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1.
J Surg Oncol ; 129(3): 601-608, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37965813

RESUMEN

BACKGROUND AND OBJECTIVES: This multicenter retrospective series of consecutive extra-spinal aneurysmal bone cysts aims to identify risk factors for treatment failure. METHODS: Aneurysmal bone cysts treated within seven collaborating centers with over 12-months follow-up were eligible for inclusion. Survival analyses were performed to identify variables associated with recurrence using log-rank tests and Cox proportional hazard regression. RESULTS: One hundred and fifteen (M:F 60:55) patients were included. Median age at presentation was 13 years and median follow-up was 27 months. Seventy-five patients underwent surgical curettage and 27% of these required further intervention for recurrence. Of the 30 patients who underwent biopsy with limited percutaneous curettage as initial procedure, 47% required no further treatment. Patients under 13 years (log-rank p = 0.006, HR 2.3, p = 0.011) and those treated who had limited curettage (log-rank p = 0.001, HR 2.7, p = 0.002) had a higher risk of recurrence/persistence. CONCLUSIONS: There is a high risk of recurrence following surgical treatment for aneurysmal bone cysts and this risk is higher in young patients. However, the cyst heals in a substantial number of patients who have a limited curettage at the time of biopsy.


Asunto(s)
Quistes Óseos Aneurismáticos , Humanos , Quistes Óseos Aneurismáticos/cirugía , Quistes Óseos Aneurismáticos/patología , Legrado/efectos adversos , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Reino Unido , Niño , Adolescente , Masculino , Femenino
2.
Epilepsy Behav ; 154: 109745, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38521027

RESUMEN

There are no well-validated treatments for functional seizures. While specialist psychotherapy is usually recommended, the evidence for its benefit is qualified, and it can be difficult to obtain. Given the association between hyperventilation and functional seizures we explored an alternative modality, breathing control training, in a multi-site open label pilot trial. Participants with functional seizures over the age of 16 received an hour of breathing training from a respiratory physiotherapist, with a half-hour booster session a month later. Seizure frequency and Nijmegen scores (a measure of hyperventilation) were reported at baseline and follow-up, 3-4 months later. Eighteen subjects were recruited, and 10 completed follow-up. Seven of these 10 had improved seizure frequency, and 3 did not (Wilcoxon signed rank test, p = 0.09), with seizure frequency correlating with Nijmegen score (Spearman's rank correlation = 0.75, p = 0.034). The intervention was well tolerated, with no adverse events reported. These preliminary results support a potentially new approach to treating functional seizures that should prove cost-effective and acceptable, though require confirmation by a randomised controlled trial.


Asunto(s)
Ejercicios Respiratorios , Convulsiones , Humanos , Proyectos Piloto , Masculino , Femenino , Adulto , Convulsiones/fisiopatología , Convulsiones/terapia , Ejercicios Respiratorios/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , Adolescente , Trastornos de Conversión/rehabilitación , Trastornos de Conversión/terapia , Estudios de Seguimiento
3.
Epilepsy Behav ; 148: 109456, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37804600

RESUMEN

BACKGROUND: A history of adverse life events (ALE) is a risk factor for functional seizures (FS). Their influence on long-term outcome remains unclear. International guidelines recommend assessing ALE in patients presenting with associated disorders. It is not clear to what extent patients evaluated for FS are regularly asked about ALE. OBJECTIVES: We hypothesised that the presence of ALE would relate to worse outcome at follow-up and, that the rate of detection of ALE in clinical work-up would be inferior to that based on self-report questionnaires. METHODS: 53 patients with FS from the National Centre for Epilepsy in Norway, aged 16-62 years were included. Symptom severity, health-related quality of life (HRQoL), and antecedent ALE were assessed at baseline. Medical records were examined for disclosure of ALE. At a mean of 70.45 (SD 29.0, range 22-130) months after inclusion, participants were inquired about FS status, FS-related health care utilization and HRQoL. FINDINGS: A history of emotional abuse documented in the medical record was an independent risk factor for worse HRQoL at follow-up. Prevalence of ALE documented in medical records was lower compared with rates measured by a self-report questionnaire. CONCLUSIONS: These findings indicate an association between antecedent ALE and HRQoL years after diagnosis. A substantial proportion of the adverse life events by a self-report questionnaire had not been documented in the clinical records. CLINICAL IMPLICATIONS: The supplemental use of a self-report questionnaire in the diagnostic work-up of patients with FS may be valuable for detecting ALE.


