Reconstruction of the Ascending Reticular Activating System with Diffusion Tensor Tractography in Patients with a Disorder of Consciousness after Traumatic Brain Injury

Giant aneurysms have been treated with endovascular approaches like general, balloon-assisted and stent-assisted coiling, and flow diverter stent-assisted techniques. Few cases have been reported to be treated with both normal and large coils. Despite the mass effect, an adequate revascularization has been reported. An initial use of these coils is being reported in the current study. This is a case which has been successfully treated using a stent-assisted coiling with both small and large coils i.e., Penumbra Coil 400 (Penumbra, Inc., Alameda, California)

Traumatic Axonal Injury in Patients with Mild Traumatic Brain Injury

Mild traumatic brain injury (TBI) is a subtype of TBI that is classified by the severity of head trauma, whereas traumatic axonal injury (TAI) is a diagnostic term with a pathological meaning. In this chapter, TAI in patients with mild TBI is described in terms of definition, history, and diagnostic approach. The presence of TAI in patients with mild TBI has been demonstrated by autopsy studies since the 1960s. However, because conventional brain CT or MRI are not powered with contrast resolution to determine TAI in mild TBI, diagnosis of TAI in live patients with mild TBI was impossible. Since the introduction of diffusion tensor imaging, hundreds of studies have demonstrated TAI in live patients with mild TBI in the 2000s. The precise diagnosis of TAI in patients with mild TBI is clinically important for proper management and prognosis prediction following mild TBI. Several requirements are necessary for diagnosis of TAI in mild TBI: first, head trauma history; second, development of new clinical symptoms and signs after head trauma; third, evidence of TAI of the neural tracts on diffusion tensor imaging or diffusion tensor tractography; and fourth, coincidence of the newly developed clinical features and the function of injured neural tracts

Sex Differences in Sex Hormone Profiles and Prediction of Consciousness Recovery After Severe Traumatic Brain Injury

Objective: The clinical course of unconsciousness after traumatic brain injury (TBI) is commonly unpredictable and it remains a challenge with limited therapeutic options. The aim of this study was to evaluate the early changes in serum sex hormone levels after severe TBI (sTBI) and the use of these hormones to predict recovery from unconsciousness with regard to sex.Methods: We performed a retrospective study including patients with sTBI. A statistical of analysis of serum sex hormone levels and recovery of consciousness at 6 months was made to identify the effective prognostic indicators.Results: Fifty-five male patients gained recovery of consciousness, and 37 did not. Of the female patients, 22 out of 32 patients regained consciousness. Male patients (n = 92) with sTBI, compared with healthy subjects (n = 60), had significantly lower levels of follicular stimulating hormone (FSH), testosterone and progesterone and higher levels of prolactin. Female patients (n = 32) with sTBI, compared with controls (n = 60), had significantly lower levels of estradiol, progesterone, and testosterone and significantly higher levels of FSH and prolactin. Testosterone significantly predicted consciousness recovery in male patients. Normal or elevated testosterone levels in the serum were associated with a reduced risk of the unconscious state in male patients with sTBI. For women patients with sTBI, sex hormone levels did not contribute to the prediction of consciousness recovery.Conclusion: These findings indicate that TBI differentially affects the levels of sex-steroid hormones in men and women patients. Plasma levels of testosterone could be a good candidate blood marker to predict recovery from unconsciousness after sTBI for male patients

Gliomas difusos en áreas elocuentes: avances diagnósticos y terapéuticos

Objetivo: presentar los avances diagnósticos, moleculares y radiológicos, así como en las estrategias terapéuticas para gliomas difusos en los últimos 5 años (2018-2023) en la Fundación Universitaria de Ciencias de la Salud (FUCS), Bogotá D.C., Colombia. Materiales y métodos: se describen las técnicas diagnósticas y terapéuticas utilizadas para gliomas difusos con casos ilustrativos. Resultados: se muestran los avances de las herramientas diagnósticas y terapéuticas para el manejo de gliomas difusos. Discusión: en los últimos 5 años se ha avanzado en la clasificación, diagnóstico y tratamiento de los gliomas difusos, gracias a los avances tecnológicos como los marcadores moleculares, la tractografía y la fusión de imágenes para la neuronavegación y las técnicas de estimulación cortical. Esto ha permitido que el tratamiento de los pacientes con dichos tumores mejore la tasa de morbilidad, la calidad de vida libre de enfermedad y la supervivencia global. Conclusiones: las técnicas de diagnóstico como la tractografía, la fusión integral de imágenes intraoperatorias y el mapeo cerebral electrofisiológico con estimulación cortical y subcortical han mejorado el diagnóstico y tratamiento de los gliomas difusos

