Clinical and Brain Morphometry Predictors of Deep Brain Stimulation Outcome in Parkinson's Disease.

Subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in advanced Parkinson's disease (PD) and to enable a reduction of anti-parkinsonian medication. While the levodopa challenge test and disease duration are considered good predictors of STN-DBS outcome, other clinical and neuroanatomical predictors are less established. This study aimed to evaluate, in addition to clinical predictors, the effect of patients' individual brain topography on DBS outcome. The medical records of 35 PD patients were used to analyze DBS outcomes measured with the following scales: Part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) off medication at baseline, and at 6-months during medication off and stimulation on, use of anti-parkinsonian medication (LED), Abnormal Involuntary Movement Scale (AIMS) and Non-Motor Symptoms Questionnaire (NMS-Quest). Furthermore, preoperative brain MRI images were utilized to analyze the brain morphology in relation to STN-DBS outcome. With STN-DBS, a 44% reduction in the UPDRS-III score and a 43% decrease in the LED were observed (p<0.001). Dyskinesia and non-motor symptoms decreased significantly [median reductions of 78,6% (IQR 45,5%) and 18,4% (IQR 32,2%) respectively, p=0.001 - 0.047]. Along with the levodopa challenge test, patients' age correlated with the observed DBS outcome measured as UPDRS-III improvement (ρ= -0.466 - -0.521, p<0.005). Patients with greater LED decline had lower grey matter volumes in left superior medial frontal gyrus, in supplementary motor area and cingulum bilaterally. Additionally, patients with greater UPDRS-III score improvement had lower grey matter volume in similar grey matter areas. These findings remained significant when adjusted for sex, age, baseline LED and UPDRS scores respectively and for total intracranial volume (p=0.0041- 0.001). However, only the LED decrease finding remained significant when the analyses were further controlled for stimulation amplitude. It appears that along with the clinical predictors of STN-DBS outcome, individual patient topographic differences may influence DBS outcome. Clinical Trial Registration Number: NCT06095245, registration date October 23, 2023, retrospectively registered.

Levodopa-Entacapone-Carbidopa Intestinal Gel Treatment in Advanced Parkinson's Disease: A Single-Center Study of 30 Patients.

BACKGROUND: Levodopa-entacapone-carbidopa intestinal gel (LECIG) is a novel device assisted treatment option for advanced Parkinson's disease (PD). It has been available in Finland since 2020. There is paucity of scientific studies considering LECIG treatment in clinical practice. OBJECTIVES: Objectives of this study were to evaluate the changes in medication, adverse events and early discontinuations of LECIG treatment in real life clinical practice. METHODS: The records of 30 consecutive patients, who received LECIG between years 2020 and 2022 in Helsinki University Hospital, were retrospectively analyzed. Data considering changes in medication, discontinuations, and adverse events during the first six months of LECIG treatment was collected. RESULTS: Mean levodopa equivalent daily dose (LEDD) rose significantly between baseline before LECIG and six months with treatment (1230 mg vs. 1570 mg, P = 0.001). Three patients were discarded during nasojejunal tube test phase and seven discontinued the treatment during six-month follow-up. Most common reasons for discontinuation were difficulty in finding suitable infusion rate and neuropsychiatric problems. Safety issues encountered were similar to those reported with levodopa-carbidopa intestinal gel (LCIG) treatment. One case of rhabdomyolysis due to severe dyskinesia during LECIG treatment was observed. Patients were satisfied with the small size of the pump system. CONCLUSIONS: LEDD seems to increase during the first months of LECIG treatment. When compared to studies on LCIG, safety profile of LECIG appears similar, but early discontinuation rate is higher than expected. However, long-term studies are lacking. Only clear advantage to LCIG appears to be the smaller LECIG pump size.

Attitudes Toward the Adoption of Remote Patient Monitoring and Artificial Intelligence in Parkinson's Disease Management: Perspectives of Patients and Neurologists.

OBJECTIVE: Early detection of Parkinson's Disease (PD) progression remains a challenge. As remote patient monitoring solutions (RMS) and artificial intelligence (AI) technologies emerge as potential aids for PD management, there's a gap in understanding how end users view these technologies. This research explores patient and neurologist perspectives on AI-assisted RMS. METHODS: Qualitative interviews and focus-groups were conducted with 27 persons with PD (PwPD) and six neurologists from Finland and Italy. The discussions covered traditional disease progression detection and the prospects of integrating AI and RMS. Sessions were recorded, transcribed, and underwent thematic analysis. RESULTS: The study involved five individual interviews (four Italian participants and one Finnish) and six focus-groups (four Finnish and two Italian) with PwPD. Additionally, six neurologists (three from each country) were interviewed. Both cohorts voiced frustration with current monitoring methods due to their limited real-time detection capabilities. However, there was enthusiasm for AI-assisted RMS, contingent upon its value addition, user-friendliness, and preservation of the doctor-patient bond. While some PwPD had privacy and trust concerns, the anticipated advantages in symptom regulation seemed to outweigh these apprehensions. DISCUSSION: The study reveals a willingness among PwPD and neurologists to integrate RMS and AI into PD management. Widespread adoption requires these technologies to provide tangible clinical benefits, remain user-friendly, and uphold trust within the physician-patient relationship. CONCLUSION: This study offers insights into the potential drivers and barriers for adopting AI-assisted RMS in PD care. Recognizing these factors is pivotal for the successful integration of these digital health tools in PD management.

