Browsing by Subject "Parkinson Disease"
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Item Open Access Coronal plane spinal malalignment and Parkinson's disease: prevalence and associations with disease severity.(The spine journal : official journal of the North American Spine Society, 2015-01) Choi, Hong June; Smith, Justin S; Shaffrey, Christopher I; Lafage, Virginie C; Schwab, Frank J; Ames, Christopher P; Matsumoto, Morio; Baik, Jong Sam; Ha, YoonBackground context
Parkinson's disease (PD) is a progressive degenerative disorder of the central nervous system. Patients with PD often present with abnormal posturing.Purpose
To investigate coronal plane deformities in patients with PD, and to evaluate the correlation between clinical features, coronal parameters related to spine alignment, and disease severity.Study design
A cross-sectional study.Patient sample
Eighty-nine patients with PD and 89 controls were included.Outcome measures
A medical history was collected from the medical records.Methods
This study was a prospective assessment of consecutive patients with PD. Clinical and demographic parameters were collected from medical records and outpatient interviews. Full-length standing anteroposterior and lateral spine radiographs were used to assess the spinal parameters. The threshold for scoliosis was set at a 10° Cobb angle, and the curve type was classified using Schwab classification.Results
A total of 178 patients (89 in PD and 89 in control groups) were included. Scoliosis was identified in 27 patients (30%) and 22 controls (p=.502). However, coronal imbalance was more common in patients with PD than in controls (11 vs. 0 patients, p=.001). Scoliosis was more common in women than in men (male:female=8:19, p=.04). Back pain was more common in patients with scoliosis than in those without scoliosis (14 of 27 vs. 17 of 62, p=.036). Schwab Type IV (thoracolumbar major) was the most common type of scoliosis in patients with PD and Type V (lumbar major) was the most common type in controls. With adjustment for patient age and gender, multiple linear regression analysis revealed that severity of PD (Unified Parkinson's Disease Rating Scale, p=.037) and magnitude of global coronal malalignment (p=.003) were associated with the scoliosis Cobb angle (p=.037, B=0.139). Direction of scoliosis and side of global coronal malalignment were not significantly correlated with the laterality of predominant PD symptoms (p>.05).Conclusions
Global coronal malalignment is more prevalent in patients with PD than in controls. Greater severity of PD was significantly associated with greater magnitude of scoliosis Cobb angle, even after adjusting for the effects of patient age and gender. However, direction of scoliosis and side of global coronal malalignment were not significantly associated with the dominant laterality of PD symptoms.Item Open Access Dissecting the Domains of Parkinson's Disease: Insights from Longitudinal Item Response Theory Modeling.(Movement disorders : official journal of the Movement Disorder Society, 2022-09) Luo, Sheng; Zou, Haotian; Stebbins, Glenn T; Schwarzschild, Michael A; Macklin, Eric A; Chan, James; Oakes, David; Simuni, Tanya; Goetz, Christopher G; Parkinson Study Group SURE-PD3 InvestigatorsBackground
Longitudinal item response theory (IRT) models previously suggested that the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor examination has two salient domains, tremor and nontremor, that progress in time and in response to treatment differently.Objective
Apply longitudinal IRT modeling, separating tremor and nontremor domains, to reanalyze outcomes in the previously published clinical trial (Study of Urate Elevation in Parkinson's Disease, Phase 3) that showed no overall treatment effects.Methods
We applied unidimensional and multidimensional longitudinal IRT models to MDS-UPDRS motor examination items in 298 participants with Parkinson's disease from the Study of Urate Elevation in Parkinson's Disease, Phase 3 (placebo vs. inosine) study. We separated 10 tremor items from 23 nontremor items and used Bayesian inference to estimate progression rates and sensitivity to treatment in overall motor severity and tremor and nontremor domains.Results
