Publications by authors named "Beata Zakrzewska-Pniewska"

30 Publications

  • Page 1 of 1

Impact of Immunoablation and Autologous Hematopoietic Stem Cell Transplantation (AHSCT) on Treatment Cost of Multiple Sclerosis: Real-World Nationwide Study.

Value Health Reg Issues 2021 Apr 14;25:104-107. Epub 2021 Apr 14.

Medical University of Warsaw, Hematology, Oncology, and Internal Diseases, Warsaw, Poland. Electronic address:

Objectives: To provide real-world data on the impact of autologous hematopoietic stem cell transplantation (AHSCT) on treatment costs of patients with multiple sclerosis (MS) in Poland.

Methods: Medical data of 105 patients who underwent AHSCT in the years 2011 to 2016 were obtained from the National Health Fund (NHF) database. Treatment costs were calculated from the public payer's perspective per patient-year for the total available period as well as 12 months before and after AHSCT. The statistical analysis was performed using MATLAB 2016b.

Results: Mean treatment-related costs covered by the NHF per patient-year before and after the transplantation were €4314.9 and €1188.8 , respectively. The average cost of disease-modifying drugs per patient was reduced from €2497.9/year before to €65.3/year after AHSCT.

Conclusions: Although the initial cost of AHSCT is high, the costs involving AHSCT and post-AHSCT treatment could, according to our analysis, pay off in 3.9 years, when compared to the costs of disease-modifying drug therapy in aggressive MS. The study provides evidence that the AHSCT can lead to significant savings in treatment costs of aggressive MS from the public payer's perspective.
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http://dx.doi.org/10.1016/j.vhri.2020.10.008DOI Listing
April 2021

Clinical course and outcome of SARS-CoV-2 infection in multiple sclerosis patients treated with disease-modifying therapies - the Polish experience.

Neurol Neurochir Pol 2021 15;55(2):212-222. Epub 2021 Apr 15.

Medical University of Białystok, Poland.

Introduction: The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited.

Materials And Methods: This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health.

Results: There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used.

Conclusions And Clinical Implications: Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs.
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http://dx.doi.org/10.5603/PJNNS.a2021.0031DOI Listing
May 2021

Search for viral agents in cerebrospinal fluid in patients with multiple sclerosis using real-time PCR and metagenomics.

PLoS One 2020 28;15(10):e0240601. Epub 2020 Oct 28.

Department of Adult Infectious Diseases, Medical University of Warsaw, Warsaw, Poland.

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disease of the central nervous system of unclear etiology, but there is some evidence that viral infections could be responsible for triggering autoimmune mechanisms against myelin. We searched for viral RNA and DNA in cerebrospinal fluid (CSF) of 34 MS patients and 13 controls using RT-PCR/PCR against common neurotropic viruses. In addition, shotgun DNA- and RNA-based metagenomics were done in 13 MS patients and 4 controls. Specific quantitative real-time RT-PCR/PCR testing revealed the presence of viral nucleic acid in seven (20.59%) MS patients and in one (7.69%) control patient. In MS patients the most frequently detected was human herpesvirus type 6 (HHV-6; 3 cases; 8.82%); followed by Epstein-Barr virus (EBV; 2 cases; 5.88%), varicella zoster virus (VZV; 1 case; 2.94%) and Enterovirus (EV; 1 case; 2.94%). The single identified virus among controls was EBV (7.69%). DNA and RNA metagenomic assays did not identify any known eukaryotic viruses even though three of the analyzed samples were low-level positive by specific quantitative real-time PCR. In conclusion, we detected the presence of Herpesviridae and occasionally Enteroviridae in CSF from patients with MS but their prevalence was not significantly higher than among controls. Metagenomic analysis seems to be less sensitive than real-time RT-PCR/PCR and it did not detect any potential viral pathogens.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240601PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592794PMC
December 2020

The relationship between aquaporin-4 antibody status and visual tract integrity in neuromyelitis optica spectrum disorders: A visual evoked potential study.

Mult Scler Relat Disord 2020 Sep 6;44:102265. Epub 2020 Jun 6.

Department of Neurology, Medical University of Warsaw, Warsaw, Poland. Electronic address:

Background: Optic neuritis (ON) is one of the hallmark symptomatic features of neuromyelitis optica spectrum disorders (NMOSD). The majority of patients with NMOSD present highly specific autoantibodies against aquaporin-4 (AQP4). A number of studies have reported poor visual acuity outcomes in individuals with AQP4 seropositive NMOSD, but no such relationship has been found with regard to visual evoked potentials (VEP) parameters such as the amplitude and latency of the P100 component. In this paper, we aimed (i) to describe VEP responses in patients with NMOSD; (ii) to analyze those results based on a scoring system; and (iii) to investigate the association between the VEPs and AQP4 antibody status.

Methods: We retrospectively analysed the VEP responses of 40 patients with a diagnosis of NMOSD (according to the 2015 IPND criteria), including 16 with AQP4-postive status (AQP4[+]) and 24 with AQP4-negative status (AQP4[-]). In the first step, we measured the P100 peak latency and P100-N2 peak-to-peak amplitude in each patient. In the second, we converted these measures to the VEP score (0-10) using the scoring proposed by Jung et al. (2008). All recordings were performed using the same VEP device and testing protocol.

