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

BACKGROUND 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.

Transcranial direct current stimulation effects in disorders of consciousness.

OBJECTIVE: To assess the efficacy of transcranial direct current stimulation (tDCS) on improving consciousness in patients with persistent unresponsive wakefulness syndrome (UWS) (previously termed persistent vegetative state [PVS]) or in a minimally conscious state (MCS). DESIGN: Prospective, case series trial with follow-up at 12 months. SETTING: General and research hospital. PARTICIPANTS: Inpatients in a PVS/UWS or MCS (N=10; 7 men, 3 women; age range, 19-62y; etiology: traumatic brain injury, n=5; anoxia, n=4; postoperative infarct, n=1; duration of PVS/UWS or MCS range, 6mo-10y). No participant withdrew because of adverse effects. INTERVENTION: All patients received sham tDCS for 20 minutes per day, 5 days per week, for 1 week, and real tDCS for 20 minutes per day, 5 days per week, for 2 weeks. An anodal electrode was placed over the left primary sensorimotor cortex or the left dorsolateral prefrontal cortex, with cathodal stimulation over the right eyebrow. One patient in an MCS received a second round of 10 tDCS sessions 3 months after initial participation. MAIN OUTCOME MEASURE: JFK Coma Recovery Scale-Revised. RESULTS: All patients in an MCS showed clinical improvement immediately after treatment. The patient who received a second round of tDCS 3 months after initial participation showed further improvement and emergence into consciousness after stimulation, with no change between treatments. One patient who was in an MCS for <1 year before treatment (postoperative infarct) showed further improvement and emergence into consciousness at 12-month follow-up. No patient showed improvement before stimulation. No patient in a PVS/UWS showed immediate improvement after stimulation, but 1 patient who was in a PVS/UWS for 6 years before treatment showed improvement and change of status to an MCS at 12-month follow-up. CONCLUSIONS: tDCS seems promising for the rehabilitation of patients with severe disorders of consciousness. Severity and duration of pathology may be related to the degree of tDCS' beneficial effects.

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.

Prognosis 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.

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

OBJECTIVE: This international multicenter, prospective, observational study aimed at identifying predictors of short-term clinical outcome in patients with prolonged disorders of consciousness (DoC) due to acquired severe brain injury. METHODS: Patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in minimally conscious state (MCS) were enrolled within 3 months from their brain injury in 12 specialized medical institutions. Demographic, anamnestic, clinical, and neurophysiologic data were collected at study entry. Patients were then followed up for assessing the primary outcome, that is, clinical diagnosis according to standardized criteria at 6 months postinjury. RESULTS: We enrolled 147 patients (44 women; mean age 49.4 [95% confidence interval 46.1-52.6] years; VS/UWS 71, MCS 76; traumatic 55, vascular 56, anoxic 36; mean time postinjury 59.6 [55.4-63.6] days). The 6-month follow-up was complete for 143 patients (VS/UWS 70; MCS 73). With respect to study entry, the clinical diagnosis improved in 72 patients (VS/UWS 27; MCS 45). Younger age, shorter time postinjury, higher Coma Recovery Scale-Revised total score, and presence of EEG reactivity to eye opening at study entry predicted better outcome, whereas etiology, clinical diagnosis, Disability Rating Scale score, EEG background activity, acoustic reactivity, and P300 on event-related potentials were not associated with outcome. CONCLUSIONS: Multimodal assessment could identify patients with higher likelihood of clinical improvement in order to help clinicians, families, and funding sources with various aspects of decision-making. This multicenter, international study aims to stimulate further research that drives international consensus regarding standardization of prognostic procedures for patients with DoC.

Neurocognitive and behavioral functioning in frontal lobe epilepsy: a review.

Frontal lobe epilepsy (FLE) is a seizure disorder with a lower prevalence than temporal lobe epilepsy (TLE). Despite its consequences on cognitive and emotional well-being, the neuropsychology of FLE has not been well studied. By contrast, TLE has been studied meticulously, leading to a relevant understanding of memory and the functional characteristics of the temporal and limbic circuits. The neuropsychological studies on FLE report deficits in motor coordination and planning, reduced attention span, and difficulties in response inhibition in complex cognitive tasks. This review aims to illustrate the most relevant neurocognitive dimensions, psychiatric comorbidity, and postoperative neuropsychological outcome of FLE. Methodological suggestions for future research are also included by critically reviewing the existing literature.

