The potential significance of hepcidin evaluation in progressive supranuclear palsy.

INTRODUCTION: Hepcidin is a peptide associated with controlling the distribution of iron in tissues. Growing interest is linked with its impact on neurodegenerative diseases, as disruption of the iron regulation may be considered an initiatory element of pathological protein accumulation. The possible impact of hepcidin was not previously sufficiently explored in progressive supranuclear palsy (PSP). METHODS: Twelve patients with PSP-Richardson's syndrome (PSP-RS), 12 with PSP-Parkinsonism Predominant (PSP-P), and 12 controls were examined using Unified Parkinson's Disease Rating Scale-III part (UPDRS-III) in OFF stage and analyzed in the context of hepcidin levels in the serum. RESULTS: The work revealed increased levels of hepcidin in PSP-RS when compared to PSP-P and controls. Moreover, hepcidin was found to be negatively correlated with UPDRS-III results in PSP-RS, whereas positively in PSP-P. CONCLUSION: The work may suggest a possible impact of hepcidin in PSP, possibly differing depending on its subtype.

The significance of glial cell line-derived neurotrophic factor analysis in Progressive Supranuclear Palsy.

Progressive Supranuclear Palsy (PSP) is an atypical parkinsonism. Major subtypes of the disease: PSP-Richardson's Syndrome (PSP-RS) and PSP Parkinsonism Predominant (PSP-P) vary in clinical features, the pathomechanism remains unexplored. The aim of this work is to analyze the relevance of glial cell line-derived neurotrophic factor (GDNF) evaluation in the serum and cerebrospinal fluid (CSF) in PSP subtypes and to verify its significance as a possible factor in the in vivo examination. Authors assessed the concentration of GDNF in the serum and CSF of 12 patients with PSP-RS, 12 with PSP-P and 12 controls. Additionally authors evaluated patients using Unified Parkinson's Disease Rating Scale-III part (UPDRS-III), Frontal Assessment Battery (FAB) and Magnetic Resonance Imaging (MRI). The evaluation revealed significantly increased concentrations of GDNF in the CSF among PSP-RS patients and substantially increased concentrations of GDNF in the serum in PSP-P. Though the GDNF concentrations differentiated PSP subtypes, no correlations between with clinical factors were observed however certain correlations with atrophic changes in MRI were detected. GDNF is a factor which may impact the pathogenesis of PSP. Possible implementation of GDNF as a therapeutic factor could be a perspective in the search for therapy in this currently incurable disease.

Glucose Metabolism and Cognitive Decline in Progressive Supranuclear Palsy and Corticobasal Syndrome: A Preliminary Study.

Multiple studies have analyzed the possible correlations between diabetes and Alzheimer's disease. Less is known about the context of cognitive deterioration among patients with atypical Parkinsonian syndromes and glucose metabolism impairment. The aim of this study was to evaluate the association between the impaired glucose metabolism and cognitive decline among patients with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The study included 22 patients with PSP and CBS with disease durations varying from 3 to 6 years. The levels of glycated hemoglobin (HbA1C), fasting blood glucose, fasting C-peptide and the presence of microalbuminuria were evaluated, and oral glucose tolerance tests (OGTT) were performed. Based on the OGTT results, the glycemic variability, mean glycemia, glycemia standard deviation (SD) and coefficient of variation (%CV) were calculated. All patients underwent a three-Tesla brain magnetic resonance (MRI) examination and neuropsychological cognitive assessment with the use of standardized scales: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). A statistical analysis revealed that poor control of glycemia with high glycemic variability and increased atrophy of the medial temporal lobe among patients with PSP and CBS correlated with worse cognitive performance independent of age or sex, even among patients who did not fulfill the criteria for diabetes. The study results indicate the importance of glucose metabolism control and optimal treatment in the context of cognition maintenance among patients with PSP and CBS. Due to the relatively small number of analyzed patients, the issue requires further assessment. To the best of our knowledge, this is the first study discussing the role of glycemic variability in atypical Parkinsonian syndromes.

Clinical Phenotypes of Progressive Supranuclear Palsy-The Differences in Interleukin Patterns.

Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome based on tau pathology; its clinical phenotype differs, but PSP with Richardson's syndrome (PSP-RS) and the PSP parkinsonism predominant (PSP-P) variant remain the two most common manifestations. Neuroinflammation is involved in the course of the disease and may cause neurodegeneration. However, an up-to-date cytokine profile has not been assessed in different PSP phenotypes. This study aimed to evaluate possible differences in neuroinflammatory patterns between the two most common PSP phenotypes. Serum and cerebrospinal fluid (CSF) concentrations of interleukin-1 beta (IL-1ß) and IL-6 were analyzed using enzyme-linked immunosorbent assay (ELISA) kits in 36 study participants-12 healthy controls and 24 patients with a clinical diagnosis of PSP-12 PSP-RS and 12 PSP-P. Disease duration among PSP patients ranged from three to six years. All participants underwent basic biochemical testing, and neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values were calculated. Due to a lack of neuropathological examinations, as all patients remain alive, total tau levels were assessed in the CSF. Tau levels were significantly higher in the PSP-P and PSP-RS groups compared to the healthy controls. The lowest concentrations of serum and CSF interleukins were observed in PSP-RS patients, whereas PSP-P patients and healthy controls had significantly higher interleukin concentrations. Furthermore, there was a significant correlation between serum IL-6 levels and PLR in PSP-RS patients. The results indicate the existence of distinct neuroinflammatory patterns or a neuroprotective role of increased inflammatory activity, which could cause the differences between PSPS phenotypes and clinical course. The causality of the correlations described requires further studies to be confirmed.

The Role of the Evans Index and the Maximal Width of the Frontal Horns of the Lateral Ventricles in the Diagnostic Imaging of Progressive Supranuclear Palsy and Multiple-System Atrophy.

Progressive Supranuclear Palsy and Multiple-System Atrophy are entities within the spectrum of atypical parkinsonism. The role of imaging methods in the diagnosis and differentiation between PSP and MSA is limited and Magnetic Resonance Imaging (MRI) is currently used as a reference modality. In this study, the authors examined a group of patients with atypical parkinsonism using a 1.5 T MRI system and aimed to find simple and repeatable measurements that may be useful to distinguish between these diseases. The results of the study indicate that the maximal width of the frontal horns of the lateral ventricles and Evans' Index may, to some extent, be useful as basic and simple measurements in the diagnostic imaging of patients with atypical parkinsonism.

Inflammation in multiple system atrophy.

Misfolding protein aggregation inside or outside cells is the major pathological hallmark of several neurodegenerative diseases. Among proteinopathies are neurodegenerative diseases with atypical Parkinsonism and an accumulation of insoluble fibrillary alpha-synuclein (synucleinopathies) or hyperphosphorylated tau protein fragments (tauopathies). As there are no therapies available to slow or halt the progression of these disea ses, targeting the inflammatory process is a promising approach. The inflammatory biomarkers could also help in the differential diagnosis of Parkinsonian syndromes. Here, we review inflammation's role in multiple systems atrophy pathogenesis, diagnosis, and treatment.

Role of orexin in pathogenesis of neurodegenerative parkinsonisms.

INTRODUCTION: The pathogenesis of parkinsonisms is not fully understood. Among possible factors which may influence the course of neurodegenerative diseases, endocrine abnormalities may be interpreted as having been underevaluated. STATE OF THE ART: Growing interest is associated with the role of neuropeptides such as orexin. Orexin is a neuropeptide produced by orexigenic neurons in the lateral parts of the hypothalamus and is linked with excitement, wakefulness and appetite. An extended analysis of this neuropeptide might answer whether changes in the metabolism of orexin is more likely to be a cause or a consequence of neurodegeneration. CLINICAL SIGNIFICANCE: Orexin is a neuropeptide produced by orexigenic neurons in the lateral parts of the hypothalamus and is linked with excitement, wakefulness and appetite. The aim of this study was to discuss the role of this factor and its abnormalities in the pathogenesis and course of parkinsonian syndrome. FUTURE DIRECTIONS: Understanding the role of orexin in these diseases may be interpreted as an important feature in evolving therapeutical methods. Further evaluation based on larger groups of patients is required.

