Ambra Stefani

Ambra Stefani
Massachusetts General Hospital | MGH · Neurological Clinical Research Institute

MD PhD

About

192
Publications
23,660
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3,060
Citations
Citations since 2017
164 Research Items
2993 Citations
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20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
Introduction
Ambra Stefani currently works at the Department of Neurology, Medical University of Innsbruck. Ambra does research in Neurology and Sleep Medicine.
Additional affiliations
October 2009 - February 2013
University of Verona
Position
  • Medical internship and medical volunteer

Publications

Publications (192)
Preprint
Full-text available
Isolated/idiopathic REM sleep behavior disorder (iRBD) and Lewy body dementia (LBD) are synucleinopathies that have partial genetic overlap with Parkinson’s disease (PD). In this study, we examined if the human leukocyte antigen ( HLA ) locus plays a similar role in iRBD, LBD and PD. The DQA1*01:02∼DQB1*06:02∼DRB1*15:01 haplotype is associated with...
Article
We welcome the remarks by Ferri and colleagues regarding the practical application of the International rapid eye movement (REM) sleep Behavior Disorder (RBD) Study Group (IRBDSG) video-polysomnography (vPSG) guidelines for RBD diagnosis. As highlighted in their letter, the rich body of literature continuously confirming isolated RBD (iRBD) as a ne...
Article
Full-text available
Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD ri...
Article
Full-text available
REM sleep without atonia (RSWA) is a key feature for the diagnosis of rapid eye movement (REM) sleep behaviour disorder (RBD). We introduce RBDtector, a novel open-source software to score RSWA according to established SINBAR visual scoring criteria. We assessed muscle activity of the mentalis, flexor digitorum superficialis (FDS), and anterior tib...
Article
Differentiation of central disorders of hypersomnolence (DOH) is challenging but important for patient care. This study aimed to investigate whether biomarkers derived from sleep structure evaluated both by manual scoring as well as with artificial intelligence (AI) algorithms allow distinction of patients with different DOH. We included video-poly...
Article
Full-text available
Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD ri...
Preprint
Full-text available
NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C, a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to ev...
Article
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Myoclonus and other jerky movements form a large heterogeneous group of disorders. Clinical neurophysiology studies can have an important contribution to support diagnosis but also to gain insight in the pathophysiology of different kind of jerks. This review focuses on myoclonus, tics, startle disorders, restless legs syndrome, and periodic leg mo...
Conference Paper
Introduction: Large body movement during sleep are often accompanied by sleep stage shifts, arousals, awakenings, respiratory events, and autonomic changes, therefore likely having relevant clinical implications. The current American Academy of Sleep Medicine scoring manual (AASM Version-2.6) does not contain clear rules to define and score large b...
Article
Full-text available
Was gibt es Neues? Diagnose/Zusatzuntersuchungen Die essenziellen Diagnosekriterien für die Diagnose des Restless Legs Syndroms (RLS) wurden 2014 durch die International Restless Legs Syndrome Study Group (IRLSSG) erarbeitet und in einer Konsensuskonferenz abgestimmt. Sie schließen, anders als in den vorherigen Diagnosekriterien, nun auch explizit...
Article
Study objectives: Sleep disorders, daytime sleepiness and autonomic dysfunction are commonly reported among patients with multiple system atrophy (MSA) and Parkinson disease (PD). We aimed to assess sleep and autonomic function in these patients to evaluate the relationships between sleep disorders, excessive daytime sleepiness (EDS) and autonomic...
Conference Paper
Movements during sleep characterize sleep disorders, which can disturb sleep or its onset, impacting sleep quantity and quality. Video-polysomnography is the current gold standard to assess movements during sleep, but its availability is limited. Using data recorded with a 3D time of flight sensor, we developed a novel method of encoding temporal a...
Article
Full-text available
Sleep spindles are the hallmark of N2 sleep and are attributed a key role in cognition. Little is known about the impact of epilepsy on sleep oscillations underlying sleep-related functions. This study assessed changes in the global spindle rate in patients with epilepsy, analysed the distribution of spindles in relation to the epileptic focus, and...
