Effect of subthalamic nucleus deep brain stimulation on balance in Parkinson’s disease: A static posturographic analysis

BackgroundThe effect of subthalamic deep brain stimulation on balance in Parkinson’s disease remains unclear.ObjectiveTo evaluate the effect of subthalamic nucleus stimulation on balance in Parkinson’s disease using posturography.Methods16 patients (9 women) who underwent subthalamic deep brain stimulation [mean age 59.6 years (46–70); mean disease duration 15.6 years (7–25); mean duration of subthalamic stimulation 32.1 months (3.0–69.6)] and 13 healthy age-matched controls were evaluated using a static posturography analysis. Patients were assessed under four conditions: 1) off medication/off stimulation; 2) off medication/on stimulation; 3) on medication/off stimulation and 4) on medication/on stimulation in ten experimental paradigms, some reproducing common situations of daily living. The displacement of the centre of pressure was analyzed using 14 posturographic parameters. The Mann-Whitney test was used to compare patients with controls. The Wilcoxon signed rank test was used to compare patients under different clinical conditions.ResultsPatients off medication/off stimulation showed larger and more rapid displacements of the centre of pressure than controls in most paradigms (p < 0.05), particularly when performing a dual task. Subthalamic stimulation alone reduced the lateral excursion and anterior-posterior velocity of the centre of pressure in quite stance paradigms (p < 0.05). Subthalamic stimulation combined with antiparkinsonian medication did not induce statistically significant changes in posturagraphic measures in any experimental paradigm.ConclusionsAlthough subthalamic stimulation alone may induce some positive effect on balance, subthalamic stimulation in addition to antiparkinsonian medication, which is the usual treatment in clinical practice, did not modify balance as assessed by static posturography in patients with Parkinson’s disease.     

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.     

Dopamine transporter imaging and the effects of deep brain stimulation in patients with Parkinson’s disease

Purpose Single-photon emission computed tomography (SPECT) with [¹²³I]FP-CIT is a marker for loss of presynaptic dopamine transporters in the striatum in Parkinson’s disease (PD). We used [¹²³I]FP-CIT SPECT in order to evaluate binding to the dopamine transporter before and after neurosurgical treatment with bilateral stimulation in the subthalamic nucleus (STN). Methods Thirty-five patients with levodopa-responsive PD were examined with [¹²³I]FP-CIT SPECT pre-operatively (baseline scan: mean 3 months before surgery), and 3 and 12 months after surgery. Results Pre-operatively, all patients already had substantial signs of severe nigrostriatal neuronal loss as determined from the [¹²³I]FP-CIT SPECT scans. One year after surgery the specific [¹²³I]FP-CIT binding to the striatum was significantly reduced by 10.3% compared with the pre-operative baseline scan. The mean time span from the baseline scan before surgery to the follow-up scan 1 year after surgery was 16.2 months. Hence, the rate of reduction equals a mean annual reduction of 7.7%. A comparable control group of patients with PD who did not undergo surgery was also examined longitudinally. In this group the specific binding of [¹²³I]FP-CIT was reduced by 6.7% per year. Conclusion The specific binding of [¹²³I]FP-CIT was reduced equally in the STN-stimulated patients and a group of non-operated PD patients with advanced disease. Our study does not support the notion that electrode implantation and STN stimulation exert a neuroprotective effect by themselves.     

Unilateral deep brain stimulation of the pedunculopontine tegmental nucleus in idiopathic Parkinson’s disease: Effects on gait initiation and performance

The pedunculopontine tegmental nucleus (PPTg) is a component of the locomotor mesencephalic area. In recent years it has been considered a new surgical site for deep brain stimulation (DBS) in movement disorders. Here, using objective kinematic and spatio-temporal gait analysis, we report the impact of low frequency (40 Hz) unilateral PPTg DBS in ten patients suffering from idiopathic Parkinson’s disease with drug-resistant gait and axial disabilities. Patients were studied for gait initiation (GI) and steady-state level walking (LW) under residual drug therapy. In the LW study, a straight walking task was employed. Patients were compared with healthy age-matched controls. The analysis revealed that GI, cadence, stride length and left pelvic tilt range of motion (ROM) improved under stimulation. The duration of the S1 and S2 sub-phases of the anticipatory postural adjustment phase of GI was not affected by stimulation, however a significant improvement was observed in the S1 sub-phase in both the backward shift of centre of pressure and peak velocity. Speed during the swing phase, step width, stance duration, right pelvic tilt ROM phase, right and left hip flexion-extension ROM, and right and left knee ROM were not modified.Overall, the results show that unilateral PPTg DBS may affect GI and specific spatio-temporal and kinematic parameters during unconstrained walking on a straight trajectory, thus providing further support to the importance of the PPTg in the modulation of gait in neurodegenerative disorders.     

