Przestrzeganie zaleceń terapeutycznych u pacjentów chorych na stwardnienie rozsiane

Introduction. Multiple sclerosis is a chronic, inflammatory, immune demyelinating disease of the central nervous system. The effectiveness of MS treatment depends primarily on the effectiveness of drugs and the patient’s compliance with the principles of therapy.Aim. The main aim of the study was to assess the level of adherence to therapeutic recommendations in patients with multiple sclerosis.Material and Methods. The research was carried out at the Department of Neurology and Clinical Neuroimmunology of the Regional Specialist Hospital in Grudziądz. On average 165 patients suffering from multiple sclerosis were qualified for the study. The study was conducted using the method of diagnostic survey. The variables were measured using the proprietary questionnaire containing sociodemographic and medical data and the standardized adherence scale in chronic diseases (ACDS).Results. The analysis of own research showed that patients with high-level multiple sclerosis adhere to the therapeutic recommendations (p = 0.001). The study group reported the fatigue syndrome at all ACDS levels (p = 0.002). There was no relationship between the occurrence of adverse effects of pharmacotherapy and the level of compliance with therapeutic recommendations (p > 0.05).Conclusions. It was found that the level of adherence to therapeutic recommendations in patients suffering from multiple sclerosis in the study group remained at a high level. (JNNN 2020;9(3):103–107)Wstęp. Stwardnienie rozsiane jest przewlekłą, zapalną chorobą demielinizacyjną ośrodkowego układu nerwowego o podłożu immunologicznym. Skuteczność leczenia SM zależy przede wszystkim od efektywności działania leków oraz związanego z tym przestrzegania zasad terapii przez pacjenta.Cel. Głównym celem badań była ocena poziomu przestrzegania zaleceń terapeutycznych u pacjentów chorych na stwardnienie rozsiane.Materiał i metody. Badania przeprowadzono w Oddziale Neurologii i Neuroimmunologii Klinicznej Regionalnego Szpitala Specjalistycznego w Grudziądzu. Do badań zakwalifikowano 165 pacjentów chorujących na stwardnienie rozsiane. Badanie przeprowadzono za pomocą metody sondażu diagnostycznego. Do pomiaru zmiennych wykorzystano autorski kwestionariusz ankiety zawierający dane socjodemograficzne i medyczne oraz standaryzowaną skalę adherence w chorobach przewlekłych (ACDS).Wyniki. Analiza badań własnych wykazała, że pacjenci ze stwardnieniem rozsianym na poziomie wysokim przestrzegają zaleceń terapeutycznych (p = 0,001). Badana grupa na wszystkich poziomach w skali ACDS zgłaszała występowanie zespołu zmęczenia (p = 0,002). Nie stwierdzono związku pomiędzy występowaniem działań niepożądanych stosowanej farmakoterapii, a poziomem przestrzegania zaleceń terapeutycznych (p > 0,05).Wnioski. Stwierdzono że, poziom przestrzegania zaleceń terapeutycznych u pacjentów chorych na stwardnienie rozsiane w badanej grupie utrzymuje się na wysokim poziomie. (PNN 2020;9(3):103–107

Polish validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS battery): correlation of cognitive impairment with mood disorders and fatigue

