Non-pharmacological Methods of Treating Headaches

Glavobolja je jedno od najčešćih neuroloških stanja koje zahtijeva akutno ili u određenim slučajevima profilaktično liječenje. Detaljnija klasifikacija glavobolja objašnjena je u Međunarodnoj klasifikaciji glavobolja. Iako je zbog same komponente boli kod glavobolje najvažnije provesti akutno liječenje, u određenim slučajevima važno je djelovati profilaktično (primjerice, kod migrene ili cluster glavobolje). S obzirom na mogućnost prekomjerne upotrebe analgetika, velik broj liječnika i pacijenata postaje skloniji nefarmakološkim metodama liječenja glavobolja. Nefarmakološke metode liječenja glavobolje koje navodimo u ovom radu uključuju: akupunkturu, psihološke tehnike (kognitivno bihevioralna terapija, neurofeedback), neuromodulaciju i prehranu.Headache is one of the most common neurological conditions that requires acute, chronic or preventative treatment. A detailed classification of headaches is explained in the International Classification of Headache Disorders. Although it is most important to provide acute treatment due to the component of pain in headache attacks, in certain cases it is important to act prophylactically (for example in migraine or cluster headache). Given the possibility of overuse of analgesics, a large number of physicians and patients are becoming more prone to nonpharmacological methods of treating headaches. Non-pharmacological methods of headache treatment listed in this paper include: acupuncture, psychological techniques (cognitive behavioral therapy, neurofeedback), neuromodulation and nutrition

GUIDELINES FOR TREATMENT OF PRIMARY HEADACHES BY THE CROATIAN SOCIETY FOR NEUROVASCULAR DISORDERS OF THE CROATIAN MEDICAL ASSOCIATION AND CROATIAN SOCIETY FOR PAIN PREVENTION

Glavobolja je jedno od najčešćih neuroloških stanja koje iziskuje veliku potrebu za lijekovima i ostalim metodama liječenja same akutne faze glavobolje, a po potrebi i za prevenciju ostalih napada glavobolje. Prema Međunarodnoj klasifi kaciji glavobolja razlikujemo primarne glavobolje (migrena i njeni podtipovi, tenzijska glavobolja i njeni podtipovi, trigeminalne autonomne glavobolje i njeni podtipovi) i sekundarne glavobolje (povezane s infekcijom, traumom glave i vrata, kranijskim ili cervikalnim vaskularnim poremećajima, nevaskularnim intrakranijalnim poremećajima, prestankom uzimanja određenih tvari, psihijatrijskim poremećajima, poremećajima kranija, vrata, očiju, ušiju, nosa, sinusa, ustiju te drugih facijalnih ili kranijskih struktura). Kod samog liječenja glavobolja važno je razlučiti primarnu od sekundarne glavobolje, postaviti dijagnozu primarne glavobolje te odlučiti se za liječenje akutne ili preventivne faze. Od analgetika se najčešće primjenjuju nespecifi čni analgetici koji djeluju na široku paletu boli te specifi čni analgetici koji djeluju samo na određenu vrstu glavobolje (npr. triptani kod migrenoznih napada). Osim navedenog u tekstu su spomenute i ostale metode koje se koriste u liječenju glavobolja, a koje uključuju promjenu životnog stila, izbjegavanje provocirajućih faktora, akupunkturu te primjenu botulinum toksina.Introduction: Headache is one of the most common neurologic conditions, which means that there is a great need for medications and other methods of headache treatment for acute pain relief and chronic prevention of headache. Aim: Knowing that headache is one of the most common conditions, we wanted to summarize its treatment. Methods: We performed MEDLINE search about treatment of primary headaches. We also explored HRČAK, the Croatian scientifi c base. Results: We found articles in both scientifi c bases, but we chose only the most systematized ones. Discussion: According to the International Headache Classifi cation, there are two main types of headaches: primary headaches (migraine ant its subtypes, tension type headache ant its subtypes, trigeminal autonomic cephalgias) and secondary headaches (attributed to infection, head or neck trauma, cranial or cervical vascular disorders, non-vascular intracranial disorders, substance withdrawal, psychiatric conditions, pain attributed to disorders of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or other facial or cervical structures). When managing diagnosis of primary headache, it is important to make a difference between primary and secondary headache, manage the right diagnosis of primary headache, and decide on the right treatment for acute or preventive phase of headache. The most widely used medications in headache treatment are nonspecifi c analgesics, which can treat headache but also other pain disorders. Specifi c headache medications include those that can treat only a specifi c type of headache. Besides these, there are other methods in headache treatment, which include lifestyle modifi cation, avoiding provocative factors, acupuncture, and treatment with botulinum toxin. Conclusion:For primary headache treatment, it is important to establish the accurate diagnosis and act fast in treatment of acute headache attack. For some patients, it is important to start prophylactic treatment but also try to prevent medication overuse headache. When treating a headache of any kind, it is also important to take the whole picture of a patient and his/hercomorbidities and think of the possible side effects. Lifestyle modifi cation and some complementary methods can help us in treating chronic headaches

