Biomedical subjects

Pamela J Thompson

Publications and source records attributed to Pamela J Thompson.

15 recordsLinked to original sources

PubMed2006

Mortality and morbidity rates are increased in people with epilepsy: is stress part of the equation?

People with epilepsy (PWE), particularly those with more severe seizures, are at risk of premature death. The contribution of deaths unrelated to epilepsy to this risk is likely to be significant. Recent studies indicate that comorbid conditions are similarly increased in PWE. The reason for these increases in unrelated deaths and comorbid conditions is unclear. In this article, we argue that having seizures is psychologically stressful, and that this stress can lead to a whole range of pathophysiological changes that may trigger various physical illnesses. Hence, psychological stress may be a significant factor contributing to the increase in mortality and comorbidity rates in PWE. This speculation is unlikely to be proven at this stage because of the complexity of the trials required. In PWE who continue to have seizures, more needs to be done to help them cope with the stress. Additionally, attention needs to be paid to improve nutritional status and physical fitness. These steps are likely to enhance the overall health of PWE and may reduce premature mortality and comorbidity rates.

Epilepsy↗

PubMed2006

A neuropsychological study of patients with temporal lobe epilepsy and chronic interictal psychosis.

PURPOSE: To characterize the pattern of cognitive deficits in patients with temporal lobe epilepsy (TLE) and interictal (schizophrenia-like) psychosis and to examine the relationship between neuropsychological deficits and Magnetization transfer imaging. METHODS: Twenty patients with TLE and interictal psychosis were compared to 20 non-psychotic TLE patients. Patients were matched with respect to premorbid IQ, age and conventional MRI findings. A battery of neuropsychological tests was administered. The neuropsychological tests which showed significant group differences were used for correlational analysis with magnetization transfer ratio (MTR) which provides a quantitative measure of macromolecular structural integrity. RESULTS: Patients with interictal psychosis were significantly more impaired on executive and semantic memory tasks than the non-psychotic TLE group. Vocabulary test scores correlated significantly with MTR reduction in the left fusiform gyrus in the psychotic but not the non-psychotic group. DISCUSSION: In this study, patients with TLE and interictal psychosis were more cognitively impaired than non-psychotic TLE patients. Our findings suggest that the cognitive deterioration in these patients may occur as the illness progresses and the causes for this are probably multifactorial. Our study also provides further evidence that MTR may be useful in investigating structural correlates of cognitive impairment.

Adult↗

PubMed2006

A novel homeobox mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome associated with brain, ocular, and dental phenotypes.

Axenfeld-Rieger Syndrome (ARS) is a genetically heterogeneous birth defect characterized by malformation of the anterior segment of the eye associated with glaucoma. Mutation of the PITX2 homeobox gene has been identified as a cause of ARS. We report a novel Arg5Trp missense mutation in the PITX2 homeodomain, which is associated with brain abnormalities. One patient had a small sella turcica likely to reflect hypoplasia of the pituitary gland and consistent with the critical role identified for Pitx2 in pituitary development in mice. Two patients had an enlarged cisterna magna, one with a malformed cerebellum, and two had executive skills deficits one in isolation and one in association with a below average intellectual capacity. The mutation caused a typical ARS ocular phenotype. All affected had iris hypoplasia, anterior iris to corneal adhesions, and corectopia. The ocular phenotype varied significantly in severity and showed some asymmetry. All affected also had redundant peri-umbilical skin, a hypoplastic maxilla, microdontia, and hypodontia missing between 20 and 27 teeth with an unusual pattern of tooth loss. Dental phenotypes were documented as they are often poorly characterized in ARS patients. All affected individuals showed an absence of first permanent molars with variable absence of other rarely absent teeth: the permanent upper central incisors, maxillary and mandibular first and second molars, and the mandibular canines. Based on the distinctive dental anomalies, we suggest that the dental phenotype can assist in predicting the presence of a PITX2 mutation and the possibility of brain abnormalities.

Abnormalities, Multiple↗

PubMed2006

The impact of levetiracetam on challenging behavior.

