Impact of Physical Exercise on Levodopa Therapy Across Parkinson's Disease Stages.

Background: Levodopa is the gold standard of treatment in Parkinson's disease (PD). Its clinical effect changes as the disease progresses. Wearing off is a frequent first manifestation of motor fluctuations. Some patients with advanced PD report faster wearing off after physical exercise. Objective: The aim was to assess if pharmacokinetics of levodopa is influenced by physical exercise in patients with different disease advancement. Methods: 22 patients with PD (12 untreated with levodopa and 10 with motor fluctuations) and 7 healthy controls (HC) were included. Plasma samples were collected at 9 fixed timepoints following administration of levodopa/benserazide 200/50 mg for two days: rest day and standardized physical exercise day. Clinical assessment with Unified Parkinson Disease Rating Scale part III (UPDRS III) was performed in fixed timepoints. Liquid chromatography-tandem mass spectrometry was used to measure levodopa concentrations. Results: No differences between the HC, levodopa naïve and advanced PD groups were observed regarding selected pharmacokinetic parameters. In advanced PD and HC no differences in pharmacokinetic parameters of levodopa with and without effort were observed. In levodopa naïve PD group higher mean residence time after rest than after exercise (168.9±48.3 min vs. 145.5±50.8 min; p = 0.026) was observed. In advanced PD group higher UPDRS III score (14.45±5.5 versus 20.9±6.1 points, p = 0.04) was observed after exercise. Conclusions: The deterioration of motor status of advanced PD patients after physical effort is not reflected by changes in pharmacokinetics but rather mediated by central mechanisms.

Unilateral gamma knife thalamotomy for tremor safety and efficacy in multimodal assessment: a prospective case-control study with two-year follow-up.

INTRODUCTION: Unilateral gamma knife thalamotomy (GKT) is a treatment option for pharmacoresistant tremor of various aetiologies. There have been to date no randomised controlled trials performed to assess its safety and efficacy. Our aim was to summarise a two-year multimodal observation of patients with tremor caused by Parkinson's Disease (PD) or essential tremor (ET). MATERIAL AND METHODS: 23 patients with PD (n = 12) or ET (n = 11) were included. They underwent assessments before, V0 (n = 23), and 12 months, V12 (n = 23), and 24 months, V24 (n = 15), after unilateral GKT. Patients were assessed with psychological tests and acoustic voice analysis. Tremor assessment was performed with a digitising table using the Fahn-Tolosa-Marin rating scale (FTMRS). The Unified Parkinson's Disease rating scale part III (UPDRS-III) was also used in the PD group. Gait and balance was assessed using clinical tests, stabilometric platform, and treadmill. RESULTS: No side effects were observed in a two-year follow-up. There was no notable deterioration observed in the patients' psychological evaluation, speech, or assessment of gait and balance. The scores were significantly lower (p = 0.01) in parts A and B of FTMRS one year after GKT. In post hoc analysis, the scores did not differ significantly between V0 and V24. In FTMRS part C (activities of daily living), no significant change was observed. There was no significant difference in total UPDRS part III score or in score of UPDRS part III domains 3 and 4 ('tremor at rest' and 'action and postural tremor of hands') between measurements. CONCLUSIONS: UGKT may be a safe treatment modality if performed in an experienced centre. Tremor reduction may diminish over time, and UGKT did not lead to cognitive, gait or speech deterioration in a long-term observation.

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.

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.

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.

Microbiota Dysbiosis in Parkinson Disease-In Search of a Biomarker.

