Search Results (44)

Objectives: With the development of advanced neuroimaging techniques, including resting-state functional magnetic resonance imaging and diffusion tensor imaging, Parkinson’s disease (PD) has increasingly been recognized as a complex brain network disorder. In this review, we summarized research on brain networks in PD to elucidate the network abnormalities underlying its four major motor symptoms and to identify the networks modulated by deep brain stimulation (DBS). Materials and Methods: We searched PubMed and Web of Science for the most recent literature on brain network alterations in PD. Eligible studies included those investigating the general PD network (n = 10), symptom-specific networks—tremor-dominant (n = 13), postural instability and gait disorder (n = 9), freezing of gait (n = 9), akinetic-rigidity (n = 3)—as well as DBS-modulated networks (n = 14). Based on these studies, we integrated the findings and used BrainNet Viewer to generate schematic network visualizations. Results: The symptom-specific networks exhibited common abnormalities within the sensorimotor network. Evidence from DBS studies suggested that therapeutic effects were associated with modulation of the motor cortex through both functional and structural connectivity. Moreover, the four motor symptoms each demonstrated distinct network features. Specifically, the tremor network was characterized by widespread alterations in the cortico-thalamic-cerebellar circuitry; the postural instability and gait disorder network showed more severe disruptions within the striatum and visual cortex; the freezing of gait network exhibited disruptions in midbrain regions, notably the pedunculopontine nucleus; and the akinetic-rigidity network involved changes in cognition-related networks, particularly the default mode network. Conclusions: PD motor symptoms exhibit both distinct network features and shared alterations within the sensorimotor network. DBS modulates large-scale brain networks, especially motor-related networks, contributing to the alleviation of motor symptoms. Characterizing symptom-specific networks may support precision DBS target selection and parameter optimization. Full article

Background/Objective: Central pathophysiological heterogeneity among Parkinson’s disease (PD) motor subtypes has been increasingly recognized, yet subtype-specific peripheral disturbances are limited. We aimed to characterize demographic, biochemical, and neurophysiological differences among PD motor subtypes, evaluate hematoinflammatory effects on peripheral and proximal motor conduction, and identify prognostic phenotypic biomarkers. Methods: A total of 110 participants (60 idiopathic PD patients (30 akinetic-rigid (AR), 30 tremor-predominant (TD), and 50 age- and sex-matched healthy controls (HCs)) were enrolled. Demographic data, nerve conduction studies (NCS) including detailed F-wave analysis, and hematoinflammatory markers were collected. Kruskal–Wallis, linear mixed models, multivariable regression, and ROC analyses were applied. Results: Hematoinflammatory indices were elevated in both subtypes compared with HCs, with more pronounced changes in AR (mean platelet volume (MPV) H = 4.367, p = 0.003; systemic inflammatory response index (SIRI) H = 3.929, p = 0.004). AR showed severe upper-limb–predominant motor involvement (median motor onset latency H = 55.30, p < 0.001; amplitude H = 50.52, p = 0.04; conduction velocity H = 49.15, p < 0.001), whereas TD showed milder, lower-limb–predominant changes (tibial motor onset latency H = 19.89, p < 0.001; amplitude H = 51.50, p = 0.02; velocity H = 15.39, p < 0.001). AR also demonstrated prolonged minimal (Fmin)/mean (Fmean) ulnar F-wave latencies versus TD (respectively, H = 10.51, p = 0.001; H = 8.79, p = 0.003), with both showing increased tibial Fmean/Fmax latencies. Platelet–eosinophil indices independently predicted ulnar F-latencies (B = 0.104–0.105; p = 0.001; model R² = 0.21–0.39). Select F-wave metrics yielded ROC AUCs ≈ 0.65–0.92 (ulnar Fmin AUC ≈ 0.92 vs. HCs); AR achieved sensitivity/specificity ≈ 70–74%. Conclusions: The AR subtype showed increased hematoinflammatory changes, specifically in MPV and SIRI, as well as a tendency toward more pronounced proximal motor and peripheral nerve conduction impairment compared with TD. Platelet–eosinophil indices and F-wave metrics may represent potential candidate markers for diagnostic or stratification purposes in PD subtyping and could possibly aid in prognostic estimation. Full article

