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.     

Heatstroke in patients with Parkinson’s disease

We present two Parkinson's disease (PD) patients, who experienced heatstroke. Both patients manifested central nervous system dysfunction with elevated core temperature. Despite adequate lowering of the body temperature, multiorgan-dysfunction syndrome including encephalopathy, rhabdomyolysis, acute renal failure, acute respiratory failure, and disseminated intravascular coagulopathy was noted in one patient, leading to permanent neurologic damage. Because the ensuing multiorgan dysfunction could determine the functional prognosis in heatstroke patients, it is important to provide information about the prevention of heatstroke to patients, who are isolated or are severely disabled in the advanced stages of 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.     

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.     

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.     

The plasma alpha-synuclein levels in patients with Parkinson’s disease and multiple system atrophy

Summary. α-Synuclein, a synaptic protein of unknown function, is a major component of Lewy bodies and may play a role in the pathophysiological process of Parkinson’s disease (PD). In this study, we measured the plasma α-synuclein levels in 105 patients with PD, 38 patients with multiple system atrophy (MSA), and 51 age-matched controls. The α-synuclein level was significantly elevated in patients with PD (79.9 ± 4.0 pg/ml, p < 0.001) and in those with MSA (78.1 ± 3.5 pg/ml, p = 0.019) compared with the level in controls (76.1 ± 3.9 pg/ml). The α-synuclein level was higher in patients with PD than in those with MSA (79.9 ± 4.0 vs 78.1 ± 3.5, p = 0.016). Our study demonstrated that the α-synuclein level in plasma is elevated in patients with PD and MSA.     

Studies on homocysteine and dehydroepiandrosterone sulphate plasma levels in alzheimer’s disease patients and in Parkinson’s disease patients

Homocysteine (HC) and dehydroepiandrosterone sulphate (DHEAS) plasma levels have been evaluated in groups of male and female patients with Parkinson's disease (PD) and in a group of female patients with Alzheimer's disease (AD) and compared with the corresponding plasma levels observed in a group of age-matched subjects. It has been confirmed that HC plasma levels are enhanced in both PD and AD patients. As far as the DHEAS plasma levels are concerned no changes have been observed in PD patients while a marked decrease has been observed in AD patients. These results support the view that while the pro-oxidant effects of HC and its agonist action at NMDA receptors can play a role in both neurodegenerative diseases, the role of DHEAS is more complex and may be an important factor only in certain neurodegenerative diseases. Thus, according to the present study DHEAS is likely to be involved in AD but not in PD.     

Shifting from constant-voltage to constant-current in Parkinson’s disease patients with chronic stimulation

The study aimed to evaluate safety and efficacy of shifting stimulation settings from constant-voltage (CV) to constant-current (CC) programming in patients with Parkinson’s disease (PD) and chronic subthalamic nucleus deep brain stimulation (STN DBS). Twenty PD patients with chronic STN DBS set in CV programming were shifted to CC and followed for 3 months; the other stimulation settings and the medication regimen remained unchanged. Side effects, motor, non-motor, executive functions, and impedance were assessed at baseline and during follow-up. No adverse events were observed at time of shifting or during CC stimulation. Motor and non-motor measures remained unchanged at follow-up despite impedance decreased. Compared to baseline, inhibition processes improved at follow-up. The shifting strategy was well tolerated and the clinical outcome was maintained with no need to adjust stimulation settings or medications notwithstanding a decrease of impedance. Improvement of inhibition processes is a finding which needed further investigation.     

Switch from selegiline to rasagiline is beneficial in patients with Parkinson’s disease

The objective of this study is to demonstrate that application of rasagiline instead of selegiline with concomitant determination of l-amphetamine and l-methamphetamine in plasma is safe and well tolerated and influences sleep, mood, and motor behavior in patients with Parkinson’s disease on a stable drug therapy. 30 patients, who took 7.5 mg selegiline daily for at least 3 months, were switched to 1 mg rasagiline. Then they were followed over an interval of 4 months. The remaining drug therapy remained stable. This changeover was safe and well tolerated. l-Amphetamine and l-methamphetamine only appeared during selegiline treatment. Motor behavior, motor complications, mood and sleep improved during rasagiline administration. Amphetamine-like derivatives of selegiline could contribute to sleep disturbances, which may be involved in worsening of mood. Motor behavior and motor complications probably became better due to the additional glutamate receptor antagonizing properties of rasagiline in this open label study.     

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.     

Growth hormone response in low-dose apomorphine test correlates with nigrostriatal dopamine transporter binding in patients with Parkinson’s disease

Summary. Challenge with low-dose apomorphine causes a rise in growth hormone (GH) in patients with Parkinson’s disease (PD). We studied 18 patients with early PD, who showed an increase of GH in the low-dose apomorphine test, by means of [¹²³I] FP-CIT-SPECT. The mean specific dopamine transporter binding of the 18 patients was 1.50 ± 0.56 in the striatum, 1.20 ± 0.59 in the putamen, and 1.76 ± 0.59 in the caudate nucleus. The increase of GH (1.05 ± 1.01 ng/ml at baseline to 9.46 ± 6.36 ng/ml 45 min after apomorphine injection; p < 0.001) was significant. There was a significant negative correlation of the increase of GH with the mean specific dopamine transporter binding in all three regions (r between −0.490 and −0.587; p between 0.04 and 0.01). Challenge with low-dose apomorphine may therefore be used as an indirect tool to measure the extent of nigrostriatal neurodegeneration in early PD.