Sleep disturbances in progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS).

INTRODUCTION: Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are clinical manifestations of tauopathies. They are commonly associated with rapid motor and cognitive deterioration. Sleep disturbances are less frequently described as a feature of these diseases, though they are reported among 50-75% of PSP patients. STATE OF THE ART: Apart from various clinical manifestations, sleep abnormalities in PSP and CBS seem to be a factor enhancing pathogenesis as well its consequences. Multiple researchers have looked into the issue of whether the complexity of sleep disturbances in PSP and CBS could be linked to atrophic changes within structures crucial for daytime regulation, coexisting pathologies, or other less explored mechanisms. CLINICAL SIGNIFICANCE: Among sleep abnormalities in PSP and CBS have been reported excessive daytime sleepiness, night-time insomnia, reduction of total sleep time, more pronounced sleep fragmentation, restless leg syndrome (RLS), agrypnia excitata, periodic limb movements, sleep respiratory disturbances, rapid-eye movement behaviour disorder, and others. FUTURE DIRECTIONS: The aim of this review was to elaborate upon the significance of sleep abnormalities in tauopathic parkinsonian syndromes, and to determine their usefulness in differential diagnosis with synucleinopathic parkinsonian syndromes. Extended analyses of sleep disturbances may provide a different perspective on atypical parkinsonisms.

Could hyperlipidemia be a risk factor for corticobasal syndrome? - a pilot study.

INTRODUCTION: Corticobasal syndrome (CBS) is a specific clinical manifestation shared by multiple pathologies. The exact mechanism of this phenomenon remains unclear. Differential diagnosis of CBS in everyday clinical practice is challenging, as this syndrome can overlap with other entities, especially progressive supranuclear palsy Richardson-Steele phenotype (PSP-RS). Several papers have suggested a possible role of vascular pathology as a linking factor in the pathogenesis of CBS based on different neuropathologies. This paper analyses differences in the occurrence of the most common vascular risk factors such as hypertension and lipid profile with respect to dietary habits among patients who fulfill the diagnostic criteria for probable/possible CBS and PSP-RS. MATERIAL AND METHODS: Seventy (70) patients in total were included in the study. Exclusion criteria comprised hydrocephalus, stroke in the past, the presence of marked vascular changes in white matter defined as the presence of vascular change ≥ 1 mm in 3T MRI, medical history of hyperlipidemia or the use of drugs that could impact upon lipid metabolism before the initiation of the neurodegenerative disease, and neoplastic focuses in the central nervous system. Patients with diabetes, or with BMI exceeding 18-25, or who were smokers, or who were affected by chronic stress were also excluded. Data was analysed statistically using the Shapiro-Wilk test, the U Mann-Whitney test for group comparison, and a Bonferroni correction to control the false discovery rate (FDR). RESULTS: Our obtained results indicated a statistically significantly higher level of total cholesterol in the CBS group (p = 0.0039) without a correlation with dietary habits. CONCLUSIONS AND CLINICAL IMPLICATIONS: The results obtained in our study may suggest a possible role of vascular pathology in CBS development. This issue requires further research.

The Use of Cerebellar Hypoperfusion Assessment in the Differential Diagnosis of Multiple System Atrophy with Parkinsonism and Progressive Supranuclear Palsy-Parkinsonism Predominant.

The differential diagnosis of MSA-P and PSP-P remains a difficult issue in clinical practice due to their overlapping clinical manifestation and the lack of tools enabling a definite diagnosis ante-mortem. This paper describes the usefulness of SPECT HMPAO in MSA-P and PSP-P differentiation through the analysis of cerebellar perfusion of small ROIs. Thirty-one patients were included in the study­20 with MSA-P and 11 with PSP-P; the analysis performed indicated that the most significant difference in perfusion was observed in the anterior quadrangular lobule (H IV and V) on the left side (p < 0.0026). High differences in the median perfusion between the groups were also observed in a few other regions, with p < 0.05, but higher than premised p = 0.0026 (the Bonferroni correction was used in the statistical analysis). The assessment of the perfusion may be interpreted as a promising method of additional examination of atypical parkinsonisms with overlapping clinical manifestation, as in the case of PSP-P and MSA-P. The results obtained suggest that the interpretation of the differences in perfusion of the cerebellum should be made by evaluating the subregions of the cerebellum rather than the hemispheres. Further research is required.