Results: Abnormal VEPs were recorded in 25 of 40 patients (62.6%). Of these, 17 (42.5%) had prolonged P100 latency, and 8 (20%) had no response detected in at least one eye. The patients with ON as the initial relapse symptom had significantly higher median VEP scores than those who experienced the longitudinally extensive transverse myelitis (LETM) at the disease onset (7.0 [in-terquar-tile range (IQR), 2.0-8.0] vs. 0.0 [IQR, 0.0-4.0], p<0.001). A lack of VEP response in at least one eye was detected more frequently in the AQP4[+] group than the AQP4[-] group (7/16 vs. 1/24, p<0.005). Logistic regression model controlling for age, gender, disease duration, and the type of relapse at onset showed an independent impact of AQP4[+] status (OR=35.45, p = 0.018) on the higher rate of absent VEP responses. In the entire group of patients (n = 40), those with AQP4[+] showed a small tendency towards a higher median VEP score (4.0 [IQR, 0.0-7.8] vs. 1.0 [IQR, 0.0-4.0], p = 0.304). Among individuals with abnormal responses (n = 25), the patients with AQP4[+] had significantly higher median VEP scores (7.0 [IQR, 4.0-8.5] vs. 3.0 [IQR, 1.0-7.0], p = 0.034) and more common bilateral involvement of the optic tracts (80% vs. 40%, p = 0.048) than those who were seronegative for anti-AQP4 antibody. A median regression analysis model controlling for age, gender, disease duration, type of onset, and number of relapses in last 12 months showed an independent association between the AQP4-positive status and a higher VEP score in patients with NMOSD (t = 2.882, df=2, p = 0.007).

Conclusion: VEP study remains a useful tool in the assessment of NMOSD patients. Due to the high prevalence of absent VEPs in NMOSD patients, the scoring system appears to be more applicable for the precise analysis of VEP recordings. There is a positive association between the AQP-positive serostatus and the poorer outcome in VEP responses, especially in patients with severe impairment of the optic nerve(s).
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http://dx.doi.org/10.1016/j.msard.2020.102265DOI Listing
September 2020

Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder.

N Engl J Med 2019 11;381(22):2114-2124

From the Department of Immunology, National Institute of Neuroscience, and the Multiple Sclerosis Center, National Center of Neurology and Psychiatry (T.Y.), and Chugai Pharmaceutical (H.Y., Y.K.), Tokyo, and the Department of Multiple Sclerosis Therapeutics, Fukushima Medical University, and the Multiple Sclerosis and Neuromyelitis Optica Center, Southern Tohoku Research Institute for Neuroscience, Koriyama (K.F.) - all in Japan; the Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, and Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg - both in Germany (I.K.); the Department of Clinical Neurology, John Radcliffe Hospital, Oxford (J.P.), and Chugai Pharma Europe, London (P.W.) - both in the United Kingdom; the Department of Neurology, University of Texas Southwestern Medical Center, Dallas (B.G.); the Department of Neurology, Warsaw Medical University, Warsaw, Poland (B.Z.-P.); the Department G.F. Ingrassia, Neuroscience Section, University of Catania, Catania, Italy (F.P.); the Neurologic Institute, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan (C.-P.T.); the Service of Neurology, Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer, University of Barcelona, Barcelona (A.S.); and the Department of Neurology, Hôpital de Hautepierre, Clinical Investigation Center, INSERM 1434, and Fédération de Médecine Translationelle, INSERM 1119 - all in Strasbourg, France (J.D.S.).

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system and is associated with autoantibodies to anti-aquaporin-4 (AQP4-IgG) in approximately two thirds of patients. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. The efficacy of satralizumab added to immunosuppressant treatment in patients with NMOSD is unclear.

Methods: In a phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with NMOSD who were seropositive or seronegative for AQP4-IgG to receive either satralizumab, at a dose of 120 mg, or placebo, administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter, added to stable immunosuppressant treatment. The primary end point was the first protocol-defined relapse in a time-to-event analysis. Key secondary end points were the change from baseline to week 24 in the visual-analogue scale (VAS) pain score (range, 0 to 100, with higher scores indicating more pain) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (range, 0 to 52, with lower scores indicating more fatigue). Safety was also assessed.

Results: A total of 83 patients were enrolled, with 41 assigned to the satralizumab group and 42 to the placebo group. The median treatment duration with satralizumab in the double-blind period was 107.4 weeks. Relapse occurred in 8 patients (20%) receiving satralizumab and in 18 (43%) receiving placebo (hazard ratio, 0.38; 95% confidence interval [CI], 0.16 to 0.88). Multiple imputation for censored data resulted in hazard ratios ranging from 0.34 to 0.44 (with corresponding P values of 0.01 to 0.04). Among 55 AQP4-IgG-seropositive patients, relapse occurred in 11% of those in the satralizumab group and in 43% of those in the placebo group (hazard ratio, 0.21; 95% CI, 0.06 to 0.75); among 28 AQP4-IgG-seronegative patients, relapse occurred in 36% and 43%, respectively (hazard ratio, 0.66; 95% CI, 0.20 to 2.24). The between-group difference in the change in the mean VAS pain score was 4.08 (95% CI, -8.44 to 16.61); the between-group difference in the change in the mean FACIT-F score was -3.10 (95% CI, -8.38 to 2.18). The rates of serious adverse events and infections did not differ between groups.

Conclusions: Among patients with NMOSD, satralizumab added to immunosuppressant treatment led to a lower risk of relapse than placebo but did not differ from placebo in its effect on pain or fatigue. (Funded by Chugai Pharmaceutical; ClinicalTrials.gov number, NCT02028884.).
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http://dx.doi.org/10.1056/NEJMoa1901747DOI Listing
November 2019

Real-world effectiveness of fingolimod in Polish group of patients with relapsing-remitting multiple sclerosis.

Clin Neurol Neurosurg 2019 Sep 23;184:105453. Epub 2019 Jul 23.

Department of Neurology, Military Institute of Medicine in Warsaw, Poland.

Objectives: Fingolimod is indicated for the treatment of relapsing-remitting multiple sclerosis (RRMS) patients with highly aggressive disease characterized by frequent relapses and active magnetic resonance imaging. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. Fingolimod in licensed in Europe since 2011 but with a growing number of disease-modifying drugs (DMD) becoming available for RRMS, it is important to gather real-world evidence data regarding long-term effectiveness in treated patients with MS. The aim of this study was to assess fingolimod effectiveness in a real life Polish group of RRMS patients receiving fingolimod as second line treatment.

