected persons, presenting with fever, altered mental status, seizures, and potential permanent CNS impairment (encephalopathy) 1, 2
• Symptoms typically appear during or shortly after the acute measles illness, with onset of neurological signs occurring around 10 days after initial infection 1
• Brain endothelial cells become infected during acute measles, providing the portal of entry for CNS invasion, with reactive microgliosis evident on pathology 3
• The case fatality rate for measles in the United States is 1-2 per 1,000 cases, with permanent brain damage possible in survivors of encephalitis 2

Subacute Sclerosing Panencephalitis (SSPE)

• SSPE is a rare but invariably fatal late complication appearing years after the initial measles infection (not during active viremia), caused by persistent mutant measles virus in the CNS 2, 4
• Clinical presentation includes insidious personality changes, intellectual decline progressing to dementia, myoclonic jerks with characteristic 1:1 EEG periodic complexes, motor deterioration, coma, and death 5
• Occurs in approximately 4-11 per 100,000 measles-infected individuals, with highest risk in those infected at young ages 4
• Diagnosis relies on detection of intrathecal synthesis of measles-specific antibodies in CSF, indicating local CNS production rather than systemic antibody leakage 5

Measles Inclusion Body Encephalitis (MIBE)

• Occurs in immunocompromised patients with direct CNS infection, sometimes without the typical measles rash 2, 6
• Represents a distinct entity from SSPE, occurring in the context of immune deficiency 7

Vaccine-Strain Measles Neurological Events

Encephalopathy Risk Assessment

• Encephalopathy after MMR vaccination occurs at approximately 1 case per 2 million doses distributed—vastly lower than the 1 per 1,000 risk with wild-type measles 1
• When encephalopathy cases occur after vaccination, onset follows a non-random distribution with symptoms appearing approximately 10 days post-vaccination, consistent with the timing of wild-type measles encephalopathy 1
• Four independent U.S. surveillance systems (CDC measles surveillance 1963-1971, MSAEFI 1979-1990, VAERS 1991-1996, and VICP) identified only 166 encephalopathy cases occurring 6-15 days after vaccination out of 313 million doses distributed 1

Febrile Seizures (Not True Encephalitis)

• MMR vaccination causes febrile seizures in approximately 1 per 3,000 doses, but these are simple febrile seizures without residual neurological sequelae 1
• These seizures do not represent direct neuronal infection but rather fever-induced events 1

Critical Distinction: SSPE and Vaccination

• The CDC and ACIP definitively state that MMR vaccine does not increase SSPE risk 1, 2, 5
• When rare SSPE cases occur in vaccinated children without known measles history, evidence indicates they had unrecognized wild-type measles infection before vaccination—the SSPE resulted from natural infection, not the vaccine 1, 2, 5
• Measles vaccination has essentially eliminated SSPE in countries with high vaccination coverage 2

Mechanism of CNS Invasion

Entry and Spread

• The known measles receptors (CD46 and CD150/SLAM) are not expressed in the CNS, making the mechanism of neuronal entry incompletely understood 6, 8
• Brain endothelial cell infection during acute measles provides the likely portal of entry for subsequent CNS complications 3
• Viral spread within the CNS involves disruption of F protein function, raising possibilities for fusion-inhibiting molecule treatments 7

Clinical Algorithm for Recognition

Acute Presentation (Days to Weeks After Measles)

• Monitor for fever, altered mental status, seizures, or focal neurological signs during or shortly after measles illness 1, 2
• Acute encephalitis presents around day 10 of infection 1

Delayed Presentation (Years After Measles)

• Consider SSPE in any patient with progressive neurological deterioration and history of measles infection (even if remote or unrecognized) 2, 4
• Look for the characteristic triad: personality/cognitive changes, myoclonic jerks, and periodic EEG complexes 5
• Obtain CSF for measles-specific antibody testing showing intrathecal synthesis 5

Treatment Considerations

Acute Measles Management

• Vitamin A supplementation: 100,000 IU for children <12 months, 200,000 IU for children ≥12 months 2
• Supportive care with treatment of secondary bacterial infections 2

SSPE Treatment

• Intrathecal ribavirin has been attempted with limited success 5
• Fusion-inhibiting molecules represent potential future therapies 7
• Currently, SSPE and MIBE remain lethal diseases without effective treatment 7

Common Pitfalls to Avoid

• Do not confuse acute post-vaccination febrile seizures (benign, 1 per 3,000 doses) with encephalopathy (extremely rare, 1 per 2 million doses) 1, 5
• Do not attribute SSPE to vaccination—it results from wild-type measles infection, and vaccination prevents it 1, 2, 5
• Do not confuse acute post-infectious measles encephalitis (APME), which involves immune-mediated damage without direct brain infection, with direct viral CNS infection seen in SSPE and MIBE 6