Deep brain stimulation in disorders of consciousness: 10 years of a single center experience.

Disorders of consciousness (DoC), namely unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), represent severe conditions with significant consequences for patients and their families. Several studies have reported the regaining of consciousness in such patients using deep brain stimulation (DBS) of subcortical structures or brainstem nuclei. Our study aims to present the 10 years' experience of a single center using DBS as a therapy on a cohort of patients with DoC. Eighty Three consecutive patients were evaluated between 2011 and 2022; entry criteria consisted of neurophysiological and neurological evaluations and neuroimaging examinations. Out of 83, 36 patients were considered candidates for DBS implantation, and 32 patients were implanted: 27 patients had UWS, and five had MCS. The stimulation target was the centromedian-parafascicular complex in the left hemisphere in hypoxic brain lesion or the one better preserved in patients with traumatic brain injury. The level of consciousness was improved in seven patients. Three out of five MCS patients emerged to full awareness, with the ability to interact and communicate. Two of them can live largely independently. Four out of 27 UWS patients showed consciousness improvement with two patients emerging to full awareness, and the other two reaching MCS. In patients with DoC lasting longer than 12 months following traumatic brain injury or 6 months following anoxic-ischemic brain lesion, spontaneous recovery is rare. Thus, DBS of certain thalamic nuclei could be recommended as a treatment option for patients who meet neurological, neurophysiological and neuroimaging criteria, especially in earlier phases, before occurrence of irreversible musculoskeletal changes. Furthermore, we emphasize the importance of cooperation between centers worldwide in studies on the potentials of DBS in treating patients with DoC.

Regional Homogeneity Alterations in Patients with Impaired Consciousness. An Observational Resting-State fMRI Study.

PURPOSE: It is always challenging to correctly differentiate between minimally conscious state (MCS) and vegetative state/unresponsive wakefulness syndrome (VS/UWS) among disorders of consciousness (DOC) patients. However, the underlying neural mechanisms of awareness identification remain incompletely understood. METHODS: Using regional homogeneity (ReHo) analysis, we evaluated how regional connectivity of brain regions is disrupted in MCS and VS/UWS patients. Resting-state functional magnetic resonance imaging was conducted in 14 MCS patients, 25 VS/UWS patients, and 30 age-matched healthy individuals. RESULTS: We found that MCS and VS/UWS patients demonstrated DOC-dependent reduced ReHo within widespread brain regions including posterior cingulate cortices (PCC), medial prefrontal cortices (mPFC), and bilateral fronto-parieto-temporal cortices and showed increased ReHo in limbic structures. Moreover, a positive correlation between Coma Recovery Scale-Revised (CRS-R) total scores and reduced ReHo in the left precuneus was observed in VS/UWS patients, despite the linear trend was not found in MCS patients. In addition, ReHo were also observed reduced in three mainly intrinsic connectivity networks (ICNs), including default mode network (DMN), executive control network (ECN), and salience network (SN). Notably, as the clinical symptoms of consciousness disorders worsen from MCS to VS/UWS, ReHo in dorsal DMN, left ECN, and posterior SN became significantly reduced. CONCLUSION: These findings make a further understanding of the underlying neural mechanism of regional connectivity among DOC patients and provide additional neuroimaging-based biomarkers for the clinical diagnosis of MCS and VS/UWS patients.

Dopaminergic brainstem disconnection is common to pharmacological and pathological consciousness perturbation.

