Laucius, Ovidijus

Neurodegeneracinės ligos, tokios kaip Parkinsono liga ir šoninė amiotrofinė sklerozė, pasižymi progresuojančia eiga, sudėtinga ankstyva diagnostika ir reikšmingu poveikiu pacientų gyvenimo kokybei. Pastaraisiais metais vis daugiau dėmesio skiriama periferinės nervų sistemos bei autonominės nervų sistemos pažeidimams, kurie gali pasireikšti ankstyvose ligos stadijose ir būti potencialūs neinvaziniai biožymenys. Šiame darbe tirti klajoklio ir diafragminio nervų ultragarsiniai parametrai pacientams, sergantiems Parkinsono liga ir šonine amiotrofine skleroze, bei jų sąsajos su autonominės nervų sistemos funkcijos sutrikimais. Tyrimo metu atliktas aukštos raiškos periferinių nervų ultragarsinis tyrimas, vertinti autonominiai simptomai bei širdies ritmo variabilumo rodikliai. Nustatyti periferinių nervų struktūriniai pokyčiai ir jų ryšys su klinikiniais bei funkciniais rodikliais. Gauti rezultatai parodė, kad periferinių nervų ultragarsiniai pokyčiai gali būti susiję su autonominės nervų sistemos pažeidimu ir turėti diagnostinę reikšmę vertinant neurodegeneracines ligas. Tyrimo rezultatai prisideda prie neinvazinių biožymenų paieškos bei ankstyvesnės neurodegeneracinių ligų diagnostikos galimybių plėtros.

Postoperative delirium is a common complication following sub-thalamic nucleus deep brain stimulation surgery in Parkinson's disease patients. Postoperative delirium has been shown to prolong hospital stays, harm cognitive function, and negatively impact outcomes. Utilizing radiomics as a predictive tool for identifying patients at risk of delirium is a novel and personalized approach. This pilot study analyzed preoperative T1-weighted and T2-weighted magnetic resonance images from 34 Parkinson's disease patients, which were used to segment the thalamus, amygdala, and hippocampus, resulting in 10,680 extracted radiomic features. Feature selection using the minimum redundancy maximal relevance method identified the 20 most informative features, which were input into eight different machine learning algorithms. A high predictive accuracy of postoperative delirium was achieved by applying regularized binary logistic regression and linear discriminant analysis and using 10 most informative radiomic features. Regularized logistic regression resulted in 96.97% (±6.20) balanced accuracy, 99.5% (±4.97) sensitivity, 94.43% (±10.70) specificity, and area under the receiver operating characteristic curve of 0.97 (±0.06). Linear discriminant analysis showed 98.42% (±6.57) balanced accuracy, 98.00% (±9.80) sensitivity, 98.83% (±4.63) specificity, and area under the receiver operating characteristic curve of 0.98 (±0.07). The feed-forward neural network also demonstrated strong predictive capacity, achieving 96.17% (±10.40) balanced accuracy, 94.5% (±19.87) sensitivity, 97.83% (±7.87) specificity, and an area under the receiver operating characteristic curve of 0.96 (±0.10). However, when the feature set was extended to 20 features, both logistic regression and linear discriminant analysis showed reduced performance, while the feed-forward neural network achieved the highest predictive accuracy of 99.28% (±2.71), with 100.0% (±0.00) sensitivity, 98.57% (±5.42) specificity, and an area under the receiver operating characteristic curve of 0.99 (±0.03). Selected radiomic features might indicate network dysfunction between thalamic laterodorsal, reuniens medial ventral, and amygdala basal nuclei with hippocampus cornu ammonis 4 in these patients. This finding expands previous research suggesting the importance of the thalamic-hippocampal-amygdala network for postoperative delirium due to alterations in neuronal activity.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including cognitive decline and reduced quality of life. Identifying reliable biomarkers for disease progression and symptom severity remains a critical challenge. In this study, levels of oxidative stress-related microRNAs (miR-24-3p, miR-103a-3p, miR-320a-3p, miR-494-3p, miR-126-5p, and miR-543) within blood serum extracellular vesicles (EVs) were examined in a cohort of 93 PD patients to assess their associations with cognitive function, symptom severity, quality of life, and other clinical characteristics. The methods included microRNA extraction from blood serum EVs, followed by cDNA synthesis and RT-qPCR for expression analysis. Upregulation of miR-126-5p, as well as downregulation of miR-24-3p showed the strongest associations with symptom severity and cognitive decline, whereas downregulated miR-320a-3p levels correlated with patient-reported quality of life in PD patients. Downregulation of miR-103a-3p, and miR-543 expression showed slight associations with motor symptoms, cognitive function, and quality of life domains; however, some of these associations lacked statistical power. These findings indicate that specific microRNA expression profiles in extracellular vesicles are associated with PD symptom severity and progression, supporting their further evaluation as biomarkers in larger independent cohorts.