Article
Full-text available
Purpose: Homodyne filtering is a standard preprocessing step in the estimation of SWI. Unfortunately, SWI is not quantitative, and QSM cannot be accurately estimated from filtered phase images. Compared with gradient-echo sequences suitable for computing QSM, SWI is more readily available and is often the only susceptibility-sensitive sequence acq...
Article
Restless legs syndrome (RLS) is a common sleep-related movement disorder in populations of European descent and disease risk is strongly influenced by genetic factors. Common variants have been assessed extensively in several genome-wide association studies, but the contribution of rarer genetic variation has not been investigated at this scale. We...
Article
Full-text available
This manuscript presents an overview of REM sleep behaviour disorder (RBD) with a special focus on European contributions. After an introduction examining the history of the disorder, we address the pathophysiological and clinical aspects, as well as the diagnostic issues. Further, implications of RBD diagnosis and biomarkers are discussed. Contrib...
Article
Full-text available
Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by an urge to move the limbs with a circadian pattern (occurring in the evening/at night), more prominent at rest, and relieved with movements. RLS is one of the most prevalent sleep disorders, occurring in 5-10% of the European population. Thomas Willis first descri...
Article
Full-text available
Study objectives Studies on brain iron content in restless legs syndrome (RLS) using magnetic resonance imaging (MRI) are heterogeneous. In this study, we sought to leverage the availability of a large dataset including a range of iron-sensitive MRI techniques to reassess the association between brain iron content and RLS with added statistical pow...
Chapter
Sleep-related movement disorders, for example, restless legs syndrome and sleep related bruxism, interfere with acquisition of good quality sleep. These disorders can interfere with onset or maintenance of sleep, and underlying motor events lead to micro-arousals during sleep. Hence, patients suffering from sleep-related movement disorders can show...
Article
Full-text available
Objective Video-polysomnography (VPSG) and prolonged video-EEG-monitoring (pVEEG-M) are multimodal neurophysiological investigation modalities. Depending on indication either is performed, but occasionally patients undergo both (during the same or separate stays). We sought to assess the reasons and potential benefits of dual diagnostic assessments...
Article
Full-text available
Study objectives To identify a fast and reliable method for rapid eye movement (REM) sleep without atonia (RWA) quantification. Methods We analyzed 36 video-polysomnographies (v-PSGs) of isolated REM sleep behavior disorder (iRBD) patients and 35 controls’ v-PSGs. Patients diagnosed with RBD had: i) RWA, quantified with a reference method, i.e. au...
Article
Objectives To follow up predictive factors for α-synuclein-related neurodegenerative diseases in a multicenter cohort of idiopathic/isolated REM sleep behavior disorder (iRBD). Methods Patients with iRBD from 12 centers underwent a detailed assessment for potential environmental and lifestyle risk factors via a standardized questionnaire at baseli...
Article
Full-text available
Background Augmentation is a paradoxical reaction mainly to dopaminergic medication in patients with restless legs syndrome (RLS), but the exact pathomechanism remains unclear. Objectives The aim of this study was to identify factors associated with augmentation in RLS patients. Methods RLS patients with and without current or previous augmentati...
Article
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment, abnormal jerks and movements during REM sleep. Isolated RBD (iRBD) is recognized as the early stage of alpha-synucleinopathies, i.e. dementia with Lewy bodies, Parkinson’s disease and multiple system atrophy. The certain diagnosis of iRBD requir...
Article
Video-polysomnography (v-PSG) is essential for diagnosing rapid eye movement (REM) sleep behavior disorder (RBD). Although there are current American Academy of Sleep Medicine standards to diagnose RBD, several aspects need to be addressed to achieve harmonization across sleep centers. Prodromal RBD is a stage in which symptoms and signs of evolvin...
Article
Video-polysomnography (v-PSG) is essential for diagnosing rapid eye movement (REM) sleep behavior disorder (RBD). Although there are current American Academy of Sleep Medicine standards to diagnose RBD, several aspects need to be addressed to achieve harmonization across sleep centers. Prodromal RBD is a stage in which symptoms and signs of evolvin...
