Bülent Elibol

Background Sensory-motor-cognitive integration deficits are common in Parkinson’s disease(PD) and significantly limit functional performance, highlighting the growing need for holistic training approaches that target these domains simultaneously. Aims This study aimed to examine the effects of sensory-motor-cognitive integration training on balance and gait in patients with Parkinson’s disease (PwPD). Methods A total of 40 PwPD, aged between 45 and 75 years, were included. The intervention group received 24 sessions (3 days per week for 8 weeks) of 60-minute sensory-motor-cognitive integration training. The control group was placed on a waiting list and continued their routine daily activities. All participants were assessed at baseline, at the end of the 8th week, and at the 12th week. Static posturography was used to evaluate balance [Limits of Stability and the Modified Sensory Integration and Balance Clinical Test] and gait (Walk Across test). Additionally, balance was assessed using the Functional Reach Test (FRT), and gait performance was evaluated with the Modified Dynamic Gait Index (mDGI). Results Significant time × group interactions were observed for functional balance and gait outcomes. The intervention group showed significant improvements in FRT and mDGI scores over time (p < 0.001), whereas no significant changes were observed in the control group. Static posturography also demonstrated significant time-related changes and group differences for most parameters (p < 0.05), except for movement velocity, directional control, and step length symmetry. Conclusion These findings suggest that individualized, multidomain sensory–motor–cognitive integration training may represent a particularly effective rehabilitation approach for enhancing balance and gait in PwPD.

L-DOPA-induced dyskinesia (LID) remains the most challenging complication of dopamine replacement therapy in Parkinson’s disease, correlated with maladaptive plasticity within corticostriatal circuits. Perineuronal nets (PNNs), extracellular matrix structures enwrapping mainly parvalbumin interneurons (PV-INs), are key regulators of neuronal stability and plasticity, yet their contribution to LID is unknown. Using a unilateral 6-hydroxydopamine rat model of Parkinsonism followed by chronic L-DOPA administration, we quantified PNN–PV associations by Wisteria floribunda agglutinin (WFA) and PV immunolabeling across striatal and motor cortical territories. Dopamine loss markedly reduced PNN density and intensity in the dorsolateral striatum (DLS), which only partially recovered after L-DOPA. In LID, canonical WFA⁺/PV⁺ cells remained low, whereas non-canonical WFA⁻/PV⁺ populations expanded in both DLS and M1 motor cortex (M1), indicating region-specific remodeling toward a high-plasticity state. To assess causality, we used Chondroitinase ABC (ChABC) for PNN degradation. DLS-targeted ChABC exacerbated abnormal involuntary movements and increased local PV density, while M1-ChABC had no behavioral effect but altered PV metrics within the DLS–M1 axis. These findings identify the DLS as a critical node where PNN fragility amplifies dyskinesia, highlight a functional coupling between striatal and cortical PNN–PV remodeling, and suggest that stabilizing extracellular matrix integrity could mitigate maladaptive plasticity underlying LID.

Objective: Idiopathic normal pressure hydrocephalus (iNPH) is a reversible cause of cognitive impairment in older adults, characterized by gait disturbance, urinary incontinence, and cognitive decline. While ventriculoperitoneal (VP) shunt surgery can improve the classical triad, its cognitive and emotional effects remain under characterized. In this study we aim to investigate neuropsychiatric outcomes following VP shunt surgery in iNPH patients and to identify predictors of postoperative cognitive improvement. Material and Methods: This retrospective single-center study included 55 patients with iNPH who underwent VP shunt surgery between 2020 and 2024. Neuropsychological testing was conducted preoperatively and at a median of 11 months postoperatively, evaluating global cognition, memory, attention, executive and visuospatial functions, and mood. Pre- and postoperative performances were compared, and multivariate regression models were used to determine independent predictors of cognitive gain. Results: Significant postoperative improvements were observed in MMSE (median 24.0 to 27.0, p < 0.001), memory scores (ERCT: 40.0 to 45.0, p < 0.001), attention/executive functions and depression severity (BDI: 12.0 to 9.0, p < 0.001). Stratified regression analysis showed that patients in the lowest baseline MMSE and ERCT tertile experienced the greatest improvement shortly after surgery, with longer follow-up associated with diminishing gains (MMSE: β = –0.76, p < 0.001, ERCT: β = –0.76, p < 0.001). Conclusion: Cognitive improvement after VP shunt surgery in iNPH is strongly influenced by baseline cognitive status and the timing of follow-up. Patients with lower preoperative scores benefit the most when evaluated in the early postoperative phase. These findings emphasize the need for timely intervention and tailored neuropsychological monitoring to optimize outcomes.

Objectives: Wilson’s disease (WD) leads to copper accumulation in the liver and brain. It generates oxidative stress, which can damage the liver and central nervous system (CNS). The concentrations of oxidized lipid products, such as prostaglandins and isoprostanes, in blood and urine can indicate both the presence and the extent of damage. However, there is limited research specifically investigating these oxidative stress biomarkers in WD, making this study a novel contribution to the field. Methods: In this study, serum and 24-h urine samples were collected from a total of 64 individuals, including 22 WD patients with hepatic involvement (HI-WD), 17 with neurological-hepatic involvement (NHI-WD), and 25 healthy controls (HC). A liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated to quantify specific prostaglandins and isoprostanes in serum and urine samples. Results: The results showed significant differences in the levels of iPF _2α -III, 2,3-dinor-iPF _2α -III, 5-iPF _2α -VI in serum as well as PGE ₂ , PGD ₂ , PGF _2α , iPF _2α -III and 5-iPF _2α -VI in 24-h urine samples between WD and HC groups. Notably, the concentration of PGD ₂ in urine was significantly higher in the NHI-WD group compared to both the HC and HI-WD groups. Our novel urine biomarker panel has the potential to be used for grading disease severity, monitoring therapy and assessing CNS involvement in WD. Conclusions: It represents one of the first to explore a panel of oxidative stress biomarkers, particularly prostaglandins and isoprostanes, in both serum and urine samples in WD patients, making it an original contribution to the current literature on WD.

