Konrad Rejdak

Publications of Konrad Rejdak

• Neurofilament heavy chain and heat shock protein 70 as markers of seizure-related brain injury.

  Authors: Konrad Rejdak, Jens Kuhle, Stephan Rüegg, Raija L P Lindberg, Axel Petzold, Dorota Sulejczak, Ewa Papuc, Robert Rejdak, Zbigniew Stelmasiak, Paweł Grieb

  Epilepsia. 04/2012;

  Purpose:  Status epilepticus (SE) has deleterious effects on brain tissue, but whether brief recurrent seizures may also damage neurons represents a matter of controversy. Therefore, it remains aPurpose:  Status epilepticus (SE) has deleterious effects on brain tissue, but whether brief recurrent seizures may also damage neurons represents a matter of controversy. Therefore, it remains a central area of epilepsy research to identify individuals at risk where disease progression can be potentially prevented. Biomarkers may serve as tools for such identification. Thus the present study aimed at analyzing the levels of heat shock protein 70 (HSP-70, also designated as HSPA1A) and neurofilament heavy chain protein (NfH(SMI35) ) in cerebrospinal fluid (CSF) of patients with seizures of different severity. Methods:  Forty-one patients were included, of whom 20 patients had a single generalized tonic-clonic seizure (GTCS) episode (SS), 11 had repetitive GTCS (RS), and 10 experienced convulsive SE. The control group consisted of 18 subjects. HSP-70 levels were measured using a conventional enzyme-linked immunosorbent assay (ELISA), whereas the NfH(SMI35) protein levels were detected by an electrochemiluminescence (ECL) immunoassay. Key Findings:  Patients with SE (p < 0.001) and RS (p < 0.05) had significantly higher NfH(SMI35) levels than controls, and SE was associated with increased concentrations when compared with SS (p < 0.001). NfH(SMI35) levels in SS did not differ from controls. Patients with SE had significantly raised HSP-70 levels compared to RS (p < 0.05), SS (p < 0.05), and controls (p < 0.001). SS and RS did not differ from each or from controls. Levels of NfH(SMI35) and HSP-70 showed a significant correlation (r = 0.34; p = 0.007) in the group of all study subjects, which was not apparent when controls and patients with seizures were considered separately. The correlation between NfH(SMI35) and HSP-70 tended to be inverse in patients with SE, but it did not reach statistical significance (r = -0.3; p > 0.05). Significance:  Studying biochemical markers as additional quantitative tools for the measurement of neuronal damage (especially subclinical), complementary to available techniques of imaging, and clinical assessment might prove useful for identifying patients at risk of accumulating neuronal injury resulting from uncontrolled seizures. NfH(SMI35) and HSP-70 are of potential value as sensitive and specific biomarkers of seizure-related pathologic events. Future longitudinal studies are needed to monitor such patients by correlating biochemical, neuroimaging, and clinical methods of assessment.

• The Prognostic Value of Brain Extracellular Fluid Nitric Oxide Metabolites After Traumatic Brain Injury.

  Authors: Martin M Tisdall, Konrad Rejdak, Neil D Kitchen, Martin Smith, Axel Petzold

  Neurocritical care. 10/2011;

  BACKGROUND: Nitric oxide (NO) is a compound with both protective and damaging effects on neurons. Quantification of NO metabolites in humans is limited by sample contamination with blood. In vivoBACKGROUND: Nitric oxide (NO) is a compound with both protective and damaging effects on neurons. Quantification of NO metabolites in humans is limited by sample contamination with blood. In vivo cerebral microdialysis may offer an alternative approach as sampling of extracellular fluid (ECF) adjacent to neurons becomes possible. We investigate the prognostic value of brain ECF NO metabolites in patients with traumatic brain injury (TBI). METHODS: A prospective case cohort of 195 ECF samples collected from 11 cases over 4 days following TBI was collected. Nitrate and nitrite concentrations ([NO( x )]) were quantified using a vanadium-based colorimetric assay. RESULTS: Early ECF [NO( x )] (<48 h post TBI) were significantly higher in non-survivors (median 59.2 μmol/l, n = 7) compared to survivors (23.3 μmol/l, n = 4) (P = 0.04). Late (48-96 h) ECF [NO( x )] remained higher in non-survivors (47.9 μmol/l) compared to survivors (23.0 μmol/l) but this was not significant (P = 0.29). Receiver operator characteristic analysis shows an optimized cutoff level for ECF [NO( x )] of 26.5 μmol/l measured <48 h post TBI for predicting non-survival (sensitivity 100%, specificity 75%). CONCLUSION: Early ECF NO( x ) concentrations are of prognostic value after TBI. ECF NO( x ) may be a useful biomarker for treatment trials targeted at nitric oxide metabolism.

