Supplemental Case Information Leypoldt et al. page1 of1
Herpes Simplex Virus-1 Encephalitis can Trigger Anti-NMDA Receptor Encephalitis – A Case Report
Supplemental case information:
Additional information on clinical course of HSVE during the acute disease (day 1-21): The patients’ course was complicated by global respiratory insufficiency necessitating mechanical ventilation (day 2-6). Six days after admission after stopping of mechanical ventilation, a first grand mal seizure occurred and he was treated with valproic acid 600mg b.i.d.
EEG findings at time of HSVE (day 8): Occipital alpha (8Hz) with short increase in frequency upon stimulation. Intermittent bi-fronto-temporal slowing. At relapse (day 41): Occipital alpha (9Hz), no focal or generalized slowing, no spikes or sharp waves.
HSV-1 serology at HSVE (day 2), at relapse (day 41) and during follow-up (day 160) showing increase in serum and CSF antibody titers and intrathecal synthesis of HSV-1 specific antibodies: At HSVE (day 2 after symptom onset): serum IgG 1:2000, CSF serology not done. At relapse (day 41 after HSVE onset) serum IgG 1:32.000, IgM qualitatively weakly positive extinction 0.101; in CSF IgG 1:790, HSV-index 5.5. At follow-up (day 61): HSV-1 serum IgG 1:23.000, IgM negative, CSF IgG 1:750, HSV-index 7.1. At follow-up day 160: HSV-1 serum IgG 1:20.000, IgM negative, CSF IgG 1:720, HSV-index 8.1.
No other infectious causes of encephalitis could be identified at relapse. Tests performed to exclude infectious differential diagnoses at relapse (day 41 after onset of symptoms):
CSF PCR was negative for:HSV-1 (cut-off 100 genome equivalents/µl), EBV, CMV, HHV6, VZV, JCV, West-Nile virus (WNV), 16s-rRNA and 18s-rRNA. Serology for CMVwas negative (serum IgG negative, IgM negative; CSF: IgG negative), for EBV showed prior non-acute infection (serum: IgG 66.000U/ml, VCA-IgM EIA negative, VCA-IgG EIA positive, EBNA-IgG EIA positive; CSF: IgG 1.300U/ml), for VZV showed prior non-acute infection (serum IgG 2500mIU/ml, IgM negative; CSF 110mIU/ml), for measles showed prior immunization (serum IgG 1:1400, IgM negative; CSF IgG negative). Serology in CSF and serum formumps and rubella showed prior immunization, and was clearly negative for borrelia burgdorferii, tremponema pallidum, tropheryma whipplei, WNV, Venezuelan-Equine-encephalitis virus, St. Louis-encephalitis virus, for HIV-1/2 IgG and for HIV-1 antigen, for HTLV I/II, Hepatitis-B/-C virus and parvo-virus and showed no evidence of CNS infection.
Increased intrathecal antibody production was observed for VZV (ab index 9.81), EBV (ab index 4.39) and measles (ab index 7.833) compatible with polyclonal activation.
Other paraneoplastic and encephalitis-associated antibodies were negative at relapse (day 41): AMPA-receptor, GABA(b)-receptor, LGI1, CASPR2, glycine-receptor, Hu, Yo, Ri, Tr, Ma/Ta, amphiphysin, GAD65, AQP4.
Lymphomatous meningitis was excluded at relapse:Differential blood count showed normal numbers of leukocytes, B-lymphocytes, natural-killer cells, T-cells, normal CD4+/CD8+ ratio, no sign of antigen-loss for T-cells no signs of light-chain restriction for B-cells. CSF cytology at relapse showed 95% lymphocytes, 5% monocytes, with 1% activated lymphocytes. CSF flow-cytometry showed 57% T-lymphocytes without antigen-loss (CD4, CD7, CD8), 6% B-cells without light-chain restriction.