Showing papers by "Klaus Seppi published in 2017"

Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria

Abstract: Background: PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome. Objective: We aimed to provide an evidence- and consensus-based revision of the clinical diagnostic criteria for PSP. Methods: We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy-confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2-day meeting, and refined in three further Delphi rounds. Results: Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context-dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features. Conclusions: Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence.

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Abstract: Summary Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT . Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10 −10 ) on chromosome 5 spanning three genes: MSH3, DHFR , and MTRNR2L2 . The genes in this locus were associated with progression in TRACK-HD ( MSH3 p=2·94 × 10 −8 DHFR p=8·37 × 10 −7 MTRNR2L2 p=2·15 × 10 −9 ) and to a lesser extent in REGISTRY ( MSH3 p=9·36 × 10 −4 DHFR p=8·45 × 10 −4 MTRNR2L2 p=1·20 × 10 −3 ). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10 −8 ), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation. Funding The European Commission FP7 NeurOmics project; CHDI Foundation; the Medical Research Council UK; the Brain Research Trust; and the Guarantors of Brain.

Magnetic resonance imaging for the diagnosis of Parkinson’s disease

Abstract: The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology and error rates in the clinical diagnosis can be high even at specialized centres. Despite several limitations, magnetic resonance imaging (MRI) has undoubtedly enhanced the diagnostic accuracy in the differential diagnosis of neurodegenerative parkinsonism over the last three decades. This review aims to summarize research findings regarding the value of the different MRI techniques, including advanced sequences at high- and ultra-high-field MRI and modern image analysis algorithms, in the diagnostic work-up of Parkinson’s disease. This includes not only the exclusion of alternative diagnoses for Parkinson’s disease such as symptomatic parkinsonism and atypical parkinsonism, but also the diagnosis of early, new onset, and even prodromal Parkinson’s disease.

Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder

Abstract: Objective: To determine the usefulness of dopamine transporter (DAT) imaging to identify idiopathic REM sleep behavior disorder (IRBD) patients at risk for short-term development of clinically-defined synucleinopathy. Methods: Eighty-seven patients with polysomnography-confirmed IRBD underwent 123I-FP-CIT DAT-SPECT. Results were compared with 20 matched controls without RBD who underwent DAT-SPECT. In patients, FP-CIT uptake was considered abnormal when values were two standard deviations below controls' mean uptake. After DAT-SPECT, patients were followed-up during 5.7 ± 2.2 (range, 2.6-9.9) years. Results: Baseline DAT deficit was found in 51 (58.6%) patients. During follow-up 25 (28.7%) subjects developed clinically-defined synucleinopathy (Parkinson disease in 11, dementia with Lewy bodies in 13, multiple system atrophy in one) with mean latency of 3.2 ± 1.9 years from imaging. Kaplan-Meier survival analysis showed increased risk of incident synucleinopathy in patients with abnormal DAT-SPECT than with normal DAT-SPECT (20% vs. 6% at three years, 33% vs. 18% at five years; log rank test, p=0.006). Receiver operating characteristics curve revealed that reduction of FP-CIT uptake in putamen greater than 25% discriminated patients with DAT deficit who developed synucleinopathy from patients with DAT deficit that remained disease-free after three years of follow-up. At 5-year follow-up, DAT-SPECT had 75% sensitivity, 51% specificity, 44% positive predictive value, 80% negative predictive value, and like-hood ratio 1.54 to predict synucleinopathy. Interpretation: DAT-SPECT identifies IRBD patients at short-term risk for synucleinopathy. Decreased FP-CIT putamen uptake greater than 25% predicts synucleinopathy after three years follow-up. These observations may be useful to select candidates for disease-modification trials in IRBD. This article is protected by copyright. All rights reserved.

Meta-analysis of dorsolateral nigral hyperintensity on magnetic resonance imaging as a marker for Parkinson's disease.

