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Papers by jitka hanzalova
Journal of the Neurological Sciences, Oct 1, 2017
Ceska A Slovenska Neurologie A Neurochirurgie, Jun 30, 2020
Neurologie pro praxi, Apr 21, 2023
Journal of Neurology, Dec 1, 2022
Ceska A Slovenska Neurologie A Neurochirurgie, Jul 27, 2015
Ceska A Slovenska Neurologie A Neurochirurgie, May 31, 2017
PLOS ONE
Background The possibility to better predict the severity of the disease in a patient newly diagn... more Background The possibility to better predict the severity of the disease in a patient newly diagnosed with multiple sclerosis would allow the treatment strategy to be personalized and lead to better clinical outcomes. Prognostic biomarkers are highly needed. Objective To assess the prognostic value of intrathecal IgM synthesis, cerebrospinal fluid and serum IL-2, IL-6, IL-10, chitinase 3-like 2 and neurofilament heavy chains obtained early after the onset of the disease. Methods 58 patients after the first manifestation of multiple sclerosis were included. After the initial diagnostic assessment including serum and cerebrospinal fluid biomarkers, all patients initiated therapy with either glatiramer acetate, teriflunomide, or interferon beta. To assess the evolution of the disease, we followed the patients clinically and with MRI for two years. Results The IL-2:IL-6 ratio (both in cerebrospinal fluid) <0.48 (p = 0.0028), IL-2 in cerebrospinal fluid ≥1.23pg/ml (p = 0.026), and chi...
Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of t... more Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Its immunopathogenesis has been proposed to include early cerebrospinal fluid (CSF) lymphocytosis, subsequent CNS disease restriction and B cell mechanism predominance. There are limited data regarding T cell involvement in the disease. To contribute to the current knowledge, we investigated the complex system of chemokines and cytokines related to B and T cell functions in CSF and sera samples from anti-NMDAR encephalitis patients at different time-points of the disease. One patient in our study group had a long-persisting coma and underwent extraordinary immunosuppressive therapy. Methods Twenty-seven paired CSF/serum samples were collected from nine patients during the follow-up period (median 12 months, range 1–26 months). The patient samples were stratified into three periods after the onset of the first disease symptom and compared with the controls...
Uvod: Protilatky proti N-metyl D-aspartatovemu receptoru (anti-NMDAR) jsou přimo patogen ni autop... more Uvod: Protilatky proti N-metyl D-aspartatovemu receptoru (anti-NMDAR) jsou přimo patogen ni autoprotilatky sdružene s difuzni encefalitidou. V posledni době byly popsany připady, kdy s nalezem těchto protilatek byly sdruženy projevy demyelinizacniho onemocněni, a to i u pa cientů bez klinických projevů NMDAR encefalitidy. Cilem prace je popsat charakteristiky demyelinizacniho onemocněni u pa cientů s pozitivitou anti-NMDAR v nasem souboru. Metodika a soubor: Vysetřeni anti-NMDAR bylo indikovano při klinickem podezřeni na autoimunitni encefalitidu a bylo provedeno v seru a v likvoru nepřimou imunofl urescenci metodou cel l-based as say na fi xovaných buňkach transfekovaných pro daný antigen. Klinický průběh a MR nalez odpovidajici demyelinizacnimu onemocněni byl hodnocen dle přislusných dia gnostických kriterii. Výsledky: V obdobi 2012– 2015 jsme identifi kovali 11 pa cientů s autoimunitni encefalitidou a pozitivitou anti- -NMDAR. Deset z nich splňovalo kriteria NMDAR encefalitidy, u...
Ceska A Slovenska Neurologie A Neurochirurgie, 2018
Roztrousena skleroza je chronicke, autoimunitni a neurodegenerativni onemocněni centralniho nervo... more Roztrousena skleroza je chronicke, autoimunitni a neurodegenerativni onemocněni centralniho nervoveho systemu. Průběh choroby je interindividualně znacně variabilni. I přes významný pokrok v diagnostice roztrousene sklerozy v poslednich desetiletich stale neexistuje spolehlivý test, který by identifikoval pacienty s relativně přiznivým průběhem a pacienty s těžkou agresivni formou nemoci. Prognozu onemocněni je do urcite miry možne predikovat dle klinických projevů ci charakteru postiženi na magneticke rezonanci. V soucasne době se hledaji nove parametry lepe vyjadřujici průběh onemocněni již na jeho zacatku. Přesnějsi stratifikace nemoci ma umožnit volbu terapie přiměřenou formě nemoci. V clanku předkladame aktualni přehled potencialnich biomarkerů průběhu roztrousene sklerozy z periferni krve a likvoru a v bližsim detailu představujeme ty, ktere jsou v soucasne době středem zajmu – neurofilamenta, chitinase 3-like proteiny, vitamin D, mikroRNA.
