Resting state fMRI reveals a default mode dissociation between retrosplenial and medial prefrontal subnetworks in ASD despite motion scrubbing

In resting state functional magnetic resonance imaging (fMRI) studies of autism spectrum disorders (ASDs) decreased frontal-posterior functional connectivity is a persistent finding. However, the picture of the default mode network (DMN) hypoconnectivity remains incomplete. In addition, the functional connectivity analyses have been shown to be susceptible even to subtle motion. DMN hypoconnectivity in ASD has been specifically called for re-evaluation with stringent motion correction, which we aimed to conduct by so-called scrubbing. A rich set of default mode subnetworks can be obtained with high dimensional group independent component analysis (ICA) which can potentially provide more detailed view of the connectivity alterations. We compared the DMN connectivity in high-functioning adolescents with ASDs to typically developing controls using ICA dual-regression with decompositions from typical to high dimensionality. Dual-regression analysis within DMN subnetworks did not reveal alterations but connectivity between anterior and posterior DMN subnetworks was decreased in ASD. The results were very similar with and without motion scrubbing thus indicating the efficacy of the conventional motion correction methods combined with ICA dual-regression. Specific dissociation between DMN subnetworks was revealed on high ICA dimensionality, where networks centered at the medial prefrontal cortex and retrosplenial cortex showed weakened coupling in adolescents with ASDs compared to typically developing control participants. Generally the results speak for disruption in the anterior-posterior DMN interplay on the network level whereas local functional connectivity in DMN seems relatively unaltered

Epilepsy in young adulthood : medical, psychosocial and functional aspects

The aim of this thesis was to describe the medical, cognitive and psychosocial consequences of epilepsy in young adulthood. Four studies were carried out with this patient group. The first two papers were based on a follow-up study regarding young adults with epilepsy that investigated medical and psychosocial aspects and compared the present results with those five years earlier. We then conducted focus group interviews with young adults with epilepsy and subjective cognitive decline to assess the deeper meaning of living with epilepsy accompanied by cognitive difficulties. In the fourth study we studied cognitive dysfunction further, choosing the language function in young adults with epilepsy. We firstly examined whether language impairments were associated to functional brain alterations and secondly related the language performance to demographics, clinical data, Quality of Life (QoL) and self-esteem. The five-year follow up of 97 young adults with uncomplicated epilepsy revealed no improvement regarding seizure frequency or side effects from anti-epileptic drugs (AEDs) over time, even though many new-generation AEDs had been established during this period. During the study period 21% had recovered from epilepsy, Seizure frequency among those who still had epilepsy had not improved, and 42% had experienced seizures during the past year. New-generation anti-epileptic drugs (AEDs) had been introduced to PWE, especially to women. There is still need for new and more effective treatment options for this group in the future. It is essential to find alternative approaches to develop better treatment options for this group in the future. However QoL was normal compared to the general population, indicating that new options regarding treatment can have made an impact. Lower QoL was correlated to high seizure frequency and to cognitive side effects. Self-esteem and Sence of Coherence were impaired compared to the situation at adolescence. Self-esteem was correlated to seizure frequency and to side-effects of antiepileptic drugs. Sence of Coherence was not correlated to epilepsy-related factors in the same way as QoL, but mirrored the phenomenon of epilepsy. The qualitative study showed that the consequences of epilepsy are not only restricted to the consequences of seizures, but also concerns many other aspects of life. The interviews revealed four themes: “affecting the whole person“, “influencing daily life”, ”affecting relations” and ”meeting ignorance in society”. Another important factor was language function; when one loses some language ability, this gives a feeling of losing one’s capability. The fourth study examined language by neuropsychological methods and correlated this function to brain activation measured by fMRI. Language functions measured in verbal fluency and abstract language comprehension were impaired in participants with both generalized epilepsy and epilepsy of focal onset. Age at onset of epilepsy and education are the most important factors correlating to language function. An additional factor that impacts abstract language comprehension is the frequency of convulsive seizures, while use of topiramate /zonisamide affect verbal fluency negatively. QoL was not correlated to language impairments, but for patients with focal onset seizures there was a correlation between self-esteem and abstract language comprehension. The fMRI investigation revealed altered activity during language tasks in participants with epilepsy compared to controls. In epilepsy with focal seizures originating in the left hemisphere, we found increased bilateral activation of supporting areas, in the anterior mid-cingulate cortex and the anterior ventral insulae, indicating a compensational functional reorganization. In generalized epilepsy, the functional language network showed an imbalance, as this group expressed an inadequate suppression of activation in the anterior temporal lobe during semantic processing. Subtle language impairment can, even if it does not occur in everyday dialogue, be of importance and have consequences for the person affected. The negative consequences of language decline must be addressed in people with epilepsy of different etiology. Young adults with epilepsy are still substantially affected by the condition. The consequences are not only restricted to the seizures, but concern many aspects of life and there is a great need for new treatment options for this group in the future