Abstract: Background Dorsolateral nigral hyperintensity on iron-sensitive magnetic resonance imaging (MRI) sequences seems to be a typical finding in Parkinson's disease (PD), but most studies have involved small samples and have had heterogeneous control populations. Objectives The objective of this study was to perform a meta-analysis on dorsolateral nigral hyperintensity as an imaging marker for PD. Methods The methods included a systematic literature search and a hierarchical summary receiver operating characteristics curve approach. Results Of the 16 identified studies, 10 were suitable for analysis, including 364 PD and 231 control cases. The meta-analysis showed an overall sensitivity and specificity of the absence of dorsolateral nigral hyperintensity for PD versus controls of 97.7% and 94.6% (3 and 7 Tesla) and of 94.6% and 94.4% (3 Tesla only). Descriptive analysis among the 4 studies including patients with non-PD parkinsonism showed that dorsolateral nigral hyperintensity was absent in 89.4% of cases with atypical parkinsonian disorders (n = 74), but only in 21.7% of cases with non-neurodegenerative parkinsonism (n = 69). Moreover, in 2 of these studies, the absence of dorsolateral nigral hyperintensity predicted ipsilateral dopamine-transporter deficiency with 87.5% sensitivity and 83.6% specificity. Conclusions Visual assessment of dorsolateral nigral hyperintensity on iron-sensitive MRI sequences provides excellent diagnostic accuracy for PD versus controls. Moreover, its loss appears to be a marker of nigral pathology and holds the potential for the differentiation of neurodegenerative from non-neurodegenerative parkinsonian disorders. © 2017 International Parkinson and Movement Disorder Society

The role of high-field magnetic resonance imaging in parkinsonian disorders: Pushing the boundaries forward

Abstract: Historically, magnetic resonance imaging (MRI) has contributed little to the study of Parkinson's disease (PD), but modern MRI approaches have unveiled several complementary markers that are useful for research and clinical applications. Iron- and neuromelanin-sensitive MRI detect qualitative changes in the substantia nigra. Quantitative MRI markers can be derived from diffusion weighted and iron-sensitive imaging or volumetry. Functional brain alterations at rest or during task performance have been captured with functional and arterial spin labeling perfusion MRI. These markers are useful for the diagnosis of PD and atypical parkinsonism, to track disease progression from the premotor stages of these diseases and to better understand the neurobiological basis of clinical deficits. A current research goal using MRI is to generate time-dependent models of the evolution of PD biomarkers that can help understand neurodegeneration and provide reliable markers for therapeutic trials. This article reviews recent advances in MRI biomarker research at high-field (3T) and ultra high field-imaging (7T) in PD and atypical parkinsonism. © 2017 International Parkinson and Movement Disorder Society.

Differences in MDS‐UPDRS Scores Based on Hoehn and Yahr Stage and Disease Duration

Abstract: BACKGROUND: The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) is a newly developed tool to assess Parkinson's disease (PD). Changes in scores on the scale over the course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS‐UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD. METHODS: For this cross‐sectional study, demographic data and MDS‐UPDRS scores were collected, including HY stage. Subscores on MDS‐UPDRS Parts I through IV were analyzed using 1‐way analyses of variance for each HY stage and in 5‐year increments of disease duration. Part III (motor assessment) scores were analyzed separately for on and off states. RESULTS: The mean age of the 3206 patients was 65.8 ± 10.6 years, 53.3% were men, the mean disease duration was 11.5 ± 4.6 years, and the median HY stage was 2 (range, 0–5); 2156 patients were examined in an on state and 987 were examined in an off state. Scores for all MDS‐UPDRS parts increased significantly through HY stages 1 through 5, with an average increase of 3.8, 7.7, 14.6, and 2.0 points consecutively for parts I through IV, respectively. For the 5‐year increments of disease duration, MDS‐UPDRS subscores increased by an average of 1.6, 3.3, 4.2, and 1.4 points consecutively for parts I through IV, respectively. This increase was significant only during the first 15 years of disease for all 4 parts, including part III scores evaluated in both on and off states. CONCLUSIONS: MDS‐UPDRS scores for all 4 parts increase significantly with every HY stage and also with 5‐year increments of disease duration in the first 15 years of the disease.

