Giangennaro Coppola

Università degli Studi di Salerno, Fisciano, Campania, Italy

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Publications (111)277.66 Total impact

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    ABSTRACT: Mozart's sonata for two pianos in D major, K448, has been shown to decrease interictal EEG discharges and recurrence of clinical seizures in both adults and young patients. In this prospective, open-label study, we evaluated the effect of listening to a set of Mozart's compositions, according to the Tomatis method, on sleep quality and behavioral disorders, including auto-/hetero-aggression, irritability, and hyperactivity, in a group of children and adolescents with drug-resistant epilepsy. The study group was composed of 11 outpatients (7 males and 4 females), between 1.5years and 21years of age (mean age: 11.9years), all suffering from drug-resistant epileptic encephalopathy (n=11). All of them had a severe/profound intellectual disability associated with cerebral palsy. During the study period, each patient had to listen to a set of Mozart's compositions 2h per day for fifteen days for a total of 30h, which could be distributed over the day depending on the habits and compliance of each patient. The music was filtered by a device preferably delivering higher sound frequencies (>3000Hz) according to the Tomatis principles. The antiepileptic drug therapy remained unchanged throughout the study period. During the 15-day music therapy, 2 out of 11 patients had a reduction of 50-75% in seizure recurrence, and 3 out of 12 patients had a reduction of 75-89%. Overall, 5 (45.4%) out of 11 patients had a ≥50% reduction in the total number of seizures, while the percentage decrease of the total seizure number (11/11) compared with baseline was -51.5% during the 15-day music therapy and -20.7% in the two weeks after the end of treatment. All responders also had an improvement in nighttime sleep and daytime behavior. Copyright © 2015 Elsevier Inc. All rights reserved.
    Epilepsy & Behavior 06/2015; 50:18-22. DOI:10.1016/j.yebeh.2015.05.038 · 2.06 Impact Factor
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    ABSTRACT: Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and whole-exome sequencing and identified three heterozygous missense mutations co-segregating with the syndrome. Subsequent analysis of 15 small ADLTE-affected families revealed four additional missense mutations. 3D modeling predicted that all mutations have structural effects on protein-domain folding. Overall, RELN mutations occurred in 7/40 (17.5%) ADLTE-affected families. RELN encodes a secreted protein, Reelin, which has important functions in both the developing and adult brain and is also found in the blood serum. We show that ADLTE-related mutations significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on protein secretion. We also show that Reelin and LGI1 co-localize in a subset of rat brain neurons, supporting an involvement of both proteins in a common molecular pathway underlying ADLTE. Homozygous RELN mutations are known to cause lissencephaly with cerebellar hypoplasia. Our findings extend the spectrum of neurological disorders associated with RELN mutations and establish a link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 06/2015; 96(6):992-1000. DOI:10.1016/j.ajhg.2015.04.020 · 10.99 Impact Factor
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    ABSTRACT: The ketogenic diet is known to have an anti-epileptic effect; in fact it is currently used to treat drug resistant epilepsies. The efficacy of this diet is thought to be correlated to the elevation of blood ketone bodies. Because of problems with compliance to this diet, there is an interest in evaluating alternative pharmacological treatments that can have anti-seizure effects by elevating ketone bodies. In the present experiment, an orally administered synthetic ketone ester (R,S - 1,3 - butanediol acetoacetate diester, or BD-AcAc2) was evaluated for its anti-seizure efficacy in a rat model. The threshold for seizure induction with progressive intravenous infusion of pentylenetrazole (PTZ) was evaluated in anesthetized Wistar rats two hours after a single 1ml intragastric administration of BD-AcAc2 (i.e. 4g/Kg b.w., treated group) or water (control group). After correction for the dose of anesthetic, the results showed that the administration of BD-AcAc2 induced an elevation of the PTZ threshold (140±11mg/Kg for the treated group, 122±6mg/Kg for the control group), along with an increased level of blood β-hydroxybutyrate (2.7±0.3mM for the treated group, 1.4±0.1mM for the control group). This result suggests that ketone esters may pave the road towards the establishment of a "ketogenic diet in a pill". Copyright © 2015. Published by Elsevier B.V.
