Monika Figura

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.

Neurologia i Neurochirurgia Polska

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.

Background/Objectives: Parkinson’s Disease (PD) is a neurodegenerative disorder resulting in bradykinesia, rigidity and tremor, as well as numerous non-motor symptoms. Malnutrition in PD is correlated with levodopa-induced dyskinesia, decreased food intake, gastrointestinal symptoms and neurodegenerative processes. With disease progression, oral levodopa treatment becomes insufficient. One of the therapies used in advanced PD is levodopa–carbidopa intestinal gel. Its effect on the weight and nutrition of PD patients is poorly understood. The aim of this prospective single-center observational cohort study was to assess the effect of this treatment on weight, body composition and biochemical parameter changes over a two-year-long observation. The mood, cognition and motor status of the patients were also assessed. Methods: This study included 15 patients with advanced PD treated with levodopa–carbidopa intestinal gel. Body composition analysis, anthropometric measurements, blood tests, psychological assessments and disease control measurements were carried out over a span of two years after the initiation of therapy. Results: Significant improvement in disease management was observed. Anthropometric measurements, biochemical parameters and psychological assessments did not show significant differences. Among the body composition parameters, only resting metabolic rate and extracellular and intracellular water percentages were significantly affected. Conclusions: Our findings indicate a lack of negative effects of levodopa–carbidopa intestinal gel treatment on weight loss in patients with Parkinson’s Disease in a 2-year long observation period. Furthermore, better disease management may result in a lower energy expenditure due to less time with dyskinesia. The limitations of our study include a small study group and limited follow-up.

Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by numerous motor and non-motor symptoms. Recent data highlight a potential interplay between the gut microbiota and the pathophysiology of PD. The degeneration of dopaminergic neurons in PD leads to motor symptoms (tremor, rigidity, and bradykinesia), with antecedent gastrointestinal manifestations, most notably constipation. Consequently, the gut emerges as a plausible modulator in the neurodegenerative progression of PD. Key molecular changes in PD are discussed in the context of the gut–brain axis. Evidence suggests that the alterations in the gut microbiota composition may contribute to gastroenteric inflammation and influence PD symptoms. Disturbances in the levels of inflammatory markers, including tumor necrosis factor-α (TNF α), interleukin -1β (IL-1β), and interleukin-6 (IL-6), have been observed in PD patients. These implicate the involvement of systemic inflammation in disease pathology. Fecal microbiota transplantation emerges as a potential therapeutic strategy for PD. It may mitigate inflammation by restoring gut homeostasis. Preclinical studies in animal models and initial clinical trials have shown promising results. Overall, understanding the interplay between inflammation, the gut microbiota, and PD pathology provides valuable insights into potential therapeutic interventions. This review presents recent data about the bidirectional communication between the gut microbiome and the brain in PD, specifically focusing on the involvement of inflammatory biomarkers.