Hemispherics

En este episodio de Hemispherics hablamos sobre el daño axonal difuso tras un traumatismo craneoencefálico, una de las formas de lesión cerebral más frecuentes y, al mismo tiempo, más difíciles de comprender desde la clínica y la neuroimagen convencional. A lo largo del episodio revisamos cómo las fuerzas de aceleración y rotación pueden producir una lesión de desconexión en las redes cerebrales, profundizando en conceptos como la axotomía secundaria, la neuroinflamación, la vía del SARM1 o la lesión axonal traumática. También abordamos qué sabemos actualmente sobre resonancia magnética, tensor de difusión y biomarcadores como GFAP, UCH-L1 o neurofilamento ligero. Más allá de la biología, el episodio intenta trasladar todo esto a la realidad clínica y terapéutica. Hablamos de las expresiones cognitivas, conductuales y motoras que pueden aparecer en estos pacientes, de las limitaciones actuales del pronóstico y de cómo entender el daño axonal difuso no como una única lesión focal, sino como una alteración dinámica de redes cerebrales. Referencias del episodio: 1. Adams, J. H., Doyle, D., Ford, I., Gennarelli, T. A., Graham, D. I., & McLellan, D. R. (1989). Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology, 15(1), 49–59. https://doi.org/10.1111/j.1365-2559.1989.tb03040.x (https://pubmed.ncbi.nlm.nih.gov/2767623/). 2. Bayley, M. T., Janzen, S., Harnett, A., Teasell, R., Patsakos, E., Marshall, S., Bragge, P., Velikonja, D., Kua, A., Douglas, J., Togher, L., Ponsford, J., & McIntyre, A. (2023). INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury: Methods, Overview, and Principles. The Journal of head trauma rehabilitation, 38(1), 7–23. https://doi.org/10.1097/HTR.0000000000000838 (https://pubmed.ncbi.nlm.nih.gov/36594856/). 3. Castaño-Leon, A. M., Sánchez Carabias, C., Hilario, A., Ramos, A., Navarro-Main, B., Paredes, I., Munarriz, P. M., Panero, I., Eiriz Fernández, C., García-Pérez, D., Moreno-Gomez, L. M., Esteban-Sinovas, O., Garcia Posadas, G., Gomez, P. A., & Lagares, A. (2022). Serum assessment of traumatic axonal injury: the correlation of GFAP, t-Tau, UCH-L1, and NfL levels with diffusion tensor imaging metrics and its prognosis utility. Journal of neurosurgery, 138(2), 454–464. https://doi.org/10.3171/2022.5.JNS22638 (https://pubmed.ncbi.nlm.nih.gov/35901687/). 4. Frati, A., Cerretani, D., Fiaschi, A. I., Frati, P., Gatto, V., La Russa, R., Pesce, A., Pinchi, E., Santurro, A., Fraschetti, F., & Fineschi, V. (2017). Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review. International journal of molecular sciences, 18(12), 2600. https://doi.org/10.3390/ijms18122600 (https://pubmed.ncbi.nlm.nih.gov/29207487/). 5. Geiger, P., Gmeiner, R., Schön, V., Petr, O., Thomé, C., & Pinggera, D. (2025). Timing of Magnetic Resonance Imaging (MRI) in Moderate and Severe TBI: A Systematic Review. Journal of clinical medicine, 14(12), 4078. https://doi.org/10.3390/jcm14124078 (https://pubmed.ncbi.nlm.nih.gov/40565823/). 6. Henninger, N., Bouley, J., Sikoglu, E. M., An, J., Moore, C. M., King, J. A., Bowser, R., Freeman, M. R., & Brown, R. H., Jr (2016). Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1. Brain : a journal of neurology, 139(Pt 4), 1094–1105. https://doi.org/10.1093/brain/aww001 (https://pubmed.ncbi.nlm.nih.gov/26912636/). 7. Johnson, V. E., Stewart, W., & Smith, D. H. (2013). Axonal pathology in traumatic brain injury. Experimental neurology, 246, 35–43. https://doi.org/10.1016/j.expneurol.2012.01.013 (https://pubmed.ncbi.nlm.nih.gov/22285252/). 