Survival and clinical characteristics of patients with disorders of consciousness in a developing country between 2002 and 2018.

OBJECTIVE: Describe the survival, sociodemographic and clinical characteristics of subjects with disorders of consciousness in a reference rehabilitation center, in a developing country. METHODS: Patients with disorders of consciousness (DoC) caused by acquired neurological injuries, admitted between the years 2002-2018 in a neurorehabilitation center. Extracted data covered demographics, clinical details, survival time, and discharge information. Cox proportional hazard model and Kaplan-Meier analysis were used to reveal, associations with survival. RESULT: Out of 5064 neurological cases, 159 patients were diagnosed with DoC. The demographic data showed a male dominance (65%), with an average injury age of 42 years. The most common causes were traumatic (41%), anoxic (36%), and vascular (10%), with traffic accidents accounting for 71% of traumatic injuries. The study found that 75% of patients remained in a vegetative state (VS), and 25% in a minimally conscious state (MCS), with an average survival of 2110 days. CONCLUSION: There were no significant differences in survival days between patients in MCS and VS. Patients with traumatic injuries showed a higher survival rate than those with non-traumatic injuries. Age and etiology were identified as factors associated with a higher risk of death.

Factors influencing recovery in a pediatric sample with disorders of consciousness: insights from an observational study.

OBJECTIVE: To estimate rates and time to reach emergence of consciousness from vegetative state/unresponsive wakefulness syndrome (VS/UWS), and explore factors associated with improved recovery in children and adolescents with disorders of consciousness (DoC) following severe traumatic and non-traumatic brain injury. METHODS: Analytical, retrospective, cohort study. Clinical records of consecutively referred patients admitted in VS/UWS to a neurological rehabilitation institute in Argentina, between 2005 and 2021 were reviewed. Seventy children and adolescents were included in the analysis. A specialized 12-week rehabilitation program was administered, and emergence was defined by scores ≥44 points on the Western Neuro Sensory Stimulation Profile (WNSSP), sustained for at least 3 weeks on consecutive weekly evaluations. RESULTS: Emergence from VS/UWS to consciousness occurred within 5.4 (SD 2.6) weeks in almost one-third of patients. Multivariate Cox regression analysis showed emergence was significantly lower in patients with hypoxic ischemic encephalopathy compared to patients with other non-traumatic etiologies [HRadj 0.23 (95% CI 0.06-0.89); p = 0.03)]. CONCLUSIONS: Our findings reinforce growing evidence on the impact of etiology on DoC recovery in pediatric populations, ultimately influencing treatment and family-related decisions in child neurorehabilitation.

Jahi McMath, a New Disorder of Consciousness / Jahi McMath, un nuevo trastorno de la conciencia / Jahi McMath, um novo transtorno da consciencia

Abstract: In this paper, I review the case of Jahi McMath, who was diagnosed with brain death (BD). Nonetheless, ancillary tests performed nine months after the initial brain insult showed conservation of intracranial structures, EEG activity, and autonomic reactivity to the "Mother Talks" stimulus. She was clinically in an unarousable and unresponsive state, without evidence of self-awareness or awareness of the environment. However, the total absence of brainstem reflexes and partial responsiveness rejected the possibility of a coma. Jahi did not have UWS because she was not in a wakefulness state and showed partial responsiveness. She could not be classified as a LIS patient either because LIS patients are wakeful and aware, and although quadriplegic, they fully or partially preserve brainstem reflexes, vertical eye movements or blinking, and respire on their own. She was not in an MCS because she did not preserve arousal and preserved awareness only partially. The CRS-R resulted in a very low score, incompatible with MCS patients. MCS patients fully or partially preserve brainstem reflexes and usually breathe on their own. MCS has always been described as a transitional state between a coma and UWS but never reported in a patient with all clinical BD findings. This case does not contradict the concept of BD but brings again the need to use ancillary tests in BD up for discussion. I concluded that Jahi represented a new disorder of consciousness, non-previously described, which I have termed "reponsive unawakefulness syndrome" (RUS).