Free water improves detection of changes in the substantia nigra in parkinsonism: A multisite study

Abstract: Background Imaging markers that are sensitive to parkinsonism across multiple sites are critically needed for clinical trials. The objective of this study was to evaluate changes in the substantia nigra using single- and bi-tensor models of diffusion magnetic resonance imaging in PD, MSA, and PSP. Methods The study cohort (n = 425) included 107 healthy controls and 184 PD, 63 MSA, and 71 PSP patients from 3 movement disorder centers. Bi-tensor free water, free-water-corrected fractional anisotropy, free-water-corrected mean diffusivity, single-tensor fractional anisotropy, and single-tensor mean diffusivity were computed for the anterior and posterior substantia nigra. Correlations were computed between diffusion MRI measures and clinical measures. Results In the posterior substantia nigra, free water was greater for PSP than MSA and PD patients and controls. PD and MSA both had greater free water than controls. Free-water-corrected fractional anisotropy values were greater for PSP patents than for controls and PD patients. PSP and MSA patient single-tensor mean diffusivity values were greater than controls, and single-tensor fractional anisotropy values were lower for PSP patients than for healthy controls. The parkinsonism effect size for free water was 0.145 in the posterior substantia nigra and 0.072 for single-tensor mean diffusivity 072. The direction of correlations between single-tensor mean diffusivity and free-water values and clinical scores was similar at each site. Conclusions Free-water values in the posterior substantia nigra provide a consistent pattern of findings across patients with PD, MSA, and PSP in a large cohort across 3 sites. Free water in the posterior substantia nigra relates to clinical measures of motor and cognitive symptoms in a large cohort of parkinsonism. © 2017 International Parkinson and Movement Disorder Society

Brain structural profile of multiple system atrophy patients with cognitive impairment.

Abstract: Current consensus diagnostic criteria for multiple system atrophy (MSA) consider dementia a non-supporting feature, although cognitive impairment and even frank dementia are reported in clinical practice. Mini-Mental State Examination (MMSE) is a commonly used global cognitive scale, and in a previous study, we established an MSA-specific screening cut-off score <27 to identify cognitive impairment. Finally, MSA neuroimaging findings suggest the presence of structural alterations in patients with cognitive deficits, although the extent of the anatomical changes is unclear. The aim of our multicenter study is to better characterize anatomical changes associated with cognitive impairment in MSA and to further investigate cortical and subcortical structural differences versus healthy controls (HC). We examined retrospectively 72 probable MSA patients [50 with normal cognition (MSA-NC) and 22 cognitively impaired (MSA-CI) based on MMSE <27] and compared them to 36 HC using gray- and white-matter voxel-based morphometry and fully automated subcortical segmentation. Compared to HC, MSA patients showed widespread cortical (bilateral frontal, occipito-temporal, and parietal areas), subcortical, and white-matter alterations. However, MSA-CI showed only focal volume reduction in the left dorsolateral prefrontal cortex compared with MSA-NC. These results suggest only a marginal contribution of cortical pathology to cognitive deficits. We believe that cognitive dysfunction is driven by focal fronto-striatal degeneration in line with the concept of “subcortical cognitive impairment”.

Diffusion-weighted MRI distinguishes Parkinson disease from the parkinsonian variant of multiple system atrophy: A systematic review and meta-analysis

Abstract: Background Putaminal diffusivity in brain magnetic resonance diffusion-weighted imaging (DWI) is increased in patients with the parkinsonian variant of multiple system atrophy (MSA-P) compared to Parkinson disease (PD) patients. Purpose We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of DWI to distinguish MSA-P from PD. Methods Studies on DWI were identified through a systematic PubMed and Clarivate Analytics® Web of Science® Core Collection search. Papers were selected based on stringent inclusion criteria; minimum requirement was the inclusion of MSA-P and PD patients and documented true positive, true negative, false positive and false negative rates or overall sample size and reported sensitivity and specificity. Meta-analysis was performed using the hierarchical summary receiver operating characteristics curve approach. Results The database search yielded 1678 results of which 9 studies were deemed relevant. Diagnostic accuracy of putaminal diffusivity measurements were reported in all of these 9 studies, whereas results of other regions of interest were only reported irregularly. Therefore, a meta-analysis could only be performed for putaminal diffusivity measurements: 127 patients with MSA-P, 262 patients with PD and 70 healthy controls were included in the quantitative synthesis. The meta-analysis showed an overall sensitivity of 90% (95% confidence interval (CI): 76.7%-95.8%) and an overall specificity of 93% (95% CI: 80.0%-97.7%) to distinguish MSA-P from PD based on putaminal diffusivity. Conclusion Putaminal diffusivity yields high sensitivity and specificity to distinguish clinically diagnosed patients with MSA-P from PD. The confidence intervals indicate substantial variability. Further multicenter studies with harmonized protocols are warranted particularly in early disease stages when clinical diagnosis is less certain.