Numerous studies have highlighted the role of the gastrointestinal system in Parkinson disease pathogenesis. It is likely triggered by proinflammatory markers produced by specific gut bacteria. This review's aim is to identify gut bacterial biomarkers of Parkinson disease. A comprehensive search for original research papers on gut microbiota composition in Parkinson disease was conducted using the PubMed, Embase, and Scopus databases. Research papers on intestinal permeability, nasal and oral microbiomes, and interventional studies were excluded. The yielded results were categorized into four groups: Parkinson disease vs. healthy controls; disease severity; non-motor symptoms; and clinical phenotypes. This review was conducted in accordance with the PRISMA 2020 statement. A total of 51 studies met the eligibility criteria. In the Parkinson disease vs. healthy controls group, 22 bacteria were deemed potentially important. In the disease severity category, two bacteria were distinguished. In the non-motor symptoms and clinical phenotypes categories, no distinct pathogen was identified. The studies in this review report bacteria of varying taxonomic levels, which prevents the authors from reaching a clear conclusion. Future research should follow a unified methodology in order to identify potential biomarkers for Parkinson disease.

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.

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.

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.

Neuroimaging in Parkinson's Disease: necessity or exaggeration?

INTRODUCTION: Neuroimaging plays an increasingly important role in the diagnosis of parkinsonian syndromes. AIM OF THE STUDY: In this paper, the authors elaborate on the necessity of using magnetic resonance imaging (MRI) in Parkinson's Disease (PD) and its potential role in differential diagnosis versus other neurodegenerative parkinsonian syndromes such as dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy and corticobasal syndrome. STATE OF THE ART: The currently known characteristic abnormalities are listed and tabulated, current recommendations are summarised and sample images are provided. As routine MRI scanning in PD remains controversial, the authors' aim is to show the pros and cons in clinical practice. Additionally, the rationale for functional imaging examination, including [123I]-FP-CIT SPECT (DaTSCAN) and [99mTc]- HMPAO-SPECT, [18F]-FDG-PET, [123I]-mIBG-SPECT is discussed. CLINICAL VIGNETTE: This paper is accompanied by two illustrative clinical cases in which neuroimaging studies played a key role in diagnosis and further management. CONCLUSIONS: Neuroimaging can be helpful in differentiating PD from both atypical and symptomatic parkinsonism. Nevertheless, extensive neurological assessment in a majority of PD cases is sufficient to make a diagnosis. A network of specialists in movement disorders should be established in order to enable better, faster and more precise diagnosis of parkinsonism.

Proteomic Profile of Saliva in Parkinson's Disease Patients: A Proof of Concept Study.

Parkinson's disease (PD) is a progressive neurodegenerative disorder. It affects many organs. Lewy bodies-a histopathological "hallmark" of PD-are detected in about 75% of PD submandibular gland samples. We hypothesize that saliva can be a source of biomarkers of PD. The aim of the study was to evaluate and compare the salivary proteome of PD patients and healthy controls (HC). Salivary samples from 39 subjects (24 PD patients, mean age 61.6 ± 8.2; 15 HC, mean age 60.9 ± 6.7) were collected. Saliva was collected using RNA-Pro-Sal kits. Label-free LC-MS/MS mass spectrometry was performed to characterize the proteome of the saliva. IPA analysis of upstream inhibitors was performed. A total of 530 proteins and peptides were identified. We observed lower concentrations of S100-A16, ARP2/3, and VPS4B in PD group when compared to HC. We conclude that the salivary proteome composition of PD patients is different than that of healthy controls. We observed a lower concentration of proteins involved in inflammatory processes, exosome formation, and adipose tissue formation. The variability of expression of proteins between the two groups needs to be considered.

Mechanisms of Neurodegeneration in Various Forms of Parkinsonism-Similarities and Differences.

Parkinson's disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world's aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene (MAPT) and the α-synuclein gene (SNCA). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.

Frequency of mutations in PRKN, PINK1, and DJ1 in Patients With Early-Onset Parkinson Disease from neighboring countries in Central Europe.

