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Millions of individuals around the world are afflicted with Parkinson's disease (PD), a prevalent and incapacitating neurodegenerative disorder. Dr. Reichmann, a distinguished professor and neurologist, has made substantial advancements in the domain of PD research, encompassing both fundamental scientific investigations and practical applications. His research has illuminated the etiology and treatment of PD, as well as the function of energy metabolism and premotor symptoms. As a precursor to a number of neurotransmitters and neuromodulators that are implicated in the pathophysiology of PD, he has also investigated the application of tryptophan (Trp) derivatives in the disease. His principal findings and insights are summarized and synthesized in this narrative review article, which also emphasizes the challenges and implications for future PD research. This narrative review aims to identify and analyze the key contributions of Reichmann to the field of PD research, with the ultimate goal of informing future research directions in the domain. By examining Reichmann's work, the study seeks to provide a comprehensive understanding of his major contributions and how they can be applied to advance the diagnosis and treatment of PD. This paper also explores the potential intersection of Reichmann's findings with emerging avenues, such as the investigation of Trp and its metabolites, particularly kynurenines, which could lead to new insights and potential therapeutic strategies for managing neurodegenerative disorders like PD. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS). Immune cell infiltration can lead to permanent activation of macrophages and microglia in the parenchyma, resulting in demyelination and neurodegeneration. Thus, neurodegeneration that begins with acute lymphocytic inflammation may progress to chronic inflammation. This chronic inflammation is thought to underlie the development of so-called smouldering lesions. These lesions evolve from acute inflammatory lesions and are associated with continuous low-grade demyelination and neurodegeneration over many years. Their presence is associated with poor disease prognosis and promotes the transition to progressive MS, which may later manifest clinically as progressive MS when neurodegeneration exceeds the upper limit of functional compensation. In smouldering lesions, in the presence of only moderate inflammatory activity, a toxic environment is clearly identifiable and contributes to the progressive degeneration of neurons, axons, and oligodendrocytes and, thus, to clinical disease progression. In addition to the cells of the immune system, the development of oxidative stress in MS lesions, mitochondrial damage, and hypoxia caused by the resulting energy deficit and iron accumulation are thought to play a role in this process. In addition to classical immune mediators, this chronic toxic environment contains high concentrations of oxidants and iron ions, as well as the excitatory neurotransmitter glutamate. In this review, we will discuss how these pathobiochemical markers and mechanisms, alone or in combination, lead to neuronal, axonal, and glial cell death and ultimately to the process of neuroinflammation and neurodegeneration, and then discuss the concepts and conclusions that emerge from these findings. Understanding the role of these pathobiochemical markers would be important to gain a better insight into the relationship between the clinical classification and the pathomechanism of MS. [ABSTRACT FROM AUTHOR]

The analysis of the gas expansion in the test bench of the ITER DMS Support Laboratory is discussed. For this purpose, numerical FEM simulations were performed during the design phase of the laboratory. These are compared with experimental data, that have been obtained after the construction of the test bench was finished. The numerical and experimental results have been found to agree well. Both indicate the emergence of pressure waves in the acceleration barrel. These contribute to the pellet detachment from the barrel wall. Supersonic velocities have been also observed in the simulations, and an indirect indication for their presence has been found in the experimental results. The main processes during the propellant gas expansion inside the propellant gas recovery chamber are discussed, and a rough estimate for the amount of gas entering the flight tube of the test bench before the pellet is presented. • ITER Disruption Mitigation System Test Bench. • FEM simulation of propellant gas expansion. • Occurrence of pressure waves, shock waves. • Estimations for behaviour with moving pellet. • Experimental validation of simulations. [ABSTRACT FROM AUTHOR]

The onset and disease course of NDDs may well be understood by envisioning a disease in analogy to a position vector: a position being the initial domain of symptoms; magnitude being severity in scales from molecular, tissue, neural correlate, to functional levels; and a direction being the domain of secondary symptoms. The articles published in the Special Issue have featured Alzheimer's disease (AD), Parkinsons's disease (PD), multiple sclerosis (MS), dementia with Lewy bodies, and salicylate-induced tinnitus. This Special Issue has focused on dissecting the neuroprotective and neurodegenerative components of neurological and neuropsychiatric diseases, highlighting the latest advance in understanding the etiology, pathomechanism, biomarkers, imaging techniques, and novel therapeutic targets of neurodegenerative diseases (NDDs). NDDs are multifactorial diseases in which genetic susceptibility, environmental factors, infections, nutrition, and/or lifestyle make a complex interaction to form an initial causative complex which later progresses to formation of secondary complex, eventually leading to the onset of diseases [[1]]. [Extracted from the article]

A method is presented for the swift reconstruction of electron density profiles measured by the alkali beam emission spectroscopy. It is based on the linearization of the governing rate equations and leads to a direct calculation for obtaining the profiles. The uncertainties of the measurement are incorporated into the problem through the utilization of Tikhonov regularization and the generalized least squares method. An approximation for the uncertainty of the reconstructed density data is calculated as well. The applicability of the method is tested against both simulated and real experimental results of the W7-X stellarator. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of visual axis positioning on the optical performance of the Tecnis MIOL and the Diff-aA MIOL. Methods: In this prospective, randomized comparative study, 70 eyes of 35 subjects with senile cataract were implanted with the spherical aberration–correcting diffractive, bifocal Tecnis ZLB00 IOL and 60 eyes of 30 age-matched subjects with the spherical aberration neutral, diffractive, bifocal Diffractiva IOL. Observation procedure was performed 1, 3, and 6 months postoperatively. Main outcome measures included uncorrected and corrected distance and near visual acuity, manifest refraction, ocular aberrations, and visual quality metrics with 2 mm and 4 mm pupil and the position of visual axis. Results: At the 6-month visit, no significant difference was found in monocular and binocular uncorrected (UDVA) and corrected (CDVA) distance and near (UNVA, CNVA) visual acuity between the groups. Spherical and coma-like aberrations were similar measured with a 2-mm pupil, but with a 4-mm pupil, the SA was significantly larger (in negative direction) in the Diffractiva group. The higher-order Strehl ratio and MTF was significantly larger in the Diffractiva group measured at 2 mm entrance pupil; however, this difference disappeared by the 4-mm pupil measurements. Postoperative angle alpha distance had a significant influence on HO Strehl value. Conclusions: The size of angle alpha is a predictive factor of image quality by multifocal IOL patients. Trial Registration: Trial registration number and date of registration: NCT04274088, 14.02.2020. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Considering the devastating symptoms, high prevalence, and lack of definitive diagnostic test, there is an urgent need to identify possible biomarkers and new therapeutic targets. Genes identified and/or proposed to be linked to PD encode proteins that fulfill diverse roles in cellular functions. There is a growing interest in identifying common traits which lead to the disease. Long non-coding RNAs have recently emerged as possible regulatory hubs of complex molecular changes affecting PD development. Among them, NEAT1 has attracted particular interest. It is a major component and the initiator of nuclear paraspeckles, thus regulating transcription and modifying protein functions. This review summarizes data available on the role of NEAT1 in PD. NEAT1 upregulation in PD has repeatedly been reported, however, whether this is part of a protective or a damaging mechanism is still a topic of debate. It has been proposed that NEAT1 propagates PD via its interaction with PINK1 and several micro RNAs and by modulating SNCA expression. On the other hand, findings of NEAT1 acting as a bona fide LRRK2 inhibitor argue for its protective role. These contradictory results could be due to the different disease models implemented. This calls attention to the difficulties posed by the complex patho-mechanisms of neurodegenerative disorders and the limitations of disease models. However, the potential of NEAT1 as a biomarker and as a therapeutic target for PD highly warrants further research to elucidate its exact role in this neurodegenerative disorder. [ABSTRACT FROM AUTHOR]

