Encephalopathy with parkinsonian features in children following bone marrow transplantations and high‐dose amphotericin B

Abstract

Encephalopathy, leukoencephalopathy, and secondary parkinsonism occurred in 3 children with refractory leukemia undergoing allogenic bone marrow transplantation (BMT) who were treated with high-dose amphotericin B for pulmonary aspergillosis or sinus aspergillosis that did not involve the nervous system. Treatment included high-dose cytosine arabinoside, cyclophosphamide, and total body irradiation prior to the BMT. The children developed a progressively worsening encephalopathy and parkinsonian features, characterized by resting tremor, cogwheel rigidity, and masklike facies. Neuroimaging studies showed cerebellar, cerebral, and basal ganglia atrophy, as well as frontal and temporal lobe white matter involvement. Two of the 3 patients recovered, although 1 has residual intellectual impairment. The third succumbed to non-central nervous system Epstein-Barr virus-lymphoproliferative disease and had autopsy-confirmed leukoenephalopathy.

A prospective study of acute movement disorders in children

“…Drug-induced movement disorders are classically induced by dopaminergic or dopamine antagonists, serotonin reuptake inhibitors, stimulants, antiepileptic drugs, chemotherapeutics, antifungals, or drug withdrawal. [9][10][11][12][13] Drug-induced movement disorders are reviewed in detail elsewhere. 9,13 Acute-onset movement disorders can occur as a life-threatening illness or a movement disorder emergency, such as status dystonicus or neuroleptic malignant syndrome.…”

Movement disorder emergencies

“…MRI of the brain revealed leukoencephalopathy, and four of five patients treated with high-dose methylprednisolone experienced a complete recovery [80]. Three patients were reported who developed a similar syndrome after undergoing treatment with high-dose cytosine arabinoside, cyclophosphamide, total body irradiation and amphotericin B [93]. Other patients have been reported to develop parkinsonism shortly after receiving chemotherapy.…”

Drug Repositioning for Parkinson�s Disease Based on Adverse Drug Reactions Detected from Social Media (Preprint)

“…Several reports of neurotoxicity have been caused by the increasing use of intrathecal amphotericin B, for instance, transient signs of parkinsonism occurred in one patient receiving the drug for cryptococcal meningitis [37], and in three children receiving it for pulmonary aspergillosis or sinus aspergillosis [38]. Although the indications of amphotericin b do not involve the nervous system, it was thought to have a direct toxic effect on the nervous tissue.…”