Heart-rate variability as a new marker for freezing predisposition in Parkinson's disease.

INTRODUCTION: Freezing of gait (FoG) is a debilitating symptom of advanced Parkinson's disease (PD) characterized by a sudden, episodic stepping arrest despite the intention to continue walking. The etiology of FoG is still unknown, but accumulating evidence unraveled physiological signatures of the autonomic nervous system (ANS) around FoG episodes. Here we aim to investigate for the first time whether detecting a predisposition for upcoming FoG events from ANS activity measured at rest is possible. METHODS: We recorded heart-rate for 1-min while standing in 28 persons with PD with FoG (PD + FoG), while OFF, and in 21 elderly controls (EC). Then, PD + FoG participants performed walking trials containing FoG-triggering events (e.g., turns). During these trials, n = 15 did experience FoG (PD + FoG+), while n = 13 did not (PD + FoG-). Most PD participants (n = 20: 10 PD + FoG+ and 10 PD + FoG-) repeated the experiment 2-3 weeks later, while ON, and none experienced FoG. We then analyzed heart-rate variability (HRV), i.e., the fluctuations in time intervals between adjacent heartbeats, mainly generated by brain-heart interactions. RESULTS: During OFF, HRV was significantly lower in PD + FoG + participants, reflecting imbalanced sympathetic/parasympathetic activity and disrupted self-regulatory capacity. PD + FoG- and EC participants showed comparable (higher) HRV. During ON, HRV did not differ among groups. HRV values did not correlate with age, PD duration, levodopa consumption, nor motor -symptoms severity scores. CONCLUSIONS: Overall, these results document for the first time a relation between HRV at rest and FoG presence/absence during gait trials, expanding previous evidence regarding the involvement of ANS in FoG.

Upward perturbations trigger a stumbling effect.

BACKGROUND: Vertical perturbations are one major cause of falling. Incidentally, while conducting a comprehensive study comparing effects of vertical versus horizontal perturbations, we commonly observed a stumbling-like response induced by upward perturbations. The present study describes and characterizes this stumbling effect. METHODS: Fourteen individuals (10 male; 27 ± 4 yr) walked self-paced on a treadmill embedded in a moveable platform and synchronized to a virtual reality system. Participants experienced 36 perturbations (12 types). Here, we report only on upward perturbations. We determined stumbling based on visual inspection of recorded videos, and calculated stride time and anteroposterior, whole-body center of mass (COM) distance relative to the heel, i.e., COM-to-heel distance, extrapolated COM (xCOM) and margin of stability (MOS) before and after perturbation. RESULTS: From 68 upward perturbations across 14 participants, 75% provoked stumbling. During the first gait cycle post-perturbation, stride time decreased in the perturbed foot and the unperturbed foot (perturbed = 1.004 s vs. baseline = 1.119 s and unperturbed = 1.017 s vs. baseline = 1.125 s, p < 0.001). In the perturbed foot, the difference was larger in stumbling-provoking perturbations (stumbling: 0.15 s vs. non-stumbling: 0.020 s, p = 0.004). In addition, the COM-to-heel distance decreased during the first and second gait cycles after perturbation in both feet (first cycle: 0.58 m, second cycle: 0.665 m vs. baseline: 0.72 m, p-values<0.001). During the first gait cycle, COM-to-heel distance was larger in the perturbed foot compared to the unperturbed foot (perturbed foot: 0.61 m vs. unperturbed foot: 0.55 m, p < 0.001). MOS decreased during the first gait cycle, whereas the xCOM increased during the second through fourth gait cycles post-perturbation (maximal xCOM at baseline: 0.5 m, second cycle: 0.63 m, third cycle: 0.66 m, fourth cycle: 0.64 m, p < 0.001). CONCLUSIONS: Our results show that upward perturbations can induce a stumbling effect, which - with further testing - has the potential to be translated into balance training to reduce fall risk, and for method standardization in research and clinical practice.

Dopaminergic medication reduces interhemispheric hyper-synchronization in Parkinson's disease.

