Early Screening for the Parkinson Variant of Multiple System Atrophy: A 6-Item Score.

BACKGROUND: A 4-item score based on ≥2 features out of orthostatic hypotension, overactive bladder, urinary retention and postural instability was previously shown to early distinguish the Parkinson-variant of multiple system atrophy (MSA-P) from Parkinson's disease (PD) with 78% sensitivity and 86% specificity. OBJECTIVES: To replicate and improve the 4-item MSA-P score. METHODS: We retrospectively studied 161 patients with early parkinsonism [ie, ≤2 years disease duration or no postural instability, aged 64 (57; 68) years, 44% females] and a diagnosis of clinically established MSA-P (n = 38) or PD (n = 123) after ≥24 months follow-up. RESULTS: The 4-item MSA-P score had a 92% sensitivity and 78% specificity for a final MSA-P diagnosis. By including dopaminergic responsiveness and postural deformities into a 6-item score (range: 0-6), reaching ≥3 points at early disease identified MSA-P patients with 89% sensitivity and 98% specificity. CONCLUSIONS: The 6-item MSA-P score is a cost-effective tool to pinpoint individuals with early-stage MSA-P.

Long-term outcome of patients with neurological form of Wilson's disease compliant to the de-coppering treatment.

BACKGROUND: A substantial proportion of Wilson's disease (WD) patients exhibit residual neurological symptoms. Data on the prognostic value of initial clinical features and treatment choices in WD patients compliant to the therapy is relatively sparse. AIM: The aim of the present study was to identify predictors of the long-term outcome of patients with WD with good treatment adherence. METHODS: Forty patients with neurological form of WD were evaluated before the de-coppering treatment initiation (based on the medical records) and after mean 15.25 ± 11.24 years of the stable treatment. Severity of neurological symptoms were assessed with a tier two of Global Assessment Scale (GAS) for Wilson's Disease. RESULTS: The most frequent symptoms prior to treatment initiation were dysarthria (90%), tremor (90%), clumsiness (67.5%), depression (67.5%), and gait disturbance (62.5%). Significant decrease in the frequency of dysarthria, clumsiness, tremor, gait disturbance, postural instability and an improvement in school/work performance were observed after the long-term treatment, while frequency of dysphagia, drooling, bradykinesia and rigidity, dystonic and choreatic features did not change. Overall symptom severity decreased over time. Presence of dystonia before treatment initiation was the only identified predictor of worse residual GAS score. Greater severity of residual dystonia was associated with female gender and longer disease duration. CONCLUSION: Although patients with neurological form of WD compliant to de-coppering treatment had favorable disease outcome, a significant burden of residual neurological symptoms was observed after the long-term follow-up. Dystonia at disease onset was the only identified predictor of the worse long-term outcome.

Effect of CytoSorb Coupled with Hemodialysis on Interleukin-6 and Hemodynamic Parameters in Patients with Systemic Inflammatory Response Syndrome: A Retrospective Cohort Study.

Excessive release of cytokines during systemic inflammatory response syndrome (SIRS) often leads to refractory hypotension and multiple organ failure with high mortality. Cytokine removal with hemoadsorption has emerged as a possible adjuvant therapy, but data on interleukin-6 (IL-6) reduction and outcomes in clinical practice are scarce. We aimed to evaluate the effect of CytoSorb hemoadsorption on laboratory and clinical outcomes in shocked patients with SIRS. We designed a retrospective analysis of all patients with SIRS treated with CytoSorb in intensive care units (ICU). IL-6, laboratory and hemodynamic parameters were analyzed at approximate time intervals during CytoSorb treatment in the whole cohort and in a subgroup with septic shock. Observed and predicted mortality rates were compared. We included 118 patients with various etiologies of SIRS (septic shock 69%, post-resuscitation shock 16%, SIRS with acute pancreatitis 6%, other 9%); in all but one patient, CytoSorb was coupled with renal replacement therapy. A statistically significant decrease in IL-6 and vasopressor index with an increase in pH and mean arterial pressure was observed from 6 h onward. The reduction of lactate became significant at 48 h. Results were similar in a subgroup of patients with septic shock. Observed ICU and in-hospital mortalities were lower than predicted by Sequential Organ Failure Assessment (SOFA) (61% vs. 79%, p = 0.005) and Acute Physiology and Chronic Health Evaluation (APACHE) II (64% vs. 78%, p = 0.031) scores. To conclude, hemoadsorption in shocked patients with SIRS was associated with a rapid decrease in IL-6 and hemodynamic improvement, with improved observed vs. predicted survival. These results need to be confirmed in a randomized study.

