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, in collaboration with neuropsychologists, biologists and biotechnologists, are studying mechanisms of neurodegenerative processes, focused on glutamate excitotoxicity, oxidative stress, proteotoxicity and neuroinflammation. 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 translational research lines are focused on ischemic stroke and post-cardiac arrest encephalopathy. Genetic and functional studies on ion channel involvement in epilepsy are also in progress. Phase II and III trials are ongoing in patients with Alzheimer’s disease and mild cognitive impairment, multiple sclerosis and stroke. Ongoing international and national projects include: ‘Genetic epidemiology of Parkinson disease’, ‘New frontiers of engineered nanovectors to improve treatment efficacy and safety in neurological disorders (NEVERMIND)’, ‘Multi-center Translational trial of Remote Ischemic Conditioning in acute ischemic Stroke (TRICS). A collaborative study from the Italian Stroke Organization (ISO) Basic Science network’, ‘Brain cholesterol transport mechanisms: potential new targets in Alzheimer’s disease (AGAINST-AD)’, ‘Head Down Tilt 15° as a COLLATERAL therapeutic in acute ischemic Stroke (HDT15° COLLATERALS)’, ‘Selective cerebrospinal fluid hypothermia: bioengineering development and in vivo study of an intraVentricular COOLing device for acute stroke therapy (V-COOL)’, SUPER-refractory status epilepticus after CArdiac arrest: aggressive Treatment guided by multimodal prognostic indicators (SUPER-CAT)’, ‘Epileptogenic encephalopathies and complex generalized epilepsies of infancy: NGS analysis and functional characterization of novel causative variants for an efficient diagnosis and a personalized treatment’.

The main areas of research for Neurosurgeons are neuro-oncology with studies on 1. the molecular and genetic aspects of high grade gliomas in vitro and in murine models by the development of glioma cells lines from glioblastoma patients and 2. studies of the neurocognitive functions architecture via human direct brain mapping during surgery as well as 3. studies on the pre and post-operative neuropsychological involvement of brain tumor patients with the integration of advanced anatomical and functional neuroimaging tools. Other areas of research interest are cerebrovascular diseases, in particular for the identification of novel diagnostic and therapeutic methods for vasospasm in subarachnoid haemorrhage, minimally invasive surgical techniques for the treatment of craniofacial and craniovertebral junction malformations and validation of intraoperative brain and spine ultrasound for brain tumor and vascular surgery.

Otolaryngology researchers are focused on distinct areas of interest. We are dedicated to head and neck oncology, in particular, relevant international collaborations have been developed in order to investigate epidemiology, etiology and risk factors for head and neck cancer. Pediatric otolaryngologists are especially concentrated on neonatal airway diseases, management of pediatric sleep apnea syndrome, treatment of juvenile recurrent parotitis, PFAPA syndrome, thyroglossal duct cysts and laryngopharyngeal reflux. Regarding voice and swallow disorders we are investigating dysphagia after thyroid surgeries and dysphonia in elderly. With respect to otologic disorders the attention is mainly focused on intratympanic treatment for sudden deafness; in sinonasal areas, we are concentrated on studying nasal polyps. Recently, we have introduced a novel research on olfactory and gustatory dysfunctions in patients with SARS-Cov-2 infection.

The main areas of activity of Maxillofacial surgery are aimed at the study and treatment of head and neck tumors with collaborations with specialties such as ENT, Neurosurgery, Pathology and others. In particular, the maxillofacial group has developed microsurgical reconstructive methods with a strong commitment to the evolution of 3D CAD CAM technology and Surgical Navigation, implementing the experience by promoting technological development. Another important field of scientific interest are craniofacial malformations such as craniosynostosis, craniofacial synostosis, facial microsomia, and all the rare craniofacial malformation pathology. Collaborations with other specialties are numerous. The group is included in the European Reference Networks for rare and complex diseases (ERN) in particular for the study and treatment of craniofacial malformations. Strong interest is the study and development of distraction osteogenesis techniques for the treatment of Obstructive Sleep Apnea (OSAS) in adults, but in particular in children with application of the method even in newborns with severe respiratory problems due especially to malformations.

