The Role of Treatment-Related Parameters and Brain Morphology in the Lesion Volume of Magnetic-Resonance-Guided Focused Ultrasound Thalamotomy in Patients with Tremor-Dominant Neurological Conditions.

PURPOSE: To determine the best predictor of lesion volume induced by magnetic resonance (MR)-guided focused ultrasound (MRgFUS) thalamotomy in patients with tremor-dominant symptoms in Parkinson's disease (PD) and essential tremor (ET) patients. METHODS: Thirty-six neurological patients with medication-refractory tremor (n°19 PD; n°17 ET) were treated using a commercial MRgFUS brain system (Exablate Neuro 4000, Insightec) integrated with a 1.5 T MRI unit (Sigma HDxt; GE Medical System). Linear regression analysis was used to determine how the demographic, clinical, radiological (Fazekas scale), volumetric (total GM/WM/CSF volume, cortical thickness), and MRgFUS-related parameters [Skull Density Ratio (SDR), n° of transducer elements, n° of sonications, skull area, maximal energy delivered (watt), maximal power delivered (joule), maximal sonication time delivered, maximal mean temperature reached (T°C_max), accumulated thermal dose (ATD)] impact on ventral intermediate (VIM)-thalamotomy-related 3D volumetric lesions of necrosis and edema. RESULTS: The VIM thalamotomy was clinically efficacious in improving the tremor symptoms of all the patients as measured at 1 week after treatment. Multiple regression analysis revealed that T°C_max and n° of transducer elements were the best predictors of the necrosis and edema volumes. Moreover, total WM volume also predicted the size of necrosis. CONCLUSIONS: Our study provides new insights into the clinical MRgFUS procedures that can be used to forecast brain lesion size and improve treatment outcomes.

Smartphone-Based Cognitive Telerehabilitation: A Usability and Feasibility Study Focusing on Mild Cognitive Impairment.

The implementation of cognitive health apps in patients with mild cognitive impairment (MCI) is challenging because of their cognitive, age, and other clinical characteristics. In this project, we aimed to evaluate the usability and feasibility of the Rehastart app tested in MCI patients. Eighteen subjects affected by MCI due to neurodegenerative disorders (including Parkinson's disease, multiple sclerosis, and amnestic/multidomain MCI) and eighteen healthcare professionals were recruited to this study. Patients were registered on the app by clinicians and they were assigned a protocol of specific cognitive exercises. The recruitment was conducted in the period between March and June 2023. The trial testing of the app consisted of three sessions per week for three weeks, with each session lasting about 30 min. After three weeks, the participants as well as medical personnel were invited to rate the usability and feasibility of the Rehastart mobile application. The instruments employed to evaluate the usability and feasibility of the app were the System Usability Scale (SUS), The Intrinsic Motivation Inventory (IMI) and the Client Satisfaction Questionnaire (CSQ). We did not find statistically significant differences on the SUS (p = 0.07) between healthcare professionals and patients. In addition, we found promising results on subscales of the Intrinsic Motivation Inventory, suggesting high levels of interest and enjoyment when using the Rehastart app. Our study demonstrated that smartphone-based telerehabilitation could be a suitable tool for people with MCI due to neurodegenerative disorders, since the Rehastart app was easy to use and motivating for both patients and healthy people.

Changes in cerebral cortex activity during a simple motor task after MRgFUS treatment in patients affected by essential tremor and Parkinson's disease: a pilot study using functional NIRS.

Objective.Magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) is a non-invasive thermal ablation method that involves high-intensity focused ultrasound surgery (FUS) and Magnetic Resonance Imaging for anatomical imaging and real-time thermal mapping. This technique is widely employed for the treatment of patients affected by essential tremor (ET) and Parkinson's disease (PD). In the current study, functional near-infrared spectroscopy (fNIRS) was used to highlight hemodynamics changes in cerebral cortex activity, during a simple hand motor task, i.e. unimanual left and right finger-tapping, in ET and PD patients.Approach.All patients were evaluated before, one week and one month after MRgFUS treatment.Main results.fNIRS revealed cerebral hemodynamic changes one week and one month after MRgFUS treatment, especially in the ET group, that showed a significant clinical improvement in tremor clinical scores.Significance.To our knowledge, our study is the first that showed the use of fNIRS system to measure the cortical activity changes following unilateral ventral intermediate nucleus thalamotomy after MRgFUS treatment. Our findings showed that therapeutic MRgFUS promoted the remodeling of neuronal networks and changes in cortical activity in association with symptomatic improvements.

Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study.

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 LED of safinamide 50 and 100 mg. Methods: In this multicenter, longitudinal, case-control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N = 130), safinamide 50 mg (N = 144), or rasagiline 1 mg (N = 97) for 9 ± 3 months and a control group of patients never treated with any iMAO-B (N = 129). Results: Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED. Conclusions: We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings.

The Role of Telemedicine in the Treatment of Cognitive and Psychological Disorders in Parkinson's Disease: An Overview.

BACKGROUND: This literature review evaluates the use and efficacy of telemedicine in cognitive and psychological treatment in Parkinson's disease. METHODS: Studies performed between 2016 and 2021 that fulfilled inclusion criteria were selected from PubMed, Scopus, Cochrane, and Web of Science databases. All articles were evaluated by title, abstract, and text. All studies that examined the cognitive and psychological/psychotherapy treatment of patients with Parkinson's disease by telemedicine were included. RESULTS: Telehealth improved cognitive status and emotional/behavioral disorders in this population, and had positive effects on the patients' and caregivers' quality of life. CONCLUSIONS: Our literature review supports the development and efficacy of cognitive and psychological treatment with telemedicine, but the methodology of the study must be reviewed considering its limitations so as to highlight the benefits and risks of treatment via telemedicine.

The effect of Computer Assisted Rehabilitation Environment (CAREN) in cognitive impairment and coping strategies in Parkinson's disease: a preliminary study.

Parkinson's disease is a neurodegenerative disorder characterized by different motor, vegetative, behavioral, and cognitive impairments, with worsening quality of life. Virtual reality devices have given promising results in neurorehabilitation as they can provide multisensory stimulation in a realistic environment. This study aims to test the efficacy of virtual reality training by using Computer Assisted Rehabilitation Environment in cognitive impairment in a sample of PD. 31 patients affected by PD were enrolled. All PD patients underwent 24 sessions of Computer Assisted Rehabilitation Environment training. The participants were assessed at baseline (T0) and after two months (T1). Our results suggested that Computer Assisted Rehabilitation Environment training may be effective in the cognitive and emotional domains, particularly by improving executive function, anxiety, and depressive symptoms. These changes have helped to improve self-efficacy and coping strategies. These results indicate greater cognitive and physical effort to overcome stressors. Our results show that Computer Assisted Rehabilitation Environment training was beneficial in improving cognitive functions. Longer duration training may be especially beneficial for patients with mild cognitive impairment. Our findings open the door to tailored personalized treatments based on the patient's motor and cognitive profiles.

Lower Prevalence of Chronic Pain in Manifest Huntington's Disease: A Pilot Observational Study.

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-sectional study was conducted in a cohort of HD gene carriers compared to not gene carriers (n.134 HD subjects, n.74 not gene mutation carriers). A specific pain interview, alongside a neurological, cognitive and behavioural examination, was performed in order to classify the type of pain, subjective intensity. A significant prevalence of "no Pain" in HD was found, which tended to increase with HD progression and a reduced frequency of pain in the last 3 months. A clear difference was found between manifest and premanifest HD in terms of intensity of pain, which did not change significantly with HD progression; however, a tendency emerges to a progressive reduction. No significant group difference was present in analgesic use, type and the site of pain. These findings could support a lower prevalence of chronic pain in manifest HD. Prevalence and intensity of chronic pain seem directly influenced by the process of neurodegeneration rather than by an incorrect cognitive and emotional functioning.

The impact of SARS-COV2 infection on people in residential care with Parkinson Disease or parkinsonisms: Clinical case series study.

