HHV-6 encephalitis should be considered even among immunocompetent patients presenting with encephalitis and having signs of temporal lobe involvement (Shahani 2014). A NINDS study found HHV-6 DNA in the CSF of 40% of 35 immunocompetent patients with encephalitis of unknown etiology (Yao 2009). HHV-6 encephalitis/encephalopathy associated with primary infection in infants has an unexpectedly poor outcome. In a nationwide survey in Japan, 46.9% of 81 cases resulted in neurological sequelae or death (Yoshikawa 2009). One study found that out of 983 cases of acute encephalopathy in Japan, 17% were caused by HHV-6. 64% of the severe cases with biphasic seizures in this study were attributed to HHV-6, only half of which survived without permanent neurological sequelae (Hoshino 2012).
Opsoclonus-myclonus Syndrome (OMS) associated with human herpesvirus-6 rhomboencephalitis
Opsoclonus-myoclonus syndrome (OMS) is characterized by opsoclonus and arrhythmic-action myoclonus that predominantly involves the trunk, limbs, and head. Human herpes virus-6 (HHV-6) can rarely cause encephalitis in immunocompetent children and adults. A case study by Belcastro, et al., reports on a case of OMS associated with HHV-6 rhomboencephalitis (Belcastro 2014). HHV-6 infection should be considered in OMS adults and detection of cell-free viral DNA, indicative of active infection, is mandatory in such cases.
In cancer patients, neurological symptoms are usually due to brain metastases. A case report by Mordenti, et al., showed that in a cancer patient, any non-specific neurological symptoms should be carefully evaluated in order to exclude a non-oncologic cause. This is particularly true if the therapies for the oncological and neurological diseases are effective (Mordenti 2013).
POLG Mutations (Alpers-Huttenlocher Syndrome)
POLG mutations are associated with Alpers-Huttenlocher syndrome. A study reports two previously healthy young boys with human herpesvirus 6-associated encephalitis who developed a progressive, and ultimately fatal, encephalopathy with refractory movement disorder concurrent with acquisition of acute human herpesvirus 6 infection. Both children were treated with the antiviral ganciclovir without improvement of their neurological symptoms, although quantitative HHV6 PCR of CSF and/or blood confirmed a decline in viral load with treatment. The clinical course in both cases was most consistent with Alpers-Huttenlocher syndrome, given the intractable seizures, developmental regression, and, ultimately, death due to liver and renal failure. Postmortem analysis identified both children to be compound heterozygous for mutations in the mitochondrial polymerase gamma-gene, POLG. It is possible the POLG mutation phenotype becomes unmasked and/or exacerbated by human herpesvirus 6 infection in these 2 patients, potentially contributing to a more rapid clinical deterioration (Al-Zubeidi 2014)
Tick-borne Encephalitis and Enteroviral Meningoencephalitis
In a study investigating the frequency of HHV DNA detection in CSF of immunocompetent patients with meningoencephalitis of other than HHV origin, 96 patients with clinically and laboratory proven tick-borne encephalitis (TBE) and 77 patients with a confirmed diagnosis of enteroviral meningitis, along with a control group of 107 patients without evidence of inflammation in the CSF were retrospectively tested by nested PCR for the presence of DNA of the neurotropic herpesviruses HSV1, HSV2, VZV, and HHV6 in the CSF. HHV DNA was found in the CSF of 12 (6.9%) patients (6.3% and 7.8% in the TBE and EVM groups, respectively) and in 1 (0.9%) control patient. In all patients, the disease had a mild course without permanent sequelae. The presence of herpesviral DNA in the CSF had no significant influence on disease outcome. Low frequency and negligible impact of herpesvirus reactivation in TBE or EVM patients do not argue for routine herpesvirus testing in these diseases (Labska 2015).