Asunto(s)
Epilepsia , Calidad de Vida , Humanos , Convulsiones/diagnóstico , Convulsiones/epidemiología , Convulsiones/psicología , Epilepsia/psicología , Encuestas y Cuestionarios , Autoinforme
4.
Epilepsy Behav ; 135: 108890, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36037581

RESUMEN

INTRODUCTION: Insecure and fearful attachment styles have been reported in psychogenic nonepileptic seizures (PNES). We have investigated associations between long-term clinical outcome in PNES, parenting and attachment styles and demographic, clinical, and neuropsychiatric factors. MATERIAL AND METHODS: Patients aged at least 16 years and with documented PNES, according to criteria from the International League Against Epilepsy, were prospectively recruited to this study. They were assessed at baseline to determine clinical characteristics, experience of attachment and perceptions of experienced parenting styles, trauma history, dissociation, and health-related quality of life. At a mean of 70.45 (SD 29.0, range 22-130) months after inclusion, participants were contacted by telephone and asked about their current medical status and psychiatric/psychological interventions. RESULTS: Of 53 patients included in the study, 51 (96 %) provided follow-up data. Most (84.9 %) patients were female, and the mean age of PNES onset was 25.6 years. At follow-up, 20 patients (39 %) were free of PNES. Those patients that had achieved PNES freedom at follow-up had lower levels of attachment anxiety (p = 0.01) and reported to have experienced their fathers as less controlling (p = 0.02) and their mothers as more caring (p = 0.04) at baseline compared with those patients still suffering from PNES. Seizure freedom at follow-up was predicted by male gender, younger age at PNES onset, and less attachment anxiety. CONCLUSION: In our cohort from a tertiary epilepsy center the long-term prognosis of PNES is poor. Attachment anxiety is a risk factor for persistent PNES. It may be of therapeutic relevance to assess attachment patterns in patients with PNES.


Asunto(s)
Epilepsia , Convulsiones , Adulto , Electroencefalografía , Epilepsia/psicología , Femenino , Humanos , Masculino , Estudios Prospectivos , Convulsiones Psicógenas no Epilépticas , Calidad de Vida/psicología , Convulsiones/psicología
5.
Stroke ; 52(3): 1087-1090, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33588597

RESUMEN

BACKGROUND AND PURPOSE: In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients. METHODS: We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0-2) at day 90. RESULTS: There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% [95% CI, 0.4-5.3]) tenecteplase patients compared with 7 (2.7% [95% CI, 1.1-5.7]) alteplase patients (P=0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 [2.4%; 95% CI, 0.7-6.2] versus 1 [0.4%; 95% CI, 0.01-2.2], P=0.08) or 90-day functional independence (100 [61%] versus 140 [57%], P=0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 [95% CI, 0.14-2.80], P=0.53) or functional independence (odds ratio tenecteplase, 1.20 [95% CI, 0.74-1.95], P=0.46). CONCLUSIONS: Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.


