Idiopathic Parkinson's Disease Patients Research Articles

Free-Water Imaging of the Substantia Nigra in GBA Pathogenic Variant Carriers.

Pathogenic variants in the glucocerebrosidase gene (GBA) have been identified as the most common genetic risk factor for Parkinson's disease (PD). However, the features of substantia nigra damage in GBA pathogenic variant carriers remain unclear. We aimed to evaluate the microstructural changes in the substantia nigra in non-manifesting GBA pathogenic variant carriers (GBA-NMC) and PD patients with GBA pathogenic variant (GBA-PD) with free-water imaging. First, we compared free water values in the posterior substantia nigra between non-manifesting non-carriers (NMNC, n=29), GBA-NMC (n=26), and GBA-PD (n=16). Then, free water values in the posterior substantia nigra were compared between GBA-PD and early- (n=19) and late-onset (n=40) idiopathic PD (iPD) patients. Furthermore, we examined whether the baseline free water values could predict the progressions of clinical symptoms. The free water values in the posterior substantia nigra were significantly higher in the GBA-NMC and GBA-PD groups compared to NMNC, and were significantly increased in the GBA-PD group than both early- and late-onset iPD. Free water values in the posterior substantia nigra could predict the progression of anxiety and cognitive decline in GBA-NMC and GBA-PD groups. We demonstrate that free water values are elevated in the substantia nigra and predict the development of non-motor symptoms in GBA-NMC and GBA-PD. Our findings demonstrate that a significant nigral impairment already exists in GBA-NMC, and nigral injury may be more severe in GBA-PD than in iPD. These results support that free-water imaging can as a potential early marker of substantia nigra damage. © 2023 International Parkinson and Movement Disorder Society.

Supportive care of neurodegenerative patients.

Neurodegenerative illnesses are notorious for paucity of treatments and relentless clinical progression. Illness may follow a relatively acute presentation, as is seen with primary brain tumors such as glioblastoma or have a more insidious onset with a slower yet unyielding course, such as that seen in Parkinson's disease. Though disparate in presentation, these neurodegenerative illnesses are universally terminal, and both the patients and their families benefit from the intervention of supportive care in conjunction with primary disease management. Supportive palliative care has been shown to improve quality of life, enhance patient outcomes, and often extend patient life-but such care needs to be tailored. This clinical commentary examines the role of supportive palliative care in the management of neurologic patients, comparing and contrasting glioblastoma patients with idiopathic Parkinson's disease patients. Both patient populations are high utilizers of healthcare resources, require active management of multiple symptoms, and have high caregiver burden which underscores the need for supportive services in conjunction with disease management provided by the primary care team. Review of prognostication, patient and family communication, trust and relationship building, and complementary medicinal approaches are explored for these two diseases which broadly represent two differing poles of incurable neurological illness.

Serum neurofilament light chain in LRRK2 related Parkinson’s disease: A five years follow-up

BackgroundStudies revealed that serum neurofilament light chain (NFL) levels not only increase considerably over time in Parkinson's disease (PD) but also have a significant association with disease progression. However, there is no evidence of the level of serum NFL in PD patients with leucine-rich repeat kinase 2 (LRRK2) mutation (LRRK2-PD) which is the most common mutation that causes familial and sporadic PD. AimHere we aimed to investigate the difference and longitudinal alteration of the serum level of NFL in LRRK2-PD and idiopathic PD (iPD) patients. MethodsWe entered 228 iPD and 103 LRRK2-PD patients and 176 healthy controls (HCs) from PPMI. We compared the level of serum NFL at baseline, six months, one year, two years, three years, and five years visits. Also, we used linear mixed models to assess longitudinal changes of serum NFL over six months, one year, two years, three years, and five years within groups. ResultsWe found a significant difference in the level of serum NFL between three groups at baseline, two years, three years, and five years time points. Also, our analysis showed that LRRK2-PD patients had significantly lower serum NFL compared to iPD subjects at baseline. In the longitudinal analysis, there was no significant change in the HCs group over five years. The level of serum NFL was significantly increased after two, three, and five years from baseline in LRRK2-PD patients. Also, we found similar results for iPD subjects after three and five years from baseline. ConclusionWe can conclude that the overall neurodegeneration might be similar in LRRK2-PD and healthy subjects and lower than the idiopathic form of PD at the early stages, which may disappear in the later stages. Moreover, our findings suggest that the serum NFL might be a more accurate biomarker to distinguish iPD from healthy subjects rather than all PD patients or LRRK2-PD from healthy subjects at the early stages.