Remission of drug-resistant epileptic psychosis following left selective amygdalohippocampectomy.

We describe two female patients with drug-resistant mesial temporal lobe epilepsy and chronic drug-resistant psychosis. In both patients, MRI scans revealed left mesial temporal sclerosis. After clinical assessment, ictal video/EEG monitoring, and a neuropsychological evaluation including Wada testing, the patients underwent selective left amygdalohippocampectomy. Since the operation, the two patients have remained free of seizures for 17 and 15 months. During the same period, both patients have sustained a full remission of the psychosis.

Peak alpha frequency: an electroencephalographic measure of cognitive preparedness.

OBJECTIVE: Electroencephalographic (EEG) peak alpha frequency (PAF) (measured in Hz) has been correlated to cognitive performance between healthy and clinical individuals, and among healthy individuals. PAF also varies within individuals across developmental stages, among different cognitive tasks, and among physiological states induced by administration of various substances. The present study suggests that, among other things, PAF reflects a trait or state of cognitive preparedness. METHODS: Experiment 1 involved 19-channel EEG recordings from 10 individuals with traumatic brain injury (TBI) and 12 healthy matched controls, before, during, and after tasks of visual and auditory attention. Experiment 2 involved EEG recordings from 19 healthy young adults before and after a working memory task (WAIS-R Digit Span), repeated on 2 different days to measure within-individual differences. RESULTS: Experiment 1 showed significantly lower PAF in individuals with TBI, mostly during post-task rest. Experiment 2 showed PAF during pre-task baseline to be significantly correlated with Digit Span performance of the same day but not with Digit Span performance of another day. Moreover, PAF was significantly increased after Digit Span for those participants whose PAF was lower than the sample median before the task, but not for those who had it higher. Finally, both PAF and Digit Span performance were increased during the second day. CONCLUSIONS: PAF was shown to detect both trait and state differences in cognitive preparedness, as well as to be affected by cognitive tasks. Traits are better reflected during post-task rest, whereas states are better reflected during initial resting baseline recordings.

Electroencephalographic peak alpha frequency correlates of cognitive traits.

EEG peak alpha frequency (PAF) has been shown to differentiate groups of adults with higher memory performance from those of lower performance, groups of children with advanced reading ability from matched controls, and to predict state-dependent working memory. The present study attempted to explore PAF as a predicting variable for verbal and attentional cognitive trait abilities in young adults. Nineteen undergraduate students had their EEG recorded during initial rest, reading, and post-reading rest, and at a different day were evaluated on reading, vocabulary, and attentional performance. Results showed significant correlations of reading vocabulary and response control with PAF during reading and post-reading recordings, but not during initial rest. PAF may reflect some general cognitive ability that is not necessarily memory or reading, possibly response control or the ability to acquire vocabulary. It is suggested that cognitive ability traits may reflect the ability to induce cognitive states.

EEG neurofeedback: a brief overview and an example of peak alpha frequency training for cognitive enhancement in the elderly.

Neurofeedback (NF) is an electroencephalographic (EEG) biofeedback technique for training individuals to alter their brain activity via operant conditioning. Research has shown that NF helps reduce symptoms of several neurological and psychiatric disorders, with ongoing research currently investigating applications to other disorders and to the enhancement of non-disordered cognition. The present article briefly reviews the fundamentals and current status of NF therapy and research and illustrates the basic approach with an interim report on a pilot study aimed at developing a new NF protocol for improving cognitive function in the elderly. EEG peak alpha frequency (PAF) has been shown to correlate positively with cognitive performance and to correlate negatively with age after childhood. The present pilot study used a double-blind controlled design to investigate whether training older individuals to increase PAF would result in improved cognitive performance. The results suggested that PAF NF improved cognitive processing speed and executive function, but that it had no clear effect on memory. In sum, the results suggest that the PAF NF protocol is a promising technique for improving selected cognitive functions.