12 research outputs found
Prediktivni Äimbenici za rano prepoznavanje farmakorezistentne epilepsije
Epilepsy is one of the most common neurologic diseases. Despite improved diagnostic and therapeutic possibilities seizures remain refractory in more than 30% of patients with epilepsy. The aim of this study was to analyze the possible predictive factors for the development of pharmacoresistance in cryptogenic partial complex epilepsy. Patients were divided into two groups based on the number of seizures, clinical response to antiepileptic drugs and duration of the disease. One group consisted of patients resistant to anticonvulsant drugs and the other group of patients with well controlled seizures. Disease onset, electroencephalographic (EEG) findings and frequency of secondary generalization of partial complex seizures were analyzed in both groups. The results obtained showed a statistically significantly earlier occurrence of first epileptic seizure in the group of patients with pharmacoresistant epilepsy. The group of pharmacoresistant patients also had a statistically significantly higher proportion of secondary generalization of complex partial seizures as well as a higher proportion of patients with focal changes in EEG. These findings suggest that the onset of the disease at an earlier age, focal changes in EEG and secondary generalization of partial seizures may be early predictive factors for the development of pharmacoresistance in patients with cryptogenic partial complex epilepsy.Epilepsija je jedna od najuÄestalijih neuroloÅ”kih bolesti. Usprkos napretku dijagnostiÄkih i terapijskih moguÄnosti epileptiÄni napadaji ostaju refraktorni u viÅ”e od 30% bolesnika s epilepsijom. Cilj ovoga istraživanja bio je analizirati moguÄe prediktivne Äimbenike za razvoj farmakorezistencije kod bolesnika s kriptogenom parcijalnom kompleksnom epilepsijom. Na temelju broja napadaja, uÄinkovitosti antiepileptiÄne terapije te duljine trajanja bolesti bolesnike s parcijalnom kompleksnom epilepsijom podijelili smo u dvije skupine. Jednu skupinu su Äinili bolesnici s medikamentno rezistentnim oblikom bolesti, dok su drugu skupinu Äinili bolesnici s dobrim odgovorom na antiepileptiÄnu terapiju. U obje skupine se ispitivala dob poÄetka bolesti, analizirao se nalaz elektroencefalograma (EEG) te uÄestalost sekundarne generalizacije parcijalnih kompleksnih napadaja. Dobiveni rezultati su pokazali da je u skupini bolesnika s farmakorezistentnim oblikom bolesti statistiÄki znaÄajna ranija dob pojave prvog napadaja. TakoÄer je utvrÄeno da je u skupini farmakorezistentnih bolesnika statistiÄki znaÄajno veÄi udio bolesnika kod kojih dolazi do sekundarne generalizacije parcijalnih kompleksnih napadaja, kao i veÄi udio bolesnika sa žariÅ”nim promjenama u EEG-u. Dobiveni rezultati ukazuju na to da ranija dob poÄetka bolesti, žariÅ”ne promjene u EEG-u i sekundarna generalizacija parcijalnih epileptiÄnih napadaja mogu biti rani prediktivni Äimbenici za razvoj medikamentne rezistencije u bolesnika s kriptogenom parcijalnom kompleksnom epilepsijom
Prediktivni Äimbenici za rano prepoznavanje farmakorezistentne epilepsije
Epilepsy is one of the most common neurologic diseases. Despite improved diagnostic and therapeutic possibilities seizures remain refractory in more than 30% of patients with epilepsy. The aim of this study was to analyze the possible predictive factors for the development of pharmacoresistance in cryptogenic partial complex epilepsy. Patients were divided into two groups based on the number of seizures, clinical response to antiepileptic drugs and duration of the disease. One group consisted of patients resistant to anticonvulsant drugs and the other group of patients with well controlled seizures. Disease onset, electroencephalographic (EEG) findings and frequency of secondary generalization of partial complex seizures were analyzed in both groups. The results obtained showed a statistically significantly earlier occurrence