Patients And Methods: The observational study with retrospective data collection was performed at 13 sites that were asked to document eligible patients in consecutive chronological order to avoid selection bias. Demographic and clinical data from 253 adult patients with RRMS treated with fingolimod were analyzed.

Results: Mean treatment time with fingolimod was 42 months. Relapses reduction during 3 years treatment period was observed (2.0 v 0.2) and majority of patients were free of relapses. Mean EDSS score was stable during the time of observation. The proportion of patients who were free from any clinical disease activity, i.e. without relapses and disability progression, was over 70%. During the first and second year of observation significant reduction of new MRI lesions was observed.

Conclusion: In the Polish group of patients with RRMS treated with fingolimod, the majority of them showed freedom from relapses, disability progression and reduction of new MRI lesions. Switching from injectable immunomodulatory drugs to fingolimod is associated with fewer relapses and lower disability progression.
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http://dx.doi.org/10.1016/j.clineuro.2019.105453DOI Listing
September 2019

Electrophysiological and clinical assessment of dysautonomia in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP): a comparative study.

Neurol Neurochir Pol 2019;53(1):26-33. Epub 2019 Jan 8.

Department of Neurology, Medical University of Warsaw, 8 Kondratowicza str, 03-242 Warsaw, Poland.

Clinical Rationale For The Study: Autonomic nervous system (ANS) involvement in different parkinsonian syndromes has been frequently discussed. It is well established in multiple system atrophy (MSA), whereas it is less evident in progressive supranuclear palsy (PSP).

Aims Of The Study: The aims were to assess the presence and pattern of ANS involvement in MSA and PSP using noninvasive tests i.e. the sympathetic skin response (SSR) test and the R-R interval variation (RRIV) test; to analyse the relationship between clinical and electrophysiological abnormalities in both disorders; and to assess whether an autonomic profile might help to differentiate them.

Materials And Methods: Clinical and electrophysiological assessments of dysautonomia were performed in 59 patients with MSA (24 cases of MSA-C and 35 cases of MSA-P), these 59 cases including 31 females, mean disease duration 4.2 ± 2.7 years, mean age 60.3 ± 8.4 years, and in 37 patients with PSP (12 females, mean disease duration 4.6 ± 3.6 years, mean age 67.5 ± 6.1 years) and the results were compared to the results obtained from 23 healthy controls matched for age and sex.

Results: Clinical dysautonomia assessed by an Autonomic Symptoms Questionnaire was observed in 97% of the MSA patients and in 84% of the PSP patients. SSR was abnormal in 64% and RRIV was abnormal in 73% of MSA cases. In PSP cases, these figures were 78% and 81% respectively. Dysautonomia was clinically more pronounced in MSA compared to PSP (p < 0.05), whereas electrophysiological testing revealed frequently subclinical ANS damage in PSP patients.

Conclusions And Clinical Implications: Our results point to the complementary role of electrophysiological tests in the diagnostic work-up of dysautonomia in parkinsonian syndromes.
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http://dx.doi.org/10.5603/PJNNS.a2019.0005DOI Listing
June 2019

Evaluation of reproductive health in female patients with multiple sclerosis in Polish population.

J Clin Neurosci 2018 Jul;53:117-121

1st Department of Obstetrics and Gynaecology, Medical University of Warsaw, Pl. Starynkiewicza 1/3, 02-015, Poland.

Multiple sclerosis (MS) is a chronic disease, which affects mostly women and has an early onset. Due to progress in treatment patients maintain a high quality of life for a long period and participate in all of its fields. One of them is reproductive health with all of its aspects. The aim of the study was to evaluate the reproductive health of female MS patients with regard to various features of MS. It was a cross-sectional study. The data was collected via anonymous survey distributed among patients with MS hospitalized at the Department of Neurology, Medical University of Warsaw and online. The study group consisted of 218 women diagnosed with MS. The survey consisted of demographic questions, questions assessing features of MS, reproductive health, sexual performance and psychological comorbidities, including depression and fatigue. 53.01% of MS patients declared interest in maternity. Patients interested in pregnancy were significantly younger (p < .01), often nulliparous (p < .001), had lower EDSS score (p < .006) and lower motor deficit (p < .001). History of at least one labour (p < .02) had a negative impact on the frequency of gynaecologic admissions. More advanced age (p < .003), unemployment (p < .01), at least one labour (p < .043), stronger balance problems (p < .003) and more intense motor deficit (p < .002) were related to less frequent Pap smears. Reproductive health of women with MS is similar to that of background population. Therefore, the general gynaecological care in those women should not be neglected.
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http://dx.doi.org/10.1016/j.jocn.2018.04.012DOI Listing
July 2018

Sexual dysfunction in female patients with relapsing-remitting multiple sclerosis.

Brain Behav 2017 06 14;7(6):e00699. Epub 2017 Apr 14.

1st Department of Obstetrics and Gynecology Medical University of Warsaw Warsaw Poland.

Introduction: Sexual dysfunction (SD) is one of the common symptoms of multiple sclerosis (MS) and is often underdiagnosed, especially in women. Relapsing-remitting multiple sclerosis (RRMS) is the most widespread form of the disease, but the data on SD occurrence in this particular group of patients is limited. The aim of the study was to analyze the associations between demographic factors, symptoms and signs of MS, psychiatric comorbidities and SD in female patients with RRMS.

Material & Methods: A subgroup of 86 sexually active women with RRMS out of 218 total MS respondents was analyzed. Exclusion criteria included active relapse, EDSS score equal or higher than 6.5, and current pregnancy. All patients completed questionnaires including demographic data, questions about symptoms and signs of MS, Female Sexual Function Index (FSFI) for sexual performance, Patient Health Questionnaire 9 (PHQ-9) for depression, and Fatigue Severity Scale (FSS) for fatigue evaluation.