NEUROLOGICAL MANIFESTATIONS OF POST-COVID-19 SYNDROME

Uvod: Krajem 2019. otkrivena je nova bolest nazvana COVID-19. Bolest je uzrokovana novim koronavirusom SARS-CoV-2. Ubrzo je Svjetska zdravstvena organizacija (SZO) proglasila pandemiju. Osim dišnih simptoma uočeno je da se bolest može očitovati i neurološkom simptomatologijom te da se tijekom i nakon liječenja COVID-19 mogu javiti neurološke komplikacije. Nakon preboljenja COVID-19, neovisno o težini kliničke slike, dio bolesnika žali se na zaostale neurološke simptome. U tim slučajevima govorimo o post-COVID-19 sindromu. Za simptome koji se javljaju tjednima ili mjesecima nakon COVID-19 simptoma u literaturi su korišteni različiti termini kao što su npr. od "dugi-COVID", "post–COVID sindrom", "posljedice SARSCoV-2 infekcije". Simptomi podrazumijevaju različita očitovanja organskih sustava koji se jave i/ili traju dulje od 4 tjedna. Cilj: Napraviti pregled trenutnih znanstvenih činjenica povezano sa sindromom post-COVID-19. Metode: Pretražili smo bazu podataka MEDLINE s ključnim riječima: post-COVID-19, neurološka očitovanja i dugi COVID-19 u vremenu od 2020. godine. Rezultati: Prema podatcima koje smo prikupili postoje četiri stadija COVID-19. Akutni COVID-19 podrazumijeva simptome i znakove bolesti koji traju do 4 tjedna. Produljeni simptomatski COVID-19 podrazumijeva simptome i znakove koji traju od 4 do12 tjedana. Post-COVID-19 sindrom podrazumijeva simptome i znakove koji se jave nakon akutne bolesti te traju dulje od 12 tjedana, a nisu objašnjeni drugom dijagnozom. Sindrom post-COVID-19 podrazumijeva znakove i simptome koji se pojavljuju tijekom ili nakon COVID-19 te traju dulje od 12 tjedana, a nisu objašnjeni drugom dijagnozom. Simptomi se mogu preklapati i varirati u intenzitetu. Dugi COVID podrazumijeva COVID-19 i sindrom post-COVID-19. Što se neuroloških post-COVID-19 očitovanja tiče, kod bolesnika su najčešće prisutni slabost i umor, mialgija, smetnje raspoloženja i smetnje spavanja. Također, u literaturi se navode i trajna glavobolja, smetnje koncentracije koje su nazvane moždanom maglom (od engl. brain fog), parestezije, poremećaj ili gubitak okusa, poremećaj ili gubitak mirisa te smetnje autonomnog živčanog sustava. Postoji nekoliko pretpostavljenih načina kojima virus dođe do središnjeg živčanog sustava: njušni, dišni i probavni. Središnji živčani sustav može biti oštećen izravno i neizravno. Moždana magla i smetnje pamćenja objašnjeni su središnjom i respiratornom hipoksijom te proupalnim odgovorom organizma. U slučaju sumnje na sindrom post-COVID-19 pri postavljanju dijagnoze uvijek treba uzeti u obzir i ostale moguće dijagnoze. U mnogim slučajevima potrebno je učiniti magnetsku rezonanciju (MR) mozga i vratne kralježnice. Ponekad je potrebno u dijagnosticiranje bolesti uključiti i ostale specijaliste. Zaključak: Sindrom post-COVID-19 može se očitovati nizom neuroloških poremećaja kao što su kognitivni simptomi, nesanica i promjene raspoloženja, disautonomija, smetnje mirisa i okusa, sindrom postintenzivne skrbi.Introduction: At the end of 2019, a new disease named