Antiparkinsonian Drug Reduction After Directional Versus Omnidirectional Bilateral Subthalamic Deep Brain Stimulation.

BACKGROUND: Several pilot trials and the Clinical Evaluation of the Infinity Deep Brain Stimulation System (PROGRESS) study have found that directional stimulation can provide a wider therapeutic window and lower therapeutic current strength than omnidirectional stimulation. OBJECTIVE: We conducted a single-center, open-label, registry-based, comparative trial to test the hypothesis that directional stimulation can be associated with a greater reduction in the total daily dose of antiparkinsonian medications (ApMeds) than omnidirectional stimulation. MATERIALS AND METHODS: A total of 52 patients with directional and 57 subjects with omnidirectional bilateral subthalamic deep brain stimulation (STN-DBS) were enrolled. Preoperatively and 12 months postoperatively, the dose of different ApMeds, the number of tablets used daily, the severity of motor and nonmotor symptoms using the Movement Disorder Society-sponsored Unified Parkinson Disease Rating Scale, and the health-related quality of life (HRQoL) using the 39-item Parkinson's Disease Questionnaire (PDQ-39) were assessed. RESULTS: According to the changes in the levodopa equivalent daily dose, directional STN-DBS led to a 13% greater reduction in the total daily dose of ApMed. The 10.3% greater reduction in the dose of levodopa was the main contributor to this difference. The number of different ApMed types also could be decreased in a greater manner with directional stimulation. The improvement in the severity of motor and nonmotor symptoms was comparable; however, we detected a 15.8% greater improvement in the global HRQoL among patients with directional stimulation according to the changes in the summary index of the PDQ-39. The total electrical energy delivered per second was comparable between the groups at 12-month postoperative visit, whereas the amplitude of stimulation was significantly lower and the impedance was significantly higher with directional leads. CONCLUSIONS: Directional programming can further increase the reduction in the total daily dose of ApMed after STN-DBS. In addition, directional stimulation can have additional beneficial effects on the global HRQoL. The greater reduction of ApMed doses did not require more energy-consuming stimulation with directional stimulation.

The Impact of Trimetazidine on Disease Severity and Quality of Life in Parkinson's Disease.

Trimetazidine is contraindicated in movement disorders, however, a not negligible part of trimetazidine users is still patients with Parkinson's disease (PD). The present study aimed to objectively determine the impact of trimetazidine on the severity of symptoms and the health-related quality of life of patients with PD by measuring changes after its withdrawal. A consecutive series of 42 patients with PD using trimetazidine underwent detailed neurological and neuropsychological assessments at baseline and three months after the discontinuation of trimetazidine. Clinically relevant improvements were achieved with discontinuation of trimetazidine according to changes in scores of each part of the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (Part I: -25.7%, p < 0.001; Part II: -23.8%, p < 0.001; Part III: -28.5%, p < 0.001; Part IV: -30.1%, p = 0.004) and total scores of the Non-Motor Symptoms Scale (-25.6%, p = 0.004) and the Montgomery-Asberg-Depression Rating Scale (-20.1%, p = 0.001). Benefits resulting from the withdrawal of the drug also manifested in the improvement of the health-related quality of life based on changes in the summary index of the 39-item Parkinson's Disease Questionnaire (-18.2%, p = 0.031). Our results provide clinical rationale for strictly avoiding the use of trimetazidine in PD. Discontinuation of trimetazidin results in clinically relevant improvements in Parkinsonian symptoms.

Which Scale Best Detects Treatment Response of Tremor in Parkinsonism?

BACKGROUND: Several scales are available for rating the severity of tremor at present. However, the sensitivity to change of these instruments has remained to be clarified. OBJECTIVE: To compare the sensitivity of the Fahn-Tolosa-Marin Tremor Rating Scale, the Part III of the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the MDS-UPDRS Tremor Scale to the effects of various antitremor treatments. METHODS: Enrolling subjects with parkinsonism associated with tremor, we analyzed two scenarios: (1) tremor changes associated with acute levodopa challenge (n = 287) and (2) a 12-month outcome of different treatment options (n = 512) including deep brain stimulation (n = 146), levodopa/carbidopa intestinal gel infusion (n = 30), and initiating (n = 63) or adjusting oral antiparkinsonian medication (n = 273). Changes in tremor scales were assessed by effect size values (Cohen's d and eta-square). RESULTS: Part B of the Fahn-Tolosa-Marin Tremor Rating Scale was the most sensitive to acute levodopa challenge (Cohen's d = -1.04, η2 = 0.12). However, Part A of the Fahn-Tolosa-Marin Tremor Rating Scale showed the highest effect size, which was a small one (Cohen's d = -0.33, η2 = 0.03), for detecting a treatment-related change in the severity of tremor during long-term follow-up. CONCLUSIONS: The Fahn-Tolosa-Marin Tremor Rating Scale has a better ability to capture changes due to levodopa challenge or antiparkinsonian treatment than MDS-UPDRS Part III or MDS-UPDRS Tremor Scale.