INTRODUCTION: We previously reported on interhemispheric cortical hyper synchronization in PD. The aim of the present study was to address the hypothesis that increased interhemispheric cortical synchronization in PD is related to dopamine deficiency and is correlated with motor function. METHODS: We studied participants with PD and characterized cortical synchronization with reference to brain regions. Electroencephalography (EEG) was recorded from 20 participants with PD while OFF and ON their dopaminergic medications (two separate visits), during quiet standing and straight-line walking. Cortical interactions in the theta, alpha, beta, and gamma brain wave frequency bands were evaluated using interhemispheric phase synchronization (inter-PS). RESULTS: Inter-PS values were found to be significantly higher during the OFF state as compared to the ON state in standing and walking trials for theta, alpha and beta bands. In addition, inter-PS reduction from OFF to ON was associated with mobility improvement evaluated by the Timed Up and Go test, and with daily levodopa equivalent dose across individuals. Higher differences in inter-PS values between OFF and ON states were evident mainly in the occipital-parietal cortex. CONCLUSIONS: Persons with PD have increased inter-PS during the OFF state compared to their ON state, and this increase in inter-PS is associated with the clinical improvement between OFF and ON. We speculate that these findings, together with previous evidence of higher inter-PS in PD as compared to healthy older adults, reflect neuronal processes consequential to asymmetric subcortical dopamine deficiency.

Patterns of whole-body muscle activations following vertical perturbations during standing and walking.

BACKGROUND: Falls commonly occur due to losses of balance associated with vertical body movements (e.g. reacting to uneven ground, street curbs). Research, however, has focused on horizontal perturbations, such as forward and backward translations of the standing surface. This study describes and compares muscle activation patterns following vertical and horizontal perturbations during standing and walking, and investigates the role of vision during standing postural responses. METHODS: Fourteen healthy participants (ten males; 27±4 years-old) responded to downward, upward, forward, and backward perturbations while standing and walking in a virtual reality (VR) facility containing a moveable platform with an embedded treadmill; participants were also exposed to visual perturbations in which only the virtual scenery moved. We collected bilateral surface electromyography (EMG) signals from 8 muscles (tibialis anterior, rectus femoris, rectus abdominis, external oblique, gastrocnemius, biceps femoris, paraspinals, deltoids). Parameters included onset latency, duration of activation, and activation magnitude. Standing perturbations comprised dynamic-camera (congruent), static-camera (incongruent) and eyes-closed sensory conditions. ANOVAs were used to compare the effects of perturbation direction and sensory condition across muscles. RESULTS: Vertical perturbations induced longer onset latencies and shorter durations of activation with lower activation magnitudes in comparison to horizontal perturbations (p<0.0001). Downward perturbations while standing generated earlier activation of anterior muscles to facilitate flexion (for example, p=0.0005 and p=0.0021 when comparing the early activators, rectus femoris and tibialis anterior, to a late activator, the paraspinals), whereas upward perturbations generated earlier activation of posterior muscles to facilitate extension (for example, p<0.0001 and p=0.0004, when comparing the early activators, biceps femoris and gastrocnemius, to a late activator, the rectus abdominis). Static-camera conditions induced longer onset latencies (p=0.0085 and p<0.0001 compared to eyes-closed and dynamic-camera conditions, respectively), whereas eyes-closed conditions induced longer durations of activation (p=0.0001 and p=0.0008 compared to static-camera and dynamic-camera, respectively) and larger activation magnitudes. During walking, downward perturbations promptly activated contralateral trunk and deltoid muscles (e.g., p=0.0036 for contralateral deltoid versus a late activator, the ipsilateral tibialis anterior), and upward perturbations triggered early activation of trunk flexors (e.g., p=0.0308 for contralateral rectus abdominis versus a late activator, the ipsilateral gastrocnemius). Visual perturbations elicited muscle activation in 67.7% of trials. CONCLUSION: Our results demonstrate that vertical (vs. horizontal) perturbations generate unique balance-correcting muscle activations, which were consistent with counteracting vertical body extension induced by downward perturbations and vertical body flexion induced by upward perturbations. Availability of visual input appears to affect response efficiency, and incongruent visual input can adversely affect response triggering. Our findings have clinical implications for the design of robotic exoskeletons (to ensure user safety in dynamic balance environments) and for perturbation-based balance and gait rehabilitation.

