Jorge Uriel Máñez‐Miró

The subthalamic nucleus (STN) modulates basal ganglia output and plays a fundamental role in the pathophysiology of Parkinson’s disease (PD). Blockade/ablation of the STN improves motor signs in PD. We assessed the topography of focused ultrasound subthalamotomy ( n = 39) by voxel-based lesion-symptom mapping to identify statistically validated brain voxels with the optimal effect against each cardinal feature and their respective cortical connectivity patterns by diffusion-weighted tractography. Bradykinesia and rigidity amelioration were associated with ablation of the rostral motor STN subregion connected to the supplementary motor and premotor cortices, whereas antitremor effect was explained by lesioning the posterolateral STN projection to the primary motor cortex. These findings were corroborated prospectively in another PD cohort ( n = 12). This work concurs with recent deep brain stimulation findings that suggest different corticosubthalamic circuits underlying each PD cardinal feature. Our results provide sound evidence in humans of segregated anatomy of subthalamic-cortical connections and their distinct role in PD pathophysiology and normal motor control.

Social cognition (SC) encompasses a set of cognitive functions that enable individuals to understand and respond appropriately to social interactions. Although focused ultrasound subthalamotomy (FUS‐STN) effectively treats Parkinson's disease (PD) clinical motor features, its impact and safety on cognitive‐behavioral interactions/interpersonal awareness are unknown. This study investigated the effects of unilateral FUS‐STN on facial emotion recognition (FER) and affective and cognitive theory of mind (ToM) in PD patients from a randomized sham‐controlled trial (NCT03454425). Subjects performed SC evaluation before and 4 months after the procedure while still under blind assessment conditions. The SC assessment included the Karolinska Directed Emotional Faces task for FER, the Reading the Mind in the Eyes (RME) test for affective ToM, and The Theory of Mind Picture Stories Task (ToM PST) (order, questions, and total score) for cognitive ToM. The active treatment group showed anecdotal‐to‐moderate evidence of no worsening in SC after FUS‐STN. Anecdotal evidence for an improvement was recognized in the SC score changes, from baseline to post‐treatment, for the active treatment group compared with sham for the RME, ToM PST order, ToM PST total, FER total, and recognition of fear, disgust, and anger. This study provides the first evidence that unilateral FUS‐STN does not impair social cognitive abilities, indicating that it can be considered a safe treatment approach for this domain in PD patients. Furthermore, the results suggest FUS‐STN may even lead to some improvement in social cognitive outcomes, which should be considered as a preliminary finding requiring further investigation with larger samples sizes. © 2024 International Parkinson and Movement Disorder Society.

Background and Objectives: Unilateral Magnetic Resonance-guided Focused Ultrasound subthalamotomy (FUS-STN) has been shown to improve the cardinal motor features of Parkinson’s disease (PD). Whether this effect is sustained is not known. This study aims to report the long-term outcome of PD patients treated with unilateral FUS-STN. Methods: We conducted a prospective, open-label study of asymmetrical PD patients who underwent unilateral FUS-STN. All patients were evaluated up to 36 months after treatment. The primary outcome was the difference from baseline to 36 months after FUS-STN in the score of the Movement Disorders Society-Unified Rating scale (MDS-UPDRS) motor part (III) for the treated hemibody in the off-medication state. The safety outcome included all adverse events occurring during follow-up. Secondary outcomes were the change in the MDS-UPDRS III score on-medication; sub-scores of rigidity, bradykinesia, tremor, and axial features; total MDS-UPDRS III; and the MDS-UPDRS part IV. Functional disability and quality of life were assessed using the MDS-UPDRS II and the PDQ39, respectively. Patient impression of change and satisfaction with the treatment were self-assessed. The Wilcoxon signed-rank test with subsequent Bonferroni’s correction was used for data analysis. Results: Thirty-two PD patients were evaluated 36 months after treatment. The mean (±SD) age at baseline was 56.0±10.1 years, with a mean disease duration of 6.8±2.8 years. The MDS-UPDRS III score for the treated hemibody off-medication was improved by 52.3% from baseline to 3 years (score reduction from 19.0±3.2 to 8.9±3.3, 95% confidence interval [95CI] 8.7 to 11.6, PP<0.001). The MDS-UPDRS II, IV, and PDQ39 scores and levodopa dose were equivalent to those at baseline. Discussion: The benefit of unilateral FUS-STN on PD motor features is sustained in the long term. FUS-STN contributes to better clinical control over several years of evolution. NCT02912871/03454425. Classification of Evidence: This study provides Class IV evidence on the utility of focused ultrasound unilateral subthalamotomy in the treatment of people with Parkinson9s disease.

