Pediatric Epilepsy Pioneers in Italy

Vincenzo Belcastro was born in 1976 Reggio Calabria, Italy. After obtaining his medical degree in 2001, he completed his clinical training in Neurology from the University of Perugia in 2007 under the guidance of Prof. Paolo Calabresi. At the University of Perugia, he worked in the Calabresi laboratory investigating experimental models of Parkinson's disease (PD)[1] and mechanisms of abnormal synaptic plasticity in basal ganglia structures of PD patients with a particular focus on the nucleus striatum. Between 2006 and 2008, he joined the epilepsy clinic at the University of Perugia where he had the chance to treat large cohorts of patients affected by different early-onset epileptic syndromes. He obtained his undergraduate degree in Physiopathology of Cerebrovascular Diseases in 2011 and then completed the Neurology training program at the University of Perugia. Since July 2010, he has been working as a neurologist at the Saint Anna Hospital (Como, Italy) where he attends to both children and adults affected by a range of epileptic syndromes ([Fig. 1]).

Fig. 1 Prof. Vincenzo Belcastro.

His particular focus has been on the relationship between migraine and epilepsy,[2] with a special interest in the clinical assessment of childhood epilepsy. As a board-certified neurologist, Dr. Belcastro has conducted studies on the efficacy of antiepileptic drugs (AEDs) in different forms of symptomatic epilepsies[3] and participated in clinical trials of AEDs in patients affected by seizure disorders. Dr. Belcastro is actively involved in multicenter projects in Italy and other parts of the world. He is a member of the Board of Italian League against Epilepsy (LICE), a scientific association focused on promoting knowledge of epilepsy among people and physicians to improve the patient care. Dr. Belcastro is also the secretary of the Italian Society on Pediatric Neurology (SINP). In the past 10 years, his research has particularly focused on the clinical relationship and electroencephalography (EEG) findings between epilepsy and migraine. Since then, Dr. Belcastro has slowly but continuously built up a collection of fruitful collaborations with leading pediatric epilepsy research groups across Italy, including a long-standing collaboration with Profs. Pasquale Striano (University of Genoa, Italy) and Pasquale Parisi (Sapienza University of Rome, Italy). Vincenzo, Pasquale, and Pasquale constantly exchange thoughts and research ideas and work to secure grants to investigate the pathophysiological relationship between migraine and epilepsy in childhood.

His scientific publications include more than 130 articles published in several peer-reviewed journals with an H-index of 27 (Scopus). He is currently a member of the Editorial Board of Frontiers in Pediatrics and Frontiers in Neurology.

Pasquale Parisi was born in Naples (Italy) in 1957, where he grew up and completed his basic training in Pediatrics at the “Federico II” University in Naples. In 1988, he moved to Rome where he completed his undergraduate degrees and then a PhD in Pediatric Neurology and Neurosciences. Between 1988 and 1999, he completed his further basic training in Clinical Neurosciences from the Sapienza University in Rome under the guidance of Prof. Paola Iannetti. Since 2000, he joined the Sapienza University in Rome where in 2014 he was appointed as an Associate Professor of Pediatrics and Pediatric Neurology at the NESMOS department ([Fig. 2]).

Fig. 2 Prof. Pasquale Parisi.

Prof. Parisi has a longstanding experience in pediatric neurology and he could be regarded as one of the most prominent pioneers of pediatric epilepsy in Italy. He has been working in this field since 1984 from a clinical and molecular research perspective. In particular, he has been deeply fascinated by the potential causal correlation between headaches and epilepsies. In many of his published manuscripts, he suggests a common (shared) pathophysiological mechanism underlying epilepsy and headache.[4] After about a decade spent on recruiting a large cohort of patients with both epilepsy and headache (in collaboration with Profs. Striano and Belcastro), Prof. Parisi proposed the diagnostic term “ictal epileptic headache,”[5] [6] to define a condition characterized by headache as the only (isolated) symptom of a seizure attack. Prof. Parisi has also conducted studies on the efficacy of antiepileptic drugs (AEDs) in different forms of symptomatic and idiopathic epilepsies and participated in clinical trials of AEDs in patients affected by epileptic disorders. He has very often been involved in multicenter research projects in Italy and other places focused on pediatric rare epileptic syndromes. In collaboration with Prof. Ramon Brugada (Girona, Spain) and Prof. Pasquale Striano (Genova, Italy), he has also worked on the relationship between epilepsy and abnormal cardiac rhythm.[7] He is currently a member of the Editorial Board of the journal “Epilepsia.” He has been a member of the SINP Scientific Committee since 1986. His scientific publications include more than 300 articles published in peer-reviewed journals with an H-index of 36 (Scopus).

