Maria Salsone

Institute of Bioimaging and Molecular Physiology, National Research Council · Neuroimaging Unit

Robust evidence suggests that the glymphatic system plays a key role in preserving brain health. Indeed, its activity in maintaining homeostasis by clearing neurotoxic proteins such as beta-amyloid from the human brain is essential. Sleep represents the factor that mainly influences this system, since it is selectively active during the night, in p...

Most patients with idiopathic REM sleep behavior disorder (iRBD) present peculiar repetitive leg jerks during sleep in their clinical spectrum, called periodic leg movements (PLMS). The clinical differentiation of iRBD patients with and without PLMS is challenging, without polysomnographic confirmation. The aim of this study is to develop a new Mac...

Pieces of evidence support the association between sleep disorders and sexual dysfunctions. The main biological link between these two conditions is related to the circadian secretion of testosterone. Indeed, nocturnal testosterone secretion is modulated by the sleep stages, starting to rise at sleep onset and reaching a peak during the first REM s...

Objective: In this Italian population-based study, we aimed to evaluate the neurological complications after the first and/or second dose of COVID-19 vaccines and factors potentially associated with these adverse effects. Methods: Our study included adults aged 18 years and older who received two vaccine doses in the vaccination hub of Novegro (...

The issue of sleep need and duration is highly heterogeneous across individuals and during aging and represents only a small part of a healthy sleep. Indeed, according to the most recent classification of sleep disorders (International Classification of Sleep Disorders 3rd edition, ICSD-3), sleep disturbances are more than 60, ranging from abnormal...

Herein we focus on connections between genetics and some central disorders of hypersomnolence - narcolepsy types 1 and 2 (NT1, NT2), idiopathic hypersomnia (IH), and Kleine-Levin syndrome (KLS) - for a better understanding of their etiopathogenetic mechanisms and a better diagnostic and therapeutic definition. Gene pleiotropism influences neurologi...

Background and purpose: Growing evidence suggests that Machine Learning (ML) models can assist the diagnosis of neurological disorders. However, little is known about the potential application of ML in diagnosing idiopathic REM sleep behavior disorder (iRBD), a parasomnia characterized by a high risk of phenoconversion to synucleinopathies. This st...

Recent evidence demonstrated that neuropsychological assessment may be considered a valid marker of neurodegeneration in idiopathic REM sleep behaviour disorder (iRBD). However, little is known about the possible neuropsychological heterogeneity within the iRBD population. This retrospective study aimed to identify and describe different neuropsych...

Background and aimsThis paper aimed to investigate the usefulness of applying machine learning on resting-state fMRI connectivity data to recognize the pattern of functional changes in essential tremor (ET), a disease characterized by slight brain abnormalities, often difficult to detect using univariate analysis.Methods We trained a support vector...

Objective In this Italian population-based study, we aimed to evaluate neurological complications after first and/or second dose of COVID-19 vaccines and factors potentially associated with adverse effects. Methods Our study included adults aged-18 years and older, receiving two vaccine doses in vaccination Hub Novegro (Lombardy) between July 7–16...

This study aimed to investigate the structural covariance between the striatum and large-scale brain regions in patients with vascular parkinsonism (VP) compared to Parkinson’s disease (PD) and control subjects, and then explore the relationship between brain connectivity and the clinical features of our patients. Forty subjects (13 VP, 15 PD, and...

Background and aims: To explore the cognitive functioning of ET patients without dementia and delineate its imaging counterpart. Methods: We enrolled 99 subjects (49 non-demented ET patients and 50 education-matched healthy controls) that underwent neuropsychological and MRI evaluation. In order to identify the cognitive parameters that better r...

Sleep is a global phenomenon affecting the whole brain and in which the brain activity dynamically changes across the stages. Sophisticated imaging techniques have been developed to investigate the intriguing interaction: sleep-brain. This chapter critically reviews the main applications of imaging studies in the field of sleep research. The neural...

Objective Structural abnormalities in thalami and basal ganglia, in particular the globus pallidus (GP), are a neuroimaging hallmark of hereditary aceruloplasminemia (HA), yet few functional imaging data exit in HA carriers. This study investigated the iron-related structural and functional abnormalities in an Italian HA family.Methods Multimodal i...

Visually appreciable white matter (WM) changes have been described in obstructive sleep apnea (OSA). However, few data exist on the involvement of silent WM abnormalities. This prospective study investigated the microstructural integrity of normal‐appearing white matter (NAWM) in male OSA patients before and after continuous positive airway pressur...

