Francesca Morgante

• MD, PhD
• Reader in Neurology at St George's, University of London

Objective. Local field potential (LFP) recordings using chronically implanted sensing-enabled stimulators are a powerful tool for indexing symptom presence and severity in neurological and neuropsychiatric disorders, and for enhancing our neurophysiological understanding of brain processes. LFPs have gained interest as input signals for closed-loop...

Freezing of gait (FOG) is a devastating symptom of Parkinson's disease (PD) often resulting in disabling falls and loss of independence. It affects half of patients, yet current therapeutic strategies are insufficient, and the underlying neural mechanisms remain poorly understood. This study investigated beta oscillation dynamics in the STN during...

Introduction Functional neurological disorder (FND) and autism spectrum disorder (ASD) are two complex neuropsychiatric conditions that have been historically classified within psychiatric domains, resulting in a lack of extensive research, insufficient clinical recognition, and persistent societal stigma. In recent years, there has been an increas...

Objective: Understanding the neural mechanisms underlying movement initiation is crucial for advancing movement-driven adaptive deep brain stimulation therapies for tremor disorders. We investigated the feasibility of decoding pre-movement periods of upper limb movements by machine learning using thalamic local field potentials (LFPs) and scalp ele...

Essential tremor (ET) is one of the most common movement disorders in adults. Deep brain stimulation (DBS) of the ventralis intermediate nucleus (VIM) of the thalamus and/or the posterior subthalamic area (PSA) has been shown to provide significant tremor suppression in patients with ET, but with significant inter-patient variability and habituatio...

Background Deep brain stimulation is a treatment for advanced Parkinson's disease and currently tuned to target motor symptoms during daytime. Parkinson's disease is associated with multiple nocturnal symptoms such as akinesia, insomnia, and sleep fragmentation, which may require adjustments of stimulation during sleep for best treatment outcome....

Background Little is known about factors modulating pain and pain‐related functional impairment in isolated cervical dystonia (CD). Objective The aim was to assess the prevalence and interrelationship between pain‐modulating factors and pain‐related determinants of functional impairment and quality of life in CD. Methods We analyzed pain‐aggravat...

Neuropsychiatric symptoms are common and disabling in Parkinson’s disease (PD), with troublesome anxiety occurring in one-third of patients. Management of anxiety in PD is challenging, hampered by insufficient insight into underlying mechanisms, lack of objective anxiety measurements, and largely ineffective treatments. In this study, we assessed t...

Essential tremor (ET) is one of the most common movement disorders in adults. Deep brain stimulation (DBS) of the ventralis intermediate nucleus (VIM) of the thalamus and/or the posterior subthalamic area (PSA) has been shown to provide significant tremor suppression in patients with ET, but with significant inter-patient variability and habituatio...

Background: Deep brain stimulation is a treatment for advanced Parkinson's disease and currently tuned to target motor symptoms during daytime. Parkinson's disease is associated with multiple nocturnal symptoms such as akinesia, insomnia and sleep fragmentation which may require adjustments of stimulation during sleep for best treatment outcome. Ob...

Background Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are...

Background People with functional neurological disorder (FND) have abnormalities in sensory processing. Loss of ticklishness has been rarely reported. Objectives To describe associated clinical features in people with FND and loss of ticklishness and explore correlations with sensory changes. Methods Retrospective audit of clinical letters of peo...

Background Neuropsychiatric symptoms are common and disabling in Parkinson's disease (PD), with troublesome anxiety occurring in one-third of patients. Management of anxiety in PD is challenging, hampered by insufficient insight into underlying mechanisms, lack of objective anxiety measurements, and largely ineffective treatments. In this study, we...

Background Autonomic dysfunction is common and disabling in Parkinson's disease (PD). The effects of deep brain stimulation (DBS) on the cardiovascular system in PD remain poorly understood. We aimed to assess the effect of DBS on cardiovascular symptoms and objective measures in PD patients. Methods We conducted a systematic literature search in...

Functional Motor Disorders are common and disabling. Clinical diagnosis has moved from one of exclusion of other causes for symptoms to one where positive clinical features on history and examination are used to make a “rule in” diagnosis wherever possible. Clinical neurophysiological assessments have developed increasing importance in assisting wi...

Background Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are not fully known. Objective We aimed to determine the prevalence, clinical correlates, and predictive value of SCCs in PD. Methods We conducted a systematic review and met...

