18F-FDG PET brain findings in disease-discordant monozygotic mosaic twins with Cri du Chat (5p-) syndrome.

We describe the first report on the genotype-phenotype patterns and [18F] fluoro-deoxygluycose (18F-FDG) Positron Emission Tomography (PET) findings in two disease-discordant monozygotic twins with Cri du Chat syndrome (CdcS) presenting deletion of 5p, 46, XY, del(5)(p14)/46, XY. One twin showed a severe phenotype; significant 18F-FDG PET hypometabolism (p=0.001) was revealed in the left and right hemispheres, thalamus, cerebellum, and midbrain, whereas hypermetabolism was detected in the left premotor cortex. The other twin presented a mild phenotype; significant hypometabolism was detected only in the right side (parahippoccampal gyrus and cerebellum). Further studies should investigate the causes of phenotypic discordance in twins with CdcS.

New pharmacological and neuromodulation approaches for impulsive-compulsive behaviors in Parkinson's disease.

INTRODUCTION: A significant proportion of patients with Parkinson's disease (PD) display a set of impulsive-compulsive behaviors at some point during the course of illness. These behaviors range from the so-called behavioral addictions to dopamine dysregulation syndrome, punding and hoarding disorders. These behaviors have been consistently linked to the use of dopaminergic medications used to treat PD motor symptoms (dopamine agonists, levodopa, and other agents) and less consistently to neuromodulation techniques such as deep brain stimulation (DBS). Since there are still no approved treatments for these conditions, their pharmacological management is still a big challenge for clinicians. METHODS: We conducted an extensive review of current pharmacological and neuromodulation literature for the management of impulsive-compulsive disorders in PD patients. RESULTS: Pharmacological treatment approaches for impulsive-compulsive behaviors and DDS in PD patients include reduction of levodopa (LD), reduction/cessation of dopamine agonist (DA), and initiation of infusion therapies (apomorphine infusion and duodopa). Also, atomoxetine, a noradrenergic agent approved for the treatment of attention deficit hyperactivity disorder, showed some interesting preliminary results but there is still a lack of controlled longitudinal studies. Finally, while DBS effects on impulsive-compulsive disorders are still controversial, non-invasive techniques (such as transcranial magnetic stimulation and transcranial direct current stimulation) could have a potential positive effect but, again, there is still a lack of controlled trials. CONCLUSION: Managing impulsivity and compulsivity in PD patients is still a non-evidence-based challenge for clinicians. Controlled trials on promising approaches such as atomoxetine and non-invasive neuromodulation techniques are needed.

Skin picking disorder in 97 Italian and Spanish Cri du chat patients.

Skin picking (SP) disorder is characterized by recurrent SP resulting in skin lesions. Several studies estimated its prevalence as approximately 2-4 % of the general population. It is also present in a high percentage of patients with intellectual and developmental disabilities, such as Cri du chat (CdC) syndrome, a rare genetic disorder caused by variable size deletions of the short arm of chromosome 5. The aim of this study was to evaluate, in 97 patients with CdC syndrome, the following data: frequency of SP, patient's age at onset, type, and topographic-anatomic distribution of the lesions presented. The results show that 85% of patients confirm a SP disorder, usually concentrated on the hands, fingers, and the face, with onset between 6 and 10 years of age, regardless of patient's sex. Evidence for early appearance of SP behavior, high prevalence in stressful circumstances, and efficacy of distracting actions immediately suggest the possibility that proper parental information about SP behavior and parental education concerning the methods to deal with this problem may result in its efficient reduction already in childhood.

Focal Vibration Training (Equistasi®) to Improve Posture Stability. A Retrospective Study in Parkinson's Disease.

