Underwater gait analysis in Parkinson’s disease

Although hydrotherapy is one of the physical therapies adopted to optimize gait rehabilitation in people with Parkinson disease, the quantitative measurement of gait-related outcomes has not been provided yet. This work aims to document the gait improvements in a group of parkinsonians after a hydrotherapy program through 2D and 3D underwater and on land gait analysis. Thirty-four parkinsonians and twenty-two controls were enrolled, divided into two different cohorts. In the first one, 2 groups of patients underwent underwater or land based walking training; controls underwent underwater walking training. Hence pre-treatment 2D underwater and on land gait analysis were performed, together with post-treatment on land gait analysis. Considering that current literature documented a reduced movement amplitude in parkinsonians across all lower limb joints in all movement planes, 3D underwater and on land gait analysis were performed on a second cohort of subjects (10 parkinsonians and 10 controls) who underwent underwater gait training. Baseline land 2D and 3D gait analysis in parkinsonians showed shorter stride length and slower speed than controls, in agreement with previous findings. Comparison between underwater and on land gait analysis showed reduction in stride length, cadence and speed on both parkinsonians and controls. Although patients who underwent underwater treatment exhibited significant changes on spatiotemporal parameters and sagittal plane lower limb kinematics, 3D gait analysis documented a significant (p < 0.05) improvement in all movement planes. These data deserve attention for research directions promoting the optimal recovery and maintenance of walking ability.     

Validation of cardiac 123I-MIBG scintigraphy in patients with Parkinson’s disease who were diagnosed with dopamine PET

Purpose  

The aim of this study was to evaluate the diagnostic potential of cardiac ¹²³I-labelled metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy in idiopathic Parkinson’s disease (PD). The diagnosis was confirmed by positron emission tomography (PET) imaging with ¹¹C-labelled 2β-carbomethoxy-3β-(4-fluorophenyl)-tropane (¹¹C-CFT) and ¹¹C-raclopride (together designated as dopamine PET).     

Fractal analysis of gait in people with Parkinson’s disease: three minutes is not enough

BackgroundThe fractal dynamics of gait variability in people with Parkinson’s disease has been studied by applying the detrended fluctuation analysis (DFA) to short time series (<200 strides). However, DFA is sensitive to time series length, and it is unclear if DFA results from short time series are reliable and if they reflect the fractal dynamics of longer time series.Research questionIs DFA reliable when applied to short time series?MethodsWe applied DFA to stride time series from five 3-min trials and one 15-min trial in 12 people with Parkinson’s disease, 14 healthy older adults and 14 healthy young adults walking overground. Within each group, intraclass correlations (ICC 3,1) were performed to assess the reliability of i) the five 3-min trials together, ii) each 3-min trials to the 15-min trial, and iii) the first 150 strides from the 15-min trial to the full 15-min trial.ResultsOur three main findings are that 1) stride time α-DFA values are not consistent from trial-to-trial for short stride time series, 2) stride time α-DFA values from each 3-min trials are not consistent when compared to stride time α-DFA values from a 15-min trial, and 3) stride time α-DFA values from the first 150 strides of the 15-min trial are not consistent when compared to α-DFA values from the full 15-min trial.SignificanceOur results confirm that α-DFA values from 3-min walking trials are not reliable, and that they do not reflect the scale invariant properties of longer time series. This suggests that previous studies assessing the fractal dynamics of gait variability from about 3-min walking must be interpreted with caution. A major clinical implication is that DFA cannot be used to study gait in people unable to perform 500 strides continuously.     

