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Neurophysiological markers can overcome the limitations of behavioural assessments of Disorders of Consciousness (DoC). EEG alpha power emerged as a promising marker for DoC, although long-standing literature reported alpha power being sustained during anesthetic-induced unconsciousness, and reduced during dreaming and hallucinations. We hypothesized that EEG power suppression caused by severe anoxia could explain this conflict. Accordingly, we split DoC patients (n = 87) in postanoxic and non-postanoxic cohorts. Alpha power was suppressed only in severe postanoxia but failed to discriminate un/consciousness in other aetiologies. Furthermore, it did not generalize to an independent reference dataset (n = 65) of neurotypical, neurological, and anesthesia conditions. We then investigated EEG spatio-spectral gradients, reflecting anteriorization and slowing, as alternative markers. In non-postanoxic DoC, these features, combined in a bivariate model, reliably stratified patients and indexed consciousness, even in unresponsive patients identified as conscious by an independent neural marker (the Perturbational Complexity Index). Crucially, this model optimally generalized to the reference dataset. Overall, alpha power does not index consciousness; rather, its suppression entails diffuse cortical damage, in postanoxic patients. As an alternative, EEG spatio-spectral gradients, reflecting distinct pathophysiological mechanisms, jointly provide a robust, parsimonious, and generalizable marker of consciousness, whose clinical application may guide rehabilitation efforts.
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Anestesia , Estado de Consciência , Humanos , Estado de Consciência/fisiologia , Transtornos da Consciência , Eletroencefalografia , Inconsciência/induzido quimicamenteRESUMO
BACKGROUND: Cortical excitability is higher in unconsciousness than in wakefulness, but it is unclear how this relates to anaesthesia. We investigated cortical excitability in response to dexmedetomidine, the effects of which are not fully known. METHODS: We recorded transcranial magnetic stimulation (TMS) and EEG in frontal and parietal cortex of 20 healthy subjects undergoing dexmedetomidine sedation in four conditions (baseline, light sedation, deep sedation, recovery). We used the first component (0-30 ms) of the TMS-evoked potential (TEP) to measure cortical excitability (amplitude), slope, and positive and negative peak latencies (collectively, TEP indices). We used generalised linear mixed models to test the effect of condition, brain region, and responsiveness on TEP indices. RESULTS: Compared with baseline, amplitude in the frontal cortex increased by 6.52 µV (P<0.001) in light sedation, 4.55 µV (P=0.003) in deep sedation, and 5.03 µV (P<0.001) in recovery. Amplitude did not change in the parietal cortex. Compared with baseline, slope increased in all conditions (P<0.02) in the frontal but not parietal cortex. The frontal cortex showed 5.73 µV higher amplitude (P<0.001), 0.63 µV ms-1 higher slope (P<0.001), and 2.2 ms shorter negative peak latency (P=0.001) than parietal areas. Interactions between dexmedetomidine and region had effects over amplitude (P=0.004) and slope (P=0.009), with both being higher in light sedation, deep sedation, and recovery compared with baseline. CONCLUSIONS: Transcranial magnetic stimulation-evoked potential amplitude changes non-linearly as a function of depth of sedation by dexmedetomidine, with a region-specific paradoxical increase. Future research should investigate other anaesthetics to elucidate the link between cortical excitability and depth of sedation.
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Anestesia , Dexmedetomidina , Humanos , Estimulação Magnética Transcraniana , Dexmedetomidina/farmacologia , Potenciais Evocados , Lobo FrontalRESUMO
Psychogenic non-epileptic seizures resemble epileptic seizures but their pathophysiological mechanisms differ. Despite being quite frequent, they are often misunderstood, regularly leading to a misdiagnosis and therapeutic errors. The objective of this article is to provide a short review of the current knowledge about this pathology. We will detail the main epidemiological data of psychogenic non-epileptic seizures. We will then discuss the diagnostic approach, emphasizing the semiological differences that exist between psychogenic non-epileptic seizures and epileptic seizures. Then, we will detail the main therapeutic actions and discuss the importance of communication between clinicians, the patient and his/her family. Finally, we will discuss the long-term prognosis of this pathology, which remains quite poor.
