Stanisław Szlufik

Inflammation and gut dysbiosis are increasingly recognized as important contributors to the pathophysiology of Parkinson’s disease (PD). Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy aimed at restoring gut microbial balance and modulating inflammatory pathways. The aim of the study was to evaluate the effect of single fecal microbiota transplantation on systemic and gut-related inflammatory biomarkers in patients with PD. This exploratory analysis was conducted as part of the randomized, double-blind, placebo-controlled EFFACE-PD study. Fifty-nine participants with PD were randomized to receive either donor-derived FMT or placebo. Serum levels of IL-18 and calprotectin were measured using ELISA before intervention and 3 months after the procedure. Ferritin, leukocyte count, neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR) were assessed at baseline and after twelve months. No statistically significant between-group differences in changes in inflammatory biomarker concentrations were observed. Broader inflammatory markers, including ferritin and leukocyte parameters, also did not differ significantly between groups. We conclude that single FMT did not induce significant changes in systemic inflammatory biomarkers in this exploratory cohort of PD patients. Larger studies with standardized inflammatory assessments are needed to clarify the immunomodulatory effects of FMT in PD.

Background/Objectives: MR-guided focused ultrasound (MRgFUS) Vim thalamotomy targets medication-refractory tremor in essential tremor (ET) and tremor-dominant Parkinson’s disease (PD). We examined longitudinal patient-reported outcomes alongside early motor changes. Methods: This retrospective cohort included 30 patients (12 ET, 18 PD). PDQ-39, PDQ-8, and EQ-VAS were analyzed using random-intercept mixed models. Multiplicity correction covered 16 visit contrasts, including four contrasts for a secondary. A sensitivity analysis included 11 participants with confirmed pretreatment W1 dates and numeric patient-reported data. Results: The paired motor analysis showed a median 12-point TRS reduction and median individual tremor improvement of 64.7% (n = 23; p < 0.001). Median original UPDRS Part III reductions in PD were 5 points OFF (p = 0.010) and 9 points ON medication (p = 0.004). Patient-reported outcomes were available for 25, 21, and 10 participants at W1, W2, and W3. No categorical-visit contrast met the corrected significance threshold in either the full-cohort or restricted analysis. Conclusions: MRgFUS was followed by substantial early tremor reduction and PD motor-score reductions compatible with clinically meaningful improvement against external benchmarks. This post hoc interpretation provides clinical context for motor change; the patient-reported analyses did not establish a consistent or durable quality-of-life benefit. Safety outcomes were not evaluated in this study.

Background/Objectives: Magnetic resonance-guided focused ultrasound (MRgFUS) ventral intermediate nucleus (Vim) thalamotomy is an established treatment for medication-refractory tremor, but longitudinal cognitive and affective data remain limited. We described global cognition, depressive symptoms, and anxiety after unilateral MRgFUS Vim thalamotomy in essential tremor (ET) and tremor-dominant Parkinson’s disease (PD). Methods: This exploratory, descriptive analysis of a retrospective single-center cohort included 25 participants (ET n = 11; PD n = 14). Montreal Cognitive Assessment (MoCA), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scores were analyzed from baseline to the final available complete follow-up. Random-intercept mixed-effects models used all 54 complete observations. Sensitivity analyses examined first follow-up (W2), baseline-adjusted BDI comparisons, and random slopes. Holm correction addressed primary-outcome multiplicity; exploratory cognitive tests used false-discovery-rate correction. Results: Median assessment follow-up was 12.7 months (interquartile range 9.0–15.2; maximum 22.6). No significant whole-cohort change was detected in MoCA (mean change −0.12, 95% CI −1.33 to 1.09; Holm-adjusted p = 0.927), BDI (−0.36, −1.99 to 1.27; p = 0.927), or BAI (−2.60, −5.24 to 0.04; p = 0.188). The exploratory ET BDI change was −2.73 points at final follow-up (95% CI −4.51 to −0.95; Holm-adjusted p = 0.029) and −1.45 at W2 (−4.72 to 1.81; p = 0.262). The random-intercept time-by-diagnosis interaction for BDI was significant (β = 0.365 points/month, 95% CI 0.124 to 0.607; Holm-adjusted p = 0.009), whereas the four baseline-adjusted diagnostic contrasts did not survive joint Holm correction. No individual cognitive test remained significant after false-discovery-rate correction. Conclusions: These findings are descriptive and exploratory. No statistically significant cohort-level cognitive or affective change was detected. Diagnosis-related BDI findings were sensitive to endpoint definition and baseline adjustment and cannot be attributed causally to MRgFUS in this uncontrolled cohort.