Clinical research into consciousness has long focused on cortical macroscopic networks and their disruption in pathological or pharmacological consciousness perturbation. Despite demonstrating diagnostic utility in disorders of consciousness (DoC) and monitoring anesthetic depth, these cortico-centric approaches have been unable to characterize which neurochemical systems may underpin consciousness alterations. Instead, preclinical experiments have long implicated the dopaminergic ventral tegmental area (VTA) in the brainstem. Despite dopaminergic agonist efficacy in DoC patients equally pointing to dopamine, the VTA has not been studied in human perturbed consciousness. To bridge this translational gap between preclinical subcortical and clinical cortico-centric perspectives, we assessed functional connectivity changes of a histologically characterized VTA using functional MRI recordings of pharmacologically (propofol sedation) and pathologically perturbed consciousness (DoC patients). Both cohorts demonstrated VTA disconnection from the precuneus and posterior cingulate (PCu/PCC), a main default mode network node widely implicated in consciousness. Strikingly, the stronger VTA-PCu/PCC connectivity was, the more the PCu/PCC functional connectome resembled its awake configuration, suggesting a possible neuromodulatory relationship. VTA-PCu/PCC connectivity increased toward healthy control levels only in DoC patients who behaviorally improved at follow-up assessment. To test whether VTA-PCu/PCC connectivity can be affected by a dopaminergic agonist, we demonstrated in a separate set of traumatic brain injury patients without DoC that methylphenidate significantly increased this connectivity. Together, our results characterize an in vivo dopaminergic connectivity deficit common to reversible and chronic consciousness perturbation. This noninvasive assessment of the dopaminergic system bridges preclinical and clinical work, associating dopaminergic VTA function with macroscopic network alterations, thereby elucidating a critical aspect of brainstem-cortical interplay for consciousness.

Structural changes in brains of patients with disorders of consciousness treated with deep brain stimulation.

Disorders of consciousness (DOC) are one of the major consequences after anoxic or traumatic brain injury. So far, several studies have described the regaining of consciousness in DOC patients using deep brain stimulation (DBS). However, these studies often lack detailed data on the structural and functional cerebral changes after such treatment. The aim of this study was to conduct a volumetric analysis of specific cortical and subcortical structures to determine the impact of DBS after functional recovery of DOC patients. Five DOC patients underwent unilateral DBS electrode implantation into the centromedian parafascicular complex of the thalamic intralaminar nuclei. Consciousness recovery was confirmed using the Rappaport Disability Rating and the Coma/Near Coma scale. Brain MRI volumetric measurements were done prior to the procedure, then approximately a year after, and finally 7 years after the implementation of the electrode. The volumetric analysis included changes in regional cortical volumes and thickness, as well as in subcortical structures. Limbic cortices (parahippocampal and cingulate gyrus) and paralimbic cortices (insula) regions showed a significant volume increase and presented a trend of regional cortical thickness increase 1 and 7 years after DBS. The volumes of related subcortical structures, namely the caudate, the hippocampus as well as the amygdala, were significantly increased 1 and 7 years after DBS, while the putamen and nucleus accumbens presented with volume increase. Volume increase after DBS could be a result of direct DBS effects, or a result of functional recovery. Our findings are in accordance with the results of very few human studies connecting DBS and brain volume increase. Which mechanisms are behind the observed brain changes and whether structural changes are caused by consciousness recovery or DBS in patients with DOC is still a matter of debate.

Objective and graded calibration of recovery of consciousness in experimental models.

PURPOSE OF REVIEW: Experimental preclinical models of recovery of consciousness (ROC) and anesthesia emergence are crucial for understanding the neuronal circuits restoring arousal during coma emergence. Such models can also potentially help to better understand how events during coma emergence facilitate or hinder recovery from brain injury. Here we provide an overview of current methods used to assess ROC/level of arousal in animal models. This exposes the need for objective approaches to calibrate arousal levels. We outline how correlation of measured behaviors and their reestablishment at multiple stages with cellular, local and broader neuronal networks, gives a fuller understanding of ROC. RECENT FINDINGS: Animals emerging from diverse coma-like states share a dynamic process of cortical and behavioral recovery that reveals distinct states consistently sequenced from low-to-high arousal level and trackable in nonhuman primates and rodents. Neuronal activity modulation of layer V-pyramidal neurons and neuronal aggregates within the brainstem and thalamic nuclei play critical roles at specific stages to promote restoration of a conscious state. SUMMARY: A comprehensive, graded calibration of cortical, physiological, and behavioral changes in animal models is undoubtedly needed to establish an integrative framework. This approach reveals the contribution of local and systemic neuronal circuits to the underlying mechanisms for recovering consciousness.

