Efficacy and tolerability of the ketogenic diet versus high-dose adrenocorticotropic hormone for infantile spasms: A single-center parallel-cohort randomized controlled trial.

OBJECTIVE: To compare the efficacy and safety of the ketogenic diet (KD) with standard adrenocorticotropic hormone (ACTH) treatment in infants with West syndrome. METHODS: In this parallel-cohort (PC) randomized controlled trial (RCT), infants were randomly allocated to KD or high-dose ACTH. Those who could not be randomized were followed in a PC. Primary end point was electroclinical remission at day 28. Secondary end points were time to electroclinical remission, relapse after initial response, seizure freedom at last follow-up, adverse effects, and developmental progress. RESULTS: One hundred one infants were included: 32 in the RCT (16 KD; 16 ACTH) and 69 in the PC (37 KD; 32 ACTH). Electroclinical remission at day 28 was similar between KD and ACTH (RCT: 62% vs 69%; PC: 41% vs 38%; combined cohort: 47% vs 48%; KD vs ACTH, respectively). In the combined cohort, time to electroclinical remission was similar between both treatments (14 days for KD, 16 days for ACTH). However, relapse rates were 16% (KD) and 43% (ACTH, P = 0.09), and seizure freedom at last follow-up was 40% (KD) and 27% (ACTH, P = 0.18). Adverse effects needing acute medical intervention occurred more often with ACTH (30% with KD, 94% with ACTH, P < 0.001). Age-appropriate psychomotor development and adaptive behavior were similar. Without prior vigabatrin (VGB) treatment, remission at day 28 was 47% (KD) and 80% (ACTH, P = 0.02); relapse rates were 29% (KD) and 56% (ACTH, P = 0.13). Consequently, seizure freedom at last follow-up was similar. In infants with prior VGB, seizure freedom at last follow-up was 48% (KD) and 21% (ACTH, P = 0.05). SIGNIFICANCE: The study is underpowered; therefore, its results should be interpreted with caution. KD is as effective as ACTH in the long term but is better tolerated. Without prior VGB treatment, ACTH remains the first choice to achieve short-term remission. However, with prior VGB, KD was at least as effective as ACTH in the short term and was associated with lower relapse rates in the long term; therefore, it represents an appropriate second-line treatment after VGB.

Correlates of electroencephalographic resting states and erythrocyte membrane docosahexaenoic and eicosapentaenoic acid levels in individuals at ultra-high risk of psychosis.

OBJECTIVE: Abnormal levels of polyunsaturated fatty acids (PUFAs) have been reported in individuals suffering from schizophrenia. The main aim of the present study was to investigate the relationship between erythrocyte membrane fatty acid levels and resting-state brain activity occurring in individuals at ultra-high risk (UHR) of psychosis. METHOD: The association between erythrocyte membrane fatty acids levels and resting-state brain activity and its value in predicting psychosis was examined in 72 UHR individuals. RESULTS: In the frontal area, the activity in the fast frequency band Beta2 was positively associated with docosahexaenoic acid (DHA) levels (R = 0.321, P = 0.017), and in the fronto-central area, Beta2 activity showed a positive correlation with eicosapentaenoic acid (EPA) levels (R = 0.305, P = 0.009), regardless of psychosis transition status. Conversely, the slow frequency band Theta was significantly negatively associated with EPA levels in the parieto-occipital region (R = -0.251, P = 0.033. Results also showed that Alpha power was negatively correlated with DHA levels in UHR individuals who did not transition to psychosis, while this correlation was not present in individuals who later transitioned. CONCLUSION: Our results suggest that individuals at UHR for psychosis who have higher basal omega-3 fatty acids levels present with resting EEG features associated with better states of alertness and vigilance. Furthermore, the improvement in the Alpha synchrony observed along with increased DHA levels in participants who did not transition to psychosis is disturbed in those who did transition. However, these interesting results are limited by the small sample size and low statistical power of the study.

Pairwise and higher-order measures of brain-heart interactions in children with temporal lobe epilepsy.

