Neurophysiopathology and epileptology

Description

The team carries out its research activity in the Clinical Neurophysiology Unit, which was established at the Institute “La Nostra Famiglia” Bosisio Parini, even before the foundation of the IRCCS "E. Medea".

From the outset it has been dealing with: 1) Clinical-diagnostic and rehabilitative activity for patients with Epilepsy. 2) Electroencephalographic diagnostic activity, even in prolonged monitoring (Ambulatory-EEG and video-polygraphic recordings). 3) Research on childhood epileptology.

The Unit has progressively expanded its expertise in clinical neurophysiology, also dealing with electromyography, evoked potential and differential diagnosis of paroxysmal phenomena also in the adult age.

Referring to the patients’ number, the level of diagnostic performances and the load of patients followed, the Unit has been included in the Network of Epilepsy Centers of the Lombardy Region (EpiNetwork) as a third level center for infancy and second level for adulthood.

At the moment over 1800 patients are followed, mainly children and adolescents with symptomatic epilepsies, usually followed for rehabilitation therapies at the Recovery Units and the Rehabilitation Centers of IRCCS Medea.

Research activity:

Current (RC) and Finalized Researches (RF) with Health Ministry grants has always focused on three main issues:

1. Synthetic and cryptogenic focal epilepsy, particularly:
   Classification and neuropsychological functional aspects (RC 1986, 1987, 1988), correlations between electroclinical features and structural abnormalities (RC 1990), age-dependent expressions (RC 1991), infantile epileptic encephalopathies symptomatic of cerebral malformations (RC 1996, 1997), neurophysiological aspects in epilepsy associated with channelopathies (RC 2006, 2007, 2008), simultaneous analysis of EEG and f-MRI signals (RC 2015, 2016, 2017).

2. Atypical Forms of Generalized Idiopathic Epilepsy and Generalized Cryptogenic Epilepsy, particularly:
   Atypical Forms of Epilepsy Absence of Infancy (RC 1993, 1995), photosensitivity as a genetic tract (RC 1994).

3. Cryptogenic epileptic seizures associated with neurologic damage: neuroradiologic, molecular and cytogenetic, clinical neurophysiological aspects (RC 2008, 2009, 2010, 2011, 2012, 2013).

4. Drug resistant epilepsies particularly:
   Neurochemical markers (RF 1993, 1997), early definition and neurosurgery indications (RF 1998), predictive electroclinical criteria (RC 2001, 2002, 2003), pharmacogenomic bases (RF 2003), observational studies on efficacy and tolerability of antiepileptic therapies (2016-2017).

Research with Health Ministry grants have also been carried out on more general clinical neurophysiology issues such as: analysis of clinical neurophysiology standards in different developmental abnormalities (RC 1987, RC 1988), study of clinical neurophysiogical aspects of language developmental abnormalities (RC 1998), EEG and evoked potential studies in patients with brain injuries (sub-acute and chronic outcome), myoclonus studies in epileptic and non-epileptic encephalopathies.

The Unit has carried on research programs with other grants in collaboration with:

• a) University Institutes and other IRRCS: “Università dell'Insubria di Varese” (study of neuropsychological aspects in children with idiopathic or cryptogenic epilepsy). Faculty of Engineering of Milan and Lecco “Politecnico” (Automatic EEG spontaneous and evoked signal analysis-Simultaneous EEG and f-MRI signal analysis). IRCCS "M. Negri " in Milan (epidemiological study on Epilepsy in Lecco’s district).
• b) Italian League Against Epilepsy (LICE): The Unit participated in the EPISCREEN research project providing data of 650 patients and over 2300 clinical reports. It also participates in the LICE study groups on genetics of epilepsy, neuropsychology and epilepsy and pregnancy.
• c) European Union: The Unit participated in a study on the clinical neurophysiology and genetic aspects of Alternating Hemiplegia of Childhood included in the EC's Sixth Framework Program (2005-2007). He was Associated Partner of the European Network of Expertise for Rare Pediatric Neurological Diseases – (NEUROPED) co-funded by the EU under the Public Health Program 2007-2010.
• d) International Partners: is a member of the International Research Consortium (IAHCRC) for the Research on Alternative Hemiplegia of Childhood and other ATP1A3-related diseases

In addition, controlled trials (Phase IIIb / IV) and clinical trials on the use, tolerability, and efficacy of antiepileptic drugs have been performed.

