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• Epilepsy is one of the main neurological conditions among children with Wolf-Hirschhorn syndrome. It is mostly associated with frequent and difficult-to-control seizures, due to which long-term developmental outcomes may be impaired. In contrast, the course of epilepsy, when diagnosed efficiently by physicians and appropriate treatment is initiated, can have a good prognosis, with no cognitive deterioration. Therefore, we believe that our systematic review, in which we provide a summary of knowledge about epilepsy in WHS, its characteristics and treatment efficacy, can be a comprehensive source of information for all health care professionals who care for patients with Wolf-Hirschhorn syndrome. Wolf–Hirschhorn syndrome (WHS) is araredisorderwithan estimated prevalence being around 1 in 50,000 births. The syndrome is caused by the deletion of a critical region (Wolf–Hirschhorn Syndrome Critical region- WHSCR) on chromosome 4p16.3. WHS is clinically characterized by pre-and postnatal growth restriction, hypotonia, intellectual disability, craniofacial dysmorphismand congenital fusion anomalies. The clinical aspects are variable due to the deletion size.Consistently, epilepsy is one of the major concerns for parents and professionals caring for children with WHS. Seizures tend to occur in over 90% of patients, with onset within the first 3 years of life, and a peak incidence at around 6–12 months of age. Approximately 20% of patients had the first seizure onset within the first 6 months of age, almost 50% at 6 to 12 months of age and about 25% later than 12 months of age. The main types of epileptic seizures occurring in patients with WHS were generalized tonic–clonic seizures (around 70%). These were followed by tonic spasms (20%); focal seizures with impaired awareness (12%) and clonicseizures in 7% of patients.Seizures are often triggered by fever, followed by infections of various systems. Particularly, half of WHS patients experience status epilepticus in the first years of life, which can be fatal. Due to limited number of reports on the topic of EEG abnormalities in epilepsy among WHS patients, it is difficult to determine whether there are any characteristic deviations for WHS. Although more than 300 persons with WHS have been reported in the literature, there is sparse knowledge about epilepsy and methods of its anti-seizure medication (ASM) management with an assessment of their effectiveness. The purpose of this systematic review is to briefly summarize achievements and advances in the field of epilepsy in Wolf-Hirschhorn syndrome. [ABSTRACT FROM AUTHOR]

Background: Epilepsy has been associated with an increased risk of cardiovascular events. Anti-seizure medication (ASM) may contribute to vascular risk by several mechanisms, including increased homocysteine levels. This study aims to assess the global vascular burden in hyperhomocysteinemic people with epilepsy (PWE) on long-term ASM before and after folic acid supplementation and in subgroups of PWE treated with single enzyme-inducing or single non-enzyme inducing ASM.Methods: One hundred and seventy-four hyperhomocysteinemic (HHcy) PWE who met the inclusion criteria were enrolled. Carotid Doppler ultrasonography, FMD and ultrasound assessment of the brachial artery properties at the baseline and after 90 days of folic acid supplementation were performed. The vascular biomarkers MMP-9 and TIMP-1 were also detected.Results: After folic acid supplementation, in HHcy patients homocysteine levels reduced from 26.8 ± 10.5 to 20.2 ± 5.3 μmol/L, carotid Intima-Media-Thickness reduced from 0.83+0.06 mm to 0.79±0.05 mm, and FMD, distensibility coefficient and β-stiffness improved (p < 0.05). Moreover, MMP-9 and TIMP-1 reduced after supplementation (p < 0.05). PWE treated with a single enzyme-inducing ASM showed an impairment of vascular parameters compared to patients treated with non-enzyme inducing ASM.Conclusions: The results highlight the importance of assessing homocysteine levels and estimating the cardiovascular risk of PWE, preferring non-enzyme inducing ASM in high cardiovascular-risk patients. An adequate correction of homocysteine levels with folate supplementation should be considered to improve the cardiovascular profile. [ABSTRACT FROM AUTHOR]