Background and Clinical Significance: Creutzfeldt–Jakob disease (CJD) is a rare and fatal neurodegenerative disorder caused by prion protein misfolding. The disease poses significant diagnostic challenges, particularly when its initial symptoms mimic other conditions, such as transient ischemic attacks. Early recognition and differentiation from other neurological conditions are critical, as misdiagnosis may lead to unnecessary interventions. This case highlights a unique presentation of CJD in a male Caucasian patient with a history of cardiac surgery and mitral valve prosthesis, emphasizing the role of multidisciplinary evaluation in complex neurological cases. Case Presentation: A male patient in his mid-sixties with a history of mitral valve mechanical prosthesis and prior infective endocarditis presented with progressive cognitive decline, memory impairment, and episodes of confusion. Initial cardiovascular investigations suggested mitral valve prosthesis thrombosis, while neurological assessment pointed toward transient brain ischemia. However, brain imaging remained inconclusive. Given the rapid deterioration of cognitive and motor functions, further diagnostic workup was performed. MRI findings revealed cortical diffusion restrictions consistent with probable CJD. Despite symptomatic management, the patient’s condition worsened, leading to akinetic mutism and death within eight days of diagnosis. Conclusions: This case underscores the diagnostic complexity of CJD, particularly when initial symptoms overlap with transient ischemic events. It highlights the importance of comprehensive neuroimaging and an interdisciplinary approach in recognizing atypical neurodegenerative diseases to improve diagnostic accuracy and patient management. Full article

Background/Objectives: Impaired balance and general mobility are common complications of Parkinson‘s disease (PD) and are largely caused by bradykinesia and hypokinesia. Although previous studies have shown that patients can increase the speed and amplitude of movement with training, apathy, which is also common among people with PD, reduces this prospect. Training with light pods was originally developed for athletes to enhance agility in a way that is motivating. However, this type of training could be ideal for individuals with PD and possibly reduce bradykinesia and its effects. This study used a longitudinal interventional design without a control group to explore the effects of a four-week agility training with light equipment on balance and general mobility in patients with PD, as well as to assess motivational properties. Methods: Seven individuals with PD of the motor subtype “akinetic–rigid” participated in this study. Each participant received training three times per week for four weeks. The training session consisted of five rounds; in each round, participants had to turn off 20 lights. Measurements were performed one and a half weeks before training, at the beginning of the program, and at the end of the program. Balance was assessed with Mini-BESTest, general mobility with Timed Up and Go (TUG), transfer skills with 5× Sit to Stand, walking speed with the 10 m walking test, and the ability to turn on a spot with the 360° Turn Test. Motivational aspects of training were assessed after each training session, with scoring on a scale of 0–10. Results: The training significantly improved overall balance (p < 0.001), especially reactive postural control, sensory orientation, and dynamic gait, while anticipatory balance remained unchanged. Turning ability improved, but mobility, transfer ability, and walking speed did not. Motivation remained consistently high across participants. Conclusions: A four-week light-based agility training program can improve balance and turning ability in people with PD and appears to be motivating. However, no clear effects were found for general mobility, transfer skills, or walking speed. Given the small sample size and absence of a control group, these findings should be interpreted with caution. Full article

Olfactory impairment was assessed in akinetic-rigid (PD_AR) and tremor-predominant (PD_T) subtypes of Parkinson’s disease (PD), classified based on motor symptoms. Seventeen PD_AR, fifteen PD_T, and twenty-four cognitively normal (CN) participants completed the University of Pennsylvania Smell Identification Test (UPSIT). Groups were well-matched for age and demographic variables, with cognitive performance statistically controlled. Resting-state fMRI (rs-fMRI) and seed-based functional connectivity (FC) analyses were conducted to characterize olfactory network (ON) connectivity across groups. UPSIT scores were significantly lower in PD_AR compared to PD_T. Consistently, ON FC values were reduced in PD_AR relative to both PD_T and CN. FC of the primary olfactory cortex (POC) significantly differed between CN and the PD subtypes. Furthermore, connectivity in the orbitofrontal cortex and insula showed significant differences between PD_AR and PD_T, as well as between PD_AR and CN. Notably, ON FC between the left hippocampus and the posterior cingulate cortex (PCC) also differed significantly between PD_AR and PD_T. These findings reveal distinct ON FC patterns across PD_AR and PD_T subtypes. Variations in UPSIT scores suggest that motor symptom subtype is associated with olfactory performance. Moreover, ON connectivity closely paralleled the UPSIT scores, reinforcing a neural basis for olfactory deficits in PD. Given the accelerated motor and cognitive decline often observed in the PD_AR, these results support the potential of olfactory impairment as a clinical marker for disease severity. Full article