of first epileptic seizure in the group of patients with pharmacoresistant epilepsy. The group of pharmacoresistant patients also had a statistically significantly higher proportion of secondary generalization of complex partial seizures as well as a higher proportion of patients with focal changes in EEG. These findings suggest that the onset of the disease at an earlier age, focal changes in EEG and secondary generalization of partial seizures may be early predictive factors for the development of pharmacoresistance in patients with cryptogenic partial complex epilepsy.Epilepsija je jedna od najuÄestalijih neuroloÅ”kih bolesti. Usprkos napretku dijagnostiÄkih i terapijskih moguÄnosti epileptiÄni napadaji ostaju refraktorni u viÅ”e od 30% bolesnika s epilepsijom. Cilj ovoga istraživanja bio je analizirati moguÄe prediktivne Äimbenike za razvoj farmakorezistencije kod bolesnika s kriptogenom parcijalnom kompleksnom epilepsijom. Na temelju broja napadaja, uÄinkovitosti antiepileptiÄne terapije te duljine trajanja bolesti bolesnike s parcijalnom kompleksnom epilepsijom podijelili smo u dvije skupine. Jednu skupinu su Äinili bolesnici s medikamentno rezistentnim oblikom bolesti, dok su drugu skupinu Äinili bolesnici s dobrim odgovorom na antiepileptiÄnu terapiju. U obje skupine se ispitivala dob poÄetka bolesti, analizirao se nalaz elektroencefalograma (EEG) te uÄestalost sekundarne generalizacije parcijalnih kompleksnih napadaja. Dobiveni rezultati su pokazali da je u skupini bolesnika s farmakorezistentnim oblikom bolesti statistiÄki znaÄajna ranija dob pojave prvog napadaja. TakoÄer je utvrÄeno da je u skupini farmakorezistentnih bolesnika statistiÄki znaÄajno veÄi udio bolesnika kod kojih dolazi do sekundarne generalizacije parcijalnih kompleksnih napadaja, kao i veÄi udio bolesnika sa žariÅ”nim promjenama u EEG-u. Dobiveni rezultati ukazuju na to da ranija dob poÄetka bolesti, žariÅ”ne promjene u EEG-u i sekundarna generalizacija parcijalnih epileptiÄnih napadaja mogu biti rani prediktivni Äimbenici za razvoj medikamentne rezistencije u bolesnika s kriptogenom parcijalnom kompleksnom epilepsijom
Incidencija akutnih simptomatskih napadaja kod bolesnika s COVID-19: monocentriÄno istraživanje
The most common neurological symptoms in patients with SARS-CoV-2 infection
are headache, myalgia, encephalopathy, dizziness, dysgeusia and anosmia, making more than 90
percent of neurological manifestations of COVID-19. Other neurological manifestations such as
stroke, movement disorder symptoms or epileptic seizures are rare but rather devastating, with possible
lethal outcome. The primary aim of this study was to estimate the prevalence of acute symptomatic
seizures among COVID-19 patients, while secondary aim was to determine their possible etiology.
Out of 5382 patients with COVID-19 admitted to Dubrava University Hospital from November
1, 2020 until June 1, 2021, 38 (seizure rate 0.7%) of them had acute symptomatic seizures. Of these 38
patients, 29 (76.3%) had new-onset epileptic seizures and nine (23.7%) patients with previous epilepsy
history had breakthrough seizures during COVID-19. Although acute symptomatic seizures are
an infrequent complication of COVID-19, seizure risk must be considered in these patients, particularly
in the group of patients with a severe course of the disease. Accumulation of proinflammatory
cytokines may contribute to the occurrence of seizures in patients with COVID-19, but seizures may
also be secondary to primary brain pathology related to COVID-19, such as stroke or encephalitis.NajÄeÅ”Äi neuroloÅ”ki simptomi kod bolesnika s infekcijom SARS-CoV-2 su glavobolja, mialgija, encefalopatija, vrtoglavica,
disgeuzija i anosmija, a Äine viÅ”e od 90% neuroloÅ”kih manifestacija ove bolesti. Ostala neuroloÅ”ka zbivanja poput moždanog
udara, poremeÄaja pokreta ili epileptiÄkih napada nisu Äesta, ali su potencijalno teÅ”ke komplikacije s moguÄim smrtnim
