INTRODUCTION: Neuroinflammation, a key secondary injury mechanism following traumatic brain injur... more INTRODUCTION: Neuroinflammation, a key secondary injury mechanism following traumatic brain injury (TBI), involves humoral and cellular components. The cellular component includes recruitment of haematogenous inflammatory cells (polymorphonuclear leukocytes and monocytes) and the activation of resident innate immune cells (microglia). While measurement of inflammatory mediators in jugular venous blood and brain microdialysate can characterise global and focal inflammation in TBI, they do not provide a means of mapping spatial variations in neuroinflammation across the brain. A recent study used [11C](R)PK11195 positron emission tomography (PET) to demonstrate persistent thalamic inflammation years after TBI, which was related to outcome.1 We have applied [11C](R)PK11195 to map the spatiotemporal patterns of microglial activation in acute moderate/severe TBI. METHODS: Seven patients (Table 1) underwent [11C]PK11195 PET and MR imaging twice at a median (range) of 5 (3 − 11) and 15 (13 − 22) days post TBI with a GE Advance, following an i.v. bolus of 485 (296 – 569) MBq of [11C]PK11195; specific activity ~220 GBq/μmol. Fifty-eight frames of emission data were acquired over 90 minutes post-injection. Arterial blood samples were obtained throughout each PET scan to measure whole blood and plasma radioactivity concentrations, together with the plasma parent fraction.2 Voxel-wise total volume of distribution (VT) was calculated using Logan graphical analysis with a metabolite-corrected plasma input function. [11C](R)PK11195 binding potentials were calculated in core, perilesional oedema, basal ganglia, white matter and in normal appearing areas of the brain. RESULTS: There was substantial inter-subject heterogeniety in the spatiotemporal patterns of microglial activation. While some subjects showed early perilesional and lesional [11C]PK11195 binding that increased over time, in other patients, such early binding disappeared at later time points. Given the past demonstration of persistent thalamic microglial activation [...]
is a clinical neuropsychologist and PhD student with her main research interest being in pediatri... more is a clinical neuropsychologist and PhD student with her main research interest being in pediatric traumatic brain injury. As a clinician she has more than 15 years of experience in rehabilitation of children and youth with TBI along with holistic pediatric rehabilitation program.
Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in ... more Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice. Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries. Results: Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N = 426;20%) and deferred consent (N = 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%). Conclusions: Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers.
Background: We aimed to study the associations between pre-and in-hospital tracheal intubation an... more Background: We aimed to study the associations between pre-and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity. Methods: Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n¼4509). For prehospital intubation, we excluded selfpresenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests. Results: In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio¼1.01; 95% confidence interval, 0.79e1.28; P¼0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio¼0.86; 95% confidence interval, 0.65e1.13; P¼0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P¼0.009 and P¼0.02, respectively), whereas inhospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P¼0.01): inhospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower. Conclusion: The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting. Clinical trial registration: NCT02210221.
The cholinergic nuclei in the basal forebrain innervate frontal cortical structures regulating at... more The cholinergic nuclei in the basal forebrain innervate frontal cortical structures regulating attention. Our aim was to investigate if cognitive test results measuring attention relate to the longitudinal volume change of cholinergically innervated structures following traumatic brain injury (TBI). During the prospective, observational TBIcare project patients with all severities of TBI (n = 114) and controls with acute orthopedic injuries (n = 17) were recruited. Head MRI was obtained in both acute (mean 2 weeks post-injury) and late (mean 8 months) time points. T1-weighted 3D MR images were analyzed with an automatic segmentation method to evaluate longitudinal, structural brain volume change. The cognitive outcome was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses included 16 frontal cortical structures, of which four showed a significant correlation between post-traumatic volume change and the CANTAB test results. The strongest correlation was found between the volume loss of the supplementary motor cortex and motor screening task results (R-sq 0.16, p < 0.0001), where poorer test results correlated with greater atrophy. Of the measured sum structures, greater cortical gray matter atrophy rate showed a significant correlation with the poorer CANTAB test results. TBI caused volume loss of frontal cortical structures that are heavily innervated by cholinergic neurons is associated with neuropsychological test results measuring attention.
