Effectiveness of home-based rehabilitation using active video games on quality of life, cognitive and motor functions in people with Parkinson's disease: a systematic review.

PURPOSE: We summarized the effectiveness of home-based active video game interventions on physical and cognitive functions, as well as quality of life in adults with Parkinson's disease. We also assessed the feasibility, safety, adherence, and retention of benefits of these interventions. METHOD: We searched studies in eight databases from 1st March to 30th November 2020. Two authors independently performed the selection, data extraction and risk of bias evaluation (PROSPERO ID: CRD42020178138). RESULTS: Nine studies were included in this systematic review (412 participants). All in all, home-based active video games were found effective in improving gait and balance functions in people with Parkinson's disease, equivalent to usual care and conventional therapy. No conclusion can be drawn on cognition and quality of life. Home-based active video games seemed feasible, safe, and were enjoyed by people with Parkinson's disease. The optimal dose, the need for supervision and the retention of benefits of these interventions are still to be determined. These results should be interpreted carefully, considering the limited number of included studies and their small sample sizes, the widespread heterogeneity of included studies and their medium average methodological quality. CONCLUSION: Future research should focus on the effects of home-based active video games on impairments specific to Parkinson's disease, such as falls, freezing of gait and attention, as well as the dose, need for supervision and retention of the benefits of these interventions.IMPLICATIONS FOR REHABILITATIONHome-based active video games are effective in improving motor functions in people with PD.No conclusion can be drawn regarding cognition in people with PD.No conclusion can be drawn regarding quality of life in people with PD.Home-based active video games seem feasible and safe, and are enjoyed by people with PD.The dose, need for control and retention of the benefits still need to be determined.

Antibody-nucleotide conjugate as a substrate for DNA polymerases.

Here we report on the development of an antibody-modified nucleotide and its sequence-selective incorporation into nascent DNA catalysed by DNA polymerases. Although the modification of the nucleotide is several orders of magnitude larger than the natural dNTP substrate and even exceeds the size of the DNA polymerase, it is well accepted by the enzyme. Moreover, the recognition of the antibody is not abolished by the conjugation but can be recognized by a secondary antibody that is conjugated to a signal-generating enzyme (i.e., horse radish peroxidase). This product can thus be exploited for a colorimetric read-out of nucleotide incorporation by the naked eye that allows detection of DNA as low as 10 amol. In future, assays like the one described herein might allow nucleic acid diagnostics at single nucleotide resolution without any laboratory equipment.

Leptin (rs7799039) and solute carrier family 30 zinc transporter (rs13266634) polymorphisms in Euro-Brazilian pregnant women with gestational diabetes.

Leptin (LEP), a protein that plays a fundamental role in the metabolism of energy reserves, and the solute carrier family 30 A8 zinc transporter (SLC30A8) have been consistently associated with diabetes. Women with gestational diabetes are at moderate risk of developing diabetes type 1 and 2 after pregnancy, in addition to complications to the fetus. We investigated the association of the polymorphisms rs7799039 (LEP) and rs13266634 (SLC30A8) in a case-control study in Euro-Brazilians with gestational diabetes (GDM, N = 134) and healthy pregnant women (control, N = 180). Real-time PCR with fluorescent probes (TaqMan system) was applied to genotyping. All polymorphisms were in Hardy-Weinberg equilibrium. The minor allele frequencies, for healthy and GDM, respectively, for the A-allele (LEP gene rs7799039) were 40.3% (95%CI = 35-45%) vs 36.6% (95%CI = 31-42%), P = 0.345; and for the T-allele (SLC30A8 gene rs13266634) were 27.8% (95%CI = 23-32%) vs 23.5% (95%CI = 18-29%), P = 0.227. Genotype comparisons for both polymorphisms showed no significant difference (P > 0.05). The polymorphisms rs7799039 and rs13266634 were not associated with GDM in the population studied (P > 0.05). The minor allele frequencies for both polymorphisms were similar to those of other Caucasian populations.

"De-novo" consultation: Evaluation of an outpatient's clinic dedicated to early diagnosis of parkinsonian syndromes.