Radiofrequency (RF) thalamotomy is a neurosurgical management option for medically-refractory tremor. In this observational study, we evaluate the magnetic resonance imaging (MRI) features of the resultant lesion, their temporal dynamics, and how they vary depending on surgical factors. We report on lesion characteristics including size and locatio...

ABSTRACT Background Functional motor disorders (FMD) are a frequent neurological condition affecting patients with movement disorders. Commonly described in younger adults, their manifestation can be also associated to an elderly onset. Objective To assess the prevalence and describe the clinical manifestations of FMD with elderly and younger onse...

Introduction Safinamide is a recent antiparkinsonian drug that modulates both dopaminergic and glutamatergic systems with positive effects on motor and nonmotor symptoms of Parkinson’s disease (PD). Here, we aimed to describe the efficacy and safety of safinamide in the Italian PD patients in real-life conditions. Methods We performed a sub-analys...

Objective: Opicapone (OPC) is a third-generation peripheral catechol-O-methyl transferase inhibitor (COMT-i) approved as add-on therapy to levodopa/DOPA decarboxylase inhibitors (DDCI) combinations in Parkinson's disease (PD) patients with end-of-dose motor fluctuations. While the OPC effectiveness on motor symptoms is well known, there is still u...

Chorea-acanthocytosis (ChAc) is a rare genetic neurodegenerative disorder caused by biallelic VPS13A pathogenic variants. The phenotype is characterized by progressive chorea, neuropsychiatric features, seizures, hyperCKemia due to myopathy, that may often be subclinical, and neuropathy. Here, we present a case of ChAc without chorea, but with prom...

Introduction: Previous studies have suggested an association between Impulsive Compulsive Behaviour (ICB) and dyskinesia in Parkinson's disease (PD). However, none of these studies have employed an objective home-based measure of dyskinesia. Objectives: To evaluate in advanced PD the relationship between ICB and dyskinesia, objectively measured...

Subthalamic nucleus (STN) beta-triggered adaptive deep brain stimulation (ADBS) has been shown to provide clinical improvement comparable to conventional continuous DBS (CDBS) with less energy delivered to the brain and less stimulation induced side-effects. However, several questions remain unanswered. First, there is a normal physiological reduct...

Background Memory deficits in mild cognitive impairment related to Parkinson's disease (PD‐MCI) are quite heterogeneous, and there is no general agreement on their genesis. Objectives To define memory phenotypes in de novo PD‐MCI and their associations with motor and non‐motor features and patients’ quality of life. Methods From a sample of 183 e...

Background: Pain in a common symptom in adult-onset idiopathic dystonia (AOID). An appropriate tool to understand this symptom is needed to improve AOID patients’ care. We developed a rating instrument for pain in AOID and validated it in cervical dystonia (CD). Methods: Development and validation of the Pain in Dystonia Scale (PIDS) in three phase...

Background: A better understanding of pain in adult-onset idiopathic dystonia (AOID) is needed to implement effective therapeutic strategies. Objective: To develop a new rating instrument for pain in AOID and validate it in cervical dystonia (CD). Methods: Development and validation of the Pain in Dystonia Scale (PIDS) comprised three phases....

Background. The organization of care has a deep impact on the variability in the quality of care provided to patients and on the equity of care access. The lack of coordination of care, the lack of communication among health care providers, healthcare professionals and patients, the duplication of many services that are provided to the patients, re...

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people wit...

Periodic features of neural time series data, such as local field potentials (LFP), are often quantified using power spectra. While the aperiodic exponent of spectra is typically disregarded, it is nevertheless modulated in a physiologically-relevant manner and was recently hypothesised to reflect excitation/inhibition (E/I) balance in neuronal pop...

Tremor is part of the phenomenological spectrum of dystonia. Treatments available for tremor in dystonia are oral medications (OM), botulinum neurotoxin (BoNT), and brain surgery (deep brain stimulation or thalamotomy). There is limited knowledge regarding the outcome of different treatment options, and evidence is especially scarce for the tremor...

Background: Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches. Objectives: To estimate LE...

Parkinson’s disease (PD) is a common neurological disorder, with bradykinesia being one of its cardinal features. Objective quantification of bradykinesia using computer vision has the potential to standardise decision-making, for patient treatment and clinical trials, while facilitating remote assessment. We utilised a dataset of part-3 MDS-UPDRS...

Evoked resonant neural activity (ERNA) is induced by subthalamic deep brain stimulation (DBS) and was recently suggested as a marker of lead placement and contact selection in Parkinson's disease. Yet, its underlying mechanisms and how it is modulated by stimulation parameters are unclear. Here, we recorded local field potentials from 27 Parkinson'...