The Predictive Value of Oxidative Stress Index in Patients with Confirmed SARS-COV-2 Infection.

Disbalance balance between oxidants and antioxidants is called oxidative stress and could be presented as oxidative stress index (OSI). OSI is determined by the reactive oxygen metabolites (d-ROM test) to assess oxidants and the plasma antioxidant capacity test (PAT test) to measure antioxidants. The aim of the study was to evaluate the predictive value of OSI in the disease COVID-19. d-ROMs results were the highest in the SARS-CoV-2 POSITIVE group (365+/-112), lower in the SARS-CoV-2 NEGATIVE group (314+/-72.4), and the lowest in an INTENSIVE CARE UNIT group (ICU) (277+/-142) U.Carr. PAT test values were the lowest in the SARS-CoV-2 POSITIVE group (2762+/-387), higher in the ICU group (2772 +/-786), and the highest in the SARS-CoV-2 NEGATIVE group (2808+/-470), and are not statistically significantly different (P>0.05), while OSI was: healthy with average value of 49 and the critical ill with average value of 109 (P = 0.016). Cut-offs for predicting ICUs admission was at OSI 62, with 80.0% sensitivity and 68.2% specificity.

Successful Immunomodulatory Treatment of COVID-19 in a Patient With Severe ACTH-Dependent Cushing's Syndrome: A Case Report and Review of Literature.

Introduction: Patients with Cushing's syndrome (CS) represent a highly sensitive group during corona virus disease 2019 (COVID-19) pandemic. The effect of multiple comorbidities and immune system supression make the clinical picture complicated and treatment challenging. Case report: A 70-year-old female was admitted to a covid hospital with a severe form of COVID-19 pneumonia that required oxygen supplementation. Prior to her admission to the hospital she was diagnosed with adrenocorticotropic hormone (ACTH)-dependent CS, and the treatment of hypercortisolism had not been started yet. Since the patient's condition was quickly deteriorating, and with presumend immmune system supression due to CS, we decided on treatement with intraveonus immunoglobulins (IVIg) that enabled quick onset of immunomodulatory effect. All comorbidities were treated with standard of care. The patient's condition quickly stabilized with no direct side effects of a given treatment. Conclusion: Treatment of COVID-19 in patients with CS faces many challenges due to the complexity of comorbidity effects, immunosupression and potential interactions of available medications both for treatment of COVID-19 and CS. So far, there are no guidelines for treatment of COVID-19 in patients with active CS. It is our opinion that immunomodulating therapies like IVIg might be an effective and safe treatment modality in this particularly fragile group of patients.

Long-Duration Progressive Supranuclear Palsy: Clinical Course and Pathological Underpinnings.

OBJECTIVES: To identify the clinical characteristics of the subgroup of benign progressive supranuclear palsy with particularly long disease duration; to define neuropathological determinants underlying variability in disease duration in progressive supranuclear palsy. METHODS: Clinical and pathological features were compared among 186 autopsy-confirmed cases with progressive supranuclear palsy with ≥10 years and shorter survival times. RESULTS: The 45 cases (24.2%) had a disease duration of ≥10 years. The absence of ocular motor abnormalities within the first 3 years from disease onset was the only significant independent clinical predictor of longer survival. Histopathologically, the neurodegeneration parameters in each survival group were paralleled anatomically by the distribution of neuronal cytoplasmic inclusions, whereas the tufted astrocytes displayed anatomically an opposite severity pattern. Most interestingly, we found significantly less coiled bodies in those who survive longer, in contrast to patients with less favorable course. INTERPRETATION: A considerable proportion of patients had a more "benign" disease course with ≥10 years survival. They had a distinct pattern and evolution of core symptoms compared to patients with short survival. The inverted anatomical patterns of astrocytic tau distribution suggest distinct implications of these cell types in trans-cellular propagation. The tempo of disease progression appeared to be determined mostly by oligodendroglial tau, where the high degree of oligodendroglial tau pathology might affect neuronal integrity and function on top of neuronal tau pathology. The relative contribution of glial tau should be further explored in cellular and animal models. ANN NEUROL 2022;92:637-649.