Exploring the perceptions and stigmatizing experiences of Israeli family caregivers of people with Parkinson's disease.

Providing care to people with Parkinson's disease (PD) poses challenges for family carers, including experiencing stigmatic beliefs -i.e., family stigma. However, to the best of our knowledge, there is no empirical study examining the stigmatic experiences of family members of people with PD. This was the aim of the present study. Three focus groups with 22 Israeli spouses of people with PD were conducted. Data were analyzed using theory-led thematic analysis. Overall, the spouses in our study shared mainly experiences of the stigma attached to the illness and/or to their loved ones, and not to themselves as carers. Three major themes emerged: the stereotypes that typify PD, stigmatizing behaviors towards the person with the disease, and structural stigma. Our findings highlight the profound stigma confronting carers of persons with PD, particularly when it comes to structural stigma.

Advanced virtual reality-based rehabilitation of balance and gait in clinical practice.

BACKGROUND: Extensive research shows that virtual reality (VR) enhances motor learning and has advantages in balance and gait rehabilitation of neurological patients. There is still uncertainty, however, as for the practicality and efficacy of VR in long-term clinical routine. The objective of this study was to report on 3 years of clinical practice conducting VR-based rehabilitation of balance and gait in a large medical center. METHODS: This retrospective study systematically analyzed clinical records of patients who received VR-based rehabilitation in a large rehabilitation center during 3 years. We evaluated the effect of VR-based rehabilitation treatments on balance and gait, cognitive dual-task load, patient's balance confidence (ABC-scale) and perception of suitability. Patients were either neurological patients, allocated to five groups: Parkinson's disease (PD), poststroke (PS), multiple sclerosis, traumatic brain injury, and 'other conditions', or non-neurological patients. RESULTS: Records of 167 patients were analyzed. The availability of multiple VR systems and environments contributed to highly personalized interventions that tailored specific deficits with therapeutic goals. VR-based rehabilitation significantly improved balance and gait (measured by 10-Meter Walk Test, Timed-Up-and-Go, Berg Balance Scale, and Mini BESTest). Patients with PD and PS decreased dual-task cost while walking. Patients increased balance confidence and deemed VR suitable for rehabilitation. CONCLUSIONS: Our results suggest that VR-based rehabilitation is practicable and effective in clinical routine. Functional measures of balance and gait show significant improvements following VR-based interventions. Clinical approaches should exploit VR advantages for promoting motor learning and motivation. This study serves to aid transition to long-term clinical implementation of VR.

Excessive phase synchronization in cortical activation during locomotion in persons with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is characterized by gait disturbances, which become severe during the advanced stages of the disease. Though gait impairments in Parkinson's disease have been extensively described in terms of spatiotemporal gait parameters, little is known regarding associated patterns of cortical activity. The objective of the present study is to test if interhemispheric synchronization differs between participants with PD and healthy elderly controls (NPD). We analyzed electroencephalography (EEG) signals recorded during bilateral movements, i.e., locomotion and hand tapping. METHODS: Fifteen participants with PD ('OFF' their anti-parkinsonian medications) and eight NPD were assessed during quiet standing, straight-line walking, turning, and hand tapping tasks. Using a 32-electrode EEG array, we quantified the synchronization in periodic cortical activation between the brain hemispheres (interhemispheric phase synchronization; inter-PS). Theta, alpha, beta, and gamma bands were evaluated. RESULTS: In all bands, inter-PS was significantly higher for the PD group as compared with the NPD group during standing and walking (p < 0.001) and during bimanual tasks (p = 0.026). CONCLUSIONS: Persons with PD exhibit increased inter-PS as compared with NPD participants. These findings support previous evidence from animal studies, that bilateral cortical hypersynchronization emerges from the asymmetric neural degeneration that is at the base of the disease. Future studies should elucidate the long-term temporal development of this hypersynchronization and its clinical relevance (e.g., can it 'serve' as prodromal marker?).

