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Valproate is the most effective medication for generalised epilepsies, and several specific epilepsy syndromes. For some people, it will be the only medication to establish seizure remission, and withdrawing it carries risks of seizure recurrence and Sudden Unexpected Death in Epilepsy (SUDEP). It is also of proven efficacy for bipolar disorder and migraine prevention. Guidelines based on observational and epidemiological studies stress that maternal valproate related teratogenicity and neurodevelopmental effects are significantly higher than for other antiseizure medications (ASMs). It should, therefore, only be used if other medications are ineffective and after balancing the teratogenicity risk. Regulatory restrictions have changed prescribing practices and reduced valproate use. The number of other medications that must be trialled in the different conditions for which valproate has effectiveness and the consequences of the lack of efficacy of those drugs leading to significant harm including death remains unexplored. Risk minimisation measures (RMMs) for valproate, chiefly Pregnancy Prevention practices (PPP), consider foetal risk and not risk to people living with epilepsy. In the United Kingdom (UK), limitations relating to valproate use in all people < 55 years commenced in January 2024. While the evidence in child-bearing women is not disputed, the data in males are based on animal models, case reports, and one commissioned, unpublished, non-peer reviewed report unavailable to the UK public, stakeholder charities or professionals. Evidence suggests that 30-40% of people switching from valproate have breakthrough seizures. Thus, an estimated 21,000-28000 people in the UK will imminently be exposed to the potential hazards of breakthrough seizures, including death. There is little government investment in monitoring the effects of these changes to valproate prescribing on patient health and quality of life. This review summarises the history of valproate regulation, evidence underpinning it and argues how the latest regulations in the UK do not align with the country's medical regulatory bodies ethical principles nor with the Montgomery principles of informed patient choice and autonomy. It dissects how such regulations infringe Common Law principles, nor give due regard for patient outcomes beyond reproduction. The paper looks to provide recommendations to redress these concerns while appreciating the core need for such governance to emerge in the first place., (© 2024. The Author(s).)

Competing Interests: The authors report no conflicts of interest.

Background: We aimed to create a multidisciplinary consensus clinical guideline for best practice in the diagnosis, investigation and management of spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid leak based on current evidence and consensus from a multidisciplinary specialist interest group (SIG)., Methods: A 29-member SIG was established, with members from neurology, neuroradiology, anaesthetics, neurosurgery and patient representatives. The scope and purpose of the guideline were agreed by the SIG by consensus. The SIG then developed guideline statements for a series of question topics using a modified Delphi process. This process was supported by a systematic literature review, surveys of patients and healthcare professionals and review by several international experts on SIH., Results: SIH and its differential diagnoses should be considered in any patient presenting with orthostatic headache. First-line imaging should be MRI of the brain with contrast and the whole spine. First-line treatment is non-targeted epidural blood patch (EBP), which should be performed as early as possible. We provide criteria for performing myelography depending on the spine MRI result and response to EBP, and we outline principles of treatments. Recommendations for conservative management, symptomatic treatment of headache and management of complications of SIH are also provided., Conclusions: This multidisciplinary consensus clinical guideline has the potential to increase awareness of SIH among healthcare professionals, produce greater consistency in care, improve diagnostic accuracy, promote effective investigations and treatments and reduce disability attributable to SIH., Competing Interests: Competing interests: JA: remuneration for consultancy advice and education provision from Allergan/AbbVie and TEVA. HA-L: lectures and education paid by International Medical Press, Sanofi and Eisai. LCJ: lecture fees received from Radiopaedia. SC: research fellowship sponsored by Abbott. LD'A: supported by an NIHR Academic Clinical Fellowship and was the recipient of a research fellowship sponsored by B Braun. BD: remuneration for consultancy advice and education provision from TEVA, Allergan and Lilly. PJD: shareholding in BMS, Regeneron and Ionis Pharma. SE: owns the North Midlands Neurosciences. VI: reports speaker fees and honoraria from Theravance Biopharma and Jensen, outside of the present work; supported by the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre. SL: received fees for attending advisory meetings, presentations and preparing presentation materials from Allergan, TEVA, Eli Lilly and Novartis. MSM: chair of the medical advisory board of the CSF Leak Association, serves on the advisory board for Abbott, Allergan, Novartis, Eli Lilly, Medtronic, Autonomic Technologies and TEVA, and has received payment for the development of educational presentations from Allergan, electroCore, Eli Lilly, Novartis and TEVA. CJ, SM, JP, RS, TT: members of CSF Leak Association. S-JW: received honoraria as a moderator from