Diagnostic value of PET imaging in clinically unresponsive patients.

Rapid advancements in the critical care management of acute brain injuries have facilitated the survival of numerous patients who may have otherwise succumbed to their injuries. The probability of conscious recovery hinges on the extent of structural brain damage and the level of metabolic and functional cerebral impairment, which remain challenging to assess via laboratory, clinical, or functional tests. Current research settings and guidelines highlight the potential value of fluorodeoxyglucose-PET (FDG-PET) for diagnostic and prognostic purposes, emphasizing its capacity to consistently illustrate a metabolic reduction in cerebral glucose uptake across various disorders of consciousness. Crucially, FDG-PET might be a pivotal tool for differentiating between patients in the minimally conscious state and those in the unresponsive wakefulness syndrome, a persistent clinical challenge. In patients with disorders of consciousness, PET offers utility in evaluating the degree and spread of functional disruption, as well as identifying irreversible neural damage. Further, studies that capture responses to external stimuli can shed light on residual or revived brain functioning. Nevertheless, the validity of these findings in predicting clinical outcomes calls for additional long-term studies with larger patient cohorts suffering from consciousness impairment. Misdiagnosis of conscious illnesses during bedside clinical assessments remains a significant concern. Based on the clinical research settings, current clinical guidelines recommend PET for diagnostic and/or prognostic purposes. This review article discusses the clinical categories of conscious disorders and the diagnostic and prognostic value of PET imaging in clinically unresponsive patients, considering the known limitations of PET imaging in such contexts.

Cerebral electrometabolic coupling in disordered and normal states of consciousness.

We assess cerebral integrity with cortical and subcortical FDG-PET and cortical electroencephalography (EEG) within the mesocircuit model framework in patients with disorders of consciousness (DoCs). The mesocircuit hypothesis proposes that subcortical activation facilitates cortical function. We find that the metabolic balance of subcortical mesocircuit areas is informative for diagnosis and is associated with four EEG-based power spectral density patterns, cortical metabolism, and α power in healthy controls and patients with a DoC. Last, regional electrometabolic coupling at the cortical level can be identified in the θ and α ranges, showing positive and negative relations with glucose uptake, respectively. This relation is inverted in patients with a DoC, potentially related to altered orchestration of neural activity, and may underlie suboptimal excitability states in patients with a DoC. By understanding the neurobiological basis of the pathophysiology underlying DoCs, we foresee translational value for diagnosis and treatment of patients with a DoC.

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.

Lysergic acid diethylamide differentially modulates the reticular thalamus, mediodorsal thalamus, and infralimbic prefrontal cortex: An in vivo electrophysiology study in male mice.

BACKGROUND: The reticular thalamus gates thalamocortical information flow via finely tuned inhibition of thalamocortical cells in the mediodorsal thalamus. Brain imaging studies in humans show that the psychedelic lysergic acid diethylamide (LSD) modulates activity and connectivity within the cortico-striato-thalamo-cortical (CSTC) circuit, altering consciousness. However, the electrophysiological effects of LSD on the neurons in these brain areas remain elusive. METHODS: We employed in vivo extracellular single-unit recordings in anesthetized adult male mice to investigate the dose-response effects of cumulative LSD doses (5-160 µg/kg, intraperitoneal) upon reticular thalamus GABAergic neurons, thalamocortical relay neurons of the mediodorsal thalamus, and pyramidal neurons of the infralimbic prefrontal cortex. RESULTS: LSD decreased spontaneous firing and burst-firing activity in 50% of the recorded reticular thalamus neurons in a dose-response fashion starting at 10 µg/kg. Another population of neurons (50%) increased firing and burst-firing activity starting at 40 µg/kg. This modulation was accompanied by an increase in firing and burst-firing activity of thalamocortical neurons in the mediodorsal thalamus. On the contrary, LSD excited infralimbic prefrontal cortex pyramidal neurons only at the highest dose tested (160 µg/kg). The dopamine D2 receptor (D2) antagonist haloperidol administered after LSD increased burst-firing activity in the reticular thalamus neurons inhibited by LSD, decreased firing and burst-firing activity in the mediodorsal thalamus, and showed a trend towards further increasing the firing activity of neurons of the infralimbic prefrontal cortex. CONCLUSION: LSD modulates firing and burst-firing activity of reticular thalamus neurons and disinhibits mediodorsal thalamus relay neurons at least partially in a D2-mediated fashion. These effects of LSD on thalamocortical gating could explain its consciousness-altering effects in humans.

