Publications by authors named "Nicola Pietrafusa"

34 Publications

New paradigms for the treatment of pediatric monogenic epilepsies: Progressing toward precision medicine.

Epilepsy Behav 2021 Apr 15:107961. Epub 2021 Apr 15.

UCL NIHR BRC Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.

Despite the availability of 28 antiseizure medications (ASMs), one-third of people with epilepsy fail to achieve sustained freedom from seizures. Clinical outcome is even poorer for children with developmental and epileptic encephalopathies (DEEs), many of which are due to single-gene mutations. Discovery of causative genes, however, has paved the way to understanding the molecular mechanism underlying these epilepsies, and to the rational application, or development, of precision treatments aimed at correcting the specific functional defects or their consequences. This article provides an overview of current progress toward precision medicine (PM) in the management of monogenic pediatric epilepsies, by focusing on four different scenarios, namely (a) rational selection of ASMs targeting specifically the underlying pathogenetic mechanisms; (b) development of targeted therapies based on novel molecules; (c) use of dietary treatments or food constituents aimed at correcting specific metabolic defects; and (d) repurposing of medications originally approved for other indications. This article is part of the Special Issue "Severe Infantile Epilepsies".
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http://dx.doi.org/10.1016/j.yebeh.2021.107961DOI Listing
April 2021

Juvenile myoclonic epilepsy: Long-term prognosis and risk factors.

Brain Dev 2021 Jun 27;43(6):688-697. Epub 2021 Mar 27.

Department of Neurological Sciences, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network on Rare and Complex Epilepsies EpiCARE, Rome, Italy. Electronic address:

Objective: Our goal was to investigate the long-term clinical course of juvenile myoclonic epilepsy (JME) in a cohort of patients and to identify prognostic factors for refractoriness and seizure relapse after anti-seizure medications (ASMs) withdrawal. A literature review is also presented to consolidate and compare our findings with the previously reported cases.

Methods: We retrospectively studied a series of patients diagnosed with JME with 15 years or more of evolution. We collected clinical, neurophysiological and neuroimaging data from patients who met defined inclusion and exclusion criteria.

Results: Study involved 61 patients (65.5% female) with mean age at study of 37.6 years, and mean age at its outset of 14.8 years. Median follow-up was 31.0 years (mean 28.9, range 15-53). They presented more frequently with a combination of myoclonic and generalized tonic-clonic seizures (GTCS) (65.6%). Sixty-five percent of patients (n = 40) had a 5-year terminal remission with a mean age at last seizure of 27.4 years. Thirty-two percent of seizure-free patients (n = 13) withdrew ASMs: 6 out of 13 had a recurrence of the seizures while 7 remained seizure-free (mean age at ASMs withdrawal 21.0 versus 35.7 years, p < 0.05). In the multivariate model, a high GTCS frequency at onset (p = 0.026) was a prognostic factor of drug resistance.

Conclusion: JME is often regarded as a benign epileptic syndrome, although a quarter of the individuals have refractory epilepsy. The possibility of withdrawing ASMs in patients who have been free of seizures over an extended time seems feasible.
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http://dx.doi.org/10.1016/j.braindev.2021.02.005DOI Listing
June 2021

Deciphering the premature mortality in PIGA-CDG - An untold story.

Epilepsy Res 2021 Feb 9;170:106530. Epub 2020 Dec 9.

Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark; Department for Regional Health Services, University of Southern Denmark, Odense, Denmark.

Objective: Congenital disorder of glycosylation (CDG) due to a defective phosphatidylinositol glycan anchor biosynthesis class A protein (PIGA) is a severe X-linked developmental and epileptic encephalopathy. Seizures are often treatment refractory, and patients have intellectual disability and global developmental delay. Previous reports have suggested that patients with PIGA-CDG have a high risk of premature mortality. This study aimed to evaluate the observed high mortality and the causes of death in PIGA-CDG patients.

Methods: We reviewed the literature and collected additional unpublished patients through an international network.

Results: In total, we reviewed the data of 88 patients of whom 30 patients born alive were deceased, and the overall mortality before the age of 20 years was 30 % (26/88). Age at death ranged from 15 days to 48 years of life. The median age at death was two years and more than half of the patients deceased in early childhood. The PIGA-specific mortality rate/1000 person-years was 44.9/1000 person-years (95 %, CI 31.4-64.3). There were no cases of definite or probable sudden unexpected death in epilepsy (SUDEP) and half of the patients died due to respiratory failure (15/30, 50 %) or possible SUDEP (3/30, 10 %). Three patients (10 %) died from severe cardiomyopathy, liver failure and gastrointestinal bleeding, respectively. The cause of death was unclassified in nine patients (30 %). Autopsies were rarely performed and the true cause of death remains unknown for the majority of patients.

Significance: Our data indicate an increased risk of premature death in patients with PIGA-CDG when compared to most monogenic developmental and epileptic encephalopathies.
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http://dx.doi.org/10.1016/j.eplepsyres.2020.106530DOI Listing
February 2021

Impact of COVID-19 pandemic on pediatric patients with epilepsy - The caregiver perspective.

Epilepsy Behav 2020 12 24;113:107527. Epub 2020 Nov 24.

Department of Neurological Sciences, Bambino Gesù Children's Hospital IRCCS, Full Member of European Reference Network EpiCARE Rome, Italy.

The recent COVID-19 pandemic has disrupted care systems around the world. We assessed how the COVID-19 pandemic affected children with epilepsy in Italy, where lockdown measures were applied from March 8 to May 4, 2020. We compiled an Italian-language online survey on changes to healthcare and views on telehealth. Invitations were sent to 6631 contacts of all patients diagnosed with epilepsy within the last 5 years at the BambinoGesù Children's Hospital in Rome. Of the 3321 responses received, 55.6% of patients were seizure-free for at least 1 year before the COVID-19-related lockdown, 74.4% used anti-seizure medications (ASMs), and 59.7% had intellectual disability. Only 10 patients (0.4%) became infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Seizure frequency remained stable for most patients during the lockdown period (increased in 13.2%; decreased in 20.3%), and seizure duration, use of rescue medications, and adherence to treatment were unchanged. Comorbidities were more affected (behavioral problems worsened in 35.8%; sleep disorder worsened in 17.0%). Visits were canceled/postponed for 41.0%, but 25.1% had remote consultation during the lockdown period (93.9% were satisfied). Most responders (67.2%) considered continued remote consultations advantageous. Our responses support that patients/caregivers are willing to embrace telemedicine for some scenarios.
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http://dx.doi.org/10.1016/j.yebeh.2020.107527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683298PMC
December 2020

Neuronal Ceroid Lipofuscinosis: Potential for Targeted Therapy.