Journal of the Neurological Sciences, 2017
Česká a slovenská neurologie a neurochirurgie, 2018
Biomarkers of dis ease course and prognosis in multiple sclerosis patients Souhrn Roztroušená skl... more Biomarkers of dis ease course and prognosis in multiple sclerosis patients Souhrn Roztroušená skleróza je chronické autoimunitní a neurodegenerativní onemocnění CNS. Průběh choroby je interindividuálně značně variabilní. I přes významný pokrok v dia gnostice RS v posledních desetiletích stále neexistuje spolehlivý test, který by identifikoval pa cienty s relativně příznivým průběhem a pa cienty s těžkou agresivní formou nemoci. Prognózu onemocnění je do určité míry možné stanovit dle klinických projevů či charakteru postižení na MR. V současné době se hledají nové parametry lépe vyjadřující průběh onemocnění již na jeho začátku. Přesnější stratifikace nemoci má umožnit volbu terapie přiměřenou formě nemoci. V článku předkládáme aktuální přehled potenciálních bio markerů průběhu RS vyšetřovaných v séru, periferní krvi a likvoru. V bližším detailu představujeme ty, které jsou v současné době středem zájmuneurofilamenta, chitinase 3-like proteiny, vitamin D a mikroRNA.
Česká a slovenská neurologie a neurochirurgie, 2014
European Journal of Neurology
Background and purposeN‐methyl‐d‐aspartate receptor (NMDAR) and leucine‐rich glioma‐inactivated p... more Background and purposeN‐methyl‐d‐aspartate receptor (NMDAR) and leucine‐rich glioma‐inactivated protein 1 (LGI1) encephalitis are important types of autoimmune encephalitis (AE) with significant morbidity. In this study, we used a proteomic approach in search of novel clinically relevant biomarkers in these types of encephalitides.MethodsSwedish and Czech tertiary neuroimmunology centers collaborated in this retrospective exploratory study. Fifty‐eight cerebrospinal fluid (CSF) samples of 28 patients with AE (14 definite NMDAR, 14 with definite LGI1 encephalitis) and 30 controls were included. CSF samples were analyzed using proximity extension assay technology (Olink Target 96 Inflammation panel). For each CSF sample, 92 proteins were measured. Clinical variables were retrospectively collected, and correlations with protein levels were statistically analyzed.ResultsPatients and controls differed significantly in the following 18 biomarkers: TNFRSF9, TNFRSF12, TNFRSF14, TNFβ, TNFα, ...
Chemokine and cytokine levels in CSF and peripheral blood. The Wilcoxon signed ranked test was us... more Chemokine and cytokine levels in CSF and peripheral blood. The Wilcoxon signed ranked test was used for pairwise analyses of the CSF and sera samples to detect differences between the CNS compartment and the peripheral blood. The interesting differences in the general chemokine and cytokine levels between the CNS compartment and the peripheral blood are depicted. A) The CXCL10 concentration was markedly higher in CSF than in serum, whereas B) the CXCL13 and D) BAFF concentrations showed the opposite trend. Because patient No. 1 provided more than 1 sample per period, the average value for this patient was used for multiple-group analysis; a special sign marks this value. (TIF 79 kb)
Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of t... more Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Its immunopathogenesis has been proposed to include early cerebrospinal fluid (CSF) lymphocytosis, subsequent CNS disease restriction and B cell mechanism predominance. There are limited data regarding T cell involvement in the disease. To contribute to the current knowledge, we investigated the complex system of chemokines and cytokines related to B and T cell functions in CSF and sera samples from anti-NMDAR encephalitis patients at different time-points of the disease. One patient in our study group had a long-persisting coma and underwent extraordinary immunosuppressive therapy. Methods Twenty-seven paired CSF/serum samples were collected from nine patients during the follow-up period (median 12 months, range 1–26 months). The patient samples were stratified into three periods after the onset of the first disease symptom and compared with the controls...