    Brain research 05/2015; 1618. DOI:10.1016/j.brainres.2015.05.023 · 2.83 Impact Factor
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    ABSTRACT: Oral-facial-digital type VI syndrome (OFDVI) is a rare phenotype of Joubert syndrome (JS). Recently, C5orf42 was suggested as the major OFDVI gene, being mutated in 9 of 11 families (82 %). We sequenced C5orf42 in 313 JS probands and identified mutations in 28 (8.9 %), most with a phenotype of pure JS. Only 2 out of 17 OFDVI patients (11.7 %) were mutated. A comparison of mutated vs. non-mutated OFDVI patients showed that preaxial and mesoaxial polydactyly, hypothalamic hamartoma and other congenital defects may predict C5orf42 mutations, while tongue hamartomas are more common in negative patients.
    Human Genetics 11/2014; DOI:10.1007/s00439-014-1508-3 · 4.52 Impact Factor
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    ABSTRACT: Among male patients affected by Kallmann syndrome, a genetically determined disease due to defective neural migration leading to hypogonadropic hypogonadism and hypo/anosmia, about 40% present the peculiar phenomenon of mirror movements, i.e. involuntary movements mirroring contralateral voluntary hand movements. Several pathogenic hypotheses have been proposed, but the ultimate neurological mechanisms are still elusive. The aim of the present study was to investigate brain anatomical substrates of mirror movements in Kallmann syndrome by means of a panel of quantitative MRI analyses. Forty-nine male Kallmann syndrome patients underwent brain MRI. The study protocol included 3D-T1-weighted gradient echo, fluid attenuated inversion recovery and diffusion tensor imaging. Voxel-based morphometry, sulcation, curvature and cortical thickness analyses and tract based spatial statistics were performed using SPM8, Freesurfer and FSL. All patients underwent a complete physical and neurological examination including the evaluation of mirror movements (according to the Woods and Teuber criteria). Kallmann syndrome patients presenting with mirror movements (16/49, 32%) displayed the following brain changes: 1) increased gray matter density in the depth of the left precentral sulcus behind the middle frontal gyrus; 2) decreased cortical thickness in the precentral gyrus bilaterally, in the depth of right precentral sulcus and in the posterior portion of the right superior frontal gyrus; and 3) decreased fractional anisotropy in the left hemisphere involving the temporal lobe and peritrigonal white matter. No differences were shown by cortical curvature and sulcation analyses. The composite array of brain changes observed in Kallmann syndrome patients with mirror movements likely represents the anatomical-structural underpinnings leading to the peculiar derangement of the complex circuitry committed to unilateral hand voluntary movements.
    NeuroImage 10/2014; 104. DOI:10.1016/j.neuroimage.2014.09.067 · 6.36 Impact Factor
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    ABSTRACT: Background Studies on the efficacy and tolerability of rufinamide in infants and young children are scarce. Here we report on an open, retrospective, and pragmatic study about safety and efficacy of rufinamide in children aged less than four years, in terms of seizures types and epilepsy syndromes. Methods Forty children (mean age 39.5 months; range 22-48) were enrolled in the study. The mean follow-up period was 12.2 months (range 5-21). Rufinamide was initiated at a mean age of 26.7 months (range 12-42). Final rufinamide mean dosage was 31.5 mg/kg/day if associated with valproic acid and 44.2 mg/kg/day if not. Results The highest seizure reduction rate was observed in the epileptic spasms (46%) and drop attacks (42%) groups. Seizure reduction was also observed in tonic seizures (35%) and in the focal seizure (30%) groups. In terms of epilepsy syndrome, rufinamide was effective in Lennox-Gastaut syndrome. Results were very poor for those affected by Dravet’s syndrome. Globally, responder rate was 27.5%, including two (5%) patients seizure-free. Adverse reactions occurred in 37.5% of children and were mainly represented by vomiting, drowsiness, irritability, and anorexia. Discontinuation rate due to treatment-emergent adverse events was 15%. Conclusion The present study concludes that rufinamide may be a safe and effective drug for a broad range of seizures and epilepsy syndromes in infants and young children and represents a valid therapeutic option in this population.