GPi-DBS-induced brain metabolic activation in cervical dystonia.

BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a highly efficacious treatment for cervical dystonia, but its mechanism of action is not fully understood. Here, we investigate the brain metabolic effects of GPi-DBS in cervical dystonia. METHODS: Eleven patients with GPi-DBS underwent brain 18F-fluorodeoxyglucose positron emission tomography imaging during stimulation on and off. Changes in regional brain glucose metabolism were investigated at the active contact location and across the whole brain. Changes in motor symptom severity were quantified using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), executive function using trail making test (TMT) and parkinsonism using Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: The mean (SD) best therapeutic response to DBS during the treatment was 81 (22)%. The TWSTRS score was 3.2 (3.9) points lower DBS on compared with off (p=0.02). At the stimulation site, stimulation was associated with increased metabolism, which correlated with DBS stimulation amplitude (r=0.70, p=0.03) but not with changes in motor symptom severity (p>0.9). In the whole brain analysis, stimulation increased metabolism in the GPi, subthalamic nucleus, putamen, primary sensorimotor cortex (PFDR<0.05). Acute improvement in TWSTRS correlated with metabolic activation in the sensorimotor cortex and overall treatment response in the supplementary motor area. Worsening of TMT-B score was associated with activation of the anterior cingulate cortex and parkinsonism with activation in the putamen. CONCLUSIONS: GPi-DBS increases metabolic activity at the stimulation site and sensorimotor network. The clinical benefit and adverse effects are mediated by modulation of specific networks.

Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson's Disease.

Directional deep brain stimulation (dDBS) is preferred by patients with advanced Parkinson's disease (PD) and by programming neurologists. However, real-life data of dDBS use is still scarce. We reviewed the clinical data of 53 PD patients with dDBS to 18 months of follow-up. Directional stimulation was favored in 70.5% of dDBS leads, and single segment activation (SSA) was used in 60% of dDBS leads. Current with SSA was significantly lower than with other stimulation types. During the 6-month follow-up, a 44% improvement in the Unified Parkinson's Disease Rating Scale (UPDRS-III) points and a 43% decline in the levodopa equivalent daily dosage (LEDD) was observed. After 18 months of follow-up, a 35% LEDD decrease was still noted. The Hoehn and Yahr (H&Y) stages and scores on item no 30 "postural stability" in UPDRS-III remained lower throughout the follow-up compared to baseline. Additionally, dDBS relieved non-motor symptoms during the 6 months of follow-up. Patients with bilateral SSA had similar clinical outcomes to those with other stimulation types. Directional stimulation appears to effectively reduce both motor and non-motor symptoms in advanced PD with minimal adverse effects in real-life clinical care.

Single-Center Study of 103 Consecutive Parkinson's Disease Patients with Levodopa-Carbidopa Intestinal Gel.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) effectively reduces off time and dyskinesia and increases on time in advanced Parkinson's disease (PD). However, patients with LCIG-infusion experience frequent complications and some discontinue treatment early on. OBJECTIVES: The objectives of this study were to find predictive factors for early dropout from the LCIG infusion, analyze the treatment burden on the tertiary health care system, and explore changes in medication during the LCIG treatment. METHODS: LCIG-infusion was administrated to 103 patients between July 2006 and May 2020 at the Helsinki University Hospital, accumulating 350 years of follow-up data. We evaluated, retrospectively, changes in medication during treatment, discontinuation of the infusion, and adverse events from the patient records. RESULTS: Living alone was a predictive factor for early dropout (OR = 3.88; 95% CI = 1.03-14.66; P = 0.045). The treatment burden on the tertiary health care system increased after the initiation of LCIG infusion mostly because of common complications related to the infusion system (median change of in- and out-patient visits +1, P = 0.03). Mean levodopa equivalent daily dose (LEDD) rose from baseline to 6 months (1246.7 vs. 1684.9, P = 0.001) and stabilized thereafter. Patients commonly switched from "polypharmacy" to "LCIG-only" or "LCIG + oral levodopa" medication-groups during long-term treatment. CONCLUSIONS: Recurrent complications related to the infusion system increase the treatment burden on tertiary healthcare system after the initiation of LCIG-infusion. Most patients continue long-term with the infusion. Few patients discontinue infusion during the first year after initiation and living alone appears to be a risk factor for this outcome.