BACKGROUND: For people with Parkinson's disease (PD), falls are a critical point. Focal vibration training (FVT) may represent a valid tool to improve postural performances and reduce the risk of falls. The aim of this study was to evaluate the efficacy of FVT to improve the postural stability in PD patients. METHODS: Since October 2015, 55 consecutive PD patients have been selected (T0) for an approach including FVT associated with a rehabilitative protocol (RP); after eight weeks (T1), those patients showing a relevant improvement in the clinical rating scales ((Timed Up and Go (TUG), Tinetti, Unified Parkinson's disease rating scale (UPDRS) Part III, Berg Balance scale (BBS) and falls rate scale), continued with the FVT protocol (FVTRP group). The remaining patients continued with only the RP (RP group). In July 2018, we have extrapolated the data of the last clinical visit (T2) to observe any differences in the rate of falls. RESULTS: The FVTRP group shows a decrement in the rate of falls from 2.1 to 1.25 (p 0.036) and a stability of the levodopa equivalent daily dosage (LEDD). The RP group shows an increment of LEDD and stability in falls. CONCLUSIONS: FVT has been confirmed as a valid tool to enhance the effect of the rehabilitation protocol aimed at postural training.

An Integrated Multi-Sensor Approach for the Remote Monitoring of Parkinson's Disease.

The increment of the prevalence of neurological diseases due to the trend in population aging demands for new strategies in disease management. In Parkinson's disease (PD), these strategies should aim at improving diagnosis accuracy and frequency of the clinical follow-up by means of decentralized cost-effective solutions. In this context, a system suitable for the remote monitoring of PD subjects is presented. It consists of the integration of two approaches investigated in our previous works, each one appropriate for the movement analysis of specific parts of the body: low-cost optical devices for the upper limbs and wearable sensors for the lower ones. The system performs the automated assessments of six motor tasks of the unified Parkinson's disease rating scale, and it is equipped with a gesture-based human machine interface designed to facilitate the user interaction and the system management. The usability of the system has been evaluated by means of standard questionnaires, and the accuracy of the automated assessment has been verified experimentally. The results demonstrate that the proposed solution represents a substantial improvement in PD assessment respect to the former two approaches treated separately, and a new example of an accurate, feasible and cost-effective mean for the decentralized management of PD.

A Self-Managed System for Automated Assessment of UPDRS Upper Limb Tasks in Parkinson's Disease.

A home-based, reliable, objective and automated assessment of motor performance of patients affected by Parkinson's Disease (PD) is important in disease management, both to monitor therapy efficacy and to reduce costs and discomforts. In this context, we have developed a self-managed system for the automated assessment of the PD upper limb motor tasks as specified by the Unified Parkinson's Disease Rating Scale (UPDRS). The system is built around a Human Computer Interface (HCI) based on an optical RGB-Depth device and a replicable software. The HCI accuracy and reliability of the hand tracking compares favorably against consumer hand tracking devices as verified by an optoelectronic system as reference. The interface allows gestural interactions with visual feedback, providing a system management suitable for motor impaired users. The system software characterizes hand movements by kinematic parameters of their trajectories. The correlation between selected parameters and clinical UPDRS scores of patient performance is used to assess new task instances by a machine learning approach based on supervised classifiers. The classifiers have been trained by an experimental campaign on cohorts of PD patients. Experimental results show that automated assessments of the system replicate clinical ones, demonstrating its effectiveness in home monitoring of PD.

Utility of Boston Qualitative Scoring System for Rey-Osterrieth Complex Figure: evidence from a Parkinson's Diseases sample.

This study examined the ability of the Boston Qualitative Scoring System (BQSS) in comparison to the Osterrieth scoring method to separate Parkinson's Disease patients without dementia from healthy controls at the Rey-Osterrieth Complex Figure (ROCF) copy. 30 PD participants and 30 healthy participants completed ROCF copy. The performance was scored according to both methods. The results indicated that PD patients performed significantly worse on ROCF. According to ROC analyses, BQSS Copy Total score represented the most suitable index to distinguish between the two groups: a score below or equal to 16 indicates an impaired performance. Moreover, PD participants reported lower performance in the BQSS scores of Planning and Neatness. PD patients' poor performance in ROCF copy was related to executive difficulties, specifically in terms of planning and impulsivity, instead of global visuo-constructional impairments. An extensive evaluation of copy drawings allowing to disentangle between different involved cognitive domains would be suitable, specifically in those clinical conditions like PD, in which motor impairments affect drawing performance.

Disentangling the relationship between cognitive estimation abilities and executive functions: a study on patients with Parkinson's disease.