Pasquale Striano was born in 1975 and completed his basic training in Clinical Neurology at “Federico II” University in Napoli in 2004 under the guidance of his father Salvatore, Prof. of Neurology and a skilled epileptologist. Under his guidance, Pasquale learnt how EEG may help to exclude a diagnosis, support a diagnosis, or render treatment for epilepsy. He obtained his undergraduate degree in Neurosciences in 2006 and then completed the training program at the Gaslini Children's Hospital in Genova. Since 2010, he has been working at the Gaslini Children's Hospital in Genova, Italy. He is also the Associate Professor of Pediatrics at the University of Genova since 2014 ([Fig. 3]).

Fig. 3 Prof. Pasquale Striano.

His main field of interest is molecular genetics of idiopathic epilepsies with a special interest in clinical assessment of children with epilepsy and to study genotype–phenotype correlations.[8] [9] [10] [11] [12] As a board-certified neurologist and pediatric neurologist, Prof. Striano has conducted translational studies on different forms of genetic epilepsies and participated in clinical trials of antiepileptic drugs in patients affected by seizure disorders. Dr. Striano is actively included in multicenter projects in Italy, United Kingdom, Germany, Turkey, and United States. He is also a member of the LICE.

Dr. Striano is also a member of the European Epicure Consortium that obtained a financial support for 4 years from the European Community about the Sixth Framework Program (Project Epicure: Functional genomics and Neurobiology of epilepsy: a basis for new therapeutic strategies) involving more than 30 epilepsy centers in 11 different countries. In this project, Dr. Striano was specifically involved in subproject 1 (SP1), with a specific aim to identify genetic factors associated with idiopathic generalized epilepsy through genome-wide association studies, sequencing studies, and linkage analysis of candidate genes. In particular, Dr. Striano coordinated the selection of Italian patients. Dr. Striano is also an associate partner of the EuroEPINOMICS consortium formed for the study of genetic epilepsies through next generation sequencing (NGS) techniques. The project involves the sequencing of coding region of the genome of patients with undiagnosed epileptic encephalopathies and familiar forms with dominant or recessive inheritance. In addition, Dr. Striano has been a member of the EpiPGX European consortium, funded by the European Community for pharmacogenomics studies in epilepsy in the Seventh Framework program EpiPGX. The project entitled “Epilepsy pharmacogenomics: delivering biomarkers for clinical use,” is aimed at identifying genetic factors related to response to antiepileptic drugs, adverse and idiosyncratic reactions, teratogenicity of valproic acid during pregnancy, and development and diffusion of predictive tests for clinical use. Within this project, Dr. Striano is a member of the clinical team to define the inclusion clinical criteria and is responsible for coordinating the sample collection at the national level. Pasquale Striano joined the International Consortium of ILAE about the genetics of epilepsy. Dr. Striano was awarded the Young Investigator Award at the European Congress of Epileptology, London, November 2012 by the ILAE. Since 2013, he is a member of the Pediatric Committee of Italian Medicines Agency (AIFA). His scientific publications include more than 400 articles published in peer-reviewed journals with an H-index of 45 (Scopus). He has been the Associate Editor of The Open Neurosurgery and Advances in Medicine and member of the Editorial Board of Epilepsia and World Journal of Neurology. He is currently the Associate Editor of International Neuropsychiatric Disease Journal, Epilepsia Open, and Frontiers in Pediatrics ([Fig. 4]).

Fig. 4 From left to the right: Vincenzo Belcastro, Pasquale Parisi, and Pasquale Striano.