An observational longitudinal design was employed to evaluate whether treatment with the antiepileptic drug levetiracetam (LEV) adversely impacts behavior in people with intellectual disabilities and/or acquired brain damage. Thirty-five adults were assessed once off the drug and once when on LEV therapy, with a 2-month interval between assessments. Behaviors were rated using an adaptation of the Yale-Brown Obsessive Compulsive Scale and the Challenging Behaviour Scale. Challenging behaviors were rated as more frequent and severe when individuals were taking LEV. Behavioral worsening was not related to better seizure control or increased levels of engagement in activities. Families and professionals need to be aware of the potential reversible adverse effects of this drug.

Adult↗

PubMed2006

Role of SOX2 mutations in human hippocampal malformations and epilepsy.

PURPOSE: Seizures are noted in a significant proportion of cases of de novo, heterozygous, loss-of-function mutations in SOX2, ascertained because of severe bilateral eye malformations. We wished to determine the underlying cerebral phenotype in SOX2 mutation and to test the candidacy of SOX2 as a gene contributing to human epilepsies. METHODS: We examined high-resolution MRI scans in four patients with SOX2 mutations, two of whom had seizures. We determined the Sox2 expression pattern in developing murine brain. We searched for SOX2 mutation in 24 patients with typical hippocampal sclerosis and for common variations in SOX2 in 655 patients without eye disease but with epilepsy, including 91 patients with febrile seizures, 93 with hippocampal sclerosis, and 258 with temporal lobe epilepsy. RESULTS: Striking hippocampal and parahippocampal malformations were seen in all cases, with a history of febrile seizures or epilepsy in two of four cases. The Sox2 expression pattern in developing mouse brain supports the pattern of malformations observed. Mutation screening in patients with epilepsy did not reveal any abnormalities in SOX2. No associations were found between any clinical epilepsy phenotype and common variation in SOX2. CONCLUSIONS: SOX2 haploinsufficiency causes mesial temporal malformation in humans, making SOX2 dysfunction a candidate mechanism for mesial temporal abnormalities associated with chronic epilepsy. However, although mutation of SOX2 in humans causes hippocampal malformation, SOX2 mutation or variation is unlikely to contribute commonly to mesial temporal lobe epilepsy or its structural (hippocampal sclerosis) or historic (febrile seizures) associations in humans.

Adolescent↗

PubMed2006

Diffusion tensor imaging findings and their correlation with neuropsychological deficits in patients with temporal lobe epilepsy and interictal psychosis.

PURPOSE: To examine frontotemporal white-matter integrity in patients with temporal lobe epilepsy (TLE) and interictal psychosis. METHOD: Patients with TLE and interictal psychosis (IP; n = 20) were compared with age-matched TLE patients without psychosis (NIP; n = 20). Patients had either no focal lesions or hippocampal sclerosis on conventional MRI. Complete diffusion tensor imaging (DTI) data were available in 18 IP and 20 NIP patients. A region-of-interest (ROI) approach was used to determine the DTI measures, fractional anisotropy (FA) and mean diffusivity (MD), in the middle frontal and middle temporal gyri. The relation between the DTI measures and neuropsychological tests previously identified as impaired in the IP group was examined. RESULTS: The IP group had significantly lower FA values in both frontal and temporal regions and significantly higher MD in bilateral frontal regions. We found that performance on some neuropsychological tests was significantly related to frontotemporal FA reductions. CONCLUSIONS: Our findings suggest that subtle abnormalities in the frontotemporal white matter of patients with interictal psychosis may be undetectable on conventional MRI. These abnormalities may contribute to the cognitive deficits detected in these patients.

Adult↗

PubMed2005

Heterozygous mutations of OTX2 cause severe ocular malformations.

