Dissertations / Theses on the topic 'Neurological Disorder'
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1
Coy, G. "Emotion processing in functional neurological disorder." Thesis, Canterbury Christ Church University, 2018. http://create.canterbury.ac.uk/17707/.
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Objective: Alexithymia and hypomentalization, two traits associated with childhood emotional abuse/neglect, have not previously been studied in people with mixed-symptom functional neurological disorder (FND). This case-control study these traits in people with FND compared to healthy control participants, and explored the relationships between alexithymia, mentalization, and somatic and neurological symptoms of a generalized nature. Method: Twenty-nine participants with FND and 41 healthy control participants completed a battery of self-report measures. Between-group differences in alexithymia and hypomentalization were investigated using parametric tests, and binary logistic regression analyses examined whether alexithymia and hypomentalization were predictive of FND (vs control) group status, after controlling for depressive symptoms, anxiety symptoms and education attainment. Linear regression analyses examined whether alexithymia and hypomentalization were also associated with physical and neurological symptoms across the entire sample. Results: Participants with FND had significantly higher score on measures of alexithymia, hypomentalization, somatic symptoms and neurological symptoms compared to healthy control participants. Between-group differences in alexithymia and neurological symptoms remained significant after controlling for covariates. High scores on the alexithymia and mentalization measures were also predictive of high scores on the measures of somatic and neurological symptoms across the entire sample. Conclusion: Alexithymia and hypomentalization do appear to be significant issues for people with FND, and may contribute to the tendency to express distress via physical symptoms. Exploring these traits with individual service users may contribute to a more comprehensive conceptualisation of their difficulties, and inform treatment approaches that are engaging and supportive.
2
Williams, Isobel Anne. "Emotion regulation in patients with Functional Neurological Disorder." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/21430/.
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3
Shaw, P. J. "Neurological and neurophysiological complications of coronary artery bypass graft surgery." Thesis, University of Newcastle Upon Tyne, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380746.
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4
Ichikawa, Shoji. "The molecular genetic analysis of three human neurological disorders." free online free to MU campus, others may purchase, 2002. http://wwwlib.umi.com/cr/mo/preview?3074409.
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5
Phoenix, Danielle. "Exploring how males who encounter phenomena they identify as 'Conversion Disorder'/'Functional Neurological Disorder' experience agency in their lives." Thesis, Middlesex University, 2017. http://eprints.mdx.ac.uk/21822/.
Full textAbstract:
This research investigates the way that males who identify with the diagnostic label ‘conversion disorder/functional neurological disorder (CD/FND)’ experience agency in their lives. The historical developments, controversies and complexities around ‘CD/FND’ form the backdrop of this exploration into the lived experience of agency. A sample of eight participants were recruited via social networking sites and charities, and the data was collected through Skype-based interviews and analysed using the qualitative Interpretative Phenomenological Analysis (IPA) approach. The analysis showed the following five main themes: ‘paradox of control’, ‘living within a dualistic framework’, ‘disconnection from self and others’, ‘engaged in a battle or fight’ and ‘meaning and reality as dependent on other people’. These master themes and their related subordinate themes are presented in light of existing research. The findings highlight the difficulty experienced by participants who identify with a diagnostic label that is at odds with a medicalised approach to understanding and treating illness. The limitations of this study and the potential avenues for future research are also discussed.
6
Beckh, Johanna [Verfasser]. "Is Functional Neurological Symptom Disorder (FNSD) a (somatic) stress disorder with altered emotion processing? : An approach to an answer via different methods, disorders an over time / Johanna Beckh." Konstanz : KOPS Universität Konstanz, 2019. http://d-nb.info/1206096772/34.
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7
Beasley, Brooke, Aubrey Sciara, Tiffani Carrasco, Gregory Dr Ordway, and Michelle Dr Chandley. "Laser Capture Microdissection Analysis of Inflammatory-Related Alterations in Postmortem Brain Tissue of Autism Spectrum Disorder." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/34.
Full textAbstract:
Autism spectrum disorder (ASD) is a social, sensory and developmental condition that affects one in 59 children and specifically one in 42 boys. Despite the 15% increase in prevalence in the last two years, there is no specific etiology, objective diagnostic criteria, or drug treatment. However, up-regulation of inflammation in ASD patients has been demonstrated in blood samples. Increased peripheral inflammation could have devastating effects on the developing brain. Peripheral inflammation in the blood could cross the blood-brain-barrier to stimulate microglia in the brain to produce aberrant levels of cytokines that regulate neuroinflammation such as insulin-like growth factor one (IGF1) that could alter neuronal cell-surface expression and neurotransmission. Additionally, arginase serves as a marker of inflammation, produced and expressed during cellular remodeling during brain injury. A balance of neurotransmitters, glutamate and gamma-aminobutyric acid (GABA), is critical to facilitate inter-regional signaling in the brain. Alterations of inflammatory molecules and the effects on glutamatergic neurons ability to uptake GABA in certain brain areas is currently unknown in ASD. Pathological changes in brain areas associated with social behaviors have been identified in postmortem tissue from ASD donors when compared to typically developing (TD) age and gender matched control tissue, as well as, in imaging scans of living individuals with ASD. We hypothesize that expression of inflammatory related molecules are increased in the identified brain areas related to symptoms of ASD and can be associated with altered gene expression changes in neurons as shown by gamma-aminobutyric acid type A receptor alpha 1 subunit (GABRA1). Dysfunction of GABRA1 on glutamatergic neurons could disrupt the typical neuronal balance of glutamate and GABA signaling. Inflammatory markers, IGF1 and insulin-like growth factor one receptor (IGF1R), were evaluated using quantitative polymerase chain reaction (QPCR). Additionally, IGF1 and arginase were evaluated using immunohistochemistry in both white and gray matter from the anterior cingulate cortex (ACC). Laser capture microdissection (LCM) was used to obtain single cell captures of glutamatergic neurons. IGF1R and GABRA1 gene expression was measured using end point PCR. A significant increase in IGF1 expression was obtained in the white matter punch in comparison to typically developed age-matched subjects using QPCR during initial statistical significance, however, was ultimately not significant. Additionally, IGF1R expression was significantly increased in ASD neurons in comparison to TD subjects utilizing the LCM method. However, a decrease expression in GABRA1 trended significance indicating a possible alteration in the neuron’s ability to facilitate proper signaling. These findings are the foundation of future investigations of signaling pathways in ASD that may uncover cell-specific etiologies and drug therapies for a condition that is only projected to increase in prevalence.
8
Chetram, Sursatie. "Neurodevelopmental Basis of Autism Spectrum Disorder based on Age and Gender." ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/4720.
Full textAbstract:
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects communication, socialization, and restricted/repetitive behaviors. In 2012, one out of every 55 children (1 in 42 boys and 1 in 189 girls) have been diagnosed with ASD in the United States. Only 30-40% of ASD has a known etiology (e.g., genetic predisposition) and the other 60-70% is unknown. Prior to this study, there was no known literature on age and gender differences related to neuro-developmental functioning of ASD. The purpose of this study was to examine how the differences in age and gender of people with ASD were related to total and domain scores, as measured by the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). This quantitative research study included a sample size of 80 and 2 independent variables: age groupings (ages 1-4, 5-8, 9-17, and 18-older), and gender (male and female). The 4 dependent variables were the total and domain scores measured by the ADOS-2. The statistical analyses included a multiple analysis of variance (MANOVA) and a 2-way analysis of variance (ANOVA) to examine age and gender differences in the ADOS-2 domain and total scores. There was a statistically signi�cant difference for age on the domain dependent variables, F(9, 171) = 2.64, p = .007; Wilks' Lambda = .73; partial η2 = .10. However, there were no statistically significant differences for gender on domain scores and there were no statistically significant differences for age and gender on the overall scores. Those with ASD between ages 5-8 were more severely impaired for socialization when compared to other age groups and other domains. This research can be used for the improvement of intervention strategies for the diverse ASD population, and to improve the understanding of the neurodevelopmental functioning of individuals with ASD based on age and gender.
9
Law, Cecilia. "Everyday Memory Difficulties in Children and Adults with Neurological Disorders: Mixed Method Studies." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29743.
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Memory difficulties are prevalent in patients with neurological disorders across lifespan. However, little is known about how memory difficulties are experienced in everyday life, and their functional impacts. This thesis aimed to improve the assessment of children’s everyday memory and explore patients’ lived experience and coping with an under-researched memory disorder—accelerated long-term forgetting (ALF). Chapter 1 presented a general introduction to everyday memory difficulties in patients with neurological disorders. In Chapter 2, a systematic review evaluated currently available paediatric memory questionnaires and found that all, except one memory questionnaire, lacked evidence base to be used as assessment tools. Hence, exploratory factor analyses (EFA) were conducted to establish factorial structures of two commonly administered questionnaires, the Parent Memory Questionnaire (PMQ) and Child Memory Questionnaire (Child MQ), in a neurotypical paediatric sample (Chapter 3) and a clinical sample (Chapter 4). The two EFAs successfully established a comparable three-factor structure for the PMQ, but not the Child MQ. Next, Chapter 5 and 6 provided the first evidence of the lived experience of ALF of adults with epilepsy using a mixed method approach. Quantitative and qualitative findings from Chapter 5 revealed that ALF was associated with profound losses across personal, relationship and functional domains, and multiple psychosocial challenges. Chapter 6 documented findings from semi-structured interviews with patients, their family members, and health professionals on coping strategies for ALF and ALF-inflicted psychosocial difficulties. These coping strategies were categorised into avoidance, emotion-focused, memory-focused, seizure control. Overall, findings informed on the measurement of everyday memory problems and urged for the development of comprehensive intervention for patients with neurological disorders who also experience memory difficulties.
10
Colson, Natalie, and n/a. "The Role of Hormonal and Vascular Genes in Migraine." Griffith University. School of Medical Science, 2007. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20071121.104112.
