The "plus" side of epilepsy phenotyping

No abstract available

Ictal epileptic headache. an old story with courses and appeals

The term "ictal epileptic headache" has been recently proposed to classify the clinical picture in which headache is the isolated ictal symptom of a seizure. There is emerging evidence from both basic and clinical neurosciences that cortical spreading depression and an epileptic focus may facilitate each other, although with a different degree of efficiency. This review address the long history which lead to the 'migralepsy' concept to the new emerging pathophysiological aspects, and clinical and electroencephalography evidences of ictal epileptic headache. Here, we review and discuss the common physiopathology mechanisms and the historical aspects underlying the link between headache and epilepsy. Either experimental or clinical measures are required to better understand this latter relationship: the development of animal models, molecular studies defining more precise genotype/phenotype correlations as well as multicenter clinical studies with revision of clinical criteria for headache-/epilepsy-related disorders represent the start of future research. Therefore, the definition of ictal epileptic headache should be used to classify the rare events in which headache is the only manifestation of a seizure. Finally, using our recently published criteria, we will be able to clarify if ictal epileptic headache represents an underestimated phenomenon or not

Dual operative radar for vehicle to vehicle and vehicle to infrastructure communication

The research presented in this Thesis deals with the concepts of joint radar and communication system for automotive application. The novel systems developed include a joint radar and communication system based on the fractional Fourier transform (FrFT) and two interference mitigation frameworks. In the joint radar and communication system the FrFT is used to embed the data information into a radar waveform in order to obtain a signal sharing Linear Frequency Modulation (LFM) characteristics while allowing data transmission. Furthermore, in the proposed system multi user operations are allowed by assigning a specific order of the FrFT to each user. In this way, a fractional order division multiplexing can be implemented allowing the allocation of more than one user in the same frequency band with the advantage that the range resolution does not depend on the number of the users that share the same frequency band but only from the assigned of the FrFT. Remarkably, the predicted simulated radar performance of the proposed joint radar and communication system when using Binary Frequency Shift Keying (BFSK) encoding is not significantly affected by the transmitted data. In order to fully describe the proposed waveform design, the signal model when the bits of information are modulated using either BFSK or Binary Phase Shift Keying (BPSK) encoding is derived. This signal model will result also useful in the interference mitigation frameworks. In multi user scenarios to prevent mutual radar interference caused by users that share the same frequency band at the same time, each user has to transmit waveforms that are uncorrelated with those of other users. However, due to spectrum limitations, the uncorrelated property cannot always be satisfied even by using fractional order division multiplexing, thus interference is unavoidable. In order to mitigate the interference, two frameworks are introduced. In a joint radar communication system, the radar also has access to the communication data. With a near-precision reconstruction of the communication signal, this interference can be subtracted. In these two frameworks the interfering signal can be reconstructed using the derived mathematical model of the proposed FrFT waveform. In the first framework the subtraction between the received and reconstructed interference signals is carried out in a coherent manner, where the amplitude and phase of the two signals are taken into account. The performance of this framework is highly depend on the correct estimation of the Doppler frequency of the interfering user. A small error on the Doppler frequency can lead to a lack of synchronization between the received and reconstructed signal. Consequently, the subtraction will not be performed in a correct way and further interference components can be introduced. In order to solve the problem of the lack of the synchronization an alternative framework is developed where the subtraction is carried out in non-coherent manner. In the proposed framework, the subtraction is carried out after that the received radar signal and the reconstructed interference are processed, respectively. The performance is tested on simulated and real signals. The simulated and experimental results show that this framework is capable of mitigating the interference from other users successfully.The research presented in this Thesis deals with the concepts of joint radar and communication system for automotive application. The novel systems developed include a joint radar and communication system based on the fractional Fourier transform (FrFT) and two interference mitigation frameworks. In the joint radar and communication system the FrFT is used to embed the data information into a radar waveform in order to obtain a signal sharing Linear Frequency Modulation (LFM) characteristics while allowing data transmission. Furthermore, in the proposed system multi user operations are allowed by assigning a specific order of the FrFT to each user. In this way, a fractional order division multiplexing can be implemented allowing the allocation of more than one user in the same frequency band with the advantage that the range resolution does not depend on the number of the users that share the same frequency band but only from the assigned of the FrFT. Remarkably, the predicted simulated radar performance of the proposed joint radar and communication system when using Binary Frequency Shift Keying (BFSK) encoding is not significantly affected by the transmitted data. In order to fully describe the proposed waveform design, the signal model when the bits of information are modulated using either BFSK or Binary Phase Shift Keying (BPSK) encoding is derived. This signal model will result also useful in the interference mitigation frameworks. In multi user scenarios to prevent mutual radar interference caused by users that share the same frequency band at the same time, each user has to transmit waveforms that are uncorrelated with those of other users. However, due to spectrum limitations, the uncorrelated property cannot always be satisfied even by using fractional order division multiplexing, thus interference is unavoidable. In order to mitigate the interference, two frameworks are introduced. In a joint radar communication system, the radar also has access to the communication data. With a near-precision reconstruction of the communication signal, this interference can be subtracted. In these two frameworks the interfering signal can be reconstructed using the derived mathematical model of the proposed FrFT waveform. In the first framework the subtraction between the received and reconstructed interference signals is carried out in a coherent manner, where the amplitude and phase of the two signals are taken into account. The performance of this framework is highly depend on the correct estimation of the Doppler frequency of the interfering user. A small error on the Doppler frequency can lead to a lack of synchronization between the received and reconstructed signal. Consequently, the subtraction will not be performed in a correct way and further interference components can be introduced. In order to solve the problem of the lack of the synchronization an alternative framework is developed where the subtraction is carried out in non-coherent manner. In the proposed framework, the subtraction is carried out after that the received radar signal and the reconstructed interference are processed, respectively. The performance is tested on simulated and real signals. The simulated and experimental results show that this framework is capable of mitigating the interference from other users successfully