Indications and optimal timing for tracheostomy in traumatic brain-injured (TBI) patients are unc... more Indications and optimal timing for tracheostomy in traumatic brain-injured (TBI) patients are uncertain. This study aims to describe the patients' characteristics, timing, and factors related to the decision to perform a tracheostomy and differences in strategies among different countries and assess the effect of the timing of tracheostomy on patients' outcomes. Methods: We selected TBI patients from CENTER-TBI, a prospective observational longitudinal cohort study, with an intensive care unit stay ≥ 72 h. Tracheostomy was defined as early (≤ 7 days from admission) or late (> 7 days). We used a Cox regression model to identify critical factors that affected the timing of tracheostomy. The outcome was assessed at 6 months using the extended Glasgow Outcome Score. Results: Of the 1358 included patients, 433 (31.8%) had a tracheostomy. Age (hazard rate, HR = 1.04, 95% CI = 1.01-1.07, p = 0.003), Glasgow coma scale ≤ 8 (HR = 1.70, 95% CI = 1.22-2.36 at 7; p < 0.001), thoracic trauma (HR = 1.24, 95% CI = 1.01-1.52, p = 0.020), hypoxemia (HR = 1.37, 95% CI = 1.05-1.79, p = 0.048), unreactive pupil (HR = 1.76, 95% CI = 1.27-2.45 at 7; p < 0.001) were predictors for tracheostomy. Considerable heterogeneity among countries was found in tracheostomy frequency (7.9-50.2%) and timing (early 0-17.6%). Patients with a late tracheostomy were more likely to have a worse neurological outcome, i.e., mortality and poor neurological sequels (OR = 1.69, 95% CI = 1.07-2.67, p = 0.018), and longer length of stay (LOS) (38.5 vs. 49.4 days, p = 0.003). Conclusions: Tracheostomy after TBI is routinely performed in severe neurological damaged patients. Early tracheostomy is associated with a better neurological outcome and reduced LOS, but the causality of this relationship remains unproven.
Objectives: To investigate functioning measured with the 12-item World Health Organization Disabi... more Objectives: To investigate functioning measured with the 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0) in patients with mild, moderate and severe traumatic brain injury, and to compare patients' experiences with assessments made by their significant others and by consultant neurologists. Methods: A total of 112 consecutive patients with traumatic brain injury (29 mild, 43 moderate, 40 severe) and their significant others completed a 12item WHODAS 2.0 survey. A neurologist assessed functioning with the International Classification of Functioning, Disability and Health minimal generic set. Results: The total patient and proxy WHODAS 2.0 sum score was rated as severe, and impairments in household tasks, learning, community life, emotional functions, concentrating, dealing with strangers, maintaining friendships, and working ability as around moderate in all 3 severity groups. In standing, walking, washing, and dressing oneself the reported impairments increased from mild in mild traumatic brain injury to moderate in severe traumatic brain injury. A neurologist rated the overall functioning, working ability, and motor activities most impaired in severe traumatic brain injury, while there were no between-group differences in energy and drive functions and emotional functions. Conclusion: Patients with chronic traumatic brain injury perceive a diversity of significant difficulties in activities and participation irrespective of the severity of the injury. We recommend assessing disability in traumatic brain injury with the short and understandable WHODAS 2.0 scale, when planning client-oriented services.