Monoamine oxidase B (MAO-B) inhibitors have an established role in the treatment of Parkinson's disease as monotherapy or adjuvant to levodopa. Two major recognitions were required for their introduction into this therapeutic field. The first was the elucidation of the novel pharmacological properties of selegiline as a selective MAO-B inhibitor by Knoll and Magyar and the original idea of Riederer and Youdim, supported by Birkmayer, to explore its effect in parkinsonian patients with on–off phases. In the 1960s, MAO inhibitors were mainly studied as potential antidepressants, but Birkmayer found that combined use of levodopa and various MAO inhibitors improved akinesia in Parkinson's disease. However, the serious side effects of the first non-selective MAO inhibitors prevented their further use. Later studies demonstrated that MAO-B, mainly located in glial cells, is important for dopamine metabolism in the brain. Recently, cell and molecular studies revealed interesting properties of selegiline opening new possibilities for neuroprotective mechanisms and a disease-modifying effect of MAO-B inhibitors. [ABSTRACT FROM AUTHOR]

Migraine, a primary headache disorder whose mechanism remains incompletely understood, appears to involve the activation of the trigeminovascular system (TS) during attacks. Research suggests that inflammatory processes mediated by the immune system may play a role in migraine pathophysiology. Neuroinflammation is often associated with migraine attacks, with cytokines serving as crucial mediators in the process. Elevated levels of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), have been observed in the blood and cerebrospinal fluid of individuals experiencing migraine attacks. These cytokines have the capacity to sensitize pain pathways in the brain, thereby increasing sensitivity to pain stimuli. This phenomenon, known as central sensitization, is believed to contribute to the intensity and persistence of migraine pain. Kynurenines, endogenous mediators of glutamatergic mechanisms, can significantly influence the pathophysiology of primary headache disorders. The kynurenine system is collectively known as the kynurenine pathway (KP), which can act on multiple receptors, such as glutamate receptors, aryl hydrocarbon receptors (AhRs), G protein-coupled receptors 35 (GPR35), and α-7 nicotinic acetylcholine (α7 nACh) receptors. These receptors are also found on various cells of the immune system, so the role of the KP in the pathomechanism of primary headaches may also be mediated through them. In this review, our goal is to show a possible link between the receptors of the KP and immune system in the context of inflammation and migraine. Migraine research in recent years has focused on neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as potential pathogenic factors and possible therapeutic approaches. These peptides share many similarities in their characteristics and roles. For instance, they exhibit potent vasodilation, occur in both the peripheral and central nervous systems, and play a role in transmitting nociception and neurogenic inflammation. The investigation of potential connections between the aforementioned neuropeptides and the kynurenine pathway could play a significant role in uncovering the pathomechanism of migraine and identifying new drug candidates. [ABSTRACT FROM AUTHOR]

This document is a summary of an article titled "Navigating the Neurobiology of Migraine: From Pathways to Potential Therapies." The article explores the complex nature of migraines, a neurological disorder characterized by recurring headaches accompanied by sensory disturbances, nausea, and sensitivity to light and sound. It discusses the genetic, environmental, and neurobiological factors involved in migraines and highlights recent advances in migraine research using experimental models. The article also explores the role of neuroplasticity, receptors such as CGRP, TRPV1, and P2X3, and potential therapeutic targets for migraine treatment. The document summarizes specific topic articles on CGRP, tryptophan metabolism, and experimental models in migraine research. It emphasizes the need for collaboration between researchers and clinicians to develop personalized treatment approaches for managing migraines. The goal is to improve patient outcomes and quality of life. [Extracted from the article]

Mild cognitive impairment (MCI) refers to a measurable deficit in cognition in the absence of dementia or impairment in activities of daily living. Working memory impairment is among the earliest signs of MCI. Oscillatory analysis of working memory might be a potential tool for identifying patients at increased risk of developing dementia. Our study aimed to assess the temporospatial pattern of spectral differences during working memory maintenance between MCI patients and healthy controls and to compare the sources of oscillatory activity between the two groups. Event-related spectral perturbation of 17 MCI patients and 21 healthy control participants was studied with 128-channel EEG during the Sternberg working memory task. Source localization was performed by using the eLORETA software. Among the participants, 13 MCI and 15 control participants underwent a structural brain MRI examination. Event-related synchronization (ERS) in the alpha and beta frequency band was significantly lower in MCI patients compared to healthy control participants during retention. Both study groups showed significant memory load-related enhancement in both frequency band. In the MCI group, source localization revealed significantly attenuated beta oscillatory activity in the inferior and middle temporal gyrus, in the fusiform gyrus, and in the cuneus. Beta ERS correlated significantly with the size of the hippocampus, entorhinal cortex, and parahippocampal gyrus. During the retention period, MCI is characterized by decreased alpha and beta ERS compared to controls indicating early impairment in neural networks serving working memory maintenance. The assessment of electrophysiological changes in the beta frequency range may provide a useful diagnostic tool for the early detection of cognitive impairment. [ABSTRACT FROM AUTHOR]