Article
Background: PSAP encodes saposin C, the co-activator of glucocerebrosidase, encoded by GBA. GBA mutations are associated with idiopathic/isolated REM sleep behavior disorder (iRBD), a prodromal stage of synucleinopathy. Objective: To examine the role of PSAP mutations in iRBD. Methods: We fully sequenced PSAP and performed Optimized Sequence K...
Preprint
Full-text available
REM sleep behavior disorder (RBD) represents both an early marker and key symptom of synucleinopathies, mainly Parkinson disease (PD) and Lewy body dementia (LBD), and a strong opportunity for early clinical intervention for these conditions. Yet, the genetics of RBD are currently not well characterized. In this study, we perform the first genome-w...
Article
Full-text available
Several classical writers had an impressive power of observation and often depicted medical conditions in their works long before medical literature did. Sleep paralysis is a common and frightening experience, in particular when occurring for the first time. Therefore, it is not surprising that it has been frequently described in the classical lite...
Article
Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerat...
Article
Full-text available
Objective: Friedreich ataxia (FRDA) is an inherited neurological disease defined by progressive movement incoordination. We undertook a comprehensive characterization of the spatial profile and progressive evolution of structural brain abnormalities in people with FRDA. Methods: A coordinated international analysis of regional brain volume using...
Preprint
Full-text available
PSAP encodes saposin C, the co-activator of glucocerebrosidase, encoded by GBA. Since GBA mutations are associated with idiopathic/isolated REM sleep behavior disorder (iRBD), a prodromal stage of synucleinopathy, we examined the role of PSAP mutations in iRBD. We fully sequenced PSAP and performed Optimized Sequence Kernel Association Test in 1,11...
Article
Several classical writers had an impressive power of observation and often depicted medical conditions in their works long before medical literature did. Sleep paralysis is a common and frightening experience, in particular when occurring for the first time. Therefore, it is not surprising that it has been frequently described in the classical lite...
Article
Objectives To evaluate skin biopsies of patients with early- and late onset restless legs syndrome (RLS) for concomitant small fiber neuropathy (SFN) and to determine cutaneous sympathetic innervation and microvascularization in comparison to healthy individuals. Methods Density of intraepidermal nerve fibers (IENFD), adrenergic nerve fibers and d...
Article
Full-text available
Patients with restless legs syndrome (RLS) use various terms when describing their symptoms. Whether gender might influence this has not been investigated so far. The aim of this study was to evaluate possible gender differences in spontaneous descriptions of RLS symptoms. This prospective study, conducted in 100 consecutive German‐speaking RLS pat...
Article
ZUSAMMENFASSUNG Die Rapid-Eye-Movement (REM)-Schlafverhaltensstörung (RBD) ist eine Parasomnie, bei der es zu einem unwillkürlichen Ausleben von Trauminhalten während des REM-Schlafes kommt. Die physiologische Muskelatonie während des REM-Schlafes ist aufgehoben. Die Mehrheit (> 90 %) der Patienten mit einer isolierten RBD (iRBD) entwickeln im weit...
Article
Full-text available
Objective This multi‐language study employed simple speech recording and high‐end pattern analysis to provide sensitive and reliable non‐invasive biomarkers of prodromal vs. manifest alpha‐synucleinopathy in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) and early‐stage Parkinson's disease (PD). Methods We performed a...
Article
Isolated REM sleep behaviour disorder (RBD) is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological α-synuclein in peripheral tissues of patients with isolated RBD may identify those progressing to Parkinson's disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testi...
Article
Study objectives To evaluate interrater reliability for artefact correction in the context of semi-automated quantification of rapid eye movement (REM) sleep without atonia (RWA) in the mentalis and flexor digitorum superficialis (FDS) muscles. Methods We included video-polysomnographies of 14 subjects with apnea-hypopnea-index in REM sleep (AHIRE...
Article
This scientific commentary refers to ‘Sleep deprivation impairs molecular clearance from the human brain’ by Eide et al. (doi:10.1093/brain/awaa443).