On March 2019 the World Health Organization declared Coronavirus disease (COVID-19) pandemic. Several recent reports disclose that the outcome of the infection is related to age, sex and can be influenced by underlying clinical conditions. Parkinson's disease (PD) and other parkinsonisms are the most common chronic disease which can cause, directly or indirectly, the patient to be more exposed to other diseases, mostly respiratory system's ones. Our primary outcome is to evaluate if PD patients are more susceptible than non-PD to take COVID-19 infection. Second, to detect if the infection course is worse in PD-COVID+ patients versus non-PD. This is a retrospective observational study on a cohort of 18 patients (13 PD- 5 non-PD), hospitalized in a Rehabilitative Unit during the occurrence of SARS-CoV2 epidemic outbreak. All patients performed laboratory tests, lung Computed Tomography (CT) and have been tested for COVID-19 thorough pharyngeal swab. PD and non-PD groups were comparable for age, gender and Hoehn and Yahr stage. Seventy-seven (77)% of PD and 60% of non-PD resulted positive for COVID-19. PD-COVID+ and PD-COVID- did not differ for age, disease duration and L-dopa daily dose. PD COVID-19+ subjects were mainly asymptomatic (50%) while non-PD ones were all symptomatic, mostly with respiratory difficulties. PD doesn't seem to be a risk factor to take SARS-COV2 infection, even if our study is related to a limited sample size. Our results, together with those of other recent studies, highlight the need to evaluate the actual susceptibility of patients with Parkinson's disease to develop COVID-19 disease, and how the infection may influence the risk of clinical worsening and increase of mortality.

Anxiety, depression, and quality of life in Parkinson's disease: the implications of multidisciplinary treatment.

Anxiety and depression in Parkinson's disease (PD) reduce well-being of the patients. Emotional alterations influence motor skills and cognitive performance; moreover, they contribute significantly and independently to worsen rehabilitative treatment response. We investigated anxiety, depression, and quality of life in PD patients subjected to multidisciplinary rehabilitative training. The self-controlled study included 100 PD patients (49 males and 51 females with the mean age of 64.66 years) admitted to 60 days hospitalization rehabilitative program, between January 2017 and December 2018. Motor, cognitive, linguistic abilities, and functional independence were evaluated at admission (T0 baseline visit) and 60 days after (T1) the multidisciplinary rehabilitation including motor exercises, speech therapies, and cognitive intervention. The multidisciplinary rehabilitation improved functional status in PD patients and exerted its positive effects on mood, motor abilities, autonomy in the activities of daily life, perception of quality of life, cognitive performance and speech skills. Non-motor symptoms may worsen severe disability and reduce quality of life. They are often poorly recognized and inadequately treated. Nonetheless, multidisciplinary rehabilitative training represents an optimal strategy to improve disease management. The study was approved by Istituito di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro Neurolesi "Bonino-Pulejo" Ethical Committee (approval No. 6/2016) in June 2016.

Levodopa-carbidopa intrajejunal infusion in Parkinson's disease: untangling the role of age.

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 life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG. METHODS: Out of 512 PD subjects treated with LCIG at 9 Italian PD centers, we selected 25 LE-PD defined as age ≥ 80 years at last follow-up who were available to attend the study visit. Twenty-five PD patients (Control-PD, defined as age < 75 years at last follow-up) matched to LE-PD by disease and LCIG duration served as control group. The following motor and non-motor variables were ascertained: quality of life (PDQ-8), time spent in ON, wearing-off Questionnaire, Unified PD Rating Scale, freezing of gait questionnaire, Parkinson's disease sleep scale-2, Non Motor Symptoms Scale (NMSS), and MOCA. RESULTS: No statistically significant differences were found between LE-PD and Control-PD on PDQ-8 and several motor and non-motor variables. LE-PD had less frequent and milder impulsive-compulsive behaviors and milder dyskinesia. At multivariable regression, worse quality of life was associated with UPDRS-III and NMSS scores but not to age at study visit and age at LICG implant. Rate of adverse effects was similar in both groups. Drop-out rate calculated in the whole PD cohort was comparable between the two groups. CONCLUSION: Our data provide evidence that valuable LCIG infusion might be achieved in late elderly PD.

A Case-Controlled Pilot Study on Rhythmic Auditory Stimulation-Assisted Gait Training and Conventional Physiotherapy in Patients With Parkinson's Disease Submitted to Deep Brain Stimulation.