Neural correlates of different behavioral response to transcranial direct current stimulation between patients in the unresponsive wakefulness syndrome and minimally conscious state.

In this study, we used event-related potential (ERP) and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) to study the neural correlates of different behavioral response to transcranial direct current stimulation (tDCS) between patients in unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS). Thirteen patients (eight in UWS and five in MCS) underwent 20 anodal tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC). Before tDCS, all the patients and six age-matched healthy subjects underwent a cerebral FDG-PET scan and ERP test. The coma recovery scale-revised (CRS-R) results revealed that after tDCS, a significant improvement was observed only in the MCS group. The ERP results supported that MCS patients preserved more high-order cortical information processing capacities. The residual brain metabolism in the left DLPFC in MCS patients supported that a residual brain activity in the stimulated area was necessary for a behavioral response to tDCS. Our study also demonstrated that the cerebral metabolic rates of glucose (CMRgl) ratios in intrinsic network were correlated significantly with CRS-R in MCS patients. In addition, the right prefrontal region might be another potential therapeutic target for MCS patients.

Cellular stress and AMPK links metformin and diverse compounds with accelerated emergence from anesthesia and potential recovery from disorders of consciousness.

The neural correlates of consciousness and the mechanisms by which general anesthesia (GA) modulate such correlates to induce loss of consciousness (LOC) has been described as one of the biggest mysteries of modern medicine. Several cellular targets and neural circuits have been identified that play a critical role in LOC induced by GA, including the GABAA receptor and ascending arousal nuclei located in the basal forebrain, hypothalamus, and brain stem. General anesthetics (GAs) including propofol and inhalational agents induce LOC in part by potentiating chloride influx through the GABAA receptor, leading to neural inhibition and LOC. Interestingly, nearly all GAs used clinically may also induce paradoxical excitation, a phenomenon in which GAs promote neuronal excitation at low doses before inducing unconsciousness. Additionally, emergence from GA, a passive process that occurs after anesthetic removal, is associated with lower anesthetic concentrations in the brain compared to doses associated with induction of GA. AMPK, an evolutionarily conserved kinase activated by cellular stress (e.g. increases in calcium [Ca2+] and/or reactive oxygen species [ROS], etc.) increases lifespan and healthspan in several model organisms. AMPK is located throughout the mammalian brain, including in neurons of the thalamus, hypothalamus, and striatum as well as in pyramidal neurons in the hippocampus and cortex. Increases in ROS and Ca2+ play critical roles in neuronal excitation and glutamate, the primary excitatory neurotransmitter in the human brain, activates AMPK in cortical neurons. Nearly every neurotransmitter released from ascending arousal circuits that promote wakefulness, arousal, and consciousness activates AMPK, including acetylcholine, histamine, orexin-A, dopamine, and norepinephrine. Several GAs that are commonly used to induce LOC in human patients also activate AMPK (e.g. propofol, sevoflurane, isoflurane, dexmedetomidine, ketamine, midazolam). Various compounds that accelerate emergence from anesthesia, thus mitigating problematic effects associated with delayed emergence such as delirium, also activate AMPK (e.g. nicotine, caffeine, forskolin, carbachol). GAs and neurotransmitters also act as preconditioning agents and the GABAA receptor inhibitor bicuculline, which reverses propofol anesthesia, also activates AMPK in cortical neurons. We propose the novel hypothesis that cellular stress-induced AMPK activation links wakefulness, arousal, and consciousness with paradoxical excitation and accelerated emergence from anesthesia. Because AMPK activators including metformin and nicotine promote proliferation and differentiation of neural stem cells located in the subventricular zone and the dentate gyrus, AMPK activation may also enhance brain repair and promote potential recovery from disorders of consciousness (i.e. minimally conscious state, vegetative state, coma).

