Search Results (24)

Background: Different evidence on the ability of [¹⁸F] fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) imaging to assess patients in the vegetative state (VS) or unresponsive wakefulness syndrome (UWS) has been reported. Therefore, this systematic review aimed to synthesize the existing literature on this topic. Methods: A wide literature search of the PubMed/MEDLINE, Scopus, and Embase databases was conducted to find relevant published articles investigating the role of [¹⁸F]FDG PET imaging in the assessment of VS/UWS. Results: Thirty-seven studies were included in the review, and the main fields of application of this imaging modality in these patients were the evaluation of hypometabolic patterns, differentiation of disorders of consciousness (DOC), prognostic value, and ability to assess the response to particular stimuli. Conclusions: The possible role of [¹⁸F]FDG PET imaging in the assessment of VS/UWS has emerged, in particular in the differential diagnosis of other DOC or prognosis. Some insights into its value in stimulation response and therapy evaluation have also been proposed. Standardization of protocols and larger prospective studies are needed to strengthen these clinical recommendations. Full article

Objectives: Prolonged disorders of consciousness (DoC) present complex diagnostic and therapeutic challenges. This study aimed to evaluate the accuracy of two ChatGPT models (ChatGPT 4o and ChatGPT o1) in answering questions about prolonged DoC, framed as if they were posed by a patient’s relative. Secondary objectives included comparing performance across languages (English vs. Italian) and assessing whether responses conveyed an empathetic tone. Methods: Fifty-seven open-ended questions reflecting common caregiver concerns were generated in both English and Italian, each categorized into one of three domains: clinical data, instrumental diagnostics, or therapy. Each question contained a background context followed by a specific query and was submitted once to both models. Two reviewers evaluated the responses on a four-point scale, ranging from “incorrect and potentially misleading” to “correct and complete”. Discrepancies were resolved by a third reviewer. Accuracy, language differences, empathy, and recommendation to consult a healthcare professional were analyzed using absolute frequencies, percentages, the Mann–Whitney U test, and Chi-squared tests. Results: A total of 228 responses were analyzed. Both models provided predominantly correct answers (80.7–96.8%), with English responses achieving higher accuracy only for ChatGPT 4o on clinical data. ChatGPT 4o exhibited greater empathy in its responses, whereas ChatGPT o1 more frequently recommended consulting a healthcare professional in Italian. Conclusions: Both ChatGPT models demonstrated high accuracy in addressing prolonged DoC queries, highlighting their potential usefulness for caregiver support. However, occasional inaccuracies emphasize the importance of verifying chatbot-generated information with professional medical advice. Full article

Background/Objectives: Cranioplasty (CP) is the main surgical procedure aiming to repair a morphological defect in the skull. It has been shown that early CP is useful for patients with traumatic brain injury (TBI) to achieve functional recovery, whereas few studies have investigated the clinical effects of ultra-late CP on TBI outcomes. Methods: Here, we describe the clinical course over 2 years of a TBI patient who underwent CP 19 months after fronto-parietal decompressive craniectomy (DC) of a limited size. Results: We found that after ultra-late CP, a meaningful functional recovery (cognitive and motor), with emergence from a minimally conscious state and recovery of functional communication, was revealed. Conclusions: Our preliminary findings contribute to the actual debate on the timing of CP for this neurosurgical procedure’s therapeutic success, as early CP has already been shown. Full article

Brain imaging studies have recently provided some evidence in favor of covert cognitive processes that are ongoing in patients with disorders of consciousness (DoC) (e.g., a minimally conscious state and vegetative state/unresponsive wakefulness syndrome) when engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer’s motor system maps others’ actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, considering that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. The results indicate that some form of motor resonance is spared in a subset of patients with DoC, with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether diagnosed with VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and the difference between the resonance with biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials, following the stimulation of the median nerve at the wrist (i.e., the temporal marker signaling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters. Full article

