35 research outputs found
Can the quality of social research on ethnicity be improved through the introduction of guidance? Findings from a research commissioning pilot exercise
As the volume of UK social research addressing ethnicity grows, so too do concerns regarding the ethical and scientific rigour of this research domain and its potential to do more harm than good. The establishment of standards and principles and the introduction of guidance documents at critical points within the research cycle might be one way to enhance the quality of such research. This article reports the findings from the piloting of a guidance document within the research commissioning process of a major funder of UK social research. The guidance document was positively received by researchers, the majority of whom reported it to be comprehensible, relevant and potentially useful in improving the quality of research proposals. However, a review of the submitted proposals suggested the guidance had had little impact on practice. While guidance may have a role to play, it will need to be strongly promoted by commissioners and other gatekeepers. Findings also suggest the possibility that guidance may discourage some researchers from engaging with ethnicity if it raises problems without solutions; highlighting the need for complementary investments in research capacity development in this area
Dravet syndrome as epileptic encephalopathy: Evidence from long-term course and neuropathology
Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and neuropathology are not well known. We identified a series of 22 adult patients, including three adult post-mortem cases with Dravet syndrome. For all patients, we reviewed the clinical history, seizure types and frequency, antiepileptic drugs, cognitive, social and functional outcome and results of investigations. A systematic neuropathology study was performed, with post-mortem material from three adult cases with Dravet syndrome, in comparison with controls and a range of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female, were included, median age 39 years (range 20â66). SCN1A structural variation was found in 60% of the adult Dravet patients tested, including one post-mortem case with DNA extracted from brain tissue. Novel mutations were described for 11 adult patients; one patient had three SCN1A mutations. Features of Dravet syndrome in adulthood include multiple seizure types despite polytherapy, and age-dependent evolution in seizure semiology and electroencephalographic pattern. Fever sensitivity persisted through adulthood in 11 cases. Neurological decline occurred in adulthood with cognitive and motor deterioration. Dysphagia may develop in or after the fourth decade of life, leading to significant morbidity, or death. The correct diagnosis at an older age made an impact at several levels. Treatment changes improved seizure control even after years of drug resistance in all three cases with sufficient follow-up after drug changes were instituted; better control led to significant improvement in cognitive performance and quality of life in adulthood in two cases. There was no histopathological hallmark feature of Dravet syndrome in this series. Strikingly, there was remarkable preservation of neurons and interneurons in the neocortex and hippocampi of Dravet adult post-mortem cases. Our study provides evidence that Dravet syndrome is at least in part an epileptic encephalopathy
Genome-wide Polygenic Burden of Rare Deleterious Variants in Sudden Unexpected Death in Epilepsy
Peer reviewe
Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome
Mutations in PNPO are a known cause of neonatal onset seizures that are resistant to pyridoxine but responsive to pyridoxal phosphate (PLP). Mills etal. show that PNPO mutations can also cause neonatal onset seizures that respond to pyridoxine but worsen with PLP, as well as PLP-responsive infantile spasm
De novo mutations in MED13, a component of the Mediator complex, are associated with a novel neurodevelopmental disorder
Genetics of disease, diagnosis and treatmen
Climate change and epilepsy: insights from clinical and basic science studies
Climate change is with us. As professionals who place value on evidence-based practice, climate change is something we cannot ignore. The current pandemic of the novel coronavirus, SARS-CoV-2, has demonstrated how global crises can arise suddenly and have a significant impact on public health. Global warming, a chronic process punctuated by acute episodes of extreme weather events, is an insidious global health crisis needing at least as much attention. Many neurological diseases are complex chronic conditions influenced at many levels by changes in the environment. This review aimed to collate and evaluate reports from clinical and basic science about the relationship between climate change and epilepsy. The keywords climate change, seasonal variation, temperature, humidity, thermoregulation, biorhythm, gene, circadian rhythm, heat, and weather were used to search the published evidence. A number of climatic variables are associated with increased seizure frequency in people with epilepsy. Climate change-induced increase in seizure precipitants such as fevers, stress, and sleep deprivation (e.g. as a result of more frequent extreme weather events) or vector-borne infections may trigger or exacerbate seizures, lead to deterioration of seizure control, and affect neurological, cerebrovascular, or cardiovascular comorbidities and risk of sudden unexpected death in epilepsy. Risks are likely to be modified by many factors, ranging from individual genetic variation and temperature-dependent channel function, to housing quality and global supply chains. According to the results of the limited number of experimental studies with animal models of seizures or epilepsy, different seizure types appear to have distinct susceptibility to seasonal influences. Increased body temperature, whether in the context of fever or not, has a critical role in seizure threshold and seizure-related brain damage. Links between climate change and epilepsy are likely to be multifactorial, complex, and often indirect, which makes predictions difficult. We need more data on possible climate-driven altered risks for seizures, epilepsy, and epileptogenesis, to identify underlying mechanisms at systems, cellular, and molecular levels for better understanding of the impact of climate change on epilepsy. Further focussed data would help us to develop evidence for mitigation methods to do more to protect people with epilepsy from the effects of climate change. (C) 2021 Elsevier Inc. All rights reserved.Paroxysmal Cerebral Disorder
Functional Characterization of a Novel Mutation in KCNA1 in Episodic Ataxia Type 1 Associated with Epilepsy
Assessment and Predictors of Health-related Quality of Life in Dravet Syndrome
Objective: Health- related quality of life (HRQOL) has
emerged as a widely accepted measure to evaluate the impact
of chronic disease on an individualâs physical, social, and
mental well-being. There is a l ack of data focussing on
HRQOL in specific epilepsy syndromes and their associated
needs. Our aim was to identify areas of difficulty and dis-
ease-related predic tors for HRQOL in Dravet syndrome.
