Deep brain stimulation for disorders of consciousness and diminished motivation:A search for awakenings

This thesis deals with patients who are amongst the most severely affected after severe brain injury: those with permanent disorders of consciousness or diminished motivation. The research in this thesis is an attempt to improve consciousness and the general behavioral performance of these patients with the use of experimental interventions, including medication (such as zolpidem), and more invasive procedures, such as deep brain stimulation (DBS). The thesis contains extensive descriptions of the role of the intralaminar thalamus in the arousal regulation system, the importance of recognizing and treating secondary complications after brain injury, such as hydrocephalus, as well as a pathophysiological elaboration on akinetic mutism: a severe disorder of diminished motivation. Moreover, it describes the neurophysiological changes that accompany the paradoxical effects of zolpidem, a sleeping pill that temporarily induces ‘awakenings’ in some patients with severe brain injury. Further, it describes the first clinical and neurophysiological results of an N=6 trial of DBS in patients with a minimally conscious state and shows the importance of recognizing pathological changes from the brain’s ‘physiological baseline’ that seem to disturb normal brain functions. The thesis concludes with a description of the use of moral case deliberation in dealing with research dilemmas in patients with loss of autonomy after severe brain injury

Deep brain stimulation of the central thalamus restores arousal and motivation in a zolpidem-responsive patient with akinetic mutism after severe brain injury

After severe brain injury, zolpidem is known to cause spectacular, often short-lived, restorations of brain functions in a small subgroup of patients. Previously, we showed that these zolpidem-induced neurological recoveries can be paralleled by significant changes in functional connectivity throughout the brain. Deep brain stimulation (DBS) is a neurosurgical intervention known to modulate functional connectivity in a wide variety of neurological disorders. In this study, we used DBS to restore arousal and motivation in a zolpidem-responsive patient with severe brain injury and a concomitant disorder of diminished motivation, more than 10 years after surviving hypoxic ischemia. We found that DBS of the central thalamus, targeted at the centromedian-parafascicular complex, immediately restored arousal and was able to transition the patient from a state of deep sleep to full wakefulness. Moreover, DBS was associated with temporary restoration of communication and ability to walk and eat in an otherwise wheelchair-bound and mute patient. With the use of magnetoencephalography (MEG), we revealed that DBS was generally associated with a marked decrease in aberrantly high levels of functional connectivity throughout the brain, mimicking the effects of zolpidem. These results imply that 'pathological hyperconnectivity' after severe brain injury can be associated with reduced arousal and behavioral performance and that DBS is able to modulate connectivity towards a 'healthier baseline' with lower synchronization, and, can restore functional brain networks long after severe brain injury. The presence of hyperconnectivity after brain injury may be a possible future marker for a patient's responsiveness for restorative interventions, such as DBS, and suggests that lower degrees of overall brain synchronization may be conducive to cognition and behavioral responsiveness

Genetic and physiological dissection of transpiration efficiency in wheat

OBJECTIVE: To determine the incidence and prevalence of facioscapulohumeral muscular dystrophy (FSHD) in the Netherlands. METHODS: Using 3-source capture-recapture methodology, we estimated the total yearly number of newly found symptomatic individuals with FSHD, including those not registered in any of the 3 sources. To this end, symptomatic individuals with FSHD were available from 3 large population-based registries in the Netherlands if diagnosed within a 10-year period (January 1, 2001 to December 31, 2010). Multiplication of the incidence and disease duration delivered the prevalence estimate. RESULTS: On average, 52 people are newly diagnosed with FSHD every year. This results in an incidence rate of 0.3/100,000 person-years in the Netherlands. The prevalence rate was 12/100,000, equivalent to 2,000 affected individuals. CONCLUSIONS: We present population-based incidence and prevalence estimates regarding symptomatic individuals with FSHD, including an estimation of the number of symptomatic individuals not present in any of the 3 used registries. This study shows that the total number of symptomatic persons with FSHD in the population may well be underestimated and a considerable number of affected individuals remain undiagnosed. This suggests that FSHD is one of the most prevalent neuromuscular disorders

Passive movement therapy in patients with moderate to severe paratonia; study protocol of a randomised clinical trial (ISRCTN43069940)

Contains fulltext : 65492.pdf ( ) (Open Access

Nitrogen oxides, regional transport, and ozone air quality: Results of a regional-scale model for the midwestern United States

An overview of the role of NO x in the formation of rural O 3 , regional transport and its potential impact on urban air quality is presented. An analysis of a specific O 3 excursion in southeast Michigan (8-2-90) is performed based on a combined urban and regional-scale model. The regional component of the model represents transport and photochemistry from sources as far away as Texas. Results suggest that rural O 3 and regional transport sensitive to NO x emissions and relatively insensitive to changes in volatile organic carbon (VOC) emissions. This differs from the situation in urban areas, where O 3 is sensitive to both NO x and VOC. Regional transport and upwind NO x emissions have a significant impact on peak O 3 in Detroit. Implications for urban and regional-scale abatement strategies are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43908/1/11270_2004_Article_BF00480817.pd

Awakening after a sleeping pill: restoring functional brain networks after severe brain injury

This data includes the raw EEG data with analysis code and the raw MEG dataset of both the patient as healthy controls from the above described manuscript. For further information, please attend to the methodology section of the article and the README text

Cervical sagittal alignment after different anterior discectomy procedures for single-level cervical degenerative disc disease: randomized controlled trial

Contains fulltext : 179552.pdf (publisher's version ) (Open Access

Awakening after a sleeping pill: restoring functional brain networks after severe brain injury

This data includes the raw EEG data with analysis code and the raw MEG dataset of both the patient as healthy controls from the above described manuscript. For further information, please attend to the methodology section of the article in Cortex and the README text

Comparison of complication rates between umbilical and peripherally inserted central venous catheters in newborns

Item does not contain fulltextOBJECTIVE: To compare the complication rates between umbilical central venous catheters and peripherally inserted central venous catheters in newborns and to investigate whether other variables might increase complication rates. DESIGN: A retrospective observational study. SETTING: A Level III neonatal intensive care unit (NICU). PARTICIPANTS AND SETTING: Newborns (gestational age 24-42 weeks). METHODS: All central venous catheter-related complications were retrospectively analyzed in newborns. The differences in survival rates between the two types of central venous catheters were evaluated using a Kaplan-Meier survival analysis with removal because of complications as the event of interest. RESULTS: In total, 140 umbilical venous catheters and 63 peripherally inserted central catheters were included. There were no significant differences in removals due to complications between the two catheters. The central line-associated bloodstream infections had the highest complication incidence, followed by obstruction, dislocation, leakage, and extravasation. There were no influences of gestational age, birth weight, and the use of subsequent catheters on the complication incidence. CONCLUSION: A high complication incidence resulted in removal of the catheters, but it was not significantly different between the two catheters. The prevention of complications should be an important goal in the daily care of infants in the NICU