Background: Cognitive impairment is recognised as a significant clinical issue in Multiple Sclerosis (MS). It can occur at any stage of the disease, affecting quality of life, occupational activity, and adherence to therapy. This makes the availability of a validated assessment tool for detecting and monitoring cognitive dysfunction in multiple sclerosis essential. The Brief International Cognitive Assessment for Multiple Sclerosis is a practical and simple means of administering a battery of three neuropsychological tests, and does not require any formal neuropsychological training.Objective: To establish the validity of BICAMS in the Polish MS population; to assess the correlations of cognitive status with demographic and clinical factors, including affective symptoms and fatigue.Methods: BICAMS was administered to 61 MS patients and 61 HC subjects. Examination of 20 participants with MS was repeated after one to three weeks to assess test-retest reliability. The patients with MS and HC subjects also completed the Hospital Anxiety and Depression Scale (HADS) and Modified Fatigue Impact Scale (MFIS).Results: The MS group performed worse than the HC group in all three BICAMS components, obtaining the following values respectively: 51.7 and 56.1 (p = 0.02) for CVLT, 25 and 28 (p = 0.03) for BVMT-R, and 48.8 and 57.2 (p < 0.001) for SDMT. All BICAMS tests had very significant correlations in test-retest reliability (r = 0.83, p < 0.001 for CVLT; r = 0.84, p < 0.001 for BVMTR; r = 0.9, p < 0.001 for SDMT). 34% of MS patients presented cognitive dysfunction based on the criterion of one or more test scores below the 5th percentile value of the HC group. Significant anxiety and depressive symptoms were reported by 31.1% and 18.0% of MS patients. 31.1% of PwMS reported significant fatigue. BICAMS test results were not associated with HADS or MFIS scores.Conclusions: The Polish version of BICAMS is a valid and reliable tool for the assessment of cognitive impairment in patients with MS

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for the routinely used magnetic resonance imaging protocol in patients with multiple sclerosis

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis (MS) that is essential for the detection and follow-up of the disease. The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of the recommendations for examinations routinely conducted in magnetic resonance imaging departments in patients with MS, which include new data and practical comments for electroradiology technicians and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics that are necessary to establish a diagnosis as well as monitor patients with MS, which directly translates into significant clinical decisions. MS is a chronic idiopathic inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in the CNS destruction process disseminated in time and space. MRI detects focal lesions in the white and grey matter with high sensitivity (with significantly less specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume and white matter volume as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in magnetic resonance techniques, as well as the abilities of postprocessing the obtained data, has become the basis for the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MRI is unquestionably the best diagnostic tool used to follow up the course of the disease and to treat patients with MS. However, to diagnose and follow up the patients with MS on the basis of MRI in accordance with the latest standards, an MRI study must meet certain quality criteria, which are the subject of this paper

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for a protocol concerning routinely used magnetic resonance imaging in patients with multiple sclerosis

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis that is essential for the detection and follow-up of the disease.Objective: The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of their recommendations for investigations routinely conducted in magnetic resonance imaging departments in patients with multiple sclerosis. This version includes new data and practical comments for electroradiology technologists and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics necessary for establishing a diagnosis, as well as for MS patient monitoring, which directly translates into significant clinical decisions.Introduction: Multiple sclerosis (MS) is a chronic immune mediated inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in a CNS destruction process disseminated in time (DIT) and space (DIS). MRI detects focal lesions in the white and grey matter with high sensitivity (although with significantly lower specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume (GMV) and white matter volume (WMV) as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, and hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in MR techniques, as well as advances in postprocessing the obtained data, has driven the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MR imaging is unquestionably the best diagnostic tool available to follow up the course of the disease and support clinicians in choosing the most appropriate treatment strategy for their MS patient. However, to diagnose and follow up MS patients on the basis of MRI in accordance with the latest standards, the MRI study must adhere to certain quality criteria. Such criteria are the subject of this paper

