Search Results (67)

Objective: Several strategies have been described for stroke prevention, and the most commonly used medication is aspirin. Cilostazol, which is a substance with a pleiotropic effect, is still not well investigated. In this study, we aimed to delineate the effects of mono- and combinatorial pre-treatment upon neurological status and biomarkers, namely protein S100b, GFAP, procalcitonin, and galectin-3, following stroke. Methods: Twelve-week-old Sprague–Dawley rats were randomly assigned to four groups, each containing six rats: control group (normal saline), cilostazol group (30 mg/kg/daily), aspirin group (10 mg/kg/daily), and aspirin/cilostazol group. Each substance was administered by gavage for four weeks. All animals were subjected to cerebral ischemia for 2 h using intraluminal middle cerebral artery occlusion. A neurological examination was performed, serum concentrations of biomarkers were determined, and the animals were then sacrificed. Results: All treatment groups exhibited variations in the severity of immediate neurological presentation. Unlike the control group, where all rats presented with severe focal neurology or mortality, most rats in the treatment groups displayed no to moderate focal neurology. Moreover, the aspirin/cilostazol group consistently exhibited significantly lower levels in the studied biomarkers compared to other groups. Conclusions: Co-administration of cilostazol and aspirin significantly ameliorates the immediate expression of the studied biomarkers. Further large-scale studies are needed to investigate the effect of combined therapy for primary and secondary prevention of stroke, using not only serum biomarkers but other specific clinical and laboratory endpoints. Full article

Background/Objectives: This is a retrospective review of 36 patients with electrodiagnostic (EDX) confirmation of carpal tunnel syndrome (CTS) and ultrasound (US) detection of marked median nerve enlargement (defined as a cross-sectional area [CSA] of 40 mm² or greater) at the wrist. Methods: We describe the clinical, electrodiagnostic (EDX), and US findings in these patients and discuss the pathophysiologic basis of a markedly enlarged median nerve. Results: The markedly enlarged median nerve was detected by US in a total of 39 hands (36 patients, with 3 bilateral). Of the 39 hands, thenar atrophy was observed in 15 (38.5%) hands, and pinprick loss in the median nerve distribution was noted in all hands. Moderately severe or severe median nerve entrapment at the carpal tunnel (CT) was confirmed by EDX studies in 21 (53.8%) and 16 (41.0%) hands, respectively. A total of 12 (30.8%) hands had no compound muscle action potentials (CMAPs) over the abductor pollicis brevis muscle, and sensory nerve action potentials (SNAPs) were not detected in 31 (79.5%) hands. The wrist CSA was between 40 and 44 mm² in 20 (51.3%) hands, between 45 and 49 mm² in 13 (33.3%) hands, and 50 mm² or greater in 6 (15.4%) hands. Conclusions: The implications of the markedly enlarged median nerve for surgical management of CTS are unknown, and future prospective studies are needed. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative central nervous system disease. Neurodegeneration plays a central role in long-term disease progression. Materials and Methods: This cross-sectional study examined the relationship between neurodegenerative biomarkers, namely plasma neurofilament light chain (pNfL) levels and MRI-derived brain volume measurements, and clinical outcomes in 49 patients with relapsing–remitting multiple sclerosis (RRMS). Plasma NfL levels were quantified using Simoa technology, while MRI data was analyzed via FreeSurfer to measure volumes of grey and white matter, specific brain structures, and ventricular sizes. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R). Disability was evaluated using the Expanded Disability Status Scale (EDSS). Results: The results indicated significant positive correlations between SDMT scores and volumes of grey matter, white matter, and various subcortical structures, suggesting that preserved brain volume is linked to better cognitive performance. Negative correlations were observed between SDMT scores and ventricular volumes, as well as between SDMT scores and EDSS scores, implying that cognitive decline corresponds with structural brain deterioration and increased disability. No significant associations were found between BVMT-R scores and imaging data or disability measures. Plasma NfL levels showed significant correlations with early disease relapses and enlargement of the third and fourth ventricles, but not with brain volume, cognitive tests, or EDSS scores. Conclusions: These findings indicate that MRI-based brain volumetrics, particularly grey and white matter measures, are stronger indicators of cognitive function and disability in RRMS than plasma NfL. Full article

