Pathology of multiple sclerosis

Multipla skleroza (MS) je kronična autoimunosna demijelinizirajuća bolest središnjeg živčanog sustava (CNS) karakterizirana različitim neurološkim simptomima. Napredovanje bolesti u konačnici može dovesti do teške invalidnosti. Najčešće se javlja u mlađoj odrasloj populaciji i većinom zahvaća žene. Iako uzrok MS ostaje nepoznat, sigurno je da genetički čimbenici i čimbenici okoliša imaju bitnu ulogu u njenoj etiologiji. Patološki, MS je karakterizirana multifokalnim demijelinizirajućim lezijama unutar CNS-a. Iako su neke lezije smještene u sivoj tvari, većina ih zahvaća bijelu tvar velikog mozga, i to najčešće optičke živce, moždano deblo, kralježničnu moždinu kao i periventrikularna područja. Prema histološkim kriterijima, lezije su podijeljene na akutne, kronične aktivne i kronične inaktivne plakove. Na histološkim preparatima uočena je upalna infiltracija unutar plakova koja se sastoji od T limfocita, B limfocita i makrofaga. Nedavna istraživanja otkrila su veliku varijabilnost između lezija različitih bolesnika s obzirom na opsežnost upale, patologiju oligodendrocita i neuroaksonalno oštećenje. Demijelinizacija, praćena različitim stupnjem demijelinizacije, povezana je s gubitkom oligodendrocita tijekom kasnijeg stadija bolesti. Bitne patološke značajke MS jesu i oštećenje aksona zajedno s gliozom i proliferacijom astrocita. Postoji više dokaza koji upućuju na neuroaksonalno oštećenje kao ključnu značajku lezija u MS s velikim utjecajem na nastanak trajnog neurološkog deficita. Zaključno, u zadnjih nekoliko godina došlo je do značajnog napretka laboratorijskih i slikovnih metoda korištenih u istraživanju MS koje su doprinijele boljem razumijevanju imunopatogeneze, patologije i etiologije ove bolesti.Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) manifested by heterogeneous group of neurological symptoms. Progression of disease may eventually lead to severe disability. It is more common in young adults, while females are predominantly affected. Although etiology of MS remains unknown, it is certain that genetic and environmental factors play important roles. Pathologically, MS is characterized by multifocal demyelinated inflammatory lesions of the CNS. Although some lesions do appear in grey matter, most lesions appear in the white matter of the brain, most notably in the optic nerves, the brainstem, the spinal cord and in the periventricular zones. According to histologic criteria, the CNS lesions in MS are classified as acute, chronic active and chronic inactive plaques. On histological sections these plaques exert an inflammatory infiltrate consisting of T cells, B cells and macrophages. However, recent histopathological studies of MS lesions revealed a great variability within lesions of different subjects with respect to the extent of inflammation, oligodendrocyte pathology and neuroaxonal injury. Demyelination, followed by a variable degree of remyelination, is associated with oligodendrocyte loss during the chronic stage of the disease. Axonal loss and gliosis with astrocyte proliferation and glial fiber production are also important pathologic features of MS. There is an increasing evidence that neuroaxonal damage is a key feature in MS lesions and that it has a major impact on permanent neurologic deficits. Hence, in the past few years an increasing improvement of laboratory and imaging approaches to study MS lead to a better understanding of the immuno-pathogenesis, pathology and etiology of this severe disease