ishodom. Primarni cilj ove studije bio je procijeniti uÄestalost akutnih simptomatskih napadaja kod bolesnika s COVID-19,
dok je sekundarni cilj bio utvrditi njihovu moguÄu etiologiju. Od ukupno 5382 bolesnika hospitaliziranih u KliniÄkoj bolnici
Dubrava od 1. studenoga 2020. godine do 1. lipnja 2021. njih 38 (0,7%) je imalo akutne simptomatske napadaje. Od tih
38 bolesnika 29 (76,3%) ih je imalo novonastale epileptiÄke napadaje bez ranije anamneze epilepsije, dok je njih 9 (23,7%)
imalo anamnezu dobro kontrolirane epilepsije uz pojavu epileptiÄkih napadaja tijekom bolesti COVID-19. Iako su akutni
simptomatski napadaji rijetka komplikacija bolesti COVID-19, treba razmiÅ”ljati o epileptiÄkim napadajima kod ovih bolesnika,
osobito kod onih s teŔkim oblikom bolesti. Nakupljanje proupalnih citokina može doprinijeti pojavi napadaja u bolesnika
s COVID-19, ali napadaji mogu takoÄer biti posljedica primarnog zbivanja na mozgu uslijed bolesti COVID-19,
poput moždanog udara ili encefalitisa
Antiepileptics and Drug Interactions
Antiepileptici (AEL) lijekovi su u kliniÄkoj primjeni dugi niz godina, a osim u lijeÄenju epilepsija, rabe se i u drugim stanjima poput migrene, neuropatske boli ili psihijatrijskih poremeÄaja, uglavnom kao kroniÄna terapija. Iako se njihova primjena preporuÄuje u obliku monoterapije, zbog karaktera bolesti Äesto se primjenjuju i kao politerapija. Rabe se u svim dobnim skupinama, a Äesto i u bolesnika s komorbiditetom, odnosno komedikacijom, Å”to znatno poveÄava moguÄnost interakcija s drugim lijekovima, a time i rizik od nuspojava. Stoga je, s obzirom na Å”iroku primjenu u kliniÄkoj praksi, osim o indikacijskom podruÄju i uÄinkovitosti, nužno voditi raÄuna i o njihovim interakcijama s drugim lijekovima.Antiepileptic drugs (AEDs) have been used in clinical practice for many years. They have also been used for the treatment of conditions other than epilepsy, such as migraine, neuropathic pain and psychiatric conditions, mostly as chronic therapy. Although AED monotherapy is recommended, the character of the disease often requires that AEDs be used as part of polytherapy. AEDs are used in all age groups, frequently in patients with comorbidities requiring co-medication, which significantly increases the possibility of drug interactions and the risk of side effects. Thus, given the widespread use in clinical practice, it is highly important to consider not only the range of indications and the efficacy of AEDs, but also their possible interactions with other drugs
Antiepileptics and Drug Interactions
Antiepileptici (AEL) lijekovi su u kliniÄkoj primjeni dugi niz godina, a osim u lijeÄenju epilepsija, rabe se i u drugim stanjima poput migrene, neuropatske boli ili psihijatrijskih poremeÄaja, uglavnom kao kroniÄna terapija. Iako se njihova primjena preporuÄuje u obliku monoterapije, zbog karaktera bolesti Äesto se primjenjuju i kao politerapija. Rabe se u svim dobnim skupinama, a Äesto i u bolesnika s komorbiditetom, odnosno komedikacijom, Å”to znatno poveÄava moguÄnost interakcija s drugim lijekovima, a time i rizik od nuspojava. Stoga je, s obzirom na Å”iroku primjenu u kliniÄkoj praksi, osim o indikacijskom podruÄju i uÄinkovitosti, nužno voditi raÄuna i o njihovim interakcijama s drugim lijekovima.Antiepileptic drugs (AEDs) have been used in clinical practice for many years. They have also been used for the treatment of conditions other than epilepsy, such as migraine, neuropathic pain and psychiatric conditions, mostly as chronic therapy. Although AED monotherapy is recommended, the character of the disease often requires that AEDs be used as part of polytherapy. AEDs are used in all age groups, frequently in patients with comorbidities requiring co-medication, which significantly increases the possibility of drug interactions and the risk of side effects. Thus, given the widespread use in clinical practice, it is highly important to consider not only the range of indications and the efficacy of AEDs, but also their possible interactions with other drugs