Introduction: The increasing incidence of periprosthetic fractures correlates directly with the year-after-year increasing frequency of primary joint replacement surgery. The most common fracture localisation is the femur. The undisputed leader in frequency is the fracture that occurs around a total hip arthroplasty. Unfortunately, no general epidemiologic data exist dealing with exact fracture incidence numbers. Furthermore, existing classifications are lacking important information like time point of fracture occurrence, type of the implanted prosthesis and implantation technique (cemented vs. cementless). Additionally, information about mechanical quality of the bone structure and the fracture type are also missing in part.Methods: We scanned the literature for adequate and widely used classifications in the field of hip and knee arthroplasty. In a next step we analyzed those classification systems in order to find out to what extent they are able to describe the specific aspects of the fracture event. Therefore we compared the existing classifications and presented their most relevant emphasis. Furthermore, we looked at our own patient population to evaluate incidence of fracture occurrence over time and percentage of loosened components.Results: The existing classification systems address themselves specifically to the task of describing fracture localization and to some extent fracture type, or combine these two in order to calculate the possibility of loosening of the implanted prosthesis. Some of the important criteria like mechanical quality of the bone stock, primary implantation technique or time point of the prosthesis loosening (prior to or because of the fracture) remain ignored. The incidence of periprosthetic femur fractures at our department increased approximately 2.5 fold over the past two decades. The risk of suffering from a periprosthetic fracture was substantially higher after THA than after TKA. We observed a loose femoral component of the THA in about 45 % of the cases. Finally, we postulate the application of a modified classification for periprosthetic fractures as an alternative to the already published ones; not only for the femur, but also universally for all joints with an arthroplasty.Conclusion: The classification that is introduced in this study allows, in our opinion, a differentiated reflection of the given post-traumatic pathologic changes and enables the description of the fracture itself according to a generally accepted fracture classification scheme. [ABSTRACT FROM AUTHOR]

The document "Neural Correlates and Molecular Mechanisms of Memory and Learning" provides an in-depth exploration of the neural and molecular mechanisms involved in memory and learning. It discusses the role of specific brain regions and neurotransmitters in shaping memory and facilitating learning. The document includes a range of studies on topics such as multisensory stimulation, fear extinction learning, and dopamine dynamics. It emphasizes the complexity of memory and learning processes and the need for further research in this field. The text also highlights the importance of preclinical research and computational medicine in understanding cognitive functions and developing personalized treatments. [Extracted from the article]

The intestinal flora has been the focus of numerous investigations recently, with inquiries not just into the gastrointestinal aspects but also the pathomechanism of other diseases such as nervous system disorders and mitochondrial diseases. Mitochondrial disorders are the most common type of inheritable metabolic illness caused by mutations of mitochondrial and nuclear DNA. Despite the intensive research, its diagnosis is usually difficult, and unfortunately, treating it challenges physicians. Metabolites of the kynurenine pathway are linked to many disorders, such as depression, schizophrenia, migraine, and also diseases associated with impaired mitochondrial function. The kynurenine pathway includes many substances, for instance kynurenic acid and quinolinic acid. In this review, we would like to show a possible link between the metabolites of the kynurenine pathway and mitochondrial stress in the context of intestinal flora. Furthermore, we summarize the possible markers of and future therapeutic options for the kynurenine pathway in excitotoxicity and mitochondrial oxidative stress. [ABSTRACT FROM AUTHOR]

Background In diagnosing celiac disease (CD), serological tests are highly valuable. However, their role in following up children with CD after prescription of a gluten-free diet is unclear. This study aimed to compare the performance of antibody tests in predicting small-intestinal mucosal status in diagnosis vs. follow-up of pediatric CD. Methods We conducted a prospective cohort study at a tertiary-care center. 148 children underwent esophohagogastroduodenoscopy with biopsies either for symptoms±positive CD antibodies (group A; n = 95) or following up CD diagnosed ⩾ 1 year before study enrollment (group B; n = 53). Using biopsy (Marsh ⩾ 2) as the criterion standard, areas under ROC curves (AUCs) and likelihood-ratios were calculated to estimate the performance of antibody tests against tissue transglutaminase (TG2), deamidated gliadin peptide (DGP) and endomysium (EMA). Results AUCs were higher when tests were used for CD diagnosis vs. follow-up: 1 vs. 0.86 (P = 0,100) for TG2-IgA, 0.85 vs. 0.74 (P = 0,421) for TG2-IgG, 0.97 vs. 0.61 (P = 0,004) for DPG-IgA, and 0.99 vs. 0.88 (P = 0,053) for DPG-IgG, respectively. Empirical power was 85% for the DPG-IgA comparison, and on average 33% (range 13-43) for the non-significant comparisons. Among group B children, 88.7% showed mucosal healing (median 2.2 years after primary diagnosis). Only the negative likelihood-ratio of EMA was low enough (0.097) to effectively rule out persistent mucosal injury. However, out of 12 EMA-positive children with mucosal healing, 9 subsequently turned EMA-negative. Conclusions Among the CD antibodies examined, negative EMA most reliably predict mucosal healing. In general, however, antibody tests, especially DPG-IgA, are of limited value in predicting the mucosal status in the early years post-diagnosis but may be sufficient after a longer period of time. [ABSTRACT FROM AUTHOR]

Purpose. Popular beliefs exert an impact of lunar phases on elective surgery. The aim of our study was to evaluate potential correlations between complications in cataract surgery and the phases of the moon during its passage through the zodiac and Fridays that fall on the 13th. Methods. Patients with complications during cataract surgery were extracted retrospectively from the clinical database from 2010 to 2014. The dates of surgeries were viewed in relation to the phase and the position of the moon (sign of the zodiac). Results. Of 16,965 cataract surgeries, 132 eyes developed complications. 0.70% developed complications with a waxing moon, and 0.87% with a waning moon (p=0.745). After Bonferroni correction, there were no statistically significant differences between the numbers of complications under the different signs of the zodiac and no complications on Fridays that fell on the 13th. Conclusions. The analysis of “non-moon-fitting days” for surgery showed quantitative differences, without statistically significant findings. Our results revealed more complications when the moon was waning, which is in contrast to esoteric belief. Patients may be informed that phases of the moon, signs of the zodiac, or a particular date will have no impact on their surgeries. [ABSTRACT FROM AUTHOR]

