The Role of MicroRNAs in Progressive Supranuclear Palsy-A Systematic Review.

Progressive supranuclear palsy (PSP) is a rare, neurodegenerative movement disorder. Together with multiple system atrophy (MSA), Dementia with Lewy bodies (DLB), and corticobasal degeneration (CBD), PSP forms a group of atypical parkinsonisms. The latest diagnostic criteria, published in 2017 by the Movement Disorders Society, classify PSP diagnosis into defined, probable, and possible categories based on clinical examination. However, no single test is specific and sensitive for this disease. Microribonucleic acids (miRNAs) are promising molecules, particularly in the case of diseases that lack appropriate diagnostic and treatment tools, which supports exploring their role in PSP. We aimed to systematically review the current knowledge about the role of miRNAs in PSP. This study was registered in the Open Science Framework Registry, and the protocol is available online. Primary original studies, both clinical and preclinical, written in English and assessing miRNAs in PSP were included. Systematic reviews, meta-analyses, reviews, case reports, letters to editors, commentaries, conference abstracts, guidelines/statements, expert opinions, preprints, and book chapters were excluded. The following five databases were searched: Embase, Medline Ultimate, PubMed, Scopus, and Web of Science. Each database was last searched on 18 June 2024. Eventually, nine original studies relevant to the discussed area were included. The risk of bias was not assessed. The selected research suggests that miRNAs may be considered promising biomarkers in PSP. However, the exact involvement of miRNAs in the pathogenesis of PSP is still to be determined. Several microRNAs were found to be dysregulated in patients with PSP. This applies to both brain tissue and fluids like cerebrospinal fluid CSF or blood. Several miRNAs were found that could potentially be helpful in differentiating among PSP patients, PD patients, and healthy individuals. Although some correlations and alterations have already been found, this field requires much more research. MicroRNAs are exciting and promising small molecules, and their investigation into many diseases, including PSP, may lead to significant discoveries.

Exploring Fecal Microbiota Transplantation for Modulating Inflammation in Parkinson's Disease: A Review of Inflammatory Markers and Potential Effects.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by numerous motor and non-motor symptoms. Recent data highlight a potential interplay between the gut microbiota and the pathophysiology of PD. The degeneration of dopaminergic neurons in PD leads to motor symptoms (tremor, rigidity, and bradykinesia), with antecedent gastrointestinal manifestations, most notably constipation. Consequently, the gut emerges as a plausible modulator in the neurodegenerative progression of PD. Key molecular changes in PD are discussed in the context of the gut-brain axis. Evidence suggests that the alterations in the gut microbiota composition may contribute to gastroenteric inflammation and influence PD symptoms. Disturbances in the levels of inflammatory markers, including tumor necrosis factor-α (TNF α), interleukin -1ß (IL-1ß), and interleukin-6 (IL-6), have been observed in PD patients. These implicate the involvement of systemic inflammation in disease pathology. Fecal microbiota transplantation emerges as a potential therapeutic strategy for PD. It may mitigate inflammation by restoring gut homeostasis. Preclinical studies in animal models and initial clinical trials have shown promising results. Overall, understanding the interplay between inflammation, the gut microbiota, and PD pathology provides valuable insights into potential therapeutic interventions. This review presents recent data about the bidirectional communication between the gut microbiome and the brain in PD, specifically focusing on the involvement of inflammatory biomarkers.

Differential diagnosis of Huntington's disease- neurological aspects of NKX2-1-related disorders.