INTRODUCTION: Approximately 10% of patients with Parkinson disease (PD) present with early-onset disease (EOPD), defined as diagnosis before 50 years of age. Genetic factors are known to contribute to EOPD, with most commonly observed mutations in PRKN, PINK1, and DJ1 genes. The aim of our study was to analyze the frequency of PRKN, PINK1, and DJ1 mutations in an EOPD series from 4 neighboring European countries: Czech Republic, Germany, Poland, and Ukraine. METHODS: Diagnosis of PD was made based on UK Brain Bank diagnostic criteria in departments experienced in movement disorders (1 from Czech Republic, 1 from Germany, 9 from Poland, and 3 from Ukraine). EOPD was defined as onset at or before 50 years of age. Of the 541 patients recruited to the study, 11 were Czech, 38 German, 476 Polish, and 16 Ukrainian. All cohorts were fully screened with Sanger sequencing for PRKN, PINK1, and DJ1 and multiplex ligation-dependent probe amplification for exon dosage. RESULTS: PRKN homozygous or double heterozygous mutations were identified in 17 patients: 1 Czech (9.1%), 1 German (2.6%), 14 Polish (2.9%), and 1 Ukrainian (6.3%). PINK1 homozygous mutations were only identified in 3 Polish patients (0.6%). There were no homozygous or compound heterozygous DJ1 mutations in analyzed subpopulations. One novel variant in PRKN was identified in the Ukrainian series. CONCLUSION: In the analyzed cohorts, mutations in the genes PRKN, PINK1, and DJ1 are not frequently observed.

Genetics of Parkinson's disease in the Polish population.

INTRODUCTION: Genetic forms of Parkinson's disease (PD) often cluster in different ethnic groups and may present with recognisable unique clinical manifestations. Our aim was to summarise the current state of knowledge regarding the genetic causes of PD and describe the first Polish patient with SNCA duplication. METHODOLOGY: We searched the electronic database, PubMed, for studies between January 1995 and June 2020 that evaluated genetics in Polish patients with PD, using the search terms 'Parkinson's disease, 'Polish', 'genetics', 'mutations', and 'variants'. RESULTS: In total, 73 publications were included in the review; 11 genes responsible for monogenic forms and 19 risk factor genes have been analysed in the Polish population. Pathogenic variants were reported in four monogenic genes (LRRK2, PRKN, PINK1, and SNCA). Eight genes were associated with PD risk in the Polish population (GBA, TFAM, NFE2L2, MMP12, HLA-DRA, COMT, MAOB, and DBH). Multiplex ligation-dependent probe amplification and Sanger sequencing in PRKN, PINK1, DJ1, LRRK2, and SNCA revealed SNCA duplication in a 43-year-old Polish patient with PD examined by movement disorder specialists. CONCLUSION: Only a limited number of positive results have been reported in genes previously associated with PD in the Polish population. In the era of personalised medicine, it is important to report on genetic findings in specific populations.

The Role of Frontal Assessment Battery and Frontal Lobe Single-Photon Emission Computed Tomography in the Differential Diagnosis of Progressive Supranuclear Palsy Variants and Corticobasal Syndrome-A Pilot Study.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are clinical syndromes classified as atypical parkinsonism. Due to their overlapping symptomatology, recent research shows the necessity of finding new methods of examination of these clinical entities. PSP is a heterogenic disease. PSP Richardson-Steele Syndrome (PSP-RS) and parkinsonism predominant (PSP-P) are the most common clinical variants of progressive supranuclear palsy syndrome. The different clinical course and life expectancy of PSP-RS and PSP-P stress the need of efficient examination in the early stages. The aim of the study was to evaluate the possible feasibility of the combined use of frontal assessment battery (FAB) and single-photon emission computed tomography (SPECT) in the differentiation of PSP-RS, PSP-P, and CBS. The findings show that FAB may be interpreted as a possible supplementary tool in the differential diagnosis of PSP-P and PSP-RS. The differences in SPECT are less pronounced. The study does not show any advantages of performing combined frontal SPECT and FAB in the differential examination of PSP and CBS. Moreover, PSP-RS and CBS, in a detailed evaluation of the frontal lobe, do not show any significant differences. This is a relatively small study which, however, highlights the relevant features of clinical examination of these rare entities.

