The relation between cortisol and functional connectivity in people with and without stress-sensitive epilepsy.

OBJECTIVE: The most common reported seizure-precipitant is stress. We recently showed a biologic basis for stress sensitivity of seizures: cortisol levels in people with stress-sensitive epilepsy correlated with focal interictal epileptiform discharges (IEDs) on electroencephalography (EEG). Here we aimed to determine whether the effect of cortisol on the epileptic brain is global or focal, and whether cortisol affects all brains or just those of stress-sensitive people. Because epilepsy is associated with changes in functional brain connectivity, we studied the relationship between cortisol and changes in global and focal (node-centered) functional connectivity measures for individuals with stress-sensitive and non-stress-sensitive epilepsy. METHODS: Seventeen people with epilepsy underwent long-term (>24 h) EEG recording. During the first 5 h after waking, saliva was collected every 15 min for cortisol measurements. Theta-band functional connectivity was assessed for every 15 min of the recording. We calculated the average phase-lag index (PLI) between all channels as a measure of global functional connectivity. We used network Strength, the averaged PLI per channel, as focal functional connectivity measure. We correlated cortisol, global, and focal functional connectivity (Strength) with IED frequency using linear mixed models. Analyses were split for people with and without stress-sensitivity of seizures. RESULTS: Cortisol was negatively correlated with global functional connectivity in people with stress-sensitive seizures (estimate -0.0020; P < .01), whereas not in those without stress-sensitivity (estimate -0.0003; P = .46). This relationship occurred irrespective of the presence of IEDs on a channel (channels without IEDs and stress-sensitivity: estimate -0.0019; P < .01, non-stress-sensitive -0.0003; P = .41). Global and focal functional connectivity were negatively correlated with IED frequency, irrespective of stress sensitivity of seizures or channel type. SIGNIFICANCE: People with stress-sensitive epilepsy have a whole-brain neuronal response to cortisol that is different from that of people with non-stress-sensitive epilepsy. This offers a basis for understanding seizure genesis in stress-sensitive epilepsy, which might require a different treatment approach.

Cortisol fluctuations relate to interictal epileptiform discharges in stress sensitive epilepsy.

People with epilepsy often report seizures precipitated by stress. This is believed to be due to effects of stress hormones, such as cortisol, on neuronal excitability. Cortisol, regardless of stress, is released in hourly pulses, whose effect on epileptic activity is unknown. We tested the relation between cortisol levels and the incidence of epileptiform abnormalities in the electroencephalogram of people with focal epilepsy. Morning cortisol levels were measured in saliva samples obtained every 15 min. Interictal epileptiform discharges were determined in the same time periods. We investigated the relationship between cortisol levels and the epileptiform discharges distinguishing persons with from those without stress-precipitated seizures (linear mixed model), and analysed the contribution of individual, epilepsy and recording characteristics with multivariable analysis. Twenty-nine recordings were performed in 21 individuals. Cortisol was positively related to incidence of epileptiform discharges (ß = 0.26, P = 0.002) in people reporting stress-sensitive seizures, but not those who did not report stress sensitivity (ß = -0.07, P = 0.64). The relationship between cortisol and epileptiform discharges was positively associated only with stress sensitivity of seizures (ß = 0.31, P = 0.005). The relationship between cortisol levels and incidence of interictal epileptiform discharges in people with stress-sensitive seizures suggests that stress hormones influence disease activity in epilepsy, also under basal conditions.

Saliva and serum lacosamide concentrations in patients with epilepsy.

PURPOSE: Lacosamide is a new antiepileptic drug that has a novel mechanism of action, linear pharmacokinetics, and proven efficacy in the adjunctive treatment of partial-onset seizures. We ascertained the relationship between serum and saliva lacosamide concentrations so as to determine whether saliva may be a useful alternative to serum for therapeutic drug monitoring. METHODS: Blood samples were obtained from 98 people with intractable epilepsy (51 male; mean age 43 ± 12; range 19-76 years) prescribed lacosamide as adjunctive therapy. For 48 patients, concurrent saliva samples were also collected. Lacosamide concentrations in serum (free and total) and in saliva were determined by high performance liquid chromatography (HPLC). RESULTS: Linear regression analysis showed a good correlation between lacosamide dose and both total (r(2) = 0.825; n = 32) and free (r(2) = 0.815; n = 29) serum concentrations, and lacosamide serum total and free concentrations were linearly related (r(2) = 0.721; n = 97). There was also a good correlation between saliva lacosamide and both total (r(2) = 0.842; n = 49) and free (r(2) = 0.828; n = 47) serum lacosamide concentrations. Based on the saliva data, the protein binding of lacosamide in serum is calculated to be 87 ± 4% and is comparable to the value calculated by direct measurement of the free and total lacosamide concentration in serum (91 ± 4%). DISCUSSION: These data support the use of saliva as a viable alternative to serum for monitoring lacosamide therapy in patients with epilepsy.

Oral health and dental status in people with epilepsy in rural China.

PURPOSE: We evaluated the oral health and dental status of people with epilepsy, and their relationship to seizure frequency, in a community cohort in rural China. METHODS: A cross-sectional study of people with epilepsy was carried out in areas in Henan, Shanxi and Ningxia provinces of China. All participants underwent a specially designed "Oral health and Dental status Questionnaire". Univariate and multivariate analyses were used to explore the relationships between seizure frequency and oral health and dental status. RESULTS: A total of 875 people participated. Almost two thirds (65.8%) reported brushing their teeth at least once a day but 634 (73.0%) brushed their teeth for less than 3 min each time. Only 80 (9.1%) had visited a dental clinic in the previous year. Multivariate logistic regression analysis showed that having 1-4 seizures/month (OR 0.60, 95%CI 0.40-0.90) or >4 seizures/month (OR 0.38, 95%CI 0.22-0.66) was associated with decreased odds of brushing teeth at least once a day, and higher seizure frequency was associated with increased odds of dental injury due to seizures (OR 2.07, 95%CI 1.22-3.50 for <1 seizure/month; OR 2.12, 95%CI 1.25-3.58 for 1-4 seizures/month; OR 3.09, 95%CI 1.57-6.07 for >4 seizures/month). CONCLUSION: Seizure frequency was significantly associated with seizure-related dental injury, and with the lack of good oral health practice. Improvement in the oral health of people with epilepsy in resource-poor areas should be encouraged.