Differential diagnosis of posterior reversible encephalopathy syndrome and acyclovir neurotoxicity in children: A literature review of acyclovir neurotoxicity

Shotaro Haraguchi , Yoshihiro Watanabe , Yuki Inami , Mao Odaka , Hirotaka Motoi , Kentaro Shiga , Reo Tanoshima , Shuichi Ito
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Abstract

Background

Acyclovir (ACV), an antiviral drug commonly used in children, is associated with neuro- and nephron-toxicity. However, ACV neurotoxicity is mainly reported in adults and rare in children. Herein, we report the case of a boy with impaired consciousness following ACV treatment, posing challenges in differentiating posterior reversible encephalopathy syndrome (PRES) from ACV neurotoxicity. Additionally, we reviewed existing literature on ACV neurotoxicity.

Case presentation

A healthy 10-year-old boy developed severe headache and intermittent restlessness and was diagnosed with mild encephalitis/encephalopathy showing a reversible splenial lesion on magnetic resonance imaging (MRI). Since herpes simplex encephalitis could not be ruled out, ACV was initially administered. The patient later developed renal dysfunction, hypertension, and conscious disturbance. With a high serum ACV level of 14.3 μg/mL (reference; 0.4–2.0 μg/mL), we suspected PRES or ACV neurotoxicity. Upon discontinuation of ACV and starting antihypertensive therapy, the patient’s consciousness improved, leading to discharge without sequelae. In 14 pediatric cases with ACV neurotoxicity, including our case, the median age at onset was 10 years (range, 0–17 years), with renal dysfunction and high doses of ACV posing risk similar to adult cases. The mean time from ACV discontinuation to complete recovery was 5.6 ± 3.6 days, and the patients’ prognosis was good.

Conclusions

When a patient develops neurological symptoms during ACV treatment, considering the simultaneous occurrence of ACV neurotoxicity and PRES is crucial, including measuring their blood pressure, renal function, ACV levels, and MRI. Additionally, dosage should be adjusted based on ACV concentration in blood.

儿童后可逆性脑病综合征与阿昔洛韦神经毒性的鉴别诊断:阿昔洛韦神经毒性文献综述
背景阿昔洛韦(ACV)是一种常用于儿童的抗病毒药物,具有神经和肾毒性。然而,阿昔洛韦的神经毒性主要见于成人,在儿童中很少见。在此,我们报告了一名男孩在接受 ACV 治疗后出现意识障碍的病例,这给后可逆性脑病综合征(PRES)与 ACV 神经毒性的鉴别带来了挑战。病例介绍一名 10 岁健康男孩出现严重头痛和间歇性烦躁不安,被诊断为轻度脑炎/脑病,磁共振成像(MRI)显示有可逆性脾脏病变。由于无法排除单纯疱疹性脑炎的可能性,最初给他注射了 ACV。患者后来出现肾功能障碍、高血压和意识障碍。由于血清 ACV 水平高达 14.3 μg/mL(参考值:0.4-2.0 μg/mL),我们怀疑患者患有 PRES 或 ACV 神经毒性。停用 ACV 并开始降压治疗后,患者的意识有所改善,出院时未留后遗症。在包括本病例在内的 14 例 ACV 神经毒性儿科病例中,发病年龄的中位数为 10 岁(0-17 岁),肾功能障碍和大剂量 ACV 带来的风险与成人病例相似。从停用 ACV 到完全康复的平均时间为 5.6 ± 3.6 天,患者预后良好。结论当患者在 ACV 治疗期间出现神经系统症状时,考虑 ACV 神经毒性和 PRES 的同时发生至关重要,包括测量患者的血压、肾功能、ACV 水平和 MRI。此外,应根据血液中的 ACV 浓度调整剂量。
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