INTRODUCTION: In the absence of specific clinical signs, imaging or biomarkers, the differential diagnosis of degenerative parkinsonian syndromes may be difficult at early stages of the disease. To reduce the risk of misdiagnosis or delayed diagnosis and referral to multiple medical centers at disease onset, easier access to expert centers should be available. To improve the initial care of parkinsonian patients, the Parkinson's disease Expert Center (PEC) at Pitié-Salpêtrière Academic Hospital has set up a specific outpatients clinic with short waiting times dedicated to the diagnosis of early Parkinson's disease and related disorders. METHODS: The PEC setup first identifies requests for diagnostic confirmation of parkinsonian syndromes, then specific outpatients clinic visits are scheduled weekly, with examinations carried out by neurologists at the PEC on a rotating schedule. Data from the first year of the new procedure were analyzed retrospectively through self-administered questionnaires sent to patients seen during this period. The main outcomes were to confirm the ability to keep to short delays for patients' examinations and to assess patients' satisfaction with the setup. RESULTS: Both study outcomes were achieved. The creation of an outpatients clinic dedicated to the early diagnosis of parkinsonian syndromes allowed shorter delays before the first examination of 5 weeks instead of several months. Keeping to the weekly schedule and limited time taken for each visit was also achieved. Following this initial outpatients visit, diagnosis of a parkinsonian syndrome was clinically confirmed or further specified in 80% of cases. A survey of patients' satisfaction showed a rate of over 91% in terms of the timing and course of clinical examinations at our PEC. DISCUSSION/CONCLUSION: This study of our quality-improvement program for Parkinson's disease management has shown that specific consultations with shorter waiting times aiming to allow early specialized assessment of parkinsonian syndromes is beneficial for patients and reduces the risk of delayed diagnoses.

French consensus procedure for assessing cognitive function in Parkinson's disease.

INTRODUCTION: One of the objectives of the French expert centers for Parkinson's disease (NS-Park) network was to determine a consensus procedure for assessing cognitive function in patients with Parkinson's. This article presents this procedure and briefly describes the selected tests. METHODS: A group of 13 experts used the Delphi method for consensus building to define the overall structure and components of the assessment procedure. For inclusion in the battery, tests had to be validated in the French language, require little motor participation, have normative data and be recognized by the international community. Experimental tasks and tests requiring specific devices were excluded. RESULTS: Two possibilities were identified, depending on whether an abbreviated or comprehensive assessment of cognitive function was necessary. For an abbreviated assessment, the experts recommended the Montreal Cognitive Assessment (MoCA) as a screening test for cognitive impairment or dementia. For a comprehensive neuropsychological assessment, the experts recommended assessing global efficiency plus the five main cognitive domains (attention and working memory, executive function, episodic memory, visuospatial function and language) that may be impaired in Parkinson's disease, using two tests for each domain. DISCUSSION AND CONCLUSION: A common procedure for assessing cognitive function is now available across the French network dedicated to Parkinson's disease, and is recommended for both research and clinical practice. It will also help to promote standardization of the neuropsychological assessment of Parkinson's disease.

Effects of deep brain stimulation on balance and gait in patients with Parkinson's disease: A systematic neurophysiological review.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) provides an efficient treatment for the alleviation of motor signs in patients with Parkinson's disease. The effects of DBS on gait and balance disorders are less successful and may even lead to an aggravation of freezing of gait and imbalance. The identification of a substantia nigra pars reticulata (SNr)-mesencephalic locomotor region (MLR) network in the control of locomotion and postural control and of its dysfunction/lesion in PD patients with gait and balance disorders led to suggestion that DBS should be targeting the SNr and the pedunculopontine nucleus (part of the MLR) for PD patients with these disabling axial motor signs. However, the clinical results to date have been disappointing. In this review, we discuss the effects of DBS of these basal ganglia and brainstem structures on the neurophysiological parameters of gait and balance control in PD patients. Overall, the data suggest that both STN and GPi-DBS improve gait parameters and quiet standing postural control in PD patients, but have no effect or may even aggravate dynamic postural control, in particular with STN-DBS. Conversely, DBS of the SNr and PPN has no effect on gait parameters but improves anticipatory postural adjustments and gait postural control.

DNA polymerase-catalyzed incorporation of nucleotides modified with a G-quadruplex-derived DNAzyme.

We show that nucleotides which are modified with a G-quadruplex-derived DNAzyme are substrates for DNA polymerases. Based on this finding we developed a naked-eye detection system that allows the detection of single nucleotide variations in DNA.

Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy.

Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

Physical determinants of vascular network remodeling during tumor growth.

The process in which a growing tumor transforms a hierarchically organized arterio-venous blood vessel network into a tumor specific vasculature is analyzed with a theoretical model. The physical determinants of this remodeling involve the morphological and hydrodynamic properties of the initial network, generation of new vessels (sprouting angiogenesis), vessel dilation (circumferential growth), vessel regression, tumor cell proliferation and death, and the interdependence of these processes via spatio-temporal changes of blood flow parameters, oxygen/nutrient supply and growth factor concentration fields. The emerging tumor vasculature is non-hierarchical, compartmentalized into well-characterized zones, displays a complex geometry with necrotic zones and "hot spots" of increased vascular density and blood flow of varying size, and transports drug injections efficiently. Implications for current theoretical views on tumor-induced angiogenesis are discussed.

[Gait and balance disorders in patients with atypical parkinsonian syndromes]. / Les troubles de la marche et de l'équilibre dans les syndromes parkinsoniens << plus >>.

The degenerative Parkinsonian "Plus" syndromes form a heterogeneous spectrum of pathologies comprising multiple system atrophy, progressive supranuclear palsy, Lewy body disease and cortico-basal degeneration. Their developmental profile is distinguished from that of Parkinson's disease by the early appearance of gait and balance disorders, isolated freezing of gait, primary progressive freezing of gait or an isolated or "pure" akinesia. The origin of these symptoms however remains poorly understood. The association of nigrostriatal dopamine neuron loss with either cortical lesions, in the case of cortico-basal degeneration and Lewy body disease, and/or of the brainstem, in the case of progressive supranuclear palsy, explains both the severity of the motor symptoms and the lack of, or minimal, improvement following levodopa therapy. Other symptomatic drug and surgical treatments have been proposed, but with generally disappointing results. Physiotherapeutic techniques targeting balance control can bring some temporary improvements.

Influence of sensory inputs and motor demands on the control of the centre of mass velocity during gait initiation in humans.

Human gait requires the simultaneous generation of goal-directed continuous movement (locomotion) and the maintenance of balance (postural control). In adults, the centre of mass (CoM) oscillates in the vertical plane while walking. During the single support phase of gait initiation, its vertical (vCoM) velocity increases as the CoM falls and is actively reversed prior to foot-contact. In this study we investigated whether this active control, which is thought to reflect balance control during gait initiation, is controlled by visual and somatosensory inputs (Experiment 1) and whether it is modified by a change in motor demands, two steps versus one step (Experiment 2). In all healthy adults, the vCoM velocity was braked, or controlled, by contraction of the soleus muscle of the stance leg. The elimination of visual input alone had no effect on braking, although its amplitude decreased when somatosensory inputs were disrupted (-47%), and further decreased when both visual and somatosensory inputs were disrupted (-83%). When subjects performed only one step, with no trailing of the stance foot, the vCoM velocity braking also decreased (-42%). These results suggest that active braking of the CoM fall during the transition to double support, an indicator of balance control, is influenced by both multisensory integration and the demands of the current motor program. The neural structures involved in this mechanism remain to be elucidated.

The role of municipal committees in the development of an integrated urban water policy in Belo Horizonte, Brazil.

This paper discusses the challenges involved in adopting an integrated approach to urban water policies and management, a particularly problematic issue in Brazil due to the incomplete nature of urbanization, defined as the lack of adequate and/or universalized access to infrastructure and services, informal housing and conflicts between environmental protection and social housing needs. In the last two decades strong social movements have influenced urban environmental policies from national to local levels. In Belo Horizonte since 1993, decision-making processes have involved important mechanisms of democratic inclusion, which have contributed to fairer urban policies. A brief discussion of the concept of governance follows, introducing the municipal urban policy within which drainage and sanitation policies have been implemented. This paper presents the constitutional and institutional role of the five municipal committees dealing with water governance issues, as they are important arenas for civil society participation. The main constraints to achieving integrated urban water governance at the local level and the extent to which such policies are able to reduce social inequalities and promote social environmental justice in the use and appropriation of urban water, are discussed. This paper is part of the SWITCH-Sustainable Water Management Improves Tomorrow's Cities' Health-research network.