Pain assessment and management in patients with disorders of consciousness (DOC) is a challenging and important aspect of care, with implications for detecting consciousness and promoting recovery. This narrative review explores the role of pain in consciousness, the challenges of pain assessment, pharmacological treatment in DOC, and the implications of pain assessment when detecting changes in consciousness. The review discusses the Nociception Coma Scale and its revised version, which are behavioral scales used to assess pain in DOC patients, and the challenges and controversies surrounding the appropriate pharmacological treatment of pain in these patients. Moreover, we highlight recent evidence suggesting that an accurate pain assessment may predict changes in the level of consciousness in unresponsive wakefulness syndrome/vegetative state patients, underscoring the importance of ongoing pain management in these patients. Full article

Unprecedented advancements in the diagnosis and treatment of patients with disorders of consciousness (DoC) have given rise to ethical questions about how to recognize and respect autonomy and a sense of agency of the personhood when those capacities are themselves disordered, as they typically are in patients with DoC. At the intersection of these questions rests the distinction between consciousness and unconsciousness. Indeed, evaluations of consciousness levels and capacity for recovery have a significant impact on decisions regarding whether to discontinue or prolong life-sustaining therapy for DoC patients. However, in the unconsciousness domain, there is the confusing array of terms that are regularly used interchangeably, making it quite challenging to comprehend what unconsciousness is and how it might be empirically grounded. In this opinion paper, we will provide a brief overview of the state of the field of unconsciousness and show how a rapidly evolving electroencephalogram (EEG) neuroimaging technique may offer empirical, theoretical, and practical tools to approach unconsciousness and to improve our ability to distinguish consciousness from unconsciousness and also nonconsciousness with greater precision, particularly in cases that are borderline (as is typical in patients with DoC). Furthermore, we will provide a clear description of three distant notions of (un)consciousness (unconsciousness, nonconsciousness, and subconsciousness) and discuss how they relate to the experiential selfhood which is essential for comprehending the moral significance of what makes life worth living. Full article

The presence of involuntary, non-functional jaw muscle activity (NFJMA) has not yet been assessed in patients with disorders of consciousness (DOC), although the presence of bruxism and other forms of movement disorders involving facial muscles is probably more frequent than believed. In this work, we evaluated twenty-two prolonged or chronic DOC patients with a long-lasting polygraphic recording to verify NFJMA occurrence and assess its neurophysiological patterns in this group of patients. A total of 5 out of 22 patients showed the presence of significant NFJMA with electromyographic patterns similar to what can be observed in non-DOC patients with bruxism, thus suggesting a disinhibition of masticatory motor nuclei from the cortical control. On the other hand, in two DOC patients, electromyographic patterns advised for the presence of myorhythmia, thus suggesting a brainstem/diencephalic involvement. Functional, non-invasive tools such as long-lasting polygraphic recordings should be extended to a larger sample of patients, since they are increasingly important in revealing disorders potentially severe and impacting the quality of life of DOC patients. Full article

(1) Background: Cerebrospinal fluid (CSF) and blood biomarkers are emerging tools used to obtain information on secondary brain damage and to improve diagnostic and prognostic accuracy for patients with prolonged post-traumatic disorders of consciousness (DoC). We synthesized available data from studies evaluating CSF and blood biomarkers in these patients. (2) Methods: A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist to identify and synthesize data from relevant studies. Studies were identified by PubMed and manual searches. Those involving patients with unresponsive wakefulness syndrome or in a minimally conscious state for >28 days, evaluating CSF or blood biomarkers, and conducted on patients with traumatic brain injuries older than 16 years were included in the review. (3) Results: In total, 17 studies were included. Findings on neurofilament light chain, proteins, metabolites, lipids, amyloid-β, tau, melatonin, thyroid hormones, microtubule-associated protein 2, neuron-specific enolase, and brain-derived neurotrophic factor were included in the qualitative synthesis. (4) Conclusions: The most promising applications for CSF and blood biomarkers are the monitoring of secondary neurodegeneration, support of DoC diagnoses, and refinement of prognoses, although current evidence remains too scarce to recommend such uses of these biomarkers in clinical practice. Full article

