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The burden of comorbidity in people with epilepsy is high. Several diseases, including depression, anxiety, dementia, migraine, heart disease, peptic ulcers, and arthritis are up to eight times more common in people with epilepsy than in the general population. Several mechanisms explain how epilepsy and comorbidities are associated, including shared risk factors and bidirectional relations. There is a pressing need for new and validated screening instruments and guidelines to help with the early detection and treatment of comorbid conditions. Preliminary evidence suggests that some conditions, such as depression and migraine, negatively affect seizure outcome and quality of life. Further investigation is needed to explore these relations and the effects of targeted interventions. Future advances in the investigation of the comorbidities of epilepsy will strengthen our understanding of epilepsy and could play an important part in stratification for genetic studies.

Throughout the conference, it became increasingly apparent that a range of interlinked factors affect vulnerability to climate change. [...]neuroscientist Agustin Ibanez (Trinity College Dublin, Ireland) explained how physical activity, social support networks, green spaces, and financial stability bolster brain resilience. Psychiatrist Lasse Brandt (Charité—Universitätsmedizin Berlin, Germany) elaborated on direct (eg, adverse weather events), indirect (eg, displacement) and intersectional (eg, isolation) effects of climate change on mental health. Systemic solutions need to address factors that affect promotion of good health, such as availability of electricity derived from reliable renewable sources. [...]reduction in greenhouse gas emissions is essential for adaptation measures to succeed. Several common themes emerged during the conference: changes in our environment have complex consequences for brain health; most data come from the Global North, whilst the Global South faces the highest health burdens of climate change; engaging and educating clinical practice and research communities are essential.

The Lancet Countdown has already reported on the serious current and projected consequences of climate change on population health, as related at the meeting by executive director of the project Marina Romanello (UCL), but it has not systematically considered individual disease areas. Neurologist Angel Aledo-Serrano (Vithas Madrid La Milagrosa University Hospital, Madrid, Spain) and paediatric neurologist Bernadette Macrohon (Zamboanga City Medical Center, Zamboanga City, Philippines) reported their experience of practising in a warming climate. [...]heat-related illnesses (eg, hyperthermia and heat stroke) are often marked by acute or permanent neurological impairments. Health-care systems embody the weighty paradox that, while they will increasingly need to manage climate-related health effects, they are also significant producers of greenhouse gases.

Treatment failure might have occurred because of variant selection, genomic background, modifier variants in other genes, gene expression dynamics, or irreversible compensatory or secondary pathophysiology. Precision medicine for genetic epilepsies might require the same multidisciplinary planning; for example, rendering an adult patient with severe intellectual disability seizure-free, could lead to unmanageable challenging behaviour, which might preclude any benefit from seizure control. Involvement of patients and families should form the cornerstone of decision-making in precision medicine.5 Genetic diagnoses can have not only medical effects, but also psychological.6 Genetic discoveries and diagnosis nowadays often lead to the emergence of gene-based support groups, which can contribute to research, and their engagement is amongst the most rewarding facets of precision medicine.

‘We are called to be architects of the future, not its victims’—Buckminster Fuller People with chronic neurological conditions may be vulnerable to change and less able to manage its demands: neurological diseases are among the most burdensome. Whether climate change has particular effects on specific neurological diseases or not, the known impaired resilience to change affecting people with neurological diseases requires neurologists to have awareness of potential climate impacts and their management. Preparedness should include understanding of general national and local alerts and action systems, and the ability to advise patients about managing extreme weather events, particularly heatwaves, but also floods and cold snaps. At the same time, we need more research into the particular consequences of climate change on specific neurological diseases. Climate change is a serious healthcare issue, requiring the neurological community to respond as it would, or did, to other serious challenges, such as COVID-19. As disease experts, we all have a role to play.

Over 50 million people worldwide have epilepsy. In nearly 30% of these cases, epilepsy remains unsatisfactorily controlled despite the availability of over 20 antiepileptic drugs. Moreover, no treatments exist to prevent the development of epilepsy in those at risk, despite an increasing understanding of the underlying molecular and cellular pathways. One of the major factors that have impeded rapid progress in these areas is the complex and multifactorial nature of epilepsy, and its heterogeneity. Therefore, the vision of developing targeted treatments for epilepsy relies upon the development of biomarkers that allow individually tailored treatment. Biomarkers for epilepsy typically fall into two broad categories: diagnostic biomarkers, which provide information on the clinical status of, and potentially the sensitivity to, specific treatments, and prognostic biomarkers, which allow prediction of future clinical features, such as the speed of progression, severity of epilepsy, development of comorbidities, or prediction of remission or cure. Prognostic biomarkers are of particular importance because they could be used to identify which patients will develop epilepsy and which might benefit from preventive treatments. Biomarker research faces several challenges; however, biomarkers could substantially improve the management of people with epilepsy and could lead to prevention in the right person at the right time, rather than just symptomatic treatment.

[...]in influential publications about the effects of climate change on health care, rare diseases do not feature.2 Yet climate change will have important, even life-threatening, consequences for rare diseases. Representatives of rare disease groups spoke of the concerns they already have about the effects of climate change. Because of widespread perceptions that health-care professionals have little influence in this area (“what can you do about the weather, doc?”), patients, families, and carers might not voice their concerns to health-care professionals; however, the problems are real and are happening now. AM has received funding support from the Engineering and Physical Sciences Research Council, the Natural Environment Research Council, and the National Institute for Health and Care Research; has consulted for the Department for Energy Security and Net Zero; and has received honoraria from Elsevier and Tsinghua University (Beijing, China).

Alternating Hemiplegia of Childhood (AHC) is characterised by paroxysmal hemiplegic episodes and seizures. Remission of hemiplegia upon sleep is a clinical diagnostic feature of AHC. We investigated whether: 1) Hemiplegic events are associated with spectral EEG changes 2) Sleep in AHC is associated with clinical or EEG spectral features that may explain its restorative effect. We retrospectively performed EEG spectral analysis in five adults with AHC and twelve age-/gender-matched epilepsy controls. Five-minute epochs of hemiplegic episodes and ten-minute epochs of four sleep stages were selected from video-EEGs. Arousals were counted per hour of sleep. We found 1) hemispheric differences in pre-ictal and ictal spectral power (p = 0.034), during AHC hemiplegic episodes 2) 22% reduced beta power (p = 0.017) and 26% increased delta power (p = 0.025) during wakefulness in AHC versus controls. There were 98% more arousals in the AHC group versus controls (p = 0.0003). There are hemispheric differences in spectral power preceding hemiplegic episodes in adults with AHC, and sleep is disrupted. Spectral EEG changes may be a potential predictive tool for AHC hemiplegic episodes. Significantly disrupted sleep is a feature of AHC.

BackgroundHyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear.ObjectiveTo identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes.MethodsWe carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period. Hyperammonaemia was defined as ammonia level > 35 μmol/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia.ResultsWe reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic/metabolic condition than in those with structural or cryptogenic epilepsy (P = 0.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (P = 0.033). Clinical symptoms were reported in 22/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment.ConclusionsDrug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.