Subthalamic deep brain stimulation improves smooth pursuit and saccade performance in patients with Parkinson’s disease

© 2013 The Authors. Published by BMC. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1186/1743-0003-10-33Deep brain stimulation (DBS) in the subthalamic nucleus (STN) significantly reduces symptoms of Parkinson’s disease (PD) such as bradykinesia, tremor and rigidity. It also reduces the need for anti-PD medication, and thereby potential side-effects of L-Dopa. Although DBS in the STN is a highly effective therapeutic intervention in PD, its mechanism and effects on oculomotor eye movement control and particularly smooth pursuit eye movements have to date rarely been investigated. Furthermore, previous reports provide conflicting information. The aim was to investigate how DBS in STN affected oculomotor performance in persons with PD using novel analysis techniques. Methods Twenty-five patients were eligible (22 males, 3 females) according to the clinical inclusion criteria: idiopathic PD responsive to L-Dopa and having had bilateral STN stimulation for at least one year to ensure stable DBS treatment. Fifteen patients were excluded due to the strict inclusion criteria applied to avoid interacting and confounding factors when determining the effects of DBS applied alone without PD medication. One patient declined participation. Nine PD patients (median age 63, range 59–69 years) were assessed after having their PD medications withdrawn overnight. They were examined with DBS ON and OFF, with the ON/OFF order individually randomized. Results DBS ON increased smooth pursuit velocity accuracy (p < 0.001) and smooth pursuit gain (p = 0.005), especially for faster smooth pursuits (p = 0.034). DBS ON generally increased saccade amplitude accuracy (p = 0.007) and tended to increase peak saccade velocity also (p = 0.087), specifically both saccade velocity and amplitude accuracy for the 20 and 40 degree saccades (p < 0.05). Smooth pursuit latency tended to be longer (p = 0.090) approaching normal with DBS ON. Saccade latency was unaffected. Conclusions STN stimulation from DBS alone significantly improved both smooth pursuit and saccade performance in patients with PD. The STN stimulation enhancement found for oculomotor performance suggests clear positive implications for patients’ ability to perform tasks that rely on visual motor control and visual feedback. The new oculomotor analysis methods provide a sensitive vehicle to detect subtle pathological modifications from PD and the functional enhancements produced by STN stimulation from DBS alone.The authors’ wish to acknowledge the financial supported from the Swedish Medical Research Council (grant nr. 17x-05693), the Medical Faculty, Lund University, Sweden, and the Swedish Parkinson Academy. This study was performed within the Strategic Research Area Multipark at Lund University and within the context of the Centre for Ageing and Supportive environments (CASE), Lund University, Sweden, funded by the Swedish Council for Working Life and Social Research.Published versio

Applications of neuromodulation to explore vestibular cortical processing; new insights into the effects of direct current cortical modulation upon pursuit, VOR and VOR suppression

This is an accepted manuscript of an article published by IOS Press in Journal of Vestibular Research in 2014, available online: https://doi.org/10.3233/VES-140530 The accepted version of the publication may differ from the final published version.Functional imaging, lesion studies and behavioural observations suggest that vestibular processing is lateralised to the non-dominant hemisphere. Moreover, disruption of interhemispheric balance via inhibition of left parietal cortex using transcranial direct current stimulation (tDCS) has been associated with an asymmetric suppression of the vestibulo-ocular reflex (VOR). However, the mechanism by which the VOR was modulated remains unknown. In this paper we review the literature on non-invasive brain stimulation techniques which have been used to probe vestibular function over the last decade. In addition, we investigate the mechanisms whereby tDCS may modulate VOR, e.g. by acting upon pursuit, VOR suppression mechanisms or direct VOR modulation. We applied bi-hemispheric parietal tDCS in 11 healthy subjects and only observed significant effects on VOR gain (tdcs * condition p=0.041) – namely a trend for VOR gain increase with right anodal/left cathodal stimulation, and a decrease with right cathodal/left anodal stimulation. Hence, we suggest that the modulation of the VOR observed both here and in previous reports, is directly caused by top-down cortical control of the VOR as a result of disruption to interhemispheric balance, likely parietal.This work was funded by the UK Medical Research Council (MR/J004685/1).Published versio

Deep brain stimulation in the subthalamic nuclei alters postural alignment and adaptation in Parkinson’s disease

