Idiopathic Parkinson's Disease Patients Research Articles

Skin nerve phosphorylated [formula omitted]-synuclein deposits in Parkinson’s disease with orthostatic hypotension

To investigate phosphorylated α-synuclein (p-syn) deposits in skin nerves of Parkinson’s disease (PD) patients with neurogenic orthostatic hypotension (OH) and a PD matched group without dysautonomia. We enrolled 28 idiopathic PD patients with abnormal nigro-striatal DatScan and cardiac MIBG: (1) 14 of them complained of neurogenic OH (PD + OH); and (2) 14 matched patients did not complain of autonomic dysfunctions (PD-OH); 7 of them were re-evaluated over a follow-up (4 ± 2 years). Patients underwent skin biopsy in proximal (i.e. C7 paravertebral spine region) and distal (i.e. thigh and leg) sites. PD + OH showed a higher p-syn deposition than PD-OH with a widespread autonomic cholinergic and adrenergic skin nerves involvement. Over the follow-up PD-OH patients showed a marked increase in motor dysfunctions scores without autonomic symptoms and a slight increase of skin p-syn deposition but still lower than PD + OH. PD + OH showed a wide involvement of p-syn deposits in autonomic cholinergic and adrenergic skin nerves skin; (2) PD-OH showed a lower load of skin p-syn mainly restricted to adrenergic fibers of skin vessels, still persisting over a follow-up. These data supported a different pathogenesis between PD + OH and PD-OH and may help to identify a specific diagnostic trait for PD + OH patients.

Iron quantification in Parkinson's disease using an age-based threshold on susceptibility maps: The advantage of local versus entire structure iron content measurements

BackgroundElevated brain iron has been observed in Idiopathic Parkinson's disease (IPD) within the deep gray matter. Using quantitative susceptibility mapping (QSM) and a thresholded high-iron region, we quantified iron content in the midbrain of patients with Parkinson's disease as a function of age. MethodsWe used MRI to scan 24 IPD patients at 3-Tesla. Susceptibility-weighted images were collected with the following parameters, TE: 6 and 20 ms, TR: 30 ms, FA: 15°, and resolution: 0.5 × 0.5 × 2.0 mm3. QSM images were reconstructed from the source phase images. Whole-region and thresholded high-iron (RII) region boundaries for the Substantia Nigra (SN) and Red Nucleus (RN) were traced. Iron content was measured via mean susceptibilities and volumes, which were compared between the groups, as well as between right and left side of the structures within groups. ResultsTwenty patients with mild to moderate IPD were used in this study. For the SN, mean RII and whole-region iron and volumes were higher in the IPD group compared to HC, as well as mean RII for the RN, while no differences were seen between the groups when considering whole-region mean susceptibility bilaterally for the RN. ConclusionUsing a two-region of interest analysis on QSM, we showed that abnormal iron occurs in IPD patients in the SN and with greater volumes compared to HC. This method may have application as a biomarker for disease diagnosis and early intervention.

Survival rates among Parkinson's disease patients who carry mutations in the LRRK2 and GBA genes

The G2019S mutation in the LRRK2 gene generates a milder PD phenotype compared with GBA-PD; however, genetic based survival studies are lacking. To compare mortality rates between LRRK2-PD, GBA-PD, and idiopathic PD patients (iPD). Patients were screened for the G2019S mutation in the LRRK2 gene and the seven common GBA mutations among Ashkenazi Jews, classified as mild and severe (mGBA, sGBA). Motor symptoms onset and date of death were ascertained, with mortality rates calculated for each group of patients. Overall, 380 of 1,086 idiopathic PD patients, 49 of 159 LRRK2-PD, 56 of 148 mGBA-PD, and 13 of 49 sGBA-PD participants died by the time of analysis. LRRK2-PD tended to have longer survival compared to idiopathic PD whereas GBA status did not affect mortality. Genetic status did not predict mortality in a multivariate analysis. Survival of patients with PD does not seem to be related to GBA status, whereas LRRK2 might confer higher survival rates.

Role of the Cingulate Cortex in Dyskinesias-Reduced-Self-Awareness: An fMRI Study on Parkinson's Disease Patients.