Deep brain stimulation (DBS) is indicated when motor disturbances in patients with idiopathic Parkinson's disease (PD) are refractory to current treatment options and significantly impair quality of life. However, post-DBS rehabilitation is essential, with particular regard to gait. Rhythmic auditory stimulation (RAS)-assisted treadmill gait rehabilitation within conventional physiotherapy program plays a major role in gait recovery. We explored the effects of a monthly RAS-assisted treadmill training within a conventional physiotherapy program on gait performance and gait-related EEG dynamics (while walking on the RAS-aided treadmill) in PD patients with (n = 10) and without DBS (n = 10). Patients with DBS achieved superior results than those without DBS concerning gait velocity, overall motor performance, and the timed velocity and self-confidence in balance, sit-to-stand (and vice versa) and walking, whereas both groups improved in dynamic and static balance, overall cognitive performance, and the fear of falling. The difference in motor outcomes between the two groups was paralleled by a stronger remodulation of gait cycle-related beta oscillations in patients with DBS as compared to those without DBS. Our work suggests that RAS-assisted gait training plus conventional physiotherapy is a useful strategy to improve gait performance in PD patients with and without DBS. Interestingly, patients with DBS may benefit more from this approach owing to a more focused and dynamic re-configuration of sensorimotor network beta oscillations related to gait secondary to the association between RAS-treadmill, conventional physiotherapy, and DBS. Actually, the coupling of these approaches may help restoring a residually altered beta-band response profile despite DBS intervention, thus better tailoring the gait rehabilitation of these PD patients.

The effect on deep brain stimulation of subthalamic nucleus and dopaminergic treatment in Parkinson disease.

Impulsivity is a frequent non-motor symptom in Parkinson disease (PD). It comprises psycho-behavioral alterations that negatively impact quality of life. Dopaminergic treatments underpin many impulsive controls disorders however, side effects, such as increased impulsivity, are described also after neurosurgical procedure of deep brain stimulation (DBS). We investigated the effect of deep brain stimulation on psycho-behavioral alterations and quality of life (QoL) in PD patients, analyzing, also, the role of dopaminergic therapies.Twenty idiopathic PD patients with and 20 idiopathic PD patients without DBS were included in the study. All patient underwent to neuropsychological assessment for a screening of executive functions, impulsivity, anxiety and depressive symptoms and QoL.Differences were found between DBS and no DBS groups and in term of dopaminergic therapies. The comparison between 2 groups showed a greater motor and attentional impulsivity in DBS patients. Moreover, this impulsivity worse QoL and interpersonal relationships. The combination of Levodopa and dopamine agonists exerted a great impact on impulsivity behavior.The emergence of postoperative impulsivity seems to be a neurostimulator phenomenon related to the computational role of the subthalamic nucleus in modulation of behavior.

Predictors of COVID-19 outcome in Parkinson's disease.

INTRODUCTION: Specific pre-existing medical conditions (e.g. hypertension or obesity), advanced age and male sex appear linked to more severe manifestations of SARS Co-V2 infection, thus raising the question of whether Parkinson's disease (PD) poses an increased risk of morbidity and mortality in COVID-19 patients. METHODS: In order to describe the outcome of COVID-19 in multi-centre a cohort of PD patients and explore its potential predictors, we gathered the clinical information of 117 community-dwelling patients with COVID-19 followed in 21 tertiary centres in Italy, Iran, Spain, and the UK. RESULTS: Overall mortality was 19.7%, with a significant effect of co-occurrence of dementia, hypertension, and PD duration. CONCLUSIONS: The frailty caused by advanced PD poses an increased risk of mortality during COVID-19.

Do patients with PD benefit from music assisted therapy plus treadmill-based gait training? An exploratory study focused on behavioral outcomes.

Purpose: Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder, presenting not only with motor symptoms (resting tremor, bradykinesia, and muscular rigidity), but also with cognitive and behavioral problems that need to be addressed in a rehabilitation setting. Aim of the study was to evaluate the effects of a combined rehabilitative approach, using gait training coupled to music-based therapy, on cognitive and behavioral function in a sample of patients with PD.Materials and Methods: Forty patients, meeting the inclusion criteria, were enrolled in this study and were randomly divided into two groups. The control group (CG) underwent traditional over ground gait training, whilst the experimental group (EG) underwent gait training with the Biodex Gait Trainer 3 (a treadmill integrated with music therapy). Each subject was evaluated at baseline (T0) and after the training (T1), using specific neuropsychological and motor function tests.Results: The EG presented higher outcomes scores concerning mood and quality of life in all subscales of Psychological General Well-Being Index (i.e. anxiety, depression, health, vitality and positivity) and subscales of Brief-COPE, with regard to behavioral disengagement, positive reframing, planning, acceptance and use of emotional support, as compared to the CG. Moreover, a significant improvement in motor functioning, with regard to static and dynamic balance, was found in the EG.Conclusion: Music-based gait training rehabilitation may be considered an effective strategy to improve behavioral performances, coping strategies and rehabilitation outcomes in patients with PD.