Epilepsy and violence: case series concerning physical trauma in children of persons with epilepsy

Historically, epilepsy has been associated with violence, but more recent studies have emphasized genetic and psychosocial factors as more important. The case series presented here aim to highlight the difficult situation the affected children are in. We report on three cases when children have been traumatized and, in one case, even been killed by their parent who was diagnosed with epilepsy. In the first case, we describe a woman with juvenile myoclonic epilepsy who was sentenced to forensic psychiatry care for killing her child. She lived under difficult psychosocial circumstances and a suicide attempt contributed to what happened. The second case describes a man with post-traumatic seizures who was sentenced for child abuse. Ictal or postictal violence was considered in these two cases but a causal link between the violence and epilepsy has not been established. In the third case, we describe a woman with focal epilepsy and psychogenic non-epileptic seizures (PNESs). Her child was hurt and frightened in relation to violent seizures, which were regarded as PNESs. This case series demonstrates that children of parents with epilepsy can be in a vulnerable situation. No causality has been established between the seizures and these events, so consequently other factors such as psychosocial stress, low cognitive function, and a suicide attempt must also be considered as important. When a child is hurt by a parent with epilepsy the patient must be closely examined to determine the role of the seizures. Children can also be affected by PNESs. It is essential to notice especially those children of parents with epilepsy who live under difficult psychosocial circumstances and offer extra support when necessary

ISBN 978-91-7519-893-4

medical, psychosocial an

Being parents with epilepsy: thoughts on its consequences and difficulties affecting their children

Objective: Parents with epilepsy can be concerned about the consequences of epilepsy affecting their children. The aim of this paper is to describe aspects of what it means being a parent having epilepsy, focusing the parents perspectives and their thoughts on having children. Methods: Fourteen adults aged 18-35 years with epilepsy and subjective memory decline took part in focus-group interviews. The interviews were conducted according to a semi-structured guideline. Material containing aspects of parenthood was extracted from the original interviews and a secondary analysis was done according to a content-analysis guideline. Interviews with two parents for the Swedish book Leva med epilepsi [To live with epilepsy] by AM Landtblom (Stockholm: Bilda ide; 2009) were analyzed according to the same method. Results: Four themes emerged: (1) a persistent feeling of insecurity, since a seizure can occur at any time and the child could be hurt; (2) a feeling of inadequacy - of not being able to take full responsibility for ones child; (3) acknowledgment that ones children are forced to take more responsibility than other children do; and (4) a feeling of guilt - of not being able to fulfill ones expectations of being the parent one would like to be. Conclusion: The parents with epilepsy are deeply concerned about how epilepsy affects the lives of their children. These parents are always aware that a seizure may occur and reflect on how this can affect their child. They try to foresee possible dangerous situations and prevent them. These parents were sad that they could not always take full responsibility for their child and could not live up to their own expectations of parenthood. Supportive programs may be of importance since fear for the safety of the child increases the psychosocial burden of epilepsy. There were also a few parents who did not acknowledge the safety issue of their child - the authors believe that it is important to identify these parents and provide extra information and support to them.Funding Agencies|Cyberonics; Eisai; GlaxoSmithKline; Grunenthal; UCB</p