Major malformations of the human eye, including microphthalmia and anophthalmia, are examples of phenotypes that recur in families yet often show no clear Mendelian inheritance pattern. Defining loci by mapping is therefore rarely feasible. Using a candidate-gene approach, we have identified heterozygous coding-region changes in the homeobox gene OTX2 in eight families with ocular malformations. The expression pattern of OTX2 in human embryos is consistent with the eye phenotypes observed in the patients, which range from bilateral anophthalmia to retinal defects resembling Leber congenital amaurosis and pigmentary retinopathy. Magnetic resonance imaging scans revealed defects of the optic nerve, optic chiasm, and, in some cases, brain. In two families, the mutations appear to have occurred de novo in severely affected offspring, and, in two other families, the mutations have been inherited from a gonosomal mosaic parent. Data from these four families support a simple model in which OTX2 heterozygous loss-of-function mutations cause ocular malformations. Four additional families display complex inheritance patterns, suggesting that OTX2 mutations alone may not lead to consistent phenotypes. The high incidence of mosaicism and the reduced penetrance have implications for genetic counseling.

Amino Acid Motifs↗

PubMed2005

Calcitonin gene polymorphism CALCA-624 (T/C) and ovarian cancer.

In a previous analysis, we reported an inverse association of dietary calcium intake with the risk of ovarian cancer (Goodman et al. 2002. Am J Epidemiol 156:148-57). The CALCA gene codes for calcitonin, an important regulator of bone calcium metabolism. Data from a population-based case-control study conducted in Hawaii were used to examine the hypothesis that a T --> C transition 624 base pairs upstream (-624) of the translation initiation codon of the CALCA gene influences the risk of ovarian malignancy. A structured interview was conducted for 182 histologically confirmed ovarian cancer cases and 219 controls. Blood specimens were collected from the subjects at their homes. A significant negative trend (P for trend: 0.02) in the odds ratios (ORs) was found with increasing intake of calcium. Women with any CALCA C allele were at nonsignificantly higher risk of ovarian cancer (OR: 1.5, 95% CI: 0.9-2.3) compared to women with the TT genotype and the risk increased with the number of C alleles (P for trend: 0.05). When further analyzed within ethnic subgroups, a significant positive association was found among Japanese for CALCA CT (OR: 2.3, 95% CI: 1.0-5.3) and CALCA CC (OR: 7.2, 95% CI: 1.1-46.0) compared with Japanese women who were homozygous for the T allele. The trend in risk associated with the C allele was most significant among women who had used oral contraceptives (P for trend: 0.05), had been pregnant (P for trend: 0.04), and had nonmucinous histological types of ovarian cancer (P for trend: 0.02). However, the association of ovarian cancer risk with the CALCA genotype was not significantly modified by any of the dietary, nondietary, or clinical variables included in this study. These preliminary data suggest a strong positive association of the CALCA C allele with the risk of ovarian cancer among some subgroups.

Adolescent↗

PubMed2005

Epilepsy & depression: the effects of comorbidity on hippocampal volume--a pilot study.

Hippocampal sclerosis (HS) is one of the most common pathologies in medically intractable temporal lobe intractable epilepsy. Significant hippocampal volume loss has also been found in patients with chronic depression. Depression is common in chronic epilepsy populations, but the effects of this comorbidity on hippocampal volume are unknown. We examined the hippocampal volumes of 87 patients (n=31 right hippocampal sclerosis, RHS; n=56 left hippocampal sclerosis, LHS). Each subject completed the Hospital Anxiety and Depression Scale (HADS). In the group as a whole, 13 subjects (15%) recorded moderate or severe levels of depression. Depression was more common in the LHS group with 1 in 5 scoring in the moderate or severe range on the HADS (n=11). Depression scores were not significantly correlated with quantitative measures of hippocampal volume in the LHS group. However, higher degrees of hippocampal symmetry were associated with higher levels of depression in the RHS group. This suggests that the left hippocampus may be smaller in depressed patients with RHS, although our numbers were too small to confirm this statistically. Our results suggest that the depression may influence left hippocampal volume in patients with right hippocampal sclerosis. We conclude that the neuroradiological characteristics of patients with epilepsy and chronic depression deserve further examination.

Adult↗

PubMed2005

Cognitive decline in severe intractable epilepsy.

