Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical ...fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.
High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.
All patients responded well to treatment (46% mean improvement off medication UPDRS-III p < 0.0001) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = −10(−9.5), Y = −13(-1) and Z = −7(−3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.
These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.
•Optimal DBS tissue activation areas are identified in the subthalamic nucleus.•Stimulation in the supero-lateral subthalamic nucleus is most effective.•Connectivity pattern predicts improvement in cardinal symptoms in Parkinson's.
Available data suggest that there may be gender differences in the effect of STN-DBS in the treatment of Parkinson's disease (PD). The aim of this study was to review data on gender discrepancies and ...gender differences in clinical outcomes in PD patients treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). Included were original studies that specifically examined gender discrepancies or gender differences in PD patients with STN-DBS. Men receive more DBS than women, for various indications. The decision-making process for DBS in women compared to men is more influenced by personal preferences and external factors. Motor symptoms improve in both genders, but bradykinesia improves more in men. The postoperative reduction of the levodopa equivalent daily dose seems to be more pronounced in men. Men show more cognitive deterioration and less improvement than women after STN-DBS. Women show more depressive symptoms before surgery, but they improve similarly to men. Men show more improvement in impulsivity and less decrease in impulsive behaviour symptoms than women. Anxiety and personality traits remain unchanged in both genders. Voice quality improves more in men and deteriorates less often than in women. Men gain fat-free mass and fat mass, but women only gain fat mass. Regarding sexual function the evidence is inconsistent. More urinary symptoms improve in women than in men. Pain and restless leg syndrome seems to improve more in men. Regarding quality of life, the evidence seems to be inconsistent, and activities of daily living seems to improve in both genders. Better prospective controlled studies, focusing directly on gender differences in PD patients treated with STN-DBS, are needed to better explain gender differences in STN-DBS for PD.
The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease ...(PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.
•The thalamic target for surgery for tremor is not readily visible on conventional MRI.•Probabilistic tractography is used to segment the thalamus based on connectivity.•The best target area is connected to the contralateral dentate cerebellar nucleus.•GPU processing is used to segment the thalamus in a clinically feasible timescale.•This technique can map out the DRT tract with clear mesencephalic crossing.
Objective
The objectives of this study were to explore the changes in the activities of daily living (ADL) in persons with Parkinson's disease (pwPD) over time and to investigate possible differences ...in ADL performance between men and women with PD.
Materials & Methods
One hundred twenty‐nine persons (76 men) with a clinically established PD self‐assessed their ADL performance from the time of diagnosis up to 8 years follow‐up using the ADL taxonomy. Other demographic and clinical data (motor state, cognition, depression) were also collected and subjected to further analysis.
Results
Nine of 12 domains in the ADL taxonomy showed a change over time (Eating and Drinking P = .009, Mobility P < .001, Toilet activities P = .031, Dressing P < .001, Personal hygiene P < .001, Communication P < .001, Cooking P = .001, Shopping P < .001 and Cleaning P < .001). In addition to time, two domains, (Shopping P = .007 and Cleaning P = .027) also showed an effect of gender with worse scores in women. The nine ADL domains showing effect of time, showed temporary improvement at 12 months follow‐up, most probably due to dopaminergic medication. All nine domains deteriorated at later follow‐up.
Conclusions
As expected, there was deterioration in self‐assessed performance in the majority od ADL domains over time. Women assessed their ADLs worse in two domains (Shopping and Cleaning) probably reflecting a general gender‐related activity pattern rather than being a PD‐specific finding.
Habits are defined as automatic behaviours triggered by cues and performed without awareness. They are difficult to control and mentally efficient, which contrasts with goal-directed behaviour, which ...is characterised by active thought, high computational effort, and the ability to modify this behaviour in response to a changing environment and contextual demands. Habits are not only defined by the frequency with which a behaviour is performed but represent a complex construct that also includes the strength and automaticity of the habitual behaviour. We report here the development and validation of a Daily Habit Scale (DHS) to assess the frequency, automaticity, and strength of daily habits in healthy individuals. Item reduction based on factor analysis resulted in a scale with 38 items grouped into eight factors explaining 52.91% of the variance. The DHS showed very good internal consistency (
Cronbach alpha
= 0.738) and test-retest reliability (
Intraclass correlation coefficient
= 0.892,
p
<0.001) as well as convergent and divergent reliability compared to other scales measuring habits. We found a significant effect of age, gender, anxiety, and depression on the DHS. Considering certain limitations of the DHS, such as not considering the context of performance of habits, and the absence of certain items, such as transportation use, the results of this study suggest that DHS is a reliable and valid measure of daily habits that can be used by both clinicians and researchers as a measure of daily habits.