Ataxia as an initial presentation of Sporadic Creutzfeld ā Jakob disease : an atypical case report and literature review
Sporadic Creutzfeldt Jakob disease is a rare, fast-progressing neurodegenerative disease with a fatal outcome. Even though its treatment options are scarce, and there is no cure for the disease, adequate diagnosis can help patients and their families come to terms with the disease on time, and give them valuable time to plan accordingly. We report a case of a patient presenting to our emergency depart- ment with a 2-week history of ataxia, and oscillopsia. Her initial neurological examination revealed subtle dysarthria, diplopia with left gaze, wide-based ataxic gait with occasional small steps, sinistro- pulsion in the Romberg position, and ataxia of the limbs, predominantly of the left arm. The patient at that time did not exhibit cognitive impairment, movement disorders, or other neurological signs. Her initial brain MSCT was without lesions or other pathomorphological supstrate. During hospitaliza- tion, treatable causes were firstly excluded with blood and CSF lab tests excluding metabolic, toxic, infectious, autoimmune, and paraneoplastic causes. Detailed medical history revealed subtle personal- ity changes, while cognitive testing revealed moderate cognitive impairment. Brain MRI and EEG 4 days after hospitalization reported typical changes seen with advanced prion disease surprisingly being the fact that the patient had a mild to moderate clinical picture. RtQuIC analysis of the CSF was per- formed to prove probable sCJD and was positive. The patientās family were given instructions, while the wishes of the patient, and family members were fulfilled concerning planning future care. After- ward, the patientās state deteriorated rapidly as per the tragic prognosis of sCJD resulting in akinetic mutism, and death. Ataxia without cognitive impairment, rigor, or movement disorders is an uncom- mon clinical presentation for a disease with a 1:1 000 000 incidence rate. Modern diagnostic methods in way of more advanced brain MRI capabilities, and RT-QuIC obviate the need for complicated, and potentially infectious brain biopsy in diagnosing sCJD. Alongside the case report, we present a short but comprehensive literature review of modern data regarding the sCJD. This case report and literature review serve to educate clinicians about this rare but devastating disease
Smjernice za farmakoloÅ”ko lijeÄenje epilepsije
SAŽETAK
MeÄunarodne smjernice za farmakoloÅ”ko lijeÄenje epilepsija opÄenite su, sveobuhvatne i ne prepoznaju lokalne specifiÄnosti poput ekonomskih i tehniÄkih moguÄnosti u pojedinim državama, dostupnosti pojedinih antiepileptika ili drugih metoda lijeÄenja i sliÄno. Stoga se nameÄe potreba izrade nacionalnih smjernica, Äiji su zapravo temelj meÄunarodne smjernice Internacionalne lige protiv epilepsije. Hrvatske smjernice za farmakoloÅ”ko lijeÄenje epilepsija plod su suradnje svih relevantnih struÄnih druÅ”tava i referentnih centara u RH, na Äelu s Hrvatskom ligom protiv epilepsije te Hrvatskim neuroloÅ”kim druÅ”tvom i Hrvatskim druÅ”tvom za djeÄju neurologiju Hrvatskoga lijeÄniÄkog zbora, a odražavaju aktualne socioekonomske i regulatorne specifiÄnosti u naÅ”oj zemlji, najnovije spoznaje farmakoloÅ”kih profila i uÄinkovitosti pojedinih antiepileptika kao i ekspertna miÅ”ljenja. AntiepileptiÄka terapija se uvodi nakon postavljanja dijagnoze epilepsije, stoga profilaktiÄka primjena nije opravdana. Nakon postavljanja dijagnoze potrebno je bolesnika informirati o prognozi bolesti, moguÄnostima lijeÄenja i samopomoÄi, životnim ograniÄenjima te moguÄim neželjenim dogaÄajima. Ciljevi farmakoterapije epilepsija su potpuna kontrola napada uz izbjegavanje nuspojava te održavanje ili poboljÅ”anje kvalitete života. Zlatni standard lijeÄenja je monoterapija odnosno primjena adekvatnog antiepileptika u adekvatnoj dozi. Izbor i titracija lijeka su individualni, a temelje se na