Treatment of Adults with Lennox-Gastaut Syndrome: Further Analysis of Efficacy and Safety/Tolerability of Rufinamide

Management of Lennox-Gastaut syndrome (LGS) in adulthood can be particularly challenging. Published reports describing the use of rufinamide specifically in adult patients with LGS are scarce. A post hoc subgroup analysis of data from a phase III trial was conducted to investigate the efficacy and safety/tolerability of rufinamide in adults with LGS

Comorbidities in Dravet Syndrome and Lennox–Gastaut Syndrome

AbstractThis study aims to describe the main cognitive and behavioral comorbidities of Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS), their impact on the health-related quality of life (QOL) of patients and their caregivers, and provide a summary of the neuropsychological tools available for the evaluation of these comorbidities. The cognitive and behavioral comorbidities in patients with DS and LGS have a profound effect on the QOL of affected individuals and their caregivers and, as patients grow, tend to surpass the impact of the seizures. DS is a genetic condition associated with loss-of-function mutations in the SCNA1 sodium channel gene; LGS is an etiologically heterogeneous condition that is often secondary to structural brain abnormalities. The first seizures associated with DS typically present in the first year of life, and developmental delay becomes progressively evident thereafter. LGS usually starts between the ages of 3 and 8 years, with cognitive impairment becoming clinically evident in most patients within 5 years from the onset. In both DS and LGS, cognitive impairment is generally moderate to severe and is often accompanied by behavioral problems such as hyperactivity and inattention. In addition to optimal seizure control, regular assessment and active management of cognitive and behavioral comorbidities are required to meet the complex needs of patients with DS or LGS

The brain–heart interaction in epilepsy: implications fordiagnosis, therapy, and SUDEP prevention

Epilèpsia; Malalties cardiaques; Mort sobtadaEpilepsia; Enfermedades cardiacas; Muerte súbitaEpilepsy; Heart disease; Sudden deathThe influence of the central nervous system and autonomic system on cardiac activity is being intensively studied, as it contributes to the high rate of cardiologic comorbidities observed in people with epilepsy. Indeed, neuroanatomic connections between the brain and the heart provide links that allow cardiac arrhythmias to occur in response to brain activation, have been shown to produce arrhythmia both experimentally and clinically. Moreover, seizures may induce a variety of transient cardiac effects, which include changes in heart rate, heart rate variability, arrhythmias, asystole, and other ECG abnormalities, and can trigger the development of Takotsubo syndrome. People with epilepsy are at a higher risk of death than the general population, and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Although the cause of SUDEP is still unknown, cardiac abnormalities during and between seizures could play a significant role in its pathogenesis, as highlighted by studies on animal models of SUDEP and registration of SUDEP events. Recently, genetic mutations in genes co-expressed in the heart and brain, which may result in epilepsy and cardiac comorbidity/increased risk for SUDEP, have been described. Recognition and a better understanding of brain-heart interactions, together with new advances in sequencing techniques, may provide new insights into future novel therapies and help in the prevention of cardiac dysfunction and sudden death in epileptic individuals

Interference mitigation for a joint radar communication system based on the FrFT for automotive applications

In multi user scenarios to prevent interference between users that share the same bandwidth at the same time,each user has to transmit wave forms that are uncorrelated with those of other users. However, due to spectrum limitations, the uncorrelated property cannot always be satisfied meaning that interference is unavoidable. In order to alleviate the interference, a framework for interference mitigation is presented. The performance of the proposed framework is tested on simulated and real signals. The real signal is acquired in a controlled laboratory environment using a Software Defined Radio (SDR). The simulated and experimental results show that the proposed framework is capable of mitigating the interference from other users

