A Novel Tool for the Early Identification of Frailty in Elderly People: The Application in Primary Care Settings.

BACKGROUND: Frailty is a pre-disability condition in older persons providing a challenge to Health-Care Systems. Systematic reviews highlight the absence of a gold-standard for its identification. However, an approach based on initial screening by the General Practitioner (GP) seems particularly useful. On these premises, a 9-item Sunfrail Checklist (SC), was developed by a multidisciplinary group, in the context of European Sunfrail Project, and tested in the Community. OBJECTIVES: - to measure the concordance between the judgments of frailty (criterion-validity): the one formulated by the GP, using the SC, and the one subsequently expressed by a Comprehensive Geriatric Assessment Team (CGA-Team); - to determine the construct-validity through the correspondence between some checklist items related to the 3 domains (physical, cognitive and social) and the three tools used by the CGA-Team; - to measure the instrument's performance in terms of positive predictive value (PPV) and negative predictive value (NPV). DESIGN: Cross-sectional study, with a final sample-size of 95 subjects. SETTING: Two Community-Health Centers of Parma, Italy. PARTICIPANTS: Subjects aged 75 years old or more, with no disability and living in the community. MEASUREMENTS: We compared the screening capacity of the GP using the SC to that one of CGA-Team based on three tests: 4-meter Gait-Speed, Mini-Mental State Examination and Loneliness Scale. RESULTS: 95 subjects (51 women), with a mean age of 81±4 years were enrolled. According to GPs 34 subjects were frail; the CGA-Team expressed a frailty judgment on 26 subjects. The criterion-validity presented a Cohen's k of 0.353. Construct-validity was also low, with a maximum contingency-coefficient of 0.19. The analysis showed a PPV of 58.1% and a NPV equal to 84.6%. CONCLUSIONS: Our data showed a low agreement between the judgements of GP performed by SC and CGA-Team. However, the good NPV suggests the applicability of SC for screening activities in primary-care.

Far-reaching geometrical artefacts due to thermal decomposition of polymeric coatings around focused ion beam milled pigment particles.

Focused ion beam and scanning electron microscope (FIB-SEM) instruments are extensively used to characterize nanoscale composition of composite materials, however, their application to analysis of organic corrosion barrier coatings has been limited. The primary concern that arises with use of FIB to mill organic materials is the possibility of severe thermal damage that occurs in close proximity to the ion beam impact. Recent research has shown that such localized artefacts can be mitigated for a number of polymers through cryogenic cooling of the sample as well as low current milling and intelligent ion beam control. Here we report unexpected nonlocalized artefacts that occur during FIB milling of composite organic coatings with pigment particles. Specifically, we show that FIB milling of pigmented polysiloxane coating can lead to formation of multiple microscopic voids within the substrate as far as 5 µm away from the ion beam impact. We use further experimentation and modelling to show that void formation occurs via ion beam heating of the pigment particles that leads to decomposition and vaporization of the surrounding polysiloxane. We also identify FIB milling conditions that mitigate this issue.

Does the cerebellum intervene in the abnormal somatosensory temporal discrimination in Parkinson's disease?

INTRODUCTION: somatosensory temporal discrimination threshold (STDT) measures the ability to perceive two stimuli as being sequential. Altered STDT has been reported in Parkinson's disease (PD). The cerebellum seems to play a role in the pathophysiology of PD, and may consequently be involved in the pathophysiology of STDT abnormalities. METHODS: STDT was investigated in fifteen PD patients who underwent real and sham cerebellar continuous theta burst stimulation (cTBS) in the OFF condition. Eight patients underwent a further real cTBS session in ON condition. STDT was measured on both hands before, 5 and 25 min after real and sham cTBS delivered over the cerebellar hemisphere ipsilateral to the more affected side. We controlled the efficacy of our protocol by monitoring primary motor cortex (M1) excitability. Ten healthy subjects acted as control group. RESULTS: STDT values were increased in PD patients in the OFF condition compared with healthy subjects and PD patients in the ON condition. In PD patients OFF condition, real but not sham cerebellar cTBS, significantly reduced STDT values only in the hand ipsilateral to the stimulated cerebellar hemisphere. Cerebellar cTBS also decreased motor evoked potentials (MEP) size in the contralateral M1. When PD patients were tested in the ON condition, cerebellar cTBS failed to modify STDT values. CONCLUSION: cerebellar cTBS improved STDT values in PD patients exclusively in OFF condition. We hypothesize that cerebellar stimulation partially compensates for increased STDT values only when patients are OFF dopaminergic therapy. This suggests that the cerebellum may act as compensatory system in PD.