Consistency of "Probable RBD" Diagnosis with the RBD Screening Questionnaire: A Follow-up Study.

Abstract: Introduction The aim of this study was to evaluate the consistency of “probable RBD” diagnosis with the RBD screening questionnaire (RBDSQ) assessed 2 years apart in a population-based study. Methods Probable RBD was assessed by RBDSQ in 2008 and in 2010 in the Bruneck Study Cohort, with participants aged ≥60 years. Results A total of 437 participants completed the RBDSQ in 2008 and 2010. There were 29 (6.6%) and 23 (5.3%) participants with probable RBD in 2008 and in 2010, respectively. Only eight (1.8%) screened positive on both occasions. RBDSQ values 2 years apart showed low correlation with each other (Spearman rank coefficient r = 0.348, P < 0.001) and low agreement (intraclass correlation coefficient 0.388, P < 0.001). Conclusions We found low agreement between the two assessments. Possible explanations are the fluctuation of untreated RBD expression and the poor utility of the RBDSQ to detect RBD in the general population. Until further PSG validation of the RBDSQ in population-based studies, investigators must be aware of the inherent uncertainty of questionnaire-based RBD diagnosis.

Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues.

Abstract: Parkinson's disease (PD) is a neurodegenerative multisystem disorder characterized by progressive motor symptoms such as bradykinesia, tremor and muscle rigidity. Over the course of the disease, numerous non-motor symptoms, sometimes preceding the onset of motor symptoms, significantly impair patients' quality of life. The significance of non-motor symptoms may outweigh the burden through progressive motor incapacity, especially in later stages of the disease. The advanced stage of the disease is characterized by motor complications such as fluctuations and dyskinesias induced by the long-term application of levodopa therapy. In recent years, it became evident that various non-motor symptoms such as psychiatric symptoms, fatigue and pain also show fluctuations after chronic levodopa therapy (named non-motor fluctuations or NMFs). Although NMFs have moved into the focus of interest, current national guidelines on the treatment of PD may refer to non-motor symptoms and their management, but do not mention NMF, and do not contain recommendations on their management. The present article summarizes major issues related to NMF including clinical phenomenology and pathophysiology, and outlines a number of open issues and topics for future research.

Haste makes waste: Decision making in patients with restless legs syndrome with and without augmentation.

Abstract: Objectives To investigate decision making in patients with primary restless legs syndrome (RLS) with and without augmentation treated with dopaminergic medication. Methods A total of 64 non-demented RLS patients treated with dopaminergic medication with and without augmentation were included in this study. We used an information sampling task to assess how much evidence participants gather before making a decision. Performance was compared to the results of 21 healthy controls. Results All patients with and without augmentation gathered less information than healthy controls before making a decision (p<0.001), but there was no difference between the two patient groups (p = 1.0). Furthermore, both patient groups made more irrational decisions (e.g. decisions against the evidence they had at the time) than healthy controls (p≤0.002). In addition, RLS patients with augmentation made significantly more irrational decisions than RLS patients without augmentation (p = 0.037) and controls (p<0.001). Conclusions Our results show that RLS patients treated with dopaminergic drugs, regardless of having augmentation or not, jumped to conclusions and decided significantly more often against the evidence they had at the time of their decision. However, those with augmentation performed worse than all other groups and made more often irrational decisions, a phenomenon which is also common in patients with substance abuse or behavioural addictions. Thus, jumping to conclusions and deciding with a higher degree of uncertainty as well as irrational decision making is more common in RLS patients treated with dopaminergic medication particularly in those with augmentation.