Neuropsychological functions and psychiatric symptoms in late-onset manifestation of pantothenate kinase-associated neurodegeneration: a clinical case report.

Purpose of the study: Pantothenate Kinase-associated Neurodegeneration (PKAN) is a form of Neurodegeneration with brain iron accumulation (NBIA) due to gene mutations. Classical phenotype showed progressive neurological symptoms associated to a characteristic pattern of basal ganglia iron deposits. The atypical case, with adult-onset manifestation, could have neuropsychiatric symptoms with behavioral deficits. We described an adult-onset case of Pantothenate Kinase-associated Neurodegeneration.Materials and methods: The patient underwent neuropsychological and psychiatric evaluation and Magnetic Resonance Imaging, respectively for cognitive and behavioral assessment and to confirm the characteristic findings of this syndrome.Results: The patient showed atypical phenotype of Pantothenate Kinase-associated Neurodegeneration, characterized by language deficits, dixesecutive, and psychiatric manifestations, such as obsessive ideation, impulsivity, and disinhibition.Conclusions: This description could be helpful to a more correct diagnosis and clinical management.

Impaired Recognition of Facial Emotion in Patients With Parkinson Disease Under Dopamine Therapy.

INTRODUCTION: Parkinson disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms. The impaired ability to recognize facial emotion expressions represents an important nonmotor symptom. The aim of this study is to investigate the ability in recognizing facial emotion expressions in patients with PD under dopamine replacement therapy. METHODS: Thirty medicated patients with PD and 15 healthy controls (HC) were enrolled. All participants performed the Ekman 60-Faces test for emotional recognition. All patients underwent a neuropsychological evaluation for global cognitive functioning, depression, and anxiety. RESULTS: Patients with PD were impaired in recognizing emotions. Significant differences between PD and HC were found in Ekman 60-Faces test scores (P < .001), and in Ekman 60-Faces test subscales, in particular, sadness, fear, disgust, anger, and surprise (P < .001). CONCLUSIONS: The nigrostriatal dopaminergic depletion seems to determine emotional information processing dysfunction. This relevant nonmotor symptom could have consequences in daily living reducing interactions and social behavioral competence.

Quantitative assessment of Parkinsonian tremor by using biosensor device.

Parkinson disease (PD) is the second most common neurodegenerative disease which affects population older than 65 years. Tremor represents one of the main symptomatic triads in PD, particularly in rest state.We enrolled 41 idiopathic PD patients, to validate the assessment of tremor symptoms.To be enrolled in the study, patients had to fulfill the movement disorder society clinical diagnostic criteria for PD.We used an innovative home-made, low-cost device, able to quantify the frequency and amplitude of rest tremor and stress conditionOur results confirmed the presence of tremor during muscular effort in a significant number of patients and the influence of emotional stress.We suppose that this new device should be validated in clinical practice as a support of differential diagnosis and therapeutic management of PD patients.

Potential predictors of quality of life in Parkinson's Disease: Sleep and mood disorders.

Sleep Disturbances are a non motor symptom very common in Parkinson's Disease characterized by insomnia, worse quality of sleep and Excessive Daytime Sleepiness. Several factors have been associated with these disorders, especially neuropsychiatric symptoms, such as anxiety and depression. The aim of the study was to investigate the relationship between sleep quality and mood disorders and the effects on Quality of Life in Parkinson's Disease patients. We have enrolled 48 Parkinson's Disease patients divided in two group according to their quality of sleep. All of them completed standardized questionnaires such as Beck Depression Inventory, Hamilton Anxiety Rating Scale, Parkinson Disease Questionnaire, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index. Inter-group analysis showed a significant difference among two groups in anxiety, depression, excessive daytime sleepiness and quality of sleep. Sleep problems, excessive daytime sleepiness, depressive and anxiety symptoms are frequent in PD patients and are significantly associated each other.