• Analysis of ventricular late potentials in signal-averaged ECG of people with epilepsy.

  Authors: Konrad Rejdak, Andrzej Rubaj, Andrzej Głowniak, Kamila Furmanek, Andrzej Kutarski, Andrzej Wysokiński, Zbigniew Stelmasiak

  Epilepsia. 09/2011; 52(11):2118-24.

  There has been growing interest in cardiac disturbances in epilepsy patients and their etiologic role in the context of sudden death. Ventricular late potentials (VLPs) recorded on signal-averagedThere has been growing interest in cardiac disturbances in epilepsy patients and their etiologic role in the context of sudden death. Ventricular late potentials (VLPs) recorded on signal-averaged electrocardiography (SAECG) reflects delayed ventricular depolarization and identifies the structural or functional substrate for the ventricular tachycardia in the reentry mechanism. Therefore, abnormal SAECG poses the potential of identifying patients at increased risk of malignant ventricular arrhythmias and sudden cardiac death. The aim of this exploratory study was to screen epilepsy patients who were treated with established doses of antiepileptic drugs (AEDs) on the presence of VLPs. Forty-five consecutive patients with the diagnosis of epilepsy and 19 healthy volunteers, aged younger than 46 years, participated in the study. Exclusion criteria included symptoms or signs of diseases other than epilepsy, in particular relating to heart disease or medication influencing the cardiovascular system, as well as seizure reported by patients that occurred <3 days before the ECG examination. The electrocardiogram was recorded according to the standard protocol. The seizure frequency was calculated based on the available data of epileptic events within the preceding 3 months. Disease duration was estimated by determining the time from the first reported seizure to the present. There were 22 patients (48%) in the epilepsy group and only one patient (5%) in the control group fulfilling the criteria for VLP (p = 0.0005). Subsequently, epilepsy patients were divided into two subgroups according to VLP presence. Patients with VLP had longer disease duration (p = 0.03) compared to those without VLP. Similarly, patients with VLP more frequently had refractory epilepsy (p = 0.03) and had higher monthly seizure frequency (p = 0.02). Analysis of the proportions of generalized seizures (GS) and focal seizures (FS) showed a tendency for higher number of generalized tonic-clonic seizures in the VLP group, but this did not reach statistical significance (p = 0.06). VLP patients tended to be more often on polytherapy (defined as more than one AED per patient) (p = 0.07) as compared to epilepsy patients without VLP. However, if the numbers of AEDs per patients among the subgroups were compared, patients with VLP were treated with more AEDs than patients without VLP (p = 0.01). The study was not sufficiently powered to pinpoint any particular drug or AED combination to influence the appearance of VLP in epileptic patients. In particular, there was no difference in valproate or carbamazepine exposure, considering the percentage of patients exposed or the total daily dose administered. Epilepsy patients more frequently display abnormal SAECGs with VLPs as compared to the control population, and their presence correlates with the disease duration, uncontrolled seizures, and polytherapy. Further longitudinal studies are needed in order to stratify the risk of life-threatening ventricular events in epilepsy patients with VLPs.

• Atypical symptomatology of myoclonus dystonia (DYT-11) with positive response to bilateral pallidal deep brain stimulation.

  Authors: Ewa Papuć, Katarzyna Obszańska, Konrad Rejdak, Zbigniew Stelmasiak, And Tomasz Trojanowski

  Movement disorders : official journal of the Movement Disorder Society. 05/2011;

• [Efficacy and tolerability of dose-escalation with generic gabapentin--a multicenter, non-interventional study].