Asunto(s)
Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Tenecteplasa/uso terapéutico , Terapia Trombolítica/efectos adversos , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Angioedema/epidemiología , Angioedema/etiología , Estudios de Factibilidad , Femenino , Fibrinolíticos/efectos adversos , Humanos , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tenecteplasa/efectos adversos , Tiempo de Tratamiento , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento
6.
Epilepsia ; 62(7): 1528-1535, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34075579

RESUMEN

OBJECTIVE: This study was undertaken to measure the incidence and prevalence of active psychogenic nonepileptic seizures (PNES) in a Norwegian county. METHODS: Using the Norwegian patient registry, we identified patients in Møre and Romsdal County in Norway diagnosed with F44.5 (conversion disorder with seizures or convulsions) or R56.8 (convulsions, not elsewhere classified) in the period January 2010 to January 2020. A review of the patients' medical records and an assessment of diagnostic validity were performed. PNES were diagnosed according to the recommendations by the International League Against Epilepsy Nonepileptic Seizures Task Force. Point prevalence of PNES on January 1, 2020 and incidence rates for the period 2010-2019 were determined. RESULTS: Based on PNES within the past 5 years, we found a PNES prevalence of 23.8/100 000 (95% confidence interval [CI] = 17.9-29.6), including all levels of diagnostic certainty. For the highest level of diagnostic certainty (video-electroencephalographically confirmed), the prevalence was 10.6/100 000 (95% CI = 6.7-14.5). The highest prevalence was found in the age group 15-19 years, at 59.5/100 000 (95% CI = 22.6-96.3). The mean annual incidence rate between 2010 and 2019 was 3.1/100 000/year (95% CI = 2.4-3.7). SIGNIFICANCE: We report for the first time a population-based estimate of the prevalence of PNES. Our findings suggest that the prevalence of PNES is within the range of estimates from non-population-based data. We found a strikingly high prevalence of PNES in the 15-19-year age group.


Asunto(s)
Trastornos de Conversión/epidemiología , Convulsiones/epidemiología , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Trastornos de Conversión/complicaciones , Estudios Transversales , Diagnóstico Diferencial , Electroencefalografía , Femenino , Humanos , Incidencia , Masculino , Noruega/epidemiología , Población , Prevalencia , Sistema de Registros , Reproducibilidad de los Resultados , Convulsiones/complicaciones , Adulto Joven
7.
Eur J Neurol ; 28(5): 1441-1445, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33426732

RESUMEN

BACKGROUND: Functional neurological disorders (FND) represent a significant proportion of presentations to outpatient adult neurology services. There is little information relating to patients presenting to acute inpatient care. METHODS: We identified patients presenting as acute admissions with FND to Christchurch Hospital, Christchurch, New Zealand, from 2016 to 2018. We analyzed relevant demographic and clinical data from electronic records and measured incidence of presentation to secondary care and healthcare utilization. RESULTS: One hundred sixty-two patients presented on 173 occasions with FND, representing 9% of all admissions to the neurology service during the 3-year study period. The mean age was 40 (SD 17) years, 111 (69%) patients were female and the median length of stay was 3 (IQR 2-4) days. A total of 92 computed tomography brain scans, 77 magnetic resonance imaging brain scans and 42 electroencephalograms were carried out. On 22 (13%) occasions, patients were referred for outpatient psychological therapy. In the 3 years prior to each patient's last presentation in the study period, these 162 patients had a total of 671 presentations to the emergency department. Healthcare demand did not decrease after the index admission. The rate of acute inpatient admission for FND was 10 per 100,000 per year for the total Christchurch Hospital catchment, 6/100,000/year in rural areas, and 11/100,000/year in urban areas. CONCLUSION: FND represented almost 1 in 10 acute neurology admissions with significant inpatient healthcare resource utilization.


Asunto(s)
Urgencias Médicas , Enfermedades del Sistema Nervioso , Adulto , Servicio de Urgencia en Hospital , Femenino , Hospitalización , Humanos , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/terapia , Atención Secundaria de Salud
8.
Epilepsy Behav ; 102: 106667, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31846898

