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Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. The median age of disease onset is around 60 years. From a genetic point of view, PD is basically considered a sporadic, idiopathic disease, however, hereditary components can be detected in 5-10% of patients. Expanding data are available regarding the targeted molecular therapy of the disease.The aim of this current review article is to provide brief clinical and molecular insight into three important genetic forms (LRRK2, SNCA, GBA) of hereditary PD subtypes and to present the human clinical trials in relation to these forms of the disease.These small hereditary subgroups are crucially important in drug development, because the general trend is that clinical trials that treat PD patients as a large group, without any separation, do not meet expectations. As a result, no long term conclusions can currently be drawn regarding the effectiveness of the molecules tested in these phase 1 and 2 studies. Further precise studies are needed in the near future.

A relapszus-remisszió kórformájú sclerosis multiplex kezelési stratégiája az elmúlt évtizedben jelentő­sen megváltozott. Míg korábban az eszkalációs terápia volt az elfogadott terápiás módszer, napjainkban magas betegségaktivitás esetén lehetőségünk van indukciós kezelés indítására is. Vizsgálatunkban az alemtuzumabbal kezelt betegeink regiszterben rögzített adatait dolgoztuk fel. Meg­határoztuk a kezelés hatására a betegek relapszusrátájának, valamint MR-aktivitásának változását. Összehasonlítottuk továbbá ezen adatokat azon két betegcsoport között, amelyeknél indukciós, illetve eszkalációs terápia­ként alkalmaztuk az alemtuzumabot. Rögzítettük az előforduló mellékhatásokat. A vizsgálatban szereplő 49 beteg már túl van a két ciklus alemtuzumabkezelésen. Indukciós terápia­ként kilenc esetben alkalmaztuk a gyógyszert. A kezelés előtti két évben az átlag relapszusráta 1,4 ± 1,0 volt, a kezelést követő két évben ez 0,1 ± 0,3-ra csökkent. A kezelés előtti átlag EDSS-pontszám az indukciós cso­port­ban 2,7 ± 2,2, az eszkalációs csoportban 2,7 ± 1,7 volt. A kezelés után ez indukció esetén 1,6 ± 0,6-ra, eszkaláció esetén 2,5 ± 1,8-re csökkent. Klinikai és MR-progressziót négy betegnél találtunk. A mellékhatásokat tekintve citokinfelszabadulási reakció a betegek 51,0%-ánál (1. ciklus), illetve 24,5%-ánál (2. ciklus) jelentkezett, kezeléssel összefüggő fertőzés 28,6%-uknál fordult elő, autoimmun thyreoiditist a betegek 18,3%-ánál igazoltunk. A kezelt betegek szoros követése és a re­giszter dokumentációja hozzájárul ahhoz, hogy az egyes terápiák placebokontrollált klinikai vizsgálatai által ismert eredményeket a napi gyakorlat adataival összevethessük, továbbá a terápiás szemléletváltás, azaz az indukciós kezelés előnyéről információt kapjunk.

Az elmúlt évek kutatási eredményei bizonyították, hogy a B-lymphocyták döntő szerepet játszanak a sclerosis multiplex (SM) patogenezisében. A betegség folyamatának jobb megértése a B-sejteket célzó antitest-terápiák kifej­lesz­tését eredményezte, amelyek potenciális gyógyszerek lehetnek mind a relapszusos, mind a progresszív SM formáiban. A B-sejt-depletiós terápiák ezért mindinkább előtérbe kerülnek, és meghatározóak a betegség prog­ressziójának csökkentésében. Az első B-sejt-depletáló, anti-CD20 monoklonális antitest a rituximab volt, amit sclerosis multiplexben is vizsgáltak, és a kedvező eredményeket követően újabb gyógyszerek kerültek kifejlesz­tésre, hasonló támadásponttal. 2017-ben az FDA, 2018-ban az EMA is engedélyezte egy másik anti-CD20 mo­noklonális antitest, az ocrelizumab relapszáló-remittáló sclerosis multiplex (RRSM) és primer progresszív sclerosis multiplex (PPSM) terápiájában történő bevezetését. Ez különösen jelentős előrelépés volt a PPSM kezelésében, hiszen ez volt az első gyógyszer, ami bizonyítottan csök­kentette a progressziót PPSM-ben. A B-sejt-depletiós terápia új szereplőjeként nemrégiben lépett színre az ofatumumab, ami egy teljesen humán anti-CD20 mono­klonális antitest. A gyógyszer alkalmazását 2021 már­ciu­sá­ban az EMA is engedélyezte a sclerosis multiplex relapszáló formáiban (RSM). Összefoglalónkban részletesen bemutatjuk a jelenleg SM-ben alkalmazott anti-CD20 monoklonális antitest-terápiák hatásmechanizmusát és hatékonyságát.

Migraine and neuropathic pain (NP) are both painful, disabling, chronic conditions which exhibit some symptom similarities and are thus considered to share a common etiology. The calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant the search for more effective therapeutic targets for pain management. This scoping review focuses on human studies of common pathogenic factors in migraine and NP, with reference to available preclinical evidence to explore potential novel therapeutic targets. CGRP inhibitors and monoclonal antibodies alleviate inflammation in the meninges; targeting transient receptor potential (TRP) ion channels may help prevent the release of nociceptive substances, and modifying the endocannabinoid system may open a path toward discovery of novel analgesics. There may exist a potential target in the tryptophan-kynurenine (KYN) metabolic system, which is closely linked to glutamate-induced hyperexcitability; alleviating neuroinflammation may complement a pain-relieving armamentarium, and modifying microglial excitation, which is observed in both conditions, may be a possible approach. Those are several potential analgesic targets which deserve to be explored in search of novel analgesics; however, much evidence remains missing. This review highlights the need for more studies on CGRP modifiers for subtypes, the discovery of TRP and endocannabinoid modulators, knowledge of the status of KYN metabolites, the consensus on cytokines and sampling, and biomarkers for microglial function, in search of innovative pain management methods for migraine and NP.

Additional file 1: Supplementary Table1. Chromatographic data of the measured TRPmetabolites. Operating software was MassLynx V4.2SCN977. 11 calibrators were prepared to this study. Narrower linear range was obtainedin the case of 5-HIAA (first 6 solution).

Additional file 2: Supplementary Table 2. Applied MRM transition settings for TRP metabolites utilizing Waters TQ-S Micro MS. Analyte levels in human plasma were determined using data mentioned in this table.

Progressive multiple sclerosis (MS) is a chronic disease with a unique pattern, which is histologically classified into the subpial type 3 lesions in the autopsy. The lesion is also homologous to that of cuprizone (CPZ) toxin-induced animal models of demyelination. Aberration of the tryptophan (TRP)-kynurenine (KYN) metabolic system has been observed in patients with MS; nevertheless, the KYN metabolite profile of progressive MS remains inconclusive. In this study, C57Bl/6J male mice were treated with 0.2% CPZ toxin for 5 weeks and then underwent 4 weeks of recovery. We measured the levels of serotonin, TRP, and KYN metabolites in the plasma and the brain samples of mice at weeks 1, 3, and 5 of demyelination, and at weeks 7 and 9 of remyelination periods by ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) after body weight measurement and immunohistochemical analysis to confirm the development of demyelination. The UHPLC-MS/MS measurements demonstrated a significant reduction of kynurenic acid, 3-hydoxykynurenine (3-HK), and xanthurenic acid in the plasma and a significant reduction of 3-HK, and anthranilic acid in the brain samples at week 5. Here, we show the profile of KYN metabolites in the CPZ-induced mouse model of demyelination. Thus, the KYN metabolite profile potentially serves as a biomarker of progressive MS and thus opens a new path toward planning personalized treatment, which is frequently obscured with immunologic components in MS deterioration.