Drugs 2021 Jan;81(1):101-123

Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE, Rome, Italy.

Neuronal ceroid lipofuscinosis (NCLs) is a group of inherited neurodegenerative lysosomal storage diseases that together represent the most common cause of dementia in children. Phenotypically, patients have visual impairment, cognitive and motor decline, epilepsy, and premature death. A primary challenge is to halt and/or reverse these diseases, towards which developments in potential effective therapies are encouraging. Many treatments, including enzyme replacement therapy (for CLN1 and CLN2 diseases), stem-cell therapy (for CLN1, CLN2, and CLN8 diseases), gene therapy vector (for CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN10, and CLN11 diseases), and pharmacological drugs (for CLN1, CLN2, CLN3, and CLN6 diseases) have been evaluated for safety and efficacy in pre-clinical and clinical studies. Currently, cerliponase alpha for CLN2 disease is the only approved therapy for NCL. Lacking is any study of potential treatments for CLN4, CLN9, CLN12, CLN13 or CLN14 diseases. This review provides an overview of genetics for each CLN disease, and we discuss the current understanding from pre-clinical and clinical study of potential therapeutics. Various therapeutic interventions have been studied in many experimental animal models. Combination of treatments may be useful to slow or even halt disease progression; however, few therapies are unlikely to even partially reverse the disease and a complete reversal is currently improbable. Early diagnosis to allow initiation of therapy, when indicated, during asymptomatic stages is more important than ever.
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http://dx.doi.org/10.1007/s40265-020-01440-7DOI Listing
January 2021

Cannabidiol Treatment for Refractory Epilepsies in Pediatrics.

Front Pharmacol 2020 29;11:586110. Epub 2020 Sep 29.

Child Neurology, Chair of Pediatrics, NESMOS Department, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy.

Cannabis extracts in oil are becoming increasingly available, and, during the last years, there has been growing public and scientific interest about therapeutic properties of these compounds for the treatment of several neurologic diseases, not just epilepsy. The discovered role of the endocannabinoid system in epileptogenesis has provided the basis to investigate the pharmacological use of exogenously produced cannabinoids, to treat epilepsy. Although, physicians show reluctance to recommend Cannabis extracts given the lack of high-quality safety available data, from literature data cannabidiol (CBD) results to be a promising and safe anticonvulsant drug with low side-effect. In particular, according to early studies, CBD can reduce the frequency of seizures and lead to improvements in quality of life in children affected by refractory epilepsy. So, for these reasons, the detailed study of the interactions between CBD and anticonvulsant drugs (AEDs) administered simultaneously in polytherapy, is arousing increasing interest, to clarify and to assess the incidence of adverse effects and the relation between dose escalation and quality of life measures. To date, in pediatric age, CBD efficacy and safety is not supported by well-designed trials and strong scientific evidence are not available. These studies are either retrospective or small-scale observational and only during the last years Class I evidence data for a pure form of CBD have been available, as demonstrated in placebo-controlled RCTs for patients affected by Lennox-Gastaut syndrome and Dravet syndrome. It is necessary to investigate CBD safety, pharmacokinetics and interaction with other AEDs alongside performing double-blinded placebo-controlled trials to obtain conclusive data on its efficacy and safety in the most frequent epilepsies in children, not just in the epileptic encephalopathy. This review was aimed to revise the available data to describe the scientific evidence for CBD in Pediatric Epilepsies.
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http://dx.doi.org/10.3389/fphar.2020.586110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550750PMC
September 2020

POLG1-Related Epilepsy: Review of Diagnostic and Therapeutic Findings.

Brain Sci 2020 Oct 23;10(11). Epub 2020 Oct 23.

Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Full Member of European Reference Network EpiCARE, 00165 Rome, Italy.

Background: The clinical spectrum associated with gene mutations ranges from non-syndromic epilepsy or mild isolated neurological signs to neurodegenerative disorders. Our aim was to review diagnostic findings, therapeutic approaches and outcomes of reported cases of epilepsy related to mutation.

Methods: The articles for review were identified through a systematic research on PubMed and EMBASE databases from January 2003 to April 2020, searching for the terms "Epilepsy AND OR polymerase gamma," OR "".

Results: Forty-eight articles were selected for review, which included 195 patients. Two main peaks of age at epilepsy onset were found: at ages 1 and 13 years. The most frequent seizure type was myoclonic. The occurrence of Status Epilepticus was reported in 46.4% of cases. Epileptiform and slow abnormalities were most frequently seen over occipital regions. Brain Magnetic Resonance Imaging (MRI) revealed increased T2 signal intensities in thalamic regions. Genetic analysis revealed a prevalence of A467T, W748S and G848S (74.2% of patients) mutations. Survival at 5 years was estimated at very low levels (30.2% of patients).

Conclusion: In this review, we included cases with both pediatric and adult epilepsy onset. The analysis of data regarding prognosis showed that survival is related to age at onset of epilepsy.
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http://dx.doi.org/10.3390/brainsci10110768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690674PMC
October 2020

Early Onset Epilepsy Caused by Low-Grade Epilepsy-Associated Tumors and Focal Meningeal Involvement.

Brain Sci 2020 Oct 18;10(10). Epub 2020 Oct 18.

Rare and Complex Epilepsies, Department of Neurological Science, Bambino Gesù Children's Hospital, IRCCS, Member of European Reference Network EpiCARE, 00165 Rome, Italy.