RESUMEN

OBJECTIVE: Some patients with psychogenic nonepileptic seizures (PNES) remit when given the diagnosis. It is not realistically possible to test this potential therapeutic effect in an Randomized Controlled Trial (RCT) so we aim to statistically demonstrate it using the temporal relationship between the communication of the diagnosis and the timing of remission. METHOD: Re-analysis of data from a study of PNES, where diagnosis was communicated, and outcomes recorded in 54 patients. Making conservative assumptions and using the binomial distribution, the Poisson distribution and the chi-squared test distribution, we calculated likelihoods of the null hypothesis: that communication of the diagnosis and remission of seizures had occurred in random temporal relationship. RESULTS: Remission occurred in the week following communication of the diagnosis in 15 out of 54 patients. The χ2 test assigned this result a p value of <0.00001. Binomial and Poisson distribution calculations also indicated that remission was highly unlikely to have occurred by chance and that, in a dataset similar to ours, was unlikely to be due to chance if occurring in more than 9 patients (16.7%). CONCLUSIONS: We showed that the observed remissions were highly unlikely to be due to chance. Where an intervention is 'short and sharp' and the outcome can be measured with reasonable temporal acuity, then this type of method may provide an alternative to RCT methodology when the latter is impracticable.


Asunto(s)
Electroencefalografía/métodos , Trastornos Psicofisiológicos/diagnóstico , Trastornos Psicofisiológicos/psicología , Convulsiones/diagnóstico , Convulsiones/psicología , Adulto , Electroencefalografía/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Psicofisiológicos/fisiopatología , Inducción de Remisión , Estudios Retrospectivos , Convulsiones/fisiopatología
9.
Pract Neurol ; 20(1): 80-81, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31911480

RESUMEN

Endovascular thrombectomy is an effective intervention for symptomatic intracranial large-vessel occlusion. This treatment has proven benefit up to 24 hours following onset in selected patients with prestroke functional independence. Limited case reports suggest that thrombectomy beyond 24 hours may also be effective. We describe a young woman managed with endovascular thrombectomy beyond 24 hours.


Asunto(s)
Procedimientos Endovasculares/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Tiempo de Tratamiento , Femenino , Humanos , Resultado del Tratamiento , Adulto Joven
10.
Hum Mol Genet ; 26(9): 1759-1769, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-28334860

RESUMEN

Epilepsy is a serious and common neurological disorder. Expression quantitative loci (eQTL) analysis is a vital aid for the identification and interpretation of disease-risk loci. Many eQTLs operate in a tissue- and condition-specific manner. We have performed the first genome-wide cis-eQTL analysis of human hippocampal tissue to include not only normal (n = 22) but also epileptic (n = 22) samples. We demonstrate that disease-associated variants from an epilepsy GWAS meta-analysis and a febrile seizures (FS) GWAS are significantly more enriched with epilepsy-eQTLs than with normal hippocampal eQTLs from two larger independent published studies. In contrast, GWAS meta-analyses of two other brain diseases associated with hippocampal pathology (Alzheimer's disease and schizophrenia) are more enriched with normal hippocampal eQTLs than with epilepsy-eQTLs. These observations suggest that an eQTL analysis that includes disease-affected brain tissue is advantageous for detecting additional risk SNPs for the afflicting and closely related disorders, but not for distinct diseases affecting the same brain regions. We also show that epilepsy eQTLs are enriched within epilepsy-causing genes: an epilepsy cis-gene is significantly more likely to be a causal gene for a Mendelian epilepsy syndrome than to be a causal gene for another Mendelian disorder. Epilepsy cis-genes, compared to normal hippocampal cis-genes, are more enriched within epilepsy-causing genes. Hence, we utilize the epilepsy eQTL data for the functional interpretation of epilepsy disease-risk variants and, thereby, highlight novel potential causal genes for sporadic epilepsy. In conclusion, an epilepsy-eQTL analysis is superior to normal hippocampal tissue eQTL analyses for identifying the variants and genes underlying epilepsy.