8. Lagares, A., de la Cruz, J., Terrisse, H., Mejan, O., Pavlov, V., Vermorel, C., Payen, J. F., & of the BRAINI participants and investigators (2024). An automated blood test for glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) to predict the absence of intracranial lesions on head CT in adult patients with mild traumatic brain injury: BRAINI, a multicentre observational study in Europe. EBioMedicine, 110, 105477. https://doi.org/10.1016/j.ebiom.2024.105477 (https://pmc.ncbi.nlm.nih.gov/articles/PMC11647500/). 9. Mac Donald, C. L., Dikranian, K., Song, S. K., Bayly, P. V., Holtzman, D. M., & Brody, D. L. (2007). Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury. Experimental neurology, 205(1), 116–131. https://doi.org/10.1016/j.expneurol.2007.01.035 (https://pubmed.ncbi.nlm.nih.gov/17368446/). 10. Mac Donald, C. L., Yuh, E. L., Vande Vyvere, T., Edlow, B. L., Li, L. M., Mayer, A. R., Mukherjee, P., Newcombe, V. F. J., Wilde, E. A., Koerte, I. K., Yurgelun-Todd, D., Wu, Y. C., Duhaime, A. C., Awwad, H. O., Dams-O'Connor, K., Doperalski, A., Maas, A. I. R., McCrea, M. A., Umoh, N., & Manley, G. T. (2025). Neuroimaging Characterization of Acute Traumatic Brain Injury with Focus on Frontline Clinicians: Recommendations from the 2024 National Institute of Neurological Disorders and Stroke Traumatic Brain Injury Classification and Nomenclature Initiative Imaging Working Group. Journal of neurotrauma, 42(13-14), 1056–1064. https://doi.org/10.1089/neu.2025.0079 (https://pubmed.ncbi.nlm.nih.gov/40393517/). 11. Muehlschlegel, S., Rajajee, V., Wartenberg, K. E., Alexander, S. A., Busl, K. M., Creutzfeldt, C. J., Fontaine, G. V., Hocker, S. E., Hwang, D. Y., Kim, K. S., Madzar, D., Mahanes, D., Mainali, S., Meixensberger, J., Sakowitz, O. W., Varelas, P. N., Weimar, C., & Westermaier, T. (2024). Guidelines for Neuroprognostication in Critically Ill Adults with Moderate-Severe Traumatic Brain Injury. Neurocritical care, 40(2), 448–476. https://doi.org/10.1007/s12028-023-01902-2 (https://pubmed.ncbi.nlm.nih.gov/38366277/). 12. Ponsford, J. L., Downing, M. G., Olver, J., Ponsford, M., Acher, R., Carty, M., & Spitz, G. (2014). Longitudinal follow-up of patients with traumatic brain injury: outcome at two, five, and ten years post-injury. Journal of neurotrauma, 31(1), 64–77. https://doi.org/10.1089/neu.2013.2997 (https://pubmed.ncbi.nlm.nih.gov/23889321/). 13. Sassani, M., Ghafari, T., Arachchige, P. R. W., Idrees, I., Gao, Y., Waitt, A., Weaver, S. R. C., Mazaheri, A., Lyons, H. S., Grech, O., Thaller, M., Witton, C., Bagshaw, A. P., Wilson, M., Park, H., Brookes, M., Novak, J., Mollan, S. P., Hill, L. J., Lucas, S. J. E., … Fernández-Espejo, D. (2025). Current and prospective roles of magnetic resonance imaging in mild traumatic brain injury. Brain communications, 7(2), fcaf120. https://doi.org/10.1093/braincomms/fcaf120 (https://pubmed.ncbi.nlm.nih.gov/40241788/). 14. Siedler, D. G., Chuah, M. I., Kirkcaldie, M. T., Vickers, J. C., & King, A. E. (2014). Diffuse axonal injury in brain trauma: insights from alterations in neurofilaments. Frontiers in cellular neuroscience, 8, 429. https://doi.org/10.3389/fncel.2014.00429 (https://pubmed.ncbi.nlm.nih.gov/25565963/). 15. Smith, D. H., Hicks, R., & Povlishock, J. T. (2013). Therapy development for diffuse axonal injury. Journal of neurotrauma, 30(5), 307–323. https://doi.org/10.1089/neu.2012.2825 (https://pubmed.ncbi.nlm.nih.gov/23252624/). 16. Wofford, K. L., Loane, D. J., & Cullen, D. K. (2019). Acute drivers of neuroinflammation in traumatic brain injury. Neural regeneration research, 14(9), 1481–1489. https://doi.org/10.4103/1673-5374.255958 (https://pmc.ncbi.nlm.nih.gov/articles/PMC6557091/).