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a 59-year - old man was diagnosed with chronic lymphocytic leukemia ( cll ) in 2007 and managed with various chemotherapy drugs ( fludarabine , alemtuzumab , bendamustine , cyclophosphamide , doxorubicin , vincristine , prednisone and rituximab ) . however , the patient required umbilical cord blood transplantation following a reduced intensity conditioning regimen ( cyclophosphamide 50 mg kg on day 6 , fludarabine 40 mg / m daily from days 6 through 2 and total body irradiation 200 cgy on day 1 ) for treatment of resistant cll in february 2013 .
graft - versus - host disease prophylaxis comprised sirolimus 4 mg daily and mycophenolate mofetil ( 1500 mg twice per day from days 3 through + 30 ) .
cytomegalovirus immunoglobulin ( ig ) g and herpes simplex virus igg were positive , whereas epstein - barr virus ( ebv ) igg was negative .
infection prophylaxis based on internal hospital guidelines included levofloxacin ( 250 mg daily ) , voriconazole ( 200 mg twice per day for possible invasive fungal infection due to lung nodules before allogeneic hematopoietic cell transplantation [ allohct ] ) , high - dose acyclovir ( 800 mg five times per day ) , and sulfamethoxazole / trimethoprim ( 800/160 mg twice per day on mondays and tuesdays ) .
neutrophil engraftment occurred on day + 26 and the patient achieved complete remission of cll ( bone marrow biopsy showed donor chimerism of 94% and no evidence of cll ) .
the patient was immunocompromised in both cellular and humoral immune systems ( cd4 cell count 0.0210/l , cd8 cell count 0.110/l , cd4:cd8 ratio 0.24 , cd1656 cell count 0.1610/l and igg level of 427
g / l ) . the patient was found unconscious and was readmitted to the hospital on day + 34 .
the patient was in nonconvulsive status epilepticus state based on electroencephalography findings and was electively intubated for airway protection .
complete blood count , creatinine , potassium , magnesium , calcium and liver function tests were within normal limits . his sodium level ( 126
there was no evidence for transplantation - associated thrombotic microangiopathy or graft - versus - host disease .
urgent computed tomography and magnetic resonance imaging ( mri ) of the brain were normal for his age .
cerebrospinal fluid ( csf ) analysis showed five white blood cells ( comprised of lymphocytes and monocytes ) , no malignant cells , normal protein level ( 360
csf evaluation , including bacterial and fungal cultures , gram stain , india ink and viral studies ( cytomegalovirus , ebv , john cunningham virus , herpes simplex virus and herpes zoster virus polymerase chain reactions ) were all negative . despite aggressive antiepileptic therapy ( phenytoin 250 mg twice per day and levetiracetam 2 g twice per day ) , electroencephalography continued to show a pattern of acute repetitive seizures in the right and left frontotemporal regions .
high - dose midazolam drip ( 10 mg / h ) was added for seizure control .
a repeat mri on hospital day 5 showed a symmetric hyperintensity bilaterally at the basal ganglia and subtle hypertensities in bilateral mesial temporal lobes ( figure 1 ) .
csf test results for human herpesvirus 6 ( hhv6 ) were available and positive ( 379,300 copies / ml ) on day + 41 .
the concurrent serum sample was also positive for hhv6 ( 8000 copies / ml ) .
ganciclovir ( 5 mg / kg intravenous twice per day ) was started due to no improvement in his clinical condition , seizure activity and the evolving mri findings .
seizure activity was no longer detectable , and the patient had become alert and was extubated on day + 43 . a long hospitalization ensued , which was complicated by deconditioning and multiple reintubations for hyper - capnea and respiratory muscle weakness .
he completed six weeks of ganciclovir therapy ( 5 mg / kg twice per day ) .
alteration in consciousness and seizure after allohct can be caused by posterior reversible encephalopathy syndrome , immunosuppressive drug toxicities , fludarabine toxicity , transplantation - associated thrombotic microangiopathy or central nervous system infections , including hhv6 ( 13 ) .
hhv6 , a beta herpes virus , infects 95% of the population by two years of age and is the cause of exanthema subitum ( 4 ) . after acute infection
, hhv6 remains in a latent form in cd34 cells , monocytes and macrophages . on average , 50% of allohct recipients  possibly more frequent in umbilical cord blood transplant patients  will reactivate hhv6 in the first month of allohct ( range two to eight weeks ) ( 510 ) .
although the direct causative effect has never been confirmed , hhv6 reactivation is associated with several clinical syndromes , including febrile illness , delayed engraftment , pneumonitis and encephalitis after allohct ( 4,7,912 ) . among these syndromes ,
there has been accumulating evidence supporting a causal association between hhv6 and encephalitis ( 4 )
. moreover , autopsy findings are also suggestive of a pathogenic role for hhv6 ( 13 ) .
patients can present with acute mental status changes , cognitive dys - function , delirium , hallucinations , anterograde amnesia and seizure ( 12,1417 ) .
hyponatremia , resulting from the syndrome of inappropriate antidiuretic hormone secretion or sodium wasting in urine , can be observed ( 3,12,18 ) .
normal or mildly elevated protein levels and mild pleocytosis are typical csf findings ( 5,12 ) .
it shows t2 hyperintense signal abnormality of one or both hippocampi and variably involving adjacent medial temporal lobe structures of the limbic system , including amygdalae and parahippocampal gyri ( limbic encephalitis ) ( 12,14 ) .
in addition to hhv6 encephalitis , the differential diagnosis of these findings includes other infectious causes of encephalitis such as herpes zoster virus , varicella zoster virus , cytomegalovirus , ebv or neurosyphilis , autoimmune disorders , conditioning regimen toxicity and paraneoplastic syndromes ( 19 ) . in vitro and limited clinical data
although survival rates appear to be improving , hhv6 encephalitis remains associated with mortality and morbidity ( long - term sequelae , such as neuro - psychological disorders , are not uncommon ) ( 6,21,22 ) .
hhv6 should be considered in patients with nonconvulsive status epilepticus presenting with sudden unconsciousness after allohct .
no other apparent cause of seizure and the presence of hyponatremia increase the likelihood of hhv6 infection .
this article describes a case involving a 65-year - old man who experienced nonconvulsive status epilepticus after undergoing an allogenic hematopoietic cell transplantation to treat chronic lymphocytic leukemia . 
 the authors describe the diagnostic work - up and treatment of human herpesvirus 6 infection , and discuss other potential causes of nonconvulsive status epilepticus in similar scenarios .