The impact of early surgical treatment of tracheal stenosis on neurorehabilitation outcome in patients with severe acquired brain injury.

INTRODUCTION: Acquired tracheal stenosis (TS) is a potentially life-threatening condition following prolonged intubation and/or tracheostomy in adult patients with severe Acquired Brain Injury (sABI), requiring a tracheal resection and reconstruction. METHODS: We included 38 sABI adult patients with TS, admitted at a post-acute Neurorehabilitation Hospital. Disability Rating Scale (DRS) and other functional assessment measures were recorded at admission (t1), before TS surgical treatment (t2), and at discharge (t3). Patients were defined as 'improved' when they changed from a more severe to a less severe disability, between time t2 and time t3, and as "not improved" when they did not show any further improvement between t2 and t3, or they already exhibited a disability improvement since time interval t1-t2. RESULTS: Time interval between the injury onset and TS surgical treatment (t2-t0) was associated with the patient's disability improvement, suggesting the t2-t0 time interval ≤ 115 days as a cutoff value for a possible functional recovery. A t2-t0 time interval ≤ 170 days is also associated to absence of persistent dysphagia. CONCLUSIONS: Early TS surgical treatment within 115 days from the injury onset contributes to the improvement of the disability level in patients with sABI, optimizing their functional outcomes and recovery potential.

Consensus statement from the international consensus meeting on post-traumatic cranioplasty.

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

Multi-center study on overall clinical complexity of patients with prolonged disorders of consciousness of different etiologies.

Aim: to assess overall clinical complexity of patients with acquired disorders of consciousness (DoC) in vegetative state/unresponsive wakefulness syndrome (VS/UWS) vs. minimally conscious state- MCS) and in different etiologies..Design: Multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 264 patients with DoC in the post-acute phase: VS/UWS = 141, and MCS = 123 due to vascular (n = 125), traumatic (n = 83) or anoxic (n = 56) brain injury.Main Measures: Coma Recovery Scale-Revised, and Disability Rating Scale (DRS); presence of medical devices (e.g., for eating or breathing); occurrence and severity of medical complications.Results: patients in DoC, and particularly those in VS/UWS, showed severe overall clinical complexity. Anoxic patients had higher overall clinical complexity, lower level of responsiveness/consciousness, higher functional disability, and higher needs of medical devices. Vascular patients had worse premorbid clinical comorbidities. The two etiologies showed a comparable rate of MC, higher than that observed in traumatic etiology.Conclusion: overall clinical complexity is significantly higher in VS/UWS than in MCS, and in non-traumatic vs. traumatic etiology. These findings could explain the worse clinical evolution reported in anoxic and vascular etiologies and in VS/UWS patients and contribute to plan patient-tailored care and rehabilitation programmes.

Multi-center observational study on occurrence and related clinical factors of neurogenic heterotopic ossification in patients with disorders of consciousness.

Aims: to assess occurrence and clinical correlates of neurogenic heterotopic ossifications (NHO) in patients with prolonged disorder of consciousness (DoC).Design: multi-center cross-sectional observational study.Setting: 23 intensive neurorehabilitation units.Subjects: 287 patients with prolonged disorder of consciousness (DoC; 150 in vegetative state, VS, and 128 in minimally conscious state, MCS) of different etiology (vascular = 125, traumatic = 83, anoxic = 56, others = 14).Main Measures: clinical evidence of NHO confirmed by standard radiological and/or sonographic evaluation; Coma Recovery Scale-Revised; Disability Rating Scale (DRS); Early Rehabilitation Barthel Index; presence of ventilator support, spasticity, bone fractures and paroxysmal sympathetic hyperactivity.Results: 31 patients (11.2%) presented NHO. Univariate analyses showed that NHO was associated with VS diagnosis, traumatic etiology, high DRS category and total score, and high occurrence of limb spasticity and bone fractures. A cluster-corrected binary logistic regression model (excluding spasticity available in a subset of patients) showed that only lower DRS total score and presence of bone fractures were independently associated with NHO.Conclusions: NHO are relatively frequent in patients with DoC, and are independently associated with functional disability, bone fractures and spasticity. These findings contribute to identifying patients with DoC prone to develop NHO and requiring special interventions to improve functional recovery.