Improving Therapy of Pharmacoresistant Epilepsies: The Role of Fenfluramine

Epilepsy is among the most common neurological chronic disorders, with a prevalence of 0.5–1%. Despite the introduction of new antiepileptic drugs during recent years, about one third of the epileptic population remain drug-resistant. Hence, especially in the pediatric population limited by different pharmacokinetics and pharmacodynamics and by ethical and regulatory issues it is needed to identify new therapeutic resources. New molecules initially used with other therapeutic indications, such as fenfluramine, are being considered for the treatment of pharmacoresistant epilepsies, including Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). Drug-refractory seizures are a hallmark of both these conditions and their treatment remains a major challenge. Fenfluramine is an amphetamine derivative that was previously approved as a weight loss drug and later withdrawn when major cardiac adverse events were reported. However, a new role of fenfluramine has emerged in recent years. Indeed, fenfluramine has proved to be a promising antiepileptic drug with a favorable risk–benefit profile for the treatment of DS, LGS and possibly other drug-resistant epileptic syndromes. The mechanism by which fenfluramine provide an antiepileptic action is not fully understood but it seems to go beyond its pro-serotoninergic activity. This review aims to provide a comprehensive analysis of the literature, including ongoing trials, regarding the efficacy and safety of fenfluramine as adjunctive treatment of pharmacoresistant epilepsies

The Pharmacoresistant Epilepsy: An Overview on Existant and New Emerging Therapies

Epilepsy is one of the most common neurological chronic disorders, with an estimated prevalence of 0. 5 – 1%. Currently, treatment options for epilepsy are predominantly based on the administration of symptomatic therapy. Most patients are able to achieve seizure freedom by the first two appropriate drug trials. Thus, patients who cannot reach a satisfactory response after that are defined as pharmacoresistant. However, despite the availability of more than 20 antiseizure medications (ASMs), about one-third of epilepsies remain drug-resistant. The heterogeneity of seizures and epilepsies, the coexistence of comorbidities, and the broad spectrum of efficacy, safety, and tolerability related to the ASMs, make the management of these patients actually challenging. In this review, we analyze the most relevant clinical and pathogenetic issues related to drug-resistant epilepsy, and then we discuss the current evidence about the use of available ASMs and the alternative non-pharmacological approaches

Expert Opinion On The Management Of Lennox-gastaut Syndrome: Treatment Algorithms And Practical Consideration

Lennox-Gastaut syndrome (LGS) is a severe epileptic and developmental encephalopathy that is associated with a high rate of morbidity and mortality. It is characterized by multiple seizure types, abnormal electroencephalographic features, and intellectual disability. Although intellectual disability and associated behavioral problems are characteristic of LGS, they are not necessarily present at its outset and are therefore not part of its diagnostic criteria. LGS is typically treated with a variety of pharmacological and non-pharmacological therapies, often in combination. Management and treatment decisions can be challenging, due to the multiple seizure types and comorbidities associated with the condition. A panel of five epileptologists met to discuss consensus recommendations for LGS management, based on the latest available evidence from literature review and clinical experience. Treatment algorithms were formulated. Current evidence favors the continued use of sodium valproate (VPA) as the first-line treatment for patients with newly diagnosed de novo LGS. If VPA is ineffective alone, evidence supports lamotrigine, or subsequently rufinamide, as adjunctive therapy. If seizure control remains inadequate, the choice of next adjunctive antiepileptic drug (AED) should be discussed with the patient/parent/caregiver/clinical team, as current evidence is limited. Non-pharmacological therapies, including resective surgery, the ketogenic diet, vagus nerve stimulation, and callosotomy, should be considered for use alongside AED therapy from the outset of treatment. For patients with LGS that has evolved from another type of epilepsy who are already being treated with an AED other than VPA, VPA therapy should be considered if not trialed previously. Thereafter, the approach for a de novo patient should be followed. Where possible, no more than two AEDs should be used concomitantly. Patients with established LGS should undergo review by a neurologist specialized in epilepsy on at least an annual basis, including a thorough reassessment of their diagnosis and treatment plan. Clinicians should always be vigilant to the possibility of treatable etiologies and alert to the possibility that a patient's diagnosis may change, since the seizure types and electroencephalographic features that characterize LGS evolve over time. To date, available treatments are unlikely to lead to seizure remission in the majority of patients and therefore the primary focus of treatment should always be optimization of learning, behavioral management, and overall quality of life