Full textAbstract:
Migraine is a frequent debilitating neurological disorder that is considered to be genetically complex with a multifactorial mode of inheritance. It has a high prevalence with approximately 18% of women and 6% of men suffering from the disorder. Migraine is characterized by severe head pain with associated nausea, emesis, photophobia, phonophobia, and neurological disturbances. The International Headache Society (IHS) has classified various types of migraine according to their clinical features. The two main subtypes of migraine are migraine without aura (MO), occurring in ~70-75% of migraineurs, and migraine with aura (MA) which occurs in ~25% of migraineurs. Some people experience both types of attack in their lives. While the precise pathogenesis of migraine is unknown, it is widely accepted that short-term alterations in neuronal activity occur in relation to the attack, along with temporary changes in the cerebral vasculature. Trigeminal nerve activation is also considered pivotal to progression of a migraine attack. Neurotransmitters, especially serotonin (5-hydroxytryptamine, 5-HT), platelet activation and sympathetic hyperactivity all appear to play a part, whether as part of the primary triggering event, or as a response mechanism. Migraine imparts a significant burden on society, both socially and financially. The World Health Organization has identified migraine among the world's top 20 leading causes of disability, with an impact that extends far beyond individual suffering. There is significant evidence from family and twin studies to indicate a strong genetic component to migraine. The current understanding of migraine is that it is a polygenic multifactorial disorder. It has been postulated that genetic factors set the individual migraine threshold, with environmental influences playing a modulating role. It is likely that many genes may provide an important although moderate contribution to an individuals migraine susceptibility. The identification of migraine susceptibility genes has been the focus of substantial research to date and could eventually lead to improved treatments and greater understanding of the disorder. Several loci have shown promise, although these need to be followed up by both replication and functional studies to determine a definitive causative role. This research investigated the role of both hormonal and vascular related genes as candidate genes that may play a role in migraine susceptibility due to the well-known role of hormones and vascular changes in some migraineurs. The estrogen receptor (ESR) and progesterone receptor (PGR) genes are potential migraine candidates due to the recognized hormonal influence on migraine susceptibility. Migraines in women frequently occur during the childbearing years and are often influenced by significant hormonal milestones. The fluctuating hormone levels of the menstrual cycle have been implicated in migraine but a definitive role is yet to be established. It has been suggested that factors additional to circulating hormone levels may be at play. This research considered that variation in the ESR 1 and PGR genes may confer an increased migraine risk. To investigate the potential role of these genes in migraine, association studies investigating variants in ESR 1 and PGR were undertaken in two independent casecontrol cohorts. This was followed up by mutation screening and gene expression analysis in an effort to elucidate a functional role for these genes in the pathogenesis of migraine. Vascular genes also represent likely migraine candidates as alterations in both vascular function and cerebral blood flow are well known in migraine. Furthermore, cortical spreading depression (CSD), a depolarization wave that propagates across the brain cortex and has been speculated to cause the neurological symptoms that present in MA, has also been linked to vascular dysfunction. The methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTRR) genes both play a role in vascular functioning and were thus considered potential migraine candidates for this study. Both are involved in the pathway of homocysteine metabolism. Impaired activity of these enzymes can lead to mild hyperhomocysteinemia which is believed to lead to oxidative arterial damage. This may in turn impact on migraine susceptibility, possibly through the activation of trigeminal fibres. The MTHFR 677T allele results in an amino acid change in the catalytic domain of the enzyme leading to mild hyperhomocysteinemia. This particular variant has been implicated in migraine in four separate studies. One of these studies also suggested a role for the MTHFR 1298C allele in migraine. This allele also results in an amino acid change and reduced enzyme activity. Similarly, the MTRR 66G allele results in an amino acid change and has been associated with reduced activity of MTRR and increased plasma homocysteine concentration. To investigate the role of the ESR 1, PGR, MTHFR and MTRR genes in migraine, samples from two large independent case control cohorts were investigated. Cohort 1 was comprised of 275 migraineur samples and 275 age, sex and ethnicity matched controls while cohort 2 comprised 300 cases and 300 matched controls. All individuals were collected at the Genomics Research Centre with migraine diagnosis undertaken by HIS criteria and migraine affected individuals designated as MO or MA. Results of analysis of ESR 1 indicated a positive association with migraine in the two large independent cohorts for the exon 8 G594A polymorphism (P = 0.003; P = 8x10-6). Similarly, the PGR analysis showed a positive association with migraine for the PROGINS allele (P = 0.02; P = 0.003). Results also showed that individuals with both ESR 1 and PGR susceptibility alleles were 3.2 times more likely to suffer migraine those those with no susceptibility alleles. As the ESR 1 variant is synonymous, a mutation analysis was undertaken in a small sub-sample of individuals carrying the susceptibility allele, but no mutations were detected in these particular samples. Detailed mutation analysis of ESR 1 in a larger study group may be warranted. An ESR 1 and PGR expression analysis by RT-PCR was undertaken to examine if there were any notable expression level changes in migraineurs versus controls and additionally whether the susceptibility genotypes influenced gene expression. Altered expression levels may point to a functional change in the gene. Although results did not show any significant difference in expression levels in the case/control group, nor any influence in gene expression conferred by the specific susceptibility genotypes, ESR 1 expression did appear to be down-regulated in the migraine group and more specifically in the migraine susceptibility genotype subgroup. A larger study group may therefore be warranted to detect any potential genuine changes in gene expression. Overall, these results suggested that these hormonal genes appear to play a role in migraine susceptibility, although further studies are needed to define this. Results of the MTHFR 677 analysis showed that the TT genotype was significantly associated with the MA subgroup in a joint analysis of the two independent cohorts (P = 0.004). Results of analysis of MTHFR 1298, which is tightly linked to the 677 locus, showed a significant association in female migraineurs (P = 0.009). Similarly, results of the MTRR analysis also showed a significant difference between the female case and control groups with the G allele over-represented in female migraineurs (P = 0.022) These results may indicate that a significant gender effect appears in this locus as well as the MTHFR 1298 locus although results may also be due to a larger number of female migraineurs conferring increased statistical power to the gender subgroup. Interaction analysis of the MTHFR 1298 locus and the MTRR locus showed that females who carried both variants under a recessive model were 5 times more likely to suffer migraine those those with no susceptibility genotypes. Overall these results indicated that these vascular genes appear to play a role in migraine susceptibility. The final study focused on 6 genetic variants that had shown a positive association with migraine and/or MA in the same large association population analysed in this research. The aim of this study was to provide preliminary data on the potential role of genetic profiling in migraine. Using the genotypic data to create vascular and hormonal risk profiles based on positive association and interaction of MTHFR 677 T and ACE D alleles, and MTHFR 1298 AA and MTRR GG genotypes as vascular variants; and positive association and interaction of ESR 1 594 A and PGR PROGINS as hormonal variants, this study was able to demonstrate the relevance of genetic risk profiling to migraine. Results showed a significantly higher proportion of individuals with at least one genetic risk profile in the migraine group compared to those in the control group (P = 6 x 10-6). Individuals who possessed either the vascular and/or hormonal genetic risk profile were 8.6 times more likely to suffer from migraine than those who possessed a no risk profile. This indicated a greater effect than the individual effect of each of these variants. Furthermore individuals who possessed a vascular or both risk profiles were more likely to suffer nausea, emesis, phonophobia and photophobia, and have a mother who also suffered migraine. Overall, the genetic profiling approach provided interesting preliminary data on migraine susceptibility and indicated that such an approach may prove very useful for migraine diagnosis, particularly when all migraine genes have been identified. In conclusion this study provided the first indication that hormone receptor genes play a role in migraine susceptibility. Hormones have long been considered to play a role in the disorder but this study has provided the first molecular evidence to support this premise. In addition, this study showed that vascular related genes also play a role in migraine susceptibility. Finally, this study has clearly shown that migraine is a complex disorder involving multiple genes. Although a number of studies have implicated neurotransmitter related genes in the disorder, the present study is the first to show that both vascular and hormonal genes also play a role in migraine susceptibility. Thus there now appear to be three classes of genes that affect migraine susceptibility and although this study has implicated new variants, the preliminary genetic profiling study has shown that not all predisposing variants involved in the disorder have been defined.
11
Colson, Natalie. "The Role of Hormonal and Vascular Genes in Migraine." Thesis, Griffith University, 2007. http://hdl.handle.net/10072/365958.
Full textAbstract:
Migraine is a frequent debilitating neurological disorder that is considered to be genetically complex with a multifactorial mode of inheritance. It has a high prevalence with approximately 18% of women and 6% of men suffering from the disorder. Migraine is characterized by severe head pain with associated nausea, emesis, photophobia, phonophobia, and neurological disturbances. The International Headache Society (IHS) has classified various types of migraine according to their clinical features. The two main subtypes of migraine are migraine without aura (MO), occurring in ~70-75% of migraineurs, and migraine with aura (MA) which occurs in ~25% of migraineurs. Some people experience both types of attack in their lives. While the precise pathogenesis of migraine is unknown, it is widely accepted that short-term alterations in neuronal activity occur in relation to the attack, along with temporary changes in the cerebral vasculature. Trigeminal nerve activation is also considered pivotal to progression of a migraine attack. Neurotransmitters, especially serotonin (5-hydroxytryptamine, 5-HT), platelet activation and sympathetic hyperactivity all appear to play a part, whether as part of the primary triggering event, or as a response mechanism. Migraine imparts a significant burden on society, both socially and financially. The World Health Organization has identified migraine among the world's top 20 leading causes of disability, with an impact that extends far beyond individual suffering. There is significant evidence from family and twin studies to indicate a strong genetic component to migraine. The current understanding of migraine is that it is a polygenic multifactorial disorder. It has been postulated that genetic factors set the individual migraine threshold, with environmental influences playing a modulating role. It is likely that many genes may provide an important although moderate contribution to an individual’s migraine susceptibility. The identification of migraine susceptibility genes has been the focus of substantial research to date and could eventually lead to improved treatments and greater understanding of the disorder. Several loci have shown promise, although these need to be followed up by both replication and functional studies to determine a definitive causative role. This research investigated the role of both hormonal and vascular related genes as candidate genes that may play a role in migraine susceptibility due to the well-known role of hormones and vascular changes in some migraineurs. The estrogen receptor (ESR) and progesterone receptor (PGR) genes are potential migraine candidates due to the recognized hormonal influence on migraine susceptibility. Migraines in women frequently occur during the childbearing years and are often influenced by significant hormonal milestones. The fluctuating hormone levels of the menstrual cycle have been implicated in migraine but a definitive role is yet to be established. It has been suggested that factors additional to circulating hormone levels may be at play. This research considered that variation in the ESR 1 and PGR genes may confer an increased migraine risk. To investigate the potential role of these genes in migraine, association studies investigating variants in ESR 1 and PGR were undertaken in two independent casecontrol cohorts. This was followed up by mutation screening and gene expression analysis in an effort to elucidate a functional role for these genes in the pathogenesis of migraine. Vascular genes also represent likely migraine candidates as alterations in both vascular function and cerebral blood flow are well known in migraine. Furthermore, cortical spreading depression (CSD), a depolarization wave that propagates across the brain cortex and has been speculated to cause the neurological symptoms that present in MA, has also been linked to vascular dysfunction. The methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTRR) genes both play a role in vascular functioning and were thus considered potential migraine candidates for this study. Both are involved in the pathway of homocysteine metabolism. Impaired activity of these enzymes can lead to mild hyperhomocysteinemia which is believed to lead to oxidative arterial damage. This may in turn impact on migraine susceptibility, possibly through the activation of trigeminal fibres. The MTHFR 677T allele results in an amino acid change in the catalytic domain of the enzyme leading to mild hyperhomocysteinemia. This particular variant has been implicated in migraine in four separate studies. One of these studies also suggested a role for the MTHFR 1298C allele in migraine. This allele also results in an amino acid change and reduced enzyme activity. Similarly, the MTRR 66G allele results in an amino acid change and has been associated with reduced activity of MTRR and increased plasma homocysteine concentration. To investigate the role of the ESR 1, PGR, MTHFR and MTRR genes in migraine, samples from two large independent case control cohorts were investigated. Cohort 1 was comprised of 275 migraineur samples and 275 age, sex and ethnicity matched controls while cohort 2 comprised 300 cases and 300 matched controls. All individuals were collected at the Genomics Research Centre with migraine diagnosis undertaken by HIS criteria and migraine affected individuals designated as MO or MA. Results of analysis of ESR 1 indicated a positive association with migraine in the two large independent cohorts for the exon 8 G594A polymorphism (P = 0.003; P = 8x10-6). Similarly, the PGR analysis showed a positive association with migraine for the PROGINS allele (P = 0.02; P = 0.003). Results also showed that individuals with both ESR 1 and PGR susceptibility alleles were 3.2 times more likely to suffer migraine those those with no susceptibility alleles. As the ESR 1 variant is synonymous, a mutation analysis was undertaken in a small sub-sample of individuals carrying the susceptibility