Outcomes of Bone Marrow-Derived Mononuclear Cell Transplantation for Patients in Persistent Vegetative State After Drowning: Report of Five Cases

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.

Keywords: autologous; bone marrow mononuclear cells; cell therapy; drowning; persistent vegetative state.

Figure 1

The patient (case 1) before and after autologous bone marrow-derived mononuclear cell (BMMNC) transplantation. (A) The patient before BMMNC transplantation is in a VS 3 months after the drowning. He had no awareness, no motor function, and exhibited muscle spasticity at level V. (B) Brain MRI demonstrated diffuse cerebral atrophy (arrows) at supratentorial and infratentorial regions, abnormal signal intensity at bilateral cortical parietal lobe, and bilateral putamen. (C) Six months after the third transplantation, the patient could express his need by vocalization, smile during communication, and stand. (D) No abnormal signal at bilateral cortical parietal lobe and bilateral putamen was observed at 12 months after the third transplantation.

Figure 2

The patient (case 2) before and after autologous BMMNC transplantation. (A) Thirteen months after the drowning before BMMNC transplantation, the patient is in a VS without awareness, no motor function, and exhibited muscle spasticity at level V. (B) Diffuse cerebral atrophy at supratentorial region and abnormal signal at bilateral putamen on brain MRI before transplantation (arrows). (C) Six months after the fourth transplantation, the patient could respond to sound and music, smile or cry during communication, and turn and lift his head up when lying prone. (D) However, there was no significant change in brain MRI after transplantations in comparison with that before transplantation.

Figure 3

The patient (case 3) before and after autologous BMMNC transplantation. (A) The patient before BMMNC transplantation is in a VS 4 months after the drowning. He had no awareness and suffered from quadriplegia with muscle spasticity at level V. (B) Diffuse cerebral atrophy at the supratentorial and infratentorial regions on brain MRI before transplantation (arrows). (C) Six months after the third transplantation, the patient could respond to calling, recognized objects, sit up, and expressed feelings. (D) Brain MRI showed a remarkably reduced cerebral atrophy with near-normal cerebral parenchyma (arrows) after stem cell transplantation.

Figure 4

The patient (case 4) before and after autologous BMMNC transplantation. (A) Nine months after the drowning before BMMNC transplantation, the patient had no reaction during communication and could not follow objects and speak and exhibited muscle spasticity at level V. He could not sit up or crawl and had epilepsy. (B) Brain MRI revealed diffuse cerebral atrophy before transplantation (arrows). (C) Six months after the third transplantation, the patient's cognition improved progressively and could stand with support. (D) However, brain MRI showed no significant change after transplantations.

Figure 5

The patient (case 5) before and after autologous BMMNC transplantation; (A) 2.5 months after the drowning before BMMNC transplantation, the patient is in a VS. without awareness, no motor function, having tetraplegia, and exhibited muscle spasticity at level V. (B) Diffuse brain atrophy and abnormal signal at bilateral putamen on brain MRI before transplantation (arrows). (C) Six months after the second transplantation, the patient could display limited vocal capacity and turn and sit up with support. (D) There was no significant change in brain MRI after transplantations compared with before transplantation.