Method: One hundred and sixty-three in divi duals with Dra-
vet syndrome and their families participated in the study.
Detailed clinical and demographic information was avail-
able from a standardized referral form. HRQOL was eval-
uated with two epilepsy-specific instruments, the Impact of
Pediatric Epilepsy Scale and the Epilepsy and Learning
Disabilities Quality of Life scale, and two generic instru-
ments, the Pediatric Quality of Life Inventory and the
Strengths and Difficulties Questionnaire.
Results: HRQOL was lower for children with Dravet syn -
drome than a comparison group (46.8 vs 84.6; p<0.001)
and was lower in older compared with younger age gr oups
(32.4 vs 59.3; p<0.001). Overall 35% of children scored in
the abnormal range for âconduct problemsâ and 66% for
âhyperactivity/inattentionâ. Young age at seizure onset
(p=0.019), presence of myoclonic seizures (p=0.029), motor
disorder (p=0.048), learning difficulties (p=0.002), epilepsy
severity (p<0.001) and b ehavioural difficulties (p<0.001)
each independently predicted poorer HRQOL, beha-
vioural problems being the strongest predictor.
Conclusions: HRQOL in Dravet synd rome depends on sev-
eral independent factors including seizure control, beha-
viour, cognitive, and motor problems. This illustrates how
a well-defined epilepsy syndrome will require a distinct
multidimensional approach to treatment in order to
address specific needs
Assessment and Predictors of Health-related Quality of Life in Dravet Syndrome
Objective: Health- related quality of life (HRQOL) has
emerged as a widely accepted measure to evaluate the impact
of chronic disease on an individualâs physical, social, and
mental well-being. There is a l ack of data focussing on
HRQOL in specific epilepsy syndromes and their associated
needs. Our aim was to identify areas of difficulty and dis-
ease-related predic tors for HRQOL in Dravet syndrome.
Method: One hundred and sixty-three in divi duals with Dra-
vet syndrome and their families participated in the study.
Detailed clinical and demographic information was avail-
able from a standardized referral form. HRQOL was eval-
uated with two epilepsy-specific instruments, the Impact of
Pediatric Epilepsy Scale and the Epilepsy and Learning
Disabilities Quality of Life scale, and two generic instru-
ments, the Pediatric Quality of Life Inventory and the
Strengths and Difficulties Questionnaire.
Results: HRQOL was lower for children with Dravet syn -
drome than a comparison group (46.8 vs 84.6; p<0.001)
and was lower in older compared with younger age gr oups
(32.4 vs 59.3; p<0.001). Overall 35% of children scored in
the abnormal range for âconduct problemsâ and 66% for
âhyperactivity/inattentionâ. Young age at seizure onset
(p=0.019), presence of myoclonic seizures (p=0.029), motor
disorder (p=0.048), learning difficulties (p=0.002), epilepsy
severity (p<0.001) and b ehavioural difficulties (p<0.001)
each independently predicted poorer HRQOL, beha-
vioural problems being the strongest predictor.
Conclusions: HRQOL in Dravet synd rome depends on sev-
eral independent factors including seizure control, beha-
viour, cognitive, and motor problems. This illustrates how
a well-defined epilepsy syndrome will require a distinct
multidimensional approach to treatment in order to
address specific needs