Asunto(s)
Epilepsia/genética , Convulsiones Febriles/genética , Encéfalo/metabolismo , Encéfalo/fisiología , Expresión Génica , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/métodos , Hipocampo/metabolismo , Hipocampo/fisiología , Humanos , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo/genética , Factores de Riesgo
11.
Psychosom Med ; 81(7): 622-628, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31274823

RESUMEN

OBJECTIVE: Medically unexplained symptoms (MUS) are common and associated with high consumption of health care resources. Cross-sectional studies in selected and clinical populations show consistent linkages between history of childhood sexual abuse (CSA) and presentation with MUS and somatization. However, there are almost no well-controlled prospective studies in population samples. METHODS: Data were gathered in a longitudinal study of a New Zealand birth cohort born in 1977. Hospital e-record data for the period 2008-2015 (age, 30-38 years) were searched for a subsample of 408 study participants who were resident in one District Health Board region, and details of MUS contacts were recorded. Retrospective reports of CSA (<16 years) were obtained at ages 18 and 21 years. Associations between CSA and MUS were sequentially adjusted using logistic regression methods for both childhood confounders assessed before age 16 years and potential mediating mental health/family context up to age 30 years. RESULTS: Twenty (4.9%) participants were classified as having MUS, of whom 11 had a history of CSA. Severe CSA involving attempted/completed sexual penetration was strongly associated with risk of MUS (odds ratio = 11.6, 95% confidence interval = 4.3-31.7, p < .001). A substantial association remained after statistically adjusting for confounding and mediating mental health/family context (adjusted odds ratio = 5.1, 95% confidence interval = 1.2-21.3, p = .024). This strong association was specific to severe CSA (as opposed to childhood physical abuse) and to MUS rather than medically explained symptoms. CONCLUSIONS: CSA involving attempted/completed penetration was strongly associated with attendance at secondary level care for MUS. Implications for prevention and treatment of MUS are discussed.


Asunto(s)
Experiencias Adversas de la Infancia/estadística & datos numéricos , Abuso Sexual Infantil/estadística & datos numéricos , Síntomas sin Explicación Médica , Adolescente , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Nueva Zelanda/epidemiología , Adulto Joven
12.
J Neuropsychiatry Clin Neurosci ; 31(4): 361-367, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31117907

RESUMEN

OBJECTIVE: Functional movement and seizure disorders are still widely misunderstood and receive little public and academic attention. This is in stark contrast to their high prevalence and levels of associated disability. In an exploratory observational study, the authors examined whether the relative lack of media coverage of functional neurological disorders is in part due to misidentification in "human interest" news stories. METHODS: Thirteen recent news stories from high-impact English-language media outlets that portrayed patients with complex symptoms either attributed to other diagnoses or presented as medical mysteries were identified using online keyword searches. All selected news stories contained video or still images displaying relevant symptoms. Cases were categorized into movement disorders or seizure disorders and were then independently assessed by 10 respective expert raters. For each category, one story of a patient whose symptoms were due to a well-recognized neurological disease was also included. Both the diagnostic category and the respective confidence level were reported by each rater for each case. The interrater agreement was calculated for each group of disorders. RESULTS: The raters confirmed almost unanimously that all presented news stories except the negative control cases portrayed misidentified functional movement or seizure disorders. The interrater agreement and average diagnostic confidence were high. CONCLUSIONS: Functional neurological disorders are often wrongly considered a rare medical curiosity of the past. However, these findings suggest that, while they are largely absent from public discourse, they often appear in the news incognito, hiding in plain sight.


Asunto(s)
Concienciación , Epilepsia/epidemiología , Medios de Comunicación de Masas , Trastornos del Movimiento/epidemiología , Adolescente , Adulto , Epilepsia/psicología , Femenino , Humanos , Masculino , Trastornos del Movimiento/psicología
13.
Sociol Health Illn ; 40(7): 1250-1267, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30076628

RESUMEN

The normative view that patients should be offered more choice both within and beyond the UK's National Health Service (NHS) has been increasingly endorsed. However, there is very little research on whether - and how - this is enacted in practice. Based on 223 recordings of neurology outpatient consultations and participants' subsequent self-reports, this article shows that 'option-listing' is a key practice for generating the perception of choice. The evidence is two-fold: first, we show that neurologists and patients overwhelmingly reported that choice was offered in those consultations where option-listing was used; second, we demonstrate how option-listing can be seen, in the interaction itself, to create a moment of choice for the patient. Surprisingly, however, we found that even when the patient resisted making the choice or the neurologist adapted the practice of option-listing in ways that sought acceptance of the neurologist's own recommendation, participants still agreed that a choice had been offered. There was only one exception: despite the use of option-listing, the patient reported having no choice, whereas the neurologist reported having offered a choice. We explore this deviant case in order to shed light on the limits of option-listing as a mechanism for generating the perception of choice.