Background: Sunflower syndrome (SFS) is a rare childhood-onset generalized epilepsy characterized by photosensitivity, heliotropism, and drug-resistant stereotyped seizures maybe self-induced by hand-waving maneuvers. Data on the long-term prognosis are scantly and evidence over best treatment strategies is lacking.Methods: We retrospectively describe the electroclinical features, and therapeutic response in a group of 21 patients with SFS, without intellectual disability.Results: 16 patients were female (67%), with a median age at onset of 7 years. In all patients, ictal episodes began with sun-staring, and hand-waving in front of the sunlight, accompanied by brief typical absence seizures. 17 patients (81%) showed interictal EEG abnormalities, mainly characterized by spike and polyspike-and-wave discharges. Ictal epileptiform activity occurred approximately less than one second after the start of hand-waving. At the last follow-up (median length 8.2 years), 12 patients (57%) were drug-resistant. Nine of them (75%) achieved seizure control with the use of tainted lenses, either alone or compared with anti-seizure medications (ASM). Disappearance of seizures was associated with EEG improvement/normalization when tinted glasses were used during EEG recordings.Conclusion: While the clinical and EEG characteristics of SFS are well defined, the best therapeutic approaches are still under debate. Our data confirms a high rate of drug-resistance and frequent need of polytherapy. Of note, in drug-resistant patients, lenses (but not ASM) were able to suppress PPR in our patients while wearing lenses. Regarding the role of lenses, we do not only rely on the PPR reduction but also clinically by the reduction of seizures. Although additional data are needed, lenses seem to have a powerful potential role for the management of SFS. [ABSTRACT FROM AUTHOR]

Purpose: Triple X syndrome, is an often undiagnosed chromosomal abnormality with an incidence of 1/1000 females. Main associated disorders are urogenital malformations, premature ovarian failure or primary amenorrhea, gastrointestinal problems, psychiatric disorders and epilepsy. To date, triple X is not related to a specific epileptic syndrome. Therefore, the purpose of this clinical series is to analyze seizure semiology, electroencephalogram features and the long-term outcome of 13 patients with epilepsy and triple X syndrome.Methods: We retrospectively evaluated the long-term seizure outcome in patients with triple X syndrome who had been referred to 11 Epilepsy Centers in Italy. A close electroclinical follow-up was made for at least 2 years and outcomes were reported.Results: Our case series confirms that epilepsy is not an occasional finding but part of the phenotypic spectrum of this syndrome. The seizure semiology shows an higher prevalence of focal seizures in 62% of patients. EEG findings of focal epileptic activity were reported in 85% of patients. Anti-seizure medications were successful in all our patients whom in most cases were responsive to monotherapy.Conclusion: According to our case series most successful drugs were VPA and LEV. Long term prognosis of epilepsy in our case series was good. Our experience suggests that all triple X patients achieve good seizure control and in 69% of cases normalization of the EEG. [ABSTRACT FROM AUTHOR]

Purpose: Although international guidelines exist, the clinical heterogeneity of Lennox-Gastaut syndrome (LGS) and the increasing availability of new and repurposed drugs (e.g., fenfluramine and cannabidiol) requires a practical guide to patient management in the clinical context. We report the results of a consensus survey among 42 Italian experts in the diagnosis and treatment of LGS.Methods: The consensus procedure followed a modified Delphi approach. Statements were formulated, based on the most recent published evidence and the clinicians' personal experience, then discussed, and agreed upon by the experts through a two-round voting procedure. Approval of a statement was reached with an average score ≥7.Results: Thirteen statements dealing with three main topics (i.e., clinical diagnosis and prognosis, impact on the Quality of Life (QoL), and treatment strategies) were generated. Six statements achieved a level of agreement sufficient for approval on the first voting round. Following the discussion and a few consequent amendments, most of the statements increased their level of agreement and all 13 were approved.Conclusions: Overall, the statements draw a slightly more benign picture of this rare and severe disease, highlighting the possibility of remission - albeit modest -, an apparent trend towards lower mortality, and the availability of several effective drugs, to which greater accessibility would be hoped for. Valproate remains a major therapeutic option in LGS patients although lamotrigine, rufinamide, topiramate, cannabidiol, and clobazam are popular therapeutic options in Italy, allowing for a tailor-made antiseizure therapy. [ABSTRACT FROM AUTHOR]