Deep Learning Algorithm of 12-Lead Electrocardiogram for Parkinson Disease Screening.

Although idiopathic Parkinson's disease (IPD) is increasing with the aging population, there is no adequate screening test for early diagnosis of IPD. Cardiac autonomic dysfunction begins in the early stages of IPD, and an electrocardiogram (ECG) contains precise information on the heart. This study is to develop an ECG deep learning algorithm that can efficiently screen for IPD. Data were collected from 751 IPD patients (2,138 ECGs), 751 age and sex-matched non-IPD patients (2,673 ECGs) as a control group, and 297 drug-induced Parkinsonism (DPD) patients (875 ECGs) as a disease control group. ECG data were randomly divided into training set, validation set, and test set at a ratio of 6:2:2. We developed a deep-convolutional neural network (CNN) consisting of 16 layers with Bayesian optimization that classified IPD patients by ECG data. The robustness of the deep learning model was verified through 5-fold cross-validation. The AUROC of the model for detection of IPD was 0.924 (95% CI, 0.913-0.936) in the test set. That for detecting DPD was 0.473 (95% CI, 0.453-0.504). The sensitivities of the model according to Unified Parkinson's Disease Rating Scale III and Hoehn & Yahr scale were also similar. In conclusion, the CNN-based deep learning model using ECG data showed quite good performance in identifying IPD patients. Standardized 12-lead ECG test could be one of the clinically feasible candidate methods for early screening of IPD in the future.

In Vivo Investigation of Glucose Metabolism in Idiopathic and PRKN-Related Parkinson's Disease.

Alterations in mitochondrial dysfunction have been implicated in the pathogenesis of Parkinson's disease (PD). Mitochondrial energy production is linked to glucose metabolism, and diabetes is associated with PD. However, studies investigating glucose metabolism in vivo in genetically stratified PD patients and controls have yet to be performed. The objectives of this study were to explore glucose production, gluconeogenesis, and the contribution of gluconeogenesis to glucose production in idiopathic and PRKN PD compared with healthy controls with state-of-the-art biochemical methods. We applied a dried-blood sampling/gas chromatography/mass spectrometry approach to monitor fluxes in the Cori cycle in vivo. The contribution of gluconeogenesis to total glucose production is increased in idiopathic PD patients (n=33), but not in biallelic PRKN mutation carriers (n=5) compared with healthy controls (n=13). We provide first-time in vivo evidence for alterations in glucose metabolism in idiopathic PD, in keeping with the epidemiological evidence for an association between PD and diabetes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Functional connectome automatically differentiates multiple system atrophy (parkinsonian type) from idiopathic Parkinson's disease at early stages.

