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.

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.

OBJECTIVES:Changes in the gut microbiome may be involved in the pathogenesis and progression of Parkinson's disease (PD). This randomized, placebo-controlled, double-blinded study aimed to assess the effects of fecal microbiota transplantation (FMT) on the manifestation of the motor symptoms of PD (The Movement Disorders Society - Unified Parkinson's Disease Rating Scale Part III [MDS-UPDRS III]) over a 12 month long observation and non-motor symptoms as secondary objectives: the Movement Disorders Society-Non-Motor Rating Scale; EuroQol-5 Dimension; PD Quality-of-Life Questionnaire; Montreal Cognitive Assessment (MoCA); UPDRS I, II, and IV; Gastrointestinal Dysfunction Scale for PD; modified Constipation Assessment Scale; and levodopa equivalent dose. METHODS:The patients were randomly assigned to receive either fecal microbiota (Mbiotix, Human Biome Institute) or placebo (auto-fecal microbiota, prepared from the patient's stool) in a 1:1 ratio. The fecal microbiota transplantation was performed via colonoscopy. Assessments were performed before and after 12 months for the MoCA and at 1, 3, 6, and 12 months for the other scales. Intention-to-treat analysis was performed using a multivariable mixed regression model. RESULTS:Of the 59 patients included, 28 were randomly assigned to the Mbiotix group (median age = 65 years; 15 male patients) and 31 to the placebo group (median age = 63 years; 14 male patients). No significant differences were observed in the MDS-UPDRS III "OFF" state score at 12 months between groups (1.50 points, 95% confidence interval [CI] = -4.28 to 7.28, p = 1.00), however, some non-motor symptoms improved in different study timepoints. INTERPRETATION:A single FMT does not influence motor symptoms manifestation in patients with PD but could improve non-motor functioning via gut-brain axis. Trial registration information: Clinical Trial ID NCT05204641 was submitted on November 29, 2021. The first patient was enrolled on January 4, 2022. ANN NEUROL 2026;100:10-21.

Continuous foslevodopa/foscarbidopa subcutaneous infusion (LDp/CDp) is a new therapeutic option for advanced Parkinson’s disease (PD). The treatment is effective, but might be associated with psychotic symptoms (PS). The aim of the study was to assess the prevalence and factors associated with PS during LDp/CDp therapy, defined as delusions and formed hallucinations with or without preserved insight. A retrospective chart review was performed in 6 tertiary movement disorders centers in Poland, and 198 patients were included. Demographic data, PD course, MDS-UPDRS p.III OFF, and treatment before and after LDp/CDp initiation were recorded. Fifty-seven (28.8%) patients developed PS, leading to LDp/CDp treatment discontinuation in 16 (8.1%) patients. A univariate analysis was performed, and factors with p < 0.15 were included in the logistic regression model. Regression analysis revealed that the only statistically significant factor associated with PS after LDp/CDp initiation was the presence of PS at any time during the PD course (OR 6.89; 95%CI 2.76–17.15; p < 0.001). Psychotic symptoms associated with LDp/CDp treatment in the real-world setting are more common than in randomized controlled trials, and related to the presence of PS at any time before LDp/CDp initiation. Patients with a previous history of PS should be selected with caution and monitored after treatment initiation.

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.

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.

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.

Hyperechogenicity of the substantia nigra (SN) is observed using transcranial ultrasonography in patients with Parkinson’s Disease. In this study, we investigated whether monogenic forms of PD are more prevalent in these patients and clinically defined their characteristics. Eighty-eight PD patients were part of the analysis. All patients received clinical diagnoses from experienced movement disorder specialists. Each patient underwent transcranial ultrasonography and genetic testing for mutations in the SNCA, PRKN, LRRK2, DJ1, and PINK1 genes. SN hyperechogenicity was identified in 48 patients. Compared to the non-hyperechogenicity group, these patients did not have monogenic forms of PD more frequently, but they did have REM sleep behavior disorder significantly more often, lived in rural areas, and experienced a later age of disease onset. Our study indicated no association between substantia nigra echogenicity and the presence of mutations in the SNCA, LRRK2, DJ1, PRKN, and PINK1 genes. Hyperechogenicity of the substantia nigra, however, remains a common finding in patients with Parkinson’s Disease, correlating with certain features of the disease.

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.