Benign hereditary chorea (BHC) is an inherited neurological disorder consisting of childhood-onset, nonprogressive chorea, generally without any other manifestations. In most reported cases, the inheritance of BHC is autosomal dominant but both incomplete penetrance and variable expressivity are observed and can be caused by NKX2-1 mutations. The spectrum contains choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome. The neurological symptoms can be misdiagnosed as Huntington's disease (HD). The two Polish families were diagnosed with NKX2-1 gene mutations and a literature review concerning the NKX2-1-related disorders was conducted. All family members were examined by experienced movement disorders specialists. PubMed database was searched to obtain previously described NKX2-1 cases. Whole exome sequencing (WES) was performed in one proband (Family A) and direct NKX2-1 sequencing in the second (Family B). Two Polish families were diagnosed with NKX2-1 gene mutations (p.Trp208Leu and p.Cys117Alafs*8). In one family, the co-occurrence of HD was reported. Forty-nine publications were included in the literature review and symptoms of 195 patients with confirmed NKX2-1 mutation were analyzed. The most common symptoms were chorea and choreiform movements, and delayed motor milestones. The NKX2-1 mutation should always be considered as a potential diagnosis in families with chorea, even with a family history of HD. Lack of chorea does not exclude the NKX2-1-related disorders.

Validation of Polish version of Gastrointestinal Dysfunction Scale for Parkinson's Disease.

AIM OF STUDY: The Gastrointestinal Dysfunction Scale for Parkinson's Disease (GIDS-PD) is a novel, disease-specific self-report questionnaire used to quantitatively assess features of gastrointestinal dysfunction symptoms in patients with Parkinson's Disease. The aim of this paper was to validate the Polish translation of the scale, to summarise its consistency with the English language version, and to assess its clinimetric properties. CLINICAL RATIONALE FOR STUDY: Gastrointestinal dysfunction is a common and often debilitating manifestation of Parkinson's Disease (PD). Gastrointestinal symptoms are also considered to be prodromal features of this disease. To date, there has been no scale in Polish that has precisely assessed gastrointestinal symptoms in patients with PD. MATERIAL AND METHODS: The GIDS-PD was translated into Polish by two investigators (M.K. and J.N.). A back-translation was completed by two separate investigators (M.F. and A.A.) who were not involved in the original translation. Afterwards, 10 Polish PD patients underwent cognitive pre-testing. After the final translation was officially approved by the Movement Disorder Society, it was tested on 64 individuals with PD during field testing. For the purpose of testing scale reliability, 20 of the patients recruited for field testing underwent the GIDS-PD for a second time after 8-12 weeks. RESULTS: The GIDS-PD demonstrated overall good consistency (Cronbach's alpha of 0.74, ICC of 0.74). Regarding the individual domains, the constipation subscore demonstrated good reliability, the bowel irritability subscore demonstrated moderate reliability, and the upper GI subscore demonstrated poor reliability. Upper GI symptoms seem to be less pronounced, and also more varied, in the Polish PD population than in its English language counterpart. CONCLUSIONS AND CLINICAL IMPLICATIONS: This paper provides a validated Polish translation of the GIDS-PD questionnaire. We highly recommend using the GIDS-PD for research purposes, as well as everyday clinical practice in the Polish PD population.

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.

Pyruvate dehydrogenase-E1α deficiency presenting as generalized dystonia: A genetic diagnosis with important clinical implications.

Pyruvate dehydrogenase complex (PDC) deficiency is a genetic mitochondrial disease mostly associated with severe lactic acidosis, rapid progression of neurological symptoms and death during childhood. We present a 33-year-old male with PDC deficiency caused by a Val262Leu mutation in PDHA1gene. He demonstrated generalized dystonia affecting trunk and upper extremities and paraparesis as the most significant features, with onset of symptoms at age 8. Brain MRI showed bilaterally increased signal within the globus pallidus, typical of Leigh syndrome. A periodic lactate increase in serum and cerebrospinal fluid was detected. We describe a case of pyruvate dehydrogenase deficiency being diagnosed only 25 years after the onset of symptoms and highlight PDHC deficiency as a possible cause of treatable dystonia in childhood, which may respond well to thiamine and levodopa treatment.

Glymphatic System Pathology and Neuroinflammation as Two Risk Factors of Neurodegeneration.