Article
There is a gap in the manuals for scoring sleep-related movements because of the absence of rules for scoring large movements. A taskforce of the International Restless Legs Syndrome Study Group elaborated rules that define the detection and quantification of movements involving large muscle groups. Consensus on each of the criteria in this paper w...
Article
Sleep disorders in Parkinson disease have attracted the attention of clinicians and researchers for decades. Recently, major advances in their clinical characterization, polysomnographic description, pathophysiologic understanding, and treatment took place. Parkinson disease encompasses the whole spectrum of sleep medicine: every category of sleep...
Article
Full-text available
Background: Augmentation (AUG) in patients with restless legs syndrome (RLS) can be associated with impulse control disorder (ICD) symptoms, such as compulsive sexual behavior, gambling disorder or compulsive shopping. In this study, we wanted to assess whether RLS patients with AUG differ in decision making from those patients who have augmentati...
Article
STUDY OBJECTIVES:To evaluate inter-rater reliability (IRR) between manual sleep stage scoring performed in two European sleep centers and automatic sleep stage scoring performed by the previously validated artificial intelligence-based Stanford-STAGES algorithm (Stephansen et al., 2018). METHODS: Full night polysomnographies of 1066 participants w...
Article
Study objectives To evaluate macro sleep architecture and characterize REM sleep without atonia (RWA) by using the SINBAR EMG montage including mentalis and upper extremity muscles in early and advanced Parkinson’s disease (PD). Methods We recruited 30 patients with early- and advanced-stage of PD according to Movement Disorder Society (MDS) Clini...
Article
Objective Sleep complaints are frequent after acute COVID-19. Aim of this study was to videopolysomnographically evaluate sleep and sleep disorders after SARS-Cov2 infection. Methods Patients with suspected sleep disorders after acute COVID-19 underwent video-polysomnography (v-PSG) at the Sleep Disorders Clinic, Department of Neurology, Medical U...
Article
We sought to gain a better understanding of the relationship between epilepsy and sleep quality and daytime sleepiness by performing a literature search of PubMed for case-control studies that compared patients with epilepsy to controls and reported the Pittsburgh sleep quality index (PSQI) and/or the Epworth sleepiness scale (ESS). Study-specific...
Article
Full-text available
Study objectives Rapid eye movement sleep behavior disorder (RBD) is frequent in dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), and poses a risk of injury to patients and their bed partners. We assessed the efficacy of nelotanserin, a selective 5-HT(2A) inverse agonist, for symptomatic treatment of RBD using systematic vide...
Article
Full-text available
Objective: To examine the role of genes identified through genome-wide association studies (GWASs) of Parkinson disease (PD) in the risk of isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD). Methods: We fully sequenced 25 genes previously identified in GWASs of PD, in a total of 1,039 iRBD patients and 1,852 controls. The role of ra...
Article
Full-text available
Background: In current clinical practice, sleep is manually scored in discrete stages of 30-s duration. We hypothesize that modelling sleep automatically as continuous and dynamic process predicts healthy ageing better than traditional scoring. Methods: Sleep electroencephalography of 15 young healthy subjects (aged ≤40 years) was used to train...
Article
Objectives/Background Most middle-aged and older adult patients with isolated (idiopathic) REM sleep behavior disorder (RBD) eventually develop parkinsonism, dementia with Lewy bodies, or multiple system atrophy. We aimed to describe the current sleep medicine specialist approach toward RBD prognostic counseling, and to determine physician beliefs...
Article
Full-text available
Nightmare disorder and recurrent isolated sleep paralysis are rapid eye movement (REM) parasomnias that cause significant distress to those who suffer from them. Nightmare disorder can cause insomnia due to fear of falling asleep through dread of nightmare occurrence. Hyperarousal and impaired fear extinction are involved in nightmare generation, a...
Article
BACKGROUND Functional connectivity studies revealed alterations within thalamic, salience, and default mode networks in restless legs syndrome patients. METHODS 82 patients with restless legs syndrome (untreated, n=30; on dopaminergic medication, n=42; on alpha-2-delta ligands as mono- or polytherapy combined with dopaminergic medication, n=10) an...