Results: According to FSFI, SD occurred in 21 (27.27%) of the respondents. SD occurrence was associated with depression ( < .05) and speech disturbances ( < .04). A negative effect on sexual performance was associated with depression intensity ( < .003), fatigue intensity ( < .05), more advanced age at diagnosis ( < .02), lower education level ( < .05), and smaller area of residence ( < .002).

Conclusions: SD in women with RRMS is mostly associated with psychosocial parameters. Patients who are more depressed, presenting speech problems, less educated, and from smaller towns, should be considered high-risk for sexual dysfunction.
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http://dx.doi.org/10.1002/brb3.699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474705PMC
June 2017

Bone metabolism and vitamin D status in patients with multiple sclerosis.

Neurol Neurochir Pol 2016 Jul-Aug;50(4):251-7. Epub 2016 Apr 27.

Department of Neurology, Medical University of Warsaw, Warsaw, Poland.

Background: Vitamin D (VD), an important factor for bone health immobilization and immune regulation, has been shown to have low serum concentration in multiple sclerosis (MS) patients. Those patients have also multiple fracture risk factors, including progressive immobilization and long-term glucocorticoids treatment. The aim of the study was to analyze bone health (osteopenia or osteoporosis prevalence) and VD serum concentration in MS patients as well as the influence of disease activity and treatment on bone health.

Materials And Methods: The study involved 72 MS patients: 52 women and 20 men. Mean age was 40.3±10.5 yrs, mean EDSS (Expanded Disability Status Scale) 3.3±1.9. Bone health was analyzed using standard densitometry in the lumbar spine and femoral neck. Serum levels of VD, calcium, phosphate and parathormone were assessed. We compared two groups of patients with multiple sclerosis: relapsing - remitting MS (RRMS) and progressive relapsing MS (PRMS).

Results: Densitometry revealed osteopenia in twenty-six (36.1%) patients and osteoporosis in eleven (15.3%), no bone fractures were presented. Sixty-eight MS patients (94.4%) had lower VD serum level if compared to population referential values. Thirteen patients (18.1%) had severe VD deficiency. Densitometry parameter (T-score of the lumbar spine) worsened with EDSS increase (r=-0.43, P=0.001). There was a statistically significant negative correlation between VD concentration and EDSS score (r=-0.31; P=0.009).

Conclusions: Our study indicates that patients with MS have high incidence of osteopenia and osteoporosis and vitamin D deficiency. Bone health disturbances studied by densitometry are related to the disability caused by MS.
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http://dx.doi.org/10.1016/j.pjnns.2016.04.010DOI Listing
December 2016

Metagenomic Analysis of Cerebrospinal Fluid from Patients with Multiple Sclerosis.

Adv Exp Med Biol 2016 ;935:89-98

Department of Immunopathology of Infectious and Parasitic Diseases, Warsaw Medical University, 3C Pawińskiego Street, Warsaw, 02-106, Poland.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of central nervous system of unknown etiology. However, some infectious agents have been suggested to play a significant role in its pathogenesis. Next-generation sequencing (NGS) and metagenomics can be employed to characterize microbiome of MS patients and to identify potential causative pathogens. In this study, 12 patients with idiopathic inflammatory demyelinating disorders (IIDD) of the central nervous system were studied: one patient had clinically isolated syndrome, one patient had recurrent optic neuritis, and ten patients had multiple sclerosis (MS). In addition, there was one patient with other non-inflammatory neurological disease. Cerebrospinal fluid (CSF) was sampled from all patients. RNA was extracted from CSF and subjected to a single-primer isothermal amplification followed by NGS and comprehensive data analysis. Altogether 441,608,474 reads were obtained and mapped using blastn. In a CSF sample from the patient with clinically isolated syndrome, 11 varicella-zoster virus reads were found. Other than that similar bacterial, fungal, parasitic, and protozoan reads were identified in all samples, indicating a common presence of contamination in metagenomics. In conclusion, we identified varicella zoster virus sequences in one out of the 12 patients with IIDD, which suggests that this virus could be occasionally related to the MS pathogenesis. A widespread bacterial contamination seems inherent to NGS and complicates the interpretation of results.
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http://dx.doi.org/10.1007/5584_2016_25DOI Listing
December 2017

Aquaporin-4: A novel diagnostic biomarker for seronegative neuromyelitis optica.

Mult Scler 2016 Jan 2;22(1):125-6. Epub 2015 Mar 2.

Department of Neurology, Medical University of Warsaw, Poland.

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http://dx.doi.org/10.1177/1352458515575173DOI Listing
January 2016

Multiple metastatic intracranial lesions associated with left atrial myxoma.

Pol J Radiol 2014 15;79:262-7. Epub 2014 Aug 15.

Department of Neurology, Medical University of Warsaw, Warsaw, Poland.

Background: One of the most common cardiac tumors is myxoma. Despite its predominantly benign course, diverse cardiological, systemic as well as neurological complications have been reported.

Case Report: We are the first from Poland to present the case of a patient with multiple central nervous system metastases associated with the left atrial myxoma. Various diagnostic, neuroradiological and histopathological procedures were described. The patient underwent cardiac surgery.

Conclusions: Follow-up studies excluded the recurrence of the heart tumor and confirmed partial resolution of brain metastases. Nevertheless, subsequent neurological assessment was advised according to the literature data and possible late relapses mainly due to cerebral emboli.
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http://dx.doi.org/10.12659/PJR.890332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140721PMC
August 2014

The N-terminal pro-brain natriuretic peptide as a marker of mitoxantrone-induced cardiotoxicity in multiple sclerosis patients.

Neurol Neurochir Pol 2014 23;48(2):111-5. Epub 2014 Jan 23.

Department of Neurology, Warsaw Medical University, Warsaw, Poland.