Objective.While it is well-known that epilepsy has a clear impact on the activity of both the central nervous system (CNS) and the autonomic nervous system (ANS), its role on the complex interplay between CNS and ANS has not been fully elucidated yet. In this work, pairwise and higher-order predictability measures based on the concepts of Granger Causality (GC) and partial information decomposition (PID) were applied on time series of electroencephalographic (EEG) brain wave amplitude and heart rate variability (HRV) in order to investigate directed brain-heart interactions associated with the occurrence of focal epilepsy.Approach.HRV and the envelopes ofδandαEEG activity recorded from ipsilateral (ipsi-EEG) and contralateral (contra-EEG) scalp regions were analyzed in 18 children suffering from temporal lobe epilepsy monitored during pre-ictal, ictal and post-ictal periods. After linear parametric model identification, we compared pairwise GC measures computed between HRV and a single EEG component with PID measures quantifying the unique, redundant and synergistic information transferred from ipsi-EEG and contra-EEG to HRV.Main results.The analysis of GC revealed a dominance of the information transfer from EEG to HRV and negligible transfer from HRV to EEG, suggesting that CNS activities drive the ANS modulation of the heart rhythm, but did not evidence clear differences betweenδandαrhythms, ipsi-EEG and contra-EEG, or pre- and post-ictal periods. On the contrary, PID revealed that epileptic seizures induce a reorganization of the interactions from brain to heart, as the unique predictability of HRV originated from the ipsi-EEG for theδwaves and from the contra-EEG for theαwaves in the pre-ictal phase, while these patterns were reversed after the seizure.Significance.These results highlight the importance of considering higher-order interactions elicited by PID for the study of the neuro-autonomic effects of focal epilepsy, and may have neurophysiological and clinical implications.

The Surplus Effect in Adaptive Behaviour in Down Syndrome: What Can Promote It?

BACKGROUND: In Down syndrome (DS), adaptive behaviour often shows a "surplus effect" (i.e., higher adaptive abilities than expected from cognitive skills). As inclusive schooling has become mandatory in Italy, we studied the impact of school inclusion on the surplus effect of adaptive behaviour in adult DS, considering potential confounding factors such as parental education. METHODS: All consecutive DS individuals from three different sites were queried prospectively regarding type of schooling (inclusive and non-inclusive). Demographic data were documented; cognitive abilities and adaptive behaviour were assessed (Coloured Progressive Matrices and Vineland Adaptive Behaviour Scales). The aim was to establish the presence of a surplus effect in adaptive behaviour, primarily in the overall level and secondarily in the main domains and subdomains. A multivariable-adjusted logistic regression model was used for the association of schooling, and parental education. RESULTS: The majority (65%) showed a surplus effect in adaptive behaviour and had attended inclusive schools (85%). Higher adaptive skills as well as early and longer functional treatment programmes were more readily available for younger individuals. In the group of inclusive schooling, the surplus effect on overall adaptive behaviour was present in 70% as opposed to 38% in the group without inclusive schooling, significant when adjusted for gender and maternal education. This was also observed in socialisation, written, and community, and after adjustment in playing and leisure time. CONCLUSIONS: Adaptive behaviour showed a surplus effect in the majority of DS adults, even more so after inclusive schooling. Younger adults showed higher adaptive skills. Moreover, female gender and higher maternal educational level significantly enhanced this surplus effect.

The Ketogenic Diet Including Breast Milk for Treatment of Infants with Severe Childhood Epilepsy: Feasibility, Safety, and Effectiveness.

Objective: The ketogenic diet (KD) is a high-fat and restricted carbohydrate diet for treating severe childhood epilepsy. In infants, breast milk is usually fully replaced by a ketogenic formula. At our center, mothers are encouraged to include breastfeeding into the KD if still breastfeeding. This retrospective study describes achievement and maintenance of ketosis with or without inclusion of breast milk. Methods: Data were retrieved from a prospective longitudinal database of children treated with KD for epilepsy analyzing infants <1 year of age. The time to achieve clinically relevant ketosis (≥2 mmol/L beta-hydroxybutyrate) was compared with and without inclusion of breast milk into standard KD. Ketosis, nutritional intakes, effectiveness, adverse effects, and successful continuation of breastfeeding were evaluated. Results: A total of 79 infants were eligible for analysis. In 20% (16), breast milk was included. Infants with breast milk included into the KD achieved relevant ketosis in 47 hours (interquartile range [IQR] 24-95) compared with 41 hours (IQR 22-70; p = 0.779) in infants with standard KD. Beta-hydroxybutyrate at day 2 was 3.1 mmol/L (IQR 0.5-4.9) and 3.8 mmol/L (IQR 2.2-4.9). Infants with breast milk included received higher amounts of carbohydrates at baseline and calories at 3 months. Seizure freedom and adverse effects showed no relevant differences. No infections occurred in infants receiving breast milk. In two infants, KD was initiated with breast-feds after bottle-feeding KD formula. In 31%, breastfeeding was continued after the KD, and in 25%, inclusion of breast milk and breastfeeding was maintained until complete weaning. Before discharge from hospital, the amount of breast milk included was median 90 mL/day (IQR 53-203) equivalent to median 9% (IQR 6-15). Conclusions: Appropriate ketosis was achieved in most infants and maintained within 48 hours. Incorporation of breast milk into KD is feasible, safe, and effective.

