BACKGROUND: Alemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment. OBJECTIVES: To evaluate the effectiveness and safety of the use of ALEM and to analyse subsequent disease-modifying treatments (DMTs). A multidimensional prediction model was developed to make a patient-specific prognosis regarding the response to ALEM. DESIGN: A multicentre, prospective, non-controlled, non-interventional, observational cohort study. METHODS: Relapsing multiple sclerosis patients (RMSp) who received ⩾1 dose of ALEM were enrolled. In each treatment year, the following baseline and prospective data were collected: age, MS history, number, type and duration of previous disease-modifying treatment (PDMT), relapse rate (REL), expanded disability status scale (EDSS), magnetic resonance imaging and serious adverse events (AE). In cases of reactivation of MS, all data about the subsequent DMT were collected. RESULTS: A total of 142 RMSp from 10 MS Slovak Centres fulfilled the inclusion criteria. The average age was 35 years (standard error 8.56). The overall average EDSS was 3.87 (1.46) when ALEM was started. The average duration of PDMT was 6.0 (4.04) years, and the median number of PDMTs was 3 (0-5), while the patients were mostly treated with 2 or 3 DMTs (>65.00%). Post-ALEM treatment was needed in 39 cases (27.46%). The most frequent post-ALEM treatment indicated was ocrelizumab, followed by natalizumab (NAT), siponimod and cladribine. The ocrelizumab and NAT treatment bring little benefit to patients. Siponimod showed less EDSS increase in contrast to ocrelizumab and NAT. Another repopulation therapy, cladribine, may also be an effective option. Statistically significant predictors for the expected EDSS are age (p-value <0.0001), number of ALEM cycles (0.0066), high number of PDMT (0.0459) and the occurrence of relapses (<0.0001). There was no statistically significant effect on the patient's gender (0.6038), duration of disease-modifying treatment before alemtuzumab (0.4466), or the occurrence of AE (0.6668). CONCLUSION: The study confirms the positive effect of ALEM on clinical and radiological outcomes. We need more data from long-term sequencing studies.

• Publikační typ
• časopisecké články MeSH

MOTIVATION: The association between weather conditions and stroke incidence has been a subject of interest for several years, yet the findings from various studies remain inconsistent. Additionally, predictive modelling in this context has been infrequent. This study explores the relationship of extremely high ischaemic stroke incidence and meteorological factors within the Slovak population. Furthermore, it aims to construct forecasting models of extremely high number of strokes. METHODS: Over a five-year period, a total of 52,036 cases of ischemic stroke were documented. Days exhibiting a notable surge in ischemic stroke occurrences (surpassing the 90th percentile of historical records) were identified as extreme cases. These cases were then scrutinized alongside daily meteorological parameters spanning from 2015 to 2019. To create forecasts for the occurrence of these extreme cases one day in advance, three distinct methods were employed: Logistic regression, Random Forest for Time Series, and Croston's method. RESULTS: For each of the analyzed stroke centers, the cross-correlations between instances of extremely high stroke numbers and meteorological factors yielded negligible results. Predictive performance achieved by forecasts generated through multivariate logistic regression and Random Forest for time series analysis, which incorporated meteorological data, was on par with that of Croston's method. Notably, Croston's method relies solely on the stroke time series data. All three forecasting methods exhibited limited predictive accuracy. CONCLUSIONS: The task of predicting days characterized by an exceptionally high number of strokes proved to be challenging across all three explored methods. The inclusion of meteorological parameters did not yield substantive improvements in forecasting accuracy.

• MeSH
• incidence MeSH
• ischemická cévní mozková příhoda * epidemiologie   MeSH
• lidé MeSH
• logistické modely MeSH
• meteorologické pojmy MeSH
• počasí * MeSH
• předpověď * metody   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH

• MeSH
• kladribin * aplikace a dávkování   ekonomika   farmakologie   MeSH
• klinické rozhodování MeSH
• lidé MeSH
• monitorování léčiv metody   statistika a číselné údaje   MeSH
• roztroušená skleróza * farmakoterapie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Slovenská republika MeSH

INTRODUCTION: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory central nervous system (CNS) disorder, chiefly involving the brainstem, especially the pons. The diagnosis is challenging, requires careful exclusion of alternative diagnoses and a targeted therapeutic approach. CLIPPERS is known to respond well to corticosteroids, but the treatment needs to be long-term and can cause significant side-effects. Moreover, subsequent corticosteroid withdrawal often leads to a relapse. It has been suggested that anti-CD20 molecules could benefit several antibody-mediated CNS inflammatory diseases, including CLIPPERS. CASE REPORT: This paper describes two cases of CLIPPERS. The first demonstrates the benefit of early introduction of corticosteroids with side effects in cases of long-term use. The second demonstrates the efficacy of ocrelizumab (anti-CD20 molecule) in a severe course of CLIPPERS. CONCLUSION: These two cases bring attention to this rare, often misdiagnosed but treatable disease.

• MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• nemoci centrálního nervového systému * komplikace   diagnóza   farmakoterapie   MeSH
• pons MeSH
• progrese nemoci MeSH
• steroidy terapeutické užití   MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• kazuistiky MeSH

INTRODUCTION: Loss of consciousness (LOC) is used as a diagnostic feature of mild traumatic brain injury (MTBI). However, only 10% of concussions result in LOC. There are only a limited number of in-vivo studies dealing with unconsciousness and structural and functional integrity of the brainstem in patients with MTBI. The aim of our pilot study was to assess the sensitivity of proton magnetic resonance spectroscopy (1H-MRS) to detect metabolic changes in the brainstem in patients after MTBI with unconscioussness. METHODS: Twenty-four patients (12 with LOC, and 12 without LOC) within 3 days of MTBI and 19 healthy controls were examined. All subjects underwent single-voxel 1H-MRS examination of the upper brainstem. Spectra were evaluated using LCModel software. Ratios of total N-acetylaspartate (tNAA), total choline-containing compounds (tCho) and glutamate plus glutamine (Glx) to total creatine (tCre) were used for calculations. RESULTS: We found a significant decrease in tNAA/tCre and tCho/tCre ratios in the patient group with LOC when compared with the control group of healthy volunteers (P=0.002 and P=0.041, respectively), and a significant decrease in the tNAA/tCre ratio in the LOC group when compared with patients without LOC (P=0.04). Other metabolite ratios in the brainstem did not show any significant group differences. CONCLUSION: Our findings indicate that decrease of tNAA/tCre ratio in the upper brainstem using single-voxel 1H-MRS may provide a potential biomarker for MTBI associated with LOC.

• MeSH
• bezvědomí etiologie   MeSH
• komoce mozku * komplikace   diagnostické zobrazování   metabolismus   MeSH
• lidé MeSH
• mozkový kmen diagnostické zobrazování   metabolismus   MeSH
• pilotní projekty MeSH
• protonová magnetická rezonanční spektroskopie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cieľ: Voľné ľahké reťazce kappa (kappa free light chains; k-fLC) v likvore sú perspektívnym novým markerom intratekálnej syntézy imunoglobulínov (Ig) u pacientov s RS, pričom publikované referenčné hodnoty nie sú jednotné. Cieľom našej práce bolo analyzovať diagnostickú hodnotu k-fLC (hladiny v likvore, kvocientu, indexu) a rutinne vyšetrovaných markerov (IgG index, IgGReiber) v diagnostike RS, v predikcii pozitivity oligoklonálnej skladby (oligoclonal bands; OCB) a u OCB negatívnych pacientov. Metódy: Párované vzorky séra a likvoru boli analyzované v súbore 46 pacientov s RS a 63 kontrolných jedincov s nezápalovými a inými zápalovými ochoreniami CNS. Koncentrácia k-fLC bola meraná imunoturbidimetricky (SPA PLUS®, Freelite®). Pre jednotlivé markery a ich cut-off hodnoty, určené s použitím Youdenovho indexu, boli porovnané ROC krivky, diagnostické senzitivity a špecificity. Výsledky: Optimálne cut-off hodnoty boli: 0,76 pre IgG index; 0,89 mg/l pre IgGReiber; 1,08 mg/l pre hladinu k-fLC v likvore; 0,0994 pre k-fLC kvocient; 18,15 pre k-fLC index. K odlíšeniu RS od control boli zistené najvyššie kombinované diagnostické senzitivity/špecificity pre k-fLC index (0,76/0,98), nasledované k-fLC kvocientom (0,76/0,97), hladinou k-fLC v likvore (0,76/0,95), intratekálnou syntézou IgGReiber (0,70/0,91) a IgG indexom (0,65/0,89). Senzitivita a špecificita OCB vyšetrenia bola 0,83 a 1,00. V predikcii OCB pozitivity malo použitie nových k-fLC markerov excelentnú diagnostickú využiteľnosť so senzitivitou/špecificitou: 0,92/0,99 pre k-fLC index; 0,92/0,97 pre k-fLC kvocient; 0,92/0,96 pre hladinu k-fLC v likvore, v porovnaní s 0,76/0,89 pre IgG index a 0,76/0,86 pre IgGReiber. U OCB negatívnych RS pacientov s použitím navrhnutých cut-off bola najvyššia diagnostická senzitivita (0,38) detekovaná pre IgGReiber, nasledovaná senzitivitou 0,13 pre IgG index a prekvapivo 0,00 senzitiviou pre k-fLC markery. Záver: V diagnostike RS a pri predikcii OCB pozitivity sme detekovali pre všetky analyzované k-fLC markery lepšie diagnostické senzitivity a špecificity v porovnaní s rutinne používaným IgG indexom a IgGReiber, tieto však nedosiahli senzitivitu a špecificitu OCB vyšetrenia. Pre dôkaz intratekálnej syntézy Ig u pacientov so suspektnou RS odporúčame paralelné vyšetrenie OCB spolu s použitím k-fLC indexu a kvocientu, a to predovšetkým ak OCB nález je nejednoznačný alebo negatívny.