OBJECTIVE: The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, bu... more OBJECTIVE: The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, but recent studies suggest pathology within the nervous system at multiple levels. This study aimed to investigate in detail the contribution of either focal or generalized alterations within the peripheral nervous system (PNS) in the etiopathogenesis of BMS. SUBJECTS AND METHODS: Intraepithelial nerve fiber density (IENFD) of tongue mucosa was assessed in 10 carefully characterized BMS, and the results were compared to 19 age-and gender-matched cadaver controls, 6 with lifetime diabetes. Extensive neurophysiologic and psychophysical examinations of the trigeminal system and distal extremities were performed to profile PNS function in BMS. RESULTS: Patients with BMS had significantly fewer intraepithelial nerve fibers (0,27, s.e. 0,18 mm À1 ; P = 0.0253) than non-diabetic controls (0,92, s.e. 0,15 mm À1). In the subepithelial space, the amount of nerve fibers did not differ between the groups. The majority (9/10) of patients with BMS showed neurophysiologic or psychophysical signs of a more generalized PNS dysfunction. CONCLUSIONS: Our results in neurophysiologically optimally characterized BMS patients confirm that pure focal small fiber neuropathy of the oral mucosa has a role in the pathophysiology of primary BMS. Furthermore, BMS may be related to a more generalized, yet subclinical peripheral neuropathy.
Aim: The aim of this article is to report the findings of a study were: (1) to assess the current... more Aim: The aim of this article is to report the findings of a study were: (1) to assess the current needs of survivors of traumatic brain injury and (2) to assess current service provision for these clients. Design: A questionnaire survey design was used. Sample and setting data were collected from 31 service users and 67 service and 29 education providers in South West England in 2002-03. Results: The findings showed that up to 10 years after the injury, all respondents experienced at least one related health problem and 13 were taking medication for pain and/or depression. Only one had returned to their pre-injury occupation, and only eight had been assessed for return to work or education. Service provision by charitable organizations covered a variety of specific services for this client group, including life skills and leisure activities. Some also offered informal training and help with seeking work. Eight education providers had a total of 42 students with traumatic brain injur...
The distribution of SP receptors was studied both in the normal human brain and in the parkinsoni... more The distribution of SP receptors was studied both in the normal human brain and in the parkinsonian brain by means of tritiated SP. The highest levels of binding were found in the striatal areas and in the NbM. The distribution was similar to that found in laboratory animals in earlier studies. In PD the binding was significantly reduced in the NbM and parietal cortex as compared with controls. The level of SPLI was reduced in both parts of the SN, in the NbM, and in the GPi.
The multidimensional nature of the neglect syndrome constitutes a challenge for clinical assessme... more The multidimensional nature of the neglect syndrome constitutes a challenge for clinical assessments. This study evaluates the sensitivity of different clinical measures to detect neglect and explores ways to evaluate the diversity of the syndrome in a clinical sample. An extensive battery of tests was used to examine aspects of visuospatial, representational, and personal neglect. A total of 31 normal control participants and 34 patients with right hemisphere stroke were examined 16.8 days post-stroke, on average. Of the patients, 24 showed neglect in at least one task. The Random shape cancellation test, Star cancellation, and two line bisection tasks appeared to be the most sensitive tests of visuospatial neglect. Personal neglect and neglect in far space occurred only together with extrapersonal neglect. Besides near space, other spatial aspects of neglect are important to consider in clinical assessments, but standardized methods are needed. In this patient group a minimum of 10 tests were needed to cover various aspects of detection, dissociations, and severity of neglect. A multifactorial approach in clinical testing of neglect is recommended.
There is evidence that the cholinergic system is frequently involved in the cognitive consequence... more There is evidence that the cholinergic system is frequently involved in the cognitive consequences of traumatic brain injury (TBI). We studied whether the brain cholinergic function is altered after TBI in vivo using PET. Cholinergic function was assessed with [methyl-(11)C]N-methylpiperidyl-4-acetate, which reflects the acetylcholinesterase (AChE) activity, in 17 subjects more than 1 year after a TBI and in 12 healthy controls. All subjects had been without any centrally acting drugs for at least 4 weeks. The AChE activity was significantly lower in subjects with TBI compared to controls in several areas of the neocortex (-5.9% to -10.8%, p=0.053 to 0.004). Patients with chronic cognitive symptoms after TBI show widely lowered AChE activity across the neocortex.
The strength of evidence underpinning care and treatment recommendations in traumatic brain injur... more The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. All 71 centers completed the questionnaires. Median concordance rate...