Introduction: Myotonia is a rare neuromuscular condition characterized by impaired muscle relaxation. In this study, we provide normative values for clinical tests related to myotonia in the Hungarian population and compare them to patients with myotonic dystrophy type 1 (DM1). Methods: Relaxation tests (10 eye openings, tongue extension, and palm openings), handgrip strength, and the nine-hole peg test were conducted on 139 healthy individuals and 31 patients with DM1. Results: We observed non-significant declines in handgrip strength and relaxation tests with age (p < 0.05). Significant differences were found between controls (n:139) and patients with DM1 (n = 31) in all tests (p < 0.05). Sex differences were noted in the healthy population: men (n:68/139) had stronger handgrip (mean of men 42.45 ± 1.15 vs. women 24.3 ± 0.9) and slower relaxation tests (mean of eye openings in men 3.6 ± 0.2 vs. in women 4.2 ± 0.2, tongue extensions in men 3.7 ± 0.2 vs. in women 4.2 ± 0.2, palm openings in men 4 ± 0.2 vs. in women 4.9 ± 0.2 However, these differences were not present among patients with DM1. Discussion: Normal values for relaxation tests across different age groups were established. These results might be useful for further clinical investigations. Our study supports the usage of averages of healthy population instead of age groups of relaxation tests and their clinical relevance in the evaluation of patients with myotonia. Full article

Background: Cerebrotendinous Xanthomatosis (CTX) is a rare, inherited metabolic disease caused by pathogenic variants in CYP27A1. The clinical presentation of this progressive disease includes cognitive deficits, ataxia, peripheral neuropathy, and pyramidal signs, as well as bilateral cataracts and tendon xanthomas. In some cases, CTX also includes parkinsonism. The goals of this study are to develop a data source that provides improved characterization and awareness of parkinsonism in CTX. Methods: We conducted a systematic review of the literature according to PRISMA guidelines to identify all published individuals diagnosed with CTX and parkinsonism. Clinical signs, imaging findings and treatment response to both chenodeoxycholic acid and dopaminergic medications were examined for 72 subjects. Results: The average age of onset of parkinsonism in these CTX patients was 42 years, illustrating the early onset nature of parkinsonism in CTX. Functional dopaminergic imaging revealed the loss of presynaptic dopaminergic neurons in the substantia nigra which points to neurodegeneration of the dopaminergic system as the underlying pathophysiology for parkinsonism in CTX. Brain MRI showed abnormalities in the basal ganglia in 38% of subjects. MRI also showed abnormalities in the cerebellum in 88% of subjects which is typical for CTX and can be utilized to distinguish subjects with CTX and parkinsonism from individuals with other forms of atypical parkinsonism. Dopaminergic medication mitigated parkinsonism signs in most individuals with CTX. Conclusion: CTX is a neurometabolic disease that can result in levodopa-responsive parkinsonism that should be included in the differential for atypical parkinsonism. Full article

Background/Objectives: Endovascular thrombectomy has become a mainstay in the treatment of acute ischemic stroke caused by large vessel occlusion. Among the multiple factors that influence outcomes, the choice of anesthetic technique—general anesthesia (GA), conscious sedation (CS), or local anesthesia (LA)—remains controversial. This narrative review aims to critically examine and synthesize current evidence comparing the efficacy and safety of different anesthetic strategies in endovascular stroke treatment. Methods: A structured search of the PubMed^® database was conducted using the terms “stroke treatment”, “endovascular stroke treatment”, “anesthesia”, “general anesthesia”, “conscious sedation”, and “local anesthesia”. The search focused on clinical trials involving human subjects published in English. Studies were included if they compared at least two anesthetic techniques during thrombectomy and reported outcomes such as neurological recovery, mortality, or complication rates. Reviews, case reports, and animal studies were excluded. Results: Several randomized controlled trials and observational studies show comparable functional outcomes between GA and CS, though CS may confer advantages in early neurological recovery and reduced complications. Local anesthesia, though less studied, may offer favorable outcomes in selected patients. General anesthesia appears to be associated with greater hemodynamic variability and a higher risk of post-procedural infections, particularly in unsuccessful interventions. Maintaining stable blood pressure and minimizing ventilation duration are crucial to improving patient prognosis. Conclusions: While both GA and CS are viable options during thrombectomy, CS and LA may provide a safer profile in selected patients by preserving hemodynamic stability and reducing infectious risk. Personalized anesthetic strategies and further high-quality trials are warranted. Full article