COVID-19 was discovered. The disease is caused by the new coronavirus SARS-CoV-2. A global pandemic was soon declared by the World Health Organization (WHO). The disease mostly presents by respiratory simptoms. It can also be presented by neurological symptoms and neurological complications may occur during and after treatment of COVID-19. Regardless of COVID-19 symptoms, some patients complain of persistent symptoms. In such cases, we talk of so-called post-COVID-19 syndrome. Various terms have been used in the literature for the spectrum of symptoms that occur weeks or months after COVID-19 symptoms, such as "long-COVID", "post-COVID syndrome", "consequences of SARS-CoV-2 infection". Symptoms include various manifestations of organ systems that occur and/or last longer than 4 weeks. Aim: Our aim was to analyze scientifi c papers on the topic of post-COVID-19 syndrome. We also wanted to describe the proposed pathophysiological mechanisms of post-COVID-19 syndrome and highlight the possible diagnostic algorithm. Methods: We searched the MEDLINE database using the following key features:„postCOVID-19“, „neurological manifestations“ and „long-COVID-19“ back to the year 2020. Results: Accoding to our fi ndings, there are several stages of COVID-19. Acute COVID-19 includes acute disease that lasts for 4 weeks. Ongoing symptomatic COVID-19 includes symptoms that last for 4 to 12 weeks. Post-COVID-19 syndrome involves signs and symptoms that occur during or after COVID-19 infection, last for more than 12 weeks, and cannot be explained by another diagnosis. Symptoms can affect different organ systems and may overlap and fl uctuate in intensity. The term „long COVID-19“ describes ongoing symptomatic COVID-19 and post-COVID-19 syndrome. Neurological manifestations of post-COVID-19 syndrome include weakness and fatigue, myalgia, mood disorders, and sleep disturbances. Persistent headaches, impaired concentration ("brain fog"), paresthesias, dysgeusia, hyposmia and disorders of the autonomic nervous system have also been reported in the literature. There are several proposed routes for SARS-CoV-2 to reach the central nervosu system: olfactory, hematogenous and gastointestinal. The central nervous system can be damaged directly and indirectly. "Brain fog" and memory diffi culties are explained by central and respiratory hypoxia (especially), as well as proinfl ammatory body response. In case of post-COVID-19 neurolgical symptoms, there always have to be a diagnostic approach that considers and searches for alternative diagnosis in the patient context. Basic laboratory workup with possible later extension has to be done. Also, proper neuroimaging methods, mostly brain and/or spine magnetic resonance imaging, should be performed. In some cases, a multidisciplinary approach may be required. Conclusion: We have made a review of neurological postCOVID-19 symptoms and their pathophysiological mechanism with the initial care proposed. We would also like to note that there still are numerous data on the topic that will certainly be revealed with time