Neutrophil-to-lymphocyte ratio (NLR) at boundaries of Progressive Supranuclear Palsy Syndrome (PSPS) and Corticobasal Syndrome (CBS).

AIM OF THE STUDY: To examine possible features of neuroinflammation in progressive supranuclear palsy - Richardson syndrome and corticobasal syndrome (CBS). CLINICAL RATIONALE FOR THE STUDY: Neutrophil-to-lymphocyte ratio (NLR) is a parameter reflecting inflammation used in numerous branches of medicine. The search for pathogenesis of the diseases partly related to inflammatory processes confirms the need to obtain possible factors which could be relatively easily verified. NLR is a benchmark routinely evaluated in most hospitalised patients. MATERIALS AND METHODS: 23 patients with a clinical diagnosis of PSP-RS, 18 patients with CBS, and 32 healthy controls, were included in the study. Blood samples were assessed in the context of neutrophil and lymphocyte rates. Subsequently, the results were transformed into neutrophil-to-lymphocyte ratio (NLR). The NLRs from each group were statistically assessed using a Kruskal-Wallis test and post-hoc analysis. RESULTS: Statistical analysis confirmed significant differences in NLR between PSP-RS and control group. No other significant differences were observed. CLINICAL IMPLICATIONS: The possible use of NLR in the additional examination of atypical parkinsonisms. CONCLUSIONS: To the best of our knowledge, this is the first study comparing this aspect of neuroinflammation in PSP and CBS. It presents NLR as a promising non-specific parameter in neurodegenerative diseases.

Influence of Bilateral Subthalamic Nucleus Deep Brain Stimulation on the Lipid Profile in Patients With Parkinson's Disease.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is a valuable alternative to pharmacotherapy alone in an advanced Parkinson's disease (PD). Given the growing number of patients with STN-DBS, its impact on the comorbidities should be considered. Aim: The aim of this study was to evaluate the influence of bilateral STN-DBS on the lipid profile in patients with PD. Methods: Three groups of parkinsonian patients were included: 20 treated pharmacologically-PHT group, 20 newly qualified for STN-DBS-DBS group, and 14 postoperative patients (median 30 months after surgery)-POP group. Plasma concentrations of the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and body weight were measured thrice in 9 ± 2 month intervals. Results: A significant increase in the LDL-C concentration is observed early after surgery in the DBS group (11.4 mg/dl, P < 0.01) followed by adverse changes in the HDL-C (-7.7 mg/dl, P = 0.01) and TG (14.1 mg/dl, P = 0.05) plasma levels. In the POP group, the average level of TC at the first visit was significantly higher (P < 0.01) than in the other groups and the TG level was higher than in the PHT group during the follow-up (P < 0.01). A strong positive correlation with body weight alteration after surgery was observed only for long-term changes in the TG levels. Conclusions: Our data indicate that STN-DBS may negatively affect the cardiometabolic profile of patients. Similarly to body weight gain, an increase in the LDL-C concentration occurred early after surgery while adverse changes in the HDL-C and TG plasma levels were more gradual.

Microglial Activation and Inflammation as a Factor in the Pathogenesis of Progressive Supranuclear Palsy (PSP).

Progressive supranuclear palsy (PSP) is a neurodegenerative disease based on four-repeat tauopathy pathology. Currently, this entity is not fully recognized in the context of pathogenesis or clinical examination. This review evaluates the association between neuroinflammation and microglial activation with the induction of pathological cascades that result in tauopathy pathology and the clinical manifestation of PSP. Multidimensional analysis was performed by evaluating genetic, biochemical, and neuroimaging biomarkers to determine whether neurodegeneration as an effect of neuroinflammation or neuroinflammation is a consequence of neurodegeneration in PSP. To the best of our knowledge, this review is the first to investigate PSP in this context.