Thesis (doctoral)--Munich, 1934. / Includes bibliographical references (p. 19).

A small subset of individuals that have experienced mild traumatic brain injury (mTBI) may experience persistent cognitive deficits more than a year following the head injury. Neuroimaging studies reveal structural and functional changes in frontal areas of the brain, exacerbated when loss of consciousness is experienced, and indicate that these changes may be progressive in nature for some people. Social support and social participation have, however, been suggested to confer cognitive reserve - neurocognitive protection against cognitive decline. Analyses were run on Canadian Longitudinal Study on Aging (CLSA) neuropsychological data, consisting of individuals who experienced mTBI with loss of consciousness (n = 536 for less than 1 minute, and n = 435 for unconsciousness between 1 and 20 minutes) more than a year prior, and 13,163 no-head injury comparisons. These same individuals were re-assessed three years later. The results presented in this thesis suggest that at a year or more after a single mTBI with loss of consciousness, a small subset of individuals are more likely to be impaired on prospective memory and other executive functioning tasks, relative to comparisons. In addition, when examined at three-year follow-up, those who experienced mTBI with longer duration of unconsciousness were more likely to exhibit cognitive decline relative to those who experienced less unconsciousness or comparisons. Moreover, greater social participation over the past year, and more perceived social support were predictive of lessened cognitive deterioration in those individuals.

Patients presenting with an abrupt loss of postural control are commonly said to have had ‘collapse?cause’. This is a common presentation, accounting for up to 6% of emergency department cases, and 3% of hospital admissions. However, collapse?cause is a ‘catch-all’ term and there are many different causes which include falls, transient ischemic attacks, cerebrovascular accidents, road traffic accidents, metabolic abnormalities, intoxication, and transient loss of consciousness, (TLOC or ‘blackout’). A majority of patients fall into the latter category. Where TLOC has occurred, the causes are syncope, epilepsy and psychogenic blackouts. The clinical features of these three conditions can often be similar, albeit with subtle differences. A wide variation exists in the way such patients are assessed, investigated and managed, who manages them and where. There is an absence of simple clinical tools for assessment, poor risk stratification, inappropriate and overuse of investigations. Hospitalisation is often unnecessary and misdiagnoses are common. In this thesis, the problem of TLOC has been addressed in four projects. Section 1 (Chapter II): reports a simple new risk stratification scheme for patients presenting with TLOC, assessed in a specialist nurse lead, cardiologist supervised (SP), Rapid Access Blackouts Triage Clinic - RABTC. Frequently, after triage, a patient may be deemed to be at low risk, but blackouts continue, the cause remains unclear, and conventional tests, have been unhelpful. In Chapter III, we describe the option of investigating such patients by long term (up to 3 years) ECG monitoring using an implantable loop recorder (ILR). In order to address the specific question of misdiagnosis of epilepsy where convulsive syncope might be the true diagnosis, the REVISE Study- REVeal in the Investigation of Syncope and Epilepsy was undertaken, which is described in Chapter IV. Lastly, convulsive syncope is the likely explanation for a misdiagnosis in patients diagnosed with epilepsy, but the incidence of cardiac disease in patients with brain injury and epilepsy is unknown. Therefore a cohort of patients in a residential epilepsy centre was studied. In this setting, residents typically had a history of brain injury and suffered from recurrent epileptic seizures. The findings of cardiology assessment are presented in Section 4 (Chapter V).

Blast-related mild traumatic brain injury (mTBI) is a common injury among Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans due to the frequent use of improvised explosive devices (IEDs). A significant minority of veterans with blast-related mTBI complain of postconcussion symptoms (PCS) and cognitive difficulties, even years after the injury. Studies have suggested that these behavioral sequelae are primarily linked to mental health disorders such as posttraumatic stress disorder (PTSD). However, mTBI is associated with neural changes and the impact of these changes on behavioral sequelae is unclear. As such, this dissertation had three goals. First, this dissertation assessed whether the severity of PCS in blast-exposed individuals is associated with the extent of mTBI-related neural injury. Results revealed that individuals with mTBI with loss of consciousness (LOC) had significantly more white matter abnormalities than no-TBI controls and that these white matter abnormalities were spatially variable across individuals. Importantly, the extent of white matter abnormality was associated with physical PCS severity and mediated the relationship between mTBI with LOC and physical PCS. Second, this dissertation examined whether these white matter abnormalities were also associated with overall cognitive impairment. In light of the observed variability in white matter injury, a measure of overall cognitive status that takes into account heterogeneity of cognitive impairment was used. Results showed that the extent of white matter abnormality was associated with cognitive status and mediated the relationship between mTBI with LOC and cognitive impairment. Third, this dissertation examined performance and brain function in the context of an experimental measure of cognitive control known to be sensitive to residual effects of mTBI. Results revealed that although behavioral performance was similar across groups, the mTBI group had enhanced functional connectivity between brain networks important for task performance, suggesting a potential compensatory mechanism in mTBI. Together, the findings of this dissertation suggest that mTBI is associated with structural and functional connectivity alterations years after the injury. Further, this dissertation suggests that whereas structural connectivity changes may have negative behavioral consequences, changes in functional connectivity may serve as a compensatory mechanism for successful performance.

