A team of Chinese investigators led by Dr. Jin-Mei Li at West China Hospital has identified a possible synergy between a polymorphism of Apolipoprotein E (ApoE) and HHV-6B infection, resulting in a higher viral load and seizure frequency in these patients. HHV-6B DNA was found in 39% of 46 MTLE resections. However the prevalence increased to 57% in patients positive for ApoE4, compared to just 10% of controls. Significantly, viral loads of the HHV-6B+ patients were much higher in those with ApoE4. The viral load for MTLE patients positive for both ApoE4 and HHV-6B DNA was 126 copies/million cells, compared to 11 copies/million cells in control HHV-6B+ trauma patients, in analysis of their hippocampus tissues.
The authors point to past studies, which suggest that HHV-6B results in inflammation and the production of NF-kB, IL-1 and other pro-inflammatory cytokines and chemokines, which contribute to hyper-excitability and may be the reason for the increased seizure frequency (Fotheringham 2007, Li, 2011). They also note that although ApoE4 by itself was not associated with increased seizure activity, ApoE4 may facilitate HHV-6 reactivation, viral protein expression resulting in increased seizure frequency.
Apolipoprotein E (ApoE) is a major component of low-density lipoproteins that play an important role in the central nervous system. ApoE4 has been tied in several studies to an increased risk of seizures and earlier onset of epilepsy. It has also been linked to an increased risk of Alzheimer’s and is believed to facilitate HSV-1 infection. Patients positive for ApoE4 have increased oral herpetic lesions (Koelle 2010) and ocular HSV-1 (Bhattacharjee 2008).
HHV-6B causes one-third of status epilepticus cases (Epstein 2012) as well as encephalitis in 8-10% of cord blood transplant patients (Scheurer 2012, Hill 2012). Patients with refractory epilepsy often have surgery to remove focal lesions in their temporal lobe, to reduce seizure frequency.
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