GUIDELINES FOR TREATMENT OF PRIMARY HEADACHES BY THE CROATIAN SOCIETY FOR NEUROVASCULAR DISORDERS OF THE CROATIAN MEDICAL ASSOCIATION AND CROATIAN SOCIETY FOR PAIN PREVENTION

Glavobolja je jedno od najčešćih neuroloških stanja koje iziskuje veliku potrebu za lijekovima i ostalim metodama liječenja same akutne faze glavobolje, a po potrebi i za prevenciju ostalih napada glavobolje. Prema Međunarodnoj klasifi kaciji glavobolja razlikujemo primarne glavobolje (migrena i njeni podtipovi, tenzijska glavobolja i njeni podtipovi, trigeminalne autonomne glavobolje i njeni podtipovi) i sekundarne glavobolje (povezane s infekcijom, traumom glave i vrata, kranijskim ili cervikalnim vaskularnim poremećajima, nevaskularnim intrakranijalnim poremećajima, prestankom uzimanja određenih tvari, psihijatrijskim poremećajima, poremećajima kranija, vrata, očiju, ušiju, nosa, sinusa, ustiju te drugih facijalnih ili kranijskih struktura). Kod samog liječenja glavobolja važno je razlučiti primarnu od sekundarne glavobolje, postaviti dijagnozu primarne glavobolje te odlučiti se za liječenje akutne ili preventivne faze. Od analgetika se najčešće primjenjuju nespecifi čni analgetici koji djeluju na široku paletu boli te specifi čni analgetici koji djeluju samo na određenu vrstu glavobolje (npr. triptani kod migrenoznih napada). Osim navedenog u tekstu su spomenute i ostale metode koje se koriste u liječenju glavobolja, a koje uključuju promjenu životnog stila, izbjegavanje provocirajućih faktora, akupunkturu te primjenu botulinum toksina.Introduction: Headache is one of the most common neurologic conditions, which means that there is a great need for medications and other methods of headache treatment for acute pain relief and chronic prevention of headache. Aim: Knowing that headache is one of the most common conditions, we wanted to summarize its treatment. Methods: We performed MEDLINE search about treatment of primary headaches. We also explored HRČAK, the Croatian scientifi c base. Results: We found articles in both scientifi c bases, but we chose only the most systematized ones. Discussion: According to the International Headache Classifi cation, there are two main types of headaches: primary headaches (migraine ant its subtypes, tension type headache ant its subtypes, trigeminal autonomic cephalgias) and secondary headaches (attributed to infection, head or neck trauma, cranial or cervical vascular disorders, non-vascular intracranial disorders, substance withdrawal, psychiatric conditions, pain attributed to disorders of the cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or other facial or cervical structures). When managing diagnosis of primary headache, it is important to make a difference between primary and secondary headache, manage the right diagnosis of primary headache, and decide on the right treatment for acute or preventive phase of headache. The most widely used medications in headache treatment are nonspecifi c analgesics, which can treat headache but also other pain disorders. Specifi c headache medications include those that can treat only a specifi c type of headache. Besides these, there are other methods in headache treatment, which include lifestyle modifi cation, avoiding provocative factors, acupuncture, and treatment with botulinum toxin. Conclusion:For primary headache treatment, it is important to establish the accurate diagnosis and act fast in treatment of acute headache attack. For some patients, it is important to start prophylactic treatment but also try to prevent medication overuse headache. When treating a headache of any kind, it is also important to take the whole picture of a patient and his/hercomorbidities and think of the possible side effects. Lifestyle modifi cation and some complementary methods can help us in treating chronic headaches

