Delivery of care, seizure control and medication adherence in women with epilepsy during pregnancy.

PURPOSE: To evaluate service access for women with epilepsy (WWE) during pregnancy; to determine seizure frequency and rates of adherence to anti-seizure medication (ASM). METHODS: Between June 2019-June 2020, pregnant WWE within NHS Greater Glasgow and Clyde health-board were identified from the National Obstetric Register. A manual review of electronic patient records was undertaken to ensure diagnostic accuracy, as well as determine contact with epilepsy services and documented seizures. Medication dispensing records were obtained six months before and six months after midwifery booking and measures of ASM adherence calculated. RESULTS: Between June 2019-June 2020, 4592 women were registered with a pregnancy. Eighty-five (1.9%) were identified as having active epilepsy (generalised- 40/85 (47.0%), focal- 35/85 (41.2%), unclassified- 10/85 (11.8%)). Preconceptually, 42/85 WWE (49.4%) had input from epilepsy services. Only 59/85 (69.4%) were reviewed during pregnancy (First trimester- 21/59 (35.6%), Second trimester- 25/59 (42.4%) and Third trimester- 13/59 (22.0%)). Seizure occurrence was documented in 37/85 WWE (43.5%) during the antenatal/postnatal period. 71/85 WWE (83.5%) were prescribed ASM. Poor adherence was noted in 50/85 (58.9%) and a documented seizure recorded in 26/50 (52.0%) of these women. CONCLUSION: Too many WWE do not receive input from epilepsy services during pregnancy, leaving some with poor ASM adherence and continued seizures. We aim to use "near-live" obstetric and dispensing data to facilitate early identification of WWE, promoting timely access to epilepsy specialists. This will also provide an opportunity to address concerns regarding ASM safety and allow medication dose changes to be considered.

Medication adherence, utilization of healthcare services, and mortality of patients with epilepsy on opiate replacement therapy: A retrospective cohort study.

INTRODUCTION: Substance misuse is not uncommonly recognized in people with epilepsy (PWE). Mortality is significantly greater in those with comorbid substance misuse, but it remains unclear whether epilepsy care and management contribute to this. This cohort study aimed to compare the rates of mortality in PWE receiving opiate replacement therapy (ORT) and PWE alone, as well as evaluate their medication adherence, levels of engagement with epilepsy services as currently delivered, and utilization of unscheduled hospital care. MATERIAL AND METHODS: A 5-year historical cohort for PWE was identified and manually validated using electronic patient records registered with NHS Tayside. Overall incidence rates for mortality and contact with emergency health care services were calculated for PWE receiving ORT and PWE alone. Engagement with outpatient epilepsy services was also noted. Adherence to antiepileptic drugs (AEDs) was expressed in terms of medication possession ratio (MPR). RESULTS: Of the 1297 PWE attending a tertiary care epilepsy service, 68 (5.3%) PWE were receiving ORT. The mortality rate was significantly greater in PWE on ORT in comparison to PWE only (7.4% vs 1.7 %; P < 0.05; relative risk of death: 4.34, 95% CI 1.19-15.7), as well as the incidence of emergency healthcare services contact being higher (24.5% vs 17.7%; P < 0.05; incidence rate ratio: 1.39, 95% CI: 1.12-1.71). Poor adherence to AEDs was also more common in PWE on ORT (28.4% vs 23.5%; P = 0.02), as well as failure to engage with elective outpatient services (8.4% vs 3.0%; P < 0.05; rate ratio 2.77, 95% CI: 1.86-4.1). CONCLUSION: People with epilepsy on ORT are less likely to engage with elective epilepsy services as currently delivered or take AEDs as prescribed despite most of these patients having daily attendance at a community pharmacist. This may contribute to the significantly increased rates of mortality and unscheduled hospital care. Clinicians and policymakers should consider service redesign to meet the demands of this high-risk population in an attempt to reduce mortality and morbidity.