Background: Spinal muscular atrophy (SMA) is a treatable motor neuron disease. Biomarkers for skeletal muscle atrophy are extremely important for measuring the effects of treatment and monitoring the natural course of the disease. The urinary titin N fragment (UNT) has recently been proven to be related to muscle damage. Methods: The UNT was measured in 41 patients with SMA and 41 healthy controls. Clinical data, functional tests, and laboratory findings were also recorded. Results: We found significantly higher UNT levels in the patient samples than in the healthy subjects. The UNT was not related to disease type, functional test results, or serum creatine kinase levels. Conclusions: This cross-sectional study highlights the importance of the UNT as a potential noninvasive biomarker for spinal muscular atrophy. Its role can potentially be verified through longitudinal studies. Full article

Introduction: The figure-of-eight walk test (F8WT) assesses gait on a curved path, reflecting everyday walking complexity. Despite recognized validity among elderly individuals, its application in neurological disorders remains inadequately explored. This scoping review summarizes evidence regarding F8WT use, validity, and clinical applicability among individuals with neurological disorders. Methods: A systematic literature search was conducted in the PubMed, Scopus, Embase, and Web of Science databases. After reading the full text of the selected studies and applying predefined inclusion criteria, seven studies, involving participants with multiple sclerosis (n = 3 studies), Parkinson’s disease (n = 2 studies), and stroke (n = 2 studies), were included based on pertinence and relevance to the topic. Results: F8WT demonstrated strong reliability and validity across various neurological populations and correlated significantly with established measures of gait, balance, and disease severity. Preliminary evidence supports its ability to discriminate individuals at increased fall risk and detect subtle motor performance changes. Discussion: The F8WT emerges as a valuable tool, capturing multifaceted gait impairments often missed by linear walking assessments. Sensitive to subtle functional changes, it is suitable for tracking disease progression and intervention efficacy. Conclusions: F8WT is reliable and clinically relevant, effectively identifying subtle, complex walking impairments in neurological disorders. Full article

The ergogenic effects of music have been well described across various modes of exercise with widespread use across competitive athletes and recreational exercisers alike. Underlying the acute beneficial effects of music during exercise are profound physiological and psychological changes which involve an array of different organ systems, including but not limited to cardiovascular, endocrine, skeletal muscle, and nervous systems. While the use of music to enhance physical performance and improve associated mechanisms has been largely optimized in healthy individuals, the investigations of the translation to individuals with neurological conditions are still ongoing. Recently, it has been established that the personalization of music interventions greatly influences performance-enhancing benefits and aids in physical performance optimization in healthy individuals. Self-selected music (SSM) has been documented to impart ergogenic advantages over pre-determined or non-preferred music, including improved cardiorespiratory endurance, power development, and velocity of movement which are characterized by adaptative physiological and psychological changes. Evidence of the benefits of SSM has progressed to the degree to which the overlap of possible benefits between healthy and clinical populations is becoming more apparent. This aim of this theoretical review is to discuss how personalized music influences psychophysiological determinants of exercise ability in healthy individuals and consider how these findings may be applicable to neurological conditions to enhance exercise capacity. The current knowledge on the role of SSM in augmenting physiological and psychological responses to exercise in healthy individuals is presented along with how these mechanisms might be leveraged to overcome exercise limitations in neurological conditions. Overall, SSM appears to have theoretical support to be a promising therapeutic approach to improving exercise ability in neurological conditions through similar ergogenic mechanisms documented in healthy individuals, but further investigation is warranted. Full article