PURPOSE To aid preoperative risk assessment by identifying anatomic parameters corresponding with a higher risk of intraoperative floppy iris syndrome (IFIS) during cataract surgery. METHODS Prospective cohort study of 55 patients with α1-adrenergic receptor antagonist (α1-ARA) treatment and 55 controls undergoing cataract surgery. Anterior segment optical coherence tomography (AS-OCT), video pupilometer, and biometry measurements were performed preoperatively and analyzed regarding anatomic parameters that corresponded with a higher rate of IFIS. Those statistically significant parameters were evaluated with logistic regression analysis and receiver operating characteristic (ROC) curve. RESULTS Pupil diameter was significantly smaller in patients who developed IFIS compared to those who did not develop IFIS (AS-OCT 3.29 ± 0.85 vs. 3.63 ± 0.68, p = 0.03; Pupilometer 3.56 ± 0,87 vs. 3.95 ± 0.67, p = 0.02). Biometric evaluation revealed shallower anterior chambers in the IFIS group (ACD 3.12 ± 0.40 vs. 3.32 ± 0.42, p = 0.02). Cutoff values for 50% IFIS probability (p = 0.5) were PD = 3.18 mm for pupil diameter and ACD = 2.93 mm for anterior chamber depth. ROC curves of combined parameters were calculated for α1-ARA medication with pupil diameter and anterior chamber depth, which yielded an AUC of 0.75 for all IFIS grades. CONCLUSION The combination of biometric parameters with history of α1-ARA medication can improve assessment of risk stratification for IFIS incidence during cataract surgery.

The small molecule non-peptide calcitonin gene-related peptide (CGRP) receptor antagonists named gepants offer a breakthrough novel approach in migraine acute and prophylactic drug treatment. This review aimed to determine the place of gepants in the treatment of episodic and chronic migraine.The new-generation gepants are ubrogepant, atogepant, rimegepant and zavegepant. Ubrogepant is ratified for acute migraine treatment, atogepant is validated for preventive therapy, whereas rimegepant is retified for both indications, all via oral administration, while zavegepant is administered intranasally for migraine attacks. Gepants are effective, safe, and well-tolerated in the acute or prophylactic therapy. The PubMed literature search included randomized controlled trials, meta-analyses, real-world data, and review articles published in English until January 2023.Whether gepants will be real game changers in the acute treatment of migraine compared to triptans and ditans, or in the prophylactic therapy compared to standard-of-care preventive drugs or CGRP-targeting monoclonal antibodies can not be answered yet based on the available literature data.

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.

PURPOSE The purpose of the study was to evaluate glaucoma patients' quality of life (QoL) as measured by National Eye Institute Visual Functioning Questionnaire (NEI VFQ-39) and to examine the influence of patient characteristics and disease stage measured by visual field loss on QoL. METHODS A prospective survey of patients with an established diagnosis of glaucoma without concomitant eye disease was conducted. Patients completed a validated German translation of the NEI VFQ-39 questionnaire. Visual field defects were graded using simplified Hodapp's classification. VFQ-39 scores were compared between groups. RESULTS We included 60 patients, 28 of whom were classified as early, 16 as moderate, and 16 as advanced stage glaucoma. No differences were found in sex, visual acuity of the better eye, near visual acuity, treatment type, and VFQ rating for "General health" between groups. In the advanced group, VFQ-39 (p = 0.01) and VFQ-25 (p = 0.01) composite scores were significantly lower than in the early group. In addition, distance visual acuity (worse eye) was significantly worse in the advanced than in early stage patients (p = 0.04, Table 4). Patients with advanced glaucoma had significantly lower VFQ-39 subscale scores for "General vision" (p = 0.023), "Near activities" (p = 0.02), "Distance activities" (p = 0.003), "Mental health" (p = 0.008), "Driving" (p = 0.011), and "Peripheral vision" (p = 0.017) than early glaucoma patients. Patients with moderate glaucoma had significantly lower scores for "Distance activities" (p = 0.028) than early stage glaucoma patients. VFI (better eye: r = 0.65, worse eye: r = 0.5) and MD (better eye: r = 0.6, worse eye: r = 0.49) were significantly (p

Therapeutic strategy of relapse-remitting multiple sclerosis has changed significantly during the past decade. While earlier escalating therapy was widely applied, recently, in case of high disease activity, induction therapy has become available.In our study, we processed the data of our alemtuzumab treated patients from our register. Alte-ra-tions in relapse rate and MRI activity due to the treatment were determined. These data were compared in patients treated with alemtuzumab as an escalating and as an induction therapy. We noted the observed side effects.The 49 patients observed in the study had undergone two cycles of alemtuzumab therapy. The drug was applied as an induction therapy in 9 cases. Average relapse rate during the two years was 1.4±1.0, which decreased to 0.1±0.3 in the two years following the therapy. The average EDSS before therapy was 2.7±2.2 in the induction therapy group and 2.7±1.7 in the escalating therapy group. After the treatment, this score decreased to 1.6±0.6 and 2.5±1.8 in the induction and the escalating therapy group, respectively. We found clinical and MRI progression in case of 4 patients. As regards to side effects, cytokine release was detected in 51.0% of the patients following the first cycle, and 24.5% of the patients following the second cycle of the therapy. Infection related to the therapy was observed in 28.6%, while autoimmune thyreoiditis was diagnosed in 18.3% of the patients.The tight follow-up of the treated patients and the precise documentation of the register enable the comparison of results yielded by placebo controlled clinical studies with daily practice, as well as to gain information on the benefits of induction therapy as a paradigm shift in treating MS patients.pA relapszus-remisszioacute; koacute;rformaacute;juacute; sclerosis multiplex kezeleacute;si strateacute;giaacute;ja az elmuacute;lteacute;vtizedben jelentőshy;sen megvaacute;ltozott. Miacute;g koraacute;bban az eszkalaacute;cioacute;s teraacute;pia volt az elfogadott teraacute;piaacute;s moacute;dszer, napjainkban magas betegseacute;gaktivitaacute;s eseteacute;n lehetőseacute;guuml;nk van indukcioacute;s kezeleacute;s indiacute;taacute;saacute;ra is./p.pVizsgaacute;latunkban az alemtuzumabbal kezelt betegeink regiszterben rouml;gziacute;tett adatait dolgoztuk fel. Megshy;hataacute;roztuk a kezeleacute;s hataacute;saacute;ra a betegek relapszusraacute;taacute;jaacute;nak, valamint MR-aktivitaacute;saacute;nak vaacute;ltozaacute;saacute;t.Ouml;sszehasonliacute;tottuk tovaacute;bbaacute; ezen adatokat azon keacute;t betegcsoport kouml;zouml;tt, amelyekneacute;l indukcioacute;s, illetve eszkalaacute;cioacute;s teraacute;piashy;keacute;nt alkalmaztuk az alemtuzumabot. Rouml;gziacute;tettuuml;k az előforduloacute; melleacute;khataacute;sokat./p.pA vizsgaacute;latban szereplő 49 beteg maacute;r tuacute;l van a keacute;t ciklus alemtuzumabkezeleacute;sen. Indukcioacute;s teraacute;piashy;keacute;nt kilenc esetben alkalmaztuk a gyoacute;gyszert. A kezeleacute;s előtti keacute;teacute;vben azaacute;tlag relapszusraacute;ta 1,4plusmn; 1,0 volt, a kezeleacute;st kouml;vető keacute;teacute;vben ez 0,1plusmn; 0,3-ra csouml;kkent. A kezeleacute;s előttiaacute;tlag EDSS-pontszaacute;m az indukcioacute;s csoshy;portshy;ban 2,7plusmn; 2,2, az eszkalaacute;cioacute;s csoportban 2,7plusmn; 1,7 volt. A kezeleacute;s utaacute;n ez indukcioacute; eseteacute;n 1,6plusmn; 0,6-ra, eszkalaacute;cioacute; eseteacute;n 2,5plusmn; 1,8-re csouml;kkent. Klinikaieacute;s MR-progresszioacute;t neacute;gy betegneacute;l talaacute;ltunk. A melleacute;khataacute;sokat tekintve citokinfelszabadulaacute;si reakcioacute; a betegek 51,0%-aacute;naacute;l (1. ciklus), illetve 24,5%-aacute;naacute;l (2. ciklus) jelentkezett, kezeleacute;sselouml;sszefuuml;ggő fertőzeacute;s 28,6%-uknaacute;l fordult elő, autoimmun thyreoiditist a betegek 18,3%-aacute;naacute;l igazoltunk./p.pA kezelt betegek szoros kouml;veteacute;seeacute;s a reshy;giszter dokumentaacute;cioacute;ja hozzaacute;jaacute;rul ahhoz, hogy az egyes teraacute;piaacute;k placebokontrollaacute;lt klinikai vizsgaacute;lataiaacute;ltal ismert eredmeacute;nyeket a napi gyakorlat adataivalouml;sszevethessuuml;k, tovaacute;bbaacute; a teraacute;piaacute;s szemleacute;letvaacute;ltaacute;s, azaz az indukcioacute;s kezeleacute;s előnyeacute;ről informaacute;cioacute;t kapjunk./p.

