Diagnostic impact of intrathecally synthesized specific anti-viral antibodies

Introduction: The cerebral spinal fluid PCR is the gold standard to prove a cerebral viral infection. Its diagnostic sensitivity is reduced in diseases with low cerebral viral loads and when the diagnosis is delayed so that the viral loads have already decreased. As a complementary method, the intrathecal synthesis of specific antibodies (antibody specific index, ASI) can be measured which, however, lacks epidemiological data.

Methods: A retrospective database analysis was performed to detect all pediatric patients with positive ASI treated at Aachen University Hospital between 1999 and 2005. The clinical and virological data were analysed by descriptive statistics.

Results: 61 patients were studied, including 4 with encephalomyelitis disseminata (ED), 9 with cerebral vasculitis, 12 with neuritis, 3 with hearing loss, 14 with encephalitis, 1 with meningitis, 5 with severe cephalgia, 5 with psychiatric symptoms, 3 with white matter diseases and 3 with seizures. 6 had several positive ASI among them only 1 ED patient. Of the 51 patients with a single ASI (ED excluded), 16 showed a positive ASI for HSV, 13 for VZV, 4 for CMV, 9 for EBV, 2 for measles, 3 for rubella and 4 for mumps virus. Frequent combinations were VZV and vasculitis (n=8), hearing loss and mumps (n=2), neuritis and HSV (n=6), as well as VZV (n=4) respectively EBV (n=5) and encephalitis. Matched PCR and ASI data were available in 25 patients. Three of them showed a positive PCR.

Discussion: Our ASI data show a similar spectrum of pathogens as known from epidemiologic PCR studies. ASI studies clearly complement the CSF PCR, being of special diagnostic impact in cases of delayed investigations when the PCR has already become negative. ASI should be investigated in all patients with assumed cerebral infections, as this increases the chance to establish the diagnosis. ASI studies are indispensable to diagnose VZV-related stroke and mumps-related hearing loss.