Purpose: EEG anomalies and epilepsy are a not so rare clinical manifestation in patients with Phosphatase and tensin homolog (PTEN) variants. The main aim of this study is to analyze the characteristics of EEG traces, neuroimaging findings and epilepsy to better define the neurological aspects in a set of patients with PTEN variants collected in four Italian Centres. As a secondary aim, we describe the neurodevelopmental profile and the psychiatric comorbidities of this cohort.Methods: Patients with PTEN variants, identified by Sanger sequencing or target resequencing, were enrolled. For each subjects, clinical data were retrospectively extracted from medical charts, with a focus on epilepsy and neuroimaging data.Results: 54 patients with PTEN variants were enrolled, with a mean age of 18.8 years. 72.2% have at least one psychiatric diagnosis, being Autism Spectrum Disorder and Intellectual Disability the most frequent diagnosis (29 and 25 cases, respectively). 22 subjects show an abnormal EEG and 8 received a diagnosis of epilepsy, mainly focal epilepsy (7/8), with a mean age at seizure onset of 3.8 years. 3/8 subjects have a drug resistant epilepsy, independently from the underlying neuroimaging pattern. The finding of a Focal cortical dysplasia is significantly associated with both an abnormal EEG (p = 0.02) and the occurrence of seizures (p = 0.002).Conclusion: EEG should be taken into consideration in the first-line diagnostic flowchart of subjects with PTEN variants. The onset of a focal epilepsy, independently from its response to antiepileptic drugs, highly recommends to carry out a neuroimaging exam. [ABSTRACT FROM AUTHOR]

A growing appreciation that the intestinal microbiota might exert changes on the central nervous system via the gut-brain has emerged as a new research frontier in neurological disorders. Moreover, new approaches for studying and manipulating the gut microbiome, including metabolomics and faecal microbiota transplantation, have highlighted the tremendous potential that microbes have on neuroinflammation, metabolic, and neuroendocrine signaling pathways. Despite the large proliferation of studies in animal models examining the linkage between microbial disequilibrium and epilepsy, intestinal profiles at a functional level in humans have remained scarce. We reviewed the scientific evidence on gut microbiota's role in epilepsy, both in clinical and experimental studies, to better understand how targeting the gut microbiota could serve as a diagnostic or prognostic research tool. Likewise, translating microbial molecular mechanisms to medical settings could fill the gaps related to alternative therapies for patients with epilepsy, mainly in cases with refractory phenotypes. [ABSTRACT FROM AUTHOR]

Familial adult myoclonic epilepsy (FAME), also described with different acronyms (ADCME, BAFME, FEME, FCTE and others), is a high-penetrant autosomal dominant condition featuring cortical hand tremors, myoclonic jerks, and occasional/rare convulsive seizures. Prevalence is unknown since this condition is often under-recognized, but it is estimated to be less than 1/35,000. The disease usually starts in the second decade of life and has been genetically associated with at least 4 different loci (8q24, 2p11.1-q12.2, 5p15.31-p15 and 3q26.32-3q28). Recently, the expansion of non coding TTTTA and TTTCA repeats has been identified as the causative mutation in Japanese families linked to the 8q24. The diagnosis is supported by clinical features and electrophysiological investigations as jerk-locked back averaging, C-reflex, and somatosensory-evoked potential. Photic stimulation, emotional stress, and sleep deprivation may trigger both tonic-clonic and myoclonic seizures. FAME has a slow but progressive clinical course occurring with intellectual disability and worsening of both tremor and myoclonus although with a less severe decline compared to other progressive myoclonic epilepsies. Valproate, levetiracetam, and benzodiazepines are considered the first-line treatments. [ABSTRACT FROM AUTHOR]

Purpose: Gluten-related disorders (GRDs) are a group of immune-mediated diseases often associated to neurologic manifestations. Epilepsies with cerebral calcifications, with or without coeliac disease (CD), are rare neurological disorders characterized by childhood-onset focal seizures, often refractory to antiepileptic drugs. Transglutaminase 6 antibodies (anti-TG6) have been considered a biomarker for gluten-related ataxia and neuropathy, but their prevalence in epilepsies with cerebral calcifications is unknown. The aim of this study is to evaluate anti-TG6 prevalence in patients with epilepsies and cerebral calcifications.Method: this was a cross-sectional study conducted at five Italian epilepsy centres. The following groups were included. Group 1: nine patients with CD, posterior cerebral calcifications and epilepsy (CEC); group 2: nine patients with epilepsy and posterior cerebral calcifications, without CD; group 3: twenty patients with focal epilepsy of unknown etiology; group 4: twenty-two healthy controls (HC). All subjects were tested for serological evidence of anti-TG6 IgA and IgG. Differences among groups were analysed using χ ² test.Results: anti-TG6 were present in 1/9 subjects (11%) of group 1, 2/9 subjects (22%) of group 2, 0/20 subjects in group 3, 3/22 (13.6%) of HC. No significant difference was found among the 4 groups.Conclusions: Anti-TG6 do not seem to be associated to epilepsies with cerebral calcifications. [ABSTRACT FROM AUTHOR]