The key to the effective treatment of neurodegenerative disorders is a thorough understanding of their pathomechanism. Neurodegeneration and neuroinflammation are mutually propelling brain processes. An impairment of glymphatic system function in neurodegeneration contributes to the progression of pathological processes. The question arises as to how neuroinflammation and the glymphatic system are related. This review highlights the direct and indirect influence of these two seemingly independent processes. Protein aggregates, a characteristic feature of neurodegeneration, are correlated with glymphatic clearance and neuroinflammation. Glial cells cannot be overlooked when considering the neuroinflammatory processes. Astrocytes are essential for the effective functioning of the glymphatic system and play a crucial role in the inflammatory responses in the central nervous system. It is imperative to acknowledge the significance of AQP4, a protein that exhibits a high degree of polarization in astrocytes and is crucial for the functioning of the glymphatic system. AQP4 influences inflammatory processes that have not yet been clearly delineated. Another interesting issue is the gut-brain axis and microbiome, which potentially impact the discussed processes. A discussion of the correlation between the functioning of the glymphatic system and neuroinflammation may contribute to exploring the pathomechanism of neurodegeneration.

ADCY5-related dyskinesia - case series with literature review.

INTRODUCTION: ADCY5-related dyskinesia is a rare neurological disease caused by mutations in the gene encoding the adenylyl cyclase 5 (ADCY5) isoform, a protein that plays an important role in intracellular transmission. Variants in ADCY5 are associated with a spectrum of neurological disease encompassing dyskinesia, chorea, and dystonia. State of the-art. ADCY5 mutations result in clinically heterogeneous manifestations which comprise a range of core and less to highly variable symptoms. Due to the heterogeneous nature and difficulty in diagnosis of the disorder, available treatments are highly limited. CLINICAL IMPLICATIONS: ADCY5-related dyskinesia was reported in 52 individuals in the literature over a five-year period (January 2017 to January 2022). We have listed all the symptoms and their frequency. The most common symptom reported in these patients was dystonia. Over 50% of patients developed dyskinesia and chorea. We report two cases of familial occurrence of symptomatic ADCY5-related dyskinesia. A 45-year-old patient presented with involuntary movements which had been occurring since childhood. The proband's neurological examination revealed dysarthria, involuntary myoclonic twitches, and choreic movements. The patient's 9-year-old son had developed involuntary movements, mainly chorea and dystonia. FUTURE DIRECTIONS: This paper aims to summarise the recent literature on ADCY5-related neurological disorders and to present a new case of a Polish family with ADCY5 mutation. Genetic diagnostics are important in the context of possible future targeted treatments.

Microglia and Stem Cells for Ischemic Stroke Treatment-Mechanisms, Current Status, and Therapeutic Challenges.

Ischemic stroke is one of the major causes of death and disability. Since the currently used treatment option of reperfusion therapy has several limitations, ongoing research is focusing on the neuroprotective effects of microglia and stem cells. By exerting the bystander effect, secreting exosomes and forming biobridges, mesenchymal stem cells (MSCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and multilineage-differentiating stress-enduring cells (Muse cells) have been shown to stimulate neurogenesis, angiogenesis, cell migration, and reduce neuroinflammation. Exosome-based therapy is now being extensively researched due to its many advantageous properties over cell therapy, such as lower immunogenicity, no risk of blood vessel occlusion, and ease of storage and modification. However, although preclinical studies have shown promising therapeutic outcomes, clinical trials have been associated with several translational challenges. This review explores the therapeutic effects of preconditioned microglia as well as various factors secreted in stem cell-derived extracellular vesicles with their mechanisms of action explained. Furthermore, an overview of preclinical and clinical studies is presented, explaining the main challenges of microglia and stem cell therapies, and providing potential solutions. In particular, a highlight is the use of novel stem cell therapy of Muse cells, which bypasses many of the conventional stem cell limitations. The paper concludes with suggestions for directions in future neuroprotective research.