Effects of the ketogenic diet on platelet counts and global coagulation tests in childhood epilepsy.

PURPOSE: Several antiseizure drugs (ASD), especially Valproic acid (VPA), influence platelet counts and coagulation parameters. The ketogenic diet (KD), established in drug-resistant epilepsy, is combined with ASDs. Bruising and prolonged bleeding times during KD have been described, but whether hemostatic changes result from the KD or from concomitant ASDs, remains unclear. Aim of the present study was to evaluate bleeding, platelet counts and global coagulation tests prior to and during KD in childhood epilepsy. METHOD: Consecutive children treated with KD were systematically observed for bleeding. Serial measurements of platelet counts and global coagulation tests (APTT, PT and fibrinogen) were obtained at baseline and during KD (at 1, 3, 6 and 12 months). Children with KD monotherapy, concomitant VPA, or other ASDs were compared. RESULTS: Among 162 children receiving KD, we observed neither bleeding in daily life nor perioperative bleeding in those undergoing surgery (n = 25). Most children had normal platelet counts and coagulation parameters. Only a few had transient mild thrombocytopenia and mildly prolonged APTT values, not indicative of a bleeding risk. Even KD combined with VPA did not cause relevant coagulopathy. Unexpectedly, we found mild thrombocytosis in 24 % of patients prior to KD, which was most pronounced in yet untreated epilepsy. Thrombocytosis steadily resolved during KD. CONCLUSIONS: During KD treatment of childhood epilepsy, we observed neither bleeding symptoms nor laboratory results indicating a bleeding risk. Unexpectedly, mild thrombocytosis was present in 24 % at baseline, normalising during KD. Thrombocytosis may reflect the underlying inflammatory process of untreated epilepsy and requires further study.

Brain-heart interactions considering complex physiological data: processing schemes for time-variant, frequency-dependent, topographical and statistical examination of directed interactions by convergent cross mapping.

BACKGROUND: A multitude of complex methods is available to quantify interactions in highly complex physiological systems. Brain-heart interactions play an important role in identifying couplings between the central nervous system and the autonomic nervous system during defined physiological states or specific diseases. The crucial point of those interaction analyses is adequate pre-processing taking into account nonlinearity of data, intuitive graphical representation and suitable statistical evaluation of the achieved results. OBJECTIVE: The aim of this study is to provide generalized processing schemes for such investigations taking into account pre-processing, graphical representation and statistical analysis. APPROACH: Two defined data sets were used to develop these processing schemes. Brain-heart interactions in children with temporal lobe epilepsy during the pre-ictal, ictal and post-ictal periods as well as in patients with paranoid schizophrenia and healthy control subjects during the resting state period were investigated by nonlinear convergent cross mapping (CCM). Surrogate data, bootstrapping and linear mixed-effects model approaches were utilized for statistical analyses. MAIN RESULTS: CCM was able to reveal specific and statistically significant time- and frequency-dependent patterns of brain-heart interactions for children with temporal lobe epilepsy and provide a statistically significant pattern of topographic- and frequency-dependent brain-heart interactions for schizophrenic patients, as well as to show the differences from healthy control subjects. Suitable statistical models were found to quantify group differences. SIGNIFICANCE: Generalized processing schemes and crucial points of pre-processing, adapted interaction analysis and performed statistical analysis are provided. The general concept of analyses is transferable also to other methods of interactions analysis and data representing even more complex physiological systems.

