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Comorbidities are associated with adverse patient outcomes. The authors conducted a systematic review according to a pre-determined protocol, established PRISMA guidelines and reporting standards to estimate the prevalence of common comorbidities in people with epilepsy, and to explore whether the burden is greater in more deprived populations. In total, 107 studies were included and reviewed. The results indicate that the most common comorbidities in people with epilepsy are anxiety (19.2%) and major depressive disorder (17.4%). Among adults with epilepsy, common comorbidities include hypertension (18.2%), stroke (14.5%), heart disease (11%), diabetes (10.2%) and arthritis (9.2%). There was no evidence that the income status of a country was a moderating factor for the prevalence of anxiety and depression in people with epilepsy. However, prevalence rates for hypertension and stroke were lower for lower-income countries where epilepsy is a more common symptom of brain infection or injury. The analyses were affected by the heterogeneity of the included studies and should therefore be interpreted cautiously.

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After going virtual, the European Academy of Neurology 2020 Congress became the biggest neurology meeting in history. The overarching theme was ‘Time for action: predict, prevent, repair’ — three upcoming Reviews in Nature Reviews Neurology, written by speakers at the congress, highlight the importance of the theme across neurology.

SummaryObjective Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. We report retention, efficacy, and tolerability in a cohort of patients with MTLE-HS. Methods Clinical data were collected from a European database of patients with epilepsy. We estimated retention, 12-month seizure freedom, and adverse drug reaction (ADR) rates for the 10 most commonly used AEDs in patients with MTLE-HS. Results Seven hundred sixty-seven patients with a total of 3,249 AED trials were included. The highest 12-month retention rates were observed with carbamazepine (85.9%), valproate (85%), and clobazam (79%). Twelve-month seizure freedom rates varied from 1.2% for gabapentin and vigabatrin to 11% for carbamazepine. Response rates were highest for AEDs that were prescribed as initial treatment and lowest for AEDs that were used in a third or higher instance. ADRs were reported in 47.6% of patients, with the highest rates observed with oxcarbazepine (35.7%), topiramate (30.9%), and pregabalin (27.4%), and the lowest rates with clobazam (6.5%), gabapentin (8.9%), and lamotrigine (16.6%). The most commonly reported ADRs were lethargy and drowsiness, dizziness, vertigo and ataxia, and blurred vision and diplopia. Significance Our results did not demonstrate any clear advantage of newer versus older AEDs. Our results provide useful insights into AED retention, efficacy, and ADR rates in patients with MTLE-HS.

The epileptic encephalopathies (EEs) are a devastating group of epilepsies in which epileptic activity and seizures contribute to cognitive impairment or regression.1 Most EEs begin in infancy or early childhood and are associated with poor developmental outcome. Although the cause is unknown in the majority of cases, recent studies confirm that de novo mutations and copy number variants (CNVs) play an important role.2, 3 We recently reported exome sequencing data in 264 parent–proband trios with infantile spasms (n = 149) or Lennox–Gastaut syndrome (LGS; n = 115) without syndromic features or magnetic resonance imaging (MRI) abnormalities from the Epilepsy Phenome/Genome Project (EPGP) cohort, identifying likely pathogenic, de novo sequence changes in >10% of patients.2 Here we report results of copy number analysis derived from the exome data of this cohort and 85 additional patients to further elucidate the genetic architecture of these paradigmatic EEs. Our exome‐based CNV calling yields similar results to array‐based studies for confirmed, de novo, likely pathogenic CNVs.

We present visibility measurements of the nearby Mira-like star R Doradus taken over a wide range of wavelengths (650-990 nm). The observations were made using MAPPIT (Masked APerture-Plane Interference Telescope), an interferometer operating at the 3.9-m Anglo-Australian Telescope. We used a slit to mask the telescope aperture and prism to disperse the interference pattern in wavelength. We observed in R Dor strong decreases in visibility within the TiO absorption bands. The results are in general agreement with theory but differ in detail, suggesting that further work is needed to refine the theoretical models., Comment: 2 pages. Poster at IAU Symposium 205: Galaxies and their Constituents at the Highest Angular Resolutions, Manchester UK, August 2000. Proceedings to be published by ASP, edited by R. Schilizzi, S. Vogel, F. Paresce, M. Elvis

MAPPIT is an optical interferometer installed at the coude focus of the 3.9-m Anglo-Australian Telescope. The instrument combines non-redundant masking with wavelength dispersion and is able to record fringes simultaneously over a wide bandwidth. For typical observations centred near 600 nm, the bandwidth is 55 nm and the spectral resolution is 3 nm. This paper describes the instrument and the data processing methods and presents some results. We find the star sigma Sgr to be a close binary; the system is only partially resolved, with a separation of (11.5 +/- 2) milliarcsec (assuming the components to have equal magnitudes). We also give angular diameter measurements of two red giant stars, alpha Sco and beta Gru. The observations of beta Gru (spectral type M5 III) resolve the star for the first time and give an equivalent uniform-disk diameter of (27 +/- 3) milliarcsec., Comment: Accepted for publication in Astronomy and Astrophysics. (9 pages, uuencoded and compressed PostScript; hardcopy on request from tbedding@eso.org). ESO-BRM0494