Seizure, 2018
Epileptic seizures are a common manifestation of autoimmune encephalitis, but the role of neural ... more Epileptic seizures are a common manifestation of autoimmune encephalitis, but the role of neural antibodies in long-term epilepsy remains unclear. The aim of this study was to assess the prevalence of neuralsurface antibodies (NSAbs) and antibodies against glutamic acid decarboxylase (GAD) in patients with chronic temporal lobe epilepsy (TLE). Method: Patients with an electro-clinical diagnosis of TLE and a disease duration longer than one year were included. NSAbs (LGI1, CASPR2, AMPAR1/2, NMDAR, GABA B R) and antibodies against GAD were detected. Only patients with significant antibody levels in serum, and/or positivity in CSF (according to antibody subtype), were enrolled in the seropositive group. Cohorts of seropositive and seronegative patients were compared regarding clinical and imaging data. Results: Significant serum levels of antibodies were detected in eight out of 163 (5%) TLE patients (CASPR2 n = 2, GAD n = 3, LGI1 n = 2, and GABA B R n = 1). In four of them, antibodies were detected in the CSF as well (CASPR2 in one, GAD in three). Five seropositive patients had uni-or bilateral temporal lobe lesions on MRI and three patients were non-lesional. All seropositive patients had TLE of unknown cause. Seropositive patients had higher age at epilepsy onset and autoimmune comorbidity, but did not differ in other clinical, EEG or neuroimaging characteristics. Response to immunotherapy (seizure reduction > 50%) was observed in three of the six patients treated. Conclusions: Besides older age at epilepsy onset and autoimmune comorbidity, seropositive patients cannot be distinguished from seronegative patients on the basis of clinical, EEG or neuroimaging data.
![Research paper thumbnail of Experimental therapy with 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP): origin of resistance](https://attachments.academia-assets.com/96969396/thumbnails/1.jpg)
](Folia biologica, 2007
The role of MRP4 and MRP5 transporters in the acyclic nucleoside phosphonate PMEDAP efflux was st... more The role of MRP4 and MRP5 transporters in the acyclic nucleoside phosphonate PMEDAP efflux was studied in vitro (CCRF-CEM cells) and in vivo (spontaneous transplantable T-cell lymphoma of SD/Cub inbred rats). The increased resistance against the cytostatic agent PMEDAP during longterm treatment was found to be associated with overexpression of MRP4 and MRP5 genes. The course of both gene activation differs significantly. While the MRP5 function is important in the onset of PMEDAP resistance, the intensity of the relative MRP4 gene expression increases rather continuously. Our data indicate cooperative acting of both MRP4 and MRP5 genes during the PMEDAP resistance development.
Journal of the Neurological Sciences, Oct 1, 2017
Ceska A Slovenska Neurologie A Neurochirurgie, Jun 30, 2020
Neurologie pro praxi, Apr 21, 2023
Journal of Neurology, Dec 1, 2022
Ceska A Slovenska Neurologie A Neurochirurgie, Jul 27, 2015
Ceska A Slovenska Neurologie A Neurochirurgie, May 31, 2017
PLOS ONE
Background The possibility to better predict the severity of the disease in a patient newly diagn... more Background The possibility to better predict the severity of the disease in a patient newly diagnosed with multiple sclerosis would allow the treatment strategy to be personalized and lead to better clinical outcomes. Prognostic biomarkers are highly needed. Objective To assess the prognostic value of intrathecal IgM synthesis, cerebrospinal fluid and serum IL-2, IL-6, IL-10, chitinase 3-like 2 and neurofilament heavy chains obtained early after the onset of the disease. Methods 58 patients after the first manifestation of multiple sclerosis were included. After the initial diagnostic assessment including serum and cerebrospinal fluid biomarkers, all patients initiated therapy with either glatiramer acetate, teriflunomide, or interferon beta. To assess the evolution of the disease, we followed the patients clinically and with MRI for two years. Results The IL-2:IL-6 ratio (both in cerebrospinal fluid) <0.48 (p = 0.0028), IL-2 in cerebrospinal fluid ≥1.23pg/ml (p = 0.026), and chi...
Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of t... more Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Its immunopathogenesis has been proposed to include early cerebrospinal fluid (CSF) lymphocytosis, subsequent CNS disease restriction and B cell mechanism predominance. There are limited data regarding T cell involvement in the disease. To contribute to the current knowledge, we investigated the complex system of chemokines and cytokines related to B and T cell functions in CSF and sera samples from anti-NMDAR encephalitis patients at different time-points of the disease. One patient in our study group had a long-persisting coma and underwent extraordinary immunosuppressive therapy. Methods Twenty-seven paired CSF/serum samples were collected from nine patients during the follow-up period (median 12 months, range 1–26 months). The patient samples were stratified into three periods after the onset of the first disease symptom and compared with the controls...