Les crises non épileptiques psychogènes ressemblent à des crises d'épilepsie, mais leurs mécanismes physiopathologiques diffèrent. Elles sont fréquentes, mais souvent méconnues, menant régulièrement à des erreurs diagnostiques et thérapeutiques. L'objectif de cet article est de dresser une synthèse des connaissances actuelles de cette pathologie. Nous y détaillerons les principales données épidémiologiques des crises non épileptiques psychogènes. Nous aborderons ensuite la démarche diagnostique en insistant sur les différences sémiologiques qui existent entre les crises non épileptiques psychogènes et les crises épileptiques. Nous présenterons ensuite les principales actions thérapeutiques existantes et parlerons de l'importance de la communication entre les cliniciens, le patient et son entourage. Enfin, nous discuterons du pronostic à long terme de cette pathologie, qui reste assez péjoratif.
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Epilepsia , Convulsões , Humanos , Feminino , Masculino , Convulsões/diagnóstico , Convulsões/etiologia , Convulsões/terapia , Epilepsia/diagnóstico , Epilepsia/terapia , Prognóstico , Comunicação , Eletroencefalografia , Diagnóstico DiferencialRESUMO
To date, no guideline exists for the management of epilepsy in patients with prolonged Disorders of Consciousness (DoC). This review aimed to assess the occurrence of epilepsy and epileptic abnormalities (EA) in these patients, to determine their impact on recovery; and to review the effect of antiepileptic drugs (AED) and therapeutic interventions on seizure occurrence and consciousness recovery. A structured search for studies on prolonged DoC and epilepsy was undertaken following PRISMA guidelines. From an initial search resulting in 5,775 titles, twelve studies met inclusion criteria. The occurrence of epilepsy and EA in DoC was poorly and inconsistently reported across studies. The results estimated a seizure prevalence of 27% in DoC. No conclusive data were found for the effects of AED on recovery nor on the influence of any therapeutic interventions on seizure occurrence. Given the scarcity of data, it is premature to make evidence-based recommendations on epilepsy in prolonged DoC. Based on this review and current clinical practices the following are recommended: (1) repeated standard EEG for detecting seizures and EA; (2) treating epilepsy while avoiding AEDs with sedating or cognitive side-effects. Future research should use standardized classification systems for seizures and EA.
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Estado de Consciência , Epilepsia , Anticonvulsivantes/uso terapêutico , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Humanos , Convulsões/tratamento farmacológico , Convulsões/epidemiologiaRESUMO
Different behavioural signs of consciousness can distinguish patients with an unresponsive wakefulness syndrome from patients in minimally conscious state (MCS). The Coma Recovery Scale-Revised (CRS-R) is the most sensitive scale to differentiate the different altered states of consciousness and eleven items detect the MCS. The aim of this study is to document the prevalence of these items. We analysed behavioural assessments of 282 patients diagnosed in MCS based on the CRS-R. Results showed that some items are particularly frequent among patients in MCS, namely fixation, visual pursuit, and reproducible movement to command, which were observed in more than 50% of patients. These responses were also the most probably observed items when the patients only showed one sign of consciousness. On the other hand, some items were rarely or never observed alone, e.g., object localisation (reaching), object manipulation, intelligible verbalisation, and object recognition. The results also showed that limiting the CRS-R assessment to the five most frequently observed items (i.e., fixation, visual pursuit, reproducible movement to command, automatic motor response and localisation to noxious stimulation) detected 99% of the patients in MCS. If clinicians have only limited time to assess patients with disorders of consciousness, we suggest to evaluate at least these five items of the CRS-R.
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Transtornos da Consciência/diagnóstico , Transtornos da Consciência/epidemiologia , Movimentos Oculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Prevalência , Reconhecimento Psicológico , Recuperação de Função Fisiológica , Estudos Retrospectivos , FalaRESUMO
OBJECTIVE: Validating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness-the Perturbational Complexity Index (PCI)-in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). METHODS: The benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). RESULTS: We found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. INTERPRETATION: Given its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718-729.