  Authors: Konrad Rejdak, Aurelia Lipa, Krzysztof Kaczyński, Zbigniew Stelmasiak

  Wiadomości lekarskie (Warsaw, Poland : 1960). 01/2011; 64(2):91-6.

  The aim of this study was to determine the efficacy and tolerability of 1800-2400 mg/day of generic gabapentin (Gabapentin Teva) as add-on treatment for refractory partial - onset epilepsy. This wasThe aim of this study was to determine the efficacy and tolerability of 1800-2400 mg/day of generic gabapentin (Gabapentin Teva) as add-on treatment for refractory partial - onset epilepsy. This was a multicenter, open-label, dose-escalation study of patients with refractory epilepsy (median age of 45.5 years [41-50; 25-75% percentile range], male 45.6%, female 47.8%). The inclusion criteria were insufficient partial-onset epilepsy control, defined as at least 1 seizure per month, while on adjunctive therapy with gabapentin used on daily doses below 1200 mg. The baseline seizure number was assessed over 3 months of observation in patients being on stable doses of their AED therapy and those subjects who met the inclusion criteria were enrolled into the study by their neurologist (Visit 0). Subsequently, patients were seen, and their data were evaluated at Visit I i.e. after the target dose of 1800 mg per day was achieved (mean duration of 3.6 [0.1-28.3] weeks) and 4 weeks later at Visit II, after the target dose up to 2400 mg per day. Primary efficacy was assessed by seizure frequency (number/month). Tolerability was assessed by adverse events and clinical evaluations. All the study periods were completed by 916 patients. A substantially lower median seizure frequency was observed at all gabapentin dosing periods (visit I - 2.0 [0-40] seizures per month and visit II - 1.0 [0-13] seizures per month; median and range) compared with the baseline period (3.0 [1-20] seizures per month) (Wilcoxon test p<0.001). In addition, the gradual increase of GBP dose led to raising proportion of patients rendered seizure free (Visit I - 1.1% and Visit II - 28.5%) compared with the baseline period 0.0% (McNemar test p<0.001). The dose escalation with GBP was well tolerated by the majority of patients. The most common adverse events during visit II were somnolence (2.8%) and dizziness (1.8%). In conclusion, gabapentin dose escalation to a dose range of 1800-2400 mg/d over 8 [1-32] week period proved to be an effective and well tolerated in patients with insufficient seizure control on lower doses with partial-onset epilepsy.

• Presence of L-kynurenine aminotransferase III in retinal ganglion cells and corpora amylacea in the human retina and optic nerve.

  Authors: Robert Rejdak, Carmen Rummelt, Eberhart Zrenner, Paweł Grieb, Konrad Rejdak, Etsuo Okuno, Sebastian Thaler, Katarzyna Nowomiejska, Friedrich Kruse, Waldemar Turski, Anselm Gm Junemann

  Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences. 01/2011; 49(2):132-7.

  Corpora amylacea (CAm) are a hallmark of aging and neurodegeneration. The presence of kynurenine aminotransferases I and II (KAT I and II) in CAm in the human retina and optic nerve has been alreadyCorpora amylacea (CAm) are a hallmark of aging and neurodegeneration. The presence of kynurenine aminotransferases I and II (KAT I and II) in CAm in the human retina and optic nerve has been already shown. The present study aimed to examine kynurenine aminotransferase III (KAT III) immunoreactivity in CAm in the human retina and optic nerve. Polyclonal antibody against KAT III was used on sections of human eyes enucleated due to malignant uveal melanoma. PAS-stained sections of CAm were compared with KAT III stained ones. KAT III immunoreactivity was observed in CAm in the retina, prelaminar, laminar and retrolaminar region of the optic nerve with similar location to PAS-stained sections. The most intense staining was observed in the retrolaminar part of the optic nerve. KAT III immunoreactivity was also present in the cytoplasm of retinal ganglion cells. Expression of KAT III in CAm in the human retina and optic nerve indicates that this enzyme may be relevant in mechanisms of neurodegeneration leading to CAm formation.