Background Parkinson’s disease is associated with increased impulsivity, which can be divided into several domains: motor (consisting of proactive and reactive subdomains), reflection, and cognitive ...impulsivity. Evidence suggests that both dopaminergic medication and subthalamic nucleus deep brain stimulation can affect impulsivity. Therefore, we set out to investigate the effects of dopaminergic medication and subthalamic nucleus deep brain stimulation on motor, reflection, and cognitive impulsivity in Parkinson’s disease patients. Methods Twenty Parkinson’s disease patients who underwent subthalamic nucleus deep brain stimulation were tested ON and OFF dopaminergic medication and ON and OFF subthalamic nucleus deep brain stimulation. They performed three different impulsivity tasks: the AX continuous performance task (AX-CPT) to test for motor impulsivity, the Beads task for reflection impulsivity, and the Delay discounting task for cognitive impulsivity. Results The combination of subthalamic nucleus deep brain stimulation and dopaminergic medication led to an increase in motor impulsivity ( p = 0.036), both proactive ( p = 0.045) and reactive ( p = 0.006). There was no effect of either dopaminergic medication or subthalamic nucleus deep brain stimulation on reflection and cognitive impulsivity. Conclusion The combination of dopaminergic medication and subthalamic nucleus deep brain stimulation leads to increased motor, but not cognitive or reflection, impulsivity in patients with Parkinson’s disease. Both proactive and reactive motor impulsivity were impaired by the combination of dopaminergic medication and subthalamic nucleus deep brain stimulation.
Inflammation and oxidative stress are recognized as important contributors to Parkinson's disease pathogenesis. As such, genetic variability in these pathways could have a role in susceptibility for ...the disease as well as in the treatment outcome. Dopaminergic treatment is effective in management of motor symptoms, but poses a risk for motor and non-motor adverse events. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in genes involved in inflammation and oxidative stress on Parkinson's disease susceptibility and the occurrence of adverse events of dopaminergic treatment.
In total, 224 patients were enrolled, and their demographic and clinical data on the disease course were collected. Furthermore, a control group of 146 healthy Slovenian blood donors were included for Parkinson's disease' risk evaluation. Peripheral blood was obtained for DNA isolation. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1β rs16944, IL1β rs1143623, IL6 rs1800795, CAT rs1001179, CAT rs10836235, SOD2 rs4880, NOS1 rs2293054, NOS1 rs2682826, TNF-α rs1800629, and GPX1 rs1050450. Logistic regression was used for analysis of possible associations.
We observed a nominally significant association of the IL1β rs1143623 C allele with the risk for Parkinson's disease (OR = 0.59; 95%CI = 0.38-0.92, p = 0.021). CAT rs1001179 A allele was significantly associated with peripheral edema (OR = 0.32; 95%CI = 0.15-0.68; p = 0.003). Other associations observed were only nominally significant after adjustments: NOS1 rs2682826 A allele and excessive daytime sleepiness and sleep attacks (OR = 1.75; 95%CI = 1.00-3.06, p = 0.048), SOD2 rs4880 T allele and nausea/vomiting (OR = 0.49, 95%CI = 0.25-0.94; p = 0.031), IL1β rs1143623 C allele and orthostatic hypotension (OR = 0.57, 95%CI = 0.32-1.00, p = 0.050), and NOS1 rs2682826 A allele and impulse control disorders (OR = 2.59; 95%CI = 1.09-6.19; p = 0.032). We did not find any associations between selected polymorphisms and motor adverse events.
Apart from some nominally significant associations, one significant association between CAT genetic variability and peripheral edema was observed as well. Therefore, the results of our study suggest some links between genetic variability in inflammation- and oxidative stress-related pathways and non-motor adverse events of dopaminergic treatment. However, the investigated polymorphisms do not play a major role in the occurrence of the disease and the adverse events of dopaminergic treatment.