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Lesões Encefálicas/diagnóstico , Córtex Cerebral/fisiopatologia , Transtornos da Consciência/diagnóstico , Eletroencefalografia/métodos , Potenciais Evocados/fisiologia , Índice de Gravidade de Doença , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas/complicações , Transtornos da Consciência/classificação , Transtornos da Consciência/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índices de Gravidade do Trauma , Adulto JovemRESUMO
Predicting recovery of consciousness in patients who survive their coma but evolve to a vegetative state (recently coined unresponsive wakefulness syndrome) remains a challenge. Most previous prognostic studies have focused on the acute coma phase. A novel outcome scale (combining behavioural, aetiology, electroencephalographic, sleep electroencephalographic and somatosensory evoked potential data) has been proposed for patients in subacute unresponsive wakefulness syndrome. The scale's clinical application awaits validation in a larger population.
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Monitorização Neurofisiológica/métodos , Estado Vegetativo Persistente/classificação , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: This review discusses the advantages of transcranial magnetic stimulation combined with high-density electroencephalography (TMS-hdEEG) over other current techniques of brain imaging. METHODS AND RESULTS: Its application was reviewed, focusing particularly on disorders of consciousness, in the perspective of recent theories of consciousness. Assessment of non-communicative patients with disorders of consciousness remains a clinical challenge and objective measures of the level of consciousness are still needed. Current theories suggest that a key requirement for consciousness is the brain's capacity to rapidly integrate information across different specialized cortical areas. TMS-EEG allows the stimulation of any given cortical area and the recording of the immediate electrical cortical response. This technique has recently been successfully employed to measure changes in brain complexity under physiological, pharmacological and pathological conditions. CONCLUSIONS: This suggests that TMS-EEG is a reliable tool to discriminate between conscious and unconscious patients at the single subject level. Future works are needed to validate and implement this technique as a clinical tool.
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Lesões Encefálicas/diagnóstico , Lesões Encefálicas/fisiopatologia , Transtornos da Consciência/fisiopatologia , Eletroencefalografia , Estimulação Magnética Transcraniana , Lesões Encefálicas/complicações , Transtornos da Consciência/diagnóstico , Transtornos da Consciência/etiologia , Humanos , Recuperação de Função Fisiológica , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
Recently, neuroscientists and clinicians have seen the rapid evolution of diagnoses in disorders of consciousness. The unresponsive wakefulness syndrome-vegetative state, the minimally conscious state plus and minus, and the functional locked-in syndrome have been defined using new neuroimaging techniques. Diffusion tensor imaging, positron emission tomography, functional magnetic resonance imaging, electroencephalography, and transcranial magnetic stimulation techniques have all promoted important discoveries in the field of disorders of consciousness. This has led to a better understanding of these patients' condition and to the development of new prognosis, therapeutic, and communication tools. However, low sensitivity and artifacts problems need to be solved to bring these new technologies to the single-patient level; they also need to be studied in larger scale and randomized control trials. In addition, new ethics questions have arisen and need to be investigated.
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Pesquisa Biomédica , Transtornos da Consciência/diagnóstico , Transtornos da Consciência/terapia , Guias de Prática Clínica como Assunto , Transtornos da Consciência/história , História do Século XX , História do Século XXI , Humanos , NeuroimagemRESUMO
ABSTRACT: Neuro-orthopedic disorders are common in patients with disorders of consciousness (DOC) and can lead to potential pain. However, the patients' inability to communicate makes pain detection and management very challenging for clinicians. In this crossover randomized double-blind placebo-controlled study, we investigated the effects of an analgesic treatment on the presence of nociception-related behaviors. At baseline, the Nociception Coma Scale-Revised (NCS-R) was performed in 3 conditions: a non-noxious stimulation, a noxious stimulation, and during a physiotherapy session. Patients with a NCS-R total score during physiotherapy equal or above the score observed after the noxious stimulation could participate to the clinical trial, as well as patients with a score above 5. They received an analgesic treatment and a placebo on 2 consecutive days in a randomized order followed by an assessment with the NCS-R. Of the 18 patients, 15 displayed signs of potential pain during physiotherapy. Patients showed higher NCS-R scores during physiotherapy compared with the other conditions, suggesting that mobilizations were potentially painful. Of these 15 patients, 10 met the criteria to participate in the placebo-controlled trial. We did not find any effect of analgesic treatment on the NCS-R scores. This study highlights that physiotherapy may be potentially painful for patients with DOC, while analgesic treatments did not reduced NCS-R scores. Therefore, careful monitoring with appropriate assessment and treatment before and during mobilization should become a priority in clinical settings. Future studies should focus on the development of assessment tools sensitive to analgesic dosage to manage pain in DOC.