Progressive Myoclonus Epilepsies (PMEs) are a group of uncommon clinically and genetically heterogeneous disorders characterised by myoclonus, generalized epilepsy, and neurological deterioration, including dementia and ataxia. PMEs may have infancy, childhood, juvenile or adult onset, but usually present in late childhood or adolescence, at variance from epileptic encephalopathies, which start with polymorphic seizures in early infancy. Neurophysiologic recordings are suited to describe faithfully the time course of the shock-like muscle contractions which characterize myoclonus. A combination of positive and negative myoclonus is typical of PMEs. The gene defects for most PMEs (Unverricht-Lundborg disease, Lafora disease, several forms of neuronal ceroid lipofuscinoses, myoclonus epilepsy with ragged-red fibers [MERRF], and type 1 and 2 sialidoses) have been identified. PMEs are uncommon disorders, difficult to diagnose in the absence of extensive experience. Thus, aetiology is undetermined in many patients, despite the advance in molecular medicine. Treatment of PMEs remains essentially symptomaticof seizures and myoclonus, together with palliative, supportive, and rehabilitative measures. The response to therapy may initially be relatively favourable, afterwards however, seizures may become more frequent, and progressive neurologic decline occurs. The prognosis of a PME depends on the specific disease. The history of PMEs revealed that the international collaboration and sharing experience is the right way to proceed. This emerging picture and biological insights will allow us to find ways to provide the patients with meaningful treatment. [ABSTRACT FROM AUTHOR]

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy with a prevalence of 1-2% of all patients with epilepsy. It is characterized by multiple pharmaco-resistant seizure types, including tonic, atypical absences and tonic or atonic drop attacks, and the presence of electroencephalographic abnormalities, such as slow-spike waves and paroxysmal fast rhythms. Intellectual disability, behavioural and psychiatric disorders are common comorbidities; these disturbances have a multi-factorial pathogenesis. The selection of the most appropriate drug must be tailored to each patient and guided by the prevalent seizure type. In this paper available pharmacological options are discussed and for each pharmacological agent, current evidence of efficacy and tolerability is provided. Valproic acid represents one of the first-line options in the treatment of LGS. Anyway, other antiepileptic drugs (AEDs) may be considered and added: lamotrigine, rufinamide, topiramate, clobazam can be efficacious. The use of felbamate must be carefully evaluated because of its adverse events. Perampanel, zonisamide, levetiracetam and fenfluramine have shown to be useful in the treatment of selected patients; nevertheless, the lack of RCTs does not allow to recommend their use in a systematic way. Recently, cannabidiol has provided high evidence of efficacy against LGS seizures; however, these data must be confirmed by long-term extensive studies and by trials comparing different AEDs, one to each other. [ABSTRACT FROM AUTHOR]

Purpose: InvDup(15) syndrome is one of the most common chromosomal abnormalities associated with epilepsy. Here we review the seizure types described in InvDup(15) patients and the main electroclinical, therapeutic, and prognostic aspects of the syndrome.Methods: A literature search of PubMed, MEDLINE, and EMBASE was performed to identify papers examining InvDup(15) syndrome and epilepsy.Results: About 65% of the InvDup(15) patients described in the literature had multiple seizure types with a predominance (40.4%) of tonic-clonic seizures. Age at seizure onset was before 10 years in more than half of them. Patients suffered from a variety of EEG abnormalities, generalized spike activity being the most frequent. Brain MRI was unremarkable in the majority of patients. Treatment was with several anticonvulsant drugs used as mono- or polytherapy. Valproic acid was the most common treatment against generalized seizures and was often effective, although drug resistance was a major concern in a large number of cases. Finally, more than 30% of the children suffered from infantile spasms, and status epilepticus was described in nearly 20% of patients, occasionally resulting in death.Conclusion: Seizures are very common in InvDup(15) patients, who suffer from a variety of seizure types. Information about EEG and brain MRI findings, seizure treatment, and prognosis is often poor. The overall prognosis is fair. Prospective studies of larger samples are needed, to gain further insights into the natural history of InvDup(15) syndrome. [ABSTRACT FROM AUTHOR]