    European Journal of Paediatric Neurology 09/2014; 18(5). DOI:10.1016/j.ejpn.2014.05.001 · 1.93 Impact Factor
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    ABSTRACT: Background: Epilepsy is a frequent and severe feature of Menkes disease (MD) but only few studies described the long-term evolution of these children. We report a series of 28 epileptic MD patients, with clinical characteristics, EEG abnormalities, brain malformations and long-term outcome. Methods: EEG, clinical characteristics and neuroimaging features in 28 MD patients were analyzed at the onset of epilepsy and after long-term follow-up (at least 4 years). We subdivided the patients into two groups: Group 1, 16 patients who received a subcutaneous copper-histidine treatment, and Group 2 including 12 patients who did not get any therapies. Results: The large majority of our patients presented at the onset of epilepsy focal seizures (FS) and infantile spasms (IS). Five patients had recurrent status epilepticus (SE). During the follow-up, patients showed multiple seizure types: 6 patients had generalized tonic clonic seizures (GC), 6 patients presented IS, 10 children had FS, 11 had myoclonic jerks and 3 had SE. Therapy with various antiepileptic drugs had poor efficacy, except in three patients who showed seizure disappearance with consequent discontinuation of antiepileptic therapy. There was no difference of neurological outcome among the two groups analyzed. Conclusions: Epilepsy in MD is a difficult to treat problem. At the onset, the most frequent type of seizures are FC and IS; in the next months, other kinds of seizures can appear. Many children are drug resistant. Institution of replacement therapy with copper-histidine seems to be not beneficial for epilepsy.
    Epilepsy Research 08/2014; 108(9). DOI:10.1016/j.eplepsyres.2014.08.006 · 2.19 Impact Factor
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    ABSTRACT: Schizencephaly is an uncommon malformation of cortical development. Patients with schizencephaly present with a broad range of severe neurologic symptoms including pharmacoresistant epilepsy. Rufinamide is a new antiepileptic drug approved for use as adjunctive therapy of seizures associated with Lennox-Gastaut syndrome and it is also effective for refractory partial seizures. We report 3 cases of pediatric patients aged 7.2, 8.1, and 10.1 years, respectively, with intractable epilepsy associated with bilateral open-lip schizencephaly and septo-optic dysplasia. The follow-up ranged from 3.8 to 4.1 years. In our patients, the introduction of rufinamide as adjunctive drug led to a dramatic decline in the number of seizures and an improvement in EEG epileptic activity without side effects. Rufinamide seems to be efficacious and safe in patients with epileptic encephalopathies associated with pharmacoresistant epilepsy; further and larger clinical reports and controlled studies could confirm the usefulness of this anticonvulsant drug.
    Journal of Child Neurology 07/2014; 30(8). DOI:10.1177/0883073814542951 · 1.67 Impact Factor
  • Alberto Verrotti · Alessia Carelli · Giangennaro Coppola
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    ABSTRACT: Menkes disease is a lethal multisystemic disorder of copper metabolism characterized by connective tissue abnormalities, progressive neurodegeneration and peculiar "kinky hair." Epilepsy is one of the main clinical features of this disease but it has been described in detail by only a few authors. Most patients develop seizures from 2 to 3 months of age, accompanied by a neurodevelopmental regression. The history of epilepsy is usually characterized by 3 stages: an early stage with focal clonic seizures and status epilepticus, an intermediate stage with infantile spasms, and a late stage with multifocal, myoclonic, and tonic seizures. At the onset, epilepsy can be controlled with anticonvulsant therapy, whereas with the progression of disease, it becomes extremely resistant to all antiepileptic drugs. In this article, we analyze clinical and electroencephalographic (EEG) characteristics of epilepsy in patients with this syndrome.