Chronic disorders of consciousness: a case report with longitudinal evaluation of disease progression using 7 T magnetic resonance imaging.

BACKGROUND: Outcome prediction for patients with disorders of consciousness (DOC) is essential yet challenging. Evidence showed that patients with DOC lasting 1 year or longer after a brain injury were less likely to recover. However, the reasons why outcomes of DOC patients differ greatly remain unclear. With a variety of analytical methods and through quantitative behavioral assessments, we aimed to track the progression of a patient with severe brain injury, in order to advance our understanding of the underlying mechanisms of DOC. CASE PRESENTATION: We performed a longitudinal study for a 52-year-old male DOC patient who has remained in the state for 1.5 years with comprehensive rehabilitative therapies. The patient underwent 3 times of assessments of Coma Recovery Scale-Revised (CRS-R) and ultra-high-field 7 T magnetic resonance imaging (MRI). Both topologic properties and brain microstructure were analyzed to track disease progression. We observed dynamic increases of fiber densities with measurements at three time points (t1:1.5 M, t2:7.5 M t3:17.5 M). Specifically, fiber densities of the superior longitudinal fasciculus and arcuate fasciculus nerve fiber bundles improved mostly in the visual, verbal, and auditory subscales, which was consistent with the CRS-R scores. Moreover, the graph-theory analyses demonstrated that network topologic properties showed an improvement although the disease duration exceeded 1 year. CONCLUSIONS: DOC patients with a course longer than 1 year remain possible to improve, and including evaluation methods such as WM connectome analysis and graph theory could be potentially valuable for a more precise assessment of patients with a longer course of DOC.

Prognostic models for prolonged disorders of consciousness: an integrative review.

Disorders of consciousness (DoC) are acquired conditions of severe altered consciousness. During the past decades, some prognostic models for DoC have been explored on the basis of a variety of predictors, including demographics, neurological examinations, clinical diagnosis, neurophysiology and brain images. In this article, a systematic review of pertinent literature was conducted. We identified and evaluated 21 prognostic models involving a total of 1201 DoC patients. In terms of the reported accuracies of predicting the prognosis of DoC, these 21 models vary widely, ranging from 60 to 90%. Using improvement of consciousness level as favorable outcome criteria, we performed a quantitative meta-analysis, and found that the pooled sensitivity and specificity of the hybrid model that combined more than one technique were both superior to those of any single technique, including EEG and fMRI at the tasks and resting state. These results support the view that any single technique has its own advantages and limitations; and the integrations of multiple techniques, including diverse brain images and different paradigms, have the potential to improve predictive accuracy for DoC. Then, we provide methodological points of view and some prospects about future research. Totally, in comparison to a great many diagnostic methods for the DoC, the research of prognostic models is sparse and preliminary, still largely in its infancy with many challenges and opportunities.

The Relation Between Loss of Consciousness, Severity of Traumatic Brain Injury, and Injury of Ascending Reticular Activating System in Patients With Traumatic Brain Injury.

OBJECTIVE: Loss of consciousness is an indicator of the severity of traumatic brain injury and the ascending reticular activating system has been considered as a main structure for consciousness. However, no study on the relation between loss of consciousness and ascending reticular activating system injury in traumatic brain injury has been reported. We investigated the relation between loss of consciousness, severity of traumatic brain injury, and ascending reticular activating system injury using diffusion tensor tractography. DESIGN: One hundred twenty patients were recruited. Three components of ascending reticular activating system, fractional anisotropy, and tract volume were measured. RESULTS: In lower dorsal and ventral ascending reticular activating system, fractional anisotropy and tract volume value in mild group were higher than those of moderate and severe groups, and there was no difference between moderate and severe groups. In upper ascending reticular activating system, fractional anisotropy value in mild group was higher than in moderate group, and it was higher than in moderate group than in severe group. Tract volume value in mild group was higher than in severe group. Loss of consciousness showed moderate negative correlations with tract volume value of lower dorsal ascending reticular activating system (r = -0.348), fractional anisotropy value of lower ventral ascending reticular activating system (r = -0.343), and fractional anisotropy value of upper ascending reticular activating system (r = -0.416). CONCLUSIONS: Injury severity was different among the three traumatic brain injury groups in upper ascending reticular activating system but did not differ between moderate and severe groups in lower dorsal and ventral ascending reticular activating system.