The progression rate was faster in the tremor domain than the nontremor domain before levodopa treatment. Inosine treatment had no effect on either domain relative to placebo. Levodopa treatment was associated with greater slowing of progression in the tremor domain than the nontremor domain regardless of inosine exposure. Linear patterns of progression were observed. Despite different domain-specific progression patterns, tremor and nontremor severities at baseline and over time were significantly correlated.Conclusions
Longitudinal IRT analysis is a novel statistical method addressing limitations of traditional linear regression approaches. It is particularly useful because it can simultaneously monitor changes in different, but related, domains over time and in response to treatment interventions. We suggest that in neurological diseases with distinct impairment domains, clinical or anatomical, this application may identify patterns of change unappreciated by standard statistical methods. © 2022 International Parkinson and Movement Disorder Society.Item Open Access Electrical stimulation of the dorsal columns of the spinal cord for Parkinson's disease.(Movement disorders : official journal of the Movement Disorder Society, 2017-06) Yadav, Amol P; Nicolelis, Miguel ALSpinal cord stimulation has been used for the treatment of chronic pain for decades. In 2009, our laboratory proposed, based on studies in rodents, that electrical stimulation of the dorsal columns of the spinal cord could become an effective treatment for motor symptoms associated with Parkinson's disease (PD). Since our initial report in rodents and a more recent study in primates, several clinical studies have now described beneficial effects of dorsal column stimulation in parkinsonian patients. In primates, we have shown that dorsal column stimulation activates multiple structures along the somatosensory pathway and desynchronizes the pathological cortico-striatal oscillations responsible for the manifestation of PD symptoms. Based on recent evidence, we argue that neurological disorders such as PD can be broadly classified as diseases emerging from abnormal neuronal timing, leading to pathological brain states, and that the spinal cord could be used as a "channel" to transmit therapeutic electrical signals to disrupt these abnormalities. © 2017 International Parkinson and Movement Disorder Society.Item Open Access Guidance for switching from off-label antipsychotics to pimavanserin for Parkinson's disease psychosis: an expert consensus.(CNS spectrums, 2018-12) Black, Kevin J; Nasrallah, Henry; Isaacson, Stuart; Stacy, Mark; Pahwa, Rajesh; Adler, Charles H; Alva, Gustavo; Cooney, Jeffrey W; Kremens, Daniel; Menza, Matthew A; Meyer, Jonathan M; Patkar, Ashwin A; Simuni, Tanya; Morrissette, Debbi A; Stahl, Stephen MPatients with Parkinson's disease psychosis (PDP) are often treated with an atypical antipsychotic, especially quetiapine or clozapine, but side effects, lack of sufficient efficacy, or both may motivate a switch to pimavanserin, the first medication approved for management of PDP. How best to implement a switch to pimavanserin has not been clear, as there are no controlled trials or case series in the literature to provide guidance. An abrupt switch may interrupt partially effective treatment or potentially trigger rebound effects from antipsychotic withdrawal, whereas cross-taper involves potential drug interactions. A panel of experts drew from published data, their experience treating PDP, lessons from switching antipsychotic drugs in other populations, and the pharmacology of the relevant drugs, to establish consensus recommendations. The panel concluded that patients with PDP can be safely and effectively switched from atypical antipsychotics used off label in PDP to the recently approved pimavanserin by considering each agent's pharmacokinetics and pharmacodynamics, receptor interactions, and the clinical reason for switching (efficacy or adverse events). Final recommendations are that such a switch should aim to maintain adequate 5-HT2A antagonism during the switch, thus providing a stable transition so that efficacy is maintained. Specifically, the consensus recommendation is to add pimavanserin at the full recommended daily dose (34 mg) for 2-6 weeks in most patients before beginning to taper and discontinue quetiapine or clozapine over several days to weeks. Further details are provided for this recommendation, as well as for special clinical circumstances where switching may need to proceed more rapidly.Item Open Access Impact of Movement Disorders on Management of Spinal Deformity in the Elderly.