Recent observations suggest that autism spectrum disorder (ASD) co-occurs in people with a functional neurological disorder (FND), but little systematic data are available on the relationship between FND and autism. The study aimed to assess the self-reported autistic traits via a standardized questionnaire and the prevalence of previously diagnose...

Background: Subthalamic nucleus (STN) stimulation is an effective treatment for Parkinson's disease and induced local field potential (LFP) changes that have been linked with clinical improvement. STN stimulation has also been used in dystonia although the internal globus pallidus is the standard target where theta power has been suggested as a ph...

Subthalamic nucleus (STN) beta-triggered adaptive deep brain stimulation (ADBS) has been shown to provide clinical improvement comparable to conventional continuous DBS (CDBS) in people with Parkinson's disease (PD) with less energy delivered to the brain and less stimulation induced side-effects. However, several questions remain unanswered. First...

Introduction Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications...

KMT2B-related dystonia (DYT-KMT2B, also known as DYT28) is an autosomal dominant neurological disorder characterized by varying combinations of generalized dystonia, psychomotor developmental delay, mild-to-moderate intellectual disability, and short stature. Disease onset occurs typically before ten years of age. We report the clinical and genetic...

KMT2B-related dystonia (DYT-KMT2B, also known as DYT28) is an autosomal dominant neurological disorder characterized by varying combinations of generalized dystonia, psychomotor developmental delay, mild-to-moderate intellectual disability and short stature. Disease onset occurs typically before 10 years of age. We report the clinical and genetic f...

Pain is a minor problem compared with other Huntington Disease (HD) symptoms. Nevertheless, in HD it is poorly recognized and underestimated. So far, no study evaluated the presence of chronic pain in HD. The aim of this pilot study was to evaluate the presence and features of chronic pain in a cohort of HD gene carriers. An observational cross-sec...

Background The degree of involvement of the autonomic nervous system in progressive supranuclear palsy (PSP) has been investigated in several studies, often providing conflicting results. There is a need for a better characterization of autonomic dysfunction in PSP, to enhance our understanding of this highly disabling neurodegenerative disease inc...

A bstract Periodic features of neural time series data, such as local field potentials (LFP), are often quantified using power spectra. While the aperiodic exponent of spectra is typically disregarded, it is nevertheless modulated in a physiologically-relevant manner and was recently hypothesised to reflect excitation/inhibition (E/I) balance in ne...

The aim of this study is to assess changes in the body distribution and the semeiology of functional motor disorder (FMD) in patients who reported only one or more than one body site affected at FMD onset. Data were obtained from the Italian Registry of Functional Motor Disorders, which included patients with a diagnosis of clinically definite FMDs...

Background The construct of Essential Tremor plus (ET-plus) refers to patients who also have rest tremor and/or mild neurologic signs of unknown significance. It is unclear whether soft signs represent confounding factors or are useful in suspecting an alternative condition. Methods Using a Bayesian approach to ET-plus patients recruited in The IT...

Magnetic resonance imaging (MRI) in patients with implanted deep brain stimulation (DBS) systems is subject to strict guidelines in order to ensure patient safety. Criteria include limits on the number of implanted leads. Here, we describe the case of a 29-year-old patient with generalized dystonia implanted with 4 DBS electrodes and 2 implantable...

Pain is a minor problem compared with other Huntington Disease (HD) symptoms. Nevertheless, in HD it is poorly recognized and underestimated. So far, no study evaluated the presence of chronic pain in HD. The aim of this pilot study was to evaluate the presence and features of chronic pain in a cohort of HD gene carriers. An observational cross-sec...

Introduction: The recently released classification has revised the nosology of tremor, defining essential tremor (ET) as a syndrome and fueling an enlightened debate about some newly conceptualized entities such as ET-plus. As a result, precise information of demographics, clinical features, and about the natural history of these conditions are la...

Functional dystonia is one of the most common subtypes of functional movement disorder. In this chapter, we first provide the reader with two illustrative clinical vignettes – highlighting the complexities of clinical presentation and management. Thereafter, we review the approach to diagnosing functional dystonia, emphasizing the role of positive...

Gamma oscillations comprise a loosely defined, heterogeneous group of functionally different activities between 30-100 Hz in the cortical and subcortical local field potential (LFP) of the motor network. Two distinct patterns seem to emerge which are easily conflated: Finely-tuned gamma (FTG) oscillations-a narrowband activity with peaks between 60...

