Apathy in patients with Parkinson’s disease

Apathy is a common feature of basal ganglia disorders such as Parkinson's disease (PD), yet it is often 'invisible' to the clinician, patient and family. Factors responsible for the lack of recognition of apathy include confusion between the presence of depression and apathy and the overlap of symptoms of apathy with the phenomenology of PD. Raising awareness of apathy in PD is important because apathy contributes to PD-related disability and has an important impact on quality of life. The neurotransmitter dopamine is central to normal motivational behavior. Therefore, PD, a disorder of primary dopamine deficiency, is an ideal model for the study of apathy and its management.     

Cerebral microbleeds in patients with Parkinson’s disease

Cerebral microbleeds (CMBs) are known to be associated with cognitive impairments in the elderly and in patients with various diseases; however, the nature of this association has not yet been evaluated in Parkinson’s disease (PD). In the present study, we analyzed the incidence of CMBs in PD according to cognitive status, and the impact of CMBs on cognitive performance was also evaluated. The CMBs in PD with dementia (n = 36), mild cognitive impairment (MCI, n = 46), or cognitively normal (n = 41) were analyzed using conventional T2*-weighted gradient-recalled echo images. Additionally, the relationship between the presence of CMBs and cognitive performance on individual tests of cognitive subdomains was analyzed using a detailed neuropsychological test. CMBs occurred more frequently in PD patients with dementia (36.1 %) compared to those with MCI (15.2 %), those who are cognitively normal (14.6 %), and normal controls (12.2 %, p = 0.025). However, the significant association of CMBs with PD dementia disappeared after adjusting white matter hyperintensities (WMHs) as a covariate. The frequencies of deep, lobar, and infratentorial CMBs did not differ among the four groups. After adjusting for age, sex, years of education, and WMHs, PD patients with CMBs had poorer performance in attention domain compared with those without CMBs (34.9 vs 42.6, p = 0.018). The present data demonstrate that even though CMBs were inseparably associated with the presence of WMHs, CMBs occur more commonly in PD patients with dementia than in those without dementia. Additionally, the burden of CMBs may contribute to further cognitive impairment in PD.     

Pain perception in patients with Parkinson’s disease

Abnormalities in pain perception are a part of the clinical picture in Parkinson’s disease (PD) and belong to the category of non-motor symptoms. Two groups of patients were included in this study: (i) an experimental group of 36 patients with PD who were eligible for subthalamic deep brain stimulation (the experimental group [EG]) and (ii) a control group (CG) of 34 patients with a space-occupying lesion who were admitted for a framed stereotactic biopsy. Stereotactic frame fixation was used in both groups as a nociceptive stimulus. All participants were assessed for pain perception with two kinds of visual analogue scales (VAS) (a non-color VAS [ncVAS] and a color VAS [cVAS]) immediately after the stimulus (EG – ncVAS 1 and cVAS 1; CG – ncVAS 3 and cVAS 3) and 24 hours later (EG – ncVAS 2 and cVAS 2; CG – ncVAS 4 and cVAS 4). The means for the two pain scores assessed directly after frame fixation were 3.59 (ncVAS 1) and 3.06 (cVAS 1) for patients in the EG, while the mean ncVAS was 3, and the mean cVAS 3 was 6.1 for those in the CG. The pain intensity was significantly lower for patients with PD (EG) compared to those in the CG for both ncVAS and cVAS (p < 0.05 for each measure). The mean pain scores for ncVAS and cVAS measured 24 hours after the procedure were 3.18 and 2.79 for patients with PD (EG) and 6.10 and 5.77 for those in the CG, respectively. Pain intensity measured 24 hours after the procedure was significantly lower in those with PD (EG) compared to the CG. This study has demonstrated that pain perception in patients with PD is significantly lower than pain perception in non-parkinsonian patients.     

Development of Parkinson’s disease in patients with Narcolepsy

Although amphetamine drugs can damage dopaminergic axons, it is unknown whether chronic treatment with amphetamine increases the risk of developing Parkinson's disease (PD). Of 1,152 consecutive PD patients, 3 had a prior diagnosis of narcolepsy. This rate is five times higher than expected (p = 0.02). These patients had typical onset of narcolepsy and underwent treatment with amphetamine. Although preliminary, this observation raises the possibility that some factors intrinsic to narcolepsy or its treatment may be a risk factor for PD.     

