Aim. Caregiver burden (CB) in epilepsy constitutes an understudied area. Here we attempt to identify the magnitude of this burden, the factors associated with it, and its impact to caregiver quality of life (QOL). Methods. 48 persons with epilepsy (PWE) underwent video-EEG monitoring and their caregivers completed questionnaires providing demographic, disease-related, psychiatric, cognitive, sleep, QOL, and burden information. Results. On regression analysis, higher number of antiepileptic drugs, poorer patient neuropsychological performance, lower patient QOL score, and lower caregiver education level were associated with higher CB. Time allocated to patient care approximated but did not attain statistical significance. A moderate inverse correlation between CB and caregiver QOL physical component summary score and a stronger inverse correlation between CB and caregiver QOL mental component summary score were seen. Conclusion. In a selected cohort of PWE undergoing video-EEG monitoring, we identified modest degree of CB, comparable to that reported in the literature for other chronic neurological conditions. It is associated with specific patient and caregiver characteristics and has a negative effect on caregiver QOL.

A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost-effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.

We present the star formation history (SFH) of the isolated (D ∼ 970 kpc) Local Group dwarf galaxy Wolf-Lundmark-Melotte (WLM) measured from colour-magnitude diagrams (CMDs) constructed from deep Hubble Space Telescope imaging. Our observations include a central (0.5 rh) and outer field (0.7 rh) that reach below the oldest main-sequence turn-off. WLM has no early dominant episode of star formation: 20 per cent of its stellar mass formed by ∼12.5 Gyr ago (z ∼ 5). It also has an SFR that rises to the present with 50 per cent of the stellar mass within the most recent 5 Gyr (z < 0.7). There is evidence of a strong age gradient: the mean age of the outer field is 5 Gyr older than the inner field despite being only 0.4 kpc apart. Some models suggest such steep gradients are associated with strong stellar feedback and dark-matter core creation. The SFHs of real isolated dwarf galaxies and those from the Feedback in Realistic Environment suite are in good agreement for M*(z = 0) ∼ 107-109M☉, but in worse agreement at lower masses (M*(z = 0) ∼ 105-107 M☉). These differences may be explainable by systematics in the models (e.g. reionization model) and/or observations (HST field placement). We suggest that a coordinated effort to get deep CMDs between HST/JWST (crowded central fields) and WFIRST (wide-area halo coverage) is the optimal path for measuring global SFHs of isolated dwarf galaxies.

A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost-effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.

OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. RESULTS: Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions.

OBJECTIVE: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. METHODS: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. RESULTS: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). CONCLUSIONS: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

Objective

To determine whether a less-invasive approach to surgery for medically refractory temporal lobe epilepsy is associated with lower health care costs and costs of lost productivity over time, compared to open surgery.

Methods

We compared direct medical costs and indirect productivity costs associated with treatment with stereotactic radiosurgery (SRS) or anterior temporal lobectomy (ATL) in the ROSE (Radiosurgery or Open Surgery for Epilepsy) trial. Health care use was abstracted from hospital bills, the study database, and diaries in which participants recorded health care use and time lost from work while seeking care. Costs of use were calculated using a Medicare costing approach used in a prior study of the costs of ATL. The power of many analyses was limited by the sample size and data skewing.

Results

Combined treatment and follow-up costs (in thousands of US dollars) did not differ between SRS (n = 20, mean = $76.6, 95% confidence interval [CI] = 50.7-115.6) and ATL (n = 18, mean = $79.0, 95% CI = 60.09-103.8). Indirect costs also did not differ. More ATL than SRS participants were free of consciousness-impairing seizures in each year of follow-up (all P < 0.05). Costs declined following ATL (P = 0.005). Costs tended to increase over the first 18 months following SRS (P = 0.17) and declined thereafter (P = 0.06). This mostly reflected hospitalizations for SRS-related adverse events in the second year of follow-up.

Significance

Lower initial costs of SRS for medial temporal lobe epilepsy were largely offset by hospitalization costs related to adverse events later in the course of follow-up. Future studies of less-invasive alternatives to ATL will need to assess adverse events and major costs systematically and prospectively to understand the economic implications of adopting these technologies.

Purpose

Stereotactic radiosurgery (SRS) may be an alternative to anterior temporal lobectomy (ATL) for mesial temporal lobe epilepsy (MTLE). Visual field defects (VFD) occur in 9-100% of patients following open surgery for MTLE. Postoperative VFD after minimally invasive versus open surgery may differ.

Methods

This prospective trial randomized patients with unilateral hippocampal sclerosis and concordant video-EEG findings to SRS versus ATL. Humphries perimetry was obtained at 24 m after surgery. VFD ratios (VFDR = proportion of missing homonymous hemifield with 0 = no VFD, 0.5 = complete superior quadrantanopsia) quantified VFD. Regressions of VFDR were evaluated against treatment arm and covariates. MRI evaluated effects of volume changes on VFDR. The relationships of VFDR with seizure remission and driving status 3 years after surgery were evaluated.

Results

No patients reported visual changes or had abnormal bedside examinations, but 49 of 54 (91%) of patients experienced VFD on formal perimetry. Neither incidence nor severity of VFDR differed significantly by treatment arm. VFDR severity was not associated with seizure remission or driving status.

Conclusion

The nature of VFD was consistent with lesions of the optic radiations. Effective surgery (defined by seizure remission) of the mesial temporal lobe results in about a 90% incidence of typical VFD regardless of method.

We measure homogeneous distances to M31 and 38 associated stellar systems (−16.8 ≤ MV ≤ −6.0), using time-series observations of RR Lyrae stars taken as part of the Hubble Space Telescope Treasury Survey of M31 Satellites. From >700 orbits of new/archival Advanced Camera for Surveys imaging, we identify >4700 RR Lyrae stars and determine their periods and mean magnitudes to a typical precision of 0.01 day and 0.04 mag. Based on period–Wesenheit–metallicity relationships consistent with the Gaia eDR3 distance scale, we uniformly measure heliocentric and M31-centric distances to a typical precision of ∼20 kpc (3%) and ∼10 kpc (8%), respectively. We revise the 3D structure of the M31 galactic ecosystem and: (i) confirm a highly anisotropic spatial distribution such that ∼80% of M31's satellites reside on the near side of M31; this feature is not easily explained by observational effects; (ii) affirm the thin (rms 7–23 kpc) planar “arc” of satellites that comprises roughly half (15) of the galaxies within 300 kpc from M31; (iii) reassess the physical proximity of notable associations such as the NGC 147/185 pair and M33/AND XXII; and (iv) illustrate challenges in tip-of-the-red-giant branch distances for galaxies with MV > − 9.5, which can be biased by up to 35%. We emphasize the importance of RR Lyrae for accurate distances to faint galaxies that should be discovered by upcoming facilities (e.g., Rubin Observatory). We Original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. Any further provide updated luminosities and sizes for our sample. Our distances will serve as the basis for future investigation of the star formation and orbital histories of the entire known M31 satellite system.