Carmen Gasca-Salas

Background: Unilateral focused ultrasound subthalamotomy (STN‐FUS) improves motor features of Parkinson's disease (PD) for up to 3 years. Objectives: To assess the efficacy of unilateral STN‐FUS in PD 5 years post‐procedure. Methods: Prospective, open‐label study including PD patients treated with STN‐FUS. Primary outcome: change from baseline in the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale‐Part III (MDS‐UPDRS‐III) off‐medication for the treated side. Secondary outcomes: global motor state, motor complications, functional disability, quality of life, medication, and safety. Results: Forty‐five patients were included; 32 completed 5 years of follow‐up. While off‐medication, the MDS‐UPDRS‐III on the treated side showed 54% improvement from baseline (19.0 [95% CI 17.9–20.1] to 8.8 [7.5–10.1], P < 0.001). The total MDS‐UPDRS‐III was reduced by 27% (37.1 [34.9–39.3] to 27.1 [24.3–29.9], P < 0.001). At 5 years, motor complications, quality of life, and functional disability were equivalent to baseline. Levodopa equivalent daily dose (LEDD) increased from 739.2 (650.1–828.4) to 1053.3 (946.3–1160.3) milligrams ( P < 0.001). Mild‐to‐moderate levodopa‐induced dyskinesias (n = 7) were reported. No late adverse events occurred. Conclusion: Unilateral STN‐FUS for PD may provide sustained motor benefits after 5 years. © 2026 International Parkinson and Movement Disorder Society.

Objectives: Social Cognition (SC) can be impaired in Parkinson’s Disease (PD), yet its longitudinal evolution relative to cognitive status is unclear. This study examined whether SC deficits in PD patients suffers different changes based on baseline cognitive status and cognitive progression. Methods: In this observational study 48 non‐demented PD patients (32 with normal cognition [PD‐CN], 16 with mild cognitive impairment [PD‐MCI]), and 22 healthy controls (HC) were assessed at baseline and after three years. SC was assessed for facial emotion recognition (FER), affective and cognitive Theory of Mind (ToM), and social behavior. A comprehensive neuropsychological battery provided domain-specific z-scores. Cognitive classification followed MDS Level II criteria. Adjusted linear mixed models examined SC changes. Delta scores for SC tasks and z-score changes were correlated. Results: At baseline, PD-MCI patients scored lower on cognitive ToM than PD-CN and HC, with no significant group differences in affective ToM, FER, or social behavior. Over three years, PD-MCI patients experienced a significant decline in cognitive ToM compared to PD-CN and HC, while affective ToM and emotion recognition declined only relative to HC. The converters (n = 16) to a worse cognitive state (PD-CN to PD-MCI or PD-MCI to PDD) showed lower baseline cognitive ToM and steeper decline than stable patients. All SC changes correlated with visuospatial ability; affective ToM also correlated with memory, language and attention, and FER with memory and executive function. Conclusions: Cognitive ToM declines in parallel with cognitive deterioration in PD, while remaining stable in PD-CN. SC measures may help identify patients at higher risk of cognitive decline.

Background: Apathy, defined as a quantitative reduction in goal-directed activity, is a non-motor manifestation that can be present in Parkinson's disease (PD). It seems to be a risk factor for conversion to dementia (PDD) in this population. Amyloid-β deposition also predicts progression to PDD. Objective: We aimed to investigate whether PD patients with apathy showed higher amyloid burden than those without, as well as how these features may influence the rate of progression to dementia. Methods: We conducted an observational cross-sectional and longitudinal study. Forty-eight PD patients were recruited, including 20 with apathy and 28 without it according to the Starkstein Apathy Scale. They underwent clinical and cognitive evaluations and [ ¹⁸ F]-Flutemetamol PET. The neuropsychological assessment was repeated after 3 years. The predictive value of apathy and amyloid burden for conversion was assessed via logistic regression. Longitudinal trajectories across neuropsychological tests were modeled with linear mixed-effects. Results: Patients with apathy showed worse performance on several cognitive domains. Using disease duration and global cognition Z-score as covariates, amyloid burden was higher in apathetic vs. non-apathetic patients, mainly in the frontal and temporal cortices. Non-apathetic patients did not have regions with higher amyloid burden in comparison with apathetic patients. After 3 years’ follow-up, the conversion rate to worse cognitive state was significantly higher in apathetic (47.4%) vs. non-apathetic (12.0%) patients (p < 0.05). Logistic regression showed that amyloid burden, but not apathy, predicted 3-year cognitive conversion (χ² = 9.95, p < 0.05). Conclusions: Apathetic patients exhibit greater amyloid burden and higher cognitive deterioration over time than their non-apathetic counterparts.

