Mining Biomarkers Of Epilepsy From Large-Scale Intracranial Electroencephalography

Epilepsy is a chronic neurological disorder characterized by seizures. Affecting over 50 million people worldwide, the quality of life of a patient with uncontrolled epilepsy is degraded by medical, social, cognitive, and psychological dysfunction. Fortunately, two-thirds of these patients can achieve adequate seizure control through medications. Unfortunately, one-third cannot. Improving treatment for this patient population depends upon improving our understanding of the underlying epileptic network. Clinical therapies modulate this network to some degree of success, including surgery to remove the seizure onset zone or neuromodulation to alter the brain\u27s dynamics. High resolution intracranial EEG (iEEG) is often employed to study the dynamics of cortical networks, from interictal patterns to more complex quantitative features. These interictal patterns include epileptiform biomarkers whose detection and mapping, along with seizures and neuroimaging, form the mainstay of data for clinical decision making around drug therapy, surgery, and devices. They are also increasingly important to assess the effects of epileptic physiology on brain functions like behavior and cognition, which are not well characterized. In this work, we investigate the significance and trends of epileptiform biomarkers in animal and human models of epilepsy. We develop reliable methods to quantify interictal patterns, applying state of the art techniques from machine learning, signal processing, and EEG analysis. We then validate these tools in three major applications: 1. We study the effect of interictal spikes on human cognition, 2. We assess trends of interictal epileptiform bursts and their relationship to seizures in prolonged recordings from canines and rats, and 3. We assess the stability of long-term iEEG spanning several years. These findings have two main impacts: (1) they inform the interpretation of interictal iEEG patterns and elucidate the timescale of post-implantation changes. These findings have important implications for research and clinical care, particularly implantable devices and evaluating patients for epilepsy surgery. (2) They provide an analytical framework to enable others to mine large-scale iEEG datasets. In this way we hope to make a lasting contribution to accelerate collaborative research not only in epilepsy, but also in the study of animal and human electrophysiology in acute and chronic conditions

Executive functioning and the interpretation of social information following traumatic brain injury

Traumatic brain injury (TBI) is commonly associated with problems in social functioning. There have been very few studies conducted to elucidate the specific contribution of cognitive deficits to these problems. Previous studies have suggested that executive impairment might be related to poor social decision-making. This study aimed to examine whether TBI was related to problems with the interpretation of social information and to what extent any problems were associated with executive impairment. The performance of seventeen TBI non-aphasic participants was compared to seventeen healthy control group participants matched in age, sex and NART IQ on neuropsychological tests of executive function, theory-of-mind-type social comprehension tasks and three real- life-type social tasks involving the interpretation of social information. The social interpretation tasks consisted of a pragmatic judgment task, a social skill judgment task and a conversation judgment task. The first two tasks presented a series of short written social interactions between pairs of characters. It was necessary to rate alternative verbal responses made by one character, which varied in their degree of context appropriateness and skill. The third task involved judging the manner and para-linguistic features of characters in an audible conversation. The TBI group performed more poorly on the pragmatic judgment and social skill judgment tasks. They demonstrated poor inferential sensitivity by failing to differentiate adequately between alternative responses. They were also significantly impaired on the measures of attention, executive function and theory-of-mind-type social comprehension, compared to the Control group. It was argued that difficulty appreciating the appropriateness and skilfulness of responses reflected poor inhibitory control resulting from deficits in executive functioning. Despite a lack of correlational evidence to support an executive explanation, this was considered more plausible to an account in terms of selective theory of mind impairment. TBI group performance on the conversation judgment task was generally similar to the Control group. They judged the manner of the characters as accurately as the Control group. However, they appeared less sensitive to the presence of para-linguistic features. It was speculated that this might have been due to poor attention or difficulties retaining and retrieving information. Overall, the findings suggest that there is a need for further research examining the interpretation of social information in TBI patients. The implications for rehabilitation were discussed

Participation and Well Being Among Children and Youth With Childhood Onset Disabilities

Participation, defined as involvement in life situations, is important for children’s health and development. This Special Issue advances the knowledge about participation interventions and outcomes for children with disabilities in different settings and includes the perspectives of clinicians, families, and children. This is a collection of research from across the globe that advances knowledge in the following areas: - Participation interventions; - Measurement/assessment of participation outcomes; - Participation of special populations (i.e., ABI, ADHD, and ASD); and - Impact of participation on health and well being