Pathology of multiple sclerosis

Multipla skleroza (MS) je kronična autoimunosna demijelinizirajuća bolest središnjeg živčanog sustava (CNS) karakterizirana različitim neurološkim simptomima. Napredovanje bolesti u konačnici može dovesti do teške invalidnosti. Najčešće se javlja u mlađoj odrasloj populaciji i većinom zahvaća žene. Iako uzrok MS ostaje nepoznat, sigurno je da genetički čimbenici i čimbenici okoliša imaju bitnu ulogu u njenoj etiologiji. Patološki, MS je karakterizirana multifokalnim demijelinizirajućim lezijama unutar CNS-a. Iako su neke lezije smještene u sivoj tvari, većina ih zahvaća bijelu tvar velikog mozga, i to najčešće optičke živce, moždano deblo, kralježničnu moždinu kao i periventrikularna područja. Prema histološkim kriterijima, lezije su podijeljene na akutne, kronične aktivne i kronične inaktivne plakove. Na histološkim preparatima uočena je upalna infiltracija unutar plakova koja se sastoji od T limfocita, B limfocita i makrofaga. Nedavna istraživanja otkrila su veliku varijabilnost između lezija različitih bolesnika s obzirom na opsežnost upale, patologiju oligodendrocita i neuroaksonalno oštećenje. Demijelinizacija, praćena različitim stupnjem demijelinizacije, povezana je s gubitkom oligodendrocita tijekom kasnijeg stadija bolesti. Bitne patološke značajke MS jesu i oštećenje aksona zajedno s gliozom i proliferacijom astrocita. Postoji više dokaza koji upućuju na neuroaksonalno oštećenje kao ključnu značajku lezija u MS s velikim utjecajem na nastanak trajnog neurološkog deficita. Zaključno, u zadnjih nekoliko godina došlo je do značajnog napretka laboratorijskih i slikovnih metoda korištenih u istraživanju MS koje su doprinijele boljem razumijevanju imunopatogeneze, patologije i etiologije ove bolesti.Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) manifested by heterogeneous group of neurological symptoms. Progression of disease may eventually lead to severe disability. It is more common in young adults, while females are predominantly affected. Although etiology of MS remains unknown, it is certain that genetic and environmental factors play important roles. Pathologically, MS is characterized by multifocal demyelinated inflammatory lesions of the CNS. Although some lesions do appear in grey matter, most lesions appear in the white matter of the brain, most notably in the optic nerves, the brainstem, the spinal cord and in the periventricular zones. According to histologic criteria, the CNS lesions in MS are classified as acute, chronic active and chronic inactive plaques. On histological sections these plaques exert an inflammatory infiltrate consisting of T cells, B cells and macrophages. However, recent histopathological studies of MS lesions revealed a great variability within lesions of different subjects with respect to the extent of inflammation, oligodendrocyte pathology and neuroaxonal injury. Demyelination, followed by a variable degree of remyelination, is associated with oligodendrocyte loss during the chronic stage of the disease. Axonal loss and gliosis with astrocyte proliferation and glial fiber production are also important pathologic features of MS. There is an increasing evidence that neuroaxonal damage is a key feature in MS lesions and that it has a major impact on permanent neurologic deficits. Hence, in the past few years an increasing improvement of laboratory and imaging approaches to study MS lead to a better understanding of the immuno-pathogenesis, pathology and etiology of this severe disease

Abiotrophia defectiva kao uzročnik endokarditisa u djeteta – prikaz bolesnika

We present a case of endocarditis due to Abiotrophia defectiva in a child, developed as a complication of a previously unrecognized patent ductus arteriosus (PDA). The patient was successfully treated with antimicrobial therapy and later underwent transcatheter closure of PDA. As the organism may not be isolated in routine culture media, and may present with atypical clinical symptoms, a high index of suspicion should be maintained in children with subacute symptoms even with no underlying heart disease. Even patients with early appropriate antibiotic therapy and rapid achievement of bacteriological clearance remain at high risk for embolic and immune-mediated complications and irreversible valvular damage. Our case highlights the importance of careful interpretation of serologic tests and the value of good physical examination (auscultation!) in order not to miss the diagnosis of congenital heart defects.U radu prikazujemo slučaj djeteta s endokarditisom čiji je uzročnik Abiotrophia defectiva, a koji je nastao kao komplikacija prethodno neprepoznatog otvorenog Botallovog duktusa. Dijete je uspješno liječeno antimikrobnim lijekovima nakon čega je provedeno i transkatetersko zatvaranje srčane greške. S obzirom na to da se ovaj uzročnik teško izolira na rutinskim bakterijskim podlogama i može uzrokovati atipične simptome, potreban je poseban oprez čak i u one djece koja nemaju podležeću srčanu bolest, ali se klinički prezentiraju sa subakutnim simptomima. Imunološke komplikacije, embolizacije i trajno oštećenje zalistaka često se javljaju čak i u onih bolesnika s pravovremeno započetim ispravnim antibiotskim liječenjem i kod kojih je brzo postignut terapijski učinak antibiotika. Također ističemo važnost pažljive interpretacije seroloških testova kao i kvalitetnog fizičkog pregleda (auskultacije!) zbog mogućnosti propuštanja dijagnoze prirođene, dotad neprepoznate, srčane greške