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdia...

Objective Several evidences demonstrate that pre-sleep habits may negatively impact adolescent sleep, yet few data exist on Italian population. This study aimed to investigate the relationship between pre-sleep habits, use of technology/activity and sleep in Italian adolescents. Methods Self-report questionnaires including Italian version of Schoo...

In recent decades, the crucial association between primary insomnia (PI) and autonomic nervous system (ANS) dysfunction has been widely investigated by clinicians and researchers. A bidirectional nature of this association has been proposed, although the chronopathological sequence currently remains unknown. Given its clinical relevance, a growing...

Neurological disorders and coronavirus 2019 (COVID-19) pandemic are two conditions with a recent well-documented association. Intriguing evidences showed that COVID-19 infection can modify clinical spectrum of manifested neurological disorders but also it plays a crucial role in the development of future diseases as long-tem consequences. In this v...

Obstructive sleep apnea (OSA) and Alzheimer’s disease (AD) are two common chronic diseases with a well-documented association. Whether the association is causal has been highlighted by recent evidence reporting a neurobiological link between these disorders. This narrative review discusses the brain regions and networks involved in OSA as potential...

Progressive supranuclear palsy (PSP) is a rare, rapidly progressive neurodegenerativedisease. Richardson’s syndrome (PSP-RS) and predominant parkinsonism (PSP-P) arecharacterized by wide range of cognitive and behavioural disturbances, but these variantsshow similar cognitive pattern of alterations, leading difficult differential diagnosis. For this...

Progressive supranuclear palsy (PSP) is a rare, rapidly progressive neurodegenerative disease. Richardson’s syndrome (PSP-RS) and predominant parkinsonism (PSP-P) are characterized by wide range of cognitive and behavioural disturbances, but these variants show similar cognitive pattern of alterations, leading difficult differential diagnosis. For...

Purpose of the review: There is evidence that, before the coronavirus pandemic 2019 (COVID-19), healthcare workers did not experience good sleep quality with relevant consequences on health. By contrast, little is known about the sleep quality of medical staff during the COVID-19 pandemic. In this review, we aimed to contribute with a review of th...

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by repeated episodes of upper airway obstruction during sleep that leads to consequent chronic intermittent hypoxia and sleep fragmentation. These nocturnal deficits result in daytime impairments such as excessive daytime impairment, tiredness, insomnia, anxiety, stre...

Introduction Cognitive-Behavioral Therapy for Insomnia (CBT-I) is the first-line treatment for Insomnia disorder (ID). We aimed to identify ID patients’ subtypes based on clinical features and their response to CBT-I. Methods 294 chronic insomnia patients (61.6% female, mean age 40.7 ± 12.3 yrs) underwent 7-sessions group CBT-I. By use of latent cl...

Background Idiopathic normal pressure hydrocephalus and PSP share several clinical and radiological features, making differential diagnosis, at times, challenging. Objectives To differentiate idiopathic normal pressure hydrocephalus from PSP using MR volumetric and linear measurements. Methods Twenty‐seven idiopathic normal pressure hydrocephalus...

Purpose of the review There is strong evidence for a bidirectional association between sleep disorders and Alzheimer’s disease (AD). In particular, insomnia may be a potentially modifiable risk factor for AD. The present review summarizes recent advances in treatment of sleep disorders in AD. Recent findings Some studies investigated the efficacy...

Introduction: We investigated the disease progression rate in patients with progressive supranuclear palsy-Richardson syndrome (PSP-RS) and PSP-parkinsonism (PSP-P) in comparison with Parkinson disease (PD) patients, using MRPI (Magnetic Resonance Parkinsonism Index), and MRPI 2.0. Methods: Fifteen PSP-RS patients (disease duration, y, mean ± SD...

Introduction: There is growing evidence that a proportion of patients with Essential Tremor (ET) may develop a memory impairment over time. However, no studies have evaluated whether hippocampal damage really occur in ET. This study investigated the macro and micro-structural integrity of the hippocampus in ET subjects using a multimodal MRI appro...

According to embodied cognition, processing language with motor content involves a simulation of this content by the brain motor system. Patients with brain lesions involving the motor system are characterized by deficits in action verbs processing in the absence of dementia. We sought to assess whether action verbs interfere with the motor behavio...

Introduction: Rapid Eye Movement (REM) sleep Behavior disorder (RBD) is a REM sleep parasomnia characterized by dream enacting behaviors allowed by the loss of physiological atonia during REM sleep. This disorder is recognized as a prodromal stage of neurodegenerative disease, in particular Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DL...