    Journal of Child Neurology 07/2014; 29(12). DOI:10.1177/0883073814541469 · 1.67 Impact Factor
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    ABSTRACT: Background and aims Several neuromotor disorders share exclusive, although often overlooked, nutritional problems. The objective of this study is therefore to delineate the frequency of malnutrition, evaluate the effectiveness of nutritional care, and identify issues needing to be possibly strengthened when caring for these patients into a general pediatrics department. Patients and methods The study included 30 patients, 21 males and 9 females, aged between 2 and 15 years, affected by cerebral palsy, epileptic encephalopathy, and severe psychomotor developmental delay. Nutritional status was assessed by a dietary questionnaire administered to parents to investigate feeding difficulties; 3 days food diary to quantify daily calorie intake; anthropometrical (weight, height/length, body mass index percentiles, plicometry, specific body segments measurement) and blood (blood count, serum iron, albumin, transferrin, calcium, phosphorus) parameters. More than 44% individuals of the study population was at risk of malnutrition, according to feeding difficulties, progressive depletion of weight, reduced daily calorie intake, reduced albumin and transferrin levels. This occurred despite a massive caregivers commitment, as documented by almost universal parental constant assistance during their long-duration meals. Our results individuate the nutritional aspect being still a problem in the care of children with severe neuromotor disability.
    Italian Journal of Pediatrics 07/2014; 40(1):61. DOI:10.1186/1824-7288-40-61 · 1.52 Impact Factor
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    ABSTRACT: Purpose: The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients. This paper summarizes the views of a panel of experienced European epileptologists with regard to the current role of rufinamide in the treatment of childhood epilepsies. Results: Rufinamide is effective in decreasing the seizure frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic seizures. It might consequently be preferred to other drugs as a second-line treatment for LGS when drop-attacks are frequent. The mean responder rate in the published studies is 38% with seizure freedom achieved in 2.4% of patients. Rufinamide has shown some efficacy in epileptic encephalopathies other than LGS. It can be also effective as adjunctive therapy in children and adolescents with drug-resistant partial seizures. The available data suggest that rufinamide has an acceptable risk/benefit ratio with quite a low risk of aggravating seizures. Common adverse effects (somnolence, nausea and vomiting) are usually mild and self-limiting; they are more frequently observed during titration than in the maintenance phase, suggesting that low escalation rates might be associated with fewer adverse effects. Rufinamide appears to have a favourable cognitive profile compared with other antiepileptic drugs. Conclusion: Rufinamide is only approved for adjunctive treatment of seizures associated with LGS in children 4 years of age and older. There are very few data on rufinamide treatment at the onset of LGS or early in the course of the disorder; whether early treatment will improve outcome has yet to be determined.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 05/2014; 18(6). DOI:10.1016/j.ejpn.2014.05.008 · 1.93 Impact Factor
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    ABSTRACT: We analyzed by next-generation sequencing (NGS) 67 epilepsy genes in 19 patients with different types of either isolated or syndromic epileptic disorders and in 15 controls to investigate whether a quick and cheap molecular diagnosis could be provided. The average number of nonsynonymous and splice site mutations per subject was similar in the two cohorts indicating that, even with relatively small targeted platforms, finding the disease gene is not an univocal process. Our diagnostic yield was 47% with nine cases in which we identified a very likely causative mutation. In most of them no interpretation would have been possible in absence of detailed phenotype and familial information. Seven out of 19 patients had a phenotype suggesting the involvement of a specific gene. Disease-causing mutations were found in six of these cases. Among the remaining patients, we could find a probably causative mutation only in three. None of the genes affected in the latter cases had been suspected a priori. Our protocol requires 8-10 weeks including the investigation of the parents with a cost per patient comparable to sequencing of 1-2 medium-to-large-sized genes by conventional techniques. The platform we used, although providing much less information than whole-exome or whole-genome sequencing, has the advantage that can also be run on 'benchtop' sequencers combining rapid turnaround times with higher manageability.European Journal of Human Genetics advance online publication, 21 May 2014; doi:10.1038/ejhg.2014.92.