A migraine is a neurological condition that can cause multiple symptoms. It is up to three times more common in women than men, thus, estrogen may play an important role in the appearance attacks. Its exact pathomechanism is still unknown; however, the activation and sensitization of the trigeminal system play an essential role. We aimed to use an animal model, which would better illustrate the process of repeated episodic migraine attacks to reveal possible new mechanisms of trigeminal pain chronification. Twenty male (M) and forty ovariectomized (OVX) female adult rats were used for our experiment. Male rats were divided into two groups (M + SIF, M + IS), while female rats were divided into four groups (OVX + SIF, OVX + IS, OVX + E2 + SIF, OVX + E2 + IS); half of the female rats received capsules filled with cholesterol (OVX + SIF, OVX + IS), while the other half received a 1:1 mixture of cholesterol and 17β-estradiol (OVX + E2 + SIF, OVX + E2 + IS). The animals received synthetic interstitial fluid (SIF) (M + SIF, OVX + SIF, OVX + E2 + SIF) or inflammatory soup (IS) (M + IS, OVX + IS, OVX + E2 + IS) treatment on the dural surface through a cannula for three consecutive days each week (12 times in total). Behavior tests and immunostainings were performed. After IS application, a significant decrease was observed in the pain threshold in the M + IS (0.001 < p < 0.5), OVX + IS (0.01 < p < 0.05), and OVX + E2 + IS (0.001 < p < 0.05) groups compared to the control groups (M + SIF; OVX + SIF, OVX + E2 + SIF). The locomotor activity of the rats was lower in the IS treated groups (M + IS, 0.01 < p < 0.05; OVX + IS, p < 0.05; OVX + E2 + IS, 0.001 < p < 0.05), and these animals spent more time in the dark room (M + IS, p < 0.05; OVX + IS, 0.01 < p < 0.05; OVX + E2 + IS, 0.001 < p < 0.01). We found a significant difference between M + IS and OVX + E2 + IS groups (p < 0.05) in the behavior tests. Furthermore, IS increased the area covered by calcitonin gene-related peptide (CGRP) immunoreactive (IR) fibers (M + IS, p < 0.01; OVX + IS, p < 0.01; OVX + E2 + IS, p < 0.001) and the number of neuronal nitric oxide synthase (nNOS) IR cells (M + IS, 0.001< p < 0.05; OVX + IS, 0.01 < p < 0.05; OVX + E2 + IS, 0.001 < p < 0.05) in the caudal trigeminal nucleus (TNC). There was no difference between M + IS and OVX + IS groups; however, the area was covered by CGRP IR fibers (0.01 < p < 0.05) and the number of nNOS IR cells was significantly higher in the OVX + E2 + IS (p < 0.05) group than the other two IS- (M + IS, OVX + IS) treated animals. Overall, repeated administration of IS triggers activation and sensitization processes and develops nociceptive behavior changes. CGRP and nNOS levels increased significantly in the TNC after IS treatments, and moreover, pain thresholds and locomotor activity decreased with the development of photophobia. In our model, stable high estradiol levels proved to be pronociceptive. Thus, repeated trigeminal activation causes marked behavioral changes, which is more prominent in rats treated with estradiol, also reflected by the expression of the sensitization markers of the trigeminal system.

Migraine is a primary headache disorder characterized by a unilateral, throbbing, pulsing headache, which lasts for hours to days, and the pain can interfere with daily activities. It exhibits various symptoms, such as nausea, vomiting, sensitivity to light, sound, and odors, and physical activity consistently contributes to worsening pain. Despite the intensive research, little is still known about the pathomechanism of migraine. It is widely accepted that migraine involves activation and sensitization of the trigeminovascular system. It leads to the release of several pro-inflammatory neuropeptides and neurotransmitters and causes a cascade of inflammatory tissue responses, including vasodilation, plasma extravasation secondary to capillary leakage, edema, and mast cell degranulation. Convincing evidence obtained in rodent models suggests that neurogenic inflammation is assumed to contribute to the development of a migraine attack. Chemical stimulation of the dura mater triggers activation and sensitization of the trigeminal system and causes numerous molecular and behavioral changes; therefore, this is a relevant animal model of acute migraine. This narrative review discusses the emerging evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology of migraine, presenting the most recent advances in preclinical research and the novel therapeutic approaches to the disease.

The tryptophan-kynurenine metabolic pathway plays the most essential role in tryptophan metabolism, producing various endogenous bioactive molecules. The activation of the metabolic pathway is linked to the pathogenesis of a wide range of diseases. The calibration of the levels and the ratio of kynurenines has been attempted in search of biomarkers and diagnostic targets. This editorial introduces biosystems in close interaction with the kynurenine system and potential measures to assess a state of stress, which may lead to illnesses.