Migraine is a primary headache disorder, which is an enormous burden to the healthcare system. While some aspects of the pathomechanism of migraines remain unknown, the most accepted theory is that activation and sensitization of the trigeminovascular system are essential during migraine attacks. In recent decades, it has been suggested that ion channels may be important participants in the pathogenesis of migraine. Numerous ion channels are expressed in the peripheral and central nervous systems, including the trigeminovascular system, affecting neuron excitability, synaptic energy homeostasis, inflammatory signaling, and pain sensation. Dysfunction of ion channels could result in neuronal excitability and peripheral or central sensitization. This narrative review covers the current understanding of the biological mechanisms leading to activation and sensitization of the trigeminovascular pain pathway, with a focus on recent findings on ion channel activation and modulation. Furthermore, we focus on the kynurenine pathway since this system contains kynurenic acid, which is an endogenous glutamate receptor antagonist substance, and it has a role in migraine pathophysiology. [ABSTRACT FROM AUTHOR]

This document emphasizes the significance of translational research in understanding and treating neurological and psychiatric diseases. It discusses the importance of in vivo and in vitro models in studying the complex mechanisms of these conditions. The document also highlights the role of sex/gender and aging in the development of neuropsychiatric disorders. The research topic includes 25 papers that cover various topics, such as novel preclinical models, research techniques, and the potential of stem-cell-based therapies. These papers provide valuable insights into the underlying pathology of neurological and psychiatric diseases and offer potential avenues for new treatments. The document also discusses the importance of preclinical models in advancing research on these disorders, identifying potential biomarkers, and discovering innovative treatments. It emphasizes the role of neuropharmacological research in developing therapeutic agents and the significance of advanced imaging techniques in studying brain structure and function. The ultimate goal is to improve the quality of life for individuals with these complex mental health conditions through personalized care and support. [Extracted from the article]

The effects of thermal coupling between two thin liquid layers separated by a gas layer are discussed. The liquid layers undergo long-wavelength instabilities driven by gravitational and thermocapillary stresses. To study the dynamics, both a linear stability analysis and a full numerical solution of the thin-film equations are performed. The results demonstrate that the stability properties of the combined system differs substantially from the case where both layers evolve independently from each other. Most prominently, oscillatory instabilities, not present in single-liquid layer configurations, may occur. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that autologous chondrocyte implantation (ACI) has a better treatment effect than microfracture (MF), and increasing superiority over the years, when performed under similar patient-specific and defect-specific conditions. Methods: We scanned four electronic databases for controlled clinical trials or controlled prospective observational studies. We conducted random-effects meta-analyses of equivalent data using standardized mean differences as the outcome measure of choice at 1, 2, and 5-year follow-up. We assessed heterogeneity with the I2 index and publication bias with funnel plots and Kendall’s tests. Results: Our literature search revealed six study populations (nine papers) which satisfied our eligibility criteria. Overall, 399 patients aged between 16 and 60 years with 1–10 cm 2 chondral defects were available. The MF and the ACI study groups were well matched regarding patient baseline characteristics. For all papers, microfracture was performed according to Steadman, whereas three generations of ACI were applied. When all were combined, non-significant superiority of ACI over MF was revealed; surprisingly, this superiority decreased over the years. However, our meta-analyses combining solely second and third-generation ACI revealed significant standardized differences, becoming smaller over the years, but always representing a large effect. Nevertheless, our approximate estimate of the difference between the treatment effects provoked by second and third-generation ACI and by MF is not indicative of clinically relevant superiority of ACI over MF at 5-year follow-up. Conclusions: Both series of meta-analyses (combining either all ACI modifications or solely the second and third generations of ACI) suggest that the treatment effects resulting from ACI and MF converge over the years. [ABSTRACT FROM AUTHOR]

The article focuses on Gerhard Küntscher, who developed intramedullary osteosynthesis and intramedullary locked nailing. It provides a brief history from his birth on December 1, 1900 to his heath on December 17, 1972. It also describes his volunteer service in the German army, research, and success in the academic hierarchy.

. Purpose: Modern therapy of neovascular age-related macular degeneration consists in intravitreal injections of inhibitors of the vascular endothelial growth factor. An increasing number of these injections is required not only in monthly but also in as-needed treatment regimen. In this study, it should be examined whether an additional administered photodynamic therapy (PDT) can considerably reduce the number of injection. Methods: In this prospective, randomized study carried out in three large hospitals of Vienna eyes with neovascular age-related macula degeneration were included. Patients were randomized to either Ranibizumab monotherapy or combined standard fluence PDT and Ranibizumab therapy. All patients received a loading dose of three intravitreal Ranibizumab injections and were thereafter treated in an as-needed regimen based on distance acuity and retinal thickness values. In the combined treatment group, PDT was administered 1 day after the first Ranibizumab injection. Results: Fifty-one patients were randomized, 44 were finally included (four screening failures and three withdrawals). Twenty-four patients were assigned to the monotherapy and 20 patients to the combined treatment group. Fewer injections were required in the combined treatment group (4.7 versus 6.3). Overall the patients lost 0.5 letters; in the combined treatment group, the patients lost mean 7.1 letters; in the monotherapy group, they gained mean 5.1 letters. Retinal thickness decreased significantly in both groups. Conclusion: A significant reduction of the number of required intravitreal injections could be achieved by the additional PDT treatment, but was accompanied by a worse functional outcome in this group. [ABSTRACT FROM AUTHOR]

Various pathologies of the central nervous system (CNS) are accompanied by alterations in tryptophan metabolism. The main metabolic route of tryptophan degradation is the kynurenine pathway; its metabolites are responsible for a broad spectrum of effects, including the endogenous regulation of neuronal excitability and the initiation of immune tolerance. This Review highlights the involvement of the kynurenine system in the pathology of neurodegenerative disorders, pain syndromes and autoimmune diseases through a detailed discussion of its potential implications in Huntington's disease, migraine and multiple sclerosis. The most effective preclinical drug candidates are discussed and attention is paid to currently under-investigated roles of the kynurenine pathway in the CNS, where modulation of kynurenine metabolism might be of therapeutic value. [ABSTRACT FROM AUTHOR]