Background: Dopamine replacement therapy reduces most motor and nonmotor features of Parkinson's disease. However, with disease progression, adjustments of dopaminergics and the application of advanced therapies must be considered.Objectives: To validate the OPTIMIPARK questionnaire as a tool to help clinicians make therapeutic decisions on patients treated with levodopa.Methods: We tested a questionnaire including 9 items encompassing motor and nonmotor signs, complications, and disability in a multicenter, observational, cross‐sectional study. A neurologist (neurologist 1 [N1]) assessed patients according to regular clinical practice and blinded to the OPTIMIPARK questionnaire score. Therapeutic decisions were classified as “no changes,” “adjustment of conventional treatment,” and “advanced therapy indicated.” External neurologists (neurologist 3 [N3] and neurologist 4 [N4]), who only knew the patient age, years of disease, and current treatment, made their therapeutic decisions based on the OPTIMIPARK score. Concordance between the criterion of the N1 versus the OPTIMIPARK‐based N3–N4 consensus was analyzed applying weighted κ. The area under Receiving Operating Characteristic (ROC) curves was calculated for OPTIMIPARK scores.Results: A total of 113 patients with Parkinson's disease were included. The OPTIMIPARK‐based decision led to a higher proportion of patients requiring therapeutic modification than N1 assessment (74% vs. 60%; P = 0.002). Concordance between the N1 and N3–N4 decisions was moderate, whereas interobserver agreement among N3 and N4 was high. Area Under the Curve(AUC) values of 0.83 and 0.82 were found for “no changes” and “advanced therapy indicated” decisions by the N1 neurologist.Conclusions: OPTIMIPARK might be more sensitive than regular clinical practice in suggesting the need for a therapeutic change. Furthermore, the low and high scores identify with high accuracy well‐adjusted patients and candidates for advanced therapy, respectively.

Background: The subthalamic nucleus (STN) is considered a key structure in motor, behavioral, and emotional control. Although identification of the functional topography of the STN has therapeutic implications in the treatment of the motor features of Parkinson's disease (PD), the details of its functional and somatotopic organization in humans are not well understood.Objective: The aim of this study was to characterize the functional organization of the STN and its correlation with the motor outcomes induced by subthalamotomy.Methods: We used diffusion‐weighted imaging to assess STN connectivity patterns in 23 healthy control subjects and 86 patients with PD, of whom 39 received unilateral subthalamotomy. Analytical tractography was used to reconstruct structural cortico‐subthalamic connectivity. A diffusion‐weighted imaging/functional magnetic resonance imaging–driven somatotopic parcellation of the STN was defined to delineate the representation of the upper and lower limb in the STN.Results: We confirmed a connectional gradient to sensorimotor, supplementary‐motor, associative, and limbic cortical regions, spanning from posterior‐dorsal‐lateral to anterior‐ventral‐medial portions of the STN, with intermediate overlapping zones. Functional magnetic resonance imaging–driven parcellation demonstrated dual segregation of motor cortico‐subthalamic projections in humans. Moreover, the relationship between lesion topography and functional anatomy of the STN explains specific improvement in bradykinesia, rigidity, and tremor induced by subthalamotomy.Conclusions: Our results support an interplay between segregation and integration of cortico‐subthalamic projections, suggesting the coexistence of parallel and convergent information processing. Identifying the functional topography of the STN will facilitate better definition of the optimal location for functional neurosurgical approaches, that is, electrode placement and lesion location, and improve specific cardinal features in PD. © 2021 International Parkinson and Movement Disorder Society

Multiple sclerosis (MS)-related tremor is frequent and can often be refractory to medical treatment, which makes it a potential source of major disability. Functional neurosurgery approaches such as thalamic deep brain stimulation (DBS) or radiofrequency thalamotomy are proven to be effective, but the application of invasive techniques in MS tremor has so far been limited. Magnetic resonance (MR)-guided focused ultrasound thalamotomy, which has already been approved for treating essential and parkinsonian tremor, provides a minimally invasive approach that could be useful in the management of MS tremor. We report for the first time a patient with medically refractory MS-associated tremor successfully treated by focused ultrasound thalamotomy.

Background: Because of the prevalence and impact of sleep disorders in Parkinson's disease (PD), valid instruments for their evaluation and monitoring are necessary. However, some nocturnal sleep disorders may go unnoticed by patients themselves.Objectives: To validate a pan‐Spanish version of the Parkinson's Disease Sleep Scale Version 2 (PDSS‐2) and to test the relationships between the PDSS‐2 and a PDSS‐2 roommate version.Methods: PD patients (n = 399) from seven Spanish‐speaking countries were included. In addition to the tested PDSS‐2 scales, valid measures for sleep disorders and both motor and nonmotor manifestations were applied. Acceptability, dimensionality, reliability, precision, and construct validity were explored, as well as discrepancies and agreement between the PDSS‐2 and the roommate version.Results: PDSS‐2 showed negligible floor and ceiling effects. Four factors (57% of the variance) were identified. Reliability parameters were satisfactory: alpha = 0.84; item homogeneity coefficient = 0.27; corrected item total correlation = 0.28 to 0.61; and test‐retest reliability (average kappa = 0.70; intraclass correlation coefficient [ICC] = 0.83). The standard error of measurement was 5.84, and correlations with other scales assessing nocturnal sleep were high (r_S = 0.62–0.56). In comparison to the patient‐based total score, the by proxy total score showed no significant difference, high correlation (r_S = 0.70), and acceptable agreement (ICC = 0.69), but there were discrepancies in two or more points in 18% of item scores.Conclusions: The Spanish version of the PDSS‐2 has shown satisfactory clinimetric attributes. Acceptability and precision data are presented for the first time. The PDSS‐2 roommate version could be useful to complement the patient‐based evaluation, but additional studies are needed.