ganciclovir , a drug against cytomegalovirus ( cmv ) infection , is generally well tolerated , but can cause neurotoxicity such as encephalopathy .
although ganciclovir - induced encephalopathy has been described in several reports , a literature search revealed that ganciclovir concentrations in the blood or cerebrospinal fluid were previously measured in only 3 patients with encephalopathy .
prompt and accurate diagnosis is thus sometimes difficult , and is derived solely from accumulated clinical information of definite cases , since ganciclovir concentrations , not routinely measured , become available after several days or a few weeks .
here , we summarize clinical information of all patients with definite ganciclovir - induced encephalopathy including our own patient , who had severe symptoms , with the highest reported trough concentration of ganciclovir in the blood , and underwent therapeutic dialysis with complete recovery .
encephalopathy can be caused by neurotoxicity with prophylactically or therapeutically administered drugs such as acyclovir , ganciclovir , and their prodrugs , valacyclovir and valganciclovir .
the drugs are structurally similar nucleoside analogues , but their effects on neurons are poorly understood .
acyclovir - induced encephalopathy is more widely known than ganciclovir - induced encephalopathy , possibly because acyclovir is used against herpes virus infection , which is more common than cytomegalovirus ( cmv ) infection , for which ganciclovir is used .
ganciclovir was also reported to be effective against hepatitis b infection , but has rarely been used for this indication recently .
although ganciclovir - induced encephalopathy has been documented previously , a literature search revealed that ganciclovir concentrations in the blood or cerebrospinal fluid ( csf ) have been reported in only 3 patients [ 1 , 2 , 3 ] .
previous reports on patients with such definite ganciclovir - induced encephalopathy have suggested that the trough concentration of ganciclovir in the blood is important . here , we summarize clinical information of patients with definite ganciclovir - induced encephalopathy including our own patient , who had severe symptoms , with the highest reported trough concentration of ganciclovir in the blood , and underwent therapeutic dialysis .
a 55-year - old man started to receive hemodialysis because of diabetic renal failure 2 years previously .
he underwent renal transplantation 1.5 years previously , and had been receiving immunosuppressants since then .
eight months after transplantation , the serum creatinine level increased to 4.4 mg / dl .
he had cmv enteritis with occult blood in the stool and an elevated cmv pp65 ( c7-hrp ) antigen level in blood mononuclear cells .
intravenous ganciclovir ( 150 mg / day ) was administered for 11 days , followed by valganciclovir ( 450 mg / day ) . because the enteritis was very severe , ganciclovir and valganciclovir
two days after starting valganciclovir , he had unsteady gait , but could walk unaided . on the next day , the patient needed assistance with walking .
his consciousness was mildly disturbed ( e3 , v5 , and m6 on the glasgow coma scale ) .
two days later , he was found on the floor after falling , without major injuries .
nine days after starting valganciclovir , his level of consciousness worsened ( e3 , v3 , and m5 ) , and he could not receive oral drugs , including valganciclovir .
encephalitis was unlikely , since no meningeal signs or fever was noted ; the cell count was normal ( 0.33 cells/l ) in the csf , and the protein concentration marginally elevated ( 54 mg / dl ) .
cmv , herpes simplex virus , varicella - zoster virus , and epstein - barr virus dna was later found to be negative in the csf .
because of the risk of further falls , hemodialysis using a vps-15 ha membrane , a vitamin e - coated polysulfone membrane ( asahi kasei kuraray medical , japan ) was performed twice in 2 days .
his consciousness improved considerably after the first session of dialysis ( e3 , v4 , and m6 ) and was completely restored on the next morning after the second session ( e4 , v5 , and m6 ) .
the trough levels of ganciclovir in the serum and csf were retrospectively measured and are shown in table 1 .
generally , ganciclovir is well tolerated , but caution is required in patients with renal impairment . additionally , the severe symptoms in our patient may have been attributed to high doses of ganciclovir or valganciclovir for treatment of severe cmv enteritis .
although the trough blood ganciclovir concentration in our patient was the highest reported to date , his csf ganciclovir concentration was the second highest among the 4 patients reported to date in the literature .
such discrepancies between the csf data and blood data may be explained by other factors , including penetration rates ( how much ganciclovir passes through the blood - brain barrier ) , which are reported to vary among individuals .
however , csf concentrations may not necessarily reflect the severity of encephalopathy . as an extreme example , 1 previous patient with an undetectable level of ganciclovir in the csf ( patient 2 in table 1 ) still had disturbed consciousness .
we speculate that the severe symptoms in our patient might have been attributed to peripheral nervous system involvement , which may be more sensitive to blood ganciclovir concentrations .
although definitive conclusions must await further studies , blood trough concentrations of ganciclovir may be more closely related to symptom severity than csf concentrations .
however , a fall , as observed in our patient , can cause devastating complications , an extended hospital stay , or both . in such patients
dialysis also has a positive effect on the function of the transplanted kidney . in summary
, our experience suggests that therapeutic dialysis is a safe and effective treatment for encephalopathy as well as for a damaged transplanted kidney
. the measurement of ganciclovir concentrations in the csf may not be feasible for the management of encephalopathy in individual patients because it is not routinely performed , and because several days to several weeks are required for the results .
nonetheless , measurement of ganciclovir concentrations can play an important role in confirming the diagnosis and evaluating disease severity .
we believe that accumulated knowledge on such patients with confirmed encephalopathy will lead to prompter and more accurate diagnoses .
 backgroundganciclovir , a drug against cytomegalovirus ( cmv ) infection , is generally well tolerated , but can cause neurotoxicity such as encephalopathy . 
 although ganciclovir - induced encephalopathy has been described in several reports , a literature search revealed that ganciclovir concentrations in the blood or cerebrospinal fluid were previously measured in only 3 patients with encephalopathy . 
 symptoms usually include confusion and disturbed consciousness , which mimic cmv encephalitis . 
 prompt and accurate diagnosis is thus sometimes difficult , and is derived solely from accumulated clinical information of definite cases , since ganciclovir concentrations , not routinely measured , become available after several days or a few weeks.case presentationhere , we summarize clinical information of all patients with definite ganciclovir - induced encephalopathy including our own patient , who had severe symptoms , with the highest reported trough concentration of ganciclovir in the blood , and underwent therapeutic dialysis with complete recovery.conclusionour summary of patients with definite encephalopathy could lead to prompt and accurate diagnoses . 
Background
Case Presentation
Conclusion
Introduction
Case Presentation
Discussion