Objectives: The detection of dyskinesias-reduced-self-awareness (DRSA), in Parkinson’s disease (PD), was previously associated to executive and metacognitive deficits mainly due to dopaminergic overstimulation of mesocorticolimbic circuits. Response-inhibition dysfunction is often observed in PD. Apart from being engaged in response-inhibition tasks, the anterior cingulate cortex (ACC), is part of a functional system based on self-awareness and engaged across cognitive, affective and behavioural contexts. The purpose of the study was to examine the relationship between response-inhibition disabilities and DRSA using whole-brain event-related functional magnetic resonance imaging (fMRI), over the course of a specific executive task.Methods: Twenty-seven cognitively preserved idiopathic PD patients – presenting motor fluctuations and dyskinesias – were studied. They underwent a neurological and neuropsychological evaluation. The presence of DRSA was assessed using the Dyskinesias Subtracted-Index (DS-I). Cingulate functionality was evaluated with fMRI, while patients performed an ACC-sensitive GO-NoGO task. Association between blood oxygenation level dependent response over the whole-brain during the response-inhibition task and DS-I scores was investigated by regression analysis.Results: The presence of DRSA was associated with reduced functional recruitment in the bilateral ACC, bilateral anterior insular cortex and right dorsolateral prefrontal cortex (pFWE<0.05). Moreover, DS-I scores significantly correlated with percent errors on the NoGO condition (r = 0.491, pFWE = 0.009).Discussion: These preliminary findings add evidence to the relevant role of executive dysfunctions in DRSA pathogenesis beyond the effects of chronic dopaminergic treatment, with a key leading role played by ACC as part of a functionally impaired response-inhibition network. Imaging biomarkers for DRSA are important to be studied, especially when the neuropsychological assessment seems to be normal.

Patient's perception: shorter and more severe prodromal phase in GBA-associated PD.

Prevalence and time of occurrence of prodromal symptoms of Parkinson's disease (PD) in relation to the onset of classical motor manifestation varies between patients. Possible modifying factors might be different genetic architectures predisposing to varying burden of manifestations. To characterize the prodromal phase in PD patients with heterozygous mutations in the GBA gene compared to PD patients without GBA mutation. In a retrospective design, 151 participants [47 PD patients carrying a GBA mutation (PDGBA ), 52 idiopathic PD patients (PDidiopathic ), 52 healthy elderly (CON)] underwent a validated structured interview designed to assess prevalence and time of occurrence of prodromal symptoms. PDGBA showed a higher prevalence of prodromal symptoms and almost simultaneous occurrence of non-motor and early motor symptoms shortly before PD diagnosis whereas PDidiopathic reported a longer prodromal phase starting with non-motor symptoms. The short and severe prodromal phase in PDGBA might call for shorter assessment intervals in yet premanifest GBA mutation carriers.

Virtual Footprints Can Improve Walking Performance in People With Parkinson's Disease.

In Parkinson's disease (PD) self-directed movement, such as walking, is often found to be impaired while goal directed movement, such as catching a ball, stays relatively unaltered. This dichotomy is most clearly observed when sensory cueing techniques are used to deliver patterns of sound and/or light which in turn act as an external guide that improves gait performance. In this study we developed visual cues that could be presented in an immersive, interactive virtual reality (VR) environment. By controlling how the visual cues (black footprints) were presented, we created different forms of spatial and temporal information. By presenting the black footprints at a pre-specified distance apart we could recreate different step lengths (spatial cues) and by controlling when the black footprints changed color to red, we could convey information about the timing of the foot placement (temporal cues). A group of healthy controls (HC; N = 10) and a group of idiopathic PD patients (PD, N = 12) were asked to walk using visual cues that were tailored to their own gait performance [two spatial conditions (115% [N] and 130% [L] of an individual's baseline step length) and three different temporal conditions (spatial only condition [NT], 100 and 125% baseline step cadence)]. Both groups were found to be able to match their gait performance (step length and step cadence) to the information presented in all the visual cue conditions apart from the 125% step cadence conditions. In all conditions the PD group showed reduced levels of gait variability (p < 0.05) while the HC group did not decrease. For step velocity there was a significant increase in the temporal conditions, the spatial conditions and of the interaction between the two for both groups of participants (p < 0.05). The coefficient of variation of step length, cadence, and velocity were all significantly reduced for the PD group compared to the HC group. In conclusion, our results show how virtual footsteps presented in an immersive, interactive VR environment can significantly improve gait performance in participants with Parkinson's disease.