Dopaminergic pathway is the most disrupted pathway in the pathogenesis of Parkinson's disease. Several studies reported associations of dopaminergic genes with the occurrence of adverse events of ...dopaminergic treatment. However, none of these studies adopted a pathway based approach. The aim of this study was to comprehensively evaluate the influence of selected single nucleotide polymorphisms of key dopaminergic pathway genes on the occurrence of motor and non-motor adverse events of dopaminergic treatment in Parkinson's disease. In total, 231 Parkinson's disease patients were enrolled. Demographic and clinical data were collected. Genotyping was performed for 16 single nucleotide polymorphisms from key dopaminergic pathway genes. Logistic and Cox regression analyses were used for evaluation. Results were adjusted for significant clinical data. We observed that carriers of at least one
rs165815 C allele had lower odds for developing visual hallucinations (OR = 0.34; 95% CI = 0.16-0.72;
= 0.004), while carriers of at least one
rs6280 C allele and CC homozygotes had higher odds for this adverse event (OR = 1.88; 95% CI = 1.00-3.54;
= 0.049 and OR = 3.31; 95% CI = 1.37-8.03;
= 0.008, respectively). Carriers of at least one
rs921451 C allele and CT heterozygotes had higher odds for orthostatic hypotension (OR = 1.86; 95% CI = 1.07-3.23;
= 0.028 and OR = 2.30; 95% CI = 1.26-4.20;
= 0.007, respectively). Heterozygotes for
rs3837091 and
rs628031 AA carriers also had higher odds for orthostatic hypotension (OR = 1.94; 95% CI = 1.07-3.51;
= 0.028 and OR = 2.57; 95% CI = 1.11-5.95;
= 0.028, respectively). Carriers of the
rs628031 AA genotype had higher odds for peripheral edema and impulse control disorders (OR = 4.00; 95% CI = 1.62-9.88;
= 0.003 and OR = 3.16; 95% CI = 1.03-9.72;
= 0.045, respectively). Finally, heterozygotes for
rs628031 and carriers of at least one
rs628031 A allele had lower odds for dyskinesia (OR = 0.48; 95% CI = 0.24-0.98,
= 0.043 and OR = 0.48; 95% CI = 0.25-0.92;
= 0.027, respectively). Gene-gene interactions, more specifically
, and
, also significantly influenced the occurrence of some adverse events. Additionally, haplotypes of
and
were associated with the occurrence of visual hallucinations (AT vs. GC: OR = 0.34; 95% CI = 0.16-0.72;
= 0.005) and orthostatic hypotension (ATG vs. ACG: OR = 2.48; 95% CI: 1.01-6.07;
= 0.047), respectively. Pathway based approach allowed us to identify new potential candidates for predictive biomarkers of adverse events of dopaminergic treatment in Parkinson's disease, which could contribute to treatment personalization.
Muscle vibration activates muscle spindles and when applied over posterior neck muscles during stance modulates global body orientation. This is characterised by a tonic forward sway response that is ...reportedly diminished or absent in patients with idiopathic cervical dystonia.
To investigating the impact of the sensory trick on vibration-induced postural responses.
20 patients with idiopathic cervical dystonia and a sensory trick, 15 patients without a trick, and 16 healthy controls were recruited. Neck muscle vibration was applied bilaterally over the upper trapezius under three different conditions: 1) Quiet standing; 2) standing while performing the trick (or trick-like movement in non-responders); 3) standing while elevating the flexed arm without touching any part of the body. Centre of pressure position and whole-body orientation in the sagittal plane were analysed.
Patients with a sensory trick responded similarly to healthy controls: neck muscle vibration led to an initial forward sway of the body that slowly increased during the prolonged vibration for all three conditions. This response was mainly mediated by ankle flexion. In patients without a trick, the initial sagittal sway was significantly reduced in all three conditions and the later slow increase was absent. Performance of the trick did not have an effect on any aspect of the response in either cervical dystonia group.
The whole-body response to neck vibration in cervical dystonia differs depending on the effectiveness of the sensory trick to alleviate the dystonic neck posture. Variable pathophysiology of proprioceptive processing may be the common factor.
•Vibration-induced sways were comparable in CD patients with a trick and controls.•The sways were smaller in CD patients with no tricks than in those with a trick.•Focal and global postural responses were diminished in CD patients with no tricks.•The trick itself did not modulate the sways thus suggesting additional mechanisms.
Device-aided therapies (DAT), such as continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of the subthalamic nucleus ...(STN-DBS), have markedly changed the treatment landscape of advanced Parkinson's disease (aPD). In some patients, it is necessary to switch or combine DATs for various reasons. The aim of this retrospective study was to explore the frequency and reasons for switching between or combining DATs in two movement disorders centres in Slovenia and Israel.
We collected and analysed demographic and clinical data from aPD patients who switched between or combined DATs. Motor and non-motor reasons, adverse events for switching/combining, and their frequency were examined, as was the effect of DAT using the Global Improvement subscale of the Clinical Global Impression Scale, Movement Disorders Society Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination, and Parkinson's Disease Questionnaire 39. Descriptive statistics and non-parametric tests were used to analyse the data.
Of 505 aPD patients treated with DATs at both centres between January 2009 and June 2021, we identified in a total of 30 patients (6%) who either switched DAT (
= 24: 7
, 1
, 5
, 8
, 1
, 1
, and 1
) or combined DATs (
= 6:5
and 1
). In most of these patients, an inadequate control of motor symptoms was the main reason for switching or combining DATs, but non-motor reasons (related to the disease and/or DAT) were also identified.
Switching between and combining DATs is uncommon, but in some patients brings substantial clinical improvement and should be considered in those who have either inadequate symptom control on DAT treatment or have developed DAT-related complications.
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