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.
Koivu M
，Sihvonen AJ
，Eerola-Rautio J
，Pauls KAM
，Resendiz-Nieves J
，Vartiainen N
，Kivisaari R
，Scheperjans F
，Pekkonen E
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Dopaminergic responsiveness and dopaminergic challenge tests of Parkinson's disease: a systematic review and meta-analysis.
The assessment and quantification of dopaminergic responsiveness are crucial for the diagnosis and management of Parkinson's disease (PD). This study aimed to summarize and compare motor improvements in patients with PD and atypical parkinsonian syndromes (APS) across three types of dopaminergic challenge tests, as well as evaluate their diagnostic performance.
PubMed, Embase, Cochrane Library, and Web of Science were searched to identify eligible studies reporting the improvement rate of the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) or MDS-UPDRS-III in dopaminergic challenge tests for PD or APS, or diagnostic outcomes in differential diagnosis between PD and APS. A random-effects model was conducted to pool improvement rates and standardized mean differences (SMDs) in patients with PD or APS during dopaminergic challenge tests. Subgroup analysis and meta-regression were used to investigate the sources of heterogeneity. A bivariate mixed-effects model was employed to evaluate the diagnostic performance of these tests.
A total of 58 studies (3641 PD and 711 APS) were included. In the acute levodopa challenge test, patients with PD, APS, and multiple system atrophy (MSA) demonstrated pooled UPDRS-III improvement rates of 41.5% [95% confidence interval (CI) 38.5%-44.5%; I2 = 98.8%], 14.7% (95% CI 6.8%-22.7%; I2 = 96.5%), and 6.3% (95% CI - 4.0% to 16.7%), respectively. Subgroup analyses showed the pooled improvement rate of de novo PD patients (25.9%; 95% CI 15.1%-36.7%) was significantly lower than treated PD patients (42.4%; 95% CI 38.6%-46.2%) (p = 0.005), overlapping with APS patients with off-state H-Y stage ≤ 2.5 (21.2%; 95% CI 14.5%-27.9%). PD patients with off-state H-Y stage ≤ 2.5 (35.4%; 95% CI 31.1%-39.7%) or UPDRS-III score ≤ 30 (30.5%; 95% CI 23.4%-35.7%) had significantly lower improvement rate than PD patients with off-state H-Y stage > 2.5 (44.1%; 95% CI 37.0%-51.3%) (p = 0.041) or UPDRS-III scores > 30 (47.0%; 95% CI 43.7%-50.4%) (p < 0.001). The pooled improvement rate in acute levodopa challenge tests of PD with 100 mg levodopa (17.0%; 95% CI 11.3%-22.8%) was significantly lower than that in tests with 200-250 mg levodopa (34.3%; 95% CI 30.6%-38.0%) (p < 0.001). Meta-regression showed the improvement rate of PD was positively correlated with off-state UPDRS-III scores (p = 0.007). In the acute apomorphine challenge test, PD patients showed a pooled UPDRS-III improvement rate of 40.1% (95% CI 36.9%-43.3%). To differentiate between PD and APS, the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) for the acute levodopa challenge test were 0.81, 0.77, 13.91, and 0.85; for the acute apomorphine challenge test, they were 0.84, 0.85, 29.94, and 0.91; and for chronic levodopa therapy, they were 0.82, 0.71, 11.54, and 0.72. The pooled sensitivity, specificity, DOR, and AUC of the acute levodopa challenge test for distinguishing PD from MSA were 0.82, 0.78, 15.74, and 0.79; for PD vs. PSP, they were 0.77, 0.78, 11.54, and 0.84; and for PD vs. DLB, they were 0.65, 0.58, 2.65, and 0.64.
The overall dopaminergic responsiveness is greater in PD patients compared to those with APS. However, there is significant heterogeneity in the pooled motor improvement of dopaminergic responsiveness within PD or APS, with overlap between de novo PD and early-stage APS. All three types of dopaminergic challenge tests demonstrate moderate diagnostic performance in differentiating PD from APS.
Kou W
，Cai H
，Cui Y
，Zhu J
，Li S
，Yang C
，Chen H
，Feng T
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ResearchGate
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