Surprisingly, although HHV-6B has been linked to febrile seizures, febrile status epilepticus and temporal lobe epilepsy, the report contains no mention of the virus.
Febrile seizures (FS) – seizures occurring in a child with a fever – occur in 2% to 5% of young children, most often in the second year of life. Sometimes, the seizures last long enough to meet the criteria for febrile status epilepticus (FSE), a seizure lasting 30 minutes or more, often with adverse consequences. During the second year of life, FSE accounts for 70% of all cases of status epilepticus. Children with one episode of FSE have a much greater likelihood of recurrent FSE.
Children with FSE also have a greater likelihood of subsequently developing acute injury to the hippocampus and temporal lobe, documented by MRI. Those with such injuries have an increased risk of future FSE, as well as an increased risk for a structural change in the brain: hippocampal sclerosis (HS), a permanent injury often seen in adults with temporal lobe epilepsy.
In children with FSE, hippocampal or temporal lobe injury are often seen on MRI. About 10% of individuals with hippocampal injury evident by MRI (either T2 hyperintensity, reflecting inflammation, or retarded growth of hippocampal volume) go on to develop hippocampal sclerosis.
Are infants with FS and FSE more likely to go on to develop epilepsy later in life? Three separate cohorts were assembled to investigate this possibility. The study involved over 200 infants, most of whom had brain MRIs within 4 days of FSE, and again 1, 5 and 10 years later. The main results:
- Of 22 subjects with hippocampal T2 hyperintensities during FSE, 14 returned for follow-up MRIs: 10/14 had developed definite HS and 2 possible HS.
- Of the subjects with FSE as infants, 44 developed epilepsy later in life. The 10-year cumulative incidence of epilepsy was significantly higher in infants with FSE who had hippocampal T2 hyperintensities.
- Infants with FSE who did not have hippocampal T2 hyperintensities did not go on to develop MRI abnormalities, or epilepsy, later in life.
Thus, this careful study supports the hypothesis that infants who have FSE, and MRI abnormalities at the time of FSE, are more likely to develop progressive MRI abnormalities and epilepsy later in life.
Why is an HHV-6/7 newsletter summarizing this study?
So, why is a newsletter about research on HHV-6A/B and HHV-7 bothering to summarize this study? Because of what Sir Arthur Conan Doyle would have called “the dog that didn’t bark”: the absence of any mention of HHV-6.
HHV-6B in FS and FSE. Previous research has reported substantial evidence that:
- Primary infection with HHV-6B occurs in the first two years of life—the most common age at which FS and FSE occur
- FS and FSE are associated with primary infection by HHV-6B (and, possibly, occasionally HHV-6A) in 20% of children with FSE, and with reactivated infection in about 10% of children with FSE, as determined by detection of plasma viremia (studies of cerebrospinal fluid rarely have revealed virus)
- In contrast, primary HHV-6B viremia was never found in any of 582 infants and young children with acute nonfebrile illnesses nor in 352 healthy controls (Hall 1994).
These findings previously have led many investigators to conclude that primary infection with HHV-6B is neurotropic and is correlated with both FS and FSE (Hall 1994; Caserta 1994; Epstein 2012). These previous studies have been conducted by some of the same investigators, reporting results from the same patient group, as in this study.
HHV-6 in epilepsy. Some evidence indicates that mesial temporal lobe epilepsy may also be triggered, in some cases, by HHV-6, as summarized in detail elsewhere (Kawamura 2015; Komaroff 2020; Theodore 2021; Bartolini 2021,). The main evidence is:
- HHV-6A/B nucleic acid and antigens by immunohistochemistry are present in diseased tissue, in most cases, and in higher abundance than in non-diseased tissue.
- HHV-6A/B nucleic acid is demonstrated in cells relevant to disease pathology.
- HHV-6A/B (more often than other human herpesviruses) is present in brain tissue that has been surgically resected to treat epilepsy
Given that this study finds that febrile status epilepticus (FSE) in infants is associated later in life with the development of temporal lobe epilepsy, and with MRI changes associated with temporal lobe epilepsy, and given prior work linking HHV-6B to both FSE and mesial temporal lobe epilepsy, it is surprising that the authors make no mention of any virological studies. Perhaps these are being summarized in another report. As it stands, it is puzzling that the “dog didn’t bark” and that the question was begged.
Read the full article: Lewis 2024