allele, but no mutations were detected in these particular samples. Detailed mutation analysis of ESR 1 in a larger study group may be warranted. An ESR 1 and PGR expression analysis by RT-PCR was undertaken to examine if there were any notable expression level changes in migraineurs versus controls and additionally whether the susceptibility genotypes influenced gene expression. Altered expression levels may point to a functional change in the gene. Although results did not show any significant difference in expression levels in the case/control group, nor any influence in gene expression conferred by the specific susceptibility genotypes, ESR 1 expression did appear to be down-regulated in the migraine group and more specifically in the migraine susceptibility genotype subgroup. A larger study group may therefore be warranted to detect any potential genuine changes in gene expression. Overall, these results suggested that these hormonal genes appear to play a role in migraine susceptibility, although further studies are needed to define this. Results of the MTHFR 677 analysis showed that the TT genotype was significantly associated with the MA subgroup in a joint analysis of the two independent cohorts (P = 0.004). Results of analysis of MTHFR 1298, which is tightly linked to the 677 locus, showed a significant association in female migraineurs (P = 0.009). Similarly, results of the MTRR analysis also showed a significant difference between the female case and control groups with the G allele over-represented in female migraineurs (P = 0.022) These results may indicate that a significant gender effect appears in this locus as well as the MTHFR 1298 locus although results may also be due to a larger number of female migraineurs conferring increased statistical power to the gender subgroup. Interaction analysis of the MTHFR 1298 locus and the MTRR locus showed that females who carried both variants under a recessive model were 5 times more likely to suffer migraine those those with no susceptibility genotypes. Overall these results indicated that these vascular genes appear to play a role in migraine susceptibility. The final study focused on 6 genetic variants that had shown a positive association with migraine and/or MA in the same large association population analysed in this research. The aim of this study was to provide preliminary data on the potential role of genetic profiling in migraine. Using the genotypic data to create vascular and hormonal risk profiles based on positive association and interaction of MTHFR 677 T and ACE D alleles, and MTHFR 1298 AA and MTRR GG genotypes as vascular variants; and positive association and interaction of ESR 1 594 A and PGR PROGINS as hormonal variants, this study was able to demonstrate the relevance of genetic risk profiling to migraine. Results showed a significantly higher proportion of individuals with at least one genetic risk profile in the migraine group compared to those in the control group (P = 6 x 10-6). Individuals who possessed either the vascular and/or hormonal genetic risk profile were 8.6 times more likely to suffer from migraine than those who possessed a ‘no risk’ profile. This indicated a greater effect than the individual effect of each of these variants. Furthermore individuals who possessed a vascular or both risk profiles were more likely to suffer nausea, emesis, phonophobia and photophobia, and have a mother who also suffered migraine. Overall, the genetic profiling approach provided interesting preliminary data on migraine susceptibility and indicated that such an approach may prove very useful for migraine diagnosis, particularly when all migraine genes have been identified. In conclusion this study provided the first indication that hormone receptor genes play a role in migraine susceptibility. Hormones have long been considered to play a role in the disorder but this study has provided the first molecular evidence to support this premise. In addition, this study showed that vascular related genes also play a role in migraine susceptibility. Finally, this study has clearly shown that migraine is a complex disorder involving multiple genes. Although a number of studies have implicated neurotransmitter related genes in the disorder, the present study is the first to show that both vascular and hormonal genes also play a role in migraine susceptibility. Thus there now appear to be three classes of genes that affect migraine susceptibility and although this study has implicated new variants, the preliminary genetic profiling study has shown that not all predisposing variants involved in the disorder have been defined.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
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Tomioka, Maiko. "Expression of ABCA13 in the brain and the effect of neurological disorder-related SNPs on the function." Kyoto University, 2013. http://hdl.handle.net/2433/175051.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第17622号
農博第1984号
新制||農||1010(附属図書館)
学位論文||H25||N4743(農学部図書室)
30388
京都大学大学院農学研究科応用生命科学専攻
(主査)教授 植田 和光, 教授 植田 充美, 教授 阪井 康能
学位規則第4条第1項該当
13
Hölscher, Sara, Barbara Leinweber, Harald Hefter, Ulrike Reuner, Peter Günther, Karl Heinz Weiss, Wolfgang H. Oertel, and Jens Carsten Möller. "Evaluation of the Symptomatic Treatment of Residual Neurological Symptoms in Wilson Disease." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133378.
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The intention of this analysis was to identify patients with treated Wilson disease (WD) and residual neurological symptoms in order to determine whether or not they were undergoing any treatment in addition to the common decoppering medication. Moreover, the effects of any symptomatic medication were analyzed. Two samples of WD patients were investigated either by a mailed questionnaire survey (n = 135) or by a retrospective analysis (n = 75). A considerable proportion of patients still suffered from neurological symptoms (n = 106, 50.5%), of whom a relatively small proportion was treated symptomatically (n = 33, 31.1%). The documented effects varied substantially, with anticholinergics and botulinum toxin (against dystonia) and primidone (against tremor) apparently being the most promising compounds. Further studies are required to analyze the symptomatic treatment of WD patients with residual neurological symptoms in more detailDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Ahmed, Fida Al Noor. "Rhodiola Rosea L.- An Evaluation of Safety and Efficacy in the Context of a Neurological Disorder, Alzheimer Disease." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/33374.
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This thesis examined the safety and efficacy of Rhodiola rosea L. (Crassulaceae), a medicinal plant used traditionally by the Inuit of Nunavik, Québec, for the maintenance of mental and physical health. To assess the effects of Nunavik R. rosea on the central nervous system, a phytochemically characterized extract was tested in behavioural assays of anxiety with rats. Significant changes in behaviour were observed, particularly in the conditioned emotional response test. R. rosea was not a potent modulator of the benzodiazepine site of the GABAA receptor, indicating possible involvement of other neurotransmitters implicated in the neurobiology of anxiety.
Safety of Nunavik R. rosea, its marker phytochemicals, and additional R. rosea products was assessed by evaluating the risk of drug interaction potential. Inhibitory capacity was tested on major human drug metabolizing enzymes, the cytochrome P450s. Further, effects on the metabolism of repaglinide, an anti-diabetic drug, were examined in human liver microsomes. While the overall risk of interactions was low, variable impacts of R. rosea products on the formation of glucuronide metabolites of repaglinide necessitate caution.
In the TgCRND8 model of Alzheimer disease, R. rosea chronic administration led to modest improvements in the survival of male transgenic mice, which exhibit accelerated rates of mortality. Effects on learning and memory performance in the Morris water maze were limited to alterations in the patterns of use of search strategies as determined by our automated scoring algorithm, MWM Visual; changes in escape latencies were not observed.
Nunavik R. rosea administration resulted in elevated plasma levels of anandamide (20:1, n-9), a member of the endocannabinoid family, tentatively identified using an untargeted metabolomics approach via ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry. R. rosea phytochemicals were either eliminated via the renal pathway, or transformed into potential metabolites.
Collectively, the anxiolytic activity of Nunavik R. rosea in rats, its protective effects on high background mortality in an aggressive Alzheimer disease model, low risk of inhibition of major enzymes involved in drug metabolism, and its ability to induce detectable changes in in vivo metabolic pathways are supportive scientific evidence for the use of this traditional medicine for general well-being by the Inuit.
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Kwan, Cheung Keith A. "Monitoring of cannabinoid-based medicines for the treatment of neurological disorders to improve clinical outcomes in minors." Thesis, Queensland University of Technology, 2022. https://eprints.qut.edu.au/228475/1/Keith_Kwan%20Cheung_Thesis.pdf.
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The exact interactions between the endocannabinoid system (ECS) and cannabinoids are still ill-defined, and could lead to more effective treatment if better understood. This project investigated the use of liquid chromatography tandem mass spectrometry (LC-MS/MS) in the measurement of potential biomarkers of cannabinoid and ECS metabolism. Measurement of eicosanoids in human saliva by LC-MS/MS was comparable to their plasma measurement. Cannabidiol (CBD) and CBD metabolites were successfully measured in plasma and saliva.
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Buervenich, Silvia. "Candidate genes and the dopamine system : possible implications in complex neurological and psychiatric disease /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-202-7.
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Hölscher, Sara, Barbara Leinweber, Harald Hefter, Ulrike Reuner, Peter Günther, Karl Heinz Weiss, Wolfgang H. Oertel, and Jens Carsten Möller. "Evaluation of the Symptomatic Treatment of Residual Neurological Symptoms in Wilson Disease." Karger, 2010. https://tud.qucosa.de/id/qucosa%3A27508.
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The intention of this analysis was to identify patients with treated Wilson disease (WD) and residual neurological symptoms in order to determine whether or not they were undergoing any treatment in addition to the common decoppering medication. Moreover, the effects of any symptomatic medication were analyzed. Two samples of WD patients were investigated either by a mailed questionnaire survey (n = 135) or by a retrospective analysis (n = 75). A considerable proportion of patients still suffered from neurological symptoms (n = 106, 50.5%), of whom a relatively small proportion was treated symptomatically (n = 33, 31.1%). The documented effects varied substantially, with anticholinergics and botulinum toxin (against dystonia) and primidone (against tremor) apparently being the most promising compounds. Further studies are required to analyze the symptomatic treatment of WD patients with residual neurological symptoms in more detail.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Gitchel, George Thomas Jr. "Development of an Accurate Differential Diagnostic Tool for Neurological Movement Disorders Utilizing Eye Movements." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/4109.
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Parkinson’s disease and Essential tremor are the two most prevalent movement disorders in the world, but due to overlapping clinical symptoms, accurate differential diagnosis is difficult. As a result, approximately 60% of patients with movement disorders symptoms will have their diagnosis changed at least once before death. By their subjective nature, clinical exams are inherently imprecise, leading to the desire to create an objective, quantifiable test for movement disorders; a test that currently is elusive. Eye movements have been studied for a century, and are widely appreciated to be quantifiably affected in those with neurological disease. Through a collaborative effort between the VA hospital and VCU, over 1,000 movement disorder subjects had their eye movements recorded, utilizing an SR Research Eyelink 2. Patients with Parkinson’s disease exhibited an ocular gaze tremor during fixation, normal reflexive saccades, and reduced blink rate. Subjects with Essential tremor exhibited slowed saccadic dynamics, with increased latencies, in addition to a larger number of square wave jerk interruptions of otherwise stable fixation. After diagnostic features of each disorder were identified, prospective data collection could occur in a blinded fashion, and oculomotor features used to predict clinical diagnoses. It was determined that measures of fixation stability were capable of almost perfectly differentiating subjects with PD, and a novel, combined parameter was capable of similar results in ET. As a group, it appears as if these symptoms do not progress as the disease does, but subanalyses show that individual patients on constant pharmaceutical doses tracked over time do slightly change and progress. The near perfect separation of disease states suggest the ability of oculomotor recording to be a powerful biomarker to be used for the differential diagnosis of movement disorders. This tool could potentially impact and improve the lives of millions of people the world over.
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Rothman, David J. "An Investigation of Neurological soft signs as a discriminating factor between Veterans with Post-traumatic Stress Disorder, mild Traumatic Brain Injury, and co-occurring Post-traumatic Stress Disorder and mild Traumatic Brain Injury." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5915.
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While multiple Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans suffer from mild Traumatic Brain Injury (mTBI), Post-traumatic Stress Disorder (PTSD), and co-morbid mTBI and PTSD, there remains difficulty disentangling the specific symptoms associated with each disorder using self-report and neurocognitive assessments. We propose that neurological soft signs (NSS), which are tasks associated with general neurologic compromise, may prove useful in this regard. Based on our review of the literature we hypothesized that individuals with PTSD would present with a greater number of NSS than controls or individuals with mTBI. Further, we hypothesized a synergistic effect, such that individuals with mTBI + PTSD would present with the greatest number of NSS. To test these hypotheses, we analyzed a subset of individuals (N=238) taken from a larger study of neurocognitive functioning in veterans. Participants completed a battery of neuropsychological measures, which included the Behavioral Dyscontrol Scale (BDS), the current study’s measure of NSS. A subset of other neuropsychological measures were also included to examine the utility of NSS over and above traditional neuropsychological measures. Individuals were removed from the study if they sustained a moderate/severe TBI or did not meet validity criteria on the Green’s Word Memory Test or the Negative Impression Management subscale of the Personality Assessment Inventory. Binomial logistic and multinomial logistic regression were used to examine the ability of NSS to discriminate between the study groups, first by themselves and then after the variance explained by the traditional neuropsychological measures was accounted for. Exploratory cluster analyses were performed on neuropsychological measures and NSS to identify profiles of cognitive performance in the data set. Results indicated that individuals in the mTBI and/or PTSD group had more NSS compared to controls. Of the individual NSS items only a go/no-go task of the BDS discriminated between groups, with worse performance among individuals in the mTBI, PTSD, and mTBI + PTSD group compared to controls. In contrast, the overall BDS score and individual NSS, in general, did not discriminate between the mTBI, PTSD, and mTBI + PTSD group. Overall, the current study suggests that, when eliminating participants who do not meet validity criteria, NSS do not aid in discriminating between individuals with mTBI, PTSD, and mTBI + PTSD.