COVID-19 AND NEUROLOGICAL MANIFESTATIONS

Uvod: Krajem 2019. god. otkrivena je nova bolest nazvana COVID-19 (od engl. Corona Virus Disease-2019). Bolest je uzrokovana novim koronavirusom SARS-CoV-2 (od engl. Severe acute respiratory syndrome coronavirus 2), a s obzirom na brzo širenje od strane Svjetske zdravstvene organizacije (SZO) ubrzo je proglašena pandemija. Na početku pandemije ustanovljeno je da se COVID-19 osim dišnim simptomima može očitovati simptomima drugih organskih sustava. Između ostalog COVID-19 može se očitovati neurološkom simptomatologijom, a neurološki simptomi mogu se javiti i kao komplikacija COVID-19 te nakon preboljenja same bolesti. Cilj: nastojali smo prikupiti najnovije spoznaje o COVID-19 i neurološkim očitovanjima i komplikacijama. Također, željeli smo istaknuti i moguće razlike pri postavljanju dijagnoze i liječenja. Metode: Pretražili smo bibliografsku bazu podataka MEDLINE s ključnim riječima neurološki simptomi, komplikacije, COVID-19 sve do 2020. godine. Rezultati: Do sada su prema izvješću SZO ustanovljena 23 neurološka simptoma i 14 neuroloških dijagnoza. Prema podatcima SZO do sada je 1/3 hospitaliziranih bolesnika imala neurološke simptome. Kod bolesnika starijih od 66 godina najčešća je dijagnoza bila encefalopatija, a očitovala se agitacijom, smetenošću, delirijem te poremećajima stanja svijesti. Također, encefalopatija je bila pokazatelj lošijeg ishoda bolesti. Incidencija ishemijskih i hemoragijskih moždanih udara bila je veća kod COVID-19 pozitivnih bolesnika u odnosu na opću populaciju što se objašnjava proupalnim odgovorom i povećanom sklonosti koagulaciji tijekom bolesti. Prethodni čimbenici rizika za moždani udar kao što su pušenje, šećerna bolest i arterijska hipertenzija pridonose mehanizmu nastanka moždanog udara i lošijem ishodu. Manje učestali bili su neuromišićni poremećaji kao što su kljenut facijalnog živca i Gillian Barréov sindrom. Druge infektivne bolesti kao što je meningoencefalitis javljale su se rjeđe. Poremećaji mirisa i okusa obično bi se povukli unutar dva mjeseca. Dijagnostika i liječenje neuroloških očitovanja COVID-19 ne razlikuje se od uobičajenih postupaka. Nema specifičnog lijeka za liječenje neuroloških poremećaja tijekom COVID-19. Važno je napomenuti da bolesnici koji već imaju određenu neurodegenerativnu bolest i veći stupanj onesposobljenosti mogu imati lošiji ishod COVID-19. Također, kod dijela kroničnih neuroloških bolesti moguće je da se tijekom COVID-19 liječenje mora promijeniti. Zaključak: Tijekom pandemije neurolozi su se susreli i s različitim načinima reorganizacije bolničkog sustava liječenja neuroloških bolesnika, praćenja kroničnih neuroloških bolesnika, liječenja kroničnih bolesnika zbog pandemije te hitnih neuroloških stanja kod COVID-19 pozitivnih bolesnika. Zato je neurološka struka morala reorganizirati i osigurati neurološku dijagnostiku i liječenje za ostale bolesnike.Introduction: At the end of 2019, a new disease called COVID-19 was discovered. The disease was caused by the new coronavirus SARS-CoV-2. Due to its rapid spread, a global pandemic was soon declared by the World Health Organization (WHO). At the beginning of the pandemic, it was established that COVID-19 usually presented with respiratory symptoms but that it could also be presented with symptoms of other organs. COVID-19 can be manifested by neurological symptoms. Neurological symptoms can also occur as a complication due to COVID-19 and persist long after the disease has been overcome. Aim: We aimed to analyze scientifi c papers on neurological manifestations and complications in COVID-19 positive patients. We also wanted to highlight the possible differences in neurological diagnosis and treatment strategies. Methods: We searched MEDLINE database using the following key features: "neurological manifestations", "neurological symptoms" and "COVID-19" back to the year 2020. Results: According to a WHO report, 23 neurological symptoms and 14 neurological diagnoses have been described so far. One-third of hospitalized patients had neurological symptoms. Encephalopathy was the most common neurological condition in patients older than 66 years. Those patients presented with different symptoms including agitation, delirium, and consciousness disorders. According to some studies, encephalopathy was also a predictor of poor outcome. The number of cases of strokes (ischemic and hemorrhagic) was higher in COVID-19 positive patients than usual. This fact is explained by the tendency to a hypercoagulable state and proinfl ammatory process while having COVID-19. Also, a great number of patients have already had some risk factors (smoking, hypertension, diabetes mellitus), which contributed to the pathogenesis of stroke and also poorer outcomes. Less often neurological manifestations include neuromuscular disorders such as Guillain-Barré syndrome and facial palsy. Guillain-Barré syndrome mostly presented with sensorimotor manifestations. Other infective diseases such as meningoencephalitis occurred in rare cases. Hyposmia, anosmia, and dysgeusia occurred in most cases but resolved mostly within two months of infection. The diagnosis and treatment of neurological manifestations caused by COVID-19 do not differ from the usual diagnostic methods and treatment strategies. There is no specifi c drug to be used during COVID-19 infection and certain neurological diagnoses. Important information is that patients who already have certain neurodegenerative diseases and a higher degree of neurological disability may have worse outcome while having COVID-19. Also, in several neurological patients with a preexisting neurological diagnosis, the strategy and treatment of the underlying neurological disease had to change depending on whether or not the person had COVID-19. Conclusion: In conclusion, during the pandemic, neurologists met with different ways to reorganize the hospital system for treatment of neurological patients, monitoring of chronic neurological patients, treatment of chronic patients due to the pandemic, and emergency neurological conditions in COVID-19 positive patients. Also, the neurologists had to organize normal functioning of neurological diagnostic methods and treatment for other patients