PURPOSE: To explore the relation between seizure-related variables and cognitive change in patients with severe intractable epilepsy. METHODS: A retrospective analysis of data from 136 patients who had undergone a cognitive assessment on two occasions at an interval of > or =10 years. Cognitive measures included tests of memory and executive skills in addition to intelligence quotients (IQ). Details were available regarding seizure type and frequency in the intertest interval. RESULTS: Cognitive decline was severe and occurred across a wide range of cognitive functions. The frequency of generalised tonic-clonic seizures was the strongest predictor of decline. Complex partial seizure frequency was associated with a decline in memory and executive skills but not in IQ. Seizure-related head injuries and advancing age carried a poor cognitive prognosis, whereas periods of remission were associated with a better cognitive outcome. Early age at onset was not implicated, and duration of epilepsy was a much less potent predictor of cognitive decline than has been reported in cross-sectional studies. No evidence indicated that a higher level of cognitive function protected against cognitive decline. CONCLUSIONS: Our findings, together with those from animal studies and surgically treated patients, suggest that seizures can have a direct adverse effect on cognition and that good seizure control even after years of intractability can have a beneficial impact on cognitive prognosis. This study was based on individuals who merited two cognitive assessments > or =10 years apart and hence is biased in favor of those with the most severe forms of refractory epilepsy and those with decline.

Adult↗

PubMed2004

Pre-operative verbal memory fMRI predicts post-operative memory decline after left temporal lobe resection.

Functional MRI (fMRI) of cognitive tasks depends on technology widely available in the clinical sphere, but has yet to show a role in the investigation of patients. We report here the first demonstration of a clinically valuable role for cognitive fMRI. Temporal lobe epilepsy (TLE) is commonly caused by hippocampal sclerosis and is frequently resistant to drug treatment. Surgical resection of the left hippocampus in this setting can cure seizures, but may produce significant verbal memory decline, which is hard to predict. We report 10 right-handed TLE patients with left hippocampal sclerosis who underwent left hippocampal resection. We compared currently used data for the prediction of post-operative verbal memory decline in such patients with a novel fMRI assessment of verbal memory encoding. Multiple regression analyses showed that fMRI provided the strongest independent predictor of memory outcome after surgery. At the individual subject level, the fMRI data had high positive predictive value for memory decline.

Adult↗

PubMed2004

Polymorphisms of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, and IL-18 and the risk of ovarian cancer.

OBJECTIVE: Recent studies of ovarian cancer have suggested a role for inflammation in carcinogenesis. Data from a population-based case-control study in Hawaii were examined to assess the relation between polymorphisms in cytokines involved with the inflammatory response, specifically members of the interleukin (IL) family and the incidence of ovarian cancer. PATIENTS AND METHODS: The analysis of 182 epithelial ovarian cancer cases and 219 controls focused on the polymorphisms in the following genes: IL-1alpha, IL-1beta, IL-6, IL-10, and IL-18. Genotype data were obtained from blood samples collected in participants' homes, and reproductive, demographic, and lifestyle histories were collected during interview. RESULTS: There were no significant odds ratios (ORs) for ovarian cancer by allelic variants in any of the IL genes after adjusting for age, ethnicity, education, oral contraceptive pill use, pregnancy, and history of tubal ligation. Although there was a significantly reduced risk of ovarian cancer risk among women with an IL-1alpha (-4845) T allele compared to women with two G alleles (OR: 0.59; 95% confidence interval: 0.37-0.97) after adjustment for age and ethnicity, the trend was not significant (p = 0.10). Further examination of the data suggested that women with at least one IL-18 variant allele (a G to C transition at position -137) were at significantly decreased risk of advanced ovarian cancer (OR: 0.51; 95% confidence interval: 0.28-0.90) compared to women with the IL-18 GG genotype. There was a significant difference in the risk of ovarian cancer associated with the IL-18 C allele by stage at diagnosis (p = 0.04 for homogeneity in the ORs): cases with IL-18 GC or CC genotypes were less likely to be diagnosed at regional/distant stages. Analysis of the data within ethnic subgroups revealed a significant positive association of the heterozygous IL-18 GC genotype with ovarian cancer risk among Native Hawaiian women (OR: 9.96; 95% CI: 1.88-52.90). The OR for ovarian cancer was not significant for Native Hawaiian women homozygous for the IL-18 C allele, but only one case and control had the IL-18 CC genotype. CONCLUSIONS: Overall, this study does not support an association of selected IL-1alpha, IL-1beta, IL-6, IL-10, or IL-18 polymorphisms with the risk for ovarian cancer. However, the IL-18 G137C variant may be a marker for ovarian cancer progression or metastasis.