Cranial kinesis in Neornithes is enabled by a complex system of bones, muscles, ligaments, and joints, allowing variable degrees of movement between the upper jaw and the neurocranium. Particularly, cranial prokinesis—mobility of the upper jaw relative to the neurocranium—is the most widespread form. It has been stated that Phorusrhacidae (Aves, Cariamiformes) were incapable of performing cranial kinesis. To assess potential functional differences within the clade, all known cranial flexion zones were analyzed and compared with the kinetic systems of extant Neornithes. In Psilopterinae and Mesembriornithinae, fusion of the ventral palatal flexion zones indicates a rigid, immobile palate. In larger taxa such as Patagornithinae and Phorusrhacinae, the pronounced thickening and fusion of the craniofacial flexion zone confirms the loss of prokinetic capabilities. The functional implications of such akinesis include simplification of food processing and a significant increase in bite force, which correlates with the predatory skills of the group. In a phylogenetic framework, phorusrhacids evolved from a kinetic ancestral condition, representing the only truly akinetic group among Neornithes. Full article

Background/Objectives: Cognitive impairment (CI) in Parkinson’s disease (PD) is a major burden and significantly affects patients’ quality of life. Previous studies found that older age at onset and presence of the akinetic–rigid (AR) subtype are associated with an increased likelihood of CI in PD. The present study aimed to assess factors that are related to the development of CI in PD. Methods: Eighty-three PD patients were consecutively recruited. Demographic information, clinical details, Montreal cognitive assessment (MoCA), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), walking speed, and instrumental activity of daily living (IADL) were assessed. Resting motor threshold (rMT), was also assessed for subgroup of patients with versus without cognitive impairment. Results: According to the MoCA cut-off score of 26, 45 had PD without CI (PD-NCI) (54.22%) and 38 cases (45.78%) had PD with CI (PD-CI). The age and age at onset were significantly older in the PD-CI group (p = 0.006 and 0.018, respectively). The patients were reclassified into AR and tremor-dominant (TR) phenotype. PD-CI patients were more likely to have the AR (81.6%). Walking speed, MDS-UPDRS score, and IADL scores were significantly worse in PD-CI than in PD-NCI. Stepwise linear regression analysis of risk factors associated CI revealed that higher MDS-UPDRS scores, later age of onset, and higher rMT values were considered risk factors for developing CI. Conclusions: Higher UPDRS score, later age of onset, and higher rMT values were considered as risk factors associated CI in PD patients and provide valuable insights for further investigation and potential clinical considerations. Full article

The freshwater cyanobacterium Raphidiopsis raciborskii is an invasive species that was originally described as tropical and is now widely distributed in temperate regions. The current taxonomic position was established based on a multilevel approach with the morphological description of natural populations as well as their ultrastructural, physiological and molecular characterization. The practical problem in identifying this species is that the morphology of the trichome in the natural environment can vary considerably during population growth. The aim of this study was to investigate the morphological variability of R. raciborskii during its blooming in a temperate floodplain lake on the Middle Danube (Europe). In both cases, only straight trichomes were found. Young trichomes with one or two acuminate ends and without heterocytes, referred to as primary filaments, can be exclusively monodominant at the beginning of bloom formation and remain dominant throughout the year, leading to taxonomic confusion. In mature populations, the different morphological forms of secondary filaments may differ in the size of the filaments and in the number and size of akinetes and heterocytes formed in the trichomes. The correct taxonomic identification and early detection of R. raciborskii in natural freshwaters is extremely important for the successful control of the spread of this potentially toxic species. Full article

Background and Objectives. Distinct pressure curve differences exist between akinetic (A-LVA) and dyskinetic (D-LVA) aneurysms. In D-LVA, left ventricular (LV) ejection pressure decreases relative to the aneurysm size, whereas A-LVA does not impact pressure curves, indicating that the decrease in stroke volume (SV) and cardiac output is proportional to the size of dyskinesia. This study aimed to assess the frequency of A-LVA and D-LVA, determine aneurysm size parameters (volume and surface area), and evaluate predictive parameters using echocardiography in A-LVA and D-LVA. Furthermore, it aimed to compare individual echocardiographic parameters, according to ejection fraction (EF) and SV, with hemodynamic events shown in experimental models of A-LVA and D-LVA and their significance in everyday clinical practice. Materials and Methods. This clinical study included patients with post-infarction left ventricular aneurysm (LVA) admitted to the cardiovascular institute ‘’Dedinje”, Serbia. Echocardiographic volume and surface area of LV and LVA were determined (by the area–length method) along with EF (by Simpson’s method). Results. A-LVA was present in 62.9% of patients, while D-LVA was present in 37.1%. Patients with D-LVA had significantly higher systolic aneurysm volume (LVAVs) (94.07 ± 74.66 vs. 51.54 ± 53.09, p = 0.009), systolic aneurysm surface area (LVAAs) (23.22 ± 11.73 vs. 16.41 ± 8.58, p = 0.018), and end-systolic left ventricular surface areas (LVESA) (50.79 ± 13.33 vs. 42.76 ± 14.11, p = 0.045) compared to patients with A-LVA. The ratio of LVA volume to LV volume was higher in the D-LVA in systole (LVAVs/LVESV). The end-diastolic volume of LV (LVEDV) and end-systolic volume of LV (LVESV) did not significantly differ between D-LVA and A-LVA. EF (21.25 ± 11.92 vs. 28.18 ± 11.91, p = 0.044) was significantly lower among patients with D-LVA. Conclusions. Differentiating between A-LVA and D-LVA using echocardiography is crucial since D-LVA causes greater hemodynamic disturbances in LV function, and thus surgical resection of the aneurysm or LV reconstruction must have a positive effect regardless of myocardial revascularization surgery. Full article