Alterations in Brain Metabolites in Patients with Epilepsy with Impaired Consciousness: A Case-Control Study of Interictal Multivoxel 1H-MRS Findings.

BACKGROUND AND PURPOSE: Previous studies have shown perfusion abnormalities in the thalamus and upper brain stem in patients with epilepsy with impaired consciousness. We hypothesized that these areas associated with consciousness will also show metabolic abnormalities. However, metabolic abnormalities in those areas correlated with consciousness has not been characterized with multiple-voxel 1H-MRS. In this study, we investigated the metabolic alterations in these brain regions and assessed the correlation between seizure features and metabolic alterations. MATERIALS AND METHODS: Fifty-seven patients with epilepsy and 24 control subjects underwent routine MR imaging and 3D multiple-voxel 1H-MRS. Patients were divided into 3 subgroups: focal impaired awareness seizures (n = 18), primary generalized tonic-clonic seizures (n = 19), and secondary generalized tonic-clonic seizures (n = 20). The measured metabolite alterations in NAA/Cr, NAA/(Cr + Cho), and Cho/Cr ratios in brain regions associated with the consciousness network were compared between the patient and control groups. ROIs were placed in the bilateral inferior frontal gyrus, supramarginal gyrus, cingulate gyrus, precuneus, thalamus, and upper brain stem. Correlations between clinical parameters (epilepsy duration and seizure frequency) and metabolite alterations were analyzed. RESULTS: Significantly lower NAA/Cr and NAA/(Cho + Cr) ratios (P < .05 and < .01, respectively) were observed in the bilateral thalamus and upper brain stem in all experimental groups, and significantly high Cho/Cr ratios (P < .05) were observed in the right thalamus in the focal impaired awareness seizures group. There were no significant differences in metabolite ratios among the 3 patient groups (P > .05). The secondary generalized tonic-clonic seizures group showed a negative correlation between the duration of epilepsy and the NAA/(Cr + Cho) ratio in the bilateral thalamus (P < .05). CONCLUSIONS: Metabolic alterations were observed in the brain stem and thalamus in patients with epilepsy with impaired consciousness.

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.

Influence of inter-stimulus interval of spinal cord stimulation in patients with disorders of consciousness: A preliminary functional near-infrared spectroscopy study.

Spinal cord stimulation (SCS) is a promising treatment for disorders of consciousness (DOC), but the underlying mechanism and most effective procedures remain uncertain. To optimize the protocol, previous studies evaluated the frequency-specific effects of SCS on neurophysiological activities. However, whether and how the inter-stimulus interval (ISI) parameter affects the SCS neuromodulation in DOC remains unknown. We enrolled nine DOC patients who had implanted SCS devices and conducted three different durations of ISIs. Using functional near-infrared spectroscopy (fNIRS), we monitored the blood volume fluctuations in the prefrontal and occipital cortices during the SCS. The results showed that short stimuli (30 s) induced significant cerebral blood volume changes, especially in the prefrontal cortex, an important area in the consciousness system. By comparing the mean value of the responses from the first and the last block in each session, a shorter ISI was found to improve the blood volume in the prefrontal cortex. This phenomenon was more significant for the subgroup of patients with a favorable prognosis. These preliminary results imply that the ISI may be an important factor for SCS. The research paradigm proposed here also provides insights for further quantitative evaluations of the therapeutic effects of neuromodulation.

Early risk factors for mortality in children with seizure and/or impaired consciousness accompanied by fever without known etiology.

