Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Traumatic brain injury (TBI) has a 20% mortality rate and a 10-15% rate of resultant permanent disability. The consequences of TBI range from brief loss of consciousness, to prolonged coma or death. Mild TBI is amongst the common causes of admission to trauma centers all over the world. Future technologies such as magnetic resonance elastography and robotic surgery demand information about the physical properties of brain tissue. Walsh and Schettini described the mechanical behavior of brain tissue under normal status as nonlinear viscoelastic behavior and defined the associated biomechanical changes and responses in a quantitative measurement of the material changes. Yet, there is still a lack of data concerning time-dependent deformation and mechanical property changes associated with TBI. My goal in this project was to describe these mechanical responses and to create a system for measuring and evaluating the mechanical response of brain tissue in vivo. This was to be achieved by inducing cortical contusions with a calibrated weight-drop method in seventy-four young adult male Sprague-Dawley rats. Instrumented indentation was performed on control brains and 1 hour to 3 weeks after contusion with intact dura using a 4-mm-diameter flat punch indenter to a maximum depth of 1.2 mm at loading. Loading rates did not exceed 0.34 N/min and 1.2 mm/min. In order to obtain force displacement data, we studied the elastic response of the traumatized brain tissue and the deformation process (creep) during the loading and unloading of indenter. After euthanasia, the brain was removed and evaluated histologically with different methods to reveal acute and chronic changes related to the contusion. The results revealed that the biomechanical properties of the brain tissue were changed after cortical contusion. Brain tissue elasticity decreased in the edematous brain at one day following the contusion and increased at 3 weeks, in association with reactive astroglial changes. This experimental technique, combined with mathematical modeling, might eventually lead to a better understanding of the physical changes in brain following TBI.

Traumatic brain injury (TBI) has a 20% mortality rate and a 10-15% rate of resultant permanent disability. The consequences of TBI range from brief loss of consciousness, to prolonged coma or death. Mild TBI is amongst the common causes of admission to trauma centers all over the world. Future technologies such as magnetic resonance elastography and robotic surgery demand information about the physical properties of brain tissue. Walsh and Schettini described the mechanical behavior of brain tissue under normal status as nonlinear viscoelastic behavior and defined the associated biomechanical changes and responses in a quantitative measurement of the material changes. Yet, there is still a lack of data concerning time-dependent deformation and mechanical property changes associated with TBI. My goal in this project was to describe these mechanical responses and to create a system for measuring and evaluating the mechanical response of brain tissue in vivo. This was to be achieved by inducing cortical contusions with a calibrated weight-drop method in seventy-four young adult male Sprague-Dawley rats. Instrumented indentation was performed on control brains and 1 hour to 3 weeks after contusion with intact dura using a 4-mm-diameter flat punch indenter to a maximum depth of 1.2 mm at loading. Loading rates did not exceed 0.34 N/min and 1.2 mm/min. In order to obtain force displacement data, we studied the elastic response of the traumatized brain tissue and the deformation process (creep) during the loading and unloading of indenter. After euthanasia, the brain was removed and evaluated histologically with different methods to reveal acute and chronic changes related to the contusion. The results revealed that the biomechanical properties of the brain tissue were changed after cortical contusion. Brain tissue elasticity decreased in the edematous brain at one day following the contusion and increased at 3 weeks, in association with reactive astroglial changes. This experimental technique, combined with mathematical modeling, might eventually lead to a better understanding of the physical changes in brain following TBI.