(Neurosurgery, 2015-10) Ha, Yoon; Oh, Jae Keun; Smith, Justin S; Ailon, Tamir; Fehlings, Michael G; Shaffrey, Christopher I; Ames, Christopher PSpinal deformities are frequent and disabling complications of movement disorders such as Parkinson disease and multiple system atrophy. The most distinct spinal deformities include camptocormia, antecollis, Pisa syndrome, and scoliosis. Spinal surgery has become lower risk and more efficacious for complex spinal deformities, and thus more appealing to patients, particularly those for whom conservative treatment is inappropriate or ineffective. Recent innovations and advances in spinal surgery have revolutionized the management of spinal deformities in elderly patients. However, spinal deformity surgeries in patients with Parkinson disease remain challenging. High rates of mechanical complications can necessitate revision surgery. The success of spinal surgery in patients with Parkinson disease depends on an interdisciplinary approach, including both surgeons and movement disorder specialists, to select appropriate surgical patients and manage postoperative movement in order to decrease mechanical failures. Achieving appropriate correction of sagittal alignment with strong biomechanical instrumentation and bone fusion is the key determinant of satisfactory results.Item Open Access In-Hospital Complications and Resource Utilization Following Lumbar Spine Surgery in Patients with Parkinson Disease: Evaluation of the National Inpatient Sample Database.(World neurosurgery, 2017-10) Baker, Joseph F; McClelland, Shearwood; Line, Breton G; Smith, Justin S; Hart, Robert A; Ames, Christopher P; Shaffrey, Chris; Bess, ShayBackground
Previous reports suggest that patients with Parkinson disease (PD) have elevated rates of complications following spine surgery; however, these reports are limited by small patient series. In this study, we used the National Inpatient Sample (NIS) database to compare in-hospital complications following elective lumbar spine surgery in patients with a diagnosis of PD and patients without PD.Methods
The NIS database was accessed to identify patients with PD and those without PD who underwent lumbar spine surgery. All patients identified had a diagnosis code consistent with degenerative lumbar spine pathology. The patients were evaluated for the presence or absence of PD and divided into 4 lumbar spine procedure groups: decompression alone, lateral fusion, posterior fusion, and anterior fusion technique. Propensity score matching (PSM) was performed for the PD versus non-PD patients in each procedure group to control for confounding demographic variables, and in-hospital complications were compared between the 2 groups.Results
Between 2001 and 2012, a total of 613,522 lumbar spine surgery patient episodes were identified, of which 4492 (0.7%) involved a diagnosis of PD. Following PSM for patient age, sex, and race, the patients with PD were at increased risk for acute postoperative hemorrhagic anemia, increased blood transfusion requirements, and increased genitourinary, neurologic, and cardiac complications compared with the patients without PD.Conclusions
PSM analysis of the NIS database demonstrated that patients with PD are at increased risk for acute in-hospital complications and greater blood transfusion requirements than those without PD. Surgeons should be aware of the increased risks and differing requirements when treating spinal pathology in patients with PD.Item Open Access Mindfulness based stress reduction in people with Parkinson's disease and their care partners.(Complementary therapies in clinical practice, 2021-05) Shah-Zamora, Deepal; Allen, Allison M; Rardin, Lacy; Ivancic, Margaret; Durham, Katie; Hickey, Patrick; Cooney, Jeffrey W; Scott, Burton L; Mantri, SnehaBackground
Parkinson's Disease (PD) leads to poor quality of life and caregiver burden. Mindfulness-based stress reduction (MBSR) may improve these symptoms. We assessed the impact of a 9-week MBSR course on people with PD (PwP) and their care partners (CPs).Methods