© 2021 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0259862Parkinson’s disease (PD) can produce postural abnormalities of the standing body position such as kyphosis. We investigated the effects of PD, deep brain stimulation (DBS) in the subthalamic nucleus (STN), vision and adaptation on body position in a well-defined group of patients with PD in quiet standing and during balance perturbations. Ten patients with PD and 25 young and 17 old control participants were recruited. Body position was measured with 3D motion tracking of the ankle, knee, hip, shoulder and head. By taking the ankle as reference, we mapped the position of the joints during quiet standing and balance perturbations through repeated calf muscle vibration. We did this to explore the effect of PD, DBS in the STN, and vision on the motor learning process of adaptation in response to the repeated stimulus. We found that patients with PD adopt a different body position with DBS ON vs. DBS OFF, to young and old controls, and with eyes open vs. eyes closed. There was an altered body position in PD with greater flexion of the head, shoulder and knee (p≤0.042) and a posterior position of the hip with DBS OFF (p≤0.014). With DBS ON, body position was brought more in line with the position taken by control participants but there was still evidence of greater flexion at the head, shoulder and knee. The amplitude of movement during the vibration period decreased in controls at all measured sites with eyes open and closed (except at the head in old controls with eyes open) showing adaptation which contrasted the weaker adaptive responses in patients with PD. Our findings suggest that alterations of posture and greater forward leaning with repeated calf vibration, are independent from reduced movement amplitude changes. DBS in the STN can significantly improve body position in PD although the effects are not completely reversed. Patients with PD maintain adaptive capabilities by leaning further forward and reducing movement amplitude despite their kyphotic posture.Published onlin

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

This is an accepted manuscript of an article published by Elsevier in Gait and Posture, available online: https://doi.org/10.1016/j.gaitpost.2021.03.023 The accepted version of the publication may differ from the final published version.Background The characteristics of Parkinson’s disease (PD) include postural instability and resting tremor. However, reductions of tremor amplitude do not always improve postural stability. Research question What 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. Methods Ten 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. Results DBS 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. Significance There 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.Published versio

Strategic alterations of posture are delayed in Parkinson’s disease patients during deep brain stimulation

© 2021 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/s41598-021-02813-yParkinson’s disease (PD) is characterized by rigidity, akinesia, postural instability and tremor. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor but the effects on postural instability are inconsistent. Another component of postural control is the postural strategy, traditionally referred to as the ankle or hip strategy, which is determined by the coupling between the joint motions of the body. We aimed to determine whether DBS STN and vision (eyes open vs. eyes closed) affect the postural strategy in PD in quiet stance or during balance perturbations. Linear motion was recorded from the knee, hip, shoulder and head in 10 patients with idiopathic PD with DBS STN (after withdrawal of other anti-PD medication), 25 younger adult controls and 17 older adult controls. Correlation analyses were performed on anterior–posterior linear motion data to determine the coupling between the four positions measured. All participants were asked to stand for a 30 s period of quiet stance and a 200 s period of calf vibration. The 200 s vibration period was subdivided into four 50 s periods to study adaptation between the first vibration period (30–80 s) and the last vibration period (180–230 s). Movement was recorded in patients with PD with DBS ON and DBS OFF, and all participants were investigated with eyes closed and eyes open. DBS settings were randomized and double-blindly programmed. Patients with PD had greater coupling of the body compared to old and young controls during balance perturbations (p ≤ 0.046). Controls adopted a strategy with greater flexibility, particularly using the knee as a point of pivot, whereas patients with PD adopted an ankle strategy, i.e., they used the ankle as the point of pivot. There was higher flexibility in patients with PD with DBS ON and eyes open compared to DBS OFF and eyes closed (p ≤ 0.011). During balance perturbations, controls quickly adopted a new strategy that they retained throughout the test, but patients with PD were slower to adapt. Patients with PD further increased the coupling between segmental movement during balance perturbations with DBS ON but retained a high level of coupling with DBS OFF throughout balance perturbations. The ankle strategy during balance perturbations in patients with PD was most evident with DBS OFF and eyes closed. The increased coupling with balance perturbations implies a mechanism to reduce complexity at a cost of exerting more energy. Strategic alterations of posture were altered by DBS in patients with PD and were delayed. Our findings therefore show that DBS does not fully compensate for disease-related effects on posture.The authors’ wish to acknowledge the financial supported from the Swedish Medical Research Council (grant nr. 17x-05693).Published versio