The Assessment of Subregions in the Frontal Lobe May Be Feasible in the Differential Diagnosis of Progressive Supranuclear Palsy-Parkinsonism Predominant (PSP-P) and Multiple System Atrophy (MSA).

Progressive Supranuclear Palsy-Parkinsonism Predominant (PSP-P) is associated with moderate responsiveness to levodopa treatment and a possible lack of typical PSP milestones. The clinical manifestation of PSP-P poses difficulties in neurological examination. In the early stages it is often misdiagnosed as Parkinson's Disease, and in the more advanced stages PSP-P shows more symptoms in common with Multiple System Atrophy-Parkinsonian type (MSA-P). The small number of tools enabling differential diagnosis of PSP-P and MSA leads to the necessity of searching for parameters facilitating in vivo diagnosis. In this study, 14 patients with PSP-P and 21 patients with MSA-P were evaluated using Single Photon Emission Computed Tomography. Considering the fact that PSP is linked with frontal deficits, regions of the frontal lobe were assessed in the context of hypoperfusion and their possible usefulness in the differential diagnosis with MSA-P. The outcome of the work revealed that the right middle frontal gyrus was the region most significantly affected in PSP-P.

The Significance of Asymmetry in the Assessment of Brain Perfusion in Atypical Tauopathic Parkinsonian Syndromes.

Progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS) are clinical manifestations of tauopathic Parkinsonian syndromes. Due to their overlapping symptomatology, the differential diagnosis of these entities may be difficult when bounded to clinical assessment. The manifestations are commonly associated with pathological entities-corticobasal degeneration and progressive supranuclear palsy, which are four-repeat tauopathies. In this study, the authors attempted to find whether the asymmetry typically associated with CBS may be feasible in the interpretation of perfusion single-photon computed tomography. The analysis based on the examination of patients with progressive supranuclear palsy-Richardson syndrome (PSP-RS), progressive supranuclear palsy-Parkinsonism predominant (PSP-P), and corticobasal syndrome (CBS) revealed significant asymmetry of perfusion of the amygdala in corticobasal syndrome. The more pronounced abnormalities of perfusion were observed in the left amygdala among patients with more severe Parkinsonian syndromes in CBS on the right. This study shows that the comparison of the perfusion of tauopathic Parkinsonian syndromes should be extended by asymmetry analysis. Interestingly, the differentiating potential of brain perfusion is present in the comparison of CBS and PSP-RS, but not in CBS and PSP-P. This phenomenon could be explained by more distinct asymmetry in the perfusion observed in PSP-P, which diminishes the differentiating potential of this parameter when it comes to the comparison of PSP-P and CBS. To the best of our knowledge, this is the first study evaluating which structures can be interpreted as significantly asymmetrical in the context of perfusion in CBS.

Is MRPI 2.0 More Useful than MRPI and M/P Ratio in Differential Diagnosis of PSP-P with Other Atypical Parkinsonisms?

Differential diagnosis of progressive supranuclear palsy remains difficult, especially when it comes to the parkinsonism predominant type (PSP-P), which has a more favorable clinical course. In this entity, especially during the advanced stages, significant clinical overlaps with other tauopathic parkinsonian syndromes and multiple system atrophy (MSA) can be observed. Among the available additional diagnostic methods in every-day use, magnetic resonance imaging (MRI) focused specifically on the evaluation of the mesencephalon seems to be crucial as it is described as a parameter associated with PSP. There is growing interest in relation to more advanced mesencephalic parameters, such as the magnetic resonance parkinsonism index (MRPI) and MRPI 2.0. Based on the evaluation of 74 patients, we demonstrate that only the mesencephalon/pons ratio and MRPI show a significant difference between PSP-P and MSA-parkinsonian type (MSA-P). Interestingly, this differential feature was not maintained by MRPI 2.0. The mesencephalon to pons ratio (M/P), MRPI and MRPI 2.0 were not found to be feasible for the differentiation of PSP-P from other atypical tauopathic syndromes.