There is developing interest in the role of the kynurenines in the immune function. A considerable amount of evidence has accumulated as concerns interactions between the kynurenine pathway, cytokines and the nervous system. Indoleamine 2,3-dioxygenase (IDO) occupies a key position connecting the immune system and the kynurenine pathway. There are evidences of the immunosuppressive effect of IDO. Following the interferon (IFN)-mediated activation of antigen presenting cells, the induction of IDO and the kynurenine system exerts a counter-regulating effect, maintaining the homeostasis. Inhibition of T cell functions, activation of the regulatory T cells, and the inhibition of Natural Killer cells are among the important factors in the immunosuppressive effects of IDO and kynurenines. There is a close connection between cytokines (IFN-α, IFN-γ, TNF-α, TGF-β, IL-4 and IL-23) and the kynurenine system, and an imbalance in the TH1/TH2 cytokine profile may possibly lead to neurologic or psychiatric disorders. As the tryptophan metabolic pathway is activated by pro-inflammatory stimuli, the anti-inflammatory effect of kynurenic acid provides a further feedback mechanism in modulating the immune responses. [ABSTRACT FROM AUTHOR]

Abstract: Automated classification of duodenal texture patches with histological ground truth in case of pediatric celiac disease is proposed. The classical focus of classification in this context is a two-class problem: mucosa affected by celiac disease and unaffected duodenal tissue. We extend this focus and apply classification according to a modified Marsh scheme into four classes. In addition to other techniques used previously for classification of endoscopic imagery, we apply local binary pattern (LBP) operators and propose two new operator types, one of which adapts to the different properties of wavelet transform subbands. The achieved results are promising in that operators based on LBP turn out to achieve better results compared to many other texture classification techniques as used in earlier work. Specifically, the proposed wavelet-based LBP scheme achieved the best overall accuracy of all feature extraction techniques considered in the two-class case and was among the best in the four-class scheme. Results also show that a classification into four classes is feasible in principle however when compared to the two-class case we note that there is still room for improvement due to various reasons discussed. [Copyright &y& Elsevier]

Background: Increase of antibiotic resistance is a worldwide problem. Within the 4 years before the turn of the millennium Helicobacter pylori strains isolated in children living in Vienna, Austria, showed a primary clarithromycin and metronidazole resistance of 20% and 16%, respectively. The aim of this retrospective follow-up survey was to assess the further development and current antimicrobial resistance status. Methods: Children having undergone upper endoscopy between March 2002 and March 2008 at the same two co-operating pediatric gastroenterology units which had also been collaborating on the prior assessment were included. H. pylori infection was diagnosed by rapid urease test, histology, and culture. If the latter was positive, susceptibility testing to amoxicillin, clarithromycin and metronidazole by E-test followed. From March 2004 onwards, susceptibility to levofloxacin, tetracycline and rifampin was additionally assessed. Results: Out of 897 children, 153 had a proven infection with H. pylori and no history of prior eradication treatment. Their median age was 11.5 years (range 0.5–20.9 years). Primary resistance to clarithromycin and metronidazole were 34% and 22.9%, respectively; dual resistance was found in 9.8% of the strains; 0.9% was resistant to tetracycline and rifampin, respectively. No case of amoxicillin resistance was detected. The only independent risk factor for clarithromycin resistance turned out to be the origin of a child from Austrian parents. Conclusions: In the last decade, the rate of primary resistance of H. pylori to clarithromycin continued to rise. No significant change was found regarding primary resistance to metronidazole or dual resistance to metronidazole and clarithromycin, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Previous studies have revealed a selective functional loss of the large, high-threshold motor units in the paretic muscles after lesion of the upper motor neuron. We set out to study the degree and the time course of the reorganization of the motor units following a stroke. Methods: Examinations were performed on 59 patients with a unilateral ischemic stroke in the territory of the middle cerebral artery, and on 42 healthy controls. The duration of hemiparesis ranged from 2weeks to 48months. The fiber density (FD) in the abductor digiti minimi muscle was determined by means of single-fiber electromyography on both the hemiparetic and the unaffected side in the patients, and unilaterally in the control subjects. Results: The FD was increased on the hemiparetic side relative to the unaffected side and the control group. This change correlated with the severity of the clinical signs. The FD increased during the first 10months following the stroke and subsequently remained stable. Conclusions: The process of reinnervation in the muscles takes place in the acute phase after stroke. These changes are related to the severity of the symptoms. Significance: Our findings suggest that trans-synaptic degeneration of the spinal motor neurons occurs shortly after the lesion of the upper motor neurons. [Copyright &y& Elsevier]

Abstract: Objective: Previous studies have revealed a loss of functioning motor units in stroke patients. However, it remained unclear whether the motor units are affected randomly or in some specific pattern. We assessed whether there is a selective loss of the large (high recruitment threshold) or the small (low recruitment threshold) motor units following a stroke. Methods: Forty-five stroke patients and 40 healthy controls participated in the study. Macro-EMG was recorded from the abductor digiti minimi muscle at two levels of force output (low and high). The median macro motor unit potential (macro-MUP) amplitude on the paretic side was compared with those on the unaffected side and in the controls. Results: In the control group and on the unaffected side, the macro-MUPs were significantly larger at the high force output than at the low one. However, on the paretic side the macro-MUPs at the high force output had the same amplitude as those recorded at the low force output. These changes correlated with the severity of the paresis. Conclusions: Following a stroke, there is a selective functional loss of the large, high-threshold motor units. These changes are related to the severity of the symptoms. Significance: Our findings furnish further insight into the pathophysiology of the motor deficit following a stroke. [Copyright &y& Elsevier]

The article studies the posterior atlanto-axial arthrodesis of odontoid nonunions and the radiological and clinical long-term results of the procedure. Research findings indicate that there is an overall satisfactory clinical outcome after the surgical treatment of odontoid nonunions in patients with severe motion pain and atlanto-axial instability in the cervical spine.

