Multidisciplinary consensus guideline for the diagnosis and management of spontaneous intracranial hypotension.

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.

Valproate prescribing practices for women with intellectual disability across Europe.

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.

Treatment decisions in women of childbearing age on valproate.

INTRODUCTION: There are little data on the understanding and participation of women of childbearing age in decisions about their choice of antiepileptic drugs (AEDs). Valproate carries a risk of major congenital malformations, developmental and behavioural delay. For some, valproate is the only medication to prevent potentially life-threatening seizures. MATERIALS & METHODS: This was a cross-sectional study of two groups of women of childbearing age; 50 taking valproate and 50 controls. Each patient completed a patient questionnaire and structured telephone interview assessing understanding of the risks and benefits of AEDs in relation to pregnancy. Analysis used unpaired two-tailed t test and chi-squared test, with Bonferroni correction. Follow-up at 12 months showed that 8% of the women taking valproate had switched to other medication. RESULTS: Hundred patients participated in the study, 89 on AEDs for epilepsy, 4 for migraine, and 7 for both. 55% of participants stated they were not involved in decision-making. More patients in the valproate group were informed about (64% vs 42%, P < .005), and expressed understanding of (64%vs 32%, P < .001), the risks involved with treatment. 59% of all patients wanted more information. The minority of women surveyed took folic acid (37%) or used contraceptives (29%). Valproate was used following failure of other AEDs to control seizures in 80%. DISCUSSION: This in-depth survey suggests more information is needed for women taking AEDs, using a range of formats. Women taking valproate are better informed than those on levetiracetam or lamotrigine. Information provision on the use of folic acid and contraception needs improvement.

Valproate risk form-Surveying 215 clinicians involving 4775 encounters.

OBJECTIVES: Annual completion of a Valproate Risk Acknowledgement Form (RAF) is mandated in the United Kingdom due to neurodevelopmental risks of in utero valproate exposure. The number of women of childbearing potential taking valproate, the uptake of the RAF within this population and their clinical outcomes is not known or monitored. This study surveyed responses of clinicians administering the RAF to women of childbearing potential taking valproate medications. MATERIALS AND METHODS: Study design-national online survey distributed to clinical specialists throughout the United Kingdom via their national organizations. Participants-clinicians qualified to counsel and administer the valproate RAF (as defined by the Medicines and Healthcare products Regulatory Agency). Main outcome measures-quantitative and qualitative responses regarding identification, uptake, effects and reactions to the RAF. Trial registration-registered at the Clinical Governance and Audit Committee at Royal Free London NHS Foundation Trust Hospital. RESULTS: 215 respondents covering more than 4775 patient encounters were captured. Most patients continued on valproate, 90% with epilepsy as the indication. Respondents reported that seizure control deteriorated when switched to levetiracetam (33%) and lamotrigine (43%), compared to 7% when continuing valproate (P < .001). CONCLUSIONS: 33%-43% of clinicians reported seizure control deterioration in women changed to alternatives to valproate. Informed consent requires women considering a change are given this information. Systematic capture of data automated through online RAFs and linked to patient outcomes is needed. There remains little data on valproate given for indications other than epilepsy.

Valproate, sexual health, and men: A narrative review.

OBJECTIVE: This article explores current evidence about the effects of valproate (VPA) medicines on sexual health in men, how to monitor symptoms, communicate with patients, and improve clinical outcomes. There has been a lot of focus on VPA use in women of childbearing age following recent changes to prescribing regulations owing to the well-established and significant teratogenic risk. Concerns have been raised by patients and clinicians as to the risk of adverse sexual effects of VPA use in men. RESULTS: The evidence base for the effect of VPA on sexual function compared with other antiepileptic drugs (AEDs) in men is limited with no randomized controlled trials. Sexual function in men with epilepsy is complex, and there is no direct relationship between objective measures of sexual function and sexual satisfaction. Epilepsy, comorbidities, psychosocial factors, and most AEDs including VPA may cause sexual dysfunction in men, including reduced sexual desire, erectile dysfunction, and fertility problems. Sexual and reproductive function should be discussed with men prior to treatment with AEDs including VPA. CONCLUSION: Early and proactive discussion of sexual and reproductive functioning mitigates, rather than increases, the risk of sexual problems and potentially improves adherence. Sexual dysfunction in men with cognitive impairment [such as intellectual disability (ID) and dementia] may present with behavioral disturbance. Identification of sexual adverse effects of medication could significantly change treatment plans which is of particular importance for individuals with treatment resistance. We provide an information fact sheet for men to help guide prescribing discussions.

Out of sight: a lesson in drug errors.