Interhemispherical Anatomical Disconnection in Disorders of Consciousness Patients.

In patients with disorder of consciousness (DOC), the corpus callosum (CC) and subcortical white matter (SWM) integrity were shown to discriminate between diagnostic categories. The aims of the study were: (1) to clarify the link between the integrity of CC and of SWM and the clinical status in DOC patients, disentangling the role played by the different brain injuries (traumatic or hemorrhagic brain injury); (2) to investigate the relationship between the CC integrity and the brain metabolism. We assessed the diagnostic accuracy of the CC and SWM integrity, using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (sMRI), in a sample of DOC individuals, well balanced for diagnosis and etiology. The CC DTI-derived measures were correlated with the brain metabolism, computed with fluorodeoxyglucose positron emission tomography. Our results showed that the CC macrostructural DTI-derived measures discriminate between diagnosis and correlate with the clinical status of DOC patients irrespective of the etiology. Moreover, the CC DTI-derived measures strongly correlate with the metabolism of the right hemisphere. No significant diagnostic accuracy emerged for the CC sMRI evaluation and the SWM measures. Our results indicate that: (1) the degree of the interhemispherical anatomical disconnection is a marker of the level of consciousness independent from the type of brain injury; (2) CC alterations might be the consequence of the reduced brain metabolism. Remarkably, our results suggest that the functional interplay between the two hemispheres is linked tightly to the level of consciousness.

Electrographic Seizures in Patients with Acute Encephalitis.

INTRODUCTION: Clinical seizures and status epilepticus are frequent complications of encephalitis, can lead to depressed level of consciousness, and are associated with poor outcome. We sought to determine the frequency, risk factors, and clinical impact of electrographic seizures detected with continuing electroencephalography (cEEG) in patients with encephalitis and altered level of consciousness. METHODS: We retrospectively identified all patients with presumed or definite viral or autoimmune encephalitis who underwent cEEG monitoring at Henry Ford Hospital from January 2012 to October 2017. Clinical data and cEEG monitoring reports were abstracted and recorded. The primary outcome was electrographic seizures detected by cEEG. RESULTS: Of 1,735 patients who underwent a minimum of 12 h of cEEG monitoring, we identified 54 with a verified discharge diagnosis of encephalitis. Twenty-two of these patients (41%) had electrographic seizures on cEEG. Compared with encephalitis patients without seizures, electrographic seizures were associated with lower serum sodium levels (137 ± 5 vs 141 ± 7, P = 0.027) and more often were on antiepileptic therapy (100% vs 78%, P = 0.033) on the first day of monitoring. Seizures were also associated with a higher frequency of cortical imaging abnormalities (68% vs 28%, P = 0.005), lateralized periodic discharges (LPDs; 50% vs 16%, P = 0.014), delta background frequency (81% vs 45%, P = 0.010), low or suppressed voltage (96% vs 62%, P = 0.005), and focal slowing (86% vs 47%, P = 0.004). There was no association between electrographic seizures and clinical outcome at discharge. CONCLUSION: Electrographic seizures occur in approximately 40% of patients with acute encephalitis. Low serum sodium, cortical imaging abnormalities, and on cEEG LPDs and background abnormalities are associated factors. The lack of association with short-term outcome suggests that with aggressive treatment, the clinical impact of electrographic seizures in encephalitis can be minimized.

