–Fondazione IRCCS Istituto Neurologico “Carlo Besta” (Italy)
Giuliano Avanzini, ph. +39
02/23942253, fax +39 02/70600775, email@example.com
INNCB is a public, governative
recognized as a centre of excellence for the studies of the basic mechanisms of
Prof. Giuliano Avanzini, who
will act as the Project Coordinator, was also elected by INNCB as Principal
investigator, coordinating the research activities carried out by the two participating
units of the INNCB involved.
Avanzini (M, 40%), MD.
Former chairman of the department of Clinical Neurosciences; Present Research
Coordinator at INNCB. President of the Italian League against Epilepsy
(1987-1989); Member Executive Committee of the International League against
Epilepsy (ILAE) since 1993; President of ILAE (2001-2005), now past-President;
vice-president of European Epilepsy Academy EUREPA; President of the
International School of Neurological Sciences and Director of the Epilepsy
Summer School, S. Servolo- Venice. IBE-ILAE Ambassador for Epilepsy; Research
Award of the American Epilepsy Society; Research interests: Thalamo-cortical
system; basic mechanisms of epilepsy; cortical dysphasia; epileptogenic
Recent relevant publications/patents
1. Canafoglia L., Ciano C., Panzica F., Scaioli V., Zucca C., Agazzi P., Visani E., Avanzini G., Franceschetti S. (2004 Dec 28) Sensorimotor cortex excitability in Unverricht-Lundborg disease and Lafora body disease. Neurology 63(12):2309-15.
2. Curia G., Aracri P., Sancini G., Mantegazza M., Avanzini G., Franceschetti S. (2004) Protein-kinase C-dependent phosphorylation inhibits the effect of the antiepileptic drug topiramate on the persistent fraction of sodium currents.Neuroscience 127(1):63-8.
3. Avanzini G., Franceschetti S., Avoni P., Liguori R. (2004) Molecular biology of channelopathies: impact on diagnosis and treatment. Expert Rev Neurother 4:519-39.
4. Chan E.M., Young E.J., Ianzano L., Munteanu I., Zhao X., Christopoulos C.C., Avanzini G., Elia M., Ackerley C.A., Jovic N.J., Bohlega S., Andermann E, Rouleau GA,Delgado-Escueta A.V., Minassian B.A., Scherer S.W. (2003) Mutations in NHLRC1 cause progressive myoclonus epilepsy. Nat Genet. 35:125-7.
5. Ganesh S., Delgado-Escueta A.V., Suzuki T., Francheschetti S., Riggio C., Avanzini G., Rabinowicz A., Bohlega S., Bailey J., Alonso M.E., Rasmussen A., Thomson A.E., Ochoa A., Prado A.J., Medina M.T., Yamakawa K. (2002) Genotype-phenotype correlations for EPM2A mutations in Lafora's progressive myoclonus epilepsy: exon 1 mutations associate with an early-onset cognitive deficit subphenotype. Hum Mol Genet. 15;11:1263-71.
For the purposes of EPICURE,
the following participating units will be involved:
Franceschetti, Phone: 39 0223942250, Fax 39 02.70600775; e-mail firstname.lastname@example.org
and current research performed: The Division of Neurophysiopatology of the
INNCB includes the Clinical Neurophysiology Laboratories, the Epilepsy Center,
a Bioengineering Unit and Laboratories devoted to experimental neurophysiology.
The Laboratories of Clinical neurophysiology provide the clinical and technical
expertise for all aspects of various neurodiagnostic and testing procedures on
patients of various ages and medical conditions. The Epilepsy Center
performs long-term EEG monitoring suitable to establish a definite diagnosis in
patients with complex form of epilepsy or episodic symptoms of uncertain cause.
The Laboratory of bioengineering sets up and applies special techniques of
digital signal processing and analysis to be applied for diagnostic support,
research purposes and innovative clinical applications. The laboratory research
is based on a multidisciplinary approach to nervous diseases, namely
epilepsies, combining the expertise of clinical, experimental
electrophysiological and molecular biology techniques. The research fields
include study of in vitro preparation of cortical structures to evaluate
intrinsic excitability changes and epileptogenesis at cellular level underlying
neocortical epilepsies and experimental models of genetically determined
epilepsies (expression of mutants in cell lines and cultured neurons, and study
of gene targeted animal models).
