Clinical Neuroscience

Carlo Ferrarese
Carlo Ferrarese Email: clinical@neuromi.it
The research activity of the Clinical Neuroscience Area spans from clinical to neurobiological and psychosocial issues in the fields of Neurology, Neurosurgery, Neurotology, Maxillo-facial Surgery, Psychiatry, Child Neuropsychiatry, Geriatric Medicine and Neurorehabilitation. Clinical and translational studies are performed on patients, animal and cellular models of diseases to elucidate the mechanisms involved in the pathophysiology of neurologic and mental disease at the molecular, cellular and system levels, and to translate these findings into clinical diagnosis, treatment and prevention strategies. Genetic and epidemiological studies are performed in large cohorts of patients, in collaborations with international networks.

Neurologists are studying mechanisms of neurodegenerative processes, focused on glutamate excitotoxicity, oxidative stress, the amyloid cascade and vascular damage in the brain. These phenomena are studied in both central and peripheral human models, with the aim to identify molecular markers of disease and to test possible pharmacological interventions. In parallel, neuropsychological and imaging projects are carried out for a better characterization of neurodegenerative disorders (typical and atypical dementias and mild cognitive impairment, Parkinson’s disease and amyotrophic lateral sclerosis), and for the development of accurate diagnostic tools (with a special interest for Positron Emission Tomography tracers and non conventional MR imaging).
Other projects concern the epigenetics and genetics of neurological diseases: the international ‘Genetic epidemiology of Parkinson disease’ project; a screening study of mutations of ion channels HCN in idiopathic epilepsy; a regional project for the study and clinical management of cerebrovascular diseases with monogenic inheritance; an international study of genetic determinants of cervical artery dissections (CADISP); a national study on molecular variants of mannose-binding lectin (MBL) haplotypes and their association with stroke severity.
Phase II and III trials are ongoing in patients with Alzheimer’s disease and mild cognitive impairment, multiple sclerosis and stroke. A multi-national observational registry on acute stroke recanalization therapies is ongoing since 2005, and a translational research programme of experimental neurology and neurosurgery using rat models of focal cerebral ischemia and intracerebral haemorrhage is being carried out since 2011. International, multicentric clinical trials on chemotherapy-induced peripheral neurotoxicity are coordinated by researchers of this area, but interest is also focused on metabolic, inflammatory and inherited neuropathies.

The main areas of research for Neurosurgeons are neurooncology, with studies on molecular and genetic aspects and immunological treatment of high grade gliomas in murine models, Deep Brain Stimulation in movement disorders, cerebrovascular disease, in particular for the identification of novel diagnostic and therapeutic methods for vasospasm in subarachnoid haemorrhage, miniinvasive surgical techniques for the treatment of craniofacial and craniovertebral junction malformations and neuroendoscopy for pediatric hydrocephalus and neural tube defects.

Child Neuropsychiatrists are working on other neurological disorders or neurological aspects of various pediatric on cerebral palsy, autism spectrum diseases or chromosomal and genetic abnormalities. The Child Neuropsychiatry department is member of the Italian Group for Children’s Cerebral Palsy and part of the World Children and Adolescent Headache Project. Furthermore, it is involved in a multicenter international study on correlations between psychomotor/cognitive development and functioning of the nervous system in Down syndrome.
The section is also member of the regional groups for the preparation of guidelines for pediatric emergencies and for the diagnosis and therapy of bipolar disorder in children and adolescents, and is participating to projects for the treatment of learning disorders funded by Regione Lombardia. One such studies is focused on the evaluation of efficacy of a novel technique, a hearing-perceptive training, in pre-school children with specific language disorders. Finally, Child Neuropsychiatry specialists are interested in a fine-grained psychopathological description of developmental profile of premature babies, along with the dynamics of couples whose children are affected by psychiatric disorders, and with the clinical endophenotypes and possible biological correlates of anorexia nervosa and borderline personality.

Neurorehabilitation specialists are working on neuromotor, neuropsychological and physical rehabilitation projects.
A motion-capture tool is available for studies on treatment of movement dysfunctions (eg. low back pain) and paretic hand. The neuropsychological research spans from the use of Transcranial Direct Current stimulation for the improvement of focal deficits like apraxia and hemianopia, to the use of specific operative strategies like the Constrain Induced Aphasia Therapy. The Neurorehabiliation cognitive unit is also involved in a multicentric project of the Italian Neurorehabilitation Society on rehabilitation of neglect, and in studies on posttraumatic psychological and behavioral sequelae. Finally, the section is also active in studying vegetative and minimal conscience states, in particular for the scheduling of procedures for respiratory and swallowing problems.

Psychiatry Researchers are working on specific aspects of psychiatric disorders, such as social cognition in schizophrenia, correlations between personality and mood disorders, or impact of severe mental disorders on family members. Moreover, they investigate the psychopathological implications of various medical conditions (HIV, hepatic disorders, pregnancy, Alzheimer’s disease), with the final aim to elaborate new diagnostic instruments, plan adequate psychosocial interventions, and identify predictors of outcome..
A major area of interest of Psychiatrists is also addiction. They are partners of the ‘Addiction Psychiatry’ section of the Italian Society of Psychiatry and of the International Society of Addiction Medicine, and are involved in multicenter national (PADDI; ARIANNA) and international (ORION) projects aimed at prevention of addiction in young population. Moreover, they are involved in three innovative regional plans in the areas of adolescence psychopathology, jail mental health and professional reintegration of patients with severe psychiatric disorders.

Geriatricians are dedicated to clinical and epidemiological research on elderly patients, focusing especially on geriatric cognitive syndromes such as delirium, Alzheimer’s disease and other dementias. Special attention has been devoted to the development of an electronic Minimum Data Set, which includes more than a thousand patients and represents a valid instrument for epidemiological research and internal audit. The outpatients Psychogeriatrics service and Alzheimer Evaluation Unit are currently taking care of about one thousand patients for treatment, follow-up and research purposes. Delirium is widely investigated, in collaboration with national and international research groups, and the Italian version of a new instrument for the screening of delirium was recently validated in collaboration with the University of Cambridge, the Centre for Cognitive Ageing and Cognitive Epidemiology of Edinburgh, and the Edinburgh Delirium Research Group (UK). The role of amyloid burden in patients developing delirium after hip fracture will be investigated in a multicenter study involving 18-Flutemetamol PETscan, MRI, EEG and clinical assessments.

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