HHV-6 reactivation with status epilepticus and hyponatremia after transplantation
A report published by a group from the University of Minnesota details the case of a 59-year-old male who developed non-convulsive status epilepticus and hyponatremia in addition to HHV-6 reactivation following umbilical cord blood transplantation.
While status epilepticus following alloHCT is rare, several studies have documented a relationship between HHV-6 encephalitis and hyponatremia following hematopoietic stem cell transplantation (HCST), umbilical cord blood transplantation, and bone marrow transplantation. A retrospective study published by group of researchers in Japan reported several patients who developed hyper- (>145 mEq/L) or hyponatremia (<133 mEq/L) associated with post-HCST HHV-6 encephalitis (Shimazu 2013). It should be noted that patients with hypernatremia demonstrated a shift to hyponatremia after the development of encephalitis in these cases (Shimazu 2013). Three case reports also describe patients diagnosed with HHV-6 encephalitis who developed hyponatremia after undergoing either unrelated umbilical cord transplant or unrelated bone marrow transplantation (Chik 2002, de Souza 2014). In both the retrospective study and the case reports, patients demonstrated seizures, confusion, and/or loss of consciousness (Chik 2002, de Souza 2014).
Hyponatremia is an electrolyte abnormality that reportedly occurs in 20–40% of allo-SCT patients (Kawaguchi 2013). Severe hyponatremia, which is characterized as a serum sodium level of <125 mEq/L, may cause seizures, confusion, brain damage, respiratory arrest, and death in patients (Kawaguchi 2013). It is reported that approximately 50% of allogeneic hematopoietic cell transplantation (alloHCT) patients will experience a reactivation of HHV-6 within the first month following alloHCT. This reactivation is often associated with febrile illness, delayed engraftment, pneumonitis, and encephalitis.
In this case, a 65-year-old male who underwent umbilical cord blood transplantation for chronic lymphocytic leukemia (CLL), experienced complete remission of CLL, but on day 34 was found unconscious and diagnosed with nonconvulsive status epilepticus. Despite receiving antiepileptic therapy, the patient continued to demonstrate acute repetitive seizures. He had a moderately low sodium level of 126 mEq/L. On day 41, the patient’s CSF and serum both tested positive for HHV-6 (379,300 copies/mL and 8,000 copies/mL, respectively). Treatment with ganciclovir was initiated, and by day 43, seizure activity was no longer detectable. After HHV-6 was isolated from bronchoalveolar lavage fluid, foscarnet was added to the treatment regimen. The patient’s cognitive function improved with prolonged rehabilitation.
Taken together, the findings of these studies suggest that low serum sodium values following transplantation may be indicative of HHV-6 reactivation and/or incipient encephalitis. HHV-6B has also been associated with febrile status epilpeticus in infants (Epstein 2012) as well as immunocompetent adults (Shahani 2014).