Summary: Purpose:: To delineate the clinical spectrum and patterns of evolution of epilepsy with gelastic seizures related to hypothalamic hamartoma (HH). Patients and methods:: We evaluated patients with HH, observed between 1986 and 2002 for whom at least one ictal video-EEG or EEG recording of gelastic seizures was available. Results:: Six subjects (four male, two female) with sessile HH between 0.8 and 1.7cm in diameter were identified. The onset of gelastic seizures was between 2 months and 20 years. It evolved to secondary generalized epilepsy in one case, and to drug-resistant partial epilepsy in the other five from 2 to 13 years after onset. No patient showed precocious puberty. Severe cognitive impairment developed in the patient with secondary generalized epilepsy, and a mild cognitive defect in two others. Patients with an HH below 1cm did not show neuropsychological or behavioural disturbances. Drug resistance occurred in all cases. Surgical removal of HH markedly improved the clinical evolution in two patients. Conclusions:: Gelastic epilepsy-HH syndrome can differ in severity and evolution. A catastrophic evolution and drug resistance can be reversed by surgical or by gamma-knife ablation of HH. [Copyright &y& Elsevier]

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Seizure 50 (2017) 80-82, http://dx.doi.org/10.1016/j.seizure.2017.06.011. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the various types of epilepsy in subjects with chromosome 18 aberrations in order to define epilepsy and its main clinical, electroclinical and prognostic aspects in chromosome 18 anomalies.Methods: A careful overview of recent works concerning chromosome 18 aberrations and epilepsy has been carried out considering the major groups of chromosomal 18 aberrations, identified using MEDLINE and EMBASE database from 1980 to 2015.Results: Epilepsy seems to be particularly frequent in patients with trisomy or duplication of chromosome 18 with a prevalence of up to 65%. Approximately, over half of the patients develop epilepsy during the first year of life. Epilepsy can be focal or generalized; infantile spasms have also been reported. Brain imagines showed anatomical abnormalities in 38% of patients. Some antiepileptic drugs as valproic acid and carbamazepine were useful for treating seizures although a large majority of patients need polytherapy.Conclusion: Children with chromosomal 18 abnormalities can present different types of epilepsy, more frequently focal seizures in individuals with 18q- deletion syndrome, while both complex partial seizures and generalized tonic-clonic seizures have been described in patients who suffer for trisomy 18. Outcome in term of seizures frequency and duration seems to be variable and epilepsy is drug resistant in half of the children, especially in children with trisomy 18 and generalized epilepsy. [ABSTRACT FROM AUTHOR]

Purpose: When we published the diagnostic criteria for "ictal epileptic headache" in 2012, we deliberately and consciously chose to adopt restrictive criteria that probably underestimate the phenomenon, rather than spread panic among patients and physicians who are reluctant to accept this entity.Methods: Here we discuss four intriguing clinical cases to highlight why we believe, to this day, that it is necessary to follow these restrictive diagnostic criteria.Conclusions: EEG is not recommended as a routine examination for children diagnosed with headache, but it is mandatory and must be carried out promptly in cases of prolonged headache that does not respond to antimigraine drugs, if epilepsy is suspected or has been diagnosed previously. This is not a marginal or irrelevant question because possible isolated, non-motor, ictal manifestations should be taken into account before declaring that an epileptic patient is "seizure free" so as to ensure that any decision taken to suspend anticonvulsant therapy is safe. [ABSTRACT FROM AUTHOR]