Background: Dystonia is a heterogeneous hyperkinetic movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and postures. Although numerous genes associated with dystonia have been identified, the genetic background remains unknown in many patients. Data on genotype–phenotype correlations in Polish populations remain limited. Objective: To analyze the clinical characteristics of patients with generalized dystonia and compare clinical features between individuals with and without genetically confirmed dystonia-causative variants in a Polish cohort. Methods: A retrospective analysis of patients diagnosed with generalized dystonia at a single neurological center was performed. Diagnosis was established according to MDS criteria. Genetic analysis included whole-exome sequencing, targeted NGS genetic panel, MLPA, Sanger sequencing and PCR_RFLP analysis. Clinical and demographic data were extracted from medical records. Clinical characteristics of individuals with and without causative variants were compared. Results: A total of 113 patients with generalized dystonia were included. Genetic variants were identified in 13 patients (11.5%). These included variants within the TOR1A, THAP1, SGCE, GCH1, NKX2-1, SLC2A1, KMT2B, PDHA1, MFN2, and GNAL genes. We found detailed clinical data of 46 patients included in the study. Our comparative analysis of patients with causative (n = 7) and without causative variants (n = 39) revealed no statistically significant differences in age of onset, initial symptom localization, treatment response, family history, or associated neurological features. Conclusions: In this cohort of Polish patients with generalized dystonia, we identified pathogenic variants in approximately 11.5% of cases. No significant clinical differences were observed between patients with genetically confirmed dystonia and those without identified variants. In this study, we report the first two Polish cases with DYT-GNAL variants. Further studies are required to reveal the clinical heterogeneity of dystonia and characterize dystonia subtypes.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that primarily presents with motor and non-motor symptoms and significantly affects patients’ quality of life (QoL). Although bilateral subthalamic nucleus deep brain stimulation (STN DBS) is recognized as an effective advanced treatment (AT), disease progression may lead to diminished therapeutic outcomes, with recurrence of motor complications, including dyskinesia and fluctuations. This study evaluates the clinical effectiveness and QoL outcomes associated with adding a second advanced therapy (either levodopa-carbidopa intestinal gel [LCIG] or continuous subcutaneous apomorphine infusion [CSAI]) to bilateral STN DBS in six patients experiencing symptom recurrence despite optimized stimulation settings and oral pharmacotherapy. Clinical assessments included motor performance (UPDRS part III), medication dosage (LEDD), electrode positioning using Lead-DBS software, and patient-reported QoL outcomes (EQ- -5D, PDQ-39, PDSS-1, and VAS scales). Four patients demonstrated motor improvement following the introduction of dual therapy. Combined therapies effectively managed refractory symptoms, reduced medication dosages, and significantly enhanced patients’ quality of life. This study highlights the clinical potential of integrating multiple advanced therapeutic approaches in managing complex cases of advanced Parkinson’s disease. Keywords: advanced Parkinson’s disease deep brain stimulation (DBS) subthalamic nucleus (STN) levodopa-carbidopa intestinal gel (LCIG) continuous subcutaneous apomorphine infusion (CSAI) device-aided therapies (DAT)

Introduction. Bilateral subthalamic nucleus deep brain stimulation (DBS STN) is a very effective surgical method of treating motor symptoms in Parkinson’s disease (PD) patients. The long-term cognitive outcome after the surgery is still discussed. This study compared the impact of DBS STN to best medical treatment (BMT) in patients with PD on cognitive function and mood over a 36-month observation period. Material and methods. The study included PD patients divided into two groups: the BMT group (n = 17), receiving pharmacotherapy alone throughout the entire 36-month observation period, and the DBS group (n = 20), which underwent DBS STN after the baseline visit, and was subsequently observed for the next 36 months. Both groups were examined at Baseline, 9 months, 18 months and 36 months using neuropsychological assessment and the Unified Parkinson’s Disease Rating Scale (UPDRS) motor examination. Results. At 36 months, neither group demonstrated a significant decline in visuospatial abilities, executive functions, or memory. Both groups showed longitudinal deterioration in attention/working memory measures; however, these changes were not associated with significant between-group differences. Language performance [Wechsler Adult Intelligence Scale — Revised (WAIS-R similarities)] improved over follow-up in the DBS group relative to BMT, and DBS was associated with a marked reduction in medication across all follow-up timepoints (p < 0.05). Conclusions. The study suggests that DBS STN does not have a significant additional impact on cognition performance in PD patients. Our results also suggest that while active DBS STN continues to improve motor symptoms, it did not prevent the longitudinal worsening of OFF-motor severity (UPDRS III OFF), which progressed similarly in both groups. Keywords: deep brain stimulation Parkinson’s disease neuropsychological outcome subthalamic nucleus

