Relationship between sleep quality and cognitive performance in patients with epilepsy.

PURPOSE: To investigate the relationship between self-reported sleep quality and cognitive function in patients with epilepsy (PWE), as well as anxiety and depressive symptoms and patient quality of life (QoL). METHODS: This multicenter cross-sectional study included PWE aged ≥12 years who were receiving ≥1 anti-seizure medication (ASM) and had not been diagnosed with a sleep disorder. Patients completed the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Montreal Cognitive Assessment test (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Quality of Life in Epilepsy Inventory-10 (QOLIE-10). RESULTS: The study enrolled 150 patients aged 16-83 years, mean age (standard deviation [SD]) 40.6 (15.2) years; 58.7% were female and 75.3% had focal epilepsy. Mean (SD) PSQI score was 4.71 (3.08), 44.4% of patients had impaired sleep quality (PSQI score ≥5), 19.9% had pathologic excessive daytime sleepiness (ESS score >12), and 32.7% had mild cognitive impairment (MoCA score <26). Within the PSQI, sleep disturbance (P = 0.036) and use of sleep medication (P = 0.006) scores were significantly higher in patients with mild cognitive impairment. Multiple regression analysis showed older age (regression coefficient [B], -0.086; 95% confidence interval [CI], -0.127, -0.045; P < 0.001) and the use of sleep medication component of the PSQI [B, -1.157; 95% CI, -2.064, -0.220; P = 0.013) were independently associated with lower MoCA score. Poor sleep quality was associated with probable anxiety and depression symptoms, and directly correlated with reduced QoL. CONCLUSIONS: In PWE, sleep quality was not significantly independently associated with mild cognitive impairment, although poor sleep quality had a negative effect on mood and QoL.

Perampanel in routine clinical use across Europe: Pooled, multicenter, observational data.

OBJECTIVE: To pool observational data on the routine use of perampanel to obtain information on real-world outcomes and data in populations typically underrepresented in clinical trials. METHODS: Individual-level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1-year retention rate, 1-year seizure freedom rate (duration ≥6 months), and incidence of treatment-emergent adverse events (TEAEs). In addition, relationships were explored with logistic regression analyses. RESULTS: The full analysis set comprised 2396 people: 95% had focal seizures; median epilepsy duration was 27 years; median number of concomitant antiepileptic drugs (AEDs) was 2; and median prior AEDs was 6. One-year retention rate was 48% (1117/2332; 95% confidence interval [CI] 46-50%), and 1-year seizure-free rate (≥6-month duration) was 9.2% (74/803; 95% CI 7-11%). Median treatment duration was 11.3 months (1832 patient-years); median dose was 8 mg. In 388 individuals with available data at 3, 6, and 12 months, responder rates were 42%, 46%, and 39%, respectively. During the first year, TEAEs were reported in 68% of participants (1317/1497; 95% CI 66-70%). Logistic regression found higher age at perampanel initiation was associated with higher seizure-free rate, and higher number of prior AEDs with lower seizure-free rate and lower rates of somatic TEAEs. In 135 individuals aged ≥65 years, 1-year retention rate was 48% and seizure-free rate was 28%. SIGNIFICANCE: Across a large, treatment-resistant population, add-on perampanel was retained for ≥1 year by 48% of individuals, and 9% were seizure-free for ≥6 months. TEAEs were in line with previous reports in routine clinical use, and less frequent than in the clinical trial setting. No new or unexpected TEAEs were seen. Despite the limitations of observational studies, our data indicate that some individuals may derive a marked benefit from the use of perampanel.

Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12-month GENERAL study.

OBJECTIVE: To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). METHODS: This multicenter, retrospective, 1-year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. RESULTS: The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic-clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure-free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add-on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. SIGNIFICANCE: In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real-world evidence with perampanel across different seizure types in IGE.

Cardiovascular autonomic and hemodynamic responses to vagus nerve stimulation in drug-resistant epilepsy.

PURPOSE: Vagus nerve stimulation (VNS) is used as an adjunctive therapy for treating patients with drug-resistant epilepsy. The impact of VNS on cardiovascular autonomic function remains to be fully understood. We determined changes in cardiovascular sympathetic and parasympathetic, and hemodynamic function in association with VNS in patients with drug-resistant focal epilepsy. METHOD: Longitudinal (n=15) evaluation of beat-to-beat blood pressure (BP) and heart rate variability (HRV), baroreflex sensibility, and hemodynamic function performed before VNS implantation, 6-months after implantation, and a mean of 12-months after implantation; and cross-sectional study (n=14) of BP and HR variability and baroreflex sensitivity during VNS on and VNS off. RESULTS: In the longitudinal study, no differences were observed between the baseline, the 6-month visit, and the final visit in markers of parasympathetic cardiovagal tone or baroreflex sensitivity. Systolic and diastolic BP upon 5-min of head-up tilt increased significantly after VNS implantation (Systolic BP: -16.69±5.65mmHg at baseline, 2.86±16.54mmHg at 6-month, 12.25±12.95mmHg at final visit, p=0.01; diastolic BP: -14.84±24.72mmHg at baseline, 0.86±16.97mmHg at 6-month, and 17±12.76mmHg at final visit, p=0.001). CONCLUSION: VNS does not seem to produce alterations in parasympathetic cardiovagal tone, regardless of the laterality of the stimulus. We observed a slight increase in sympathetic cardiovascular modulations. These changes had no significant hemodynamic implications. These findings contribute to the understanding of potential mechanisms of action of VNS.

Monozygotic twins suffering from Huntington's disease show different cognitive and behavioural symptoms.

Monozygotic male twins, carrying the same number of trinucleotide repeats in the IT 15 Huntington disease (HD) gene, showed a different clinical course. Patient 1 presented with anxiety and chorea at the age of 40. Patient 2 showed persecution paranoia and motor impersistence at the age of 42. Both patients were monitored for 30 months using currently recommended motor and behaviour scales. No differences were observed in motor scoring besides small interevaluation fluctuations. However, on the cognitive and behaviour scales, patient 1 showed a significant worsening when compared with patient 2. Our cases support the belief that the motor symptoms and signs in HD are highly dependent on the trinucleotide expansion. However, the differences in the evolution of mental status in our patients suggest that other still unknown environmental factors are important in the phenotypic expression of Huntington's disease.