Participants completed questionnaires at screening, at the end of the course, and at 3-month follow-up: Parkinson's Disease Quality-39 (PDQ-39, PD only), Zarit Burden Inventory (ZBI, CP only) and Mindful Attention Awareness Scale (MAAS, both). The primary outcome measure was change in PDQ-39 (for PwP) or ZBI (for CP). Patient-reported scales were analyzed quantitatively; qualitative data on perceived effectiveness was collected.Results
53.8% PwP and 100% CPs completed the course. Among PwP, there was a significant reduction in MAAS(p < 0.001) and in PDQ-39 (p = 0.008). CPs experienced an increase in MAAS (p = 0.02) but no change in ZBI (p = 0.239). Qualitatively, both PwP and CPs expressed satisfaction with the course.Discussion
MBSR improves mindful awareness in CPs and improves health-related quality of life in PwP.Item Open Access Neuropsychiatric Issues in Parkinson's Disease.(Current neurology and neuroscience reports, 2016-05) Cooney, Jeffrey W; Stacy, MarkCognitive and neuropsychiatric symptoms are common in Parkinson's Disease and may surpass motor symptoms as the major factors impacting patient quality of life. The symptoms may be broadly separated into those associated with the disease process and those that represent adverse effects of treatment. Symptoms attributed to the disease arise from pathologic changes within multiple brain regions and are not restricted to dysfunction in the dopaminergic system. Mood symptoms such as depression, anxiety, and apathy are common and may precede the development of motor symptoms by years, while other neuropsychiatric symptoms such as cognitive impairment, dementia, and psychosis are more common in later stages of the disease. Neuropsychiatric symptoms attributed to treatment include impulse control disorders, pathologic use of dopaminergic medications, and psychosis. This manuscript will review the current understanding of neuropsychiatric symptoms in Parkinson's Disease.Item Open Access Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial.(Lancet Neurol, 2015-08) Investigators, NINDSNET-PDFS-ZONEBACKGROUND: A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. METHODS: Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0·10. The study is registered at ClinicalTrials.gov, number NCT01280123. FINDINGS: 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4·42 (95% CI 2·55-6·28) for 15 mg pioglitazone, 5·13 (95% CI 3·17-7·08) for 45 mg pioglitazone, and 6·25 (95% CI 4·35-8·15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was -1·83 (80% CI -3·56 to -0·10) and the null hypothesis could not be rejected (p=0·19). The mean difference between the 45 mg and placebo groups was -1·12 (80% CI -2·93 to 0·69) and the null hypothesis was rejected in favour of futility (p=0·09). Planned sensitivity analyses of the primary outcome, using last value carried forward (LVCF) to handle missing data and using the completers' only sample, suggested that the 15 mg dose is also futile (p=0·09 for LVCF, p=0·09 for completers) but failed to reject the null hypothesis for the 45 mg dose (p=0·12 for LVCF, p=0·19 for completers). Six serious adverse events occurred in the 15 mg group, nine in the 45 mg group, and three in the placebo group; none were thought to be definitely or probably related to the study interventions. INTERPRETATION: These findings suggest that pioglitazone at the doses studied here is unlikely to modify progression in early Parkinson's disease. Further study of pioglitazone in a larger trial in patients with Parkinson's disease is not recommended. FUNDING: National Institute of Neurological Disorders and Stroke.Item Open Access Prevalence and type of cervical deformities among adults with Parkinson's disease: a cross-sectional study.(Journal of neurosurgery. Spine, 2016-04) Moon, Bong Ju; Smith, Justin S; Ames, Christopher P; Shaffrey, Christopher I; Lafage, Virginie; Schwab, Frank; Matsumoto, Morio; Baik, Jong Sam; Ha, YoonObject
To identify the characteristics of cervical deformities in Parkinson's disease (PD) and the role of severity of PD in the development of cervical spine deformities, the authors investigated the prevalence of the cervical deformities, cervical kyphosis (CK), and cervical positive sagittal malalignment (CPSM) in patients with PD. They also analyzed the association of severity of cervical deformities with the stage of PD in the context of global sagittal spinopelvic alignment.Methods