• Orphenadrine induces secondarily generalized convulsive status epilepticus in rats.

  Authors: Konrad Rejdak, Dorota Nieoczym, Mirosław Czuczwar, Jacek Kiś, Piotr Wlaź, Waldemar A Turski

  Brain research bulletin. 01/2011; 84(6):389-93.

  The current study was aimed to assess the convulsant potency of orphenadrine (ORPH) in rats together with a screen of different conventional antiepileptic drugs (AEDs) on their efficacy to suppressThe current study was aimed to assess the convulsant potency of orphenadrine (ORPH) in rats together with a screen of different conventional antiepileptic drugs (AEDs) on their efficacy to suppress it. ORPH was administered intraperitoneally (i.p.) in doses of 50-80 mg/kg in male Wistar rats. The latency to first seizure, the number of seizure episodes and the duration of overt status epilepticus (SE) as well as the incidence of deaths was scored with simultaneous electroencephalographic (EEG) recordings. Subsequently, the effects of conventional AEDs on ORPH-evoked (80 mg/kg) seizure incidence were studied. ORPH dose-dependently induced seizures in increasing number of animals, reaching 100% at a dose of 80 mg/kg, associated with low mortality and no drug-related neurotoxicity. Epileptic attacks started as complex partial fits consisting of stereotyped behavior, limb movements, head shaking and myoclonic twitches of the body. Subsequently, an overt generalized convulsive SE appeared, lasting for approximately 2h. Among conventional AEDs: carbamazepine, ethosuximide and phenytoin had no effect while valproate (p<0.001), diazepam (p<0.01), and phenobarbital (p<0.001) dose-dependently suppressed seizure activity. All the above characteristics make the new model, a useful, easy to perform experimental tool to study the pathophysiology of SE as well as the effects of new AEDs.

• Consensus Guidelines for CSF and Blood Biobanking for CNS Biomarker Studies.

  Authors: Charlotte E Teunissen, Hayrettin Tumani, Jeffrey L Bennett, Frode S Berven, Lou Brundin, Manuel Comabella, Diego Franciotta, Jette L Federiksen, John O Fleming, Roberto Furlan [......] Axel Petzold, Cecilia Rajda, Konrad Rejdak, Hollie K Schmidt, Vincent van Pesch, Emmanuelle Waubant, Christian Wolf, Florian Deisenhammer, Gavin Giovannoni, Bernhard Hemmer

  Multiple sclerosis international. 01/2011; 2011:246412.

  There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in cerebrospinal fluid (CSF) are being used inThere is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in cerebrospinal fluid (CSF) are being used in clinical practice. Anti-aquaporin-4 antibodies in serum are currently useful for the diagnosis of neuromyelitis optica (NMO), but we could expect novel CSF biomarkers that help define prognosis and response to treatment for this disease. One of the most critical factors in biomarker research is the inadequate powering of studies performed by single centers. Collaboration between investigators is needed to establish large biobanks of well-defined samples. A key issue in collaboration is to establish standardized protocols for biobanking to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by pre-analytical factors. Here, consensus guidelines for CSF collection and biobanking are presented, based on the guidelines that have been published by the BioMS-eu network for CSF biomarker research. We focussed on CSF collection procedures, pre-analytical factors and high quality clinical and paraclinical information. Importantly, the biobanking protocols are applicable for CSF biobanks for research targeting any neurological disease.

• CSF hypocretin-1 concentrations correlate with the level of fatigue in multiple sclerosis patients.

  Authors: Ewa Papuć, Zbigniew Stelmasiak, Stelmasiak Zbigniew, Paweł Grieb, Grieb Paweł, Konrad Rejdak, Rejdak Konrad

  Neuroscience letters. 02/2010; 474(1):9-12.

