Predicting Long-Term Recovery of Consciousness in Prolonged Disorders of Consciousness Based on Coma Recovery Scale-Revised Subscores: Validation of a Machine Learning-Based Prognostic Index.

peer reviewedPrognosis of prolonged Disorders of Consciousness (pDoC) is influenced by patients' clinical diagnosis and Coma Recovery Scale-Revised (CRS-R) total score. We compared the prognostic accuracy of a novel Consciousness Domain Index (CDI) with that of clinical diagnosis and CRS-R total score, for recovery of full consciousness at 6-, 12-, and 24-months post-injury. The CDI was obtained by a combination of the six CRS-R subscales via an unsupervised machine learning technique. We retrospectively analyzed data on 143 patients with pDoC (75 in Minimally Conscious State; 102 males; median age = 53 years; IQR = 35; time post-injury = 1-3 months) due to different etiologies enrolled in an International Brain Injury Association Disorders of Consciousness Special Interest Group (IBIA DoC-SIG) multicenter longitudinal study. Univariate and multivariate analyses were utilized to assess the association between outcomes and the CDI, compared to clinical diagnosis and CRS-R. The CDI, the clinical diagnosis, and the CRS-R total score were significantly associated with a good outcome at 6, 12 and 24 months. The CDI showed the highest univariate prediction accuracy and sensitivity, and regression models including the CDI provided the highest values of explained variance. A combined scoring system of the CRS-R subscales by unsupervised machine learning may improve clinical ability to predict recovery of consciousness in patients with pDoC

Risk factors for 2-year mortality in patients with prolonged disorders of consciousness: An international multicentre study.

peer reviewedBACKGROUND AND PURPOSE: Patients with prolonged disorders of consciousness (pDoC) have a high mortality rate due to medical complications. Because an accurate prognosis is essential for decision-making on patients' management, we analysed data from an international multicentre prospective cohort study to evaluate 2-year mortality rate and bedside predictors of mortality. METHODS: We enrolled adult patients in prolonged vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) after traumatic and nontraumatic brain injury within 3 months postinjury. At enrolment, we collected demographic (age, sex), anamnestic (aetiology, time postinjury), clinical (Coma Recovery Scale-Revised [CRS-R], Disability Rating Scale, Nociception Coma Scale-Revised), and neurophysiologic (electroencephalogram [EEG], somatosensory evoked and event-related potentials) data. Patients were followed up to gather data on mortality up to 24 months postinjury. RESULTS: Among 143 traumatic (n = 55) and nontraumatic (n = 88) patients (VS/UWS, n = 68, 19 females; MCS, n = 75, 22 females), 41 (28.7%) died within 24 months postinjury. Mortality rate was higher in VS/UWS (42.6%) than in MCS (16%; p < 0.001). Multivariate regression in VS/UWS showed that significant predictors of mortality were older age and lower CRS-R total score, whereas in MCS female sex and absence of alpha rhythm on EEG at study entry were significant predictors. CONCLUSIONS: This study demonstrated that a feasible multimodal assessment in the postacute phase can help clinicians to identify patients with pDoC at higher risk of mortality within 24 months after brain injury. This evidence can help clinicians and patients' families to navigate the complex clinical decision-making process and promote an international standardization of prognostic procedures for patients with pDoC

Multicenter prospective study on predictors of short-term outcome in disorders of consciousness

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Eye blink rate increases as a function of cognitive load during an auditory oddball paradigm

Previous evidence suggests that changes in spontaneous eye blink rate (EBR) in human adults might reflect the amount of attentional demand (i.e. cognitive load) during cognitive tasks. However, the actual direction of this relation is uncertain, since most studies investigated the role of cognitive load on EBR by employing visual tasks only. Here we aimed at elucidating the relationship between EBR and cognitive load in non-visual tasks. Sixteen healthy participants performed two auditory oddball tasks, i.e. passive listening to auditory tones versus active counting of target tones; each oddball task was immediately followed by a rest phase. Throughout the oddball tasks we assessed EBR and recorded the P300 on ERPs as an electrophysiological measure of attention. The results showed that participants' EBR increased during the active task compared to the respective rest phase. Amplitude and latency of the P300 too differed between passive and active tasks, but changes in EBR and P300 features were not correlated with each other. Our findings demonstrated that an increase in cognitive load is associated with an increase in EBR in cognitive tasks not involving visual attention. These findings are consistent with previous evidence suggesting shared neurobiological bases between attention and EBR

Modulating interoception by insula stimulation: A double-blinded tDCS study

Interoception consists in the perception and processing of internal body signals, such as heartbeat. Previous neuroimaging studies revealed that attention to heartbeat activated bilateral insula and premotor regions. In the present double-blind study, we aimed at testing the role of insula in interoception by means of transcranial direct current stimulation (tDCS) interfering with its activity. Sixteen healthy participants responded to a questionnaire to evaluate the tendency to be internally focused and performed a heartbeat counting task before and after tDCS in three sessions (left insula stimulation, right insula stimulation, sham stimulation). Real and reported heartbeat were recorded and used to calculate the accuracy scores. A significant interaction between stimulation condition and time (pre- and post-stimulation) was found due to a significant improvement of the interoceptive accuracy in the sham condition only. Our results demonstrated that stimulation over the insula reduced the possibility to improve the precision with which individuals detect internal signals

Left inferior parietal and posterior temporal cortices mediate the effect of action observation on semantic processing of objects: evidence from rTMS