[Selection of the optimal device-aided therapy in Parkinson's disease]. / Elorehaladott Parkinson-kór kezelési lehetoségei: az optimális terápia kiválasztásának szempontjai.

For the treatment of advanced Parkinson's disease the deep brain stimulation (DBS) and the levodopa/carbidopa intestinal gel (LCIG) therapies are available in Hungary. Although they may have similar impact on the health-related quality of life and disabilities associated with the disease, they have different indications, and inclusion- and exclusion criteria. Consequently, the patient population treated with DBS and LCIG may be different. In the present review, the authors try to help the process of selection of the optimal device-aided therapy for the patients with advanced Parkinson's disease.

Trimetazidine and parkinsonism: A prospective study.

BACKGROUND: Although trimetazidine may induce parkinsonian symptoms in some patients, no systematic characterization has been reported on parkinsonism occurring during trimetazidine treatment since the first case reports. OBJECTIVE: To systematically investigate parkinsonism occurring during trimetazidine use. METHODS: Thirty-three consecutive patients on trimetazidine treatment with previously unrecognized parkinsonian symptoms were enrolled. Detailed neurological and neuropsychological examinations were performed at baseline and 1 and 12 months after trimetazidine withdrawal. In cases with persisting parkinsonian symptoms and suspected de novo Parkinson's disease, antiparkinsonian treatment was initiated. Twenty of the 33 patients underwent DaTSCAN imaging. RESULTS: After trimetazidine withdrawal, parkinsonism was completely resolved in 11 cases. The comparison of baseline data of patients with reversible and persisting parkinsonism showed that trimetazidine-induced reversible parkinsonism was mainly characterized by akinesia, rigidity, postural instability and gait disturbances (PIGD; PIGD scores: 5.3 ±â€¯3.8 vs. 2.0 ±â€¯1.6 points, p = 0.006) rather than tremors (tremor scores: 1.5 ±â€¯2.2 vs. 7.7 ±â€¯4.6 points, p = 0.000). Trimetazidine-induced reversible parkinsonism was also more symmetrical (asymmetry index: 3.1 ±â€¯3.6 vs. 40.1 ±â€¯22.2, p = 0.000) and milder in severity (MDS-UPDRS Part III. scores: 10.5 ±â€¯19. vs. 30.5 ±â€¯11.3, p = 0.040) than nonreversible parkinsonism. DaTSCAN images were normal in all trimetazidine-induced reversible parkinsonism patients, while these images were abnormal in every patient with nonreversible parkinsonism. In cases of nonreversible parkinsonism, preexisting, incipient Parkinson's disease was suspected by clinical appearance and a good response to antiparkinsonian medication. CONCLUSIONS: Mild and symmetrical appearance of parkinsonism with normal DaTSCAN results can indicate drug-induced parkinsonism. Trimetazidine discontinuation generally results in permanent remission in such cases.

Comparing Sensitivity and Specificity of Addenbrooke's Cognitive Examination-I, III and Mini-Addenbrooke's Cognitive Examination in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by numerous motor and nonmotor symptoms. Neurocognitive disorders (NCD) are one of the most troublesome problems and their diagnosis is often challenging. METHODS: We compared the sensitivity and specificity of several versions of Addenbrooke Cognitive Examination (ACE, ACE-III, and Mini-ACE) on 552 subjects with PD. Normal cognition, mild and major NCD were judged in accordance with the respective criteria of the Diagnostic and Statistical Manual of Mental Disorders 5th edition. Subsequently, we applied the receiver operation characteristic (ROC) analysis in comparison of different education levels. RESULTS: For subjects with education level 0-8 and 9-12 years, the ACE-III had the best discriminating capabilities for mild NCD (cut-off scores: 83.5 and 85.5 points, respectively), while Mini-ACE was the best for subjects having education > 12 years (cut-off score: 25.5 points). For detecting major NCD, ACE-III had the best diagnostic accuracy in all levels of education (cut-off scores: 70.5, 77.5, and 78.5 points for subjects having education level 0-8, 9-12, and >12 years, respectively). CONCLUSION: ACE-III and its nested version, the Mini-ACE, had the best screening abilities for detecting mild and major NCD in PD.