Gait alterations in Parkinson's disease at the stage of hemiparkinsonism-A longitudinal study.

BACKGROUND: Progressive gait impairment in Parkinson's disease (PD) leads to significant disability. Quantitative gait parameters analysis provides valuable information about fine gait alterations. OBJECTIVES: To analyse change of gait parameters in patients with early PD at the stage of hemiparkinsonism and after 1 year of follow up, taking into account clinical asymmetry. METHODS: Consecutive early PD outpatients with strictly unilateral motor features underwent clinical and neuropsychological assessment at the study entry and after 1 year of follow up. Gait was assessed with GAITRite walkway using dual-task methodology. Spatiotemporal gait parameters (step time and length, swing time and double support time) and their coefficients of variation (CV), gait velocity and heel-to-heel base support were evaluated. RESULTS: We included 42 PD patients with disease duration of 1.3 years (±1.13). Progression of motor and non-motor symptoms, without significant cognitive worsening, was observed after 1 year of follow up. Significant shortening of the swing time, prolongation of the double support and increase of their CVs were observed during all task conditions similarly for most parameters on symptomatic and asymptomatic bodysides, except for CV for the swing time under the combined task. CONCLUSION: Alterations of the swing time and double support time are already present even at the asymptomatic body side, and progress similarly, or even at faster pace, at this side, despite dopaminergic treatment These parameters deserve further investigation in larger, prospective studies to address their potential to serve as markers of progression in interventional disease modifying trials with early PD patients.

Severe COVID-19 Infection Management in a Patient with Mild Haemophilia-A Case Report.

Patients with haemophilia present a significant challenge when admitted into the intensive care unit. To prevent haemorrhagic complications related to the infection or due to invasive procedures factor (F) VIII/IX must be substituted. As thromboembolic complications are frequent among critically ill COVID-19 patients, thromboprophylaxis is also applied to patients with haemophilia. This requires careful monitoring of FVIII/IX activity as well as other haemostatic parameters, such as D-dimer and antiXa. We describe a 44-year old patient with mild haemophilia A (FVIII activity of 6%), who required a prolonged intensive care unit stay due to a severe SARS-CoV-2 infection. FVIII was substituted via boluses, and dalteparin was given according to recommendations. The patient successfully recovered from the disease.

Tau deposition patterns are associated with functional connectivity in primary tauopathies.

Tau pathology is the main driver of neuronal dysfunction in 4-repeat tauopathies, including cortico-basal degeneration and progressive supranuclear palsy. Tau is assumed to spread prion-like across connected neurons, but the mechanisms of tau propagation are largely elusive in 4-repeat tauopathies, characterized not only by neuronal but also by astroglial and oligodendroglial tau accumulation. Here, we assess whether connectivity is associated with 4R-tau deposition patterns by combining resting-state fMRI connectomics with both 2nd generation 18F-PI-2620 tau-PET in 46 patients with clinically diagnosed 4-repeat tauopathies and post-mortem cell-type-specific regional tau assessments from two independent progressive supranuclear palsy patient samples (n = 97 and n = 96). We find that inter-regional connectivity is associated with higher inter-regional correlation of both tau-PET and post-mortem tau levels in 4-repeat tauopathies. In regional cell-type specific post-mortem tau assessments, this association is stronger for neuronal than for astroglial or oligodendroglial tau, suggesting that connectivity is primarily associated with neuronal tau accumulation. Using tau-PET we find further that patient-level tau patterns are associated with the connectivity of subcortical tau epicenters. Together, the current study provides combined in vivo tau-PET and histopathological evidence that brain connectivity is associated with tau deposition patterns in 4-repeat tauopathies.