Mortality from External Causes and Behavioral Mechanisms : An examination of data from low- and middle-income countries

External causes of mortality are among the leading causes of mortality, especially in low- and middle-income countries. External causes of mortality disproportionately affect youth and young adults, including those who are economically active. The aim of the following study series was to investigate trends and demographic associations of the injury-related mortality burden and suicidal behavior in low- and middle-income countries. Study I examined trends of external causes of mortality in Seychelles over a period of 30 years using civil registration data. At least three-quarters of injury deaths occurred among males. The leading causes of mortality among males was drowning, followed by road traffic injuries; and other unintentional injuries among females. The injury mortality declined over time; however, the injuries from road traffic crashes increased, especially among males. Study II analyzed trends of traumatic brain injury (TBI) related mortality in Seychelles over a span of 30 years using civil registration data. Males were more likely to die from TBI related injuries. TBIs contributed to one in five deaths from all the recorded external causes. Road traffic crashes were the leading mechanism of TBI related mortality. Study III estimated the prevalence of suicidal behavior and the associated contextual factors among adolescents in low- and middle-income countries using the Global School-based Student Health Survey data. Ten to eleven percent of adolescents had considered suicide, made a suicide plan, or attempted suicide in each case. The lowest prevalence was reported in the South East Asian region, while a higher prevalence was recorded in the low-income country regions of the Americas. The findings imply that effective policies tailored for low- and middle-income countries are required to reduce the high rates of injury mortality. Reducing injury mortality will contribute towards each respective economy by minimizing the losses of income faced by the economically active age groups, which will in turn be beneficial for the countries.Ulkoiset kuolinsyyt ovat nuorten aikuisten merkittävimpiä kuolinsyistä matala- ja keskituloisissa maissa. Tässä väitöstutkimuksessa tutkittiin tapaturmaisten vammojen aiheuttaman kuolleisuusuuden ja itsemurhakäyttäytymisen ilmaantuvuuden muutoksia matala- ja keskituloisissa maissa. Tutkimuksessa I tutkittiin ulkoisten kuolinsyiden kehityssuuntia Seychellien tasavallassa 30 vuoden ajanjaksolla hyödyntäen väestöpohjaisia rekistereitä. Tapaturmien osuus kaikista kuolemista koko väestössä oli 8,5 %. Miesten kuolemat kattoivat lähes 3/4 kaikista tapaturmaisista kuolemantapauksista. Miehillä yleisin kuolinsyy oli hukkuminen, ja naisilla muut tahattomat vammat. Koko väestössä tapaturmaiset kuolemantapaukset vähenivät tarkasteluajanjakson aikana. Tutkimuksessa II tutkittiin tapaturmaisten aivovammojen aiheuttamien kuolemantapauksien määrien kehityssuuntia Seychellien tasavallassa 30 vuoden ajanjaksolla käyttäen väestöpohjaisia rekistereitä. Miehet kuolivat naisia todennäköisemmin aivovammoihin ja niihin liittyviin muihin vammoihin. Aivovammat aiheuttivat joka viidennen kuoleman kaikista kuolemista, joissa oli ulkoinen syy. Tieliikenneonnettomuudet olivat aivovammojen aiheuttamien kuolemien yleisin mekanismi. Tutkimuksessa III tutkittiin itsemurhakäyttäytymisen esiintyvyyttä ja siihen liittyviä tekijöitä eräiden matala- ja keskituloisten maiden nuorten keskuudessa hyödyntäen Global School Health Survey -aineistoa. 10–11 % nuorista oli harkinnut itsemurhaa, tehnyt itsemurhasuunnitelman tai yrittänyt itsemurhaa. Alhaisin esiintyvyys havaittiin Kaakkois-Aasian alueella, kun taas korkein esiintyvyys Väli- ja Etelä-Amerikan matalatuloisten maiden alueilla. Tulokset osoittavat, että matala- ja keskituloisille maille räätälöityjä käytäntöjä tarvitaan tapaturmakuolleisuuden vähentämiseksi. Tapaturmakuolleisuuden tehokas vähentäminen vähentää työikäisten ikäryhmien menetettyjä työvuosia ja tuottaa merkittäviä taloudellisia säästöjä

Small vessel disease lesion type and brain atrophy: The role of co‐occurring amyloid

