A systematic review of the effects of low-frequency repetitive transcranial magnetic stimulation on cognition The original version of this article unfortunately contained a mistake. The author would like to include the below acknowledgement section.

Bound, free, and total l -dopa measurement in plasma of Parkinson’s disease patients Abstract Peaks and troughs of levodopa in plasma contribute to pulsatile postsynaptic dopamine receptor stimulation in patients with Parkinson’s disease. Measurement of levodopa plasma levels mostly only considers the total levodopa plasma concentration. Objectives were to determine bound, free, and total plasma levodopa and to investigate their correlations to each other. We employed reversed-phase high-performance liquid chromatography combined with electrochemical detection. Bound levodopa was computed as difference between total and free l-dopa values. Close correlations between free and total (R = 0.93, p < 0.0001), bound and total (R = 0.91, p < 0.0001) plasma levodopa appeared. A considerable variability of levodopa concentrations occurred. The ratio between bound and free levodopa did not differ in patients with a higher and lower oral daily levodopa dosing. Free, bound, and total levodopa plasma levels are closely related. Estimation of the total levodopa level only seems to be meaningful.

Late-onset Niemann–Pick disease type C overlapping with frontotemporal dementia syndromes: a case report Abstract The diagnosis of adult-onset Niemann–Pick disease type C (NPC) could be difficult because its primary symptoms [dementia and vertical supranuclear gaze palsy (VSGP)] are mainly seen in neurodegenerative dementias and progressive supranuclear palsy (PSP). Our patient with dementia and asymmetric parkinsonism resembled corticobasal syndrome and after the appearance of VSGP, the criteria of PSP were fulfilled too. Cerebellar symptoms appeared late during the course of the disease, leading to the diagnosis of NPC at the age of 59 years.

“New methods of assessing autonomic disorders in Parkinson disease patients: skin-galvanic reaction” Abstract The aim of this study was to assess quantitatively sweating in PD patients. In the study, the galvanic-skin reaction (GSR) was used. The GSR was tested using eSense Skin Reaction device. The results show that sweating in patients with Parkinson’s disease on drugs (PD ON) and control patients is similar, while patients with PD without levodopa (PD OFF) have higher perspiration.

Children’s Friendship Training Program for Israeli elementary school age children with attention-deficit/hyperactivity disorder Abstract The present study examined whether the effectiveness of the Children’s Friendship Training (CFT) in children with ADHD is maintained following treatment endpoint and whether it is effective in a different culture outside the USA. Parent reports of social skills, behavioral problems, conflict, and children’s social knowledge were collected at baseline, pre-treatment (week-12), post-treatment (week-24) and follow-up (week-36) (treatment group: N = 25, waitlist: N = 20). Relative to waitlist, children’s social knowledge, social skills and conflict resolution were improved at post-treatment and improvement was maintained at follow-up.

PKC inhibitor reversed the suppressive effect of orexin-A on IPSCs of locus coeruleus neurons in naloxone-induced morphine withdrawal Abstract The locus coeruleus (LC) as a target of addictive drugs receives a dense projection of orexinergic fibres from the lateral hypothalamus (LH) and is accordingly a candidate site for the expression of the somatic aspects of morphine withdrawal. Recently it has been shown that the inhibitory synaptic currents of LC neurons decrease partly through orexin type 1 receptors in the context of naloxone-induced morphine withdrawal; however, its cellular mechanism remains unclear. In this study, whole-cell patch clamp recordings of LC neurons in brainstem slices were used to investigate the impact of protein kinase C (PKC) on GABAergic inhibitory post-synaptic currents (IPSCs) in the context of naloxone-induced morphine withdrawal. Male Wistar rats (P14–P21) received morphine (20 mg/kg, i.p.) daily for 7 consecutive days to induce morphine dependency. Our results showed that the application of PKC inhibitor (Go 6983; 1 µM) alone did not decrease the probability of GABA release in the LC neurons of the morphine-treated rats in the presence of naloxone. Although, Go 6983 reversed the reduction of the amplitude of evoked IPSCs (eIPSCs) and spontaneous IPSCs (sIPSCs) frequency induced by orexin-A but did not change the sIPSCs amplitude. These results indicate that the suppressive effect of orexin-A on IPSCs is probably reversed by PKC inhibitor in the LC neurons of morphine-treated rats in the context of naloxone withdrawal.

Subthalamic nucleus deep brain stimulation improves dyskinesias in Parkinson’s disease beyond levodopa reduction Abstract Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves motor fluctuations and dyskinesias in patients with Parkinson's disease (PD). Dyskinesia improvement with STN DBS is believed to result entirely from levodopa reduction. However, some studies suggest that STN DBS may also directly suppress dyskinesias. To determine whether bilateral STN DBS improves dyskinesias beyond what would be expected from levodopa reduction alone, we analyzed pre-operative and post-operative dyskinesia scores (sum of MDS-UPDRS items 4.1 and 4.2) from 61 PD patients with bilateral STN DBS. A multiple regression model (adjusted for disease severity, disease duration, active contacts above the STN, use of amantadine, high pre-operative levodopa-equivalent dose (LED), sex, and interaction between active contacts above the STN and amantadine use) was created to describe the relationship between dyskinesia scores and LED prior to DBS. Using this model, a post-operative dyskinesia score was estimated from post-operative LED and compared to the actual post-operative dyskinesia score. The regression model was statistically significant overall (p = 0.003, R2 = 0.34, adjusted R2 = 0.24). The actual post-operative dyskinesia score (1.0 ± 1.4) was significantly lower than the score predicted by the model (3.0 ± 1.1, p < 0.0001). Dyskinesias after STN DBS improved more than predicted by levodopa reduction alone. Our data support the idea that STN stimulation may directly improve dyskinesias.