A 76-year-old male patient presented to the emergency room with acute decompensated right heart failure and presyncope episodes. Upon admission, his electrocardiogram (ECG) showed sustained monomorphic ventricular tachycardia at 180 bpm, which was electrically cardioverted, and the patient was subsequently admitted to the intensive care unit. The echocardiography showed a very dilated right ventricle (RV) with global systolic dysfunction and akinetic anterior and lateral walls. The coronary angiography was normal. The cardiac magnetic resonance showed signs of fibro-fatty replacement of the RV myocardium. Furthermore, the ECG after cardioversion showed inverted T waves and an epsilon wave in V1–V3 leads and late potentials by signal-averaged ECG. As such, a diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) was suspected. However, he presented no familial history of ARVC, was 76 years of age at the time of diagnosis and was asymptomatic until now. Given these considerations, we performed a right ventricular angiography which showed dilatation of the RV with akinetic/dyskinetic bulging, creating the “pile d’assiettes” image suggestive of ARVC. In the case of this patient, the RV angiography contributed to establish a diagnosis of ARVC with a very late presentation, to our knowledge the latest presentation in terms of age described in the literature. Full article

Most cyanobacteria that form harmful algal blooms (HABs) in inland waterbodies can overwinter in sediments. This field demonstration within an urban pond was conducted to bolster a database on the novel use of algaecide treatments to proactively target overwintering cyanobacteria located in sediments prior to HAB formation. In March 2023, a peroxide-based algaecide was applied to sediments of a water feature located in urban Kansas City, Kansas, and cyanobacteria responses were measured over subsequent weeks and months. Multiple lines of evidence were used to discern the impacts of proactive treatments on overwintering cells in sediments and HAB severity throughout the growing season. Although results of the measured cyanobacterial responses were mixed, three of five lines of evidence indicated proactive algaecide treatments were effective at decreasing the transfer of cyanobacteria to the water column and HAB severity during months when HABs tended to occur. Microcystin concentrations immediately post-treatment (hours) remained at the analytical detection limit (0.10 µg/L) and were below USEPA risk-based thresholds, highlighting the benefits of application prior to the exponential growth phase of toxin-producing cyanobacteria. These results expand the dataset and methodology for field-scale proactive algaecide applications targeting overwintering cyanobacterial cells in sediment to mitigate and delay HAB development. Full article

Eutrophic freshwater ecosystems are vulnerable to toxin-producing cyanobacteria growth or harmful algal blooms. Cyanobacteria belonging to the Nostocales order form akinetes that are similar to the seeds of vascular plants, which are resting cells surrounded by a thick membrane. They overwinter in sediment and germinate when conditions become favorable, eventually developing into vegetative cells and causing blooms. This review covers the cyanobacterial akinete of the Nostocales order and summarizes the environmental triggers and cellular responses involved in akinete germination and formation based on data from the literature. It also emphasizes the intimate and dynamic relationship that exists between the germination and formation of akinete in the annual life cycle of cyanobacteria. After comparing many published data, it is found that the tolerance ranges for factors affecting both akinete germination and formation do not differ significantly and are broadly consistent with the tolerance ranges for vegetative cell growth. However, the optimal range varies with different species and strains of cyanobacteria. The life cycle of cyanobacteria, as a result of akinete germination and formation, has a seasonal periodicity and spatial connectivity between the water column and the sediment. However, during the summer growing season, intimate coupling between akinete formation and germination can occur in the water column, and this can contribute to high population densities being maintained in the water column. During this time, shallow sediment could also provide suitable conditions for akinete germination, thereby contributing to the establishment of water column populations. The information summarized in this review is expected to help improve our shared understanding of the life cycle of the Nostocales cyanobacteria while also providing insights into the monitoring and management of harmful algal blooms. Full article

