Brivaracetam as add-on treatment in focal epilepsy: A real-world time-based analysis.

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio [adj HR] = 1.07, 95% CI = 1.02-1.13, P = .009) and baseline monthly seizure frequency (adj HR = 1.004, 95% CI = 1.001-1.008, P = .028) were independently associated with the primary endpoint. Add-on BRV improved seizure control in LEV-naive and LEV-prior patients. The time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.

Multimodal responses induced by cortical stimulation of the parietal lobe: a stereo-electroencephalography study.

The functional complexity of the parietal lobe still represents a challenge for neurophysiological and functional neuroimaging studies. While the somatosensory functions of the anterior parietal cortex are well established, the posterior parietal cortex has a relevant role in processing the sensory information, including visuo-spatial perception, visual attention, visuo-motor transformations and other complex and not completely understood functions. We retrospectively analysed all the clinical manifestations induced by intracerebral bipolar electrical stimulation in 172 patients suffering from drug-resistant focal epilepsy (mean age 25.6, standard deviation 11.6; 44% females and 56% males) with at least one electrode stereotactically implanted in the parietal cortex. A total of 1186 electrical stimulations were included in the analysis, of which 88 were subsequently excluded because of eliciting pathological electric activity or inducing ictal symptomatology. In the dominant parietal lobe, clinical responses were observed for 56 (25%) of the low-frequency stimulations and for 76 (50%) of the high-frequency stimulations. In the non-dominant parietal lobe, 111 (27%) low-frequency and 176 (55%) high-frequency stimulations were associated with a clinical response. Body scheme alteration was the only clinical effect showing a lateralization, as they were evoked only in the non-dominant hemisphere. The occurrence of somatosensory sensations, motor symptoms, dysarthria and multimodal responses were significantly associated with stimulation of the postcentral gyrus (odds ratio: 5.83, P < 0.001; odds ratio: 8.77, P < 0.001; odds ratio: 5.44, P = 0.011; odds ratio: 8.33, P = 0.006; respectively). Stimulation of the intraparietal sulcus was associated with the occurrence of sensory illusions or hallucinations (odds ratio: 8.68, P < 0.001) and eyeball/eyelid movements or sensations (odds ratio: 4.35, P = 0.047). To our knowledge, this is the only currently available complete revision of electrical stimulation of the entire parietal cortex with the aim to evaluate the neurophysiology of this relevant brain region. Our analysis offers a general overview of the multiple roles of the parietal cortex and supports its crucial involvement in different networks related to complex integrative functions.media-1vid110.1093/brain/awv187_video_abstractawv187_video_abstract.

About ATMPs, SOPs and GMP: The Hurdles to Produce Novel Skin Grafts for Clinical Use.

BACKGROUND: The treatment of severe full-thickness skin defects represents a significant and common clinical problem worldwide. A bio-engineered autologous skin substitute would significantly reduce the problems observed with today's gold standard. METHODS: Within 15 years of research, the Tissue Biology Research Unit of the University Children's Hospital Zurich has developed autologous tissue-engineered skin grafts based on collagen type I hydrogels. Those products are considered as advanced therapy medicinal products (ATMPs) and are routinely produced for clinical trials in a clean room facility following the guidelines for good manufacturing practice (GMP). This article focuses on hurdles observed for the translation of ATMPs from research into the GMP environment and clinical application. RESULTS AND CONCLUSION: Personalized medicine in the field of rare diseases has great potential. However, ATMPs are mainly developed and promoted by academia, hospitals, and small companies, which face many obstacles such as high financial burdens.

Altered cortical and subcortical local coherence in obstructive sleep apnea: a functional magnetic resonance imaging study.