Asunto(s)
Conducta de Elección , Prioridad del Paciente , Humanos , Percepción , Medicina Estatal/organización & administración , Reino Unido
14.
Hum Mol Genet ; 24(15): 4306-16, 2015 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-25941323

RESUMEN

Numerous diverse biological pathways are dysregulated in the epileptic focus. Which of these pathways are most critical in producing the biological abnormalities that lead to epilepsy? Answering this question is key to identifying the primary causes of epilepsy and for discovering new therapeutic strategies with greater efficacy than currently available antiepileptics (AEDs). We have performed the largest genome-wide transcriptomic analysis to date comparing epileptic with normal human hippocampi. We have identified 118 differentially expressed and, for the first time, differentially connected pathways in the epileptic focus. Using network mapping techniques, we have shown that these dysregulated pathways, though seemingly disparate, form a coherent interconnected central network. Using closeness centrality analysis, we have identified that the most influential hub pathways in this network are signalling through G protein-coupled receptors, in particular opioid receptors, and their downstream effectors PKA/CREB and DAG/IP3. Next, we have objectively demonstrated that genetic association of gene sets in independent genome-wide association studies (GWASs) can be used to identify causally relevant gene sets: we show that proven causal epilepsy genes, which cause familial Mendelian epilepsy syndromes, are associated in published sporadic epilepsy GWAS results. Using the same technique, we have shown that central pathways identified (opioid receptor and PKA/CREB and DAG/IP3 signalling pathways) are genetically associated with focal epilepsy and, hence, likely causal. Published functional studies in animal models provide evidence of a role for these pathways in epilepsy. Our work shows that these pathways play a central role in human focal epilepsy and that they are important currently unexploited antiepileptic drug targets.


Asunto(s)
Epilepsias Parciales/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Hipocampo/metabolismo , Epilepsias Parciales/etiología , Epilepsias Parciales/metabolismo , Epilepsias Parciales/patología , Regulación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Hipocampo/patología , Humanos , Transducción de Señal
15.
J Neurol Neurosurg Psychiatry ; 88(5): 425-429, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28235779

RESUMEN

BACKGROUND: Psychogenic non-epileptic seizures (PNES) are classified with other functional neurological symptoms as 'Conversion Disorder', but there are reasons to wonder whether this symptomatology constitutes a distinct entity. METHODS: We reviewed the literature comparing PNES with other functional neurological symptoms. RESULTS: We find eight studies that directly examined this question. Though all but one found significant differences-notably in presenting age, trauma history, and dissociation-they were divided on whether these differences represented an important distinction. CONCLUSION: We argue that the aetiological and mechanistic distinctions they support, particularly when bolstered by additional data, give reason to sustain a separation between these conditions.


Asunto(s)
Trastornos de Conversión/diagnóstico , Convulsiones/psicología , Trastornos de Conversión/clasificación , Trastornos de Conversión/psicología , Diagnóstico Diferencial , Humanos , Trastornos Psicofisiológicos , Convulsiones/diagnóstico
16.
Epilepsy Behav ; 75: 18-24, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28818810

