Understanding the aetiology of epilepsy is essential both for clinical management of patients and for conducting neurobiological research that will direct future therapies. The aetiology of epilepsy ...was formerly regarded as unknown in about three-quarters of patients; however, massively parallel gene-sequencing studies, conducted in a framework of international collaboration, have yielded a bounty of discoveries that highlight the importance of gene mutations in the aetiology of epilepsy. These data, coupled with clinical genetic studies, suggest a new paradigm for use in the clinic: many forms of epilepsy are likely to have a genetic basis. Enquiry about a genetic cause of epilepsy is readily overlooked in the clinic for a number of understandable but remediable reasons, not least an incomplete understanding of its genetic architecture. In addition, the importance of de novo mutagenesis is often underappreciated, particularly in the epileptic encephalopathies. Other genomic surprises are worth emphasizing, such as the emerging evidence of a genetic contribution to focal epilepsies-long regarded as acquired conditions-and the complex role of copy number variation. The importance of improved understanding of the genetics of the epilepsies is confirmed by the positive outcomes, in terms of treatment selection and counselling, of receiving a genetic diagnosis.
The mitochondrial epilepsies Lim, Albert; Thomas, Rhys H
European journal of paediatric neurology
24
Journal Article
Recenzirano
Mitochondria are vital organelles within cells that undertake many important metabolic roles, the most significant of which is to generate energy to support organ function. Dysfunction of the ...mitochondrion can lead to a wide range of clinical features, predominantly affecting organs with a high metabolic demand such as the brain. One of the main neurological manifestations of mitochondrial disease is metabolic epilepsies. These epileptic seizures are more frequently of posterior quadrant and occipital lobe onset, more likely to present with non-convulsive status epilepticus which may last months and be more resistant to treatment from the onset. The onset of can be of any age. Childhood onset epilepsy is a major phenotypic feature in mitochondrial disorders such as Alpers-Huttenlocher syndrome, pyruvate dehydrogenase complex deficiencies, and Leigh syndrome. Meanwhile, adults with classical mitochondrial disease syndrome such as MELAS, MERFF or POLG-related disorders could present with either focal or generalised seizures. There are no specific curative treatments for mitochondrial epilepsy. Generally, the epileptic seizures should be managed by specialist neurologist with appropriate use of anticonvulsants. As a general rule, especially in disorders associated with mutation in POLG, sodium valproate is best avoided because hepato-toxicity can be fulminant and fatal.
•Viruses and immune function have been associated with psychosis through genetic and epidemiological research.•We critically evaluate the case for psychosis in COVID-19 through analysis of reported ...cases and historical precedents.•Potential infectious, post-infectious and neurodevelopmental aetiologies are explored.•Further appraisal of potential neurobiological and psychosocial mechanisms of ‘COVID-19 psychosis’ is urgently needed.
Historical epidemiological perspectives from past pandemics and recent neurobiological evidence link infections and psychoses, leading to concerns that COVID-19 will present a significant risk for the development of psychosis. But are these concerns justified, or mere sensationalism? In this article we review the historical associations between viral infection and the immune system more broadly in the development of psychosis, before critically evaluating the current evidence pertaining to SARS-CoV-2 and risk of psychosis as an acute or post-infectious manifestation of COVID-19. We review the 42 cases of psychosis reported in infected patients to date, and discuss the potential implications of in utero infection on subsequent neurodevelopment and psychiatric risk. Finally, in the context of the wider neurological and psychiatric manifestations of COVID-19 and our current understanding of the aetiology of psychotic disorders, we evaluate possible neurobiological and psychosocial mechanisms as well as the numerous challenges in ascribing a causal pathogenic role to the infection.
Artificial intelligence (AI) has been supporting our digital life for decades, but public interest in this has exploded with the recognition of large language models, such as GPT-4. We examine and ...evaluate the potential uses for generative AI technologies in epilepsy and neurological services. Generative AI could not only improve patient care and safety by refining communication and removing certain barriers to healthcare but may also extend to streamlining a doctor’s practice through strategies such as automating paperwork. Challenges with the integration of generative AI in epilepsy services are also explored and include the risk of producing inaccurate and biased information. The impact generative AI could have on the provision of healthcare, both positive and negative, should be understood and considered carefully when deciding on the steps that need to be taken before AI is ready for use in hospitals and epilepsy services.
•Quality of life (QoL) in people with drug-resistant epilepsy (DRE) perceives a considerable burden of disease, which goes beyond the direct effects of seizure frequency and type.•Their QoL is ...impaired by the interference of medical and psychological comorbidities in their daily activities and anxiety in engaging in social interactions.•Neurologists can work with the patient towards a better QoL by acting on several fronts: addressing side effects and what the patient is willing to tolerate in favour of seizure reduction, taking advantage of added benefits of newer antiseizure medications (ASMs), promptly referring patients with complex management to specialized centres as needed, or to less-known interventions such as cognitive rehabilitation.
Despite the many therapeutic options for epilepsy available today, a third of patients still have poorly controlled epilepsy. Over the years, their transition through lines of treatment exposes them to increased risk of disease progression, mortality, morbidity, mental distress, and not least significantly impaired quality of life (QoL).
The present review explores the multiple factors contributing to the impairment of health-related QoL in PWE–including both seizure-related and non seizure-related. The analysis aims to identify potential areas of intervention and strategies for a more holistic approach to epilepsy care and inform policy-makers and healthcare providers in their approach to this condition.
The Epilepsy Deaths Register (EDR) differs from typical registries which concentrate primarily on clinical information. It is completed by bereaved relatives and focuses on the circumstances ...immediately before, and the support following, a death. It can be augmented by copies of death certificates from the families of the deceased, and all epilepsy associated deaths can be entered. The EDR is underpinned by the research and experience of the SUDEP Action team and the clinical advisors who helped design the methodology and the web-based platform. The EDR has been open since 2013 and currently has over 750 entries from over 20 different countries, the majority from the United Kingdom and the Republic of Ireland. The bereaved have shown that they place their trust in the register as a vehicle to be involved in research, even under the most difficult of circumstances. As the EDR matures, we hope to identify the common and rarer patterns of epilepsy-associated death; maintaining our dual ambitions to remain committed to listen, and to make every death count.
This paper is for the Special Issue: Prevent 21: SUDEP Summit - Time to Listen.
•The EDR focuses on the circumstances immediately before, and the support following, a death.•The EDR has been open since 2013 and currently has over 750 entries from over 20 different countries.•Normalising the identification of epilepsy-associated deaths is an important factor in addressing medical error.•The EDR is well-situated to study SUDEP deaths in minority groups such as children and the elderly.
PDF