Resumen: En este artículo, revisó el caso de Jahi McMath, quién fue diagnosticada con muerte encefálica (ME). No obstante, exámenes complementarios realizados nueve meses después de la lesión cerebral inicial mostraron conservación de las estructuras intracraneales, actividad en electroencefalografía EEG, y reactividad autonómica a estímulos llamados "Conversación de Madre". Ella estaba clínicamente en un estado sin respuesta a los estímulos, sin evidencia de autoconciencia o conciencia del ambiente. Sin embargo, la ausencia total de reflejos del tronco encefálico y la capacidad de respuesta parcial rechazaron la posibilidad de un coma. Jahi no tenía síndrome de vigilia sin respuesta SVSR porque no estaba en un estado de vigilia y mostró una capacidad de respuesta parcial. Tampoco pudo ser clasificada como paciente LIS porque los pacientes LIS están despiertos y conscientes, y aunque tetrapléjicos, conservan total o parcialmente los reflejos del tronco encefálico, los movimientos oculares verticales u el parpadeo, y respiran por sí mismos. Ella no estaba en un EMC porque no preservaba la excitación y preservaba la conciencia solo parcialmente. La CRS-R dio una puntuación muy baja, incompatible con pacientes de EMC. Los pacientes de EMC preservan total o parcialmente los reflejos del tronco encefálico y, por lo general, respirar por sí solos. El EMC siempre se ha descrito como un estado de transición entre un coma y SVSR pero nunca se ha reportado en paciente con todos los hallazgos clínicos de ME. Este caso no contradice el concepto de ME pero vuelve a plantear la discusión acerca de la necesidad de utilizar exámenes complementarios en ME. Llegué a la conclusión de que Jahi representaba un nuevo trastorno de la conciencia, no descrito anteriormente, que he denominado "síndrome de no despertar con respuesta" (SNDR).

Resumo: Neste artigo, foi revisado o caso Jahi McMath, que foi diagnosticada com morte encefálica (ME). Contudo, exames complementares realizados nove meses depois da lesão cerebral inicial mostraram conservação das estruturas intracranianas, atividade em eletroencefalografia (EEG) e reatividade autonômica a estímulos chamados "Conversación de Madre". Ela estava clinicamente em um estado sem resposta aos estímulos, sem evidência de autoconsciência ou consciência do ambiente. Contudo, a ausência total de reflexos do tronco encefálico e a capacidade de resposta parcial rejeitaram a possibilidade de um coma. Jahi não tinha síndrome de vigia sem resposta (SVSR), porque não estava em um estado de vigia e mostrou uma capacidade de resposta parcial. Também nao pode ser classificada como paciente LIS, porque estes estão acordados e conscientes, e ainda que tetraplégicos, conservam total ou parcialmente os reflexos do tronco encefálicos, os movimentos oculares verticais ou cintilação, e respiram por si próprios. Ela não estava em um EMC porque não preservava a excitação e preservava a consciencia somente parcialmente. A CRS-R deu uma pontuação muito baixa, incompatível com pacientes de EMC. Os pacientes de EMC preservam total ou parcialmente os reflexos do tronco encefálico e, em geral, respirar por si só. O EMC sempre foi descrito como um estado de transição entre coma e SVSR, mas nunca foi relatado em paciente com todos os achados clínicos de ME. Esse caso não contradiz o conceito de ME, mas volta a colocar a discussão sobre a necessidade de utilizar exames complementares em ME. Cheguei a conclusão de que Jahi representava um novo transtorno da consciencia, nao descrito anteriormente, que denominei "síndrome de resposta sem vigília" (SRSV)

Time-Delay Latency of Resting-State Blood Oxygen Level-Dependent Signal Related to the Level of Consciousness in Patients with Severe Consciousness Impairment.