This study was a prospective assessment of consecutively treated patients (n = 89) with PD. A control group of the age- and sex-matched patients was selected from patients with degenerative cervical spine disease but without PD. Clinical and demographic parameters including age, sex, duration of PD, and Hoehn and Yahr (H&Y) stage were collected. Full-length standing radiographs were used to assess spinopelvic parameters. CK was defined as a C2-7 Cobb angle < 0°. CPSM was defined as C2-7 sagittal vertical axis (SVA) > 4 cm.Results
A significantly higher prevalence of CPSM (28% vs. 1.1%, p < 0.001), but not CK (12% vs. 10.1%, p = 0.635), was found in PD patients compared with control patients. Among patients with PD, those with CK were younger (62.1 vs. 69.0 years, p = 0.013) and had longer duration of PD (56.4 vs. 36.2 months, p = 0.034), but the severity of PD was not significantly different. Logistic regression analysis revealed that the presence of CK was associated with younger age, higher mismatch between pelvic incidence and lumbar lordosis, and lower C7-S1 SVA. The patients with CPSM had significantly greater thoracic kyphosis (TK) (p < 0.001) and a trend toward more advanced H&Y stage (p = 0.05). Logistic regression analysis revealed that CPSM was associated with male sex, greater TK, and more advanced H&Y stage.Conclusions
Patients with PD have a significantly higher prevalence of CPSM compared with age- and sex-matched control patients with cervical degenerative disease but without PD. Among patients with PD, CK is not associated with the severity of PD but is associated with overall global sagittal malalignment. In contrast, the presence of CPSM is associated more with the severity of PD than it is with the presence of global sagittal malalignment. Collectively, these data suggest that the neuromuscular pathogenesis of PD may affect the development of CPSM more than of CK.Item Open Access Ranbp2 haploinsufficiency mediates distinct cellular and biochemical phenotypes in brain and retinal dopaminergic and glia cells elicited by the Parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).(Cell Mol Life Sci, 2012-10) Cho, Kyoung-In; Searle, Kelly; Webb, Mason; Yi, Haiqing; Ferreira, Paulo AMany components and pathways transducing multifaceted and deleterious effects of stress stimuli remain ill-defined. The Ran-binding protein 2 (RanBP2) interactome modulates the expression of a range of clinical and cell-context-dependent manifestations upon a variety of stressors. We examined the role of Ranbp2 haploinsufficiency on cellular and metabolic manifestations linked to tyrosine-hydroxylase (TH(+)) dopaminergic neurons and glial cells of the brain and retina upon acute challenge to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonian neurotoxin, which models facets of Parkinson disease. MPTP led to stronger akinetic parkinsonism and slower recovery in Ranbp2 (+/-) than wild-type mice without viability changes of brain TH(+)-neurons of either genotype, with the exception of transient nuclear atypia via changes in chromatin condensation of Ranbp2 (+/-) TH(+)-neurons. Conversely, the number of wild-type retinal TH(+)-amacrine neurons compared to Ranbp2 (+/-) underwent milder declines without apoptosis followed by stronger recoveries without neurogenesis. These phenotypes were accompanied by a stronger rise of EdU(+)-proliferative cells and non-proliferative gliosis of GFAP(+)-Müller cells in wild-type than Ranbp2 (+/-) that outlasted the MPTP-insult. Finally, MPTP-treated wild-type and Ranbp2 (+/-) mice present distinct metabolic footprints in the brain or selective regions thereof, such as striatum, that are supportive of RanBP2-mediated regulation of interdependent metabolic pathways of lysine, cholesterol, free-fatty acids, or their β-oxidation. These studies demonstrate contrasting gene-environment phenodeviances and roles of Ranbp2 between dopaminergic and glial cells of the brain and retina upon oxidative stress-elicited signaling and factors triggering a continuum of metabolic and cellular manifestations and proxies linked to oxidative stress, and chorioretinal and neurological disorders such as Parkinson.Item Open Access Sagittal spinopelvic malalignment in Parkinson disease: prevalence and associations with disease severity.(Spine, 2014-06) Oh, Jae Keun; Smith, Justin S; Shaffrey, Christopher I; Lafage, Virginie; Schwab, Frank; Ames, Christopher P; Matsumoto, Morio; Baik, Jong Sam; Ha, YoonStudy design