smjernicama za lijeÄenje pojedinih vrsta napada, karakteristikama bolesnika i regulatorno specifiÄnim Äimbenicima. Nakon neuspjeha inicijalne monoterapije, potrebna je reevalucija anamnestiÄkih i dijagnostiÄkih podataka te potom postupna i spora zamjena antiepileptika. Racionalna politerapija podrazumijeva kombinaciju dvaju antiepileptika razliÄitih mehanizama djelovanja, prvog ili eventualno drugog izbora za postavljenju dijagnozu, niskoga interakcijskog potencijala, razliÄitog profila nuspojava i sinergistiÄkog ili aditivnog djelovanja. Zamjena generiÄkih ili originalnog i generiÄkog oblika lijeka nije preporuÄljiva, a poglavito nakon postizanja remisije ili prilikom uzimanja visokih doza lijeka. Ukidanje antiepileptiÄke terapije treba biti postupno i sporo, u sluÄaju politerapije jedan po jedan lijek, a u donoÅ”enju odluke o ukidanju, kao i o uvoÄenju antiepileptika, mora biti ukljuÄen bolesnik i njegova obitelj
Influence of genetic polymorphisms of UGT1A4 and UGT2B7 enzymes and ABCB1 and ABCG2 transport proteins on lamotrigine serum concentrations
Uvod: Lamotrigin karakterizira znaÄajna interindividualna varijabilnost farmakokinetiÄkih parametara te je posljediÄno tome prisutna varijabilnost u uÄinkovitosti i razvoju Å”tetnih uÄinaka. Do sada nije razjaÅ”njena uloga polimorfizama metaboliÄkih enzima UGT1A4 i UGT2B7 te transportnih proteina ABCB1 i ABCG2 na bioraspoloživost lamotrigina.
Svrha: Cilj ovog istraživanja bio je procijeniti razlikuju li se nositelji varijantnog alela UGT2B7 c.-161C>T (rs7668258), UGT1A4*3 c.142T>G (rs2011425), ABCB1 c.1236C>T (rs1128503) i ABCG2 c.421C>A (rs2231142) od odgovarajuÄih kontrola divljeg tipa (engl. wild type, wt) s obzirom na izloženost lamotriginu.
Metode: U istraživanje su ukljuÄeni adolescenti i odrasle osobe s epilepsijom koji su uzimali monoterapiju lamotrigina ili politerapiju lamotrigina i valproata te su bili podvrgnuti rutinskom terapijskom praÄenju lijeka. Ispitanici su inaÄe bili zdravi i nisu uzimali druge lijekove koji bi mogli stupiti u interakciju s lamotriginom i valproatom. UkljuÄeni ispitanici genotipizirani su za UGT2B7 c.-161C>T, UGT1A4*3 c.142T>G, ABCB1 c.1236C>T i ABCG2 c.421C>A. Heterozigotni i varijantni homozigotni ispitanici usporeÄivani su sa svojim kontrolama divljeg tipa za ostatne koncentracije lamotrigina (standardizirane po dozi)
s prilagodbom prema dobi, spolu, tjelesnoj težini, ostalim ispitivanim polimorfizmima i razinama izloženosti valproatu. Za āujednaÄavanjeā vrijednosti kovarijata koriÅ”teno je uravnoteživanje entropije.
Rezultati: UkljuÄena je ukupno 471 osoba s epilepsijom, od Äega je njih 328 (69.6%) bilo na monoterapiji, a 143 su bili na politerapiji lamotrigina i valproata. Rezultati su pokazali da su nositelji varijantnog alela ABCG2 c.421C>A imali koncentracije lamotrigina niže za 25% u odnosu na kontrole divljeg tipa u sluÄaju da su ispitanici bili na monoterapiji lamotriginom (valproat 0) ili na kombiniranoj terapiji lamotrigina i valproata (LAM + VAL) ukoliko su koncantracije valproata bile ispod razine kvantifikacije (engl. below the lower limit of quantification, BLOQ). Nije dokazana razlika u koncentracijama lamotrigina izmeÄu nositelja
varijatnog alela i nositelja divljeg tipa kod ispitanika na kombiniranoj terapiji LAM + VAL ukoliko je koncentracija valproata bila 364 Ī¼mol/L [āvisok valproatā - unutar terapijskog raspona ili viÅ”e (GMR =1.37, 1.03-1.82 frekvencionistiÄka procjena, 1.31, 0.93-1.84, Bayes procjena)]. Nadalje, procijenjen je efekt valproata na dvije razine ABCG2 c.421C>A polimorfizma, tj. u kontrola ādivljeg tipaā i nositelja varijantnog alela. Efekt āvisokog valproataā bio je izraženiji u nositelja varijantnog alela nego u homozigota divljeg tipa (omjer GMR 1.80), kao i efekt āniskog valproataā (omjer GMR 1.50). Ostatne koncentracije lamotrigina (standardizirane prema dozi) bile su podjednake u nositelja varijantnih alela i kontrola divljeg tipa za UGT2B7 c.-161C>T, UGT1A4*3 c.142T>G i ABCB1 c.1236C>T.