  Considering the multiplicity of symptoms associated with multiple sclerosis (MS), there is possibility that hypocretin system function might be involved in the pathogenesis of the disease. TheConsidering the multiplicity of symptoms associated with multiple sclerosis (MS), there is possibility that hypocretin system function might be involved in the pathogenesis of the disease. The current study aimed to investigate the hypocretin-1 levels in cerebrospinal fluid (CSF) of MS patients in relation to different neurological deficit measures including: Ambulation Index (AI), Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), and Epworth Sleepiness Scale (ESS) in relapse-onset MS patients. 53 subjects were included into the study: 38 patients with a diagnosis of MS and 15 healthy controls. Among MS patients, 25 had relapsing-remitting and 13 secondary progressive MS. CSF hypocretin-1 levels did not differ between MS patients and healthy controls (p>0.05). A positive correlation between hypocretin-1 level and fatigue level was found in MS patients (p<0.05) and this effect was even stronger in the MS subgroup suffering from fatigue (p=0.01). Hypocretin system seems to be generally unchanged in MS but a positive correlation between hypocretin-1 level and fatigue may indicate involvement of some compensatory mechanisms stimulating the production of the neuropeptide in MS patients.

• Neurology training around the world: asking the trainees.

  Authors: Konrad Rejdak, Axel Petzold, Karl Ng, Judit Afra, Irena Dujmovic, Zbigniew Stelmasiak, Danuta Ryglewicz, Hubert Kwiecinski, Wolfgang Grisold, Laszlo Vecsei

  Lancet neurology. 01/2010; 9(1):32-3.

• Multiple sclerosis: a practical overview for clinicians.

  Authors: Konrad Rejdak, Samuel Jackson, Gavin Giovannoni

  British medical bulletin. 01/2010; 95:79-104.

  Multiple sclerosis (MS) is the commonest disabling neurological condition to afflict young adults and therefore has a high social burden. Over several decades, there has been a considerable progressMultiple sclerosis (MS) is the commonest disabling neurological condition to afflict young adults and therefore has a high social burden. Over several decades, there has been a considerable progress in the understanding of the disease pathogenesis as well as in the clinical management of MS patients. The emphasis in managing MS patients has shifted to multidisciplinary teams working in specialist groups. A review of the literature was conducted using MedLine to identify recent advances in MS. The current consensus is that MS is an autoimmune disease triggered by environmental agents acting in genetically susceptible people. Based on that concept, new methods of immune intervention procedures have been introduced into clinical practice. Licensed first-line disease-modifying therapies reduce the MS attack or relapse rate by a third and delaying short-term disease progression. More effective therapies have emerged; however, these are associated with increased risks. New clinical and pathological insights are making us question the aetiology and pathogenesis of MS. The recognition of pathological heterogeneity has raised the question of whether MS is a single disease entity or a syndrome. Recent evidence suggests that the pathological subtype may predict therapeutic response to specific therapies. A new novel auto-antibody has defined a subset of neuromyelitis optica or Devic's disease as being distinct from MS. This is an attractive concept that is not widely accepted. The observation that MS progresses despite immunosuppressive therapy suggests that MS may be a neurodegenerative disease with overlapping immune activation possibly in response to the release of central nervous system auto-antigens. The development of neuroprotective therapies for MS is required to prevent the devastating effects of long-term disability as a result of progressive disease.

• Neurofilament ELISA validation.

  Authors: Axel Petzold, Ayse Altintas, Laura Andreoni, Ales Bartos, Achim Berthele, M A Blankenstein, Luc Buee, Massimiliano Castellazzi, Sabine Cepok, Manuel Comabella [......] Vincent van Pesch, Hugo Vanderstichele, Christian Vedeler, Marcel M Verbeek, Luisa Maria Villar, Robbert Weissert, Brigitte Wildemann, Cui Yang, Karen Yao, Charlotte Teunissen

  Journal of immunological methods. 10/2009;

  BACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study isBACKGROUND: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. METHODS: The UmanDiagnostics NF-light (R)enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses. RESULTS: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R=0.60, p<0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R=0.98, p<0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics. CONCLUSION: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.

• A novel biomarker for retinal degeneration: vitreous body neurofilament proteins.