Research results in recent years have demonstrated that B-lymphocytes play a crucial role in the pathogenesis of multiple sclerosis (MS). The increased understanding of the disease process has resulted in the development of B cell-targeting antibodies as potential drugs for both relapsing and progressive forms of MS. Therefore, B-cell depletion therapies are becoming more prominent and determining in reducing disease progression. The first B-cell depleting anti-CD20 monoclonal antibody was rituximab, which has also been studied in MS and, following favourable results, new drugs have been developed with a similar point of attack. In 2017, the FDA and in 2018, the EMA approved ocrelizumab, another anti-CD20 monoclonal antibody, for the treatment of relapsing-remitting (RRMS) and primary progressive multiple sclerosis (PPMS). This was a particularly significant advance in the treatment of PPMS, as it was the first medication with a proven effect of reducing progression in PPMS. Ofatumumab, a fully human anti-CD20 monoclonal antibody, has emerged recently as a new player in B-cell depletion therapy. The drug has also recently been approved by the EMA in March 2021 for use in relapsing forms of MS. In this review, we detail the mechanism of action and efficacy of anti-CD20 therapies currently used in MS.Az elmúlt évek kutatási eredményei bizonyították, hogy a B-lymphocyták döntő szerepet játszanak a sclerosis multiplex (SM) patogenezisében. A betegség folyamatának jobb megértése a B-sejteket célzó antitest-terápiák kifej­lesz­tését eredményezte, amelyek potenciális gyógyszerek lehetnek mind a relapszusos, mind a progresszív SM formáiban. A B-sejt-depletiós terápiák ezért mindinkább előtérbe kerülnek, és meghatározóak a betegség prog­ressziójának csökkentésében. Az első B-sejt-depletáló, anti-CD20 monoklonális antitest a rituximab volt, amit sclerosis multiplexben is vizsgáltak, és a kedvező eredményeket követően újabb gyógyszerek kerültek kifejlesz­tésre, hasonló támadásponttal. 2017-ben az FDA, 2018-ban az EMA is engedélyezte egy másik anti-CD20 mo­noklonális antitest, az ocrelizumab relapszáló-remittáló sclerosis multiplex (RRSM) és primer progresszív sclerosis multiplex (PPSM) terápiájában történő bevezetését. Ez különösen jelentős előrelépés volt a PPSM kezelésében, hiszen ez volt az első gyógyszer, ami bizonyítottan csök­kentette a progressziót PPSM-ben. A B-sejt-depletiós terápia új szereplőjeként nemrégiben lépett színre az ofatumumab, ami egy teljesen humán anti-CD20 mono­klonális antitest. A gyógyszer alkalmazását 2021 már­ciu­sá­ban az EMA is engedélyezte a sclerosis multiplex relapszáló formáiban (RSM). Összefoglalónkban részletesen bemutatjuk a jelenleg SM-ben alkalmazott anti-CD20 monoklonális antitest-terápiák hatásmechanizmusát és hatékonyságát.

Nearly half a century has passed since the discovery of cytoplasmic inheritance of human chloramphenicol resistance. The inheritance was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, a number of mutations in mtDNA were identified as a cause of severe inheritable metabolic diseases with neurological manifestation, and the impairment of mitochondrial functions has been probed in the pathogenesis of a wide range of illnesses including neurodegenerative diseases. Recently growing number of preclinical studies has revealed that animal behaviors are influenced by the impairment of mitochondrial functions and possibly by the loss of mitochondrial stress resilience. Indeed, as high as 54% of patients with one of the most common primary mitochondrial diseases, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, present psychiatric symptoms including cognitive impairment, mood disorder, anxiety, and psychosis. Mitochondria are multifunctional organelles which produce cellular energy and play a major role in other cellular functions including homeostasis, cellular signaling, and gene expression, among other. Mitochondrial functions are observed to be compromised and to become less resilient under continuous stress. Meanwhile, stress and inflammation have been linked to the activation of the tryptophan (Trp)-kynurenine (KYN) metabolic system, which observably contributes to development of pathological conditions including neurological and psychiatric disorders. This narrative review discusses the functions of mitochondria and the Trp-KYN system, the interaction of the Trp-KYN system with mitochondria, and the current understanding of the involvement of mitochondria and the Trp-KYN system in preclinical and clinical studies of major neurological and psychiatric diseases.

Seit mehreren Jahrzehnten werden die Auswirkungen von Konservierungsmitteln in Augentropfen in vitro und in vivo beforscht und klinisch untersucht. Nachweislich schadigen Konservierungsmittel die Zellen der Oberflache des Auges (Bindehaut, Hornhaut), penetrieren jedoch auch ins Auge und verandern dort ebenso Strukturen (Trabekelwerk). Trockenes Auge und Glaukom sind chronische Erkrankungen, die meist einer Dauertherapie bedurfen. Dadurch reichern sich toxische Stoffe im Auge an. Es wird ein Uberblick uber den Stellenwert der konservierungshaltigen und -freien Antiglaukomatosa gegeben. Es wurden einige der zahlreichen Publikationen betreffend dieses Thema inhaltlich zusammengefasst. Dass sich Konservierungsmittel in Antiglaukomatosa schadigend auswirken, ist evident. Bei den meist alteren Glaukompatienten besteht oft zusatzlich ein trockenes Auge. Subjektive Symptome und objektive Zeichen treten gehauft auf oder verschlechtern sich. Dazu zahlen Jucken, Brennen, Stechen, Fremdkorpergefuhl, Trockenheitsgefuhl sowie Blepharitis, Meibomitis, Abnahme der Muzinschicht, Anfarbbarkeit der Hornhaut bis zur Keratitis filiformis und im schlimmsten Fall die Ausbildung eines Pseudopemphigoids. Nicht immer lassen sich Allergie, Toxizitat, Unvertraglichkeit und Uberempfindlichkeit voneinander klar trennen, da die Schadigungen komplex sind. Nicht alle Patienten benotigen konservierungsfreie Antiglaukomatosa – aber viele profitieren von einem Wechsel. Spezielle Fragebogen und zielgerichtete Untersuchungen auf Risikofaktoren erleichtern die Entscheidung. Risikogruppen bedurfen a priori einer konservierungsmittelfreien Glaukomtherapie. Sorgfaltige Befragung und Untersuchungen helfen, diese Patienten zu finden und entsprechend zu behandeln. Bei subjektiven Beschwerden und objektiven Befunden einer Augenoberflachenerkrankung ist eine Umstellung auf konservierungsfreie Antiglaukomatosa sinnvoll.