Ketogenic parenteral nutrition in 17 pediatric patients with epilepsy.

Objective: Ketogenic parenteral nutrition (kPN) is indicated when enteral intake is temporarily limited or impossible, but evidence-based prescriptions are lacking. Objective was to evaluate the efficacy and safety of kPN in children with epileptic encephalopathies using a new computer-based algorithm for accurate component calculating. Methods: Children with epilepsy receiving kPN were included. A computer-based algorithm was established on the basis of guidelines of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN): fat intake not exceeding 4 g/kg/day, age-adequate supply of protein, electrolytes, vitamins, and trace elements, but reduced carbohydrates. Primary outcome was successfully reaching relevant ketosis, defined as beta-hydroxybutyrate plasma level of ≥ 2 mmol/L. Efficacy was defined as seizure reduction ≥50% in de novo kPN and maintenance of response in children already on a ketogenic diet (KD). Safety was assessed by adverse effects, laboratory findings, and the appropriateness of nutritional intake. Results: Seventeen children (median 1.84 years) were studied, of which 76% (13/17) were already on an oral ketogenic diet. Indications for kPN were surgery, status epilepticus, vomiting, food refusal, and introduction of enteral feeding in neonates. The parenteral fat/nonfat ratio was mean 0.9 (±0.3; range 0.6-1.5). Relevant ketosis was reached in 10 children (median 2.9 mmol/L), but not in 7 (median = 1.4 mmol/L). In de novo kPN, significant response was observed in 50% (2/4); in patients previously responding to the KD (77%, 10/13), response was maintained. A significant correlation between the degree of ketosis and seizure reduction (correlation coefficient = 0.691; p = .002) was observed. Only mild and transient adverse events occurred during kPN. Significance: KPN with fat intake of 3.5-4.0 g/kg/day was safe and effective. KPN was tailored according to guidelines and individual nutritional needs. In nearly half of the patients, ketosis was lower than during oral KD. Despite this, seizures remained controlled.

Nonlinear Directed Interactions Between HRV and EEG Activity in Children With TLE.

OBJECTIVE: Epileptic seizure activity influences the autonomic nervous system (ANS) in different ways. Heart rate variability (HRV) is used as indicator for alterations of the ANS. It was shown that linear, nondirected interactions between HRV and EEG activity before, during, and after epileptic seizure occur. Accordingly, investigations of directed nonlinear interactions are logical steps to provide, e.g., deeper insight into the development of seizure onsets. METHODS: Convergent cross mapping (CCM) investigates nonlinear, directed interactions between time series by using nonlinear state space reconstruction. CCM is applied to simulated and clinically relevant data, i.e., interactions between HRV and specific EEG components of children with temporal lobe epilepsy (TLE). In addition, time-variant multivariate Autoregressive model (AR)-based estimation of partial directed coherence (PDC) was performed for the same data. RESULTS: Influence of estimation parameters and time-varying behavior of CCM estimation could be demonstrated by means of simulated data. AR-based estimation of PDC failed for the investigation of our clinical data. Time-varying interval-based application of CCM on these data revealed directed interactions between HRV and delta-related EEG activity. Interactions between HRV and alpha-related EEG activity were visible but less pronounced. EEG components mainly drive HRV. The interaction pattern and directionality clearly changed with onset of seizure. Statistical relevant interactions were quantified by bootstrapping and surrogate data approach. CONCLUSION AND SIGNIFICANCE: In contrast to AR-based estimation of PDC CCM was able to reveal time-courses and frequency-selective views of nonlinear interactions for the further understanding of complex interactions between the epileptic network and the ANS in children with TLE.

Matching Pursuit-Based Time-Variant Bispectral Analysis and its Application to Biomedical Signals.