  Authors: Axel Petzold, Anselm Junemann, Konrad Rejdak, Tomasz Zarnowski, Sebastian Thaler, Pawel Grieb, Friedrich Kruse, Eberhart Zrenner, Robert Rejdak

  Journal of neural transmission (Vienna, Austria : 1996). 09/2009;

  Retinal degeneration leads to release of cell-type specific proteins into the adjacent compartment. Here we investigated whether the neurofilament heavy chain protein (NfH) could be measured from theRetinal degeneration leads to release of cell-type specific proteins into the adjacent compartment. Here we investigated whether the neurofilament heavy chain protein (NfH) could be measured from the vitreous body and anterior chamber fluid. This prospective study included 85 patients who underwent vitrectomy (44 retinal detachment, 12 macular hole, 15 epiretinal gliosis, 8 organ donors) or trabelectomy (six glaucoma). The cut-off level was calculated from the organ donors. An established enzyme-linked immunosorbent assay (ELISA, SMI35) was used for quantification of NfH (190-210 kDa). Measurable levels of NfH were detected from the vitreous body homogenate, but not from the anterior chamber fluid. The cut-off level was 0.29 ng/mL. A significant proportion of patients suffering from retinal detachment (43.2%, mean 0.74 ng/mL) had vitreous body NfH levels above cut-off when compared to organ donors (0%, 0.12 ng/mL, p = 0.02), epiretinal sclerosis (1.6%, 0.05 ng/mL, p = 0.01), macular hole (0%, 0.04 ng/mL, p = 0.004). Following retinal detachment, vitreous NfH-SMI35 levels correlated with time from onset (R = -0.3, p < 0.05), persisting for up to 2 years. This study shows that NfH can be quantified from the human vitreous body and may be a useful novel biomarker for retinal degeneration. The method can be applied for investigating the dynamics of retinal degeneration and the response to neuroprotective strategies in a broad range of retinal diseases in either clinical or experimental research.

• Decreased cerebrospinal fluid hypocretin-1 (orexin A) in patients after repetitive generalized tonic-clonic seizures.

  Authors: Konrad Rejdak, Ewa Papuć, Paweł Grieb, Zbigniew Stelmasiak

  Epilepsia. 02/2009;

  Summary The effects of seizures on the hypocretin/orexin system have not yet been investigated in epileptic patients. The present study aimed to assay hypocretin-1 in the cerebrospinal fluid (CSF) ofSummary The effects of seizures on the hypocretin/orexin system have not yet been investigated in epileptic patients. The present study aimed to assay hypocretin-1 in the cerebrospinal fluid (CSF) of patients after generalized tonic-clonic (GTC) seizures. Study groups consisted of 21 patients after GTC seizures and 19 controls. Diagnostic lumbar puncture was performed in control and epileptic patients within 48 h after the GTC seizures. Hypocretin-1 levels were measured in unextracted CSF samples, using a standardized commercial radioimmunoassay. There was a significant overall difference in median CSF hypocretin-1 concentrations between controls and patients with GTC patients (p < 0.001). The lowest concentrations were noted in a subgroup of patients with repetitive GTC seizures (RS) compared to those with a single GTC seizure (SS) (p > 0.05) or controls (p < 0.001). The current results suggest that the hypocretin-1 system deficiency contributes to the complex pathophysiology of repetitive GTC seizures and status epilepticus (SE) and could be associated with typical somnolence after seizure attacks.

• Biventricular versus right ventricular pacing decreases immune activation and augments nitric oxide production in patients with chronic heart failure.

  Authors: Andrzej Rubaj, Piotr Ruciński, Konrad Rejdak, Krzysztof Oleszczak, Dariusz Duma, Paweł Grieb, Andrzej Kutarski

  European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology. 10/2006; 8(6):615-20.