Aim: Kappa free light chains (-fLC) in cerebrospinal fl uid (CSF) were suggested as promising novel markers of intrathecal immunoglobulin (Ig) synthesis in MS patients, with reported discrepant reference values. We aimed to analyse the diagnostic accuracy of k-fLC (CSF concentration, quotient, index) and routinely used markers (IgG index, IgGReiber) in MS diagnostics, in prediction of oligoclonal bands (OCB) positivity and in OCB negative patients. Methods: Serum/CSF paired samples were analysed from 46 MS patients and 63 controls with non-inflammatory and non-MS inflammatory diseases of CNS. The concentrations of k-fLC were measured immunoturbidimetrically (SPA PLUS®, Freelite®). The ROC curves, diagnostic sensitivities and specificities were analysed with respect to the cut-offs, which were determined using Youden’s index. Results: The optimal cut-off values were defined as: 0.76 for IgG index; 0.89 mg/L for IgGReiber; 1.08 mg/L for CSF k-fLC level; 0.0994 for k-fLC quotient; 18.15 for k-fLC index. To distinguish MS patients from controls, the highest combined sensitivities/specificities were observed for k-fLC index (0.76/0.98), followed by k-fLC quotient (0.76/0.97), CSF k-fLC level (0.76/0.95), IgGReiber (0.70/0.91) and IgG index (0.65/0.89). The OCB detection showed the sensitivity 0.83 and the specificity 1.00. In prediction of OCB positivity, the novel k-fLC markers showed excellent diagnostic accuracy with sensitivities/specificities: 0.92/0.99 for k-fLC index, 0.92/0.97 for k-fLC quotient, and 0.92/0.96 for CSF k-fLC level, compared to 0.76/0.89 for IgG index and 0.76/0.86 for IgGReiber. Applying our cut-offs in OCB negative MS patients, the highest diagnostic sensitivity (0.38) was found for IgGReiber, followed by 0.13 for IgG index, and surprisingly by 0.00 for all k-fLC markers. Conclusion: In MS diagnostics and in prediction of OCB positivity, all novel k-fLC markers showed better sensitivities and specificities than routinely used IgG index and IgGReiber, but did not reach those of OCBs. To proove the intrathecal Ig synthesis in patients with suspected MS, we recommend to use k-fLC index and quotient along with OCB, especially if OCB findings are equivocal or negative.