OBJECTIVE: Principle aim of this study is to investigate the performance of a matching pursuit (MP)-based bispectral analysis in the detection and quantification of quadratic phase couplings (QPC) in biomedical signals. Nonlinear approaches such as time-variant bispectral analysis are able to provide information about phase relations between oscillatory signal components. METHODS: Time-variant QPC analysis is commonly performed using Gabor transform (GT) or Morlet wavelet transform (MWT), and is affected by either constant or frequency-dependent time-frequency resolution (TFR). The matched Gabor transform (MGT), which emerges from the incorporation of GT into MP, can overcome this obstacle by providing a complex time-frequency plane with an individually tailored TFR for each transient oscillatory component. QPC analysis was performed by MGT, and MWT was used as the state-of-the-art method for comparison. RESULTS: Results were demonstrated using simulated data, which present the general case of QPC, and biomedical benchmark data with a priori knowledge about specific signal components. HRV of children during temporal lobe epilepsy and EEG during burst-interburst pattern of neonates during quiet sleep were used for the biomedical signal analysis to investigate the two main areas of biomedical signal analysis: The cardiovascular-cardiorespiratory system and neurophysiological brain activities, respectively. Simulations were able to show the applicability and reliability of the MGT for bispectral analysis. HRV and EEG analysis demonstrate the general validity of the MGT for QPC detection by quantifying statistically significant time patterns of QPC. CONCLUSION AND SIGNIFICANCE: Results confirm that MGT-based bispectral analysis provides significant benefits for the analysis of QPC in biomedical signals.

Efficacy and tolerability of the ketogenic diet in Dravet syndrome - Comparison with various standard antiepileptic drug regimen.

UNLABELLED: There is strong evidence for the use of the ketogenic diet (KD) in Dravet syndrome (DS). The purpose of this study was to evaluate both effectiveness and tolerability in comparison with various antiepileptic drugs (AEDs). METHODS: 32 children (19 males) with genetically confirmed DS treated at our center since 1999 were analyzed retrospectively. Data collected from patients' files included type of mutation, age at treatment initiation and treatment lag, overall seizure frequency and frequency of different seizure types, especially prolonged seizures and status epilepticus (SE). Efficacy and safety of the KD were evaluated. In addition, the effect on seizure count was compared with that of various AED regimen and the vagus nerve stimulation (VNS). RESULTS: Overall response to the KD was 70% at 3 months and 60% at 12 months. No SE occurred while patients were on the diet, and the frequencies of prolonged generalized and myoclonic seizures were reduced. No severe side effects requiring withdrawal of the KD were observed. Although the effect of the KD was independent of age at initiation, it had to be withdrawn due to noncompliance more frequently in solid fed older children compared with infants treated with the liquid ketogenic formula. The KD was not significantly inferior to the current gold standard AED triple combination of Stiripentol+Valproate+Clobazam (89%), Bromides (78%), Valproate alone (48%), Topiramate (35%) and VNS (37%) and significantly more effective than Levetiracetam (30%; p=0.037, Pearson's Chi-square). SIGNIFICANCE: These data suggest that the KD ranks among currently used AEDs as an effective treatment for seizures in DS. According to our results (good effect on SE and prolonged seizures, good tolerability, less compliance problems due to formula treatment) the KD should be considered as an early treatment option in infants with DS.

The ketogenic diet in infants--Advantages of early use.

OBJECTIVE: To evaluate the efficacy and safety of the ketogenic diet (KD) in infants (< 1.5 years of age) compared with older children. METHODS: Patients with complete follow-up data of ≥ 3 months after initiation of the KD were analyzed retrospectively. Infants < 1.5 years at initiation of the KD (Group A) were compared with children > 1.5 years (Group B). RESULTS: 127 children were screened, 115 (Group A: 58/Group B: 57) were included. There were no significant differences between groups with respect to responder rates (63.8% vs. 57.9% at 3 months), but more infants became seizure free (34.5% vs. 19% at 3 months; 32.7% vs. 17.5% at 6 and 12 months). This result remained stable also after termination of the KD (30.6% vs. 3.9% at last follow-up) (p = 0.000). Looking at infants < 9 months of age separately (n = 42), this result was even stronger with significantly more infants being seizure free at 6 and at 12 months (p = 0.005, p = 0.014, respectively). In addition, a significantly higher number of infants remained seizure free in the long-term (p = 0.001). No group differences between infants and children with respect to safety were observed. Overall 52/115 patients (45.21%) reported side effects, but withdrawal of the KD was only necessary in one infant. Acceptance of the KD was better in infants compared with children at 3 months (0 vs. 14, p = 0.000), but became difficult when solid food was introduced (16 vs. 14; n.s.). SIGNIFICANCE: According to our results, the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is more often achieved and maintained in infants. Acceptance of the diet is better before the introduction of solid food. Therefore, we recommend the early use of the KD during the course of epilepsy.