Cardiac sympathetic denervation in Parkinson’s disease patients with SWEDDs

Dopamine transporter scans of some patients who have been clinically diagnosed with Parkinson’s disease (PD) fail to reveal abnormal dopaminergic functioning and are referred to as scans without evidence of dopaminergic deficits (SWEDDs). In this study, we investigated the differences between SWEDDs patients and PD patients using ¹²³I-metaiodobenzylguanidine (MIBG) scans. This study enrolled 20 patients with SWEDDs, 30 patients with early PD and 50 healthy controls. Cardiac ¹²³I-MIBG scans were performed on all subjects, and parameters including the early and delayed heart-to-mediastinum ratios (H/M) and the washout rate were compared among the three groups. The mean delayed H/M ratio in the PD group (mean ± standard deviation, 1.45 ± 0.23) was the lowest of the three groups, and the scans in the group without evidence of dopaminergic deficits exhibited a lower mean delayed H/M ratio (2.15 ± 0.48) than the control group (2.56 ± 0.55) (p < 0.05). The intermediate status of cardiac MIBG uptake in the SWEDDs patients in our study may have been due to the heterogeneity of the SWEDDs patients; some of these patients had Parkinsonism with unknown characteristics, some may have had early PD with false-negative dopamine transporter imaging, and some have had primary dystonia that was misdiagnosed as PD. These uncharacterised SWEDDs patients accounted for a larger proportion of the heterogeneous SWEDDs than observed in previous studies, but our results suggest that cardiac ¹²³I-MIBG scans may help to differentiate patients with SWEDDs from patients with PD.     

Mechanisms of unilateral STN-DBS in patients with Parkinson’s disease

Bilateral symptoms and signs of Parkinson’s disease (PD) are often improved by unilateral subthalamic nucleus deep brain stimulation (STN-DBS). However, the mechanism for such bilateral effects is unknown. This study was intended to examine effects of unilateral STN-DBS using positron emission computed tomography (PET) and to elucidate mechanisms for bilateral improvement achieved by unilateral stimulation. We conducted ¹⁸F-fluorodeoxyglucose (¹⁸FDG) and ¹⁸F-fluorodopa (¹⁸F-DOPA ) PET scans in PD patients whose bilateral limb symptoms and axial symptoms were improved by unilateral DBS. Two scans were performed in each PET study: when DBS was on and off. We compared those images using statistic parametric mapping (SPM) 99. The significant clinical improvement obtained by unilateral DBS was shown as improvements in bilateral motor limb, axial, and gait subscores of the Unified PD Rating Scale (UPDRS). Moreover, ¹⁸FDG PET revealed significant metabolic increases in the ipsilateral ventrolateral thalamic areas and metabolic decrease at the contralateral globus pallidus interna (GPi). In contrast, ¹⁸F-DOPA PET showed no significant differences between DBS on and off. Ipsilateral thalamic activation might induce ipsilateral motor cortical activation, which explains the improvement of contralateral limb symptoms. Furthermore, deactivation of the contralateral GPi might disinhibit the thalamus and contralateral motor cortex, which explains reduction of ipsilateral limb symptoms. These results suggest the mechanisms for bilateral improvement achieved by unilateral DBS.     

Evaluation of corneal parameters in patients with Parkinson’s disease

The aim of this study was to evaluate blink rate (BR), tear tests and corneal parameters by Scheimpflug imaging and also to clarify the associations between the severity of disease and corneal parameters in patients with Parkinson’s disease (PD). Forty patients with PD and 40 healthy subjects were included in this study. All participants underwent a detailed neurological and ophthalmological evaluation. The severity of disease was measured according to Hoehn–Yahr (H–Y) scale. BR was determined for participants. Corneal parameters were measured using Pentacam. Additionally, Schirmer test, tear break-up time (TBUT), corneal fluorescein staining, and Ocular Surface Disease Index (OSDI) scores were assessed. Corneal parameters were significantly different between the patients with PD and healthy controls. The mean central corneal thickness (538.95 ± 30.9 μm versus 557.60 ± 26.6 μm, p = 0.005) was significantly reduced in patients with PD compared to healthy controls. The BR and the values of TBUT and Schirmer test scores were significantly lower in patients with PD than in controls. Also, corneal fluorescein staining and OSDI scores were higher in patients with PD than in controls. The BR was significantly negative correlated with the severity of the disease. Factors related to the corneal thickness were BR, TBUT and Schirmer test (p < 0.05 for all). Corneal thickness may decrease in patients with PD which may be affected by reduced BR and tear dysfunction.     

