Attila Makkos

Screening Mild and Major Neurocognitive Disorders in Parkinson’s Disease

Introduction. Among the nonmotor features of Parkinsons disease (PD), cognitive impairment is one of the most troublesome problems. New diagnostic criteria for mild and major neurocognitive disorder (NCD) in PD were established by Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). The aim of our study was to establish the diagnostic accuracy of widely used screening tests for NCD in PD. Methods. Within the scope of our study we evaluated the sensitivity and specificity of different neuropsychological tests (Addenbrookes Cognitive Examination (ACE), Mattis Dementia Rating Scale (MDRS), Mini Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA)) in 370 PD patients without depression. Results. MoCA and ACE feature the finest diagnostic accuracy for detecting mild cognitive disorder in PD (DSM-5) at the cut-off scores of 23.5 and 83.5 points, respectively. The diagnostic accuracy of these tests was 0.859 (95% CI: 0.818–0.894, MoCA) and 0.820 (95% CI: 0.774–0.859, ACE). In the detection of major NCD (DSM-5), MoCA and MDRS tests exhibited the best diagnostic accuracy at the cut-off scores of 20.5 and 132.5 points, respectively. The diagnostic accuracy of these tests was 0.863 (95% CI: 0.823–0.897, MoCA) and 0.830 (95% CI: 0.785–0.869, MDRS). Conclusion. Our study demonstrated that the MoCA may be the most suitable test for detecting mild and major NCD in PD.

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...

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.

Changes in Quality of Life in Parkinson's Disease: How Large Must They Be to Be Relevant

Background: Minimal clinically important difference (MCID) is the smallest change in an outcome, which a patient identifies as meaningful. Although the 2 most frequently applied Parkinsons disease (PD) “quality of life” questionnaires (the PDQ-39 and PDQ-8) provide encouragingly similar results, their MCID thresholds appear to be vastly different. Our aim was to calculate the MCID estimates for both PDQ-39 and PDQ-8 Summary Indices (PDQ-39-SI and PDQ-8-SI) by the utilization of both anchor- and distribution-based techniques. Methods: Nine hundred eighty-five paired investigations of 365 patients were included. Three different techniques were used simultaneously to calculate the MCID values. Results: First, we replicated the previously published results demonstrating how both PDQ-39-SI and PDQ-8-SI provide similar values and respond in a similar way to changes. Subsequently, we calculated the MCID thresholds. The most optimal estimates for MCID thresholds for PDQ-39-SI were -4.72 and +4.22 for detecting minimal clinically important improvement and worsening. For PDQ-8-SI, these estimates were -5.94 and +4.91 points for detecting minimal clinically important improvement and worsening respectively. Conclusions: Our study is the first one that directly compared the MCID estimates for both PDQ-39-SI and PDQ-8-SI on a large pool of patients including all disease severity stages. These MICD estimates varied across PD severity.

Deep Brain Stimulation Can Preserve Working Status in Parkinson’s Disease

Objectives. Our investigation aimed at evaluating if bilateral subthalamic deep brain stimulation (DBS) could preserve working capability in Parkinsons disease (PD). Materials. We reviewed the data of 40 young (<60 year-old) PD patients who underwent DBS implantation and had at least 2 years of follow-up. Patients were categorized based on their working capability at time of surgery: “active job” group (n = 20) and “no job” group (n = 20). Baseline characteristics were comparable. Quality of life (EQ-5D) and presence of active job were evaluated preoperatively and 2 years postoperatively. Results. Although similar (approximately 50%) improvement was achieved in the severity of motor and major nonmotor symptoms in both groups, the postoperative quality of life was significantly better in the “active job” group (0.687 versus 0.587, medians, p < 0.05). Majority (80%) of “active job” group members were able to preserve their job 2 years after the operation. However, only a minimal portion (5%) of the “no job” group members was able to return to the world of active employees (p < 0.01). Conclusions. Although our study has several limitations, our results suggest that in patients with active job the appropriately “early” usage of DBS might help preserve working capability and gain higher improvement in quality of life.

How Efficient Is Subthalamic Deep Brain Stimulation in Reducing Dyskinesia in Parkinson's Disease

Background: Dyskinesia is among the most troublesome symptoms of advanced Parkinsons disease (PD). The recently developed Unified Dyskinesia Rating Scale (UDysRS) can simultaneously measure several subjective and objective aspects of dyskinesia, irrespective of the other motor symptoms of PD. Despite the advantages of deep brain stimulation (DBS), previous studies on DBS have not used the UDysRS yet. Methods: In this prospective study, 71 consecutive patients undergoing DBS implantation were enrolled. Patients were examined twice: 1 week prior to the DBS implantation (baseline) and 12 months postoperatively. The severity of PD-related symptoms was assessed by the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS). The presence and severity of dyskinesia were specifically measured by the UDysRS and patient diaries. Results: At baseline, all 71 patients had dyskinesia, but 1 year after DBS implantation, 25 patients were dyskinesia-free, and an additional 19 had only mild dyskinesia. The total score on the UDysRS decreased from 38.0 ± 17.8 to 10.8 ± 13.0 (p < 0.001). Besides this, all parts of the UDysRS showed significant improvement after STN DBS treatment, and the magnitude of these changes had a large effect size. The total score of MDS-UPDRS improved from 76.5 ± 24.3 to 60.4 ± 21.4 points (p < 0.001). Conclusions: Based on our results, UDysRS can reliably detect improvements in dyskinesia after DBS implantation.

Are the MDS-UPDRS-based composite scores clinically applicable?

Background: The International Parkinson and Movement Disorder Society–sponsored UPDRS (MDS‐UPDRS) is a powerful clinical outcome measure.