Aim of study. To investigate the treatment strategies of Parkinson's Disease (PD) among movement disorder specialists in tertiary centres in Poland, and how literature warnings (levodopa and dopamine agonist phobia) have influenced their practice. Material and methods. The survey was conducted between 30 November, 2020 and 18 October, 2021, in four Polish tertiary referral centres for PD (two in Gdansk, one in Sosnowiec, and one in Warsaw). Movement disorder specialists collected information on the treatment of 494 consecutive patients diagnosed with PD.The questionnaire included information on the age of the patient, the duration of PD, the Hoehn&Yahr (H&Y) stage, comorbidities, pharmacotherapy, and advanced PDtherapies i.e. deep brain stimulation (DBS), levodopa/carbidopa intestinal gel (LCIG), and continuous subcutaneous apomorphine infusions (CSAI). Results. Levodopa was the most prescribed medication (n = 465/494), followed by dopamine agonists (n = 292/494).The mean dose of levodopa was 810.58 +/- 473.11 mg, and it did not exceed 2,000 mg/d in 98.5% of patients.The mean doses of dopamine agonists used were relatively low (ropinirole 8.64 +/- 3.94 mg, pramipexole base 1.76 +/- 0.65mg). Amantadine (n = 197/494) and MAO-B inhibitors (n = 202/494) were prescribed less frequently. Catechol-o-methyltransferase (COMT) inhibitors (n = 7/494) and anticholinergics (n = 4/494) were rarely used in the studied population. Complex polytherapy with three or more PD medications was the most often used treatment strategy (n = 223/494). Conclusions and clinical implications. Levodopa remains the gold standard in PD treatment in tertiary movement disorder centres in Poland. Dopamine agonists formed the second most frequently prescribed group of medications; however, the observed low dosages of both levodopa and dopamine agonists may suggest a cautious approach by clinicians. Amantadine and MAO-B inhibitors (mainly rasagiline) constituted important elements of PD pharmacotherapy.The high prevalence of complex polytherapy underlines the complexity of PD management, the cautious use of single medication at high doses, and the need for personalised therapeutic strategies.

Neurodegenerative disorders, including Alzheimer’s disease (AD), are a growing problem in aging society. The amyloid cascade hypothesis has recently been questioned, and therapies based on it have not yielded the expected results. However, the role of amyloid-β (Aβ) in AD pathogenesis cannot be rejected. It appears that some of the key players in the pathogenesis of the disease are the soluble amyloid-β oligomers. Soluble amyloid-β oligomers have neurotoxic effects by disrupting intracellular Ca2+ homeostasis and impairing mitochondrial function. The glymphatic system is an important pathway for the removal of soluble amyloid forms from the brain. The decline in the activity of this system is observed in aging brains, which is correlated with the occurrence of Alzheimer’s disease, primarily among the elderly population. Therefore, the question arises as to whether the glymphatic system could be another potential target for therapeutic interventions in Alzheimer’s disease. In this regard, it is imperative to pay attention to the factors that contribute to the pathogenesis of Alzheimer’s disease and also impact the glymphatic system, such as sleep, physical activity, alcohol consumption, and supplementation with polyunsaturated fatty acids. The question remains whether the glymphatic system will become the key to treating Alzheimer’s disease.

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.

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.

Primary progressive apraxia of speech (PPAOS) is a rare neurodegenerative disorder that saliently affects motor speech programming and planning. Linguistic function remains intact in the early stages of PPAOS.Although PPAOS shares a similar symptomatology to conditions such as primary progressive aphasia (PPA) and dysarthria, it is important to remember that this disorder constitutes its own distinct clinical syndrome. PPAOS is characterized by an individually variable disease course, with a steady progression in speech deterioration. In later stages, this disorder may additionally present with symptoms such as oral apraxia, dysarthria, dysphagia, aphasia, and parkinsonian syndromes similar to either progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS). 4-repeat tauopathy is the most common pathology associated with PPAOS. In this study, we present a case of a female patient suffering from PPAOS, detailing her clinical course during a 44-year long follow-up. As PPAOS is a disorder with a worldwide poorly-documented prevalence, there is limited data in literature on the subject. We thus bring this case to public discussion. We also recommend further investigating this disorder, as we would then be able to unify diagnostic and therapeutic approaches for PPAOS.

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.

Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In most reported cases, the inheritance of BHC is autosomal dominant but both incomplete penetrance and variable expressivity are observed and can be caused by NKX2-1 mutations. The spectrum contains choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome. The neurological symptoms can be misdiagnosed as Huntington's disease (HD). The two Polish families were diagnosed with NKX2-1 gene mutations and a literature review concerning the NKX2-1-related disorders was conducted. All family members were examined by experienced movement disorders specialists. PubMed database was searched to obtain previously described NKX2-1 cases. Whole exome sequencing (WES) was performed in one proband (Family A) and direct NKX2-1 sequencing in the second (Family B). Two Polish families were diagnosed with NKX2-1 gene mutations (p.Trp208Leu and p.Cys117Alafs*8). In one family, the co-occurrence of HD was reported. Forty-nine publications were included in the literature review and symptoms of 195 patients with confirmed NKX2-1 mutation were analyzed. The most common symptoms were chorea and choreiform movements, and delayed motor milestones. The NKX2-1 mutation should always be considered as a potential diagnosis in families with chorea, even with a family history of HD. Lack of chorea does not exclude the NKX2-1-related disorders.

Gliomas are a wide group of common brain tumors, with the most aggressive type being glioblastoma multiforme (GBM), with a 5-year survival rate of less than 5% and a median survival time of approximately 12–14 months. The standard treatment of GBM includes surgical excision, radiotherapy, and chemotherapy with temozolomide (TMZ). However, tumor recurrence and progression are common. Therefore, more effective treatment for GBM should be found. One of the main obstacles to the treatment of GBM and other gliomas is the blood–brain barrier (BBB), which impedes the penetration of antitumor chemotherapeutic agents into glioblastoma cells. Nowadays, one of the most promising novel methods for glioma treatment is Magnetic Resonance-guided Focused Ultrasound (MRgFUS). Low-intensity FUS causes the BBB to open transiently, which allows better drug delivery to the brain tissue. Under magnetic resonance guidance, ultrasound waves can be precisely directed to the tumor area to prevent side effects in healthy tissues. Through the open BBB, we can deliver targeted chemotherapeutics, anti-tumor agents, immunotherapy, and gene therapy directly to gliomas. Other strategies for MRgFUS include radiosensitization, sonodynamic therapy, histotripsy, and thermal ablation. FUS can also be used to monitor the treatment and progression of gliomas using blood-based liquid biopsy. All these methods are still under preclinical or clinical trials and are described in this review to summarize current knowledge and ongoing trials.

The key to the effective treatment of neurodegenerative disorders is a thorough understanding of their pathomechanism. Neurodegeneration and neuroinflammation are mutually propelling brain processes. An impairment of glymphatic system function in neurodegeneration contributes to the progression of pathological processes. The question arises as to how neuroinflammation and the glymphatic system are related. This review highlights the direct and indirect influence of these two seemingly independent processes. Protein aggregates, a characteristic feature of neurodegeneration, are correlated with glymphatic clearance and neuroinflammation. Glial cells cannot be overlooked when considering the neuroinflammatory processes. Astrocytes are essential for the effective functioning of the glymphatic system and play a crucial role in the inflammatory responses in the central nervous system. It is imperative to acknowledge the significance of AQP4, a protein that exhibits a high degree of polarization in astrocytes and is crucial for the functioning of the glymphatic system. AQP4 influences inflammatory processes that have not yet been clearly delineated. Another interesting issue is the gut–brain axis and microbiome, which potentially impact the discussed processes. A discussion of the correlation between the functioning of the glymphatic system and neuroinflammation may contribute to exploring the pathomechanism of neurodegeneration.

Poźne dyskinezy polekowe, mimo stosowania w leczeniu now­szych lekow neuroleptycznych, nie przestaly byc problemem klinicznym. W obrazie chorobowym dominują pląsawicze ruchy oromandibularne oraz polekowa dystonia, na przyklad szyjna. Szczegolne okoliczności terapeutyczne (np. koniecznośc konty­nuacji leczenia podstawowego schorzenia) powodują, ze leczenie czesto jest malo skuteczne, szczegolnie gdy objawy trwają zbyt dlugo. Celem przedstawionych rekomendacji interdyscyplinarnej grupy ekspertow jest przyblizenie spektrum objawow klinicznych, epidemiologii, patofizjologii i sposobow postepowania (farma­kologicznego, zabiegowego), ze szczegolnym uwzglednieniem dostepnego od kilku lat w Polsce leku o nazwie tetrabenazyna.