BACKGROUND: Children who present with seizure and/or impaired consciousness accompanied by fever without known etiology (SICF) may be diagnosed with either acute encephalopathy (AE) or febrile seizure (FS). Although approximately 5% of AE cases are fatal, it is difficult to identify fatal cases among children with SICF, which are often critical by the time of diagnosis. Thus, early prediction of outcomes for children with SICF, prior to diagnosis, may help to reduce mortality associated with AE. The aim of the present study was to identify clinical and laboratory risk factors for mortality acquired within 6 h of onset among children with SICF. METHODS: We retrospectively reviewed the medical records of children who had been admitted to Kobe Children's Hospital (Kobe, Japan) with SICF between October 2002 and September 2015. We compared clinical and laboratory characteristics acquired within 6 h of onset and outcomes between survivors and non-survivors using univariate and multivariate analyses. RESULTS: The survivor and non-survivor groups included 659 and nine patients, respectively. All patients in the non-survivor group received a final diagnosis of AE. Univariate analysis revealed significant differences between the groups with regard to seizure duration and the following laboratory parameters: aspartate transaminase (AST), alanine aminotransferase, lactate dehydrogenase, sodium, and lactate. The multivariate analysis identified AST as a significant independent factor associated with mortality. CONCLUSIONS: Elevation of AST within 6 h of onset is independently correlated with mortality in children with SICF. Our result may elucidate earlier intervention for patients with high risk of mortality.

A new infectious encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX).

Acute infectious encephalopathy is often observed in children in East Asia including Japan. More than 40% of the patients remain unclassified into specific syndromes. To investigate the underlying pathomechanisms in those with unclassified encephalopathy, we evaluated brain metabolism by MR spectroscopy. Among seven patients with acute encephalopathy admitted to our hospital from June 2016 to May 2017, three were classified into acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). The other four showed consciousness disturbance lasting more than three days with no parenchymal lesion visible on MRI, which led to a diagnosis of unclassified encephalopathy. MR spectroscopy in these four patients, however, revealed an increase of glutamine with a normal N-acetyl aspartate level on days 5 to 8, which had normalized by follow-up studies on days 11 to 16. The four patients clinically recovered completely. Among 27 patients with encephalopathy, including the present seven patients, admitted to our hospital from January 2015 to March 2017, seven (26%) were classified into this type, which we propose is a new encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX). MEEX is the second most common subtype, following AESD (30%). This study suggests that excitotoxicity may be a common underlying pathomechanism of acute infectious encephalopathy, and prompt astrocytic neuroprotection from excitotoxicity may prevent progression of MEEX into AESD.

Comparison of analytical methods of brain [18F]FDG-PET after severe traumatic brain injury.

BACKGROUND: Loss of consciousness has been shown to reduce cerebral metabolic rates of glucose (CMRglc) measured by brain [18F]FDG-PET. Measurements of regional metabolic patterns by normalization to global cerebral metabolism or cerebellum may underestimate widespread reductions. NEW METHOD: The aim of this study was to compare quantification methods of whole brain glucose metabolism, including whole brain [18F]FDG uptake normalized to uptake in cerebellum, normalized to injected activity, normalized to plasma tracer concentration, and two methods for estimating CMRglc. Six patients suffering from severe traumatic brain injury (TBI) and ten healthy controls (HC) underwent a 10min static [18F]FDG-PET scan and venous blood sampling. RESULTS: Except from normalizing to cerebellum, all quantification methods found significant lower level of whole brain glucose metabolism of 25-33% in TBI patients compared to HC. In accordance these measurements correlated to level of consciousness. COMPARISON WITH EXISTING METHODS: Our study demonstrates that the analysis method of the [18F]FDG PET data has a substantial impact on the estimated whole brain cerebral glucose metabolism in patients with severe TBI. Importantly, the SUVR method which is often used in a clinical setting was not able to distinguish patients with severe TBI from HC at the whole-brain level. CONCLUSION: We recommend supplementing a static [18F]FDG scan with a single venous blood sample in future studies of patients with severe TBI or reduced level of consciousness. This can be used for simple semi-quantitative uptake values by normalizing brain activity uptake to plasma tracer concentration, or quantitative estimates of CMRglc.