Primary objective: To evaluate the effectiveness of rivastigmine for chronic sequels of traumatic... more Primary objective: To evaluate the effectiveness of rivastigmine for chronic sequels of traumatic brain injury (TBI). Research design: Randomized, placebo-controlled, double-blind crossover trial. Methods and procedures: Of 772 outpatients with TBI treated during 1993-2002, all eligible patients were contacted and 102 patients volunteered. They were randomized to receive either rivastigmine (Exelon) or placebo. The study included two periods with titration to the highest tolerated or maximum dose (12 mg rivastigmine daily) and a maintenance period of 8 weeks, separated by a 4-week washout. Computerized neuropsychological testing and standardized clinical interviews were used to assess the outcome. Main outcomes and results: Sixty-nine patients completed the study and 17 withdrew because of adverse effects. In two measures of computerized testing (subtraction test, p ¼ 0.034 and correct answers in the 10-15 minute vigilance test, p ¼ 0.048) rivastigmine was better than placebo. The clinical interviews did not yield significant results. After the study, 45% of patients considered rivastigmine beneficial compared to 20% with placebo. Conclusions: A weak trend favouring rivastigmine for chronic symptoms of TBI was observed. The clinical significance of the results and the problems in conducting drug trials for chronic TBI symptoms are discussed. Brain Inj Downloaded from informahealthcare.com by Tykslab on 03/25/15 For personal use only. Brain Inj Downloaded from informahealthcare.com by Tykslab on 03/25/15 For personal use only.
Reproducibility of two different methods for quantifying fiber tracts by using a diffusion tensor... more Reproducibility of two different methods for quantifying fiber tracts by using a diffusion tensor imaging (DTI) sequence suitable for clinical magnetic resonance imaging (MRI) protocols was evaluated. DTI of 15 subjects was used to analyze intra-rater and inter-rater reproducibility. Another 10 subjects underwent MRI twice for assessment of between-scan reliability. Ten long association tracts were defined by fiber tracking using inclusion and exclusion regions of interest (ROIs). Whole-tract analysis and tractography-based core analysis were performed, and the effect of fractional anisotropy (FA 0.15/0.30) and turning angle threshold (27°/60°) on reproducibility was evaluated. Additionally, ROI measurements were performed in the core of the tracts. For the tract-based methods, intra-rater and inter-rater reliabilities of FA and mean diffusivity (MD) measurements were excellent. Between-scan reproducibility was good or excellent in 127 of 130 of the measurements. There was no system...
Apparent diffusion coefficient (ADC) values derived from diffusion-weighted magnetic resonance im... more Apparent diffusion coefficient (ADC) values derived from diffusion-weighted magnetic resonance imaging (MRI) can provide information about traumatic changes not visible in conventional MRI. The ADC values in acute traumatic brain injury (TBI) were measured and correlated with initial severity and outcome scores. In this study 22 unselected patients were studied 1 week (mean 7 ± 2 days) after TBI of variable severity. In conventional MRI 7 patients were without visible findings, 15 showed cortical contusions or traumatic axonal injury and 14 healthy subjects served as controls. The ADC values were measured from 46 brain regions away from the visible traumatic changes and compared between the groups. Regional ADC values and the number of abnormal regions were correlated with the Glasgow coma scale (GCS) on arrival in hospital and the Glasgow outcome scale (extended version, GOS-E) at 1 year after injury. The ADC values of TBI patients with and without visible lesions did not show any ...
Posterior cortical atrophy (PCA) is a rare form of degenerative dementia, which is characterized ... more Posterior cortical atrophy (PCA) is a rare form of degenerative dementia, which is characterized by progressive atrophy of occipital and parietal cortical areas. It usually manifests as increasing difficulties of visuoperceptive abilities. Later on, memory and other cognitive functions are involved. Various pathologies have been associated with clinical PCA presentation, but most of the patients with autopsy have had Alzheimer-type pathology. Thus, PCA has been considered to be a rare form of Alzheimer-type dementia with unusual pathological distribution. Here we describe a patient who had a typical clinical course for this syndrome and who showed a positive accumulation of amyloid-beta in posterior areas studied with positron emission tomography.