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Shafran, Rosamund Lucy. "An investigation into the cognitive-behavioural model of obsessive-compulsive disorder (O.C.D.) : can this be reconciled with a neurological deficit model?" Thesis, King's College London (University of London), 1995. https://kclpure.kcl.ac.uk/portal/en/theses/an-investigation-into-the-cognitivebehavioural-model-of-obsessivecompulsive-disorder-ocd--can-this-be-reconciled-with-a-neurological-deficit-model(825d532c-226d-486e-ba58-c8f7c114f0f6).html.
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O'Connell, Nicola. "Functional neurological disorder in acute stroke and mental health services : a mixed methods assessment of experiences, prevalence, associated clinical factors, and treatment." Thesis, King's College London (University of London), 2018. https://kclpure.kcl.ac.uk/portal/en/theses/functional-neurological-disorder-in-acute-stroke-and-mental-health-services(c6f40fea-3c02-40ac-aed3-2f662107589d).html.
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Functional neurological disorders (FND) present as neurological disease for which no organic cause can be found. These disorders are common, debilitating, and patients can present to a range of medical services. Little is known of the prevalence of patients with functional symptoms presenting to stroke settings, their experience once admitted to stroke wards, the demographic and clinical features of functional motor disorder (FMD) patients treated in psychiatric settings, or their response to psychological treatment. This thesis addresses this paucity of evidence. A systematic review and meta-analysis found functional stroke patients consistently present to stroke settings, constituting 1.7% (95% CI: 1.3% - 2.2%) of all patients with suspected stroke, with weakness the most commonly presenting functional symptom. A qualitative study using in-depth interviews with 14 hyper acute stroke clinicians, found participants named a range of potential causes of functional stroke presentations, but many felt unsure in how to discuss a functional diagnosis with patients. In a survey of 120 staff in hyper acute stroke wards in England, 90% of clinicians stated they do not believe there are clear guidelines on how to manage functional patients and 95.8% believed further research is necessary. A qualitative study involving interviews with 30 patients with functional stroke symptoms at one hyper acute stroke ward found many reported strong negative emotions in response to their admission and while on the ward, many believed they had had a stroke. Two months after discharge, many patients were uncertain about the cause of their admission and 40% experienced residual physical symptoms. Many expressed a desire for a more detailed explanation about the potential cause of their symptoms. A case-control study of 322 FMD patients found the disorder more commonly affects women, patients more frequently work in social or health care settings, patients often have carers or are themselves carers, and more frequently have comorbid physical and functional disorders when compared to a random sample of psychiatric patients from South London and the Maudsley NHS Trust. We found no association between experience of childhood sexual or physical abuse and an FMD diagnosis; however tentative evidence suggests patients experience precipitating events that could be defined as ‘disruptions to interpersonal relationships’. Finally, our case-control cognitive behavioural therapy (CBT) study indicates that both FMD patients and patients with organic disease respond to outpatient CBT. Half of the FMD group saw improvements in their physical symptoms, and measures of psychological distress and depression showed significant clinical improvement between first and last treatment sessions. Dropout rates from treatment were comparable between FMD and control patients. We conclude that functional disorder symptoms occur in multiple medical settings and present to newly established hyper acute stroke wards. A lack of understanding amongst clinicians about the nature of FND coupled with increasing financial pressure on the health service may serve to entrench patients’ symptoms, and worsen experiences in medical settings. Within mental health services, FMD appears to have distinct epidemiological characteristics but the fragmentation of neurological and mental health services mean patients are often under-served and lack continuity of care.
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Martorano, Lisa. "Analysis of Brain Structure in a Community Sample of Women with Posttraumatic Stress Disorder as a Result of Chile Abuse Exposure." Wittenberg University Honors Theses / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=wuhonors1239029267.
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Negash, Alemayehu. "Bipolar disorder in rural Ethiopia : community-based studies in Butajira for screening, epidemiology, follow-up, and the burden of care." Doctoral thesis, Umeå universitet, Psykiatri, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-21743.
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Background: The challenges of research in economically stunted countries’ settings remains a profound concern and is linked to socioeconomic development of these countries. More research is needed regarding psychiatric morbidity in rural areas of the developing and poverty stricken countries. The present studies were undertaken within the framework of a broader ongoing community-based project on the course and outcome of major psychiatric disorders in the rural Butajira district located in Ethiopia. This thesis treats the course and outcome of bipolar I disorder in the district. Objectives: Through appraising mental health and population based research in a rural Ethiopian district, to evaluate the utility of modern research instruments, and to obtain baseline information relating to bipolar I disorder in the poverty stricken rural Butajira district of Ethiopia. The specific objectives were: 1. Evaluating and comparing two different screening methods of case detection and identification for schizophrenia and bipolar I disorder in the adult population of Butajira district. 2. Assesing the prevalence and clinical characteristics of of bipolar I disorder in Butajira at the community level. 3. Evaluating short-term outcome at follow-up of bipolar I disorder in the Butajira district. 4. Determining Neurological Soft Signs in community-identified cases of bipolar I disorder in Butajira district in comparison with healthy controls. 5. Assessing the burden of care among caregivers of those affected by bipolar I disorder identified in the Butajira Study. Methods: The district’s entire adult population aged 15-49 was identified through a double-sampling design. In the first stage of screening, door-to-door interviews were conducted by lay trained high school completed individuals who knew the culture of the people. Females interviewed females whereas males interviewed males. Additionally, the key-informants method was used to identify cases that would be missed by the CIDI or otherwise. The final confirmatory diagnostic interview was conducted by clinicians using the SCAN on door-to-door basis as well. The probable cases that fulfilled the lifetime DSM-IV diagnosis of bipolar I disorder were assigned for assessment by other baseline research instruments such as Neurological Evaluation vii Scale (NES), Young Mania Rating Scale, Hamilton Rating Scale for Depression, LCSS, PANS and SANS, BISS, BII, FIS and so on. Cases so identified with bipolar I disorder were subject to a follow-up for upto 2.5 years on the average (range 1 to 4 years). Two of the main clinical outcomes assessed were relapse to a mood episode, and remission from a mood episode. Outcomes were assessed annually by the instruments, and were further assessed monthly by trained psychiatric nurses. We also did a cross-sectional study of caregivers of bipolar I disorder cases, and assessed objective burden on the caregivers as considered from social, family strain, occupational and financial domains. Results: Information provided by the key informants was better at detecting schizophrenia or chronic psychiatric disease, whereas the CIDI was better at detecting affective disorders. Of the around 100 000 adults living in Butajira, 83.3% were found by the project’s census, of which 82% (68,378 subjects) were successfully screened by the CIDI, yielding 2,161 CIDI positive. These, together with 719 cases identified by the key informants, were invited for the SCAN interview, of which 74.7% agreed. This yielded 315 SCAN positive cases for bipolar I disorder, and complete information could be collected on 295 of these. Lifetime prevalence was estimated as 0.6% for males and 0.3% for females. The mean age of onset of the manic phase was 22.0 years and that of the depressive phase was 23.4 years. For 22.7% of the cases the illness started with a depressive episode and for the remaining 77.3% it started with a manic episode. Over half of the cases (55.9%) had never sought help from modern health care sector, and only 13.2% had ever been admitted to psychiatric hospital. At follow-up, 65.9% had exprerienced a relapse and 31.1% had persistent illness, while only 5% of the patients were in remission for most of the follow-up time. The bipolar I cases, as compared with healthy controls, performed worse on several items of NES, thus having more neurological dysfunction compared to controls. Caregives were largely (80.3%) first-degree relatives and spouses. Overall, 84% of the caregivers reported difficulties in at least one of the domains of family burden. Of these, 58.7% reported a severe degree of difficulties. Caregivers reported a high level of difficulties in intrafamilial relationships and social restrictions, disruption in earning a livelihood, and financial difficulties. Conclusions: The prevalence of bipolar I disorder is comparable to the prevalences reported from other countries, and our findings support the cross-cultural validity of the concept of bipolar I disorder. Majority of the cases are not treated in contrast to that in the developed countries. The burden of care for the caregivers is substantial in the population studied.
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Chikhani, Sherin. "The Potential Role of GATA4, ESR1, GRIA3 and SCN1A Genes in Migraine Susceptibility." Thesis, Griffith University, 2009. http://hdl.handle.net/10072/366267.
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Migraine is a common and painful neurological disorder, with genetic and environmental components. The prevalence of migraine varies between different racial groups, being higher in Caucasian populations (12%). Several conditions have been shown to be comorbid with migraine. One heart disorder that has been associated with migraine is a cardiac malformation affecting the interatrial septum and leading to patent foramen ovale (PFO), resulting from an incomplete anatomic fusion of the atrial septum primum and secundum. Mutations in the development regulatory gene GATA-4, located on human chromosome 8p23.1-p22, have been found to be responsible for some cases of congenital heart defects including PFO. To determine whether the GATA-4 gene is involved in migraine, the present study performed an association analysis of a common GATA-4 variant that results in a change of amino acid (S377G), in a large case/control population (275 unrelated Caucasian migraineurs versus 275 control individuals). Samples were genotyped for the single nucleotide polymorphism (SNP) using FACSArray flow cytometer and frequencies for this variant compared in migraine cases and age, sex and ethnicity matched controls...Thesis (Masters)
Master of Philosophy (MPhil)
School of Medical Science
Griffith Health
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Mackay, Gillian Moira. "Kynurenines in neurological disorders." Thesis, University of Glasgow, 2007. http://theses.gla.ac.uk/39/.