European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness.

BACKGROUND AND PURPOSE: Patients with acquired brain injury and acute or prolonged disorders of consciousness (DoC) are challenging. Evidence to support diagnostic decisions on coma and other DoC is limited but accumulating. This guideline provides the state-of-the-art evidence regarding the diagnosis of DoC, summarizing data from bedside examination techniques, functional neuroimaging and electroencephalography (EEG). METHODS: Sixteen members of the European Academy of Neurology (EAN) Scientific Panel on Coma and Chronic Disorders of Consciousness, representing 10 European countries, reviewed the scientific evidence for the evaluation of coma and other DoC using standard bibliographic measures. Recommendations followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The guideline was endorsed by the EAN. RESULTS: Besides a comprehensive neurological examination, the following suggestions are made: probe for voluntary eye movements using a mirror; repeat clinical assessments in the subacute and chronic setting, using the Coma Recovery Scale - Revised; use the Full Outline of Unresponsiveness score instead of the Glasgow Coma Scale in the acute setting; obtain clinical standard EEG; search for sleep patterns on EEG, particularly rapid eye movement sleep and slow-wave sleep; and, whenever feasible, consider positron emission tomography, resting state functional magnetic resonance imaging (fMRI), active fMRI or EEG paradigms and quantitative analysis of high-density EEG to complement behavioral assessment in patients without command following at the bedside. CONCLUSIONS: Standardized clinical evaluation, EEG-based techniques and functional neuroimaging should be integrated for multimodal evaluation of patients with DoC. The state of consciousness should be classified according to the highest level revealed by any of these three approaches.

The effects of aquatic therapy during post-acute neurorehabilitation in patients with severe traumatic brain injury: a preliminary randomized controlled trial.

OBJECTIVE: The primary aim is to verify the effectiveness of an aquatic training (AT) in inpatients with severe Traumatic Brain Injury (sTBI) on balance. The secondary aims are to explore the effects on gait, activities of daily living, and quality of life, comparing to a land-based conventional protocol. METHODS: Two-arm, randomized controlled trial. Twenty inpatients with sTBI, Glasgow Coma Scale score ≤8, and Level of Cognitive Functioning ≥7 were recruited and randomly assigned to the aquatic therapy group (ATG) or to the Conventional Training Group (CTG). Patients underwent 12 individual rehabilitation sessions (3 days/week, 4 weeks), in a rehabilitation pool during the post-acute intensive neurorehabilitation. The primary outcome measure was the Berg Balance Scale (BBS). Secondary outcome measures were the Modified Barthel Index (MBI), Disability Rating Scale (DRS), Tinetti Gait Balance Scale (TBG) and Quality of Life After Brain Injury (QOLIBRI). All the evaluations were performed at the baseline and after 4 weeks of training. RESULTS: The within-subjects analysis showed a significant improvement both in ATG and CTG in MBI, BBS, TBG, and QOLIBRI. CONCLUSION: Our results may support the use of AT during post-acute phase to improve motor functions and quality of life in patients with sTBI.

Psychological status and role of caregivers in the neuro-rehabilitation of patients with severe Acquired Brain Injury (ABI).

OBJECTIVE: To investigate the relationships between (a) the psychological status of the caregiver, (b) the specific features of caregiving as perceived by the cognitive therapist in neuro-rehabilitation, (c) the caregivers' subjective approach to neuro-rehabilitation, and (d) the functional outcome of the patient. METHODS: Twenty-four patients with severe acquired brain injury and their 24 caregivers participated in this observational study. Caregivers underwent a psychological assessment examining emotional distress, burden and family strain; their subjective approach to neuro-rehabilitation has been evaluated by two specific answers. The patients' cognitive therapists responded to an ad-hoc questionnaire, namely the "Caregiving Impact on Neuro-Rehabilitation Scale" (CINRS), evaluating the features (i.e., amount and quality) of caregiving. Finally, the functional outcome of the patient was assessed through standardized scales of disability and cognitive functioning. RESULTS: The caregivers' psychological well-being was associated to the features of caregiving, to the subjective approach to neuro-rehabilitation, and to the functional recovery of their loved ones. A better caregivers' approach to neuro-rehabilitation was also associated to an overall positive impact of caregiving in neuro-rehabilitation and to a better functional outcome of the patients. CONCLUSIONS: We posited a virtuous circle involving caregivers within the neuro-rehabilitation process, according to which the caregivers' psychological well-being could be strictly associated to a better level of caregiving and to a better functional outcome of the patients that, in turn, could positively influence the caregivers' psychological well-being. Although preliminary, these results suggest a specific psycho-educational intervention, aimed at improving the caregivers' psychological well-being and at facilitating their caring of the loved one.