Antimicrobial Use in Hospitalised Patients with COVID-19: An International Multicentre Point-Prevalence Study.

Studies suggest that the incidence of coinfections in patients with the coronavirus disease 2019 (COVID-19) is low, but a large number of patients receive antimicrobials during hospitalisation. This may fuel a rise in antimicrobial resistance (AMR). We conducted a multicentre point-prevalence survey in seven tertiary university hospitals (in medical wards and intensive care units) in Croatia, Italy, Serbia and Slovenia. Of 988 COVID-19 patients, 521 were receiving antibiotics and/or antifungals (52.7%; range across hospitals: 32.9-85.6%) on the day of the study. Differences between hospitals were statistically significant (χ2 (6, N = 988) = 192.57, p < 0.001). The majority of patients received antibiotics and/or antifungals within 48 h of admission (323/521, 62%; range across hospitals: 17.4-100%), their most common use was empirical (79.4% of prescriptions), and pneumonia was the main indication for starting the treatment (three-quarters of prescriptions). The majority of antibiotics prescribed (69.9%) belonged to the "Watch" group of the World Health Organization AWaRe classification. The pattern of antimicrobial use differed across hospitals. The data show that early empiric use of broad-spectrum antibiotics is common in COVID-19 patients, and that the pattern of antimicrobial use varies across hospitals. Judicious use of antimicrobials is warranted to prevent an increase in AMR.

Genetic and phenotypic variability in adult patients with Niemann Pick type C from Serbia: single-center experience.

BACKGROUND: Niemann Pick type C is an autosomal recessive lysosomal storage disorder caused by mutations in NPC1 and NPC2 genes. It is a neuro-visceral disease with a heterogeneous phenotype. Clinical features depend on the age at onset. Visceral manifestations are more prominent in the early onset (infantile) form, while neuro-psychiatric symptoms are more prominent in the late disease onset (juvenile and adult forms). METHODS: A total number of 150 patients have been screened for changes in NPC1 and NPC2 gene at the Neurology Clinic, University Clinical Centre of Serbia in the period 2012-2020. Clinical data were extracted for patients with biallelic mutations. RESULTS: Fifteen patients carried biallelic mutations in the NPC1. Out of eight different reported NPC1 variants, four are novel (c.1204_1205TT>GC, p.F402A; c.2486T>G, p.L829R; c.2795+5 G>C; c.3722T>A, p.L1241*). The mean age at the disease onset was 20.3 ± 11.9 years with the average diagnostic delay of 7.7 ± 4.3 years. Movement disorders and psychiatric or cognitive disturbances were the most common initial symptoms (in 33% and 28% patients, respectively). The average age at the first neurological manifestation was 21 ± 12.0 years. At the last examination, eye movement abnormalities (vertical slow saccades or vertical supranuclear gaze palsy), and ataxia were present in all patients, while dystonia was common (in 78.6% of patients). Presence of c.2861C>T, p.S954L mutation in homozygous state was associated with older age at the neurological symptom onset. CONCLUSIONS: Clinical findings were in line with the expected, but the diagnostic delay was common. We hypothesize that the presence of c.2861C>T, p.S954L mutation may contribute to the phenotype attenuation.

Formulation of topical acidic products and acidification of the skin - Contribution of glycolic acid.

