No HHV-6 DNA found in the spinal fluid of immunocompetent adults evaluated for limbic encephalitis

While HHV-6B is well known to cause limbic encephalitis in transplant patients it does not appear to play a role in other forms of limbic encephalitis.

Post-transplant acute limbic encephalitis (PALE) has been convincingly linked to reactivated infection with HHV-6 (particularly HHV-6B). Reimers et al (2021) at University Hospital Bonn, Germany sought to determine if other forms of limbic encephalitis (LE) might also be linked to HHV-6, and also sought evidence that autoantibodies were present that might be causally related to the seizure disorder. An earlier study conducted by Linnola et al (2016) concluded that that HHV-6 DNA was present in serum or CSF in an occasional patient with possible autoimmune encephalitis.

The researchers obtained serum/CSF samples from adult patients who presented with “early diagnosis” of possible LE (diagnosis <= 30 months after first seizure event, n=94) and adults with late diagnosis of possible LE (diagnosis >= 97 months after first seizure event, n=45).

Using immunoblot and immunofluorescence assays, autoantibodies were detected in 21.3% of the early diagnosis patients and in 8.4% of the late diagnosis group, a significant difference (p<0.05). Autoantibodies targeting different antigens characterized the early diagnosis vs. late diagnosis groups: anti-LGI1 and anti-onconeural autoantibodies in the early diagnosis group, and autoantibodies against superficial structures (NMDAR, VGKC complex and GAD65) in the late diagnosis group. 

There was little evidence of HHV-6A/B DNA in either group.

This study does not suggest that reactivated HHV-6A/B play an important role in cases of limbic encephalitis not associated with the post-transplantation period. However, the study did not attempt to study the possible role that the immune response to an earlier reactivation of HHV-6A/B might have played in limbic encephalitis. In addition, selection bias is also present in this study as only patients exhibiting pharmacorefractory seizures as the main symptom were selected. Prospective, longitudinal studies with broader selection criteria, are warranted to investigate further.

Read the full article: Reimers 2021