INTRODUCTION: Neuroinflammation, a key secondary injury mechanism following traumatic brain injur... more INTRODUCTION: Neuroinflammation, a key secondary injury mechanism following traumatic brain injury (TBI), involves humoral and cellular components. The cellular component includes recruitment of haematogenous inflammatory cells (polymorphonuclear leukocytes and monocytes) and the activation of resident innate immune cells (microglia). While measurement of inflammatory mediators in jugular venous blood and brain microdialysate can characterise global and focal inflammation in TBI, they do not provide a means of mapping spatial variations in neuroinflammation across the brain. A recent study used [11C](R)PK11195 positron emission tomography (PET) to demonstrate persistent thalamic inflammation years after TBI, which was related to outcome.1 We have applied [11C](R)PK11195 to map the spatiotemporal patterns of microglial activation in acute moderate/severe TBI. METHODS: Seven patients (Table 1) underwent [11C]PK11195 PET and MR imaging twice at a median (range) of 5 (3 − 11) and 15 (13 − 22) days post TBI with a GE Advance, following an i.v. bolus of 485 (296 – 569) MBq of [11C]PK11195; specific activity ~220 GBq/μmol. Fifty-eight frames of emission data were acquired over 90 minutes post-injection. Arterial blood samples were obtained throughout each PET scan to measure whole blood and plasma radioactivity concentrations, together with the plasma parent fraction.2 Voxel-wise total volume of distribution (VT) was calculated using Logan graphical analysis with a metabolite-corrected plasma input function. [11C](R)PK11195 binding potentials were calculated in core, perilesional oedema, basal ganglia, white matter and in normal appearing areas of the brain. RESULTS: There was substantial inter-subject heterogeniety in the spatiotemporal patterns of microglial activation. While some subjects showed early perilesional and lesional [11C]PK11195 binding that increased over time, in other patients, such early binding disappeared at later time points. Given the past demonstration of persistent thalamic microglial activation [...]
is a clinical neuropsychologist and PhD student with her main research interest being in pediatri... more is a clinical neuropsychologist and PhD student with her main research interest being in pediatric traumatic brain injury. As a clinician she has more than 15 years of experience in rehabilitation of children and youth with TBI along with holistic pediatric rehabilitation program.
Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in ... more Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice. Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries. Results: Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N = 426;20%) and deferred consent (N = 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%). Conclusions: Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers.
Background: We aimed to study the associations between pre-and in-hospital tracheal intubation an... more Background: We aimed to study the associations between pre-and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity. Methods: Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n¼4509). For prehospital intubation, we excluded selfpresenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests. Results: In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio¼1.01; 95% confidence interval, 0.79e1.28; P¼0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio¼0.86; 95% confidence interval, 0.65e1.13; P¼0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P¼0.009 and P¼0.02, respectively), whereas inhospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P¼0.01): inhospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower. Conclusion: The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting. Clinical trial registration: NCT02210221.
The cholinergic nuclei in the basal forebrain innervate frontal cortical structures regulating at... more The cholinergic nuclei in the basal forebrain innervate frontal cortical structures regulating attention. Our aim was to investigate if cognitive test results measuring attention relate to the longitudinal volume change of cholinergically innervated structures following traumatic brain injury (TBI). During the prospective, observational TBIcare project patients with all severities of TBI (n = 114) and controls with acute orthopedic injuries (n = 17) were recruited. Head MRI was obtained in both acute (mean 2 weeks post-injury) and late (mean 8 months) time points. T1-weighted 3D MR images were analyzed with an automatic segmentation method to evaluate longitudinal, structural brain volume change. The cognitive outcome was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses included 16 frontal cortical structures, of which four showed a significant correlation between post-traumatic volume change and the CANTAB test results. The strongest correlation was found between the volume loss of the supplementary motor cortex and motor screening task results (R-sq 0.16, p < 0.0001), where poorer test results correlated with greater atrophy. Of the measured sum structures, greater cortical gray matter atrophy rate showed a significant correlation with the poorer CANTAB test results. TBI caused volume loss of frontal cortical structures that are heavily innervated by cholinergic neurons is associated with neuropsychological test results measuring attention.