Background Frequency of Advanced Parkinson’s Disease (APD) and its clinical characteristics are still not well defined. Here, we aimed to assess APD prevalence in the Italian OBSERVE-PD cohort, as well as treatment eligibility to device-aided therapies (DAT), and to compare the APD clinical judgment with the established Delphi criteria. Methods Th...

There is growing interest in using adaptive neuromodulation to provide a more personalized therapy experience that might improve patient outcomes. Current implant technology, however, can be limited in its adaptive algorithm capability. To enable exploration of adaptive algorithms with chronic implants, we designed and validated the ‘Picostim DyNeu...

Introduction Functional motor disorders (FMDs) are usually categorized according to the predominant phenomenology; however, it is unclear whether this phenotypic classification mirrors the underlying pathophysiologic mechanisms. Objective To compare the characteristics of patients with different FMDs phenotypes and without co-morbid neurological d...

Background The ability to arise from a sitting to a standing position is often impaired in Parkinson's disease (PD). This impairment is associated with an increased risk of falling, and higher risk of dementia. We propose a novel approach to estimate Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) ratings for “item 3.9” (arising from...

BACKGROUND Parkinson's disease is the second most common neurodegenerative condition and associated with increasing cognitive dysfunction as the disease progresses. However, subtle cognitive deficits can be detected at diagnosis in 42% of individuals, suggesting that damage may already be present. Our aim was to determine clinical and structural di...

Gait is a core motor function and is impaired in numerous neurological diseases, including Parkinson’s disease (PD). Treatment changes in PD are frequently driven by gait assessments in the clinic, commonly rated as part of the Movement Disorder Society (MDS) Unified PD Rating Scale (UPDRS) assessment (item 3.10). We proposed and evaluated a novel...

Objective We aimed to describe the prevalence and clinical-demographical features of patients with functional gait disorders (FGDs) and to compare them to patients with functional motor disorders (FMDs) without FGDs (No-FGDs). Methods In this multicenter observational study, we enrolled patients with a clinically definite diagnosis of FMDs in 25 t...

This case had young onset parkinsonism beginning at age 45 mainly affecting the right side with foot dystonia and limb pain as an early and prominent feature.1 There was a family history of renal disease in one sister, stroke like episodes and dementia in another sister, and ischemic cardiac disease in the father. Single-photon emission computed to...

Background Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. Objectives 1) To develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; 2) to evaluate whether presence of tremor associated with dystonia influences model pr...

The study aimed to investigate cross-sectionally the associations of cognitive reserve (CR) and premorbid IQ with cognitive and functional status in a cohort of older outpatients. Additionally, we evaluated the association of CR and premorbid IQ with the worsening of patients’ cognitive status at one-year follow-up. We originally included 141 outpa...

Changes in corticospinal excitability have been well documented in the preparatory period before movement, however, their mechanisms and physiological role have not been entirely elucidated. We aimed to investigate the functional changes of excitatory corticospinal circuits during a reaction time (RT) motor task (thumb abduction) in healthy subject...

Improved care for people with dystonia presents a number of challenges. Major gaps in knowledge exist with regard to how to optimize the diagnostic process, how to leverage discoveries in pathophysiology into biomarkers, and how to develop an evidence base for current and novel treatments. These challenges are made greater by the realization of the...

The original version of this article unfortunately contained a mistake.

Pain is a frequent and poorly treated symptom of Parkinson’s disease, mainly due to scarce knowledge of its basic mechanisms. In Parkinson’s disease, deep brain stimulation of the subthalamic nucleus is a successful treatment of motor symptoms, but also might be effective in treating pain. However, it has been unclear which type of pain may benefit...

Background: Impulsivity is common in people with Parkinson's disease (PD), with many developing impulsive compulsive behavior disorders (ICB). Its pathophysiological basis remains unclear. Objectives: We aimed to investigate local field potential (LFP) markers of trait impulsivity in PD and their relationship to ICB. Methods: We recorded subth...

Objectives Levodopa–Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson’s disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of l...

Background: Evidence supports that neurodevelopmental diseases, such as Tourette syndrome (TS), may involve dysfunctional neural-immune crosstalk. This could lead to altered brain maturation and differences in immune and stress responses. Dendritic cells (DCs) play a major role in immunity as professional antigen-presenting cells; changes in their...

Background Despite enormous advances in identifying genetic variants responsible for many neurological diseases, access to genetic testing access to genetic testing may be limited in clinical practice. Objectives To assess worldwide access to genetic tests for movement disorders and factors impacting their utilization. Methods The Rare Movement D...

The emerging science of fatigue has soundly endorsed the need for its unified definition, shared terminology and increased recognition in neurological illnesses. Nevertheless, the real impact of fatigue remains under-recognized. Fatigue describes a sense of tiredness, lack of energy or need for increased effort often perceived as overwhelming, perv...

Introduction A three-level model of interoception has recently been defined. We aim to study the interoceptive processing in individuals with functional motor disorder (FMD). Methods Twenty-two patients with FMD were compared to 23 healthy controls. They underwent a protocol measuring different levels of interoception including: accuracy (an heart...

Finely-tuned gamma (FTG) oscillations can be recorded from cortex or the subthalamic nucleus (STN) in patients with Parkinson"s disease (PD) on dopaminergic medication, and have been associated with dyskinesias. When recorded during deep brain stimulation (DBS) on medication the FTG is entrained to half the stimulation frequency. We investigated wh...

Objectives: Externalization of deep brain stimulation (DBS) leads is performed to allow electrophysiological recording from implanted electrodes as well as assessment of clinical response to trial stimulation before implantable pulse generator (IPG) insertion. Hypothetically, lead externalization provides a route for inoculation and subsequent inf...

Objective 1) to describe the clinical manifestations of functional motor disorders (FMDs) coexisting with other neurological diseases (“comorbid‐FMDs”); 2) to compare comorbid‐FMDs to FMDs not overlapping with other neurological diseases (“pure FMDs”). Methods For this multicenter observational study, we enrolled outpatients with a definite diagno...

Despite being introduced in clinical practice more than 20 years ago, selection criteria for deep brain stimulation (DBS) in Parkinson’s disease (PD) rely on a document published in 1999 called ‘Core Assessment Program for Surgical Interventional Therapies in Parkinson’s Disease’. These criteria are useful in supporting the selection of candidates....

Background: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. Objectives: We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. Methods: Sa...

Objective: Functional movement and seizure disorders are still widely misunderstood and receive little public and academic attention. This is in stark contrast to their high prevalence and levels of associated disability. In an exploratory observational study, the authors examined whether the relative lack of media coverage of functional neurologic...

Objective We sought to evaluate demographic, clinical, and habits/occupational variables between phenotypic extremes in Parkinson’s disease (PD).Methods Databases from nine movement disorders centers across seven countries were retrospectively searched for subjects meeting criteria for very slowly progressive, benign, PD (bPD) and rapidly progressi...

Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic reg...

Background Functional motor disorders (FMDs) are abnormal movements that are significantly altered by distractive maneuvers and are incongruent with movement disorders seeing in typical neurological diseases. Objective 1) to describe the clinical manifestations of FMDs, including non‐motor symptoms and occurrence of other functional neurological d...

Objectives Impulsive compulsive behaviour disorders (ICB) and dyskinesia are common and disabling complications occurring during the course of Parkinson’s disease (PD). Their pathophysiology is not clear yet, however an association has been suggested. In the present study we aimed to evaluate the relationship between the presence of dyskinesia obje...

The authors wish to make the following erratum to this paper [...]

Background Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. Objectives We determined the frequency of GBA ‐related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. Methods Sang...

Objective Hypomimia is a prominent clinical feature in people with Parkinson’s disease, though it remains under‐investigated. We aimed here to examine the clinical correlates of hypomimia in Parkinson's disease and to test if this is a levodopa‐responsive sign. Methods We included 89 people with Parkinson’s disease. Hypomimia was assessed from dig...

Introduction Since vascular endothelial growth factor (VEGF) regulates several aspects of the central nervous system, particularly in dopaminergic neurons, VEGF inhibitors may be linked to Parkinson-like events and dementia, or variants of these diseases. Two recent case reports have found a potential link between intravitreal anti-VEGF use and Par...

Background: There is large variability in the diagnostic approach and clinical management in functional movement disorders (FMD). This study aimed to examine whether opinions and clinical practices related to FMD have changed over the past decade. Methods: A survey to members of the International Parkinson and Movement Disorder Society (MDS). R...

Objectives We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. Methods A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previou...

A fundamental question in advancing Parkinson disease (PD) research is whether it represents one disorder or many. Does each genetic PD inform a common pathobiology or represent a unique entity? Do the similarities between genetic and idiopathic forms of PD outweigh the differences? If aggregates of α-synuclein in Lewy bodies and Lewy neurites are...