Circadian rhythm of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy.

OBJECTIVE: To determine whether patients with drug-resistant mesial temporal lobe epilepsy present with an alteration in the autonomic circadian regulation of blood pressure. METHODS: A prospective case‒control study was designed, with a case group comprising patients with drug-resistant mesial temporal lobe epilepsy and a control group comprising healthy volunteers. Twenty-four-hour outpatient blood pressure monitoring was performed to assess the existence of a normal (dipping) or altered (non-dipping) circadian pattern. In addition, analytical and ultrasound parameters (carotid intima-media thickness) of vascular risk and sleep quality were evaluated. RESULTS: Twenty-four subjects were recruited in each study group, amongst whom no demographic differences or history of vascular risk were observed. A higher percentage of participants with a non-dipping pattern was observed in the group of patients with epilepsy (62.5% vs. 12.5, p = 0.001). In the case group, significant differences were also observed in carotid intima-media thickness, with a greater probability of presenting with pathological values (p = 0.022). CONCLUSION: The results suggest a disorder of the central autonomic control of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy, with a greater probability of developing an alteration of the circadian rhythm of blood pressure. This dysfunction may be a factor involved in the increased cardiovascular risk in this population.

Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME. Methods: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/). Findings: Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73). Interpretation: We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools. Funding: MING fonds.

COVID-19 prevalence and mortality in people with epilepsy: A nation-wide multicenter study.

BACKGROUND: To assess the prevalence, severity, and mortality of COVID-19 in people with epilepsy (PWE) and evaluate seizure control in PWE during and after COVID-19. METHODS: Retrospective, observational, multicenter study conducted in 14 hospitals. Medical records of randomly selected PWE followed at neurology outpatient clinics were reviewed. Proportion of PWE with a positive test for SARS-CoV-2 during 2020 was calculated. Risk factors associated with COVID-19 and its morbimortality were evaluated. RESULTS: 2751 PWE were included, mean age 48.8 years (18-99), 72.4% had focal epilepsy, and 35% were drug-refractory. COVID-19 prevalence in PWE was 5.53%, while in the Spanish population was 4.26%. Proportion of admissions to hospital, ICU, and deaths in PWE were 17.1%, 2%, and 4.61% of COVID-19 cases, while in Spanish population were 10.81%, 0.95%, and 2.57%, respectively. A severe form of COVID-19 occurred in 11.8%; dyslipidemia, institutionalization at long-term care facilities, intellectual disability, and older age were associated risk factors. Older age, hypertension, dyslipidemia, cardiac disease, and institutionalization were associated with mortality from COVID-19. Seizure control was stable in 90.1% of PWE during acute COVID-19, while 8.6% reported an increase in seizure frequency. During post-COVID-19 follow-up, 4.6% reported seizure control worsening. CONCLUSIONS: COVID-19 was moderately prevalent in PWE. One out of 5 patients required medical attention and 4.6% died due to COVID-19. Older age, dyslipidemia, institutionalization, and intellectual disability were significant risk factors associated with severe COVID-19. Seizure control remained stable during COVID-19 and throughout long-term follow-up in most PWE who contracted the infection.

Cognitive performance in patients with episodic cluster headache outside and inside the active cluster.

BACKGROUND: Previous studies have shown worse cognitive performance in cluster headache (CH) patients compared to healthy controls; however, little is known about cognitive performance in episodic CH (ECH) patients outside and inside the active cluster (AC). OBJECTIVE: Our aim is to compare cognitive function in ECH patients outside and inside the AC. METHODS: In this cross-sectional, observational study, four neuropsychological tests (Trail Making Test [TMT], Stroop Test [ST], verbal fluency [VF], and Symbol Digit Modalities Test [SDT]) were completed by 21 ECH patients at two different points in time: outside and inside the AC. We also assessed self-reported sleep quality and the presence of anxiety or depressive symptoms. Scores were compared. RESULTS: There was not any difference between the scores of the neuropsychological tests performed outside and inside the AC (TMT-A: 23 vs. 23.5; p = 0.984; TMT-B: 96.5 vs. 85.9; p = 0.104; ST word reading: 101.0 vs. 101.2; p = 0.938; ST color naming: 73.0 vs. 73.4; p = 0.858; ST color word: 44.0 vs. 46.0; p = 0.498; SDMT: 44.0 vs. 44.6; p = 0.961; VF phonemic: 29.5 vs. 30.2; p = 0.714; VF semantic: 20 vs. 21; p = 0.489). We found a worsening in the sleep quality component of the Pittsburgh Sleep Quality Index median scores in patients outside the AC (2 vs. 1; p = 0.046). CONCLUSIONS: Our findings suggest that patients with ECH have a similar cognitive performance outside and during the AC.

Efficacy and tolerability of perampanel as a first add-on therapy with different anti-seizure drugs.