Anti-IgLON5 Disease - The Current State of Knowledge and Further Perspectives.

Anti-IgLON5 disease is a relatively new neurological entity with the first cases reported in 2014. So far, less than 70 articles on this topic have been published. Due to its unspecific symptomatology, diverse progression, novelty and ambiguous character, it remains a difficulty for both clinical practitioners and scientists. The aim of this review is to summarize the current knowledge concerning anti-IgLON5 disease; mechanisms underlying its cause, symptomatology, clinical progression, differential diagnosis and treatment, which could be helpful in clinical practice and future research.

The Strengths and Obstacles in the Differential Diagnosis of Progressive Supranuclear Palsy-Parkinsonism Predominant (PSP-P) and Multiple System Atrophy (MSA) Using Magnetic Resonance Imaging (MRI) and Perfusion Single Photon Emission Computed Tomography (SPECT).

Multiple System Atrophy-Parkinsonism Predominant (MSA-P) and Progressive Supranuclear Palsy-Parkinsonism Predominant (PSP-P) are the clinical manifestations of atypical parkinsonism. Currently, there are no efficient in vivo methods available relating to neuroimaging or biochemical analysis in the examination of these entities. Among the advanced methods available, using positron emission tomography is constrained by high cost and low accessibility. In this study the authors examined patients with two types of atypical parkinsonism-MSA-P and PSP-P, which are difficult to differentiate, especially in the early years of their development. The aim of this study was to assess whether the examination of patients in the period following the early years (3-6-year duration of symptoms) could be enhanced by perfusion single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI) or evaluation of cognitive abilities. Extended examination using MRI and perfusion SPECT showed that the evaluation of the mesencephalon/pons ratio, mesencephalic volume decrease, the Magnetic Resonance Parkinsonism Index (MRPI) and frontal perfusion should be considered more feasible than screening cognitive evaluation in MSA-P and PSP-P with a 3-6-year duration of symptoms.

Differential Diagnosis of Rare Subtypes of Progressive Supranuclear Palsy and PSP-Like Syndromes-Infrequent Manifestations of the Most Common Form of Atypical Parkinsonism.

Presently, there is increasing interest in rare PSP (progressive supranuclear palsy) variants, including PSP-PGF (PSP-progressive gait freezing), PSP-PI (PSP-postural instability), PSP-OM (PSP-ocular motor dysfunction), PSP-C (PSP-predominant cerebellar ataxia), PSP-CBS (PSP-corticobasal syndrome), PSP-SL (PSP-speech/language disorders), and PSP-PLS (PSP-primary lateral sclerosis). Diagnosis of these subtypes is usually based on clinical symptoms, thus thorough examination with anamnesis remains a major challenge for clinicians. The individual phenotypes often show great similarity to various neurodegenerative diseases and other genetic, autoimmune, or infectious disorders, manifesting as PSP-mimicking syndromes. At the current stage of knowledge, it is not possible to isolate a specific marker to make a definite ante-mortem diagnosis. The purpose of this review is to discuss recent developments in rare PSP phenotypes and PSP-like syndromes.

Platelet-to-lymphocyte ratio and neutrophil-tolymphocyte ratio may reflect differences in PD and MSA-P neuroinflammation patterns.