RESUMEN

OBJECTIVE: The objective of this study was to evaluate the contribution of validated screening tools for antiepileptic drug (AED) adverse effects, depression, and anxiety to measure the quality of life (QoL) in people with epilepsy (PWE). METHODS: Patients in a tertiary epilepsy service were screened for quality of life (using QOLIE-31), major depressive disorder (MDD) (NDDI-E), generalized anxiety disorder (GAD) (GAD-7), and AED effects (AEP). Mini International Neuropsychiatric Interview (MINI) generalized anxiety disorder module was also performed. For AEP validation in French, the internal structural validity was analyzed. Dimensional (NDDI-E and GAD-7 scores) and categorical (MDD and GAD) analyses were performed to investigate interactions between QoL and AEP. RESULTS: A total of 132 (87 females) subjects were included. The French version of the AEP demonstrated satisfactory psychometric properties (Cronbach's α 0.87). Correlations between NDDI-E, GAD-7, AEP, and QOLIE-31 scores were high, and significant for all subscales of QOLIE-31; no effect of seizure-related variables was seen. Some sex differences in QOLIE-31 subscales were found, and mean AEP score was higher in females. Age, sex, NDDI-E, GAD-7, and AEP scores accounted for 61% of variance of QOLIE-31 scores. Differential effects were seen on QOLIE-31 subscales: AEP strongly correlated with all subscales; GAD-7 scores more strongly correlated with "Seizure Worry"; NDDI-E with "Energy-Fatigue"; and both NDDI-E and GAD-7 scores strongly correlated with "Emotional Well-Being". Categorical analysis of groups with MDD alone, GAD alone, MDD+GAD, and neither MDD nor GAD showed significant differences in AEP and QOLIE-31 scores, with MDD+GAD showing the most AED effects and the poorest QoL. SIGNIFICANCE: The combination of screening tools for depression (NDDI-E), anxiety (GAD-7), and AED effects (AEP) has a strong power for evaluating QoL in PWE. Coexisting MMD and GAD were associated with the poorest quality of life and the highest AEP scores.


Asunto(s)
Ansiedad/psicología , Depresión/psicología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/psicología , Epilepsia/psicología , Psicometría/instrumentación , Calidad de Vida/psicología , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
18.
Epilepsia ; 57(9): 1467-74, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27421837

RESUMEN

OBJECTIVE: Many different gene families are currently being investigated for their potential role in epilepsy and in the response to antiepileptic drugs. A common research challenge is identifying the members of a gene family that are most significantly dysregulated within the human epileptic focus, before taking them forward for resource-intensive functional studies. Published data about transcriptomic changes within the human epileptic focus remains incomplete. A need exists for an accurate in silico system for the prediction of dysregulated genes within the epileptic focus. We present such a bioinformatic system. We demonstrate the validity of our approach by applying it to the solute carrier (SLC) gene family. There are >400 known SLCs. SLCs have never been systematically studied in epilepsy. METHODS: Using our in silico system, we predicted the SLCs likely to be dysregulated in the epileptic focus. We validated our in silico predictions by identifying ex vivo the SLCs dysregulated in epileptic foci, and determining the overlap between our in silico and ex vivo results. For the ex vivo analysis, we used a custom oligonucleotide microarray containing exon probes for all known SLCs to analyze 24 hippocampal samples obtained from surgery for pharmacoresistant mesial temporal lobe epilepsy and 24 hippocampal samples from normal postmortem controls. RESULTS: There was a highly significant (p < 9.99 × 10(-7) ) overlap between the genes identified by our in silico and ex vivo strategies. The SLCs identified were either metal ion exchangers or neurotransmitter transporters, which are likely to play a part in epilepsy by influencing neuronal excitability. SIGNIFICANCE: The identified SLCs are most likely to mediate pharmacoresistance in epilepsy by enhancing the intrinsic severity of epilepsy, but further functional work will be needed to fully evaluate their role. Our successful in silico strategy can be adapted in order to prioritize genes relevant to epilepsy from other gene families.