Physical and mental health comorbidities of epilepsy: Population-based cross-sectional analysis of 1.5 million people in Scotland.

PURPOSE: To measure the prevalence of physical and mental health comorbidities in people with epilepsy in a large population cohort, and to examine the prevalence of depression accounting for other physical comorbidity. METHODS: Population-based, cross-sectional descriptive epidemiology analysis of primary care electronic records for 1,510,742 people aged 14+ years, examining the prevalence of 39 comorbidities. RESULTS: 12,720 people with epilepsy were identified (prevalence 8.4/1000 population, 95% CI 8.3-8.5). Physical and mental health comorbidity was more common with epilepsy (mean of an additional 1.02 physical conditions difference, 95% CI 0.99-1.06). 69.9% of people with epilepsy had one or more comorbid health conditions and 18.6% had four or more, compared to 46.9% and 9.0% of people without epilepsy. Depression was present in 16.3% of people with epilepsy compared to 9.5% of those without (adjusted OR 1.57, 95% CI 1.49-1.65). The prevalence of comorbid depression in epilepsy increased as the number of physical comorbidities increased (OR 5.82, 95% CI 4.90-6.91 for 4+ physical comorbidities vs none) and with increasing deprivation, similar to the patterns observed in other common physical conditions. CONCLUSION: People with epilepsy have higher rates of both physical and mental health comorbidity than people without even after adjustment for age, gender and levels of deprivation. Depression is more common than in the general population but the prevalence is similar to other physical health conditions, and is strongly associated with the total burden of physical conditions. This study highlights the complexity in caring for people with epilepsy.

Multifocal dysembryoplastic neuroepithelial tumour with intradural spinal cord lipomas: report of a case.

We report a case of temporal lobe epilepsy and incomplete Brown-Sequard syndrome of the thoracic cord. Computed tomography and magnetic resonance (MR) imaging showed multiple supratentorial masses with the classical radiological appearances of multifocal dysembryoplastic neuroepithelial tumour (DNET). Spinal MR imaging revealed intradural lipomas, not previously reported in association with multifocal DNET. Presentation and imaging findings are discussed along with classification and natural history of the tumour.

Validation of diagnostic criteria for variant Creutzfeldt-Jakob disease.

OBJECTIVE: Variant Creutzfeldt-Jakob disease (vCJD), a novel form of human prion disease, was recognized in 1996. The disease affected a younger cohort than sporadic CJD, and the early clinical course was dominated by psychiatric and sensory symptoms. In an attempt to aid diagnosis and establish standardization between surveillance networks, diagnostic criteria were established. These were devised from the features of a small number of cases and modified in 2000 as the clinical phenotype was established. Since then, only minor changes have been introduced; revalidation of the criteria in the current format is overdue. METHODS: Included in this study are autopsy/cerebral biopsy-proven cases of vCJD referred to the National CJD Surveillance Unit (NCJDSU) between 1995 and 2004 and suspect cases in which an alternative diagnosis was identified following autopsy/cerebral biopsy. RESULTS: Over the 10-year period, 106 definite cases of vCJD and 45 pathologically confirmed "noncases" were identified from the archives of the NCJDSU. The median age at onset of the cases was significantly younger than that of the noncases (27 years [range, 12-74 years] vs 43 years [range, 10-64 years]), and the median duration of illness was significantly shorter (14 months [range, 6-39 months] vs 22 months [range, 2-139 months]). The most commonly identified core clinical feature in cases was dementia; persistent painful sensory symptoms were the least frequent. Eighty-eight of 106 (83%) vCJD cases were retrospectively classified as probable in life, 6 cases were classified as possible. Most cases were classified as probable on the basis of core clinical features and brain magnetic resonance imaging. To date, the diagnostic criteria remain 100% specific, with no autopsy/cerebral biopsy-proven noncases classified as probable in life. INTERPRETATION: This study confirms that the diagnostic criteria for vCJD are sensitive and specific and provide a useful standard framework for case classification in a surveillance setting.