A Diffusion Tensor Imaging Study of Motor Fibre Path Integrity and Overt Responsiveness in Disorders of Consciousness

This study investigated the relationship between motor thalamo-cortico-cerebellar fibre path integrity and overt responsiveness in patients with disorders of consciousness (DOC). Additionally, we investigated the potential of imaging these motor tracts at ultra-high fields. Study I and II aimed to map the white matter connections of motor execution fibres in DOC patients. Our results showed significant reductions in motor fibre path integrity across DOC diagnostic categories. Study III and IV aimed to develop a 7T MRI Diffusion Tensor Imaging (DTI) sequence. We optimized this sequence to image motor fibre paths in DOC patients. We concluded that, in healthy controls, probabilistic tractography of these tracts at ultra-high fields was superior to tractography at lower magnetic fields. Further investigation is needed to determine the advantages of imaging these motor tracts at ultra-high fields in patients with disorders of consciousness

Jahi McMath, um novo transtorno da consciência

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).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).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 não 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 consciência 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 à conclusão de que Jahi representava um novo transtorno da consciência, não descrito anteriormente, que denominei “síndrome de resposta sem vigília” (SRSV)

Sommeil du stade aigu à chronique à la suite d’un traumatisme craniocérébral modéré à sévère : relation avec la récupération cognitive et les dommages neuroanatomiques