Correlation between cortical plasticity, motor learning and BDNF genotype in healthy subjects.

There is good evidence that synaptic plasticity in human motor cortex is involved in behavioural motor learning; in addition, it is now possible to probe mechanisms of synaptic plasticity using a variety of transcranial brain-stimulation protocols. Interactions between these protocols suggest that they both utilise common mechanisms. The aim of the present experiments was to test how well responsiveness to brain-stimulation protocols and behavioural motor learning correlate with each other in a sample of 21 healthy volunteers. We also examined whether any of these measures were influenced by the presence of a Val66Met polymorphism in the BDNF gene since this is another factor that has been suggested to be able to predict response to tests of synaptic plasticity. In 3 different experimental sessions, volunteers underwent 5-Hz rTMS, intermittent theta-burst stimulation (iTBS) and a motor learning task. Blood samples were collected from each subject for BDNF genotyping. As expected, both 5-Hz rTMS and iTBS significantly facilitated MEPs. Similarly, as expected, kinematic variables of finger movement significantly improved during the motor learning task. Although there was a significant correlation between the effect of iTBS and 5-Hz rTMS, there was no relationship in each subject between the amount of TMS-induced plasticity and the increase in kinematic variables during motor learning. Val66Val and Val66Met carriers did not differ in their response to any of the protocols. The present results emphasise that although some TMS measures of cortical plasticity may correlate with each other, they may not always relate directly to measures of behavioural learning. Similarly, presence of the Val66Met BDNF polymorphism also does not reliably predict responsiveness in small groups of individuals. Individual success in behavioural learning is unlikely to be closely related to any single measure of synaptic plasticity.

Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease.

In this study in patients with Parkinson's disease (PD), off and on dopaminergic therapy, with and without L-dopa-induced dyskinesias (LIDs), we tested intermittent theta-burst stimulation (iTBS), a technique currently used for non-invasively inducing long-term potentiation (LTP)-like plasticity in primary motor cortex (M1). The study group comprised 20 PD patients on and off dopaminergic therapy (11 patients without and 9 patients with LIDs), and 14 age-matched healthy subjects. Patients had mild-to-moderate PD, and no additional neuropsychiatric disorders. We clinically evaluated patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The left M1 was conditioned with iTBS at 80% active motor threshold intensity. Twenty motor evoked potentials (MEPs) were recorded from right first interosseous muscle before and at 5, 15 and 30 min after iTBS. Between-group analysis of variance (ANOVA) testing healthy subjects versus patients with and without LIDs, on and off therapy showed a significant interaction between factors "Group" and "Time". After iTBS, MEP amplitudes in healthy subjects increased significantly at 5, 15 and 30 min (p<0.01 at all time-points) but in PD patients with and without LIDs, on and off therapy, remained unchanged. In PD patients with and without LIDs, on and off therapy iTBS fails to increase MEP responses. This finding suggests lack of iTBS-induced LTP-like plasticity in M1 in PD regardless of patients' clinical features.

Dopamine influences primary motor cortex plasticity and dorsal premotor-to-motor connectivity in Parkinson's disease.