Motor and non-motor function predictors of mortality in Parkinson’s disease Abstract Doubts persist regarding the influence of Parkinson’s disease (PD) on mortality. Our objective was to assess mortality rates in a prospectively followed cohort of PD patients and the impact of motor and non-motor symptoms in survival. 130 consecutive PD patients were followed during a 4-year period or until death. Baseline assessment included motor function (UPDRSIII, Hoehn and Yahr—HY), incapacity (Schwab and England—S&E, UPDRS II), Health-Related quality of life (EuroQol), non-motor symptoms (Non-Motor Symptom Scale—NMSS, MoCA, REM sleep behavior disorder symptoms questionnaire) and comorbidity burden (Charlson Comorbidity Index—CCI). These were used as predictor variables. Standardized mortality rates (SMR) were calculated, comparing with the general population. The association between mortality and predictors was tested with univariate and multivariate Cox proportional hazard regression models. Overall and gender-related SMRs were similar to the general population. SMR for pneumonia was five times higher than in the general population. Age, disease duration, CCI, EuroQol, dementia, MoCA, S&E, NMSS Hallucinations, HY, and PIGD motor phenotype were significantly associated with mortality. Adjusting for age, gender and disease duration, S&E remained significantly associated with mortality. In multivariate logistic regression analysis, death was significantly associated with disease duration, CCI and NMSS—mood/cognition scores. PD was not associated with an excess of mortality, but conferred a higher probability of dying from pneumonia. Comorbidity was a major determinant, but disease duration, baseline incapacity, cognition, psychosis, mood complaints and HRQL also contributed significantly to mortality.

Hyposmia as a marker of (non-)motor disease severity in Parkinson’s disease Abstract The aim of this study was to evaluate the relationship of hyposmia in Parkinson’s disease (PD) with other motor and non-motor symptoms and with the degree of nigrostriatal dopaminergic cell loss. A total of 295 patients with a diagnosis of PD were included. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Motor symptoms were rated using the Unified Parkinson’s Disease Rating Scale motor subscale (UPDRS III). To evaluate other non-motor symptoms, we used the Mini-Mental State Examination (MMSE) as a measure of global cognitive function and validated questionnaires to assess sleep disturbances, psychiatric symptoms, and autonomic dysfunction. A linear regression model was used to calculate correlation coefficients between UPSIT score and motor and non-motor variables [for psychiatric symptoms a Poisson regression was performed]. In a subgroup of patients (n = 155) with a dopamine transporter (DaT) SPECT scan, a similar statistical analysis was performed, now including striatal DaT binding. In the regression models with correction for age, sex, disease duration, and multiple testing, all motor and non-motor symptoms were associated with UPSIT scores. In the subgroup of patients with a DaT-SPECT scan, there was a strong association between olfactory test scores and DaT binding in both putamen and caudate nucleus. Hyposmia in PD is associated with various motor and non-motor symptoms, like cognition, depression, anxiety, autonomic dysfunction and sleep disturbances, and with the degree of nigrostriatal dopaminergic cell loss. This finding adds further confirmation that hyposmia holds significant promise as a marker of disease progression.

Salivary alpha-synuclein as a biomarker for Parkinson’s disease: a systematic review Abstract The search for a reliable, early-disease biomarker for Parkinson’s disease (PD) that reflects underlying pathology is a high priority in PD research. Salivary alpha-synuclein (α-Syn) is an easily accessible biomarker for PD with promising results. Our aim was to evaluate the performance of salivary α-Syn as a diagnostic biomarker of PD. We identified 476 studies through a systematic literature review according to PRISMA guidelines. Finally, eight studies reporting data on salivary α-Syn were included in the review (1240 participants). The quality of studies was assessed by Newcastle–Ottawa scale. (1) Three studies showed that the total α-Syn levels were significantly lower in PD patients compared to healthy controls, while in another five there was no significant association. (2) In some studies, total salivary α-Syn was associated with demographic and clinical features; however, no consistent pattern emerged. In one study, total α-Syn levels were associated with poor cognitive performance in PD patients. (3) Four studies showed a higher salivary oligomeric α-Syn and oligomeric α-Syn/total α-Syn ratio in PD compared to healthy controls, while in another four there was no association. (4) One study concluded that genetic polymorphisms may influence total salivary α-Syn in PD patients. Taken together, the potential of salivary total α-Syn as a PD biomarker is still uncertain, whereas salivary oligomeric α-Syn appears quite promising. Pre-analytical and analytical factors of included studies were important limitations to justify the introduction of salivary α-Syn into clinical practice.