Neurological Practice

Clinical Neurophysiology offers a series of diagnostic investigations essential to a wide range of pathologies affecting the Central and Peripheral Nervous System and the Skeletal Muscle, from the state of "brain death" to trauma of the peripheral nerve, from epilepsies to amyotrophic lateral sclerosis (ALS), from encephalitis to muscular dystrophies.

The best known methods, but not the only ones, are Electroencephalography (EEG), Electromyography / Electroneurography (EMG / ENG) and Cerebral Evoked Potentials (PE).

Our Laboratory, one of the first in Italy, has been active since 1952 and was completely innovated from a technical point of view around 1990, then renovated in 2010. We have numerous equipment for "routine" investigations, alongside other more sophisticated ones, dedicated to applied scientific research. The field we have developed most is that of Transcranial Magnetic Stimulation (TMS).

The Laboratory is open to anyone who wants to learn or apply neurophysiological techniques in clinical practice and in research.

Research staff

• Prof. R. Cantello, Director of Neurological Practice
• Dr. C. Varrasi, Medical Director
• P.Badano, E. Brigatti, G. Cassani, E. Ragazzo, D. Sozzani; Neurophysiopathology technicians

Research Activity

Traditionally, the Laboratory has developed studies on the applications of TMS to neurological diseases. Of particular scientific interest is the first description of the so-called "Cortical silent period" and its alterations in Parkinson's disease. It is a neurophysiological variable that allows us to study the neuronal inhibition of the primary motor cortex (Cantello et al., 1991,1992).

Research on cortical inhibition in epilepsies and in certain sleep pathologies is also much cited in the international literature.

In the field of epilepsy, we highlighted the importance of TMS as a means of measuring cortical excitability. For example, our work demonstrates how cortical excitability is pathologically increased in at least one third of patients with the first diagnosis of partial epilepsy, never treated with antiepileptics (Varrasi et al., 2004). This result paves the way for a more extensive use of TMS in epilepsy, with the prospect of correlating the trend of cortical excitability to the effect of antiepileptic therapies.

As part of the study of the sleep-wake rhythm and sleep pathologies, we have described the changes in cortical excitability resulting from sleep deprivation in the normal subject (Civardi et al., 2001).

Lately, our interest has focused on neural inhibition in the visual system and on the alterations observed in patients with photosensitive epilepsies. In these studies, the method of investigation is that of visual PE from pairs of flashes ("paired-pulse flash-visual evoked potentials") (Cantello et al., 2011). 

References

• Cantello R, Gianelli M, Civardi C, Mutani R. Magnetic brain stimulation: the silent period after the motor evoked potential. Neurology. 1992;42:1951-9.
• Cantello R, Gianelli M, Bettucci D, Civardi C, De Angelis MS, Mutani R. Parkinson's disease rigidity: magnetic motor evoked potentials in a small hand muscle. Neurology. 1991;41:1449-56.
• Varrasi C, Civardi C, Boccagni C, Cecchin M, Vicentini R, Monaco F, Cantello R. Cortical excitability in drug-naive patients with partial epilepsy: a cross-sectional study. Neurology 2004;63:2051-55.
• Civardi C, Boccagni C, Vicentini R, Bolamperti L, Tarletti R, Varrasi C, Monaco F, Cantello R. Cortical excitability and sleep deprivation: a transcranial magnetic stimulation study. J Neurol Neurosurg Psychiatry. 2001;71:809-12.
• Cantello R, Strigaro G, Prandi P, Varrasi C, Mula M, Monaco F. Paired-pulse flash-visual evoked potentials : new methods revive an old test. Clin Neurophysiol 2011;122(8):1622-