Purpose: To evaluate the potential benefit of microperimetry and preferential hyperacuity perimeter (PHP) to document visual performance objectively in patients with macular hole and macular pucker undergoing macular surgery. Design: Observational case series. Methods: In 19 patients with macular hole and 18 with macular pucker, best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution units), central retinal sensitivity, and presence and extent of metamorphopsia were documented before and four and 12 weeks after surgery. Macular sensitivity (mean sensitivity decibel [dB], stability of fixation) was determined using MP1 microperimetry (Nidek, Padova, Italy). The PreView-PHP (Carl Zeiss Meditec, Dublin, California, USA) was used to quantify metamorphopsia. Results: Before surgery, mean BCVA was 0.68 ± 0.25 (macular holes) and 0.58 ± 0.25 (macular pucker). Microperimetry demonstrated a mean retinal sensitivity of 11.3 ± 2.5 dB (macular holes) and 10.7 ± 2.8 dB (macular pucker). Twelve weeks after surgery, mean BCVA improved to 0.53 ± 0.26 (macular holes) and 0.33 ± 0.26 (macular pucker; P = .042 and P = .004). Accordingly, retinal sensitivity increased significantly with 12.8 ± 1.9 dB (macular holes) and 12.7 ± 2.5 dB (macular pucker; P = .04 and P = .02) as well as stability of fixation. At 12 weeks, 47.3% of macular hole eyes and 66.7% of macular pucker eyes improved in BCVA, but a significantly higher number (68.4% [macular holes] and 77.8% [macular pucker]) demonstrated improvement in microperimetry results. PHP results showed no significant change of scotomas, patient reliability, or presence of metamorphopsia at any interval. Conclusions: A higher number of patients improved in microperimetry than in visual acuity testing. Therefore, microperimetry highlights the value of functional macular mapping for these patients and indicates that BCVA may underestimate functional benefit of surgery. [Copyright &y& Elsevier]

Hydrosoluble diclofenac epolamine (DHEP) represents an interesting approach to acute migraine attacks, where gastrointestinal motility and drug absorption are often reduced. Its efficacy was investigated in a randomized, crossover, double-blind trial on 155 patients who treated four consecutive mild-to-moderate migraine attacks, either with DHEP (65-mg sachet) or placebo. If pain was not relieved within 1 h, a second dose was given. The total number of treated attacks was 481. A pain-free condition was achieved within 2 h in 45.8% and 25.1% of attacks treated, respectively, with DHEP or placebo ( P < 0.0001), with a therapeutic gain of 20.7%. Time to attack resolution, light and noise sensitivity and impact on working ability were significantly reduced by DHEP compared with placebo. Moreover, significantly fewer patients required a second drug dose or a rescue medication when treated with DHEP than with placebo. No adverse reaction was recorded. In conclusion, DHEP was effective and safe for pain relief in patients with an acute mild-to-moderate migraine attack. [ABSTRACT FROM AUTHOR]

The article offers news briefs about the International Danube Neurology Association of Central and East Europe. The 38th International Danube Symposium was held in Brno, Czech Republic on April 6-8, 2006. According to the Danube Curatorium Meeting, the financial sources of the association from all meetings should be divided 70:30 between the local organizers and the permanent symposium head office in Hungary. The web site of the association consists of several important topics.

Recent US registry data and a European multicenter study described increased risk of peritonitis in young children on peritoneal dialysis (PD). No underlying age-specific risk factors could be defined in these reports. Therefore, we analyzed risk factors for peritonitis in children treated by PD as primary renal replacement therapy at the Kinderdialyse, Vienna, and particularly searched for age-specific aspects. Thirty children (15 boys, mean age 4.6 years) received PD [21 automated peritoneal dialysis (APD), nine continuous ambulatory peritoneal dialysis (CAPD)] for 13 months (3–49 months). During the total observation period of 395 dialysis months, 27 peritonitis episodes were diagnosed (1:14.6 months or 0.82/patient per year). Of our population, 43% remained peritonitis free; seven patients suffered from more than one peritonitis episode. Ten potential risk factors [age, gender, PD modality, duration of PD, exit-site status, urine volume, residual glomerular filtration rate (GFR), Kt/V, normalized protein catabolic rate (nPCR), albumin] and four indices of peritonitis outcome (peritonitis incidence, peritonitis burden, risk of suffering more than one episode of peritonitis and chance of staying free from peritonitis) were analyzed. Our study identified six risk factors in univariate analysis, namely age, APD treatment, exit-site infections, low urinary volume, low residual GFR and low nPCR, which were significantly correlated with two or more of the outcome indices. Multivariate analysis identified exit-site infection and residual urine volume as strong independent predictors. In summary, our study identified several age-dependent and age-independent risk factors for peritonitis in pediatric PD. These data demonstrate that the risk for peritonitis in small children is not pre-determined but might be open to therapeutic interventions, such as optimizing exit-site care, dialysis prescription and nutrition management. [ABSTRACT FROM AUTHOR]

Cardiovascular events are among the most frequent causes for long-term morbidity and mortality in children after renal transplantation. The aim of this study was to analyze the effects of post-transplant changes in arterial hypertension, as assessed by 24-h ambulatory blood pressure measurement (ABPM), on myocardial architecture, as assessed by echocardiography. In a retrospective chart review analysis, 39 children were identified in whom 24-h ABPM and echocardiography had been assessed within a 3-month interval after a mean of 4 years post transplantation; 20 repeated pairs of measurements after a mean of 2 years of follow-up were available to analyze the longitudinal effects of post-transplant changes of blood pressure control on left ventricular mass index (LVMI). Arterial hypertension (59%) and left ventricular hypertrophy (50%) were highly prevalent in children after renal transplantation. Renal allograft function and number of antihypertensive medications, but not ABPM variables, were correlated with LVMI at the initial observation. However, at repeat assessment, a significant correlation between ABPM and LVMI was found. In the longitudinal assessment, left ventricular remodeling was dependent on change of dosage of cyclosporine and interval changes of blood pressure levels. Hence, control of blood pressure correlates with changes of LVMI in children with renal allografts. These results clearly underline the importance of blood pressure control for the maintenance of the myocardial architecture. [ABSTRACT FROM AUTHOR]

