The activities of the laboratory refer to the epidemiology of neurologicaldisorders (observational studies on the frequency, risk factors and prognosis; randomized trials on drugs, therapeutic strategies and devices for the treatment of neurological disorders).
The main research field are:
- amyotrophic lateral sclerosis (ALS) and other motor neuron diseases
- Parkinson disease
- Peripheral neuropathies
- Physical medicine and rehabilitation
The laboratory is the coordinator of population-based registries in ALS.
ALS: Effects of pharmacological treatment on biomarkers and overall efficacy
In the absence of treatments preventing or at least slowing the progression of ALS, experimental trials have moved their focus to the study of biomarkers of disease in the intent to couple the action of new drugs on molecules involved in the mechanisms of the disease to symptoms and signs of progression. One of the investigational drugs is RNS60, a product active on the mechanisms of inflammation whose efficacy in ALS has been documented by in vitro studies and in experimental animals. The study, coordinated by the Laboratory of Neurological Diseases, aims at verifying the effects of the drug on 6 biomarkers and a series of clinical parameters in patients in the early phase of the disease.
Environmental risk factors in ALS
The observation of a high number of patients with ALS among former soccer players led researchers to verify if and by which mechanisms professional soccer is a risk factor for ALS. The Laboratory of Neurological Diseases showed in the past an association between ALS and repeated traumatic events and an earlier onset of symptoms in ALS patients who had been physically active. On this background, a retrospective cohort study is ongoing to verify whether former soccer players are at higher risk of hospital admission or death for ALS or other neurodegenerative diseases (Alzheimer and Parkinson disease) than the Italian population.
Regional ALS Registry
Since 1998 in Lombardy, Northern Italy, a regional ALS registry has been active for the calculation of the incidence of the disease, the assessment of long-term prognosis and the study of a number of putative risk factors (trauma, physical exercise, diet). A new study in the same area has shown no substantial trends in the incidence of ALS in a 10-year period. This observation is in contrast with reports showing a recent increase of the incidence of the disease. The registry is included in a consortium of active Italian and European registries for the study of genetic and environmental risk factors. The patients included in the Lombardy registry are also investigated for the study of therapeutic prescriptions in search of inappropriate and/or potentially noxious treatments.
Epilepsy: comparison between different therapeutic strategies
Epilepsy can be treated with several marketed anti-seizure medications (ASM). However, accurate data about the maintenance dose of drugs to be administered in patients with newly diagnosed epilepsy and the time for discontinuation of ASM in seizure-free patients are missing. The Laboratory of Neurological Disorders designed a multicenter pragmatic randomized trial comparing standard doses of ASM and the half of the same doses (low doses) in patients with newly diagnosed epilepsy. The study will verify the impact of the two therapeutic strategies on the recurrence of seizures and the achievement of prolonged periods of remission. The Laboratory is also collaborating with the Epilepsy Center of the University of Catanzaro to carry out a randomized multicenter trial comparing rapid ASM withdrawal (2 months) versus slow withdrawal (6 months). In both studies, patients are enrolled in epilepsy centers located throughout Italy.
Psychogenic non-epileptic seizures (PNES)
The Laboratory is involved in the conduction of a national study which intends to evaluate whether a home video is a sufficient tool to make a differential diagnosis between psychogenic non-epileptic seizures (PNES) and other events (epileptic seizures, syncope, parasomnia, movement disorders, etc.). The current diagnostic gold standard recommends that attacks must be recorded on video with concomitant EEG/ECG monitoring, a technique available only in high-level healthcare settings. In this study we will also analyze the diagnostic value of questionnaires for the patient and for the witness of the seizures, in addition to home videos. Currently, there are no studies assessing the cumulative diagnostic value of gathering such data in addition to home videos before undergoing a full investigation with video-EEG monitoring.
Epilepsy: new antiseizure medications (Anakinra)
The epileptic encephalopathies FIRES (Febrile Infection-Related Epilepsy Syndrome) and NORSE (New-Onset Refractory Status Epilepticus) are rare forms of epilepsy present in subjects in developmental and, respectively, adult age. These forms are severe, drug-resistant and presumably with immune pathogenesis. Recently, international research groups have shown the possibility of improving the clinical conditions of affected patients using Anakinra (an interleukin-1 receptor antagonist). This prompted us to undertake a retrospective observational study to evaluate the efficacy of Anakinra in a cohort of children and adults. This study involves intensive care units and centers for the treatment of pediatric and adult epilepsy.
Epilepsy: Long-term prognosis and drug-resistance (Pro-long)
tudies on the long-term prognosis of epilepsy have shown that the disease evolves according to different patterns which involve the concept of resistance to drug treatments (drug resistance). As observed in previous studies, drug-resistance is a dynamic concept and refractoriness to treatment depends only in part on the classification of each patient into well-defined syndromic categories. The Laboratory of Neurological Disorders has recently completed a study about prognostic factors and drug resistance in a large cohort of patients recruited in epilepsy centers located throughout the country.
Epilepsy: sudden unexpected death in epilepsy (SUDEP)
Incidence of sudden unexpected death in epilepsy (SUDEP) is 1 per 1000 people with epilepsy (PWE) per year and is 27 times higher than in the general population. The Laboratory is the Italian coordinator of an international case-control study in which SUDEP cases are prospectively identified and matched to living subjects with epilepsy to identify factors associated with an increased risk of SUDEP and prevent avoidable deaths. The study is part of a larger project called EpiNet which includes observational and experimental studies performed using a centralized international web platform.
Epidemiology of epilepsy and other neurological disorders (GBD)
The growth and aging of the world population and the effects of campaigns for the prevention and control of communicable diseases in developing countries have contributed to significantly change the impact of diseases in the world. The Laboratory is collaborating with the Institute of Health Metrics and Evaluation in Seattle to analyze the data collected on epilepsy and neurological diseases globally and, more specifically, in the European Union. Analyses of these data pointed out that the burden of idiopathic epilepsy (premature mortality and residual disability) has progressively decreased since 1990, while an inverse trend has been observed for Alzheimer's disease and Parkinson's disease.
Neurological disorders and COVID-19
The Laboratory is involved in the preparation of surveillance tools for the neurological manifestations associated with the COVID-19 pandemic. The tools include a European registry promoted by the European Academy of Neurology (EAN) and modules for the collection of global data on acute and post-acute phases of the pandemic promoted by the World Health Organization (WHO).
International Consensus on Cardiopulmonary Resuscitation.