Nociception Coma Scale with personalized painful stimulation versus standard stimulus in non-communicative patients with disorders of consciousness.

INTRODUCTION: Persons with disorders of consciousness (DoC) may perceive pain without being able to communicate their discomfort. Nociception Coma Scale (NCS) and its revised form (NCS-R) have been proposed to assess nociception in coma survivors with DoC. OBJECTIVE: Aim of the present study was to compare, in non-communicative patients with DoC, NCS-R scores obtained with the standard pressure on fingernail bed (standard stimulus, SS) versus other personalized painful stimuli (PS), to verify possible correlations between NCS-R and Coma Recovery Scale-Revised (CRS-R). MATERIALS AND METHODS: Twenty-one patients with DoC were included in the study. Responsiveness and pain perception were assessed by CRS-R and NCS-R with standard stimulus (NCS-R-SS) and personalized stimulation (NCS-R-PS). Statistical analysis was performed with the nonparametric Wilcoxon test for comparison of both total NCS-R-SS and NCS-R-PS scores. RESULTS: NCS-R at admission showed that 9 of 21 patients (42.8%) had higher scores in response to personalized stimulus compared to standard stimulus. Significant correlation with CRS-R were found for both NCS-R-SS (R = 0.701, p = .008) and NCS-R-PS (R = 0.564, p = .045). Discussion: The preliminary results obtained in the present study suggest that NCS-R-PS may disclose pain perception in a larger number of non-communicative patients with DoC, compared to NCS-R-SS.

Depression, apathy and impaired self-awareness following severe traumatic brain injury: a preliminary investigation.

Primary Objective: The primary aim of this study was to determine the frequency of severe impaired self-awareness (ISA) in patients with severe traumatic brain injury (TBI) and the correlates of selected clinical, neuropsychiatric and cognitive variables. The secondary aim of the study was to assess depression and apathy on the basis of their level of self-awareness. Methods: Thirty patients with severe TBI and 30 demographically matched healthy control subjects (HCs) were compared on measures of ISA, depression, anxiety, alexithymia, neuropsychiatric symptoms and cognitive flexibility. Results: Twenty percent of the patients demonstrated severe ISA. Severe post-acute ISA was associated with more severe cognitive inflexibility, despite the absence of differences in TBI severity, as evidenced by a Glasgow Coma Scale (GCS) score lower than 9 in all cases in the acute phase. Patients with severe ISA showed lower levels of depression and anxiety but tended to show more apathy and to have greater difficulty describing their emotional state than patients with severe TBI who showed minimal or no disturbance in self-awareness. Conclusion: These findings support the general hypothesis that severe ISA following severe TBI is typically not associated with depression and anxiety, but rather with apathy and cognitive inflexibility.

