Idiopathic focal epilepsies: the "lost tribe".

The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many "treats" for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The term "benign" is often used in connection with the IFEs and is increasingly being challenged. Certainly most of these disorders are not associated with the devastating cognitive and behavioural problems seen with early childhood epileptic encephalopathies, such as West or Dravet syndromes. However, it is clear that specific, and sometimes persistent, neuropsychological deficits in attention, language and literacy accompany many of the IFEs that, when multiplied by the large numbers affected, make up a significant public health problem. Understanding the nature, distribution, evolution, risk and management of these is an important area of current research. A corollary to such questions regarding comorbidities is the role of focal interictal spikes and their enduring impact on cognitive functioning. What explains the paradox that epilepsies characterised by abundant interictal epileptiform abnormalities are often associated with very few clinical seizures? This is an exciting area in both clinical and experimental arenas and will eventually have important implications for clinical management of the whole child, taking into account not just seizures, but also adaptive functioning and quality of life. For several decades, we have accepted an evidence-free approach to using or not using antiepileptic drugs in IFEs. There is huge international variation and only a handful of studies examining neurocognitive outcomes. Clearly, this is a situation ready for an overhaul in practice. Fundamental to understanding treatment is knowledge of aetiology. In recent years, there have been several significant discoveries in IFEs from studies of copy number variation, exome sequencing, and linkage that prompt reconsideration of the "unknown cause" classification and strongly suggest a genetic aetiology. The IFE are strongly age-related, both with regards to age of seizure onset and remission. Does this time window solely relate to a similar age-related gene expression, or are there epigenetic factors involved that might also explain low observed twin concordance? The genetic (and epigenetic) models for different IFEs, their comorbidities, and their similarities to other neurodevelopmental disorders deserve investigation in the coming years. In so doing, we will probably learn much about normal brain functioning. This is because these disorders, perhaps more than any other human brain disease, are disorders of functional brain systems (even though these functional networks may not yet be fully defined). In June 2012, an international group of clinical and basic science researchers met in London under the auspices of the Waterloo Foundation to discuss and debate these issues in relation to IFEs. This Waterloo Foundation Symposium on the Idiopathic Focal Epilepsies: Phenotype to Genotype witnessed presentations that explored the clinical phenomenology, phenotypes and endophenotypes, and genetic approaches to investigation of these disorders. In parallel, the impact of these epilepsies on children and their families was reviewed. The papers in this supplement are based upon these presentations. They represent an updated state-of-the-art thinking on the topics explored. The symposium led to the formation of international working groups under the umbrella of "Luke's Idiopathic Focal Epilepsy Project" to investigate various aspects of the idiopathic focal epilepsies including: semiology and classification, genetics, cognition, sleep, high-frequency oscillations, and parental resources (see www.childhood-epilepsy.org). The next sponsored international workshop, in June 2014, was on randomised controlled trials in IFEs and overnight learning outcome measures.

Epilepsy and anxiety: epidemiology, classification, aetiology, and treatment.

Anxiety in epilepsy has recently become a focus of interest for a number of reasons. Epidemiological studies have established that anxiety disorders are twice as common in patients with epilepsy compared to the general population, while in referral centres their prevalence is even higher. In addition, it has been recently appreciated that anxiety exerts a significant negative impact on the quality of life of patients with epilepsy of any age. With regard to the pathogenesis of anxiety in epilepsy, a number of theories have been put forward including those based on psychodynamics, learning-cognition, and neurobiology. From a clinical point of view, anxiety may occur as a comorbid disorder with epilepsy or be directly linked with epilepsy as a preictal, ictal, postictal or interictal phenomenon. The treatment of anxiety in patients with epilepsy requires a comprehensive, multidisciplinary, clinical assessment. Regarding pharmacological therapies, it should be recognised that some drugs prescribed for anxiety disorders are associated with a high risk of seizures, whereas some antiepileptic drugs possess anxiolytic properties that could be of use in the management of epileptic patients with anxiety. The correct diagnosis and successful treatment of anxiety is expected to have significant benefits for the quality of life of epileptic patients.