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. OBJECTIVES: To evaluate the feasibility of various MDS-UPDRS-based composite scores and determine their minimal clinically important difference threshold values. METHODS: Overall, 1,113 paired investigations of 452 patients were reviewed implementing three different techniques simultaneously. RESULTS: Based on the ordinal regression modeling, the MDS-UPDRS II+III, MDS-UPDRS I+II+III, and the total score of MDS-UPDRS are clinically applicable outcome measures. Any improvement greater than 4.9 points or any worsening more than 4.2 points on MDS-UPDRS II+III represent a minimal, yet clinically meaningful, change. In reference to MDS-UPDRS I+II+III, the smallest changes considered clinically relevant were 6.7 and 5.2 points for improvement and deterioration, respectively. The thresholds for the total score of MDS-UPDRS were 7.1 points for improvement and 6.3 points for worsening. CONCLUSIONS: Our findings support the application of various MDS-UPDRS-based composite scores. © 2018 International Parkinson and Movement Disorder Society.

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

BACKGROUND: Dyskinesia is among the most troublesome symptoms of advanced Parkinson's 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.

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. OBJECTIVES: We aimed to calculate these threshold values in association with the International Parkinson and Movement Disorder Society UPDRS (MDS-UPDRS) Parts I and II and to evaluate the feasibility of the composite score of Part I and II (MDS-UPDRS I+II) as an outcome. METHODS: Nine hundred eighty-five paired investigations of 365 patients were reviewed, implementing three different techniques simultaneously. RESULTS: Based on the ordinal regression modeling, the MDS-UPDRS I+II score is an applicable outcome measure. Any improvement greater than 2.64 points or any worsening more than 2.45 points on MDS-UPDRS Part I represent a minimal, yet clinically meaningful change. In reference to Part II, the smallest changes considered clinically relevant were 3.05 and 2.51 points for improvement and deterioration, respectively. The thresholds for MDS-UPDRS I+II were 5.73 points for improvement and 4.70 points for worsening. CONCLUSIONS: Our minimal clinically important difference thresholds can be utilized in clinical practice in judging clinical relevance. © 2016 International Parkinson and Movement Disorder Society.

Levodopa/carbidopa intestinal gel can improve both motor and non-motor experiences of daily living in Parkinson's disease: An open-label study.

BACKGROUND: Levodopa/carbidopa intestinal gel therapy (LCIG) can efficiently improve several motor and non-motor symptoms of advanced Parkinson's disease (PD). The recently developed Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) improved the original UPDRS making it a more robust tool to evaluate therapeutic changes. However, previous studies have not used the MDS-UPDRS and the Unified Dyskinesia Rating Scale (UDysRS) to assess the efficacy of LCIG. OBJECTIVES: Our aim was to determine if the MDS-UPDRS and UDysRS could detect improvement in the experiences of daily living following 1-year LCIG treatment. METHODS: In this prospective, multicenter, open-label study, 34 consecutive patients undergoing LCIG treatment were enrolled. Patients were examined twice: prior to LCIG initiation and 12 months later. Impact of PD-related symptoms and dyskinesia was assessed by the MDS-UPDRS and UDysRS. RESULTS: Non-motor Experiences of Daily Living part of MDS-UPDRS improved from 20 (median, interquartile-range, IQR:14-23) to 16 points (median, IQR:12-20, p = 0.044) and the Motor Experiences of Daily Living ameliorated from 24 (median, IQR:20-29) to 18 points (median, IQR:13-25, p = 0.025). Health-related quality of life, measured by PDQ-39, also improved from 35.4 (median, IQR:26.9-50.3) to 27.0 (median, IQR:21.3-31.4) points (p = 0.003). The total score of UDysRS decreased from 47 (median, IQR:36-54) to 34 (median, IQR:21-45) points (p = 0.003). CONCLUSIONS: As far as the authors are aware of, our paper is the first to evaluate the impact of LCIG on dyskinesia by the means of UDysRS. Changes in MDS-UPDRS and UDysRS confirm that LCIG treatment can efficiently improve experiences of daily living in advanced PD.

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 Parkinson's 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.