Scientific Research collaborations

• Università di Siena, Dipartimento di Neuroscienze, Sezione Neurologia (Dr Simone Rossi)
• Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA, USA; Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. (Dr. Erica Bae, Prof. Alvaro Pascual-Leone, Dr. Alex Rotenberg)
• Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London. (Prof. John C. Rothwell)
• Department of Neurology, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, University of Melbourne, Victoria, Australia; Brain Research Institute, Florey Neuroscience Institutes Heidelberg West, Victoria, Australia. (Dr. Radwa A. Badawy)

"Top five papers from the Laboratory”

• Cantello R, Gianelli M, Civardi C, Mutani R. Magnetic brain stimulation: the silent period after the motor evoked potential. Neurology. 1992;42:1951-9.
• Cantello R, Gianelli M, Bettucci D, Civardi C, De Angelis MS, Mutani R. Parkinson's disease rigidity: magnetic motor evoked potentials in a small hand muscle. Neurology. 1991;41:1449-56.
• Civardi C, Cantello R, Asselman P, Rothwell JC. Transcranial magnetic stimulation can be used to test connections to primary motor areas from frontal and medial cortex in humans. Neuroimage 2001; 14: 1444-53.
• Cantello R, Tarletti R, Civardi C. Transcranial magnetic stimulation and Parkinson's disease. Brain Res Brain Res Rev. 2002;38:309-27.
• Civardi C, Vicentini R, Cavalli A, Naldi P,Varrasi C, Cantello R. Hemispheric asymmetries of cortico-cortical connections in human hand motor areas. Clin Neurophysiol 2000;111: 624-629.

The Multiple Sclerosis Center (MS) of Novara, opened in 2000, aims to provide a complete and multidisciplinary service dedicated to the diagnosis and treatment of patients with multiple sclerosis and other demyelinating diseases. Our goal is to minimize hospitalisation of the patient, allowing the patient to stay in his/her daily environment as much as possible.

The Center provides a therapeutic Day Hospital, Day Service, neurological and neuropsychology specialist clinic. Patients are admitted via a dedicated telephone line, active 5 days a week (with about 130 phone calls in 5 days), which allows us not only to manage appointments, but also to provide information on symptoms and therapies, reducing the number of outpatient visits. Furthermore, the Center directly manages all the multidisciplinary consultations required in the diagnosis and treatment of demyelinating diseases.

Research Staff

• Dr. M. Leone (Centre Manager), Dr.ssa P. Naldi; Medical Managers
• Prof. C. Comi; Medical Director and University Professor

Research Activity

The research activity is mainly aimed at the epidemiology of demyelinating diseases. The Center manages the MS Registry in the Province of Novara, which includes about 350 patients, and a clinical database including another 450 patients.

The main lines of research in progress are:

Characterisation of the course and prognosis of MS

In this field we have studied the clinical features that determine the severity of MS relapses and the possibility of residual damage.

Search for new genes implicated in the susceptibility and course of MS.

In collaboration with the Genetics Laboratory of the Department of Medical Sciences of the University of Eastern Piedmont (directed by Prof. S. D'Alfonso) and with the S. Raffaele Institute (Milan), numerous studies are underway aimed at identifying new genes implicated in the susceptibility and course of the disease. In particular, we have promoted the Italian multicentre study PROGEMUS (PROgnostic GEnetic factors in Multiple Sclerosis) which has allowed us to recruit more than 1,600 patients so far.

Our Centre participated in an international research consortium (International Multiple Sclerosis Genetics Consortium) which recently published a study in the journal Nature (Nature 2011; 476: 214-9): 29 new genetic variants associated with MS, mostly related to the immune system.

We participated in the design and development of an Italian prospective multicentre study (GERONIMUS) which followed 180 patients with MS for five years and evaluated the influence of clinical and psychological factors on the progress of the disease.

Search for immunological markers implicated in the course of MS.

Our Centre collaborates with the Immunology Laboratory (directed by Prof. U. Dianzani) of the Department of Medical Sciences of the University of Eastern Piedmont for the study of some markers (FAS, osteopontin) involved in the inflammatory and degenerative process of MS to evaluate their possible influence on the course of the disease.