A model of free-living gait: A factor analysis in Parkinson’s disease

IntroductionGait is a marker of global health, cognition and falls risk. Gait is complex, comprised of multiple characteristics sensitive to survival, age and pathology. Due to covariance amongst characteristics, conceptual gait models have been established to reduce redundancy and aid interpretation. Previous models have been derived from laboratory gait assessments which are costly in equipment and time. Body-worn monitors (BWM) allow for free-living, low-cost and continuous gait measurement and produce similar covariant gait characteristics. A BWM gait model from both controlled and free-living measurement has not yet been established, limiting utility.Methods103 control and 67 PD participants completed a controlled laboratory assessment; walking for two minutes around a circuit wearing a BWM. 89 control and 58 PD participants were assessed in free-living, completing normal activities for 7 days wearing a BWM. Fourteen gait characteristics were derived from the BWM, selected according to a previous model. Principle component analysis derived factor loadings of gait characteristics.ResultsFour gait domains were derived for both groups and conditions; pace, rhythm, variability and asymmetry. Domains totalled 84.84% and 88.43% of variance for controlled and 90.00% and 93.03% of variance in free-living environments for control and PD participants respectively. Gait characteristic loading was unambiguous for all characteristics apart from gait variability which demonstrated cross-loading for both groups and environments. The model was highly congruent with the original model.ConclusionsThe conceptual gait models remained stable using a BWM in controlled and free-living environments. The model became more discrete supporting utility of the gait model for free-living gait.     

Comparative value of brain perfusion SPECT and [123I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease

Purpose Both decreased occipital perfusion on brain single-photon emission computed tomography (SPECT) and reduction in cardiac ¹²³I-metaiodobenzylguanidine (MIBG) uptake are characteristic features of dementia with Lewy bodies (DLB), and potentially support the clinical diagnosis of DLB. The aim of this study was to compare the diagnostic value of these two methods for differentiation of DLB from Alzheimers disease (AD).Methods The study population comprised 19 patients with probable DLB and 39 patients with probable AD who underwent both SPECT with N-isopropyl-p-[¹²³I]iodoamphetamine and MIBG myocardial scintigraphy. Objective and quantitative measurement of perfusion in the medial occipital lobe, including the cuneus and lingual gyrus, was performed by the use of three-dimensional stereotactic surface projections.Results Medial occipital perfusion was significantly decreased in the DLB group compared with the AD group. The mean heart/mediastinum ratios of MIBG uptake were significantly lower in the DLB group than in the AD group. Although SPECT failed to demonstrate significant hypoperfusion in the medial occipital lobe in five patients with DLB, marked reduction of MIBG uptake was found in all patients with DLB. Receiver operating characteristic analysis revealed that MIBG myocardial scintigraphy enabled more accurate discrimination between DLB and AD than was possible with perfusion SPECT.Conclusion MIBG myocardial scintigraphy may improve the sensitivity in the detection of DLB. In particular, this method may provide a powerful differential diagnostic tool when it is difficult to distinguish cases of DLB from AD using brain perfusion SPECT.An editorial commentary on this paper is available at     

Use of ACE-inhibitors and falls in patients with Parkinson’s disease

Falls represent a major concern in patients with Parkinson’s disease (PD); however, currently acknowledged treatments for PD are not effective in reducing the risk of falling. The aim was to assess the association of use of ACE-inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) with falls among patients with PD.We analysed data of 194 elderly with PD attending a geriatric Day Hospital. Self-reported history of falls that occurred over the last year, as well as use of drugs, including ACEIs and angiotensin II receptor blockers (ARBs) were recorded. The association of the occurrence of any falls with use of ACEIs, and ARBs was assessed by logistic regression analysis. The association between the number of falls and use of ACEIs, and ARBs was assessed according to Poisson regression.In logistic regression, after adjusting for potential confounders, use of ACEIs was associated with a reduced probability of falling over the last year (OR = 0.15, 95% CI = 0.03–0.81; P = 0.028). This association did not vary with blood pressure levels (P for the interaction term = 0.528). Also, using Poisson regression, use of ACEIs predicted a reduced number of falls among participants who fell (PR = 0.31; 95% CI = 0.10–0.94; P = 0.039). No association was found between use of ARBs and falls.Our results indicate that use of ACEIs might be independently associated with reduced probability, and a reduced number of falls among patients with PD. Dedicated studies are needed to define the single agents and dosages that might most effectively reduce the risk of falling in clinical practice.     