Previous studies showed that motor information related to tool use (i.e., functional actions) could affect processing of objects semantic properties, whereas motor information related to grasping or moving tool (i.e., structural actions) cannot. However, little is known about the neural correlates mediating such interaction between motor and semantic information. Here, healthy participants performed a semantic judgment task requiring identification of semantic relations among objects, after observing a functional, a structural or a pointing action prime. In a within-subject design, during prime presentation the participants underwent repetitive transcranial magnetic stimulation (rTMS) over the left supramarginal gyrus (SMG), the left posterior middle temporal gyrus (pMTG) or received sham stimulation. Results showed that in the sham condition observing functional actions (vs. structural and pointing actions) favoured processing of semantic relations based on function similarity (i.e., taxonomic relations), but not of relations based on co-occurrence within an event schema (i.e., thematic relations). Moreover, stimulation of both left SMG and pMTG abolished the effect of functional action primes worsening subsequent judgment about taxonomic relations, and this effect was greater after pMTG stimulation. rTMS did not affect processing of thematic semantic relations. We suggest that action observation triggers activation of functional motor information within left inferior parietal cortex, and that integration between functional motor and conceptual information in left temporal cortex could impact high-level semantic processing of tools

Depression and Anxiety Symptoms “Among the Waves” of the COVID-19 Pandemic in Obsessive Compulsive Disorder and Adjustment Disorder Patients

The COVID-19 pandemic and the associated restrictions caused great psychological suffering to the general population and psychiatric patients. We aimed to explore the course of depression and anxiety symptoms in obsessive compulsive disorder (OCD) patients, adjustment disorder (AD) patients, and participants without psychiatric disorders (control group, CG) across the different phases of the pandemic: the first lockdown, a temporary interruption of restrictions, and the second lockdown. Out of the 158 patients screened, we enrolled 46 OCD and 19 AD patients as well as 29 CG participants. The Beck Depression Inventory-II and the State-Trait Anxiety Inventory-Y were administered to all participants at each time point. The results showed different symptom severities among the groups throughout the whole study, with OCD patients always scoring higher than AD patients and the CG, and the AD patients always scoring higher than the CG. The symptom course within each group was different. OCD patients’ symptoms sharply worsened during the first lockdown and then remained stable irrespective of the subsequent pandemic phases. In the AD and CG groups, symptoms waxed and waned following the fluctuations of the restriction provisions, with a complete return to the baseline when the restrictions were stopped only in the CG. These findings suggest that the influence of the pandemic and of the associated restrictions on depression and anxiety manifestations may vary depending on the particular pre-existing mental health status

Predicting Long-Term Recovery of Consciousness in Prolonged Disorders of Consciousness Based on Coma Recovery Scale-Revised Subscores: Validation of a Machine Learning-Based Prognostic Index.

peer reviewedPrognosis of prolonged Disorders of Consciousness (pDoC) is influenced by patients' clinical diagnosis and Coma Recovery Scale-Revised (CRS-R) total score. We compared the prognostic accuracy of a novel Consciousness Domain Index (CDI) with that of clinical diagnosis and CRS-R total score, for recovery of full consciousness at 6-, 12-, and 24-months post-injury. The CDI was obtained by a combination of the six CRS-R subscales via an unsupervised machine learning technique. We retrospectively analyzed data on 143 patients with pDoC (75 in Minimally Conscious State; 102 males; median age = 53 years; IQR = 35; time post-injury = 1-3 months) due to different etiologies enrolled in an International Brain Injury Association Disorders of Consciousness Special Interest Group (IBIA DoC-SIG) multicenter longitudinal study. Univariate and multivariate analyses were utilized to assess the association between outcomes and the CDI, compared to clinical diagnosis and CRS-R. The CDI, the clinical diagnosis, and the CRS-R total score were significantly associated with a good outcome at 6, 12 and 24 months. The CDI showed the highest univariate prediction accuracy and sensitivity, and regression models including the CDI provided the highest values of explained variance. A combined scoring system of the CRS-R subscales by unsupervised machine learning may improve clinical ability to predict recovery of consciousness in patients with pDoC

International survey on the implementation of the European and American guidelines on disorders of consciousness

Diagnostic, prognostic, and therapeutic procedures for patients with prolonged disorders of consciousness (pDoCs) vary significantly across countries and clinical settings, likely due to organizational factors (e.g., research vs. non-academic hospitals), expertise and availability of resources (e.g., financial and human). Two international guidelines, one from the European Academy of Neurology (EAN) and one from the American Academy of Neurology (AAN) in collaboration with the American Congress of Rehabilitation Medicine (ACRM) and the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR), were developed to facilitate consistent practice among professionals working with this challenging patient population. While the recommendations of both guidelines agree in principle, it remains an open issue how to implement them into clinical practice in the care pathway for patients with pDoCs. We conducted an online survey to explore health professional clinical practices related to the management of patients with pDoCs, and compare said practices with selected recommendations from both the guidelines. The survey revealed that while some recommendations are being followed, others are not and/or may require more honing/specificity to enhance their clinical utility. Particular attention should be given to the implementation of a multimodal assessment of residual consciousness, to the detection and treatment of pain, and to the impact of restrictions imposed by COVID-19 pandemics on the involvement of patients’ families/representatives.Alfonso Magliacano and Anna Estraneo contributed equally to the paper.</p