Parkinson’s disease (PD) is a neurodegenerative disease caused by complex interaction between genetic and environmental factors. There is a growing body of evidence of the involvement of sirtuins (SIRTs) in disease pathomechanism. SIRTs are NAD+-dependent histone deacetylases which take part in various cellular functions. However, available data of the relationship between SIRT gene polymorphisms and PD is limited. Our aim was to investigate the possible association of 10 SNPs identified within non-mitochondrial SIRTs, SIRT1, -2 and -6 with the risk of PD in Hungarian population, and to compare the expression level of these SIRTs between healthy controls and PD patients. Our results showed that rs3740051 and rs3818292 of SIRT1 and rs350843, rs350844, rs107251, rs350845 and rs350846 of SIRT6 show weak association with PD risk. On the contrary rs12778366 and rs3758391 of SIRT1 and rs10410544 of SIRT2 did not show association with PD. Moreover, we detected that mRNA level of SIRT1 was down-regulated, and mRNA level of SIRT6 was up-regulated, while SIRT2 mRNA level was not altered in the peripheral blood of PD patients as compared to controls. The difference in both cases was more pronounced when comparing the early-onset PD group to the control cohort. Nevertheless, mRNA level changes did not show any association with the presence of any of the investigated SNPs either in the PD or in the control group. In conclusion, our findings suggest that non-mitochondrial sirtuins, SIRT1 and -6 but not SIRT2 might contribute to the pathogenesis of PD in the Hungarian population both via their altered mRNA levels and via gene alterations identified as specific SNPs.

Nearly 30 years have passed since the first selective 5-HT1 receptor agonist sumatriptan became a choice of treatment for migraineurs. Recently, a new class of antimigraine drugs has joined antimig...

Autoimmune pancreatitis is a rare, distinct and increasingly recognized form of chronic inflammatory pancreatic disease secondary to an underlying autoimmune mechanism. We report on a 14-year-old boy who developed autoimmune pancreatitis, while he was under treatment with eltrombopag for chronic immune thrombocytopenia. Therapy with corticosteroids resulted in complete remission of both. This is the first report on the co-occurrence of autoimmune pancreatitis and chronic immune thrombocytopenia in childhood, and clinicians should be aware of this rare association, because early diagnosis and therapy of autoimmune pancreatitis may prevent severe complications.

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.

To evaluate the effect of visual axis positioning on the optical performance of the Tecnis MIOL and the Diff-aA MIOL. 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. 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. The size of angle alpha is a predictive factor of image quality by multifocal IOL patients. Trial registration number and date of registration: NCT04274088, 14.02.2020.

Diffuse midline gliomas, H3 K27M-mutant, World Health Organization (WHO) grade IV represent a distinct glioma entity with a predominantly paediatric presentation and remarkably poor prognosis. This report presents a case of a 73-year-old woman with a diffuse midline glioma, H3 K27M-mutant, WHO grade IV with a remarkable longitudinal extension, extending from the cervical myelon to the basal ganglia. On imaging, the lesion was predominantly suggestive of inflammatory oedema, and it was clinically associated with progressive hemi- and later tetraparesis with severe autonomic and bulbar symptoms. Laboratory examinations suggested a generalized inflammatory process; however, neither infectious nor autoimmune aetiology could be confirmed. Biopsy was deemed unfeasible given the critical localization. Presuming a seronegative autoimmune encephalomyelitis, high-dose corticosteroid therapy and plasma exchanges were conducted, resulting in a modest but transient relief. The patient passed away two months after hospitalization. Neuropathological examination of the lesion revealed a high-grade diffuse glioma with H3 K27M mutation (grade IV). Although originally considered as a paediatric entity, our case confirms reports from recent years that diffuse midline gliomas, H3 K27M-mutant, WHO grade IV can occur in adults, even among the elderly, and can mimic inflammatory alterations, posing diagnostic difficulty. Our case is one of the oldest patients reported with this pathology, the oldest with an extensive diffusely infiltrating growth pattern, and with the most extensive lesion reported in adulthood.

Background Migraine is a primary headache with genetic susceptibility, but the pathophysiological mechanisms are poorly understood, and it remains an unmet medical need. Earlier we demonstrated significant differences in the transcriptome of migraineurs' PBMCs (peripheral blood mononuclear cells), suggesting the role of neuroinflammation and mitochondrial dysfunctions. Post-transcriptional gene expression is regulated by miRNA (microRNA), a group of short non-coding RNAs that are emerging biomarkers, drug targets, or drugs. MiRNAs are emerging biomarkers and therapeutics; however, little is known about the miRNA transcriptome in migraine, and a systematic comparative analysis has not been performed so far in migraine patients. Methods We determined miRNA expression of migraineurs’ PBMC during (ictal) and between (interictal) headaches compared to age- and sex-matched healthy volunteers. Small RNA sequencing was performed from the PBMC, and mRNA targets of miRNAs were predicted using a network theoretical approach by miRNAtarget.com™. Predicted miRNA targets were investigated by Gene Ontology enrichment analysis and validated by comparing network metrics to differentially expressed mRNA data. Results In the interictal PBMC samples 31 miRNAs were differentially expressed (DE) in comparison to healthy controls, including hsa-miR-5189-3p, hsa-miR-96-5p, hsa-miR-3613-5p, hsa-miR-99a-3p, hsa-miR-542-3p. During headache attacks, the top DE miRNAs as compared to the self-control samples in the interictal phase were hsa-miR-3202, hsa-miR-7855-5p, hsa-miR-6770-3p, hsa-miR-1538, and hsa-miR-409-5p. MiRNA-mRNA target prediction and pathway analysis indicated several mRNAs related to immune and inflammatory responses (toll-like receptor and cytokine receptor signalling), neuroinflammation and oxidative stress, also confirmed by mRNA transcriptomics. Conclusions We provide here the first evidence for disease- and headache-specific miRNA signatures in the PBMC of migraineurs, which might help to identify novel targets for both prophylaxis and attack therapy.

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) [...]

Background During the first wave of the coronavirus disease 2019 (COVID-19) pandemic in 2020 outpatient care of neovascular age-related macular degeneration (nAMD) patients was severely reduced due to lockdown. Missed visits are known to be detrimental to patients in need of continued anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVIs). The purpose of the study was to assess the effect of a month-long pause of regular visits and anti-VEGF IVIs in nAMD patients. Methods A retrospective study was performed. Patients were treated in a pro re nata (“as needed”) scheme. Distance (logMAR) and near (logRAD) visual acuity (VA), optical coherence tomography, delay between planned and actual visit date and the indication for IVI were assessed for 3 continous visits in the 6 months before lockdown (V-3, -2, -1) and the 2 visits after lockdown (V0, V + 1). For analysis of long-term impact, records for visits 1 years before and after lockdown (V-3, V + 2) were gathered. Results We included 166 patients (120 female, 46 male) with a median (range) age of 80.88 (59.8–99.36) years. Compared to V-1, distance VA was significantly worse at both V0 (0.27 ± 0.21 vs 0.31 ± 0.23 logMAR, p p = 0.021). Near VA was significantly worse at both V0 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.037) and V + 1 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.02). Visit delay (VD) at V0 was significantly longer than at V + 1 (30.81 ± 20.44 vs 2.02 ± 6.79 days, p p = 0.0223). There was a significant loss of distance VA (p = 0.02) in the year after the lockdown period (n = 125) compared to the year before. Loss of reading acuity was not significantly increased (p = 0.3). One year post lockdown, there was no correlation between VA change and visit delay after lockdown (p > 0.05). Conclusions In nAMD patients whose visits and treatment were paused for a month during the first wave of the COVID-19 pandemic, we found a loss of VA immediately after lockdown, which persisted during follow-up despite re-established anti-VEGF treatment. In the short term, length of delay was predictive for loss of reading VA. The comparison of development of VA during the year before and after the lockdown showed a progression of nAMD related VA loss which may have been accelerated by the disruption of regular visits and treatment. Trial registration This article does not report the outcome of a health care intervention. This retrospective study was therefore not registered in a clinical trials database.

