Search

OBJECTIVE: This experiment tested if balance performance differed between a standardized treadmill surface perturbation task and a clinical pull test and was affected by medication or the presence of body weight support in people with Parkinson’s disease (PD). METHODS: Twenty-seven individuals were tested (14 PD in both ON- and OFF-medication states). Clinical pull test and rapid forward (backward fall) translations of the support surface were applied to induce postural reactions requiring at least 1 step to restore balance. The effects of pull type (clinical vs. treadmill), partial bodyweight support (0 vs 20% body weight) and group (control, PD ON-meds and PD OFF-meds) on reactive stepping as well as practice/learning effect were examined. The number of steps taken and the first step duration were entered in linear repeated-measures mixed-effect models separately. RESULTS: The effects of pull type, group, and bodyweight support were all significant in both metrics, as was ON- vs. OFF-medication. A significant interaction term (group x pull type) was found in the first step duration, showing that the group difference was greater in treadmill compared to the clinical pull test. A significant practice effect was also observed within and across testing sessions. CONCLUSIONS: A standardized treadmill perturbation performed slightly better than the classical pull test in distinguishing between groups, and partial weight support did not substantially degrade the test’s performance to detect the balance deficits in people with PD.

In the study of frustrated quantum magnets, it is essential to be able to control the nature and degree of site disorder during the growth process, as many measurement techniques are incapable of distinguishing between site disorder and frustration-induced spin disorder. Pyrochlore-structured spinel oxides can serve as model systems of geometrically frustrated three-dimensional quantum magnets; however, the nature of the magnetism in one well-studied spinel, ZnFe 2 O 4 , remains unclear. Here, we demonstrate simultaneous control of both stoichiometry and inversion disorder in the growth of ZnFe 2 O 4 single crystals, directly yielding a revised understanding of both the collective spin behavior and lattice symmetry. Crystals grown in the stoichiometric limit with minimal site inversion disorder contravene all the previously suggested exotic spin phases in ZnFe 2 O 4 . Furthermore, the structure is confirmed on the F 4 ¯ 3 m space group with broken inversion symmetry that induces antiferroelectricity. The effective tuning of magnetic behavior by site disorder in the presence of robust antiferroelectricity makes ZnFe 2 O 4 of special interest to multiferroic devices.

Background: Subtle gait deficits can be seen in people with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), a prodromal stage of Parkinson’s disease (PD) and related alpha-synucleinopathies. It is unknown if the presence and level of REM sleep without atonia (RSWA, the electromyographic hallmark of RBD) is related to the severity of gait disturbances in people with PD. Objective: We hypothesized that gait disturbances in people with mild-to-moderate PD would be greater in participants with RSWA compared to those without RSWA and matched controls, and that gait impairment would correlate with measures of RSWA. Methods: Spatiotemporal characteristics of gait were obtained from 41 people with PD and 21 age-matched controls. Overnight sleep studies were used to quantify muscle activity during REM sleep and group participants with PD into those with RSWA (PD-RSWA+, n = 22) and normal REM sleep muscle tone (PD-RSWA-, n = 19). Gait characteristics were compared between groups and correlated to RSWA. Results: The PD-RSWA+ group demonstrated significantly reduced gait speed and step lengths and increased stance and double support times compared to controls, and decreased speed and cadence and increased stride velocity variability compared to PD-RSWA- group. Larger RSWA scores were correlated with worse gait impairment in the PD group. Conclusion: The presence and level of muscle tone during REM sleep is associated with the severity of gait disturbances in PD. Pathophysiological processes contributing to disordered gait may occur earlier and/or progress more rapidly in people with PD and RBD.

Background Assessing postural stability in Parkinson’s disease (PD) often relies on measuring the stepping response to an imposed postural perturbation. The standard clinical technique relies on a brisk backwards pull at the shoulders by the examiner and judgement by a trained rater. In research settings, various quantitative measures and perturbation directions have been tested, but it is unclear which metrics and perturbation direction differ most between people with PD and controls. Objectives (1) Use standardized forward vs. backward perturbations of a support surface to evaluate reactive stepping performance between PD and control participants. (2) Evaluate the utility of using principal components analysis to capture the dynamics of the reactive response and differences between groups. Methods Sixty-two individuals participated (40 mild-to-moderate PD, off medication). Standardized rapid translations of the support surface were applied, requiring at least one step, backward or forward, to restore balance. The number of steps taken and the projection of the first principal component (PC1) of the center of pressure (COP) time series were entered in linear repeated-measures mixed effect models. Results Forward falls required significantly fewer steps to recover than backward falls. PC1 captured more than half of the variance in the COP trajectory. Analysis of the PC1 projection revealed a significant interaction effect of group (PD vs. controls) by direction, such that there was a group difference in forward stepping, but not backward. Significance Forward reactive stepping in PD differed from controls more than backward-stepping. PC1 projections of the COP trajectory capture the dynamics of the postural response and differ between PD and controls.

To elucidate the role of the basal ganglia during REM sleep movements in Parkinson’s disease (PD) we recorded pallidal neural activity from four PD patients. Unlike desynchronization commonly observed during wakeful movements, beta oscillations (13-35 Hz) synchronized during REM sleep movements; furthermore, high-frequency oscillations (150-350 Hz) synchronized during movement irrespective of sleep-wake states. Our results demonstrate differential engagement of the basal ganglia during REM sleep and awake movements.

Some symptoms treated with Deep Brain Stimulation (DBS) such as gait in Parkinson’s disease (PD), are often poorly responsive to DBS. This may be because DBS settings are usually optimized to other symptoms. To test this, we require an efficient, safe optimization algorithm. To develop such a tool, we extend the BayesOpt algorithm whose successful application to DBS settings we previously published [Louie et al 2021 J Neuroeng Rehabil], using, as a test bed, a simulated cost function constructed for biological plausibility, with measurement noise based on experimental data.We found that the SafeOpt algorithm [Sui et al 2015 Proc Machine Learning Res] converged to the optimum as well, and as fast as the BayesOpt algorithm, while avoiding high-cost points much more effectively. In three dimensions, SafeOpt converged in about 30 iterations, which is a feasible number for physical experiments in real patients. Convergence was slower when measurement nose was greater, but this could be overcome by running it for more iterations. The algorithm was relatively robust to misspecification of hyperparameters, and considerably more robust when hyperparameter fitting was incorporated into the algorithm. The algorithm did not perform as well when the quantization of stimulation settings was coarser, suggesting that it will work better with neurostimulators capable of independent current control. Finally, the algorithm was able to cope with a cost function having multiple local minima.

BackgroundDeep brain stimulation (DBS) targeting the subthalamic nucleus (STN) often shows variable outcomes on treating gait dysfunction in Parkinson’s disease (PD). Such variability may stem from which specific neuronal pathways are modulated by DBS and the extent to which those pathways are modulated relative to one another.ObjectiveLeveraging ultra-high-field (7T) imaging data and subject-specific computational models, this study investigated how activation of seven distinct pathways in and around STN, including the pallidopeduncular and pedunculopallidal pathways, affect step length at clinically-optimized STN-DBS settings.MethodsPersonalized computational models were developed for 10 subjects with a clinical diagnosis of PD and with bilateral STN-DBS implants.ResultsThe subject-specific pathway activation models showed a significant positive association between activation of the pedunculopallidal pathway and increased step length, and negative association on step length with pallidopeduncular pathway and hyperdirect pathway activation.ConclusionsThe STN region includes multiple pathways, including fibers of passage to and from the mesencephalic locomotor area. Future clinical optimization of STN-DBS should consider these fibers of passage in the context of treating parkinsonian gait.

Background Deep brain stimulation (DBS) is a treatment option for Parkinson’s disease patients when medication does not sufficiently manage their symptoms. DBS can be a highly effect therapy, but only after a time-consuming trial-and-error stimulation parameter adjustment process that is susceptible to clinician bias. This trial-and-error process will be further prolonged with the introduction of segmented electrodes that are now commercially available. New approaches to optimizing a patient’s stimulation parameters, that can also handle the increasing complexity of new electrode and stimulator designs, is needed. Methods To improve DBS parameter programming, we explored two semi-automated optimization approaches: a Bayesian optimization (BayesOpt) algorithm to efficiently determine a patient’s optimal stimulation parameter for minimizing rigidity, and a probit Gaussian process (pGP) to assess patient’s preference. Quantified rigidity measurements were obtained using a robotic manipulandum in two participants over two visits. Rigidity was measured, in 5Hz increments, between 10–185Hz (total 30–36 frequencies) on the first visit and at eight BayesOpt algorithm-selected frequencies on the second visit. The participant was also asked their preference between the current and previous stimulation frequency. First, we compared the optimal frequency between visits with the participant’s preferred frequency. Next, we evaluated the efficiency of the BayesOpt algorithm, comparing it to random and equal interval selection of frequency. Results The BayesOpt algorithm estimated the optimal frequency to be the highest tolerable frequency, matching the optimal frequency found during the first visit. However, the participants’ pGP models indicate a preference at frequencies between 70–110 Hz. Here the stimulation frequency is lowest that achieves nearly maximal suppression of rigidity. BayesOpt was efficient, estimating the rigidity response curve to stimulation that was almost indistinguishable when compared to the longer brute force method. Conclusions These results provide preliminary evidence of the feasibility to use BayesOpt for determining the optimal frequency, while pGP patient’s preferences include more difficult to measure outcomes. Both novel approaches can shorten DBS programming and can be expanded to include multiple symptoms and parameters.

Patients who suffer from Parkinson’s Disease are more prone to postural instability, a major risk factor for falls. One of the most common clinical methods of gauging the severity of a patient’s postural instability is with the retropulsion test [1], in which a clinician perturbs the balance of the patient and then rates their response to the perturbation. This test is subjective and largely based on the observations made by the clinician. In order to improve postural instability diagnosis and encourage more meaningful therapies for this cognitive-motor symptom, there is a clinical need to enable more objective, quantifiable approaches to measuring postural instability. In this paper, we describe a novel computational approach to quantifying the number, length, and trajectory of steps taken during a retropulsion test or other type of balance perturbation from a single camera facing the anterior side (front) of the subject. The computational framework involved first analyzing the video data using markerless pose estimation algorithms to track the movement of the subject’s feet. These pixel data were then converted from 2D to 3D using calibrated transformation functions, and then analyzed for consistency when compared to the known step lengths. The testing data showed accurate step length estimation within 1 cm, which suggests this computational approach could have utility in a variety of clinical environments.

Background Abnormal oscillatory neural activity in the beta-frequency band (13-35 Hz) is thought to play a role in Parkinson's disease (PD); however, increasing evidence points to alterations in high-frequency ranges (>100 Hz) also having pathophysiological relevance. Objectives Studies have found that power in subthalamic nucleus (STN) high-frequency oscillations is increased with dopaminergic medication and during voluntary movements, implicating these brain rhythms in normal basal ganglia function. The objective of this study was to investigate whether similar signaling occurs in the internal globus pallidus (GPi), a nucleus increasingly used as a target for deep brain stimulation (DBS) for PD. Methods Spontaneous and movement-related GPi field potentials were recorded from DBS leads in 5 externalized PD patients on and off dopaminergic medication, as well as from 3 rhesus monkeys before and after the induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. Results In the parkinsonian condition, we identified a prominent oscillatory peak centered at 200-300 Hz that increased during movement. In patients the magnitude of high-frequency oscillation modulation was negatively correlated with bradykinesia. In monkeys, high-frequency oscillations were mostly absent in the naive condition but emerged after the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. In patients, spontaneous high-frequency oscillations were significantly attenuated on-medication. Conclusions Our findings provide evidence in support of the hypothesis that exaggerated, movement-modulated high-frequency oscillations in the GPi are pathophysiological features of PD. These findings suggest that the functional role(s) of high-frequency oscillations may differ between the STN and GPi and motivate additional investigations into their relationship to motor control in normal and diseased states.

Abnormal oscillatory neural activity in the basal ganglia is thought to play a pathophysiological role in Parkinson’s disease. Many patient studies have focused on beta frequency band (13-35 Hz) local field potential activity in the subthalamic nucleus, however increasing evidence points to alterations in neural oscillations in high frequency ranges (>100 Hz) having pathophysiological relevance. Prior studies have found that power in subthalamic high frequency oscillations (HFOs) is positively correlated with dopamine tone and increased during voluntary movements, implicating these brain rhythms in normal basal ganglia function. Contrary to this idea, in the current study we present a combination of clinical and preclinical data that support the hypothesis that HFOs in the internal globus pallidus (GPi) are a pathophysiological feature of Parkinson’s disease. Spontaneous and movement-related pallidal field potentials were recorded from deep brain stimulation (DBS) leads targeting the GPi in five externalized Parkinson’s disease patients, on and off dopaminergic medication. We identified a prominent oscillatory peak centered at 200-300 Hz in the off-medication rest recordings in all patients. High frequency power increased during movement, and the magnitude of modulation was negatively correlated with bradykinesia. Moreover, high frequency oscillations were significantly attenuated in the on-medication condition, suggesting they are a feature of the parkinsonian condition. To further confirm that GPi high frequency oscillations are characteristic of dopamine depletion, we also collected field potentials from DBS leads chronically implanted in three rhesus monkeys before and after the induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). High frequency oscillations and their modulation during movement were not prominent in the normal condition but emerged in the parkinsonian condition in the monkey model. These data provide the first evidence demonstrating that exaggerated, movement-modulated high frequency oscillations in the internal globus pallidus are a pathophysiological feature of Parkinson’s disease, and motivate additional investigations into the functional roles of high frequency neural oscillations across the basal ganglia-thalamocortical motor circuit and their relationship to motor control in normal and diseased states. These findings also provide rationale for further exploration of these signals for electrophysiological biomarker-based device programming and stimulation strategies in patients receiving deep brain stimulation therapy.

The success of deep brain stimulation (DBS) surgeries for the treatment of movement disorders relies on the accurate placement of an electrode within the motor portion of subcortical brain targets. However, the high number of electrodes requiring relocation indicates that today's methods do not ensure sufficient accuracy for all patients. Here, with the goal of aiding DBS targeting, we use 7 Tesla (T) MRI data to identify the functional territories and parcellate the globus pallidus pars interna (GPi) into motor, associative and limbic regions in individual subjects. 7 T MRI scans were performed in seventeen patients (prior to DBS surgery) and one healthy control. Tractography-based parcellation of each patient's GPi was performed. The cortex was divided into four masks representing motor, limbic, associative and “other” regions. Given that no direct connections between the GPi and the cortex have been shown to exist, the parcellation was carried out in two steps: 1) The thalamus was parcellated based on the cortical targets, 2) The GPi was parcellated using the thalamus parcels derived from step 1. Reproducibility, via repeated scans of a healthy subject, and validity of the findings, using different anatomical pathways for parcellation, were assessed. Lastly, post-operative imaging data was used to validate and determine the clinical relevance of the parcellation. The organization of the functional territories of the GPi observed in our individual patient population agrees with that previously reported in the literature: the motor territory was located posterolaterally, followed anteriorly by the associative region, and further antero-ventrally by the limbic territory. While this organizational pattern was observed across patients, there was considerable variability among patients. The organization of the functional territories of the GPi was remarkably reproducible in intra-subject scans. Furthermore, the organizational pattern was observed consistently by performing the parcellation of the GPi via the thalamus and via a different pathway, going through the striatum. Finally, the active therapeutic contact of the DBS electrode, identified with a combination of post-operative imaging and post-surgery DBS programming, overlapped with the high-probability “motor” region of the GPi as defined by imaging-based methods. The consistency, validity, and clinical relevance of our findings have the potential for improving DBS targeting, by increasing patient-specific knowledge of subregions of the GPi to be targeted or avoided, at the stage of surgical planning, and later, at the stage when stimulation is adjusted.

The goal of this study was to characterize the spectral characteristics and spatial topography of local field potential (LFP) activity in the internal segment of the globus pallidus (GPi) in patients with Parkinson's disease utilizing directional (segmented) deep brain stimulation (dDBS) leads. Data were collected from externalized dDBS leads of three patients with idiopathic Parkinson's disease after overnight withdrawal of parkinsonian medication at rest and during a cued reach-to-target task. Oscillatory activity across lead contacts/segments was examined in the context of lead locations and contact orientations determined using co-registered preoperative 7 Tesla (T) MRI and postoperative CT scans. Each of the three patients displayed a unique frequency spectrum of oscillatory activity in the pallidum, with prominent peaks ranging from 5 to 35 Hz, that modulated variably across subjects during volitional movement. Despite subject-specific spectral profiles, a consistent finding across patients was that oscillatory power was strongest and had the largest magnitude of modulation during movement in LFPs recorded from segments facing the postero-lateral “sensorimotor” region of GPi, whereas antero-medially-directed segmented contacts facing the internal capsule and/or anterior GPi, had relatively weaker LFP power and less modulation in the 5 to 35 Hz. In each subject, contact configurations chosen for clinically therapeutic stimulation (following data collection and blinded to physiology recordings), were in concordance with the contact pairs showing the largest amplitude of LFP oscillations in the 5–35 Hz range. Although limited to three subjects, these findings provide support for the hypothesis that the sensorimotor territory of the GPi corresponds to the site of maximal power of oscillatory activity in the 5 to 35 Hz and provides the greatest benefit in motor signs during stimulation in the GPi. Variability in oscillatory activity across patients is likely related to Parkinson's disease phenotype as well as small differences in recording location (i.e. lead location), highlighting the importance of lead location for optimizing stimulation efficacy. These data also provide compelling evidence for the use of LFP activity for the development of predictive stimulation models that may optimize patient benefits while reducing clinic time needed for programming.

ObjectiveTo determine using a repeated-measures, prospective design whether deep brain stimulation (DBS) results in changes in the importance of symptom and behavioral goals individually identified by patients with Parkinson disease (PD) before DBS surgery.MethodsFifty-two participants recruited from a consecutive series completed a semistructured interview soliciting their rank-ordered symptom and behavioral goals and corresponding visual analog scales measuring perceived symptom severity and limits to goal attainment. Rank orders were reassessed at 2 times after DBS. Changes in rank order over time were examined with χ2 analyses. The relationships between change in symptom severity/limits to behavioral goal attainment and change in rank order were examined with mixed-effects linear regression models.ResultsMost participants changed the rank order of their symptom (81%) and behavioral (77%) goals 3 months after DBS surgery. Change in rank order of symptom goals was significantly related to change in severity ratings such that improvements in self-reported symptom severity were associated with reductions in rank. In contrast, no such relationship was evident for the behavioral goals.ConclusionThese data illustrate how patients' primary goals for DBS shift early in stimulation and highlight the important differences between symptom and behavioral goals. Changes in the rank order of symptom goals were related to changes in symptom severity, whereas subtler shifts in behavioral goals were unrelated to improvements after DBS. This observation suggests that DBS does not affect goals that may be more reflective of core personal values. The findings provide empiric data that can help improve the informed consent process.

Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease.This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396.Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation.This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes.Boston Scientific.

Extensive research has examined how current goals influence spatial attention. Yet the allocation of spatial attention is also guided by previous experience, which may induce consistent spatial preferences when a visual search target is frequently found in one region of space. Here, we examined the role of the dopaminergic system in acquiring and maintaining location probability learning. We tested Parkinson's patients and age-matched controls in a difficult visual search task in two sessions. In Session 1, unbeknownst to the participants, the target appeared most often in one quadrant in an early, training phase of the experiment. The target was randomly located in a later, testing phase. Both Parkinson's patients and controls acquired an attentional preference toward the high-probability quadrant during training that persisted in the testing phase. Learning yielded a large reduction in response time (345 ms) in Parkinson's patients, and this effect was highly significant. In Session 2, administered several days later, the target's high-probability quadrant changed. Both groups acquired a new preference for Session 2's high-probability quadrant, demonstrating reversal learning. These findings contrast with previously observed deficits in PD in acquiring probabilistic learning and contextual cueing. This result suggests that not all habit-like behaviors depend on the basal ganglia and the dopaminergic system. Instead, preservation of location probability learning may compensate for other types of attentional deficits in PD.

Background The aim of this work was to describe utilization patterns of dopamine transporter (DaT) scan and its influence on patient management at a single movement disorders center. DaT scan helps differentiate between neurodegenerative from non-neurodegenerative parkinsonism and essential tremor (ET). It has been recently approved in the United States in 2011. Methods We conducted a retrospective review of all patients, observed by movement disorders neurologists, who received a DaT scan. Demographic data, medication use, and prescan diagnosis were collected. Results A total of 216 DaT scans were performed at our center from 1 June 2011 to 31 October 2012. A total of 175 scans were included for analysis. Rates of DaT scan utilization varied from 5 to 33 per 100 new patients observed. When our specialists suspected neurodegenerative parkinsonism before the scan (N = 70), the scan was abnormal in 57%. When non-neurodegenerative parkinsonism was prescan diagnosis (N = 46), the scan was normal in 65%. When essential/dystonic tremor was suspected (N = 14), the scan was normal in 79%. When psychogenic disorder was the prescan diagnosis (N = 15), the scan was normal in only 47%. Only 4% of patients with abnormal scan remained off anti-PD medications, whereas 24% of patients with negative scan were still on anti-PD medications. Conclusions DaT scan utilization among specialists varied greatly. Scan results correlated most when prescan diagnosis was ET than when working diagnosis was neurodegenerative parkinsonism or other non-neurodegenerative parkinsonism. Scan result was least consistent when prescan diagnosis was psychogenic disorder. Finally, DaT scans influenced medical treatment more when it was abnormal, compared to when it was normal.

Background Presence of dementia is a contraindication for DBS treatment of Parkinson's disease. Recent evidence suggests that borderline cognitive function, as measured with a common screening measure, the Mattis Dementia Rating Scale, has a negative impact on quality of life (QoL) after DBS of the STN. Methods We attempted to replicate and extend this finding in a larger group of patients with a wider range of preoperative global cognitive performance. Results Our data indicate that performance on the screening measure is not associated with QoL or medical outcomes, even with scores well below the cutoff for identifying dementia. Conclusions This cognitive screening measure lacks sufficient sensitivity to warrant its use in predicting which patients will show QoL benefit from DBS. © 2015 International Parkinson and Movement Disorder Society

Introduction Unlike dementia, the effect of mild cognitive impairment (MCI) on outcomes after deep brain stimulation (DBS) in Parkinson's disease (PD) is less clear. We aimed to examine the effect of MCI on short- and long-term DBS outcomes. Methods To study the effect of MCI type, cognitive domains (attention, language, visuospatial, memory, executive function), and Dementia Rating Scale (DRS) score on immediate postoperative outcomes (postoperative confusion, hospitalization days), PD patients who underwent DBS at our Center from 2006 to 2011 were analyzed. To determine cognitive predictors of intermediate (6-month) and long-term (1-year) post-operative outcomes, the changes in functional and quality-of-life (QOL) scores were analyzed in a smaller group with available preoperative health status measures. Results We identified 130 patients [71% male, mean age: 63 ± 9.1, mean PD duration: 10.7 ± 5.1]. At preoperative assessment, 60% of patients had multiple-domain MCI, 21% had single-domain MCI, and 19% had normal cognition. MCI presence and type as well as DRS performance did not affect immediate outcomes. Attention impairment predicted longer postoperative hospitalization (P = 0.0015) and showed a trend towards occurrence of postoperative confusion (P = 0.089). For intermediate and long-term outcomes we identified 56 patients [73.2% male, mean age: 61.3 ± 9.6, mean PD duration: 10.6 ± 4.7]. Visuospatial impairment showed a trend towards less improvement in 6-month functional score (P = 0.0652), and 1-year QOL score (P = 0.0517). Conclusion The presence of MCI did not affect DBS outcomes. However, the types of impaired domains were more detrimental. Detailed cognitive testing can help stratify low- and high-risk patients based on their pattern of cognitive dysfunction.

Objective:To report prospective repeated measures data detailing the perceived benefit of deep brain stimulation (DBS) on the most commonly cited symptom and activity goals identified by patients with Parkinson disease.Methods:Fifty-two participants were recruited from a consecutive series. Participants completed a semi-structured interview soliciting their symptom and behavioral goals and corresponding visual analog scales measuring perceived symptom severity and limits to goal attainment. Severity ratings were completed prior to and at 2 times following DBS. Changes in severity over time were assessed using a mixed effects linear model. The pattern of relationships between the severity ratings and standard clinical research (SCR) measures routinely administered were examined using Pearson correlations.Results:The most common symptom goals were improvements in tremor, gait, and nonmotor symptoms, whereas the most frequent behavioral goals related to interpersonal relationships, work, and avocational pursuits. Most severity ratings were significantly correlated with each other but not with the SCR measures. Significant improvements were evident on all SCR measures after DBS. Participants' severity ratings for their symptom and behavioral goals improved significantly over time although not all severity ratings changed in the same manner.Conclusions:These data illustrate that improvements in participants' individually defined goals were evident over time and that some of these improvements occurred in areas in which the benefits associated with DBS are not as well-documented. The participants' severity ratings were not redundant with SCR measures, suggesting that novel and potentially important information can be gleaned by systematically assessing patients' goals.

A sizable proportion of medication refractory tremor patients may not respond satisfactorily to deep brain stimulation (DBS) to the ventralis intermedialis nucleus of the thalamus (Vim). Implanting a second DBS lead ipsilaterally to the first one is thought to be beneficial based on scarce and unblinded data. This article aims to report a double-blind assessment of five patients with a second DBS lead for refractory tremor. Tremor was assessed by two blinded movement disorder specialists using a videotaped tremor rating scale (TRS) evaluation of each patient in four conditions: both leads OFF, Vim ON/2nd lead OFF, Vim OFF/2nd lead ON, and both leads ON. Paired t-test was used to determine if double stimulation was different than stimulation of Vim alone or than stimulation of the 2nd lead alone. Each hypothesis was tested with the total TRS as well as the contralateral upper limb score and the contralateral hemibody score. Tremor was secondary to multiple sclerosis in two patients and to essential tremor in three. The second lead was in the ventralis oralis anterior nucleus of the thalamus in three patients and in the prelemniscal radiations in two patients. There was improvement with the 2nd lead or double ON in four patients compared to stimulating the Vim alone. However, when taken as a group, the results were not statistically significant. These results were constant with the three different ratings used. The lack of overall statistically significant improvement might be secondary to the small size and the heterogeneity of our sample. However, four patients had 17 to 60 % tremor improvement after the implant of the 2nd lead on double-blinded evaluation. We report objective improvement after addition of a second DBS lead in patients with tremor refractory to Vim DBS. Larger studies are needed to confirm these results.

BACKGROUND The effectiveness of simulation-based training of critical care nurses in sterile techniques has not been determined. OBJECTIVE To evaluate the effectiveness of simulation-based training of critical care nurses to use sterile techniques during central vein catheterization and the effect of such training on infection rates. METHODS A prospective controlled study with 12-month observational follow-up to assess the rate of catheter-related bloodstream infections in a 23-bed medical, surgical, neurological critical care unit. RESULTS Forty-six critical care nurses completed assessment and training in sterile technique skills in the simulation laboratory. Performance scores at baseline were poor: median scores in each category ranging from 0 to 2 out of a maximum score of 4 and a median total score of 7 out of a maximum score of 24. After simulation-based training, nurses' median scores in each ST category and their total scores improved significantly, with the median total score increasing to 23 (P < .01; median difference, 15; 95% CI, 14-16). After completion of the simulation-based training intervention, the mean infection rate in the unit was reduced by 85% from 2.61 to 0.4 infections per 1000 catheter-days (P = .02). The incidence rate-ratio derived from the Poisson regression (0.15; 95% CI, 0.03-0.78) indicates an 85% reduction in the incidence of catheter-related bloodstream infections in the unit after the intervention. CONCLUSION Simulation-based training of critical care nurses in sterile technique is an important component in the strategy to reduce the occurrence of such infections and promote patient safety.

Background and importance Chorea acanthocytosis is a progressive hereditary neurodegenerative disorder characterized by hyperkinetic movements, seizures, and acanthocytosis in the absence of any lipid abnormality. Medical treatment is typically limited and disappointing. Clinical presentation We report on a 32-year-old patient with chorea acanthocytosis with a failed attempt at awake deep brain stimulation (DBS) surgery due to intraoperative seizures and postoperative intracranial hematoma. He then underwent a second DBS operation, but under general anesthesia and with intraoperative magnetic resonance imaging guidance. Marked improvement in his dystonia, chorea, and overall quality of life was noted 2 and 8 months postoperatively. Conclusion DBS surgery of the bilateral globus pallidus pars interna may be useful in controlling the hyperkinetic movements in neuroacanthocytosis. Because of the high propensity for seizures in this disorder, DBS performed under general anesthesia, with intraoperative magnetic resonance imaging guidance, may allow successful implantation while maintaining accurate target localization.

Drug-induced parkinsonism (DIP) is the second commonest cause of akinetic-rigid syndrome in the western world. Differentiating DIP from Parkinson's disease (PD) may be a challenge to clinicians. One of the factors distinguishing DIP from PD is that discontinuation of the neuroleptic agent in DIP should relieve the symptoms of parkinsonism. The majority of the literature uses the 6-month timeframe between the neuroleptic withdrawal and resolution of the symptoms of parkinsonism.We report two cases of DIP wherein the symptoms of parkinsonism persisted more than 6-months from withdrawal of the dopamine receptor blocking agent (DRBA) and the results of their ioflupane iodine-123 (DaT) single-photon emission computed tomography (SPECT) scan. DaT scan is a newly approved radiopharmaceutical in the United States indicated for striatal dopamine transporter visualization to assist in the evaluation of adult patients with suspected parkinsonian syndromes.The first case is a patient who developed parkinsonism from risperidone, while the second case developed parkinsonism from metoclopramide. In both cases, parkinsonism persisted 6 months after discontinuation of the DRBA, therefore DaT scan was obtained, showing normal striatal dopamine transporter uptake. Nine months after the discontinuation of the DRBA, parkinsonism was significantly improved in both patients but not completely resolved.Our two cases illustrate the possibility of persistent parkinsonism beyond 6-9 months from the time of neuroleptic withdrawal without evidence of presynaptic dopaminergic neuronal loss that would be suggestive of conversion to PD. We recommend that the official recommendation of the minimum time of neuroleptic withdrawal be modified to at least 1 year before entertaining the diagnosis of PD conversion in patients with exposure to DRBAs.

Background In deep brain stimulation (DBS) of the subthalamic nucleus for treatment of Parkinson's Disease, a commonly encountered stimulation side effect is involuntary muscle contractions from spread of electrical current to cortico-spinal and cortico-bulbar fibers in the internal capsule. During surgery, a variety of techniques, including microelectrode recording (MER), are used to avoid positioning the DBS electrode too close to the internal capsule. At some centers, MER includes stimulating through the microelectrode (microstimulation). Objective To assess if intraoperative microstimulation can help avoid positioning the DBS electrode too close to the internal capsule. Materials and Methods From clinical records, we compiled microelectrode and DBS-electrode locations, microstimulation effect thresholds and DBS side effect thresholds. Results We found that capsular macrostimulation thresholds were significantly lower in cases where capsular microstimulation effects were observed. In addition, we found that lower-threshold for microstimulation-induced involuntary muscle contractions from a given DBS electrode contact predicts a lower threshold for involuntary muscle contractions as a side effect of stimulation with that contact. Specifically, our results suggest that capsular macrostimulation thresholds below 2V are avoided when the product of microstimulation threshold (in µA) and distance (in mm) is greater than 500. Conclusions intraoperative microstimulation can help avoid positioning the DBS electrode too close to the internal capsule.

Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson’s disease (PD) and shows great promise for the treatment of several other disorders. However, while the clinical analysis of DBS has received great attention, a relative paucity of quantitative techniques exists to define the optimal surgical target and most effective stimulation protocol for a given disorder. In this study we describe a methodology that represents an evolutionary addition to the concept of a probabilistic brain atlas, which we call a probabilistic stimulation atlas (PSA). We outline steps to combine quantitative clinical outcome measures with advanced computational models of DBS to identify regions where stimulation-induced activation could provide the best therapeutic improvement on a per-symptom basis. While this methodology is relevant to any form of DBS, we present example results from subthalamic nucleus (STN) DBS for PD. We constructed patient-specific computer models of the volume of tissue activated (VTA) for 163 different stimulation parameter settings which were tested in six patients. We then assigned clinical outcome scores to each VTA and compiled all of the VTAs into a PSA to identify stimulation-induced activation targets that maximized therapeutic response with minimal side effects. The results suggest that selection of both electrode placement and clinical stimulation parameter settings could be tailored to the patient’s primary symptoms using patient-specific models and PSAs.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become the surgical therapy of choice for medically intractable Parkinson’s disease. However, quantitative understanding of the interaction between the electric field generated by DBS and the underlying neural tissue is limited. Recently, computational models of varying levels of complexity have been used to study the neural response to DBS. The goal of this study was to evaluate the quantitative impact of incrementally incorporating increasing levels of complexity into computer models of STN DBS. Our analysis focused on the direct activation of experimentally measureable fiber pathways within the internal capsule (IC). Our model system was customized to an STN DBS patient and stimulation thresholds for activation of IC axons were calculated with electric field models that ranged from an electrostatic, homogenous, isotropic model to one that explicitly incorporated the voltage-drop and capacitance of the electrode-electrolyte interface, tissue encapsulation of the electrode, and diffusion-tensor based 3D tissue anisotropy and inhomogeneity. The model predictions were compared to experimental IC activation defined from electromyographic (EMG) recordings from eight different muscle groups in the contralateral arm and leg of the STN DBS patient. Coupled evaluation of the model and experimental data showed that the most realistic predictions of axonal thresholds were achieved with the most detailed model. Furthermore, the more simplistic neurostimulation models substantially overestimated the spatial extent of neural activation.

Objective: Deep brain stimulation (DBS) surgeries commonly rely on brain atlases and microelectrode recordings (MER) to help identify the target location for electrode implantation. We present an automated method for optimally fitting a 3-dimensional brain atlas to intraoperative MER and predicting a target DBS electrode location in stereotactic coordinates for the patient. Methods: We retrospectively fit a 3-dimensional brain atlas to MER points from 10 DBS surgeries targeting the subthalamic nucleus (STN). We used a constrained optimization algorithm to maximize the MER points correctly fitted (i.e., contained) within the appropriate atlas nuclei. We compared our optimization approach to conventional anterior commissure-posterior commissure (AC/PC) scaling, and to manual fits performed by four experts. A theoretical DBS electrode target location in the dorsal STN was customized to each patient as part of the fitting process and compared to the location of the clinically defined therapeutic stimulation contact. Results: The human expert and computer optimization fits achieved significantly better fits than the AC/PC scaling (80, 81, and 41% of correctly fitted MER, respectively). However, the optimization fits were performed in less time than the expert fits and converged to a single solution for each patient, eliminating interexpert variance. Conclusions and Significance: DBS therapeutic outcomes are directly related to electrode implantation accuracy. Our automated fitting techniques may aid in the surgical decision-making process by optimally integrating brain atlas and intraoperative neurophysiological data to provide a visual guide for target identification.

In nine patients with essential tremor (14 thalami), the authors varied frequency, voltage, and pulsewidth of thalamic deep brain stimulation, and quantified postural tremor. Low frequency stimulation aggravated tremor; the effect increased with increasing voltage. High frequency stimulation had a U-shaped relation to voltage, with minimum tremor at an optimal voltage characteristic of the individual thalamus and increases in voltage beyond the optimum reduced tremor suppression. Based on the hypothesis that tremor response to deep brain stimulation resulted from two competing processes, the authors successfully modeled the relationship of tremor to voltage and frequency of stimulation using a mathematical model. The optimum voltage predicted by the model agreed with the empirically measured value. Moreover, the model made accurate predictions at high stimulation frequency based on measurements made at low stimulation frequency. Our results indicate there is an optimal voltage for tremor suppression by thalamic deep brain stimulation in most patients with essential tremor. The optimum varies across patients, and this is related to electrode position. A mathematical model based on “competing processes” successfully predicts optimum voltage in individual patients. This supports a competing processes model of deep brain stimulation effects.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) orglobus pallidus pars interna (GPi) is well established as a treatment for advanced Parkinson’s disease. In general, one of the 2 targets is chosen based on the clinical features of each patient. Stimulation of both targets could be viewed as redundant, given that the 2 targets are directly connected. However, it is possible that each target has different mechanisms, with clinical effects mediated by orthodromic or antidromic stimulation. The authors report the case of a patient with severe Parkinson’s disease who had previously undergone bilateral subthalamic stimulation with excellent benefits. However, he presented with significant worsening associated with disease progression and pharmacological treatment, and then underwent bilateral GPi DBS. Follow-up assessment was conducted clinically as well as through blinded ratings of video recordings. Pallidal DBS may be a safe and useful strategy to manage dystonic features and behavioral complications of subthalamic stimulation and pharmacological management. While combined stimulation was quite successful in the reported patient, further studies with larger samples and longer follow-up periods will be necessary before recommending the addition of pallidal DBS as a routine strategy for patients previously implanted with STN DBS.