Indications and optimal timing for tracheostomy in traumatic brain-injured (TBI) patients are unc... more Indications and optimal timing for tracheostomy in traumatic brain-injured (TBI) patients are uncertain. This study aims to describe the patients' characteristics, timing, and factors related to the decision to perform a tracheostomy and differences in strategies among different countries and assess the effect of the timing of tracheostomy on patients' outcomes. Methods: We selected TBI patients from CENTER-TBI, a prospective observational longitudinal cohort study, with an intensive care unit stay ≥ 72 h. Tracheostomy was defined as early (≤ 7 days from admission) or late (> 7 days). We used a Cox regression model to identify critical factors that affected the timing of tracheostomy. The outcome was assessed at 6 months using the extended Glasgow Outcome Score. Results: Of the 1358 included patients, 433 (31.8%) had a tracheostomy. Age (hazard rate, HR = 1.04, 95% CI = 1.01-1.07, p = 0.003), Glasgow coma scale ≤ 8 (HR = 1.70, 95% CI = 1.22-2.36 at 7; p < 0.001), thoracic trauma (HR = 1.24, 95% CI = 1.01-1.52, p = 0.020), hypoxemia (HR = 1.37, 95% CI = 1.05-1.79, p = 0.048), unreactive pupil (HR = 1.76, 95% CI = 1.27-2.45 at 7; p < 0.001) were predictors for tracheostomy. Considerable heterogeneity among countries was found in tracheostomy frequency (7.9-50.2%) and timing (early 0-17.6%). Patients with a late tracheostomy were more likely to have a worse neurological outcome, i.e., mortality and poor neurological sequels (OR = 1.69, 95% CI = 1.07-2.67, p = 0.018), and longer length of stay (LOS) (38.5 vs. 49.4 days, p = 0.003). Conclusions: Tracheostomy after TBI is routinely performed in severe neurological damaged patients. Early tracheostomy is associated with a better neurological outcome and reduced LOS, but the causality of this relationship remains unproven.
Objectives: To investigate functioning measured with the 12-item World Health Organization Disabi... more Objectives: To investigate functioning measured with the 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0) in patients with mild, moderate and severe traumatic brain injury, and to compare patients' experiences with assessments made by their significant others and by consultant neurologists. Methods: A total of 112 consecutive patients with traumatic brain injury (29 mild, 43 moderate, 40 severe) and their significant others completed a 12item WHODAS 2.0 survey. A neurologist assessed functioning with the International Classification of Functioning, Disability and Health minimal generic set. Results: The total patient and proxy WHODAS 2.0 sum score was rated as severe, and impairments in household tasks, learning, community life, emotional functions, concentrating, dealing with strangers, maintaining friendships, and working ability as around moderate in all 3 severity groups. In standing, walking, washing, and dressing oneself the reported impairments increased from mild in mild traumatic brain injury to moderate in severe traumatic brain injury. A neurologist rated the overall functioning, working ability, and motor activities most impaired in severe traumatic brain injury, while there were no between-group differences in energy and drive functions and emotional functions. Conclusion: Patients with chronic traumatic brain injury perceive a diversity of significant difficulties in activities and participation irrespective of the severity of the injury. We recommend assessing disability in traumatic brain injury with the short and understandable WHODAS 2.0 scale, when planning client-oriented services.