Objectives To evaluate relationships between retinal nerve fiber layer (RNFL) changes and clinical symptoms, disability and disease course in patients with multiple sclerosis (MS). Materials and Methods We conducted a retrospective medical documentation review of patients diagnosed with MS according to the 2010/2017 McDonald criteria, treated at the Department of Neurology of Kaunas Clinics, Lithuanian University of Health Sciences (LUHS) Hospital. Approval was obtained from the Kaunas Regional Biomedical Research Ethics Committee (No. BE-2-113). RNFL thickness was measured by optical coherent tomography (OCT) at baseline and, for some patients, follow-up; to minimize bias from optic neuritis, thickness was defined as the mean of both healthy eyes or, if unilateral optic neuritis had occurred, the measurement from the unaffected eye. Disability assessed according to Expanded Disability Status Scale (EDSS). Results A total of 84 MS patients (27 men, 57 women) were included (mean age 33 ± 9 vs. 34 ± 9 years; 68 % urban). Most patients have relapsing-remitting MS disease course (85 %). At baseline, 78 % of men and 77 % of women had never experienced optic neuritis (ON); at follow-up, similar proportions remained ON-free (64 % vs. 62 %). The thinner baseline RNFL was associated with higher baseline disability (EDSS; r = –0.232, p = 0.017) and greater EDSS worsening over time (r = –0.310, p = 0.002). RNFL correlated more strongly with pyramidal system impairment (r = –0.409, p < 0.001) and pelvic organ dysfunction (r = –0.316, p = 0.002) than with visual acuity (r = 0.068, p = 0.270). Older age correlated with thinner RNFL (r = –0.278, p = 0.005) and higher baseline EDSS (r = 0.273, p = 0.006). In adjusted linear regression (controlling for age and sex), each 20 µm reduction in RNFL predicted a 0.46-point increase in EDSS (B = –0.023, p = 0.015; model p = 0.013) and a 0.32-point rise in cerebellar EDSS score (B = –0.016, p = 0.007; model p = 0.037). Pelvic function decline was significantly linked to sex (B = –0.257, p = 0.008; R² = 0.105, p = 0.037) but not to RNFL or age. Trends toward thinner RNFL and older age predicting reduced 6-minute walk distance were observed (p ≈ 0.06). Among the 45 patients with repeat OCT, baseline RNFL again predicted EDSS progression (r = –0.310, p = 0.002), and RNFL change correlated with EDSS change (r = –0.273, p = 0.042), pyramidal (r = –0.336, p = 0.016), and brainstem impairments (r = –0.385, p = 0.006). Conclusions The thinner baseline RNFL significantly correlated with higher baseline disability, greater disability progression, more pronounced pyramidal and sensory impairment and reduced walking distance. Each 20 µm decrease in RNFL predicted a 0.46-point increase in EDSS and a 0.32-point increase in cerebellar EDSS. RNFL thinning between OCT visits likewise predicted future disability worsening.

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms, including autonomic dysfunction. Structural alterations in the vagus nerve (VN) may contribute to PD pathophysiology, though existing data remain inconsistent. Objective: This study aimed to evaluate morphological changes in the VN using high-resolution ultrasound (USVN) and to investigate associations with autonomic symptoms, heart rate variability (HRV), and clinical characteristics in PD patients. Methods: A cross-sectional study was conducted involving 60 PD patients and 60 age- and sex-matched healthy controls. USVN was performed to assess VN cross-sectional area (CSA), echogenicity, and homogeneity bilaterally. Autonomic symptoms were measured using the Composite Autonomic Symptom Scale 31 (COMPASS-31). HRV parameters—SDNN, RMSSD, and pNN50—were obtained via 24 h Holter monitoring. Additional clinical data included Unified Parkinson’s Disease Rating Scale (UPDRS) scores, transcranial sonography findings, and third ventricle width. Results: PD patients showed significantly reduced VN CSA compared to controls (right: 1.90 ± 0.19 mm2 vs. 2.07 ± 0.18 mm2; left: 1.74 ± 0.21 mm2 vs. 1.87 ± 0.22 mm2; p < 0.001 and p < 0.02). Altered echogenicity and decreased homogeneity were also observed. Right VN CSA correlated with body weight, third ventricle size, and COMPASS-31 scores. Left VN CSA was associated with body size parameters and negatively correlated with RMSSD (p = 0.025, r = −0.21), indicating reduced vagal tone. Conclusions: USVN detects structural VN changes in PD, correlating with autonomic dysfunction. These findings support its potential as a non-invasive biomarker for early autonomic involvement in PD.

Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons, leading to the rapid decline of motor function. In recent years, dysfunction of the autonomic nervous system (ANS) has also been increasingly recognized as a contributing factor in various neurodegenerative diseases, including ALS. This study is the second publication from our ALS research cohort at Kaunas Clinics. Our previous work examined ultrasonographic changes in the phrenic nerve as a supplementary diagnostic approach for ALS. Materials and Methods: In the present study, we investigated ultrasonographic alterations of the vagus nerve within the same ALS cohort, aiming to explore correlations with ANS involvement. We performed high-resolution ultrasonography of the vagus nerve (VN), collected clinical data, conducted heart rate monitoring, and evaluated respiratory function. Results: We prospectively included 32 ALS patients meeting “Gold Coast” criteria and 64 age- and sex-matched control patients. The average onset of ALS was 57.97 ± 9.22 years, and the duration of the disease was15.41 ± 9.04 months. For ALS patients, we found significantly reduced vagus nerve cross-sectional area (CSA) at the level of the carotid artery bifurcation bilaterally compared to controls (right VN 1.86 ± 0.21 vs. 2.07 ± 0.18 mm2, p < 0.001; left VN 1.69 ± 0.21 vs. 1.87 ± 0.21 mm2, p < 0.001). Reduced values of the left VN positively correlated with the reduced values of FEV1% and sO2. Conclusions: Our findings revealed a significant bilateral reduction in vagus nerve size in ALS patients compared to controls, suggesting that vagal atrophy may serve as a potential marker of autonomic dysfunction in ALS.

Introduction X-linked adrenoleukodystrophy (ADL) is a rare genetic disorder caused by a congenital defect in the ABCD1 gene (1,2). Its onset age varies widely and disease progression is usually slow but unpredictable (2,3). Clinical presentation might include adrenal insufficiency, myelopathy, polyneuropathy, and leukodystrophy (1-4). Case Presentation A 31-year-old man complained of leg weakness and spasticity, which worsened with physical activity. In addition, the patient experienced disrupted sleep due to night-time leg myoclonus. Symptoms progressed for 6 years. His medical history is significant for primary Adisson’s disease, diagnosed in 2009, and irritable bowel syndrome (continuous complaints of frequent defecation, changes in stool consistency, and abdominal pain). The family history is relevant as the patient's mother and grandfather were diagnosed with Parkinson's disease. During a neurological examination, increased muscle tone is observed in both legs, reflexes in the legs are accentuated, and a pathological Babinski reflex is present on both sides. An MRI of the brain and spinal cord was conducted - no pathological changes in the intensity of the MR signal were detected. Sanger sequencing of the ABCD1 gene coding regions revealed a potentially pathogenic hemizygous variant NM_000033.4(ABCD1):c.[1772G>C];[0], which is responsible for an amino acid change in the structure of the protein NP_000024.2:p.[(Arg591Pro)];[(0)]. The patient's symptoms are currently more consistent with an adrenomyeloneuropathic (AMN) form of the disease. Discussion The estimated prevalence of ALD is 1:17000 (1,2). Several clinical phenotypes of ALD exist - AMN is the most common for adult males (1-3). Every young male with primary adrenal insufficiency should be suspected of ALD; neurological deficits usually start to show later in life and have a wider differential diagnosis (2-4). There is no current treatment for AMN, therefore timely diagnosis is required for the best multidisciplinary supportive care (4,5). Conclusions This clinical case highlights the importance of considering congenital disorders in the differential diagnosis of a young patient presenting with a history of unexplained and debilitating symptoms. Early recognition and timely referral for genetic counseling can improve diagnostic accuracy and patient care.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, and although the diagnosis is primarily based on clinical criteria, ENMG, as the "gold standard", does not always show detectable changes. Therefore, our study suggests that alterations in echogenicity and heterogeneity of the phrenic nerve (PN) may serve as potential additional diagnostic tools for ALS. Methods: Our study included 32 patients in the ALS group and 64 individuals in the control group. Each participant underwent an interview and completed questionnaires to collect clinical and demographic data, including age, gender, height, body mass index (BMI), hip and waist circumference, duration of illness, ALS-FRS-R score, comorbidities, and medication use. Ultrasound examinations of the PN were performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine equipped with a linear 4-18 MHz transducer. The ALS group participants underwent PN sonography and conduction examinations, arterial blood gas (ABG) analysis, respiratory function tests (RFT), and electroneuromyography (ENMG). Results: The study demonstrated that the phrenic nerve is significantly smaller on both sides in patients with ALS compared to the control group (p < 0.01). Changes in the homogeneity and echogenicity of the PN were also observed on both sides. On the right side, 43.8% of the nerves showed heterogeneity, 40.6% were isoechoic, and 21.9% were hyperechoic. On the left side, 59.4% of the nerves exhibited heterogeneity, 34.4% were isoechoic, and 28.1% were hyperechoic. Moreover, sonography on both sides showed significant correlation with ALS-FRS-R, COMPASS-31, and ENMG results. Conclusions: Our study highlights the importance of phrenic nerve ultrasound as a promising supplementary diagnostic tool for ALS. The significant differences in phrenic nerve size, echogenicity, and homogeneity between patients with ALS and the control group demonstrate that ultrasound imaging can detect morphological changes in the phrenic nerve. Incorporating phrenic nerve ultrasound into routine diagnostic protocols could improve early detection, enhance disease monitoring, and offer a more comprehensive understanding of the neurodegenerative processes in ALS.