Bendras darbo tikslas: Įvertinti asmenų, patyrusių trauminį galvos smegenų pažeidimą, pažintinių funkcijų ir savarankiškumo sutrikimus ūmiu ligos periodu, panaudojant specializuotus vertinimo metodus bei Tarptautinę funkcionavimo, negalumo, ir sveikatos klasifikaciją. 1. Potemės „Pažintinių funkcijų vertinimas asmenims, patyrusiems trauminį galvos smegenų pažeidimą“ uždaviniai: 1. Įvertinti pacientų, patyrusių galvos smegenų traumą, pažintinių funkcijų lygį ūmiame periode. 2. Nustatyti pacientų, patyrusių galvos smegenų traumą, pažintinių funkcijų lygį, priklausomai nuo amžiaus, galvos smegenų traumos sunkumo. 3. Įvertinti pacientų, patyrusių galvos smegenų traumą, pažintines funkcijas panaudojant Tarptautinę funkcionavimo, negalumo ir sveikatos klasifikaciją. 4. Įvertinti pacientų, patyrusių galvos smegenų traumą, pažintinių funkcijų pokytį priklausomai nuo amžiaus, galvos smegenų traumos sunkumo. 2. Potemės „Savarankiškumo vertinimas asmenims, patyrusiems trauminį galvos smegenų pažeidimą“ uždaviniai: 1. Įvertinti pacientų, patyrusių galvos smegenų traumą, savarankiškumo gebėjimus ūmiame periode. 2. Nustatyti pacientų savarankiškumo lygį, priklausomai nuo amžiaus, galvos smegenų traumos sunkumo bei pažintinių funkcijų lygio. 3. Įvertinti pacientų, patyrusių galvos smegenų traumą, savarankiškumą panaudojant Tarptautinę funkcionavimo, negalumo ir sveikatos klasifikaciją. 4. Įvertinti pacientų, patyrusių galvos smegenų traumą, savarankiškumo gebėjimų pokytį priklausomai nuo... [toliau žr. visą tekstą] / The aim of the study: Evaluation of cognitive functions and self-dependence during the period of acute disease for the persons after traumatic brain injury (TBI), using specialized methods of evaluation and International Classification of Functioning, Disability and Health. 1.Goals of sub-theme: ,,Evaluation of cognitive functions and self-dependence for the patients after traumatic brain injury (TBI). 1. Evaluate person‘s after traumatic brain injury cognitive level in acute period. 2. Determine patient‘s level of cognitive functions after traumatic brain injury, according to their age, difficulty of brain injury. 3. Evaluate patient‘s after traumatic brain injury, cognitive functions with the help of International Classification of Functioning, Disability and Health. 4. Evaluate patient‘s after traumatic brain injury change of cognitive functions according to their age, difficulty of brain injury . 2. Goals of sub-theme: „Evaluation of self-dependence for the persons after traumatic brain injury (TBI)“: 1.Evaluate person‘s abilities of self-dependence during the acute period. 2. Determine patient’s after traumatic brain injury, level of cognitive functions, according to their age, difficulty of brain injury. 3. Evaluate patient‘s after brain injury change of cognitive functions with the help of International Classification of Functioning, Disability and Health. 4. Evaluate patient‘s after traumatic brain injury change of cognitive functions, according to their age... [to full text]

The overall goal of my research was to advance our understanding of the potential for novel compliant flooring systems to reduce the risk for fall-related injuries in older adults, including fall-related traumatic brain injury (TBI). This entailed an assessment of how these floors affect the competing demands of fall-related TBI – impact severity attenuation in concert with minimal concomitant impairments to balance control and postural stability. Two studies are included as part of this thesis. The first study used a mechanical drop tower to assess the effects of four traditional flooring systems and six novel compliant flooring conditions on the impact dynamics of a surrogate headform during the impact phase of simulated ‘worst- case’ head impacts. The second study entailed an assessment of the effect of two traditional and three novel compliant floors on the initial phase of the compensatory balance reactions of older adult men and women living in a residential-care facility environment following an externally induced perturbation using a tether-release paradigm. Overall, this thesis demonstrates that novel compliant floors substantially attenuate the forces and accelerations applied to the head during simulated worst- case impacts when compared to traditional flooring surfaces such as vinyl and carpet with underpadding. These benefits are achieved without compromising indices of balance control, supported by the finding that parameters characterizing early compensatory balance reactions were unaffected by the novel compliant floors tested. This work supports the introduction of pilot installations of novel compliant flooring systems into environments with high incidences of falls to test their effectiveness at reducing fall-related injuries in clinical settings.