The cognitive estimation test (CET) measures cognitive estimation abilities: it assesses the ability to apply reasoning strategies to answer questions that usually cannot lead to a clear and exact reply. Since it requires the activation of an intricate ensemble of cognitive functions, there is an ongoing debate in the literature regarding whether the CET represents a measurement of global cognitive abilities or a pure measure of executive functions. In the present study, CET together with a neuropsychological assessment focused on executive functions was administered in thirty patients with Parkinson's disease without signs of dementia. The CET correlated with measures of verbal working memory and semantic knowledge, but not with other dimensions of executive domains, such as verbal phonemic fluency, ability to manage real-world interferences, or visuospatial reasoning. According to our results, cognitive estimation abilities appeared to trigger a defined cognitive path that includes executive functions, namely, working memory and semantic knowledge.

Break in volition: a virtual reality study in patients with obsessive-compulsive disorder.

Research in obsessive-compulsive disorder (OCD) produced inconsistent results in demonstrating an association between patients' symptom severity and their cognitive impairments. The process involved in volition aspects of behavioral syndromes can be extensively analyzed using specific tests developed in virtual environments, more suitable to manipulate rules and possible breaks of the normal task execution with different, confusing or stopping instructions. The study involved thirty participants (15 OCD patients and 15 controls) during task execution and the relative interferences. At this purpose, the virtual version of Multiple Errands Test was used. Virtual reality setting, with a higher ecological validity respect to a classic neuropsychological battery, allowed us to take into account deficits of volition and the relative dysexecutive functions associated with OCD patients. The proposed paradigm also allows the development of innovative prototypes of coevolving technologies based on new theories and models and deeper understanding of human behavior.

Esophageal Cancer with Early Onset in a Patient with Cri du Chat Syndrome.

BACKGROUND: In Cri du Chat (CdC), cancer as comorbidity is extremely rare. In databases from Denmark, Spain, Australia, New Zealand, and Japan, no cancer was reported; in Italy and Germany, four cancers were identified out of 321 CdCs. METHODS: In a 29-year-old CdC patient, clinical investigations following hematemesis led to the diagnosis of esophageal adenocarcinoma (EAC). A high pain threshold was also observed. Conventional and molecular cytogenetic defined the size of the deletion, and exome analysis on the trio completed the molecular work. RESULTS: Cytogenetic analysis showed a de novo chromosomal alteration: 46,XY,ishdel(5)(p14.3)(D5S28-) and arr[GRCh37] 5p15.33p14.3(1498180_19955760)x1. A quantitative sensory test demonstrated a high heat threshold. A 18f-fluorodeoxyglucose PET/TC scan of the brain failed to detect reduction of metabolism in the somatosensory area or insular cortex. Exome analysis in the trio (patient and parents) failed to identify variants to be interpreted as a likely risk factor for EAC. CONCLUSION: We conclude that the presence of well-known risk factors (maleness, obesity, gastroesophageal reflux, and Barrett's metaplasia) in a patient with very limited capability of expressing discomfort or referring clinical symptoms have been the main risk factors for developing EAC. At present, based on the available data, there is no evidence of any increased risk of developing cancer in CdC patients.

Virtual help for real surgery: the case of awake surgery.

Awake surgery can be highly stressful for patients. In fact, being awake, patients could perceive that the environmental demands are taxing or exceed their adaptive abilities. We proposed the use of Virtual Reality as a functional and effective tool for a new class of clinical applications aimed at helping patients to cope with these specific stressful situations. Using coping skills that have been learnt during the virtual experience, patients can reduce their psychological stress and improve their collaboration and - in general - the outcome of the intervention.

Could Proprioceptive Stimuli Change Saddle Pressure on Male Cyclists during Different Hand Positions? An Exploratory Study of the Effect of the Equistasi® Device.