ZakljuÄak: Rezultati istraživanja sugeriraju da polimorfizam ABCG2 c.421C>A moderira uÄinak valproata na izloženost lamotriginu, dok polimorfizmi UGT2B7 c.-161C>T, UGT1A4*3 c.142T>G i ABCB1 c.1236C>T nemaju relevatnog uÄinka na bioraspoloživost lamotrigina u osoba s epilepsijom.Introduction: Lamotrigine is characterized by significant interindividual variability in pharmacokinetic parameters and, consequently, there is variability in efficacy and the risk for adverse reactions. The role of polymorphisms of UGT1A4 and UGT2B7 metabolic enzymes as well as ABCB1 and ABCG2 transport proteins on the lamotrigine bioavailability has not
yet been clarified.
Purpose: To estimate whether epilepsy patients with variant UGT2B7 c.-161C>T (rs7668258), UGT1A4*3 c.142T>G (rs2011425), ABCB1 c.1236C>T (rs1128503) and ABCG2 c.421C>A (rs2231142) alleles differ from their wild-type (wt) peers in exposure to lamotrigine.
Methods: Consecutive adults on lamotrigine monotherapy or lamotrigine and valproate cotreatment undergoing routine therapeutic drug monitoring, otherwise generally healthy and free of interacting drugs, were genotyped for UGT2B7 -161C>, UGT1A4*3 c.142T>G, ABCB1 c.1236C>T (rs1128503) and ABCG2 c.421C>A. Heterozygous and variant homozygous subjects were compared to their wt controls for dose-adjusted lamotrigine troughs with adjustment for age, sex, body weight, other evaluated polymorphisms, and level of exposure to valproate using covariate entropy balancing.
Results: Of the 471 included patients, 328 (69.6%) were on monotherapy and 143 were cotreated with valproate. The results showed that c.421C>A variant allele carriers had by 25% lower lamotrigine concentrations compared to wild-type controls if the subjects were on lamotrigine monotherapy or lamotrigine and valproate (LAM + VAL) polytherapy if valproate troughs were below the lower limit of quantification (BLOQ). Variant c.421C>A allele had no obvious effect on lamotrigine troughs if valproate concentrations were 364 Ī¼mol/L [target/high valproate (GMR =1.37, 1.03-1.82 frequentist; 1.31, 0.93-1.84, Bayesian)]. Furthermore, we evaluated the effect of valproate on two levels of the ABCG2 c.421C>A polymorphism ("wild type" controls and variant allele carriers). The "high valproate" effect was more pronounced in the variant allele carriers than in the wild-type homozygotes (GMR ratio 1.80), as was the "low valproate" effect (GMR ratio 1.50). Dose-adjusted lamotrigine troughs in UGT2B7 c.-161C>T, UGT1A4*3 c.142T>G and ABCB1 c.1236C>T variant allele carriers were closely similar to those in their wt controls.