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Estado de Consciência , Nociceptividade , Analgésicos/uso terapêutico , Transtornos da Consciência/tratamento farmacológico , Transtornos da Consciência/etiologia , Método Duplo-Cego , Humanos , Nociceptividade/fisiologia , Medição da Dor , Modalidades de FisioterapiaRESUMO
Consciousness can be defined by two components: arousal (wakefulness) and awareness (subjective experience). However, neurophysiological consciousness metrics able to disentangle between these components have not been reported. Here, we propose an explainable consciousness indicator (ECI) using deep learning to disentangle the components of consciousness. We employ electroencephalographic (EEG) responses to transcranial magnetic stimulation under various conditions, including sleep (n = 6), general anesthesia (n = 16), and severe brain injury (n = 34). We also test our framework using resting-state EEG under general anesthesia (n = 15) and severe brain injury (n = 34). ECI simultaneously quantifies arousal and awareness under physiological, pharmacological, and pathological conditions. Particularly, ketamine-induced anesthesia and rapid eye movement sleep with low arousal and high awareness are clearly distinguished from other states. In addition, parietal regions appear most relevant for quantifying arousal and awareness. This indicator provides insights into the neural correlates of altered states of consciousness.
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Lesões Encefálicas , Aprendizado Profundo , Anestesia Geral , Nível de Alerta/fisiologia , Estado de Consciência/fisiologia , Eletroencefalografia , Humanos , Vigília/fisiologiaRESUMO
Epileptic seizures/post-traumatic epilepsy (ES/PTE) are frequent in persons with brain injuries, particularly for patients with more severe injuries including ones that result in disorders of consciousness (DoC). Surprisingly, there are currently no best practice guidelines for assessment or management of ES in persons with DoC. This study aimed to identify clinician attitudes toward epilepsy prophylaxis, diagnosis and treatment in patients with DoC as well as current practice in regards to the use of amantadine in these individuals. A cross-sectional online survey was sent to members of the International Brain Injury Association (IBIA). Fifty physician responses were included in the final analysis. Withdrawal of antiepileptic drug/anti-seizure medications (AED/ASM) therapy was guided by the absence of evidence of clinical seizure whether or not the AED/ASM was given prophylactically or for actual seizure/epilepsy treatment. Standard EEG was the most frequent diagnostic method utilized. The majority of respondents ordered an EEG if there were concerns regarding lack of neurological progress. AED/ASM prescription was reported to be triggered by the first clinically evident seizure with levetiracetam being the AED/ASM of choice. Amantadine was frequently prescribed although less so in patients with epilepsy and/or EEG based epileptic abnormalities. A minority of respondents reported an association between amantadine and seizure. Longitudinal studies on epilepsy management, epilepsy impact on neurologic prognosis, as well as potential drug effects on seizure risk in persons with DoC appear warranted with the goal of pushing guideline development forward and improving clinical assessment and management of seizures in this unique, albeit challenging, population.
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Establishing an accurate diagnosis is crucial for patients with disorders of consciousness (DoC) following a severe brain injury. The Coma Recovery Scale-Revised (CRS-R) is the recommended behavioral scale for assessing the level of consciousness among these patients, but its long duration of administration is a major hurdle in clinical settings. The Simplified Evaluation of CONsciousness Disorders (SECONDs) is a shorter scale that was developed to tackle this issue. It consists of six mandatory items, observation, command-following, visual pursuit, visual fixation, oriented behaviors, and arousal, and two conditional items, communication and localization to pain. The score ranges between 0 and 8 and corresponds to a specific diagnosis (i.e., coma, unresponsive wakefulness syndrome, minimally conscious state minus/plus, or emergence from the minimally conscious state). A first validation study on patients with prolonged DoC showed high concurrent validity and intra- and inter-rater reliability. The SECONDs requires less training than the CRS-R and its administration lasts about 7 minutes (interquartile range: 5-9 minutes). An additional index score allows the more precise tracking of a patient's behavioral fluctuation or evolution over time. The SECONDs is therefore a fast and valid tool for assessing the level of consciousness in patients with severe brain injury. It can easily be used by healthcare staff and implemented in time-constrained clinical settings, such as intensive care units, to help decrease misdiagnosis rates and to optimize treatment decisions. These administration guidelines provide detailed instructions for administering the SECONDs in a standardized and reproducible manner, which is an essential requirement for achieving a reliable diagnosis.