Purpose: To assess if absence seizures (ASs) occur in patients with myoclonic epilepsy of infancy (MEI).Methods: A retrospective chart review was conducted in 37 patients with MEI followed at seven different paediatric epilepsy centres in Italy, between 2002 and 2014. To assess the possible occurrence of pure ASs or absences associated with myoclonias, ASs were defined according to the following criteria: (i) a sudden onset and interruption of ongoing activities; (ii) bilateral polyspikes or spike-and-wave (SW) complexes; spike SW complexes at 2-4Hz; (iii) duration of AS: 3-30seconds.Results: Thirty-seven MEI patients (25 boys and 12 girls) were identified. Nine patients (24.3%) had a history of simple FS during the first year of life. Ten patients (27%) had a family history of epilepsy, and six patients (16.2%) had a family history of FS. In 7/37 (18.9%) patients, during the occurrence of MSs, a total of nineteen brief ASs were captured by video-EEG recordings. ASs occurred both during a brief cluster of rhythmic MSs than after single myoclonic jerks. The ictal EEG abnormalities observed in patients with ASs were similar to the ictal EEG patterns associated with only myoclonias. No differences in relation to gender, family history, ictal EEG discharge were found between patients with myoclonic seizures with ASs and myoclonias without ASs.Conclusions: Absence seizures can occur in approximately 20% of MEI patients and the occurrence of ASs, though not essential to formulate the diagnosis, do not automatically exclude the diagnosis of MEI. [ABSTRACT FROM AUTHOR]

Purpose: Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and may be associated with acquired central nervous system lesions or could be genetic. Various susceptibility genes and environmental factors are believed to be involved in the aetiology of TLE, which is considered to be a heterogeneous, polygenic, and complex disorder. Rare point mutations in LGI1, DEPDC5, and RELN as well as some copy number variations (CNVs) have been reported in families with TLE patients.Methods: We perform a genetic analysis by Array-CGH in a patient with dysmorphic features and temporal lobe epilepsy.Results: We report a de novo duplication of the long arm of chromosome 12.Conclusion: We confirm that 12q22-q23.3 is a candidate locus for familial temporal lobe epilepsy with febrile seizures and highlight the role of chromosomal rearrangements in patients with epilepsy and intellectual disability. [ABSTRACT FROM AUTHOR]

Purpose The 22q13.3 deletion syndrome, also known as Phelan–McDermid syndrome, is a rare genetic disorder characterized by hypotonia, severely impaired development of speech and language, autistic-like behaviour, and minor dysmorphic features. Neurologic problems may include seizures of different types, such as febrile, generalized tonic–clonic, focal, and absence seizures. No peculiar EEG features have been associated with 22q13 deletion syndrome to date. In order to verify if a peculiar clinical and EEG pattern is present in 22q13.3 deletion syndrome, we studied six Italian patients with this chromosome abnormality. Method Array CGH analysis was carried out in the six subjects (1 male, 5 females, age range 11–30 years, median 19.5). They underwent a complete general and neurologic examinations. The EEG study consisted of at least one awake and one nap–sleep video-EEG recordings and evaluation of other EEGs performed elsewhere. Results Three subjects suffered from myoclonic or generalized tonic–clonic seizures with a rather benign course; all showed multifocal paroxysmal abnormalities on EEG recording, predominant over the frontal–temporal regions, activated during sleep. Conclusion 22q13.3 deletion syndrome seems to be associated, at least in a subgroup of patients, with a peculiar clinical and EEG pattern, characterized by a childhood epilepsy with a rather benign evolution and with multifocal paroxysmal EEG abnormalities activated by sleep. [ABSTRACT FROM AUTHOR]

Purpose To better define the convulsive status epilepticus (CSE) as a possible manifestation at the onset of Panayiotopoulos syndrome (PS) and to assess its prognostic value in these children. Methods Children with CSE and diagnostic criteria of PS were identified, followed clinically and compared with a group of patients with PS without CSE from 1993 to 2012. Results We identified 37 patients with CSE at the onset of PS. During the same period we identified 72 children with autonomic symptoms of PS without CSE. The first episode of CSE occurred at a mean age of 6.5 years. Generalized clonic seizures were the most common ictal event and one-third of the patients required admission to Intensive Care Units. Interictal EEGs showed occipital spike activity in 31 (83.7%) subjects. Only 14 (37.8%) patients were treated with valproic acid and for two of them (5.40%) it was necessary to administer other drugs. There were no intractable cases. The overall prognosis was excellent. After the first event, 15 subjects (40.54%) experienced at least another typical PS seizure, but all patients were seizure free at the last follow-up. Conclusion CSE is not uncommon in PS and it may occur at the onset of benign childhood epilepsy, without leading to a poor prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Cornelia de Lange (CdLS) syndrome is characterized by multiple congenital anomalies and mental retardation. Epilepsy is a clinical feature found in about 20% of cases, but there are no data about its electroclinical features and long-term outcome. Methods: we describe a clinical series of fourteen Caucasian CdLS paediatric patients who developed epilepsy, with special reference to the long term prognosis. Results: Epilepsy manifested between age 0.6 and 16.3 years. The majority of patients (64.3%) presented with partial seizures and interictal EEGs mainly revealed focal epileptic paroxysms involving temporal and parietal areas. Thirteen of 14 children became seizure-free with treatment. Valproate monotherapy was used in eight patients (57.1%), controlling seizures in seven. Otherwise monotherapy with topiramate, levetiracetam, carbamazepine and oxcarbazepine appeared to be effective in controlling seizures in four cases. At the end of the follow-up (age range, 7.3–24.2 years; follow-up, 8.2±3.9 years), thirteen patients were seizure free (three still in therapy), while in one patient seizures were not controlled. Conclusions: Partial epilepsy is the most common type of epilepsy in CdLS patients. In the majority of cases the prognosis of this epilepsy is favourable and therapy can be withdrawn after few years of complete seizure control. [Copyright &y& Elsevier]