NEUROMYELITIS OPTICA AND DIFFERENTIAL DIAGNOSIS OF NEUROMYELITIS OPTICA

Optički neuromijelitis (NMO, od engl. neuromyelitis optica) je autoimuna demijelinizacijska bolest središnjeg živčanog sustava koja zahvaća uglavnom očne živce i kralježničnu moždinu. Više rasprave o bolesti pokrenuto je 2004. godine kada su otkrivena ciljna protutijela, tzv. anti-akvaporinska protutijela (AQP4-IgG) koja imaju glavnu ulogu u samom mehanizmu nastanka. Za postavljanje dijagnoze potrebno je zadovoljiti dva glavna kriterija i dva od tri suportivna kriterija. Dva glavna kriterija uključuju: optički neuritis i mijelitis, a suportivni kriteriji uključuju: MR mozga koji ne ispunjava kriterije za dijagnozu multiple skleroze, prisutnost seropozitivnih AQP4-IgG (NMO-IgG) protutijela, longitudinalno ekstenzivni transverzalni mijelitis (LETM) u T2 vremenu na MR. Kako određena skupina pacijenata nije upotpunjavala sve kriterije za postavljanje dijagnoze NMO, 2007. godine uveden je pojam tzv. NMO-spektar poremećaja (NMOSD od engl. neuromyelitis optica spectrum disorder). Godine 2015. pokušalo se ujediniti termin NMO i NMOSD te su donijeti kriteriji za postavljanje dijagnoze NMOSD. Terapija koja se primjenjuje uglavnom je orijentirana na akutno zbrinjavanje simptoma dok je cilj dugoročne terapije sprječavanje egzacerbacija bolesti i novih relapsa. U radu je prikazana defi nicija, dijagnostika, diferencijalna dijagnostika te liječenje NMO/NMOSD.Introduction: Neuromyelitis optica (NMO) is an autoimmune demyelinating disease of the central nervous system that mainly affects optic nerve and spinal cord. The disease can be clinically presented similar to multiple sclerosis. Even though the disease was described in the late 19th century, discussion about the disease was initiated in 2004 when antibodies against aquaporin (AQP4-IgG) were discovered. They play the main role in the mechanism of the disease. Aim: Knowing that NMO can be presented similar to multiple sclerosis, our aim was to collect and review data about NMO and differential diagnosis of NMO. Methods: We performed MEDLINE search for NMO and included literature dating back from the year 2010. We also explored the Croatian scientifi c database Hrčak. Results: We found 334 review articles by exploring MEDLINE but chose only the most systemized ones. On Hrčak, we found 3 articles in Croatian language. Discussion: The prevalence of the disease is 1-4.4/100 000 in Western countries. In some Asian countries, NMO accounts for 50% of demyelinating disease diagnoses. Searching through the literature, NMO was found to be more common in women as compared with men (9:1 ratio). The disease can be associated with other autoimmune diseases such as systemic lupus erythematosus, sarcoidosis and Sjögren syndrome. The disease can be clinically presented by optic neuritis, symptoms of transverse myelitis, nausea, and other brain stem symptoms. At the beginning of defi ning criteria for diagnosing NMO, there were two main criteria and supportive criteria. The two main diagnostic criteria included optic neuritis and myelitis. Supportive criteria included brain magnetic resonance imaging (MRI) not meeting the criteria for multiple sclerosis (MS) diagnosis positive AQP4-IgG antibody and longitudinally extensive transverse myelitis (LETM) on T2-weighted imaging on MRI. A group of patients did not meet the criteria for NMO diagnosis, so in 2007 the term NMO spectrum disorder (NMOSD) was introduced. In 2015, there was a tendency to unite the NMO and NMOSD terms; so diagnostic criteria for NMOSD were developed by Wingerchuk et al. The criteria were extended to those with AQP4-IgG positive and AQP4-IgG negative or unknown status. In the article, were also mention the so called ‘red fl ags’ that help in differential diagnosing of NMO/NMOSD. Treatment is still limited to treating acute exacerbations by methylprednisolone or plasmapheresis. Long-term therapy is focused on reducing the frequency and intensity of exacerbations. Conclusions: Even though NMO is more common in some Asian countries, it can also occur in other countries. Clinically, it is similar to MS but treatment is different. There are some data that medications used in the treatment of MS can worsen the course of the disease in NMO. That is why it is important to make a correct diagnosis

NEUROLOGIC COMPLICATIONS OF ANDERSON-FABRY DISEASE

Anderson-Fabryjeva bolest je rijetka X-vezana recesivna bolest u kojoj je prisutna smanjena aktivnost lizosomalnog enzimaIntroduction: Anderson-Fabry disease is a rare X-linked inborn error and one of the most prevalent lysosomal storage diseases. It is characterized by defi ciency of the lysosomal enzym