Syncope-like epileptic seizures in Panayiotopoulos syndrome.

OBJECTIVE: To describe the clinical features of syncope-like epileptic seizures (SLES) and their frequency in Panayiotopoulos syndrome (PS). METHODS: This was a 6-year prospective study of all children aged 1-15 years referred for an EEG. PS was defined by the occurrence of at least one autonomic seizure (AS) in a neurodevelopmentally normal child and at least one EEG with focal spikes. SLES were defined as self-terminating events of sudden loss of postural tone and unresponsiveness, occurring either concurrently with other ictal autonomic symptoms and signs that characterize PS (AS + SLES) or on their own (pure SLES). RESULTS: PS was diagnosed in 33 of 394 consecutive children with at least one afebrile seizure (8.4%). SLES occurred at least once in 17 of 33 children (51.5%); 12 presented SLES in all their AS, and 5 had also AS without SLES. Overall, 53 of 74 AS manifested with SLES (71.6%); 25 were AS + SLES and 28 were pure SLES. The latter occurred in 7 children suddenly and without premonition or obvious triggers while standing, sitting, lying down, or asleep, did not resolve in the horizontal position, and were not associated with stiffening or any involuntary movements, even when longer than a few minutes. Concurrent autonomic symptoms during AS + SLES included emesis, incontinence, mydriasis, miosis, and cardiorespiratory abnormalities. CONCLUSIONS: SLES is a common ictal manifestation of PS and should be considered in the differential diagnosis of suspected syncope, particularly when clinical signs are atypical for neurocardiogenic syncope and the EEG shows focal spikes.

Benign childhood focal epilepsies: assessment of established and newly recognized syndromes.

A big advance in epileptology has been the recognition of syndromes with distinct aetiology, clinical and EEG features, treatment and prognosis. A prime and common example of this is rolandic epilepsy that is well known by the general paediatricians for over 50 years, thus allowing a precise diagnosis that predicts an excellent prognosis. However, rolandic is not the only benign childhood epileptic syndrome. Converging evidence from multiple and independent clinical, EEG and magnetoencephalographic studies has documented Panayiotopoulos syndrome (PS) as a model of childhood autonomic epilepsy, which is also common and benign. Despite high prevalence, lengthy and dramatic features, PS as well as autonomic status epilepticus had eluded recognition because emetic and other ictal autonomic manifestations were dismissed as non-epileptic events of other diseases. Furthermore, PS because of frequent EEG occipital spikes has been erroneously considered as occipital epilepsy and thus confused with the idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), which is another age-related but rarer and of unpredictable prognosis syndrome. Encephalitis is a common misdiagnosis for PS and migraine with visual aura for ICOE-G. Pathophysiologically, the symptomatogenic zone appears to correspond to the epileptogenic zone in rolandic epilepsy (sensory-motor symptomatology of the rolandic cortex) and the ICOE-G (occipital lobe symptomatology), while the autonomic clinical manifestations of PS are likely to be generated by variable and widely spread epileptogenic foci acting upon a temporarily hyperexcitable central autonomic network. Rolandic epilepsy, PS, ICOE-G and other possible clinical phenotypes of benign childhood focal seizures are likely to be linked together by a genetically determined, functional derangement of the systemic brain maturation that is age related (benign childhood seizure susceptibility syndrome). This is usually mild but exceptionally it may diverge to serious epileptic disorders such as epileptic encephalopathy with continuous spike and wave during sleep. Links with other benign and age-related seizures in early life such as febrile seizures, benign focal neonatal and infantile seizures is possible. Overlap with idiopathic generalized epilepsies is limited and of uncertain genetic significance. Taking all these into account, benign childhood focal seizures and related epileptic syndromes would need proper multi-disciplinary re-assessment in an evidence-based manner.