New Radiosurgical Paradigms to Treat Epilepsy Using Synchrotron Radiation

  • Pantaleo RomanelliEmail author
  • Alberto Bravin
  • Erminia Fardone
  • Giuseppe Battaglia
Part of the Contemporary Clinical Neuroscience book series (CCNE)


Synchrotron-generated X-ray microplanar beams (microbeams) are characterized by peculiar biological properties such as a remarkable tissue-sparing effect in healthy tissues including the central nervous system and, as a direct consequence, the ability to deliver extremely high doses without induction of radionecrosis. Growing experimental evidence is showing remarkable tolerance of brain and spinal cord to irradiation with microbeam arrays delivering doses up to 400 Gy with a beam width up to 0.7 mm. Submillimetric beams can be delivered following a stereotactic design bringing to the target doses in the range of hundreds of Gray without harm to the surrounding tissues. Microbeam arrays can be used to generate cortical transections or subcortical lesions, thus enabling the non-invasive modulation of brain networks. This novel microradiosurgical approach is of great interest for the treatment of a variety of brain disorders, including epilepsy.


Epilepsy Synchrotron Therapy Neuromodulation 


  1. Blattmann H et al (2005) Applications of synchrotron X-rays to radiotherapy. Nucl Instrum Methods Phys Res 548(1–2):17–22CrossRefGoogle Scholar
  2. Brauer-Krisch E et al (2010) Potential high resolution dosimeters for MRT. In Siu KKW (ed) 6th international conference on medical applications of synchrotron radiation, American Institute of Physics, USA, pp 89–97Google Scholar
  3. Chervin RD, Pierce PA, Connors BW (1988) Periodicity and directionality in the propagation of epileptiform discharges across neocortex. J Neurophysiol 60(5):1695–1713PubMedGoogle Scholar
  4. Danilov AI et al (2006) Neurogenesis in the adult spinal cord in an experimental model of multiple sclerosis. Eur J Neurosci 23(2):394–400PubMedCrossRefGoogle Scholar
  5. Denekamp J, Daşu A, Waites A (1998) Vasculature and microenvironmental gradients: the missing links in novel approaches to cancer therapy? Adv Enzyme Regul 38:281–299PubMedCrossRefGoogle Scholar
  6. Dilmanian FA et al (2002) Response of rat intracranial 9 L gliosarcoma to microbeam radiation therapy. Neuro Oncol 4(1):26–38PubMedCentralPubMedCrossRefGoogle Scholar
  7. Fardone E (2013) A new application of microbeam radiation therapy (MRT) on the treatment of epilepsy and brain disorders. University Joseph Furier of Grenoble [Thesis]Google Scholar
  8. Go C, Snead OC (2008) Pharmacologically intractable epilepsy in children: diagnosis and preoperative evaluation. Neurosurg Focus 25(3):E2PubMedCrossRefGoogle Scholar
  9. Gould E (1999) Neurogenesis in the neocortex of adult Primates. Science 286(5439):548–552PubMedCrossRefGoogle Scholar
  10. Gould E (2007) How widespread is adult neurogenesis in mammals? Nat Rev Neurosci 8(6):481–488PubMedCrossRefGoogle Scholar
  11. Gould E et al (2001) Adult-generated hippocampal and neocortical neurons in macaques have a transient existence. Proc Natl Acad Sci U S A 98(19):10910–10917PubMedCentralPubMedCrossRefGoogle Scholar
  12. Kokaia Z et al (2006) Regulation of stroke-induced neurogenesis in adult brain–recent scientific progress. Cereb Cortex 16(Suppl 1):i162–i167 (New York, NY 1991)Google Scholar
  13. Koketsu D et al (2003) Nonrenewal of neurons in the cerebral neocortex of adult Macaque Monkeys. J Neurosci 23(3):937–942PubMedGoogle Scholar
  14. Kornack DR, Rakic P (2001) Cell proliferation without neurogenesis in adult primate neocortex. Science 294(5549):217–2130 (New York, NY)CrossRefGoogle Scholar
  15. Kuzniecky R, Devinsky O (2007) Surgery Insight: surgical management of epilepsy. Nat Clin Pract Neurol 3(12):673–681PubMedCrossRefGoogle Scholar
  16. Laissue JA et al (1998) Neuropathology of ablation of rat gliosarcomas and contiguous brain tissues using a microplanar beam of synchrotron-wiggler-generated X rays. Int J Cancer (Journal international du cancer) 78(5):654–660CrossRefGoogle Scholar
  17. Magavi SS, Leavitt BR, Macklis JD (2000) Induction of neurogenesis in the neocortex of adult mice. Nature 405(6789):951–955PubMedCrossRefGoogle Scholar
  18. Morrell F, Hanbery JW (1969) A new surgical technique for the treatment of focal cortical epilepsy. Electroencephalogr Clin Neurophysiol 26(1):120PubMedGoogle Scholar
  19. Morrell F et al (1989) Multiple subpial transection: a new approach to the surgical treatment of focal epilepsy. J Neurosurg 70:231–239Google Scholar
