Improved treatment of severe brain injuries has resulted in increased survival rates. While some of these patients regain consciousness after a transient state of coma, others may develop a disorder of consciousness (DoC). Diagnosis of DoC currently relies on standardized behavioral assessment. The importance of accuracy in such diagnosis cannot be overstated, as it guides critical decisions on treatment (including pain management), and could underlie end-of-life decisions. Despite this importance, current behavioral diagnosis often fails, if because of the major sensory and motor deficits associated with DoC, or because of the heterogeneous etiology and pathophysiology associated with the condition. Finally, the need for accurate diagnosis and prognosis transcends the needs of the patients alone: caregiving of these patients is very stressful, principally for the large uncertainty associated with them. Thus, more accurate diagnosis and prognosis provide major relief for caregivers, and paradoxically, even if the news is not "good". For all these reasons it is critical to developing personalized diagnosis and prognosis prediction tools that permit a stratified analysis at the single-patient level. The PerBrain Project will benefit from the multidisciplinary partners' expertise, and the unique opportunity to perform longitudinal assessments in four clinical sites through both established and novel electrophysiological, neuroimaging, and physiological techniques. Based on the collected data, the investigators will develop a multimodal personalized diagnostic tool for DoC patients using state-of-the-art computational tools, such as machine learning, in order to better determine the current state (diagnosis) and future outcome (prognosis). The overall aim of this project will provide for a better understanding of the pathophysiological mechanisms in DoC, which will, in turn, allow personalized rehabilitation strategies, and improved single-patient predictions of state and prognosis.

• Recruitment is taking place in:

  • France, Paris, Pitie-Salpetriere Hospital;
  • Italy, Milan, Dipartimento di Cura e Riabilitazione delle Gravi Cerebrolesioni Acquisite (GCA);
  • Israel, Raanana, Loewenstein Hospital;
  • Germany, Munich: intensive care units of the University Clinic LMU Munich and Therapiezentrum Burgau

• Inclusion criteria:

  • Disorder of consciousness (UWS and MCS) patients and their caregiver/legal guardian
  • Patient age: 18-85 years
  • Informed consent signed by legal guardian

• Exclusion criteria:

  • Pregnancy
  • Pre-existing coma/VS/MCS
  • Continuous medical sedation (induced coma)
  • Use of barbiturates for sedation
  • Terminal malignant disease, as it increases the likelihood of not being alive for the 12-month follow-up
  • Prediction of a highly unlikely survival until the time of the 12-month follow-up due to conditions such as multi-organ failure based on the judgement of a critical care physician
  • Withdrawal of life-support
  • Palliative care setting
  • Epileptic seizures (TMS contraindication)
  • MRI contraindications (magnetic material in or on person such as pacemakers, cochlear implants, shell splinters, metal plates, certain prosthetic joints/limbs, copper-based intrauterine device, magnetic clips or stents, some large tattoos)

intensive care units and rehabilitation centres