Schädel-Hirn-Traumata sind die häufigste Ursache von Tod und Behinderung bei jungen Erwachsenen und oftmals ein Grund für Erwerbsunfähigkeit. Deshalb sind das Verständnis der zugrundeliegenden Pathomechanismen und die Entwicklung von Rehabilitationsstrategien von höchster Wichtigkeit. Einer der Hauptschädigungsmechanismen sind diffuse axonale Schädigungen. Diese treten insbesondere in frontalen Hirnregionen auf und führen entsprechend zu einer Beeinträchtigung exekutiver Funktionen und Veränderungen im Verhalten noch Jahre nach dem Ereignis. Unsere Studie mit Patienten im chronischen Stadium zielte auf eine genauere Charakterisierung frontaler Funktionen nach Schädel-Hirn-Trauma. In einem ersten behavioralen Experiment setzten wir zwei Paradigmen ein, die einerseits mit dem frontolateralen (Stroop-Interferenz-Aufgabe) und andererseits mit dem frontomedianen Kortex (Aufgabe zur Unterdrückung von Handlungsimitation) assoziiert sind (Schroeter et al., 2007). Die Patienten waren spezifisch in der Aufgabe zur Unterdrückung von Handlungsimitation als Hinweis auf eine Alteration des anterioren frontomedianen Kortex beeinträchtigt. Die Defizite waren hierbei eng mit Veränderungen des Verhaltens und der posttraumatischen Amnesie, die das Outcome nach Schädel-Hirn-Trauma vorhersagt, verbunden. In einem zweiten fMRT-Experiment überprüften wir die Hypothese einer frontomedianen Dysfunktion mittels eines Paradigmas, das spezifisch frontomediane Strukturen beansprucht. Hierbei wurden evaluative Urteile mit semantischen Gedächtnisinhalten kontrastiert („Angela Merkel ist eine gute Bundeskanzlerin“ vs. „Angela Merkel ist Bundeskanzlerin“). Die Ergebnisse bestätigen, dass Patienten nach Schädel-Hirn-Trauma durch persistierende frontomediane Beeinträchtigungen charakterisiert sind. Unsere Ergebnisse stimmen gut mit der Literatur überein, welche Defizite bei der „Theory of Mind“ und sozialen Kognition, die ebenfalls wesentlich mit dem frontomedianen Kortex verbunden sind, berichtet. Die Studie trägt zum Verständnis der Pathomechanismen nach Schädel-Hirn-Trauma bei. Frontomediane Alterationen scheinen wesentlich für die Langzeitfolgen verantwortlich zu sein. Deshalb sollten frontomediane Funktionen in der Diagnostik, insbesondere zur Einschätzung der Prognose, und der Rehabilitation eine stärkere Beachtung finden.

Epilepsy is a common neurological disease affecting 6 million people in Europe. Early prevention and accurate diagnosis and treatment are of importance to obtain seizure freedom. In this thesis new applications of carbon-11-labelled tracers in PET and autoradiographic studies were explored in focal epilepsy. Patients with low-grade gliomas often experience epileptic seizures. A retrospective PET-study assessing seizure activity, metabolic rate measured with 11C-methionine and other known prognostic factors was performed in patients with glioma. No correlation was found between seizure activity and uptake of methionine. The presence and termination of early seizures was a favourable prognostic factor. Activation of the neurokinin-1 (NK1) receptor by substance P (SP) induces epileptic activity. PET with the NK1 receptor antagonist GR205171 was performed in patients with temporal lobe epilepsy (TLE) and healthy controls. In TLE patients an increased NK1 receptor availability was found in both hemispheres, most pronounced in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptors and seizure frequency was observed in ipsilateral medial structures consistent with an intrinsic network using the NK1-SP receptor system for transmission of seizure activity. The uptake of 18F-fluoro-deoxy-glucose (FDG) is related to cerebral blood flow (CBF). Previously, methods to estimate blood flow from dynamic PET data have been described. A retrospective study was conducted in 15 patients undergoing epilepsy surgery investigation, including PET with 11C-FDG and 11C-Flumazenil (FMZ). The dynamic FMZ dataset and pharmacokinetic modeling with a multilinear reference tissue model were used to determine images of relative CBF. Agreement between data of FDG and CBF was analyzed showing a close association between interictal brain metabolism and relative CBF. Epilepsy often occurs after traumatic brain injuries. Changes in glia and inhibitory neuronal cells contribute to the chain of events leading to seizures. Autoradiography with 11C-PK11195, 11C-L-deprenyl and 11C-Flumazenil in an animal model of posttraumatic epilepsy studied the temporal and spatial distribution of microglia, astrocytes and GABAergic neurons. Results showed an instant increase in microglial activity that subsequently normalized, a late formation of astrogliosis and an instant and prolonged decease in GABA binding. The model can be used to visualize pathophysiological events during the epileptogenesis.