Pituitary Metastasis in a Patient with Pulmonary Adenocarcinoma Presenting with a Disturbance of Consciousness.

BACKGROUND: Brain metastases are one of the main causes of morbidity and mortality of patients with oncological disease. In non-small cell lung carcinoma (NSCLC), the risk of CNS secondary development is 30-50%. An unusual diagnostic and therapeutic problem is the finding of suspicious pituitary lesions. Obtaining a differential diagnosis relies on evaluating the clinical course of the disease (visual disturbances, diabetes insipidus (DI), weakness etc.), and performing endocrinological examinations and imaging analyses (CT, but mainly MRI). Sometimes, however, definitive resolution of the problem requires histological assessment of the tumor. CASE REPORT: A 65-year-old patient with a newly diagnosed metastatic lung adenocarcinoma was admitted to our department for a first cycle of chemotherapy consisting of cisplatin and navelbine. However, at the beginning of hospitalization, the patient developed qualitative disturbances in consciousness and disorientation. Emergency CT of the CNS revealed a tumor of the pituitary gland, and a subsequent MRI showed intraseller and suprasellar masses making contact with the optic chiasma. An endocrinological examination revealed panhypopituitarism. Pituitary metastasis of NSCLC was confirmed by tumor histology using the trans-sphenoid approach. CONCLUSION: Lung and breast carcinomas are among the most common cancers to metastasize to the pituitary gland. The incidence of pituitary metastases is reported to be 0.4-28.1%. Clinically, they are mostly silent, but may manifest as endocrine disorders, such as DI, hypothyroidism, and hypocorticism, or as visual disturbances due to compression of the optic nerve. Management depends on the establishment of a correct diagnosis. Key words: hypopituitarism - magnetic resonance imaging - pituitary neoplasm - radiosurgery - targeted therapy The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 26. 4. 2018 Accepted: 27. 6. 2018.

White Matter Deficits Underlying the Impaired Consciousness Level in Patients with Disorders of Consciousness.

In this study, we aimed to (1) identify white matter (WM) deficits underlying the consciousness level in patients with disorders of consciousness (DOCs) using diffusion tensor imaging (DTI), and (2) evaluate the relationship between DTI metrics and clinical measures of the consciousness level in DOC patients. With a cohort of 8 comatose, 8 unresponsive wakefulness syndrome/vegetative state, and 14 minimally conscious state patients and 25 patient controls, we performed group comparisons of the DTI metrics in 48 core WM regions of interest (ROIs), and examined the clinical relevance using correlation analysis. We identified multiple abnormal WM ROIs in DOC patients compared with normal controls, and the DTI metrics in these ROIs were significantly correlated with clinical measures of the consciousness level. Therefore, our findings suggested that multiple WM tracts are involved in the impaired consciousness levels in DOC patients and demonstrated the clinical relevance of DTI for DOC patients.

Minimally conscious state or cortically mediated state?

Durable impairments of consciousness are currently classified in three main neurological categories: comatose state, vegetative state (also recently coined unresponsive wakefulness syndrome) and minimally conscious state. While the introduction of minimally conscious state, in 2002, was a major progress to help clinicians recognize complex non-reflexive behaviours in the absence of functional communication, it raises several problems. The most important issue related to minimally conscious state lies in its criteria: while behavioural definition of minimally conscious state lacks any direct evidence of patient's conscious content or conscious state, it includes the adjective 'conscious'. I discuss this major problem in this review and propose a novel interpretation of minimally conscious state: its criteria do not inform us about the potential residual consciousness of patients, but they do inform us with certainty about the presence of a cortically mediated state. Based on this constructive criticism review, I suggest three proposals aiming at improving the way we describe the subjective and cognitive state of non-communicating patients. In particular, I present a tentative new classification of impairments of consciousness that combines behavioural evidence with functional brain imaging data, in order to probe directly and univocally residual conscious processes.