Relapsing-remitting multiple sclerosis (RRMS) is a degenerative, inflammatory disease of the central nervous system in which symptoms and disability progression vary significantly among patients. Teri-REAL was a prospective, real-world observational study that examined quality-of-life (QoL) and treatment outcomes in a Hungarian cohort of RRMS patients treated with once-daily oral teriflunomide. QoL was assessed at baseline, 12, and 24 months with the Multiple Sclerosis Quality of Life-54 (MSQoL-54) questionnaire. Other measurements included disease progression (Patient Determined Disease Steps [PDDS]), clinical efficacy (relapses), fatigue (Fatigue Impact Scale [FIS]), depression (Beck Depression Inventory [BDI]), cognition (Brief International Cognitive Assessment in MS [BICAMS]), persistence and safety. 212 patients were enrolled (69.1% female, 50.5% treatment naïve), with 146 (69%) completing the study. Statistically significant improvements in subscales of the MSQoL-54 versus baseline were found at Month 12 and Month 24. Significant improvements were also observed for individual components of the BICAMS score at 24 months, while PDDS, FIS and BDI scores remained stable. The mean annualised relapse rate was 0.08 ± 0.32. There were 93 safety events, most of which were mild to moderate. Improved QoL and cognitive outcomes in teriflunomide-treated patients over 2 years offer a unique perspective to this real-world study.

In 2018 multiple sclerosis (MS) care unit (MSCU) recommendations were defined. Nevertheless, the information on MS care, and whether MS centres fulfil the international recommendation is limited. Thus our objectives were to assess whether centres meet the MSCU recommendations and gain a comprehensive overview of MS care in Central-Eastern European countries.A self-report questionnaire assessing aspects of the MSCU recommendations, disease-modifying therapy (DMT) and registry use and the patient number was assembled and sent to nine Central-Eastern European countries. Furthermore, one Danish and one German centre were contacted as a reference.In 9/9 countries, MS care was pursued in centres by MS neurologists and MS nurses. In Austria and the Czech Republic, management of MS was conducted under strict regulations displaying a referral centre system, fundamentally similar to but independent of the MSCU criteria. Several centres fulfilled all aspects of the MSCU criteria, while others had similar insufficiencies consisting of a speech therapist, continence, pain and spasticity specialist, neuro-ophthalmologist, and oto-neurologist. In 9/9 countries, DMTs were reimbursed. However, some centres did not provide every available DMT. A national registry was available in 4/9 countries with mandatory registry use only in Austria and the Czech Republic.In countries where MSCU recommendations are not fulfilled, a strictly regulated centre system similar to the Austrian and Czech model with a registry-based quality control might ensure appropriate care for people with MS.

Relapsing-remitting multiple sclerosis (RRMS) is a degenerative, inflammatory disease of the central nervous system in which symptoms and disability progression vary significantly among patients. Teri-REAL was a prospective, real-world observational study that examined quality-of-life (QoL) and treatment outcomes in a Hungarian cohort of RRMS patients treated with once-daily oral teriflunomide. QoL was assessed at baseline, 12, and 24 months with the Multiple Sclerosis Quality of Life-54 (MSQoL-54) questionnaire. Other measurements included disease progression (Patient Determined Disease Steps [PDDS]), clinical efficacy (relapses), fatigue (Fatigue Impact Scale [FIS]), depression (Beck Depression Inventory [BDI]), cognition (Brief International Cognitive Assessment in MS [BICAMS]), persistence and safety. 212 patients were enrolled (69.1% female, 50.5% treatment naïve), with 146 (69%) completing the study. Statistically significant improvements in subscales of the MSQoL-54 versus baseline were found at Month 12 and Month 24. Significant improvements were also observed for individual components of the BICAMS score at 24 months, while PDDS, FIS and BDI scores remained stable. The mean annualised relapse rate was 0.08 ± 0.32. There were 93 safety events, most of which were mild to moderate. Improved QoL and cognitive outcomes in teriflunomide-treated patients over 2 years offer a unique perspective to this real-world study.

Due to the coronavirus disease 2019 (COVID-19) pandemic, nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great concern to clinicians of all specialties. Currently there are no published data available on the prevalence of the infection in ophthalmology patients presenting for intravitreal injection (IVI). The purpose of this retrospective study was to estimate the prevalence of SARS-CoV‑2 infection in patients presenting for IVI at our hospital.Patients presenting for IVI in April 2020 at our hospital who had been screened for SARS-CoV‑2 infection using nasopharyngeal and oropharyngeal specimen for real-time reverse transcription polymerase chain reaction analysis were included in a retrospective study. To assess the representativity of this sample for IVI patients, characteristics were compared with patients presenting for IVI during March-April 2019.The study included 279 patients and 319 historic control patients. Of 277 valid test results, one SARS-CoV‑2 positive patient was found, resulting in a carrier rate of 0.36% with a 95% Clopper-Pearson confidence interval of 0.01-1.99%. No differences in sex (57.7% vs. 59.9% female,The study provides an estimate for the prevalence of SARS-CoV‑2 infection in asymptomatic patients presenting for IVI. While these data may be used as a baseline, further research is needed to assess the development of SARS-CoV‑2 prevalence in this patient group in order to support risk assessment and infection prevention strategies.Durch die „coronavirus disease 2019“-(COVID-19)-Pandemie ist die nosokomiale Übertragung des „severe acute respiratory syndrome coronavirus 2“ (SARS-CoV-2) von großer Bedeutung für Kliniker aller Fachrichtungen. Derzeit liegen keine Daten zur Prävalenz der Infektion bei ophthalmologischen Patienten vor, die intravitreale Injektionen benötigen. Zielsetzung dieser retrospektiven Studie war die Abschätzung der Prävalenz der Infektion mit SARS-CoV‑2 bei Patienten vor intravitrealer Injektion.Patienten, die im April 2020 vor intravitrealer Injektion mittels eines naso- und oropharyngealen Abstrichs und reverser Echtzeit-Polymerasekettenreaktion auf SARS-CoV‑2 gescreent worden waren, wurden in eine retrospektive Studie einbezogen. Um die Repräsentativität der Stichprobe zu untersuchen, wurden die Charakteristika mit Patienten vor intravitrealer Injektion aus den Monaten März bis April 2019 verglichen.In die Studie wurden 279 Patienten und 319 historische Kontrollpatienten eingeschlossen. Unter 277 validen Testergebnissen wurde ein SARS-CoV-2-positiver Patient gefunden. Die Prävalenz betrug daher 0,36 % mit einem 95 %-Clopper-Pearson-Konfidenzintervall von 0,01–1,99 %. Es wurden keine Unterschiede bei Geschlecht (57,7 vs. 59,9 % weiblich;Die Studie liefert eine Schätzung der Prävalenz der SARS-CoV-2-Infektion bei asymptomatischen Patienten vor intravitrealer Injektion, die als Grundlage für zukünftige Untersuchungen dienen kann. Weitere Untersuchungen sind notwendig, um den Verlauf der Prävalenz von SARS-CoV‑2 in dieser Patientengruppe zu bestimmen und somit die Risikoabschätzung und Infektionspräventionsstrategien zu unterstützen.