Background. Many patients with severe brain damage may survive and remain in a prolonged disorder of consciousness (PDoC), impacting the quality of life (QoL) and needs of their family caregivers. However, the current literature on the factors influencing these needs is contradictory. We aim to describe the needs, QoL, and emotional distress of caregivers of patients with PDoC. Methods. Questionnaires investigating the importance and satisfaction of six categories of needs (i.e., health information, emotional, instrumental, and professional supports, community support network, and involvement in care), QoL, and emotional distress were completed by the main caregivers of PDoC patients. Results. We analyzed 177 questionnaires. Seventy-nine percent of the needs were considered as important or very important, and 44% were partially met or unmet. The needs for health information and professional support were the most important, while the needs for involvement in care and for health information were the most satisfied. Mean QoL was low and emotional distress high. Variables such as care setting and time since brain injury affected the level of QoL and distress. Conclusion. The needs for health information and professional support should receive particular attention. Given their low QoL and high distress, adequate support structures should be provided to caregivers of PDoC patients. Full article

In recent decades, significant progress has been achieved in understanding the mechanisms of disturbance and restoration of consciousness in patients after severe brain damage resulting in prolonged disorders of consciousness (pDOC). MicroRNAs (miRs) may be potential candidates as possible biomarkers for the classification of disease subtypes, and prognosis in patients with pDOC. The aim of the study was to analyze miRs expression levels (hsa-miR-21-5p, hsa-miR-93-5p, hsa-miR-191-5p, mmu-miR-499-5p, hsa-let-7b-5p) by a real-time polymerase chain reaction in plasma and cerebrospinal fluid (CSF) from patients with pDOC and to identify a potential biomarker for dividing patients into groups according to disease severity. We analyzed the levels of investigated miRs in pDOC patients, divided by etiology, CRSI, and the total group compared with controls. Our results showed that dividing patients with pDOC into groups according to the etiology of the disease resulted in the most significant differences in the levels of miR-93, -21, and -191 in CSF and plasma samples between groups of patients. Among the analyzed miRs, we did not find a marker that would help to distinguish VS/UWS patient groups from MCS. Examining of miRs as possible prognostic markers in patients with pDOC, the starting point seems to be the cause that led to the development of the disease. Full article

Objectives: In this retrospective study, we investigated how spasticity developed in patients diagnosed with a prolonged DOC over an almost two-year observation period (21 months), and how it related to the patients’ age, gender, time since injury, etiology, level of consciousness, and anti-spastic medications. Methods: In total, 19 patients with a severe brain injury and prolonged DOC admitted to a long-term care facility were included in this study (14 male, age: 45.8 ± 15.3 years, 10 traumatic brain injury, 1.01 ± 0.99 years after brain injury, 11 minimally conscious state vs. 8 vegetative state). Each patient was assessed at admission and then quarterly, totaling eight assessments over 21 months. Spasticity was measured with the Modified Ashworth Scale (MAS) for both upper and lower limbs. The Western Neuro Sensory Stimulation Profile (WNSSP) was administered to assess the level of consciousness. Any other medical and demographic information of interest was obtained through medical records. Linear mixed models were used to assess each variable’s impact on the change of spasticity over time. Results: Significant differences were observed in the evolution of spasticity in patients based on their etiology for the upper limbs [F (7, 107.29) = 2.226; p = 0.038], and on their level of consciousness for the lower limbs [F (7, 107.07) = 3.196; p = 0.004]. Conclusion: Our preliminary results suggest that spasticity evolves differently according to the type of brain lesion and the level of consciousness. Spasticity in DOCs might therefore be mediated by different mechanisms and might have to be treated differently among patients. Future longitudinal studies should be performed prospectively in a bigger cohort and with data collection beginning earlier after brain injury to confirm our results and better understand the evolution of spasticity in this population. Full article