Obstructive sleep apnea (OSA) syndrome is the most common sleep-related breathing disorder, characterized by excessive snoring and repetitive apneas and arousals, which leads to fragmented sleep and, most importantly, to intermittent nocturnal hypoxaemia during apneas. Considering previous studies about morphovolumetric alterations in sleep apnea, in this study we aimed to investigate for the first time the functional connectivity profile of OSA patients and age-gender-matched healthy controls, using resting-state functional magnetic resonance imaging (fMRI). Twenty severe OSA patients (mean age 43.2 ± 8 years; mean apnea-hypopnea index, 36.3 h(-1) ) and 20 non-apneic age-gender-body mass index (BMI)-matched controls underwent fMRI and polysomnographic (PSG) registration, as well as mood and sleepiness evaluation. Cerebro-cerebellar regional homogeneity (ReHo) values were calculated from fMRI acquisition, in order to identify pathology-related alterations in the local coherence of low-frequency signal (<0.1 Hz). Multivariate pattern classification was also performed using ReHo values as features. We found a significant pattern of cortical and subcortical abnormal local connectivity in OSA patients, suggesting an overall rearrangement of hemispheric connectivity balance, with a decrease of local coherence observed in right temporal, parietal and frontal lobe regions. Moreover, an increase in bilateral thalamic and somatosensory/motor cortices coherence have been found, a finding due possibly to an aberrant adaptation to incomplete sleep-wake transitions during nocturnal apneic episodes, induced by repetitive choke sensation and physical efforts attempting to restore breathing. Different hemispheric roles into sleep processes and a possible thalamus key role in OSA neurophysiopathology are intriguing issues that future studies should attempt to clarify.

A retrospective multicentric study on the effectiveness of intravenous brivaracetam in seizure clusters: Data from the Italian experience.

OBJECTIVE: Nearly half of people with epilepsy (PWE) are expected to develop seizure clusters (SC), with the subsequent risk of hospitalization. The aim of the present study was to evaluate the use, effectiveness and safety of intravenous (IV) brivaracetam (BRV) in the treatment of SC. METHODS: Retrospective multicentric study of patients with SC (≥ 2 seizures/24 h) who received IV BRV. Data collection occurred from January 2019 to April 2022 in 25 Italian neurology units. Primary efficacy outcome was seizure freedom up to 24 h from BRV administration. We also evaluated the risk of evolution into Status Epilepticus (SE) at 6, 12 and 24 h after treatment initiation. A Cox regression model was used to identify outcome predictors. RESULTS: 97 patients were included (mean age 62 years), 74 (76%) of whom had a history of epilepsy (with drug resistant seizures in 49% of cases). BRV was administered as first line treatment in 16% of the episodes, while it was used as first or second drug after benzodiazepines failure in 49% and 35% of episodes, respectively. On the one hand, 58% patients were seizure free at 24 h after BRV administration and no other rescue medications were used in 75 out of 97 cases (77%) On the other hand, SC evolved into SE in 17% of cases. A higher probability of seizure relapse and/or evolution into SE was observed in patients without a prior history of epilepsy (HR 2.0; 95% CI 1.03 - 4.1) and in case of BRV administration as second/third line drug (HR 3.2; 95% CI 1.1 - 9.7). No severe treatment emergent adverse events were observed. SIGNIFICANCE: In our cohort, IV BRV resulted to be well tolerated for the treatment of SC and it could be considered as a treatment option, particularly in case of in-hospital onset. However, the underlying etiology seems to be the main outcome predictor.

Podoplanin-Fc reduces lymphatic vessel formation in vitro and in vivo and causes disseminated intravascular coagulation when transgenically expressed in the skin.

Podoplanin is a small transmembrane protein required for development and function of the lymphatic vascular system. To investigate the effects of interfering with its function, we produced an Fc fusion protein of its ectodomain. We found that podoplanin-Fc inhibited several functions of cultured lymphatic endothelial cells and also specifically suppressed lymphatic vessel growth, but not blood vessel growth, in mouse embryoid bodies in vitro and in mouse corneas in vivo. Using a keratin 14 expression cassette, we created transgenic mice that overexpressed podoplanin-Fc in the skin. No obvious outward phenotype was identified in these mice, but surprisingly, podoplanin-Fc-although produced specifically in the skin-entered the blood circulation and induced disseminated intravascular coagulation, characterized by microthrombi in most organs and by thrombocytopenia, occasionally leading to fatal hemorrhage. These findings reveal an important role of podoplanin in lymphatic vessel formation and indicate the potential of podoplanin-Fc as an inhibitor of lymphangiogenesis. These results also demonstrate the ability of podoplanin to induce platelet aggregation in vivo, which likely represents a major function of lymphatic endothelium. Finally, keratin 14 podoplanin-Fc mice represent a novel genetic animal model of disseminated intravascular coagulation.