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The kynurenine pathway is thought to be involved in neurological disorders but its precise role and the mechanisms involved have yet to be established. Tryptophan can be metabolised via this pathway to produce the neurotoxic N-methyl-D-aspartate (NMDA) receptor agonist, quinolinic acid (QUIN), and the direct generators of reactive oxygen species, 3-hydroxykynurenine (3HKYN) and 3-hydroxyanthranilic acid (3HANA), as well as the neuroprotective NMDA receptor antagonist, kynurenic acid (KYNA). High performance liquid chromatography (HPLC) methods were successfully developed and validated for measuring tryptophan, kynurenine, KYNA, 3HANA and anthranilic acid (ANA) in blood samples, using absorbance and fluorescence detection. The method for determining 3HKYN using electrochemical detection was more problematic and was only used for tryptophan loaded samples and their respective baseline samples. Using HPLC, the concentrations of tryptophan, kynurenine, KYNA, 3HKYN and 3HANA were measured in the blood of Huntington's disease (HD) patients and patients with chronic brain injury, where the injury had occurred at least one year previously. QUIN was also determined for these patients using gas chromatography-mass spectrometry (GC-MS). In addition, the dynamics of the kynurenine pathway were investigated following oral tryptophan depletion and loading. In contrast to these chronic conditions, patients with acute stroke were also studied. The concentrations of tryptophan, kynurenine, KYNA, ANA and 3HANA were determined in the blood of the stroke patients, examining any changes in these concentrations during the two weeks after the stroke. The extent of inflammation and oxidative stress were also assessed for all patients, by measuring the levels of neopterin and the lipid peroxidation products, malondialdehyde and 4-hydroxynonenal. Patients with late stage HD showed abnormal tryptophan metabolism via the kynurenine pathway, together with increased inflammation and oxidative stress. Increased levels of kynurenine together with increased kynurenine: tryptophan (K:T) ratios, indicating greater indoleamine 2,3-dioxygenase (IDO) activity, were observed in blood samples from HD patients in comparison with healthy control subjects. In conjunction with this increased IDO activity, there was a decrease in the ratios of KYNA: kynurenine, suggesting decreased kynurenine aminotransferase (KAT) activity. Inflammation, which may be stimulating IDO activity, could also be decreasing KAT activity, suggested by negativecorrelations between the KYNA: kynurenine ratios and the inflammatory marker, neopterin. The inactivity of KAT suggests a small deficiency in KYNA over a long period of time which could cause a reduction in NMDA receptor antagonism, resulting in slow progressive excitotoxicity contributing to the neurodegeneration in HD. Low KYNA: kynurenine ratios were observed in baseline and tryptophan depleted samples, but after tryptophan loading, HD patients showed similar ratios compared with control subjects. This suggests that loading may be beneficial for HD patients, as more of the neuroprotectant, KYNA can potentially be produced. However, the results suggest that concentrations of the neurotoxin, QUIN, may also be increasing after tryptophan loading. Low concentrations of 3HKYN and 3HANA, with no change in QUIN levels, were also observed in the blood of HD patients. 3HANA levels continued to be decreased for the HD patients after loading. This may suggest degradation of 3HKYN and 3HANA by autoxidation producing reactive oxygen species which could contribute to the high levels of oxidative stress found in these patients. Tryptophan loading in healthy control subjects showed significant increases in the inflammatory marker, neopterin, and in the lipid peroxidation products. These results should be considered when tryptophan loading is used in psychiatric practice and in diets high in tryptophan, such as the Atkins diet. Patients with severe chronic brain injury showed similar alterations in kynurenine pathway metabolism as HD patients, at baseline and throughout the loading and depletion protocols. Although the brain injury had occurred at least one year previously, these patients showed persistent inflammation and oxidative stress, demonstrated by their increased levels of neopterin and lipid peroxidation products compared with healthy controls. In baseline blood samples, there were increased K:T ratios indicating greater IDO activity in the patients. Patients with chronic brain injury showed decreased concentrations of the neuroprotectant, KYNA, as well as low KAT activity, indicated by the decreased KYNA: kynurenine ratios. After tryptophan loading, K:T ratios decreased and the KYNA: kynurenine ratios increased in patients in comparison with controls, suggesting a reversal in the activities of the enzymes IDO and KAT. Similar levels of the inflammatory marker, neopterin, were observed in patients and controls after tryptophan loading. This suggests that these changes in IDO and KAT activities may be related to inflammation. As for the HD patients, patients with chronic brain injury showed lower levels of 3HKYN and 3HANA in their blood, with no change in QUIN levels. These metabolites may be undergoing autoxidation, producing reactive oxygen species which contribute to the ongoing oxidative stress in these patients.The kynurenine pathway was activated following an acute stroke, as indicated by the increased K:T ratios, suggesting greater IDO activity. Stroke patients also had raised levels of neopterin and lipid peroxidation products, indicating inflammation and oxidative stress. There were no changes in the blood concentrations of kynurenines, neopterin or lipid peroxidation products during the fourteen days after a stroke. Stroke patients had reduced levels of 3HANA in their blood, as observed for the HD and chronic brain injury patients. There were negative correlations between the concentration of 3HANA and the volume of the brain lesion, measured by computed tomography (CT) scan, demonstrating the importance of the decreased concentrations of 3HANA. In addition, there were increased levels of ANA in the blood of the stroke patients and the ratios of 3HANA: ANA also correlated with brain lesion volume. Another measurement which correlated with lesion volume was lipid peroxidation, suggesting that oxidative stress contributes to the extent of the brain damage after a stroke. This may suggest that the role of 3HANA in stroke is related to its autoxidation and the generation of reactive oxygen species. Increased concentrations of KYNA were observed in patients who died within three weeks of having a stroke. These high levels of KYNA may have been produced following excitotoxicity and the generation of free radicals, and may cause excessive NMDA receptor blockade or reduced mitochondrial adenosine triphosphate (ATP) synthesis, thus contributing to cell death. The kynurenine pathway was activated and showed abnormal metabolism in all the patient groups, suggesting a potential role for these metabolites in neuronal dysfunction in HD, chronic brain injury and acute stroke. Further work is required to elucidate the role of tryptophan metabolites and whether they may have a direct contribution to neuronal damage in neurological disorders.
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Hammarlund, Silje. "An Occupational Therapy Needs Assessment for an organization attending to children with autism spectrum disorder in Addis Ababa, Ethiopia : To identify the occupational therapy needs for an organization attending to children with autism spectrum disorder in Addis Ababa, Ethiopia." Thesis, Hälsohögskolan, Högskolan i Jönköping, HHJ, Avd. för rehabilitering, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-27964.
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Syfte: Att identifiera behovet för arbetsterapi i Nehemiah Autism Center genom att utföra en behovsanalys. Metod: Mixad-metod användas för att utveckla en passande behovsanalys för att identifiera behovet för arbetsterapi. Resultat: Alla områden där en arbetsterapeut kan bidrag till valdes. Kommunikation och sociala färdigheter rapporterades mest frekvent och beteende förvaltning rankades som viktigast bland vårdnadshavare. Bland anställda, fritid och lek rapporterades mest frekvent och stresshantering rankades som viktigast. Utbildningsmöjligheter, kommunikation mellan anställda och medarbetare relation identifierades som stödjande faktorer för att uppnå målet på Nehemiah Autism Center. Stigma, religion och kulturell mångfald rapporterades som icke-stödjande faktorer för att uppnå målet på Nehemiah Autism Center. Slutsats: Det finns ett behov för arbetsterapi för att möta behovet hos barn med autism på Nehemiah Autism Center i Addis Ababa, Etiopien.Aim: To identify the occupational therapy needs at the Nehemiah Autism Center by completing a needs assessment. Method: A mixed-methods design was adopted to construct a comprehensive needs assessment to identify the occupational therapy needs. Result: All areas of what an occupational therapist could assist with were selected as an area of need. Communication and social skills were most frequently reported and behavior management was ranked as most important among caregivers. Among staff members, leisure and play was reported most frequently and stress management was ranked as most important. Training opportunities, communication among staff members, and co-worker relationship were identified to be supporting factors in achieving the goal at Nehemiah Autism Center. Stigma, religion, and cultural diversity were reported to be unsupportive factors in achieving the goal at Nehemiah Autism Center. Conclusion: There is a great need for occupational therapy services to attend to children with autism spectrum disorder at Nehemiah Autism Center in Addis Ababa, Ethiopia.
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Griffiths, Timothy D. "Neurological and physical abnormalities in familial and sporadic schizophrenia : a study of the phenotype of schizophrenic subjects and their relatives from populations with a high or a low genetic risk of the disorder." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364042.
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Domarski, Shannon. "Neurological disorders: A model for parsimony." Honors in the Major Thesis, University of Central Florida, 2005. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/752.
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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucfBachelors
Arts and Sciences
Psychology
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Manole, A. A. "Functional genetics of rare neurological disorders." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1572333/.
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The study of rare Mendelian disorders is able to provide unique insights into neurological disorders that may seem unrelated. This thesis reports mechanistic investigations of five neurological disorders presenting with progressive or episodic neurological symptoms. First, riboflavin transporter neuronopathy represents a phenotypic spectrum of motor, sensory and cranial nerve neuropathy, often with respiratory problems. Our main findings implicate mitochondrial dysfunction as a downstream consequence of riboflavin transporter gene defects and validate riboflavin esters as a potential therapeutic strategy. Second, novel sequence variants in the SBF1 gene are described as potential mutations in patients with severe axonal neuropathy and bulbar features. Our findings suggest that SBF1 mutations may cause a syndromic form of autosomal recessive axonal neuropathy in addition to demyelinating Charcot-Marie-Tooth disease. Third, novel frameshift mutations in SPG11, investigated using mRNA, are described in patients with complex hereditary spastic paraplegia (HSP) consistent with SPG11. The findings that mutations in SPG11 are the cause of a spectrum of clinical features including the late manifestation of severe axonal neuropathy are extended. Fourth, a family with HSP carrying a de novo mutation in KCNA2 is described. Our results using two-electrode voltage clamp recordings confirm that the mutation is pathogenic, exerting a loss-of-function effect. The discovery of KCNA2 mutations in epilepsy, ataxia, and HSP extends the phenotypes that can be associated with this gene. Finally, a novel KCNA1 mutation associated with episodic ataxia and a possible link with malignant hyperthermia is reported. Our work broadens the phenotypes associated with KCNA1 mutations to include possible susceptibility to malignant hyperthermia, and shows the potential of using induced pluripotent stem cell derived neurons to determine the neuronal consequences of the Kv1.1 mutation. The diverse methods used in this thesis advance the understanding, and potential treatment, of a group of neurological disorders caused by single gene defects.
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Fedele, Laura. "Dysfunctional NMDA receptors in neurological disorders." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10043277/.
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N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors that together with a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and kainate receptors mediate the vast majority of the fast excitatory neurotransmission in the central nervous system. Given this role, any dysfunction in neurotransmission is likely to have a severe impact on brain physiology. Recent mutations have been reported in NMDAR subunits that cause patients to suffer with a variety of neurodevelopmental disorders. Here, we use multidisciplinary structural modelling, site-directed mutagenesis, electrophysiology and kinetic modelling techniques to investigate how de novo missense mutations in distinct regions of the GluN2B subunit, affect NMDAR function. We predicted that these mutations would have pathophysiological implications and we sought to examine their effects on the cellular and molecular function of NMDARs. We developed a virtually complete 3D model of the human GluN1-GluN2B receptor based on the recently solved crystal structures of the frog and rat NMDARs. The human NMDAR structure locates the positions of the residues of interest, allows deductions about their potential impact on the protein as well as provides insight into the binding sites for Mg2+ and memantine using molecular docking. The functional effects of the missense mutations were first analysed in recombinant NMDARs and revealed gain-of-function and loss-of-function phenotypes, with some lacking an overt phenotype. We selected four most profound phenotypes for study in hippocampal cultured neurons revealing how these mutations can compromise excitatory neurotransmission. In addition, we also explored the therapeutic potential of the FDA-approved channel blocker memantine both in heterologous system as well as on excitatory neurotransmission as a potential therapeutic. Overall, the results suggest strong correlations between the effects of the missense mutations with patient phenotypes. Moreover, the study indicates which pharmacotherapeutic interventions are most likely to be successful as targeted therapies.
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Smertenko, Tetyana. "Exome sequencing in rare neurological disorders." Thesis, University of Newcastle upon Tyne, 2016. http://hdl.handle.net/10443/3359.