MULTIPLE SCLEROSIS TREATMENT

Liječenje multiple skleroze se osobito tijekom posljednjeg desetljeća intenziviralo te obuhvaća liječenje osnovne bolesti imunomodulacijskom terapijom i primjenu simptomske terapije za redukciju popratnih simptoma. Imunomodulacijsku terapiju multiple skleroze čine interferon beta-a1 (Avonex, Rebif), interferon beta-1b (Betaseron, Extavia), peginterferon beta- 1a (Plegridy), glatiramer-acetat (Copaxone), mitoksantron (Novantrone), terifl unomid (Aubagio), dimetil fumarat (Tecfi dera), fi ngolimod (Gilenya), natalizumab (Tysabri), alemtuzumab (Lemtrada), daclizumab (Zinbryta) i ocrelizumab (Ocrevus). Lijekovi se prema redoslijedu primjene dijele na lijekove prve, druge i treće linije. U liječenju bolesnika teži se postizanju koncepta NEDA („No Evidence Of Disease Activity“) čiji ciljevi su da nema relapsa, nema povećanja onesposobljenosti, nema novih ili aktivnih lezija na MR slikama, nema znakova atrofi je mozga. Postizanje cilja NEDA podrazumijeva ranu dijagnozu, ranu primjenu indiciranog lijeka uz mogućnost zamjene terapije učinkovitijim lijekom. U kliničkoj praksi se trenutno provode dva različita terapijska pristupa: eskalacijski i indukcijski. Eskalacijska terapija uključuje rano započinjanje primjene prve linije imunomodulacijske terapije te ako su lijekovi djelomično učinkoviti ili neučinkoviti brzi prelazak na drugu liniju liječenja. Indukcijska terapija uključuje ranu upotrebu imunosupresivnih lijekova nakon koje slijedi dugoročna terapija održavanja imunomodulacijskim lijekovima. Sigurnosni profi l lijekova za indukciju ukazuje na potrebu stratifi kacije rizika i pažljivu selekciju bolesnika.Introduction: Lately, treating multiple sclerosis is becoming ever more challenging. It includes a combination of immunomodulatory and symptomatic treatments. There is an expansion of immunomodulatory agents, especially monoclonal antibodies. New drugs to treat relapse-remittent multiple sclerosis (RRMS) and a drug for primary progressive multiple sclerosis have been introduced. Also, a new concept of treating, named No Evidence of Disease Activity (NEDA) appeared with an aim to achieve a patient that is free of relapses, free of new EDSS deteriorations, free of new or newly enlarged lesions on magnetic resonance imaging, and free of brain atrophy. It would encompass early diagnosis, early therapy implementation, and the possibility of therapy changing. To achieve NEDA, two approaches are available, escalating and induction therapy. Escalating therapy includes the use of fi rst-line drugs with the possibility of changing to second-line agents in case of therapy failure. The induction therapy approach considers induction with immunosuppressants followed by maintenance therapy with immunomodulatory agents. Aim: Our aim was to search through scientifi cally published papers for medically valid data in order to provide the best medical advice for both physicians and patients in search for appropriate treatment. Methods: We performed extensive MEDLINE search, dating from 1993. Results and Discussion: The interferons, glatiramer acetate, terifl unomide and dimethyl fumarate are considered as the fi rst-line RRMS therapy, while other available medications represent second- or even third-line therapy. Avonex, Betaseron, Extavia, Glatopa and Copaxone can be utilized as an early treatment of clinically isolated syndrome. Ocrelizumab is a monoclonal antibody used to treat primary progressive form of multiple sclerosis. Secondary progressive multiple sclerosis can presumably be treated with interferon beta, terifl unomide, fi ngolimod, alemtuzumab and dimethyl fumarate while they express an effect on disease activity control, otherwise mitoxantrone is another option available. Conclusion: The goal would be to collect as much data as possible and re-evaluate all relevant data on multiple sclerosis immunomodulatory therapy that does not include monoclonal antibodies. Also, the goal would be to notice adverse effects and special recommendations on pre-treatment concerns, as much as control of certain parameters during and after the application of disease modifying agents. The best approach to patient management is through multiple sclerosis centers where interdisciplinary team can effectively resolve all the concomitant events