Background: Administering intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) on direct oral anticoagulants (DOACs) remains a clinical challenge. Current guidelines restrict IVT within 48 h of DOAC intake unless anticoagulant activity can be confidently excluded. However, reliable medication histories are often unavailable, and conventional coagulation tests inadequately detect DOAC activity. This study evaluated whether viscoelastic point-of-care testing (ClotPro^®) could identify the absence of anticoagulant effect in AIS patients on DOACs, thus enabling IVT administration and potentially improving clinical outcomes. Methods: We conducted a prospective observational cohort study of 40 AIS patients with documented DOAC use, admitted between February 2023 and May 2025. ClotPro^® was performed at admission using the Russell’s viper venom (RVV) assay for factor Xa inhibitors and the ecarin clotting time (ECT) assay for dabigatran. Subtherapeutic anticoagulation was defined as a clotting time (CT) of <100 s for RVV and <180 s for ECT, respectively. Patients identified as being subtherapeutic were assessed for IVT eligibility. To evaluate IVT effects, we performed propensity score-matched bootstrap resampling (1000 iterations), matching patients by age, admission National Institutes of Health Stroke Scale (NIHSS), and pre-stroke modified Rankin Scale (mRS). Primary endpoints were NIHSS-shift (change from admission to 72 h) and mRS-shift (change from pre-stroke mRS to 90-day mRS). Predictors of outcomes were analyzed using multivariate regression models. Results: ClotPro^® identified 15/40 patients (37.5%) as subtherapeutic, all on factor Xa inhibitors. Of these, seven received IVT. In matched analyses, IVT-treated patients showed a numerically greater neurological improvement than untreated patients (mean NIHSS-shift: −2.83 vs. 3.94; mean difference: −6.76, 95% confidence interval [CI]: −24.00 to 7.55; p = 0.495). Functional outcome by mRS-shift showed only minor differences between groups (2.74 vs. 2.10 mean difference: 0.64; 95% CI: −2.00 to 2.50; p = 0.510). IVT showed a favorable trend for early neurological recovery (p = 0.081) but was not independently associated with functional outcome (p = 0.380). Conclusions: ClotPro^® identified a substantial subset of AIS patients on DOAC therapy without measurable anticoagulant activity, enabling IVT in cases that would otherwise have been excluded based on medication history. These findings support the feasibility of ClotPro^®-guided decision-making in acute stroke care and highlight its potential to improve IVT selection by enabling real-time assessment of coagulation status at the bedside. Full article

Background/Objectives: Spasticity in children with cerebral palsy (CP) can impair motor-related functions. The objective of this exploratory, prospective study was to examine if transcutaneous electrical nerve stimulation (TENS) in a whole-body suit leads to changes in spasticity and other related effects. Methods: Thirty-one children with CP GMFCS III–V, with a median age of 11.0 years (age range of 7–17 years), were consecutively included, and they used the suit with TENS for 24 weeks. The primary outcome was spasticity measured using the Modified Ashworth Scale (MAS). Functional motor-related tasks were evaluated by the Goal Attainment Scale (SMART GAS). The Modified Tardieu Scale (MTS), passive Range of Motion (pROM), GMFM-66, and Posture and Postural Ability Scale (PPAS) assessments were performed. Results: Seventeen subjects (17/31) completed the 24 weeks. Dropout was due to difficulty in donning the suit. The level of overall spasticity, most pronounced in the proximal arms and legs, was reduced according to the MAS, but not the MTS or pROM. Subject-relevant motor-related goals improved significantly in standing/walking and hand/arm function. Changes in the GMFM-66 and PPAS were not significant. Conclusions: Although there were statistically significant but underpowered changes in the MAS after 24 weeks, there were no clinically relevant effects. Exploratorily, we found observer-reliant motor-related functional improvements, which, however, we were unable to detect when trying to quantify them. Donning the suit led to dropout throughout the study. Caregivers need to allocate time, mental capacity and have the physical skill set for donning the suit for long-term use. Full article

Background: Research concerning the genetic risk for dementia has recently been headed towards new directions. Novel findings from genome-wide association studies have highlighted the association of Alzheimer’s disease incidence with many gene polymorphisms, apart from the Apolipoprotein-E genotype. The identification of additional genetic risk factors has led to the construction of specific genetic risk scores for dementia, considering many different genetic factors and specific biological pathways related to Alzheimer’s disease. Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis method, summarizing existing data regarding genetic risk scores for Alzheimer’s disease and dementia, in order to improve the current understanding of the genetic underpinnings of dementia. In specific, five databases (PubMed/MEDLINE, Embase, Scopus, Web of science, and Cochrane Central) were searched using the keywords “genetic risk score”, “Alzheimer’s disease”, and “dementia” with specific inclusion and exclusion criteria. Results: From the 552 articles identified, we finally included 20 studies for the qualitative analysis. These reports were classified in three different categories of genetic scores: “polygenic risk scores (PRSs)” (including 11 studies), “pathway specific polygenic risk scores (p-PRSs)” (5 studies), and “complex genetic risk scores” (4 studies). Conclusions: Existing genetic risk scores have contributed to better dementia prediction and a better understanding of the underlying pathology. Novel approaches integrating multiple polygenic risk scores might ameliorate the accuracy of genetic risk scores. The combination of polygenic risk scores that are specific to related biological pathways or relevant biomarkers is of utmost importance to achieve a better predictive ability. Full article