Are there adaptive changes in the human brain of patients with Parkinson’s disease treated with long-term deep brain stimulation of the subthalamic nucleus? A 4-year follow-up study with regional cerebral blood flow SPECT

Purpose The aim of this follow-up study was to assess persistent motor and regional cerebral blood flow (rCBF) changes in patients with Parkinson’s disease (PD) treated with high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN). Methods Ten PD patients with STN-DBS underwent three rCBF SPECT studies at rest, once preoperatively in the off-drug condition (T₀), and twice postoperatively in the off-drug/off-stimulation conditions at 5 ± 2 (T₁) and 42 ± 7 months (T₂). Patients were assessed using the UPDRS, H&Y and S&E scales. SPM was used to investigate baseline rCBF changes from the preoperative condition to the postoperative conditions and the relationship between rCBF and UPDRS scores used as covariate of interest. Results Parkinsonian patients showed a clinical improvement which was significant only on follow-up at 42 months. The main effect of treatment from T₀ to T₁ was to produce baseline rCBF increases in the pre-supplementary motor area (pre-SMA), premotor cortex and somatosensory association cortex. From T₁ to T₂ a further baseline rCBF increase was detected in the pre-SMA (p < 0.0001). A correlation was detected between the slight improvement in motor scores and the rCBF increase in the pre-SMA (p < 0.0001), which is known to play a crucial role in clinical progression. Conclusion Our study suggests the presence of adaptive functional changes in the human brain of PD patients treated with long-term STN-DBS. Such adaptive processes seem to occur in the pre-SMA and to play only a slightly beneficial role in terms of functional compensation of motor impairment.     

Exclusion of brain lesions: is MR contrast medium required after a negative fluid-attenuated inversion recovery sequence?

We hypothesized that in patients with negative fluid-attenuated inversion recovery (FLAIR) images T(2) weighted fast spin-echo (FSE) images and T(1) weighted spin-echo (SE) images before and after intravenous administration of gadolinium-based contrast medium display no pathology either. Thus, we assessed the negative predictive value of FLAIR images to rule out MR-detectable brain lesions. 1026 consecutive cranial MR examinations were reviewed. Routine MRI of the brain included T(1) weighted coronal imaging before and after administration of gadopentetate dimeglumine, axial T(2) weighted FSE and fast-FLAIR imaging. The FLAIR images were rated by two radiologists into categories of 0 (without pathologic changes) and 1 (with pathologic changes). Two other radiologists analysed the complete examination. In 284 MR examinations of the brain no abnormalities were found (28%). FLAIR-ratings were false-negative in four cases and false-positive in 30 cases. Sensitivity and specificity of the FLAIR sequence for MR-detectable brain lesions were 99.5% and 89.4%. The unselective application of gadolinium avoided one false-negative MR-reading and improved the sensitivity of the MR-examination from 99.5% to 99.6%. Positive and negative predictive values were 96.1% and 98.4%, respectively. The interobserver reliability was kappa=0.93 for the FLAIR-readers and 0.89 for the readers who rated the complete examination. In conclusion, negative FLAIR images provide a high negative predictive value for MR-detectable brain lesions. Thus, in patients with negative FLAIR images the unselective application of gadolinium seems to be unnecessary.     

“Sukeroku sign” and “dent internal-capsule sign”—identification guide for targeting the subthalamic nucleus for placement of deep brain stimulation electrodes

Introduction  The purpose of this study was to assess the usefulness of signs (“Sukeroku sign” and “dent internal-capsule sign”) for the recognition of subthalamic nucleus (STN). Materials and methods  Five Parkinson’s disease cases in which there was a successful placement of deep brain stimulation (DBS) electrodes at the STN were retrospectively reviewed. Five radiologists who were not engaged in localization of STNs in clinical practice were asked to locate the STNs before and after instructions on the signs. We evaluated the deviation between the reader-located points and the location of the DBS electrode for which there had been a successful installation. Results  After instruction, there was a significant reduction in the deviation between the reader-located points and the DBS electrode. The time required for localization was also reduced after the instructions. Conclusion  Sukeroku sign and dent internal-capsule sign are feasible indicators of STN and seem to be useful in helping to identify the STN.     