Introduction: It is unknown whether different types of small vessel disease (SVD), differentially relate to brain atrophy and if co‐occurring Alzheimer's disease pathology affects this relation. / Methods: In 725 memory clinic patients with SVD (mean age 67 ± 8 years, 48% female) we compared brain volumes of those with moderate/severe white matter hyperintensities (WMHs; n = 326), lacunes (n = 132) and cerebral microbleeds (n = 321) to a reference group with mild WMHs (n = 197), also considering cerebrospinal fluid (CSF) amyloid status in a subset of patients (n = 488). / Results: WMHs and lacunes, but not cerebral microbleeds, were associated with smaller gray matter (GM) volumes. In analyses stratified by CSF amyloid status, WMHs and lacunes were associated with smaller total brain and GM volumes only in amyloid‐negative patients. SVD‐related atrophy was most evident in frontal (cortical) GM, again predominantly in amyloid‐negative patients. / Discussion: Amyloid status modifies the differential relation between SVD lesion type and brain atrophy in memory clinic patients

Staff ratings of challenging behaviour in an acquired brain injury population: evaluating the usefulness of screening measures

Current literature on sequelae of acquired brain injury reveals that behavioural disturbances such as physical and verbal aggression and disinhibited behaviour present a substantial barrier to community re-integration following severe brain injury. This study applies the concept of 'challenging behaviour', originally applied to people with learning disabilities, to behavioural disturbance following acquired brain injury. Definition of challenging behaviour, assessment, intervention, and impact on carers are discussed. Standardised measures of challenging behaviour are reviewed.The study has two aims. Firstly, to investigate the degree of shared understanding of the concept of challenging behaviour within a group of staff working in a specialist unit for people with behavioural disturbances following acquired brain injury. Twenty-eight members of staff (21 nurses and 7 other professional staff) completed questionnaires, consisting of four brief case vignettes. Each vignette was rated on five-point scales for important defining aspects of challenging behaviour: overall management difficulty, threat to the physical safety of the patient and others, and impact on the patients' access to community facilities. Results were analysed for agreement between raters, taking consideration of demographic variables.Secondly, the usefulness of screening measures in application to challenging behaviour was evaluated within the same unit. The measures chosen were the Agitated Behaviour Scale (Corrigan 1989) and the Checklist of Challenging Behaviour (Harris et. al. 1994). Three members of staff (2 trained nurses and one other member of therapeutic staff) rated each patient's behaviour during the preceding week. A total of 22 patients were assessed, some on more than one occasion, and results examined for inter-rater reliability and concordance with clinical records. In addition, the behavioural profile of this clinical population is delineated. The application of standardised screening measures in general to challenging behaviour, methodological issues and future research implications are discussed

Is There Chronic Brain Damage in Retired NFL Players? Neuroradiology, Neuropsychology, and Neurology Examinations of 45 Retired Players