Conclusion: Data suggests that ABCG2 c.421C>A polymorphism moderates the effect of valproate on exposure to lamotrigine, while dose-adjusted lamotrigine troughs in epilepsy patients with variant UGT2B7 c.-161C>T, UGT1A4*3 c.142T>G or ABCB1 c.1236C>T alleles are equivalent to those in their respective wt peers
Guidelines for pharmacological treatment of epilepsy
MeÄunarodne smjernice za farmakoloÅ”ko lijeÄenje epilepsija opÄenite su, sveobuhvatne i ne prepoznaju lokalne specifiÄnosti poput ekonomskih i tehniÄkih moguÄnosti u pojedinim državama, dostupnosti pojedinih antiepileptika ili drugih metoda lijeÄenja i sliÄno. Stoga se nameÄe potreba izrade nacionalnih smjernica, Äiji su zapravo temelj meÄunarodne smjernice Internacionalne lige protiv epilepsije. Hrvatske smjernice za farmakoloÅ”ko lijeÄenje epilepsija plod su suradnje svih relevantnih struÄnih druÅ”tava i referentnih centara u RH, na Äelu s Hrvatskom ligom protiv epilepsije te Hrvatskim neuroloÅ”kim druÅ”tvom i Hrvatskim druÅ”tvom za djeÄju neurologiju Hrvatskoga lijeÄniÄkog zbora, a odražavaju aktualne socioekonomske i regulatorne specifiÄnosti u naÅ”oj zemlji, najnovije spoznaje farmakoloÅ”kih profila i uÄinkovitosti pojedinih antiepileptika kao i ekspertna miÅ”ljenja. AntiepileptiÄka terapija se uvodi nakon postavljanja dijagnoze epilepsije, stoga profilaktiÄka primjena nije opravdana. Nakon postavljanja dijagnoze potrebno je bolesnika informirati o prognozi bolesti, moguÄnostima lijeÄenja i samopomoÄi, životnim ograniÄenjima te moguÄim neželjenim dogaÄajima. Ciljevi farmakoterapije epilepsija su potpuna kontrola napada uz izbjegavanje nuspojava te održavanje ili poboljÅ”anje kvalitete života. Zlatni standard lijeÄenja je monoterapija odnosno primjena adekvatnog antiepileptika u adekvatnoj dozi. Izbor i titracija lijeka su individualni, a temelje se na smjernicama za lijeÄenje pojedinih vrsta napada, karakteristikama bolesnika i regulatorno specifiÄnim Äimbenicima. Nakon neuspjeha inicijalne monoterapije, potrebna je reevalucija anamnestiÄkih i dijagnostiÄkih podataka te potom postupna i spora zamjena antiepileptika. Racionalna politerapija podrazumijeva kombinaciju dvaju antiepileptika razliÄitih mehanizama djelovanja, prvog ili eventualno drugog izbora za postavljenju dijagnozu, niskoga interakcijskog
potencijala, razliÄitog profila nuspojava i sinergistiÄkog ili aditivnog djelovanja. Zamjena generiÄkih ili originalnog i generiÄkog oblika lijeka nije preporuÄljiva, a poglavito nakon postizanja remisije ili prilikom uzimanja visokih doza lijeka. Ukidanje antiepileptiÄke terapije treba biti postupno i sporo, u sluÄaju politerapije jedan po jedan lijek, a u donoÅ”enju odluke o ukidanju, kao i o uvoÄenju antiepileptika, mora biti ukljuÄen bolesnik i njegova obitelj.Epilepsy is the only chronic neurological disease that can be fully controlled by drugs or introduced into permanent remission. Nonetheless, pharmacological treatment of epilepsy is often accompanied by a range of diagnostic and therapeutic challenges. Due to a wide variety of available antiepileptics, the selection of the first antiepileptic, as well as the combination of polytherapy, is extremely large. The choice of the ideal antiepileptic is individual and depends on a variety of factors based on the pharmacological properties of the drug and the disctinctiveness of every patient (type of seizure, age,sex, profession, comorbidity, co-medication, etc.) with specific regulatory limitations (availability,price, indications of regulatory bodies). The basics of rational pharmacotherapy include slow titration of antiepileptics in monotherapy to satisfactory effect, slow drug replacement in the event of failure of the first antiepileptic, combination of two antiepileptics of different mechanism of action or selection of synergistic combinations if dual therapy is necessary, avoiding three or multiple polyterapies whenever possible, and slow reduction of antiepileptic drug after achieving a long lasting remission.Current ILAE guidelines for epilepsy treatment imply basic and comprehensive recommendations that are acceptable worldwide, including countries with the lowest economic standard. Therefore, these guidelines do not reflect the ideal treatment options, especially in developed countries, and are actually the basis for making national guidelines. The Croatian guidelines for pharmacological treatment of epilepsy are the product of the co-operation of all relevant professional societies and reference centers in the Republic of Croatia, headed by the Croatian League
Against Epilepsy and the Croatian Neurological Society. These guidelines reflect the current socioeconomic specificities in our country,the latest knowledge of pharmacological profiles, and efficacy of certain antiepileptics as well as expert opinions