Predictors of Early Neurological Deterioration and Functional Outcome in Acute Ischemic Stroke : The Importance of Large Artery Disease, Hyperglycemia and Inflammatory Blood Biomarkers

Background: Early neurological deterioration (END) in acute ischemic stroke (AIS) can be associated with poor outcome. The aim of this study was to investigate the association between infarction subtypes, biomarkers and END, and to identify patients with risk of unfavorable functional outcome.Materials and Methods: This prospective study enrolled 101 patients with AIS. Neurological status was evaluated according to NIHSS at acute onset, on days 2, 3, and 90. END was defined as &amp;gt;= 2-point increase of NIHSS within 72 hours. Functional outcome was assessed using NIHSS and the modified Rankin Scale (mRS) at day 90.Results: END was observed in 20, 8%. Patients with large artery disease had higher risk of developing END compared with patients with cardioembolism or small vessel disease (p &amp;lt;0.01). Significant higher blood glucose level and leukocytes were observed in the END group. Patients with END had higher scores of mRS at day 90 (p &amp;lt;0.01). Levels of NSE, IL-6, hsCRP and NT-proBNP were higher in the patients with unfavorable compared with favorable functional outcome.Conclusion: Large artery disease, high blood glucose and leukocytes levels are associated with END. Elevated levels of blood markers NSE, IL-6, HsCRP and NT-proBNP indicate poor functional outcome at 90 days after AIS. These patients must be identified and be offered treatment immediately in order to improve the functional outcome after AIS.Funding Agencies|Faculty of Medicine and Health Sciences at Link?ping University; Faculty of Medicine and Health Sciences at Linkping University; County Council of Ostergotland and Linkoping University Hospital [LIO-799111, LIO-941169]; Henry and Ella Margareta Stahl Foundation [LIO-858051, LIO-940688]; STROKE Riksforbundet</p

Experiences of being treated with autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: A qualitative interview study.

BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) is increasingly used as a treatment for aggressive multiple sclerosis (MS) and has the potential to induce long-term remission and resolution of disease activity. Despite the extensive research on treatment outcome after AHSCT, the experience of living with MS after AHSCT has not been previously described in the scientific literature. The aim of this study was to explore long-term lived experience of people with MS treated with AHSCT.Methods and findingsTo exclude selection bias, all persons treated with AHSCT for MS at Uppsala University Hospital, Sweden, between 2004 and 2007 (n = 10), were asked to participate in the study, and all accepted. Open-ended interviews were conducted, digitally recorded, transcribed verbatim, and then subjected to qualitative content analysis with an inductive approach. Five main themes emerged from the interviews: (I) being diagnosed with MS-an unpredictable existence; (II) a new treatment-a possibility for a new life; (III) AHSCT-a transition; (IV) reclaiming life; and (V) a bright future accompanied by insecurity. AHSCT was described by the participants in terms of a second chance and an opportunity for a new life. The treatment became a transition from a state of illness to a state of health, enabling a previous profound uncertainty to wane and normality to be restored. Although participants of different age and sex were included, the main limitation of this study is the relatively small number of participants. Also, the inclusion of persons from one centre alone could restrict transferability of the results.ConclusionsThe results give a first insight into lived experience following a highly effective induction treatment for MS, and the experience of not having MS anymore. Underpinned by previously described outcome following AHSCT, the results of this study challenge the current view on MS as a chronic disease with no possible cure

Vagal Nerve Stimulation in Epilepsy : Experiences of Participants with Cognitive Deficits