Natural history of multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune disease of the central nervous system (CNS) of unknown aetiology. It affects mostly young adults and is characterised by multifocal and temporally scattered CNS damage of varied symptomatology and clinical course, eventually leading to significant motor impairment. Studies of the natural course of MS provide valuable data on the course of the disease in individual stages of multiple sclerosis. They allow to determine the frequency of relapses, duration of remission and, most importantly, to determine the motor disability increase rate and describe demographic and clinical factors of influence on benign or aggressive course of the disease. Data on the subject come mostly from four patient databases (Lyon; London, Ontario; Gothenburg; Vancouver) including from several hundred to five thousand patients. The results obtained from hitherto conducted analyses are often non - uniform. Peak MS morbidity dates between 20 and 39 years of age. In primary progressive multiple sclerosis (PPMS) patients, the disease onset occurs on average 10 years later than in relapsing-remitting multiple sclerosis (RRMS) patients. The initial symptoms have monosymptomatic character in over 75% of patients. Pyramid signs are the most important predictive factor for clinically definite multiple sclerosis (CDMS) development after a clinically isolated syndrome (CIS) episode. The conversion of RRMS to secondary progressive multiple sclerosis (SPMS) occurs on average 10 years after onset of the disease. Significant motor disability develops after 15 - 20 years of multiple sclerosis, the strongest adverse prognostic factor is PPMS.Stwardnienie rozsiane (łac. sclerosis multiplex, SM) jest przewlekłą, zapalną, autoimmunologiczną chorobą ośrodkowego układu nerwowego (OUN) o nieznanej etiologii. Występuje głównie u młodych dorosłych, cechuje się wieloogniskowym i rozsianym w czasie uszkodzeniem OUN, z różnorodną symptomatologią i przebiegiem klinicznym, prowadząc ostatecznie do znacznej niewydolności ruchowej. Badania naturalnego przebiegu SM dostarczają cennych danych dotyczących postępu choroby w poszczególnych postaciach stwardnienia rozsianego. Pozwalają określić częstość rzutów, czas trwania remisji, a przede wszystkim ustalić tempo narastania niesprawności ruchowej oraz ustalić, jakie czynniki demograficzne i kliniczne mają wpływ na łagodny bądź też agresywny przebieg choroby. Dane na temat tego zagadnienia na świecie pochodzą głównie z czterech baz chorych (Lyon, London w Ontario, Gothenburg oraz Vancouver) obejmujących od kilkuset do pięciu tysięcy chorych. Wyniki uzyskane na podstawie przeprowadzonych do tej pory analiz są często niejednorodne. Dotychczas przeprowadzone badania wykazały, że najwyższa zachorowalność na SM ma miejsce pomiędzy 20. a 39. rokiem życia. U chorych z postacią pierwotnie postępującą (PPMS) początek choroby występuje średnio o 10 lat później niż w postaci rzutowo-remisyjnej (RRMS). U ponad 75% pacjentów pierwsze objawy kliniczne mają charakter monosymptomatyczny. Objawy uszkodzenia drogi piramidowej są czynnikiem o najwyższym znaczeniu predylekcyjnym rozwoju rozwoju klinicznie pewnego stwardnienia rozsianego (CDMS) po przebyciu izolowanego zespołu klinicznego (CIS). RRMS ulega konwersji do postaci wtórnie postępującej (SPMS) średnio po 10 latach od wystąpienia pierwszych objawów chorobowych. Po 15 - 20 latach trwania SM dochodzi do rozwoju znacznej niesprawności ruchowej, najsilniejszym niekorzystnym czynnikiem rokowniczym jest PPMS