Coupling Between Leg Muscle Activation and EEG During Normal Walking, Intentional Stops, and Freezing of Gait in Parkinson's Disease.

In this paper, we apply novel techniques for characterizing leg muscle activation patterns via electromyograms (EMGs) and for relating them to changes in electroencephalogram (EEG) activity during gait experiments. Specifically, we investigate changes of leg-muscle EMG amplitudes and EMG frequencies during walking, intentional stops, and unintended freezing-of-gait (FOG) episodes. FOG is a frequent paroxysmal gait disturbance occurring in many patients suffering from Parkinson's disease (PD). We find that EMG amplitudes and frequencies do not change significantly during FOG episodes with respect to walking, while drastic changes occur during intentional stops. Phase synchronization between EMG signals is most pronounced during walking in controls and reduced in PD patients. By analyzing cross-correlations between changes in EMG patterns and brain-wave amplitudes (from EEGs), we find an increase in EEG-EMG coupling at the beginning of stop and FOG episodes. Our results may help to better understand the enigmatic pathophysiology of FOG, to differentiate between FOG events and other gait disturbances, and ultimately to improve diagnostic procedures for patients suffering from PD.

Cancer outcomes among Parkinson's disease patients with leucine rich repeat kinase 2 mutations, idiopathic Parkinson's disease patients, and nonaffected controls.

BACKGROUND: Increased cancer risk has been reported in Parkinson's disease (PD) patients carrying the leucine rich repeat kinase 2 (LRRK2) G2019S mutation (LRRK2-PD) in comparison with idiopathic PD (IPD). It is unclear whether the elevated risk would be maintained when compared with unaffected controls. METHODS: Cancer outcomes were compared among 257 LRRK2-PD patients, 712 IPD patients, and 218 controls recruited from 7 LRRK2 consortium centers using mixed-effects logistic regression. Data were then pooled with a previous study to examine cancer risk between 401 LRRK2-PD and 1946 IPD patients. RESULTS: Although cancer prevalence was similar among LRRK2-PD patients (32.3%), IPD patients (27.5%), and controls (27.5%; P = 0.33), LRRK2-PD had increased risks of leukemia (odds ratio [OR] = 4.55; 95% confidence interval [CI], 1.46-10.61) and skin cancer (OR = 1.61; 95% CI, 1.09-2.37). In the pooled analysis, LRRK2-PD patients had also elevated risks of leukemia (OR = 9.84; 95% CI, 2.15-44.94) and colon cancer (OR = 2.34; 95% CI, 1.15-4.74) when compared with IPD patients. CONCLUSIONS: The increased risks of leukemia as well as skin and colon cancers among LRRK2-PD patients suggest that LRRK2 mutations heighten risks of certain cancers. © 2019 International Parkinson and Movement Disorder Society.

Seeing Gravity: Gait Adaptations to Visual and Physical Inclines - A Virtual Reality Study.

Using advanced virtual reality technology, we demonstrate that exposure to virtual inclinations visually simulating inclined walking induces gait modulations in a manner consistent with expected gravitational forces (i.e., acting upon a free body), suggesting vision-based perception of gravity. The force of gravity critically impacts the regulation of our movements. However, how humans perceive and incorporate gravity into locomotion is not well understood. In this study, we introduce a novel paradigm for exposing humans to incongruent sensory information under conditions constrained by distinct gravitational effects, facilitating analysis of the consistency of human locomotion with expected gravitational forces. Young healthy adults walked under conditions of actual physical inclinations as well as virtual inclinations. We identify and describe 'braking' and 'exertion' effects - locomotor adaptations accommodating gravito-inertial forces associated with physical inclines. We show that purely visual cues (from virtual inclinations) induce consistent locomotor adaptations to counter expected gravity-based changes, consistent with indirect prediction mechanisms. Specifically, downhill visual cues activate the braking effect in anticipation of a gravitational boost, whereas uphill visual cues promote an exertion effect in anticipation of gravitational deceleration. Although participants initially rely upon vision to accommodate environmental changes, a sensory reweighting mechanism gradually reprioritizes body-based cues over visual ones. A high-level neural model outlines a putative pathway subserving the observed effects. Our findings may be pivotal in designing virtual reality-based paradigms for understanding perception and action in complex environments with potential translational benefits.