Selected publications (since 2015)

• Giussani G, Bianchi E, Canelli V, Erba G, Franchi C, Nobili A, Sander JW, Beghi E; EPIRES Group. Antiepileptic drug discontinuation by people with epilepsy in the general population. Epilepsia. 2017 Sep;58(9):1524-1532.
• Garavelli L, Ivanovski I, Caraffi SG, Santodirocco D, Pollazzon M, Cordelli DM, Abdalla E, Accorsi P, Adam MP, Baldo C, Bayat A, Belligni E, Bonvicini F, Breckpot J, Callewaert B, Cocchi G, Cuturilo G, Devriendt K, Dinulos MB, Djuric O, Epifanio R, Faravelli F, Formisano D, Giordano L, Grasso M, Grønborg S, Iodice A, Iughetti L, Lacombe D, Maggi M, Malbora B, Mammi I, Moutton S, Møller R, Muschke P, Napoli M, Pantaleoni C, Pascarella R, Pellicciari A, Poch-Olive ML, Raviglione F, Rivieri F, Russo C, Savasta S, Scarano G, Selicorni A, Silengo M,Sorge G, Tarani L, Tone LG, Toutain A, Trimouille A, Valera ET, Vergano SS, Zanotta N, Zollino M, Dobyns WB, Paciorkowski AR. Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients. Genet Med. 2017 Jun;19(6):691-700.
• Bonanni P, Negrin S, Volzone A, Zanotta N, Epifanio R, Zucca C, Osanni E, Petacchi E, Fabbro F. Electrical status epilepticus during sleep in Mowat-Wilson syndrome. Brain Dev. 2017 Oct;39(9):727-734.
• Giussani G, Canelli V, Bianchi E, Erba G, Franchi C, Nobili A, Sander JW, Beghi E; EPIRES Group. Long-term prognosis of epilepsy, prognostic patterns and drug resistance: a population-based study. Eur J Neurol. 2016 Jul;23(7):1218-27.
• Maggioni E, Zucca C, Reni G, Cerutti S, Triulzi FM, Bianchi AM, Arrigoni F. Investigation of the electrophysiological correlates of negative BOLD response during intermittent photic stimulation: An EEG-fMRI study. Hum Brain Mapp. 2016 Jun;37(6):2247-62.
• Strazzer S, Pozzi M, Avantaggiato P, Zanotta N, Epifanio R, Beretta E, Formica F, Locatelli F, Galbiati S, Clementi E, Zucca C. Late Post-traumatic Epilepsy in  Children and Young Adults: Impropriety of Long-Term Antiepileptic Prophylaxis and Risks in Tapering. Paediatr Drugs. 2016 Jun;18(3):235-42.
• Coelli S, Sclocco R, Barbieri R, Reni G, Zucca C, Bianchi AM EEG-based index  for engagement level monitoring during sustained attention. Conf Proc IEEE Eng Med Biol Soc. 2015 Aug;2015:1512-5.
• Giussani G, Canelli V, Bianchi E, Franchi C, Nobili A, Erba G, Beghi E; EPIRES Group. A population-based study of active and drug-resistant epilepsies in Northern Italy. Epilepsy Behav. 2016 Feb;55:30-7.
• Bonaglia MC, Zanotta N, Giorda R, D'Angelo G, Zucca C. Long-term follow-up of a patient with 5q31.3 microdeletion syndrome and the smallest de novo 5q31.2q31.3 deletion involving PURA. Mol Cytogenet. 2015 Nov 14;8:89.
• Panagiotakaki E, De Grandis E, Stagnaro M, Heinzen EL, Fons C, Sisodiya S, de Vries B, Goubau C, Weckhuysen S, Kemlink D, Scheffer I, Lesca G, Rabilloud M, Klich A, Ramirez-Camacho A, Ulate-Campos A, Campistol J, Giannotta M, Moutard ML, Doummar D, Hubsch-Bonneaud C, Jaffer F, Cross H, Gurrieri F, Tiziano D, Nevsimalova S, Nicole S, Neville B, van den Maagdenberg AM, Mikati M, Goldstein DB, Vavassori R, Arzimanoglou A; Italian IBAHC Consortium; French AHC Consortium; International AHC Consortium. Clinical profile of patients with ATP1A3 mutations  in Alternating Hemiplegia of Childhood-a study of 155 patients. Orphanet J Rare Dis. 2015 Sep 26;10:123.
• Jaffer F, Avbersek A, Vavassori R, Fons C, Campistol J, Stagnaro M, De Grandis E, Veneselli E, Rosewich H, Gianotta M, Zucca C, Ragona F, Granata T, Nardocci N, Mikati M, Helseth AR, Boelman C, Minassian BA, Johns S, Garry SI, Scheffer IE, Gourfinkel-An I, Carrilho I, Aylett SE, Parton M, Hanna MG, Houlden  H, Neville B, Kurian MA, Novy J, Sander JW, Lambiase PD, Behr ER, Schyns T, Arzimanoglou A, Cross JH, Kaski JP, Sisodiya SM. Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype. Brain. 2015 Oct;138(Pt 10):2859-74.
• Maggioni E, Molteni E, Zucca C, Reni G, Cerutti S, Triulzi FM, Arrigoni F, Bianchi AM. Investigation of negative BOLD responses in human brain through NIRS technique. A visual stimulation study. Neuroimage. 2015 Mar;108:410-22.