Psychiatry Researchers are working on clinical and biological correlates of severe mental disorders, with special focus on the characterization of different mental disorders in terms of diagnosis, prognosis, clinical course, and response to treatment. The research group has special expertise in conducting observational and clinical studies. They also carry out systematic reviews and meta-analyses, based on both PRISMA and MOOSE guidelines. Main mental disorders of interest are schizophrenia spectrum, bipolar and major depressive disorders, as well as related clinical features, including suicidal and aggressive behaviors and co-occurring substance use disorders. Additional research fields include Social and Community Psychiatry, Psychiatric Epidemiology using also publicly available large dataset, and E-Health in addictive disorders. More recently, and jointly with the Department of Informatics, Systems, and Communication (DISCo) of University of Milano Bicocca, exploiting the innovative use of big data, they have been implementing mental health surveillance research projects, using data from social media such as Twitter. In addition, they collaborate effectively with the Division of Psychiatry of University College London, being also involved in the European Schizophrenia Cohort (EuroSC) project. The research group is currently involved in other several European and National research projects. These include, among others, the EU-VIORMED (EUropean Study on VIOlence Risk and MEntal Disorders) project, that is a new collaborative research project that aims to improve the quality of forensic psychiatric care in Europe, the ERICA Project (Stopping Child Maltreament through Pan-European Multiprofessional Training Programme: Early Child Protection Work with Families at Risk), and the VESPA (Vortioxetine in the Elderly vs. SSRIs) study, that is a pragmatic, multicenter, open-label, parallel-group, superiority, randomized trial assessing the tolerability and efficacy of vortioxetine versus SSRIs in elderly patients with depression. The clinical activity is conducted in a large Mental Health and Addiction Department in the Milano Northern Area.

Child Neuropsychiatrists work on neurological disorders or neurological aspects of various pediatric diseases like pediatric hematology, metabolic disorders, cerebral palsy, neurodevelopmental disorders (e.g. autism spectrum disorders) or chromosomal and genetic abnormalities. We are interested in a fine-grained neurological and psychopathological description of developmental profile of premature babies. The Child Neuropsychiatry department of Milano-Bicocca is member of the Italian Group for Children’s Cerebral Palsy. It has been involved in a multicenter international study on correlations between psychomotor/cognitive development and functioning of the nervous system in Down syndrome. Today, it is part of the The International Network on Cancer, Infertility and Pregnancy (INCIP) which studies the development of children born after maternal cancer diagnosis and treatment during pregnancy. We collaborated with Besta institute in projects for the treatment of pre-school children with specific languge disorders. Our study evaluated a novel technique, i.e. hearing-perceptive training, in enabling children to speak. We also look at learning disorders in children of school age. One of our last studies focused on learning disorders in bilingual children. Finally, we conduct studies on coping strategies and mentalization in various neuro-psychiatric disorders, such as headache in children and adolescents. In studing disorders in children and adolescents, we also consider the dynamics of couples (parents or carers), the possibility of a correlation between the children’s disorders and parents’ attitudes. Our main focus is eating disorders in adolescents; in partiular, we are researching the clinical endophenotypes and the possible biological correlates of anorexia nervosa and of borderline personality. 

Geriatricians are working on clinical and epidemiological researches that focus on the older people, especially those with cognitive syndromes such as delirium, Alzheimer’s disease and other dementias. They also are working on the role of frailty in influencing the prognosis of older patients with pre-existing neurocognitive disorders. Delirium is widely investigated in collaboration with international research groups, with regard to the implementation in the clinical practice of specific tools for the diagnosis, the clinical phenotypes associated with delirium and the outcomes related. Special attention is provided to the pathophysiological mechanisms of delirium and of delirium superimposed on dementia, including patients with and without COVID-19. To this regard, the role of neuroinflammation is a main topic. Geriatricians are involved as board members in the European Delirium Association and will chair the 2022 yearly meeting of the EDA which will be held in Milan. Furthermore, they are involved as leaders of the Special Interest Group on Delirium on behalf of European Union of Geriatric Medicine society (EUGMS). Geriatricians are also involved in various researches focusing on outpatients who are followed at our Center for Cognitive Disorders and Dementia. 

Neurorehabilitation professionals are working on neuromotor, neuropsychological, and physical rehabilitation projects. A motion-capture laboratory is available for studies on the treatment of movement dysfunctions (e.g., low back pain, peripheral neuropathy) and the investigation of motor control in neurological populations. The neuropsychological research spans from Transcranial Direct Current Stimulation (tDCS) for the improvement of focal sensorimotor deficits (e.g., apraxia and hemianopia) to the use of specific operative strategies like the Constraint-Induced Aphasia Therapy. A major area of interest is also the rehabilitation of Parkinsonism, applying Cerebello-spinal tDCS. The Neurorehabilitation cognitive unit is also involved in a multicentric project of the Italian Neurorehabilitation Society on the rehabilitation of the upper limb using tDCS. The section is also active in studying vegetative and minimally conscious states, particularly for scheduling procedures for respiratory and swallowing problems. Notably, research activities are further aimed at investigating the diagnosis of Psychogenic non-Epileptic Seizures through conversation analysis.  Psychopathology of intellectual disabilities, epilepsy, post-traumatic pathologies, and aggression in psychiatric wards are also studied.  The section currently collaborates with the University of Rochester (USA) and the University of Messina, Italy.