BACKGROUND: Patient selection for seizure prophylaxis after traumatic brain injury (TBI) and duration of anti-epileptic drug treatment for patients with early post-traumatic seizures (PTS), remain plagued with uncertainty. In early 2017, a collaborative group of neurosurgeons, neurologists, neurointensive care and rehabilitation medicine physicians was formed in the UK with the aim of assessing variability in current practice and gauging the degree of uncertainty to inform the design of future studies. Here we present the results of a survey of clinicians managing patients with TBI in the UK and Ireland. MATERIALS AND METHODS: An online survey was developed and piloted. Following approval by the Academic Committee of the Society of British Neurological Surgeons, it was distributed via appropriate electronic mailing lists. RESULTS: One hundred and seventeen respondents answered the questionnaire, predominantly neurosurgeons (76%) from 30 (of 32) trauma-receiving hospitals in the UK and Ireland. Fifty-three percent of respondents do not routinely use seizure prophylaxis, but 38% prescribe prophylaxis for one week. Sixty percent feel there is uncertainty regarding the use of seizure prophylaxis, and 71% would participate in further research to address this question. Sixty-two percent of respondents use levetiracetam for treatment of seizures during the acute phase, and 42% continued for a total of 3 months. Overall, 90% were uncertain about the duration of treatment for seizures, and 78% would participate in further research to address this question. CONCLUSION: The survey results demonstrate the variation in practice and uncertainty in both described aspects of management of patients who have suffered a TBI. The majority of respondents would want to participate in future research to help try and address this critical issue, and this shows the importance and relevance of these two clinical questions.

Antiepileptic drug (AED) treatment is the first line strategy for seizure control in the majority of individuals with epilepsy but remains challenging, not least because of interindividual variability in efficacy, tolerability and dosing. The studies presented in this thesis set out to explore that variability from a genomic perspective in patients with newly diagnosed epilepsy from across the UK. Single nucleotide polymorphisms (SNPs) in genes encoding drug metabolising enzymes (DMEs) may be associated with the dose of carbamazepine (CBZ) required for seizure control. A cohort of 159 individuals who were seizure-free for 12 months on a stable dose of CBZ monotherapy was genotyped for 51 SNPs across six DMEs. Haplotype analysis identified 8 haplotype blocks across the genes. No single SNPs or haplotype blocks were associated with CBZ dose. Thus, it is unlikely that genetic variability in DMEs accounts for the individual differences in CBZ dose requirement. A splice site SNP (rs3812718) in the SCN1A gene was previously shown to influence maximum doses of AEDs. This SNP was genotyped in 817 patients and tested for association with maximum and maintenance doses of several AEDs. An association was identified between rs3812718 and maximum AED dose, with an interaction analysis suggestive of a drug specific effect. These findings suggest that this SCN1A variant contributes to variability in the limit of tolerability to AEDs. Response to AED treatment is multifactorial and likely to be influenced by multiple genes. Five SNPs previously reported to predict treatment outcome in epilepsy were genotyped in 772 patients and the resulting data, together with data from an Australian cohort, incorporated into a predictive algorithm. The algorithm failed to predict treatment outcome in general but was partially successful in identifying responders to CBZ and valproate. These five SNPs may be relevant to the prognosis of epilepsy, particularly when treated with specific AEDs. Primary generalised epilepsies (PGEs) are highly heritable and believed to be polygenic in origin. Predictive algorithms were employed to explore genetic influences on seizure (absence vs. myoclonus) and epilepsy (PGE vs. focal) type using 1,840 SNP genotypes available from 436 patients with PGE. Although the algorithms failed to distinguish PGE patients on the basis of genetic variants, they showed improved association over univariate methods of analysis. Such an approach may be suitable for future investigations using large genomic datasets. A recent genome-wide association study identified multiple genetic variants that approached genome-wide significance for association with 12 month remission from seizures. Five of these SNPs were genotyped in an independent cohort of 424 patients and tested for association with remission and time to remission. No significant associations were found, questioning the validity of the original observation or the method of replication. Further work is required to understand this outcome. In conclusion, the genetic bases of epilepsy, AED response and AED dose requirement are multigenic and thus far undetectable using traditional association studies in modestly-sized patient cohorts. Further advances in genomic, bioinformatics and statistical methodologies are required before the genetic contribution to heterogeneity in epilepsy-related phenotypes can be translated into improved clinical care.