Recent evidence on resting-state functional magnetic resonance imaging (rs-fMRI) suggests that healthy human brains have a temporal organization represented in a widely complex time-delay structure. This structure seems to underlie brain communication flow, integration/propagation of brain activity, as well as information processing. Therefore, it is probably linked to the emergence of highly coordinated complex brain phenomena, such as consciousness. Nevertheless, possible changes in this structure during an altered state of consciousness remain poorly investigated. In this work, we hypothesized that due to a disruption in high-order functions and alterations of the brain communication flow, patients with disorders of consciousness (DOC) might exhibit changes in their time-delay structure of spontaneous brain activity. We explored this hypothesis by comparing the time-delay projections from fMRI resting-state data acquired in resting state from 48 patients with DOC and 27 healthy controls (HC) subjects. Results suggest that time-delay structure modifies for patients with DOC conditions when compared with HC. Specifically, the average value and the directionality of latency inside the midcingulate cortex (mCC) shift with the level of consciousness. In particular, positive values of latency inside the mCC relate to preserved states of consciousness, whereas negative values change proportionally with the level of consciousness in patients with DOC. These results suggest that the mCC may play a critical role as an integrator of brain activity in HC subjects, but this role vanishes in an altered state of consciousness.

Reconfiguration of large-scale functional connectivity in patients with disorders of consciousness.

INTRODUCTION: Functional connectivity alterations within individual resting state networks (RSNs) are linked to disorders of consciousness (DOC). If these alterations influence the interaction quality with other RNSs, then, brain alterations in patients with DOC would be characterized by connectivity changes in the large-scale model composed of RSNs. How are functional interactions between RSNs influenced by internal alterations of individual RSNs? Do the functional alterations induced by DOC change some key properties of the large-scale network, which have been suggested to be critical for the consciousness emergence? Here, we use network analysis to measure functional connectivity in patients with DOC and address these questions. We hypothesized that network properties provide descriptions of brain functional reconfiguration associated with consciousness alterations. METHODS: We apply nodal and global network measurements to study the reconfiguration linked with the disease severity. We study changes in integration, segregation, and centrality properties of the functional connectivity between the RSNs in subjects with different levels of consciousness. RESULTS: Our analysis indicates that nodal measurements are more sensitive to disease severity than global measurements, particularly, for functional connectivity of sensory and cognitively related RSNs. CONCLUSION: The network property alterations of functional connectivity in different consciousness levels suggest a whole-brain topological reorganization of the large-scale functional connectivity in patients with DOC.

The state of consciousness in patients in the vegetative and minimally conscious states / O estado de consciência em pacientes em estado vegetativo e em estado de consciência minima

Brain-injured patients may, with the assistance of life support, continue to perform basic bodily functions, but yet be deficient in wakefulness, awareness, decision making or other overt manifestations of consciousness. Here, we review two neurological states observed in brain injured patients with different degrees of brain impairment, the vegetative state (VS)and the minimally conscious state (MCS), and we discuss how these states are diagnosed through assessing patient behavioral responses during clinical examination. We consider howfunctional neuroimaging has revealed preserved cognitive capacities in patients that were supposed to be in the VS and has introduced a new diagnosis, cognitive motor dissociation.We review the GW Theory proposal that consciousness arises from functional connectivity (FC) of widely separated brain regions. We discuss how such high FC underlies the DefaultMode Network (DMN), a group of neural circuits that are active when an individual is not involved with external tasks and engages in introspective thinking. Finally, we discuss thefinding that the level of FC of the DMN is diminished in brain injured patients and the proposal that the level of residual DMN FC in brain injured patients is an index of their consciousness