Le traumatisme craniocérébral (TCC) est la première cause d’invalidité chez les jeunes adultes qui entrent dans leurs années les plus productives, affectant significativement leur qualité de vie. Le TCC modéré à grave s’accompagne de dommages neuroanatomiques considérables et de conséquences neurologiques, cognitives, et sociales qui persistent à long terme, et notamment de troubles de l’éveil et du sommeil qui sont parmi les séquelles les plus communes, invalidantes et persistantes. Conséquemment, l’objectif global de cette thèse était d’investiguer comment le TCC modéré à grave affecte le sommeil subséquent pendant l’hospitalisation aigüe et à long terme, et d’évaluer comment ce sommeil subséquent affecte la récupération à la suite du TCC. Pour ce faire, nous avons usé de méthodes quantitatives, incluant la polysomnographie, afin de mesurer précisément le sommeil du stade aigu au stade chronique à la suite du TCC, ainsi que dans différents groupes contrôles hospitalisés ou non. De plus, ces mesures ont été combinées à des méthodes de neuroimagerie, notamment l’imagerie par tenseur de diffusion, ainsi qu’à diverses mesures cliniques et neuropsychologiques. Aux chapitres un et deux, un survol de la littérature pertinente à cette thèse sera d’abord présenté, abordant des concepts ayant trait au sommeil et au TCC. Les questions qui demeurent dans la littérature ainsi que les objectifs spécifiques de cette thèse seront également abordés en détail. Au chapitre trois, le sommeil au stade aigu du TCC et son association avec la fonction cognitive seront abordés au travers d’un article empirique. Puisque le TCC représente une perturbation importante pour le cerveau, spécialement au stade aigu, et que la majorité des patients ayant subi un TCC développeront des déficits cognitifs persistants, ce chapitre vise à caractériser objectivement le sommeil des patients ayant subi un TCC modéré à grave pendant leur hospitalisation aigüe, et à évaluer comment ce sommeil est associé à la cognition des années plus tard. Dans ce chapitre, nous avons d’abord démontré grâce à la polysomnographie que le TCC causait des altérations importantes du sommeil pendant l’hospitalisation aigüe, qui étaient caractérisées par un sommeil plus fragmenté et une plus grande quantité de sommeil lent profond. Nous avons ensuite démontré que ces altérations étaient associées avec la cognition des années plus tard, en accord avec le rôle attendu du sommeil dans la récupération neurologique à la suite du TCC. Ce chapitre suggère non seulement que le TCC soit directement impliqué dans l’altération du sommeil suivant la blessure, mais aussi que le sommeil subséquent puisse être un marqueur précoce ou un promoteur de la récupération cognitive à long terme, soulignant l’importance de monitorer le sommeil à la suite du TCC. Aux chapitres quatre et cinq, le sommeil au stade chronique du TCC et son association avec les dommages neuroanatomiques seront abordés au travers de deux articles empiriques. Puisque qu’il est difficile d’expliquer les plaintes chroniques de mauvaise qualité de sommeil et d’éveil par l’architecture du sommeil des patients ayant subi un TCC, et que la microarchitecture du sommeil, qui dépend fortement des réseaux étendus de matière blanche, n’a que très peu été étudiée, ces chapitres visent à caractériser la microarchitecture du sommeil des patients ayant subi un TCC modéré à grave au stade chronique, et d’investiguer comment cette microarchitecture est associée à la détérioration attendue de la matière blanche. Dans ces chapitres, nous avons démontré que les fuseaux de sommeil et les oscillations lentes n’étaient que très peu altérés au stade chronique du TCC, soulignant leur surprenante résilience, et que contrairement à nos hypothèses, ceux-ci ne sont probablement pas directement impliqués dans les troubles de sommeil et de l’éveil persistants rapportés à la suite du TCC. D’un autre côté, nous avons également démontré que la synchronisation des oscillations lentes était fortement associée à la détérioration massive de matière blanche présente chez ces patients, supportant l’hypothèse qu’il existe une forte pression homéostatique de sommeil et un besoin de sommeil augmenté qui persistent au stade chronique. Cette thèse a contribué à élucider comment le TCC affecte le sommeil à court et à long terme suivant la blessure, ainsi que l’effet du sommeil pendant l’hospitalisation aigüe sur l’évolution cognitive qui s’ensuit à long-terme.Traumatic brain injuries are the first cause of disability among young adults. This is notable considering they are entering their most productive years, significantly altering their quality of life. Moderate to severe TBI are accompanied by considerable neuroanatomical damage and neurological, cognitive, and social consequences that can persist over several years, and notably sleep-wake disturbances which are among the most common, debilitating, and persistent sequelae. Thus, the global objective of this thesis was to investigate how moderate to severe TBI affects sleep during acute hospitalization and in the long-term, and to evaluate how post-injury sleep affects recovery following TBI. To achieve this goal, we used quantitative methods, including polysomnography, to precisely measure sleep in the acute and chronic stages of TBI, and in both hospitalized and not hospitalized control groups. In addition, these measures were combined to neuroimaging methods, notably diffusion tensor imaging, and to various clinical and neuropsychological measures. In chapters one and two, an overview of the relevant literature will first be presented, touching on concepts related to sleep and TBI. Current gaps in the literature and the thesis objectives will also be detailed. In chapter three, sleep in the acute stage of TBI and its association with cognitive function will be addressed. Because TBI represents a major disruption to the brain, especially in the acute stage, and because most patients with TBI exhibit persistent cognitive deficits, this chapter aims to objectively characterize sleep during acute hospitalization following moderate to severe TBI, and to explore how sleep is associated with cognition years later. In this chapter, we first showed with polysomnography that TBI caused significant disruptions of sleep during acute hospitalization, which were characterized by a more fragmented sleep and more slow-wave sleep. We then showed that these alterations were associated with cognition years later, in line with the expected role of sleep in neurological recovery. This chapter suggests that the TBI itself is directly involved in sleep disruption following the injury, and that subsequent sleep may be an early marker or a promoter of long-term cognitive recovery, highlighting the importance of monitoring sleep following TBI. In chapters four and five, sleep in the chronic stage of TBI and its association with neuroanatomical damage is addressed. Because chronic sleep-wake complaints are not accounted for by sleep architecture following TBI, and that sleep microarchitecture, which relies on a structural backbone of white matter networks, has rarely been studied, these chapters aim to characterize sleep microarchitecture in the chronic stage following moderate to severe TBI, and to investigate how this microarchitecture is associated with the expected white matter deterioration. In these chapters, we showed that sleep spindles and slow waves were only minimally altered in the chronic stage following TBI, highlighting their surprising resilience to injury, and that contrary to our hypotheses, these sleep oscillations are probably not directly involved in the persistent sleep-wake disturbances reported following TBI. On the other hand, we also showed that slow wave synchrony was strongly associated with the massive white matter deterioration observed in these patients, supporting the hypothesis of elevated homeostatic sleep pressure and heightened need for sleep persisting in the chronic stage. This thesis contributed to elucidating how TBI affects short and long-term sleep following injury, as well as the effect of sleep during acute hospitalization on long-term cognitive outcomes