Assessment of mismatch negativity and P300 response in patients with disorders of consciousness.

OBJECTIVE: To evaluate changes in mismatch negativity (MMN) and P300 response in vegetative state (VS) and minimally conscious state (MCS) patients before and after treatment, and their value for prediction of prognosis. PATIENTS AND METHODS: Event-related potentials (ERPs), performed on 11 patients classified as VS (n = 6) or MCS (n = 5), and five healthy participants (i.e., control group). We performed a six months telephone follow-up to monitor changes in consciousness recovery. RESULTS: Comparison of the three groups showed significantly higher MMN latency elicited by salient stimuli and P300 elicited by the subject's own name for the VS group, as well as significant difference in amplitudes of MMN elicited by frequent stimuli and P300 elicited by other first names for this group. The source of MMN and P300 responses was the frontal lobe for the control group, and temporal lobe for the VS and MCS groups. CONCLUSIONS: The sudden increase in MMN amplitude and latency shortening may indicate an improvement in the state of consciousness. Neurophysiological evaluations suggest that patients with vegetative state (VS) and minimally conscious state (MCS) may preserve patterns of higher-order cerebral processing similar to those observed in conscious patients.

Brain-heart interactions reveal consciousness in noncommunicating patients.

OBJECTIVE: We here aimed at characterizing heart-brain interactions in patients with disorders of consciousness. We tested how this information impacts data-driven classification between unresponsive and minimally conscious patients. METHODS: A cohort of 127 patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS; n = 70) and minimally conscious state (MCS; n = 57) were presented with the local-global auditory oddball paradigm, which distinguishes 2 levels of processing: short-term deviation of local auditory regularities and global long-term rule violations. In addition to previously validated markers of consciousness extracted from electroencephalograms (EEG), we computed autonomic cardiac markers, such as heart rate (HR) and HR variability (HRV), and cardiac cycle phase shifts triggered by the processing of the auditory stimuli. RESULTS: HR and HRV were similar in patients across groups. The cardiac cycle was not sensitive to the processing of local regularities in either the VS/UWS or MCS patients. In contrast, global regularities induced a phase shift of the cardiac cycle exclusively in the MCS group. The interval between the auditory stimulation and the following R peak was significantly shortened in MCS when the auditory rule was violated. When the information for the cardiac cycle modulations and other consciousness-related EEG markers were combined, single patient classification performance was enhanced compared to classification with solely EEG markers. INTERPRETATION: Our work shows a link between residual cognitive processing and the modulation of autonomic somatic markers. These results open a new window to evaluate patients with disorders of consciousness via the embodied paradigm, according to which body-brain functions contribute to a holistic approach to conscious processing. Ann Neurol 2017;82:578-591.

The value of midbrain morphology in predicting prognosis in chronic disorders of consciousness: A preliminary ultrasound study.

Transcranial sonography (TCS) of the brainstem is currently used to support the clinical diagnosis of movement disorders. The aim of the study was to assess the usefulness of midbrain TCS in assessing outcome in patients with Chronic Disorders of Consciousness (DOC). Eleven patients with Minimally Conscious State (MCS) and Unresponsive Wakefulness Syndrome (UWS) were included in the study. We measured the area and echogenicity of the midbrain by encoding and digitally analyzing the corresponding images from the orbitomeatal plane, the morphology of brain parenchyma from the thalamic and cella media plane, and the intracranial circulation. All the patients showed an increase of pulsatility index and numerous morphological alterations on all the scan planes. In particular, we found a loss of the characteristic butterfly-shape of the midbrain, which appeared hypoechoic in the UWS but not in the MCS patients. After six months, the patients were clinically assessed by using Glasgow Outcome Scale Extended (GOSE). We found that a higher increase in GOSE scoring at follow-up was correlated with larger area and higher echogenicity of the midbrain at baseline. The present study suggests that TCS data of the midbrain may support clinical assessment of patients with chronic DOC to estimate their outcome.