: Low-grade epilepsy-associated neuroepithelial tumors (LEATs) are a frequent etiology in pediatric patients with epilepsy undergoing surgery. : To identify differences in clinical and post-surgical follow-up between patients with focal meningeal involvement (MI) and those without MI within our cohort of pediatric patients with LEATs. : We retrospectively reviewed all pediatric patients (<18 y) who underwent epilepsy surgery between 2011 and 2017 at our hospital. Cohort inclusion required histological diagnosis of LEATs and post-surgical follow-up of ≥2 y. We subsequently stratified patients according to presence of neuroradiological MI. : We identified 37 patients: five with MI and 32 without. Half of patients (19) were drug sensitive at surgery; similar between groups. The group with MI differed mainly for age of epilepsy-onset (0.6 vs. 7.0 y) but not for epilepsy duration (0.9 vs. 1.5 y). Post-surgery radiological follow-up (median 4.0 y; IQR 2.8-5.0 y) did not indicate disease progression. Seizure outcome was excellent in both groups, with 34 patients overall being both drug- and seizure-free. : Our study identified a new subgroup of LEATs with focal MI and excellent post-surgical outcome. Moreover, this highlights the effectiveness of early surgery in pediatric LEATs.
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http://dx.doi.org/10.3390/brainsci10100752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603244PMC
October 2020

Efficacy and safety of Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: A real-world study.

Epilepsia 2020 11 18;61(11):2405-2414. Epub 2020 Sep 18.

Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona, Verona, Italy.

Objective: Dravet syndrome (DS) is a drug-resistant, infantile onset epilepsy syndrome with multiple seizure types and developmental delay. In recently published randomized controlled trials, fenfluramine (FFA) proved to be safe and effective in DS.

Methods: DS patients were treated with FFA in the Zogenix Early Access Program at four Italian pediatric epilepsy centers. FFA was administered as add-on, twice daily at an initial dose of 0.2 mg/kg/d up to 0.7 mg/kg/d. Seizures were recorded in a diary. Adverse events and cardiac safety (with Doppler echocardiography) were investigated every 3 to 6 months.

Results: Fifty-two patients were enrolled, with a median age of 8.6 years (interquartile range [IQR] = 4.1-13.9). Forty-five (86.5%) patients completed the efficacy analysis. The median follow-up was 9.0 months (IQR = 3.2-9.5). At last follow-up visit, there was a 77.4% median reduction in convulsive seizures. Thirty-two patients (71.1%) had a ≥50% reduction of convulsive seizures, 24 (53.3%) had a ≥75% reduction, and five (11.1%) were seizure-free. The most common adverse event was decreased appetite (n = 7, 13.4%). No echocardiographic signs of cardiac valvulopathy or pulmonary hypertension were observed. There was no correlation between type of genetic variants and response to FFA.

Significance: In this real-world study, FFA provided a clinically meaningful reduction in convulsive seizure frequency in the majority of patients with DS and was well tolerated.
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http://dx.doi.org/10.1111/epi.16690DOI Listing
November 2020

Autism and Epilepsy in Patients With Tuberous Sclerosis Complex.

Front Neurol 2020 11;11:639. Epub 2020 Aug 11.

Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University, Rome, Italy.

Individuals with Tuberous Sclerosis Complex (TSC) are at increased risk of developing both epilepsy and autism spectrum disorder (ASD), but the relationship between these conditions is little understood. We reviewed published reports to elucidate the relationship between ASD, epilepsy, and TSC, and to define the genetic and neurological risk factors. Articles (January 2004-May 2019) were identified via PubMed, EMBASE, and CENTRAL databases. Article inclusion required report on individuals with TSC-associated ASD and epilepsy with prevalence, odds ratio, or rate report on the comorbidity of ASD in epileptic patients due to TSC. A total of 841 abstracts were identified in the original search. Thirty-six articles were included, which identified study populations, ASD measures used, and study confounders as bias factors. This review included 2,666 TSC patients, with a mean age of 15.9 years (range 1.94-30.3 years). The percentage of TSC patients with epilepsy autism was 33.7%. Patients with TSC autism showed more frequent seizures and earlier epilepsy onset than TSC patients without autism. ASD and intractable epilepsy were both predicted by a higher number of areas with dysplastic features revealed in brain MR scans. ASD, the onset of seizures in children <2 years of age, and >3 tubers have all been associated with an increased risk of refractory epilepsy in TSC patients. However, the direction of the relationship is not clear because a history of epilepsy, or infantile spasms in patients with TSC is also associated with an increased likelihood of ASD. Overall, 73.2% of patients carried genetic variant and, among patients with TSC and autism, the percentage of individuals was 85.6%. The complex interrelationship between TSC, autism, and epilepsy, coupled with limited knowledge on the neurobiological basis for the interrelationship, limits overall understanding and opportunities for management. The results of this review highlight the need for early identification and management to optimize favorable outcomes in the most vulnerable individuals with TSC. Regardless of whether studies are considered individually or collectively, interpretation is made difficult due to the differences between the studies, most notably between methods and diagnostic criteria used to assess intellectual ability.
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http://dx.doi.org/10.3389/fneur.2020.00639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431762PMC
August 2020

Defining the phenotype of FHF1 developmental and epileptic encephalopathy.

Epilepsia 2020 07 9;61(7):e71-e78. Epub 2020 Jul 9.

Pediatric Neurology, University Hospitals Leuven, Leuven, Belgium.