The identification of mechanisms associated with Parkinson disease (PD) development in cognitive functioning would be of great usefulness to clarify PD pathogenesis and to develop preventive and therapeutic strategies. In this study, blood serum extracellular vesicle (EV) levels of the candidate microRNAs (small noncoding RNAs that play a role in gene expression regulation):,miR-7, miR-21, miR-153, miR-155, miR-200a and miR-214, have been investigated for association with PD in a group of 93 patients with cognitive parameters, PD symptoms, affected quality of life and some clinical characteristics. MiRNA was extracted from patients’ blood serum EVs, transcribed into cDNA and their expression was evaluated using RT-PCR. The miR-153 and miR-200a showed the most plausible correlations with cognitive functioning parameters such as general intellectual functioning, psychomotor speed, mental flexibility, and nonverbal executive functions. Moreover, lower levels of miR-153 were associated with attention span, working memory and psychomotor speed with learning. Increased levels of miR-200a, miR-7, miR-214, and miR-155 were also linked with neurological functioning, such as bradykinesia, tremor, balance and others. Despite the fact that due to small sample size, our results should be considered as preliminary, our study suggests that miRNA expression in EVs could be associated with symptom severity, cognitive impairment and quality of life in PD.

Background and Objectives: Parkinson’s disease (PD) is associated with various non-motor symptoms, including minor hallucinations, comprising visual illusions and presence and passage hallucinations. Despite their occurrence, even in newly diagnosed PD patients, data regarding the prevalence and characteristics of minor hallucinations, visual illusions in particular, remain limited. The aim of this study was to address this knowledge gap by assessing the prevalence of minor hallucinations in PD patients, with a focus on visual illusions. Materials and Methods: In this prospective pilot study, we enrolled 35 PD patients without dementia and 35 age- and gender-matched PD-unaffected individuals. Cognitive function was assessed using the Montreal Cognitive Assessment, clinical data were collected, and all subjects were assessed via questionnaires regarding 20 types of visual illusions and other minor hallucinations. Results: The prevalence of minor hallucinations was significantly higher among PD patients compared to controls (45.7% vs. 11.4%, p = 0.003). PD patients reported visual illusions and presence hallucinations more frequently than the controls (37.1% vs. 8.6% and 22.9% vs. 2.9%, p = 0.009 and p = 0.028, respectively), with no significant difference in passage hallucinations (20% vs. 8.6%, p = 0.306). In the PD group, the most frequently observed visual illusions were complex visual illusions, kinetopsia, and pelopsia; the latter was also the most common visual illusion in the control group. PD patients experiencing visual illusions were more likely to report presence hallucinations compared to patients without visual illusions (53.8% vs. 4.5%, p = 0.002); no significant differences in other clinical characteristics were found. Conclusions: Minor hallucinations are a common phenomenon among PD patients without dementia, with a higher prevalence than among healthy controls. Visual illusions are the most prevalent type of minor hallucinations, affecting more than a third of PD patients, with complex visual illusions, kinetopsia, and pelopsia being the most frequently reported types.