Prospective study.Objective
Our objectives were to evaluate the prevalence of sagittal spinopelvic malalignment in a consecutive series of patients with Parkinson disease (PD) and to identify factors associated with sagittal spinopelvic deformity in this population.Summary of background data
PD is a degenerative neurological condition characterized by tremor, rigidity, bradykinesia, and loss of postural reflexes. The prevalence of spinal deformity in PD is higher than that of age-matched adults without PD.Methods
This study was a prospective assessment of consecutive patients with PD presenting to a neurology clinic during 12 months. Inclusion criteria included age more than 21 years and diagnosis of PD. Age- and sex-matched control group was selected from patients with cervical spondylosis. Clinical and demographic factors were collected including Unified Parkinson Disease Rating Scale score and Hoehn and Yahr stage. Full-length standing spine radiographs were assessed. Patients were grouped into either low C7 sagittal vertical axis (SVA) (<5 cm) or high C7 SVA (≥5 cm) and into matched (≤10°) or mismatched (>10°) pelvic incidence (PI)-lumbar lordosis.Results
Eighty-nine patients met criteria (41 males/48 females), including 52 with low C7 SVA and 37 with high C7 SVA. Significantly higher prevalence of high C7 SVA was found in PD (41.6 vs. 16.8%; P < 0.001). The high C7 SVA group was significantly older (72.4 vs. 65.1 yr; P < 0.001) and had a higher proportion of females (68% vs. 44%; P = 0.034), greater severity of PD based on Hoehn and Yahr stage (1.89 vs. 1.37; P < 0.001) and Unified Parkinson Disease Rating Scale (30.5 vs. 17.2; P = 0.002. Unified Parkinson Disease Rating Scale significantly correlated with C7 SVA (r = 0.474). Compared with the matched (≤10°) PI-lumbar lordosis group, the mismatch PI-lumbar lordosis group had higher C7 SVA, higher PI, higher pelvic tilt, lower lumbar lordosis, and lower thoracic kyphosis (P ≤ 0.003).Conclusion
Patients with PD have a high prevalence of sagittal spinopelvic malalignment than control group patients. Greater severity of PD is associated with sagittal spinopelvic malalignment.Level of evidence
3.Item Open Access Speech motor program maintenance, but not switching, is enhanced by left-hemispheric deep brain stimulation in Parkinson's disease.(International journal of speech-language pathology, 2010-10) Jones, Harrison N; Kendall, Diane L; Okun, Michael S; Wu, Samuel S; Velozo, Craig; Fernandez, Hubert H; Spencer, Kristie A; Rosenbek, John CSpeech reaction time (SRT) was measured in a response priming protocol in 12 participants with Parkinson's disease (PD) and hypokinetic dysarthria "on" and "off" left-hemispheric deep brain stimulation (DBS). Speech preparation was measured during speech motor programming in two randomly ordered speech conditions: speech maintenance and switching. Double blind testing was completed in participants with DBS of globus pallidus pars interna (GPi) (n = 5) or subthalamic nucleus (STN) (n = 7). SRT was significantly faster in the maintenance vs switch task, regardless of DBS state. SRT was faster in the speech maintenance task "on" stimulation, while there was no difference in speech switching "on" and "off" DBS. These data suggest that left-hemispheric DBS may have differential effects on aspects of speech preparation in PD. It is hypothesized that speech maintenance improvements may result from DBS-induced cortical enhancements, while the lack of difference in switching may be related to inhibition deficits mediated by the right-hemisphere. Alternatively, DBS may have little influence on the higher level motor processes (i.e., motor planning) which it is believed the switch task engaged to a greater extent than the maintenance task.Item Open Access StimVision v2: Examples and Applications in Subthalamic Deep Brain Stimulation for Parkinson's Disease.(Neuromodulation : journal of the International Neuromodulation Society, 2021-02) Noecker, Angela M; Frankemolle-Gilbert, Anneke M; Howell, Bryan; Petersen, Mikkel V; Beylergil, Sinem Balta; Shaikh, Aasef G; McIntyre, Cameron CObjective
