The potential neuromodulatory impact of subthalamic nucleus deep brain stimulation on Parkinson's disease progression.

INTRODUCTION: STN-DBS has been claimed to change progressionsymptomsin animal models of PD, but information is lacking about the possible neuromodulatory role of STN-DBS in humans. The aim of this prospective controlled study was to evaluate the long-term impact of STN-DBS on motor disabilities and cognitive impairment in PD patients in comparison to Best-Medical-Therapy (BMT) and Long-term-Post-Operative (POP) groups. MATERIAL AND METHODS: Patients were divided into 3 groups: the BMT-group consisted of 20 patients treated only with pharmacotherapy, the DBS-group consisted of 20 PD patients who underwent bilateral STN-DBS (examined pre- and postoperatively) and the POP-group consisted of 14 long-term postoperative patients in median 30 month-time after DBS. UPDRS III scale was measured during 3 visits in 9 ± 2 months periods (V1, V2, V3) in total-OFF phase. Cognitive assessment was performed during each visit in total-ON phase. RESULTS: The comparable UPDRS III OFF gain was observed in both BMT-group and POP-group evaluations (p < 0.05). UPDRS III OFF results in DBS-group revealed significant UPDRS III OFF increase in ΔV2-V1 assessment (p < 0.05) with no significant UPDRS III OFF alteration in ΔV3-V2 DBS-group evaluation (p > 0.05). Cognitive assessment revealed significant alterations between DBS-group and BMT-group in working memory, executive functions and learning abilities (p < 0.05). CONCLUSIONS: The impact of STN-DBS on UPDRS III OFF score and cognitive alterations suggest its neuromodulatory role, mainly during the first 9-18 months after surgery.

Evaluating reflexive saccades and UDPRS as markers of Deep Brain Stimulation and Best Medical Treatment improvements in Parkinson's disease patients: a prospective controlled study.

INTRODUCTION: To date, there has been no clear evidence regarding the evaluation of saccades as a monitoring tool of motor impairment in Parkinson's disease (PD) Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) patients. The aim of this study was to evaluate the long-term impact of STN-DBS and pharmacological treatment on reflexive saccades' (RS) parameters and UPDRS alterations. MATERIAL AND METHODS: The DBS group consisted of 20 PD patients who underwent bilateral STN-DBS. The Postoperative (POP) group consisted of 14 post-DBS patients. The Best Medical Therapy (BMT) group consisted of 20 patients on pharmacotherapy only. RS parameters and the UPDRS scale were measured during three visits in four phases of treatment (i.e. BMT-ON/OFF, DBS-ON/OFF). RESULTS: The significant UPDRS III and UPDRS. Total improvements were observed in all three study groups (p < 0.05), but RS latency improvement was stated only in the DBS group in the DBS-ON phase (p < 0.05). A significant correlation between RS latency increase and UPDRS III score worsening was found in all study groups, with the most evident effect in the UPDRS III ON phase (p < 0.05). CONCLUSION: RS parameters correlated with UPDRS III outcomes during the postoperative period in DBS-STN patients. Therefore, saccadic evaluation may be a good biomarker of the patient's response to surgical and/or pharmacological treatment.

The Neuromodulatory Impact of Subthalamic Nucleus Deep Brain Stimulation on Gait and Postural Instability in Parkinson's Disease Patients: A Prospective Case Controlled Study.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) has been an established method in improvement of motor disabilities in Parkinson's disease (PD) patients. It has been also claimed to have an impact on balance and gait disorders in PD patients, but the previous results are conflicting. Objective: The aim of this prospective controlled study was to evaluate the impact of STN-DBS on balance disorders in PD patients in comparison with Best-Medical-Therapy (BMT) and Long-term-Post-Operative (POP) group. Methods: DBS-group consisted of 20 PD patients (8F, 12M) who underwent bilateral STN DBS. POP-group consisted of 14 post-DBS patients (6F, 8M) in median 30 months-time after surgery. Control group (BMT-group) consisted of 20 patients (11F, 9M) who did not undergo surgical intervention. UPDRS III scale and balance tests (Up And Go Test, Dual Task- Timed Up And Go Test, Tandem Walk Test) and posturography parameters were measured during 3 visits in 9 ± 2months periods (V1, V2, V3) 4 phases of treatment (BMT-ON/OFF, DBS-ON/OFF). Results: We have observed the slowdown of gait and postural instability progression in first 9 post-operative months followed by co-existent enhancement of balance disorders in next 9-months evaluation (p < 0.05) in balance tests (Up and Go, TWT) and in posturography examination parameters (p < 0.05). The effect was not observed neither in BMT-group nor POP-group (p > 0.05): these groups revealed constant progression of static and dynamic instability (p > 0.05). Conclusions: STN-DBS can have modulatory effect on static and dynamic instability in PD patients: it can temporarily improve balance disorders. mainly during first 9 post-operative months, but with possible following deterioration of the symptoms in next post-operative months.

Multimodal Learning and Intelligent Prediction of Symptom Development in Individual Parkinson's Patients.

We still do not know how the brain and its computations are affected by nerve cell deaths and their compensatory learning processes, as these develop in neurodegenerative diseases (ND). Compensatory learning processes are ND symptoms usually observed at a point when the disease has already affected large parts of the brain. We can register symptoms of ND such as motor and/or mental disorders (dementias) and even provide symptomatic relief, though the structural effects of these are in most cases not yet understood. It is very important to obtain early diagnosis, which can provide several years in which we can monitor and partly compensate for the disease's symptoms, with the help of various therapies. In the case of Parkinson's disease (PD), in addition to classical neurological tests, measurements of eye movements are diagnostic. We have performed measurements of latency, amplitude, and duration in reflexive saccades (RS) of PD patients. We have compared the results of our measurement-based diagnoses with standard neurological ones. The purpose of our work was to classify how condition attributes predict the neurologist's diagnosis. For n = 10 patients, the patient age and parameters based on RS gave a global accuracy in predictions of neurological symptoms in individual patients of about 80%. Further, by adding three attributes partly related to patient 'well-being' scores, our prediction accuracies increased to 90%. Our predictive algorithms use rough set theory, which we have compared with other classifiers such as Naïve Bayes, Decision Trees/Tables, and Random Forests (implemented in KNIME/WEKA). We have demonstrated that RS are powerful biomarkers for assessment of symptom progression in PD.