AbbVie, Pfizer, Eli Lilly and Biogen, and has been the PI in trials sponsored by AbbVie, Novartis and Lundbeck. He has received research grants from the Taiwan Minister of Technology and Science (MOST), Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, Taipei Veterans General Hospital, Taiwan Headache Society and Taiwan branches of Eli Lilly and Novartis., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: People with epilepsy (PWE) and people with intellectual disabilities (ID) both live shorter lives than the general population and both conditions increase the risk of death further. We aimed to measure associations between certain risk factors for death in PWE and ID., Methods: A retrospective case-control study was conducted in ten regions in England and Wales. Data were collected on PWE registered with secondary care ID and neurology services between 2017 and 2021. Prevalence rates of neurodevelopmental, psychiatric and medical diagnoses, seizure frequency, psychotropic and antiseizure medications (ASM) prescribed, and health activity (epilepsy reviews/risk assessments/care plans/compliance etc.) recorded were compared between the two groups., Results: 190 PWE and ID who died were compared with 910 living controls. People who died were less likely to have had an epilepsy risk assessment but had a greater prevalence of genetic conditions, older age, poor physical health, generalized tonic-clonic seizures, polypharmacy (not ASMs) and antipsychotic use. The multivariable logistic regression for risk of epilepsy-related death identified that age over 50, medical condition prevalence, antipsychotic medication use and the lack of an epilepsy review in the last 12 months as associated with increased risk of death. Reviews by psychiatrists in ID services was associated with a 72% reduction in the odds of death compared neurology services., Conclusions: Polypharmacy and use of antipsychotics may be associated with death but not ASMs. Greater and closer monitoring by creating capable health communities may reduce the risk of death. ID services maybe more likely to provide this holistic approach., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aims: Frontal lobe epilepsy (FLE) is understudied and often misdiagnosed. We sought to comprehensively phenotype FLE and to differentiate FLE from other focal and generalised epilepsy syndromes., Methods: This was a retrospective, observational cohort study of 1078 cases of confirmed epilepsy in a tertiary neurology centre in London. Data sources were electronic health records, investigation reports and clinical letters., Results: 166 patients had FLE based on clinical findings and investigations-97 with identifiable electroencephalography (EEG) foci in frontal areas (definite FLE), while 69 had no frontal EEG foci (probable FLE). Apart from EEG findings, probable and definite FLE did not differ in other features. FLE was distinct from generalized epilepsy, which tended to present with tonic-clonic seizures and be due to genetic causes. FLE and temporal lobe epilepsy (TLE) both featured focal unaware seizures and underlying structural or metabolic aetiology. FLE, TLE and generalized epilepsy differed in their EEG (P = 0.0003) and MRI (P = 0.002) findings, where FLE had a higher rate of normal EEG and abnormal MRI findings compared to TLE., Conclusions: EEG is often normal for FLE, and abnormalities are commonly identified with MRI. There was no difference in the clinical features of definite and probable FLE, suggesting they represent the same clinical entity. The diagnosis of FLE can be made even when scalp EEG is normal. This large medical cohort provides hallmark features of FLE that differentiate it from TLE and other epilepsy syndromes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Up to 10% of people living to 80 years of age have one or more seizures; and many will not require anti-seizure medication (ASMs). In 85% of patients, the diagnosis comes from the history of the index event. One-third of patients with an apparent "first seizure" have previous events, changing their diagnosis to epilepsy. Targeted investigations are important for classification and risk prediction. Patients with a low risk of seizure recurrence are not usually offered ASM treatment. High-risk patients have multiple seizures, neurological deficits, intellectual disability and/or relevant abnormal investigations; and are offered ASMs. Individual factors modulate this decision-making. Future integrated technologies offer the game-changing potential for seizure monitoring and prediction, but are not yet robust, convenient or affordable. Therapeutic drug monitoring in patients taking ASMs may confirm ASM toxicity, or when non-adherence, malabsorption, or rapid metabolism are suspected causes of breakthrough seizures. They are less useful when these factors are intermittent or irregular. Current evidence does not favour routine monitoring of serum levels, as it neither reliably predicts control, relapse, or adverse effects. The decision to discontinue ASM should follow a full discussion with the patient of risks and benefits. Along with population risk factors for seizure recurrence, the patient's lifestyle and preferences must be considered. ASM are usually discontinued in a slow step-wise fashion, one at a time, after at least two years of remission. Seizure recurrence risk plateaus only after 2 years following ASM discontinuation, and patients need access to specialist follow-up over that period., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: A quarter of people with Intellectual Disability (ID) in the UK have epilepsy compared to 0.6% in the general population and die much younger. Epilepsy is associated