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Lesões Encefálicas , Transtornos da Consciência , Estado de Consciência , Guias como Assunto , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nível de Alerta/fisiologia , Lesões Encefálicas/fisiopatologia , Comunicação , Estado de Consciência/fisiologia , Transtornos da Consciência/diagnóstico , Fixação Ocular/fisiologia , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The Coma Recovery Scale-Revised (CRS-R) is the gold standard to assess severely brain-injured patients with prolonged disorders of consciousness (DoC). However, the amount of time needed to complete this examination may limit its use in clinical settings. OBJECTIVE: We aimed to validate a new faster tool to assess consciousness in individuals with DoC. METHODS: This prospective validation study introduces the Simplified Evaluation of CONsciousness Disorders (SECONDs), a tool composed of 8 items: arousal, localization to pain, visual fixation, visual pursuit, oriented behaviors, command-following, and communication (both intentional and functional). A total of 57 individuals with DoC were assessed on 2 consecutive days by 3 blinded examiners: one CRS-R and one SECONDs were performed on 1 day, whereas 2 SECONDs were performed on the other day. A Mann-Whitney U test was used to compare the duration of administration of the SECONDs versus the CRS-R, and weighted Fleiss' kappa coefficients were used to assess inter-/intra-rater reliability as well as concurrent validity. RESULTS: In the 57 participants, the SECONDs was about 2.5 times faster to administer than the CRS-R. The comparison of the CRS-R versus the SECONDs on the same day or the best of the 3 SECONDs led to "substantial" or "almost perfect" agreement (kappa coefficients ranging from 0.78 to 0.85). Intra-/inter-rater reliability also showed almost perfect agreement (kappa coefficients from 0.85 to 0.91 and 0.82 to 0.85, respectively). CONCLUSIONS: The SECONDs appears to be a fast, reliable and easy-to-use scale to diagnose DoC and may be a good alternative to other scales in clinical settings where time constraints preclude a more thorough assessment.
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Lesões Encefálicas , Transtornos da Consciência , Coma/diagnóstico , Transtornos da Consciência/diagnóstico , Humanos , Recuperação de Função Fisiológica , Reprodutibilidade dos TestesRESUMO
Due to life-saving medical advances, the diagnosis and treatment of disorders of consciousness (DOC) has become a more commonly occurring clinical issue. One recently developed intervention option has been non-invasive transcranial direct current stimulation. This dichotomy of patient responders may be better understood by investigating the mechanism behind the transcranial direct current stimulation (tDCS) intervention. The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) has been an important diagnostic tool in DOC patients. We therefore examined the neural response using TMS-EEG both before and after tDCS in seven DOC patients (four diagnosed as in a minimally conscious state and three with unresponsive wakefulness syndrome). tDCS was applied over the dorsolateral prefrontal cortex, while TMS pulses were applied to the premotor cortex. None of the seven patients showed relevant behavioral change after tDCS. We did, however, find that the overall evoked slow activity was reduced following tDCS intervention. We also found a positive correlation between the strength of the slow activity and the amount of high-frequency suppression. However, there was no significant pre-post tDCS difference in high frequencies. In the resting-state EEG, we observed that both the incidence of slow waves and the positive slope of the wave were affected by tDCS. Taken together, these results suggest that the tDCS intervention can reduce the slow-wave activity component of bistability, but this may not directly affect high-frequency activity. We hypothesize that while reduced slow activity may be necessary for the recovery of neural function, especially consciousness, this alone is insufficient.