PRNP variation in UK sporadic and variant Creutzfeldt Jakob disease highlights genetic risk factors and a novel non-synonymous polymorphism.

BACKGROUND: Genetic analysis of the human prion protein gene (PRNP) in suspect cases of Creutzfeldt-Jakob disease (CJD) is necessary for accurate diagnosis and case classification. Previous publications on the genetic variation at the PRNP locus have highlighted the presence of numerous polymorphisms, in addition to the well recognised one at codon 129, with significant variability between geographically distinct populations. It is therefore of interest to consider their influence on susceptibility or the clinico-pathological disease phenotype. This study aimed to characterise the frequency and effect of PRNP open reading frame polymorphisms other than codon 129 in both disease and control samples sourced from the United Kingdom population. METHODS: DNA was extracted from blood samples and genetic data obtained by full sequence analysis of the prion protein gene or by restriction fragment length polymorphism analysis using restriction enzymes specific to the gene polymorphism under investigation. RESULTS: 147 of 166 confirmed cases of variant CJD (vCJD) in the UK have had PRNP codon 129 genotyping and all are methionine homozygous at codon 129; 118 have had full PRNP gene sequencing. Of the latter, 5 cases have shown other polymorphic loci: at codon 219 (2, 1.69%), at codon 202 (2, 1.69%), and a 24 bp deletion in the octapeptide repeat region (1, 0.85%). E219K and D202D were not found in sporadic CJD (sCJD) cases and therefore may represent genetic risk factors for vCJD.Genetic analysis of 309 confirmed UK sCJD patients showed codon 129 genotype frequencies of MM: 59.5% (n = 184), MV: 21.4% (n = 66), and VV: 19.1% (n = 59). Thirteen (4.2%) had the A117A polymorphism, one of which also had the P68P polymorphism, four (1.3%) had a 24 bp deletion, and a single patient had a novel missense variation at codon 167. As the phenotype of this latter case is similar to sCJD and in the absence of a family history of CJD, it is unknown whether this is a form of genetic CJD, or simply a neutral polymorphism. CONCLUSIONS: This analysis of PRNP genetic variation in UK CJD patients is the first to show a comprehensive comparison with healthy individuals (n = 970) from the same population, who were genotyped for the three most common variations (codon 129, codon 117, and 24 bp deletion). These latter two genetic variations were equally frequent in UK sCJD or vCJD cases and a normal (healthy blood donor) UK population.

Variant Creutzfeldt-Jakob disease in France and the United Kingdom: Evidence for the same agent strain.

OBJECTIVE: Variant Creutzfeldt-Jakob disease (vCJD) was first reported in the United Kingdom in 1996. Since then, the majority of cases have been observed in the United Kingdom where there was a major epidemic of bovine spongiform encephalopathy. France was the second country affected. To address the hypothesis of the involvement of a common strain of agent, we have compared clinical, neuropathological, and biochemical data on vCJD patients from both countries. METHODS: In France and the United Kingdom, epidemiological and clinical data were obtained from analysis of medical records and direct interview of the family of the patients using the same standardized questionnaire in both countries. When brain material was available, we performed with similar methods a comparative study of brain lesions and PrP(res) glycoform ratios in both vCJD populations. RESULTS: Clinical data, genetic background, neuropathological finding, and biochemical findings in the 185 patients observed in France (n = 23) and the United Kingdom (n = 162) were similar except for age at death. Currently, blood transfusion is a risk factor identified only in the United Kingdom. INTERPRETATION: The close similarity between the cases of vCJD in France and the United Kingdom supports the hypothesis that a common strain of infectious agent is involved in both countries. The 5-year delay in the peak that we observed in France compared with the United Kingdom fits well with the increase in the importation of beef products to France from the United Kingdom between 1985 and 1995.