• MeSH
• biologické markery MeSH
• imunoglobuliny - kappa-řetězce mozkomíšní mok   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• roztroušená skleróza * diagnóza   krev   mozkomíšní mok   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Cieľ: Včasné rozpoznanie sclerosis multiplex (SM) pomáha začať liečbu pacientov skôr, a tak oddialiť progresiu ochorenia. Urobili sme analýzu metabolitov cerebro-spinálneho likvoru (cerebrospinal fluid; CSF), s cieľom zistiť prediktory včas, a tak oddialiť SM. Metódy: Do štúdie bolo zaradených 56 jedincov s podozrením na SM, pred začatím akejkoľvek liečby. Z nich bolo 28 diagnostikovaných ako definitívna SM, u 17 pacientov sme zistili klinicky izolovaný syndróm (clinically isolated syndrome; CIS) podľa McDonaldových kritérií z roku 2010, v 11 prípadoch sa jednalo o iné demyelinizačné ochorenie CNS (DEM). Kontrolnú skupinu (CON) tvorili 29 jedinci, ktorí nemali dokázané žiadne ochorenie CNS. Na meranie metabolitov CSF bola použitá protonová nukleárna magnetická rezonančná spektroskopia. Výsledky: Glutamín, ktorý koreloval s Expanded Disability Status Scale (EDSS), bol jediným metabolitom, ktorý dokázal odlíšiť CIS, SM, DEM a CON. Valín, leucín, isoleucín, znížené u CIS a SM v porovnaní s CON, sa neodlišovali od DEM. Hladiny citrátu v CSF špecifikovali SM a CIS oproti DEM, ale nepomohli v rozlíšení CIS a SM. Citrát ukazoval signifikantné korelácie s vekom, dľžkou trvania ochorenia a EDSS u SM pacientov. Acetát, aceton, pyruvát, formát, histidin v CSF neboli signifikantnými prediktormi SM alebo CIS, hoci korelovali s niektorými vybranými premennými. Záver: Táto práca ukazuje prediktívnu úlohu glutamínu v CSF v stanovení diagnózy SM od jej včasných štádií, vypichujúc tak dôležitú úlohu glutamát/glutamínového cyklu v patogenéze SM. Ďalší potenciálny prediktor SM bol citrát. Ďalšie metabolity neboli identifikované ako senzitívne CSF markery SM.

Aim: Early recognition of multiple sclerosis (MS) allows patients to begin treatment earlier and delay disease progression. We performed an analysis of cerebrospinal fluid (CSF) metabolites to find early predictors of MS. Methods: We included 56 participants with suspected MS before any treatment. Out of those, 28 patients were diagnosed with definite MS, 17 with clinically isolated syndrome (CIS) according to McDonald 2010 criteria, and 11 with other demyelinating diseases (DEM) of the CNS. The control group (CON) included 29 participants without any confirmed CNS disease. Proton nuclear magnetic resonance spectroscopy was used to measure CSF metabolites. Results: Glutamine, correlating with Expanded Disability Status Scale (EDSS), was the only metabolite capable to distinguish between CIS and MS, DEM, and CON. Valine, leucine, isoleucine, decreased in CIS and MS when compared with CON, did not differ from DEM. Citrate CSF levels specified MS and CIS against DEM but did not help to distinguish between CIS and MS. Citrate showed significant correlations with age, disease duration, and EDSS in MS patients. Acetate, acetone, pyruvate, formate and histidine CSF levels were not significant predictors of MS or CIS, although they correlated with selective variables. Conclusion: This work shows the predictive role of CSF glutamine in diagnosing MS since its early stages, pinpointing an important role of the glutamate/glutamine cycle in MS pathogenesis. Another potential predictor of MS was citrate. Other metabolites were not identified as sensitive CSF markers of MS.

• MeSH
• demyelinizační nemoci diagnostické zobrazování   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• metabolomika MeSH
• mozkomíšní mok diagnostické zobrazování   MeSH
• roztroušená skleróza * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Sclerosis multiplex je chronické ochorenie postihujúce najmä mladých dospelých ľudí. Správne načasovanie liečby určuje ďalší priebeh ochorenia a pozitívne ovplyvňuje kvalitu života. Práca prináša nové pohľady na diagnostiku a liečbu tohto ochorenia.

Multiple sclerosis is a chronic disorder, which primarily affects young adults. Timing of treatment determines further evolution of the disorder and positively influences quality of life. The work brings new insides on diagnostics and treatment of the disorder.