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General anesthesia reversibly alters consciousness, without shutting down the brain globally. Depending on the anesthetic agent and dose, it may produce different consciousness states including a complete absence of subjective experience (unconsciousness), a conscious experience without perception of the environment (disconnected consciousness, like during dreaming), or episodes of oriented consciousness with awareness of the environment (connected consciousness). Each consciousness state may potentially be followed by explicit or implicit memories after the procedure. In this respect, anesthesia can be considered as a proxy to explore consciousness. During the recent years, progress in the exploration of brain function has allowed a better understanding of the neural correlates of consciousness, and of their alterations during anesthesia. Several changes in functional and effective between-region brain connectivity, consciousness network topology, and spatio-temporal dynamics of between-region interactions have been evidenced during anesthesia. Despite a set of effects that are common to many anesthetic agents, it is still uneasy to draw a comprehensive picture of the precise cascades during general anesthesia. Several questions remain unsolved, including the exact identification of the neural substrate of consciousness and its components, the detection of specific consciousness states in unresponsive patients and their associated memory processes, the processing of sensory information during anesthesia, the pharmacodynamic interactions between anesthetic agents, the direction-dependent hysteresis phenomenon during the transitions between consciousness states, the mechanisms of cognitive alterations that follow an anesthetic procedure, the identification of an eventual unitary mechanism of anesthesia-induced alteration of consciousness, the relationship between network effects and the biochemical or sleep-wake cycle targets of anesthetic agents, as well as the vast between-studies variations in dose and administration mode, leading to difficulties in between-studies comparisons. In this narrative review, we draw the picture of the current state of knowledge in anesthesia-induced unconsciousness, from insights gathered on propofol, halogenated vapors, ketamine, dexmedetomidine, benzodiazepines and xenon. We also describe how anesthesia can help understanding consciousness, we develop the above-mentioned unresolved questions, and propose tracks for future research.
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BACKGROUND: The Perturbational Complexity Index (PCI) was recently introduced to assess the capacity of thalamocortical circuits to engage in complex patterns of causal interactions. While showing high accuracy in detecting consciousness in brain-injured patients, PCI depends on elaborate experimental setups and offline processing, and has restricted applicability to other types of brain signals beyond transcranial magnetic stimulation and high-density EEG (TMS/hd-EEG) recordings. OBJECTIVE: We aim to address these limitations by introducing PCIST, a fast method for estimating perturbational complexity of any given brain response signal. METHODS: PCIST is based on dimensionality reduction and state transitions (ST) quantification of evoked potentials. The index was validated on a large dataset of TMS/hd-EEG recordings obtained from 108 healthy subjects and 108 brain-injured patients, and tested on sparse intracranial recordings (SEEG) of 9 patients undergoing intracranial single-pulse electrical stimulation (SPES) during wakefulness and sleep. RESULTS: When calculated on TMS/hd-EEG potentials, PCIST performed with the same accuracy as the original PCI, while improving on the previous method by being computed in less than a second and requiring a simpler set-up. In SPES/SEEG signals, the index was able to quantify a systematic reduction of intracranial complexity during sleep, confirming the occurrence of state-dependent changes in the effective connectivity of thalamocortical circuits, as originally assessed through TMS/hd-EEG. CONCLUSIONS: PCIST represents a fundamental advancement towards the implementation of a reliable and fast clinical tool for the bedside assessment of consciousness as well as a general measure to explore the neuronal mechanisms of loss/recovery of brain complexity across scales and models.