Vascular remodelling of an arterio-venous blood vessel network during solid tumour growth.

We formulate a theoretical model to analyze the vascular remodelling process of an arterio-venous vessel network during solid tumour growth. The model incorporates a hierarchically organized initial vasculature comprising arteries, veins and capillaries, and involves sprouting angiogenesis, vessel cooption, dilation and regression as well as tumour cell proliferation and death. The emerging tumour vasculature is non-hierarchical, compartmentalized into well-characterized zones and transports efficiently an injected drug-bolus. It displays a complex geometry with necrotic zones and "hot spots" of increased vascular density and blood flow of varying size. The corresponding cluster size distribution is algebraic, reminiscent of a self-organized critical state. The intra-tumour vascular-density fluctuations correlate with pressure drops in the initial vasculature suggesting a physical mechanism underlying hot spot formation.

Effects of nigral stimulation on locomotion and postural stability in patients with Parkinson's disease.

The physiopathology of gait and balance disorders in Parkinson's disease patients is still poorly understood. Levodopa treatment and subthalamic nucleus (STN) stimulation improve step length and walking speed, with less effect on postural instability. These disorders have been linked to dysfunction of the descending basal ganglia outputs to brainstem structures. In this study, we evaluated the effects of stimulation of the substantia nigra pars reticulata (SNr), on locomotion and balance in Parkinson's disease patients. Biomechanical parameters and leg muscle activity were recorded during gait initiation in seven selected patients operated for bilateral STN stimulation, out of 204 stimulated patients, with one contact of each electrode located within the SNr. Step length, anteroposterior and vertical velocities of the centre of gravity were studied, with special reference to the subjects' ability to brake the centre of gravity fall before foot-contact, and compared to seven controls. In Parkinson's disease patients, five treatment conditions were tested: (i) no treatment, (ii) levodopa treatment, (iii) STN stimulation, (iv) SNr stimulation and (v) combined levodopa treatment and STN stimulation. The effects of these treatments on motor parkinsonian disability were assessed with the UPDRS III scale, separated into 'axial' (rising from chair, posture, postural stability and gait) and 'distal' scores. Whereas levodopa and/or STN stimulation improved 'axial' and 'distal' motor symptoms, SNr stimulation improved only the 'axial' symptoms. Compared to controls, untreated Parkinson's disease patients showed reduced step length and velocity, and poor braking just prior to foot-contact, with a decrease in both soleus (S) and anterior tibialis (AT) muscle activity. Step length and velocity significantly increased with levodopa treatment alone or in combination with STN stimulation in both natural and fast gait conditions, and with STN stimulation alone in the fast gait condition. Conversely, SNr stimulation had no significant effect on these measures in either condition. In the natural gait condition, no fall in the centre of gravity occurred as step length was low and active braking was unnecessary. In the fast gait condition, braking was improved with STN or SNr stimulation but not with levodopa treatment, with an increase in the stance leg S muscle activity. These results suggest that anteroposterior (length and velocity) and vertical (braking capacity) gait parameters are controlled by two distinct systems within the basal ganglia circuitry, representing respectively locomotion and balance. The SNr, a major basal ganglia output known to project to pontomesencephalic structures, is postulated as being particularly involved in balance control during gait.

[Can subthalamic nucleus stimulation reveal parkinsonian rest tremor?]. / La stimulation du noyau subthalamique peut-elle révéler un tremblement de repos parkinsonien ?

INTRODUCTION: Rest tremor, one of the main symptoms in Parkinson's disease (PD), is dramatically improved following subthalamic nucleus stimulation (STN). Results are often better than after l-dopa treatment. The occurrence of rest tremor after neurosurgery in patients without preoperative tremor is uncommon. AIM: The aim of this work was to investigate the role of subthalamic nucleus stimulation in the appearance of parkinsonian rest tremor. PATIENTS-RESULTS: Thirty PD patients (14%) out of 215 undergoing STN deep brain stimulation had an akinetorigid form of the disease, without preoperative tremor 11 years after onset of the disease. Six of them experienced the appearance of tremor six months after bilateral STN stimulation when the stimulator was switched off in the Off medication state. This de novo parkinsonian tremor was improved by l-dopa treatment and disappeared when the stimulator was turned on. CONCLUSION: This finding suggests that infraclinical parkinsonian tremor is probably present in all PD patients.