Clinical research of MS.

The Centre participates in therapeutic multicentre trials and observational studies. 

References

• Comi C, Leone M, Bonissoni, DeFranco S, Bottarel F, Mezzatesta C, Chiocchetti A, Perla F, Monaco F, Dianzani U. Defective T cell fas function in patients with multiple sclerosis. Neurology 2000:55;921-927.

• Leone MA, Bonissoni S, Collimedaglia L, Tesser F, Calzoni S, Stecco A, Naldi P, Monaco F. Factors predicting incomplete recovery from relapses in multiple sclerosis: a prospective study. Mult Scler 2008;14:485-493.

• Bergamaschi L, Ban M, Barizzone N, Leone M, Ferrante D, Fasano ME, Guerini FR, Corrado L, Naldi P, Dametto E, Agliardi C, Salvetti M, Mechelli R, Galimberti D, Scarpini E, Cavalla P, Bargiggia V, Caputo D, Cordera S, Monaco F, Momigliano-Richiardi P, D'Alfonso S. Association of HLA class I markers with multiple sclerosis in the Italian and UK population: evidence of two independent protective effects. J Med Genet. 2011;48:485-92.

• Naldi P, Collimedaglia L, Vecchio D, Rosso MG, Perla F, Stecco A, Monaco F, Leone MA. Predictors of attack severity and duration in multiple sclerosis: a prospective study. Open Neurol J. 2011;5:75-82.

• Bergamaschi L, Leone MA, Fasano ME, Guerini FR, Ferrante D, Bolognesi E, Barizzone N, Corrado L, Naldi P, Agliardi C, Dametto E, Salvetti M, Visconti A, Galimberti D, Scarpini E, Vercellino M, Bergamaschi R, Monaco F, Caputo D, Momigliano-Richiardi P, D'Alfonso S. HLA-class I markers and multiple sclerosis susceptibility in the Italian population. Genes Immun. 2010;11:173-80.

Scientific Research Partnerships

The Center belongs to IRCAD (Interdisciplinary Research Centre for Autoimmune Diseases) - Novara of the "Amedeo Avogadro" University of Eastern Piedmont.

We also collaborate with:

•  Università di Bologna, Dipartimento di Neuroscienze (Prof. Roberto D’Alessandro)
• Laboratorio di Neuroepidemiologia, Istituto Neurologico “C. Besta”, Milano (G. Filippini, A. Solari)
• Dipartimento di Neurologia e Laboratorio di genetica di malattie neurologiche complesse, Istituto di Neurologia Sperimentale INSPE, Ospedale San Raffaele, Milano, (Dr. F. Martinelli-Boneschi)
• Queen Mary University of London, Neuroimmunology Group, Blizard Institute, Centre for Neuroscience and Trauma, Barts and The London School of Medicine and Dentistry, London E1 2AT, United Kingdom (Prof. G. Giovannoni)
• The International Multiple Sclerosis Genetics Consortium: University of Cambridge, Department of Clinical Neurosciences, Addenbrooke’s Hospital, Cambridge, UK. (Prof. D. Sawcer)
• Dipartimento di Neurologia, Università di Minsk, Bielorussia (Prof. A. Fedulov)

Manager

• Dr. Letizia Mazzini; Medical Director

The Regional Amyotrophic Lateral Sclerosis Expert Center (ALS, Resolution of the Regional Council 30 December 2009, n. 27-12969) represents a national and international reference point for the diagnosis, treatment and clinical research of motor neuron diseases. Every year more than 200 new patients, from all the Italian Regions and some neighboring European countries, come to the Centre. The activity is divided into a specialist neurological clinic and a multidisciplinary day service in which all the problems inherent to neurological pathology and related complications are assessed through a preferential network of consultancies. The Centre also carries out consultancy and support activities for NHS doctors, training activities for health workers and volunteers, information for patients and associations on the disease and therapies. The Centre participates in the definition of clinical protocols for the diagnosis and management of treatment and research with the exchange of information with other national and international Centres and organisations

Research Activity

Research on adult stem cells from biological aspects to those of manipulation for therapeutic purposes in ALS represent a topic of great scientific involvement of our Centre. These studies are conducted in collaborations with numerous prestigious national and international research centres, particularly in the United States.