Cervical dystonia and no oculomotor apraxia as new manifestation of ataxia-telangiectasia-like disorder 1 - case report and review of the literature.

Ataxia-telangiectasia-like disorder 1 (ATLD1) is a rare neurodegenerative disorder associated with early onset ataxia and oculomotor apraxia. The genetic determination of ATLD1 is a mutation in the MRE11 gene (meiotic recombination 11 gene), which causes DNA-double strand break repair deficits. Clinical features of patients with ATLD1 resemble those of ataxia telangiectasia (AT), with slower progression and milder presentation. Main symptoms include progressive cerebellar ataxia, oculomotor apraxia, cellular hypersensitivity to ionizing radiations. Facial dyskinesia, dystonia, dysarthria have also been reported. Here we present a 45-year old woman with cervical and facial dystonia, dysarthria and ataxia, who turned out to be the first case of ATLD without oculomotor apraxia, and with dystonia as a main manifestation of the disease. She had presented those non-specific symptoms for years, before whole exome sequencing confirmed the diagnosis.

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.

Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations: Experience from the MJFF Global Genetic Parkinson's Disease Project.

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.

Assessment of factors influencing glymphatic activity and implications for clinical medicine.

The glymphatic system is a highly specialized fluid transport system in the central nervous system. It enables the exchange of the intercellular fluid of the brain, regulation of the movement of this fluid, clearance of unnecessary metabolic products, and, potentially, brain immunity. In this review, based on the latest scientific reports, we present the mechanism of action and function of the glymphatic system and look at the role of factors influencing its activity. Sleep habits, eating patterns, coexisting stress or hypertension, and physical activity can significantly affect glymphatic activity. Modifying them can help to change lives for the better. In the next section of the review, we discuss the connection between the glymphatic system and neurological disorders. Its association with many disease entities suggests that it plays a major role in the physiology of the whole brain, linking many pathophysiological pathways of individual diseases.

Defects in Mitochondrial Biogenesis Drive Mitochondrial Alterations in PINK1-deficient Human Dopamine Neurons.

Mutations and loss of activity in the protein kinase PINK1 play a role in the pathogenesis of Parkinson's disease (PD). PINK1 regulates many aspects of mitochondrial quality control including mitochondrial autophagy (mitophagy), fission, fusion, transport, and biogenesis. Defects in mitophagy are though to play a predominant role in the loss of dopamine (DA) neurons in PD. Here we show that, although there are defects in mitophagy in human DA neurons lacking PINK1, mitochondrial deficits induced by the absence of PINK1 are primarily due to defects in mitochondrial biogenesis. Upregulation of PARIS and the subsequent down regulation of PGC-1a accounts for the mitochondrial biogenesis defects. CRISPR/Cas9 knockdown of PARIS completely restores the mitochondrial biogenesis defects and mitochondrial function without impacting the deficits in mitophagy due to the absence of PINK1. These results highlight the importance mitochondrial biogenesis in the pathogenesis of PD due to inactivation or loss of PINK1 in human DA neurons.

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.

Glymphatic System and Mitochondrial Dysfunction as Two Crucial Players in Pathophysiology of Neurodegenerative Disorders.

Neurodegenerative diseases are a complex problem affecting millions of people around the world. The pathogenesis is not fully understood, but it is known that both insufficiency of the glymphatic system and mitochondrial disorders affect the development of pathology. It appears that these are not just two independent factors that coexist in the processes of neurodegeneration, but that they often interact and drive each other. Bioenergetics disturbances are potentially associated with the accumulation of protein aggregates and impaired glymphatic clearance. Furthermore, sleep disorders characteristic of neurodegeneration may impair the work of both the glymphatic system and the activity of mitochondria. Melatonin may be one of the elements linking sleep disorders with the function of these systems. Moreover, noteworthy in this context is the process of neuroinflammation inextricably linked to mitochondria and its impact not only on neurons, but also on glia cells involved in glymphatic clearance. This review only presents possible direct and indirect connections between the glymphatic system and mitochondria in the process of neurodegeneration. Clarifying the connection between these two areas in relation to neurodegeneration could lead to the development of new multidirectional therapies, which, due to the complexity of pathogenesis, seems to be worth considering.