  20. Morrell F et al (1995) Landau-Kleffner syndrome. Treatment with subpial intracortical transection. Brain: A Journal of Neurology 118(Pt 6):1529–1546CrossRefGoogle Scholar
  21. Morrell F et al (1999) Multiple subpial transection. Adv Neurol 81:259–270PubMedGoogle Scholar
  22. Mountcastle VB (1957) Modality and topographic properties of single neurons of cat’s somatic sensory cortex. J Neurophysiol 20(4):408–434PubMedGoogle Scholar
  23. Mulligan LP, Spencer DD, Spencer SS (2001) Multiple subpial transections: the Yale experience. Epilepsia 42(2):226–229PubMedCrossRefGoogle Scholar
  24. Niranjan A et al (2012) Intracranial radiosurgery: an effective and disruptive innovation in neurosurgery. Stereotact Funct Neurosurg 90(1):1–7PubMedCrossRefGoogle Scholar
  25. Orbach D et al (2001) Late seizure recurrence after multiple subpial transections. Epilepsia 42(10):1130–1133PubMedGoogle Scholar
  26. Parent JM et al (2002) Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 52(6):802–813PubMedCrossRefGoogle Scholar
  27. Patil AA, Andrews R (2013) Long term follow-up after multiple hippocampal transection (MHT). Seizure: The Journal of the British Epilepsy Association 22(9):731–734CrossRefGoogle Scholar
  28. Patil AA et al (2004) Is epilepsy surgery on both hemispheres effective? Stereotact Funct Neurosurg 82(5–6):214–221PubMedCrossRefGoogle Scholar
  29. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, LondonGoogle Scholar
  30. Romanelli P, Anschel DJ (2006) Radiosurgery for epilepsy. Lancet Neurol 5:613–620Google Scholar
  31. Romanelli P, Bravin A (2011) Synchrotron-generated microbeam radiosurgery: a novel experimental approach to modulate brain function. Neurol Res 33(8):825–831PubMedCrossRefGoogle Scholar
  32. Romanelli P et al (2012) Non-resective surgery and radiosurgery for treatment of drug-resistant epilepsy. Epilepsy Res 99(3):193–201PubMedCrossRefGoogle Scholar
  33. Romanelli P et al (2013) Synchrotron-generated microbeam sensorimotor cortex transections induce seizure control without disruption of neurological functions. PloS One 8(1):e53549PubMedCentralPubMedCrossRefGoogle Scholar
  34. Scott BW et al (1998) Kindling-induced neurogenesis in the dentate gyrus of the rat. Neurosci Lett 248(2):73–76PubMedCrossRefGoogle Scholar
  35. Serduc R et al (2006) In vivo two-photon microscopy study of short-term effects of microbeam irradiation on normal mouse brain microvasculature. Int J Radiat Oncol Biol Phys 64(5):1519–1527PubMedCrossRefGoogle Scholar
  36. Slatkin DN et al (1995) Subacute neuropathological effects of microplanar beams of x-rays from a synchrotron wiggler. Proc Natl Acad Sci U S A 92(19):8783–8787PubMedCentralPubMedCrossRefGoogle Scholar
  37. Slatkin DN et al (2007) Prospects for microbeam radiation therapy of brain tumours in children. Dev Med Child Neurol 49(2):163Google Scholar
  38. Smilowitz HM et al (2002) Synergy of gene-mediated immunoprophylaxis and microbeam radiation therapy for advanced intracerebral rat 9 L gliosarcomas. J Neurooncol 78(2):135–143CrossRefGoogle Scholar
  39. Telfeian AE, Connors BW (1998) Layer-specific pathways for the horizontal propagation of epileptiform discharges in neocortex. Epilepsia 39(7):700–708PubMedCrossRefGoogle Scholar
  40. Thored P et al (2006) Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 24(3):739–747 (Dayton, Ohio)PubMedCrossRefGoogle Scholar
  41. Van De Looij Y et al (2006) Cerebral edema induced by Synchrotron Microbeam Radiation Therapy in the healthy mouse brain. Characterization by means of Diffusion Tensor Imaging. In Proceedings 14th Scientific Meeting International Society for Magnetic Resonance in Medicine, p 1472Google Scholar
  42. Zhang L et al (2014) Hippocampal CA field neurogenesis after pilocarpine insult: the hippocampal fissure as a neurogenic niche. J Chem Neuroanat 56:45–57PubMedCrossRefGoogle Scholar
  43. Zhong N et al (2003) Response of rat skin to high-dose unidirectional x-ray microbeams: a histological study. Radiat Res 160(2):133–142PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Pantaleo Romanelli
    • 1
    Email author
  • Alberto Bravin
    • 2
  • Erminia Fardone
    • 2
  • Giuseppe Battaglia
    • 3
  1. 1.Centro Diagnostico ItalianoMilanoItaly
  2. 2.European Synchrotron Radiation FacilityGrenobleFrance
  3. 3.Istituto di Ricovero e Cura a Carattere Scientifico NeuromedPozzilli (IS)Italy

Personalised recommendations