Background And Purpose: Mitoxantrone (MTX) has been shown to reduce progression of disability and number of clinical exacerbations in patients with progressive multiple sclerosis (MS). Prolonged administration of MTX, however, is limited by the risk of cardiotoxicity. Cardiac monitoring in MTX-treated patients includes usually measurement of left ventricular ejection fraction (LVEF) by means of echocardiography. The N-terminal pro-brain natriuretic peptide (NT-proBNP) represents a novel diagnostic tool in the assessment of heart failure. This study was aimed to evaluate the usefulness of NT-proBNP for early detection of MTX-induced cardiotoxicity in MS patients.

Materials And Methods: We measured the NT-proBNP plasma levels in 45 MS patients who completed 24-month MTX therapy and in 37 MS patients of control group.

Results: The median NT-proBNP plasma value was 15.12pg/mL. In 12 MTX-treated patients (27%), NT-proBNP plasma values were elevated, though this subgroup of patients neither clinical showed evidence of myocardial damage nor had the LVEF value <50%. In five patients with normal NT-proBNP, we observed LVEF decline >10%. We did not observe correlations between the NT-proBNP levels and patient age, MS duration, relapses index, Extended Disability Status Scale (EDSS), MTX single dose and the total cumulative dose of MTX. In 8 patients (22%) from control group, NT-proBNP plasma levels were also elevated.

Conclusions: The results of our study confirm that MTX therapy is safe for carefully selected and closely monitored MS patients. We believe that serial evaluation of NT-proBNP levels (before, during and after MTX therapy) can identify MS patients at high risk for MTX-induced cardiotoxicity.
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http://dx.doi.org/10.1016/j.pjnns.2013.12.005DOI Listing
August 2014

Clinical and neuroimaging correlation of movement disorders in multiple sclerosis: case series and review of the literature.

Folia Neuropathol 2014 ;52(1):92-100

Prof. Marek Gołębiowski, 1st Department of Clinical Radiology, Medical University of Warsaw, 5 Chałubińskiego Str., 02-004 Warsaw, Poland, e-mail:

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, in which movement disorders (MD) have been reported very rarely. Anatomopathological studies of MS indicate two main processes: inflammation and neurodegeneration. The occurrence of the movement disorders symptoms in MS revises the question of aetiology of these two diseases. During the 10 years of observation in our out-patient clinic and MS units we examined about 2500 patients with clinically definite MS diagnosed according to the revised McDonald's criteria. Only in 10 cases we found coexistence of MS and MD signs. Below we present rare cases of patients with coexistence of MS and chorea, pseudoathetosis, dystonia and parkinsonism. Searching for the strategic focal lesion in our case series showed demyelinating plaques placed in the thalamus most often. Detailed analysis of the clinical, pharmacological and neuroimaging correlations may help to explain the character of movement disorders in MS.
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http://dx.doi.org/10.5114/fn.2014.41747DOI Listing
April 2015

Long lasting dysautonomia due to botulinum toxin B poisoning: clinical-laboratory follow up and difficulties in initial diagnosis.

BMC Res Notes 2013 Oct 30;6:438. Epub 2013 Oct 30.

Department of Neurology, Medical University of Warsaw, Banacha 1a Street, 02-097 Warsaw, Poland.

Background: Botulism is an acute form of poisoning caused by one of four types (A, B, E, F) toxins produced by Clostridium botulinum, ananaerobic, spore forming bacillus. Usually diagnosis of botulism is considered in patients with predominant motor symptoms: muscle weakness with intact sensation and preserved mental function.

Case Presentation: We report a case of 56-year-old Caucasian female with a history of arterial hypertension, who presented with acute respiratory failure and bilateral ptosis misdiagnosed as brainstem ischemia. She had severe external and internal ophtalmoplegia, and autonomic dysfunction with neither motor nor sensory symptoms from upper and lower limbs. Diagnosis of botulinum toxin poisoning was made and confirmed by serum antibody testing in the mouse inoculation test.

Conclusions: Ophtalmoplegia, autonomic dysfunction and respiratory failure can be caused by botulism. Early treatment and intensive care is essential for survival and recovery. The electrophysiological tests are crucial to correct and rapid diagnosis. Botulism (especially type B) should be considered in any case of acute or predominant isolated autonomic dysfunction.
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http://dx.doi.org/10.1186/1756-0500-6-438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816205PMC
October 2013

Polymorphisms of paraoxonase 1 and 2 genes and the risk of multiple sclerosis in the Polish population.

Neurol Neurochir Pol 2013 Jan-Feb;47(1):49-52

Katedra i Klinika Neurologii, Warszawski Uniwersytet Medyczny, Warszawa, Polska.

Background And Purpose: The aim of this study was to test the hypothesis that polymorphisms of the paraoxonase genes PON1 and PON2 may be associated with increased risk of developing multiple sclerosis (MS) in the Polish population.

Material And Methods: We studied the significance of the PON gene polymorphisms C311S, A162G, Q192R and L55M in 221 patients (including 145 women) with MS and in 661 healthy controls. In the MS population, mean Expanded Disability Status Scale score was 2.92, mean age was 36.8 years, and mean disease duration was 7.7 years. PON genotyping was determined using polymerase chain reaction and restriction enzyme digestion.

Results: According to our results, the PON1 and PON2 genotypes distribution did not differ between the MS patients and the controls.

Conclusions: The polymorphisms of the PON genes studied are not related to increased risk of MS in the Polish population.
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http://dx.doi.org/10.5114/ninp.2013.32935DOI Listing
June 2013

Charcot-Marie-Tooth type 1C disease coexisting with progressive multiple sclerosis: a study of an overlapping syndrome.

Folia Neuropathol 2012 ;50(4):369-74

Department of Neurology, Medical University of Warsaw, Poland.