When pedaling, the excessive pressure on the seat has the potential to produce injuries and this can strongly affect sport performance. Recently, a large effort has been dedicated to the reduction of the pressure occurring at the saddle region. Our work aims to verify the possibility of modifying cyclists' pedaling posture, and consequently the pressure on the saddle, by applying a proprioceptive stimulus. Equistasi® (Equistasi srl, Milano, Italy) is a wearable device that emits focal mechanical vibrations able to transform the body temperature into mechanical vibratory energy via the embedded nanotechnology. The data acquired through a pressure mapping system (GebioMized®) on 70 cyclists, with and without Equistasi®, were analyzed. Pedaling in three positions was recorded on a spin trainer: with hands on the top, hands on the drop handlebar, and hands on the lever. Average force, contact surface, and average and maximum pressure each in different regions of the saddle were analyzed, as well as integral pressure time and center of pressure. In the comparisons between hands positions, overall pressure and force variables were significantly lower in the drop-handlebar position at the rear saddle (p < 0.03) and higher in hand-on-lever and drop-handlebar positions at the front saddle (p < 0.01). When applying the Equistasi device, the contact surface was significantly larger in all hand positions (p < 0.05), suggesting that focal stimulation of the lumbar proprioceptive system can change cyclists' posture.

Electrogastrographyc activity in Parkinson's disease patients with and without motor fluctuations.

BACKGROUND: Gastroenteric dysfunctions are very common in Parkinson's disease, but their relationship with dopaminergic response and motor fluctuations is still unclear. Electrogastrography is a noninvasive method for measuring gastric myoelectrical activity. METHODS: We evaluated the effects of levodopa intake on the motility of empty stomachs in Parkinson's disease patients with and without motor fluctuations. RESULTS: The electrogastrography findings showed a normal pattern not influenced by levodopa intake, unrelated to plasmatic levodopa concentrations and to clinical parameters. CONCLUSIONS: Our results suggest that at rest gastric activity of Parkinson's disease patients is normal and plasmatic levodopa variability is not influenced by gastric motility.

Sleep dysfunctions influence decision making in undemented Parkinson's disease patients: a study in a virtual supermarket.

In the early-middle stages of Parkinson's disease (PD), polysomnographic studies show early alterations of the structure of the sleep, which may explain frequent symptoms reported by patients, such as daytime drowsiness, loss of attention and concentration, feeling of tiredness. The aim of this study was to verify if there is a correlation between the sleep dysfunction and decision making ability. We used a Virtual Reality version of the Multiple Errand Test (VMET), developed using the NeuroVR free software (http://www.neurovr2.org), to evaluate decision-making ability in 12 PD not-demented patients and 14 controls. Five of our not-demented 12 PD patients showed abnormalities in the polysomnographic recordings associated to significant differences in the VMET performance.

Use of surface EMG for evaluation of upper limb spasticity during botulinum toxin therapy in stroke patients.

The clinical assessment of spasticity in stroke patients generally includes descriptive scales, such as the Modified Ashworth Scale (MAS) and the Global Pain Scale (GPS), however these may not be sufficiently sensitive to accurately detect improvements, especially at upper limb level; electromyography (EMG) may be the answer to this clinical requirement. The aim of this study was to quantify the effects of botulinum toxin type A (BTX) in treating upper extremity spasticity in stroke patients, using clinical evaluation (MAS and GPS) and EMG. Ten patients were assessed before, 30 days and 180 days after BTX injection using clinical evaluations and EMG. At 30 days all clinical measures improved significantly. Whereas MAS scores, after recording an improvement at the first evaluation session, were worse at the second assessment, GPS scores improved over time, both at the first and at the second evaluation session. A reduction of EMG activity was found 30 days after injections, in particular at baseline and during passive flexion movement. Our results demonstrated that measurement of EMG activity may be an effective means of detecting functional improvements and of monitoring the effects of treatment in post-stroke patients.

Executive functions in a virtual world: a study in Parkinson's disease.

In Parkinson's disease executive functions are altered. We used a Virtual Reality version of the Multiple Errand Test in order to evaluate decision-making ability in 12 patients and 14 controls. Patients with Parkinson's disease, even if not-demented, showed strategies full of errors, suggesting that impulse control disorder, very frequent in course of disease, could precede cognitive dysfunctions.

Is bimanual interference affected in the case of a central proprioceptive loss? New insight from a left-brain-damaged single-case study.