Fibroblast growth-factor homologous factor (FHF1) gene variants have recently been associated with developmental and epileptic encephalopathy (DEE). FHF1 encodes a cytosolic protein that modulates neuronal sodium channel gating. We aim to refine the electroclinical phenotypic spectrum of patients with pathogenic FHF1 variants. We retrospectively collected clinical, genetic, neurophysiologic, and neuroimaging data of 17 patients with FHF1-DEE. Sixteen patients had recurrent heterozygous FHF1 missense variants: 14 had the recurrent p.Arg114His variant and two had a novel likely pathogenic variant p.Gly112Ser. The p.Arg114His variant is associated with an earlier onset and more severe phenotype. One patient carried a chromosomal microduplication involving FHF1. Twelve patients carried a de novo variant, five (29.5%) inherited from parents with gonadic or somatic mosaicism. Seizure onset was between 1 day and 41 months; in 76.5% it was within 30 days. Tonic seizures were the most frequent seizure type. Twelve patients (70.6%) had drug-resistant epilepsy, 14 (82.3%) intellectual disability, and 11 (64.7%) behavioral disturbances. Brain magnetic resonance imaging (MRI) showed mild cerebral and/or cerebellar atrophy in nine patients (52.9%). Overall, our findings expand and refine the clinical, EEG, and imaging phenotype of patients with FHF1-DEE, which is characterized by early onset epilepsy with tonic seizures, associated with moderate to severe ID and psychiatric features.
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http://dx.doi.org/10.1111/epi.16582DOI Listing
July 2020

Refractory Status Epilepticus in Genetic Epilepsy-Is Vagus Nerve Stimulation an Option?

Front Neurol 2020 12;11:443. Epub 2020 Jun 12.

Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Member of European Reference Network EpiCARE, Rome, Italy.

Refractory and super-refractory status epilepticus (RSE, SRSE) are severe conditions that can have long-term neurological consequences with high morbidity and mortality rates. The usefulness of vagus nerve-stimulation (VNS) implantation during RSE has been documented by anecdotal cases and in systematic reviews; however, the use of VNS in RSE has not been widely adopted. We successfully implanted VNS in two patients with genetic epilepsy admitted to hospital for SRSE; detailed descriptions of the clinical findings and VNS parameters are provided. Our patients were implanted 25 and 58 days after status epilepticus (SE) onset, and a stable remission of SE was observed from the seventh and tenth day after VNS implantation, respectively, without change in anti-seizure medication. We used a fast ramp-up of stimulation without evident side effects. Our results support the consideration of VNS implantation as a safe and effective adjunctive treatment for SRSE.
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http://dx.doi.org/10.3389/fneur.2020.00443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303322PMC
June 2020

Neonatal seizures: When semiology points to etiology.

Seizure 2020 Aug 18;80:161-165. Epub 2020 Jun 18.

Neurology Department, Ospedale Pediatrico Bambino Gesù, Roma, Italy. Electronic address:

Objective: The aim of our study was to evaluate the relationship between seizure semiology and etiological factors in our population of neonates, in pointing out that specific kinds of clinical presentation are strictly related to specific etiologies.

Methods: We selected neonates which presented clinical seizures during video-EEG monitoring performed in Neonatal and Neurological Units between 2010 and 2017. We excluded patients with electrographic seizures only or video-EEGs of poor quality. Seizures were divided into the main subgroups "motor" (focal clonic, focal tonic and myoclonic) and "non motor". For each patient we evaluated etiology, considering two major categories: acute and remote symptomatic.

Results: The study included 65 patients, including 44 with an acute symptomatic cause and 21 with remote symptomatic etiology. Focal motor clonic seizures were almost exclusively associated to acute symptomatic etiology (p < 0.05), mainly to stroke and infective causes. Focal motor tonic seizures were the prevalent type of seizures in remote symptomatic etiologies (p < 0.05). They were observed mainly in patients with Developmental Epileptic Encephalopathy. Focal non motor seizures were more represented in acute symptomatic causes (p = 0.01) and were the main type of seizure in HIE.

Conclusions: Seizure semiology in neonates may help physicians in the early recognition of specific etiologies. In particular, focal clonic seizures are strongly suggestive of acute symptomatic causes, allowing an early diagnosis and treatment.
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http://dx.doi.org/10.1016/j.seizure.2020.06.025DOI Listing
August 2020

New-onset refractory status epilepticus and febrile infection-related epilepsy syndrome.

Dev Med Child Neurol 2020 08 5;62(8):897-905. Epub 2020 May 5.

Rare and Complex Epilepsy Unit, Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children Hospital, Rome, Italy.

New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) are relatively rare clinical presentations. They are characterized by de novo onset of refractory status epilepticus (RSE) without clearly identifiable acute or active cause (structural, toxic, or metabolic). We reviewed the literature using PubMed reports published between 2003 and 2019 and summarized the clinical, neurophysiological, imaging, and treatment findings. Focal motor seizures, which tend to evolve into status epilepticus, characterize the typical presentation. Disease course is biphasic: acute phase followed by chronic phase with refractory epilepsy and neurological impairment. Aetiology is unknown, but immune-inflammatory-mediated epileptic encephalopathy is suspected. Electroencephalograms show variety in discharges (sporadic or periodic, focal, generalized, or more frequently bilateral), sometimes with a multifocal pattern. About 70% of adult NORSE have abnormal magnetic resonance imaging (MRI); in paediatric series of FIRES, 61.2% of patients have a normal brain MRI at the beginning and only 18.5% during the chronic phase. No specific therapy for FIRES and NORSE currently exists; high doses of barbiturates and ketogenic diet can be used with some effectiveness. Recently, anakinra and tocilizumab, targeting interleukin pathways, have emerged as potential specific therapies. Mortality rate is around 12% in children and even higher in adults (16-27%).
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http://dx.doi.org/10.1111/dmcn.14553DOI Listing
August 2020

Treatment of infantile spasms: why do we know so little?

Expert Rev Neurother 2020 06 19;20(6):551-566. Epub 2020 Jun 19.

Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University , 00133, Rome, Italy.

Introduction: Infantile spasm (IS) is an epileptic syndrome with typical onset within the first 2 years of life. This condition might be caused by several etiologies. IS is associated with pathological neuronal networks; however, definite hypotheses on neurobiological processes are awaited.

Areas Covered: Changes in NMDA and GABA receptors and increase of Ca conductance are some of the possible pathophysiological mechanisms. Animal models can help, but most have only some features of IS. Outcome is strongly affected by etiology and the timing of treatment, which relies still on ACTH, oral steroids, and vigabatrin. No significant differences in terms of efficacy have been documented, though a combination of ACTH and vigabatrin seems to be associated with better long-term outcomes. Despite the increasing knowledge about the etiology and pathophysiology of IS, in the last years, no new treatment approaches have been recognized to be able to modify the neurobiological process underlying IS. Precision medicine has far to come in IS.