Asunto(s)
Proteínas de Transporte de Catión/genética , Epilepsia/genética , Perfilación de la Expresión Génica , Predisposición Genética a la Enfermedad/genética , Adulto , Anciano , Anciano de 80 o más Años , Niño , Biología Computacional , Femenino , Pruebas Genéticas , Genómica , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Adulto Joven
19.
Epilepsy Behav ; 59: 9-12, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27084977

RESUMEN

BACKGROUND: Many patients with psychogenic nonepileptic seizures (PNES) have other medically unexplained symptoms (MUS). In order to assess their long-term contribution to ill-health and unemployment, we recorded MUS, employment, healthcare utilization, and seizure outcomes in a cohort of patients with PNES. METHODS: We had complete computerized healthcare records and employment information in 120 patients with PNES, 5-10years postdiagnosis. We analyzed these data to assess the contribution of MUS to ill-health and to determine whether MUS could explain differences among seizure, employment, and healthcare utilization outcomes in PNES. RESULTS: At 5-10years, 41/120 patients (34.2%) were attending primary or secondary care for seizures, 42/120 patients (35.0%) had MUS other than PNES, and 36/120 patients (30.0%) were employed. Unemployment was predicted by age at presentation (OR: 0.90 (0.86-0.94), p<0.001), presenting to primary or secondary care with seizures (OR: 0.16 (0.05-0.52), p=0.003), and contact with psychiatric services at 5-10years (OR: 0.16 (0.05-0.58), p=0.005). No outcome measures were predicted by additional MUS, though MUS themselves were predicted by psychiatric contact (OR: 2.27 (1.01-5.01), p=0.048). CONCLUSIONS: Our data suggest that MUS do not contribute independently to unemployment in the population with PNES, whereas psychiatric morbidity appears to do so. Nonetheless, MUS and psychiatric morbidity persist in the long term in a substantial minority of patients with PNES. We found no evidence that seizures in patients whose PNES have resolved are replaced with other MUS.


Asunto(s)
Empleo/estadística & datos numéricos , Síntomas sin Explicación Médica , Convulsiones/psicología , Convulsiones/terapia , Trastornos Somatomorfos/psicología , Trastornos Somatomorfos/terapia , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Aceptación de la Atención de Salud , Resultado del Tratamiento
20.
Practitioner ; 260(1793): 30-2, 3, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27382917

RESUMEN

The most common cause of adolescent heel pain is calcaneal apophysitis also known as Sever's disease. The condition may occur in adolescent athletes, particularly those involved in running or jumping activities, during the pubertal growth spurt. The mean age of presentation in Sever's disease is ten, (range 7-15). It presents with posterior heel pain that is worse with activity and relieved by rest in most cases. Sever's disease, Osgood Schlatter's disease (tibial tuberosity) and Sinding-Larsen Johansson syndrome (distal patella) are all overuse syndromes brought about by repetitive submaximal loading and microtrauma. They are, however, entirely self-limiting and resolve at skeletal maturity or earlier. Careful assessment is required to differentiate them from other rare pathologies. Achilles tendinitis is rare under the age of 14. As in Sever's disease, it may occur in jumping athletes, those who suddenly increase their sporting activities and in individuals with relative gastrosoleus tightness. It may also occur in those with inflammatory arthropathies and merit rheumatological investigation if there are other suggestive signs or symptoms. Benign and malignant tumours of the adolescent calcaneus are extremely rare In a unilateral case, atypical features such as night pain or absence of a precipitating activity should raise the index of suspicion. There may be localised swelling and bony expansion.


Asunto(s)
Calcáneo , Trastornos de Traumas Acumulados , Talón , Dolor , Adolescente , Traumatismos en Atletas/complicaciones , Bursitis/complicaciones , Bursitis/fisiopatología , Calcáneo/patología , Calcáneo/fisiopatología , Niño , Trastornos de Traumas Acumulados/diagnóstico , Trastornos de Traumas Acumulados/etiología , Trastornos de Traumas Acumulados/fisiopatología , Diagnóstico Diferencial , Talón/patología , Talón/fisiopatología , Humanos , Dolor/diagnóstico , Dolor/etiología , Dimensión del Dolor/métodos , Tendinopatía/complicaciones , Tendinopatía/fisiopatología
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