Huntington’s disease is an autosomal dominantly inherited progressive neurodegenerative disorder. The mutant gene has been localised to chromosome 4p16.3. The gene product huntingtin is widely distributed in both neurones and extraneuronal tissues. The mutation in Huntington’s disease involves the expansion of a trinucleotide (CAG) repeat encoding glutamine. The etiology of Huntington’s disease is yet unknown but increasing evidence suggests important role of altered gene transcription, mitochondrial dysfunction and excitotoxicity. The expanded polyglutamine stretch leads to a conformational change and abnormal protein-protein interactions. Mutant huntingtin can bind to transcription factors, resulting in reduced levels of acetylated histones. One consequence of this appears to be a decreased expression of genes which may play critical roles in neuronal survival. To date, a number of palliative therapies have been demonstrated to be effective in reducing the motor features, and particularly the chorea, but no treatment is at hand for the other symptoms of Huntington’s disease. However, these treatments produce very limited symptomatic benefit. In the absence of disease-modifying treatment, the other avenue is the neural transplantation.However, recent advances in understanding have furnished new hope that a therapeutic strategy may one day be possible. [ABSTRACT FROM AUTHOR]

ABSTRACT. Purpose: There is increasing evidence that the common respiratory human pathogen Chlamydia pneumoniae has a causative role in atherosclerosis. We investigated the association of this pathogen with acute central retinal artery occlusion (CRAO). Patients and Methods: Sera of 14 consecutive patients with CRAO and of 14 age- and sex-matched control subjects were examined. Antibodies against chlamydial lipopolysaccharide (LPS) and outer membrane proteins of C. pneumoniae were determined by an enzyme-linked immunosorbent assay (ELISA). Results: In the CRAO group, seven patients (50%) were found to be IgA positive, 12 (86%) were IgG positive and one (7%) was IgM positive for chlamydial LPS antibodies. In the control group 36%, 79% and 14% were IgA, IgG and IgM positive, respectively. The results showed no significant difference between the groups. In the CRAO group, IgA, IgG and IgM antibodies to C. pneumoniae were found in 43%, 79% and 0% of subjects, respectively. These findings did not differ significantly from those pertaining to matched controls. Conclusions: These data do not support an association between acute CRAO and current C. pneumoniae infection. [ABSTRACT FROM AUTHOR]

We performed a systematic search and meta-analysis of available literature to determine the safety profile of Cerebrolysin in acute ischemic stroke, filling existing safety information gaps and inconsistent results. We searched EMBASE, PubMed, and Cochrane Databases of Systematic Reviews and Clinical Trials up to the end of February 2021. Data collection and analysis were conducted using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. All safety outcomes were analyzed based on risk ratios (RR) and their 95% confidence intervals. The meta-analysis pooled 2202 patients from twelve randomized clinical trials, registering non-statistically significant (p > 0.05) differences between Cerebrolysin and placebo throughout main and subgroup analyses. The lowest rate of Serious Adverse Events (SAE), as compared to placebo, was observed for the highest dose of Cerebrolysin (50 mL), highlighting a moderate reduction (RR = 0.6). We observed a tendency of superiority of Cerebrolysin regarding SAE in high dose treatment courses for moderate-severe ischemic stroke, suggesting some effect of the agent against adverse events. This comprehensive safety meta-analysis confirms the safety profile for patients treated with Cerebrolysin after acute ischemic stroke, as compared to placebo. [ABSTRACT FROM AUTHOR]

Chronic pain conditions have a high socio-economic impact and represent a burden for patients, and their management is a challenge for healthcare professionals. Chronic migraine is one of the chronic primary headache disorders, which belong to chronic primary pain syndromes as per the new concept of multiple parenting. The aims of this review were to provide an overview of the latest classification systems involving both entities, the epidemiological data, and the currently recommended prophylactic treatment options for chronic migraine. Randomized controlled clinical trials, meta-analyses, real-world data, and review articles were analyzed. Chronic migraine is a prevalent and highly burdensome disease and is associated with high headache-related disability and worsening health-related quality of life. Treatment of chronic migraine includes pharmacological or, in drug-refractory cases, non-pharmacological (e.g., neuromodulatory) approaches. Among pharmacological treatment options, injectable botulinum toxin type A and calcitonin gene-related peptide-targeting human and fully humanized monoclonal antibodies (i.e., eptinezumab, erenumab, fremanezumab, and galcanezumab) are highly recommended in the preventive treatment of chronic migraine. Novel migraine-specific therapies offer a solution for this devastating and difficult-to-treat chronic pain condition. [ABSTRACT FROM AUTHOR]

Migraine is a chronic neurological disorder that affects approximately 12% of the population. The cause of migraine headaches is not yet known, however, when the trigeminal system is activated, neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P (SP) are released, which cause neurogenic inflammation and sensitization. Advances in the understanding of migraine pathophysiology have identified new potential pharmacological targets. In recent years, transient receptor potential (TRP) channels have been the focus of attention in the pathophysiology of various pain disorders, including primary headaches. Genetic and pharmacological data suggest the role of TRP channels in pain sensation and the activation and sensitization of dural afferents. In addition, TRP channels are widely expressed in the trigeminal system and brain regions which are associated with the pathophysiology of migraine and furthermore, co-localize several neuropeptides that are implicated in the development of migraine attacks. Moreover, there are several migraine trigger agents known to activate TRP channels. Based on these, TRP channels have an essential role in migraine pain and associated symptoms, such as hyperalgesia and allodynia. In this review, we discuss the role of the certain TRP channels in migraine pathophysiology and their therapeutic applicability. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography‐purified IVIG; (IGIV‐C) in patients with generalized MG undergoing standard care.Sixty‐two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV‐C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG‐Activities of Daily Living (MG‐ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs).The change in QMG at 24 weeks was −5.1 for IGIV‐C and −3.1 for placebo (p = .187). Seventy percent of patients in the IGIV‐C group had improvement in MG‐ADL (≥2‐point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3‐point decrease) were 70.0% for IGIV‐C versus 59.4% for placebo (p = .442) and 60.0% for IGIV‐C versus 53.1% for placebo (p = .610). IGIV‐C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV‐C arm with one death.Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG. [ABSTRACT FROM AUTHOR]