Pacientes com lesão cerebral, quando assistidos, podem continuar a desempenhar funções fisiológicas básicas, mesmo estando com a vigília, a atenção, a capacidade de decisão e outras funções de consciência prejudicadas. Revisamos aqui dois níveis de distúrbio de consciência o estado vegetativo (VS) e o nível de consciência mínima (MCS), e discutimos como são diagnosticados através das respostas comportamentais durante o exame clínico. Abordamos como a neuroimagem funcional revelou capacidades cognitivas preservadas em pacientes supostamente em estado vegetativo, introduzindo um novo diagnóstico: a dissociação cognitivo-motora. Revisamos a proposta da Global Workspace (GW) teoria de que a consciência surge a partir de um alto grau de conectividade funcional (FC) entre áreas cerebrais distantes. Discutimos como esta alta conectividade é a base do Default Mode Network (DMN), uma rede neural ativada quando o indivíduo não está envolvido com tarefas externas e se volta para atividade mental introspectiva. Finalmente, discutimos os achados de redução do nível de FC no DMN em pacientes com lesão cerebral e a proposta de que o mesmo poderia ser um índice do nível de consciência nesses pacientes.

The State of Consciousness in Patients in the Vegetative and Minimally Conscious States / O estado de consciência em pacientes em estado vegetativo e em estado de consciência minima

Brain-injured patients may, with the assistance of life support, continue to perform basic bodily functions, but yet be deficient in wakefulness, awareness, decision making or other overt manifestations of consciousness. Here, we review two neurological states observed in brain injured patients with different degrees of brain impairment, the vegetative state (VS)and the minimally conscious state (MCS), and we discuss how these states are diagnosed through assessing patient behavioral responses during clinical examination. We consider howfunctional neuroimaging has revealed preserved cognitive capacities in patients that were supposed to be in the VS and has introduced a new diagnosis, cognitive motor dissociation.We review the GW Theory proposal that consciousness arises from functional connectivity (FC) of widely separated brain regions. We discuss how such high FC underlies the DefaultMode Network (DMN), a group of neural circuits that are active when an individual is not involved with external tasks and engages in introspective thinking. Finally, we discuss thefinding that the level of FC of the DMN is diminished in brain injured patients and the proposal that the level of residual DMN FC in brain injured patients is an index of their consciousness.(AU)

Pacientes com lesão cerebral, quando assistidos, podem continuar a desempenhar funções fisiológicas básicas, mesmo estando com a vigília, a atenção, a capacidade de decisão eoutras funções de consciência prejudicadas. Revisamos aqui dois níveis de distúrbio de consciência o estado vegetativo (VS) e o nível de consciência mínima (MCS), e discutimoscomo são diagnosticados através das respostas comportamentais durante o exame clínico. Abordamos como a neuroimagem funcional revelou capacidades cognitivas preservadas empacientes supostamente em estado vegetativo, introduzindo um novo diagnóstico: a dissociação cognitivo-motora. Revisamos a proposta da Global Workspace (GW) teoria de que a consciência surge a partir de um alto grau de conectividade funcional (FC) entre áreas cerebrais distantes. Discutimos como esta alta conectividade é a base do Default Mode Network (DMN), uma rede neural ativada quando o indivíduo não está envolvido com tarefas externas e se volta para atividade mental introspectiva. Finalmente, discutimos os achadosde redução do nível de FC no DMN em pacientes com lesão cerebral e a proposta de que o mesmo poderia ser um índice do nível de consciência nesses pacientes.(AU)

Intervenciones musicoterapéuticas para la activación del sistema reticular / Music therapeutic interventions for reticular activating system

La musicoterapia es una disciplina que progresivamente está ampliando su campo de abordaje. Dentro de las nuevas intervenciones se pueden mencionar las implementadas en pacientes con estado alterado de conciencia y cuadros patológicos, producto de lesiones neuronales adquiridas que involucran al sistema reticular. La formación reticular es una red neuronal que establece conexiones con gran parte del sistema nervioso, regulando el alerta general, la dirección de la atención y la transición entre sueño y vigilia. A partir de esto, el trabajo que se informa está centrado en una descripción general de los diferentes estados alterados de conciencia y las intervenciones de una disciplina científica, con técnicas no invasivas que utiliza el sonido y sus elementos específicamente en el diagnóstico y abordaje terapéutico de pacientes en estado de mínima conciencia y su efecto en la formación reticular, teniendo como objetivo principal la rehabilitación del paciente y el aumento de sus niveles de alerta. Las técnicas en musicoterapia se basan en los resultados positivos del efecto de ciertos parámetros sonoros tales como la melodía, los aspectos temporales, la armonía, sobre indicadores fisiológicos (frecuencia respiratoria y cardíaca, conductancia de la piel, niveles de cortisol, etc.), que proporcionan un marco organizativo. A través de dicho marco las personas pueden responder e interactuar por medio de las propuestas musicales, determinadas por características, tales como la simplicidad, la utilización de la voz sin acompañamiento, improvisando vocales, melodías repetitivas, música de baja densidad cronométrica unida a la velocidad respiratoria del paciente y que pertenezca a su entorno familiar.