Topography of Dopamine Transporter Availability in the Cerebellar Variant of Multiple System Atrophy.

Abstract: Background Voxel-wise comparison of [123I]-2β-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]β-CIT) radioligand distribution measured by single-photon emission computed tomography (SPECT) revealed distinct patterns of reduced dopamine transporter (DAT) availability in the Parkinson's variant of MSA (MSA-P). The aim of this study was to identify the monoamine transporter distribution pattern in patients with the cerebellar variant of MSA (MSA-C). Additionally, monoamine transporter availability was investigated in a small cohort of patients with sporadic adult-onset ataxia (SAOA). Methods [123I]β-CIT SPECT was performed in patients with MSA-C (n = 12), MSA-P (n = 14), SAOA (n = 5), and controls (n = 15) matched for age. Parametric images of [123I]β-CIT binding potential (BPND) were generated and analyzed by statistical parametric mapping (SPM) and region of interest (ROI) analysis. Results SPM localized significant reductions of [123I]β-CIT BPND in the striatum, midbrain, and pons in MSA-C compared to controls. When compared with MSA-P, the striatal DAT decline was significantly less affected in MSA-C. ROI analysis revealed reductions of striatal and midbrain [123I]β-CIT binding in MSA-C compared to SAOA, whereas no significant difference was apparent between the SAOA and control groups. Conclusions Midbrain and pontine monoaminergic transporter binding was severely impaired in MSA-C, matching the underlying pathological features. Striatal DAT availability was relatively less affected in MSA-C compared to MSA-P, reflecting measureable, but less-profound, degeneration of the nigrostriatal dopaminergic projections. Preliminary results of reduced striatal and midbrain [123I]β-CIT binding in MSA-C, compared to SAOA, suggest that the potential of DAT-SPECT as a surrogate marker in the diagnostic workup of patients with adult-onset cerebellar ataxia should be further investigated.

Very late-onset pure autonomic failure.

Abstract: to result in a deficiency of mature PDGF-BB. Although the clinical episodes exhibited by our patients resembled MR-1-associated PNKD, they showed several atypical features: MR-1-associated PNKD attacks are frequently triggered by alcohol, coffee, tea, fatigue, or stress, whereas our patients reported no clear precipitants; MR-1associated PNKD attacks usually last from several minutes to hours, whereas the attacks observed in our patients lasted for a much shorter period ( 1 minute). Etiologically, PNKD could be primary or secondary to an identifiable cause, such as multiple sclerosis, stroke, trauma, and metabolic disorders. Notably, coexistence of PNKD and brain calcification in a 23-year-old man has been reported in the literature, in which similar clinical episodes were described. Because the PNKD phenotype cosegregated with brain calcification in this family, and no mutation was found in the MR-1 gene, we speculate that the PNKD symptoms exhibited by our patients might be secondary to brain calcification. While the manuscript was under revision, another study has reported the c.232C>T PDGFB mutation in a sporadic PFBC patient with memory impairment and headache. It is notable that the clinical feature of our patients is different from that shown in the sporadic case. This might be related with their genetic background differences.

Letter re: Incident parkinsonism in older adults without Parkinson disease.

Abstract: We read with interest the article by Buchman et al.,1 which reported that depressive symptoms, neuroticism, urinary incontinence, sleep complaints, and chronic health conditions were associated with incident parkinsonism (48.2% over 5 years) in the elderly. We previously reported on incidence and risk factors of mild parkinsonian signs, a similar concept to possible parkinsonism,1 in the cohort of the prospective population-based Bruneck Study of 2005.2 We now present an analysis of risk factors for parkinsonism according to the definition used by Buchman et al. in this population. Of 393 participants without parkinsonism at baseline undergoing 5-year follow-up, a markedly lower proportion of 16.0% (95% confidence interval [CI] 12.7%–20.0%) developed incident parkinsonism (excluding participants developing secondary parkinsonism). A logistic regression analysis adjusted for age and sex revealed that, out of single markers for prodromal Parkinson disease as defined per movement disorder society research criteria,3 assessed in the Bruneck study,4 substantia nigra hyperechogenicity on transcranial sonography (odds ratio 1.99; 95% CI 1.10–3.62, p = 0.024), probable REM sleep behavior disorder (6.88; 95% CI 1.10–43.10, p = 0.039), olfactory loss (1.96; 95% CI 1.01–3.81, p = 0.047), urinary dysfunction (5.15; 95% CI 1.65–16.14, p = 0.005), and depression/anxiety (2.85; 95% CI 1.28–6.36, p = 0.011) were significantly associated with incident parkinsonism, thus confirming and expanding the findings of Buchman et al.