Sleep-disordered breathing and epicardial adipose tissue in patients with heart failure.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) is common in patients with heart failure (HF), contributes to the progression of cardiac disease, and is associated with adverse prognosis. Previous evidence indicates that epicardial adipose tissue (EAT) is independently associated with sleep apnea in obese individuals. We explored the relationship between SDB and EAT in HF patients. METHODS AND RESULTS: EAT thickness was assessed by echocardiography in 66 patients with systolic HF undergoing nocturnal cardiorespiratory monitoring. A significantly higher EAT thickness was found in patients with SDB than in those without SDB (10.7 ± 2.8 mm vs. 8.3 ± 1.8 mm; p = 0.001). Among SDB patients, higher EAT thickness was found in both those with prevalent obstructive sleep apnea (OSA) and those with prevalent central sleep apnea (CSA). Of interest, EAT thickness was significantly higher in CSA than in OSA patients (11.9 ± 2.9 vs. 10.1 ± 2.5 p = 0.022). Circulating plasma norepinephrine levels were higher in CSA than in OSA patients (2.19 ± 1.25 vs. 1.22 ± 0.92 ng/ml, p = 0.019). According to the apnea-hypopnea index (AHI), patients were then stratified in three groups of SDB severity: Group 1, mild SDB; Group 2, moderate SDB; Group 3, severe SDB. EAT thickness progressively and significantly increased from Group 1 to Group 3 (ANOVA p < 0.001). At univariate analysis, only left ventricular ejection fraction and AHI significantly correlated with EAT (p = 0.019 and p < 0.0001, respectively). At multivariate analysis, AHI was the only independent predictor of EAT (ß = 0.552, p < 0.001). CONCLUSIONS: Our results suggest an association between the presence and severity of sleep apneas and cardiac visceral adiposity in HF patients.

Production of human pro-relaxin H2 in the yeast Pichia pastoris.

BACKGROUND: Initially known as the reproductive hormone, relaxin was shown to possess other therapeutically useful properties that include extracellular matrix remodeling, anti-inflammatory, anti-ischemic and angiogenic effects. All these findings make relaxin a potential drug for diverse medical applications. Its precursor, pro-relaxin, is an 18 kDa protein, that shows activity in in vitro assays. Since extraction of relaxin from animal tissues raises several issues, prokaryotes and eukaryotes were both used as expression systems for recombinant relaxin production. Most productive results were obtained when using Escherichia coli as a host for human relaxin expression. However, in such host, relaxin precipitated in the form of inclusion bodies and, therefore, required several expensive recovery steps as cell lysis, refolding and reduction. RESULTS: To overcome the issues related to prokaryotic expression here we report the production and purification of secreted human pro-relaxin H2 by using the methylotrophic yeast Pichia pastoris as expression host. The methanol inducible promoter AOX1 was used to drive expression of the native and histidine tagged forms of pro-relaxin H2 in dual phase fed-batch experiments on the 22 L scale. Both protein forms presented the correct structure, as determined by mass spectrometry and western blotting analyses, and demonstrated to be biologically active in immune enzymatic assays. The presence of the tag allowed to simplify pro-relaxin purification obtaining higher purity. CONCLUSIONS: This work presents a strategy for microbial production of recombinant human pro-relaxin H2 in Pichia pastoris that allowed the obtainment of biologically active pro-hormone, with a final concentration in the fermentation broth ranging between 10 and 14 mg/L of product, as determined by densitometric analyses.

Modification of the Patient Competency Rating Scale to Measure Anosodiaphoria after Severe Acquired Brain Injury: Preliminary Findings.

OBJECTIVE: Impaired self-awareness (ISA) of altered functional capacities is a common sequelae of severe acquired brain injury that can severely hamper neuro-rehabilitation in this clinical population. ISA is frequently associated with anosodiaphoria and/or apathy. Although several scales are available to measure apathy, no tools have been published to specifically assess anosodiaphoria after acquired brain injury. In this paper, we reported an initial effort to develop an anosodiaphoria subscale in a commonly used measure of ISA, that is, the Patient Competency Rating scale-neurorehabilitation form (PCRS-NR). METHOD: A sample of 46 participants with severe acquired brain injury completed a functional, ISA, apathy, and anosodiaphoria assessment. One informal caregiver of each patient participated in the study. Thus, we were able to obtain external data on his/her level of functional competencies, and self-awareness, which allowed separating patients with low self-awareness (LSA) from those with high self-awareness (HSA). Finally, the patients were compared with 44 healthy age-gender-years of formal education matched control participants (HCs). RESULTS: Compared to both patients with HSA and HCs, patients with LSA demonstrated greater anosodiapvhoria and lower levels of functioning than both HSA patients and HCs. A stronger relationship emerged between ISA and anosodiaphoria rather than with apathy. CONCLUSIONS: These initial findings provide support that PCRS scale can be adapted to measure anosodiaphoria as well as ISA. The findings reveal a stronger correlation between this measure of anosodiaphoria and ISA compared with the correlation of apathy to ISA. The present method for measuring anosodiaphoria takes into account the actual levels of patients' functioning.