Polyneuropathy monitoring in Parkinson's disease patients treated with levodopa/carbidopa intestinal gel.

OBJECTIVES: Levodopa-carbidopa-intestinal-gel (LCIG) infusion is an effective treatment for advanced PD with motor fluctuations. Polyneuropathy occurs as a complication in 10-15% of patients. We wanted to assess the frequency of polyneuropathy in Finnish advanced Parkinson's disease (PD) patients with continuous LCIG infusion, and the value of different clinical monitoring parameters during follow-up. MATERIALS AND METHODS: Patient records of PD patients started on LCIG infusion at Helsinki University Hospital who received nerve conduction studies at baseline and 6 months after treatment initiation were reviewed for epidemiological information, mini mental state examination, baseline and 6 months' UPRDS-III, weight, body mass index, levodopa dose (LD), plasma homocysteine levels, folate, vitamin B6 and B12. RESULTS: Out of 19 patients (n = 6 on B-vitamin substitution), two (10.5%) developed new-onset polyneuropathy after initiation of LCIG therapy (n = 0 with vitamin substitution). Neuropathy was associated with significant weight loss (BMI reduction > 1.5), but not with other monitoring parameters. Homocysteine rose significantly in patients not substituted with B-vitamin complex, but not in patients with B-vitamin substitution. Homocysteine changes correlated with LD changes in the absence of vitamin B substitution. After oral B-vitamin substitution, both patients' polyneuropathy remained electrophysiologically and clinically stable. CONCLUSIONS: Rates of polyneuropathy in Finnish PD patients with LCIG treatment are comparable to previous studies. Patients' weight should be included in regular follow up monitoring and can be used for patient self-monitoring. Vitamin B substitution appears to reduce coupling between levodopa dose and homocysteine and may be useful to prevent polyneuropathy related to LCIG.

Ambulatory surface electromyography with accelerometry for evaluating daily motor fluctuations in Parkinson's disease.

OBJECTIVE: To evaluate motor fluctuations in patients with advanced Parkinson's disease (PD) using a small-sized wearable device for surface electromyography (EMG) with accelerometry (ACC) for 24 hours. METHODS: Seven PD patients with medication were measured once, and nine patients with directional deep brain stimulation (dDBS) twice: before and after the dDBS reprogramming. EMG and ACC parameters were compared with clinical rating scores and patients' home diaries. RESULTS: The combination of EMG and ACC parameters (first principal component PC1) correlated significantly with patient's condition as quantified by the motor score of Unified Parkinson's Disease Rating Scale and it changed significantly with dDBS reprogramming in line with decreased PD symptoms. Monitoring data detected in comparison with the home diaries: 91 % concordance with tremor, 76 % with rigidity, and 74 % with dyskinesia. In the DBS group, the wake-up time with abnormal neuromuscular function was reduced with reprogramming in all except one patient based on measurements. CONCLUSIONS: A wearable device measuring simultaneously both muscle activity and motion can provide continuous and dynamic information about patient's condition and motor fluctuations at home. SIGNIFICANCE: The present method may help to modify pharmacologic management and DBS treatment in advanced PD.

Motor outcome and electrode location in deep brain stimulation in Parkinson's disease.

OBJECTIVES: To evaluate the efficacy and adverse effects of subthalamic deep brain stimulation (STN-DBS) in patients with advanced Parkinson's disease (PD) and the possible correlation between electrode location and clinical outcome. METHODS: We retrospectively reviewed 87 PD-related STN-DBS operations at Helsinki University Hospital (HUH) from 2007 to 2014. The changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, Hoehn & Yahr stage, antiparkinson medication, and adverse effects were studied. We estimated the active electrode location in three different coordinate systems: direct visual analysis of MRI correlated to brain atlas, location in relation to the nucleus borders and location in relation to the midcommisural point. RESULTS: At 6 months after operation, both levodopa equivalent doses (LEDs; 35%, Wilcoxon signed-rank test = 0.000) and UPDRS part III scores significantly decreased (38%, Wilcoxon signed-rank test = 0.000). Four patients (5%) suffered from moderate DBS-related dysarthria. The generator and electrodes had to be removed in one patient due to infection (1%). Electrode coordinates in the three coordinate systems correlated well with each other. On the left side, more ventral location of the active contact was associated with greater LED decrease. CONCLUSIONS: STN-DBS improves motor function and enables the reduction in antiparkinson medication with an acceptable adverse effect profile. More ventral location of the active contact may allow stronger LED reduction. Further research on the correlation between contact location, clinical outcome, and LED reduction is warranted.