Objective: Thinning of the peripapillary retinal nerve fiber layer (p-RNFL), as measured by optical coherence tomography (OCT), was recently introduced as a promising marker for cerebral neuronal loss in people with epilepsy (PwE). However, its clinical implication remains to be elucidated. We thus aimed to (1) systematically characterize the extent of the retinal neuroaxonal loss in a broad spectrum of unselected PwE and (2) to evaluate the main clinical determinants.Methods: In this prospective study, a spectral-domain OCT evaluation was performed on 98 well-characterized PwE and 85 healthy controls (HCs) (18-55 years of age). All inner retinal layers and the total macula volume were assessed. Group comparisons and linear regression analyses with stepwise backward selection were performed to identify relevant clinical and demographic modulators of the retinal neuroaxonal integrity.Results: PwE (age: 33.7 +/- 10.6 years; 58.2% female) revealed a significant neuroaxonal loss across all assessed retinal layers (global pRNFL, P = 0.001, Delta = 4.24 mu m; macular RNFL, P < 0.001, Delta = 0.05 mm(3); ganglion cell inner plexiform layer, P < 0.001, Delta = 0.11 mm(3); inner nuclear layer, INL, P = 0.03, Delta = 0.02 mm(3)) as well as significantly reduced total macula volumes (TMV, P < 0.001, Delta = 0.18 mm(3)) compared to HCs (age: 31.2 +/- 9.0 years; 57.6% female). The extent of retinal neuroaxonal loss was associated with the occurrence and frequency of tonic-clonic seizures and the number of antiseizure medications, and was most pronounced in male patients.Significance: PwE presented an extensive retinal neuroaxonal loss, affecting not only the peripapillary but also macular structures. The noninvasive and economic measurement via OCT bears the potential to establish as a practical tool to inform patient management, as the extent of the retinal neuroaxonal loss reflects aspects of disease severity and sex-specific vulnerability.

Objective: People with epilepsy (PwE) suffer from progressive brain atrophy, which is reflected as neuroaxonal loss on the retinal level. This study aims to provide initial insight into the longitudinal dynamics of the retinal neuroaxonal loss and possible driving factors.Methods: PwE and healthy controls (HC; 18–55 years of age) underwent spectral domain optical coherence tomography at baseline and 7.0 ± 1.5 and 6.7 ± 1.0 months later, respectively. The change in retinal thickness/volume and annualized percentage change (APC) were calculated for the peripapillary retinal nerve fiber layer (pRNFL), the macular RNFL (mRNFL), the ganglion cell inner plexiform layer (GCIP), the inner nuclear layer, and the total macular volume (TMV). Group comparisons and multiple linear models with stepwise backward selection were performed to evaluate associations with demographic and clinical parameters.Results: PwE (n = 44, 21 females, mean age = 35.6 ± 10.9 years) revealed a significant decrease in the pRNFL, mRNFL, GCIP, and TMV thickness or volume in the study interval. When compared to HC (n = 56, 37 females, mean age = 32.7 ± 8.3 years), the APC of the pRNFL (−.98 ± 3.13%/year) and the GCIP (−1.24 ± 2.56%/year) were significantly more pronounced in PwE (p = .01 and p = .046, respectively). Of note, atrophy of the mRNFL was significantly influenced by the number of antiseizure medications (ASMs; p = .047) and increasing age of PwE (p = .03). Contradictory results, however, were revealed for the impact of seizures.Significance: In epilepsy, progression of retinal neuroaxonal loss was already detectable at short‐term follow‐up. PwE who receive a high number of ASMs seem to be at risk for accelerated neuroaxonal loss, stressing the importance of well‐considered and effective antiseizure therapy.

Idiopathic generalized epilepsy (IGE) is typically responsive to treatment, yet some people remain poorly controlled despite multiple antiseizure medication trials. Whether this subgroup shows progressive structural brain changes remains uncertain. We aimed to investigate whether people with poorly controlled chronic IGE exhibit progressive morphological brain alterations and how these differ from those in early-stage IGE. This longitudinal case-control neuroimaging study included 2 cohorts: an early-stage IGE group from West China Hospital (Chengdu, China) and a chronic IGE group from the National Hospital for Neurology and Neurosurgery (London, United Kingdom). Participants had a history of generalized seizures and no focal pathology. Matched healthy controls were drawn from 3 public imaging data sets. Participants underwent 2 high-resolution T1-weighted MRI scans at least 12 months apart. Cortical thickness and hippocampal and subcortical volumes were measured on paired scans. Longitudinal changes were assessed using linear mixed-effects models, correcting for age and interscan interval. Structural covariance analysis was conducted to examine inter-regional relationships over time, focusing on thalamo-cortical coupling. Forty-two people with early-stage IGE and 67 with chronic IGE were recruited from 2 separate epilepsy centers, and 109 matched controls were included. The early-stage IGE group showed progressive atrophy limited to the left putamen. Chronic IGE was associated with widespread cortical thinning, primarily in frontal and temporal regions, and thickening in posterior and occipital areas. Subcortical atrophy involves the putamen, thalamus, and pallidum. People with ongoing generalized tonic-clonic seizures showed thickening in the precentral gyrus and additional thinning in the frontal cortex and precuneus. Photosensitive IGE was associated with thickening in the lingual gyrus and occipital cortex. Valproate use was associated with attenuated structural changes in motor, visual, and subcortical regions. Increased structural covariance was observed between the left thalamus and left lingual gyrus in chronic IGE. Chronic IGE, particularly with persistent generalized tonic-clonic seizures or photosensitivity, is associated with more extensive progressive brain changes compared with matched controls. Valproate may have a protective association with these structural changes, although further validation is needed. Longitudinal MRI may help monitor disease progression and treatment effects in poorly controlled IGE.