Evidence of diffuse damage in frontal and occipital cortex in the brain of patients with post-traumatic stress disorder.

A number of MRI studies have shown focal or diffuse cortical gray matter (GM) abnormalities in patients with post-traumatic stress disorder (PTSD). However, the results of these studies are unclear regarding the cortical regions involved in this condition, perhaps due to the heterogeneity of the PTSD population included or to the differences in the methodology used for the quantification of the brain structures. In this study, we assessed differences in cortical GM volumes between a selected group of 25 drug-naive PTSD patients with history of adulthood trauma and 25 matched non-traumatized controls. Analyses were performed by using two different automated methods: the structural image evaluation using normalization of atrophy (SIENAX) and the voxel-based morphometry (VBM), as we trusted that if these complementary techniques provided similar results, it would increase the confidence in the validity of the assessment. Results of SIENAX and VBM analyses similarly showed that cortical GM volume decreases in PTSD patients when compared to healthy controls, particularly in the frontal and occipital lobes. These decreases seem to correlate with clinical measures. Our findings suggest that in drug-naïve PTSD patients with a history of adulthood trauma, brain structural damage is diffuse, with a particular prevalence for the frontal and occipital lobes, and is clinically relevant.

Transient periodic lateralised epileptiform discharges (PLEDs) following internal carotid artery stenting.

Background. Periodic lateralised epileptiform discharges (PLEDs) are EEG patterns consisting of periodic or pseudoperiodic unilateral, focal or hemispheric epileptiform discharges at a rate of 1-2 Hz. PLEDs may be triggered by acute brain injuries or systemic metabolic changes such as fever, hyperglycaemia or electrolyte imbalance and may result in disturbance of consciousness and/or neurological deficits. Case report. A 58-year-old female with a history of focal epilepsy and deep brain haematoma presented with acute change in awareness, associated with EEG evidence of PLEDs, three days after a left internal carotid artery stenting procedure. Clinical examination, laboratory testing and MRI were unchanged with respect to pre-stenting investigations. Conclusion. In this patient, PLEDs may have been triggered by local haemodynamic changes due to reperfusion after stenting in a previously damaged brain area.

Vif of feline immunodeficiency virus from domestic cats protects against APOBEC3 restriction factors from many felids.

To get more insight into the role of APOBEC3 (A3) cytidine deaminases in the species-specific restriction of feline immunodeficiency virus (FIV) of the domestic cat, we tested the A3 proteins present in big cats (puma, lion, tiger, and lynx). These A3 proteins were analyzed for expression and sensitivity to the Vif protein of FIV. While A3Z3s and A3Z2-Z3s inhibited Deltavif FIV, felid A3Z2s did not show any antiviral activity against Deltavif FIV or wild-type (wt) FIV. All felid A3Z3s and A3Z2-Z3s were sensitive to Vif of the domestic cat FIV. Vif also induced depletion of felid A3Z2s. Tiger A3s showed a moderate degree of resistance against the Vif-mediated counter defense. These findings may imply that the A3 restriction system does not play a major role to prevent domestic cat FIV transmission to other Felidae. In contrast to the sensitive felid A3s, many nonfelid A3s actively restricted wt FIV replication. To test whether Vif(FIV) can protect also the distantly related human immunodeficiency virus type 1 (HIV-1), a chimeric HIV-1.Vif(FIV) was constructed. This HIV-1.Vif(FIV) was replication competent in nonpermissive feline cells expressing human CD4/CCR5 that did not support the replication of wt HIV-1. We conclude that the replication of HIV-1 in some feline cells is inhibited only by feline A3 restriction factors and the absence of the appropriate receptor or coreceptor.