Background: Cognitive fluctuations (CF) are spontaneous alterations in cognition, attention, and arousal, which are core clinical features in Lewy body dementia. A 4‐item scale from the Dementia Cognitive Fluctuation Scale (4‐item DCFS) is used in demented patients to identify CF. However, this has not been applied to non‐demented patients with Parkinson's disease (PD). Objectives: We applied the 4‐item DCFS in non‐demented PD patients to evaluate its relationship to neuropsychological tests and to determine whether this score is associated with cognitive deterioration. Methods: Fifty‐one patients underwent prospective neuropsychological assessments. Those who scored ≥3 in the 4‐item DCFS were recognized as CF positive. The Bayesian Kendall correlation test was applied to assess the relationship between the 4‐item DCFS score, cognitive tests, and amyloid burden. Forty‐five patients were followed up for 3 years. Results: Thirty‐two patients scored 0 (62.7%, no positive answers), 11 (21.6%) scored 1, 4 (7.8%) scored 2, and 4 (7.8%) scored 3 points on the 4‐item DCFS. Moderate or strong evidence showed that the 4‐item‐DCFS score correlated with worse performance on the Trail Making Test B (Bayes factor, BF ₊₀ = 4), delayed visual recall test (BF ₋₀ = 12.9), and higher amyloid burden (BF ₊₀ = 13.6). All patients who scored ≥3 converted to PD‐mild cognitive impairment or dementia at follow‐up, whereas only 29% without CFs had converted to a worse cognitive status. Conclusions: A higher score on the 4‐item DCFS is related to lower scores in executive and memory function, along with a potential connection to amyloid pathology. Patients with lower scores are less likely to develop a worse cognitive state, although larger sample sizes are needed to confirm this relationship.

BACKGROUND AND IMPORTANCE: Magnetic resonance–guided focused ultrasound (MRgFUS) ablation is a new therapeutic tool for movement disorders. Side effects after treatment are mild to moderate, and treatment-related severe complications are rare. Technical intraprocedural hurdles such as inertial cavitation can be associated with adverse events. We describe 2 patients who developed symptomatic brain bleeding during MRgFUS ablation associated with the presence of cavitation. This complication has not been reported thus far. CLINICAL PRESENTATION: Two female patients aged 74 and 68 years were treated with MRgFUS ablation for medically refractory essential tremor and Parkinson disease, respectively. The treatment progressed uneventfully, and clinical improvement was seen; however, cavitation occurred before we achieved satisfactory benefit. To mitigate cavitation, sonication power was decreased in both patients, but cavitation activity persisted. After the last sonication, both patients showed contralateral motor weakness, and the treatment was terminated. Post-treatment brain computed tomography scans in both patients showed a brain hematoma in the targeted area. One patient improved progressively within a few months, but the second remained disabled. CONCLUSION: These two cases represent 0.4% of our over 500 patients treated with MRgFUS ablation, and, thus, brain bleeding should be considered a rare complication of the therapy. However, it cannot be ruled out, particularly if uncontrollable cavitation occurs. A conservative approach should be taken in such cases to avoid it.