OBJECTIVE: The acidic skin pH is one of the regulating factors of skin barrier homeostasis. Topical products as extrinsic factors which influence skin pH could be used for acidification of the skin and consequent beneficial effect. To formulate stabile and safe topical emulsion product with low pH is on-going challenge and areas interesting to explore are related to the effect of acidic products on the skin pH together with development of protocols for these studies. Aim of our work was to investigate formulations of acidic topical products with glycolic acid (GA) stabilized with long chain alkyl polyglucoside emulsifier, in regard to the specific colloidal structure of the vehicle, together with effect of products with different concentration of acidic active on skin pH. METHODS: Investigated formulations were basic vehicle and two creams with glycolic acid (concentration 2 and 10 wt%). Microstructure was investigated by polarization microscopy, Raman spectral imaging, thermal analysis and rheological measurements. Effects on the skin were assessed by measurement of biophysical skin parameters in vivo studies (5-hour, 24-hour and 7-days). In vitro screening of antimicrobial activity was performed against bacteria Staphylococcus epidermidis. RESULTS: Polarization micrographs and Raman images have shown that GA does not disturb the specific colloidal structure. Together with rheological and thermal analysis obtained results have shown that GA in higher concentrations contributes to vehicles' lamellar structure. In 5-hour study the mean values of skin pH ranged from 3.98-4.25 and 3.89-4.10 after application of products with smaller and higher GA concentration. GA samples lowered skin surface pH to 5 and less in 24-hour and 7-day study, with stronger effect of sample with more GA. Sample with 10% of GA had significant inhibitory effect on growth of S. epidermidis in 1:1 concentration. CONCLUSIONS: Investigated APG emulsifier could be used as a stabilizer for acidic topical products with GA which are characterized by satisfactory safety profile. Topical products induce acidification of the skin after short- and long-term application without barrier impairment or sign of irritation. Acidification of the skin depends on presence of ingredients which are proton donors and their concentrations.

OBJECTIF: Le pH acide de la peau est l'un des facteurs de régulation de l'homéostasie de la barrière cutanée. Les produits topiques pourraient être utilisés en tant que facteurs extrinsèques d'influence du pH cutané pour permettre l'acidification de la peau et obtenir l'effet bénéfique qui en résulte. Formuler des émulsions topiques stables et sûres à faible pH représente un défi constant et les domaines d'étude dignes d'intérêt portent sur l'effet des produits acides sur le pH cutané et sur l'élaboration de protocoles pour ces études. L'objectif de notre travail était d'étudier des formulations de produits topiques acides à base d'acide glycolique (AG) stabilisé à l'aide d'un émulsionnant à base d'alkylpolyglucoside (APG) à longue chaîne, par rapport à la structure colloïdale spécifique de l'excipient, ainsi que l'effet des produits à différentes concentrations d'acide actif sur le pH cutané. MÉTHODES: Les formulations étudiées étaient un excipient de base et deux crèmes à base d'acide glycolique (concentration égale à 2 % et 10 % de la fraction massique). La microstructure a été étudiée par microscopie à polarisation, par spectroscopie Raman, par analyse thermique et par mesures rhéologiques. Les effets cutanés ont été évalués par la mesure des paramètres cutanés biophysiques dans des études in vivo (5 heures, 24 heures et 7 jours). Un dépistage in vitro de l'activité antimicrobienne a été effectué sur la bactérie Staphylococcus epidermidis. RÉSULTATS: Les micrographies après polarisation et les images obtenues par spectroscopie Raman ont montré que l'AG ne perturbe pas la structure colloïdale spécifique. Avec les analyses rhéologique et thermique, les résultats obtenus ont montré que l'AG à des concentrations plus élevées joue un rôle dans la structure lamellaire des excipients. Dans l'étude de 5 heures, les valeurs moyennes du pH cutané allaient de 3,98 à 4,25 et de 3,89 à 4,10 après l'application des produits présentant une concentration d'AG plus faible et plus élevée. Grâce aux échantillons d'AG, le pH de la surface cutanée a diminué, passant ainsi à une valeur de 5 et à des valeurs inférieures dans les études de 24 heures et de 7 jours, et l'échantillon contenant davantage d'AG a eu un effet plus important. L'échantillon contenant 10 % d'AG a eu un effet inhibiteur significatif sur la croissance de la bactérie S. epidermidis à une concentration de 1:1. CONCLUSION: L'émulsionnant à base d'APG étudié pourrait être utilisé comme stabilisateur pour les produits topiques acides à base d'AG caractérisés par un profil d'innocuité satisfaisant. Les produits topiques induisent une acidification de la peau après une application à court et à long terme sans altération de la barrière cutanée ou signe d'irritation. L'acidification de la peau dépend de la présence de donneurs de proton parmi les composants et de leurs concentrations.