PURPOSE: To investigate the efficacy and tolerability of perampanel (PER) when administered as a first add-on therapy to patients with focal epilepsy or idiopathic generalized epilepsy (IGE) taking one other antiseizure drug (ASD). METHODS: This multicentre, retrospective, one-year observational study collected data from patients (≥12 years) who initiated treatment with PER as first add-on therapy. Patients had to be experiencing inadequate seizure control on ASD monotherapy and tried ≤3 ASD monotherapies before initiating PER. Multivariate logistic regression analyses were performed, adjusted for the number and type of previous seizures, duration and aetiology of epilepsy. RESULTS: Of the 149 patients included in the study (mean age 41 years; 54.4 % male), 118 (79.2 %) were still receiving PER as first add-on treatment after 12 months. Mean PER dose was 6.2 mg/day. At 12 months, 45.6 % were seizure-free and 84.6 % responders. A significant difference in seizure freedom rate was found between patients with IGE and patients with focal epilepsy, but not in responders. Reduced seizure control was observed when PER was administered with strong enzyme-inducing ASDs; conversely, increased seizure control was seen when the same dose of PER was combined with enzyme-inhibiting ASDs. The most frequent adverse events were dizziness (15.4 %), irritability (14.1 %) and drowsiness (14.1 %); no differences in tolerance were observed among different combinations. CONCLUSION: PER demonstrated a good efficacy and safety profile when used as a first add-on therapy in patients who did not respond to monotherapy. PER dose adjustments may optimize seizure control when combined with strong enzyme-inducing or enzyme-inhibiting ASDs.

Myoclonus induced by amoxicillin-clavulanic acid.

•We present a patient in whom myoclonus appeared after initiation of treatment with amoxicillin-clavulanic acid.•Myoclonus and EEG abnormalities disappeared after discontinuation of antibiotic treatment.•This possible adverse effect should be considered to avoid performing aggressive therapeutic maneuvers.

Familial association of genetic generalised epilepsy with limb-girdle muscular dystrophy through a mutation in CAPN3.

•We present a family that includes members with phenotypes of generalized epilepsy and limb-girdle muscular dystrophy.•Subjects with heterozygous mutation developed epilepsy; a subject with homozygous mutation developed limb-girdle dystrophy.•Mutations in CAPN3 may play a role in the complex genetics of genetic generalized epilepsies.

Cognitive Performance in Episodic Cluster Headache.

BACKGROUND: Cluster headache is one of the most disabling of all headache conditions. Although some studies have investigated the psychological profile of patients with cluster headache, research on its impact on cognitive function in patients with episodic cluster headache outside the cluster bout is scant. METHODS: Cross-sectional study to evaluate various aspects of neuropsychological assessment and cognitive function including working memory, selective attention, verbal fluency, and executive function in 40 patients with episodic cluster headache. The patients were compared with 40 age-, gender-, and level of education-matched healthy controls. RESULTS: Episodic cluster headache patients performed significantly worse than healthy controls on all cognitive tests, except for the Interference Score (P = 0.281). They had significantly higher Hospital Anxiety Scale scores (P = 0.002). However, we found no significant association between cognitive performance, anxiety, sleep quality, and disease duration. CONCLUSIONS: Patients with episodic cluster headache outside the bout showed worse executive functioning, working memory, language, and selective attention compared with healthy controls, regardless of the duration of disease or sleep quality.

Circadian rhythm and autonomic dysfunction in presymptomatic and early Huntington's disease.

INTRODUCTION: Sleep and circadian rhythm disturbances are common in patients with neurodegenerative diseases such as Huntington's disease (HD). The aim of this study was to evaluate variability in circadian blood pressure (BP) to determine the association between abnormal circadian BP and sleep quality in patients with HD. METHODS: Cross-sectional, multicenter study of 38 HD mutation carriers (23 premanifest and 15 early stage patients) who were compared to 38 age- and sex-matched controls. BP was evaluated by ambulatory blood pressure monitoring (ABPM). Based on the percentage decrease in nocturnal BP, subjects were classified as either dippers (≥10%) or non-dippers (<10%). Sleep quality and daytime sleepiness were measured, respectively, using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Daytime Sleepiness Scale (ESS) and the scores on these indices were correlated with the ABPM findings. RESULTS: Sixty-three percent HD mutation carriers were non-dippers (86.7% of the symptomatic and 47.8% of the premanifest patients) versus 23.7% of controls (p = 0.001). In the HD group, sleep quality was significantly more impaired (PSQI>5) (p = 0.016) with more excessive daytime sleepiness (ESS>9) (p = 0.001) than in the control group. Nocturnal non-dipping was associated with worse sleep quality in patients (p = 0.011) but not in controls. CONCLUSION: These results show that patients with HD present early disturbances in the circadian rhythm of BP and that this altered nocturnal BP is associated with poor sleep quality. These findings suggest the potential role of subtle hypothalamic dysfunction in this population.