‘Advanced’ Parkinson’s disease characteristics in clinical practice: results from the OBSERVE-PD study, a cross-sectional observational study of 2615 patients (P6.001)

Abstract: Objective: To characterize clinical and non-clinical features and treatments (including invasive/device aided options) in PD patients considered ‘advanced’ by movement disorder specialists. Background: ‘Advanced’ Parkinson’s disease (PD) patients are often treated at specialized movement disorder centers. However, the defining features of ‘advanced’ PD are not well understood. Design/Methods: A cross-sectional, observational study was conducted at 128 movement disorder centers in 18 countries. The primary outcome was the proportion of PD patients identified by their physician as ‘advanced’. The clinical and non-clinical characteristics of ‘advanced’ PD patients were compared to ‘non-advanced’ PD patients using descriptive statistics. Physicians’ assessment of ‘advanced’ PD was compared to a Delphi-criteria-based classification. Results: According to the physicians’ judgment, 51.3% (n=1342/2615) of PD patients were considered ‘advanced’, but this proportion varied regionally. There was a moderate correlation between the physician’s judgment and the Delphi-consensus-based criteria for ‘advanced’ PD. ‘Advanced’ and ‘non-advanced’ patients were similar regarding age, gender, and living situation, but differed in terms of motor symptom severity (Unified Parkinson’s Disease Rating Scale [UPDRS] Part III score, mean[SD]= ‘advanced’ 30.2[14.7]; ‘non-advanced’ 21.1[11.0]), motor fluctuations (UPDRS Part IV Q32 and Q39), non-motor symptoms (Non-motor Symptom Scale total score, ‘advanced’ 58.6[43.0]; ‘non-advanced’ 34.4[30.9]), quality of life (8-item Parkinson’s Disease Questionnaire total score, ‘advanced’ 38.6[19.3]; ‘non-advanced’ 20.7[16.4]) and caregiver support status. Of the ‘advanced’ PD patients, 882/1342 (66%) were eligible for device-aided treatment; 548 (41%) had an ongoing device-aided treatment or were about to start. Conclusions: This study demonstrated that physicians judged more than half of the PD patients in movement disorder centers across 18 countries as ‘advanced’, with distinct characteristics regarding motor fluctuations, non-motor symptoms and quality of life. Study Supported by: AbbVie Inc. Disclosure: Dr. Abbvie has received personal compensation for activities with Abbvie, Boston Scientific, Medtronic, Teva, and UCB Pharma as a speaker and advisory board member. Dr. Lopiano has received personal compensation for activities with Abbvie, UCB and Zambon serving as consultant and speaker. Dr. Elibol has received personal compensation from a commercial entity. Dr. Smolentseva has received personal compensation from a commercial entity. Dr. Seppi has nothing to disclose. Dr. Takats has received personal compensation for activities with Medtronic, UCB pharma, TEVA, and AbbVie Inc as a study investigator, consultant, or speaker. Dr. Onuk has received personal compensation for activities with AbbVie Inc. as employee. Dr. Onuk holds stock and/or stock options in AbbVie Inc. Dr. Parra has received personal compensation from AbbVie Inc. as an employee, and holds stock in AbbVie Inc. Dr. Bergmann has received personal compensation for activities with AbbVie as an employee. Dr. Bergmann holds stocks and stock options in AbbVie, which sponsored research in which Dr. Bergmann was involved as an investigator. Dr. Yegin has received personal compensation for activities with AbbVie as an employee. Dr. Yegin holds stock and/or stock options in AbbVie, Inc. Dr. Pirtosek has received personal compensation for activities with AbbVie as a speaker and study investigator.