Semiology of temporal lobe epilepsy in children and adolescents. Value in lateralizing the seizure onset zone [corrected].

PURPOSE: To determine the frequency and lateralizing value of clinical seizure symptoms in children and adolescents with drug-resistant temporal lobe epilepsy (TLE). METHODS: Patients enrolled had to be <18 years of age and seizure free at follow-up for at least 12 months after epilepsy surgery. Patients were assigned to two age groups, children (age<12 years) and adolescents (age>12 and <18 years). Video-tapes were reviewed blinded to patients' demographic data and results of additional investigations by two independent raters. Clinical signs of known lateralizing significance in adults and additional clinical signs without lateralizing value were assessed. RESULTS: 14 patients (eight boys; 2-18 years) fulfilled the inclusion criteria. Inter-observer agreement was excellent (kappa coefficient: 0.82). Compared with adult series, no differences were found concerning overall occurrence of lateralizing signs and lateralizing accuracy. There were age-related differences, however, concerning the occurrence of individual signs: secondary generalization, complex automatisms and version were less frequent in children than in adolescents. CONCLUSIONS: Clinical signs of lateralizing value can also be found in children and adolescents, provided that the evaluation protocols used consider developmental aspects.

Time-variant, frequency-selective, linear and nonlinear analysis of heart rate variability in children with temporal lobe epilepsy.

The major aim of our study is to demonstrate that a concerted combination of time-variant, frequency-selective, linear and nonlinear analysis approaches can be beneficially used for the analysis of heart rate variability (HRV) in epileptic patients to reveal premonitory information regarding an imminent seizure and to provide more information on the mechanisms leading to changes of the autonomic nervous system. The quest is to demonstrate that the combined approach gains new insights into specific short-term patterns in HRV during preictal, ictal, and postictal periods in epileptic children. The continuous Morlet-wavelet transform was used to explore the time-frequency characteristics of the HRV using spectrogram, phase-locking, band-power and quadratic phase coupling analyses. These results are completed by time-variant characteristics derived from a signal-adaptive approach. Advanced empirical mode decomposition was utilized to separate out certain HRV components, in particular blood-pressure-related Mayer waves (≈0.1 Hz) and respiratory sinus arrhythmia (≈0.3 Hz). Their time-variant nonlinear predictability was analyzed using local estimations of the largest Lyapunov exponent (point prediction error). Approximately 80-100 s before the seizure onset timing and coordination of both HRV components can be observed. A higher degree of synchronization is found and with it a higher predictability of the HRV. All investigated linear and nonlinear analyses contribute with a specific importance to these results.

Advantages of signal-adaptive approaches for the nonlinear, time-variant analysis of heart rate variability of children with temporal lobe epilepsy.

Major aim of our study is to demonstrate that signal-adaptive approaches improve the nonlinear and time-variant analysis of heart rate variability (HRV) of children with temporal lobe epilepsy (TLE). Nonlinear HRV analyses are frequently applied in epileptic patients. As HRV is characterized by components with oscillatory properties frequency-selective methods are in the focus, whereby application of nonlinear analysis to linear filtered signals seems to be doubtful. Signal-adaptive methods that preserve nonlinear properties and utilize only the signal data for an automatic computation of the result could benefit to nonlinear analysis of HRV. Combinations of (1) the signal-adaptive Matched Gabor Transform with time-variant nonlinear bispectral analysis and of (2) signal-adaptive Empirical Mode Decomposition methods with time-variant nonlinear stability analysis are investigated with regard to their application in the analysis of specific HRV components (respiratory sinus arrhythmia and Mayer wave associated low-frequency HRV components) of 18 children with TLE. Changes of timing and coordination of both HRV components during preictal, ictal and postictal periods occur which can be better quantified by advanced signal-adaptive methods. Both approaches contribute with specific importance to the analysis.

Synchronization analysis between heart rate variability and EEG activity before, during, and after epileptic seizure.