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Encéfalo/fisiologia , Estado de Consciência/fisiologia , Eletroencefalografia/métodos , Pesquisa Empírica , Estimulação Magnética Transcraniana/métodos , Adulto , Feminino , Humanos , Masculino , Sono/fisiologia , Fatores de Tempo , Vigília/fisiologiaRESUMO
BACKGROUND: Previous studies have separately reported impaired functional, structural, and effective connectivity in patients with disorders of consciousness (DOC). The perturbational complexity index (PCI) is a transcranial magnetic stimulation (TMS) derived marker of effective connectivity. The global fractional anisotropy (FA) is a marker of structural integrity. Little is known about how these parameters are related to each other. OBJECTIVE: We aimed at testing the relationship between structural integrity and effective connectivity. METHODS: We assessed 23 patients with severe brain injury more than 4 weeks post-onset, leading to DOC or locked-in syndrome, and 14 healthy subjects. We calculated PCI using repeated single pulse TMS coupled with high-density electroencephalography, and used it as a surrogate of effective connectivity. Structural integrity was measured using the global FA, derived from diffusion weighted imaging. We used linear regression modelling to test our hypothesis, and computed the correlation between PCI and FA in different groups. RESULTS: Global FA could predict 74% of PCI variance in the whole sample and 56% in the patients' group. No other predictors (age, gender, time since onset, behavioural score) improved the models. FA and PCI were correlated in the whole population (r = 0.86, p < 0.0001), the patients, and the healthy subjects subgroups. CONCLUSION: We here demonstrated that effective connectivity correlates with structural integrity in brain-injured patients. Increased structural damage level decreases effective connectivity, which could prevent the emergence of consciousness.
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Lesões Encefálicas/fisiopatologia , Conectoma , Transtornos da Consciência/fisiopatologia , Adulto , Idoso de 80 Anos ou mais , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico por imagem , Transtornos da Consciência/diagnóstico por imagem , Transtornos da Consciência/etiologia , Imagem de Tensor de Difusão , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Magnética TranscranianaRESUMO
Although it remained controversial for a long time, central nervous system (CNS) involvement of graft-versus-host disease (GVHD) is now becoming recognized as a real nosological entity. Previous case reports have suggested heterogeneous clinical presentations and it is not excluded that the whole spectrum of manifestations has not yet been fully described. Here, we report the case of a 58-year-old man with chronic GVHD who developed a rapidly ingravescent encephalopathy. There was no evidence for CNS immune-mediated lesions on conventional imaging nor for cellular infiltration in the cerebrospinal fluid. Serum analyses revealed the presence of anti-neuronal antibodies directed against anti-contactin-associated protein 2 (anti-Caspr2), a protein associated with voltage-gated potassium neuronal channels. Functional imaging with 2-deoxy-2-[fluorine-18] fluoro- d-glucose integrated with computed tomography (18F-FDG PET-CT) demonstrated diffuse cortical and subcortical hypometabolism. The patient was treated with a combination of immunosuppressive agents (corticosteroids, cyclophosphamide and rituximab) and progressively recovered normal neurocognitive functions. Taken together, these data suggest that CNS-GVHD may manifest as a reversible antibody-mediated functional encephalopathy. This report suggests for the first time the interest of screening for anti-neuronal antibodies and functional imaging with brain 18F-FDG PET-CT in diagnosing this severe complication of allogeneic hematopoietic cell transplantation (alloHSCT).
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Anticorpos Anticitoplasma de Neutrófilos/líquido cefalorraquidiano , Encefalopatias/líquido cefalorraquidiano , Encefalopatias/diagnóstico por imagem , Doença Enxerto-Hospedeiro/líquido cefalorraquidiano , Doença Enxerto-Hospedeiro/diagnóstico por imagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Encefalopatias/etiologia , Doença Crônica , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos , Transplante Homólogo/tendênciasRESUMO
INTRODUCTION: Resistance to eye opening (REO) is a commonly encountered phenomenon in clinical practice. We aim to investigate whether REO is a sign of consciousness or a reflex in severely brain-injured patients. METHODS: We recorded REO in chronic patients with disorders of consciousness during a multimodal diagnostic assessment. REO evaluations were performed daily in each patient and clinical diagnosis of unresponsive wakefulness syndrome (UWS), minimally conscious state with (MCS+) or without (MCS-) preserved language processing was made using the Coma Recovery Scale-Revised (CRS-R). RESULTS: Out of 150 consecutive patients, 79 patients fit inclusion criteria. REO was seen in 19 patients (24.1%). At the group level, there was a significant relationship between the presence of REO and the level of consciousness. We also observed a difference in the repeatability of REO between patients in UWS, MCS- and MCS+. Out of 23 patients in UWS, six showed REO, in whom five showed atypical brain patterns activation. CONCLUSION: Our findings suggest a voluntary basis for REO and stress the need for multiple serial assessments of REO in these patients, especially since most patients show fluctuating levels of consciousness.