Alfonso Fasano

• Università Cattolica del Sacro Cuore

Background: The efficacy and adverse events (AEs) of bilateral magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomies for essential tremor (ET) have not been compared to those of deep brain stimulation (DBS). Furthermore, it is uncertain whether second-side thalamotomies can be positioned differently from the first without compromising...

Background The coexistence of tics with Parkinson's disease (PD) is rare, as they often emerge at different ages, follow different trajectories and involve contrasting pathophysiological mechanisms related to dopamine availability and function in the brain. Cases We present 10 individuals with primary tic disorders who later developed PD. Tic seve...

Background Stimulation‐induced dyskinesia (SID) is a poorly studied and usually transient manifestation of subthalamic deep brain stimulation (STN DBS) for Parkinson's disease (PD), which can be troubling for patients. Objectives The aim of our study was to describe the features and management of SID in PD patients undergoing STN DBS. Methods We...

Background Although deep brain stimulation of the subthalamic nucleus (STN-DBS) induces motor benefits in people with Parkinson’s disease (PwPD), its effect on motor axial symptoms (e.g., postural instability, trunk posture alterations) and gait impairments (e.g., freezing of gait) is still ambiguous. Physical therapy (PT) effectively complements p...

Objective Deep brain stimulation of the centromedian nucleus of the thalamus (CM‐DBS) is an investigational, off‐label treatment for drug‐resistant epilepsy (DRE) in children. Although emerging evidence supports its safety and efficacy for select indications, the effect of CM‐DBS on quality of life and functional outcomes such as school attendance...

Transcranial ultrasound stimulation (TUS) offers precise, non-invasive neuromodulation, though its impact on human deep brain structures remains underexplored. Here we examined TUS-induced changes in the basal ganglia of 10 individuals with movement disorders (Parkinson’s disease and dystonia) and 15 healthy participants. Local field potentials wer...

Background Background: The magnitude and factors associated with levodopa equivalent daily dose (LEDD) reduction in deep brain stimulation (DBS) of the globus pallidus interna (GPi) for Parkinson's Disease (PD) remain unclear. Objective Objective: To investigate LEDD reduction in GPi DBS and its correlation with anatomical/clinical characteristics....

Parkinson’s disease is characterized, in part, by hypoactivity of direct pathway inhibitory projections from striatum to the globus pallidus internus (GPi) and indirect pathway inhibitory projections from globus pallidus externus (GPe) to the subthalamic nucleus (STN). In people with Parkinson’s disease (n=32), we explored the potential use of intr...

Background While pharmacologic interventions remain the mainstay of Parkinson’s disease (PD) treatment, alternative approaches such as vagus nerve stimulation (VNS) have drawn attention for their potential in managing PD symptoms. Objective We aimed to conduct a systematic review to comprehensively evaluate the safety and efficacy of VNS for motor...

Objective Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy caused by SCN1A haploinsufficiency in the majority of cases. Caregivers of adults with DS often complain about the loss of previously acquired skills. We set out to explore these perceptions and determine whether abnormalities reported were detectable in validated...

Introduction Normal pressure hydrocephalus (NPH) is a syndrome characterized by the buildup of cerebrospinal fluid that results in the clinic triad of gait impairment, urinary incontinence, and cognitive impairment. NPH can be categorized as secondary, idiopathic, or familial. Here, we report a comparison of sporadic to familial types from clinical...

The success of deep brain stimulation (DBS) relies on applying carefully titrated therapeutic stimulation at specific targets. Once implanted, the electrical stimulation parameters at each electrode contact can be modified. Iteratively adjusting the stimulation parameters enables testing for the optimal stimulation settings. Due to the large parame...

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the clinical triad of gait, cognitive, and urinary dysfunction associated with ventriculomegaly on neuroimaging. Clinical evaluation before and after CSF removal via large volume lumbar puncture (the "tap test") is used to determine a patient's potential to benefit f...

Objective: There has been rapid advancement in the development of deep brain stimulation (DBS) as a treatment option for adults for neurological and neuropsychiatric conditions. Here, we present a scoping review of completed and ongoing clinical trials focused on DBS in pediatric populations, highlighting key knowledge gaps. Methods: Three datab...

Introduction: A closed-loop or feedback-control system is a process which considers the system's output in order to automatically adjust the input. Compared to a traditional open-loop system, a closed-loop system allows for a higher degree of accuracy with minimal human intervention. Novel methods of closed loop 'adaptive' deep brain stimulation D...