No description available.

Purpose/Statement of Problem: Disorders of Consciousness (DoC) are a group of disorders encompassing Coma, Unresponsive Wakefulness Syndrome (UWS), and Minimally Conscious State. These disorders are characterized by altered or absent alertness and consciousness and inability to follow commands or participate in daily activities or function. DoC can be caused by a multitude of etiologies including trauma, stroke, tumors, metabolic disarray, and many others. Individuals with severe DoC are profoundly functionally and cognitively impaired, and frequently require extensive rehabilitation in order to return to their prior level of function. Additionally, a category has recently been discovered within the umbrella of DoC called Cognitive Motor Dissociation (CMD), in which individuals may show no outward signs of the ability to follow commands but can be seen to respond appropriately to commands when monitored by Electroencephalography (EEG). The current standard of rehabilitative care for individuals with severe DoC is minimal. There are no clear guidelines for rehabilitation of these individuals, particularly in the acute stage. Rehabilitation is often initiated once individuals are awake and able to follow commands, despite evidence that earlier intervention (particularly in the form of stimulation) may accelerate recovery. In this retrospective study, we had three primary aims and one case study. The first aim was to characterize the time frame in which a cohort of individuals with severe DoC received therapy and whether the timeframe in which they received therapy was appropriate. The second aim was to retrospectively determine which therapy and demographics factors could predict better short- and long-term outcomes. The third aim was to determine whether the presence of CMD had a mediating effect on therapy. Finally, the case study was intended to determine safety of a prospective study recruiting individuals extremely early after admission for a standardized stimulation intervention. Procedures and Methods: This study was a retrospective analysis of data from a cohort of individuals who were recruited to participate in multiple studies of consciousness in the neurological intensive care unit (NICU) in an academic medical center in New York City between 2014 and 2021, heretofore referred to as the parent study. All individuals had a severe DoC, were connected to EEG, had no previous history of brain injury, and were tested for presence of CMD. Charts were examined to determine whether individuals could have received therapy earlier. Regression modeling was used to determine the effect of various therapy factors (such as timing, volume, frequency, and therapy content) as well as demographics data on a variety of short term and long-term outcome measures. These outcome measures included scores on the Coma Recovery Scale-Revised, scores on the AM-PAC “6 Clicks” Basic Mobility and Daily Activity short forms, recovery of active participation in therapy, discharge destination, and Glasgow Outcomes Scale-Extended scores. Analyses were also performed on the individual effect of each therapy variable on the effect of CMD status, and on the overall effect of CMD status on outcomes. Results: Thirty-eight of the fifty eight (65.52%) individuals in this cohort who received therapy after the median day received for the cohort could have safely received therapy earlier in the form of a standardized stimulation protocol. Multiple therapy variables were implicated in both short- and long-term outcomes. More specifically, therapy frequency, therapy volume, CMD status, sitting at edge of bed, and age were all implicated in both short- and long-term outcomes. Therapy timing was not an independent predictor for any outcomes but was significantly associated with therapy frequency. Therapy frequency was an independent predictor of multiple outcomes including discharge destination, Basic Mobility scores, and GOS-E scores. Sitting at the edge of the bed was an independent predictor of Daily Activity Score, and all therapy variables except timing were independent predictors of change in Basic Mobility Score. CMD status had a modulatory effect on multiple therapy variables (variable based on outcome) and was an independent predictor of long-term outcomes. Conclusions: Individuals with severe DoC were an underserved population from a therapy perspective. With the current standard of care, individuals with severe DoC frequently overlooked in favor of those who are more able to participate in active therapy. Analyses performed in this study indicated that individuals with severe DoC could a.) safely receive therapy sooner, b.) benefit from increased therapy frequency and specific modes of therapy, c.) could make excellent functional progress and d.) might have performed better with therapy if they had CMD. These results indicate that individuals with severe DoC might benefit earlier and more consistent therapy to maximize their chances of functional recovery.