Brain networks predict metabolism, diagnosis and prognosis at the bedside in disorders of consciousness.

Recent advances in functional neuroimaging have demonstrated novel potential for informing diagnosis and prognosis in the unresponsive wakeful syndrome and minimally conscious states. However, these technologies come with considerable expense and difficulty, limiting the possibility of wider clinical application in patients. Here, we show that high density electroencephalography, collected from 104 patients measured at rest, can provide valuable information about brain connectivity that correlates with behaviour and functional neuroimaging. Using graph theory, we visualize and quantify spectral connectivity estimated from electroencephalography as a dense brain network. Our findings demonstrate that key quantitative metrics of these networks correlate with the continuum of behavioural recovery in patients, ranging from those diagnosed as unresponsive, through those who have emerged from minimally conscious, to the fully conscious locked-in syndrome. In particular, a network metric indexing the presence of densely interconnected central hubs of connectivity discriminated behavioural consciousness with accuracy comparable to that achieved by expert assessment with positron emission tomography. We also show that this metric correlates strongly with brain metabolism. Further, with classification analysis, we predict the behavioural diagnosis, brain metabolism and 1-year clinical outcome of individual patients. Finally, we demonstrate that assessments of brain networks show robust connectivity in patients diagnosed as unresponsive by clinical consensus, but later rediagnosed as minimally conscious with the Coma Recovery Scale-Revised. Classification analysis of their brain network identified each of these misdiagnosed patients as minimally conscious, corroborating their behavioural diagnoses. If deployed at the bedside in the clinical context, such network measurements could complement systematic behavioural assessment and help reduce the high misdiagnosis rate reported in these patients. These metrics could also identify patients in whom further assessment is warranted using neuroimaging or conventional clinical evaluation. Finally, by providing objective characterization of states of consciousness, repeated assessments of network metrics could help track individual patients longitudinally, and also assess their neural responses to therapeutic and pharmacological interventions.

Investigation of UCH-L1 levels in ischemic stroke, intracranial hemorrhage and metabolic disorder induced impaired consciousness.

OBJECTIVE: We aimed to determine the levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in patients admitted to the emergency department with impaired consciousness due to metabolic or neurological reasons. MATERIALS - METHODS: The study included 80 patients with ischemic stroke (IS), 40 patients with intracranial hemorrhage (ICH), 80 patients with metabolic disorder induced impaired consciousness (MDIC) and 40 healthy controls. RESULTS: The levels of UCH-L1 [median (IQR)] were as follows: 5.59ng/mL (3.90-9.37) in IS, 5.44ng/ml (4.01-13.98) in ICH, 3.34ng/ml (2.29-5.88) in MDIC and 3.94ng/ml (3.31-7.95) in healthy volunteers. Significantly higher levels were detected in IS and ICH than in MDIC and healthy volunteers. In ROC curve analysis, we detected 63.75% sensitivity and 62.5% specificity (AUC=0.626, p<0.0199, 95% CI: 0.533-0.713) with a cutoff value of 4.336ng/ml for IS and 75% sensitivity and 55% specificity (AUC=0.664, p<0.0071, 95% CI: 0.549-0.766) with a cut-off value of 4.036ng/ml for ICH. However, the sensitivity and specificity for MDIC was 36.25% and 77.5%, respectively, with a cut-off value of 3.256ng/ml (AUC=0.525, p=0.6521, 95% CI: 0.432-0.617). UCH-L1 levels were found to increase significantly with increasing time between the onset of symptoms and blood sampling (r=0.345, p<0.001). However, no correlation was found between UCH-L1 levels and age (r=0.014, p=0.833), GCS (r=-0.115, p=0.074), mRS (r=0.063, p=0.475) and NIHSS (r=0.056, p=0.520). CONCLUSION: In this study, we detected significantly higher levels of UCH-L1 in patients with IS and ICH compared to patients with MDIC and healthy volunteers.