Rituximab therapy in generalized refractory myasthenia gravis. Case report

Background: Rituximab is a human-mouse chimeric IgG1 monoclonal antibody directed against antigen CD-20, transmembrane phosphoprotein on B cells. This drug induce depletion of B cells and subsequent reduction in antibody production. Recently there were cases of severe AChR-antibody positive and MuSK-positive myasthenia gravis (MG) successfully treated with rituximab. Case report: Forty-three-year-old women with tygorefractory MG with predominantly generalised weakness in extremities, bulbar symptoms and dyspnea, who presented for the first time in 1992. Thymectomy was perform in 1997. During 15 years of therapy patient had one crise in 1997 and one in 1999. In 2007, she had five hospital admission. She did not respond adequately to acetylcholinesterase inhibitors, thymectomy, repeat plasma exchange and conventional immunosuppressive therapy such as azathioprine, cyclophosphamide and prednisone. For this reason rituximab (MabThera®, Roche) therapy was added. Rituximab was administered at a dose of 375 mg/m2 intravenously according to a protocol every 7 days for 4 weeks. She received also prednisone at a dose of 20 mg and pyridostigmine 180 mg per day all the time. Within 4 weeks therapy she showed maintained clinical improvement. Dyspnea and bulbar symptoms were disappearanced and walking distances was longer. We did not observe serious adverse events, only after first infusion transient oedema of mucosa nasal and oral cavity with concurrent pruritus and after second infusion transient myalgia, chills and subfebrile body temperature were found. Conclusions: In this case use of rituximab leading to significant clinical improvement in refractory myasthenia gravis. The therapy was well tolerated and any serious adverse events were registered.Wstęp: Rituksymab jest chimerycznym przeciwciałem monoklonalnym klasy IgG1, skierowanym przeciwko antygenowi CD20, przezbłonowej fosfoproteinie limfocytów B. Indukuje on deplecję limfocytów B, a w związku z tym spadek produkcji przeciwciał. Ostatnio opisywano przypadki zakończonego sukcesem leczenia rituksymabem ciężkiej miastenii (MG) seropozytywnej i miastenii z obecnością przeciwciał anty-MuSK. Opis przypadku: Czterdziestotrzyletnia kobieta z lekooporną miastenią z dominującym osłabieniem kończyn, objawami opuszkowymi i dusznością, z pierwszymi objawami choroby w 1992 roku. W 1997 roku wystąpił pierwszy przełom miasteniczny, w 1999 drugi. W roku 2007 z powodu zaostrzeń choroby pacjentka była pięciokrotnie hospitalizowana. W trakcie piętnastoletniej kuracji nie uzyskano zadowalającej odpowiedzi na inhibitory acetylocholinoesterazy, tymektomię, powtarzane zabiegi plazmaferezy i konwencjonalne leczenie immunosupresyjne, w którym zastosowano azatioprynę, cyklofosfamid i prednizon. Z tych względów włączono terapię rituksymabem (MabThera®, Roche). Rituksymab podawano we wlewie dożylnym zgodnie z następującym protokołem: 375 mg/m2 co 7 dni przez 4 tygodnie. Przez cały czas chora była leczona prednizonem w dawce 20 mg i pirydostygminą w dawce 180 mg na dobę. W trakcie terapii osiągnięto znaczącą poprawę stanu klinicznego, która utrzymuje się do chwili obecnej. Uzyskano ustąpienie duszności i objawów opuszkowych oraz wydłużenie przechodzonego dystansu. Nie stwierdzono poważnych działań niepożądanych; po pierwszym wlewie wystąpił przemijający obrzęk śluzówki jamy ustnej i nosowej z towarzyszącym świądem, a po drugim ból mięśni, dreszcze i stan podgorączkowy. Wnioski:W opisanym przypadku zastosowanie rituksymabu doprowadziło do znaczącej i długotrwałej poprawy klinicznej w przebiegu miastenii lekoopornej. Terapia była dobrze tolerowana i nie zaobserwowano żadnych poważnych działań niepożądanych

Predictive Value of the Third Ventricle Width for Neurological Status in Multiple Sclerosis

The third ventricle width (3VW) is an easily calculated measure of brain atrophy. The aim of this study was to evaluate the relation of 3VW to cognitive impairment with adjustment for demographic and clinical confounders, including depression, anxiety, and fatigue, as well as to disability in patients with multiple sclerosis (MS). Symbol Digit Modalities Test, California Verbal Learning Test, Brief Visuospatial Memory Test-Revised, Expanded Disability Status Scale (EDSS), Hospital Anxiety and Depression Scale, and Modified Fatigue Impact Scale (MFIS) were analysed in 93 patients with MS. Neuropsychological performance was compared to that of 150 healthy controls. Axial images from 3D FLAIR were used to measure 3VW. In total, 25% of MS patients were impaired in at least two neuropsychological tests. Cognitive impairment and EDSS were associated with 3VW. Age and 3VW were the strongest predictors of cognitive impairment. The multiple regression model including age, 3VW, education, EDSS, and MFIS explained 63% of the variance of neuropsychological tests results, whereas 3VW, age and duration of the disease were significant predictors of EDSS. This study confirms the predictive value of 3VW for neurological status of patients with MS, especially for cognitive impairment after adjustment for demographic and clinical confounders

JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Treatment-Naïve Patients

Multiple sclerosis (MS) treatment with new agents is associated with the risk of the development of progressive multifocal leukoencephalopathy (PML). The seropositivity and a high index of anti-John Cunningham virus (JCV) antibodies are some of the risk factors for PML development. The aim of this study was to assess the seroprevalence of anti-JCVAb and JCVAb index (AI), as well as its correlations with demographic and clinical characteristics in treatment-naïve Polish MS patients. This is a multicenter, prospective, and cross-sectional study involving 665 MS patients. The overall prevalence of anti-JCVAb was 65.3%, while 63.1% of seropositive patients had an index level of >1.5. The seroprevalence was shown to increase along with the patient’s age. Except for age, the prevalence of anti-JCVAb was not associated with demographic or clinical data. No correlations between the index levels and the demographic or clinical data were observed. In Poland, the seroprevalence of anti-JCVAb in treatment-naïve MS patients is one of the highest in Europe. The majority of seropositive patients had an anti-JCV antibody level denoting a high-risk category. This means that we need further studies to be conducted on the individualization of MS treatment in order to provide patients with an appropriate therapeutic safety level

JC Virus Seroprevalence and JCVAb Index in Polish Multiple Sclerosis Patients Treated with Immunomodulating or Immunosuppressive Therapies

The use of a highly-effective treatment for multiple sclerosis (MS) is associated with a severe risk of developing complications, such as progressive multifocal leukoencephalopathy (PML) caused by the John Cunningham virus (JCV). The aim of this study was to evaluate the correlation between anti-JCV Ab seroprevalence, anti-JCV AI, demographic and clinical factors as well as the type of therapy used in the Polish MS population. This is a multicentre, prospective and cross-sectional study involving 1405 MS patients. The seroprevalence of anti-JCV Ab and anti-JCV AI levels as well as AI categories were analysed with the use of a second-generation two-step ELISA test (STRATIFY JCV DxSelect). The overall prevalence of anti-JCV Ab was 65.8%. It was shown that seroprevalence increases with the patient’s age. The seroprevalence was significantly associated with the treatment type, and the highest values (76%) were obtained from immunosuppressant-treated patients. Overall, 63.3% of seropositive patients had an antibody index (AI) level of >1.5. In the seropositive patient group, the mean AI level amounted to 2.09. Similarly to the seroprevalence, AI levels correlated with the patient’s age; AI level for patients above 40 years old and from subsequent age quintiles plateaued, amounting to at least 1.55. Patients treated with immunosuppressants and immunomodulatory drugs obtained the highest (1.67) and lowest (1.35) AI levels, respectively. Of the immunosuppressants used, the highest mean AI levels were observed in mitoxantrone and cladribine groups, amounting to 1.75 and 1.69, respectively. In patients treated with immunomodulatory drugs, the lowest AI levels were observed in the dimethyl fumarate (DMF) group (1.11). The seroprevalence rate in the Polish MS population is one of the highest in Europe. The majority of seropositive patients had an anti-JCV Ab level qualifying them for a high-risk category. The highest mean AI levels are observed in patients receiving immunosuppressants, especially mitoxantrone and cladribine. Patients receiving immunomodulatory drugs have lower AI levels compared to treatment-naïve subjects, especially when treated with DMF. Further studies, especially longitudinal studies, are required to determine the impact of MS drugs on the seroprevalence of anti-JCV Ab and AI levels