Migraine is a complex neurovascular disorder, which causes intense socioeconomic problems worldwide. The pathophysiology of disease is enigmatic; accordingly, therapy is not sufficient. In recent years, migraine research focused on tryptophan, which is metabolized via two main pathways, the serotonin and kynurenine pathways, both of which produce neuroactive molecules that influence pain processing and stress response by disturbing neural and brain hypersensitivity and by interacting with molecules that control vascular and inflammatory actions. Serotonin has a role in trigeminal pain processing, and melatonin, which is another product of this pathway, also has a role in these processes. One of the end products of the kynurenine pathway is kynurenic acid (KYNA), which can decrease the overexpression of migraine-related neuropeptides in experimental conditions. However, the ability of KYNA to cross the blood–brain barrier is minimal, necessitating the development of synthetic analogs with potentially better pharmacokinetic properties to exploit its therapeutic potential. This review summarizes the main translational and clinical findings on tryptophan metabolism and certain neuropeptides, as well as therapeutic options that may be useful in the prevention and treatment of migraine. [ABSTRACT FROM AUTHOR]

Motor units (MUs) are recruited according to the size principle. At low force output, macro-motor unit potentials (macro-MUPs) with small amplitude and area are recorded; MUs with large electrical size fire at high force output. Our objective was to elucidate whether this difference is caused by a higher fiber density (FD) of the MUs recruited at high force output. We measured the FD and respectively the amplitude and the area of the macro-MUPs via single-fiber macro electromyography (EMG) recorded at low and high force output in 48 healthy subjects. The macro-MUPs were significantly larger at high force output than at low force. The FD did not differ at the two force levels. Our findings suggest that the larger electrical size of the high recruitment threshold MUs is due not to a higher FD, but to a larger territory. FD is a robust EMG parameter, independent of the level of the force output. Muscle Nerve 40: 112-114, 2009 [ABSTRACT FROM AUTHOR]

The article presents a calendar of events in the field of neurology. The 39th International Danube Symposium in conjunction with: 1st International Congress on ADHD will be held in Germany on June 3-7, 2007. The Teaching Course of Danube Neurology Symposium will be held in Romania on March 21-22, 2007. The 40th International Danube Neurology Symposium will be held in Romania in 2008.

A patient with triosephosphate isomerase (TPI) deficiency exhibited worsening of abnormal involuntary movements of the dystonic type and developed psychiatric symptoms while on selegiline. When selegiline was stopped after 9 years of treatment, abnormal involuntary movements improved to pretreatment level and psychiatric behaviour returned to normal. Monoamine oxidase-B platelet activity was low in this patient. © 2003 Movement Disorder Society [ABSTRACT FROM AUTHOR]

We report an 8-year-old Caucasian boy who presented with steroid-resistant nephrotic syndrome. Renal biopsy showed the cellular variant of focal segmental glomerulosclerosis (FSGS). Within 1 year he received a series of therapies that have induced remission in other patients with this disease, all to no avail (conventional-dose cyclosporin A, methylprednisolone pulse therapy, high-dose cyclosporin A, and therapy with mycophenolate mofetil). He achieved remission after five sessions of plasma exchange. This case argues for aggressive therapy of resistant nephrotic syndrome in the native kidney. Plasma exchange should be considered as a possible rescue therapy arm in future study protocols. [ABSTRACT FROM AUTHOR]

An editorial is presented in which the author discusses that further investigations are needed to check can diffusion magnetic resonance imaging be the future biomarker for measuring therapeutic efficacy in multiple sclerosis. It further suggests that in clinical terms the most important biomarkers are still the T2- and T1-enhancing lesion burden but the conclusion is not definite because the rate of change in diffusion parameters

Background: Working memory (WM) impairment is a common phenomenon after stroke; however, its management in rehabilitation is less researched. This systematic review and meta-analysis aimed to provide a quantitative synthesis of the impact of computerised cognitive training (CCT) and transcranial direct current stimulation (tDCS) on WM span in post-stroke individuals. Methods: The literature search in PubMed, Embase, Scopus, and Cochrane Library focused on randomized controlled trials testing the effect of CCT and tDCS on treated stroke patients as compared to untreated controls. Neuropsychological instruments such as Digit Span Forward/Backward and Visual Span Forward Tests defined the outcome of WM span. After extracting study characteristics and quality assessment using the Cochrane Risk of Bias Tool, we conducted a meta-analysis and meta-regression using standardised mean differences. Results: The search yielded 4142 articles, nine of which (N = 461) fulfilled the inclusion criteria. In the case of CCT, we found significant improvement in Digit Span Backward Test (Z = 2.65, P = 0.008; 95% CI [0.10, 0.67]) and Visual Span Forward Test performance (Z = 3.05, P = 0.002; 95% CI [0.15, 0.69]), while for tDCS, we could not find a sufficient number of studies for the analysis. Furthermore, no significant moderating factor was found in the meta-regression. Conclusions: In conclusion, CCT appears to be a suitable choice to enhance WM span performance after stroke. However, further research is needed to investigate the effect of tDCS due to the limited number of studies. Trial registration: The meta-analysis was conducted according to PRISMA (Preferred Reporting of Systematic Reviews and Meta-Analyses) standards with a PROSPERO registration protocol (ID: CRD42023387182). [ABSTRACT FROM AUTHOR]

Fatigue is one of the most frequent complaints of patients with multiple sclerosis (MS). The Fatigue Impact Scale (FIS), one of the 30 available fatigue questionnaires, is commonly applied because it evaluates multidimensional aspects of fatigue. The chief objectives of this study were to validate FIS and evaluate the psychometric properties of MS patients in Serbia. One hundred and twenty-one (121) MS patients and one hundred and twenty-two (122) age-, gender- and education-matched healthy control (HC) subjects completed the FIS and the Beck Depression Inventory. Internal consistency of the FIS subscales was determined using Cronbach's Alpha Coefficient. Test/retest reliability with an intra-class correlation coefficient (ICC) for each FIS subscale was performed. The total FIS score and subscale scores showed statistically significant differences between the MS patients and the HC subjects in both FIS sessions. Cronbach's Alpha was 0.966. All ICCs were statistically significant (p < 0.05). The Serbian version of this instrument may be useful as a clinical measure for fatigue and functionality in patients with MS. [ABSTRACT FROM AUTHOR]