Zsuzsanna Aschermann

The Impact of Left Prefrontal Repetitive Transcranial Magnetic Stimulation on Depression in Parkinson's Disease: a Randomized, Double-Blind, Placebo-Controlled Study

Based on several open‐label and case studies, repetitive transcranial magnetic stimulation (rTMS) seems to have an antidepressive effect on patients with Parkinsons disease (PD). However, this hypothesis requires further confirmation. We conducted a randomized, double‐blind placebo‐controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex (DLPFC) on depression and various motor and nonmotor features of PD. Twenty‐two PD patients with mild or moderate depressive episodes were assigned into two groups, one receiving real‐rTMS (90% of resting motor threshold, 5 Hz, 600 pulses‐a‐day for 10 days) over the left DLPFC, and another group receiving sham‐rTMS. An investigator blinded to the treatment performed three video‐taped examinations on each patient: before stimulation (baseline), 1 day (short term), and 30 days after treatment session ended (long‐term effect). Mini‐Mental State Examination, Unified Parkinsons Disease Rating Scale (UPDRS), Hoehn‐Yahr, Epworth Sleepiness, Visual Analog and Montgomery‐Asberg Depression Rating Scales (MADRS), Beck Depression Inventory (BDI), and Trail making and Stroop tests were applied. In the actively treated group, not only depression rating scales showed significant improvement 30 days after treatment ended (BDI by 44.4% and MADRS by 26.1%), but also the accuracy of Stroop test (by 16%). We could also demonstrate an insignificant improvement in UPDRS‐III by 7.5 points (31.9%, P = 0.06). In the sham‐treated group none of the examined tests and scales improved significantly after sham stimulation. Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment. However, this result should be confirmed in patients with severe depression by further clinical trials.

Sensitivity and specificity of Addenbrooke's Cognitive Examination, Mattis Dementia Rating Scale, Frontal Assessment Battery and Mini Mental State Examination for diagnosing dementia in Parkinson's disease

INTRODUCTION Among the non-motor features of Parkinsons disease (PD), cognitive impairment is one of the most troublesome problems. Highly sensitive and specific screening instruments for detecting dementia in PD (PDD) are required in the clinical practice. METHODS In our study we evaluated the sensitivity and specificity of different neuropsychological tests (Addenbrookes Cognitive Examination, ACE; Frontal Assessment Battery, FAB and Mattis Dementia Rating Scale, MDRS) in 73 Parkinsons disease patients without depression. By receiver operating characteristic curve analysis, these screening instruments were tested against the recently established clinical diagnostic criteria of PDD. RESULTS Best cut-off score for ACE to identify PDD was 80 points (sensitivity = 74.0%, specificity = 78.1%). For FAB the most optimal cut-off value was 12 points (sensitivity = 66.3%, specificity = 72.2%); whereas for MDRS it was 125 points (sensitivity = 89.8%, specificity = 98.3%). Among the examined test batteries, MDRS had the best clinicometric profile for detecting PDD. CONCLUSION Although the types of applied screening instruments might differ from movement disorder clinic to clinic within a country, determination of the most specific and sensitive test for the given population remains to be an important task. Our results demonstrated that the specificity and sensitivity of MDRS was better than those of ACE, FAB and MMSE in Hungary. However, further studies with larger sample size and more uniform criteria for participation are required to determine the most suitable screening instrument for cognitive impairment.

Bilateral Subthalamic Stimulation can Improve Sleep Quality in Parkinson's Disease

BACKGROUND Sleep problems are among the most common non-motor symptoms of Parkinsons disease (PD). The PD Sleep Scale 2nd version (PDSS-2) improved the original PDSS by adding more items on different aspects of sleep problems, making it a more robust tool to evaluate the severity of sleep disturbances. However, previous studies on deep brain stimulation (DBS) have not used the PDSS-2. OBJECTIVE To determine if the PDSS-2 could detect improvement reliably in sleep problems after bilateral subthalamic nucleus DBS for PD. METHODS In this prospective study, 25 consecutive patients undergoing DBS implantation were enrolled. Patients were examined twice: 1 week prior to the DBS implantation (baseline) and 12 months postoperatively. Severity of PD symptoms were assessed by the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) and the Non-Motor Symptoms Scale (NMSS). Presence and severity of sleep disturbances were specifically measured by PDSS-2. RESULTS Total score of MDS-UPDRS improved from 81 (median, interquartile-range: 63-103) to 55 points (median, IQR: 46-75, p <  0.001). Health-related quality of life, measured by PDQ-39, also improved from 29 (IQR: 18-40) to 15 (IQR: 9-28) points (p = 0.002). Most domains of NMSS also improved. At baseline 13 patients reported sleep problems, but 1 year after DBS implantation only 3 did (p = 0.012). Although only 6 out of 15 items showed a significant decrease after DBS implantation, the total score of PDSS-2 decreased from 24 (IQR: 17-32) to 10 (IQR: 7-18) points (P <  0.001). CONCLUSIONS Based on our results, PDSS-2 can detect improvements in sleep quality reliably after DBS implantation.