Objective: To assess asymptomatic rates and severity of SARS-CoV-2 infection in people with epilepsy and their healthcare workers in a long-term care facility which had implemented weekly surveillance testing between April 2020 and June 2022. Methods: Questionnaires focused on objective and subjective COVID-19 symptoms for people with epilepsy residing in and their healthcare workers at the Chalfont Centre for Epilepsy in June 2022. Demographic information, comorbidities, and seizure frequency were gathered from medical records. We also collected responses on objective and subjective COVID-19 symptoms from healthcare workers who participated in a prospective study assessing the reaction to COVID-19 vaccinations (SAFER). Results: Fifty-five out of 89 (62%) residents tested positive at least once on weekly PCR testing for SARS-CoV-2 during the period of interest; 20 of those (37%) were asymptomatic. In comparison, of those 63 healthcare workers who tested positive at least once on weekly testing during the same period, only four (6%) were asymptomatic. Of the 159 healthcare workers who also participated in the SAFER study, 41 tested positive at least once, and seven (17%) were completely asymptomatic during infection with SARS-CoV-2. Significance: People with epilepsy living in a long-term care facility were more likely to present with asymptomatic SARS-CoV-2 infections than healthcare workers at the same facility. Despite possible bias in the reporting of subjective symptoms due to management-by-proxy, there is no evidence that vulnerable people living in an epilepsy long-term care facility showed reduced resilience towards infections. People with epilepsy living in care home facilities had a surprisingly high degree of asymptomatic infections with SARS-CoV-2. Very few residents had severe or fatal outcomes. This is in stark contrast to the widely reported bad outcomes for people without epilepsy in other care homes. People with epilepsy reported significantly less symptoms than their healthcare workers. No changes in seizure frequency during or after infection were observed.

Recent studies reported a significant retinal neuroaxonal loss in people with epilepsy (PWE). However, the impact of these structural alterations on visual function, i.e., visual acuity is yet unknown. In this prospective cohort study, 70 PWE and 76 healthy controls (HC), all aged 18-55 years, underwent an assessment of visual acuity with 100 % high contrast (HCVA) and 2.5 % low contrast (LCVA) Sloan letter charts. Thickness of the global peripapillary retinal nerve fiber layer (G-pRNFL) and volume of the ganglion cell inner plexiform layer (GCIP) were assessed with spectral-domain optical coherence tomography (OCT). For the statistical analyses, the epilepsy group was subdivided into PWE with sodium channel blocking (SCB)-drug intake (n = 52) and PWE without SCB-drug intake (n = 18), since an effect of SCB-drugs on visual perception has been reported previously. The overall PWE cohort presented significantly lower structural retinal measures, i.e., G-pRNFL thickness (97.57 ± 9.06 µm) and GCIP volume (1.99 ± 0.13 mm³) than HC (101.31 ± 8.28 µm, p = .01; 2.10 ± 0.15 mm³, p < .001). Subgroup analyses revealed that PWE who were treated with SCB-drugs had a significantly reduced G-pRNFL thickness (96.61 ± 9.70 µm, p = .01) and GCIP volume (1.98 ± 0.14mm³, p < .001) compared to HC, while PWE without SCB-drugs (100.36 ± 6.32 µm, 2.01 ± 0.13 mm³) did not differ from HC or PWE with SCB-drugs. In visual acuity tests (HCVA and LCVA), the overall PWE cohort (52.28 ± 8.56; 31.71 ± 8.49) scored significantly lower than HC (56.57 ± 4.74, p = .001; 35.13 ± 5.50, p = .04). In subgroup analyses only PWE with SCB-drugs presented significantly lower HCVA (51.25 ± 9.35, p = .003) and LCVA (30.04 ± 8.93, p = .03) scores compared to HC, while visual acuity scores did not differ between PWE without SCB-drugs (55.25 ± 4.75, 36.53 ± 4.50) and HC. PWE with SCB-drugs had significantly lower LCVA scores than PWE without SCB-drugs (p = .03). Importantly, no association was found between visual acuity scores and structural parameters, neither in the overall sample, nor in any of the subgroups. Retinal neuroaxonal loss in PWE was not associated with reduced visual acuity under high and low contrast. Instead, our findings reinforce SCB-drug intake as an important factor for reduced visual acuity under high and low contrast.

(1) Background: The management of epilepsy during pregnancy requires balancing effective seizure control against potential teratogenic effects of antiseizure medications (ASMs). Data on the safety of lacosamide (LCM), a third-generation ASM, during pregnancy and breastfeeding are limited. (2) Methods: To evaluate the safety and efficacy of LCM during pregnancy and breastfeeding, we report a single-centre case series and provide a comprehensive narrative review of the literature. (3) Results: In total, 22 cases of maternal exposure to LCM throughout pregnancy (1 monotherapy, 21 polytherapy) were identified, resulting in 21 live births (95.5%). Congenital malformations (atrial septal defect) were observed in one offspring exposed to LCM and levetiracetam (4.8%). Twelve newborns were breastfed (57.1%) without neurodevelopmental delay after twelve months. The literature search identified 16 studies, overall reporting data on 627 pregnancies with LCM (236 monotherapy, 391 polytherapy). Among 632 available pregnancy outcomes (3 twin pregnancies and 1 triplet in the polytherapy group) the proportion of live births was 81.3% (514/632). Major congenital malformations were reported in 2.5% (6/236) with LCM monotherapy and 11.9% (47/396) with polytherapy. (4) Conclusions: According to the literature, no major safety concerns, especially in LCM monotherapy, and no specific malformations associated with LCM exposure were identified. Conclusions are limited by the heterogeneity of studies and the small number of monotherapy-exposed cases. Larger, prospective studies with longer follow-up are required.