Functional transcranial Doppler assessment of cerebral blood flow velocities changes during attention tasks.

BACKGROUND AND PURPOSE: Aim of our study was to evaluate cerebral hemodynamic changes during performance of attention tasks and to correlate them with reaction time (RT) and percentage of right answers. METHODS: Mean flow velocity (MFV) in middle cerebral arteries was monitored in 30 subjects by transcranial Doppler during tonic alertness, phasic alertness, focused and divided attention tasks. RESULTS: Mean flow velocity increase was significantly higher during divided attention with respect to other tasks (P < .001). MFV increase was higher in the right than in the left side (P < .001). Asymmetry during attention tasks resulted significantly higher than that observed in tonic alertness condition. RT was increased during focused attention tasks (P < .001 vs. both alert tasks), with further increase during divided attention tasks (P < .001 vs. focused attention task). RT was inversely related to MFV increase only during tonic alertness (P = 0.012 for left side; P = 0.008 for right side). During the divided attention tasks, an association was found between MFV increase and correct answers (r = 0.39, P = 0.033). CONCLUSIONS: These data show a relationship between RT, correct answers and changes in blood flow velocity and suggest that this method of cerebral blood flow investigation could be a useful approach during assessment of patients with attention deficit.

Theory of Mind after Severe Acquired Brain Injury: Clues for Interpretation.

Background. Recently, increased interest has been shown in Theory of Mind (ToM) abilities of individuals with severe acquired brain injury (sABI). ToM impairment following sABI can be associated with altered executive functioning and/or with difficulty in decoding and elaborating emotions. Two main theoretical models have been proposed to explain the mechanisms underlying ToM in the general population: Theory Theory and Simulation Theory. This review presents and discusses the literature on ToM abilities in individuals with sABI by examining whether they sustain the applicability of the Theory Theory and/or Simulation Theory to account for ToM deficits in this clinical population. We found 32 papers that are directly aimed at investigating ToM in sABI. Results did not show the univocal predominance of one model with respect to the other in explaining ToM deficits in sABI. We hypothesised that ToM processes could be explained by coinvolvement of the two models, i.e., according to personal experience, cognitive features, or the emotional resources of the persons with sABI.

Changes in Caregivers Lifestyle after Severe Acquired Brain Injury: A Preliminary Investigation.

INTRODUCTION: Severe acquired brain injury (sABI) is considered the most common cause of death and disability worldwide. sABI patients are supported by their caregivers who often exhibit high rates of psychological distress, mood disorders, and changes in relationship dynamics and family roles. OBJECTIVES: To explore lifestyle changes of caregivers of sABI patients during the postacute rehabilitation, by investigating possible differences between primary and secondary caregivers. Primary caregivers spend most of the time with the patient, providing daily care and taking most responsibility for the day-to-day decisions, while secondary caregivers are those who provide additional support. METHODS: Three hundred forty-seven caregivers of sABI patients were asked to fill in an unpublished self-report questionnaire to explore their possible lifestyles changes. RESULTS: A statistically significant difference was found between primary and secondary caregivers in time spent in informal caregiving (p<0.001). The primary caregivers reduced all leisure activities compared to secondary carers (p<0.05). CONCLUSIONS: By comparing the percentage of leisure activities performed by caregivers before and after the patient's sABI onset, all caregivers showed high percentages of changes in lifestyle and habits, even though primary caregivers reported more negative lifestyle changes than secondary caregivers. Further studies are needed to investigate needs and burden experienced by caregivers of sABI patients during the postacute rehabilitation phase, also in relation to the patients' outcome, to address support interventions for them and improve their quality of life.

Low back pain after unstable extracapsular hip fractures: randomized control trial on a specific training.