Expert Opinion: Recently, no new therapeutic options for IS have emerged, probably due to the lack of reliable animal models and to the extreme variability in etiologies. Consequently, the outlook for patients and families is poor and early recognition and intervention remain research priorities.
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http://dx.doi.org/10.1080/14737175.2020.1759423DOI Listing
June 2020

Changing Times for CLN2 Disease: The Era of Enzyme Replacement Therapy.

Ther Clin Risk Manag 2020 30;16:213-222. Epub 2020 Mar 30.

Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a progressive neurodegenerative disease that results in early-onset, severe, progressive, neurological disabilities, leading to death in late childhood or early adolescence. Management has relied on symptomatic care, and supportive and palliative strategies, but the approval of the enzyme replacement therapy cerliponase alfa in the USA and Europe in 2017 brought different treatment opportunities. We describe the natural history of CLN2 disease, its diagnosis and management, and the preclinical and clinical development of cerliponase alfa. A PubMed search was undertaken for cerliponase alfa and rhTPP1 to identify preclinical and clinical studies. The hallmark-presenting symptoms of CLN2 disease are unprovoked seizures and a history of language delay, and progression involves motor dysfunction, and cognitive and visual decline. Cerliponase alfa has shown efficacy and tolerability in mouse and canine models of CLN2 disease when delivered intracerebroventricularly. Administration of cerliponase alfa in patients with CLN2 disease has led to significant reductions in the rate of decline of motor and language functions in comparison with a natural history population. The approval of cerliponase alfa has brought a new era for CLN2 disease, highlighting the need to understand different patterns of disease progression and clinical needs in treated patients.
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http://dx.doi.org/10.2147/TCRM.S241048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127909PMC
March 2020

Successful use of fenfluramine in nonconvulsive status epilepticus of Dravet syndrome.

Epilepsia 2020 04 13;61(4):831-833. Epub 2020 Mar 13.

Department of Neuroscience, Bambino Gesù Children's Hospital, Scientific Institute for Research and Health Care, Rome, Italy.

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http://dx.doi.org/10.1111/epi.16474DOI Listing
April 2020

Management of epileptic seizures in school-age children: Educational project dedicated to school staff.

Epilepsy Behav 2020 04 18;105:106951. Epub 2020 Feb 18.

Department of Neurosciences and Neurorehabilitation, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Objective: The objective of this study was to educate the school staff for a correct management of epileptic seizures in order to increase the safety of young people at school and promoting the administration of rescue drugs and in order to improve care and reduce improper calls to the health emergency number.

Methods: This project started in January 2016, and it is still ongoing at the Department of Neuroscience of Bambino Gesù Children's Hospital in Rome, Italy. There has been a data cut-off evaluation in November 2018. Two-hour training meetings with the school staff have been organized. The major topics of the training activities were as follows: report what epilepsy is, how to manage students with epileptic seizures, and how to administer rescue medications. During the meetings, the following two questionnaires were administered: one pretest in order to collect personal information and information on awareness of epilepsy, willingness to administer rescue medications, and anxiety in facing a seizure; and one posttest in order to check the knowledge acquired after the training sessions. Statistical analysis was performed using R version 3.2.3 (R Foundation for Statistical Computing, http://www.R-project.org/). Demographics (sex and age) and teaching experience were summarized with descriptive statistics for each variable. Demographics, teaching experience, awareness of disability, and knowledge of epilepsy were correlated to the management of seizures occurring in the classroom before the course; results are reported as odds ratios [OR] and 95% confidence interval (95 CI).

Results: Nine hundred school staff members (95% school staff and 5% social workers) entered in the project between January 2016 and November 2018. Seven hundred and forty (82%) returned the questionnaires fulfilled, and not all of them were completely filled. Ninety-eight percent of school staff (676/691) were aware about epilepsy; however, only in 16% (110) the awareness of epilepsy came from medical staff, scientific brochures, or participation in conventions. Thirty-five percent of school staff (248/707) believed that epilepsy reduces learning abilities, and 58% (409/703) believed that children with epilepsy need school support. After the training, 68% of school staff (496/734) correctly filled in the questionnaire related to the management of acute seizures versus 8% of them (57/718) in the prequestionnaire. After the training, 89% of school staff (601/675) were ready to administer rescue medications versus 54% (384/712) before the training. The majority of participants reported that the level of anxiety related to the management of seizures after the training significantly reduced.

Conclusions: Results of this project documented an increase in knowledge of epilepsy, a better knowledge on management of acute seizures in the school settings, a reduction in anxiety, and an increase in willingness to administer rescue medications. Further studies should be planned in order to document the changes in the real-world management of seizures, to evaluate if a reduction in hospital admittances might be reached, and to extend the project by assessing, through a questionnaire, the stigma and prejudices against the children affected by epilepsy by their classmates.
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http://dx.doi.org/10.1016/j.yebeh.2020.106951DOI Listing
April 2020

Source of cannabinoids: what is available, what is used, and where does it come from?

Epileptic Disord 2020 Jan;22(S1):1-9

UCL-Institute of Child Health, Great Ormond Street Hospital for Children, Member of the European Reference Network EpiCARE, London & Young Epilepsy, Lingfield, UK.