Abstract: Purpose: The case report published in this issue by Wang et al. offers us an opportunity to review previously published “ictal epileptic headache” cases and draw attention to the criteria that have recently been published for this condition, taking into consideration not only the clinical-EEG and physiopathogenetic investigations required to diagnose this condition, but also the therapeutic aspects of the issue. Methods: To this aim we reviewed all well-documented cases that have been reported in the literature. Results: The relationship between headache and seizures is somewhat complicated. Although the nature of this association is not yet fully clear, several plausible explanations have been proposed. Further experimental and clinical investigations are, however, warranted to gain a better understanding of this relationship. Epilepsy and idiopathic headache/migraine share several pathophysiological mechanisms; a better understanding of these mechanisms will allow us to more accurately to assess the “real burden” and prevalence of the “ictal epileptic headache” phenomenon and its therapeutic implications. Conclusions: The development of animal models and molecular studies and, above all, multicenter clinical studies conducted according to the proposed IEH criteria represent the starting point for a definitive international consensus on this intriguing topic. In addition, to improve the recognition of ictal epileptic headache, we should encourage the use of EEG recording in the emergency setting. [Copyright &y& Elsevier]

Abstract: Purpose: This multicenter, prospective study investigates the efficacy and safety of lacosamide adjunctive therapy in pediatric and adult patients with uncontrolled epilepsy. Method: This study was carried out between September 2010 and December 2011 at 16 Italian and 1 German neurologic centers. Lacosamide was added to the baseline therapy at a starting dose of 1mg/kg/day in patients aged <16 years (group A) and 100mg daily in subjects aged 16 and older (group B), and titrated to the target dose, ranging from 3 to 12mg/kg/day or from 100 to 600mg daily, respectively. After completing the titration period, patients entered a 12-month maintenance period and they were followed up at 3, 6 and 12 months. The primary assessment of efficacy was based on the change from baseline in seizure frequency per 28 days and was evaluated at 3, 6 and 12 months as follows: number and proportion of 100% responders, 50% responders, non-responders and worsening patients. Safety evaluation was also performed at 3, 6 and 12 months. Results: A total of 118 patients (59 group A, 59 group B) with uncontrolled generalized and focal epilepsy were enrolled. Patient mean±SD age was 15.9±6.80 years and the age range was 4–38 years. At 3-month evaluation, of 118 treated patients 56 subjects (47.4% group A; 47.4% group B; p =0.8537) experienced at least a 50% reduction in seizure frequency. At 6 and 12-month follow-up, the 50% responders were 57 (52.5% group A; 44.1% group B; p =0.4612) and 51 (47.4% group A; 39% group B; p =0.4573), respectively. Thirty-five subjects (30.5% group A; 28.8% group B; p =1) experienced side effects during the treatment period. The most common adverse events were dyspepsia for group A and dizziness for group B. Conclusion: Lacosamide may be a useful and safe pharmacological treatment option for both pediatric and adult patients with uncontrolled seizures. [Copyright &y& Elsevier]