Charcot-Marie-Tooth type 1C disease (CMT1C) is a rare form of hereditary demyelinating neuropathy caused by mutations in the LITAF (lipopolysaccharide-induced tumor necrosis factor-) gene. CMT1C disease was mapped to chromosome 16p12-p 13.3. To date only a few mutations in the LITAF gene have been reported. Due to a small group of CMT1C reported patients, the phenotype of CMT1C is poorly characterized. CMT1C disease is a pure demyelinating neuropathy limited to the peripheral nervous system with a mild clinical course, manifesting without any additional symptoms. To the best of our knowledge, in this study, for the first time we present a three generational CMT1C family in which in the proband, CMT1C disease coexists with central demyelination fulfilling criteria of primary progressive multiple sclerosis (PPMS). The coexistence of PPMS and CMT1C in one family may not result from a common pathogenetic trait, however only in the proband with central demyelination and CMT1C we have detected a -308G>A sequence variant in the promoter of the TNF-α gene.
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http://dx.doi.org/10.5114/fn.2012.32366DOI Listing
November 2013

Clinical and functional assessment of dysautonomia and its correlation in Alzheimer's disease.

Am J Alzheimers Dis Other Demen 2012 Dec 23;27(8):592-9. Epub 2012 Sep 23.

Department of Neurology, Medical University of Warsaw, Warsaw, Poland.

The aims were to assess dysautonomia in Alzheimer's Disease (AD), clinically and electrophysiologically, using sympathetic skin response (SSR) test and R-R interval variation (RRIV) test and to analyze the relationship between symptoms of dysautonomia and SSR/RRIV results. A tota of 54 patients with AD and 37 controls were evaluated using Autonomic Symptoms Questionnaire and SSR/RRIV test. Clinical dysautonomia was observed in 66% of patients (eg, orthostatic hypotension in 34.5%, constipation in 17.2%, urinary incontinence in 13.8%). The SSR test was abnormal in 26%, but the RRIV test was abnormal in 97.7% of cases; there was significant difference in RRIV test results between AD and controls (R mean 8.05% and 14.6%, respectively). In AD, clinical dysautonomia occurs at a various degree, and the abnormal SSR and RRIV test results were not always related to the presence of clinical dysautonomia; this observation points that the tests could be used as a useful tool in the assessment of subclinical dysautonomia.
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http://dx.doi.org/10.1177/1533317512459792DOI Listing
December 2012

Sex hormone patterns in women with multiple sclerosis as related to disease activity--a pilot study.

Neurol Neurochir Pol 2011 Nov-Dec;45(6):536-542

Department of Neurology, The Medical University of Warsaw, Poland.

Background And Purpose: The influence of sex hormones on immune system activity in multiple sclerosis (MS) has been suggested by clinical evidence. The aim of the study was to ana-lyse the pattern of sex hormones in MS women and to correlate the hormone pattern abnormalities to the disease course as well as to the magnetic resonance imaging (MRI) results.

Material And Methods: We studied the serum level of the progesterone, β-oestradiol and prolactin in 46 women with clinical definite MS aged from 19 to 65; mean disease duration was 11.80 ± 9.86 years. The evaluation of the intensity of hormonal changes was done using a scoring system (0-3). On the brain MRI, the presence of brain atrophy, of hypothalamic demyelination as well as demyelination intensity (or degree) were analysed. The evaluation of the degree of demyelination and brain atrophy was done using a scoring system (0-4).

Results: The main hormonal abnormalities consisted of decreased progesterone level, increased oestradiol level or both. The sex hormone pattern was abnormal in 56% of patients. Hypothalamic lesions were found on MRI in 53% of cases. The abnormal hormonal pattern correlated with intensity of MR changes (p < 0.05, Fisher's exact test), but neither with presence of hypothalamic changes nor with disease parameters (Expanded Disability Status Scale, relapse rate, disease duration).

Conclusions: It is important to check the hormonal pattern in MS women because according to our results it may be related to the disease activity and probably affects the type of therapeutic intervention. This pilot study will be extended in a larger population.
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http://dx.doi.org/10.1016/S0028-3843(14)60120-1DOI Listing
February 2012

[Evoked potentials in multiple sclerosis: progress or stagnation?].

Przegl Lek 2010 ;67(9):729-31

Warszawski Uniwersytet Medyczny, Warszawa.

Background: Evoked potentials (EPs): visual (VEP), short latency somatosensory (SSEP), brainstem auditory (BAEP) and motor evoked potentials (MEP) can provide objective evidence of central nervous system (CNS) abnormalities that complement the clinical and radiological findings in establishing the diagnosis of multiple sclerosis (MS).

Methods: The EPs studies may also improve the sensitivity of MS diagnosis.

Results: Abnormal EPs can provide evidence for pathology to satisfy the diagnostic criteria of lesions disseminated in space in the absence of clinical findings and for a relapse in patient with new symptoms but no changes on clinical examination. Since magnetic resonance imaging (MRI) plays a critical role in the current diagnostic criteria of MS, it is important to consider the relationship between EPs and MRI. Evoked potentials provide neurophysiological information about CNS functional abnormalities, while MRI provide anatomical localisation of CNS lesions. VEPs are even more sensitive than MRI in detecting acute and old pre-chiasmatic optic nerve lesions. The revised diagnostic criteria for MS include the provision for an abnormal VEP to serve as a diagnostic factor. Rarely, patients with spinal cord pathology may have an abnormal SEP or MEP without an observed lesions on MRI. Combining multimodality evoked potentials and MRI results in the greatest diagnostic yield.

Conclusions: More widespread use of multimodality EPs in combination with MRI might lead to better outcome measurement in clinical trials as well as in open therapeutic approach. Thought EPs have some limitations, they remain an important factor in the diagnosis and clinical management of MS patients.
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October 2011

The auditory system involvement in Parkinson disease: electrophysiological and neuropsychological correlations.

J Clin Neurophysiol 2009 Dec;26(6):430-7

Department of Neurology, Medical University of Warsaw, Warsaw, Poland.