Effects of deep brain stimulation on postural control in Parkinson's disease

This is an accepted manuscript of an article published by Elsevier in Computers in Biology and Medicine on 29/05/2020, available online: https://doi.org/10.1016/j.compbiomed.2020.103828 The accepted version of the publication may differ from the final published version.The standard approach to the evaluation of tremor and stability control in medical practice is subjective scoring. The objective of this study was to show that signal processing of physiological data, that are known to be altered by tremor and other cardinal symptoms in Parkinson's disease (PD), can quantify the postural dynamics of this disease and the effects of DBS technology. We measured postural control and its capacity to adapt to balance perturbations with a force platform and perturbed balance by altering visual feedback and using pseudo-random binary sequence perturbations (PRBS) of different durations. Our signal processing involved converting the postural control data into spectral power with Fast-Fourier Transformation across a wide bandwidth and then subdividing this into three bands (0–4 Hz, 4–7 Hz and 7–25 Hz). We quantified the amount of power in each bandwidth. From 25 eligible participants, 10 PD participants (9 males, mean age 63.8 years) fulfilled the inclusion criteria; idiopathic PD responsive to l-Dopa; >1 year use of bilateral STN stimulation. Seventeen controls (9 males, mean age 71.2 years) were studied for comparison. Participants with PD were assessed after overnight withdrawal of anti-PD medications. Postural control was measured with a force platform during quiet stance (35 s) and during PRBS calf muscle vibration that perturbed stance (200 s). Tests were performed with eyes open and eyes closed and with DBS ON and DBS OFF. The balance perturbation period was divided into five sequential 35-s periods to assess the subject's ability to address postural imbalance using adaptation. The signal processing analyses revealed that activating the DBS device did not significantly change the dynamics of postural control in the 0–4 Hz spectral power but the device reduced the use of spectral power >4 Hz; a finding that was present in both anteroposterior and lateral directions, during vibration, and more so in eyes open tests. Visual feedback, which usually improves postural stability, was less effective in participants with PD with DBS OFF across all postural sway frequencies during quiet stance and during balance perturbations. The expected adaptation of postural control was found in healthy participants between the first and last balance perturbation period. However, adaptation was almost abolished across all spectral frequencies in both the anteroposterior and lateral directions, with both eyes open and eyes closed and DBS ON and OFF in participants with PD. To conclude, this study revealed that the DBS technology altered the spectral frequency dynamics of postural control in participants through a reduction of the power used >4 Hz. Moreover, the DBS device tended to increase the stabilizing effect of vision across all spectral bands. However, the signal processing analyses also revealed that DBS was not able to restore the adaptive motor control abilities in PD

Association of the 2011 ACGME Resident Duty Hour Reforms with Mortality and Readmissions among Hospitalized Medicare Patients

Importance Patient outcomes associated with the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour reforms have not been evaluated at a national level. Objective To evaluate the association of the 2011 ACGME duty hour reforms with mortality and readmissions. Design, Setting, and Participants Observational study of Medicare patient admissions (6 384 273 admissions from 2 790 356 patients) to short-term, acute care, nonfederal hospitals (n = 3104) with principal medical diagnoses of acute myocardial infarction, stroke, gastrointestinal bleeding, or congestive heart failure or a Diagnosis Related Group classification of general, orthopedic, or vascular surgery. Of the hospitals, 96 (3.1%) were very major teaching, 138 (4.4%) major teaching, 442 (14.2%) minor teaching, 443 (14.3%) very minor teaching, and 1985 (64.0%) nonteaching. Exposure Resident-to-bed ratio as a continuous measure of hospital teaching intensity. Main Outcomes and Measures Change in 30-day all-location mortality and 30-day all-cause readmission, comparing patients in more intensive relative to less intensive teaching hospitals before (July 1, 2009–June 30, 2011) and after (July 1, 2011–June 30, 2012) duty hour reforms, adjusting for patient comorbidities, time trends, and hospital site. Results In the 2 years before duty hour reforms, there were 4 325 854 admissions with 288 422 deaths and 602 380 readmissions. In the first year after the reforms, accounting for teaching hospital intensity, there were 2 058 419 admissions with 133 547 deaths and 272 938 readmissions. There were no significant postreform differences in mortality accounting for teaching hospital intensity for combined medical conditions (odds ratio [OR], 1.00; 95% CI, 0.96-1.03), combined surgical categories (OR, 0.99; 95% CI, 0.94-1.04), or any of the individual medical conditions or surgical categories. There were no significant postreform differences in readmissions for combined medical conditions (OR, 1.00; 95% CI, 0.97-1.02) or combined surgical categories (OR, 1.00; 95% CI, 0.98-1.03). For the medical condition of stroke, there were higher odds of readmissions in the postreform period (OR, 1.06; 95% CI, 1.001-1.13). However, this finding was not supported by sensitivity analyses and there were no significant postreform differences for readmissions for any other individual medical condition or surgical category. Conclusions and Relevance Among Medicare beneficiaries, there were no significant differences in the change in 30-day mortality rates or 30-day all-cause readmission rates for those hospitalized in more intensive relative to less intensive teaching hospitals in the year after implementation of the 2011 ACGME duty hour reforms compared with those hospitalized in the 2 years before implementation

A review of standard pharmacological therapy for adult asthma - Steps 1 to 5

The aim of pharmacological therapy for asthma is to improve symptoms and lung function and minimise the risk of asthma attacks. The intensity of treatment is based on the level of asthma control and the potential risk of future deterioration. In the British asthma guidelines, treatments are divided into Step One to Five, with each Step signifying a need for an increase in therapy in response to symptoms or to prevent exacerbations. Treatments comprise of inhaled or systemic medications. Inhaled therapy includes short-acting and long-acting medication to improve symptoms and inhaled corticosteroids which reduce airway inflammation. Systemic treatments include medications which act on specific biological pathways, such as the leukotriene or IgE pathways, or systemic corticosteroids. In choosing a particular therapy, treatment benefits are balanced by the potential risks of medication-related adverse effects. This review will provide a practical guide to the key pharmacological therapies for adult asthma at Steps One to Five based on British guidelines and consider future options for new treatments