OBJECTIVE: The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, bu... more OBJECTIVE: The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, but recent studies suggest pathology within the nervous system at multiple levels. This study aimed to investigate in detail the contribution of either focal or generalized alterations within the peripheral nervous system (PNS) in the etiopathogenesis of BMS. SUBJECTS AND METHODS: Intraepithelial nerve fiber density (IENFD) of tongue mucosa was assessed in 10 carefully characterized BMS, and the results were compared to 19 age-and gender-matched cadaver controls, 6 with lifetime diabetes. Extensive neurophysiologic and psychophysical examinations of the trigeminal system and distal extremities were performed to profile PNS function in BMS. RESULTS: Patients with BMS had significantly fewer intraepithelial nerve fibers (0,27, s.e. 0,18 mm À1 ; P = 0.0253) than non-diabetic controls (0,92, s.e. 0,15 mm À1). In the subepithelial space, the amount of nerve fibers did not differ between the groups. The majority (9/10) of patients with BMS showed neurophysiologic or psychophysical signs of a more generalized PNS dysfunction. CONCLUSIONS: Our results in neurophysiologically optimally characterized BMS patients confirm that pure focal small fiber neuropathy of the oral mucosa has a role in the pathophysiology of primary BMS. Furthermore, BMS may be related to a more generalized, yet subclinical peripheral neuropathy.
Aim: The aim of this article is to report the findings of a study were: (1) to assess the current... more Aim: The aim of this article is to report the findings of a study were: (1) to assess the current needs of survivors of traumatic brain injury and (2) to assess current service provision for these clients. Design: A questionnaire survey design was used. Sample and setting data were collected from 31 service users and 67 service and 29 education providers in South West England in 2002-03. Results: The findings showed that up to 10 years after the injury, all respondents experienced at least one related health problem and 13 were taking medication for pain and/or depression. Only one had returned to their pre-injury occupation, and only eight had been assessed for return to work or education. Service provision by charitable organizations covered a variety of specific services for this client group, including life skills and leisure activities. Some also offered informal training and help with seeking work. Eight education providers had a total of 42 students with traumatic brain injur...
The distribution of SP receptors was studied both in the normal human brain and in the parkinsoni... more The distribution of SP receptors was studied both in the normal human brain and in the parkinsonian brain by means of tritiated SP. The highest levels of binding were found in the striatal areas and in the NbM. The distribution was similar to that found in laboratory animals in earlier studies. In PD the binding was significantly reduced in the NbM and parietal cortex as compared with controls. The level of SPLI was reduced in both parts of the SN, in the NbM, and in the GPi.
The multidimensional nature of the neglect syndrome constitutes a challenge for clinical assessme... more The multidimensional nature of the neglect syndrome constitutes a challenge for clinical assessments. This study evaluates the sensitivity of different clinical measures to detect neglect and explores ways to evaluate the diversity of the syndrome in a clinical sample. An extensive battery of tests was used to examine aspects of visuospatial, representational, and personal neglect. A total of 31 normal control participants and 34 patients with right hemisphere stroke were examined 16.8 days post-stroke, on average. Of the patients, 24 showed neglect in at least one task. The Random shape cancellation test, Star cancellation, and two line bisection tasks appeared to be the most sensitive tests of visuospatial neglect. Personal neglect and neglect in far space occurred only together with extrapersonal neglect. Besides near space, other spatial aspects of neglect are important to consider in clinical assessments, but standardized methods are needed. In this patient group a minimum of 10 tests were needed to cover various aspects of detection, dissociations, and severity of neglect. A multifactorial approach in clinical testing of neglect is recommended.
There is evidence that the cholinergic system is frequently involved in the cognitive consequence... more There is evidence that the cholinergic system is frequently involved in the cognitive consequences of traumatic brain injury (TBI). We studied whether the brain cholinergic function is altered after TBI in vivo using PET. Cholinergic function was assessed with [methyl-(11)C]N-methylpiperidyl-4-acetate, which reflects the acetylcholinesterase (AChE) activity, in 17 subjects more than 1 year after a TBI and in 12 healthy controls. All subjects had been without any centrally acting drugs for at least 4 weeks. The AChE activity was significantly lower in subjects with TBI compared to controls in several areas of the neocortex (-5.9% to -10.8%, p=0.053 to 0.004). Patients with chronic cognitive symptoms after TBI show widely lowered AChE activity across the neocortex.
The strength of evidence underpinning care and treatment recommendations in traumatic brain injur... more The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. All 71 centers completed the questionnaires. Median concordance rate...