Clinical characteristics of PD patients with LRRK2 G2385R and R1628P variants

LRRK2 is the most common genetic cause of PD. G2385R and R1628 P variants are the most common variants of LRRK2 in Chinese populations. Consensus on the clinical features of G2385R and R1628 P related PD has not been reached yet, although it had been widely studied. In our study, genotype analyses were conducted on 721 PD patients of Chinese origin. A total of 62 G2385R carriers, 32 R1628 P carriers and 623 idiopathic PD patients underwent the following clinical feature analysis. Motor symptoms, non-motor symptoms and co-morbidities were the targeted features to be analyzed. As a result, Neither the G2385R nor the R1628 P carriers showed significant clinical feature differences when compared to the idiopathic PD patients, so did the comparison between the G2385R and the R1628 P carriers. In conclusion, the clinical features of PD patients with LRRK2 G2385R or R1628 P variants were similar to those of idiopathic PD.

The Association Between DRD3 Ser9Gly Polymorphism and Depression Severity in PD

Background: More and more evidence suggests that dopamine receptor D3 gene (DRD3) plays an important role in the clinical manifestations and the treatment of Parkinson's disease (PD). DRD3 Ser9Gly polymorphism is the most frequently studied variant point. Our aim was to investigate the potential effect of DRD3 Ser9Gly polymorphism on modulating resting-state brain function and associative clinical manifestations in PD patients. Methods: We consecutively recruited 61 idiopathic PD patients and 47 healthy controls (HC) who were evaluated by clinical scales, genotyped for variant Ser9Gly in DRD3 and underwent resting-state functional magnetic resonance imaging. Based on DRD3 Ser9Gly polymorphism, PD patients and HCs were divided into four subgroups. Then, two-way analysis of covariance (ANCOVA) was applied to investigate main effects and interactions of PD and DRD3 Ser9Gly polymorphism on the brain function via amplitude of low-frequency fluctuations (ALFF) approach. The association between DRD3 Ser9Gly-modulated significantly different brain regions and clinical manifestations was detected by Spearman's correlations. Findings: PD patients exhibited decreased ALFF values in right inferior occipital gyrus, lingual gyrus and fusiform gyrus. A significant difference in the interaction of groups × genotypes was observed in right medial frontal gyrus. The ALFF value of the cluster showing significant interactions was positive correlated with HAMD-17 scores (r=0.489, p=0.011) in PD patients with the Ser/Gly or Gly/Gly genotypes. Interpretation: D3 gene Ser9Gly polymorphism might be associated with depression severity in PD patients. Funding Statement: This work was supported by the National Natural Science Foundation of China (No.81671258), the Science and Technology Project of Jiangsu Provincial Commission of Health and Family Planning (No.H201602), the Natural science foundation of Jiangsu Province (No.BK20141494), the Jiangsu Provincial Personnel Department “the Great of Six Talented Man Peak” Project (No.2014-WSN-013), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the Science and Technology Project of Jiangsu Bureau of Traditional Chinese Medicine (No.YB2015163). Declaration of Interests: The authors declare none. Ethics Approval Statement: This study was approved by the ethics committee of the First Affiliated Hospital of Nanjing Medical University and all participants provided us with written informed consent before participating in the experiment.

P106. Anodal tDCS over the left sensorimotor area improves motor symptoms and modulates corticocortical coherence in Parkinson’s disease