We conducted, in collaboration with the Department of Oncohematology and Cell Therapy of the Regina Margherita Hospital in Turin, the initial phase of study authorized by the Istituto Superiore Sanità with autologous mesenchymal stem cell transplantation in the spinal cord in 10 patients. The results are published in international scientific journals and widely cited.

A phase 1 clinical protocol is currently underway, authorised by the National Institute of Health, which provides for the transplantation of fetal neuronal stem cells in 18 patients with ALS. The study is conducted in collaboration with the Department of Neurosurgery of the Memorial Medical Centre in Atlanta and with the Institute of Biotechnology of the University of Milan-Bicocca.

Another topic of great scientific interest that involves our centre in close collaboration with the Genetics Laboratory of the Department of Medical Sciences of the University of Eastern Piedmont directed by Prof S. D'Alfonso is the search for new genes responsible for the familial form of the disease or that make it more vulnerable or more protected than the sporadic form. We have one of the richest DNA banks in Italy in which 400 fully clinically characterised patient DNA samples are stored. We are also part of international collaborations for the study of the genome. Also in this research area, numerous scientific papers have been published in widely cited international journals.

European research projects are also underway to identify environmental risk factors and we collaborate with regional disease registries. 

References

• Mazzini L, Ferrero I, Luparello V, Rustichelli D, Gunetti M, Mareschi K, Testa L, Stecco A, Tarletti R, Miglioretti M, Fava E, Nasuelli N, Cisari C, Massara M, Vercelli R, Oggioni GD, Carriero A, Cantello R, Monaco F, Fagioli F. Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial. Exp Neurol. 2010 May;223(1):229-37

• Corrado L, Ratti A, Gellera A, Buratti E, Castellotti B, Carlomagno Y, Ticozzi N, Mazzini L, Testa L, Taroni F, Baralle FE, Silani V, D'Alfonso S. High frequency of TARDBP gene mutations in Italian patients with Amyotrophic Lateral Sclerosis. Human Mutation Feb 17, 2009

• Corrado L,Del Bo R, Castellotti B, Ratti A, Cereda C, Penco S, Soraru G, Carlomagno Y, Ghezzi S, Pensato V, Colombrita C, Gagliardi S, Cozzi L, Orsetti V, Mancuso M, Siciliano G, Mazzini L, Comi GP, Gellera C, Ceroni M, D’Alfonso S, Silani V. Mutations of FUS Gene in Sporadic Amyotrophic Lateral Sclerosis J. Med. Genet. 2010 Mar;4 7(3):190-4.

• Chiò A, Calvo A, Moglia C, Mazzini L, Mora G; PARALS study group. Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):740-6

• Mazzini L, Mareschi K, Ferrero I, Miglioretti M, Stecco A, Servo S, Carriero A, Monaco F, Fagioli F. Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: a long-term safety study. Cytotherapy. 2012 Jan;14(1):56-60.

Staff

• Hospital Staff: Dr. F. Roggia, Dr. L. Coppo, Dr. L. Bolamperti.
• Specializing Doctors: Dr. K. Savio, Dr. M. Reggiani

Single-cycle Master's Degree Course in Medicine and Surgery:

• Neurological Semeiotics (III year)
• Neurology (5th year)
• Neurophysiology (5th year)

Bachelor's Degree Courses in Physiotherapy:

• Clinical Neurology
• Neurophysiology

Three-year Degree Course in Nursing Sciences

• Neurology

Three-year degree course in Radiology Technician

• Neurology