Primary objective: To evaluate the effectiveness of rivastigmine for chronic sequels of traumatic... more Primary objective: To evaluate the effectiveness of rivastigmine for chronic sequels of traumatic brain injury (TBI). Research design: Randomized, placebo-controlled, double-blind crossover trial. Methods and procedures: Of 772 outpatients with TBI treated during 1993-2002, all eligible patients were contacted and 102 patients volunteered. They were randomized to receive either rivastigmine (Exelon) or placebo. The study included two periods with titration to the highest tolerated or maximum dose (12 mg rivastigmine daily) and a maintenance period of 8 weeks, separated by a 4-week washout. Computerized neuropsychological testing and standardized clinical interviews were used to assess the outcome. Main outcomes and results: Sixty-nine patients completed the study and 17 withdrew because of adverse effects. In two measures of computerized testing (subtraction test, p ¼ 0.034 and correct answers in the 10-15 minute vigilance test, p ¼ 0.048) rivastigmine was better than placebo. The clinical interviews did not yield significant results. After the study, 45% of patients considered rivastigmine beneficial compared to 20% with placebo. Conclusions: A weak trend favouring rivastigmine for chronic symptoms of TBI was observed. The clinical significance of the results and the problems in conducting drug trials for chronic TBI symptoms are discussed. Brain Inj Downloaded from informahealthcare.com by Tykslab on 03/25/15 For personal use only. Brain Inj Downloaded from informahealthcare.com by Tykslab on 03/25/15 For personal use only.
Reproducibility of two different methods for quantifying fiber tracts by using a diffusion tensor... more Reproducibility of two different methods for quantifying fiber tracts by using a diffusion tensor imaging (DTI) sequence suitable for clinical magnetic resonance imaging (MRI) protocols was evaluated. DTI of 15 subjects was used to analyze intra-rater and inter-rater reproducibility. Another 10 subjects underwent MRI twice for assessment of between-scan reliability. Ten long association tracts were defined by fiber tracking using inclusion and exclusion regions of interest (ROIs). Whole-tract analysis and tractography-based core analysis were performed, and the effect of fractional anisotropy (FA 0.15/0.30) and turning angle threshold (27°/60°) on reproducibility was evaluated. Additionally, ROI measurements were performed in the core of the tracts. For the tract-based methods, intra-rater and inter-rater reliabilities of FA and mean diffusivity (MD) measurements were excellent. Between-scan reproducibility was good or excellent in 127 of 130 of the measurements. There was no system...
Apparent diffusion coefficient (ADC) values derived from diffusion-weighted magnetic resonance im... more Apparent diffusion coefficient (ADC) values derived from diffusion-weighted magnetic resonance imaging (MRI) can provide information about traumatic changes not visible in conventional MRI. The ADC values in acute traumatic brain injury (TBI) were measured and correlated with initial severity and outcome scores. In this study 22 unselected patients were studied 1 week (mean 7 ± 2 days) after TBI of variable severity. In conventional MRI 7 patients were without visible findings, 15 showed cortical contusions or traumatic axonal injury and 14 healthy subjects served as controls. The ADC values were measured from 46 brain regions away from the visible traumatic changes and compared between the groups. Regional ADC values and the number of abnormal regions were correlated with the Glasgow coma scale (GCS) on arrival in hospital and the Glasgow outcome scale (extended version, GOS-E) at 1 year after injury. The ADC values of TBI patients with and without visible lesions did not show any ...
Posterior cortical atrophy (PCA) is a rare form of degenerative dementia, which is characterized ... more Posterior cortical atrophy (PCA) is a rare form of degenerative dementia, which is characterized by progressive atrophy of occipital and parietal cortical areas. It usually manifests as increasing difficulties of visuoperceptive abilities. Later on, memory and other cognitive functions are involved. Various pathologies have been associated with clinical PCA presentation, but most of the patients with autopsy have had Alzheimer-type pathology. Thus, PCA has been considered to be a rare form of Alzheimer-type dementia with unusual pathological distribution. Here we describe a patient who had a typical clinical course for this syndrome and who showed a positive accumulation of amyloid-beta in posterior areas studied with positron emission tomography.
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