Abstract An innovative concept for synchronization analysis between heart rate (HR) components and rhythms in EEG envelopes is represented; it applies time-variant analyses to heart rate variability (HRV) and EEG, and it was tested in children with temporal lobe epilepsy (TLE). After a removal of ocular and movement-related artifacts, EEG band activity was computed by means of the frequency-selective Hilbert transform providing envelopes of frequency bands. Synchronization between HRV and EEG envelopes was quantified by Morlet wavelet coherence. A surrogate data approach was adapted to test for statistical significance of time-variant coherences. Using this processing scheme, significant coherence values between a HRV low-frequency sub-band (0.08-0.12 Hz) and the EEG δ envelope (1.5-4 Hz) occurring both in the preictal and early postictal periods of a seizure can be shown. Investigations were performed for all electrodes at 20-s intervals and for selected electrode pairs (T3÷C3, T4÷C4) in a time-variant mode. Synchronization was more pronounced in the group of right hemispheric TLE patients than in the left hemispheric group. Such a group-specific augmentation of synchronization confirms the hypothesis of a right hemispheric lateralization of sympathetic cardiac control of the low-frequency HRV components.

Frontal delta power associated with negative symptoms in ultra-high risk individuals who transitioned to psychosis.

It has recently been shown that treatment with long-chain omega-3 polyunsaturated fatty acids (PUFAs) could decrease the rate of transition to psychosis, and improve psychiatric symptoms and global functioning in people at ultra-high risk (UHR) for psychosis. Previous studies have suggested that resting state brain activity measured with electroencephalography (EEG) may represent an objective biomarker of changes in neural function associated with supplementation with omega-3 PUFAs. It has also been proposed that although resting state EEG cannot, by itself, predict transition to psychosis in UHR individuals, the combination of resting state EEG with negative symptoms may be a valid predictor of transition. The present study investigated whether treatment with omega-3 PUFAs influenced resting state EEG in UHR participants, and whether or not the association of the participants' resting state EEG with their levels of negative symptoms was dependent on their transition status. The brain activity of 73 UHR participants was recorded in the context of a randomized, placebo-controlled trial of the effects of supplementation with omega-3 PUFAs. The UHR participants who subsequently transitioned to psychosis (UHR+) did not differ from those who did not transition (UHR-) in terms of resting state EEG power in any frequency band. However, negative symptom scores were associated with increased delta activity in the frontal region of the UHR+ participants, but not in the UHR- participants. Treatment with omega-3 PUFAs did not induce changes in resting state EEG in either group. The results suggest that decreased frontal delta activity, in combination with high levels of negative symptoms, may be a risk factor for subsequent transition to psychosis in UHR individuals.

Long-term outcome and tolerability of the ketogenic diet in drug-resistant childhood epilepsy--the Austrian experience.

PURPOSE: To evaluate the long-term efficacy/tolerability of the ketogenic diet (KD) in paediatric drug-resistant epilepsies. METHODS: Data from children who were treated between 1999 and 2008 and had continuous follow-up of at least 6 months after initiation of the KD were analysed retrospectively. Response was defined as > or = 50% seizure reduction. Treatment effects on EEG, developmental outcome and the "outcome-predictive" value of various clinical factors were also assessed. RESULTS: 50 children (22 boys; mean age 4.5 years+/-3.55) were included. Mean follow-up was 3.93+/-2.95. 50% of the patients were responders, 48% of them became seizure free. 50% were non-responders, 20% of them deteriorated. In responders, EEG background activity improved significantly (p=0.014) and a significantly lower rate of epileptic discharges (p=0.009) was seen after 6 months. In addition, neurological examination findings demonstrated significant developmental progress (p=0.038). Favourable treatment outcome was associated with a shorter disease duration (p=0.025) and generalised tonic clonic seizures (p=0.059). No further significant outcome predictors were detected. However, response was 44% in patients with infantile spasms, 62.5% in those with Dravet syndrome and 50% in Lennox-Gastaut-syndrome. Side effects occurred in 28%, but discontinuation of the KD was not required in any case. They most often observed with concomitant topiramate (p=0.001) and valproate (p=0.046). CONCLUSION: Despite the retrospective nature of the study and the inhomogeneous patient sample, we found good long-term effects of the KD on seizure frequency, EEG and neurological development.