Neurokognitív zavarok diagnosztizálási és kezelési lehetőségei Parkinson-kórban

Absztrakt Az osszefoglalo kozlemenyben a szerzők reszletesen bemutatjak a Parkinson-korhoz tarsulo neurokognitiv zavarok jellegzetessegeit, felmeresuk lehetseges modjait es kezelesi lehetősegeit. A neurokognitiv zavarok meghatarozasat sokaig nehezitette a diagnosztikai kriteriumrendszerek sokszinűsege. Az Amerikai Pszichiatriai Tarsasag altal a Mentalis Rendellenessegek Kormeghatarozo es Statisztikai Kezikonyvenek otodik atdolgozasa (Diagnostic and Statistical Manual of Mental Disorders, DSM-5) magaval hozta a major es az enyhe neurokognitiv zavar megnevezeseket a demencia es az enyhe kognitiv zavar fogalmat helyettesitendően. A DSM-5 neurokognitiv zavarra vonatkozo definicioi a klinikumban jol alkalmazhatoak, am szuksegesse valt a leggyakrabban hasznalt szűrőtesztek, ugymint a Mini-Mental Status Vizsgalat, az Addenbrooke Kognitiv Vizsgalat, a Montreal Kognitiv Felmeres es a Mattis Demencia Pontozo Skala uj kriteriumrendszerhez valo adaptalasa. Magyar Parkinson-koros populacion vegzett validalasi vizsgala...

Is the MDS-UPDRS a Good Screening Tool for Detecting Sleep Problems and Daytime Sleepiness in Parkinson’s Disease?

Movement Disorder Society-sponsored Unified Parkinsons Disease Rating Scale (MDS-UPDRS) has separate items for measuring sleep problems (item 1.7) and daytime sleepiness (1.8). The aim of our study was to evaluate the screening sensitivity and specificity of these items to the PD Sleep Scale 2nd version (PDSS-2) and Epworth Sleepiness Scale (ESS). In this nationwide, cross-sectional study 460 PD patients were enrolled. Spearmans rank correlation coefficients were calculated between the individual items, domains, and the total score of PDSS-2 and item 1.7 of MDS-UPDRS. Similarly, the items and the total score of ESS were contrasted to item 1.8 of MDS-UPDRS. After developing generalized ordinal logistic regression models, the transformed and observed scores were compared by Lins Concordance Correlation Coefficient. Only item 3 difficulties staying asleep and the “disturbed sleep” domain of PDSS-2 showed high correlation with “sleep problems” item 1.7 of the MDS-UPDRS. Total score of PDSS-2 had moderate correlation with this MDS-UPRDS item. The total score of ESS showed the strongest, but still moderate, correlation with “daytime sleepiness” item 1.8 of MDS-UPDRS. As intended, the MDS-UPDRS serves as an effective screening tool for both sleep problems and daytime sleepiness and identifies subjects whose disabilities need further investigation.

Visuospatial impairment in Parkinson's disease: The role of laterality

Asymmetry is one of the unique and mysterious features of Parkinsons disease (PD). Motor symptoms develop unilaterally either on the left (LPD) or the right side (RPD). Incongruent data are available whether the side of onset has an impact on cognition in PD. The objective of this study is to compare the visuospatial performance of RPD and LPD patients. Seventy-one non-demented, non-depressive and right-handed patients were categorized into RBD (n = 36) and LPD (n = 35) groups. Rey-Osterrieth Complex Figure Test (ROCF) was evaluated by both the Taylors and Lorings scoring systems. Subsequently, we also performed subgroup analyses on patients having short disease duration (≤5 years, 15 RBD and 15 LPD patients). The standard analysis of ROCF (Taylors system) did not reveal any differences; however, the utilization of the Lorings system demonstrated that LPD patients had significantly worse visuospatial performance than the RPD subjects (3.0 vs. 2.0 points, median, p = 0.002). Correlation between the number of spatial errors and the degree of asymmetry was significant (r = −0.437, p = 0.001). However, this difference could not be observed in PD patients with short disease duration. LPD patients had worse visuospatial performance than the RPD subjects and the number of errors tightly correlated with the degree of asymmetry and long disease duration.