AIM OF THE STUDY: To assess the usefulness of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in evaluating the inflammatory process in alpha-synucleinopathies. CLINICAL RATIONALE FOR THE STUDY: The role of neuroinflammation in PD and MSA pathogenesis is indisputable. However, there is no method available in everyday use that would enable its evaluation. We suggest that NLR and PLR, as non-specific parameters of inflammation, due to its approachability could be helpful in the assessment of inflammatory activity in alpha-synucleinopathies in everyday clinical practice. MATERIAL AND METHODS: 98 patients with a clinical diagnosis of PD, 28 with MSA-P, and 99 healthy age-matched controls, were included in the study. Blood samples were analysed in order to count neutrophil and lymphocyte rates and, subsequently, NLR and PLR. The obtained parameters were compared between the groups. Results were statistically analysed. RESULTS: Our results indicate that patients with PD have higher values of NLR and PLR compared to controls. For MSA-P, only NLR was significantly higher in relation to the control group. There were no statistically significant differences between patients with PD and MSA-P in relation to NLR and PLR values. There was a positive average correlation between NLR and disease duration for MSA-P patients. CONCLUSIONS: NLR and PLR values are significantly higher in alpha-synucleinopathies (MSA-P and PD) in relation to a control group. In PD patients, both NLR and PLR values are significantly higher in relation to a control group, whereas in patients with MSA-P, only NLR is significantly increased. The observed differences may reflect distinct neuroinflammatory patterns present in these entities. CLINICAL IMPLICATIONS: NLR and PLR are features of peripheral inflammation. Their specificity is relatively low, although increased values suggest possible inflammatory pathogenesis of clinical entities. NLR is based on the observations that in chronic and acute diseases the neutrophil rate has a tendency to rise, while the lymphocyte rate tends to decline. This aspect of inflammatory processes has been primarily evaluated in Intensive Care Units. PLR is a marker presenting changes in platelet and lymphocyte counts caused by acute inflammatory or prothrombotic states. Different values of NLR and PLR in PD and MSA-P compared to healthy controls suggest that in these two alpha-synucleinopathies, different patterns of neuroinflammation might be present. The role of inflammation in the differential diagnosis of parkinsonian syndromes remains unexplored.

The Role of Stem Cells in the Therapy of Stroke.

BACKGROUND: Stroke is a major challenge in neurology due to its multifactorial genesis and irreversible consequences. Processes of endogenous post-stroke neurogenesis, although insufficient, may indicate possible direction of future therapy. Multiple research considers stem-cell-based approaches in order to maximize neuroregeneration and minimize post-stroke deficits. OBJECTIVE: Aim of this study is to review current literature considering post-stroke stem-cell- based therapy and possibilities of inducing neuroregeneration after brain vascular damage. METHODS: Papers included in this article were obtained from PubMed and MEDLINE databases. The following medical subject headings (MeSH) were used: "stem cell therapy", "post-stroke neurogenesis", "stem-cells stroke", "stroke neurogenesis", "stroke stem cells", "stroke", "cell therapy", "neuroregeneration", "neurogenesis", "stem-cell human", "cell therapy in human". Ultimate inclusion was made after manual review of the obtained reference list. RESULTS: Attempts of stimulating neuroregeneration after stroke found in current literature include supporting endogenous neurogenesis, different routes of exogenous stem cells supplying and extracellular vesicles used as a method of particle transport. CONCLUSION: Although further research in this field is required, post stroke brain recovery supported by exogenous stem cells seems to be promising future therapy revolutionizing modern neurology.

The Rate of Decrease in Brain Perfusion in Progressive Supranuclear Palsy and Corticobasal Syndrome May Be Impacted by Glycemic Variability-A Pilot Study.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are tauopathic parkinsonian syndromes, presently lacking disease-modifying treatments. Patients affected by these diseases suffer due to multidimensional deteriorations resulting in motor and cognitive impairment. Previously published research has confirmed risk factors that may impact the course of PSP and CBS, among them hypertension and diabetes. Less data is available regarding prediabetes and glycemic variability. In this study, 26 patients with clinical diagnoses of PSP and CBS were examined using glycated hemoglobin and perfusion single-photon emission tomography (SPECT). Patients were divided into two groups-PSP/CBS patients with glycated hemoglobin (HbA1c) below and above 5.7%. The results of the perfusion evaluation were compared with the values from healthy volunteers from the software's database. A decrease in perfusion in certain regions of interest was observed among patients affected by increased glycemic variability. A more pronounced decrement in perfusion was observed only in some regions of interest-the hippocampus, pons, left thalamus, right insula. The results indicated that, among PSP/CBS patients, individuals with more pronounced glycemic variability had more severe hypoperfusion in certain brain regions in comparison with PSP/CBS patients without carbohydrate metabolism disorders. Due to the fact that PSP and CBS are associated with cognitive impairment, an additional decrease in perfusion in the hippocampal area may impact the rate of cognitive deterioration.