Background: Delayed Post-Hypoxic Leukoencephalopathy (DPHL), or Grinker’s myelinopathy, is a syndrome in which extensive changes are seen in the white matter of the cerebral hemispheres with MRI weeks or months after a hypoxic episode. T₂-weighted spin echo (T₂-wSE) and/or T₂-Fluid Attenuated Inversion Recovery (T₂-FLAIR) images classically show diffuse hyperintensities in white matter which are thought to be near pathognomonic of the condition. The clinical features include Parkinsonism and akinetic mutism. DPHL is generally regarded as a rare condition. Methods and Results: Two cases of DPHL imaged with MRI nine months and two years after probable hypoxic episodes are described. No abnormalities were seen on the T₂-FLAIR images with MRI, but very extensive changes were seen in the white matter of the cerebral and cerebellar hemisphere on divided Subtraction Inversion Recovery (dSIR) images. dSIR sequences may produce ten times the contrast of conventional inversion recovery (IR) sequences from small changes in T₁. The clinical findings in both cases were of cognitive impairment without Parkinsonism or akinetic mutism. Conclusion: The classic features of DPHL may only represent the severe end of a spectrum of diseases in white matter following global hypoxic injury to the brain. The condition may be much more common than is generally thought but may not be recognized using conventional clinical and MRI criteria for diagnosis. Reappraisal of the syndrome of DPHL to include clinically less severe cases and to encompass recent advances in MRI is advocated. Full article

L-DOPA is the mainstay of treatment for Parkinson’s disease (PD). However, over time this drug can produce dyskinesia. A useful acute PD model for screening novel compounds for anti-parkinsonian and L-DOPA-induced dyskinesia (LID) are dopamine-depleted dopamine-transporter KO (DDD) mice. Treatment with α-methyl-para-tyrosine rapidly depletes their brain stores of DA and renders them akinetic. During sensitization in the open field (OF), their locomotion declines as vertical activities increase and upon encountering a wall they stand on one leg or tail and engage in climbing behavior termed “three-paw dyskinesia”. We have hypothesized that L-DOPA induces a stereotypic activation of locomotion in DDD mice, where they are unable to alter the course of their locomotion, and upon encountering walls engage in “three-paw dyskinesia” as reflected in vertical counts or beam-breaks. The purpose of our studies was to identify a valid index of LID in DDD mice that met three criteria: (a) sensitization with repeated L-DOPA administration, (b) insensitivity to a change in the test context, and (c) stimulatory or inhibitory responses to dopamine D1 receptor agonists (5 mg/kg SKF81297; 5 and 10 mg/kg MLM55-38, a novel compound) and amantadine (45 mg/kg), respectively. Responses were compared between the OF and a circular maze (CM) that did not hinder locomotion. We found vertical counts and climbing were specific for testing in the OF, while oral stereotypies were sensitized to L-DOPA in both the OF and CM and responded to D1R agonists and amantadine. Hence, in DDD mice oral stereotypies should be used as an index of LID in screening compounds for PD. Full article

The pathophysiology of tremor in Parkinson’s disease (PD) is evolving towards a complex alteration to monoaminergic innervation, and increasing evidence suggests a key role of the locus coeruleus noradrenergic system (LC-NA). However, the difficulties in imaging LC-NA in patients challenge its direct investigation. To this end, we studied the development of tremor in a reserpinized rat model of PD, with or without a selective lesioning of LC-NA innervation with the neurotoxin DSP-4. Eight male rats (Sprague Dawley) received DSP-4 (50 mg/kg) two weeks prior to reserpine injection (10 mg/kg) (DR-group), while seven male animals received only reserpine treatment (R-group). Tremor, rigidity, hypokinesia, postural flexion and postural immobility were scored before and after 20, 40, 60, 80, 120 and 180 min of reserpine injection. Tremor was assessed visually and with accelerometers. The injection of DSP-4 induced a severe reduction in LC-NA terminal axons (DR-group: 0.024 ± 0.01 vs. R-group: 0.27 ± 0.04 axons/um², p < 0.001) and was associated with significantly less tremor, as compared to the R-group (peak tremor score, DR-group: 0.5 ± 0.8 vs. R-group: 1.6 ± 0.5; p < 0.01). Kinematic measurement confirmed the clinical data (tremor consistency (% of tremor during 180 s recording), DR-group: 37.9 ± 35.8 vs. R-group: 69.3 ± 29.6; p < 0.05). Akinetic–rigid symptoms did not differ between the DR- and R-groups. Our results provide preliminary causal evidence for a critical role of LC-NA innervation in the development of PD tremor and foster the development of targeted therapies for PD patients. Full article