Association of medial prefrontal cortex connectivity with consciousness level and its outcome in patients with acquired brain injury.

Medial prefrontal cortex (mPFC) is usually known for participating in virtually all self related processing. However, few have investigated the role of mPFC in modulating conscious awareness. This study aimed to depict the relationship between the mPFC connectivity and the severity and outcome of the disorders of consciousness (DOC) among patients with acquired brain injury. Thirty-four patients with DOC (17 in a minimally conscious state and 17 in an unresponsive wakefulness syndrome/vegetative state) and 11 healthy controls were recruited, underwent clinical assessment and resting-state functional MRI scan, and were further followed up to evaluate recovery outcome using the Glasgow Outcome Scale. The mPFC connectivity was then analyzed, by comparing DOC patients to healthy controls at baseline, and by comparing "recovered consciousness" and "non-recovered consciousness" patients at follow-up, as identified by graph theory. As a result, enhanced mPFC connectivity against weakened posteromedial cortex connectivity was observed in a minimally conscious state, not in an unresponsive wakefulness syndrome/vegetative state. Besides, increased mPFC connectivity was significantly associated with consciousness recovery. In conclusion, the mPFC connectivity could possibly serve as a mark to track the severity and outcome of DOC.

Predictors of Recovery from Traumatic Brain Injury-Induced Prolonged Consciousness Disorder.

We investigated the clinical predictors of the degree of recovery in patients with prolonged disorders of consciousness (PDC) caused by traumatic brain injury. Fourteen patients with PDC underwent two diffusion tensor imaging (DTI) studies; the first and second scans were performed at 345.6 ± 192.6 and 689.1 ± 272.2 days after the injury, respectively. In addition to the temporal changes in each of these diffusion parameters, fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity were assessed over a 1-year period. Relationship of clinical and DTI parameters with recovery from PDC (RPDC) was evaluated using Spearman's rank-correlation and stepwise multiple linear regression analysis. The mean FA and number of voxels with FA values > 0.4 (VsFA0.4) were significantly decreased at the second scan. A significant positive correlation was observed between the degree of RPDC and mean FA (r = 0.60) and VsFA0.4 (r = 0.68) as well as between the difference in VsFA0.4 (r = 0.63) and AD (r = 0.54) between the first and second scans. On multiple linear regression analysis, initial severity of PDC and the difference in AD remained significantly associated with the degree of RPDC. The microstructural white matter changes observed in this study indicate their potential relation with the degree of RPDC over the longer term.

Measures of metabolism and complexity in the brain of patients with disorders of consciousness.

BACKGROUND: Making an accurate diagnosis in patients with disorders of consciousness remains challenging. 18F-fluorodeoxyglucose (FDG)-PET has been validated as a diagnostic tool in this population, and allows identifying unresponsive patients with a capacity for consciousness. In parallel, the perturbational complexity index (PCI), a new measure based on the analysis of the electroencephalographic response to transcranial magnetic stimulation, has also been suggested as a tool to distinguish between unconscious and conscious states. The aim of the study was to cross-validate FDG-PET and PCI, and to identify signs of consciousness in otherwise unresponsive patients. METHODS: We jointly applied the Coma Recovery Scale-Revised, FDG-PET and PCI to assess 24 patients with non-acute disorders of consciousness or locked-in syndrome (13 male; 19-54 years old; 12 traumatic; 9 unresponsive wakefulness syndrome, 11 minimally conscious state; 2 emergence from the minimally conscious state, and 2 locked-in syndrome). RESULTS: FDG-PET and PCI provided congruent results in 22 patients, regardless of their behavioural diagnosis. Notably, FDG-PET and PCI revealed preserved metabolic rates and high complexity levels in four patients who were behaviourally unresponsive. CONCLUSION: We propose that jointly measuring the metabolic activity and the electrophysiological complexity of cortical circuits is a useful complement to the diagnosis and stratification of patients with disorders of consciousness.