Music-therapy is a scientific discipline that in the last years has extended its work fields, to multiple populations and pathologies. Among the new interventions is the one related to altered conscious states, which are pathological disorders product of acquired neuronal lesions that involved the reticular system. Currently, there are different and varied models music-therapy that works with patients with altered consciousness states and the pathologies associated to those disorders. Parallel to the cognitive rehabilitation a branch emerged called neurological music-therapy, which is based in the neuroscientific model of musical production and perception and it is defined as the therapeutic application of music and theirs discursive elements in people who suffered motor, cognitive and sensorial deficits caused by neurological diseases. The reticular system is a neuronal network, known as a complex area due to its anatomy and functional heterogeneity. This network stablish connections with a large portion of the nervous system, acts as a filter system as it is responsible for separating incoming stimuli, discriminating between those relevant and not relevant, and it regulates the general alert, direction of attention, transition between awake, and sleep states. The lesions and deficits that involved the reticular system had been a point of scientific interest for many years. There are two main components related to conscience: the arousal or wakefulness (be aware) and the awareness (the content of conscience). The arousal is considered a preparation state to action that consists in primitive behaviors to the environment, i.e. involuntary behaviors. To maintain the arousal intervenes the ascendant reticular system. While awareness involved a complex process, a cognitive elaboration of thought. Such elaboration encompasses the process of information that is received through the senses and environmental demands. When these processes are interrupted because of traumas or anomalies could generated a coma or states where the content of conscious are affected. After the brain injury, the patients are in a coma state and from there they could emerged with different long-term results: Post-traumatic amnesia, Minimal conscious state, vegetative state or death. The music-therapy techniques used with this population are descripted in this work from a neurological model, which is based in empirical evidence. This evidence is result of the effect of specific sound parameters (as melody, rhythm, harmony) upon physiological indicators (as heart rate, respiratory frequency, skin conductance, cortisol levels, among others), as well as the use of familiar music for the patient, detecting physiological indicators during musical experiences. The music-therapy techniques provide and motivate an organizational framework through which patients with severe disorders of their expressive and receptive linguistic abilities could respond and interact through musical applications. These techniques are possible because music is an innate ability of all human beings, also because the auditive system is the first sense that develops in the intrauterine level. The characteristics of music-therapy techniques are defined for simplicity, the use of the voice, where repetitive melodies are improvised, without breaking the laws of musical expectation, with low chronometric density music; this type of music go along with the respiratory speed of the patient. Also the musical history of the patient is taken into account to enable a familiar environment. With this background, the current work focuses in a general description of the different conscious states, the implication of reticular system and the interventions of music-therapy as a scientific discipline that offers non-invasive techniques that used the sound and their elements to test, to diagnostic and to treat patients in a minimal state of conscious. This technique has the ultimate goal of rehabilitate the cognitive functions and enhance the alert levels, besides providing a reinforcement for the interdisciplinary approach.