Differentiating the parkinsonian variant of multiple system atrophy (MSA-P) from idiopathic Parkinson's disease (IPD) is challenging, especially in the early stages. This study aimed to investigate differences and similarities in the brain functional connectomes of IPD and MSA-P patients and use machine learning methods to explore the diagnostic utility of these features. Resting-state fMRI data were acquired from 88 healthy controls, 76 MSA-P patients, and 53 IPD patients using a 3.0T scanner. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 116 regions, and topological properties were evaluated through graph theory approaches. Connectome measurements were used as features in machine learning models (random forest [RF]/logistic regression [LR]/support vector machine) to distinguish IPD and MSA-P patients. Regarding graph metrics, early IPD and MSA-P patients shared network topological properties. Both patient groups showed functional connectivity disruptions within the cerebellum-basal ganglia-cortical network, but these disconnections were mainly in the cortico-thalamo-cerebellar circuits in MSA-P patients and the basal ganglia-thalamo-cortical circuits in IPD patients. Among the connectome parameters, t tests combined with the RF method identified 15 features, from which the LR classifier achieved the best diagnostic performance on the validation set (accuracy=92.31%, sensitivity=90.91%, specificity=93.33%, area under the receiver operating characteristic curve=0.89). MSA-P and IPD patients show similar whole-brain network topological alterations. MSA-P primarily affects cerebellar nodes, and IPD primarily affects basal ganglia nodes; both conditions disrupt the cerebellum-basal ganglia-cortical network. Moreover, functional connectome parameters showed outstanding value in the differential diagnosis of early MSA-P and IPD.

Treatment Reconciliation in Parkinson’s Disease Patients with Particular Reference to Wearing-off and Motor fluctuations: A Registry-based, Prospective, Observational Study

Introduction: Parkinson’s Disease (PD) is the second most frequent neurodegenerative disease and dopaminergic agents are frequently used as a treatment while ‘end of dose deterioration’ or ‘Wearing-Off (WO)’ phenomenon is common with these agents. Treatment reconciliation may be helpful in this situation and there is dearth of studies especially in India. Aim: To study the WO effects in patients of PD, their pharmacotherapy and outcome. Materials and Methods: This registry-based, prospective, observational, outcomes-based study was conducted in the Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal, India, in collaboration with Department of Neuromedicine of Kolkata Medical College and private clinics of a Neurologist from January 2020 to December 2021. An attempt was also undertaken to make a registry of Idiopathic Parkinson’s Disease (IPD) patients. WO Questionnaire 19-items (WOQ19), Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS Scale), The 39-items Parkinson’s Disease Questionnaire (PDQ-39 questionnaire), The 8-items Morisky Medication Adherence Scale (MMAS scale), suspected Adverse Drug Reaction (ADR) Reporting Form of Indian Pharmacoepia commission (version 1.3), World Health Organisation- Uppsala Monitoring Centre (WHO-UMC) Scale, Naranjo causality assessment scale, Hartwig and Seigel’s Severity Assessment Scale were used in the present study. The study was commenced after obtaining approval from institutional ethics committee. The data was then analysed with parametric or non parametric tests using (mean±Standard Deviation (SD), median, Fisher’s-exact test, Friedman’s Analysis of Variance (ANOVA) test, Wilcoxon matched pair signedrank test). Data collected and then statistically analysed by using WPS Excel version 2021 and GraphPad Prism version 9 software. Results: Total IPD patients were found to be 111 in the present study with a mean age of IPD patients as 61.85±7.20 years. Incidence of WO in the present study was found to be 40.5% among IPD patients. Most common characteristic of WO was found to be tremor in 104 (28.8%) patients followed by slowness of movement in 63 (17.5%) patients. WHO-UMC scale and Naranjo causality assesment scale both revealed 36.4% ADRs were probable category and 63.6% were possible category. MDS-UPDRS Score, PDQ-39 Score, MMAS-8 score significantly (p-value<0.05) improved during the course of treatment. Conclusion: Dose adjustment of syndopa was mostly used in the management of WO phenomenon and significant improvement in the quality of life of the patients was seen.

Neurogenic Supine Hypertension and Cardiovascular Autonomic Dysfunction in Patients with Parkinson's Disease.