Objectives: To explore the prevalence and structure of self-reported disability after mild traumatic brain injury and the impact of traumatic brain pathology on such outcome. Material and methods: In study 1-3, symptoms data were collected by use of Rivermead Post-concussion Symptoms Questionnaire (RPQ) and data on global function by use of Glasgow Outcome Scale Extended (GOSE) from 2602 patients at 3 months after MTBI. RPQ data were subject to factor and Rasch-analyses Head CT data from 1262 patients were used in a prediction analysis that also included age and gender. In study 4, MRI and symptoms data were collected at 2-3 days and at 3-7 months follow-up after MTBI in 19 patients. Global function was assessed at follow-up by use of the Rivermead Head Injury Follow-Up Questionnaire (RHIFUQ) and GOSE. Results: I. Most respondents reported no remaining symptoms but 24% reported ≥3 and 10% ≥7 remaining symptoms. The factor analysis demonstrated that all symptoms are correlated but also identified subgroups of symptoms. II. Rasch-analysis of RPQ showed disordered category function, local dependency of items, poor targeting of persons to items and indications of 3 or more dimensions. There was no differential item functioning. III. Head CT pathology with no need for acute intervention was observed in 52 patients (4%) but was not associated with either frequency of remaining symptoms or global outcome at 3 months post injury. Female gender and age over 30 years were associated with less favourable outcome with respect to symptoms and GOSE. IV. Post-acute MRI indicated trauma-related pathology in one patient and follow-up MRI indicated loss of brain volume in 4 patients. Conclusions: A substantial proportion of patients with MTBI report remaining problems at three months after MTBI. RPQ is useful but not optimal to assess symptoms outcome after MTBI and calculation of a total sum score is not recommended. Female gender and older age are negative prognostic factors while brain pathology according to CT has no effect on self-reported outcome. Loss of brain volume after MTBI according to MRI may be a sensitive marker of traumatic brain pathology and deserves further studies.

