Abstract
Aim: Anoxic brain injury (ABI) due to non-fatal drowning may cause persistent vegetative state (VS) that is currently incurable. The aim of this paper is to present the safety and feasibility of autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in five drowning children surviving in persistent VS.Methods: We used BMMNC as a novel candidate therapeutic tool in a pilot phase-I study for five patients affected by neurological sequelae after near-death drowning. Autologous BMMNCs were freshly isolated using Ficoll gradient centrifugation then infused intrathecally to five patients. The number of transplantation varied from two to four times depending on the motor function improvement of patient after transplantation. Clinical therapeutic effects were evaluated using gross motor function measure and muscle spasticity rating scales, cognitive assessments, and brain MRI before and after cell administrations.Results: Six months after BMMNC transplantation, no serious complications or adverse events were reported. All five patients displayed improvement across the major parameters of gross motor function, cognition, and muscle spasticity. Three patients displayed improved communication including the expression of words. In particular, one patient remarkably reduced cerebral atrophy, with nearly normal cerebral parenchyma after BMMNC transplantation.Conclusions: Autologous BMMNC transplantation for the treatment of children in persistent VS after drowning is safe, feasible, and can potentially improve motor function and cognition and reduce muscle spasticity. These results pave the way for a future phase II clinical trial to evaluate the efficacy of the therapy.
Highlights
Drowning is a major cause of mortality and neurological morbidity worldwide, accounting for 370,000 annual deaths in 2012 [1]
From a pathological point of view, non-fatal drowning anoxic brain injury (ABI) involves a complex accumulation of brain injuries due to ischemia, hypoxia, cytotoxicity, and combinations thereof [6]
The aim of this report is to present the safety and effectiveness of autologous Bone marrow-derived mononuclear cell (BMMNC) transplantation in five drowning children surviving in persistent vegetative states (VS)
Summary
Drowning is a major cause of mortality and neurological morbidity worldwide, accounting for 370,000 annual deaths in 2012 [1]. Children aged 0–14 years are especially susceptible with over 450 children dying and thousands more suffering debilitating injuries every day due to drowning globally [2] For those children who survived drowning, anoxic brain injury (ABI)-induced neurological morbidity is a common outcome due to oxygen deprivation [3, 4]. From a pathological point of view, non-fatal drowning ABI involves a complex accumulation of brain injuries due to ischemia, hypoxia, cytotoxicity, and combinations thereof [6] These insults deprive the brain of oxygen and of glucose and other nutrients required for neural metabolism. In severe non-fatal drowning incidents, the deprivation of these neural supporting supplements could trigger severe motor nerve deficits that largely underlie serious physical, cognitive, and behavioral complications [7] In these patients, quadriplegia resembling severe cerebral palsy is the most common consequence. Such morbidities cause a severe lifelong impact on the patients’ health and well-being and on their family [1], whereas no effective treatment is currently available
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