Cardiac autonomic indexes, including cardiac parasympathetic index and cardiac sympathetic index, have been reported to accurately identify patients with sleep disorders such as obstructive sleep apnea. Our study aimed to assess cardiac autonomic indexes in patients with obstructive sleep apnea before and during a single full‐night continuous posit...

Objective: REM sleep behavior disorder (RBD) is an important risk factor for the dementia development and for the deterioration of autonomic functions in patients with Parkinson's Disease. RBD has also been reported in patients with Essential Tremor (ET). However, its clinical significance in ET remains still unknown. We aimed to investigate clinic...

Introduction Evidences demonstrate that Heart Rate Variability (HRV)-derived measurements such as cardiac autonomic indexes may be useful for accurately identifying patients with sleep disorders including Obstructive Sleep Apnea (OSA). In particular, cardiac parasympathetic index, a measure of diurnal and nocturnal parasympathetic activity can disc...

Objective: Several evidences demonstrated the role of white matter (WM) lesions in the pathogenesis of Vascular Parkinsonism (VP), a clinical entity characterized by parkinsonism, postural instability, marked gait difficulty and poor response to levodopa. However, the involvement of normal appearing white matter (NAWM) in VP still remains unknown....

Background No prospective study of patients with Parkinson's disease (PD) has investigated the appearance of vertical gaze abnormalities, a feature suggestive of progressive supranuclear palsy (PSP). Objective To identify, within a cohort of patients with an initial diagnosis of PD, those who developed vertical gaze abnormalities during a 4‐year f...

Introduction: We investigated the imaging counterpart of two functional domains (ocular motor dysfunction and postural instability) in progressive supranuclear palsy (PSP) patients classified according to the new clinical diagnostic criteria. Methods: Forty-eight patients with probable PSP-Richardson's syndrome (PSP-RS), 30 with probable PSP-par...

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by white matter (WM) changes in different supra‐ and infratentorial brain structures. We used track density imaging (TDI) to characterize WM microstructural alterations in patients with PSP‐Richardson's Syndrome (PSP‐RS). Moreover, we investigated the diagnostic util...

Introduction: Differentiating clinically progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) may be challenging, especially in the absence of vertical supranuclear gaze palsy (VSGP). The Magnetic Resonance Parkinsonism Index (MRPI) has been reported to accurately distinguish between PSP and PD, yet few data exist on t...

Introduction: Essential tremor-Parkinson's disease (ET-PD) syndrome is a clinical condition in which individuals with a long-lasting history of Essential tremor (ET) eventually develop Parkinson's disease (PD). The aim of the study was to investigate the accuracy performances of clinical, neurophysiological, and imaging biomarkers in differentiati...

The aim of our study was to investigate the effect of apomorphine and placebo on resting tremor in tremor-dominant Parkinson's disease (tPD) patients. Fifteen tPD patients were enrolled. Each patient underwent two treatments on two consecutive days: on day one the patients received a subcutaneous injection of placebo, while on day two they received...

Heart rate variability (HRV) is commonly used to assess autonomic functions and responses to environmental stimuli. It is usually derived from electrocardiographic signals; however, in the last few years, photoplethysmography has been successfully used to evaluate beat-to-beat time intervals and to assess changes in the human heart rate under sever...

Objective To evaluate circadian fluctuations and night/day ratio of Heart Rate Variability (HRV) spectral components in patients with obstructive sleep apnea (OSA) in comparison with controls. Participants and methods This is a simultaneous HRV-polysomnographic (PSG) study including 29 patients with OSA and 18 age-sex-matched controls. Four patien...

Alzheimer's Disease (AD) and Parkinson's Disease with Dementia (PDD), are characterized by a different mnesic failure, particularly in memory cued recall. Although hippocampal involvement has been shown in both these diseases, it remains unknown if a selective damage of specific subfields within the hippocampus may be responsible of the peculiar mn...

Introduction: The aim of this study was to investigate the thalamic biochemical profile in patients with essential tremor (ET), using proton magnetic resonance spectroscopy (1H-MRS), and to explore the correlations between clinical and biochemical data. Methods: Sixteen patients with ET and 14 healthy controls participated in this study. After c...

In this work, we investigated motor network structure in patients affected by essential tremor (ET) with or without resting tremor, using probabilistic tractography of the cerebello–thalamo–basal ganglia–cortical loop. Twenty-five patients with ET, twenty-two patients with ET associated with resting tremor (rET), and twenty-five age- and sex-matche...