Background: Patients with non-penetrating traumatic brain injuries (TBI) are at high risk for damage to ventral prefrontal brain regions, due to the brain’s acceleration into the bony ridges of the anterior portions of the skull. Current neuropsychological assessments of these patients focus mainly on the assessment of so-called “executive functions,” which are associated with dorsolateral prefrontal regions. Ventral prefrontal pathology is more likely to disrupt social and emotional functions, but assessments of these abilities using objective measurements that require patients to demonstrate their competence are rare. Mounting evidence suggests that chronic social and emotional deficits are common in TBI, and that these difficulties result in significant functional impairments post-injury, making clear the need to develop and use objective assessment tools during clinical neuropsychological assessments. Methods: In the current project, the Global Interpersonal Skills Test (GIST), a questionnaire measure of social skills with both a self-rated and an informant-rated version, was developed, along with three novel or adapted performance-based measures of social and emotional functioning. The first novel measure was the Assessments of Social Context (ASC), a video-based task examining comprehension of social context using non-verbal cues, including the identification of emotions, intensions and positive or negative attitudes of one person towards another. The second task was the Awareness of Interoception Test (AIT), a heartbeat detection paradigm adapted from previous literature that measures participants’ sensitivity to their cardiac function, which is implicated in basic emotional functioning. The third task was the Social Interpretations Task (SIT), an animation-based task adapted from previous literature examining participants’ ability to apply a social interpretation to stimuli that are not inherently social in nature. All novel tasks were developed and piloted with healthy undergraduates. A group of patients with moderate to severe TBI (N = 16), and a group of non-brain damaged controls (N = 16) underwent neuropsychological testing. Standard neuropsychological measures including the Wechsler Test of Adult Reading, Digit Span and Digit Symbol Coding from the Wechsler Adult Intelligence Scale, phonemic (FAS) and semantic fluency (Animals) from the Verbal Fluency Test, and the Trail Making Test, as well as the novel measures to both patients with TBI and controls were administered. The following predictions were made: vi 1) The novel performance-based measures of social abilities would be more sensitive to the presence of moderate and severe TBI than the standard neuropsychological measures of cognition; 2) On the informant version of the GIST, but not the self-report version, patients would have scores than controls; 3) Patients’ performance on the ASC would be less accurate than controls’, and this difference would be associated with real-world social skills, measured by the informant-version of the GIST; 4) Patients’ AIT performance would be less accurate than controls’, and this would be related to their self-rated emotional changes; 5) Patients’ SIT performance would be less accurate than controls’, and this difference would be associated with real-world social skills, again measured by the informant-version of the GIST. Findings: Findings were consistent with these hypotheses: 1) A statistically significant logistic regression revealed that a Social composite variable comprising the ASC, AIT and SIT was more sensitive to the presence of TBI (β = 9.59, p < .05) than a Cognitive composite variable comprising Digit Symbol Coding, Trails B completion time, and Phonemic Fluency (β = 0.006, p = .466). 2) A multivariate analysis of variance (MANOVA) revealed that informants of patients gave lower GIST scores to patients than the informants of controls (F(1,28) = 22.2, p < 0.0001), whereas there were no differences between groups on the self-rated version of the GIST (F(1,28) = .35, p = .56); 3) Patients’ ASC performance was significantly poorer than controls’ on a MANOVA (F(1,31) = 21.7, p < .0001), and ASC total scores were significantly correlated with GIST informant scores, using Spearman’s rank-order correlations (ρ(31) = .624, p < .0001). 4) Patients’ AIT performance was significantly poorer than controls’ using an independent samples t test (t(13) = 1.43, p < 0.005), and qualitative investigation of subjective reports of emotional change among patients suggested a potential relationship between emotional changes and AIT performance. vii 5) Patients’ SIT performance was significantly poorer than controls on an independent samples t test (t(30) = -2.12, p < 0.05), and SIT scores were significantly correlated with GIST informant scores, using Spearman’s rank-order correlations (ρ(31) = .460, p < .0001). Interpretation: This research represents a preliminary step in the development of clinically useful measures of social and emotional difficulties following TBI. Given the small sample size of the patient group, and the presence of co-morbid difficulties among some of the participants in this research, further testing of these measures in larger, more homogeneous samples would strengthen the current results, as would using a comparison group of people with milder TBI, rather than neuro-typical controls. The complexity of social behaviour requires that the current measures be further validated against other real-world assessments of social ability, and that assessments of other aspects of social behaviour be conducted. Nonetheless, the measures described here are a promising start to supplementing the neuropsychological toolkit in an area that requires further development at the present time.