Metaiodobenzylguanidine (MIBG) uptake in Parkinson’s disease also decreases at thyroid

BACKGROUND: Decreased cardiac metaiodobenzylguanidine (MIBG) uptake was reported in Parkinson's disease and this contributes to the differential diagnosis between Parkinson's disease and other forms of parkinsonism such as multiple system atrophy. However, decreased MIBG uptake of the thyroid has not been demonstrated. OBJECTIVE: To compare MIBG uptake of the thyroid among Parkinson's disease, multiple system atrophy and controls. METHODS: Twenty-six patients with Parkinson's disease, 11 patients with multiple system atrophy and 14 controls were examined in this study. Planar images were taken 15 minutes (early images) and 3 hours (late images) after intravenous injection of 111 MBq 123I-MIBG. RESULTS: MIBG uptake of the thyroid on early images decreased significantly in Parkinson's disease compared to controls (p < 0.0001) and multiple system atrophy (p = 0.018). MIBG uptake of the thyroid on early images decreased significantly also in multiple system atrophy compared to controls (p = 0.027). On late images, thyroid uptake differed significantly only between Parkinson's disease and controls (p = 0.010). CONCLUSIONS: Our study is the first to demonstrate decreased MIBG uptake of the thyroid in Parkinson's disease. Sympathetic nervous denervation of Parkinson's disease occurred not only in the heart but also in the thyroid.     

Evaluation of myocardial perfusion in patients with Behçet’s disease

Aim

To estimate the prevalence of silent myocardial ischemia (SMI) in patients with Behçet’s disease (BD) and to identify a subgroup of patients at higher risk for the presence of SMI. Materials and Methods We evaluated 41 patients (mean age 42.8 ± 12.3 years) with BD and 35 healthy control subjects. Treadmill exercise test and thallium-201 myocardial perfusion single photon emission computed tomography (SPECT) were performed in all subjects. Coronary angiography was performed in all patients with a diagnosis of SMI in Behçet’s group.

Results

All subjects had normal resting electrocardiograms. Eight patients with BD (19.5%) had evidence of ischemia on exercise testing and myocardial perfusion SPECT. Only one SMI positivity (2.9%) was recorded in the control group. Significant coronary stenosis was not found with coronary angiography in the patients with a diagnosis of SMI in Behçet’s group. SMI positivity was recorded in 2 of 18 female patients (11%) and in 6 of 23 male patients (26.1%) with BD (p = 0.429). The mean duration of BD was 13.8 ± 2.6 years in patients with SMI and 7 ± 4.1 in patients without it (p < 0.001). Seven of the 8 patients (87.5%) with SMI had a duration of BD of greater than 10 years.

Conclusions

The results of this study show that the prevalence of SMI is high in patients with BD. Based on our findings, screening with myocardial perfusion scintigraphy may be recommended for patients with duration of BD greater than 10 years.     

Oxygen cost of over-ground walking in persons with mild-to-moderate Parkinson’s disease

BackgroundOxygen (O₂) cost of walking is a physiological marker of walking dysfunction and reflects the amount of O₂ consumed per kilogram of body weight per unit distance walked. The onset of walking dysfunction (i.e., reduced walking speed and shorter stride length) is commonly observed in Parkinson’s disease (PD), even in the early stages of the disease. However, the O₂ cost of walking has not been assessed in persons with PD.Research questionDoes O₂ cost of walking differ between persons with PD and controls matched by age and sex?MethodsThe sample included 31 persons with mild-to-moderate PD (Hoehn and Yahr stages 2–3) and 31 age- and sex-matched controls in this cross-sectional study. O₂ consumption (VO₂) was measured using a portable indirect calorimetry system during a 6-min period of over-ground walking at a normal comfortable speed, and the O₂ cost of walking was calculated based on the ratio of net relative VO₂ (ml kg⁻¹ min⁻¹) and speed (m min⁻¹).ResultsThere were no differences in resting VO₂, steady-state VO₂, and over-ground walking speed between persons with PD and controls (p > 0.05). There was a significant difference in the O₂ cost of walking between persons with PD and healthy controls (p < 0.01) such that persons with PD had a higher O₂ cost of walking. The mean(SD) O₂ cost of walking for persons with PD was 0.179 (0.038) ml kg⁻¹ m⁻¹, and the O₂ cost of walking for healthy controls was 0.153 (0.024) ml kg⁻¹ m⁻¹.SignificancePersons with PD demonstrated a higher O₂ cost of walking compared with controls, and this may reflect worse walking economy in PD. The possibility of worse walking economy under free-living conditions may result in reduced community ambulation and participation.     