A Modified Progressive Supranuclear Palsy Rating Scale.

BACKGROUND: The Progressive Supranuclear Palsy Rating Scale is a prospectively validated physician-rated measure of disease severity for progressive supranuclear palsy. We hypothesized that, according to experts' opinion, individual scores of items would differ in relevance for patients' quality of life, functionality in daily living, and mortality. Thus, changes in the score may not equate to clinically meaningful changes in the patient's status. OBJECTIVE: The aim of this work was to establish a condensed modified version of the scale focusing on meaningful disease milestones. METHODS: Sixteen movement disorders experts evaluated each scale item for its capacity to capture disease milestones (0 = no, 1 = moderate, 2 = severe milestone). Items not capturing severe milestones were eliminated. Remaining items were recalibrated in proportion to milestone severity by collapsing across response categories that yielded identical milestone severity grades. Items with low sensitivity to change were eliminated, based on power calculations using longitudinal 12-month follow-up data from 86 patients with possible or probable progressive supranuclear palsy. RESULTS: The modified scale retained 14 items (yielding 0-2 points each). The items were rated as functionally relevant to disease milestones with comparable severity. The modified scale was sensitive to change over 6 and 12 months and of similar power for clinical trials of disease-modifying therapy as the original scale (achieving 80% power for two-sample t test to detect a 50% slowing with n = 41 and 25% slowing with n = 159 at 12 months). CONCLUSIONS: The modified Progressive Supranuclear Palsy Rating Scale may serve as a clinimetrically sound scale to monitor disease progression in clinical trials and routine. © 2021 International Parkinson and Movement Disorder Society.

The Profile and Evolution of Neuropsychiatric Symptoms in Multiple System Atrophy: Self- and Caregiver Report.

OBJECTIVE: Recent research shows that patients with multiple system atrophy (MSA) have significant cognitive and neuropsychiatric comorbidities that can color the clinical presentation of the disease and affect their quality of life. The aims of this study were to determine the neuropsychiatric profile in a cohort of patients with the parkinsonian type of MSA (MSA-P) and their dynamic changes over a 1-year follow-up period and to compare rates of neuropsychiatric symptoms (NPSs) reported by caregivers and the patients themselves. METHODS: Forty-seven patients were assessed at baseline; of these, 25 were assessed again after 1 year. NPS assessment tools included the Neuropsychiatric Inventory (NPI), the Beck Depression Inventory, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Apathy Evaluation Scale. RESULTS: The prevalence of NPSs in patients with MSA-P was very high, with depression, sleep disturbances, apathy, and anxiety being the most frequently occurring features. The evolution of NPSs was found to be independent of motor, autonomic, and cognitive symptoms. None of the scales measuring NPSs, including the NPI, were capable of detecting changes over the 1-year follow-up period. Although the overall prevalence of depression, apathy, and anxiety obtained from caregivers and the patients themselves was similar, reports from these two sources cannot be considered interchangeable. CONCLUSIONS: The progression of neuropsychiatric symptoms was not a subject of rapid change in MSA-P, in contrast to the observed motor, autonomic, and cognitive deterioration. These findings suggest the need to investigate the utility of available instruments in capturing the evolution of NPSs in MSA over time.

Changes of Phenotypic Pattern in Functional Movement Disorders: A Prospective Cohort Study.