with two-fifths of all deaths with related polypharmacy and multi-morbidity. Epilepsy research on this population has been poor. This study describes real-world clinical and risk characteristics of a large cohort across England and Wales., Methods: A retrospective multi-centre cohort study was conducted. Information on seizure characteristics, ID severity, relevant co-morbidities, psychotropic and antiseizure drugs (ASDs), SUDEP and other risk factors was collected across a year., Results: Of 904 adults across 10 centres (male:female, 1.5:1), 320 (35%) had mild ID and 584 (65%) moderate-profound (M/P) ID. The mean age was 39.9 years (SD 15.0). Seizures were more frequent in M/P ID (p < 0.001). Over 50% had physical health co-morbidities, more in mild ID (p < 0.01). A third had psychiatric co-morbidity and a fifth had an underlying genetic disorder. Autism Spectrum Disorder was seen in over a third (37%). Participants were on median two ASDs and overall, five medications. Over quarter were on anti-psychotics. Over 90% had an epilepsy review in the past year but 25% did not have an epilepsy care plan, particularly those with mild ID (p < 0.001). Only 61% had a documented discussion of SUDEP, again less likely with mild ID or their care stakeholders (p < 0.001)., Conclusions: Significant levels of multi-morbidity, polypharmacy and a lack of systemised approach to treatment and risk exist. Addressing these concerns is essential to reduce premature mortality., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The worldwide treatment gap for migraine before COVID-19 inevitably widens as attention focuses on an international emergency. Migraine hits people particularly in their early and middle years, potentially reduces quality of life and productivity, and remains a common emergency presentation. This article examines the impact of COVID-19 on migraine, and changing aspects of migraine care during and after the pandemic. Many risk factors for severe COVID-19-older age, male gender, cardiac and respiratory diseases, diabetes, obesity, and immunosuppression-are less frequent in migraineurs. Telemedicine is effective for migraine follow-up, and needs ongoing evaluation. Most migraine treatments can start or continue in acute COVID-19, with care to avoid drug interactions. Close contact procedures (botulinum toxin, acupuncture and steroid injections) are avoided in lockdown or in the vulnerable. Secondary effects of COVID-19, including long COVID and its economic impact, are probably equal or greater in people with migraine. Migraine and other long-term conditions need adequate resourcing to prevent personal, social and economic suffering. Treating migraine, a sequel of COVID, potentially reduces the impact of long COVID., (© 2021. Crown.)

Objective: Occipital lobe epilepsies (OLE) comprise 5-10% of focal epilepsies in surgical and paediatric series; with little data from adult medical cohorts. This longitudinal study examined OLE patients, to characterise prevalence, semiology, co-morbidity and prognosis in a neurology outpatient setting., Methods: 24 adult OLE patients identified over 12 months from 1548 patients in a neurologist's service were followed over 12 years., Results: 92% of these OLE patients had simple visual hallucinations, misdiagnosed in 40% of cases. 75% had co-morbid interictal migraine and 38% had visual field defects. Only 33% achieved long-term remission, and only 2 /10 (20%) of OLE patients with a structural aetiology were seizure-free. The two patients with migralepsy achieved remission., Conclusion: Adult OLE accounted for 7.7% of focal epilepsies in this cohort, misdiagnosed or misclassified in 40%. Most patients had co-existing migraine. A minority had migralepsy characterised by a longer aura and good prognosis. Remission rates were lower than that of childhood OLE and general adult epilepsy populations, strengthening the argument for considering epilepsy surgery in drug-resistant OLE patients with a structural cause. Precision medicine will potentially refine diagnosis and management in those OLE patients without an identified cause but is predicated on accurate clinical phenotyping., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Valproate (VPA) is a known teratogen associated with greater risk of major congenital malformations and other neurodevelopmental sequelae than all other licensed antiepileptic medicines. To reduce the potential for VPA-related teratogenicity, the European Medicines Agency issued recommendations in 2018. Over two-thirds of women/girls with intellectual disability (ID) may have treatment-resistant epilepsy that could benefit from VPA treatment., Aims: This investigation compared VPA prescribing practice for women/girls with ID between European countries, specifically evaluating the practice in the UK with that in other countries., Methods: An expert working group with representation from key stake-holding organizations developed a survey for dissemination to relevant professionals across Europe., Results: Seventy one responses were received (27 UK, 44 Europe). Clinicians in the UK were more likely to report that they are working to mandatory regulations compared with European respondents (P = .015). European respondents were less likely to be aware of user-independent contraception options (P = .06). In The UK, VPA regulations were more likely to be applied to women with ID than in Europe (P = .024)., Conclusion: There is heterogeneity in the application of VPA regulations across Europe for women/girls with ID. In both the UK and Europe, the regulations lack suitable adjustments for specific ID-related factors., (© 2020 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)