Α case of seronegative autoimmune encephalitis associated with human herpesvirus‐7 (HHV‐7)

Abstract

In the last 10 years, an increased number of patients presenting with acute encephalitis is being observed, a finding that is attributed to autoimmune mechanisms.Despite the fact that autoantibodies usually target the neuronal cell surface or synaptic proteins in the central nervous system (CNS), in many cases these remain undetectable, constituting a future diagnostic and therapeutic challenge. Human herpesvirus-7 (HHV-7) is proven to be a neurotropic virus, causing various neurological complications mostly in the adult population. We present the case of a 10-year-old girl, with confirmed active HHV-7 infection of the CNS, who developed acute seronegative autoimmune encephalitis. To our best knowledge, there is no literature concerning pediatric cases of autoimmune encephalitis following HHV-7 infection.

Update on human herpesvirus 7 pathogenesis and clinical aspects as a roadmap for future research

“…The development of neurological disease is likely multifactorial depending not only on the viral strain but also on host factors such as age and immune status. As described for other herpesviruses, primary HHV-7 infections delayed into adolescence might cause more severe neurological diseases than those occurring in early childhood ( 140 , 143 , 144 , 147 , 149 , 155 , 168 ). This is because the aggressive inflammatory response produced by a more mature immune system can paradoxically lead to more tissue damage.…”

“…One study also linked the presence of HHV-7 DNA and antigens in the brain to inflammatory-mediated hippocampal sclerosis and drug-resistant epilepsy ( 166 ). Other neurological disorders such as encephalitis, meningitis, myelitis, cerebellitis, neuritis, and meningo- or myeloradiculopathy (e.g., Guillian Barré syndrome) have also been observed during ongoing HHV-7 infection ( 6 , 128 , 129 , 139 – 141 , 143 – 158 , 160 – 165 , 167 , 168 , 170 ). In most cases, CNS manifestations ranging from nausea, sensitivity to light, and a stiff neck to ataxia and paralysis were accompanied by the detection of HHV-7 nucleic acids in cerebrospinal fluid (CSF) and/or synthesis of intrathecal anti-HHV-7 antibodies ( 6 , 129 , 140 , 141 , 143 – 158 , 160 – 164 , 167 , 168 ).…”

“…Other neurological disorders such as encephalitis, meningitis, myelitis, cerebellitis, neuritis, and meningo- or myeloradiculopathy (e.g., Guillian Barré syndrome) have also been observed during ongoing HHV-7 infection ( 6 , 128 , 129 , 139 – 141 , 143 – 158 , 160 – 165 , 167 , 168 , 170 ). In most cases, CNS manifestations ranging from nausea, sensitivity to light, and a stiff neck to ataxia and paralysis were accompanied by the detection of HHV-7 nucleic acids in cerebrospinal fluid (CSF) and/or synthesis of intrathecal anti-HHV-7 antibodies ( 6 , 129 , 140 , 141 , 143 – 158 , 160 – 164 , 167 , 168 ). Of note, HHV-7-specific antibodies or DNA were usually not accompanied by the presence of other viral DNA or antibodies, ruling out potential leakage through the blood-brain barrier (BBB) and indicating that HHV-7 can invade the nervous system.…”

Human herpesvirus-7 Meningitis in an Immunocompetent Adult Patient: a Case Report

“…However, the infection is not always benign in children and rare cases of sudden child death due to HHV-7 encephalitis were described [ 12 ]. Other neurological manifestations including Guillain–Barre syndrome [ 4 ], hemiplegia [ 13 ] and seronegative autoimmune encephalitis [ 14 ] were also described in immunocompetent children.…”