Equipment for electrophysiological
recordings of dissociated cells and tissue slices; equipment for molecular
biology; Applied Biosystems ABI Prism 3100 sequencer: culture room with sterile
hoods and incubators; confocal Microscope and equipment for live cell imaging;
animal facility: operating room with equipment for stereotaxic surgery and
involved in the project
Principal investigator: Silvana Franceschetti, (F) MD,
PhD. Chief of Neurophysiology Unit
and Epilepsy Centre
at the INNCB, Milan; visiting scientist at Max
Planck Institute. Munich
(1984): PhD in Physiological sciences (1988); member
of the editorial board of Epilepsia. Research interests: experimental
epileptogenesis; early neocortical development: animal model of neuronal
migration disorder; clinical neurophysiology of neurodegenerative disorders in
infancy and childhood. Massimo
Mantegazza, (M) PhD in
Physiology. Junior group leader: Laboratory of Cellular Neurophysiology, INNCB, Milan.
Past position: Senior Fellow, Department of Pharmacology, University of Washington,
Working in the field since 1991. Human Frontier fellow. Research interests:
neuronal excitability, ion channels, epilepsy. Elisa Colombo (F) Master
Degree in Biology; PhD student; involved in electrophysiological evaluation of
sodium-dependent excitability and in cortical neurons and persistent sodium
current modulation. Paolo Scalmani
(M) Master Degree in Biology; PhD student; working on electrophysiological
evaluation of the functional effect of epileptogenic mutation of ion channels. Ferruccio Panzica (M) Bioengineer, Faculty of Electronic
Engineering, Politecnico, Milan
(Systems-Bioengineering). Bioengineer at the Neurophysiopathology and Unit and
Epilepsy center INNCB, Milan (1989-present);
tutor for students - Biomedical faculty, Politecnico of Milan; member of
working group of centres for epilepsy, Lombardy
(2004-present). Research interest: methods and mathematical models for the
analysis of EEG, evoked response and EEG-EMG relationships; development of
programs for the analysis of firing and electrotonic properties of cortical
Two PhD students will be appointed: student 1 for
mutagenesis, immunocytochemistry and electrophysiological recordings in cell
lines; student 2 for electrophysiological recordings in brain slices and
dissociated neurons, biocitin labeling, and genotyping.
Recent relevant publications/patents
Mantegazza M., G. Annesi, R.
Rusconi, E. Schiavon, R. Restano Cassulini, S. Franceschetti, A. Gambardella,
E. Wanke, A. Quattrone (2005) A Loss-of-function Mutation in the α
Subunit of Nav 1.1 Sodium Channel Causes Familial Pure Febrile
Seizures. Proceedings of the National Academy of Sciences USA (in press).
Srairi-Abid N., J.I.
Guijarro, R.B. Khalifa, M. Mantegazza, A. Cheikh, M.B. Aissa, P.Y. Haumont, M.
Delepierre and M. El Ayeb (2005) A new type of scorpion Na+-channel
toxin like polypeptide active on K+ channels. Biochemistry Journal, 388(2):455-464.
Mantegazza M., F.H. Yu, A.J.
Powell, J.J. Clare, W.A. Catterall, T. Scheuer (2005). Molecular Determinants
for Modulation of Persistent Sodium Current by G Protein bg Subunits. Journal of Neuroscience,
Mantegazza M., Cestèle S.
(2005). Beta-scorpion toxin effects suggest electrostatic interactions in
domain II of voltage-dependent sodium channels. Journal of Physiology, 568(1):13-30.
Curia G., P. Aracri, G. Sancini, M. Mantegazza, G. Avanzini, S.