Background and Objectives: Idiopathic normal pressure hydrocephalus (iNPH) primarily affects older patients. Ventriculoperitoneal (VP) shunt surgery is a standard treatment. Many iNPH patients have high cardiovascular risks and require aspirin (ASA) therapy to prevent thromboembolic events. Discontinuing ASA increases the risk of these events. This study evaluates the impact of perioperative ASA use on hemorrhagic complications in iNPH patients undergoing VP shunt surgery. Methods: This retrospective cohort study included patients who underwent VP shunt surgery for iNPH from January 2020 to September 2024. Patients were divided into two groups based on perioperative ASA use: no ASA ( n = 50) and ASA continued ( n = 51). Data collected included demographics, surgery details, ASA dosage, and indications for ASA use. Primary outcomes were early and late postoperative hemorrhage incidences. Postoperative follow-up included MRI or CT scans at regular intervals (mean ≈ one year). Statistical analyses were performed using SPSS version 23.0, with Chi-square tests and independent samples t-tests or Mann–Whitney U tests used to analyze differences between groups. Results: The study cohort had 101 patients with a mean age of 69.5 ± 7.6 years, 41.6% female and 58.4% male. Early postoperative hemorrhage occurred in 5% of patients, including epidural (1), intraparenchymal(3), and intraventricular hematoma(1). Late postoperative hemorrhages occurred in 4% of patients ( 4 patients in the no-ASA group), with two cases each of unilateral and bilateral subdural hematoma. No significant differences in hemorrhagic outcomes were observed between the ASA continuation and non-use groups ( p = 0.092). The mean follow-up period was 300 days. One patient died in non-ASA group due to neurodegenerative disease. Conclusion: Perioperative ASA use does not significantly impact the incidence of postoperative hemorrhages in iNPH patients undergoing VP shunt surgery. These findings suggest that ASA can be safely continued without increasing hemorrhagic risks. This is a particularly significant issue for patients with high cardiovascular risk.

Background and Aim: Ataxia-telangiectasia (AT) and ataxia-oculomotor apraxia type 2 (AOA2) are both autosomal recessive cerebellar ataxias characterized by elevated serum alpha-fetoprotein (AFP) levels. However, the source and clinical implications of this increase, as well as its relationship with liver diseases are unknown. In this study, we investigated the frequency of liver diseases and their relationship with high AFP in patients with AT and AOA2. Materials and Methods: The study involved 19 adult patients (13 patients with AT and 6 patients with AOA2) who were followed between January 1992 and March 2023. The demographic and clinical characteristics, serum levels of liver enzymes and AFP, liver imaging, and survival data were retrospectively reviewed. Results: The mean age of patients was 26.8±5.1 years (11 men and 8 women).While 69% (9/13) of AT patients had elevated liver enzymes and 56% (5/9) had abnormal liver imaging, both were normal in all AOA2 patients.Liver enzyme elevation was associated with the presence of comorbid disease (p=0.007), but not with AFP level (p=0.33) in AT patients. Hepatosteatosis was not associated neither with comorbidity (p=0.524) nor AFP level (p=0.905) in this group. During a median follow-up of 17 (1–29) years, 5 AT patients passed away due to cancer (4 patients) and sepsis (1 patient). AFP level was not associated with the occurrence of cancer (p=0.382). Conclusion: This study found a high prevalence of liver disease (69%) in AT, unlike in AOA, independent of AFP levels. Since comorbid diseases, especially cancer, were associated with elevated liver enzymes, adult AT patients with abnormal liver functions should be screened for the development of cancers.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson’s disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a novel gene implicated in parkinsonism and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD to perinatal lethality with neurological manifestations across 17 pedigrees with 24 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy, and may affect proteasomal abundance and assembly in patient-derived fibroblasts. Furthermore, Drosophila and mouse models of PSMF1 loss of function exhibit age-dependent motor impairment, as well as brain-wide mitochondrial membrane depolarization and dopaminergic neurodegeneration in aged flies, and diffuse gliosis in mice. Collectively, our findings unequivocally link defective PSMF1 to early-onset parkinsonism and neurodegeneration, and suggest proteasomal and mitochondrial dysfunction as mechanistic contributors.

The aim of this study was to examine whether cervical stabilization exercises (CSEs) change the effects of conventional exercises (CEs) in patients with PD. Twenty-five patients with PD were randomized into two groups. While the experimental group (EG) received CSEs in addition to CEs, the control group (CG) received only CEs. Both programs lasted 8 weeks. Eighteen participants were able to complete the study. The outcomes were the changes in posture, cervical joint position sense (JPS), balance assessment, 10-m walking tests (10MWT), and the Timed Up & Go (TUG) test. At the end of the study, significant improvement was observed in both groups in terms of trunk rotation angle and pelvic asymmetry, the time parameter of TUG, and the 10MWT (p < 0.05). In the EG, greater improvement was detected in the Berg Balance Scale, static posturography, postural alignment, JPS, and the cadence parameter of TUG (p < 0.05). CEs and CSEs could improve walking speed and posture in patients with PD, but if CSEs are added to CEs, greater improvements could be achieved in JPS and postural control.(Clinical Trials ID: NCT03854747).

Beta-propeller protein-associated neurodegeneration (BPAN) is a rare X-linked dominant neurodegenerative disease, which is characterized by iron accumulation in the basal ganglia. BPAN is associate...