Clinically mild infantile encephalopathy associated with excitotoxicity.

Acute infectious encephalopathy is very frequently observed in children in East Asia including Japan. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype in Japan; however, more than 40% of the patients remain unclassified into specific syndromes. To investigate the underlying pathomechanism in those with unclassified acute encephalopathy, we evaluated brain metabolism by MR spectroscopy. Among 20 patients with acute encephalopathy admitted to our hospital during January 2015 to May 2016, 12 could not be classified into specific syndromes. MR spectroscopy was performed in 8 of these 12 patients with unclassified encephalopathy. MR spectroscopy showed an increase of glutamine with a normal N-acetyl aspartate level on days 3 to 8 in three of the 8 patients, which had normalized by follow-up studies. The three patients clinically recovered completely. This study suggests that excitotoxicity may be the underlying pathomechanism in some patients with unclassified mild encephalopathy.

Morfeo Study II: Clinical Course and Complications in Patients With Long-Term Disorders of Consciousness.

BACKGROUND: The life expectancy of patients with disorders of consciousness (DOCs) is ever-increasing, but little is known about their clinical course over late stages. Several issues (premorbid conditions, complications and pressure sores) are to be considered for their effect on clinical outcome, risk of death and recovery of functional performance. Unfortunately, in late stages of long-term rehabilitation, these aspects are still more neglected than in acute and postacute stages. The aim of this study was to investigate the clinical course and the complications of patients in the late stages of DOCs and to explore the relationship between mortality and specific biomarkers. MATERIALS AND METHODS: A total of 112 patients, admitted over 10 years in a dedicated ward, were retrospectively studied. Sociodemographic data, preadmission and inpatient clinical features were collected. Disability Rating Scale scores, complications including pressure sores and blood markers were assessed monthly. Data were analyzed through descriptive statistics and correlations using SPSS. RESULTS: Most patients were men older than 50 years with a nontraumatic etiology and a history of hypertension (42.86%). The most common complication was pneumonia (76.79%). No association was found between sex and mortality or between etiology and mortality (P > 0.05). Mortality correlated significantly with sepsis (ρ = 0.253), albumin (ρ = -0.558), hemoglobin (ρ = -0.354) and white blood cells (ρ = 0.243). Only 42% of patients remained unchanged at Disability Rating Scale evaluation. CONCLUSIONS: These data confirmed that DOCs are not static conditions and they require ongoing monitoring and assessment of clinical status, level of consciousness and laboratory biomarkers.

Correlation between resting state fMRI total neuronal activity and PET metabolism in healthy controls and patients with disorders of consciousness.

INTRODUCTION: The mildly invasive 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established imaging technique to measure 'resting state' cerebral metabolism. This technique made it possible to assess changes in metabolic activity in clinical applications, such as the study of severe brain injury and disorders of consciousness. OBJECTIVE: We assessed the possibility of creating functional MRI activity maps, which could estimate the relative levels of activity in FDG-PET cerebral metabolic maps. If no metabolic absolute measures can be extracted, our approach may still be of clinical use in centers without access to FDG-PET. It also overcomes the problem of recognizing individual networks of independent component selection in functional magnetic resonance imaging (fMRI) resting state analysis. METHODS: We extracted resting state fMRI functional connectivity maps using independent component analysis and combined only components of neuronal origin. To assess neuronality of components a classification based on support vector machine (SVM) was used. We compared the generated maps with the FDG-PET maps in 16 healthy controls, 11 vegetative state/unresponsive wakefulness syndrome patients and four locked-in patients. RESULTS: The results show a significant similarity with ρ = 0.75 ± 0.05 for healthy controls and ρ = 0.58 ± 0.09 for vegetative state/unresponsive wakefulness syndrome patients between the FDG-PET and the fMRI based maps. FDG-PET, fMRI neuronal maps, and the conjunction analysis show decreases in frontoparietal and medial regions in vegetative patients with respect to controls. Subsequent analysis in locked-in syndrome patients produced also consistent maps with healthy controls. CONCLUSIONS: The constructed resting state fMRI functional connectivity map points toward the possibility for fMRI resting state to estimate relative levels of activity in a metabolic map.