Cannabis sativa L. is an ancient medicinal plant wherefrom over 120 cannabinoids are extracted. In the past two decades, there has been increasing interest in the therapeutic potential of cannabis-based treatments for neurological disorders such as epilepsy, and there is now evidence for the medical use of cannabis and its effectiveness for a wide range of diseases. Cannabinoid treatments for pain and spasticity in patients with multiple sclerosis (Nabiximols) have been approved in several countries. Cannabidiol (CBD), in contrast to tetra-hydro-cannabidiol (THC), is not a controlled substance in the European Union, and over the years there has been increasing use of CBD-enriched extracts and pure CBD for seizure disorders, particularly in children. No analytical controls are mandatory for CBD-based products and a pronounced variability in CBD concentrations in commercialized CBD oil preparations has been identified. Randomized controlled trials of plant-derived CBD for treatment of Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) have provided evidence of anti-seizure effects, and in June 2018, CBD was approved by the Food and Drug Administration as an add-on antiepileptic drug for patients two years of age and older with LGS or DS. Medical cannabis, with various ratios of CBD and THC and in different galenic preparations, is licensed in many European countries for several indications, and in July 2019, the European Medicines Agency also granted marketing authorisation for CBD in association with clobazam, for the treatment of seizures associated with LGS or DS. The purpose of this article is to review the availability of cannabis-based products and cannabinoid-based medicines, together with current regulations regarding indications in Europe (as of July 2019). The lack of approval by the central agencies, as well as social and political influences, have led to significant variation in usage between countries.
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http://dx.doi.org/10.1684/epd.2019.1121DOI Listing
January 2020

Pediatric status epilepticus: Identification of prognostic factors using the new ILAE classification after 5 years of follow-up.

Epilepsia 2019 12 12;60(12):2486-2498. Epub 2019 Nov 12.

Department of Neuroscience, Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.

Objective: Status epilepticus (SE) is the most common neurologic emergency in childhood. This study aimed to report on a large cohort of pediatric patients with SE, applying the International League Against Epilepsy (ILAE) Classification for SE to identify prognostic factors.

Methods: We included 173 children treated at "Bambino Gesù" Children's Hospital in Rome for SE exceeding 30 minutes (mean age 4.43 ± 4.93 years old, median 2.28, interquartile range [IQR] 0.41-7.32; follow-up for a mean of 4.9 ± 3.4 years, median 8.75, IQR 4,58-12.63). A multivariate model was constructed to predict neurocognitive outcome, recurrence of SE, development of epilepsy, and mortality. Adjusted odds ratios [ORs] were calculated with 95% confidence interval (OR, 95% CIs).

Results: We observed a different prevalence of etiologies for the different semiologies (P < .05) and for each age group (P < .05), overlapping only in part with the recent ILAE classification. After SE, patients showed 69.9% epilepsy (drug-resistant in half of them), 23.1% worsening of neurologic findings on examination, 28.9% cognitive deficit, and 28.3% recurrent SE. At multivariate analysis: superrefractory SE was correlated to an increased risk of developing cognitive (OR 6.00, 95% CI 2.09, 17.31) or neurologic sequelae (OR 4.9, 95% CI 1.75, 19.77). A similar finding was observed for patients with onset in the neonatal period for cognitive (OR 4.84, 95% CI 1.13, 17.3) and neurologic sequelae (OR 9.03, 95% CI 2.40, 34.04). Recurrence of SE was associated with unknown etiology (OR 6.15, 95% CI 1.43, 26.76), and myoclonic semiology (OR 6.1, 95% CI 1.23, 29.3). Patients with acute symptomatic etiology (OR 0.12, 95% CI 0.04, 0.40) had a lower risk for developing epilepsy.

Significance: Age at onset and duration of SE were critical independent variables associated with worse neurocognitive outcome. The risk of developing epilepsy was lower after acute symptomatic and febrile SE. Semiology and age at onset correlate with etiology of SE. For this reason, ILAE classification with respect to four axes seems an appropriate advancement.
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http://dx.doi.org/10.1111/epi.16385DOI Listing
December 2019

Introduction to the Italian section for young neurologists.

Neurol Sci 2019 Nov 14;40(11):2423-2424. Epub 2019 Jun 14.

Institute of Neurology, Catholic University of the Sacred Heart, Fondazione Policlinico Gemelli IRCCS, Rome, Italy.

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http://dx.doi.org/10.1007/s10072-019-03967-4DOI Listing
November 2019

Purified Cannabidiol for Treatment of Refractory Epilepsies in Pediatric Patients with Developmental and Epileptic Encephalopathy.

Paediatr Drugs 2019 Aug;21(4):283-290

Rare and Complex Epilepsy Unit, Division of Neurology, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.

Background: A pharmaceutical grade formulation of cannabidiol (CBD) has been approved for the treatment of Dravet syndrome and Lennox-Gastaut syndrome; however, this formulation is not yet available to patients outside the USA. In addition, CBD is thought to have broad anti-seizure properties that may be beneficial for other types of intractable epilepsy.

Objective: The aim of this study was to evaluate the efficacy, safety and tolerability of artisanal medical CBD oil in patients with developmental and epileptic encephalopathy (DEE) at the tertiary epilepsy center of Bambino Gesù Children's Hospital in Rome, Italy.

Methods: This was a single-center, prospective, open-label study. Patients aged from 1 to 18 years with DEE and seizures refractory to appropriate antiepileptic drugs (AEDs) and other alternative treatments (i.e., vagal nerve stimulator and ketogenic diet) were included. Crystalline extract CBD powder (98-99% pure) in an oil artisanal formulation was added to the baseline AED regimen at a dosage of 2-5 mg/kg/day divided for twice-daily administration, then up-titrated until intolerance or a maximum dosage of 25 mg/kg/day was reached. Patients were treated for at least 6 months. Efficacy, safety and tolerability of CBD treatment were assessed through the evaluation of seizure frequency and reports of adverse effects.

Results: Twenty-nine patients were enrolled in this study (41.4% male). The mean duration of exposure to artisanal CBD was 11.2 months [range 6-25 months; standard deviation (SD) ± 4.4 months]. Mean age at study enrollment was 9.3 years (range 1.9-16.3 years; SD ± 4.7 years). Eleven out of 29 patients (37.9%) had a ≥ 50% improvement in seizure frequency; one patient became seizure free. None of the patients reported worsening seizure frequency; however, 18 patients (62.1%) experienced no beneficial effect regarding seizure frequency. Adverse effects were reported in seven patients (24.14%), most commonly somnolence, decreased appetite and diarrhea. Adverse events were mild and transient, and no dose modification of CBD or other AEDs was required.