BACKGROUND: Neuropathology and surveys of retired National Football League (NFL) players suggest that chronic brain damage is a frequent result of a career in football. There is limited information on the neurological statuses of living retired players. This study aimed to fill the gap in knowledge by conducting in-depth neurological examinations of 30- to 60-year-old retired NFL players. HYPOTHESIS: In-depth neurological examinations of 30- to 60-year-old retired players are unlikely to detect objective clinical abnormalities in the majority of subjects. STUDY DESIGN: A day-long medical examination was conducted on 45 retired NFL players, including state-of-the-art magnetic resonance imaging (MRI; susceptibility weighted imaging [SWI], diffusion tensor imaging [DTI]), comprehensive neuropsychological and neurological examinations, interviews, blood tests, and APOE (apolipoprotein E) genotyping. LEVEL OF EVIDENCE: Level 3. METHODS: Participants\u27 histories focused on neurological and depression symptoms, exposure to football, and other factors that could affect brain function. The neurological examination included Mini-Mental State Examination (MMSE) evaluation of cognitive function and a comprehensive search for signs of dysarthria, pyramidal system dysfunction, extrapyramidal system dysfunction, and cerebellar dysfunction. The Beck Depression Inventory (BDI) and Patient Health Questionnaire (PHQ) measured depression. Neuropsychological tests included pen-and-paper and ImPACT evaluation of cognitive function. Anatomical examination SWI and DTI MRI searched for brain injuries. The results were statistically analyzed for associations with markers of exposure to football and related factors, such as body mass index (BMI), ethanol use, and APOE4 status. RESULTS: The retired players\u27 ages averaged 45.6 +/- 8.9 years (range, 30-60 years), and they had 6.8 +/- 3.2 years (maximum, 14 years) of NFL play. They reported 6.9 +/- 6.2 concussions (maximum, 25) in the NFL. The majority of retired players had normal clinical mental status and central nervous system (CNS) neurological examinations. Four players (9%) had microbleeds in brain parenchyma identified in SWI, and 3 (7%) had a large cavum septum pellucidum with brain atrophy. The number of concussions/dings was associated with abnormal results in SWI and DTI. Neuropsychological testing revealed isolated impairments in 11 players (24%), but none had dementia. Nine players (20%) endorsed symptoms of moderate or severe depression on the BDI and/or met criteria for depression on PHQ; however, none had dementia, dysarthria, parkinsonism, or cerebellar dysfunction. The number of football-related concussions was associated with isolated abnormalities on the clinical neurological examination, suggesting CNS dysfunction. The APOE4 allele was present in 38% of the players, a larger number than would be expected in the general male population (23%-26%). CONCLUSION: MRI lesions and neuropsychological impairments were found in some players; however, the majority of retired NFL players had no clinical signs of chronic brain damage. CLINICAL RELEVANCE: These results need to be reconciled with the prevailing view that a career in football frequently results in chronic brain damage

An evaluation of the palliative care unit at Groote Schuur Hospital

Background: Patients often present to the Emergency Department (ED) at the end of life. Caring for these patients present a unique set of challenges, and often the patients' and families' needs are at odds with the pervasive rescue-oriented ED culture. A potential solution to this problem is an Acute Palliative Care Unit. Groote Schuur Hospital opened such a unit in April 2011, managed by the ED staff. This kind of service was not available in this tertiary, academic state hospital prior to that. Objectives: This study aimed to evaluate aspects of care at the Groote Schuur Hospital Palliative Care unit by designing a questionnaire based on the Liverpool Care Pathway assessing elements of care, describing the population admitted demographically, recording outcomes and making recommendations based on the findings. Methods: A retrospective folder review was completed on all patients who were admitted to the unit between April 2011 and May 2013. Data was collected onto an Excel spreadsheet, and was analysed using the SmallStata 13 software package. Demographic data collected included sex, age, area from which the referral came, diagnosis, length of stay and outcomes. Data on care were grouped into physical care, psychological care, spiritual care, communication skills and bereavement care. Results: 176 folders were identified. 167 were reviewed (nine were missing). Nine folders did not meet inclusion criteria. 158 folders were included in the study. The vast majority of patients were admitted from home via the ED. Mean age was 59.49 years (95% CI 56.76 – 61.53). Median length of stay was 25 hours (IQR 7-47). 97 patients had palliative care needs in the absence of malignancy, 60 had cancer. 111 (70.7%) patients died in the unit, 5 (3.18%) died en route to the unit, 16 (10.19%) went home, 8 (5. 1%) were referred back to other specialities and 17 (10.83%) were referred to step down facilities. 96% of patients had their medication adjusted, and 128 (81.53%) were commenced on syringe drivers. Morphine, haloperidol and hyoscine butyl bromide were the commonest prescribed medicine in the syringe driver. None of the patients had an official "Do Not Resuscitate" (DNR) form completed, but more than 75% of patients had a note or clear proxy measures indicating that resuscitation is not indicated. Difficulty with communication was present in 8 (5.26%) patients and 10 (6.58%) families. Less than 15% of patients had documented psychological support and less than 30% had documented spiritual care. Bereavement care was also poorly documented. Conclusion: This study described the demographics of, and evaluated the care offered in the Groote Schuur End-of-Life unit. Much of the care is comparable to current recommendations, but there is concern that symptoms may be underestimated in the absence of formal tools. Recommendations include using different terminology w.r.t. the unit, establishing a consulting and outpatient service based at the hospital, implementing formal symptom assessment tools, implementing the formal policy w.r.t. DNR orders, and improved overall documentation. There is scope for further research on interventions such as this one, especially on its impact on staff and its cost-effectiveness. This model of care achieves care comparable to current global recommendations in end-of-life care and can be implemented in similarly resource-restricted contexts