Experimental and Model-based Approaches to Directional Thalamic Deep Brain Stimulation

University of Minnesota Ph.D. dissertation. September 2016. Major: Biomedical Engineering. Advisor: Matthew Johnson. 1 computer file (PDF); xii, 181 pages.Deep brain stimulation (DBS) is an effective surgical procedure for the treatment of several brain disorders. However, the clinical successes of DBS hinges on several factors. Here, we describe the development of tools and methodologies in the context of thalamic DBS for essential tremor (ET) to address three key challenges: 1) accurate localization of nuclei and fiber pathways for stimulation, 2) model-based programming of high-density DBS electrode arrays (DBSA) and 3) in vivo assessment of computational DBS model predictions. We approached the first challenge through a multimodal imaging approach, utilizing high-field (7T) susceptibility-weighted imaging and diffusion-weighted imaging data. A nonlinear image deformation algorithm was used in conjunction with probabilistic fiber tractography to segment individual thalamic sub-nuclei and reconstruct their afferent fiber pathways. We addressed the second challenge by developing subject-specific computational model-based algorithms built on maximizing population activating function values within a target region using convex optimization principles. The algorithms converged within seconds and only required as many finite-element simulations as the number of electrodes on the DBSA being modeled. For the third challenge, we recorded (in two non-human primates) unit-spike data from neurons in the vicinity of chronically implanted thalamic DBSAs before, during and after high-frequency stimulation. A novel entropy-based method was developed to quantify the degree and significance of stimulation-induced changes in neuronal firing pattern. Results indicated that neurons modulated by thalamic DBS were distributed and not confined to the immediate proximity of the active electrode. For those that were modulated by DBS, their responses increasingly shifted from firing rate modulation to firing pattern modulation with increased stimulation amplitude. Additionally, strong low-pass filtering effect was observed where <4% of DBS pulses produced phase-locked spikes in cells exhibiting significant excitatory firing pattern modulation. Finally, we quantified the spatial distribution of neurons modulated by DBS by developing a novel spherical statistical framework for analysis. Together, these tools and methodologies are poised to improve our understanding of DBS mechanisms and improve the efficacy and efficiency of DBS therapy

Neuroimaging investigations of the functional and structural changes of intrinsically connected brain networks in relation to habitual sleep status

This thesis uses fMRI and DTI neuroimaging modalities to investigate relationships between chronic habitual sleep status in waking control subjects and functional and structural changes in higher order intrinsically connected brain networks (ICN). Study one investigates methodologies; compares the use of deterministic and probabilistic tractography in combination with functional imaging to charaterise structural connectivity with respect to functional connectivity in a single ICN. The following chapter examines whether inter-individual differences in habitual sleep patterns are reflected in waking measurements of network functional connectivity (FC) between three ICNs. Subsequent work investigates group differences in structural connectivity with respect to habitual sleep duration and whole brain changes in white matter in relation to subjective habitual sleep quality using tract based spatial statistics (TBSS). The final chapter builds on the work from previous chapters examining a wider range of sleep features and overall network FC. Results presented in this thesis provide evidence of functional and structural brain connectivity changes, which are modulated by chronic habitual sleep status. This may help to elucidate the link between sleep, waking sleep status, cognition and explain individual differences in susceptibility to sleep deprivation, as well as potentially the networks and systems responsible for variations in sleep patterns themselves