Uvod: Protilatky proti N-metyl D-aspartatovemu receptoru (anti-NMDAR) jsou přimo patogen ni autop... more Uvod: Protilatky proti N-metyl D-aspartatovemu receptoru (anti-NMDAR) jsou přimo patogen ni autoprotilatky sdružene s difuzni encefalitidou. V posledni době byly popsany připady, kdy s nalezem těchto protilatek byly sdruženy projevy demyelinizacniho onemocněni, a to i u pa cientů bez klinických projevů NMDAR encefalitidy. Cilem prace je popsat charakteristiky demyelinizacniho onemocněni u pa cientů s pozitivitou anti-NMDAR v nasem souboru. Metodika a soubor: Vysetřeni anti-NMDAR bylo indikovano při klinickem podezřeni na autoimunitni encefalitidu a bylo provedeno v seru a v likvoru nepřimou imunofl urescenci metodou cel l-based as say na fi xovaných buňkach transfekovaných pro daný antigen. Klinický průběh a MR nalez odpovidajici demyelinizacnimu onemocněni byl hodnocen dle přislusných dia gnostických kriterii. Výsledky: V obdobi 2012– 2015 jsme identifi kovali 11 pa cientů s autoimunitni encefalitidou a pozitivitou anti- -NMDAR. Deset z nich splňovalo kriteria NMDAR encefalitidy, u...
Ceska A Slovenska Neurologie A Neurochirurgie, 2018
Roztrousena skleroza je chronicke, autoimunitni a neurodegenerativni onemocněni centralniho nervo... more Roztrousena skleroza je chronicke, autoimunitni a neurodegenerativni onemocněni centralniho nervoveho systemu. Průběh choroby je interindividualně znacně variabilni. I přes významný pokrok v diagnostice roztrousene sklerozy v poslednich desetiletich stale neexistuje spolehlivý test, který by identifikoval pacienty s relativně přiznivým průběhem a pacienty s těžkou agresivni formou nemoci. Prognozu onemocněni je do urcite miry možne predikovat dle klinických projevů ci charakteru postiženi na magneticke rezonanci. V soucasne době se hledaji nove parametry lepe vyjadřujici průběh onemocněni již na jeho zacatku. Přesnějsi stratifikace nemoci ma umožnit volbu terapie přiměřenou formě nemoci. V clanku předkladame aktualni přehled potencialnich biomarkerů průběhu roztrousene sklerozy z periferni krve a likvoru a v bližsim detailu představujeme ty, ktere jsou v soucasne době středem zajmu – neurofilamenta, chitinase 3-like proteiny, vitamin D, mikroRNA.
Journal of the Neurological Sciences, 2017
Česká a slovenská neurologie a neurochirurgie, 2018
Biomarkers of dis ease course and prognosis in multiple sclerosis patients Souhrn Roztroušená skl... more Biomarkers of dis ease course and prognosis in multiple sclerosis patients Souhrn Roztroušená skleróza je chronické autoimunitní a neurodegenerativní onemocnění CNS. Průběh choroby je interindividuálně značně variabilní. I přes významný pokrok v dia gnostice RS v posledních desetiletích stále neexistuje spolehlivý test, který by identifikoval pa cienty s relativně příznivým průběhem a pa cienty s těžkou agresivní formou nemoci. Prognózu onemocnění je do určité míry možné stanovit dle klinických projevů či charakteru postižení na MR. V současné době se hledají nové parametry lépe vyjadřující průběh onemocnění již na jeho začátku. Přesnější stratifikace nemoci má umožnit volbu terapie přiměřenou formě nemoci. V článku předkládáme aktuální přehled potenciálních bio markerů průběhu RS vyšetřovaných v séru, periferní krvi a likvoru. V bližším detailu představujeme ty, které jsou v současné době středem zájmuneurofilamenta, chitinase 3-like proteiny, vitamin D a mikroRNA.
Česká a slovenská neurologie a neurochirurgie, 2014
European Journal of Neurology
Background and purposeN‐methyl‐d‐aspartate receptor (NMDAR) and leucine‐rich glioma‐inactivated p... more Background and purposeN‐methyl‐d‐aspartate receptor (NMDAR) and leucine‐rich glioma‐inactivated protein 1 (LGI1) encephalitis are important types of autoimmune encephalitis (AE) with significant morbidity. In this study, we used a proteomic approach in search of novel clinically relevant biomarkers in these types of encephalitides.MethodsSwedish and Czech tertiary neuroimmunology centers collaborated in this retrospective exploratory study. Fifty‐eight cerebrospinal fluid (CSF) samples of 28 patients with AE (14 definite NMDAR, 14 with definite LGI1 encephalitis) and 30 controls were included. CSF samples were analyzed using proximity extension assay technology (Olink Target 96 Inflammation panel). For each CSF sample, 92 proteins were measured. Clinical variables were retrospectively collected, and correlations with protein levels were statistically analyzed.ResultsPatients and controls differed significantly in the following 18 biomarkers: TNFRSF9, TNFRSF12, TNFRSF14, TNFβ, TNFα, ...