Recent advances in PET imaging for evaluation of Parkinson’s disease

Parkinson’s disease (PD) consists of loss of pigmented dopamine-secreting neurons in the pars compacta of the midbrain substantia nigra. These neurons project to the striatum (putamen and caudate nucleus) and their loss leads to alterations in the activity of the neural circuits that regulate movement. In a simplified model, two dopamine pathways are involved: the direct pathway, which is mediated through facilitation of the D₁ receptors, and the indirect pathway through D₂ receptors (inhibitory). Positron emission tomography (PET) tracers to image the presynaptic sites of the dopaminergic system include 6-[¹⁸F]FDOPA and 6-[¹⁸F]FMT, [¹¹C]dihydrotetrabenazine, [¹¹C]nomifensine and various radiolabelled cocaine derivatives. Postsynaptically, for the dopamine D₁ subtype the most commonly used ligands are [¹¹C]SCH 23390 or [¹¹C]NNC 112 and for the D₂ subtype [¹¹C]raclopride, [¹¹C]MNPA and [¹⁸F]DMFP. PET is a sensitive and specific non-invasive molecular imaging technique that may be helpful for evaluation of PD and its differential diagnosis from other parkinsonian syndromes.     

Three-dimensional stereotactic surface projection of brain perfusion SPECT improves diagnosis of Alzheimer’s disease

OBJECTIVES: Alzheimer's disease (AD) is diagnosed by either inspection of the brain perfusion SPECT, or three-dimensional stereotactic surface display (3D-SSP). The purpose was to compare diagnostic performances of these methods. METHODS: Sixteen nuclear medicine physicians independently interpreted 99mTc-ECD SPECT in one session and SPECT with 3D-SSP in another session without clinical information for 50 studies of AD patients and 40 studies of healthy volunteers. Probabilities of AD were reported according to a subjective scale from 0% (normal) to 100% (definite AD). Receiver operating characteristics curves were generated to calculate areas under the ROC curves (Az's) for the inspection as well as for an automated diagnosis based on a mean Z value in the bilateral posterior cingulate gyri in a 3D-SSP template. RESULTS: Mean Az for visual interpretation of SPECT alone (0.679 +/- 0.058) was significantly smaller than that for visual interpretation of both SPECT and 3D-SSP (0.778 +/- 0.060). Az for the automated diagnosis (0.883 +/- 0.037) was significantly greater than that for both modes of visual interpretation. CONCLUSIONS: 3D-SSP enhanced performance of the nuclear medicine physicians inspecting SPECT. Performance of the automated diagnosis exceeded that of the physicians inspecting SPECT with and without 3D-SSP.     

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.     

Distinct spatiotemporal patterns for disease duration and stage in Parkinson’s disease

Purpose

To assess correlations between the degree of dopaminergic depletion measured using single-photon emission computed tomography (SPECT) and different clinical parameters of disease progression in Parkinson’s disease (PD).

Methods

This retrospective study included 970 consecutive patients undergoing ¹²³I-ioflupane SPECT scans in our institution between 2003 and 2013, from which we selected a study population of 411 patients according to their clinical diagnosis: 301 patients with PD (69.4?±?11.0 years, of age, 163 men) and 110 patients with nondegenerative conditions included as controls (72.7?±?8.0 years of age, 55 men). Comprehensive and operator-independent data analysis included spatial normalization into standard space, estimation of the mean uptake values in the striatum (caudate nucleus + putamen) and voxel-wise correlation between SPECT signal intensity and disease stage as well as disease duration in order to investigate the spatiotemporal pattern of the dopaminergic nigrostriatal degeneration. To compensate for potential interactions between disease stage and disease duration, one parameter was used as nonexplanatory coregressor for the other.

Results

Increasing disease stage was associated with an exponential decrease in ¹²³I-ioflupane uptake (R ² ?=?0.1501) particularly in the head of the ipsilateral caudate nucleus (p?<?0.0001), whereas increasing disease duration was associated with a linear decrease in ¹²³I-ioflupane uptake (p?<?0.0001; R ² ?=?0.1532) particularly in the contralateral anterior putamen (p?<?0.0001).

Conclusion

We observed two distinct spatiotemporal patterns of posterior to anterior dopaminergic depletion associated with disease stage and disease duration in patients with PD. The developed operator-independent reference database of 411 ¹²³I-ioflupane SPECT scans can be used for clinical and research applications.

     

Subthalamic nucleus stimulation and gait in Parkinson’s Disease: a not always fruitful relationship

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides efficient treatment for the alleviation of motor signs in patients with advanced Parkinson’s disease (PD), but its specific effects on gait is sometimes less successful as it may even lead to an aggravation of freezing of gait. To better understand when axial symptoms can be expected to improve and when they may worsen or be resistant to STN-DBS, we propose here a narrative review that considers the recent literature evidences based on instrumental gait analysis data. Our aim is to report about the efficacy of STN-DBS on PD gait, analyzing the clinical and procedural factors involved, and discussing the strategies for optimizing such effectiveness in patients with advanced PD.     

Diagnostic accuracy of short-time inversion recovery sequence in Graves’ ophthalmopathy before and after prednisone treatment

Introduction

In Graves’ Ophthalmopathy, it is important to distinguish active inflammatory phase, responsive to immunosuppressive treatment, from fibrotic unresponsive inactive one. The purpose of this study is, first, to identify the relevant orbital magnetic resonance imaging signal intensities before treatment, so to classify patients according to their clinical activity score (CAS), discriminating inactive (CAS?<?3) from active Graves’ Ophthalmopathy (GO) (CAS?>?3) subjects and, second, to follow post-steroid treatment disease.

Methods

An observational study was executed on 32 GO consecutive patients in different phases of disease, based on clinical and orbital Magnetic Resonance Imaging parameters, compared to 32 healthy volunteers. Orbital Magnetic Resonance Imaging was performed on a 1.5 tesla Magnetic Resonance Unit by an experienced neuroradiologist blinded to the clinical examinations.

Results

In pre-therapy patients, compared to controls, a medial rectus muscle statistically significant signal intensity ratio (SIR) in short-time inversion recovery (STIR) (long TR/TE) sequence was found, as well as when comparing patients before and after treatment, both medial and inferior rectus muscle SIR resulted significantly statistically different in STIR. These increased outcomes explain the inflammation oedematous phase of disease, moreover after steroid administration, compared to controls; patients presented lack of that statistically significant difference, thus suggesting treatment effectiveness.

Conclusion

In our study, we proved STIR signal intensities increase in inflammation oedematous phase, confirming STIR sequence to define active phase of disease with more sensibility and reproducibility than CAS alone and to evaluate post-therapy involvement.     

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.     

Differences in predictors for gait speed and gait endurance in Parkinson’s disease

IntroductionBoth gait speed and gait endurance directly impact independence and community engagement for individuals with Parkinson’s disease (PD). However, factors accounting for variability in gait speed and gait endurance performance are unclear. The purpose of this study was to investigate whether key factors associated with gait speed in individuals with PD also predicted gait endurance.MethodsCommunity dwelling ambulatory individuals with PD were recruited for a single session. Key measures included 10 Meter Walk Test (10MWT) and 6 Minute Walk Test (6MWT) and key factors: age, disease severity [Movement Disorders Society United Parkinson’s Disease Rating Scale (motor scale only) (MDS-UPDRS motor)], plantar flexor strength [Calf Raise Senior (CRS)], fatigue [Fatigue Severity Scale (FSS)], cognition [Montreal Cognitive Assessment (MoCA)], and balance [Four Square Step Test (FSST)]. Multiple linear regression analyses were conducted to determine clinical relationships.ResultsSeventy-two individuals with PD (mean (standard deviation) (age = 70.83 (7.91) years; 50 males; MDS-UPDRS motor = 30.67 (13.50)) completed all assessments. The model predicting gait speed was significant, F(6, 65) = 15.143, p <.001, accounting for 54 % of the variance. Of the predictor variables age, MDS-UPDRS motor, CRS, MoCA and FSST scores were significant predictors. The model predicting gait endurance was significant, F(6, 65) = 15.608, p <.001, accounting for 55 % of the variance. Of the predictor variables, age, MDS-UPDRS motor scale, and CRS scores were significant predictors.DiscussionGait speed and gait endurance are similarly influenced by age, motor impairment, and plantarflexion strength. However, cognition and balance were predictors only of gait speed, which may suggest unique task differences exist between gait speed and gait endurance.     

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.     

Test-retest reliability of stride length-cadence gait relationship in Parkinson’s disease

IntroductionThe gait pattern in Parkinson´s disease (PD) subjects is characterized by a specific deficit of the internal regulation of the stride length (SL), while the control of the cadence (Cad) remains intact. The purpose of the present study was to evaluate the reliability of the stride length-cadence relationship (SLCrel) in a group of PD subjects.MethodsThirty five PD subjects performed two sessions, separated by a three month resting period. In each session Gait speed, SL and Cad were evaluated at five different self-selected speed conditions: preferred, slow, very slow, fast and very fast. Linear regression analysis was used to explore the SLCrel and to determine the slope, intercept and coefficient of determination (R²) for each participant. Test-retest reliability for the slope and intercept was calculated using intra-class correlation coefficient (ICC), 95% confidence interval (CI), and standard error of mean (SEM).ResultsThere were no significant differences in the slope and intercept between the two sessions. The overall speed was significantly faster in the second session compared with the first one (F = 4.60, p = 0.03). The SLCrel showed high reliability across the sessions (ICC = 0.89 and ICC = 0.91; 95% CI = 0.80−0.95 and 95% CI = 0.82−0.95; SEM = 0.002 and SEM = 0.073, for the slope and interception, respectively).ConclusionsThe SLCrel in Parkinsonian gait is a reproducible measure across a period of three months, and may be a useful tool to explore the specificity of gait rehabilitation interventions in PD subjects.