[Dystonia, tremor and repetitive instrumental use]. / Dystonies et tremblements d'utilisation instrumentale répétitive.

Three characteristic observations are presented along with three tables presenting 24 patients with the following elements in common: excessively repeated use of an instrument such as a pen, a musical instrument or a tool. The appearance after that use of a central pathological phenomenon that includes a local dystonia of a hand or the mouth, a tremor, or the association of a tremor and a dystonia, all within the muscular domain corresponding to that of the use. The discussion, which is based exclusively on the clinical findings, deals with the following elements: the role of the use of the instrument rather than task itself, the predominant pathogenic factor which is the repetitive action, to which is added a genetic component in one incompletely penetrant case of DYT 1, and a probable genetic susceptibility in the others. The absence of improvement with rest distinguishes this central pathology from rheumatologic or orthopaedic problems involving repetitive activities. The evolution is slowly declining when the responsible action is continued. This occurs in three stages: a specific disorder involving only the use of the particular instrument, a more enlarged involvement affecting other activities and eventually a dystonia associated with a tremor or a postural tremor always located to the initial area. The therapeutic interventions suggested by the pathologic role of the repetitive movement is: (1) to advise a new training for the instrument that excludes the habitual movement; (2) to advise the patient to vary any newly acquired repetitive movements.

Emergent vascular network inhomogeneities and resulting blood flow patterns in a growing tumor.

Tumors acquire sufficient oxygen and nutrient supply by coopting host vessels and neovasculature created via angiogenesis, thereby transforming a highly ordered network into chaotic heterogeneous tumor specific vasculature. Vessel regression inside the tumor leads to large regions of necrotic tissue interspersed with isolated surviving vessels. We extend our recently introduced model to incorporate Fahraeus-Lindqvist- and phase separation effects, refined tissue oxygen level computation and drug flow computations. We find, unexpectedly, that collapse and regression accelerates rather than diminishes the perfusion and that a tracer substance flowing through the remodeled network reaches all parts of the tumor vasculature very well. The reason for decreased drug delivery well known in tumors should therefore be different from collapse and vessel regression. Implications for drug delivery in real tumors are discussed.

[Therapeutic management of tics in Tourette's syndrome]. / Prise en charge thérapeutique des tics dans la maladie de Gilles de Tourette.

Tourette's syndrome is a neuropsychiatric disorder characterised by both involuntary movements, tics, and psychiatric symptoms, attentional deficit disorder, hyperactivity, obsessive compulsive symptoms..., and can be the cause of major disability. Over the past 30 years, several types of treatment have been proposed for the treatment of tics in Tourette's Syndrome, ranging from psychotherapeutic approaches to neurosurgery. The education of the patient and his entourage is fundamental and must be offered to all patients. Psychotherapy does not directly improve the tics but contributes to a better adjustment of both patient and carers to his disability. The decision to start a course of drug therapy depends largely on the impact of the patient's tics on his personal life. Drug treatment relies on neuromodulators acting on a variety of neural systems and whose efficacy has been rarely demonstrated. The literature shows that the latest generation of dopaminergic antagonists have the highest benefit/risk ratio. Recently, deep brain stimulation, by modulating neuronal activity in structures involved in the pathophysiology of the disease, has become a promising therapeutical approach, producing a marked decrease in the severity of tics over that obtained with other treatments.

Subthalamic stimulation and neuronal activity in the substantia nigra in Parkinson's disease.

High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for severe forms of Parkinson's disease (PD). To study the effects of high-frequency STN stimulation on one of the main output pathways of the basal ganglia, single-unit recordings of the neuronal activity of the substantia nigra pars reticulata (SNr) were performed before, during, and after the application of STN electrical stimulation in eight PD patients. During STN stimulation at 14 Hz, no change in either the mean firing rate or the discharge pattern of SNr neurons was observed. STN stimulation at 140 Hz decreased the mean firing rate by 64% and the mean duration of bursting mode activity of SNr neurons by 70%. The SNr residual neuronal activity during 140-Hz STN stimulation was driven by the STN stimulation. How the decrease in rate and modification of firing pattern of SNr-evoked neural activity, during high-frequency STN stimulation, contribute to the improvement of parkinsonian motor disability remains to be elucidated.