Background and Objectives Pathogenic CHD2 variants are associated with neurodevelopmental disorders and developmental and epileptic encephalopathy. While pediatric CHD2 phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of adult patients with CHD2 variants. Methods Patie...

Background: Deep brain stimulation (DBS) and infusion therapies are effective treatments for the motor complications of Parkinson’s disease (PD), but less established is their role in fall prevention. This systematic review and network meta-analysis (NMA) aimed to evaluate the risk of falls associated with advanced therapies in PD. Methods: Follow...

Introduction: Freezing of gait (FOG) is a clinical phenomenon with major life impairments and significant reduction in quality of life for affected patients. FOG is a feature of Parkinson’s Disease and a hallmark of primary progressive freezing of gait (PPGF), currently reclassified as Progressive Supranuclear Palsy-progressive gait freezing (PSP-P...

Background Reduced cerebrospinal fluid (CSF) clearance may play a vital role in the pathogenesis of normal pressure hydrocephalus (NPH), but the radiologic marker is yet to be elucidated. Objectives This open‐label study presents two novel neuroimaging biomarkers based on enlarged perivascular spaces (ePVS) of the sub‐insular territory: the Hedgeh...

Background Orthostatic tremor (OT) is a rare movement disorder characterized by a feeling of unsteadiness and a high‐frequency tremor in the legs (13–18 Hz) relieved by sitting or walking. Objectives The aims were to study the brain electrophysiology captured chronically in a person with medication‐refractory OT while standing and walking and in t...

In the past few years, SARS-CoV-2 infection has substantially impacted public health. Alongside respiratory symptoms, some individuals have reported new neurological manifestations or a worsening of pre-existing neurological conditions. We previously documented two cases of essential tremor (ET) who experienced a deterioration in tremor following S...

Although deep brain stimulation of the subthalamic nucleus (STN-DBS) induces motor benefits in people with Parkinson’s disease (PwPD), the size and duration of the effects of STN-DBS on motor axial (e.g., postural instability, trunk posture alterations) and gait impairments (e.g., freezing of gait – FOG) are still ambiguous. Physical therapy (PT) e...

Background The dichotomy between the hypo- versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathwa...

Importance If history teaches, as cardiac pacing moved from fixed-rate to on-demand delivery in in 80s of the last century, there are high probabilities that closed-loop and adaptive approaches will become, in the next decade, the natural evolution of conventional Deep Brain Stimulation (cDBS). However, while devices for aDBS are already available...

Background Automated sleep detection in movement disorders may allow monitoring sleep, potentially guiding adaptive deep brain stimulation (DBS). Objectives The aims were to compare wake‐versus‐sleep status (WSS) local field potentials (LFP) in a home environment and develop biomarkers of WSS in Parkinson's disease (PD), essential tremor (ET), and...

Background A randomized trial suggested that reducing left‐sided subthalamic stimulation amplitude could improve axial dysfunction. Objectives To explore open‐label tolerability and associations between trial outcomes and asymmetry data. Methods We collected adverse events in trial participants treated with open‐label lateralized settings for ≥3...

Introduction: Parkinson's disease is characterized, in part, by hypoactivity of both direct pathway inhibitory projections from striatum to the globus pallidus internus (GPi) and indirect pathway inhibitory projections from globus pallidus externus (GPe) to the subthalamic nucleus (STN), giving rise to disrupted basal ganglia circuit activity. In t...

Background There remains high variability in clinical outcomes when the same magnetic resonance image‐guided focused ultrasound (MRgFUS) thalamotomy target is used for both essential tremor (ET) and tremor‐dominant Parkinson's disease (TDPD). Objective Our goal is to refine the MRgFUS thalamotomy target for TDPD versus ET. Methods We retrospectiv...

The dichotomy between the hypo-versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology.Investigate differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections.GPi neurons were s...

OBJECTIVE Dystonia is among the most common pediatric movement disorders and can manifest with a range of debilitating symptoms, including sleep disruptions. The duration and quality of sleep are strongly associated with quality of life in these individuals and could serve as biomarkers of dystonia severity and the efficacy of interventions such as...