Eosinophilic meningitis in children treated at the University Hospital for Infectious Diseases "Dr. Fran Mihaljević"

Eozinofilni meningitis rijedak je oblik meningitisa koji nastaje uslijed infekcije parazitima, bakterijama, gljivama i virusima, ali javlja se i zbog drugih neinfektivnih uzroka. Klinička prezentacija bolesti kao i liječenje ovisi o njenoj etiologiji, {to se posebno odnosi na slučajeve meningitisa uzrokovanih parazitima, koji su i najčešći. U ovom radu prikazat ćemo troje muške i troje ženske djece u dobi od 2 mjeseca do 7 godina koji su liječeni zbog eozinofilnog meningitisa u Klinici za infektivne bolesti "Dr. Fran Mihaljević". S obzirom na anamnestičke podatke kao i na učinjenu serološku i mikrobiološku obradu, kod navedene se djece radilo o neinfekcijskom meningitisu. Kod jednog bolesnika nije utvrđen uzrok, dok se u preostalih petero eozinofilija u likvoru javila kao reakcija na strano tijelo. Iako su ovakvi slučajevi u svakodnevnom radu rijetki, prikazani su zbog potrebe za širim diferencijalno dijagnostičkim pristupom, posebno u slučajevima nejasne etiologije. On tada mora uključivati, osim tipičnih neinfekcijskih i infekcijskih uzročnika, obradu i razmatranje mikroorganizama koji se ne smatraju čestim ili uobičajenim za tu vrstu meningitisa.Eosinophilic meningitis is a rare form of meningitis that occurs due to infection with parasites, bacteria, fungi and viruses, but also due to other non-infectious causes. The clinical presentation of disease depends on its etiology, which is particularly applicable to cases of meningitis caused by parasites, which are the most common. In this paper we present three male and three female children aged two months to seven years who have been treated for eosinophilic meningitis at the University Hospital for Infectious Diseases "Dr. Fran Mihaljević". Anamnestic data as well as serological and microbiological analysis confirmed diagnosis of noninfectious meningitis. In one patient the cause of disease was not found, while in the remaining five patients, eosinophilia in the fluid appeared as a foreign body reaction. Although such cases are rare in everyday clinical practice, they are presented here in order to stress the need for a broader differential diagnosis, especially in cases of unknown etiology. Besides typical non-infectious and infectious agents this approach must take into consideration other microorganisms that are not commonly assocciated with this type of meningitis

Clostridium neonatale kao uzročnik novorođenačkog meningitisa: prikaz bolesnika

Clostridia are rare causes of the central nervous system (CNS) infections in children. We present an unusual case of a successfully treated neonatal meningitis caused by the novel clostridial species, Clostridium neonatale. To the best of our knowledge, this is the first case report describing neonatal meningitis caused by this bacteria.Bakterije iz roda Clostridium rijetko uzrokuju infekcije središnjeg živčanog sustava (SŽS) u djece. U ovom radu prikazat ćemo slučaj uspješno liječenog meningitisa u novorođenčeta čiji je uzročnik bio Clostridium neonatale, novoopisana vrsta klostridija. Prema našim saznanjima, ovo je prvi prikaz slučaja koji opisuje novorođenački meningitis uzrokovan tom vrstom bakterija

Cefpodoxime proxetil as a therapeutic option in switching therapy for infective endocarditis in children: case reports and literature review

Infective endocarditis (IE) is uncommon in children, affecting predominantly subjects with congenital heart disease (CHD) and patients with indwelling central lines. The principles of antibiotic treatment in paediatric population are similar to those in adults. Prolonged intravenous administration of bactericidal rather than bacteriostatic agents is preferred. Outpatient intravenous therapy after initial treatment in the hospital may be considered only in selected patients. Partial oral treatment has been described in cases of left-sided, uncomplicated IE caused by common pathogens in adult patients. There are no guidelines or trials in paediatric population regarding switching therapy from intravenous to oral route. We present two cases of IE in children caused by uncommon pathogenic bacteria (Abiotrophia defectiva and Haemophilus parainfluenzae) successfully treated with oral third-generation cephalosporin - cefpodoxime proxetil after initial intravenous therapy. This paper provides observations on different therapeutic approach for IE in children as well as another potential use of cefpodoxime proxetil