    European journal of human genetics: EJHG 05/2014; 23(3). DOI:10.1038/ejhg.2014.92 · 4.23 Impact Factor
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    ABSTRACT: The outcome of benign convulsions associated with gastroenteritis (CwG) has generally been reported as being excellent. However, these data need to be confirmed in studies with longer follow-up evaluations. To assess the long-term neurological outcome of a large sample of children presenting with CwG. We reviewed clinical features of 81 subjects presenting with CwG (1994-2010) from three different Italian centers with a follow-up period of at least 3 years. Follow-up period ranged from 39 months to 15 years (mean 9.8 years). Neurological examination and cognitive level at the last evaluation were normal in all the patients. A mild attention deficit was detected in three cases (3.7%). Fourteen children (17.3%) received chronic anti-epileptic therapy. Interictal EEG abnormalities detected at onset in 20 patients (24.7%) reverted to normal. Transient EEG epileptiform abnormalities were detected in other three cases (3.7%), and a transient photosensitivity in one (1.2%). No recurrence of CwG was observed. Three patients (3.7%) presented with a febrile seizure and two (2.5%) with an unprovoked seizure, but none developed epilepsy. The long-term evaluation of children with CwG confirms the excellent prognosis of this condition, with normal psychomotor development and low risk of relapse and of subsequent epilepsy.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 04/2014; 18(5). DOI:10.1016/j.ejpn.2014.04.006 · 1.93 Impact Factor
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    ABSTRACT: Objective To evaluate the efficacy and tolerability of add-on rufinamide in children with refractory epilepsy symptomatic of neuronal migration disorders. Materials and Methods We recruited 69 patients in a prospective, open-label, add-on treatment study from six Italian and one German centers for pediatric and adolescent epilepsy care according to the following criteria: age 3 or above; focal or generalized seizures refractory to at least three previous antiepileptic drugs (AEDs), alone or in combination, secondary to neuronal migration disorders; two or more seizures per month in the last 6 months; use of another AED, but no more than three, at baseline. Informed consent from parents and/or caregivers was obtained at the time of enrollment. Results We enrolled 69 patients with a mean age of 15 years (range 3-43). Forty-three patients (62%) had a 50-99% seizure reduction, and two (3%) became seizure-free. Seizure frequency was unchanged in 18 (26%) and worsened in 6 (8.7%). Twenty-nine patients (42%) reported adverse side effects, whilst taking rufinamide. Irritability was the most common side effect (11 patients), followed by decreased appetite (10), mood shift (6), vomiting (5), drowsiness (4), and decreased attention (2). Blood levels of concomitant anticonvulsive drugs were transiently abnormal in 5 patients. Conclusion In our population of severely refractory epilepsy due to neuronal migration disorders, rufinamide appeared to be effective and generally well tolerated.
    Epilepsy research 03/2014; 108(3). DOI:10.1016/j.eplepsyres.2014.01.013 · 2.19 Impact Factor
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    Epilepsy Research 03/2014; DOI:10.1016/j.eplepsyres.2013.11.001 · 2.19 Impact Factor
  • Pasquale Striano · Giangennaro Coppola · Federico Zara · Rima Nabbout
    Annals of Neurology 02/2014; 75(2). DOI:10.1002/ana.24061 · 11.91 Impact Factor
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    ABSTRACT: Background The outcome of benign convulsions associated with gastroenteritis (CwG) has generally been reported as being excellent. However, these data need to be confirmed in studies with longer follow-up evaluations. Aim To assess the long-term neurological outcome of a large sample of children presenting with CwG. Methods We reviewed clinical features of 81 subjects presenting with CwG (1994–2010) from three different Italian centers with a follow-up period of at least 3 years. Results Follow-up period ranged from 39 months to 15 years (mean 9.8 years). Neurological examination and cognitive level at the last evaluation were normal in all the patients. A mild attention deficit was detected in three cases (3.7%). Fourteen children (17.3%) received chronic anti-epileptic therapy. Interictal EEG abnormalities detected at onset in 20 patients (24.7%) reverted to normal. Transient EEG epileptiform abnormalities were detected in other three cases (3.7%), and a transient photosensitivity in one (1.2%). No recurrence of CwG was observed. Three patients (3.7%) presented with a febrile seizure and two (2.5%) with an unprovoked seizure, but none developed epilepsy. Conclusions The long-term evaluation of children with CwG confirms the excellent prognosis of this condition, with normal psychomotor development and low risk of relapse and of subsequent epilepsy.

Publication Stats

1k Citations
277.66 Total Impact Points

Institutions

  • 2011–2015
    • Università degli Studi di Salerno
      Fisciano, Campania, Italy
  • 2002–2013
    • Second University of Naples
      Caserta, Campania, Italy
  • 2002–2012
    • University of Naples Federico II
      • Section of Pharmacology
      Napoli, Campania, Italy