Abstract: The group of idiopathic epilepsies encompasses numerous syndromes without known organic substrate. Genetic anomalies are thought to be responsible for pathogenesis, with a monogenic or polygenic model of inheritance. Over the last two decades, a number of genetic anomalies and encoded proteins have been related to particular idiopathic epilepsies and epileptic encephalopathies. Most of these mutations involve subunits of neuronal ion channels (e.g. potassium, sodium, and chloride channels), and may result in abnormal neuronal hyperexcitability manifesting with seizures. However non-ion channel proteins may also be affected. Correlations between genotype and phenotype are not easy to establish, since genetic and non-genetic factors are likely to play a role in determining the severity of clinical features. The growing number of discoveries on this topic are improving classification, prognosis and counseling of patients and families with these forms of epilepsy, and may lead to targeted therapeutic approaches in the near future. In this article the authors have reviewed the main genetic discoveries in the field of the monogenic idiopathic epilepsies and epileptic encephalopathies, in order to provide epileptologists with a concise and comprehensive summary of clinical and genetic features of these seizure disorders. [Copyright &y& Elsevier]

Abstract: Basic and clinical neuroscience research findings suggest that cortical spreading depression (CSD) and epileptic foci may facilitate each other; furthermore, the threshold required for the onset of CSD has been suggested to be lower than that required for an epileptic focus. These data may explain the prevalence of epilepsy in migraine populations (ranging from 1% to 17%) and the frequency of migraine in epileptic populations (ranging from 8.4% to 20%). There is currently a considerable amount of confusion regarding this topic in both headache and epilepsy classifications (ICHD-II and ILAE). The ICHD-II includes “migraine-triggered seizure” (coded as “1.5.5”) (so-called “migralepsy”) among the “complications of migraine”, and defines “hemicrania epileptica” (“7.6.1”) as an “ictal headache” (ipsilateral to the ictal EEG discharge) that occurs “synchronously” with a seizure (partial epileptic seizure) recognized by ILAE classification. However, neither “migralepsy” nor “hemicrania epileptica” are terms used in the current ILAE classification. On the basis of data reported in the literature and our recent findings, we suggest that the terms “migraine-triggered seizure” and “migralepsy” be deleted until unequivocal evidence of the existence of these conditions emerges. “Ictal epileptic headache” (IEH) should be used to classify those rare events in which headache represents the sole ictal epileptic manifestation. On the other hand, the term “hemicrania epileptica” should be maintained in the ICHD-II and introduced into the ILAE, and be used to classify all cases in which an “ictal epileptic headache” “coexists” and is associated synchronously or sequentially with other ictal sensory-motor events. [Copyright &y& Elsevier]

Purpose Ion channels are expressed both in the heart and in the brain, being advocated as responsible for sudden unexpected death in epilepsy but few pathogenic mutations have been identified. We aim to identify a novel gen associated with channelopathies and epilepsy in a family. Methods We assessed a family showing epilepsy concomitant with LQTS. Index case showed prolonged QT interval. His father suffers of LQT and epilepsy. We performed a direct sequencing analysis of KCNQ1 , KCNH2 , KCNE1 , KCNE2 and SCN5A genes. Results We identified a non-synonymous heterozygous missense pathogenic mutation (p.L273F) in exon 6 of the KCNQ1 gene. All clinically affected relatives carried the same mutation. Conclusion We report, for a first time, a KCNQ1 mutation in a family suffering of both phenotypes, suggesting that KCNQ1 genetic variations may confer susceptibility for recurrent seizure activity increasing the risk or lead to sudden death. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the efficacy and safety of intravenously administered lacosamide (iv LCM) in post-stroke non convulsive status epilepticus (NCSE) in elderly patients. Methods: We enrolled 16 patients (7 M/9 F; 77±7 years of age) with NCSE. iv LCM was used in all the patients as initial treatment (i.e. patients were directly started on LCM) at a loading dose of 400mg over 30min, followed by a mean maintenance dose of 400mg per day. iv LCM was considered as effective in patients who experience no NCSE for 24h following treatment, as evaluated by EEG recording and clinical observation. Results: LCM was effective in treating NCSE in eight of the sixteen patients in whom epileptic activity disappeared (7/8) or was significantly reduced (1/8) within 45–60min after administration. None of these patients relapsed in the following 24h. No adverse events were observed. A partial anterior circulation syndrome (PACS) was present in 10 patients while a total anterior circulation syndrome (TACS) in six. Conclusions: This pilot study suggests that LCM exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke NCSE in elderly patients. A prospective comparative trial is needed to confirm these preliminary data. [Copyright &y& Elsevier]