A role for all-trans-retinoic acid in the early steps of lymphatic vasculature development.

The molecular mechanisms that regulate the earliest steps of lymphatic vascular system development are unknown. To identify regulators of lymphatic competence and commitment, we used an in vitro vascular assay with mouse embryonic stem cell-derived embryoid bodies (EBs). We found that incubation with retinoic acid (RA) and, more potently, with RA in combination with cAMP, induced the expression of the lymphatic competence marker LYVE-1 in the vascular structures of the EBs. This effect was dependent on RA receptor (RAR)-α and protein kinase A signaling. RA-cAMP incubation also promoted the development of CD31+/LYVE-1+/Prox1+ cell clusters. In situ studies revealed that RAR-α is expressed by endothelial cells of the cardinal vein in ED 9.5-11.5 mouse embryos. Timed exposure of mouse and Xenopus embryos to excess of RA upregulated LYVE-1 and VEGFR-3 on embryonic veins and increased formation of Prox1-positive lymphatic progenitors. These findings indicate that RA signaling mediates the earliest steps of lymphatic vasculature development.

Physical Activity during COVID-19 Lockdown: Data from An Italian Survey.

The COVID-19 pandemic has forced governments to impose quarantines and lockdowns as containment strategy, raising concerns about mental health and low level of physical activity performed by quarantined populations. In this study, we assess the level of physical activity and psychological wellbeing in a sample of the Italian population during lockdown through an online format of International Physical Activity Questionnaire (IPAQ) and Psychological General Well-Being index-Short version (PGWB-S) . Of 317 adult responders considered, most were female (61.2%), young adults (52.4%), living in little-to-medium size cities (80.1%) and with high-level education (62.8%). Most of our sample performed physical activity mostly during leisure time and domestic activities, and 60.9% were highly active. No interactions were found between physical activity and the demographic characteristics considered. Subjects performing high level of physical activity felt more energetic and vital than those with moderate (p < 0.0001) and low levels (p < 0.0001) of physical activity. Our participants performed enough activity to satisfy the WHO Guidelines, mainly due to domestic activity and activity performed during leisure time, with an overall moderately positive psychological reaction to lockdown.

Adjunctive Perampanel in Older Patients With Epilepsy: A Multicenter Study of Clinical Practice.

BACKGROUND: Clinical data regarding use of newer antiseizure medications (ASMs) in an older population are limited. In randomized-controlled, placebo-controlled trials, older patients are under-represented, and protocols deviate markedly from routine clinical practice, limiting the external validity of results. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Perampanel is a third-generation ASM and the first and only non-competitive alfa-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist. OBJECTIVE: The aim of this study was to assess the effectiveness and tolerability of adjunctive perampanel over a 1-year period in a population of older patients with epilepsy treated in a real-world setting. METHODS: Older (≥ 65 years of age) patients prescribed add-on perampanel at 12 Italian epilepsy centers were retrospectively identified. Seizure occurrence, adverse events (AEs), and drug withdrawal were analyzed. Effectiveness outcomes included the rates of seizure response (≥ 50% reduction in baseline monthly seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes were the rate of treatment discontinuation due to AEs and the incidence of AEs. RESULTS: A total of 92 patients with a median age of 69 (range 65-88) years were included. The median daily dose of perampanel at 12 months was 6 mg (interquartile range 4-6 mg). At 12 months, 53 (57.6%) patients were seizure responders, and 22 (23.9%) patients were seizure free. Twenty (21.7%) patients discontinued perampanel; the reasons for treatment withdrawal were insufficient efficacy (n = 6/20; 30.0%), AEs (n = 12/20; 60.0%), and a combination of both (n = 2/20; 10%). The most common AEs included irritability (8.7%), somnolence (4.3%), and dizziness/vertigo (4.3%). The rate of behavioral and psychiatric AEs was higher in patients with history of psychiatric comorbidities (p = 0.044). There were no differences in the occurrence of behavioral and psychiatric AEs according to the concomitant use of levetiracetam (p = 0.776) and history of cognitive decline (p = 0.332). CONCLUSIONS: Adjunctive perampanel was associated with improvement in seizure control and good tolerability in a real-life setting and can represent a viable therapeutic option in older patients with epilepsy.