Article
Objective We assessed frontal executive functions in patients with RLS/WED with and without augmentation and compared the results to healthy controls. Methods We recruited 38 patients with RLS/WED. A total of 23 patients were treated with dopaminergic therapy and showed no signs of augmentation and 15 patients had a history of augmentation (AUG)....
Article
Background: There is only partial overlap in the genetic background of isolated rapid‐eye‐movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). Objective: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. Methods: Ten genes, comprising the recessive genes PRKN, DJ‐1 (PARK7...
Article
We thank Dr. Spector for his comments on our article. We agree that focusing on Europeans is a limitation of our study, which should have been mentioned as a limitation in the discussion. In genetic studies, to minimize bias of results due to different variant frequencies in different ethnicities, it is best practice to analyze samples of similar g...
Article
Objective: To evaluate sleep disorders and chronotype in patients with drug resistant focal and generalised epilepsy compared to healthy controls. Methods: Sixty four patients with focal and six with generalised, drug resistant epilepsy were included and compared to 70 age- and gender-matched healthy controls. Patients with any relevant comorbid...
Article
Full-text available
The role of central sleep apnea (CSA) in pacing-induced cardiomyopathy (PICM) remains speculative. In a prospective trial entitled UPGRADE, the presence of CSA was assessed by single-night polysomnography (PSG) in 54 PICM patients within 1 month after left ventricular lead implantation (with biventricular stimulation still not activated). CSA was d...
Preprint
Full-text available
Isolated REM sleep behaviour disorder is an early-stage alpha-synucleinopathy in most, if not all, affected subjects. Detection of pathological alpha-synuclein in peripheral tissues of isolated REM sleep behaviour disorder patients may identify those progressing to Parkinson's disease, dementia with Lewy bodies or multiple system atrophy, with the...
Article
Full-text available
Objective To assess emotional processing and alexithymia in patients with restless legs syndrome (RLS) with augmentation versus those who never had augmentation. Methods We recruited 26 patients who had a history of augmentation (AUG), either current or past, 27 RLS patients treated with dopamine agonists who never had augmentation (RLS controls),...
Preprint
Full-text available
Objective To examine the role of genes identified through genome-wide association studies (GWASs) of Parkinson disease (PD) in the risk of isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD). Methods We fully sequenced 25 genes previously identified in GWASs of PD, in a total of 1,039 iRBD patients and 1,852 controls. The role of rare...
Article
Full-text available
Objective To study the role of GBA variants in the risk for isolated rapid-eye-movement (REM)-sleep behavior disorder (iRBD) and conversion to overt neurodegeneration. Methods A total of 4,147 individuals were included: 1,061 iRBD patients and 3,086 controls. GBA was fully sequenced using molecular inversion probes and Sanger sequencing. We analyz...
Article
Full-text available
Study Objectives The differentiation of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) or its prodromal phase (prodromal RBD) from other disorders with motor activity during sleep is critical for identifying α-synucleinopathy in an early stage. Currently, definite RBD diagnosis requires video polysomnography (vPSG). The aim of thi...
Article
Introduction Isolated REM sleep behavior disorder (iRBD) is characterized by abnormal behaviours during REM sleep. Several studies showed that iRBD is a prodromal stage of synucleinopathies. Therefore identifying iRBD in the general population is of utmost importance. In this study we explore whether the assessment of rest‐activity rhythm features...
Article
Introduction Functional brain connectivity studies revealed alterations within thalamic, salience, and default mode networks in patients with restless legs syndrome. The objective of this study was to characterize functional connectivity and network topology in a large cohort of patients with restless legs syndrome compared to healthy controls, and...
Article
Full-text available
Background The aim of this study was to investigate the effects on subjective and objective sleepiness of a stay above a large struck singing bowl compared to a relaxation period in a silent singing bowl. Methods Fifty-eight healthy subjects were recruited for the study, 48 participated on two days, one week apart, during the same timeslot. The Ka...
Preprint
Full-text available
This study evaluated the influence of a struck singing bowl on subjective and objective sleepiness during daytime compared to a relaxation period in a silent singing bowl. Subjective sleepiness was significantly lower after relaxation above a struck singing bowl. After gender stratification, the difference was still significant in women. Objective...