Conclusions: These data suggest that CBD may have beneficial effects in patients with DEE and an acceptable safety profile. Placebo-controlled randomized trials should be conducted to formally assess the safety and efficacy of CBD in patients with DEE.
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http://dx.doi.org/10.1007/s40272-019-00341-xDOI Listing
August 2019

Outcome after hemispherotomy in patients with intractable epilepsy: Comparison of techniques in the Italian experience.

Epilepsy Behav 2019 04 16;93:22-28. Epub 2019 Feb 16.

Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children Hospital, Rome, Italy. Electronic address:

Objective: The objective of the study was to evaluate clinical characteristics and outcome of hemispherotomy in children and adolescents with hemispheric refractory epilepsy in an Italian cohort of patients.

Methods: We retrospectively evaluated the clinical course and outcome of 92 patients with refractory epilepsy who underwent hemispherotomy in three Italian epilepsy centers between 2006 and 2016. Three different approaches for hemispherotomy were used: parasagittal, modified parasagittal, and lateral.

Results: Mean age at epilepsy onset was 1.8 ± 2.51 years, and mean duration of epilepsy prior to surgery was 7.4 ± 5.6 years. Mean age at surgery was 9.2 ± 8.0 years. After a mean follow-up of 2.81 ± 2.4 years, 66 of 90 patients (two lost from follow-up, 73.3%) were seizure-free (Engel class I). The etiology of epilepsy was related to acquired lesions (encephalomalacia or gliosis) in 44 patients (47.8%), congenital malformations (cortical dysplasia, hemimegalencephaly, other cortical malformations) in 38 (41.3%), and progressive conditions (Rasmussen or Sturge-Weber syndrome) in 10 patients (10.9%). Regarding seizure outcome, we could not identify statistically significant differences between vertical and lateral approaches (p = 0.154). Seizure outcome was not statistically different in patients with congenital vs acquired or progressive etiologies (p = 0.43). Acute postoperative seizures (APOS) correlated with poor outcome (p < 0.05). On multivariate analysis, presurgical focal to bilateral tonic-clonic seizures (Odds Ratio (OR) = 3.63, 95% Confidence Interval (CI): 1.86-15.20, p = 0.048) independently predicted seizure recurrence. Twenty-one patients (22.8%) exhibited postoperative complications, with no unexpected and persistent neurological deficit. More than 50% of the patients completely tapered drugs.

Significance: Our data confirm hemispherotomy to be a safe and effective procedure in patients with drug resistant epilepsies due to hemispheric lesions. Presurgical focal to bilateral tonic-clonic seizures are the strongest predictor of seizure recurrence after surgery, independently from the type of hemispherotomy.
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http://dx.doi.org/10.1016/j.yebeh.2019.01.006DOI Listing
April 2019

Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study.

Epilepsia 2018 12 19;59(12):2260-2271. Epub 2018 Nov 19.

Epilepsy Center, San Paolo Hospital, Milan, Italy.

Objective: PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors.

Methods: We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency.

Results: At last follow-up (median = 12 years, range = 1.9-42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure-free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124).

Significance: We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long-term follow-up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems.
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http://dx.doi.org/10.1111/epi.14600DOI Listing
December 2018

Italian Wikipedia and epilepsy: An infodemiological study of online information-seeking behavior.

Epilepsy Behav 2018 04 14;81:119-122. Epub 2018 Feb 14.

'Sapienza' University of Rome, Human Neuroscience Department, Rome, Italy.

Wikipedia is the most commonly accessed source of health information by both healthcare professionals and the lay public worldwide. We aimed to evaluate information-seeking behavior of Internet users searching the Italian Wikipedia for articles related to epilepsy and its treatment. Using Pageviews Analysis, we assessed the total and mean monthly views of articles from the Italian Wikipedia devoted to epilepsy, epileptic syndromes, seizure type, and antiepileptic drugs (AEDs) from January 1, 2015 to October 31, 2017. We compared the views of the article on epilepsy with those of articles focusing on Alzheimer's disease, migraine, multiple sclerosis, syncope, and stroke and adjusted all results for crude disease prevalence. With the only exception of the article on multiple sclerosis, the adjusted views for the Italian Wikipedia article on epilepsy were higher than those for the other neurological disorders. The most viewed articles on seizure type were devoted to tonic-clonic seizure, typical absence seizure, tonic convulsive seizures, and clonic convulsive seizures. The most frequently accessed articles on epilepsy syndromes were about temporal lobe epilepsy and Lennox-Gastaut syndrome. The most frequently viewed articles on AEDs were devoted to valproic acid, carbamazepine, and levetiracetam. Wikipedia searches seem to mirror patients' fears and worries about epilepsy more than its actual epidemiology. The ultimate reasons for searching online remain unknown. Epileptologists and epilepsy scientific societies should make greater efforts to work jointly with Wikipedia to convey more accurate and up-to-date information about epilepsy.
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http://dx.doi.org/10.1016/j.yebeh.2018.01.037DOI Listing
April 2018

Photosensitivity is an early marker of neuronal ceroid lipofuscinosis type 2 disease.

Epilepsia 2017 08 20;58(8):1380-1388. Epub 2017 Jun 20.

Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS (Istituto di Ricerca e Cura a Carattere Scientifico), Rome, Italy.

Objective: This study aimed to identify early clinical, magnetic resonance imaging (MRI), and electroencephalographic (EEG) characteristics of neuronal ceroid lipofuscinosis type 2 (CLN2) disease to enable early diagnosis, thus providing the key to early treatment, and optimized care and outcomes.

Methods: Retrospective clinical chart review of a series of patients diagnosed with CLN2 disease from 2005 to 2015 at a single center in Italy. Clinical, MRI, and EEG findings were reviewed.