Background/Objectives: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for motor symptoms in Parkinson’s disease (PD), but concerns remain regarding its impact on cognitive function. Identifying neuroanatomical predictors of postoperative cognitive decline could improve patient selection and outcomes. This study aims to investigate the relationship between preoperative brain morphology and postoperative neuropsychological outcomes in PD patients undergoing bilateral STN-DBS. Methods: Thirty-eight PD patients underwent standardized neuropsychological testing and preoperative MRI before and 3–24 months after STN-DBS. Manual MRI morphometric measurements were obtained for 42 cortical, subcortical, and ventricular parameters. Changes in cognitive domains—including executive function, memory, language, visuospatial abilities, attention, and global cognition—were analyzed, and correlations between structural metrics and cognitive changes were assessed using Spearman’s coefficients. Results: Significant postoperative declines occurred selectively in language functions: verbal fluency (phonemic and semantic, d = −0.49 to −0.84) and confrontation naming (d = −0.47). Memory, executive functions, attention, and global cognition remained preserved. Enlarged lateral ventricles were consistently associated with poorer outcomes across multiple domains, while increased left precentral gyrus width correlated with executive and memory decline. Additionally, smaller midbrain and cingulate gyrus width were associated with greater executive impairment. Conclusions: STN-DBS in PD is associated with selective postoperative cognitive changes, most prominently in verbal fluency. Simple preoperative MRI morphometric measures, including ventricular size, limbic structure volumes, and specific cortical parameters, may serve as clinically feasible predictors of cognitive risk. Incorporating such measures into preoperative assessments could enhance patient selection, counseling, and individualized surgical planning.

Objective: To evaluate the long-term impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) versus best medical therapy (BMT) on static and dynamic balance as well as gait disturbances in patients with advanced Parkinson’s disease (PD). Methods: In this prospective study, 50 patients with advanced PD were randomly assigned to receive either bilateral STN-DBS (n = 28) or BMT (n = 22). Comprehensive evaluations were performed at baseline and during four consecutive visits over 36 months. Static balance was assessed using posturographic measurements (COP velocity, perimeter, ellipse area), and dynamic balance and gait were evaluated using tandem gait tasks and pivoting maneuvers. Statistical analyses included repeated measures ANOVA-Friedman and Dunn-Bonferroni post hoc tests. Results: DBS-treated patients demonstrated stable dynamic balance and gait performance over 36 months with no significant decline in tandem gait and pivot tests. Conversely, the BMT group showed a significant deterioration in dynamic balance (Walking Tandem Test; χ² = 10.63, p = 0.014) and gait function, particularly in the medication OFF state. Static balance in the DBS group worsened notably under sensory-deprived conditions (eyes closed, OFF state; χ² = 10.13, p = 0.017), whereas BMT maintained static balance stability without significant changes. Conclusions: STN-DBS effectively preserves dynamic balance and gait functions in patients with advanced PD over 36 months, but exhibits limited efficacy in maintaining static balance under sensory-deprived conditions. These findings highlight the need for individualized therapeutic approaches that emphasize combined neuromodulation and multidisciplinary rehabilitation strategies.

Dystonia-myoclonus syndrome is a rare neurological condition characterized by involuntary muscle contractions and myoclonic jerks, significantly impairing daily functioning. Pharmacological management is often ineffective, prompting consideration of alternative therapeutic interventions such as deep brain stimulation (DBS). This report describes a novel clinical case involving a 38-year-old female with severe dystonic and myoclonic symptoms associated with a pathogenic mutation in the KCNN2 gene (DYT34). Bilateral DBS targeting the internal segment of the globus pallidus (GPi) resulted in marked and sustained symptom improvement, notably reducing dystonic posturing and myoclonic movements over the 24-month follow-up period. Neuropsychological and neurologopedic assessments revealed no adverse effects on cognition or speech. This represents the first sufficient effect of GPi-DBS in a patient with a genetically confirmed KCNN2 mutation, highlighting its potential efficacy and underscoring the need for genetic testing in patients presenting with dystonia-myoclonus syndromes.

This study explores the use of machine learning models to assess the severity of Parkinson’s disease symptoms based on data from wearable and smartphone sensors. It presents models to predict the severities of individual symptoms—tremor, bradykinesia, stiffness, and dyskinesia—as well as the overall state of patients, using both clinician and patient self-assessments as labels. The dataset, although limited and imbalanced, enabled the identification of key trends. The best performance was achieved when combining data from both the MYO armband and smartphone, and when using patient self-assessments as targets. Tremor was the most predictable symptom, while others proved more challenging—especially at higher severity levels, which were poorly represented in the dataset. These results highlight the value of multimodal data and the importance of patient input in symptom monitoring. However, they also point to the need for more balanced and extensive datasets to improve prediction accuracy across all severity levels and symptoms.