As the clinical trial landscape for patients with disorders of consciousness (DoC) expands, consideration of associated ethical challenges and opportunities is of ever-increasing importance. Responsible conduct of research in the vulnerable population of persons with DoC, including those with coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), covert cortical processing (CCP), and cognitive motor dissociation (CMD), demands proactive deliberation of unique ethical issues that may arise and the adoption of robust protections to safeguard patients, surrogates, and other key stakeholders. Here we identify and critically evaluate four central categories of ethical considerations in clinical trials involving participants with DoC: (1) autonomy, respect for persons and informed consent of individuals with liminal consciousness; (2) balancing unknown benefits and risks, especially considering the epistemological gap between behavior and consciousness that complicates ordinary ascription of subjective states; (3) disclosure to surrogates and clinical teams of investigational results pertaining to consciousness; and (4) justice considerations, including equitable access to clinical trial enrollment across communities and geographies. We outline guiding principles and research opportunities for clinicians, neuroethicists, and researchers engaged in DoC clinical trials to advance ethical study design and deployment in this complex yet crucial area of investigation. Full article

(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/age-matched healthy controls. Serum NFL levels were evaluated at 1–3 and 6 months post-injury and compared with those of controls. NFL levels were compared by DOC severity (UWS vs. MCS) and etiology (TBI vs. HIBI). (3) Results: Patients’ serum NFL levels were significantly higher than those of controls at 1–3 and 6 months post-injury (medians, 1729 and 426 vs. 90 pg/mL; both p < 0.0001). NFL levels were higher in patients with UWS than in those in MCS at 1–3 months post-injury (p = 0.008) and in patients with HIBI than in those with TBI at 6 months post-injury (p = 0.037). (4) Conclusions: Patients with prolonged DOC present sustained axonal degeneration that is affected differently over time by brain injury severity and etiology. Full article

Background: We aimed to assess the effects of modulated neuroprotection with intermittent administration in patients with unresponsive wakefulness syndrome (UWS) after severe traumatic brain injury (TBI). Methods: Retrospective analysis of 60 patients divided into two groups, with and without neuroprotective treatment with Actovegin, Cerebrolysin, pyritinol, L-phosphothreonine, L-glutamine, hydroxocobalamin, alpha-lipoic acid, carotene, DL-α-tocopherol, ascorbic acid, thiamine, pyridoxine, cyanocobalamin, Q 10 coenzyme, and L-carnitine alongside standard treatment. Main outcome measures: Glasgow Coma Scale (GCS) after TBI, Extended Glasgow Coma Scale (GOS E), Disability Rankin Scale (DRS), Functional Independence Measurement (FIM), and Montreal Cognitive Assessment (MOCA), all assessed at 1, 3, 6, 12, and 24 months after TBI. Results: Patients receiving neuroprotective treatment recovered more rapidly from UWS than controls (p = 0.007) passing through a state of minimal consciousness and gradually progressing until the final evaluation (p = 0.000), towards a high cognitive level MOCA = 22 ± 6 points, upper moderate disability GOS-E = 6 ± 1, DRS = 6 ± 4, and an assisted gait, FIM =101 ± 25. The improvement in cognitive and physical functioning was strongly correlated with lower UWS duration (−0.8532) and higher GCS score (0.9803). Conclusion: Modulated long-term neuroprotection may be the therapeutic key for patients to overcome UWS after severe TBI. Full article

According to the Centers for Disease Control and Prevention (CDC), traumatic brain injury (TBI) is the leading cause of loss of consciousness, long-term disability, and death in children and young adults (age 1 to 44). Currently, there are no United States Food and Drug Administration (FDA) approved pharmacological treatments for post-TBI regeneration and recovery, particularly related to permanent disability and level of consciousness. In some cases, long-term disorders of consciousness (DoC) exist, including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) characterized by the exhibition of reflexive behaviors only or a minimally conscious state (MCS) with few purposeful movements and reflexive behaviors. Electroceuticals, including non-invasive brain stimulation (NIBS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS) have proved efficacious in some patients with TBI and DoC. In this review, we examine how electroceuticals have improved our understanding of the neuroanatomy of consciousness. However, the level of improvements in general arousal or basic bodily and visual pursuit that constitute clinically meaningful recovery on the Coma Recovery Scale-Revised (CRS-R) remain undefined. Nevertheless, these advancements demonstrate the importance of the vagal nerve, thalamus, reticular activating system, and cortico-striatal-thalamic-cortical loop in the process of consciousness recovery. Full article