Introduction: The purpose of this study was to examine patients experiences of vagal nerve stimulation (VNS) with a special interest in patients with cognitive deficit (CD). Materials and Methods: An open, retrospective study was conducted on 82 patients with pharmacoresistant epilepsy, who were treated with VNS for at least 10 months. Based on the inability to live independently, they were divided into two groups: patients with cognitive deficit (CD group) and patients without cognitive deficit (non-CD group). A specially designed questionnaire was used for semi-structured interviews about patients experiences of VNS treatment. Results: Approximately one-third described a continuous reduction of seizure frequency of 50% or more and were regarded as responders. Fewer subjects in the CD group were responders than in the non-CD group. Approximately one-third of all subjects had no positive effect of VNS treatment. More CD patients described additional improvements and the most common were milder seizures and improved alertness. The most commonly reported adverse effect was hoarseness. Discussion: VNS treatment in patients without CD had better effect on seizure frequency reduction than in patients with CD, but many patients with CD reported other benefits from the treatment

Narcolepsy treatment in Sweden : An observational study

Objectives To describe the pharmacological treatments (2005-2017) and the healthcare utilization (1997-2016) for patients with narcolepsy in Sweden in order to create a framework for future organizational and economic analyses. Material &amp; Methods Patients of all ages with a diagnosis of narcolepsy registered in the National Patient Registry in specialist care in Sweden were included and information on treatments for narcolepsy was retrieved from The Swedish Prescribed Drug Register. Results We collected 2508 patients with narcolepsy, 43,3% men and 56,7% women and 47,9% were prescribed modafenil, 33,8% metylphenidate and 26,2% amphetamine. In total, 3817 treatments were initiated. Patients treated with amphetamine had a higher mean age. More women than men used modafinil, methylphenidate, amphetamine and antidepressants. The narcolepsy population had more outpatient than inpatient healthcare. Patients treated with sodium oxybate had more outpatient visits than other narcolepsy patients, before and during treatment (p = .00). Conclusions This study gives valuable information on pharmaceutical treatments and healthcare utilization for patients with narcolepsy and can be used to estimate the healthcare cost in the future. Patients with sodium oxybate treatment had more outpatient visits than other patients before and during treatment which may be due to the need to monitor potentially severe side-effects or may indicate that patients with sodium oxybate treatment have a severe disease. The number of included patients was less than expected; however, this may depend on patients escaping our collection of data, which does not contain information from primary care.Funding Agencies|UCBUCB Pharma SA</p

Homonymous visual field defect and retinal thinning after occipital stroke

Introduction Stroke is the most common cause of homonymous visual field defects (VFD). About half of the stroke patients recover from VFD. However, relationship between VFD and retinal changes remains elusive. Purpose To investigate the association between occurrence of VFD, changes of macular ganglion cell and inner plexiform layer (GCIPL) and its axon retinal nerve fiber layer (RNFL) detected with optical coherence tomography (OCT). Patients and methods The study consists of retrospective review of medical records and follow-up examinations. Patients with acute occipital stroke were registered. VFD was identified with confrontation and/or perimetry tests at the onset. At follow-up, the patients were examined with visual field tests and OCT measurements. Results Thirty-six patients met the inclusion criteria. At onset, 26 patients (72%) had VFD. At follow-up &amp;gt;1 year after stroke, 13 patients (36%) had remaining VFD: 5 had homonymous hemianopia, 5 had homonymous quadrantanopia, and 3 had homonymous scotomas. Average thickness of GCIPL and RNFL were significantly reduced in each eye in patients with VFD compared to non-VFD (NVFD) (p &amp;lt; .01 for all comparisons). Thickness of superior and inferior RNFL quadrants was significantly reduced in VFD compared to NVFD (p &amp;lt; .01 for both). Among these 13 patients, 4 had characteristic homonymous quadrant-GCIPL thinning, 2 had characteristic homonymous hemi-GCIPL thinning, and 7 had diffuse GCIPL thinning. Conclusion GCIPL and RNFL thinning were observed in the patients with VFD. GCIPL thinning appears in two forms: atypical diffuse thinning, or homonymous hemi-GCIPL thinning. Examining GCIPL and RNFL provides easy and reliable objective measures and is therefore proposed to be of predictive value on visual function.Funding Agencies|Faculty of Medicine and Health Sciences of Linkoping University; County Council of Ostergotland [LIO 799111, LIO 858051]</p