Spectral analysis of body movement during deep brain stimulation in Parkinson’s disease

BackgroundThe characteristics of Parkinson’s disease (PD) include postural instability and resting tremor. However, reductions of tremor amplitude do not always improve postural stability.Research questionWhat is the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on spectral analysis of body movement in patients with PD when tested without anti-PD medication? The effect of visual cues was also studied.MethodsTen patients with PD (mean age 64.3 years, range 59−69 years) and 17 control participants (mean age 71.2 years, range 65–79 years) were recruited. Spectral power following a period of quiet stance (35 s) was analysed in three different spectral power bands (0−4 Hz, 4−7 Hz and 7−25 Hz). Motion markers were secured to the head, shoulder, hip, and knee, which recorded movements in two directions, the anteroposterior and lateral.ResultsDBS STN significantly changed the spectral distribution pattern across the body in the anteroposterior (p = 0.029) and lateral directions (p ≤ 0.003). DBS predominantly reduced spectral power at the head (p ≤ 0.037) and shoulder (p ≤ 0.031) in the lateral direction. The spectral power of the lower and upper body in patients with PD, with DBS ON, were more similar to the control group, than to DBS OFF. Visual cues mainly reduced spectral power in the anteroposterior direction at the shoulder (p ≤ 0.041) in controls and in patients with PD with DBS ON.SignificanceThere is an altered postural strategy in patients with PD with DBS ON as shown by an altered spectral power distribution pattern across body segments and a reduction of spectral power in the lateral direction at the head and shoulder. A reduction of spectral power in controls and in patients with PD with DBS ON suggests that visual cues are able to reduce spectral power to some extent, but not with DBS OFF where postural sway and power are larger.     

Scoring analysis of salivary gland scintigraphy in patients with Sjögren’s syndrome

The purpose of the present study was to evaluate the validity of a scoring system based on excretion rate of salivary gland scintigraphy in patients with Sjögren’s syndrome (SjS). Total scintigraphic scores were compared with the results of the Saxon test. One hundred and twenty-four subjects who were clinically diagnosed with SjS and 11 normal ones underwent salivary gland scintigraphy and the Saxon test. In salivary gland scintigraphy, the difference between maximum and minimum counts after stimulation using vitamin C divided by maximum counts was defined as the excretion rate. We then defined a scoring system with 4 grades: severe dysfunction = 3 (excretion rate < 25%), moderate dysfunction = 2 (25% ≤ excretion rate < 40%), mild dysfunction = 1 (40% ≤ excretion rate < 50%) and normal function = 0 (50% ≤ excretion rate). The summation of the total scintigraphic score (0–12) of all 4 salivary glands was used as a semi-quantitative index indicating total salivary gland function, and total scintigraphic scores were compared with the results of the Saxon test. A significant inverse linear correlation (R² = 0.95) was observed between total scintigraphic scores and mean values of the Saxon test within a range of abnormal scintigraphic scores (≥ 4). The scoring system developed in the present study is a clinically available, objective, and reproducible method for evaluation of salivary gland function in patients with SjS.     

Non-motor predictors of freezing of gait in Parkinson’s disease

BackgroundThe etiology of freezing of gait in Parkinson’s disease (PD) is yet to be clarified. Non-motor risk factors including cognitive impairment, sleep disturbance and mood disorders have been shown in freezing of gait.Research questionWe aimed to determine the predictive value of non-motor features in freezing of gait development.MethodsData were obtained from the Parkinson’s Progression Markers Initiative. Fifty PD patients with self-reported freezing of gait, and 50 PD patients without freezing of gait at the fourth year visit were included. Groups were matched for Movement Disorders Society-Unified Parkinson’s Disease Rating Scale Part III scores. Several cognitive and non-cognitive tests were used for non-motor features at baseline and over time. Executive function, visuospatial function, processing speed, learning and memory tests were used for cognition. Non-cognitive tests included sleepiness, REM sleep behavior disorder, depression and anxiety scales.ResultsPatients with freezing of gait had higher scores on sleepiness, REM sleep behavior disorder, depression and anxiety scales. However, predictor model analysis revealed that baseline processing speed, learning and sleepiness scores were predictive of self-reported freezing of gait development over time.SignificanceOur findings suggest that specific cognitive deficits and sleep disorders are predictive of future freezing of gait. These features may be helpful in identifying underlying networks in freezing of gait and should be further investigated with neuroimaging studies.     

