Intrathecal synthesis of specific antibodies as a marker of herpes simplex encephalitis in patients with negative PCR

BACKGROUND: PCR in the cerebrospinal fluid (CSF) has become the sole method used for the diagnosis of herpes simplex encephalitis (HSE). Nevertheless, PCR results may sometimes be false negative, and in this situation other techniques may be useful. METHODS: 3 patients hospitalised for meningoencephalitis with fever showed a negative result for herpes simplex virus (HSV) PCR in their CSF. We then performed a detection of intrathecal anti-HSV immunoglobulins (IgGs) in the CSF and analysed their level in relation to those in the serum, compared to albumin. RESULTS: We confirmed that IgG synthesis was the direct consequence of an immune system reaction in the 3 patients' CSF. These results were consistent with clinical signs and neurodiagnostic procedures. They prompted us to continue the treatment, which would have been stopped following the negative PCR results. The clinical progression was favourable for all patients. CONCLUSIONS: PCR, which many physicians now consider the gold standard for the detection of HSV, may sometimes yield false negative results, i.e. when performed too early after the disease onset or when the viral load is too low. The method described here, although positive a few days after PCR, may prove helpful in the diagnosis of HSE for patients with negative HSV PCR in the CSF.