NEUROMYELITIS OPTICA AND DIFFERENTIAL DIAGNOSIS OF NEUROMYELITIS OPTICA

Optički neuromijelitis (NMO, od engl. neuromyelitis optica) je autoimuna demijelinizacijska bolest središnjeg živčanog sustava koja zahvaća uglavnom očne živce i kralježničnu moždinu. Više rasprave o bolesti pokrenuto je 2004. godine kada su otkrivena ciljna protutijela, tzv. anti-akvaporinska protutijela (AQP4-IgG) koja imaju glavnu ulogu u samom mehanizmu nastanka. Za postavljanje dijagnoze potrebno je zadovoljiti dva glavna kriterija i dva od tri suportivna kriterija. Dva glavna kriterija uključuju: optički neuritis i mijelitis, a suportivni kriteriji uključuju: MR mozga koji ne ispunjava kriterije za dijagnozu multiple skleroze, prisutnost seropozitivnih AQP4-IgG (NMO-IgG) protutijela, longitudinalno ekstenzivni transverzalni mijelitis (LETM) u T2 vremenu na MR. Kako određena skupina pacijenata nije upotpunjavala sve kriterije za postavljanje dijagnoze NMO, 2007. godine uveden je pojam tzv. NMO-spektar poremećaja (NMOSD od engl. neuromyelitis optica spectrum disorder). Godine 2015. pokušalo se ujediniti termin NMO i NMOSD te su donijeti kriteriji za postavljanje dijagnoze NMOSD. Terapija koja se primjenjuje uglavnom je orijentirana na akutno zbrinjavanje simptoma dok je cilj dugoročne terapije sprječavanje egzacerbacija bolesti i novih relapsa. U radu je prikazana defi nicija, dijagnostika, diferencijalna dijagnostika te liječenje NMO/NMOSD.Introduction: Neuromyelitis optica (NMO) is an autoimmune demyelinating disease of the central nervous system that mainly affects optic nerve and spinal cord. The disease can be clinically presented similar to multiple sclerosis. Even though the disease was described in the late 19th century, discussion about the disease was initiated in 2004 when antibodies against aquaporin (AQP4-IgG) were discovered. They play the main role in the mechanism of the disease. Aim: Knowing that NMO can be presented similar to multiple sclerosis, our aim was to collect and review data about NMO and differential diagnosis of NMO. Methods: We performed MEDLINE search for NMO and included literature dating back from the year 2010. We also explored the Croatian scientifi c database Hrčak. Results: We found 334 review articles by exploring MEDLINE but chose only the most systemized ones. On Hrčak, we found 3 articles in Croatian language. Discussion: The prevalence of the disease is 1-4.4/100 000 in Western countries. In some Asian countries, NMO accounts for 50% of demyelinating disease diagnoses. Searching through the literature, NMO was found to be more common in women as compared with men (9:1 ratio). The disease can be associated with other autoimmune diseases such as systemic lupus erythematosus, sarcoidosis and Sjögren syndrome. The disease can be clinically presented by optic neuritis, symptoms of transverse myelitis, nausea, and other brain stem symptoms. At the beginning of defi ning criteria for diagnosing NMO, there were two main criteria and supportive criteria. The two main diagnostic criteria included optic neuritis and myelitis. Supportive criteria included brain magnetic resonance imaging (MRI) not meeting the criteria for multiple sclerosis (MS) diagnosis positive AQP4-IgG antibody and longitudinally extensive transverse myelitis (LETM) on T2-weighted imaging on MRI. A group of patients did not meet the criteria for NMO diagnosis, so in 2007 the term NMO spectrum disorder (NMOSD) was introduced. In 2015, there was a tendency to unite the NMO and NMOSD terms; so diagnostic criteria for NMOSD were developed by Wingerchuk et al. The criteria were extended to those with AQP4-IgG positive and AQP4-IgG negative or unknown status. In the article, were also mention the so called ‘red fl ags’ that help in differential diagnosing of NMO/NMOSD. Treatment is still limited to treating acute exacerbations by methylprednisolone or plasmapheresis. Long-term therapy is focused on reducing the frequency and intensity of exacerbations. Conclusions: Even though NMO is more common in some Asian countries, it can also occur in other countries. Clinically, it is similar to MS but treatment is different. There are some data that medications used in the treatment of MS can worsen the course of the disease in NMO. That is why it is important to make a correct diagnosis

DIAGNOSIS OF ANDERSON-FABRY DISEASE

Anderson-Fabryjeva bolest je nakon Gaucherove bolesti najčešća lizosomalna bolest nakupljanja. Bolest se nasljeđuje X-vezano recesivno. Karakterizirana je smanjenom aktivnošću enzimaIntroduction: Anderson- Fabry disease is one of the most common lysosomal storage diseases (after Gaucher disease). It is an X-linked inborn error. A disease is characterized by defi ciency of the lysosomal enzym