Subthalamic deep brain stimulation (DBS) is an established therapy for Parkinson's disease. Connectomic DBS modeling is a burgeoning subfield of research aimed at characterizing the axonal connections activated by DBS. This article describes our approach and methods for evolving the StimVision software platform to meet the technical demands of connectomic DBS modeling in the subthalamic region.Materials and methods
StimVision v2 was developed with Visualization Toolkit (VTK) libraries and integrates four major components: 1) medical image visualization, 2) axonal pathway visualization, 3) electrode positioning, and 4) stimulation calculation.Results
StimVision v2 implemented two key technological advances for connectomic DBS analyses in the subthalamic region. First was the application of anatomical axonal pathway models to patient-specific DBS models. Second was the application of a novel driving-force method to estimate the response of those axonal pathways to DBS. Example simulations with directional DBS electrodes and clinically defined therapeutic DBS settings are presented to demonstrate the general outputs of StimVision v2 models.Conclusions
StimVision v2 provides the opportunity to evaluate patient-specific axonal pathway activation from subthalamic DBS using anatomically detailed pathway models and electrically detailed electric field distributions with interactive adjustment of the DBS electrode position and stimulation parameter settings.Item Open Access The interplay between monocytes, α-synuclein and LRRK2 in Parkinson's disease.(Biochemical Society transactions, 2023-04) Strader, Samuel; West, Andrew BThe accumulation of aggregated α-synuclein in susceptible neurons in the brain, together with robust activation of nearby myeloid cells, are pathological hallmarks of Parkinson's disease (PD). While microglia represent the dominant type of myeloid cell in the brain, recent genetic and whole-transcriptomic studies have implicated another type of myeloid cell, bone-marrow derived monocytes, in disease risk and progression. Monocytes in circulation harbor high concentrations of the PD-linked enzyme leucine-rich repeat kinase 2 (LRRK2) and respond to both intracellular and extracellular aggregated α-synuclein with a variety of strong pro-inflammatory responses. This review highlights recent findings from studies that functionally characterize monocytes in PD patients, monocytes that infiltrate into cerebrospinal fluid, and emerging analyses of whole myeloid cell populations in the PD-affected brain that include monocyte populations. Central controversies discussed include the relative contribution of monocytes acting in the periphery from those that might engraft in the brain to modify disease risk and progression. We conclude that further investigation into monocyte pathways and responses in PD, especially the discovery of additional markers, transcriptomic signatures, and functional classifications, that better distinguish monocyte lineages and responses in the brain from other types of myeloid cells may reveal points for therapeutic intervention, as well as a better understanding of ongoing inflammation associated with PD.Item Open Access The role of GRK6 in animal models of Parkinson's disease and L-DOPA treatment.(Sci Rep, 2012) Managò, Francesca; Espinoza, Stefano; Salahpour, Ali; Sotnikova, Tatyana D; Caron, Marc G; Premont, Richard T; Gainetdinov, Raul RG protein-coupled Receptor Kinase 6 (GRK6) belongs to a family of kinases that phosphorylate GPCRs. GRK6 levels were found to be altered in Parkinson's Disease (PD) and D(2) dopamine receptors are supersensitive in mice lacking GRK6 (GRK6-KO mice). To understand how GRK6 modulates the behavioral manifestations of dopamine deficiency and responses to L-DOPA, we used three approaches to model PD in GRK6-KO mice: 1) the cataleptic response to haloperidol; 2) introducing GRK6 mutation to an acute model of absolute dopamine deficiency, DDD mice; 3) hemiparkinsonian 6-OHDA model. Furthermore, dopamine-related striatal signaling was analyzed by assessing the phosphorylation of AKT/GSK3β and ERK1/2. GRK6 deficiency reduced cataleptic behavior, potentiated the acute effect of L-DOPA in DDD mice, reduced rotational behavior in hemi-parkinsonian mice, and reduced abnormal involuntary movements induced by chronic L-DOPA. These data indicate that approaches to regulate GRK6 activity could be useful in modulating both therapeutic and side-effects of L-DOPA.Item Open Access Validation of the Arabic Version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.