Introduction: Functional movement disorders (FMD) refer to a group of movement disorders that present with clinical characteristics incongruent to those due to established pathophysiologic processes, as for example in the case of neurodegeneration or lesions. The aim of this study was to assess clinical features that contribute to the specific phenotypic presentations and disease course of FMD. Methods: The study consisted of 100 patients with FMD treated at Clinic for Neurology, Clinical Center of Serbia, who were longitudinally observed. Comprehensive clinical and psychiatric assessment was performed at the baseline, when initial FMD phenotype was defined. Follow-up assessment of phenotypic pattern over the time and clinical course was done after 3.2 ± 2.5 years at average. Results: We showed that 48% of FMD patients were prone to changes of phenotypic pattern during the disease course. Dystonia had tendency to remains as single and unchanged phenotype over the time (68.2%), while patients initially presented with Tremor, Gait disorder, Parkinsonism and Mixed phenotype were more susceptible to developing additional symptoms (62.5, 50, and 100%, respectively). Higher levels of somatoform experiences (p = 0.033, Exp(B) = 1.082) and higher motor severity (p = 0.040, Exp(B) = 1.082) at baseline assessment were associated with an increased likelihood of further enriching of FMD phenotype with additional functional symptoms. Also, these patients more frequently reported pain, and had higher scores on majority of applied psychiatric scales, together with more frequent presence of major depressive disorder. Conclusion: Results from this prospective study suggested tendency for progression and enrichment of functional symptoms in FMD patients over time. Besides functional core symptoms, other key psychological and physical features (like pain or multiple somatisations) were quite relevant for chronicity and significant dysability of FMD patients.

Severe immune thrombocytopenia in a critically ill COVID-19 patient.

The novel coronavirus SARS-CoV-2 can cause a severe and even fatal respiratory illness named COVID-19. Apart from respiratory failure, COVID-19 may be associated with various autoimmune complications. We present a case of a critically ill patient with COVID-19 who developed severe immune thrombocytopenia that was successfully treated with a concomitant use of corticosteroids and intravenous immunoglobulins.

A comparison of Myribase and Doublebase gel: Does qualitative similarity of emollient products imply their direct interchangeability in everyday practice?

Emollients are acknowledged as a part of standard care in therapeutic and prevention protocols as well as a part of everyday skin care routine. When it comes to making a final decision between two emollient products, the ingredient list, that is, the formulation composition could be the determining factor. In such cases the consumer, and some healthcare providers, believe that products with the same qualitative composition (ingredient list) must have the same efficacy. In this study, we have investigated the skin hydration performance of two emollient preparations (DBG and MBG), which appear to contain the same ingredients, and hence, could be considered interchangeable in everyday practice. Our studies showed that the effects of DBG were overall superior to the ones attributed to MBG at each investigated time point (1, 2, 4, and 24 h post application) when tested on normal and dry skin. Consequently, it is shown that two apparently qualitatively identical products do not necessarily provide matching efficacy.

Distribution patterns of tau pathology in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps and distribution patterns of neuronal, astroglial, and oligodendroglial tau pathologies and their combinations in different clinical subtypes of PSP in postmortem brains. We used conditional probability and logistic regression to model the sequential distribution of tau pathologies across different brain regions. Tau pathology uniformly predominates in the neurons of the pallido-nigro-luysian axis in different clinical subtypes. However, clinical subtypes are distinguished not only by total tau load but rather cell-type (neuronal versus glial) specific vulnerability patterns of brain regions suggesting distinct dynamics or circuit-specific segregation of propagation of tau pathologies. For Richardson syndrome (n = 81) we recognize six sequential steps of involvement of brain regions by the combination of cellular tau pathologies. This is translated to six stages for the practical neuropathological diagnosis by the evaluation of the subthalamic nucleus, globus pallidus, striatum, cerebellum with dentate nucleus, and frontal and occipital cortices. This system can be applied to further clinical subtypes by emphasizing whether they show caudal (cerebellum/dentate nucleus) or rostral (cortical) predominant, or both types of pattern. Defining cell-specific stages of tau pathology helps to identify preclinical or early-stage cases for the better understanding of early pathogenic events, has implications for understanding the clinical subtype-specific dynamics of disease-propagation, and informs tau-neuroimaging on distribution patterns.