We investigated abnormal premotor to motor (PMd-to-M1) connectivity in Parkinson's disease (PD) with repetitive transcranial magnetic stimulation (rTMS). We studied 28 patients off and on dopaminergic therapy and 28 healthy subjects. We delivered 5 Hz rTMS over M1 before and after conditioning PMd with 5 Hz rTMS. In healthy subjects, motor-evoked potentials (MEPs) elicited by M1-rTMS were facilitated and PMd-rTMS left MEPs unchanged. In patients, before PMd-rTMS, M1-rTMS induced no MEP facilitation, whereas after PMd-rTMS, it significantly facilitated MEPs only when patients were on therapy. In the second experiment, we delivered M1-rTMS under 3 different attention-demanding tasks: eyes closed, attention directed to the stimulated hand, and attention directed to the nonstimulated hand. In healthy subjects, a more pronounced MEP facilitation was present when subjects directed attention to the stimulated hand. In patients, the MEP facilitation was present when attention was directed to the stimulated hand only when patients were on therapy. Finally, we delivered M1-rTMS in patients on therapy while they were looking at the stimulated hand, before and after 1 Hz PMd-rTMS. PMd-rTMS reduced the attention-induced MEP facilitation. We conclude that in addition to abnormal M1 plasticity, the reduced MEP facilitation in PD also reflects altered PMd-to-M1 connectivity.

Effects of unilateral subthalamic deep brain stimulation on contralateral arm sequential movements in Parkinson's disease.

In Parkinson's disease, unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN), unlike bilateral stimulation, excludes ipsilateral confounding effects so that the contralateral effects of DBS on motor performance can be investigated alone. Because no kinematic study has yet investigated how unilateral STN-DBS affects the performance of a contralateral fast sequential motor act, we performed a kinematic analysis of the movement duration, switching time and spatial accuracy of a motor arm sequence in 10 parkinsonian patients. Patients were studied without dopaminergic therapy and when they were OFF and ON unilateral STN-DBS. We found that unilateral STN-DBS significantly improved movement time of a motor sequence and the switching time from one sequential step to the next, whereas accuracy deteriorated. We conclude that unilateral STN-DBS improves the performance of contralateral sequential arm movements in patients with Parkinson's disease.

Effects of 5 Hz subthreshold magnetic stimulation of primary motor cortex on fast finger movements in normal subjects.

We evaluated the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on motor performance and motor learning of a rapid index finger movement. Two groups of healthy right-handed subjects underwent either "real" rTMS (1800 stimuli over the first dorsal interosseous (FDI) muscle hot spot given at 5 Hz and intensity of 90% of resting motor threshold-RMT) or "sham" stimulation. Both groups performed 60 rapid abductions of the right index finger before and after rTMS. The kinematic variables measured were amplitude, duration, peak velocity and peak acceleration. We also evaluated RMT and motor-evoked potential (MEP) amplitude before, 5 and 30 min after rTMS. In both groups practice significantly increased peak velocity, peak acceleration and amplitude and decreased movement duration independently from the type of intervention ("real" and "sham"). "Real" rTMS significantly increased cortical excitability as measured by MEP amplitude whereas "sham" rTMS did not. In our study, 5 Hz rTMS failed to improve either the motor performance or the motor learning of a rapid index-finger abduction despite the increase in cortical excitability of the primary motor cortex. Since motor behaviour engages a distributed cortical and subcortical neuronal network, excitatory conditioning of the primary motor cortex is probably not sufficient to influence the behavioural output.

Early predictors of intractability in childhood epilepsy: a community-based case-control study in Copparo, Italy.

OBJECTIVES: To identify early predictors of intractability in childhood and adolescence epilepsy. MATERIALS AND METHODS: We carried out a community-based case-control study using the incidence cohort of epileptic patients living in the district of Copparo, in the province of Ferrara, Italy. The comparative study was performed in 31 cases and 95 controls. Cases were patients who averaged at least 1 unprovoked seizure per month during an observational period of at least 2 years. Controls were subjects having achieved remission for at least 5 years regardless of current therapy. RESULTS: Onset at age <1 year, remote symptomatic etiology and high frequency of seizures before therapy were found to be independent early predictors of intractability. CONCLUSION: Our study suggested that the risk of developing intractable epilepsy may, to some extent, be predicted at the time of initial diagnosis in children with early-onset epilepsy of remote symptomatic etiology, especially if seizure propensity is initially high.