Minimal clinically important differences for the experiences of daily living parts of movement disorder society–sponsored unified Parkinson's disease rating scale

Background: The minimal clinically important difference is the smallest change of scores clinically meaningful to patients.

Impact of Sex on the Nonmotor Symptoms and the Health-Related Quality of Life in Parkinson's Disease.

Background. Female Parkinsons disease (PD) patients seem to experience not only more severe motor complications and postural instability but also more pronounced depression, anxiety, pain, and sleep disturbances. Objective. The aim of the present study was to evaluate the role of sex as a possible independent predictor of HRQoL in PD. Methods. In this cross-sectional study, 621 consecutive patients treated at the University of Pécs were enrolled. Severity of PD symptoms was assessed by MDS-UPDRS, UDysRS, Non-Motor Symptoms Scale, PDSS-2, Hamilton Anxiety Scale, Montgomery-Asberg Depression Rating Scale, Lille Apathy Rating Scale, and Addenbrooke Cognitive Examination. HRQoL was assessed by PDQ-39 and EQ-5D. Multiple regression analysis was performed to estimate the PDQ-39 and EQ-5D index values based on various clinical factors. Results. Although females received significantly lower dosage of levodopa, they had significantly more disabling dyskinesia and worse postural instability. Anxiety, pain, sleep disturbances, and orthostatic symptoms were more frequent among females while sexual dysfunction, apathy, and daytime sleepiness were more severe among males. Women had worse HRQoL than men (EQ-5D index value: 0.620 ± 0.240 versus 0.663 ± 0.229, p = 0.025, and PDQ-39 SI: 27.1 ± 17.0 versus 23.5 ± 15.9, p = 0.010). Based on multiple regression analysis, sex was an independent predictor for HRQoL in PD. Conclusions. Based on our results, female sex is an independent predictor for having worse HRQoL in PD.

High-Frequency Repetitive Transcranial Magnetic Stimulation Can Improve Depression in Parkinson’s Disease: A Randomized, Double-Blind, Placebo-Controlled Study

Background: A recent evidence-based guideline demonstrated that bilateral repetitive transcranial magnetic stimulation (rTMS) over the motor cortex (M1) can improve motor symptoms of Parkinsons disease (PD). We conducted a randomized, double-blind, placebo-controlled study to evaluate the impact of bilateral M1 rTMS on depression in PD. Methods: Forty-six patients with PD and mild-to-moderate depression were randomly assigned to active (n = 23) and sham (n = 23) rTMS. Two patients in the sham group did not complete the protocol because of reasons unrelated to the study. High-frequency rTMS was applied over the primary motor cortex bilaterally for 10 days. An investigator blinded to the treatment performed three video-taped examinations on each patient: before stimulation (baseline), and 1 day (short-term effect) and 30 days after the treatment session ended (long-term effect). The primary end point was the changes in depression, while secondary end points included health-related quality of life scales and Movement Disorders Society-Unified Parkinsons Disease Rating Scale (MDS-UPDRS). Results: In the actively treated group, not only did the severity of depression improve (from 17 to 7 points, Montgomery-Åsberg Depression Rating Scale, median values, p < 0.001), but also the health-related quality of life (from 25.4 to 16.9 points, PDQ-39 summary index, median values, p < 0.001). Besides, we could also demonstrate an improvement in MDS-UPDRS Motor Examination (from 26 to 20 points, median values, p < 0.05). In the sham-treated group, none of the examined tests and scales improved significantly after treatment. Conclusions: Our results demonstrate the beneficial effects of high-frequency bilateral M1 rTMS on depression and health-related quality of life in PD. However, this effect of rTMS should also be confirmed in patients with severe depression by further clinical trials.

Test-retest validity of Parkinson's disease sleep scale 2nd version (PDSS-2).

BACKGROUND AND AIMS The aim of the present study was to measure the test-retest validity of Parkinsons Disease Sleep Scale 2nd version (PDSS-2) on PD patients with stable medication and motor symptoms over the period of 4 weeks. METHODS The subject population consisted of 92 PD patients. Besides PDSS-2, Unified PD rating scale, Montgomery-Asberg Depression Rating Scale and EQ-5D were assessed at baseline and 4 weeks later. RESULTS The total score of PDSS-2 decreased from 19.06 ± 10.78 points to 18.00 ± 9.34 points (p > 0.05). For the total score of PDSS-2 the Intra-class and Lins Concordance Correlation Coefficients were 0.782 and 0.799. The average difference between the baseline and follow-up total PDSS-2 scores was -1.06 points with the 95% confidence interval of -7.96 and +5.84 points. CONCLUSIONS Our data supports that the items and the total score of PDSS-2 have acceptable test-retest reliability over a four week period on patients with stable PD symptoms and pharmacological therapy.