Tay–Sachs disease (TSD) is a rare and severe neurodegenerative disorder inherited in an autosomal recessive manner. It is caused by a deficiency of the enzyme hexosaminidase A, which is responsible for the degradation of GM2 gangliosides—lipids that accumulate in the nerve cells of the central nervous system. The inability to break down these lipids leads to their progressive accumulation, resulting in irreversible brain damage. Mechanistically, TSD is caused by mutations in the HEXA gene, which encodes the alpha subunit of hexosaminidase A. These mutations disrupt enzyme activity and alter cellular pathways involved in lysosomal lipid degradation. Although Tay–Sachs specifically involves the alpha subunit, similar clinical features can be seen in Sandhoff disease, a related disorder caused by mutations in the HEXB gene, which encodes the beta subunit shared by hexosaminidase A and B. Tay–Sachs is classified into three clinical forms according to age of onset and symptom severity: the classic infantile form, which is the most common and severe; a juvenile (subacute) form; and an adult-onset form, which progresses more slowly and tends to present with milder symptoms. Diagnosis is based on enzymatic testing showing reduced or absent hexosaminidase A activity, confirmed by genetic testing. Prenatal diagnosis and genetic counseling play a key role in prevention and reproductive decision-making, especially in high-risk populations. Although no curative treatment currently exists, ongoing research is exploring gene therapy, enzyme replacement, and pharmacological approaches. Certain compounds, such as gemfibrozil, have shown potential to slow symptom progression. Early diagnosis and multidisciplinary care are essential to improving quality of life, although therapeutic options remain limited due to the progressive nature of the disease. Full article

Background/Objectives: Major Depression (MD) is a common disorder that has significant social and economic impacts. Approximately 30% of all MD patients are refractory to common treatments, representing a major obstacle to managing the impacts of depression. One potential explanation for the incomplete treatment efficacy in MD is a substantial divergence in the mechanisms and brain networks involved in different subtypes of the disorder. The aim of this study was to identify novel brain regional targets for MD clinical screening using a gene-informed approach. Methods: A new analysis pipeline, called “Analysis Tool for Local Association of Neuronal Transcript Expression” (ATLANTE), was generated and validated. The pipeline identifies brain regions based on the shared high expression of user-generated gene lists; in this study, the pipeline was applied to discover brain regions that may be significant to MD. Results: Nine discrete brain regions of interest to MD were identified, including the temporal pole, anterior transverse temporal gyrus (Heschl’s gyrus), olfactory tubercle, ventral tegmental area, postcentral gyrus, CA1 of the hippocampus, olfactory area, perirhinal gyrus, and posterior insular cortex. The application of network and clustering analyses identified genes of special importance, including, most notably, PRKN. Conclusions: This study provides two major insights. The first is that several brain regions have unique MD-associated genetic architectures, indicating a potential explanation for subtype-specific dysfunction. The second insight is that the PRKN gene, which is strongly associated with Parkinson’s disease, is a key player amongst the MD-associated genes. These findings reveal novel targets for the clinical screening of depression and reinforce a mechanistic connection between MD and Parkinson’s disease. Full article

Background: Huntington’s disease (HD) is a progressive, autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. Despite advances in understanding its molecular basis, epidemiological data in many countries, including Bulgaria, remain limited. This study aims to present clinical and genetic findings from a 20-year single-centre cohort. Methods: A retrospective review was conducted of patients evaluated for HD at the University Hospital “St. Marina” in Varna between 2004 and 2024. Data included demographics, CAG repeat length, clinical features, imaging, and psychiatric assessments. Statistical analysis focused on correlations between variables, with significance set at p < 0.05. Results: Out of 79 referred individuals, 43 were molecularly confirmed. The mean age of onset was 43 years, with a four-year diagnostic delay. The average CAG repeat length was 44.6, though two symptomatic patients had reduced penetrance alleles (38 and 39 repeats). Cognitive and psychiatric symptoms were each present in 72% of cases. Depression was significantly more prevalent in women (p = 0.011). Most patients had a positive family history, predominantly maternal. Conclusions: Our findings highlight diagnostic delays, gender-specific psychiatric vulnerabilities, and the importance of personalized care. Improved access to genetic counselling and early diagnosis are essential for optimizing outcomes. Full article