A novel case of prolonged Ifosfamide encephalopathy and long-term treatment with methylene blue: a case report and review of literature.

BACKGROUND: Encephalopathy following Ifosfamide treatment is a well-described phenomenon that is typically treated with Methylene Blue (MB). Chloroacetaldehyde, a potentially neurotoxic metabolite of Ifosfamide is hypothesized to cause this encephalopathy. Current guidelines for treatment is to stop Ifosfamide and provide supportive care. MB acts to inhibit Chloroacetaldehyde formation and has been described as a therapy and prophylaxis for Ifosfamide-encephalopathy. MB is effective within 30 min and lasts up to 3 days. Prolonged encephalopathy and MB therapy has not been described in the literature as lasting longer than 30 days following treatment. CASE PRESENTATION: We present the case of an 11-year-old female with autistic spectrum disorder and recurrent episodes of severe somnolence for 7 months following Ifosfamide therapy for her Non-Germinomatous Germ Cell Tumor (GCT). Periods of somnolence occurred prior to receiving cranial RT. Administration of MB gave immediate but limited response, with resolution of somnolence lasting 1-2 days between administrations. The somnolence could not be explained by neuroimaging or laboratory evaluation, but EEG indicated persistent encephalopathy. CONCLUSION: A literature review determines that neurotoxicity is a side effect of Ifosfamide, but this effect has not been described persisting longer than 30 days. Our case continued to require treatment with MB for 7 months following cessation of therapy. We report these novel clinical findings, and hypothesize that there could be a genetic/metabolic component linking this reaction to Ifosfamide with the case patient's pre-existing autism. This possible association may also correlate to the already-established link between autism and the development of GCTs. This hypothesis leads to further discussion on the suitable usage of Ifosfamide in children with co-morbidities and the necessity of screening prior to its usage.

Paroxysmal Nocturnal Hemoglobinuria: Diagnostic Challenges in Pediatric Patient.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening hematologic stem cell disorder characterized by hemoglobinuria, thrombosis, and tendency for bone marrow failure. The rare incidence of PNH in children, its nonspecific clinical presentation, and occasional absence of hemoglobinuria make the diagnosis challenging. We present a case of a 17-year-old boy who was hospitalized with a history of recurrent abdominal pain, fever, and dark-colored urine. Laboratory tests revealed anemia, thrombocytopenia, and elevated inflammatory markers. Urinalysis was positive for protein and red blood cells, too many to be counted. Complement studies were within normal limits. Abdominal computed tomography showed a segment of the small bowel with wall thickening and signs of possible microperforation. Exploratory laparotomy revealed necrosis of the small bowel, and histological evaluation was suggestive of an autoimmune process with small vessel vasculitis. Bone marrow biopsy showed hypocellular marrow with a decreased number of myeloid cells, normal number of megakaryocytes, and signs of erythroid hyperplasia. Flow cytometry detected deficiency of CD59 leading to the diagnosis of PNH. The patient was treated with eculizumab infusions resulting in significant improvement. This case highlights the need for high clinical suspicion for rare entities such as PNH in patients presenting without hemoglobinuria.