  INTRODUCTION: Immune system activation and oxidative stress are involved in the pathogenesis of heart failure (HF). We aimed to test the hypothesis that upgrading from right ventricular pacing (RVp)INTRODUCTION: Immune system activation and oxidative stress are involved in the pathogenesis of heart failure (HF). We aimed to test the hypothesis that upgrading from right ventricular pacing (RVp) to biventricular pacing (BiVp) can counteract these phenomena. METHODS: 28 HF patients, with BiVp were switched to RVp for one week, and then returned to BiVp. Immediately prior to, and 48 h after the return to BiVp, left ventricular (LV) systolic function was evaluated by echocardiography, and serum N-terminal pro-brain natriuretic peptide (NTproBNP), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL6), nitric oxide metabolites (NO(x)) and malondialdehyde (MDA) were assayed. RESULTS: LV systolic function significantly improved 48 h after switching from RVp to BiVp: Ao-VTI (p<0.001), SV (p<0.001) and CO (p<0.001), and mitral regurgitation significantly decreased (p=0.003). At the same time, indices of peripheral immune activation decreased: TNF-alpha (p=0.02) and IL6 (p<0.001). MDA decreased (p<0.001), whereas NO(x) increased (p=0.04). NTproBNP and CRP did not change. In addition, in "responders" (i.e. CO increase >10% during BiVp vs. RVp) NTproBNP decreased and NO(x) increased. However, during BiVp, the decreases in TNF-alpha, IL6, and MDA occurred both in responders and in non-responders and were accompanied by a reduction in mitral regurgitation. CONCLUSION: The beneficial effect of BiVp compared to RVp extends beyond improving cardiac haemodynamics and comprises a decrease in immune activation accompanied by an increase in serum NO(x) and decrease in serum MDA.

• Cerebrospinal fluid nitrite/nitrate correlated with oxyhemoglobin and outcome in patients with subarachnoid hemorrhage.

  Authors: Konrad Rejdak, Axel Petzold, Martyn A Sharpe, Andrew D Kay, Mary Kerr, Geoff Keir, Edward J Thompson, Gavin Giovannoni

  Journal of the neurological sciences. 04/2004; 219(1-2):71-6.

  The findings of various studies reporting temporal changes in CSF total nitrite/nitrate (NOx) levels after subarachnoid hemorrhage (SAH) vary considerably. The study group comprised 10 patients withThe findings of various studies reporting temporal changes in CSF total nitrite/nitrate (NOx) levels after subarachnoid hemorrhage (SAH) vary considerably. The study group comprised 10 patients with SAH and 10 control subjects. Total nitrite/nitrate concentration was measured by a vanadium-based assay with the colorimetric Griess reaction. CSF oxyhemoglobin level was assessed by spectrophotometry. After an initial peak (22.6+/-10.1 microM) within first 24 h after SAH, CSF NOx decreased gradually during the period of observation. There was a significant correlation between CSF concentrations of NOx and OxyHb in the entire observation period (R=0.87, p<0.001). When the impact of bleeding into CSF was considered, patients with very good outcome [Glasgow Outcome Scale (GOS)=5] had significantly lower CSF NOx (11.1+/-1.3 microM) than those with worse outcome (GOS<5) (21.8+/-11.2 microM, p<0.01). In conclusion, this study demonstrates that after aneurysm rupture CSF NOx levels correlate with OxyHb. We suggest this as a novel interpretation of other variable findings in relation to NO metabolites in the central nervous system (CNS) post SAH, and hence it could usefully be incorporated into the planning of future studies, correlating NOx with clinical outcome.

• Neurology training around the world.

  Authors: Juzar Hooker, Matthew Eccher, Kamakshi Lakshminarayan, Fabiana C Souza-Lima, Konrad Rejdak, Hubert Kwiecinski, Francesco Corea, José M Lopes Lima

  Lancet neurology. 10/2003; 2(9):572-9.

• Oral citicoline treatment improves visual pathway function in glaucoma.

  Authors: Robert Rejdak, Jerzy Toczołowski, Jacek Kurkowski, Marek L Kamiński, Konrad Rejdak, Zbigniew Stelmasiak, Paweł Grieb

  Medical science monitor : international medical journal of experimental and clinical research. 04/2003; 9(3):PI24-8.