O estupor revisitado / Stupor revisited / La stupeur revisitée / El estupor revisitado

O estupor é uma síndrome negligenciada. Isso pode ser devido à sua baixa incidência, complexidade intrínseca e boa resposta à ECT. A pobreza do material clínico não tem permitido análises estatísticas e científicas adequadas e, portanto, sua fenomenologia e neurofisiologia permanecem não esclarecidas. Questões importantes são: 1) se o estupor constitui uma forma estável de comportamento chegando a ser uma“síndrome complexa”; 2) se ele representa um comportamento pré--programado ou vestigial que pode ser desencadeado por noxa severa,seja psicogênica ou orgânica; 3) se a personalidade e causa subjacente desempenham um papel modulador e 4) se os estupores orgânicos efuncionais compartilham mecanismos subjacentes similares ou,alternativamente, se referem a estados clínicos não relacionados.Um ponto de vista evolucionário deveria integrar os estupo resneurológicos e orgânicos e justificar o uso da resposta de“congelamento” ou cataléptica ao estresse em animais como um modelode pesquisa. Isso deveria, por sua vez, sugerir predições farmacológicas de interesse para o manejo do estupor humano.

Stupor is a neglected syndrome. This may be due to its low incidence, intrinsiccomplexity and good response to ECT. Paucity of clinical material has not allowed foradequate statistical and scientific analysis and therefore its phenomenology andneurophysiology remain unclear. Important questions are whether: (1) stuporconstitutes a stable form of behavior amounting to a “symptom complex”; (2) itrepresents a preprogrammed or vestigial behavior which may be triggered off by severenoxae, whether psychogenic or organic; (3) personality and underlying cause play amodulating role and; (4) organic and functional stupors share similar underlyingmechanisms or, alternatively, refer to unrelated clinical states. An evolutionary viewshould integrate neurological and organic stupors and justify the use of the “freezing”or cataleptic response to stress in animals as a research model. This should in turnsuggest pharmacological predictions of interest for the management of human stupor.

El estupor es un síndrome negligenciado. Eso puede deberse a su baja incidencia,a la complejidad intrínseca y a la buena respuesta al ECT. La pobreza del materialclínico no ha permitido análisis estadísticas y científicas adecuadas y, por tanto, sufenomenología y neurofisiología permanecen no esclarecidas. Cuestiones importantesson: 1) saber si el estupor constituye una forma estable de comportamiento llegandoa ser un “síndrome complexo”; 2) si él representa una conducta preprogramado o unvestigio que puede ser desencadenado por una noxa severa, sea ésta psicogénica oorgánica; 3) si la personalidad y la causa subyacente desempeñan un papel moduladore 4) saber si os estupores orgánicos y funcionales comparten mecanismos subyacentessimilares o, alternativamente, se refieren a estados clínicos no relacionados.Un ponto de vista evolutivo debería integrar los estupores neurológicos eorgánicos y justificar el uso de la respuesta de “congelamiento” o cataléptica al estrésen animales como un modelo de investigación. Eso debería al mismo tiempo, sugerirpredicciones farmacológicas de interés para el manejo del estupor humano.

La stupeur est un syndrome négligé. Cela peut être dû à sa faible incidence, à sacomplexité intrinsèque et à sa bonne réponse à l’ECT. Le manque de matériel clinique ne permet pas d’effectuer des analyses statistiques et scientifiques adéquates et parconséquent sa phénoménologie et sa neurophysiologie restent floues. Il s’agit dedécouvrir si: (1) la stupeur constitue une forme stable de comportement équivalant àun ®syndrome complexe¼; (2) elle représente un comportement préprogrammé ourésiduel qui peut être déclenché par un mal sévère, soit psychogène, soit organique;(3) la personnalité et une cause sous-jacente jouent un rôle modulateur et (4) si lesstupeurs organiques et fonctionnelles partagent des mécanismes sous-jacents similairesou, à défaut, renvoient à des états cliniques indépendants. Un point de vueévolutionnaire devrait intégrer les stupeurs neurologiques et biologiques et justifier laréponse de la ®congélation¼ ou cataleptique au stress chez les animaux comme modèlede recherche. Cela devrait en revanche produire des prédictions pharmacologiquesd’intérêt pour la gestion de la stupeur humaine.