Network activity in the beta range is correlated with motor symptoms in Parkinson’s disease (PD). Anodal transcranial direct current stimulation (atDCS) over the sensorimotor area modulates cortical excitability and may alleviate motor symptoms in PD. In this study, we aimed to explore the effect of atDCS over the left sensorimotor area on clinical motor outcome, right hand fine motor performance and cortical motor network connectivity. In this double-blind randomized sham-controlled combined EEG and tDCS study, we investigated ten pharmacologically treated idiopathic PD patients after overnight withdrawal of dopaminergic medication and eleven healthy controls during an isometric precision grip task of the right hand before and after stimulation. Participants were studied and crossed-over in two sessions on different days with either ‘verum’ or ‘sham’ stimulation of atDCS (20 min; 1 mA; electrodes placed over left ‘C3’ (anode) and right ‘Fp2’ (cathode)). Cortical connectivity was expressed as corticocortical imaginary coherence in the high beta band (22–27 Hz) between ‘C3’ and all other EEG-channels; the topographic distribution was obtained from 25 cortical EEG channels placed according to the 10–20 system. Fine motor performance was expressed as accuracy error during the precision grip task with lower accuracy error indicating higher motor precision. Clinical motor outcome was measured using the UPDRS III motor score. PD patients with ‘verum’ stimulation showed an increase of corticocortical imaginary coherence in the high beta band from ‘C3’ to the right motor area 30 min after stimulation. This was paralleled by a significant decrease in the UPDRS III motor score. There was no similar modulation in PD ‘sham’ stimulation and in healthy controls in both ‘verum’ and ‘sham’ conditions. However, interestingly, HC showed beta band coupling prior to stimulation directed from ‘C3’ to the right hemisphere. Both groups showed no significant change regarding the accuracy error after stimulation. AtDCS of ‘C3’ entrains beta band coupling between ‘C3’ and the right sensorimotor area with ‘C3’ leading right hemispheric beta band oscillations in the temporal domain. We speculate that this could represent a mechanism to tone down inhibitory influences of the right hemisphere ipsilateral to the right hand, given that increased beta synchrony is associated with increasing motor inhibition in previous studies.

The Parkinson's disease VPS35[D620N] mutation enhances LRRK2-mediated Rab protein phosphorylation in mouse and human.

Missense mutations in the LRRK2 (Leucine-rich repeat protein kinase-2) and VPS35 genes result in autosomal dominant Parkinson's disease. The VPS35 gene encodes for the cargo-binding component of the retromer complex, while LRRK2 modulates vesicular trafficking by phosphorylating a subgroup of Rab proteins. Pathogenic mutations in LRRK2 increase its kinase activity. It is not known how the only thus far described pathogenic VPS35 mutation, [p.D620N] exerts its effects. We reveal that the VPS35[D620N] knock-in mutation strikingly elevates LRRK2-mediated phosphorylation of Rab8A, Rab10, and Rab12 in mouse embryonic fibroblasts. The VPS35[D620N] mutation also increases Rab10 phosphorylation in mouse tissues (the lung, kidney, spleen, and brain). Furthermore, LRRK2-mediated Rab10 phosphorylation is increased in neutrophils as well as monocytes isolated from three Parkinson's patients with a heterozygous VPS35[D620N] mutation compared with healthy donors and idiopathic Parkinson's patients. LRRK2-mediated Rab10 phosphorylation is significantly suppressed by knock-out or knock-down of VPS35 in wild-type, LRRK2[R1441C], or VPS35[D620N] cells. Finally, VPS35[D620N] mutation promotes Rab10 phosphorylation more potently than LRRK2 pathogenic mutations. Available data suggest that Parkinson's patients with VPS35[D620N] develop the disease at a younger age than those with LRRK2 mutations. Our observations indicate that VPS35 controls LRRK2 activity and that the VPS35[D620N] mutation results in a gain of function, potentially causing PD through hyperactivation of the LRRK2 kinase. Our findings suggest that it may be possible to elaborate compounds that target the retromer complex to suppress LRRK2 activity. Moreover, patients with VPS35[D620N] associated Parkinson's might benefit from LRRK2 inhibitor treatment that have entered clinical trials in humans.

The Clinical Frailty Scale Predicts Inpatient Mortality in Older Hospitalised Patients with Idiopathic Parkinson'S Disease

We conducted an observational retrospective study in a large tertiary university hospital between October 2014 and October 2016. Routinely measured patient characteristics included demographics (age and sex), Clinical Frailty Scale, acute illness severity (Emergency Department Modified Early Warning Score), the Charlson Comorbidity Index, discharge specialty, history of dementia, history of depression and the presence of a new cognitive impairment. Outcomes studied were inpatient mortality, death within 30 days of discharge, new institutionalisation, length of stay ≥ 7 days and readmission within 30 days to the same hospital. There were 393 first admission episodes of idiopathic Parkinson's disease patients aged 75 years or more; 166 (42.2%) were female. The mean age (standard deviation) was 82.8 (5.0) years. The mean Clinical Frailty Scale was 5.9 (1.4) and the mean Charlson Comorbidity Index was 1.3 (1.5). After adjustment for covariates, frailty and acute illness severity were independent predictors of inpatient mortality; odds ratio for severely/very severely frail or terminally ill = 8.1, 95% confidence interval 1.0-63.5, p = 0.045 and odds ratio for acute illness severity: 1.3, 95% confidence interval 1.1-1.6, p = 0.005). The Clinical Frailty Scale did not significantly predict other hospital outcomes. The Clinical Frailty Scale was a significant predictor of inpatient mortality in idiopathic Parkinson's disease patients admitted to the acute hospital and it may be useful as a marker of risk in this vulnerable population.