In the course of Parkinson disease (PD), apart from motor symptoms, presence of mental disturbances such as dementia and depression is common. The aims of this study were to assess the auditory system involvement in patients with PD using electrophysiological and neuropsychological tests and to correlate the cognitive impairment and the auditory evoked potentials tests results. The auditory and cognitive functions were studied in 53 patients with idiopathic PD, mean age 65.8 +/- 9.1 years; mean disease duration 7.8 +/- 5.0 years; mean motor disability score 2.5 +/- 0.8 points in Hoehn-Yahr scale compared with a control group matched for age and sex. In patients and controls, cognitive functions were analyzed electrophysiologically using middle latency auditory evoked potentials (MLAEP) and long latency (event-related potentials, P300) auditory evoked potentials. Neuropsychological testing consisted of Wisconsin Card Sorting Test (WCST). According to WCST results, patients with PD were divided into 2 subgroups: patients with normal and abnormal WCST performance (WCST(-) and WCST(+) subgroups, respectively). Sixteen of 46 patients (34.8%) showed cognitive impairment when evaluated with WCST. Statistically significant differences in middle latency auditory evoked potentials and P300 results between WCST(-) and WCST(+) groups were found consisting of P300 abnormalities in 93.8% patients in WCST(+) and 57.7% in WCST(-) group. Middle latency auditory evoked potentials were abnormal in 71.4% and 63% patients in WCST(+) and WCST(-) group, respectively. P300 was absent significantly more often (P < 0.01) in the subgroup with cognitive impairment. The difference in middle latency auditory evoked potentials results between these subgroups was statistically insignificant. The auditory evoked potentials changes were more common among patients with abnormal WCST performance. According to our results, the auditory evoked potentials of different latencies are helpful in the assessment of cognitive changes accompanying PD.
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http://dx.doi.org/10.1097/WNP.0b013e3181c2bcc8DOI Listing
December 2009

Paroxysmal non-kinesigenic dyskinesia caused by the mutation of MR-1 in a large Polish kindred.

Eur Neurol 2009 24;61(1):39-41. Epub 2008 Oct 24.

Department of Neurology, Faculty of Health Science, Medical University in Warsaw, Warsaw, Poland.

Paroxysmal non-kinesigenic dyskinesia (PNKD) is a clinical syndrome of sudden involuntary movements, mostly of dystonic type, which may be triggered by alcohol or coffee intake, stress and fatigue. The attacks of PNKD may consist of various combinations of dystonia, chorea, athetosis and balism. They can be partial and unilateral, but mostly the hyperkinetic movements are bilateral and generalized. We present a large Polish family with 7 symptomatic members of the family in 6 generations. In all affected persons, the onset of clinical symptoms was in early childhood. All male cases showed an increase in severity and frequency of the attacks with ageing, while the only living female patient noticed an improvement of PNKD during both her pregnancies and also after menopause. In addition, at the age of 55 years, she developed symptoms of Parkinson's disease with good response to levodopa treatment.
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http://dx.doi.org/10.1159/000165348DOI Listing
March 2009

[Impact of hypoglycemic episodes on nerves conduction and auditory and visual evoked potentials in children with type 1 diabetes].

Pediatr Endocrinol Diabetes Metab 2007 ;13(1):17-22

Klinika Pediatrii Centrum Zdrowia Dziecka w Warszawie.

Background: Hypoglycemia is an acute disturbance of energy, especially impacting the central nervous system, but direct influence on peripheral nervous function is not detected. The aim of the study was to establish the influence of hypoglycemic moderate and severe episodes on the function of peripheral nerves, hearing and visual pathway.

Material And Methods: 97 children with type 1 diabetes (mean age 15.4+/-2.16 years, mean duration of diabetes 8.11+/-2.9 years, mean HbA1c 8,58+/-1.06%), at least 10 years old and with at least 3 years duration of diabetes, were included to study. Nerve conduction studies, visual (VEP) and auditory (ABR) evoked potentials were performed with standard surface stimulating and recording techniques. Moderate hypoglycemic episodes were defined as events of low glycemia requiring help of another person but without loss of consciousness and/or convulsions but recurrent frequently in at least one year. Severe hypoglycemia was defined as events with loss of consciousness and/or convulsions. Univariate ANOVA tests of significance or H Kruskal-Wallis test were used, depending on normality of distribution.

Results: The subgroups with a history of hypoglycemic episodes had significant delay in all conduction parameters in the sural nerve (amplitude p<0.05, sensory latency p<0.05, and velocity p<0.005) and in motor potential amplitude of tibial nerve (p<0.005). In ABR wave III latency and interval I-III in subgroups with episodes of hypoglycemia (p<0,05) were significantly prolonged. In analyses of VEP parameters no differences were detected.

Conclusions: The study showed influence of hypoglycemic episodes on function of all sural nerve parameters and tibial motor amplitude, and in ABR on wave III and interval I-III. Frequent moderate hypoglycemic episodes were strong risk factors for damage of the peripheral and central nervous systems, comparable with impact of several severe hypoglycemias.
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September 2007

[Neurological disorders in patients with obstructive sleep apnea (OSA)].

Pneumonol Alergol Pol 2007 ;75 Suppl 1:62-4

Katedra i Klinika Neurologii Akademii Medycznej w Warszawie.

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September 2011

[A case of the Lambert-Eaton syndrome of non-neoplastic origin. Ten-year follow-up].

Neurol Neurochir Pol 2006 May-Jun;40(3):243-7

Katedra i Klinika Neurologii Akademia Medyczna w Warszawie, Warszawa.