Results: A total of 14 patients were included. For the whole group, median (range) age at disease onset was 3.0 (2.0-3.8) years. Epilepsy was the most commonly reported presenting symptom (in 50% [seven of 14] of patients), occurring at the age of 3.2 (2.6-3.8) years. First seizure was myoclonic in 36% (five of 14) of patients, followed by generalized tonic-clonic in 29% (4 of 14), atonic in 22% (three of 14), and focal with motor signs in 14% (two of 14). All patients walked independently at the age of 12.0 (11.0-18.0) months, but delayed speech or regression of acquired verbal skills was present in 100% of patients at 3 years. EEGs revealed a photoparoxysmal response (PPR) on intermittent photic stimulation in 93% (13 of 14) of patients. PPR was present from the first EEG, which was performed at 3.6 (3.1-4.0) years, in 43% (six of 14) of patients; it was documented at low (1-3 Hz) stimulation frequencies in 69% (nine of 13) and took the form of a flash-per-flash response in 69% (nine of 13). First brain MRI at the age of 3.8 (3.0-5.1) years revealed cerebellar atrophy in 100% (14 of 14) of patients and alteration of the periventricular white matter signal in the posterior hemispheric region in 79% (11 of 14).

Significance: Early photosensitivity (typically PPR at low stimulation frequencies of 1-3 Hz) is a hallmark of CLN2 disease. This diagnosis should be considered in a child presenting with any type of seizure, and particularly if it is accompanied by delayed speech and/or ataxia or MRI abnormalities (posterior white matter signal alteration or cerebellar atrophy).
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http://dx.doi.org/10.1111/epi.13820DOI Listing
August 2017

Vigabatrin efficacy in GPR56-associated polymicrogyria: The role of GABAA receptor pathway.

Epilepsia 2016 08;57(8):1337-8

Department of Neuroscience, "Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

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http://dx.doi.org/10.1111/epi.13453DOI Listing
August 2016

PCDH19-related epilepsy and Dravet Syndrome: Face-off between two early-onset epilepsies with fever sensitivity.

Epilepsy Res 2016 09 16;125:32-6. Epub 2016 Jun 16.

Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. Electronic address:

Aim of this study is to compare PCDH19-related epilepsy and Dravet Syndrome (DS) in order to find out differences between these two infantile epilepsies with fever sensitivity. We retrospectively reviewed the medical records of 15 patients with PCDH19-related epilepsy and 19 with DS. Comparisons were performed with Fisher's exact test or Student's t-test. Females prevailed in PCDH19-related epilepsy. Epilepsy onset was earlier in DS (5.0+2.1 vs 11.2+7.0months; p<0.05). The second seizure/cluster occurred after a longer latency in PCDH19-related epilepsy rather than in DS (10.1±13.6 vs 2.2±2.1months; p<0.05). Seizures were mainly single and prolonged seizures in DS, and brief and clustered in PCDH19-related epilepsy. Myoclonic and clonic seizures have been found only in DS. Other types of seizures were found in both epilepsies with a prevalence of GTCS and atypical absences in DS, and focal motor and hypomotor seizures in PCDH19-related epilepsy. Seizures with affective symptoms have been confirmed to be typical of PCDH19-related epilepsy. Status Epilepticus equally occurred in both groups. Photosensitivity was detected only in DS. No differences were found about the presence of intellectual disabilities and behavioral disturbances. We were able to find out some distinctive features, which could address the diagnosis towards DS or PCDH19-related epilepsy, since first manifestation. These considerations suggest to definitively considering PCDH19 gene as cause of a proper epileptic phenotype.
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http://dx.doi.org/10.1016/j.eplepsyres.2016.05.015DOI Listing
September 2016

Characterisation of CASPR2 deficiency disorder--a syndrome involving autism, epilepsy and language impairment.

BMC Med Genet 2016 Feb 3;17. Epub 2016 Feb 3.

Max Planck Institute for Psycholinguistics, PO Box 310, Nijmegen, 6500, AH, The Netherlands.

Background: Heterozygous mutations in CNTNAP2 have been identified in patients with a range of complex phenotypes including intellectual disability, autism and schizophrenia. However heterozygous CNTNAP2 mutations are also found in the normal population. Conversely, homozygous mutations are rare in patient populations and have not been found in any unaffected individuals.

Case Presentation: We describe a consanguineous family carrying a deletion in CNTNAP2 predicted to abolish function of its protein product, CASPR2. Homozygous family members display epilepsy, facial dysmorphisms, severe intellectual disability and impaired language. We compared these patients with previously reported individuals carrying homozygous mutations in CNTNAP2 and identified a highly recognisable phenotype.

Conclusions: We propose that CASPR2 loss produces a syndrome involving early-onset refractory epilepsy, intellectual disability, language impairment and autistic features that can be recognized as CASPR2 deficiency disorder. Further screening for homozygous patients meeting these criteria, together with detailed phenotypic and molecular investigations will be crucial for understanding the contribution of CNTNAP2 to normal and disrupted development.
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http://dx.doi.org/10.1186/s12881-016-0272-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739328PMC
February 2016

Peri-ictal water drinking: a rare automatic behaviour in temporal lobe epilepsy.

Epileptic Disord 2015 Dec;17(4):384-96

Division of Neurology, Department of Neuroscience, Bambino Gesù Children's Hospital IRCCS, Rome.

Peri-ictal water drinking (PIWD) has been reported as the action of drinking during or within two minutes of an electroclinical seizure. It is considered a peri-ictal vegetative symptom, evident both during childhood and adulthood epilepsy. The aim of this paper was to describe the clinical and electroencephalographic features of two new adult subjects suffering from symptomatic temporal lobe epilepsy with episodes of PIWD recorded by VIDEO-EEG and to review literature data in order to better define this peculiar event during seizures, a rare and probably underestimated semiological sign. To date, 51 cases with focal epilepsy and seizures associated with PIWD have been reported. All patients presented with temporal lobe epilepsy. All cases but one had symptomatic epilepsy. Most of the patients had an involvement of the right hemisphere. Water drinking was reported as an ictal sign in the majority of patients, and less frequently was reported as postictal. We believe that PIWD might be considered a rare automatic behaviour, like other automatisms. Automatisms are more frequently described in patients with temporal lobe epilepsy. PIWD was reported also to have lateralizing significance in the non-dominant temporal lobe, however, because of its rarity, this finding remains unclear.
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http://dx.doi.org/10.1684/epd.2015.0776DOI Listing
December 2015