A 76-year-old man developed recurrent encephalopathy, visual disturbance, myoclonus, generalised seizures and atonic drop attacks on a background of a gastrectomy for adenocarcinoma and stable chronic lymphocytic leukaemia. He presented to three different hospitals and was admitted twice, with normal investigations. His symptoms transiently improved during each admission (and with starting levetiracetam) but recurred each time on hospital discharge. Subsequent careful inspection of his medication box identified that his community pharmacy had in error been dispensing baclofen 80 mg per day instead of his prescribed Buscopan 80 mg per day. This case highlights the importance of physically inspecting a patient's medications and emphasises the spectrum of baclofen-related toxicity; it also highlights potential deficiencies in the pharmacy dispensary process and the need for multiple checks by patients and professionals.

Orgasmic migraine aura: Report of two cases.

BACKGROUND: Paroxysmal neurological symptoms occurring with sex cause considerable anxiety and sometimes have a serious cause. Thunderclap headache is the most well-known and requires urgent investigation at first presentation for subarachnoid haemorrhage and other significant pathologies. After exclusion of underlying causes, many prove to be primary headache associated with sexual activity. Orgasmic migraine aura without headache is not currently recognised as a clinical entity. CASE REPORTS: We report two patients with acephalgic orgasmic neurological symptoms fulfilling the criteria for migraine aura. CONCLUSIONS: The incidence of acephalgic orgasmic migraine aura is unknown. It should be considered as part of the differential of paroxysmal sex-related neurological symptoms, and clinically differentiated from fixed deficits, reversible cerebral vasoconstriction syndrome and post-orgasmic illness syndrome.

Langerhans cell histiocytosis (eosinophilic granuloma) of the skull mimicking nummular headache. Report of two cases.

Background Nummular headache is a rare, recently described topographic headache defined by the circumscribed coin-shaped area of pain. It is classified as a primary headache. There is debate about whether it is due to a peripheral or central disturbance, and its relationship to migraine. Case reports We report two patients with presumed nummular headache secondary to Langerhans cell histiocytosis, both with resolution of their headaches after surgical resection. Conclusion Imaging in patients with clinical features of nummular headache is recommended, as this and other cases highlight that it may be symptomatic. There are no distinguishing clinical features to separate nummular headache from secondary mimics, and treatment of the underlying cause may be curative.

Third cranial nerve palsy: an unusual manifestation of Mycoplasma pneumoniae.

Mycoplasma Pneumoniae (M.pneumoniae) is a well-known cause of atypical pneumonia, however it is also associated with many extra pulmonary manifestations. This report highlights a patient with gastroenterological, haematological and neurological complications, including a third cranial nerve palsy which developed after her initial treatment and discharge from hospital.

Familial limb pain and migraine: 8-year follow-up of four generations.

Background Migraine limb pain may be under-recognized in adults and children. There is little information about familial forms of this disorder. Objectives To describe the clinical and inheritance patterns of familial migraine limb pain over four generations and to review the evidence for limb pain as a manifestation of migraine. Methods Prospective clinical and pedigree analysis with an 8-year follow-up of 27 family members. Results Eight members of the family had benign recurrent limb pain associated with headache in a dominant inheritance pattern. Limb pain occurred before, during or after the headache, with probable or definite migraine with aura, migraine without aura and lower-half headache. The limb pain fulfilled the International Headache Society criteria for aura in six patients and also occurred without headache in three. Four members of the family had recurrent abdominal pain and/or motion sickness in childhood. Conclusions This is the first report of dominant familial limb pain temporally associated with migraine headache, starting in adulthood or starting in childhood and continuing into adulthood. A search for a genetic marker is indicated. Limb pain should be included as a childhood periodic syndrome linked to migraine and recognized as part of the migraine spectrum in adults.

New valproate regulations, informed choice and seizure risk.

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.

Migraine: mimics, borderlands and chameleons.

Diagnostically, headache is the easy part of migraine. It is the surrounds of migraine--the aura, prodrome and postdrome--that can be most challenging, and confused with other pathologies. This article examines the definition and variants of migraine; alternative diagnoses for which migraine may be mistaken (mimics); conditions that lie between migraine and other diagnoses (borderlands) and the possible presentations of migraine posing as other conditions (chameleons). The focus is on adults, with only passing reference to children. Migraine is more often a chameleon than a mimic; and it is the careful history that usually makes the distinction. Given migraine's prevalence of 10-15%, relatively uncommon features of migraine occur quite often, in comparison with frequent manifestations of less common diseases. Thus, even rare or under-recognised presentations of migraine come into the differential diagnosis of many presentations.

Deep phenotyping of frontal lobe epilepsy compared to other epilepsy syndromes.

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.

Antiseizure medications (antiepileptic drugs) in adults: starting, monitoring and stopping.

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.

Mortality risk in adults with intellectual disabilities and epilepsy: an England and Wales case-control study.

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.

Epilepsy related multimorbidity, polypharmacy and risks in adults with intellectual disabilities: a national study.

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.

Adult occipital lobe epilepsy: 12-years on.

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.