Parkinson disease in eldery patients: lessons from odour detection thresholds on olfacto-trigeminal interaction.

Human nasal chemosensation is mediated by two separate, though interacting sensory pathways: the trigeminal and olfactory systems. Trigeminal sensitivity and olfacto-trigeminal interactions have not yet been well studied in idiopathic Parkinsons disease (IPD). The aim of this study was to assess odour detection thresholds in elderly IPD patients, and compare them to the odour detection thresholds of healthy controls. Finally, we investigated potential interactions between trigeminal and olfactory sensitivity. 89 IPD patients aged over 65 and 89 matched healthy participants were enrolled in the study. Odour detection thresholds to 3 stimuli differentially activating olfactory and trigeminal afferents (Phenyl-ethyl alcohol, n-Butanol and Pyridine) were assessed, using an ascending staircase, binary forced-choice procedure. Detection threshold scores were able to discriminate between elderly IPD and controls. Pyridine was less effective than the two other odorants, suggesting that trigeminal pathway is less impaired than the olfactory system. We found that the detection thresholds were significantly different between IPD patients with good autonomy, and patients with impaired autonomy.

Cerebral Imaging Markers of GBA and LRRK2 Related Parkinson's Disease and Their First-Degree Unaffected Relatives.

Cerebral atrophy has been detected in patients with Parkinson's disease (PD) both with and without dementia, however differentiation based on genetic status has thus far not yielded robust findings. We assessed cortical thickness and subcortical volumes in a cohort of PD patients and healthy controls carriers of the G2019S mutation in the LRRK2 gene and the common GBA mutations, in an attempt to determine whether genetic status influences structural indexes. Cortical thickness and subcortical volumes were computed and compared between six groups of participants; idiopathic PD, GBA-PD, LRRK2-PD, non-manifesting non-carriers (NMNC), GBA-non-manifesting carriers (NMC) and LRRK2-NMC utilizing the FreeSurfer software program. All participants were cognitively intact based on a computerized cognitive assessment battery. Fifty-seven idiopathic PD patients, 9 LRRK2-PD, 12 GBA-PD, 49 NMNC, 41 LRRK2-NMC and 14 GBA-NMC participated in this study. Lower volumes among patients with PD compared to unaffected participants were detected in bilateral hippocampus, nucleus accumbens, caudate, thalamus, putamen and amygdala and the right pallidum (p = 0.016). PD patients demonstrated lower cortical thickness indexes in a majority of regions assessed compared with non-manifesting participants. No differences in cortical thickness and subcortical volumes were detected within each of the groups of participants based on genetic status. Mutations in the GBA and LRRK2 genes are not important determinants of cortical thickness and subcortical volumes in both patients with PD and non-manifesting participants. PD is associated with a general reduction in cortical thickness and sub-cortical atrophy even in cognitively intact patients.

Sensory neuropathic symptoms in idiopathic Parkinson's disease: prevalence and impact on quality of life.

Neuropathic symptoms are commonly reported in Parkinson's disease (PD), but robust data on the epidemiology of such symptoms are lacking. The present study sought to investigate the prevalence and determinants of peripheral sensory neuropathic symptoms (PSNS) in idiopathic PD (IPD) and ascertain the effects of such symptoms on the patients' quality of life (QoL). Patients with IPD and age-matched and gender-matched controls were screened for neuropathic symptoms using the Michigan Neuropathy Screening Instrument. The impact of neuropathic symptoms on QoL was investigated using the 36-Item Short Form Survey. Fifty-two patients and 52 age-matched and gender-matched controls were recruited. PSNS were reported more frequently in patients with IPD than in the control subjects (57.7 versus 28.8%, p = 0.003). No significant relationships were found between PD-related clinical characteristics (i.e. disease severity and duration, duration of exposure to levodopa) and the presence of PSNS. Significant correlations were found between the number of PSNS and physical functioning (Spearman's Rho - 0.351), even after adjusting for age, gender and Hoehn and Yahr score. Our results support the notion of a greater prevalence of PSNS in IPD patients as compared to the general population, which, at least in part, may be secondary to large and/or small fibre peripheral neuropathy. This warrants further investigation in larger studies that include detailed neurophysiological assessments.

Parkinson's disease phenotype is influenced by the severity of the mutations in the GBA gene

ObjectiveMutations in the glucocerebrosidase (GBA) gene are divided into mild and severe (mGBA, sGBA) based on their contribution to the phenotype of Gaucher disease (GD) among homozygotes. We conducted a longitudinal analysis of Parkinson's disease (PD) patients carrying mutations in the GBA gene to better characterize genotype-phenotype correlations. MethodsPatients underwent a comprehensive assessment of medical, neurological, cognitive and non-motor functions. Data from these patients was explored to evaluate differences in disease phenotype based on genotype. ResultsA total of 355 PD patients participated in this study; 152 idiopathic PD patients, 139 mGBA, 48 sGBA and 16 GD-PD. Groups were similar in age, sex, years of education and age of onset. Both sGBA and GD-PD had higher Unified Parkinson Disease Rating Scale (UPDRS) scores (p = 0.041), higher frequencies of REM sleep behavior disorder (RBD) (p = 0.022) and hallucinations (p < 0.0001) compared to the other groups of patients. sGBA experienced more non-motor symptoms (p < 0.0001), depression (p < 0.001) and worse hyposmia (p = 0.010). Trail making test was significantly longer in GD-PD followed by sGBA, mGBA and iPD (p = 0.005). DiscussionMotor, cognitive, olfactory and psychiatric symptoms are more severe in sGBA and GD-PD compared to mGBA and iPD, reinforcing the notion that the severity of the PD phenotype is related to the severity of the mutation in the GBA gene.

Incidence of sarcopenia and dynapenia according to stage in patients with idiopathic Parkinson's disease.

In this study, the aim was to identify the incidence of sarcopenia and dynapenia according to disease stage among idiopathic Parkinson's disease (IPD) patients and collect data to illuminate precautions related to reducing the disease load. The study was completed with 166 patients divided by stage according to modified Hoehn and Yahr (HYR) criteria and 249 healthy volunteers aged from 18 to 39 and 68 to 75years met the inclusion criteria. In our prospective and cross-sectional study, patients with IPD according to "UK Brain Bank" diagnostic criteria had the Unified Parkinson's Disease Rating Scale (UPDRS) and HYR scales applied. The patient and control groups had skeletal muscle mass index (SMMI), muscle power, and physical performance assessed. Diagnosis of sarcopenia used the European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic criteria. In our study, in parallel with the increase in disease stage among IPD patients, the incidence of sarcopenia (led by severe sarcopenia) and dynapenia was high compared to that among the control group of the same age. In the early stages of chronic progressive diseases like IPD, identification of sarcopenia and dynapenia is important considering the limitations of disease-preventive effects in treatments applied after diagnosis.

The cortical excitability profile of patients with the G209A SNCA mutation versus patients with sporadic Parkinson's disease: A transcranial magnetic stimulation study

Mutations in the α-synuclein gene are a rare cause of Parkinson's disease. We investigated, by single-pulse TMS, the cortical excitability profile of nine α-synuclein patients in comparison with 24 idiopathic PD patients, subdivided into "akinetic" (n=17) and "tremor-dominant" (n=7) subgroups. The comparative assessment of rest motor threshold, active MEP and Silent Period Input/Output curves indicated that the cortical excitability of α-Synuclein patients is similar to patients with the "akinetic" form of PD. Both groups of patients exhibited differences in excitatory and inhibitory brain circuits from "tremor-dominant" patients indicating that varying clinical phenotypes are associated with differential profiles of corticospinal excitability.

Interleukin-18 promoter polymorphisms and idiopathic Parkinson disease: an Egyptian study.

Etiology of sporadic Parkinson's disease (PD) is largely unknown. The contribution of genetic factors to the pathogenesis of PD is supported by the demonstration of high concordance in twins, increased risk among relatives of PD patients and existence of familial cases. This study aimed to examine the relation between interleukin 18 (IL-18) gene promoter polymorphisms and idiopathic PD, and its impact on clinical presentation and disease severity. 30 idiopathic PD patients and 15 age- and sex-matched healthy subjects were included. Disease severity was assessed using Unified Parkinson's Disease Rating Scale (UPDRS). Genetic testing for IL-18 gene promoter -607C/A single nucleotide polymorphisms (SNP) was done using real-time polymerase chain reaction (PCR) technique. A raised risk of PD development was found in patients with A/C and C/C genotypes of the site -607C/A (odds ratios = 1.83 and 1.98, respectively). The distribution of the genotypes showed no significant relation to gender or predominant clinical presentation. The age at onset of disease was significantly lower in C/C and A/A genotypes compared to A/C genotype (p = 0.001 and 0.04, respectively). Patients with A/A genotype showed significantly higher mentation score of UPDRS compared to patients with A/C and C/C genotypes (p = 0.003 and p = 0.002, respectively). Polymorphisms of IL-18 gene promoter increase the risk of developing idiopathic PD. The polymorphisms may affect phenotypic expression rather than being a direct cause of idiopathic PD.

LRRK2-associated Parkinson's disease patients have better stereopsis than idiopathic Parkinson disease

ObjectivesVisual dysfunctions are frequent and have several manifestations in idiopathic Parkinson's disease (PD). However, the characteristics of these complications in LRRK2 (leucine-rich kinase 2)-associated PD patients still lack systematic research. The purpose of this study is to assess visual functions of LRRK2-associated PD patients. Patients and methodsTwenty-five (25) PD patients with LRRK2 R1628P and G2385R variants were included in the study and compared to 28 PD patients without these variants and 28 age-matched healthy controls. The genotypes of PD patients were kept double-blinded. Information on age, sex, disease duration, the movement disorder society-unified Parkinson's disease rating scale (MDS-UPDRS), Hoehn and Yahr staging scale (H&Y), Mini-Mental Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were included. Visual functions assessment included color perception, contrast sensitivity and stereopsis. ResultsPD patients with or without LRRK2 R1628P and G2385R variants have declined contrast sensitivity, diminished color discrimination and damaged stereopsis. There was no significant difference in retinal level visual deficiency (color discrimination and contrast sensitivity) between PD with LRRK2 variants and those without, but cortex level visual function, i.e. stereopsis is better in PD with LRRK2 variants than non-carrier PD patients. The associated factors of stereopsis are different. The stereopsis is associated with MoCA scores independently in non-carrier PD patients, but with UPDRSIII scores in LRRK2-associated PD patients. ConclusionsVisual functions are similarly affected in PD patients with and without LRRK2 R1628P and G2385R variants, but LRRK2-associated PD patients have better stereopsis than idiopathic PD patients.

Qualitative postural control differences in Idiopathic Parkinson’s Disease vs. Progressive Supranuclear Palsy with dynamic-on-static platform tilt

ObjectivesWe aimed to assess whether postural abnormalities in Progressive Supranuclear Palsy (PSP) and Idiopathic Parkinson’s Disease (IPD) are qualitatively different by analysing spontaneous and reactive postural control. MethodsWe assessed postural control upon platform tilts in 17 PSP, 11 IPD patients and 18 healthy control subjects using a systems analysis approach. ResultsSpontaneous sway abnormalities in PSP resembled those of IPD patients. Spontaneous sway was smaller, slower and contained lower frequencies in both PSP and IPD as compared to healthy subjects. The amount of angular body excursions as a function of platform angular excursions (GAIN) in PSP was qualitatively different from both IPD and healthy subjects (GAIN cut-off value: 2.9, sensitivity of 94%, specificity of 72%). This effect was pronounced at the upper body level and at low as well as high frequencies. In contrast, IPD patients’ stimulus-related body excursions were smaller compared to healthy subjects. Using a systems analysis approach, we were able to allocate these different postural strategies to differences in the use of sensory information as well as to different error correction efforts. ConclusionsWhile both PSP and IPD patients show abnormal postural control, the underlying pathology seems to be different. SignificanceThe identification of disease-specific postural abnormalities shown here may be helpful for diagnostic as well as therapeutic discriminations of PSP vs. IPD.