Intravenous brivaracetam in status epilepticus: A multicentric retrospective study in Italy.

PURPOSE: to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE). METHODS: a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6 h after BRV administration. RESULTS: 56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100 mg (range 50-300 mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6 h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39-202; p = 0.002). No severe treatment emergent adverse events were observed. CONCLUSION: BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.

Restriction of equine infectious anemia virus by equine APOBEC3 cytidine deaminases.

The mammalian APOBEC3 (A3) proteins comprise a multigene family of cytidine deaminases that act as potent inhibitors of retroviruses and retrotransposons. The A3 locus on the chromosome 28 of the horse genome contains multiple A3 genes: two copies of A3Z1, five copies of A3Z2, and a single copy of A3Z3, indicating a complex evolution of multiple gene duplications. We have cloned and analyzed for expression the different equine A3 genes and examined as well the subcellular distribution of the corresponding proteins. Additionally, we have tested the functional antiretroviral activity of the equine and of several of the human and nonprimate A3 proteins against the Equine infectious anemia virus (EIAV), the Simian immunodeficiency virus (SIV), and the Adeno-associated virus type 2 (AAV-2). Hematopoietic cells of horses express at least five different A3s: A3Z1b, A3Z2a-Z2b, A3Z2c-Z2d, A3Z2e, and A3Z3, whereas circulating macrophages, the natural target of EIAV, express only part of the A3 repertoire. The five A3Z2 tandem copies arose after three consecutive, recent duplication events in the horse lineage, after the split between Equidae and Carnivora. The duplicated genes show different antiviral activities against different viruses: equine A3Z3 and A3Z2c-Z2d are potent inhibitors of EIAV while equine A3Z1b, A3Z2a-Z2b, A3Z2e showed only weak anti-EIAV activity. Equine A3Z1b and A3Z3 restricted AAV and all equine A3s, except A3Z1b, inhibited SIV. We hypothesize that the horse A3 genes are undergoing a process of subfunctionalization in their respective viral specificities, which might provide the evolutionary advantage for keeping five copies of the original gene.

Psychological Impact During the First Outbreak of COVID-19 in Italy.

The first outbreak of COVID-19 in Italy was confirmed on February 21, 2020. Subsequently, COVID-19 turned into a global pandemic, causing a global health emergency, triggering an unprecedented event in the modern era. This study assessed the immediate psychological impact of the COVID-19 epidemic on emotional health and well-being. An ad hoc questionnaire was designed for online completion to expedite data collection during the COVID-19 outbreak. People were invited to participate in the study via social media and email from 4 to 18 March 2020. The entire survey comprised of 21 questions, covering a wide range of factors, such as demographics, disease knowledge, psychological impact, daily life activities, and psychological precautionary measures. The main outcome measure was psychological impact. This was measured based on intensity and prevalence of self-reported feelings of anxiety, fear, sadness, anger, and concern during the epidemic. In total, 10,025 respondents completed the online survey. Of these, about 73% were females, and 100% of the sample possessed good knowledge of the disease. The greatest prevalence of high psychological impact was reported in the <34 years' age group and in north Italy. Additionally, the psychological impact influenced important daily life activities, such as sexuality and nutrition. Our study provides information about the immediate psychological (emotional feelings) responses of Italy's general population to the COVID-19 epidemic. The survey covers several factors that can influence mental health; our results help gauge the psychological burden on the community and offer ways to minimize the impact.

A Modified Holder Pasteurization Method for Donor Human Milk: Preliminary Data.

