Acyclovir-induced Neurotoxicity Research Articles

A Case of Herpes Zoster Complicated with Acute Renal Failure and Acyclovir-induced Neurotoxicity

A Case of Herpes Zoster Complicated with Acute Renal Failure and Acyclovir-induced Neurotoxicity

Acyclovir-induced neurotoxicity with a positive cerebrospinal fluid varicella zoster PCR result creating a management dilemma: a case report

BackgroundVaricella zoster virus central nervous system infections can present as aseptic meningitis, encephalitis, myelitis, and vasculopathy. Diagnosis is based on identification of varicella zoster virus deoxyribonucleic acid (DNA) in the cerebrospinal fluid by polymerase chain reaction. Therapy for these infections is acyclovir or valacyclovir. However, acyclovir can have neurotoxic effects that can mimic the presentation of varicella zoster virus central nervous system disease. We present a rare presentation of a patient who had acyclovir-induced neurotoxicity who also had a false-positive cerebrospinal fluid varicella zoster virus polymerase chain reaction result, creating a management dilemma. We review the clinical characteristics of acyclovir-induced neurotoxicity. In addition, we present the diagnostic characteristics of the cerebrospinal fluid viral polymerase chain reaction and alternative methods to diagnose central nervous system varicella zoster virus disease.Case presentationA 68-year-old Hispanic man with end-stage renal disease was diagnosed with cutaneous zoster at an outside facility and was started on acyclovir 4 days prior to admission. His family noted worsening confusion, agitation, speech difficulty, and hallucinations, leading them to bring him to the emergency department. His cerebrospinal fluid varicella zoster virus polymerase chain reaction result was positive, indicating the presence of varicella zoster virus deoxyribonucleic acid in the cerebrospinal fluid; however, he did not have cerebrospinal fluid pleocytosis typical of varicella zoster virus meningoencephalitis. Pharmacy records from the outside hospital revealed supratherapeutic acyclovir dosing. This led to a diagnostic dilemma over whether this patient had varicella zoster virus encephalitis or acyclovir-induced neurotoxicity. Acyclovir was discontinued, and the patient underwent two sessions of hemodialysis to remove acyclovir, which led to a full neurologic recovery.ConclusionsVaricella zoster virus encephalitis and acyclovir-induced neurotoxicity can have similar presentations. Varicella zoster virus deoxyribonucleic acid can be present in the cerebrospinal fluid during active cutaneous zoster in the absence of central nervous system disease. If concern for central nervous system varicella zoster virus disease remains high, additional testing with cerebrospinal fluid serology can be performed. Compared with central nervous system varicella zoster virus disease, acyclovir-induced neurotoxicity has a more predictable clinical resolution once drug therapy is discontinued or the patient undergoes hemodialysis, which can aid in making the diagnosis. Clinicians should be aware of this rare and dangerous complication of acyclovir. In addition, clinicians should have an understanding of the diagnostic limitations of cerebrospinal fluid viral polymerase chain reaction and have alternative approaches available to diagnose central nervous system varicella zoster virus disease when it is suspected.

Acyclovir-induced neurotoxicity in an immunocompromised patient

Acyclovir-induced neurotoxicity in an immunocompromised patient

A Case Report of Neurotoxicity After Prolonged Doses of Acyclovir in a Patient With Renal Dysfunction

Renal dysfunction is a significant risk factor for acyclovir-induced neurotoxicity and altered mentation and myoclonic movements are the most common clinical symptoms observed. In majority of reported cases, neurological sequelae associated with acyclovir-induced neurotoxicity often mimic viral infections of the central nervous system and makes diagnosis of the former challenging. Although plasma concentrations of the drug may not always correlate with neurotoxic symptoms, obtaining serum levels of acyclovir may be helpful in confirming drug-induced neurotoxicity. Hemodialysis has been shown to significantly improve altered mentation in patients with suspected or confirmed acyclovir-induced neurotoxicity. Here, we report a definite case of acyclovir-induced neurotoxicity in a patient with end-stage renal disease. Clinical improvements in neurologic symptoms were observed following discontinuation of the drug and hemodialysis.

Confusion in Patients with Shingles and Renal Failure: Acyclovir Neurotoxicity or Herpes Encephalitis

It is not uncommon for patients with shingles and renal failure who develop confusion during the course of therapy. The patient may have suffered from the adverse reaction of acyclovir or have the neurologic complication related to the dermatological herpes zoster. Acyclovir induced neurotoxicity and herpes encephalitis have similar clinical feature but their treatments are completely different. Often, doctors face challenges in differentiating the two conditions and the dilemma of whether to continue or stop acyclovir. We reported two cases of renal impairment patient who developed altered mental state after receiving oral acyclovir for the herpes skin lesion. One suffered from varicella encephalitis and the other had acyclovir‐induced neurotoxicity. The difference in clinical features among the two conditions and the management of acyclovir‐induced neurotoxicity was highlighted.

Acyclovir‐induced neuropsychosis successfully recovered after immediate hemodialysis in an end‐stage renal disease patient

A 70-year-old man developed herpes zoster over the right L5-S2 region for 3 days and was admitted for acyclovir therapy. He had a medical history of rectal cancer status post-colostomy and end-stage renal disease undergoing thrice weekly hemodialysis. Without a prior loading dose, acyclovir 500 mg (7.7 mg/kg) daily was given intravenously in two divided doses. On the third dosage, the patient became confused and agitated and developed insomnia. Within the following 24 h, delirium, visual and auditory hallucinations, disorientation to place and time, as well as impaired recent memory occurred. At the same time, a transient low grade fever (38 degrees C) was noted but resolved spontaneously after ice pillow (Fig. 1). The etiology was vigorously explored. He had no history of any neurological or psychiatric disorders. Drug history was reviewed, but no other medications besides acyclovir were currently being used. Physical examination revealed neither meningeal signs nor focal neurological deficits. Serum blood urea nitrogen, glucose, and electrolytes were within normal limits except for an elevated creatinine level at 6.2 and 5.7 mg/dl (before and after neuropsychotic symptoms, respectively). Complete blood count with differentiation was also unremarkable. Cerebrospinal fluid examination was not possible as the patient's family refused the lumbar puncture. Moreover, an electroencephalograph study and head computed tomography scan disclosed no abnormalities. Acyclovir-induced neurotoxicity was suspected. Therefore, acyclovir was discontinued. Subsequently, serum acyclovir and CMMG were checked by enzyme-linked immunosorbent assay. Serum acyclovir level was 1.6 mg/l (normal therapeutic level, 0.12-10.8 mg/l) and CMMG level was 5 mg/l. Emergent hemodialysis (4-h/session) was given; the neuropsychotic symptoms, including agitation, delirium, and visual and auditory hallucinations, greatly abated after the second session. The patient fully recovered after three consecutive days of hemodialysis; the serum was rechecked and revealed that the acyclovir level was below 0.5 mg/l and the CMMG level was undetectable. At the same time, his herpetic skin lesions resolved well.

Neurological toxicity of acyclovir: Report of a case in a six‐month‐old liver transplant recipient

Acyclovir-induced neurotoxicity is a rare adverse effect, found especially in adults with pre-existing renal failure. We report a case of neurotoxicity of acyclovir in a six-month-old liver transplant recipient. Case report and review of literature are discussed.

Acyclovir-induced Neurotoxicity Increases The Risk For Thromboembolic Events, Cerebral Hemorrhage And Death

s: Ninth International Congress of Therapeutic Drug Monitoring and Clinical Toxicology: Louisville, Kentucky April 23-28, 2005

Evaluation of Valaciclovir Dosage Reduction in Continuous Ambulatory Peritoneal Dialysis Patients

In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the L-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 ± 4 l/h and half-life (T_1/2) 22.27 ± 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections.

Acyclovir-induced neurotoxicity: Concentration-side effect relationship in acyclovir overdose

Purpose: To investigate the concentration-side effect relationship in a patient with severe acyclovir-induced neurotoxicity and to summarize the information available in the literature about central nervous system side effects due to acyclovir. Methods: Repeated blood samples were drawn in a patient with severe acyclovir overdose who developed coma and nonoliguric renal failure. The acyclovir levels measured by radioimmunoassay were related to the level of consciousness. Results: We measured the highest acyclovir serum levels reported so far ( 229.9 μmol L = 51.8 mg/L ). Impairment of consciousness developed with a remarkable temporal delay of 24 to 48 hours after occurrence of peak serum concentrations and resolved with a comparable delay after reaching the therapeutic range (anticlockwise hysteresis). Six days after discontinuation of the drug, central nervous system symptoms had resolved, and, 4 days later, renal function returned to pretreatment values. Conclusion: The observation that neurotoxicity developed with a delay of 24 to 48 hours after acyclovir peak serum concentrations could explain the wide range of acyclovir levels reported in similar cases. Single drug level measurements may therefore be of little diagnostic value. Since toxicity develops with a remarkable delay, early removal of the drug (by hemodialysis) could possibly prevent central nervous toxicity.