Decreased serum proNGF concentration in patients with Parkinson’s disease

Parkinson’s disease (PD), a progressive and age-related neurodegenerative condition, is a common neurodegenerative disorder. However, no validated biomarkers for PD have been identified to date. Accumulating evidence supports the role of proNGF-p75NTR-sortilin signaling in the neurodegeneration and pathogenesis of PD. The aim of our study was to investigate alterations in serum proNGF concentrations in PD patients and related anxiety. Seventy-seven consecutive PD patients and 39 healthy controls were enrolled, and clinical data were collected. Modified Hoehn-Yahr Staging Scale, Unified Parkinson’s Disease Rating Scale (UPDRS), and Hamilton Anxiety (HAMA) Scale scores were assessed upon admission. Serum proNGF concentration was compared between that of PD patients and healthy controls. Pearson correlation coefficients were determined to explore the relationship between proNGF concentration and UPDRS, Hoehn-Yahr, and HAMA scores. Received operating characteristic (ROC) curves and proNGF optimal cutoff point were used to distinguish PD and related anxiety. The median concentration of proNGF was significantly lower (p = 0.000) in PD patients (94.91 ng/L, range 85.92–118.06 ng/L) compared with that of healthy controls (106.67 ng/L, range 102.39–122.06 ng/L). The optimal proNGF cutoff point for distinguishing PD patients was 102.29 ng/L, and the sensitivity and specificity values were 87.0 and 100%, respectively. proNGF concentration positively correlated with UPDRS (r = 0.281, p = 0.013), Hoehn-Yahr (r = 0.260, p = 0.023), and HAMA (r = 0.276, p = 0.015) scores. Our results indicate that serum proNGF concentration may represent a biomarker for PD and its role in the pathogenesis of PD thus warrants further investigation.     

Transient gender-related effects in Parkinson’s disease patients with subthalamic stimulation

Little is known about the gender-related long-term efficacy and safety after subthalamic nucleus deep brain stimulation (STN DBS) implant for Parkinson’s disease (PD), although some differences could be expected as recently stated in a short-term report. We assessed the possible gender-related differences in clinical outcome and disease progression along a 5-year period after STN DBS for PD. A prospective cohort of PD patients who underwent STN DBS and reached the 5-year follow-up (FU) was considered. Clinical outcome, disease progression and side effects were assessed at baseline and 1, 3, and 5 years after surgery. Eleven men and nine women were included in the study. At baseline, no inter-gender difference of age at implant, disease duration and severity or levodopa responsiveness was detected. A higher motor responsiveness in men compared to women was detected only at 1-year FU: this difference was mainly related to worse lower limb akinesia and gait score in women. The difference was not confirmed at 3 and 5 years. Antiparkinsonian drugs reduction, improvement in motor fluctuations and dyskinesias, functional measures and progression of underlying PD, were comparable in both groups. Women had persistent adverse events comparable to men. The present long-term observation confirms the occurrence of slight gender-related differences in PD patients treated with STN DBS, indicating a transient poorer outcome in women. Further observational time and a wider number of patients are needed to better analyze the dimension of long-term gender-related differences.     

Lower extremity isokinetic muscle strength in patients with Parkinson’s disease

We evaluated lower extremity isokinetic muscle strength to determine affected muscle groups and their dependence on movement velocity, and to establish the relationship between muscle strength and clinical severity, as well as muscle strength and falls, in Parkinson’s disease (PD). Twenty-five patients diagnosed with PD and 24 healthy volunteers were enrolled in this study. Lower extremity muscle strength was measured using an isokinetic dynamometer. Each participant’s clinical status was examined in accordance with the Unified Parkinson’s Disease Rating Scale; fall history was also recorded. We observed a significant decrease in isokinetic muscle strength in the patient group, especially in both hip and knee flexors and extensors. Decreased muscle strength was independent of velocity, and correlated with clinical severity and falls. Movement velocity-independent lower extremity isokinetic muscle weakness has been observed in patients with PD, especially in the knee and hip joints. The evaluation of isokinetic muscle strength may be a useful tool for the assessment of clinical severity and falls in PD.     