Brain perfusion alterations in depressed patients with Parkinson’s disease

Objective

Although Parkinson’s disease (PD) is frequently accompanied by depression, brain perfusion deficits in PD with depression remain unclear. This study aimed to assess alterations in regional cerebral blood flow (rCBF) in depressed PD patients using ^99mTc hexamethyl-propylene-amine-oxime single-photon emission computed tomography (SPECT).

Methods

Among 78 patients with PD, 35 patients were classified into the depressed PD group, while the rest (43 patients) was assigned to the nondepressed PD group based on the scores of the Geriatric Depressive Scale (GDS). All participants underwent brain SPECT imaging. The voxel-wise whole-brain analysis and region-of-interest (ROI) analysis of the limbic areas were conducted to compare rCBF between the depressed and nondepressed PD groups.

Results

The depressed PD patients demonstrated higher GDS scores than nondepressed patients, whereas between-group differences in the PD severity and cognitive function were not significant. Perfusion in the left cuneus was increased, while that in the right superior temporal gyrus and right medial orbitofrontal cortex was reduced in the depressed PD patients as compared with nondepressed PD patients. In addition, the ROI analysis demonstrated rCBF decreases in the amygdala, anterior cingulate cortex, hippocampus, and parahippocampal gyrus in the depressed PD group. A positive correlation was found between the GDS scores and rCBF in the left cuneus cluster in the depressed PD patients.

Conclusion

This study identified the regional pattern of brain perfusion that distinguished depressed from nondepressed PD patients. Hyperperfusion in the occipital areas and hypoperfusion in the fronto-temporo-limbic regions may be potential imaging biomarkers for depression in PD.

     

The effects of habitual footwear in gait outcomes in people with Parkinson’s disease

Background: Gait is impaired in individuals with Parkinson's disease (PD). Although the effect of habitual footwear on gait spatiotemporal parameters has already been established in neurologically healthy individuals, its effects on people with PD is unknown.Research question: This study aimed to investigate the impact of habitual footwear on the step spatiotemporal parameters in people with PD.Methods: Sixteen individuals with PD (G-PD) and 15 neurologically healthy individuals (G-HC) were assessed. Participants walked on an 8 m long pressure sensitive walkway at their preferred speed with and without their habitual footwear (3 trials per condition). Footwear included flip-flops, shoes, sneakers and sandals. The average, variability and asymmetry for step length, width, duration, and velocity and the percentage time in the swing and stance phases were calculated.Results: The results showed in both groups a reduced percentage time in the swing phase and an increased step width, duration and length with footwear (F(1,29)>5.64; p<0.02). Additionally, habitual footwear increased step width variability in G-PD and G-HC (F(1,29)=3.97; p=0.06). Interestingly, only G-HC showed a higher step length asymmetry in the footwear condition than in the barefoot condition (p=0.02). Finally, only when habitual footwear was used, G-HC showed a higher step velocity asymmetry than G-PD (p=0.04).Significance: These results indicate a negative influence of footwear on gait spatiotemporal parameters in both groups. Furthermore, footwear induced differences between groups. These findings indicate that footwear use is an influencing factor in studies comparing people with PD and healthy elderly. Further data are needed before definitive recommendations are made.     

Functional MRI in the assessment of cortical activation in subjects with Parkinson’s disease

PURPOSE: The purpose of this study was to evaluate cortical activation patterns in patients with Parkinson's disease during a relatively complex motor task. MATERIALS AND METHODS: Seven patients (six men and one woman) with lateralised akinetic-rigid Parkinson's disease underwent functional magnetic resonance imaging (MRI) of the brain with a 1.5-T magnet. Finger tapping was chosen as a motor task. The control group included 11 volunteers (six men and five women) with no neurological disease. RESULTS: Patients showed hyperactivity of the ipsilateral and contralateral motor cortex associated with bilateral over-activation of the parietal cortex during movement of the affected hand. In some cases, there was a lack of activation of the pre-motor and supplementary motor areas whereas, when present, activation in these areas was greater during movement of the healthy hand. Finally, activation of the occipital cortex was found in all patients as a result of their tendency to control movement visually. CONCLUSIONS: Results of this study confirm a re-organisation of cortical circuits due to subcortical damage in patient's with Parkinson's disease.     