OBJECTIVE: It was suggested that the bimanual coupling effect might be linked to motor intentionality and planning, which are the top-down components of motor execution. However, previous results in pathological and healthy individuals have also underlined the pivotal role of bottom-up sensorimotor information. METHOD: In this single-case study, the Circles-Lines Coupling Task was administered to a left-parietal-brain-damaged individual. The cerebral lesion caused a central proprioceptive loss, relative to the impaired right hand, when out of the visual control. For the 1st time in literature, we sought to investigate whether the movement of the unaffected hand induced an efficient coupling effect on the movement of the affected one. The bimanual task was performed in the presence and absence of visual input. The patient's performance was compared with that of healthy controls. RESULTS: We observed the traditional bimanual coupling effect in healthy controls. Moreover, we also replicated the effect when they performed the task blindfolded. In the case of the patient, both hands showed the typical ovalization of the line trajectory when the task was performed in visual modality. It is interesting that when the patient performed the task blindfolded, the trajectories of the impaired right hand seemed to be not influenced by the concomitant circular movement of the spared left hand. CONCLUSIONS: The movement of the unaffected hand induced a bimanual coupling effect on the movement of the affected one only when the visual input was available. In absence of a visual feedback, the aberrant proprioceptive information might preclude the emerging of bimanual coupling, even in the case of a preserved motor intentionality and planning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

18F-FDG PET Identifies Altered Brain Metabolism in Patients with Cri du Chat Syndrome.

Cri du chat syndrome (CDCS) is a rare genetic disease that is caused by a deletion in the short arm of chromosome 5 (5p) and has a variable clinical spectrum. To our knowledge, no study in the literature has ever applied 18F-FDG PET/CT to investigate alterations in brain glucose metabolism in these subjects. The aims of this study were to detect differences in brain 18F-FDG metabolism in CDCS patients with different clinical presentations and identify possible brain metabolic phenotypes of this syndrome. Methods: Six patients (5 male and 1 female; age range, 10-27 y) with CDCS were assessed for the presence of cognitive and behavioral symptoms using a battery of neuropsychologic tests and then classified as having either a severe or a mild phenotype. The patients then underwent brain 18F-FDG PET/CT. The PET/CT findings were compared with an age- and sex-matched control group using statistical parametric mapping (SPM). Whether there was an association between different clinical phenotypes and 18F-FDG PET/CT findings was investigated. Results: Four patients had the severe phenotype, and 2 patients demonstrated the mild phenotype. SPM single-subject analysis, and a group analysis in comparison with the control cohort, revealed significant hypometabolism in the left temporal lobe (Brodmann areas [BAs] 20, 36, and 38), in the right frontal subcallosal gyrus (BA 34) and caudate body, and in the cerebellar tonsils (P < 0.001). Hypermetabolism (P = 0.001) was revealed in the right superior and precentral frontal gyrus (BA 6) in the patient group, compared with the control cohort. In SPM single-subject analysis, the hypermetabolic areas were detected only in patients with the severe phenotype. Conclusion: This study revealed different patterns of brain glucose metabolism in patients with the severe and mild phenotypes, compared with control subjects. In particular, abnormal hypermetabolism in the brain, as evaluated by18F-FDG PET/CT, seems to correlate with the severe CDCS phenotype.

Walking in an immersive virtual reality.

The aim of this study was to investigate the effects on gait induced by a completely immersive Virtual Reality (VR) with and without perturbation. Ten healthy subjects were analyzed during over-ground walking in different conditions: standard gait, VR gait and perturbed VR gait. Results showed that subjects immersed in the virtual environment walked slowly, with decreased cadence (-13%) and stride length (-28%) as well as increased base of support in terms of step width (+20%). The perturbation of the VR caused an interesting effect: many computed parameters, still away from the standard gait condition, improved if compared to the unperturbed VR condition. In conclusion, walking in VR leads to gait instability, which is less pronounced in presence of perturbation, probably due to the reweight of sensory inputs. This study could represent the first step for the application of the proposed VR environment to pathological subjects.

Behaviour of motor disabilities and appearance of visual hallucinations in patients with Parkinson's disease in a virtual environment.

We studied 23 Parkinson's disease (PD) non-demented patients and 15 controls in Virtual Reality (VR) environments reproducing usual daily living situations. In VR sessions, PD patients performed their actions worse than controls, in terms of time of execution in exploration and pointing, precision as objects avoiding, and in semantic incidental memory task. We observed clear differences of performances between on and off status medication, with a global worsening during off phase. Moreover, all six patients with motor fluctuations described visual hallucinations during off state, with occurrence of images not included in the virtual environment.