Non-motor symptoms in Chinese Parkinson’s disease patients

This study was designed to survey the prevalence and distribution of non-motor symptoms (NMS) in Parkinson’s disease (PD) patients in Shanghai, China, and to investigate the association between NMS and health-related quality of life (HRQoL). One hundred fifty-five PD patients were evaluated using the NMS Questionnaire 30 (NMSQuest), Unified Parkinson’s Disease Rating Scale (UPDRS) and Parkinson’s Disease Questionnaire-39 (PDQ-39). These data were compared with an international cross-sectional study, and the associations of motor and non-motor measures with HRQoL were estimated. Predictors of HRQoL were sought through multiple linear regression analyses. Each PD patient had eight different individual NMS on average. The problems of memory (65.82%), constipation (64.56%) and nocturia (61.39%) were the most frequent complaints. NMS prevalence in PD patients in Shanghai was consistent with that in the international study, although the composition proportions were different. There was a significant association of PDQ-39 score with NMSQuest score (rs = 0.433, p = 0.000), UPDRS III score (rs = 0.473, p = 0.000), Hoehn and Yahr (H-Y) stage (rs = 0.567, p = 0.000), disease duration (rs = 0.220, p = 0.005), and levodopa equivalent dosage (rs = 0.263, p = 0.001). H-Y stage (disease severity) and NMS score were the strongest predictors for PDQ-39 score. This study confirmed that NMS are common in PD, occurring across all disease stages and have a great impact on quality of life. NMS progression contributes significantly to HRQoL decline, and should be well recognized and treated.     

Hyperhomocysteinemia influenced malnutrition in Parkinson’s disease patients

Introduction

Parkinson’s disease (PD) is a neurodegenerative disease with many motor and non-motor symptoms. Hyperhomocysteinemia is reported in many PD patients. Homocysteine (Hcy) is reported to be a risk factor for some PD non-motor symptoms.

Aim

The aim was to analyze Hcy level and its correlation with physical activity and motor and some non-motor symptoms (depression and cognition) in PD patients.

Patients and methods

Patients were surveyed for physical activity and demographic data. Blood samples were obtained for Hcy, vitamin B12, and folic acid determination. The Mini Nutritional Assessment (MNA), Unified Parkinson’s Disease Rating Scale (UPDRS) parts III and IV, Hoehn and Yahr (H&Y) Scale, Beck Depression Inventory (BDI), and Mini Mental State Examination (MMSE) were used to assess nutritional status, disease stage, and motor and some non-motor symptoms (depression and cognition) of PD in study patients.

Results

We analyzed 34 PD patients. Elevated Hcy level was found in 70.6% of these patients. Patients reporting regular exercise had lower Hcy level (p?<?0.025). Hcy level yielded a statistically significant correlation with MNA score (rs?=???0.510; p?<?0.003), UPDRS part III (rs?=?0.372; p?<?0.030), vitamin B12 (rs?=???0.519; p?<?0.002), and folic acid (rs?=???0.502; p?<?0.003) but not with cognition and depression. There were no statistically significant differences in Hcy level for disease stage either for dyskinesia or “off” periods.

Conclusion

PD patients are at a risk of hyperhomocysteinemia. Regular physical activity decreases Hcy level, whereas poor motor function increases it. There is correlation between Hcy level and malnutrition in PD patients.

     

Motor learning of hands with auditory cue in patients with Parkinson’s disease

Summary. In the present research, changes in motor cortex function were observed in relation to repetitive, voluntary thumb movement (training) in patients with Parkinson’s disease (PD) and normal control subjects. Changes in the direction of thumb movement due to motor evoked potential (MEP) by transcranial magnetic stimulation (TMS), after motor training with and without rhythmic sound, were measured using a strain gauge for 12 patients with PD and 9 normal control subjects. PD patients who experienced the freezing phenomena showed poor change in direction of TMS-induced movement after self-paced movement; however, marked change in direction of TMS-induced movement was observed after training with auditory cue. PD patients who had not experienced the freezing phenomena showed positive effects with the auditory cue, producing similar results as the normal control subjects. Two routes for voluntary movement are available in the nervous system. The decreased function of basal ganglia due to PD impaired the route from the basal ganglia to the supplementary motor cortex. These data suggest that the route from sensory input to cerebellum to premotor cortex could compensate for the decreased function of the route via the basal ganglia to the premotor cortex. Once change in the motor cortex occurred, such change persisted even after the interruption of training. These phenomena suggest that motor memory can be stored in the motor cortex.