Guilherme Lepski, Valeria Modestto, Walker Jeveaux, Daniel Navarro da Rocha, Roberto Dalto Fanganiello, Jose Ricardo Muniz Ferreira, Analia Arevalo
Four months after intrathecal administration, subtle but consistent behavioral changes were observed, including more synchronized affective responses, greater environmental engagement, and the first reproducible binary interaction via eye blinking. Retrospective review of available video documentation showed an increase in the Coma Recovery Scale-Revised (CRS-R) score from 8 before treatment to 11 after treatment, with one-point improvements in auditory function, visual function, and arousal. Modified Ashworth Scale spasticity scores improved by 1 in some muscle groups. No adverse events were registered. Longitudinal quantitative EEG demonstrated persistent global slowing compatible with severe diffuse injury, with qualitative emergence of faster activity, high alpha (10-12 Hz) and low beta (12-18 Hz) in bilateral fronto-temporal areas. LORETA current-density maps showed a more anterior distribution of estimated generators toward fronto-limbic regions.
INTRODUCTION: Severe hypoxic-ischemic brain injury may evolve into prolonged disorders of consciousness, for which disease-modifying interventions remain a challenge. Mesenchymal stromal/stem cells (MSCs) are being investigated in neurological disorders predominantly through immunomodulatory and trophic paracrine mechanisms rather than neuronal replacement.
METHODS: We describe a young adult medicine student with chronic post-anoxic encephalopathy managed under national regulatory oversight for compassionate use of an advanced cellular therapy. Autologous bone marrow-derived MSCs were harvested and expanded under GMP-oriented controls with extensive biosecurity and release testing. Quantitative EEG and source localization with low-resolution electromagnetic tomography (LORETA) were performed before transplantation and 4 months thereafter.
RESULTS: Four months after intrathecal administration, subtle but consistent behavioral changes were observed, including more synchronized affective responses, greater environmental engagement, and the first reproducible binary interaction via eye blinking. Retrospective review of available video documentation showed an increase in the Coma Recovery Scale-Revised (CRS-R) score from 8 before treatment to 11 after treatment, with one-point improvements in auditory function, visual function, and arousal. Modified Ashworth Scale spasticity scores improved by 1 in some muscle groups. No adverse events were registered. Longitudinal quantitative EEG demonstrated persistent global slowing compatible with severe diffuse injury, with qualitative emergence of faster activity, high alpha (10-12 Hz) and low beta (12-18 Hz) in bilateral fronto-temporal areas. LORETA current-density maps showed a more anterior distribution of estimated generators toward fronto-limbic regions.
DISCUSSION: This case illustrates the feasibility and short-term safety of regulated autologous MSC delivered intrathecally in chronic post-anoxic encephalopathy, while emphasizing that therapeutic efficacy cannot be inferred from a single uncontrolled observation.