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.

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.

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.

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.

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.

Proprioceptive Focal Stimulation (Equistasi®) May Improve the Quality of Gait in Middle-Moderate Parkinson's Disease Patients. Double-Blind, Double-Dummy, Randomized, Crossover, Italian Multicentric Study.

Objective: The object of the study was to evaluate the efficacy of Proprioceptive Focal Stimulation on Gait in middle-advanced Parkinson (PD) patients by a crossover, randomized, double Blind double dummy study using Equistasi®, a nano-technological device of the dimension of a plaster which generates High Frequency Vibration (FV). Background: The efficacy of Gait Analysis (GA) on evaluating gait modification on Parkinson's disease (PD) Patients is already well-known. Therefore, GA was recorded in a group of PD patients using Equistasi® device and its placebo. Methods: Forty PD patients on optimal therapy were enrolled in the study. Patients were randomly assigned to receive active or sham stimulation for 8 weeks and, following a wash-out period, switched to an additional 8-week period with the reverse intervention. GA was performed at baseline and at the end of both 8-weeks treatment periods Clinical state was monitored by MDUPDRS part III. Results: Active stimulation induced a significant improvement in Mean Velocity (Velocity), Stride Length (SL), Stance (STA), and Double Support (DST) percentage, both in left and right stride. The ANOVA analysis using H&Y stage as a factor, showed that DST and MDUPDRS III scores improved significantly more in the more severely affected subjects. Conclusions: The findings obtained in this randomized controlled study show the efficacy of mechanical focal vibration, as stimulation of the proprioceptive system, in PD and encourage further investigation. The effect of the device on more severe patients may open a new possibility to identify the most appropriate candidate for the management of gait disturbances and postural instability with FV delivered with Equistasi®.

Sleep microstructure in Parkinson's disease: cycling alternating pattern (CAP) as a sensitive marker of early NREM sleep instability.

BACKGROUND: Sleep disorders are frequent in Parkinson's disease (PD). Apart from the occurrence of REM behavior disorders, in the early phase of the disease standard sleep macrostructure evaluation was inconclusive. OBJECTIVE: We analyzed non-rapid eye movement (NREM) sleep microstructure (CAP) in a group of PD patients to provide an objective measure of sleep disruption. METHODS: We recruited 31 PD patients [mean age 59.5 ± 12.4 years; mean Hoehn-Yahr (H-Y) stage: 3.4 ± 1.8] and 34 age-matched non-parkinsonian subjects (mean age 61.5 ± 15.2 years) as a control group. All patients underwent full-night laboratory polysomnography (PSG). Conventional sleep macro/microstructure analysis was performed. Patients were then divided into two groups: group 1 (H-Y stage ≤ 2) and group 2 (H-Y stage ≥ 3). RESULTS: In group 2 PD patients compared to controls, alterations of both sleep macrostructure and microstructure were found. The PD subgroup with milder disease (group 1) presented sleep macrostructure, movements and respiratory parameters not significantly different from controls, although their CAP rate was significantly higher and the proportion of the A1 phase of CAP was reduced (p = 0.03). Multivariate logistic regression showed that disease duration, disease severity, and arousal index emerged as independent predictive factors for CAP rate ≥55% and the A1 phase of CAP ≤40% (p < 0.05). CONCLUSION: The main result of our study consists in the disclosure of altered NREM sleep microstructure in PD even at an early stage of the disease, suggesting an early alteration of the central pathways involved in the NREM sleep building-up and stability.

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.

Feasibility of home exercises to enhance the benefits of tango dancing in people with Parkinson's disease.

BACKGROUND: A style of dance called tango translates clinical practice into a new philosophy and rehabilitative approach for individuals with Parkinson's disease (PD). The style of dance mixes music, self-generated and external cued strategies and social and emotional recovery. In recent years, there has been an increase in the number of studies reporting health benefits for people diagnosed with PD who dance tango. However, there are some organisational limitations to people participating in dance classes, including having trained Tango teachers, an appropriate space for dancing, and schedule that allows for participants with motor inabilities. METHODS: This pilot study involved the observation of PD patients who completed four days of home exercise plus a tango dance lesson each week for five weeks. RESULTS: Ten PD patients improved their quality of life, their motor score on the Unified Parkinson's Disease Rating Scale and their kinematic performances. CONCLUSIONS: We propose a protocol of exercises that has been derived from the tango dance and that can be performed in a patient's home.