Franceschetti (2004). PKC-dependent
phosphorilation modulates the effect of the antiepileptic drug Topiramate on
the persistent fraction of sodium currents. Neuroscience,
Epilepsy Clinic and Experimental Neurophysiology
ph. +39 02/23942242, fax +39 02/7060775, email: email@example.com
Expertise and current research
performed: the Epilepsy Clinic and Experimental
Neurophysiology Unit of INNCB is
internationally recognized as
a centre of excellence for the studies of the basic mechanisms of neurological
diseases. The unit is devoted to study epilepsies from bench to bad side and
particularly addressed to investigate the pathogenesis and physiopathology of
epileptogenic malformations of cortical development in human and animal models.
Five dedicated beds for epileptic patients (two equipped for prolonged
Video-EEG monitoring), fully equipped laboratories for neuroanatomy and
experimental neurophysiology are part of the unit. The unit is operating at
clinical and research level in synergy with the Epilepsy Surgery Centre at the Niguarda Hospital
in Milan. The unit is currently involved in the following research projects: 1)
diagnostic pre-surgical assessment and surgical guidelines for drug resistant
epileptic patients candidates for epilepsy surgery (leader of a multicenter
Italian group supported by the National Ministry of Health); 2) Mesial temporal
lobe epilepsy with and without hippocampal sclerosis: electroclinical features,
prognosis and pathogenetic mechanisms (supported by Italian Ministry of
research); 3) Role of gap junctions in infantile epilepsy and disorders of
cortical development (leader of a multicenter project sponsored by Mariani
Foundation). The unit is also involved in identification, classification and
morphofunctional correlations of malformations of cortical development in
Facilities/Equipment: five beds for epileptic patients; two of which equipped for continuous
Video-EEG monitoring (Micromed equipment). Two fully equipped anatomy labs for
routine anatomy, neuropathology, immunocytochemistry, in situ hybridization.
Two fully equipped labs for experimental neurophysiology. In addition at the
INNCB the following facilities are available: animal housing, two confocal
microscopes, laser dissecting microscope, two electron microscope, molecular
Personnel involved in the
investigator: Roberto Spreafico (M), MD,
PhD. Chief of the Epilepsy Clinic and Experimental Neurophysiology Unit;
appointed as Scientific Vice-Director of the INNCB, Milan. Camillo Golgi Award for Neuroanatomy
from the National Academy of Lincei received in1985. Invited professor of
Anatomy and Physiology at the University
of North Carolina, professor of
Anatomy and Physiology at the University
of Milan. Scientific
interests: basic to clinical neuroscience with particular focus on the
thalamo-cortical system and on developmental neuropathology and epilepsy.
Carolina Frassoni (F), degree in Biology, interest on
developmental biology, neuroanatomy, epilepsy. Rita Garbelli (F), Phd in Biology, interest on neurobiology,
epilepsy, electron microscopy. Maria Cristina
Regondi (F), technician. Flavio Villani (M), MD and specialist in
Neurology, interest on epilepsy, pre-surgical investigation, sleep disorder.
de Curtis (M). MD, Head of Laboratory of System
Physiology. Associate-Head Epilepsy Clinic and
Experimental Neurophysiology Unit. 1988-1991: Assistant Researcher Dept.
Physiology, New York University; 1997/98: Visiting scientist ETL, Tsukuba, Japan.
1999: Michael International Price. Italian MinSan grants 1992-2005; HFSPO grant
(1996-1999); EC grant VSAMUEL (1999-2002); sub-contractor EC grant LEUCHRON. Director
of Advanced International Courses Bridging
clinical with experimental epileptology 1 and 2, Venice, Italy
(2002 and 2005). Research interest: clinical and experimental neurophysiology and epileptology.
Laura Uva (F). Doctoral Degree in Biology; PhD student; Associate
Researcher; working in the field of animal models and neurophysiology since
2001. Research interests: neurophysiology; involved in experimental activities
on acute models of ictogenesis and in chronic animal models of epilepsy
(pilocarpine and PTZ-LPS). Giorgio Battaglia (M) MD. Head of the Molecular Neuroanatomy
Laboratory and Associate Professor in Clinical Epileptology in the Epilepsy Center. Research Associate at the University of North Carolina
at Chapel Hill; Secretary of the ILAE
(International League against Epilepsy) Neurophysiology subcommittee.