Natural history and disease progression in patients with Idiopathic Parkinson's Disease (PD) is quite heterogeneous. Autonomic dysfunction occurs commonly among Idiopathic PD patients. Heart rate variability and ambulatory blood pressure monitoring are used to assess cardiac autonomic dysfunction. The prevalence and magnitude of supine hypertension in Indian PD patients has not been studied to date. The present study aimed to record cardiovascular autonomic functions and supine hypertension in PD patients and to correlate them with the age of onset, duration and severity of the disease, and non-motor symptom burden. The cross-sectional study involved 60 PD patients. Webster rating scale was used to determine the disease severity. Non-motor symptom burden was assessed using the Non-Motor Symptom Scale (NMSS). Ambulatory blood pressure monitoring and heart rate variability parameters determined cardiac autonomic function. Supine hypertension was defined as Systolic Blood Pressure (SBP) ≥150 mmHg and/or DBP ≥90 mmHg. Less than 10% decrease or even increase in blood pressure during the night were classified as non-dippers. Pearson coefficient was used appropriately to establish correlation. P ≤ 0.05 was considered significant. Age of onset was 61.2 ± 8.7 years and duration of disease was 1.7 ± 1.1 years. Mean Webster and non-motor symptom scores were 12.7 ± 4.4 and 15.5 ± 8.0, respectively. About 50 patients (83%) were non-dipper, while 32 (53%) had supine hypertension. Low Frequency oscillations (LF) (r = 0.28), High Frequency oscillations (HF) (r = 0.29), Standard Deviation NN intervals (SDNN) (0.26), and Root Mean Squared Successive Differences of NN intervals (RMSSD) (r = 0.28) correlated significantly with non-motor symptoms scale. LF (r = -0.39), HF (r = -0.43), SDNN (-0.40), RMSSD (r = -0.41), NN50 (r = -0.38), PNN50 (r = -0.42), mean SBP (r = 0.26), and mean DBP (r = 0.33) correlated significantly with disease duration. PNN50 (r = -0.255), mean SBP (r = -0.29), and mean DBP (r = -0.27) correlated significantly with age at onset. Awareness regarding neurogenic supine hypertension is needed as it occurs commonly among Indian PD patients. Heart rate variability (HRV) parameters and ambulatory blood pressure are of significant help in the detection of early cardiovascular autonomic dysfunction and correlate significantly with disease duration and non-motor symptom burden among PD patients.

Retinal Vessel Density and Retinal Nerve Fiber Layer Thickness: A Prospective Study of One-Year Follow-Up of Patients with Parkinson's Disease.

This study aims to compare the superficial vascular density from the macular region and the retinal nerve fiber layer (RNFL) thickness from the optic disc region between Parkinson's disease (PD) patients and controls. We enrolled 56 idiopathic PD patients, totaling 86 eyes (PD group), and 45 sex- and age-matched healthy individuals, amounting to 90 eyes (control group). All subjects underwent examination using Zeiss wide-field vascular optical coherence tomography (OCT) (Cirrus HD-OCT 5000 Carl Zeiss, Germany), with a scanning range of 3 mm × 3 mm. We divided the images into two concentric circles with diameters of 1 mm and 3 mm at the macular fovea's center. Patients with PD were evaluated during their "off" phase using the Unified Parkinson's Disease Rating Scale III (UPDRS-III) and the Hoehn-Yahr scale (H-Y scale) to assess disease severity. The PD group exhibited significantly lower RNFL thickness (106.13±12.36 μm) compared to the control group (115.95±11.37 μm, P < 0.05). Similarly, the superficial retinal vessel length density was significantly lower in the PD group (20.7 [19.62, 22.17] mm-1) than in the control group (21.79±1.16 mm-1, P < 0.05). Correlation analysis revealed a negative correlation between RNFL thickness and UPDRS III score (rs=-0.036, P=0.037), and RNFL thickness tended to decrease with increasing severity of movement disorders. However, during the 6 and 12-month follow-up of some PD patients, we observed no progressive thinning of the RNFL or decreased superficial vascular density. PD patients show retinal structural damage characterized by RNFL thinning and reduced retinal vessel length density. However, RNFL thickness did not correlate with vascular density nor did it decrease with the disease's progression.

Mitochondrial DNA heteroplasmy distinguishes disease manifestation in PINK1/PRKN-linked Parkinson's disease.