• MeSH
• časná diagnóza MeSH
• lidé MeSH
• roztroušená skleróza * diagnóza   farmakoterapie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVE: In multiple sclerosis (MS), deep grey matter (DGM) atrophy has been recognised as a crucial component of the disease that presents early and it has been associated with disability. Although the precise mechanism underlying grey matter atrophy is unknown, several hypotheses have been postulated. Our previous research pointed to correlations of hypothalamic metabolic alterations with clinical outcomes of MS, therefore we decided to further test the relationship of these alterations with DGM atrophy. METHODS: We used 1H-Magnetic Resonance spectroscopy (1H-MRS) of the hypothalamus to test its metabolites in 26 patients with RRMS and 22 healthy age-matched controls. DGM atrophy was evaluated by simple planimetry of third ventricular width on the hypothalamic level (3VW) in T1 weighted MRI pictures. Metabolite ratios of N-acetyl aspartate (NAA), choline (Cho), glutamate and glutamine (Glx), myo-inositol (mIns) and creatine (Cr) were correlated with Multiple Sclerosis Severity Scale (MSSS) and 3VW. RESULTS: Metabolite concentrations were compared between patients and controls using multiple regression models allowing for age, 3VW and metabolites. It revealed that the only relevant predictors of MSSS were 3VW and Glx/NAA. At a significance level of P<0.05, a unit increase of 3VW was associated with a 0.35 increase of MSSS, for a typical value of Glx/NAA; P value 0.0039. A unit increase of Glx/NAA was associated with a 0.93 increase of MSSS, for a typical value of atrophy; P value 0.090. There were significant linear correlations between Glx/Cr and MSSS, Glx/NAA and MSSS, and between mIns/NAA and 3VW. CONCLUSIONS: The results suggest that both NAA and Glx are associated with neurodegeneration of hypothalamic DGM and severe disease course. Glx related 1H-MRS parameters seem to be superior to other metabolites in determining disease burden, independently of otherwise powerful 3VW planimetry. Significantly increased mIns/NAA in MS patients compared to controls point to gliosis, which parallels the atrophy of hypothalamic DGM.

• MeSH
• atrofie MeSH
• dospělí MeSH
• kyselina asparagová analogy a deriváty   metabolismus   MeSH
• kyselina glutamová metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• mladý dospělý MeSH
• prediktivní hodnota testů MeSH
• progrese nemoci MeSH
• roztroušená skleróza diagnostické zobrazování   metabolismus   patofyziologie   MeSH
• stupeň závažnosti nemoci MeSH
• thalamus patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Chronické poruchy vedomia sú novodobý fenomén. Rozpoznanie prvých známok kontaktu s okolím u pacienta po období kómy je kľúčovým momentom z hľadiska prístupu pacienta k rozšíreným možnostiam liečby a rehabilitácie aj nadviazania efektívneho kontaktu s okolím; býva tiež dôležitým prognostickým znakom. Oproti tradičnej definícii apalického syndrómu alebo pojmu bdelá kóma sú súčasné západné označenia deskriptívnejšie a presnejšie. V posledných rokoch sa vyvinuli nové metódy, ktoré umožňujú exaktnejšie skúmať poruchy mozgu. Väčšina z nich sa však používa experimentálne a nie sú dostupné v klinickej praxi, čo zvýhodňuje klinické testovanie s použitím každodenných predmetov. Vyšetrenie behaviorálnych odpovedí je tiež štandardom pre porovnanie výsledkov zistených ďalšími vyšetrovacími metódami. V našej práci predkladáme pohľad na naše vnímanie pacienta s poruchou vedomia a prehľad súčasných možností identifikácie jeho organického substrátu.

Chronic disorders of consciousness are a modern phenomenon. Recognising first behavioural signs of contact with the patient´s environment after coma plays a key role in the patient`s access to extended treatment and rehabilitation, as well as in establish;ing an effective contact with the environment; it is also considered to be an important prognostic sign. Current western terms in comparison with traditional definition of apallic syndrome or the term coma vigile are more descriptive and precise. In recent years, new methods of assessment, which enable more exact evaluation of brain disorders were established. However, most of them remain experimental and lack clinical availability, which favours clinical testing using daily objects. Behavioural response assment is the standard to compare results obtained with other methods of assment. In our work, we present our view on our perception of a patient with a disorder of consciousness and an overview of current options in identifying the underlying organic substrate.

• Klíčová slova
• stav bdění bez odpovědi,
• MeSH
• akinetický mutismus diagnóza   MeSH
• chronická nemoc MeSH
• diagnostické techniky a postupy MeSH
• elektroencefalografie metody   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• perzistentní vegetativní stav * MeSH
• poruchy vědomí * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH