Kempenhaeghe

In temporal lobe epilepsy (TLE), locally reduced glucose metabolism (i.e., hypometabolism) is indicative of the epileptogenic onset zone (EZ). Here, we investigate the potential value of resting-state fMRI (rs-fMRI) for localizing the EZ with fluorodeoxyglucose positron emission tomography (FDG-PET) as ground truth. Twelve PET-positive patients (34.1 ± 13.1 y; 5 females) with unilateral drug-resistant TLE were included. FDG-PET and rs-fMRI were acquired simultaneously at a hybrid 3T PET-MR scanner. Hypometabolic regions were identified on the FDG-PET images by a nuclear medicine expert. The FDG-PET images were compared with a clinical FDG-PET control dataset with normal glucose uptake distribution. The output z-score maps were thresholded at z < -2 to produce a binary mask of the significantly hypometabolic regions. The hypometabolism masks were mirrored onto the contralateral hemisphere for the asymmetry comparison. Regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional ALFF (fALFF) were calculated from the rs-fMRI in conventional (0.01-0.1 Hz) and slow-3 (0.073-0.198 Hz) frequency bands. Asymmetry indices (AIs) were calculated using the ipsilateral and contralateral hypometabolic masks in the PET-positive subjects and assessed via the one-sample Wilcoxon test and Spearman correlation coefficients. The AIs of conventional fALFF were significantly lower in the hypometabolic zone (p < 0.05). A significant negative correlation was found between the AIs of FDG-PET and fALFF in the slow-3 band (r = -0.62; p < 0.05). Conventional and slow-3 band fALFF showed a potential to mimic the FDG-PET findings in terms of EZ localization. Further research with extended cohorts and histopathological validation is required to determine the clinical value.

REM-sleep behavior disorder (RBD) may affect health-related quality of life (HRQoL) of people with Parkinson’s disease (PwP) and partners. We aimed to determine how RBD affects HRQoL using a mixed-methods approach. Quantitatively, we analyzed data from the PRIME-NL Parkinson Evaluation study, including 829 PwP and 452 partners, using multivariable regression models to examine the association between screen-positive RBD and HRQoL. Qualitatively, we conducted interviews with 14 dyads of PwP with self-reported RBD and their partners. RBD was negatively associated with HRQoL in both groups, primarily due to short-term effects on daily life, co-existing symptoms like impaired cognition and autonomic issues, and sleep disturbances. Impact of RBD was already felt before or during the diagnostic process, with the main challenges being sleep-related complaints, anxiety and impact on relationships. PwP and partners employed both medical and non-medical coping strategies. These findings will help to optimize care for PwP with RBD and their partners.

The development of clinical practice guidelines (CPG) has evolved into a rigorous and complex process. There is a need for training of CPG developers including methodologists, panel members and patient representatives. This study explored the educational needs and experiences of CPG developers, with specific attention to the patient perspective and economic considerations. An anonymised mixed-method survey was distributed among CPG developers and panel members in the Netherlands. The survey, developed in collaboration with Dutch CPG development organisations and patient organisations, aimed to capture insights into the developers' roles, training needs, and the incorporation of economic considerations and patient perspectives in CPG development. Data analysis involved qualitative content analysis and descriptive quantitative analysis. A total of 271 responses were analysed. Respondents described role-specific tasks and tasks overlapping between roles. Experience, guidance, and training influenced the respondents' feeling of preparedness for their tasks. Respondents expressed the need for content-related training, including CPG development methodology. They also raised the importance of process-related topics in training, such as the inclusion of different perspectives and responsibilities during CPG development. About half of the respondents (46%) indicated that economic considerations were included in their CPGs, however, there was no uniformity in approach. The patient perspective was included by 89% of the respondents, also in varying manners. Overall, respondents underscored the importance of both topics in CPG development (training) to ensure a future-proof healthcare system. This study underscores the importance of tailored CPG development training programmes addressing the specific competencies required for the different roles in CPG development. Thereby, recognising a holistic approach encompassing both content- and process-related aspects. Addressing economic considerations and the patient perspective in training will contribute to CPGs that support a patient-centred and sustainable healthcare system.

Hypocretin deficiency causes type 1 narcolepsy, a condition characterized by excessive daytime sleepiness, cataplexy, and fragmented nocturnal sleep. Two-thirds of people with narcolepsy are also overweight, of which half are obese. The pathophysiology behind weight gain in people with narcolepsy remains unknown. We assessed a possible decrease in energy expenditure as a cause for overweight in narcolepsy using respiration chamber calorimetry and doubly labeled water. Ten males with type I narcolepsy and nine matched (for age, sex, and BMI) healthy controls were enrolled. Participants stayed in a respiration chamber for 24 hours. They subsequently received doubly labeled water and wore an accelerometer for 2 weeks to assess energy expenditure and physical activity under daily living conditions. Total daily energy expenditure, resting energy expenditure (REE), overnight metabolic rate, physical activity level, and activity-induced energy expenditure were measured. No significant differences were found in REE, mean 24-hour respiration chamber energy expenditure, overnight metabolic rate, and activity-induced energy expenditure when comparing people with narcolepsy type 1 to controls. Physical activity was also comparable between groups. Energy expenditure in narcolepsy type 1 is similar to matched controls, suggesting comparable metabolism and physical activity rates. It remains possible that metabolic changes are most pronounced around disease onset. In addition, patients had to discontinue their medication which may have influenced the results. Still, our findings suggest that other factors may also play a role in weight gain in narcolepsy, such as differences in dietary behavior.

Although various wearable electroencephalography devices have been developed, performance evaluation of the devices and their associated automated sleep stage classification models is mostly limited to healthy participants. A major barrier for applying automated wearable electroencephalography sleep staging in clinical populations is the need for large-scale data for model training. We therefore investigated transfer learning as a strategy to overcome limited data availability and optimize automated single-channel electroencephalography sleep staging in people with sleep disorders. We acquired 52 single-channel frontopolar headband electroencephalography recordings from a heterogeneous sleep-disordered population with concurrent polysomnography (PSG). We compared 3 model training strategies: "pretraining" (ie, training on a larger dataset of 901 conventional PSGs), "training-from-scratch" (ie, training on wearable headband recordings), and "fine-tuning" (ie, training on conventional PSGs, followed by training on headband recordings). Performance was evaluated on all headband recordings using 10-fold cross-validation. Highest performance for 5-stage classification was achieved with fine-tuning (κ = .778), significantly higher than with pretraining (κ = .769) and with training-from-scratch (κ = .733). No significant differences or systematic biases were observed with clinically relevant sleep parameters derived from PSG. All sleep disorder categories showed comparable performance. This study emphasizes the importance of leveraging larger available datasets through deep transfer learning to optimize performance with limited data availability. Findings indicate strong similarity in data characteristics between conventional PSG and headband recordings. Altogether, results suggest the combination of the headband, classification model, and training methodology can be viable for sleep monitoring in the heterogeneous clinical population. van der Aar JF, van Gilst MM, van den Ende DA, etal. Optimizing wearable single-channel electroencephalography sleep staging in a heterogeneous sleep-disordered population using transfer learning. J Clin Sleep Med. 2025;21(2):315-323.

ObjectiveThere is currently scarce data on the electroclinical characteristics of epilepsy associated with synapsin 1 (SYN1) pathogenic variations. We examined clinical and electro‐encephalographic (EEG) features in patients with epilepsy and SYN1 variants, with the aim of identifying a distinctive electroclinical pattern.MethodsIn this retrospective multicenter study, we collected and reviewed demographic, genetic, and epilepsy data of 19 male patients with SYN1 variants. Specifically, we analyzed interictal EEG data for all patients, and electro‐clinical data from 10 epileptic seizures in 5 patients, using prolonged video‐EEG monitoring recordings. Inter‐ictal EEG functional connectivity parameters and frequency spectrum of the 10 patients over 12 years of age, were computed and compared with those of 56 age‐ and sex‐matched controls.ResultsThe main electroclinical features of epilepsy in patients with SYN1 were (1) EEG background and organization mainly normal; (2) interictal abnormalities are often rare or not visible on EEG; (3) more than 60% of patients had reflex seizures (cutaneous contact with water and defecation being the main triggers) isolated or associated with spontaneous seizures; (4) electro‐clinical semiology of seizures was mainly temporal or temporo‐insulo/perisylvian with a notable autonomic component; and (5) ictal EEG showed a characteristic rhythmic theta/delta activity predominating in temporo‐perisylvian regions at the beginning of most seizures. Comparing patients with SYN1 to healthy subjects, we observed a shift to lower frequency bands in power spectrum of interictal EEG and an increased connectivity in both temporal regions.InterpretationA distinct epilepsy syndrome emerges in patients with SYN1, with a rather characteristic clinical and EEG pattern suggesting predominant temporo‐insular involvement. ANN NEUROL 2025;97:34–50

ObjectivesThe Epilepsy Support Dog Evaluation study was commissioned by the Dutch Ministry of Health, Welfare and Sports to inform a reimbursement decision on seizure dogs. The randomized trial found that seizure dogs reduce seizure frequency and improve health-related quality of life of persons with severe refractory epilepsy (PSREs). This article examined the cost-effectiveness (CE) of adding seizure dogs to usual care for PSREs in The Netherlands. MethodsA microsimulation model was developed, informed by generalized linear mixed models using patient-level trial data from the Epilepsy Support Dog Evaluation study. The model adopted a 10-year time horizon and took a societal perspective. Seizure frequency was predicted as a function of time with the seizure dog. Patient utilities, caregiver utilities, and costs were predicted as a function of seizure frequency and time with the seizure dog. ResultsQuality-adjusted life-years (QALYs) of PSREs with a seizure dog and usual care alone were estimated at 6.28 and 5.65, respectively (Δ 0.63). For caregivers, estimated QALYs were 6.94 and 6.52, respectively (Δ 0.42). Total costs were respectively €228 691 and €226 261 (Δ €2430). Intervention costs were largely offset by savings in informal care and healthcare. The incremental CE ratio was €2314/QALY. Probabilistic sensitivity analysis indicated a 91% probability of seizure dogs being cost-effective at the €50 000/QALY threshold. The incremental CE ratio fell well below this threshold in scenario analyses. ConclusionsSeizure dogs are likely to be a cost-effective addition to usual care for PSREs in The Netherlands.

To describe the characteristics of psychogenic non-epileptic (functional) seizures (PNES) in adults with epilepsy and intellectual disability (ID) and to establish differences and risk factors regarding psychosocial functioning between individuals with and without PNES. Adults with ID and epilepsy living in epilepsy care facilities in The Netherlands were screened for PNES by a neurologist. A control group consisting of people with epilepsy and ID, without PNES, was matched according to age, sex, and level of ID. Objective data were retrieved retrospectively from clinical notes of the resident. Standardized questionnaires and tests, adjusted for people with ID, were obtained from participants and their nursing staff. Differences were analyzed using paired t tests, Wilcoxon signed-rank tests, or McNemar's tests, appropriate for matched case-control studies. Conditional logistic regression identified PNES risk factors. Five hundred forty individuals were screened, of which 42 had PNES (point prevalence 7.8%). In total, 35 cases and 35 controls gave consent. Proxy reports indicated that PNES impacted daily life in 79% by adjusting the individual's schedule, and caused minor injuries in one-third. Those with PNES were mainly female (69%); had a mild (46%) or moderate (37%) level of ID; showed more symptoms of depression (p = .024), anxiety (p = .030), self-injurious behavior (p = .015); and experienced more negative life events (p < .001). Clinically relevant predictors of PNES were the number of negative life events (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.12-2.53) and self-injurious behaviors (OR 5.27, 95% CI .97-28.81). Previously, PNES in individuals with ID and epilepsy were described mainly as a reinforced behavioral pattern, due to limited associations with psychiatric disorders. Our results demonstrate that this population does show individual psychosocial vulnerabilities when measured with instruments adjusted for this population, as indicated by proxy reports from daily caregivers. Viewing PNES as an involuntary response, especially for stress-prone individuals with ID, could reduce stigma and improve treatment.