Introduction: The objective of this study was to investigate the thalamic biochemical changes in tremor-dominant Parkinson's disease (tPD) patients in comparison with essential tremor with resting tremor (rET) patients, by using proton MR spectroscopy ((1)H-MRS). Methods: Fourteen tPD patients, 12 rET patients and 10 controls participated in thi...

Motor phenotypes of Parkinson's disease (PD) are recognized to have different prognosis and therapeutic response, but the neural basis for this clinical heterogeneity remains largely unknown. The main aim of this study was to compare differences in structural connectivity metrics of the main motor network between tremor-dominant and nontremor PD ph...

Introduction: Several studies have compared the performances of midbrain to pons area ratio (M/P) and the Magnetic Resonance Parkinsonism Index (MRPI) in distinguishing patients with Progressive Supranuclear Palsy (PSP) from those with Parkinson's disease (PD) with conflicting results. The current study aimed to compare the performance of these in...

Background and purpose: The superior cerebellar peduncle is damaged in progressive supranuclear palsy. However, alterations differ between progressive supranuclear palsy with Richardson syndrome and progressive supranuclear palsy-parkinsonism. In this study, we propose an automated tool for superior cerebellar peduncle integrity assessment and tes...

Objective To investigate heart rate variability (HRV) in patients with Essential Tremor (ET) in comparison with patients with Parkinson's Disease (PD). Methods This is a cross sectional control study including 10 patients with ET, 10 patients with PD and 10 age-sex-matched controls. In patients and controls, we measured the components of HRV analy...

Objective To identify a biomarker for predicting the appearance of vertical supranuclear gaze palsy (VSGP) in patients affected by progressive supranuclear palsy–parkinsonism (PSP-P). Methods Twenty-four patients with PSP-P were enrolled in the current study. Patients were clinically followed up every 6 months until the appearance of VSGP or the e...

Parkinson disease (PD) can be considered as a brain multisystemic disease arising from dys-function in several neural networks. The principal aim of this study was to assess whether large-scale structural topological network changes are detectable in PD patients who have not been exposed yet to dopaminergic therapy (de novo patients). Twenty-one dr...

A 65-year-old woman presented with chronic lingering headache and REM sleep behavior disorder (RBD). Head MRI (figure) showed spontaneous intracranial hypotension (SIH) with deep brain swelling (DBS),(1) and CSF opening pressure was low. She was treated with lumbar epidural blood patch. Within 3 months, she became asymptomatic with improvement of b...

Introduction Several neuroimaging studies have been carried out to gain insight on the pathological processes that cause PD, but literature findings are inconsistent. The aim of this study was to combine information carried by functional imaging with DA transporter ligands and structural MRI. Methods Forty-two untreated, de novo-PD patients and 30...

Objective: DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) fr...

Background: Parkinson’s disease is primarily a disorder of response initiation characterized by an excessive motor inhibition, whereas levodopainduced dyskinesias are clearly a clinical expression of disinhibition of movements. Objective: That levodopa-induced dyskinesias are linked to dysfunctions of inhibitory brain network has recently been prop...

Levodopa-induced dyskinesias are disabling motor complications of long-term dopamine replacement in patients with Parkinson’s disease. In recent years, several alternative models have been proposed to explain the pathophysiological mechanisms underlying this hyperkinetic motor disorder. In particular, our group has shed new light on the role of the...

Background The aim of the current study was to distinguish patients who had tremor-dominant Parkinson's disease (tPD) from those who had essential tremor with rest tremor (rET).Methods We combined voxel-based morphometry-derived gray matter and white matter volumes and diffusion tensor imaging-derived mean diffusivity and fractional anisotropy in a...

Imaging measurements, such as the ratio of the midsagittal areas of the midbrain and pons (midbrain/pons) and the Magnetic Resonance Parkinsonism Index (MRPI), have been proposed to differentiate progressive supranuclear palsy (PSP) from Parkinson's disease (PD). However, abnormal midbrain/pons values suggestive of PSP have also been reported in el...

The effectiveness of cognitive rehabilitation (CR) in Parkinson's disease (PD) is in its relative infancy, and nowadays there is insufficient information to support evidence-based clinical protocols. This study is aimed at testing a validated therapeutic strategy characterized by intensive computer-based attention-training program tailored to atten...

The aim of the current study was to distinguish patients with Parkinson disease (PD) from those with progressive supranuclear palsy (PSP) at the individual level using pattern recognition of magnetic resonance imaging data. We combined diffusion tensor imaging and voxel-based morphometry in a support vector machine algorithm to evaluate 21 patients...