Chemokine and cytokine levels in CSF and peripheral blood. The Wilcoxon signed ranked test was us... more Chemokine and cytokine levels in CSF and peripheral blood. The Wilcoxon signed ranked test was used for pairwise analyses of the CSF and sera samples to detect differences between the CNS compartment and the peripheral blood. The interesting differences in the general chemokine and cytokine levels between the CNS compartment and the peripheral blood are depicted. A) The CXCL10 concentration was markedly higher in CSF than in serum, whereas B) the CXCL13 and D) BAFF concentrations showed the opposite trend. Because patient No. 1 provided more than 1 sample per period, the average value for this patient was used for multiple-group analysis; a special sign marks this value. (TIF 79 kb)
Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of t... more Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Its immunopathogenesis has been proposed to include early cerebrospinal fluid (CSF) lymphocytosis, subsequent CNS disease restriction and B cell mechanism predominance. There are limited data regarding T cell involvement in the disease. To contribute to the current knowledge, we investigated the complex system of chemokines and cytokines related to B and T cell functions in CSF and sera samples from anti-NMDAR encephalitis patients at different time-points of the disease. One patient in our study group had a long-persisting coma and underwent extraordinary immunosuppressive therapy. Methods Twenty-seven paired CSF/serum samples were collected from nine patients during the follow-up period (median 12 months, range 1–26 months). The patient samples were stratified into three periods after the onset of the first disease symptom and compared with the controls...
Seizure, 2018
Epileptic seizures are a common manifestation of autoimmune encephalitis, but the role of neural ... more Epileptic seizures are a common manifestation of autoimmune encephalitis, but the role of neural antibodies in long-term epilepsy remains unclear. The aim of this study was to assess the prevalence of neuralsurface antibodies (NSAbs) and antibodies against glutamic acid decarboxylase (GAD) in patients with chronic temporal lobe epilepsy (TLE). Method: Patients with an electro-clinical diagnosis of TLE and a disease duration longer than one year were included. NSAbs (LGI1, CASPR2, AMPAR1/2, NMDAR, GABA B R) and antibodies against GAD were detected. Only patients with significant antibody levels in serum, and/or positivity in CSF (according to antibody subtype), were enrolled in the seropositive group. Cohorts of seropositive and seronegative patients were compared regarding clinical and imaging data. Results: Significant serum levels of antibodies were detected in eight out of 163 (5%) TLE patients (CASPR2 n = 2, GAD n = 3, LGI1 n = 2, and GABA B R n = 1). In four of them, antibodies were detected in the CSF as well (CASPR2 in one, GAD in three). Five seropositive patients had uni-or bilateral temporal lobe lesions on MRI and three patients were non-lesional. All seropositive patients had TLE of unknown cause. Seropositive patients had higher age at epilepsy onset and autoimmune comorbidity, but did not differ in other clinical, EEG or neuroimaging characteristics. Response to immunotherapy (seizure reduction > 50%) was observed in three of the six patients treated. Conclusions: Besides older age at epilepsy onset and autoimmune comorbidity, seropositive patients cannot be distinguished from seronegative patients on the basis of clinical, EEG or neuroimaging data.
Folia biologica, 2007
The role of MRP4 and MRP5 transporters in the acyclic nucleoside phosphonate PMEDAP efflux was st... more The role of MRP4 and MRP5 transporters in the acyclic nucleoside phosphonate PMEDAP efflux was studied in vitro (CCRF-CEM cells) and in vivo (spontaneous transplantable T-cell lymphoma of SD/Cub inbred rats). The increased resistance against the cytostatic agent PMEDAP during longterm treatment was found to be associated with overexpression of MRP4 and MRP5 genes. The course of both gene activation differs significantly. While the MRP5 function is important in the onset of PMEDAP resistance, the intensity of the relative MRP4 gene expression increases rather continuously. Our data indicate cooperative acting of both MRP4 and MRP5 genes during the PMEDAP resistance development.