Biallelic mutations in PINK1/PRKN cause recessive Parkinson's disease. Given the established role of PINK1/Parkin in regulating mitochondrial dynamics, we explored mitochondrial DNA integrity and inflammation as disease modifiers in carriers of mutations in these genes. Mitochondrial DNA integrity was investigated in a large collection of biallelic (n = 84) and monoallelic (n = 170) carriers of PINK1/PRKN mutations, idiopathic Parkinson's disease patients (n = 67) and controls (n = 90). In addition, we studied global gene expression and serum cytokine levels in a subset. Affected and unaffected PINK1/PRKN monoallelic mutation carriers can be distinguished by heteroplasmic mitochondrial DNA variant load (area under the curve = 0.83, CI 0.74-0.93). Biallelic PINK1/PRKN mutation carriers harbour more heteroplasmic mitochondrial DNA variants in blood (P = 0.0006, Z = 3.63) compared to monoallelic mutation carriers. This enrichment was confirmed in induced pluripotent stem cell-derived (controls, n = 3; biallelic PRKN mutation carriers, n = 4) and post-mortem (control, n = 1; biallelic PRKN mutation carrier, n = 1) midbrain neurons. Last, the heteroplasmic mitochondrial DNA variant load correlated with IL6 levels in PINK1/PRKN mutation carriers (r = 0.57, P = 0.0074). PINK1/PRKN mutations predispose individuals to mitochondrial DNA variant accumulation in a dose- and disease-dependent manner.

Effects of Focal Muscle Vibration on Gait and Balance in Parkinson Patients: Preliminary Results

Background: Postural instability has a major impact on the mobility and daily life activities of Parkinson’s disease (PD) patients as it often leads to reduced mobility, insecure stance and falls. The aim of this study was to evaluate the effect of focal vibration on the static and dynamic balance of a group of Parkinson’s disease patients. Methods: Twenty-three idiopathic PD patients (14 M; 9 F), Hoehn and Yahr (HeY) stage II–III, underwent three weeks of focal muscle vibration applied to the quadriceps, soles of the feet and trapezius muscles bilaterally in addition to conventional physiotherapy. The static and dynamic balance was assessed at baseline (T0), after 3 weeks of treatment (T1) and after 1 month from the last treatment (T2) with the Tinetti scale and stabilometry evaluations. Results: There was a statistically significant improvement in the mean Tinetti score at T1, and in the Romberg area (CE/OE) of oscillation and oscillation velocity on the x-axis with the eyes closed at T2. Conclusions: Focal muscle vibration in conjunction with physiotherapy is a useful tool in the rehabilitation of gait and balance disorders of patients with Parkinson’s disease HeY stage II–III.

The effects of surface electrical stimulation plus voice therapy in Parkinson's disease.

This study aimed to assess the effects of surface electrical stimulation plus voice therapy on voice in dysphonic patients with idiopathic Parkinson's disease. Patients were assigned to 3 treatment groups (n = 28 per group) and received daily treatment for 3 weeks on 5 days a week. All three groups received voice therapy (usual care). In addition, two groups received surface electrical stimulation, either motor-level or sensory-level stimulation. A standardised measurement protocol to evaluate therapeutic effects included the Voice Handicap Index and videolaryngostroboscopy. Voice Handicap Index and videolaryngostroboscopic assessment showed statistically significant differences between baseline and post-treatment across all groups, without any post-treatment differences between the three groups. Intensive voice therapy (usual care) improved idiopathic Parkinson's disease patients' self-assessment of voice impairment and the videolaryngostroboscopic outcome score. However, surface electrical stimulation used as an add-on to usual care did not improve idiopathic Parkinson's disease patients' self-assessment of voice impairment or the videolaryngostroboscopic outcome scores any further.

Role of middle latency auditory evoked potentials in parkinsonism

Introduction: Middle latency auditory evoked potentials (MLAEPs) allow the assessment of the function of the central part of the auditory pathway. MLAEP abnormalities have been demonstrated in patients with Alzheimer’s and Parkinson’s disease with dementia. Objective: The objective of our study was to assess the MLAEP findings in patients with idiopathic Parkinson’s disease (IPD) and atypical parkinsonism (AP) and to determine whether MLAEPs could contribute to the differential diagnosis of IPD and AP. Methods: We included 75 participants (25 IPD patients, 25 AP, and 25 age-matched healthy control subjects). MLAEPs were recorded in all patients and control subjects as per the standard procedure for MLAEP recordings. Absent waveforms (Na and Pa waves) and prolonged latencies of individual waves were considered as abnormal MLAEP readings. Results: The Pb waveform was significantly absent in the patients with IPD and AP compared to control subjects (p = 0.02). The Pb waveform was significantly absent in the AP group compared to the IPD group (p = 0.03). The Pb waveform was significantly absent in the AP group without cognitive impairment compared to the IPD group without cognitive impairment (p = 0.003). There was no statistically significant difference between the patients with IPD with and without cognitive impairment (p = 0.07). There was no significant difference among the groups with respect to Na and Pa wave latencies. Other parameters such as Na–Pa amplitude and Nb–Pb amplitudes were not significant among the groups. Conclusion: The absence of Pb potential in AP is an electrophysiological clue for the diagnosis of AP in patients presenting with parkinsonism. MLAEPs can act as an electrophysiological adjunct to the clinical imaging markers in differentiating IPD from AP.

Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients.

Characteristics of Cognitive Impairment and Their Relationship With Total Cerebral Small Vascular Disease Score in Parkinson's Disease.

BackgroundThis study aimed to investigate the characteristics of cognitive dysfunctions and their relationship with total cerebral small vascular disease (CSVD) in Parkinson’s disease (PD).MethodsA total of 174 idiopathic PD patients who underwent brain magnetic resonance imaging (MRI) were recruited. Demographic information, vascular disease risk factors, motor function (MDS-UPDRS III score), and cognitive level (MoCA, MMSE) were collected for these patients. The total CSVD burden was scored based on lacunes, enlarged perivascular spaces (EPVS), high-grade white matter hyperintensities (WMH), and cerebral microbleeds (CMBs) for each subject.ResultsCognitive scores on MoCA for language, delayed recall, and orientation were significantly reduced in PD patients with CSVD burden ≥ 1 than in those with CSVD burden = 0. Educational level, PDQ 39, and CSVD burden were significantly associated with MoCA scores in individuals with PD. For the whole group, the full model accounted for 33.6% variation in total MoCA scores. In which, CSVD burden explained 2.7% of the results, and the detection of lacunes, WMH, EPVS, and strictly lobar CMBs were significantly correlated with MoCA scores. The stability of the outcomes was confirmed by sensitivity analysis.ConclusionCSVD can independently contribute to cognitive decline in PD and cause damage in specific cognitive domains. Promoting neurovascular health may help preserve cognitive functions in PD.

Clinical profiles and outcomes of deep brain stimulation in G2019S LRRK2 Parkinson disease.

The objective of this study was to evaluate clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) and idiopathic PD (IPD). The authors conducted a clinic-based cohort study of PD patients recruited from the Mount Sinai Beth Israel Genetics database of PD studies. The cohort included 87 participants with LRRK2-PD (13 who underwent DBS) and 14 DBS participants with IPD enrolled between 2009 and 2017. The baseline clinical features, including motor ratings and levodopa-equivalent daily dose (LEDD), were compared among LRRK2-PD patients with and without DBS, between LRRK2-PD with DBS and IPD with DBS, and between LRRK2-PD with subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) DBS. Longitudinal motor scores (Unified Parkinson's Disease Rating Scale-part III) and medication usage were also assessed pre- and postoperatively. Compared to LRRK2-PD without DBS (n = 74), the LRRK2-PD with DBS cohort (n = 13) had a significantly younger age of onset, longer disease duration, were more likely to have dyskinesia, and were less likely to experience hand tremor at disease onset. LRRK2-PD participants were also more likely to be referred for surgery because of severe dyskinesia (11/13 [85%] vs 6/14 [43%], p = 0.04) and were less likely to be referred for medically refractory tremor (0/13 [0%] vs 6/14 [43%], p = 0.02) than were IPD patients. Among LRRK2-PD patients, both STN-DBS and GPi-DBS targets were effective, although the sample size was small for both groups. There were no revisions or adverse effects reported in the GPi-DBS group, while 2 of the LRRK2-PD participants who underwent STN-DBS required revisions and a third reported depression as a stimulation-related side effect. Medication reduction favored the STN group. The LRRK2-PD cohort referred for DBS had a slightly different profile, including earlier age of onset and dyskinesia. Both the STN and GPi DBS targets were effective in symptom suppression. Patients with G2019S LRRK2 PD were well-suited for DBS therapy and had favorable motor outcomes regardless of the DBS target. LRRK2-DBS patients had longer disease durations and tended to have more dyskinesia. Dyskinesia commonly served as the trigger for DBS surgical candidacy. Medication-refractory tremor was not a common indication for surgery in the LRRK2 cohort.

Effects of a rehabilitation program for Parkinson’s patients on reaction and movement time: an electromyographic study

Purpose: The aim of the study was to investigate the effects of a rehabilitation program consisting of specific exercises for Parkinson's Disease (PD) patients on reaction time (RT), movement time (MT), quality of life and disease activity.&#x0D; Materials and Methods: A total of 26 idiopathic PD patients were included in the study. The exercises specific to Parkinson’s were applied to the patients for 16 weeks. The evaluation of the patients were done before and after the treatment. The disease severity was measured with Unified Parkinson’s Disease Rating Scale (UPDRS), quality of life was measured with Short Form-36 (SF-36). RT and MT measurements were done electromyographically.&#x0D; Results: There was no statistically significant difference in UPDRS total and sub-section values and SF-36 quality of life evaluation before and after the exercise program. While a significant decrease was observed in the RT values of the patients after the 16 week exercise program compared to prior to the program (Deltoid RT 370.46 ± 25 to 219.58 ± 17, biceps RT 370.42 ± 27 to 216.49 ± 14 and triceps RT 445.21 ± 31 to 247.53 ± 23, respectively).&#x0D; Conclusion: In PD, the rehabilitation program specific to the disease leads to a significant decrease in RT. Although the exercise has no statistically significant effect on disease activity, quality of life and MT values, it was seen that it still led to improvement.

Phosphorylated alpha-synuclein in Iba1-positive macrophages in the skin of patients with Parkinson's disease.

BackgroundIncreasing evidence suggests that alpha‐synuclein (αSyn) accumulation in cholinergic and adrenergic fibers in the skin is a useful biomarker to diagnose idiopathic Parkinson's disease (IPD). It has been widely reported that phosphorylated αSyn (p‐αSyn) deposits in autonomic fibers in IPD are a biomarker in the skin, but other tissue localizations have not been fully investigated.ObjectiveIt has been previously suggested that αSyn aggregates activate peripheral macrophages and that peripheral macrophages ingest pathological αsyn aggregates in aged rats or IPD patients. However, it remains to be elucidated whether peripheral macrophages in the skin of IPD patients accumulate αSyn. We evaluated whether (1) p‐αSyn deposits in dermal macrophages might represent a useful biomarker for IPD and (2) dermal macrophages play a role in the underlying pathogenesis of IPD.MethodsWe performed an immunohistological analysis of skin biopsy specimens from IPD patients and controls.ResultsWe found that (1) p‐αSyn accumulation is present in dermal macrophages in skin biopsy specimens from patients with IPD, (2) not only dermal adrenergic fibers with p‐αSyn deposits but also dermal macrophages with p‐αSyn deposits are useful biomarkers for IPD patients and (3) the number of macrophages was significantly positively correlated with the number of macrophages with p‐αSyn deposits in the dermis of IPD patients.InterpretationOur results suggest that dermal macrophages, which are innate immune cells, play an important role in IPD patients and are a novel biomarker for IPD.