(Movement disorders : official journal of the Movement Disorder Society, 2022-04) Khalil, Hanan; Aldaajani, Zakiyah F; Aldughmi, Mayis; Al-Sharman, Alham; Mohammad, Tareq; Mehanna, Raja; El-Jaafary, Shaimaa I; Dahshan, Ahmed; Ben Djebara, Mouna; Kamel, Walaa A; Amer, Hanan A; Farghal, Mohammed; Abdulla, Fatema; Al-Talai, Nouf; Snineh, Muneer Abu; Farhat, Nouha; Jamali, Fatima A; Matar, Rawan K; Abdelraheem, Heba S; Ghonimi, Nesma AM; Al-Melh, Mishal Abu; Elbhrawy, Sonia; Alotaibi, Majid S; Elaidy, Shaimaa A; Almuammar, Shahad A; Al-Hashel, Jasem Y; Gouider, Riadh; Samir, Hatem; Mhiri, Chokri; Skorvanek, Matej; Lin, Jeffrey; Martinez-Martin, Pablo; Stebbins, Glenn T; Luo, Sheng; Goetz, Christopher G; Bajwa, Jawad ABackground
The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has become the gold standard for evaluating different domains in Parkinson's disease (PD), and it is commonly used in clinical practice, research, and clinical trials.Objectives
The objectives are to validate the Arabic-translated version of the MDS-UPDRS and to assess its factor structure compared with the English version.Methods
The study was carried out in three phases: first, the English version of the MDS-UPDRS was translated into Arabic and subsequently back-translated into English by independent translation team; second, cognitive pretesting of selected items was performed; third, the Arabic version was tested in over 400 native Arabic-speaking PD patients. The psychometric properties of the translated version were analyzed using confirmatory factor analysis (CFA) as well as exploratory factor analysis (EFA).Results
The factor structure of the Arabic version was consistent with that of the English version based on the high CFIs for all four parts of the MDS-UPDRS in the CFA (CFI ≥0.90), confirming its suitability for use in Arabic.Conclusions
The Arabic version of the MDS-UPDRS has good construct validity in Arabic-speaking patients with PD and has been thereby designated as an official MDS-UPDRS version. The data collection methodology among Arabic-speaking countries across two continents of Asia and Africa provides a roadmap for validating additional MDS rating scale initiatives and is strong evidence that underserved regions can be energically mobilized to promote efforts that apply to better clinical care, education, and research for PD. © 2022 International Parkinson and Movement Disorder Society.Item Open Access Validation of the Hebrew version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.(Parkinsonism & related disorders, 2017-12) Zitser, Jennifer; Peretz, Chava; Ber David, Aya; Shabtai, Herzl; Ezra, Adi; Kestenbaum, Meir; Brozgol, Marina; Rosenberg, Alina; Herman, Talia; Balash, Yakov; Gadoth, Avi; Thaler, Avner; Stebbins, Glenn T; Goetz, Christopher G; Tilley, Barbara C; Luo, Sheng T; Liu, Yuanyuan; Giladi, Nir; Gurevich, TanyaThe Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one.The MDS-UPDRS questionnaire was translated to Hebrew and was tested on 389 patients with PD, treated at the Movement Disorders Unit at Tel-Aviv Medical Center. The MDS-UPDRS is made up of four sections. The higher the score, the worst the clinical situation of the patient is. Confirmatory and explanatory factor analysis were applied to determine if the factor structure of the English version could be confirmed in the Hebrew version.The Hebrew version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Hebrew-version was satisfactory, with Cronbach's alpha values 0.79, 0.90, 0.93, 0.80, for parts 1 to 4 respectively. In the confirmatory factor analysis, all four parts had high (greater than 0.90) comparative fit index (CFI) in comparison to the original English MDS-UPDRS with high factor structure (0.96, 0.99, 0.94, 1.00, respectively), thus confirming the pre-specified English factor structure. Explanatory factor analysis yielded that the Hebrew responses differed from the English one within an acceptable range: in isolated item differences in factor structure and in the findings of few items having cross loading on multiple factors.The Hebrew version of the MDS-UPDRS meets the requirements to be designated as the Official Hebrew Version of the MDS-UPDRS.