To assess the effect of intravitreal anti-vascular endothelial growth factor (anti-VEGF) administration on the vitreomacular interface and retinal morphology in eyes with neovascular age-related macular degeneration (AMD) and to identify morphological markers potentially influencing disease prognosis. A total of 43 patients (51 eyes) with treatment-naive neovascular AMD subsequently treated with bevacizumab 1.25 mg (in 0.05 ml of solution) were monitored until month 12 of follow-up. Following a loading dose of three monthly intravitreal anti-VEGF injections, patients were treated as-needed (pro re nata [PRN]). Functional and morphological changes were assessed using spectral domain optical coherence tomography (SD-OCT). All study eyes showed evidence of an increase in the frequency of geographic atrophy (GA) occurrence during follow-up compared to baseline (n = 23 [45%] at month 12 compared to n = 5 [9.8%] at baseline [p > 0.05]). There was a trend towards more frequent GA in eyes diagnosed with posterior vitreomacular adhesion (PVA) at baseline that developed posterior vitreous detachment (PVD) during follow-up compared to eyes not developing PVD (35% vs. 44% GA, p 0.56). Alterations of the vitreomacular interface and retinal morphology in patients with neovascular AMD treated with bevacizumab may have a significant effect on prognosis with respect to GA development. Eyes with vitreomacular adhesion at baseline developing GA during follow-up might require more intensive anti-VEGF therapy with a decreased ability to extend treatment intervals. Findings are comparable to eyes treated with other anti-VEGF agents administered for the management of neovascular AMD.

Multiple sclerosis (MS) and Guillain–Barré syndrome (GBS) are demyelinating disorders affecting the central nervous system and peripheral nervous system (PNS), respectively. Cerebrospinal fluid (CSF) is one of the most valuable sources of diagnostic biomarkers in neurological diseases. In the present study high sensitivity shotgun mass spectrometry was used to characterise the CSF lipidome of patients with MS, GBS and controls with non-demyelinating diseases. The quantification of 222 CSF lipid molecular species revealed characteristic changes in the absolute and relative lipid concentrations in MS and GBS compared to the controls. For the GBS group, the fourfold elevation in the total lipid content was a discriminatory and a newly identified feature of PNS demyelination. In contrast, in MS, the accumulation of the myelin-derived cerebrosides represented a specific feature of demyelination. As a common feature of demyelination, we identified upregulated levels of lipid metabolic intermediates. We found strong positive correlation between total protein content and lipid concentrations in both diseases. By exploring the CSF lipidome we demonstrate usefulness of broad-range shotgun lipidomic analysis as a fast and reliable method of biomarker discovery in patients with demyelinating neurological disorders that might be a valuable diagnostic complement to existing examinations.

The aim of this study was to assess retinal pigment epithelial (RPE) and retinal structural changes in eyes with neovascular age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (anti-VEGF) during long-term follow-up and to evaluate morphological markers potentially influencing prognosis. A total of 18 eyes of 18 patients with neovascular AMD were examined subsequent to completion of the Avastin Versus Lucentis in Age Related Macular Degeneration (MANTA) study following a mean period of 84 months (range 69–93 months). After receiving a loading dose of 3 intravitreal anti-VEGF injections subsequent to baseline of the MANTA study, patients were treated as needed (pro re nata, PRN). Functional and morphological changes were assessed, the latter using spectral domain optical coherence tomography (SD-OCT). Retinal/RPE atrophy generally increased significantly during follow-up compared to baseline (fibrosis 28% vs. 89%, p = 0.0001, geographic atrophy, GA 0% vs. 67%, p = 0.0002, RPE porosity 61% vs. 100%, p = 0.009) whereas regenerative alterations tendentially increased until 3 months and then subsequently declined until the last visit (RPE thickening 28% vs. 11%, p = 0.22 and intraretinal hyperreflective foci 89% vs. 78%, p = 0.39). Atrophic alterations of the retina and RPE are progressive and may partly be induced by anti-VEGF. Morphological findings may aid in the identification of prognostic markers in the progression of neovascular AMD. This could lead to a more targeted education of affected patients.

Die Keratokonjunktivitis sicca (KCS) gewinnt mit stetig steigenden Pravalenzen vor allem in den alteren Bevolkerungsgruppen zunehmend an Bedeutung in der Augenheilkunde. Chirurgische Interventionen am Auge, im Speziellen die Katarakt-Chirurgie als haufigste durchgefuhrte Operation in der Ophthalmologie, gelten als bedeutende Risikofaktoren fur die Entwicklung einer KCS. Der folgende Artikel gibt eine Ubersicht uber Risikofaktoren, Pathophysiologie sowie pra- und postoperatives Management einer vorbestehenden oder neu aufgetretenen KCS bei Katarakt-Chirurgie.

Despite its clinical relevance, cerebral amyloid angiopathy (CAA) is underdiagnosed worldwide. This retrospective study aimed to assess the incidence, etiology, predictors, and outcome of intracerebral hemorrhages (ICHs) in this region, with special focus on possible underlying CAA. Database screening of acute cares with intracranial hemorrhage diagnosis within 01/07/2014–01/07/2018 were conducted analyzing medical records and imaging. Spontaneous ICHs were classified as deep (basal ganglionic/thalamic/brainstem) and lobar/cerebellar (i.e., CAA-compatible) ICHs. Probable/definite CAA was established using the modified Boston criteria in a subgroup with ‘complete’ radiological/neuropathological work-up. The ability of several factors to discriminate between deep and lobar/cerebellar ICHs, between probable/definite CAA and non-probable CAA cases, and to predict 1-month case fatality was assessed. Of the 213 ICHs identified, 121 were in deep and 92 in lobar/cerebellar localization. Sub-analysis of 47 lobar/cerebellar ICHs with ‘complete’ work-up identified 16 probable/definite CAA patients, yielding an estimated 14.7% prevalence of CAA-related ICHs. Chronic hypertension was the most prevalent risk factor for all types of ICHs (including CAA-related), with hypertensive excess and younger age being independent predictors of deep whereas antiplatelet use of lobar/cerebellar localization. The 1-month case fatality was 33.8%, driven predominantly by age and INR > 1.4. Probable/definite CAA diagnosis was independently predicted by age, prior intracranial hemorrhage, and antiplatelet use. First in this region and among the few in the literature, this study reports a remarkable prevalence of CAA-related ICHs, emphasizing the need for an increased awareness of CAA and its therapeutic implications, especially regarding antiplatelets among the elderly. Electronic supplementary material The online version of this article (10.1007/s00702-020-02174-2) contains supplementary material, which is available to authorized users.

