Persistent intrathecal immune activation in patients with herpes simplex encephalitis

Area of Science:

• Neuroscience
• Immunology
• Infectious Diseases

Background:

• Herpes simplex encephalitis (HSE) is a severe neurological condition.
• Distinguishing HSE from other causes of encephalopathy is crucial for timely treatment.
• Biomarkers for diagnosing and monitoring HSE are needed.

Purpose of the Study:

• To compare neopterin and beta 2-microglobulin (beta 2M) levels in cerebrospinal fluid (CSF) and serum of HSE patients versus non-HSE patients.
• To investigate the long-term persistence of these markers and intrathecal immune activity after HSE.
• To correlate neopterin levels with clinical severity in HSE.

Main Methods:

• Analysis of sequential CSF and serum samples from 20 HSE patients and 30 non-HSE patients.
• Measurement of neopterin and beta 2M levels.
• Assessment of intrathecal IgG activity.
• Correlation of neopterin levels with clinical severity in a subset of HSE patients.

Main Results:

• Markedly elevated acute phase CSF neopterin and beta 2M levels were observed in 19/20 HSE patients.
• Moderate increases in neopterin and beta 2M were seen in most non-HSE patients.
• Elevated neopterin and beta 2M persisted for over 13 years post-HSE, unlike in non-HSE.
• Intrathecal IgG activity persisted in most HSE patients.

Conclusions:

• HSE is characterized by a vigorous acute inflammatory response.
• Long-term persistence of intrathecal cellular and humoral immune activity is a hallmark of HSE.
• Neopterin and beta 2M serve as valuable biomarkers for HSE diagnosis and monitoring long-term immune sequelae.