An increased R2 recovery component of the blink reflex (R2-BRrc) has been observed in Parkinson's disease (PD), cranio-cervical dystonia, dystonic tremor and essential tremor with associated resting tremor (rET), while the BRrc was reported normal in patients with essential tremor (ET). Distinguishing rET from tremor dominant PD (tPD) may be challe...

Dopaminergic therapy in Parkinson's disease (PD) can improve some cognitive functions while worsening others. These opposite effects might reflect different levels of residual dopamine in distinct parts of the striatum, although the underlying mechanisms remain poorly understood. We used functional magnetic resonance imaging (fMRI) to address how a...

Studies have demonstrated brain iron deposition in neurodegenerative disease and in normal aging. Data on this topic are lacking in essential tremor (ET). The aim of our study was to investigate brain iron content in patients with ET, using quantitative magnetic resonance imaging (MRI) T2*-relaxometry. We enrolled 24 patients with ET and 25 age-mat...

An increased R2 recovery component of the blink reflex (R2-BRrc) has been commonly observed in Parkinson disease, cranio-cervical dystonia, and dystonic tremor, while the BRrc was reported normal in patients with essential tremor (ET). We studied BRrc in patients with ET associated with resting tremor (rET) in comparison with patients with ET. This...

Purpose: Neurodegenerative processes in Parkinson's disease (PD) patients with levodopa-induced dyskinesias (LID) are still a matter of debate. Recently, we demonstrated that this clinical phenotype is associated with an abnormal gray matter increase in the prefrontal cortex when compared to PD without LID. This evidence was found by using voxel-b...

The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been available in English since 2008. As part of this process, the MDS-UPDRS organizing team developed guidelines for development of official non-English translations. We present here the formal process for completing officially approved...

Dystonic tremor (DT) is defined as a postural/kinetic tremor with irregular amplitude and variable frequency occurring in an extremity or body part affected by dystonia.(1).

Levodopa-induced dyskinesia represents disabling complication of long-term therapy with dopaminergic drugs in treating Parkinson's disease (PD). Recently, our group demonstrated that PD patients with levodopa-induced dyskinesia were characterized by abnormal volumetric changes in the inferior prefrontal gyrus. In this study, the functional relevanc...

Mutations in the PINK1 gene represent the second most frequent cause of early-onset Parkinson's disease (EOPD). One or two mutated alleles were also reported in some sporadic or familial patients suffering from late-onset Parkinson's disease (LOPD). We aimed at assessing the frequency of mutations in this gene in our population. We performed a sequ...

Magnetic resonance parkinsonism index (MRPI) has been proposed as a powerful tool to discriminate patients with progressive supranuclear palsy (PSP) from those with Parkinson disease (PD) or other parkinsonisms, on an individual basis. We investigated the usefulness of MRPI in predicting the clinical evolution in PSP of patients with clinically unc...

Levodopa-induced dyskinesias represent disabling complications from long-term therapy with dopaminergic drugs for treating Parkinson's disease (PD). Although several neuroimaging studies have reported altered striatofrontal function that contributes to the emergence of these motor complications, the neuroanatomical correlates of this disorder are s...

Iron overload may lead to neurodegenerative disorders such as Parkinson's disease (PD) and alterations of iron-related genes might be involved in the pathogenesis of this disease. The gene of haemochromatosis (HFE) encodes the HFE protein which interacts with the transferrin receptor (TFR), lowering its affinity for iron-bound transferrin (TF). We...

Combined measurements on conventional magnetic resonance imaging (MRI), such as midbrain area/pons area or magnetic resonance parkinsonism index (MRPI) (pons area/midbrain area × middle cerebellar peduncle width/superior cerebellar peduncle width), have been proposed as powerful tools in the differential diagnosis between progressive supranuclear p...

At 1.5 T, T2*-weighted gradient echo (GE) sequences are more sensitive in revealing mineral deposition in the basal ganglia than standard T2 weighted sequences. T2*-weighted GE sequences, however, may detect putaminal hypointensities either in patients affected by parkinsonian syndromes or in healthy subjects. The aim of this study was to identify...

Rest tremor associated with essential tremor (ET) is a condition that poses challenges in diagnosing Parkinson's disease (PD). We investigated tremor parameters in PD and ET patients with rest tremor. Fifteen patients with PD and 15 patients with ET underwent electrophysiological examination to evaluate characteristics of muscle bursting in rest po...