Adult↗

PubMed2003

Effects of pro- and anti-tobacco advertising on nonsmoking adolescents' intentions to smoke.

PURPOSE: To determine the effects of pro- and anti-tobacco advertising on nonsmoking adolescents' intention to smoke in a single cohort. METHODS: All ninth graders at seven public high schools were invited to participate in a study on adolescent tobacco use; 59.0% participated (n = 1229; active positive parental consent required). Adolescents who self-identified as never having smoked even a puff of a cigarette (n = 512) completed a self-administered questionnaire that included questions on intention to smoke in the near future and tobacco advertising. Independent variables used to predict intention included exposure to, recognition of, and receptivity and attitudes toward pro-tobacco and anti-tobacco advertising. Potential confounding variables included gender, race/ethnicity, smoking influences (adult household members, siblings, and friends), socioeconomic status, stress, and depression. Data analysis used logistic regression. RESULTS DEMOGRAPHICS: 50.5% female, average age 14.9 +/- 0.4 years old at baseline, and varied race. Those variables found to be significant predictors of intention to smoke included: (positive, or increased intention) recognition of brand of favorite advertisement, willingness to use or wear tobacco-branded products, stress, and having friends who smoke and (negative, or decreased intention) agreement with anti-tobacco advertising and having a live-in father who smokes. CONCLUSIONS: Although anti-tobacco advertising has a protective effect, it was unable to counteract the effects of pro-tobacco advertising in the same cohort.

Adolescent↗

PubMed2003

Non-epileptic seizures: patients' understanding and reaction to the diagnosis and impact on outcome.

RATIONALE: The study aim was to assess patients' understanding of and reaction to a diagnosis of non-epileptic attack disorder and to explore whether these factors contribute to outcome. METHOD: Eighty-four patients diagnosed with non-epileptic attack disorder participated in the study. Participants answered questions about their seizures and understanding and reaction to the diagnosis. Data were collected by semi-structured telephone interview. Questionnaires were sent to the patients' general practitioners (GPs) to gather information regarding the patient's seizure status, prescription of anti-epileptic drugs and opinion regarding the diagnosis. RESULTS: At the time of follow-up, a third of participants reported being seizure free. A total of 63% did not have a good understanding of the diagnosis, most were unclear about the precipitating factors and the most common reaction to the diagnosis was confusion. Many reported a negative impact of NES on everyday life. Sixty-five percent reported receiving psychological follow-up but the number of sessions attended was few (median 2). There was evidence that the reaction to the diagnosis contributed to the outcome in particular an angry outcome was associated with a poor prognosis. Ten GPs did not agree with the diagnosis. CONCLUSION: Patients understanding and reactions to a diagnosis of non-epileptic attacks are important factors that should contribute to the development of more tailored treatment approaches.

Activities of Daily Living↗

PubMed2002

Using qualitative research to inform survey development on nicotine dependence among adolescents.

Researchers interested in measuring tobacco use and dependence among youth face several formidable challenges. These challenges include: most existing measures have been developed for adult samples and may not be suitable for adolescent respondents; surveys must be relevant to different youth subcultures and to both genders; questions must be developmentally appropriate and not perceived as judgmental or condescending; and the multidimensional nature of nicotine dependence in youth must be recognized and measured. This paper demonstrates how researchers can address these challenges by using qualitative techniques to obtain information on youth tobacco consumption, and then using this information to inform the development of quantitative instruments. A case study is presented where a measure of tobacco dependence originally developed for adults is adapted for use with adolescents. A seven-step formative research process is outlined, consisting of gathering information in open-ended interviews, conducting follow-up research, modification of questionnaire items and addition of new items based on the information gathered, constructing a reliable instrument that is readable and acceptable to youth, reducing the length of this instrument without significantly hurting reliability and validity, conducting additional follow-up research involving case studies, and examining cultural differences. Following a formative research process like this one will help tobacco researchers gain a better understanding of how nicotine dependence develops.

Adolescent↗