The effect of hypocalcemia on motor symptoms of Parkinson’s disease

BackgroundThe disabling nature of Parkinson’s disease (PD) impairs functional mobility and worsens quality of life. Calcium imbalances are thought to have a significant role in the progression of PD.ObjectiveTo evaluate the relation between calcium deficiency and deterioration of PD motor symptoms.MethodsA total of 28 idiopathic PD patients were subjected to motor symptoms evaluation using the modified Hoehn–Yahr scale (H–Y), Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and III and Schwab and England Activities of Daily Living Scale (S–E ADL). Total and ionized serum calcium levels were measured for the PD patients and the 30 healthy control subjects.ResultsThe level of ionized calcium was significantly lower among PD patients (4.19 mg/dl ± 0.53) than in control subjects (4.8 mg/dl ± 0.35) (p < 0.0001). The PD patients with hypocalcemia showed marked deterioration of motor symptoms and significant impairment of daily life activities when compared to PD patients with normal calcium levels regarding their scores on the modified H–Y scale (p = 0.001), UPDRS-III (p = 0.001), UPDRS-II (p = 0.001), and S–E ADL scale (p = 0.001). Ionized calcium correlated significantly with PD patients’ scores on the modified H–Y scale (p = 0.019), UPDRS-Part II (p = 0.001), UPDRS-Part III (p = 0.001) and S–E ADL scale (p = 0.001). The significant cutoff point of the ionized calcium for detection of the deteriorated PD patients that presented with stages more than grade 2 of the modified H–Y scale was < 3.99 (p = 0.037) with a sensitivity of 80% and specificity of 95%.ConclusionsOur findings conclude that calcium deficiency could contribute to the deterioration of PD motor symptoms.

Combined assessment by transcranial sonography and Sniffin’ Sticks test has a similar diagnostic accuracy compared to brain SPECT for Parkinson's disease diagnosis.

ObjectivesThis study aimed to investigate the accuracy of TCS combined with the Sniffin' sticks olfactory test (SST-16) for differentiation between idiopathic PD patients and healthy controls compared to that of 99 mTc-TRODAT-1 SPECT (TRODAT). MethodsA cross-sectional study included PD patients diagnosed in accordance with United Kingdom PD Society Brain Bank criteria and a control group of age and sex- matched healthy subjects. All patients were examined by a movement disorder specialist and underwent brain SPECT using TRODAT, TCS examination and SST-16 test. Receiver Operating Characteristic (ROC) curves were used to calculate cut-off points for TCS, striatal TRODAT binding potentials and SST-16. The area under the ROC curve determined the diagnostic accuracy of the method. ResultsTwenty patients with PD (13 males and 7 females) and nine healthy subjects were included. Median age of PD onset was 56.5 years with median disease duration of 5 years. A larger substantia nigra (SN) echogenic area was observed in the PD group (p = 0.013). SN echogenic area cut-off point of 0.22 cm2 was obtained from a ROC curve for PD diagnosis. Considering this cut-off point, TCS diagnostic accuracy was estimated at 79.2% for PD diagnosis. The cut-off value of 0.90 for striatal TRODAT binding was associated with 99% diagnostic accuracy for the diagnosis of PD. SST-16 values equal or less than 9 points showed an 85.8% diagnostic accuracy for PD diagnosis. Combination of both SST-16 and TCS improved the diagnostic accuracy to 95% for PD diagnosis. ConclusionCombined SST-16 and TCS assessment was indicated as accurate for distinguishing PD patients from healthy controls. The diagnostic accuracy of TCS combined with SST-16 for differentiation between idiopathic PD patients and healthy controls is similar to that of SPECT TRODAT.