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.

A Psychometric Tool for a Virtual Reality Rehabilitation Approach for Dyslexia.

Dyslexia is a chronic problem that affects the life of subjects and often influences their life choices. The standard rehabilitation methods all use a classic paper and pencil training format but these exercises are boring and demanding for children who may have difficulty in completing the treatments. It is important to develop a new rehabilitation program that would help children in a funny and engaging way. A Wii-based game was developed to demonstrate that a short treatment with an action video game, rather than phonological or orthographic training, may improve the reading abilities in dyslexic children. According to the results, an approach using cues in the context of a virtual environment may represent a promising tool to improve attentional skills. On the other hand, our results do not demonstrate an immediate effect on reading performance, suggesting that a more prolonged protocol may be a future direction.

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.

Body-Sensor-Network-Based Kinematic Characterization and Comparative Outlook of UPDRS Scoring in Leg Agility, Sit-to-Stand, and Gait Tasks in Parkinson's Disease.

Recently, we have proposed a body-sensor-network-based approach, composed of a few body-worn wireless inertial nodes, for automatic assignment of Unified Parkinson's Disease Rating Scale (UPDRS) scores in the following tasks: Leg agility (LA), Sit-to-Stand (S2S), and Gait (G). Unlike our previous works and the majority of the published studies, where UPDRS tasks were the sole focus, in this paper, we carry out a comparative investigation of the LA, S2S, and G tasks. In particular, after providing an accurate description of the features identified for the kinematic characterization of the three tasks, we comment on the correlation between the most relevant kinematic parameters and the UPDRS scoring. We analyzed the performance achieved by the automatic UPDRS scoring system and compared the estimated UPDRS evaluation with the one performed by neurologists, showing that the proposed system compares favorably with typical interrater variability. We then investigated the correlations between the UPDRS scores assigned to the various tasks by both the neurologists and the automatic system. The results, based on a limited number of subjects with Parkinson's disease (PD) (34 patients, 47 clinical trials), show poor-to-moderate correlations between the UPDRS scores of different tasks, highlighting that the patients' motor performance may vary significantly from one task to another, since different tasks relate to different aspects of the disease. An aggregate UPDRS score is also considered as a concise parameter, which can provide additional information on the overall level of the motor impairments of a Parkinson's patient. Finally, we discuss a possible implementation of a practical e-health application for the remote monitoring of PD patients.

Visual Hallucinations as Incidental Negative Effects of Virtual Reality on Parkinson's Disease Patients: A Link with Neurodegeneration?

We followed up a series of 23 Parkinson's disease (PD) patients who had performed an immersive virtual reality (VR) protocol eight years before. On that occasion, six patients incidentally described visual hallucinations (VH) with occurrences of images not included in the virtual environment. Curiously, in the following years, only these patients reported the appearance of VH later in their clinical history, while the rest of the group did not. Even considering the limited sample size, we may argue that VR immersive systems can induce unpleasant effects in PD patients who are predisposed to a cognitive impairment.

Automatic UPDRS Evaluation in the Sit-to-Stand Task of Parkinsonians: Kinematic Analysis and Comparative Outlook on the Leg Agility Task.

In this study, we first characterize the sit-to-stand (S2S) task, which contributes to the evaluation of the degree of severity of the Parkinson's disease (PD), through kinematic features, which are then linked to the Unified Parkinson's disease rating scale (UPDRS) scores. We propose to use a single body-worn wireless inertial node placed on the chest of a patient. The experimental investigation is carried out considering 24 PD patients, comparing the obtained results directly with the kinematic characterization of the leg agility (LA) task performed by the same set of patients. We show that i) the S2S and LA tasks are rather unrelated and ii) the UPDRS distributions (for both S2S and LA tasks) across the patients have a direct impact on the observed system 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.