BACKGROUND: Holder pasteurization (HoP) is the recommended method of pasteurization for donor human milk (DHM). The aim of the present study was to compare nutritional and microbiological impact on DHM of a new technique of pasteurization based on technical changes of HoP. METHODS: We analyzed milk samples from 25 donors. Each sample, derived from one breast milk expression, was subdivided into three aliquots according to pasteurization: The first was not pasteurized, the second pasteurized by HoP, and the third was pasteurized by modified HoP (MHoP). Each aliquot was assessed as to its microbiological and nutritional profile. Nutritional profile included calcium and triglycerides concentrations detected by spectrophotometry and amino acid levels assessed by high-performance liquid chromatography (HPLC). RESULTS: Triglycerides were significantly lower in pasteurized, by both methods, than in not pasteurized aliquots, while calcium and amino acids concentration were similar. Microbiological profile did not differ between HoP and MHoP aliquots. CONCLUSIONS: HoP and MHoP seem to have similar efficacy in preserving some nutritional characteristics of DHM and to confer similar microbiological safety. MHoP is time-saving and potentially costs-effective when compared to HoP, and it is; therefore, potentially of more interest from a practical point of view. Further studies are needed to confirm these findings.

A Cultured Autologous Dermo-epidermal Skin Substitute for Full-Thickness Skin Defects: A Phase I, Open, Prospective Clinical Trial in Children.

BACKGROUND: The management of deep partial-thickness and full-thickness skin defects remains a significant challenge. Particularly with massive defects, the current standard treatment, split-thickness skin grafting, is fraught with donor-site limitations and unsatisfactory long-term outcomes. A novel, autologous, bioengineered skin substitute was developed to address this problem. METHODS: To determine whether this skin substitute could safely provide permanent defect coverage, a phase I clinical trial was performed at the University Children's Hospital Zurich. Ten pediatric patients with acute or elective deep partial- or full-thickness skin defects were included. Skin grafts of 49 cm were bioengineered using autologous keratinocytes and fibroblasts isolated from a patient's small skin biopsy specimen (4 cm), incorporated in a collagen hydrogel. RESULTS: Graft take, epithelialization, infection, adverse events, skin quality, and histology were analyzed. Median graft take at 21 days postoperatively was 78 percent (range, 0 to 100 percent). Healed skin substitutes were stable and skin quality was nearly normal. There were four cases of hematoma leading to partial graft loss. Histology at 3 months revealed a well-stratified epidermis and a dermal compartment comparable to native skin. Mean follow-up duration was 15 months. CONCLUSIONS: In the first clinical application of this novel skin substitute, safe coverage of skin defects was achieved. Safety and efficacy phase II trials comparing the novel skin substitute to split-thickness skin grafts are ongoing. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Patient-specific seizure prediction based on heart rate variability and recurrence quantification analysis.

Epilepsy is often associated with modifications in autonomic nervous system, which usually precede the onset of seizures of several minutes. Thus, there is a great interest in identifying these modifications enough time in advance to prevent a dangerous effect and to intervene. In addition, these changes can be a risk factor for epileptic patients and can increase the possibility of death. Notably autonomic changes associated to seizures are highly depended of seizure type, localization and lateralization. The aim of this study was to develop a patient-specific approach to predict seizures using electrocardiogram (ECG) features. Specifically, from the RR series, both time and frequency variables and features obtained by the recurrence quantification analysis were used. The algorithm was applied in a dataset of 15 patients with 38 different types of seizures. A feature selection step, was used to identify those features that were more significant in discriminating preictal and interictal phases. A preictal interval of 15 minutes was selected. A support vector machine (SVM) classifier was then built to classify preictal and interictal phases. First, a classifier was set up to classify preictal and interictal segments of each patient and an average sensibility of 89.06% was obtained, with a number of false positive per hour (FP/h) of 0.41. Then, in those patients who had at least 3 seizures, a double-cross-validation approach was used to predict unseen seizures on the basis of a training on previous ones. The results were quite variable according to seizure type, achieving the best performance in patients with more stereotypical seizure. The results of the proposed approach show that it is feasible to predict seizure in advance, considering patient-specific, and possible seizure specific, characteristics.