• References

• 1 Belcastro V, Tozzi A, Tantucci M. , et al. A2A adenosine receptor antagonists protect the striatum against rotenone-induced neurotoxicity. Exp Neurol 2009; 217 (01) 231-234
• 2 Belcastro V, Striano P, Pierguidi L, Calabresi P, Tambasco N. Ictal epileptic headache mimicking status migrainosus: EEG and DWIMRI findings. Headache 2011; 51 (01) 160-162
• 3 Belcastro V, Costa C, Galletti F. , et al. Levetiracetam in newly diagnosed late-onset post-stroke seizures: a prospective observational study. Epilepsy Res 2008; 82 (2-3) 223-226
• 4 Parisi P, Striano P, Belcastro V. The crossover between headache and epilepsy. Expert Rev Neurother 2013; 13 (03) 231-233
• 5 Parisi P, Striano P, Kasteleijn-Nolst Trenite DGA, Verrotti A, Martelletti P, Villa MP, Belcastro V. Ictal epileptic headache: recent concepts for new classifications criteria. Cephalalgia 2012; 32: 723-724
• 6 Parisi P, Verrotti A, Costa P. , et al. Diagnostic criteria currently proposed for “ictal epileptic headache”: perspectives on strengths, weaknesses and pitfalls. Seizure 2015; 31: 56-63
• 7 Parisi P, Oliva A, Coll Vidal M. , et al. Coexistence of epilepsy and Brugada syndrome in a family with SCN5A mutation. Epilepsy Res 2013; 105 (03) 415-418
• 8 Zara F, Specchio N, Striano P. , et al. Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance. Epilepsia 2013; 54 (03) 425-436
• 9 Striano P, Weber YG, Toliat MR. , et al; EPICURE Consortium. GLUT1 mutations are a rare cause of familial idiopathic generalized epilepsy. Neurology 2012; 78 (08) 557-562
• 10 Striano P, Coppola A, Paravidino R. , et al. Clinical significance of rare copy number variations in epilepsy: a case-control survey using microarray-based comparative genomic hybridization. Arch Neurol 2012; 69 (03) 322-330
• 11 Fanciulli M, Santulli L, Errichiello L. , et al. LGI1 microdeletion in autosomal dominant lateral temporal epilepsy. Neurology 2012; 78 (17) 1299-1303
• 12 Striano P, Busolin G, Santulli L. , et al. Familial temporal lobe epilepsy with psychic auras associated with a novel LGI1 mutation. Neurology 2011; 76 (13) 1173-1176

• Suggested Readings

• 1 Parisi P, Striano P, Trenité DG. , et al. ‘Ictal epileptic headache’: recent concepts for new classifications criteria. Cephalalgia 2012; 32 (09) 723-724
• 2 Verrotti A, Coppola G, Spalice A. , et al. Peri-ictal and inter-ictal headache in children and adolescents with idiopathic epilepsy: a multicenter cross-sectional study. Childs Nerv Syst 2011; 27 (09) 1419-1423
• 3 Parisi P, Striano P, Negro A, Martelletti P, Belcastro V. Ictal epileptic headache: an old story with courses and appeals. J Headache Pain 2012; 13 (08) 607-613
• 4 Parisi P, Striano P, Verrotti A, Villa MP, Belcastro V. What have we learned about ictal epileptic headache? A review of well-documented cases. Seizure 2013; 22 (04) 253-258
• 5 Parisi P, Kasteleijn-Nolst Trenité DGA, Piccioli M. , et al. A case with atypical childhood occipital epilepsy “Gastaut type”: an ictal migraine manifestation with a good response to intravenous diazepam. Epilepsia 2007; 48 (11) 2181-2186
• 6 Belcastro V, Striano P, Kasteleijn-Nolst Trenité DGA, Villa MP, Parisi P. Migralepsy, hemicrania epileptica, post-ictal headache and “ictal epileptic headache”: a proposal for terminology and classification revision. J Headache Pain 2011; 12 (03) 289-294
• 7 Parisi P, Piccioli M, de Sneeuw S. , et al. Redefining headache diagnostic criteria as epileptic manifestation?. Cephalalgia 2008; 28 (04) 408-409 , author reply 409
• 8 Parisi P, Belcastro V, Verrotti A, Striano P, Kasteleijn-Nolst Trenitè DGA. “Ictal epileptic headache” and the revised International Headache Classification (ICHD-3) published in Cephalalgia 2018, vol. 38(1) 1–211: Epilepsy Behav 2018;87:243–245
• 9 Parisi P. Why is migraine rarely, and not usually, the sole ictal epileptic manifestation?. Seizure 2009; 18 (05) 309-312
• 10 Verrotti A, Coppola G, Di Fonzo A. , et al. Should “migralepsy” be considered an obsolete concept? A multicenter retrospective clinical/EEG study and review of the literature. Epilepsy Behav 2011; 21 (01) 52-59
• 11 Striano P, Belcastro V, Parisi P. From “migralepsy” to “ictal epileptic headache” concept. Epilepsy Behav 2012; 23 (03) 392
• 12 Belcastro V, Striano P, Parisi P. “Ictal epileptic headache”: beyond the epidemiological evidence. Epilepsy Behav 2012; 25 (01) 9-10
• 13 Parisi P. The complex relationship between epilepsy and headache and the concept of ictal epileptic headache. In: Striano P, ed. Epilepsy Towards the Next Decade. New Trends and Hopes in Epilepsy. Switzerland: Springer International Publishing; 2015: 139–162