Intersegmental coordination patterns are differently affected in Parkinson's disease and cerebellar ataxia.

The law of intersegmental coordination (Borghese et al. 1996) may be altered in pathological conditions. Here we investigated the contribution of the basal ganglia (BG) and the cerebellum to lower limb intersegmental coordination by inspecting the plane's orientation and other parameters pertinent to this law in patients with idiopathic Parkinson's disease (PD) or cerebellar ataxia (CA). We also applied a mathematical model that successfully accounts for the intersegmental law of coordination observed in control subjects (Barliya et al. 2009). In the present study, we compared the planarity index (PI), covariation plane (CVP) orientation, and CVP orientation predicted by the model in 11 PD patients, 8 CA patients, and two groups of healthy subjects matched for age, height, weight, and gender to each patient group (Ctrl_PD and Ctrl_CA). Controls were instructed to alter their gait speed to match those of their respective patient group. PD patients were examined after overnight withdrawal of anti-parkinsonian medications (PD-off-med) and then on medication (PD-on-med). PI was above 96% in all gait conditions in all groups suggesting that the law of intersegmental coordination is preserved in both BG and cerebellar pathology. However, the measured and predicted CVP orientations rotated in PD-on-med and PD-off-med compared with Ctrl_PD and in CA vs. Ctrl_CA. These rotations caused by PD and CA were in opposite directions suggesting differences in the roles of the BG and cerebellum in intersegmental coordination during human locomotion. NEW & NOTEWORTHY Kinematic and muscular synergies may have a role in overcoming motor redundancies, which may be reflected in intersegmental covariation. Basal ganglia and cerebellar networks were suggested to be involved in crafting and modulating synergies. We thus compared intersegmental coordination in Parkinson's disease and cerebellar disease patients and found opposite effects in some aspects. Further research integrating muscle activities as well as biomechanical and neural control modeling are needed to account for these findings.

Kufor-Rakeb Syndrome/PARK9: One Novel and One Possible Recurring Ashkenazi ATP13A2 Mutation.

Kufor-Rakeb syndrome (KRS)/PARK9 presents with autosomal recessive young onset Parkinson's disease (YOPD), spastic paraparesis, abnormal eye movements and facial myokymia. KRS is caused by homozygous/compound heterozygous inactivating mutations in ATP13A2. Two affected siblings (born to non-consanguineous Jewish parents) presenting a similar KRS phenotype (onset age 27, 23), carried compound heterozygous pathogenic variants in ATP13A2: c.217_218insG and c.3057delC. Allele frequency of the c.3057delC mutation was about 100 times higher in Ashkenazi controls in our study (1/190 = 0.00526) and in the Genome Aggregation Database, (GnomAD, 27/10132 = 0.002665) versus non-Ashkenazi controls worldwide in GnomAD (9/264566 = 0.000034018, p < 0.0001). The c.217_218insG mutation is novel and not found in controls or GnomAD. The c.3057delC mutation should be included in the genetic workup of Ashkenazi YOPD patients.

Advantages of virtual reality in the rehabilitation of balance and gait: Systematic review.

BACKGROUND: Virtual reality (VR) has emerged as a therapeutic tool facilitating motor learning for balance and gait rehabilitation. The evidence, however, has not yet resulted in standardized guidelines. The aim of this study was to systematically review the application of VR-based rehabilitation of balance and gait in 6 neurologic cohorts, describing methodologic quality, intervention programs, and reported efficacy. METHODS: This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. VR-based treatments of Parkinson disease, multiple sclerosis, acute and chronic poststroke, traumatic brain injury, and cerebral palsy were researched in PubMed and Scopus, including earliest available records. Therapeutic validity (CONTENT scale) and risk of bias in randomized controlled trials (RCT) (Cochrane Collaboration tool) and non-RCT (Newcastle-Ottawa scale) were assessed. RESULTS: Ninety-seven articles were included, 68 published in 2013 or later. VR improved balance and gait in all cohorts, especially when combined with conventional rehabilitation. Most studies presented poor methodologic quality, lacked a clear rationale for intervention programs, and did not utilize motor learning principles meticulously. RCTs with more robust methodologic designs were widely recommended. CONCLUSION: Our results suggest that VR-based rehabilitation is developing rapidly, has the potential to improve balance and gait in neurologic patients, and brings additional benefits when combined with conventional rehabilitation. This systematic review provides detailed information for developing theory-driven protocols that may assist overcoming the observed lack of argued choices for intervention programs and motor learning implementation and serves as a reference for the design and planning of personalized VR-based treatments. REGISTRATION: PROSPERO CRD42016042051.

Transethnic genome-wide scan identifies novel Alzheimer's disease loci.

INTRODUCTION: Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. METHODS: We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. RESULTS: Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 × 10-8) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence (P < 2.7 × 10-6) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10-6). DISCUSSION: Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

Cutaneous malignant melanoma and Parkinson disease: Common pathways?

The mechanisms underlying the high prevalence of cutaneous malignant melanoma (CMM) in Parkinson disease (PD) are unclear, but plausibly involve common pathways. 129Ser-phosphorylated α-synuclein, a pathological PD hallmark, is abundantly expressed in CMM, but not in normal skin. In inherited PD, PARK genes harbor germline mutations; the same genes are somatically mutated in CMM, or their encoded proteins are involved in melanomagenesis. Conversely, genes associated with CMM affect PD risk. PD/CMM-targeted cells share neural crest origin and melanogenesis capability. Pigmentation gene variants may underlie their susceptibility. We review putative genetic intersections that may be suggestive of shared pathways in neurodegeneration/melanomagenesis. Ann Neurol 2016;80:811-820.

Parkinson disease (PARK) genes are somatically mutated in cutaneous melanoma.

OBJECTIVE: To assess whether Parkinson disease (PD) genes are somatically mutated in cutaneous melanoma (CM) tissue, because CM occurs in patients with PD at higher rates than in the general population and PD is more common than expected in CM cohorts. METHODS: We cross-referenced somatic mutations in metastatic CM detected by whole-exome sequencing with the 15 known PD (PARK) genes. We computed the empirical distribution of the sum of mutations in each gene (Smut) and of the number of tissue samples in which a given gene was mutated at least once (SSampl) for each of the analyzable genes, determined the 90th and 95th percentiles of the empirical distributions of these sums, and verified the location of PARK genes in these distributions. Identical analyses were applied to adenocarcinoma of lung (ADENOCA-LUNG) and squamous cell carcinoma of lung (SQUAMCA-LUNG). We also analyzed the distribution of the number of mutated PARK genes in CM samples vs the 2 lung cancers. RESULTS: Somatic CM mutation analysis (n = 246) detected 315,914 mutations in 18,758 genes. Somatic CM mutations were found in 14 of 15 PARK genes. Forty-eight percent of CM samples carried ≥1 PARK mutation and 25% carried multiple PARK mutations. PARK8 mutations occurred above the 95th percentile of the empirical distribution for SMut and SSampl. Significantly more CM samples harbored multiple PARK gene mutations compared with SQUAMCA-LUNG (p = 0.0026) and with ADENOCA-LUNG (p < 0.0001). CONCLUSIONS: The overrepresentation of somatic PARK mutations in CM suggests shared dysregulated pathways for CM and PD.

Micrographia, much beyond the writer's hand.

INTRODUCTION: This review on micrographia aims to draw the clinician's attention to non-Parkinsonian etiologies, provide clues to differential diagnosis, and summarize current knowledge on the phenomenology, etiology, and mechanisms underlying micrographia. METHODS: A systematic review of the existing literature was performed. RESULTS: Micrographia, namely small sized handwriting has long been attributed to Parkinson's disease. However, it has often been observed as part of the clinical picture of additional neurodegenerative disorders, sometimes antedating the motor signs, or following focal basal ganglia lesions without any accompanying parkinsonism, suggesting that bradykinesia and rigidity are not sine-qua-non for the development of this phenomenon. Therefore, micrographia in a patient with no signs of parkinsonism may prompt the clinician to perform imaging in order to exclude a focal basal ganglia lesion. Dopaminergic etiology in this and other cases is doubtful, since levodopa ameliorates letter stroke size only partially, and only in some patients. Parkinsonian handwriting is often characterized by lack of fluency, slowness, and less frequently by micrographia. Deviations from kinematic laws of motion that govern normal movement, including the lack of movement smoothness and inability to scale movement amplitude to the desired size, may reflect impairments in motion planning, possible loss of automaticity and reduced movement vigor. CONCLUSIONS: The etiology, neuroanatomy, mechanisms and models of micrographia are discussed. Dysfunction of the basal ganglia circuitry induced by neurodegeneration or disruption by focal damage give rise to micrographia.

Self-selected gait speed--over ground versus self-paced treadmill walking, a solution for a paradox.

BACKGROUND: The study of gait at self-selected speed is important. Traditional gait laboratories being relatively limited in space provide insufficient path length, while treadmill (TM) walking compromises natural gait by imposing speed variables. Self-paced (SP) walking can be realized on TM using feedback-controlled belt speed. We compared over ground walking vs. SP TM in two self-selected gait speed experiments: without visual flow, and while subjects were immersed in a virtual reality (VR) environment inducing natural visual flow. METHODS: Young healthy subjects walked 96 meters at self-selected comfortable speed, first over ground and then on the SP TM without (n=15), and with VR visual flow (n=11). Gait speed was compared across conditions for four 10 m long segments (7.5 - 17.5, 30.5 - 40.5, 55.5 - 65.5 and 78.5-88.5 m). RESULTS: During over ground walking mean (± SD) gait speed was equal for both experimental groups (1.50 ± 0.13 m/s). Without visual flow, gait speed over SP TM was smaller in the first and second epochs as compared to over ground (first: 1.15 ±0.18 vs. second: 1.53 ± 0.13 m/s; p<0.05), and was comparable in the third and fourth (1.45 ± 0.19 vs. 1.49 ± 0.15 m/s; p>0.3). With visual flow, gait speed became comparable to that of over ground performance already in the first epoch (1.43 ± 0.22 m/s; p>0.17). Curve fitting analyses estimated that steady state velocity in SP TM walking is reached after shorter distanced passed with visual flow (24.6 ± 14.7 m) versus without (36.5 ± 18.7 m, not statistically significant; p=0.097). Steady state velocity was estimated to be higher in the presence of visual flow (1.61 ± 0.17 m/s) versus its absence (1.42 ± 1.19 m/s; p<0.05). CONCLUSIONS: The SP TM walking is a reliable method for recording typical self-selected gait speed, provided that sufficient distance is first passed for reaching steady state. Seemingly, in the presence of VR visual flow, steady state of gait speed is reached faster. We propose that the gait research community joins forces to standardize the use of SP TMs, e.g., by unifying protocols or gathering normative data.

Alzheimer's disease and the elderly in Israel: are we paying enough attention to the topic in the Arab population?

With the continuing rise in the elderly population, Alzheimer's disease (AD) and dementia represent an increasing public health concern worldwide. In recent years, research has focused on the relationship between AD and ethnicity. Israel, a multiethnic society, provides a natural laboratory for research on ethnicity and health. The largest ethnic group is that of Israeli Jews, followed by Arab citizens, mostly Arab Muslims, with smaller numbers of Arab Christians in addition to Druze, Circassians, and others. The aim of this review is to clarify ethnic differences in prevalence and risk factors for Alzheimer's disease. We review available literature on ethnic differences in epidemiologic and risk factors for Alzheimer's disease, including genetic differences as well as disparities in health access and quality of health services. We will conclude with research and policy implications.