Substantia innominata: MR findings in Parkinson’s disease

To elucidate MR imaging changes of the substantia innominata in Parkinsons disease (PD), using a 1.5-T superconductive MR unit, the thickness of the substantia innominata was measured on coronal thin-section images in 44 PD patients and 20 age-matched control subjects. We also evaluated the correlation between the thickness of the substantia innominata and mental status in PD patients. Mean thickness of the substantia innominata was 2.3 mm in PD patients, and 2.5 mm in control subjects. Thinning of the substantia innominata was statistically significant in PD patients compared with control subjects, although there were large overlaps. Among the PD patients, thinning was remarkable in cases with dementia. A positive correlation between thickness of substantia innominata and score of Mini-Mental-Status-Examination was also observed in PD patients. Atrophy of the substantia innominata was demonstrated, especially in PD patients with cognitive impairment, on coronal MR images, and this is compatible with the previous pathological reports.     

Split-belt treadmill walking in patients with Parkinson’s disease: A systematic review

BackgroundWalking on a split-belt treadmill (SBT) can help to modulate an asymmetric gait, particularly for people with neurological conditions, such as Parkinson’s disease (PD), where asymmetry plays a role due to the laterality of the disease.Research questionThis systematic review critically evaluates the literature on SBT in PD. First, different SBT paradigms and methodological approaches were evaluated. Second, the review explored how people with PD adapt their gait to different SBT conditions compared to healthy controls (HC).MethodsWe conducted a systematic search of the PubMED, PsychINFO, and Web of Knowledge databases. Original research articles, published in English and investigating SBT walking in people with PD, were included.ResultsFrom the 925 studies originally identified, seven met the inclusion criteria and were selected for evaluation (n = 118 individuals with PD of whom 44 had freezing of gait (FOG)). The SBT paradigms varied across studies regarding the SBT settings, definitions of gait variables, and criteria for determining dominance of body side. Gait variability and bilateral coordination were found to adapt to the SBT condition similarly in people with PD and healthy controls (HC). Inconsistent results were found with respect to the adaptation of gait asymmetry, for the differences between PD and HC participants. The subgroup of people with PD and FOG showed reduced accuracy in detecting belt speed differences and slower adaptation to SBT conditions.ConclusionIndividuals with mild to moderately severe PD adapted similarly to HCs to SBT walking for gait variability and bilateral gait coordination. However, those with FOG had impaired perception of belt speed differences and did not adapt their gait so readily. Although SBT can be useful for modulating gait asymmetry in some people with PD, it was not beneficial for all. We recommend standardization of SBT protocols for clinical practice in future studies.     

Regional CBF changes in Parkinson’s disease: a correlation with motor dysfunction

Purpose The purpose of this study was to further localize cerebral perfusion abnormalities, and to better correlate these abnormalities with the clinical severity of Parkinson’s disease (PD). Methods A single-photon emission computed tomography (SPECT) study was performed on 27 patients with PD and 24 age-matched controls. SPECT images were spatially normalized, concatenated, and then decomposed using Infomax independent component analysis (ICA). The resulting image components were separated by logistic regression into two subspaces: “disease-related” components whose subject weights differed between groups, and “disease-unrelated” components. The resultant regional cerebral blood flow (rCBF) subspace images were normalized to global CBF for each subject, and then processed using statistical parametric mapping to compare rCBF values between PD and control subjects. Results In the disease-related image subspace, patients with PD exhibited significantly higher adjusted rCBF in the putamen, globus pallidum, thalamus, brainstem, and the anterior lobe of the cerebellum, and significant hypoperfusion in the parieto-temporo-occipital cortex, the dorsolateral prefrontal cortex, the insula, and the cingulate gyrus. The motor Unified Parkinson’s Disease Rating Scale scores correlated negatively with rCBF in the insula and cingulate gyrus. In the disease-unrelated image subspace, no brain voxels exhibited a significant group difference. Conclusion ICA-based separation of normalized images into disease-related and disease-unrelated subspaces revealed many disease-related group blood flow differences. The regions revealed by ICA are consistent with the current model of PD. These rCBF changes in PD have not been fully demonstrated in any single functional imaging study previously. An editorial commentary on this paper is available at