  BACKGROUND: Increased latency and reduced amplitude of visual evoked potentials (VEP), frequently encountered in ocular hypertension or open-angle glaucoma, suggest slowed neural conduction in theBACKGROUND: Increased latency and reduced amplitude of visual evoked potentials (VEP), frequently encountered in ocular hypertension or open-angle glaucoma, suggest slowed neural conduction in the visual pathways. An improvement in VEP latency and amplitude has been reported following repeated intramuscular injections of citicoline, a neuroprotective drug. Our aim was to find whether citicoline given orally would produce a similar effect. MATERIAL/METHODS: VEP latency and amplitude were measured in 21 glaucomatous eyes prior to and after two bi-weekly courses of citicoline taken orally in a dose of 1 gram/day. The treatment courses were separated by a two-week break; post-treatment VEP measurement was performed two weeks after the end of the second treatment. RESULTS: 62% of the eyes showed a response to the treatment, with VEP latency reduced from 123.5 (3.9 SEM) ms to 111.9 (1.9 SEM) ms (P=0.0008), and VEP amplitude increased from 6.56 (1.39 SEM) to 7.88 (1.16 SEM) (P=0.04). CONCLUSIONS: Citicoline given orally improves visual evoked potentials in some glaucoma patients.

• [The assessment of development of binding antibodies to interferon beta during interferon beta 1a treatment of multiple sclerosis]

  Authors: Halina Bartosik-Psujek, Ewa Belniak, Krystyna Mitosek-Szewczyk, Konrad Rejdak, Beata Dobosz, Zbigniew Stelmasiak

  Neurologia i neurochirurgia polska. 02/2003; 37(4):799-809.

  The importance of binding antibodies (BAb) that develop during the treatment of multiple sclerosis with interferon beta has not been fully explained yet. However, they are generally regarded as oneThe importance of binding antibodies (BAb) that develop during the treatment of multiple sclerosis with interferon beta has not been fully explained yet. However, they are generally regarded as one of factors that may diminish treatment efficacy. The aim of the study was to evaluate firstly, BAb occurrence in interferon beta 1-a (IFN beta 1-a)-treated MS patients and secondly, BAb impact on clinical efficacy of this medication. In the 36-month study participants were 21 patients with relapsing-remitting multiple sclerosis, RR-MS, (14 women, 7 men, aged 29.6 +/- 8.5). All the patients were receiving intramuscular IFN beta-1a (Avonex) for 24 months, in the dose of 30 micrograms per week. Clinical parameters and serum BAb levels (the EIA method) were estimated every 3 months. Two control groups, examined only once, included 20 RR-MS patients without IFN-beta therapy and 20 healthy volunteers. While before treatment a high BAb level was found in 2 patients (9.5%), at 6 months of treatment it was found in 8 patients (38.1%). A similar number of patients with high BAb levels was seen throughout the study during the IFN-beta treatment. On therapy completion serum BAb levels decreased very rapidly. After 2 years of treatment, disability as measured by the EDSS scale was more pronounced in patients with serum BAb, but the differences were statistically not significant. No statistically significant relationship was found either between elevated BAb levels and the number of relapses during the IFN-beta treatment (including relapses that required steroid therapy).

• Decreased level of kynurenic acid in cerebrospinal fluid of relapsing-onset multiple sclerosis patients.

  Authors: Konrad Rejdak, Halina Bartosik-Psujek, Beata Dobosz, Tomasz Kocki, Pawelz Grieb, Gavin Giovannoni, Waldemar A Turski, Zbigniew Stelmasiak

  Neuroscience letters. 10/2002; 331(1):63-5.

  The present study was undertaken to measure cerebrospinal fluid (CSF) levels of kynurenic acid (KYNA) in patients with relapsing-onset multiple sclerosis (MS) during remission or not progressing forThe present study was undertaken to measure cerebrospinal fluid (CSF) levels of kynurenic acid (KYNA) in patients with relapsing-onset multiple sclerosis (MS) during remission or not progressing for at least 2 months. In these patients the levels of CSF KYNA were found to be significantly lower compared with subjects with non-inflammatory neurological diseases, as well as those with inflammatory disease (median (interquartile range): 0.41 (0.3-0.5) pmol/ml, n=26 vs. 0.67 (0.5-1.1), n=23, P<0.01 and 1.7 (1.5-2.6), n=16, P<0.001, respectively). These results provide further evidence of the alterations in the kynurenine pathway during remitting-onset MS.