Outcomes following vagus nerve stimulation (VNS) improve over years after implantation in children with drug‐resistant epilepsy. The added value of deep brain stimulation (DBS) instead of continued VNS optimization is unknown. In a prospective, non‐blinded, randomized patient preference trial of 18 children (aged 8–17 years) who did not respond to...

Background: Deep Brain Stimulation (DBS) has become increasingly prevalent in the management of paediatric movement disorders, with the globus pallidus interna (GPi) serving as the most utilized target. However, limitations exist, including variable responses in genetic versus acquired forms of movement disorder and structural damage in the GPi wou...

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal symptoms of Parkinson’s disease (PD). However, the therapeutic mechanisms are incompletely understood. By leveraging patient-specific brain responses to DBS using functional magnetic resonance imaging (fMRI) acquired during stimulation, we identify and validate...

Background: Success of deep brain stimulation (DBS) in Parkinson’s disease (PD) relies on time-consuming trial-and-error testing of stimulation settings. Here, we prospectively compared an fMRI-based stimulation optimization algorithm with >1 year of standard-of-care (SoC) programming in a double-blind, crossover, non-inferiority trial. Methods: Tw...

b> Introduction: L-2-hydroxyglutaric aciduria (L2HGA) is a rare neurometabolic disorder marked by progressive and debilitating psychomotor deficits. Here, we report the first patient with L2HGA-related refractory dystonia that was managed with deep brain stimulation to the bilateral globus pallidus internus (GPi-DBS). Case Presentation: We present...

These multi-modal findings suggest that ERNA is produced by synaptic effects of indirect pathway fiber activations and represents a spatially defined neuronal circuit signature linked to the therapeutic potential of subthalamic DBS.

Status dystonicus is the most severe form of dystonia with life‐threatening complications if not treated promptly. We present consensus recommendations for the initial management of acutely worsening dystonia (including pre–status dystonicus and status dystonicus), as well as refractory status dystonicus in children. This guideline provides a stepw...

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, the single-neuron and synaptic bases of ERNA are unsubstantiated. This study proposes that ERNA is a subcortical neu...

INTRODUCTION None of the available therapies for PD directly address the loss of dopaminergic neurons. Bemdaneprocel is an investigational cellular therapy composed of midbrain dopaminergic neuronal cells derived from human embryonic stem cells. METHODS In this open-label study 12 subjects have received 1 of 2 doses of bemdaneprocel to the putamen...

Background Reports of freezing of gait (FoG) in idiopathic normal pressure hydrocephalus (iNPH) are few and results are variable. This study’s objective was to evaluate the frequency of FoG in a large cohort of iNPH patients, identify FoG-associated factors, and assess FoG’s responsiveness to shunt surgery. Methods Videotaped standardized gait pro...

The study “A spinal cord neuroprosthesis for locomotor deficits due to Parkinson’s disease” by Milekovic et al. introduces a novel neuroprosthesis for treating locomotor deficits in late-stage Parkinson’s disease (PD). This approach employs an epidural spinal array targeting dorsal roots and electromyography to create a spatiotemporal map of muscle...

Background Normal Pressure Hydrocephalus (NPH) is an adult-onset communicating hydrocephalus characterized by an abnormal accumulation of cerebrospinal fluid. Idiopathic NPH (iNPH) is often underdiagnosed, and clear causes are not identified. Few studies have explored the potential link between iNPH and concussions despite that these entities share...

Introduction Gait impairments in Parkinson’s disease (PD) are treated with dopaminergic medication or deep-brain stimulation (DBS), although the magnitude of the response is variable between individuals. Computer vision-based approaches have previously been evaluated for measuring the severity of parkinsonian gait in videos, but have not been evalu...

The dichotomy between the hypo-versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. Investigate differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. GPi neurons were...

The dichotomy between the hypo-versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. Investigate differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections. GPi neurons were...

Background and Objectives SYNGAP1 variants are associated with rare developmental and epileptic encephalopathies (DEEs). Although SYNGAP1 -related childhood phenotypes are well characterized, the adult phenotype remains ill-defined. We sought to investigate phenotypes and outcomes in adults with SYNGAP1 variants and epilepsy. Methods Patients 18 y...

Background The unique neurovascular structure of the retina has provided an opportunity to observe brain pathology in many neurological disorders. However, such studies on neurodegeneration with brain iron accumulation (NBIA) disorders are lacking. Objectives To investigate NBIA's neurological and ophthalmological manifestations. Methods This cro...

Background Deep brain stimulation (DBS) is an approved treatment option for Parkinson’s Disease (PD), essential tremor (ET), dystonia, obsessive-compulsive disorder and epilepsy in the United States. There are disparities in access to DBS, and clear understanding of the contextual factors driving them is important. Previous studies aimed at unders...

Background Given high rates of early complications and non-reversibility, refined targeting is necessitated for magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for essential tremor (ET). Selection of lesion location can be informed by considering optimal stimulation area from deep brain stimulation (DBS). Methods 118 patients wit...

Objective We sought to better understand the workflow, outcomes, and complications of deep brain stimulation (DBS) for pediatric status dystonicus (SD). We present a systematic review, alongside a multi‐center case series of pediatric patients with SD treated with DBS. Methods We collected individual data regarding treatment, stimulation parameter...

Background Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is...

Objective: The use of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor-related disorders and other novel indications has been limited by guidelines advocating treatment of patients with a skull density ratio (SDR) above 0.45 ± 0.05 despite reports of successful outcomes in patients with a low SDR (LSDR). The author...

Background The dichotomy between the hypo-versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. Objective Investigate differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway project...

Video-based ambient monitoring of gait for older adults with dementia has the potential to detect negative changes in health and allow clinicians and caregivers to intervene early to prevent falls or hospitalizations. Computer vision-based pose tracking models can process video data automatically and extract joint locations; however, publicly avail...

Background Multiple system atrophy with parkinsonism (MSA‐P) is a progressive condition with no effective treatment. Objective The aim of this study was to describe the safety and efficacy of deep brain stimulation (DBS) of globus pallidus pars interna and externa in a cohort of patients with MSA‐P. Methods Six patients were included. Changes in...

Background The loss of the ability to swim following deep brain stimulation (DBS), although rare, poses a worrisome risk of drowning. It is unclear what anatomic substrate and neural circuitry underlie this phenomenon. We report a case of cervical dystonia with lost ability to swim and dance during active stimulation of globus pallidus internus. We...

Background: Spinal cord stimulation (SCS) has been investigated as a potential therapeutic option for managing refractory symptoms in patients with Parkinson's disease (PD). Objective: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of SCS in PD. Method: A comprehensive literature search was conducted on PubMed...

Background Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective and evidence-based treatment for idiopathic Parkinson's disease (iPD). A minority of patients does not sufficiently benefit from STN-DBS. Objective The predictive validity of the levodopa challenge for individual patients is analyzed. Methods Data from patients...

Background: Gait analysis objectively quantifies gait impairment in idiopathic normal pressure hydrocephalus (iNPH), may improve diagnosis and evaluation for surgical candidacy. Objectives: This meta-analysis aims to understand which objective gait parameters improve after tap-test (TT) and CSF shunt surgery (CSS), also comparing responders (R) wi...

Introduction: Essential Tremor (ET) is one of the most common tremor syndromes typically presented as action tremor, affecting mainly the upper limbs. In at least 30-50% of patients, tremor interferes with quality of life, does not respond to first-line therapies and/or intolerable adverse effects may occur. Therefore, surgery may be considered....

Background: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlin...

Objective: Temporary drainage of CSF with lumbar puncture or lumbar drainage has a high predictive value for identifying patients with suspected idiopathic normal pressure hydrocephalus (iNPH) who may benefit from ventriculoperitoneal shunt insertion. However, it is unclear what differentiates responders from nonresponders. The authors hypothesize...

Background: Technological advancements in deep brain stimulation (DBS) require methodological changes in programming. Fractionalization poses significant practical challenges for the most common approach for assessing DBS efficacy, monopolar review (MR). Objectives: Two DBS programming methods: MR and fixed parameter vertical and horizontal frac...

Background: Punding is a stereotyped behaviour characterized by an intense fascination with a complex, excessive, non-goal oriented, repetitive activity affecting individuals with Parkinson’s disease (PD) on dopamine replacement therapy (DRT). Objectives: In 2010 we published the first review focused on the pathophysiology of punding. This study...

Background: Split-belt treadmill (SBTM) training has been proposed to improve gait symmetry and overall gait performance of patients with Parkinson's disease (PD). Objectives: To determine whether patient's baseline features affect gait adaptation to SBTM in PD with freezing of gait (FOG). Methods: Twenty participants with idiopathic PD and tr...