Background: Patients with non-penetrating traumatic brain injuries (TBI) are at high risk for damage to ventral prefrontal brain regions, due to the brain’s acceleration into the bony ridges of the anterior portions of the skull. Current neuropsychological assessments of these patients focus mainly on the assessment of so-called “executive functions,” which are associated with dorsolateral prefrontal regions. Ventral prefrontal pathology is more likely to disrupt social and emotional functions, but assessments of these abilities using objective measurements that require patients to demonstrate their competence are rare. Mounting evidence suggests that chronic social and emotional deficits are common in TBI, and that these difficulties result in significant functional impairments post-injury, making clear the need to develop and use objective assessment tools during clinical neuropsychological assessments. Methods: In the current project, the Global Interpersonal Skills Test (GIST), a questionnaire measure of social skills with both a self-rated and an informant-rated version, was developed, along with three novel or adapted performance-based measures of social and emotional functioning. The first novel measure was the Assessments of Social Context (ASC), a video-based task examining comprehension of social context using non-verbal cues, including the identification of emotions, intensions and positive or negative attitudes of one person towards another. The second task was the Awareness of Interoception Test (AIT), a heartbeat detection paradigm adapted from previous literature that measures participants’ sensitivity to their cardiac function, which is implicated in basic emotional functioning. The third task was the Social Interpretations Task (SIT), an animation-based task adapted from previous literature examining participants’ ability to apply a social interpretation to stimuli that are not inherently social in nature. All novel tasks were developed and piloted with healthy undergraduates. A group of patients with moderate to severe TBI (N = 16), and a group of non-brain damaged controls (N = 16) underwent neuropsychological testing. Standard neuropsychological measures including the Wechsler Test of Adult Reading, Digit Span and Digit Symbol Coding from the Wechsler Adult Intelligence Scale, phonemic (FAS) and semantic fluency (Animals) from the Verbal Fluency Test, and the Trail Making Test, as well as the novel measures to both patients with TBI and controls were administered. The following predictions were made: vi 1) The novel performance-based measures of social abilities would be more sensitive to the presence of moderate and severe TBI than the standard neuropsychological measures of cognition; 2) On the informant version of the GIST, but not the self-report version, patients would have scores than controls; 3) Patients’ performance on the ASC would be less accurate than controls’, and this difference would be associated with real-world social skills, measured by the informant-version of the GIST; 4) Patients’ AIT performance would be less accurate than controls’, and this would be related to their self-rated emotional changes; 5) Patients’ SIT performance would be less accurate than controls’, and this difference would be associated with real-world social skills, again measured by the informant-version of the GIST. Findings: Findings were consistent with these hypotheses: 1) A statistically significant logistic regression revealed that a Social composite variable comprising the ASC, AIT and SIT was more sensitive to the presence of TBI (β = 9.59, p < .05) than a Cognitive composite variable comprising Digit Symbol Coding, Trails B completion time, and Phonemic Fluency (β = 0.006, p = .466). 2) A multivariate analysis of variance (MANOVA) revealed that informants of patients gave lower GIST scores to patients than the informants of controls (F(1,28) = 22.2, p < 0.0001), whereas there were no differences between groups on the self-rated version of the GIST (F(1,28) = .35, p = .56); 3) Patients’ ASC performance was significantly poorer than controls’ on a MANOVA (F(1,31) = 21.7, p < .0001), and ASC total scores were significantly correlated with GIST informant scores, using Spearman’s rank-order correlations (ρ(31) = .624, p < .0001). 4) Patients’ AIT performance was significantly poorer than controls’ using an independent samples t test (t(13) = 1.43, p < 0.005), and qualitative investigation of subjective reports of emotional change among patients suggested a potential relationship between emotional changes and AIT performance. vii 5) Patients’ SIT performance was significantly poorer than controls on an independent samples t test (t(30) = -2.12, p < 0.05), and SIT scores were significantly correlated with GIST informant scores, using Spearman’s rank-order correlations (ρ(31) = .460, p < .0001). Interpretation: This research represents a preliminary step in the development of clinically useful measures of social and emotional difficulties following TBI. Given the small sample size of the patient group, and the presence of co-morbid difficulties among some of the participants in this research, further testing of these measures in larger, more homogeneous samples would strengthen the current results, as would using a comparison group of people with milder TBI, rather than neuro-typical controls. The complexity of social behaviour requires that the current measures be further validated against other real-world assessments of social ability, and that assessments of other aspects of social behaviour be conducted. Nonetheless, the measures described here are a promising start to supplementing the neuropsychological toolkit in an area that requires further development at the present time.