AIM: This study compares the efficacy of a walking recovery rehabilitation program with or without specific back exercises in patients affected by unstable extracapsular hip fractures and secondary back pain. Further, it reports data and images about analysed tomographic changes of the psoas muscle ipsilateral to fractures. METHODS: A prospective, randomized, parallel treatment trial was carried out. Patients admitted for rehabilitation after fractures were evaluated for secondary back pain. If clinically indicated, patients were further scheduled for a computed tomography (CT) scan of the lumbar spine by which we evaluated cross-sectional changes in density and fibroadipose degeneration of the body of the psoas muscle. When back pain matched cross-sectional changes in psoas density, the patient was eligible for our study, enrolled and randomly assigned to 1 of 2 study groups. Both groups were scheduled for hip rehabilitation and walking training plus a back protocol for the study group only. Pain was evaluated subjectively with a visual analog scale to calculate treatment effectiveness and Harris hip score was used to assess the outcome after surgery. RESULTS: Thirty-seven patients out of about hundred were enrolled. In all cases CT scans showed age-related changes commonly seen in the lumbar spine and significant fibroadipose degeneration and altered density in the ipsilateral psoas muscles. With back exercises added to the standard rehabilitation protocol, all study patients recovered significantly better than control group patients (P<0.04) in only 4 weeks of treatment. CONCLUSION: Results show how hip fractures may cause psoas changes that can be of relevance for a more rational choice of physical exercises. Causes of back pain may be more complex than described by the textbooks and prognosis is more favourable following specific back training.

[Chronic lumbago after unstable intertrochanteric femoral fracture: a new syndrome or sporadic feature of hip biomechanics after surgery? A case report]. / Lombalgia cronica invalidante dopo frattura intertrocanterica instabile di femore: nuova sindrome o sporadica alterazione biomeccanica dell'anca dopo la chirurgia? Case report.

OBJECTIVE: Only in 2002, more than 86,000 hip fractures were registered in Italy in male and female patients over 45 years old, with 9% progression compared to 1999. In this paper, we report a clinic case of a patient experiencing working problems for a chronic back pain after an unstable extracapsular hip fracture. SUBJECT AND METHOD: The patient, a 54 years old woman, factory worker, complaining of low back pain weeks after the hip fracture, was evaluated and scheduled for a computer tomography examination of the lumbar spine. The C.T. scans were evaluated to assess eventual evidence of disc problems and/or cross sectional changes in density and fibro-adipose degeneration of muscular body of the psoas muscle. RESULT: Because back pain matched with the evidence of cross sectional changes in psoas density without any evidence of disc herniation, the patient was scheduled for aspecific back pain training. After a specific rehabilitation protocol the patient had 75% pain relief after four weeks. CONCLUSION: Age and diseases related changes are commonly seen in the lumbar spine, but the relationship between these changes and symptoms of back pain is not straightforward. Our case report suggest that back pain following extra capsular hip fracture may involve the psoas muscle. The prognosis might be favourable following a specific back training that is actually object of an ongoing controlled trial.

Interfacing brain with computer to improve communication and rehabilitation after brain damage.

Communication and control of the external environment can be provided via brain-computer interfaces (BCIs) to replace a lost function in persons with severe diseases and little or no chance of recovery of motor abilities (ie, amyotrophic lateral sclerosis, brainstem stroke). BCIs allow to intentionally modulate brain activity, to train specific brain functions, and to control prosthetic devices, and thus, this technology can also improve the outcome of rehabilitation programs in persons who have suffered from a central nervous system injury (ie, stroke leading to motor or cognitive impairment). Overall, the BCI researcher is challenged to interact with people with severe disabilities and professionals in the field of neurorehabilitation. This implies a deep understanding of the disabled condition on the one hand, and it requires extensive knowledge on the physiology and function of the human brain on the other. For these reasons, a multidisciplinary approach and the continuous involvement of BCI users in the design, development, and testing of new systems are desirable. In this chapter, we will focus on noninvasive EEG-based systems and their clinical applications, highlighting crucial issues to foster BCI translation outside laboratories to eventually become a technology usable in real-life realm.