Liječenje starijih bolesnika s kroničnim hepatitisom C: retrospektivno kohortno istraživanje

The prevalence of chronic hepatitis C increases in elderly patients. The aims of this study were to identify the factors associated with hepatocellular carcinoma (HCC) and end-stage liver disease development and to evaluate the efficacy and safety of pegylated interferon (PEG-IFNα) plus ribavirin (RBV) therapy in elderly patients. A retrospective cohort study included all consecutive patients with hepatitis C virus (HCV) infection treated with PEG-IFNα+RBV between 2003 and 2013. Elderly patients had a higher frequency of poor prognostic factors including genotype 1 infection, high fibrosis, and high fibrosis index based on four factors (FIB-4) score. The sustained virologic response (SVR) rate for genotype 1 was significantly lower (35.8% vs. 57.1%), while the frequency of PEG-IFNα (27.2% vs. 7.8%), RBV dose reduction (19.6% vs. 9.7%) and treatment discontinuation (13.0% vs. 4.1%) was significantly higher in elderly patients. However, age was not associated with SVR in multivariate analysis, and comparable SVR rates were achieved when adjusted for fibrosis score (Ishak ≤3: 66.7% vs. 69.8%). During the follow-up, HCC was diagnosed in 18 elderly patients (3 SVR+, 4 SVR- and 9 untreated patients). In conclusion, selected elderly patients can achieve comparable SVR rates as younger patients, but with a higher rate of side effects. Since complications of HCV infection occur more frequently in elderly patients, they should be given priority for antiviral therapy.Učestalost kroničnog hepatitisa C (KHC) raste u starijim dobnim skupinama. Ciljevi ovoga istraživanja bili su utvrditi čimbenike povezane s razvojem hepatocelularnog karcinoma (HCC) i dekompenzirane jetrene bolesti te procijeniti učinkovitost i sigurnost terapije pegiliranim interferonom (PEG-IFNα) i ribavirinom (RBV) u starijih bolesnika. Retrospektivna kohortna studija je uključila sve bolesnike s KHC koji su liječeni PEG-IFNα + RBV između 2003. i 2013. godine u Klinici za infektivne bolesti “Dr. Fran Mihaljević”. Bolesnici u dobi od >65 godina češće su imali nepovoljne prognostičke čimbenike, tj. HCV-1 genotip, uznapredovali stadij fibroze i viši zbir indeksa fibroze zasnovan na četiri čimbenika (fibrosis index based on four factors, FIB-4). Trajni virusološki odgovor (sustained virologic response, SVR) je bio značajno niži (35,8% prema 57,1%), dok je učestalost smanjenja doze PEG-IFNα (27,2% prema 7,8%), RBV (19,6% prema 9,7%) i prekida liječenja (13,0% prema 4,1%) bila značajno češća u starijih bolesnika. Dob nije bila povezana sa SVR u multivarijatnoj analizi, a stariji bolesnici su imali podjednaki SVR kao i mlađi bolesnici ovisno o stadiju fibroze (Ishak ≤3: 66,7% prema 69,8%). Tijekom praćenja HCC je dijagnosticiran u 18 bolesnika u dobi od >65 godina (3 SVR+, 4 SVR-, 9 neliječenih). Zaključno, stariji bolesnici imaju podjednaku vjerojatnost postizanja SVR kao i mlađi, ali uz češće nuspojave. Budući da se komplikacije infekcije virusom hepatitisa C češće javljaju u ovoj populaciji, stariji bolesnici trebaju imati prednost u primjeni antivirusne terapije

Clostridium neonatale kao uzročnik novorođenačkog meningitisa: prikaz bolesnika

Clostridia are rare causes of the central nervous system (CNS) infections in children. We present an unusual case of a successfully treated neonatal meningitis caused by the novel clostridial species, Clostridium neonatale. To the best of our knowledge, this is the first case report describing neonatal meningitis caused by this bacteria.Bakterije iz roda Clostridium rijetko uzrokuju infekcije središnjeg živčanog sustava (SŽS) u djece. U ovom radu prikazat ćemo slučaj uspješno liječenog meningitisa u novorođenčeta čiji je uzročnik bio Clostridium neonatale, novoopisana vrsta klostridija. Prema našim saznanjima, ovo je prvi prikaz slučaja koji opisuje novorođenački meningitis uzrokovan tom vrstom bakterija