Scholarlink

Background <p>Ifosfamide-induced encephalopathy (IIE) is a recognized complication of ifosfamide therapy, most often presenting as mild, reversible neurocognitive dysfunction. Severe cases requiring mechanical ventilation are rare and diagnostically challenging, particularly in oncology patients with multiple competing causes of altered mental status. Evidence guiding the optimal dosing, duration, and safety monitoring of methylene blue in refractory IIE remains limited.</p> Case Description <p>A 44-year-old man with metastatic retroperitoneal spindle cell sarcoma and normal baseline renal and hepatic function was admitted for chemotherapy. His clinical course was initially confounded by a recent complicated urinary tract infection treated with ciprofloxacin, followed by mild prodromal delirium. Within 24&#xa0;h of receiving combination chemotherapy with doxorubicin and ifosfamide (cumulative ifosfamide dose ~ 16.6&#xa0;g), he developed abrupt neurological deterioration progressing to coma, necessitating mechanical ventilation. Non-contrast computed tomography of the brain was unremarkable. Cerebrospinal fluid analysis showed mild lymphocytic pleocytosis (WBC 8 cells/µL), while extensive infectious, autoimmune, and paraneoplastic evaluations were negative. Immune checkpoint inhibitor–related encephalopathy from prior pembrolizumab exposure was considered unlikely given the clinical timeline. Continuous electroencephalography revealed diffuse generalized delta–theta slowing with frontal predominance. In the context of rapid post-infusion decline, a diagnosis of severe IIE was made. After confirming the absence of glucose-6-phosphate dehydrogenase deficiency and concomitant serotonergic medications, intravenous methylene blue (50&#xa0;mg every 8&#xa0;h) was initiated. Despite no improvement over the first 72&#xa0;h, therapy was extended to 5 days, after which gradual neurological recovery was observed, accompanied by EEG background normalization and successful extubation. However, a causal relationship between prolonged methylene blue therapy and clinical improvement remains uncertain.</p> Conclusions <p>This case highlights a rare, life-threatening presentation of IIE requiring mechanical ventilation. It suggests that extended-duration methylene blue therapy, guided by clinical trajectory and serial EEG monitoring, may be associated with neurological recovery in refractory cases. However, causality cannot be established. Greater recognition of severe IIE and further investigation into optimal treatment duration and predictors of response are needed.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Severe Ifosfamide-Associated Encephalopathy Requiring Mechanical Ventilation with Gradual Neurological Recovery During Methylene Blue Therapy: A Case Report

  • 期刊论文

  • 发表日期：

    2026年5月25日

查看全文
  • Yash Ranga,
  • Mohammad Alshaer,
  • Venkata Peddi

摘要

Background

Ifosfamide-induced encephalopathy (IIE) is a recognized complication of ifosfamide therapy, most often presenting as mild, reversible neurocognitive dysfunction. Severe cases requiring mechanical ventilation are rare and diagnostically challenging, particularly in oncology patients with multiple competing causes of altered mental status. Evidence guiding the optimal dosing, duration, and safety monitoring of methylene blue in refractory IIE remains limited.

Case Description

A 44-year-old man with metastatic retroperitoneal spindle cell sarcoma and normal baseline renal and hepatic function was admitted for chemotherapy. His clinical course was initially confounded by a recent complicated urinary tract infection treated with ciprofloxacin, followed by mild prodromal delirium. Within 24 h of receiving combination chemotherapy with doxorubicin and ifosfamide (cumulative ifosfamide dose ~ 16.6 g), he developed abrupt neurological deterioration progressing to coma, necessitating mechanical ventilation. Non-contrast computed tomography of the brain was unremarkable. Cerebrospinal fluid analysis showed mild lymphocytic pleocytosis (WBC 8 cells/µL), while extensive infectious, autoimmune, and paraneoplastic evaluations were negative. Immune checkpoint inhibitor–related encephalopathy from prior pembrolizumab exposure was considered unlikely given the clinical timeline. Continuous electroencephalography revealed diffuse generalized delta–theta slowing with frontal predominance. In the context of rapid post-infusion decline, a diagnosis of severe IIE was made. After confirming the absence of glucose-6-phosphate dehydrogenase deficiency and concomitant serotonergic medications, intravenous methylene blue (50 mg every 8 h) was initiated. Despite no improvement over the first 72 h, therapy was extended to 5 days, after which gradual neurological recovery was observed, accompanied by EEG background normalization and successful extubation. However, a causal relationship between prolonged methylene blue therapy and clinical improvement remains uncertain.

Conclusions

This case highlights a rare, life-threatening presentation of IIE requiring mechanical ventilation. It suggests that extended-duration methylene blue therapy, guided by clinical trajectory and serial EEG monitoring, may be associated with neurological recovery in refractory cases. However, causality cannot be established. Greater recognition of severe IIE and further investigation into optimal treatment duration and predictors of response are needed.