A case is presented of a 34-year-old man who developed weakness of the proximal muscles of the extremities, particularly lower, slight myalgia, and vegetative symptoms (dryness in the mouth). Those symptoms progressed within a month. On examination weakness of the muscles of the extremities was found as well as weak tendon reflexes, slight atrophy of muscles of the arms and thighs and apokamnosis. Edrophonium test was slightly positive. Electrostimulation revealed changes typical of the Lambert-Eaton syndrome: low amplitude of the compound muscle action potential on single stimulus, decreasing amplitude of the subsequent responses to 3 Hz stimulation, marked facilitation on 30 Hz stimulation. Neoplastic etiology was excluded by chest X-ray and CT, as well as by bronchoscopy, abdominal and prostatic USG, and thyroid USG and scintigraphy. Antibodies to AChR were not found in the serum. The titre of the antibodies against voltage-gated calcium channels was highly positive which was decisive in the diagnosing of the Lambert-Eaton syndrome. The patient was treated with pyridostigmine, corticosteroids, cyclophosphamide and immunoglobulins. Ten years of follow-up have fully confirmed the diagnosis of a non-neoplastic Lambert-Eaton syndrome.
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February 2007

Clinical versus electrophysiological assessment of dysautonomia in obstructive sleep apnea syndrome.

J Clin Neurophysiol 2004 Nov-Dec;21(6):435-9

Department of Neurology, The Medical University of Warsaw, Warsaw, Poland.

To assess the autonomic system in obstructive sleep apnea syndrome (OSAS), the sympathetic skin response (SSR) and the R-R interval variation (RRIV) tests were studied in 34 OSAS patients and in 32 healthy controls. The aim of the study was to evaluate the sympathetic and parasympathetic system function in OSAS, to define the pattern of autonomic abnormalities found in SSR and RRIV in patients, and to analyze the usefulness of both tests in paraclinical assessment of the dysautonomia, compared with clinical symptoms and signs of autonomic nervous system involvement. The correlations between both autonomic tests results were also studied. In OSAS patients, SSR test results were abnormal in about 44% and RRIV results were abnormal in about 21% of patients. The mean values of parameters studied in SSR were significantly different in OSAS patients and controls (P < 0.05), whereas the differences between RRIV results were less important. The SSR and RRIV results in patients with mild apnea (Apnea/ Hypopnea Index (AHI) < 15) were more frequently within normal limits if compared with those of patients with severe apnea, but without reaching statistical significance. The clinical studies results (according to the Autonomic Symptoms Questionnaire) were related to the SSR results (p < 0.05 on chi and Fisher exact test). According to these results, SSR and RRIV are simple paraclinical electrophysiologic tests that confirm clinical dysautonomia. They may be useful as screening tests for assessment of dysautonomia in OSAS.
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http://dx.doi.org/10.1212/01.wnl.0000135216.51489.1bDOI Listing
February 2005

[Current clinical and electrophysiological methods in the assessment of dysautonomia].

Neurol Neurochir Pol 2002 Nov-Dec;36(6):1107-20

Katedry i Kliniki Chorób Wewnetrznych, Pneumonologii i Alergologii AM, Katedry i Kliniki Neurologii AM w Warszawie.

The aim of study was to present clinical and electrophysiological methods of assessment of dysautonomia and to evaluate usefulness of these methods. We evaluated clinical symptoms of dysautonomia by Questionnaire of Autonomic Disorders, which allows the qualitative and quantitative analysis of clinical dysautonomia. We used two noninvasive methods of electrophysiological evaluation: R-R interval variation test (RRIV) and sympathetic skin response (SSR). In assessment by our questionnaire all patients studied had clinical symptoms and signs of dysautonomia. We examined 15 patients with clinical conditions accompanied by dysautonomia. The SSR were abnormal in 4 patients (increased latency or absence of response from one limb or increased latency in upper and lower limb). The results of RRIV were abnormal in 8 patients at rest and during deep breathing. Both, SSR and RRIV, were abnormal in 3 patients. The clinical examination and electrophysiological tests are useful for the assessment of the involvement of autonomic nervous system: The battery of tests is necessary for a complete evaluation of dysautonomia in different diseases.
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May 2003

[Is autonomic neuropathy a risk factor of death in dialysed patients?].

Przegl Lek 2002 ;59(10):807-10

Katedra i Klinika Chorób Wewnetrznych i Nefrologii Akademii Medycznej w Warszawie.

The aim of the study was to determine, whether autonomic neuropathy is a risk factor of death in dialysed patients. Results of autonomic tests (R-R interval variation and sympathetic skin response) which were performed 3 years ago in 51 patients were analysed. 22 of these patients died. A greater incidence of dysautonomia was found in patients who died. However, due to the small number of examined patients, it cannot be concluded, that dysautonomia is a risk factor of death in uremia.
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May 2003

Are electrophysiological autonomic tests useful in the assessment of dysautonomia in Parkinson's disease?

Parkinsonism Relat Disord 2003 Jan;9(3):179-83

Department of Neurology, The Medical University of Warsaw, Banacha 1a, Str, 02 097, Warsaw, Poland.

To assess the autonomic system in Parkinson's disease (PD), the sympathetic skin response (SSR) and the R-R interval variation (RRIV) tests were studied in 26 PD patients and in 24 healthy controls. The aim of the study was to evaluate the sympathetic and parasympathetic system function in PD, to define the pattern of autonomic abnormalities found in SSR and RRIV in parkinsonian patients as well as to analyze the usefulness of both tests in paraclinical assessment of the dysautonomia, compared with clinical symptoms and signs of the autonomic nervous system involvement. The corrrelations between both autonomic tests results were also studied. In PD patients SSR test was abnormal in about 35% and RRIV was abnormal in about 54% of patients. SSR and RRIV were both abnormal in about 27% of PD patients whereas at least one of electrophysiological autonomic tests was abnormal in about 62% of PD patients. Clinical and paraclinical signs of dysautonomia occurred in a similar proportion of patients (i.e. in about 62%). A weak correlation was found between the latency of SSR from upper limbs and the value of RRIV during deep breathing (p=0.063). Our results show that SSR and RRIV are non-invasive paraclinical electrophysiological tests that confirm clinical dysautonomia in PD and can supplement the clinical differentiation of Parkinsonian syndromes.
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http://dx.doi.org/10.1016/s1353-8020(02)00032-9DOI Listing
January 2003