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Neurological disorders are complex traits, manifesting as a range of diverse phenotypes. The current diagnostic approach involves either stepwise testing, which is expensive and time consuming, or targeted next generation sequencing with a limited portfolio of genes. Both of these approaches have a lower diagnostic yield. Whole exome sequencing may be a more advantageous and faster method to discover disease causing gene mutations. This study evaluates the use of whole exome sequencing for diagnostic purposes in neurological disorders. Whole exome sequencing was performed in a heterogeneous cohort of patients with suspected inherited ataxia as an example of a neurological disorder, with the aim to identify candidate gene mutations. The study cohort consisted of 35 affected individuals from 22 randomly selected families of white European descent with no known consanguinity. All common sporadic, inherited and metabolic causes were excluded on routine clinical investigations prior to inclusion in this study. Whole exome sequencing was performed on 30 affected individuals. In-house bioinformatic analysis was based on previously published tools. A variant filtering algorithm excluded synonymous variants and focused on protein altering variants, nonsense mutations, exonic insertions/deletions and splice site variants. Minor allele frequency (MAF) was set at 1% in dbSNP137, 1000 genomes (April 2012 data release) and NHLBI-ESP6500 databases as well as in 286 unrelated in-house controls. Selection of the remaining variants was based on mode of inheritance. The variants were prioritized for brain and nerve cell expression and defined using carefully selected criteria. Genetic analysis was supported further by molecular genetic approaches (Sanger sequencing, reverse transcription PCR, quantitative pyrosequencing, cloning for allelic cis-trans study) and proteomics (Western blotting, immunohistochemistry). Confirmed pathogenic variants were found in 9/22 probands (41%) implicating 6 genes (KCNC3, SPG7, TUBB4A, SLC1A3, SACS and NPC1). Likely de novo dominant TUBB4A mutations were found in two families. In one family quantitative pyrosequencing revealed varying degrees of mosaicism in the mildly affected mother and heterozygosity in the severely affected offspring. In silico analysis further supported pathogenicity of the mutation and revealed that it could potentially disrupt ! ! ii! polymerizations of αβ-tubulin heterodimers. Possible pathogenic variants were identified in 5/22 probands (23%) implicating 5 genes (ZFYVE26, ZFYVE27, WFS1, WNK1 and FASTKD2). A predicted splice site mutation was detected in three members of an autosomal dominant pedigree in the previously described gene ZFYVE27. The ZFYVE27 protein (protrudin) levels were increased approximately 2.5 fold in the cerebellum but not in the frontal cortex of the affected individual. Protrudin is an endoplasmic reticulum (ER) protein and its anomalies have previously been shown to cause ER stress. In this study levels of the master regulator of ER stress, BiP/GRP78, were significantly increased in the patient’s cerebellum, which may indicate the ER pathology. In one family with possible pathogenic compound heterozygous FASTKD2 mutations, the in silico splice-site prediction was validated by sequencing analysis of cDNA clones. Likely de novo compound heterozygous mutations in ZFYVE26 (SPG15) in one family was validated with sequencing of cloned alleles and the result confirmed occurrence of the mutations in trans, therefore supporting their autosomal recessive inheritance. In conclusion, the likely molecular diagnosis in 14 out of 22 families (64%) was defined; a total of 11 genes were implicated. Disease genes previously described in isolated families were validated and the clinical phenotypes of known disease genes was broadened. This study has also demonstrated genetic heterogeneity of hereditary ataxias but shows the impact of exome sequencing in a group of patients difficult to diagnose genetically.
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Pashkovskyy, V. M. "Comorbidity in neurological and mental disorders." Thesis, БДМУ, 2020. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/17640.
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Hulter, Birgitta. "Sexual function in women with neurological disorders." Doctoral thesis, Uppsala University, Department of Neuroscience, 1999. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-379.
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The purpose of this investigation was to study sexual function in women with neurological disorders at fairly distinct and separate locations. The dissertation comprises descriptive, retrospective, quantitative studies on sexual functioning in women with hypothalamo-pituitary disorders (HPD) (n:48), multiple sclerosis (MS)(n:47), and insulin-dependent diabetes mellitus (IDDM) (n:42). The results werecompared with those in an age-matched control group (C) (n:42), and as reported by representative Swedish women (n:742) in the Swedish sex survey SiS). The studies were based on comprehensive interviews, neurological examinations, incl. Vibration Perception Thresholds (IDDM), concentrations of prolactin and testosterone in serum (HPD), and a checklist on life satisfaction (IDDM, C, and SiS).
Sexual dysfunction was prevalent in almost all women with HPD and MS, and in 40% of the IDDM group. The problem of insufficient vaginal lubrication was more common in those with neurological disorders than among women in the SiS group. Sexual problems caused by reduced libido and orgasmic difficulties were more commonin the HPD and MS groups than in the SiS group. In the HPD group, women with intrasellar adenomas had better sexual function than women having expansively growing pituitary adenomas with both intra- and suprasellar extension. Normal serum testosterone values correlated to masturbation activity. Amenorrhea and older age werecorrelated with sexual problems in all groups. In the MS group, symptoms of a weak pelvic floor and of bladder and bowel dysfunction were correlated with reduced lubrication and orgasmic ability. In the IDDM group, signs of autonomic neuropathy were correlated with sexual dysfunction. Concerning life satisfaction generally,proportionately fewer women with IDDM were satisfied or very satisfied, though differing significantly from the other two groups in only two domains of life: contacts with friends, and physical health.
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Picardi, Chiara. "Characterization of neurological disorders using evolutionary algorithms." Thesis, University of York, 2018. http://etheses.whiterose.ac.uk/21702/.
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The life expectancy increasing, in the last few decades, leads to a large diffusion of neurodegenerative age-related diseases such as Parkinson’s disease. Neurodegenerative diseases are part of the huge category of neurological disorders, which comprises all the disorders affecting the central nervous system. These conditions have a terrible impact on life quality of both patients and their families, but also on the costs associated to the society for their diagnosis and management. In order to reduce their impact on individuals and society, new better strategies for the diagnosis and monitoring of neurological disorders need to be considered. The main aim of this study is investigating the use of artificial intelligence techniques as a tool to help the doctors in the diagnosis and the monitoring of two specific neurological disorders (Parkinson’s disease and dystonia), for which no objective clinical assessments exist. The evolutionary algorithms are chosen as the artificial intelligence technique to evolve the best classifiers. The classifiers evolved by the chosen technique are then compared with those evolved by two popular well-known techniques: artificial neural network and support vector machine. All the evolved classifiers are not only able to distinguish among patients and healthy subjects but also among different subgroups of patients. For Parkinson’s disease: two different cognitive impairment subgroups of patients are considered, with the aim of an early diagnosis and a better monitoring. For dystonia: two kinds of dystonia patients are considered (organic and functional) to have a better insight in the division of the two groups. The results obtained for Parkinson’s disease are encouraging and evidenced some differences among the cognitive impairment subgroups. Dystonia results are not satisfactory at this stage, but the study presents some limitations that could be overcome in future work.
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Kitchener, Erin Grace. "Selective disorders of memory in neurological patients." Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627365.
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Bilous, Iryna Ivanivna. "Neurological disorders of patients with endocrine pathology." Thesis, Буковинський деравний медичний університет, 2018. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/14444.
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Svedberg, Lena. "Cold feet in children with neurological disorders /." Gothenburg : Institute of Neuroscience and Physiology, Clinical Neuroscience and Rehabilitation, Sahlgrenska Academy, University of Gothenburg, 2009. http://hdl.handle.net/2077/21042.
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Casanova, Manuela Amaral Mucci. "Estudo da marcha da distrofia miotonica tipo 1 : parametros espaciais, temporais e cinematica." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313862.
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Orientadores: Anamarli Nuccic Alberto Cliquet JrDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-11T03:23:57Z (GMT). No. of bitstreams: 1 Casanova_ManuelaAmaralMucci_M.pdf: 2345728 bytes, checksum: f66ccc6bdf60b6250a95b5911fe73602 (MD5) Previous issue date: 2008
Resumo: A Distrofia Miotônica tipo 1 é doença multisistêmica que afeta com freqüência o músculo estriado, repercutindo na marcha, a qual pode apresentar-se em um espectro, desde muito anormal a sutis alterações de difícil caracterização através da visão humana. O objetivo deste trabalho foi analisar as variáveis espaciais, temporais e cinemáticas da marcha de afetados pela doença. Desenhou-se estudo prospectivo do tipo caso (n = 10) e controles (n = 20); os sujeitos foram investigados quanto à clínica da marcha e submetidos ao teste de força muscular. Marcadores reflexivos foram fixados em membros superiores, inferiores, tronco e pelve. A marcha, com pés descalços, ocorreu em passarela de 6 metros, capturada por 6 câmeras. Foram coletadas e analisadas 3 amostras de cada participante através do Sistema Qualisys®. Utilizou-se o Teste Exato de Fisher e o Teste de Mann-Whitney para a comparação das variáveis demográficas entre os grupos e a estatística descritiva dos casos. Encontrou-se alterações laboratoriais nos 10 pacientes, embora 04 não tivessem clínica de marcha anormal. O comprimento da passada foi diminuído em 80% dos casos, cadência menor em 30% e velocidade lenta em 40%. Anormalidade no movimento do quadril foi observada em 100% dos pacientes, da pelve em 90% e do tornozelo em 70%. O exame laboratorial da marcha permitiu diagnosticar alterações precoces, antes do aparecimento de déficit muscular à oposição de força, como ocorreu em 2 casos. A disfunção da marcha em laboratório esteve associada à fraqueza muscular distal isoladamente em 40%; e em associação com déficit proximal e distal em outros 40%
Abstract: Myotonic Dystrophy type 1 is a multisystemic disease that frequently affects the striated muscle with repercussion on gait. Gait function may be very abnormal or exhibit subtle alterations of difficult characterization by the human eyes. With objective to analyse the spatiotemporal and kinematics variables parameters of gait in patients affected by the disease, a prospective study of type case (n = 10) and controls (n = 20) was designed. The subjects were investigated in relation to clinical aspects of gait and submitted to the muscular force test. Reflexive markers were affixed in the upper and lower extremities, trunk and pelvis. A barefooted gait was performed in a 6-meter runway and captured by 6 ProReflex cameras. Three samples of each patient were collected and analyzed by the Qualisys® System. The Exact Test of Fisher and the Mann-Whitney Test were used for comparison of demographic variables between the groups and a descriptive statistic for cases. Abnormalities were found in all 10 patients, although 4 had no clinical evidence of gait problems. Stride was diminished in 80% of the cases, cadence in 30% and slow speed in 40%. Gait dysfunction was observed in 100% of the patients¿ hips, 90% of pelvis and 70% of ankles. The laboratory examination of gait allows early detection of alterations, even before the appearance of muscular deficit by manual force opposition test as occurred in two cases. Gait dysfunction observed in the laboratory was associated with distal muscular weakness in 40% of the patients and in association with proximal and distal deficits in others 40%
Mestrado
Ciencias Biomedicas
Mestre em Ciências Médicas
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Fu, Pengfei. "Causes of neurological disorders : associations of pm2.5 exposure and intestinal disorders." HKBU Institutional Repository, 2020. https://repository.hkbu.edu.hk/etd_oa/742.
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Objective: The aims of this project were to (a) perform a systematic review and meta-analysis of the associations between multiple neurological disorders (or neurological diseases) and potential influencing factors, including the association between fine particulate matter (PM 2.5) and intestinal dysfunction, and (b) investigate the mechanisms and toxicological effects of PM 2.5 exposure in the brain and intestines using a mouse model of Alzheimer's disease (AD). Design: A systematic review and meta-analysis was conducted to assess the risks of PM 2.5 exposure, as manifested by the incidence of exposure-associate neurological disorders or intestinal dysfunction. An APP/PS1 transgenic mouse model for AD was used to study the brain damage resulting from PM 2.5 exposure, and the miRNA/mRNA regulatory mechanisms contributing to this damage. The inflammatory injuries and bacterial community changes in the intestines of AD mice exposed to PM 2.5 were also investigated. Data sources: Articles for systematic review and meta-analysis were obtained by searching PubMed and China National Knowledge Infrastructure (CNKI), which were published for more than ten years. Animal experiments were conducted at Shanxi University of Taiyuan in China, and toxicological tests were performed according to the stipulated methods and protocols. Review and experimental methods: Data on the risks of incidence of neurological disorders associated with the environmental factor (PM 2.5) and biological factors (intestinal disorders and bacteria) were obtained, and random- or fixed-effects models (depending on the I 2 value) were used to pool the odds ratios (OR) with the 95% confidence intervals (CI) from individual studies. In the animal experiments, mice were divided into four groups of five animals per group, as follows: normal control mice in filtered air, AD mice in filtered air, normal control mice in PM 2.5 air, and AD mice in PM 2.5 air. PM 2.5 mice were exposed to ambient PM 2.5 in a whole-body inhalation exposure device for 8 weeks in Taiyuan, China. Well-established methods were used to explore the toxicological mechanisms by which PM 2.5 exacerbated brain damage in AD mice, namely open-field testing, enzyme-linked immunosorbent assay (ELISA), real-time quantitative RT-PCR, hematoxylin-eosin (HE) staining, and transmission electron microscopy (TEM). Brain damage and related biomarkers in the brains were measured, and miRNA and mRNA profiles were detected using high-throughput sequencing methods. The signaling pathways of miRNAs or mRNAs were predicted and summarized, and specific miRNAs and mRNAs were screened to explore the possible regulatory mechanisms of PM 2.5 -induced brain damage in AD mice. Intestinal and fecal samples from these mice were also subjected to 16S rRNA gene sequencing. HE staining, ELISA, and metagenome bacterial diversity analyses were performed to investigate the effects of PM 2.5 inhalation on intestinal tissue damage, inflammatory responses, and changes of bacterial diversity and communities in AD mice. Results: Long-term PM 2.5 exposure has been associated with increased risks of stroke, dementia, AD, autism spectrum disorder (ASD), and Parkinson's disease (PD) in humans, with the risks of ischemic and hemorrhagic stroke being higher than that of stroke in general. Furthermore, a relatively higher risk of stroke has been observed in heavily polluted countries compared to less polluted countries. It is known that some intestinal disorders and related problems such as constipation, inflammatory bowel disease, irritable bowel syndrome, small intestinal bacterial overgrowth, and diarrhea significantly increase the risks of developing AD or PD. For example, the risk estimates of Helicobacter pylori infection were significantly associated with AD and PD. From another angle, preliminary animal experimental results showed that PM 2.5 promoted brain morphological damage and decreased spatial exploration ability in AD mice, and was concomitant with increases in the concentrations of amyloid-β-42, acetylcholinesterase, tumor necrosis factor-α, and interleukin-6 and decreases in the concentrations of choline acetyltransferase. High-throughput sequencing and bioinformatics analyses revealed that miRNAs and mRNA had differential expression profiles subsequent to PM 2.5 exposure, which suggested that these species are involved in the molecular regulatory mechanisms and possible signal pathways of PM 2.5 -aggravated brain injury in AD mice. These PM 2.5 -aggravated brain injuries were correlated with pathological intestinal injury, inflammatory responses, and changes in bacterial diversity in the intestines and feces of PM 2.5 -exposed AD mice, and decreases in predominant bacteria were identified. These data will assist in delineating the ability of PM 2.5 exposure to induce pathological changes in the brain and gut tissue via the brain-gut axis and thereby aggravate AD. Conclusions: A systematic review and meta-analysis showed that there is a significant association between PM 2.5 exposure and the occurrence of stroke, dementia, AD, ASD, and PD, and a strong association between intestinal disorders and the presence of certain bacteria and the development of AD and PD. PM 2.5 (environmental factors) and intestinal disorders accompanied by changes in bacterial diversity (internal biological factors) appeared to be the two most important factors that increase the risk of developing neurological disorders. Experimental animal data showed that PM 2.5 potently damaged the brain and intestines of AD mice, and that the toxicological mechanisms of this PM 2.5 -mediated brain injury led to morphological changes, inflammation, and perturbation of miRNA/mRNA regulation in the brain. These data suggest that PM 2.5 inhalation also have modulatory effects on the abundance and diversity of intestinal bacteria in AD mice. The findings of this study have clarified positive relationships between environmental and biological factors and neurological disorders and have elucidated the potential mechanisms by which PM 2.5 may mediate the initiation or exacerbation of AD
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Doran, Graeme Paul. "Functional and genetic analysis of human neurological disorders." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543472.
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Morganbarry, Rosemarie A. "Phonetic and phonological aspects of neurological speech disorders." Thesis, University of Reading, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292502.
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Chauvin, Joshua. "Temporal expectations in healthy ageing & neurological disorders." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:79292953-64db-4b67-bc40-f7172b1994a2.
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Previous research has shown that orienting attention in time can help to improve behavioural outcomes. However, the extent to which temporal orienting can be preserved in ageing and in the context of neurological disorders remains unresolved. This thesis therefore explores temporal expectations in the healthy ageing and diseased brain by taking a neuropsychological approach. To begin, I provide an overview of the literature in Chapter 1 most relevant for the following investigation. Four chapters of experiments then follow. To examine the effects of ageing on temporal expectation, the performance of healthy young adults and healthy older adults is presented and the results are discussed in Chapter 2 and 3. Though it had been previously shown that older adults seem to experience an expectation deficit on temporal expectation tasks, these chapters demonstrate the preservation of temporal expectation in ageing. On their own, these findings represent an important and novel contribution to the literature; however, this research is incapable of establishing the causal mechanisms involved in temporal expectation. To explore the causal role of relevant brain regions in temporal expectation, Chapter 4 and 5 investigate the effects of temporal orienting in participants with damage to the basal ganglia - a brain region strongly implicated in temporal processing. In Chapter 4, the role of the basal ganglia in temporal expectations is examined using data collected from participants with Parkinson's disease and contrasts their performance with age-matched healthy controls. To complement this investigation, and to provide converging evidence for the basal ganglia's role in temporal expectations, Chapter 5 investigates the behavioural performance of individuals with focal lesions to the basal ganglia. The findings in this thesis are discussed in their wider context in Chapter 6, and directions for future research are proposed.
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Vitale, Giuseppina. "Aminergic systems in sleep disorders of neurological diseases." Doctoral thesis, Università di Catania, 2014. http://hdl.handle.net/10761/1538.
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INTRODUCTION: Dopamine is a catecholaminergic neurotransmitter. A variety of sleep disorders implicate a dysfunction in the dopaminergic system, particularly REM Behaviour Disorder (RBD), Restless Leg Syndrome (RLS) and Periodic Limb Movements during Sleep (PLMS). PLMS involve stereotyped, rhythmic extension movements of the big toe and dorsiflexion of the foot during sleep. PLMS is particularly frequent in Restless Legs Syndrome (RLS) and other sleep disorders. Few studies have documented a pathological PLMS index in patients with Epilepsy.
AIMS: The aims of this study were to evaluate the possibility of an association between Epilepsy and PLMS and to define the polysomnographic characteristics of PLMS. Given the dopaminergic nature of PLMS, the association between PLMS and Epilepsy might have represented an additional, indirect evidence of the involvement of dopamine in the pathogenesis of Epilepsy. Another aim was to evaluate the influence of some dopamine agonists commonly used in the treatment of PLMS on the PLMS pattern of some of the patients constituting our sample, as well as any impact these might have on epileptiform discharges.
MATERIALS AND METHOD: We selected all patients referred to our neurological clinic from 2008 to 2012, who had previously been diagnosed with epilepsy based on the ILAE criteria, who showed no signs of Sleep Apnea, RLS, RBD and other degenerative neurologic conditions and who were not being treated with antidopaminergic and/or antidepressant drugs. All patients underwent nocturnal video-polisomnographic recordings . We selected patients who had a PLM index considered as pathological (PLMI>5). Subsequently, 5 patients were randomly selected among those with Epilepsy who had a PLMS index > 5. All 5 patients underwent other two nocturnal video-polisomnographic recordings (before and after administration of a dopamine agonist drug, Pramipexole 0.18 mg). In both recordings, PLMS and epileptiform discharges were also counted and analysed.
RESULTS: Eighty-five patients who had been previously diagnosed with Epilepsy met the inclusion criteria for this study. Of these, 17/85 (20%) patients had a pathological PLM index (> 5).
Of the 85 patients in our sample, 12/17 (70.6%), were diagnosed with Temporal Lobe Epilepsy, 2/17 (11.8%) with Frontal Lobe Epilepsy and 3/17 (17.6%) with Juvenile Myoclonic Epilepsy.
PLMS registered in all 17 patients exhibited a mean PLMS index of 18.78 corresponding to the presence of a periodic nocturnal myoclonus of medium entity. In 58.8% PLMS appeared to be mainly distributed during the first half of the night and in 66.7% PLMS occurred during N2.
The analysis of the 5 patients who underwent two VPSG (before and after administration of a dopamine agonist drug) showed a close to 50% reduction of epileptiform discharges in patients with PLMS and Epilepsy after administration of a dopamine agonist, namely Pramipexole. CONCLUSIONS: The study confirms the presence of PLMS in patients with Epilepsy. In our sample, the frequency of PLMS episodes stood at 23%. These movements mainly occurred during the first half of the night, in connection with the N2 stage, with a severity ranging from mild to moderate. They therefore had characteristics and distributions which made them more similar to the PLMS described during RLS than to those associated to neurodegenerative conditions. In addition, the PLMS in our sample were more frequent in patients with Temporal Lobe Epilepsy.
Finally, considering the dopaminergic nature of PLMS, their occurrence in association with Epilepsy may serve to strengthen the role of dopamine in the pathophysiology of this disorder.
This could have significant repercussions even in the therapeutic field, opening up new possibilities through the employment of dopamine agonists which may well find use in the treatment of some forms of Epilepsy.
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Calinescu, Catalin. "Outcomes of educational intervention with students with neurological disorders." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0014/MQ29148.pdf.
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Spyers-Ashby, Julia Mary. "The recording and analysis of tremor in neurological disorders." Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286132.
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Candler, Paul Mark Edward. "Antigen identification in paraneoplastic and post-infectious neurological disorders." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1444133/.
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Anti-neuronal antibodies have been conclusively shown to be pathogenic in a handful of neurological disorders but their value in diagnosis is undeniable. Nevertheless, there are instances where diseases thought have an immunological component do not have clear antibody responses associated with them This thesis aimed to identify anti-neuronal antibodies and characterise their antigens in paraneoplastic and post-infectious neurological disorders. With regard to the latter. interest in the occurrence of anti-neuronal responses in post-streptococcal neurological disorders has culminated in the identification of four candidate auto-antigens. Recombinant forms of these proteins were produced and the frequency of an antibody response in patients determined. In addition, the antigen recognised by antibodies in the serum of patients with post-infectious opsoclonus-myoclonus was characterised using protein purification techniques and the frequency of an antibody response determined. Finally, a bacteriophage expression library was employed to study a novel antibody in a patient w ith paraneoplastic disease. Our findings were unable to provide support for an antibody response against the candidate auto-antigens in post-streptococcal disease. However we were able to characterise two target antigens, one in post-streptococcal opsoclonus-myoclonus and one in paraneoplastic neurological disease. Both antigens are thought to have specific roles in the nervous system and have provided interesting opportunities for further research into there roles in neuronal, and in the case of paraneoplastic disease, tumour biology. Further investigation is required to determine the importance of the antibody response in both post-infectious and paraneoplastic disease.
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Boridy, Sebastien. "Nanocarriers to modulate glial cell responses in neurological disorders." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121198.
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Macromolecular drug delivery systems, or nanocarriers, designed to improve the bioavailability of therapeutic and diagnostic agents, are promising tools for the site-specific delivery of drugs to the central nervous system (CNS). In particular, nanocarriers exhibit inherent activity that can be used to modulate glial cell responses to stimuli in the CNS microenvironment. However, we have a very poor understanding of how nanocarriers exert these effects. In particular, how their size, shape, and surface chemistry play a role. The main objective of this work was to define how nanocarriers regulate glial cell responses.In these studies, we first examined how a nanogel nanocarrier can promote chaperone-like functions to prevent glial cell responses to a pathological insult. Utilizing oligomeric forms of the 42 amino acid beta-amyloid peptide (Abeta1-42), which plays a central role in Alzheimer's disease, we show that nanogels readily bind to oligomers and prevent their induction of toxicity in both microglial and primary astroglial cell cultures. Moreover, we show that nanogels with a positive surface charge are more cytotoxic and less effective at inhibiting Abeta1-42-mediated toxicity than their neutral counterparts. These results underline the importance of characterizing nanocarrier properties to predict the influence they will exert on glial cell function. Given the central role that microglia play in neuroinflammation, we sought to elucidate the relationship between nanocarrier design and the consequent microglial inflammatory response. We focused our studies on nanocarrier shape, the responses to which are not well characterized. Gold nanoparticles are ideal nanocarriers for such studies because their shape can be easily tuned to generate nanospheres, nanorods, and nanourchins. Using transgenic mice expressing luciferase driven by the toll-like receptor 2 (TLR-2) promoter, a model of microglia activation, we observed an increased bioluminescent signal in the olfactory bulb (OB) following intranasal injection with gold nanorods and nanourchins, but not nanospheres. TLR-2 induction in the OB correlated with the recruitment of Iba1-positive microglia. Confirmatory studies in microglial cultures revealed differential pro-inflammatory cytokine release profiles that were dependent on nanoparticle shape. Our findings provide new guiding principles for the design of nanocarriers to manipulate microglial inflammatory phenotype. Uncontrolled neuroinflammation can exacerbate CNS disorders, such as neurodegenerative disease and glioblastoma multiforme (GBM). Celastrol is a novel drug with known therapeutic activity against neuroinflammation and glioma survival; however its use is limited due to instability and low solubility. We employed models of both, pro-inflammatory microglia and GBM, to promote celastrol's anti-inflammatory and anti-cancer effects, respectively, using nanocarriers.In an in vitro model of neuroinflammation where lipopolysaccharide (LPS) treatment polarizes microglia to a pro-inflammatory state, we first investigated celastrol's ability to inhibit the phenotypic switch. Celastrol blocked LPS-induced pro-inflammatory mediator release from polarized microglia, reducing tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), and nitric oxide production, but caused unwanted cytotoxicity within the same concentration range. By incorporating celastrol into anti-inflammatory poly(amidoamine) (PAMAM) dendritic nanocarriers, we successfully blocked the drug's cytotoxic effects without compromising its anti-inflammatory activity, thereby broadening celastrol's therapeutic index. Unexpectedly, we also uncovered inherent mitogen-activated protein kinase (MAPK) inhibitory activity for naked PAMAM dendrimers in microglia, an affect for which there was no prior knowledge. Preliminary studies of celastrol's anti-cancer action in glioblastoma cells uncovered proteostatic resistance mechanisms that promote gl[abbreviated]Les systèmes macromoléculaires de délivrance médicamenteuse, ou les nanovecteurs, visent à améliorer la biodisponibilité des agents thérapeutiques et diagnostiques et sont des outils prometteurs pour le traitement des maladies du système nerveux central (SNC). En particulier, les nanovecteurs présentent une activité intrinsèque qui peut être utilisé pour moduler les réponses des cellules gliales aux stimulis du micro-environnement du SNC. Cependant, nos connaissances sur la façon dont ces nanovecteurs exercent leur effets sont limités; en particulier, nous connaissons peu sur le rôle par rapport à leur grandeur, leur morphologie et la chimie de surface. L'objectif principal de cette thèse était de définir comment les nanovecteurs régulent les réponses des cellules gliales.Nous avons d'abord examiné comment les nanovecteurs nanogel peuvent promouvoir les fonctions des chaperons moléculaires pour éviter la cytotoxicité des cellules gliales lors d'une insulte pathologique. Utilisant les formes oligomériques du peptide β-amyloïde (Aβ1-42) jouant un rôle central dans la maladie d' Alzheimer, nous montrons que les nanogels se lient facilement aux oligomères, en prevenant la toxicité dans les deux cultures de cellules microgliales et astroglials primaire. Entre autre, nous montrons que les nanogels avec une charge de surface positive sont plus cytotoxiques et moins efficaces pour inhiber la toxicité de Aβ1-42- par comparaison à leurs homologues neutres. Ces résultats soulignent l'importance de la caractérisation des nanovecteurs pour prédire l'influence qu'ils exercent sur la fonction des cellules gliales. Nous avons cherché à élucider la relation entre la conception des nanovecteurs et la réponse inflammatoire des cellules gliales. Nous étions particulièrement intéressés par un trait qui n'est pas très bien caractérisé: sa morphologie. Les nanoparticules d'or (nanosphères, nanobâtonnets, nanourchins) sont des nanovecteurs idéales pour une telle étude en raison de leur construction modifiable. En utilisant des souris transgéniques qui expriment la luciférase entraînée par le récepteur Toll-like 2 (TLR-2), nous avons observé un signal bioluminescente dans le bulbe olfactif après injection intra-nasale avec des nanorods et des nanourchins, mais pas avec les nanosphères, qui corrélait avec une augmentation de microglies positifs pour Iba-1. Des études portants sur les cultures microgliales ont révélé des profils de libération de cytokines pro-inflammatoires différentielles qui étaient dépendants de la morphologie de nanoparticules, mais indépendants de la chimie de surface. Nos résultats fournissent de nouvelles directives pour la construction de nanovecteurs afin de manipuler le phénotype inflammatoire microgliale.La neuro-inflammation non contrôlée pourrait aggraver les troubles du SNC, tels que les maladies neurodégénératives et le glioblastome multiforme (GBM). Celastrol est un nouveau médicament ayant une activité thérapeutique connue contre la neuro-inflammation et le survie des gliomes, mais l'utilisation est limitée en raison de l'instabilité et de la faible solubilité. Nous avons cherché à élucider ses effets contre l'activité aberrante des cellules gliales en utilisant des nanovecteurs.Dans un modèle in vitro de la neuro-inflammation où le traitement avec lipopolysaccharide (LPS) polarise les cellules microgliales dans un état pro-inflammatoire, nous avons étudié la capacité de celastrol à inhiber le changement de son phénotype. Celastrol a bloqué la libération de médiateurs pro-inflammatoires induit par LPS dans les cellules microgliales polarisées, ce qui réduit la production d'oxyde nitrique, de facteur de nécrose tumorale alpha (TNFα), et de l'interleukine-6 (IL-6), mais a provoqué une cytotoxicité indésirable à la même concentration. En intégrant celastrol dans les polymères anti-inflammatoire (amidoamine) (PAMAM) nanovecteurs dendritiques, nous avons réussi à bloquer ses effets cytotoxiques sans compromettre[couper]
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Gannicliffe, A. "Investigations into the role of viruses in neurological disorders." Thesis, University of Liverpool, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381334.
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Beal, Maryann. "Serving Students with Neurological Disorders: A Manual for Educators." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/194131.
Full textAbstract:
During the past 20 years, the number of children and youth with neurological disorders attending schools has increased dramatically. There are two reasons for this increase. First, medical advances have resulted in more children and youth with neurological disorders surviving. Second, in the past, children with disabilities and health care needs were cared for in hospitals and residential institutions. Since 1975, however, federal legislation has mandated that all children with disabilities be provided a free appropriate public education in the nation's schools and in general education classrooms whenever possible.Unfortunately, school administrators and classroom teachers are not trained in how to accommodate students with neurological disorders. The medical literature provides information regarding the medical aspects of neurological disorders. However, neither the medical literature nor the educational literature provides the specialized knowledge and skills administrators and teachers need to plan for and provide appropriate educational and health related services to children with neurological disorders. This dissertation addresses the need to provide teacher and administrators with practical information about accommodating students with neurological disorders in schools.The purpose of this project was to develop a resource manual which describes the impact of students' neurological disorders on their education. This "user-friendly" resource manual can be used by teachers, administrators, and support staff in developing individualized educational programs for children and youth with neurological disorders. The manual focuses on six neurological disorders about which school personnel have limited knowledge. Section One includes a historical overview of the education of children with neurological disorders and the legislation which mandates that schools must provide all children with disabilities an appropriate education. Section Two describes each neurological disorder by presenting the definition of the disorder and its associated physical and cognitive conditions. Section Three addresses accommodations teachers can use in classrooms to meet the individual physical, cognitive and health care needs of these children.
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Oskoui, Maryam. "STAND: study on the transition of adolescents with neurological disorders." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=96754.
Full textAbstract:
Background: Children with chronic neurological disorders are increasingly surviving to adulthood and transitioning to adult healthcare. Our objectives were to describe, from the neurologists' perspective, current practice and views on health care transition in Quebec, including barriers and facilitators to the process, if patients experience a gap in care, and if adult neurologists are adequately trained to care for these patients.Methods: We conducted a cross sectional study using two postal surveys of all Quebec pediatric and adult neurologists.Results: The overall response rate to the mailing was 65.4%, with 51.5% participation rate. Most do not have a transition program in place but some plan to develop one in the next two years. Nearly half of neurologists believed patients experience a gap in care during the transition process. Half of neurologists agreed that adult neurologists may not have adequate training in childhood onset chronic neurological disorders to prepare them to manage these disorders in adulthood, and 60% of pediatric neurologists reported having difficulty finding an adult provider for their patients. The majority of neurologists agreed that patient's knowledge of their medical condition and medication, compliance with medication, capacity for active participation during office visits, co-existence of a communication or behavioral disorder, and need for multidisciplinary care were all important factors affecting the success of transition. Conclusion: Half of surveyed neurologists believed patients experience a gap in care during the transition period. Neurologists reported multiple barriers to the transition process including both patient and physician specific factors. Almost half of surveyed physicians believed adult neurologists are not adequately trained to care for this growing patient population.La problématique: Les enfants souffrant de troubles neurologiques chroniques vivent de plus en plus jusqu'à l'âge adulte. Nos objectifs étaient de décrire, du point de vue du neurologue au Québec, la pratique courante et les opinions à l'égard de la transition de ces adolescents des soins pédiatriques aux soins adultes, incluant les barrières au processus, si les patients éprouvent un carence en soins durant cette période, et si les neurologues pour adultes ont la formation requise pour prendre soin de ces patients.Les méthodes: Nous avons fait une étude transversale par envoyant deux questionnaires par la poste à tous les neuropédiatres et neurologues pour adultes du Québec.Résultats: Notre taux de réponses à lènvoi des questionnaires était de 65.4%, avec un taux de participation de 51.5%. La plupart nàvaient pas de programme de transition sur place, mais plusieurs planifiaient développer un programme dans les deux prochaines années. Presque la moitié des neurologues croyaient que les patients éprouvent une carence en soins durant la période de transition aux soins adultes. La moitié des neurologues croyaient que les neurologues pour adultes n`ont peut être pas la formation requise pour prendre la relève des soins des jeunes adultes ayant un trouble neurologique chronique débutant en enfance. 60% des neuropédiatres éprouvaient des difficultés à trouver un médecin pour adultes pour prendre la relève des soins de leurs patients. La majorité des neurologues croyaient que la connaissance du patient de sa maladie et de ses médicaments, la conformité aux médicaments, la capacité de participer pleinement durant les visites chez me médecin, la présence dùn trouble de communication ou de comportement, et le besoin de soins multidisciplinaires étaient des facteurs jouant des rôles importantes durant la période de transition des soins.Conclusion: La moitié des neurologues croyaient que les patients éprouvent une carence en soins durant la période de transition. Les neurologues ont fait rapport de plusieurs obstacles à la transition des soins, soit des facteurs reliés aux patients et d'autres reliés aux médecins et services de soins. Presque la moitié des neurologues croyaient que les neurologues pour adultes n'ont pas la formation requise pour prendre soin de ce groupe croissant de patients.