Atención a pacientes con estados alterados de conciencia en un hospital de pacientes crónicos y larga estancia / Care for patients with altered states of consciousness in a hospital for chronic and long-stay patients

Introducción. Un 30-40% de los pacientes con daño cerebral presenta alteraciones del nivel de conciencia, y algunos casos, estados alterados de conciencia: síndrome de vigilia sin respuesta (SVSR) o estado de mínima conciencia (EMC). La recuperación es variable y la supervivencia está amenazada por múltiples complicaciones. Objetivos. Presentar la metodología de trabajo del Hospital La Pedrera (HLP) para pacientes en SVSR o EMC y analizar las características clínicas de los pacientes atendidos, la evolución, y la situación funcional y cognitiva en el momento del alta. Pacientes y métodos. Estudio descriptivo prospectivo de pacientes atendidos en el HLP durante el período 2009-2013, con diagnóstico de SVSR o EMC. Resultados. El HLP trabaja mediante el método gestión de caso, ofreciendo una atención integral por un equipo multidisciplinar. Los pacientes se clasifican según objetivos asistenciales. Los pacientes con SVSR o EMC se incluyen en el programa de cuidados integrales y adaptación. Se atendió a 23 pacientes (86,9% varones), con una edad media de 54,9 años. Etiología: hemorragia cerebral, 30,4%; encefalopatía anóxica, 26,6%; encefalopatía metabólica, 17,3%; y otras causas, 17,3%. El 73,9% ingresó en SVSR y el resto en EMC. Evolución: el 43,4% mejoró su situación cognitiva inicial y el 88,8% presentaba una situación de dependencia total en el momento del alta. Las complicaciones más frecuentes fueron infecciones respiratorias y urinarias (53,6%). El 65,2% de los casos fueron exitus. Conclusiones. La asistencia en SVSR o EMC es compleja y precisa cuidados multidisciplinares. Casi la mitad de los pacientes mejoró su situación cognitiva, lo que justifica una actitud proactiva que intente mejorar la calidad de vida de los pacientes y sus familias (AU)

Introduction. Between 30% and 40% of patients with brain damage present alterations in their level of consciousness and, in some cases, altered states of consciousness: unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS). Recovery varies and survival is threatened by a number of complications. Aims. The purpose of this study is to present the working methodology used at the Hospital La Pedrera (HLP) for patients in UWS or MCS and to analyse the clinical characteristics of the patients attended to, their progress, and the functional and cognitive situation at the time of their discharge from hospital. Patients and methods. The work consisted in a prospective descriptive study of patients seen at the HLP over the period 2009-2013, who had been diagnosed with UWS or MCS. Results. The HLP uses the case management method, offering integrated care dispensed by a multidisciplinary team. Patients are classified according to healthcare goals. Patients with UWS or MCS are included in the integrated care and adaptation programme. A total of 23 patients (86.9% males) were attended to, the mean age being 54.9 years. Aetiology: brain haemorrhage, 30.4%; anoxic encephalopathy, 26.6%; metabolic encephalopathy, 17.3%; and other causes, 17.3%. Altogether 73.9% were admitted in UWS and the rest in MCS. Course: 43.4% improved their initial cognitive situation and 88.8% presented a situation of total dependence at the time of discharge. The most frequent complications were respiratory and urinary infections (53.6%). Death occurred in 65.2% of cases. Conclusions. Medical attention in UWS or MCS is complex and requires multidisciplinary care. Almost half of the patients improved their cognitive situation, which justifies a proactive attitude that attempts to improve the quality of life of both patients and their families (AU)