Background Kynurenic acid (KYNA) is an l-tryptophan metabolite with neuromodulatory activities, regulating the release of neurotransmitters such as glutamate, dopamine (DA), and acetylcholine (Ach). Dysregulation of the kynurenine pathway has been associated with neurodegenerative, neurological, and psychological disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, major depressive disorder, and schizophrenia. Methods The antidepressant-like effects of KYNA were studied with a modified mouse forced swimming test (FST), and the potential involvement of the serotonin (SER), norepinephrine, DA, Ach, N-methyl-d-aspartate, or gamma-aminobutyric acid subunit A (GABAA) receptors in its antidepressant-like effect was assayed by modified combination mouse FST. In combination studies, the mice were pretreated with the respective receptor antagonist, cyproheptadine (CPH), phenoxybenzamine, yohimbine, propranolol, haloperidol (HPD), atropine, MK-801, or bicuculline (BCL). Results The FST revealed that KYNA reversed immobility, climbing, and swimming times, suggesting the antidepressant-like effects of KYNA. Furthermore, the combination studies showed that CPH prevented the antidepressant-like effects of KYNA on immobility, climbing, and swimming times, whereas HPD reduced climbing time and BCL influenced immobility and climbing times and prevented the effects of KYNA on swimming time. Conclusions The results demonstrated, for the first time, the presence of antidepressant-like effects of KYNA in a modified mouse FST. Furthermore, modified combination FST showed that the antidepressant-like actions of KYNA strongly interacted with 5-hydroxytryptamine type 2 SER-ergic receptors, weakly interacted with D2, D3, D4 DA-ergic receptors, and interacted moderately with GABAA receptors.

Absztrakt: A kinureninek manapság intenzív érdeklődés tárgyát képezik, mivel számos fiziológiás és patológiás folyamatban részt vesznek. Az esszenciális aminosav triptofán elsősorban a kinurenin-útvonalon keresztül metabolizálódik. A lebomlás során kinurenin-aminotranszferázok segítségével keletkezik az egyik fontos termék, a kinurénsav. A kinurénsav excitatorikus receptorok ligandja, neuroprotektív tulajdonságú. A kinurénsav szintjének abnormális csökkenése vagy növekedése a neurotranszmitter-rendszerek egyensúlyának felborulásához vezethet, és ez számos neurodegeneratív és neuropszichiátriai betegségben megfigyelhető. A kinurénsav a poláros szerkezete miatt nehezen jut át a vér–agy-gáton, emiatt közvetlenül nem alkalmas terápiás célokra. Ezért kutatásunk célja olyan kinurénsav-analógok előállítása és farmakológiai tesztelése volt, melyek a vér–agy-gáton könnyebben átjutnak. Az újonnan szintetizált kinurénsav-analógok hatékonynak bizonyultak több idegrendszeri betegség (migrén, Huntington-kór) modelljében. A kinurénsav-származékokkal kapott eredmények szerint e vegyületek új terápiás célpontot jelenthetnek a neurodegeneratív betegségek kezelésében. Kutatási eredményeink alapján számos szabadalmi bejelentést benyújtottunk. Orv Hetil. 2020; 161(12): 443–451.

Background and purpose The majority of patients with advanced Parkinson's disease are treated at specialized movement disorder centers. Currently, there is no clear consensus on how to define the stages of Parkinson's disease; the proportion of Parkinson's patients with advanced Parkinson's disease, the referral process, and the clinical features used to characterize advanced Parkinson's disease are not well delineated. The primary objective of this observational study was to evaluate the proportion of Parkinson's patients identified as advanced patients according to physician's judgment in all participating movement disorder centers across the study. Here we evaluate the Hungarian subset of the participating patients. Methods The study was conducted in a cross-sectional, non-interventional, multi-country, multi-center format in 18 countries. Data were collected during a single patient visit. Current Parkinson's disease status was assessed with Unified Parkinson's Disease Rating Scale (UPDRS) parts II, III, IV, and V (modified Hoehn and Yahr staging). Non-motor symptoms were assessed using the PD Non-motor Symptoms Scale (NMSS); quality of life was assessed with the PD 8-item Quality-of-Life Questionnaire (PDQ-8). Parkinson's disease was classified as advanced versus non-advanced based on physician assessment and on questions developed by the Delphi method. Results Overall, 2627 patients with Parkinson's disease from 126 sites were documented. In Hungary, 100 patients with Parkinson's disease were documented in four movement disorder centers, and, according to the physician assessment, 50% of these patients had advanced Parkinson's disease. Their mean scores showed significantly higher impairment in those with, versus without advanced Parkinson's disease: UPDRS II (14.1 vs. 9.2), UPDRS IV Q32 (1.1 vs. 0.0) and Q39 (1.1 vs. 0.5), UPDRS V (2.8 vs. 2.0) and PDQ-8 (29.1 vs. 18.9). Conclusion Physicians in Hungarian movement disorder centers assessed that half of the Parkinson's patients had advanced disease, with worse motor and non-motor symptom severity and worse QoL than those without advanced Parkinson's disease. Despite being classified as eligible for invasive/device-aided treatment, that treatment had not been initiated in 25% of these patients.

CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, M-protein agglutination, disialosyl antibodies) syndrome is a rare polyneuropathy. IgM paraproteins react with ganglioside-containing disialylated epitopes resulting in dorsal root ganglionopathy and B-lymphocyte infiltration of cranial and peripheral nerves. Clinical features include ataxia, slight muscle weakness, areflexia, sensory- and cranial nerve symptoms. Case studies have reported the efficacy of rituximab and intravenous immunoglobulin (IVIg) treatments. We present the case of a 57-year-old man, who had difficulty walking, with numbness and clumsiness in all limbs. He had areflexia, vibratory sensation loss and ataxia. Laboratory tests showed IgM monoclonal components and disialosyl antibodies in the serum. Nerve conduction studies indicated severe sensorimotor demyelinating polyneuroradiculopathy. Despite IVIg and rituximab treatments, the patient's disease course gradually worsened and he died of respiratory failure. Neuropathological examination revealed dorsal column- and dorsal root atrophy with mixed mononuclear cell infiltration. This article aims to draw attention to this syndrome, and the use of early potent immunosuppressive treatment to improve patients' quality of life.

Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.

Treatment of choroidal neovascularization due to age-related macular degeneration is a challenging topic since an increasing number of patients show reduced morphological response to conventional treatment with intravitreal injections. The present study tested the hypothesis that the newly introduced anti-VEGF antibody brolucizumab does not only show promising results in pre-treated patients but is also a viable option in cases of tachyphylaxis to aflibercept or bevacizumab.Thirty-six eyes of 34 patients with a history of at least 10 anti-VEGF injections as well as persistent retinal fluid following the past 5 monthly injections with aflibercept and bevacizumab prior to first treatment with brolucizumab were included in the study. Morphological and functional treatment response was compared before and after switching to brolucizumab.Mean best-corrected visual acuity did not significantly change after treatment with brolucizumab. In contrast, central retinal thickness significantly decreased 4 weeks after treatment with brolucizumab from 340.36 to 282.22 µm (p 0.001) as well as pigment epithelial detachment from 346.73 to 280.47 µm (p 0.001). In 24 eyes (66.67%), complete resolution of intra-and subretinal fluid was observed after a single dose of brolucizumab. No serious adverse events, such as intraocular inflammation and retinal vasculitis, were reported after a single injection of brolucizumab.Brolucizumab is not only effective in treatment-naïve patients as shown in the pivotal HAWK and Harrier trials, but also in pre-treated patients as seen in the present study. Our data also suggest that brolucizumab is potent in patients with signs of tachyphylaxis to other anti-VEGF agents and thus a viable treatment option.