Machine Learning and Eye Movements Give Insights into Neurodegenerative Disease Mechanisms.

Humans are a vision-dominated species; what we perceive depends on where we look. Therefore, eye movements (EMs) are essential to our interactions with the environment, and experimental findings show EMs are affected in neurodegenerative disorders (ND). This could be a reason for some cognitive and movement disorders in ND. Therefore, we aim to establish whether changes in EM-evoked responses can tell us about the progression of ND, such as Alzheimer's (AD) and Parkinson's diseases (PD), in different stages. In the present review, we have analyzed the results of psychological, neurological, and EM (saccades, antisaccades, pursuit) tests to predict disease progression with machine learning (ML) methods. Thanks to ML algorithms, from the high-dimensional parameter space, we were able to find significant EM changes related to ND symptoms that gave us insights into ND mechanisms. The predictive algorithms described use various approaches, including granular computing, Naive Bayes, Decision Trees/Tables, logistic regression, C-/Linear SVC, KNC, and Random Forest. We demonstrated that EM is a robust biomarker for assessing symptom progression in PD and AD. There are navigation problems in 3D space in both diseases. Consequently, we investigated EM experiments in the virtual space and how they may help find neurodegeneration-related brain changes, e.g., related to place or/and orientation problems. In conclusion, EM parameters with clinical symptoms are powerful precision instruments that, in addition to their potential for predictions of ND progression with the help of ML, could be used to indicate the different preclinical stages of both diseases.

Morbidity and severity of COVID-19 in patients with Parkinson's disease treated with amantadine - A multicenter, retrospective, observational study.

BACKGROUND: After more than 2 years of the pandemic, effective treatment for COVID-19 is still under research. In recent months, publications hypothesized amantadine's potential beneficial effect on SARS-CoV-2 infection. OBJECTIVE: To compare the groups of Parkinson's Disease (PD) patients who were administered amantadine chronically and those who did not take this medication in the context of the incidence and severity of COVID-19 infection. METHODS: An observational, retrospective, multicenter cohort study was conducted among consecutive patients with idiopathic PD. The structured questionnaires were completed during the patient's follow-up visits at the Outpatient Clinic or during hospitalization. The questionnaire included the following informations: patient's age, duration of PD, Hoehn-Yahr (H-Y) stage, comorbidities, medications, COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR) swab test for SARS-CoV-2 with specified symptoms and their severity (home or hospital treatment). The vaccination status was verified as well. RESULTS: Five hundred fifty-two (n = 552) patients participated in the study - 329 men (60%). The mean H-Y stage was 2.44 (range: 1-4) and the mean duration of PD was 9.6 years (range: 1-34). One hundred four subjects (19%) had confirmed COVID-19 infection. Subjects over 50 years of age had a significantly lower incidence of COVID-19 (17% vs 38%, p = 0.0001) with difference also in mean H-Y stage (2.27 vs 2.49; p = 0.011) and disease duration (8.4 vs 9.9 years, p = 0.007). There were no differences between patients with and without co-morbidities. In the whole analyzed group 219 (40%) subjects were treated with amantadine. Comparing COVID-19 positive and negative patients, amantadine was used by 48/104 (46%) and 171/448 (38%) respectively. 22% of patients on amantadine vs. 17% of patients without amantadine developed COVID-19. These differences were not significant. There were no differences in morbidity and severity of COVID-19 between amantadine users and non-users as well. CONCLUSIONS: COVID-19 was less common in older (>50) with longer duration and more advanced patients. Amantadine did not affect the risk of developing COVID-19 or the severity of infection.

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.