Scientific interest: clinical and experimental epileptology, clinical, genetic,
and neuropathologic features of human cerebral dysgeneses, neurogenesis and
epileptogenesis in cerebral heterotopia of experimental animals, motor neuron
degeneration, pathogenetic role of the Survival Motor Neuron protein in Spinal
Muscular Atrophy. Tiziana Granata, (F) MD: Associated in Child Neurology at the INNCB. MD degree (1985);
Speciality Board in Child Neurology (1989), she is working in the field of
clinical epileptology. Professional expertises and research interest: epilepsy
in childhood, with particular interest in early onset seizures and in epileptic
disorders resulting from progressive encephalopathy, from malformation of
cortical development and from brain inflammation. Franco Taroni (M) MD. Postdoctoral studies in the Department of Human Genetics, Yale University.
Head of the Laboratory of Molecular and Cellular Pathology at the INNCB, Milan. Appointed professor
of Neurogenetics, Postdoctoral School of Medical Genetics, University of Milan.
Research interests: genetic and molecular bases of several hereditary
neurological disorders including mitochondrial Beta-oxidation defects,
peripheral neuropathies, spastic paraplegias, spinocerebellar ataxias, and
cortical dysplasias. Giorgio Lo Russo, (M) MD Head of the “C.Munari” Center for epilepsy Surgery, Niguarda, Milan. Working in the same
institution since 1993. Researcher at the Neurosurgical department, University
of Torino, Italy (1980-1993), Assistant Professor at the Neurosurgical Unit,
Hôpital S.te Anne, Paris (1989-1993) Research Interest: Epilepsy surgery and
cerebral dysplasia. Laura Tassi, (F) MD Diplome d’Etudes Approfondies,
Neuroscience, University of Lyon,
Stages at INSERM Unit-Service de Neurochirurgie, Hôpital Ste. Anne-Paris
(1989-1990) and at Stage at Neurological Clinic of thr Grenoble University,
Neurosurgery Clinic, INSERM, Grenoble (1990); Neurological
Clinic-Grenoble-France (1990-1994) assistant at Neurosurgical Department
Niguarda Hospital, Milan (1990-present). Research Interest: Epilepsy surgery
and cerebral dysplasia.
One PhD student to
Recent relevant publications/patents
Alonso-Nanclares L., Garbelli R., Sola RG., Pastor J.,
Tassi L., Spreafico R., DeFelipe J. (2005) Microanatomy of the dysplastic
neocortex from epileptic patients. Brain 128: 158-173.
Tassi L., Colombo N., Cossu M., Mai R., Francione S.,
Lo Russo G., Galli C., Bramerio M., Battaglia G., Garbelli R., Meroni
A., Spreafico R. (2005) Electroclinical, MRI and neuropathological study
of 10 patients with nodular heterotopia, with surgical outcomes. Brain 128:
Majores M., Blumcke I., Urbach H., Meroni A., Hans V.,
Holthausen H., Elger CE., Schramm J., Galli C., Spreafico R., Wiestler OD.,
Becker AJ. (2005) Distinct allelic variants of TSC1 and TSC2 in epilepsy-
associated cortical malformations without balloon cells. J Neuropathol Exp
Neurol 64(7): 629-637.
Palmini A., Najm I., Avanzini G., Babb T., Guerrini
R., Foldvary-Schaefer N., Jackson G., Luders HO., Prayson R., Spreafico R.,
Vinters H.V. (2004) Terminology and classification of the cortical dysplasias.
Neurology 62 suppl 3: 2-8.
Mai R., Tassi L., Cossu N., Francione S., Lo Russo G., Garbelli
R., Ferrario A., Galli C., Taroni F., Citterio A., Spreafico R. (2003) A
neuropathological, stereo-EEG and MRI study of subcortical band heterotopia. Neurology 60: 1834-1838.