AIM:To evaluate the real-world effectiveness, safety, and tolerability of ofatumumab in people with relapsing multiple sclerosis (pwMS) in Croatia. METHODS:We conducted a retrospective observational study in eight Croatian hospitals (March 2022-March 2025). Clinical, MRI, and laboratory data were collected before treatment initiation and every six months. Effectiveness measures included annualized relapse rate (ARR), MRI activity, and sustained accumulation of disability (SAD), and the proportion achieving no evidence of disease activity (NEDA-3). Safety assessments included adverse events (AEs), immunoglobulin levels, infections, and pregnancy outcomes. RESULTS:The study included 665 pwMS (65.6 % female; mean age 40.2 ± 10.7 years; 59.7 % treatment-naïve). Median follow-up was 1.55 years. ARR decreased from 0.70 ± 0.67 pre-treatment to 0.03 ± 0.18 post-treatment (p < 0.001). MRI activity occurred in 17.1 % of patients; 76.7 % achieved NEDA-3. SAD was observed in 6.3 % of pwMS, with male sex as the only independent predictor. Ofatumumab discontinuation occurred in 4.2 % of patients, mainly due to pregnancy. Injection reactions occurred in 15.8 % and infections in 7.4 % (3 hospitalizations). IgG and IgM declined slightly over time, with low IgM (<0.4 g/L) persisting in >10 % after two years, but without correlation to infection rates. Two malignancies were observed. Pregnancy outcomes were favorable in most cases. CONCLUSION:In a real-world Croatian cohort, ofatumumab demonstrated high effectiveness in reducing relapses and MRI activity, with a favorable safety profile over three years. These findings align with pivotal trial results, supporting ofatumumab as an effective and well-tolerated therapy for active relapsing MS in clinical practice.

Headache disorders are one of the most prevalent and disabling conditions worldwide. Headache is classified as primary or secondary according to its underlying pathophysiology. The most common primary headaches are migraines and tension-type headaches (TTH). Their diagnosis is based mostly on clinical presentation, but sometimes this can be challenging. In order to improve the differential diagnostics of these conditions, we evaluated the role of electroencephalography (EEG) in diagnostic workup. EEG records electrical activity of the brain cortex. It is mostly used to diagnose epilepsy, but EEG abnormalities are found in many headache patients as well. In this review, we provide an overview of EEG-based headache-related research. We compare their results in the hope of better understanding the neural changes in migraine and TTH. According to our findings, EEG might be helpful in the search for potential headache biomarkers, but further studies are necessary.

A multicenter molecular biomarker survey was conducted in Multiple Sclerosis (MS) centers across Central-Eastern European countries, encompassing a population of 107 million. Our aim was to provide a “snapshot” for future studies investigating the use of molecular biomarkers in MS. A self-report questionnaire was distributed via email to MS centers in seven Central-Eastern European countries (Croatia, Czech Republic, Poland, Romania, Serbia, Slovakia, and Slovenia) and to four reference centers (two in Austria, one in Germany, and one in Denmark), focusing on cerebrospinal fluid (CSF) analysis and molecular biomarkers in MS. Responding centers routinely request CSF oligoclonal band (OCB) testing in suspected MS cases, although no consensus exists on the number of CSF-restricted bands required to define OCB positivity, either within or between countries. More than half of the surveyed centers in the Czech Republic, Slovakia, Slovenia, and the reference centers request kappa free light chain (κFLC) testing in patients with suspected MS. Neurofilament light chain (NfL) is frequently used as a molecular biomarker for MS in Romania, Slovakia, and the reference centers. In summary, besides the use of CSF-specific OCB there is no consensus among the surveyed countries regarding the use of molecular biomarkers in MS.

Anderson-Fabryjeva bolest metabolička je bolest nakupljanja glikolipida u lizosomima. Multidisiciplinarni pristup neophodan je za rano prepoznavanje, liječenje i prevenciju komplikacija u oboljelih. Ove smjernice nadopuna su smjernica publiciranih u ime Referentnog centra za rijetke i metaboličke bolesti 2014. godine u Liječničkom vjesniku s obzirom na nove dijagnostičke postupke, biljege i terapijske opcije, suradnjom specijalista iz centara izvrsnosti te multidisciplinarnog tima Referentnog centra za rijetke i metaboličke bolesti odraslih Ministarstva zdravstva Republike Hrvatske. Smjernice su prezentirane na godišnjem sastanku Hrvatskog društva za rijetke bolesti Hrvatskoga liječničkog zbora te su jednoglasno prihvaćene.

Calcitonin gene-related peptide (CGRP) plays a key role in the pathophysiology of migraine, acting on CGRP receptors in the trigeminovascular system, causing neurogenic inflammation and vasodilation, and promoting nociception. Four specific monoclonal antibodies targeting CGRP are available for prevention of episodic and chronic migraine in adults with at least four migraine days per month. The aim of these guidelines is to provide evidence-based recommendations for the use of monoclonal antibodies targeting CGRP in migraine prevention in Croatia. The questions were formulated using the Patients, Intervention, Comparison, Outcome (PICO) criteria, with evidencebased answers. To assess the quality of scientific evidence, a review of the literature available in PubMed was performed. Relevant studies were reviewed by the Expert Group of the Headache Section of the Croatian Neurological Society, and served as the basis for formulating the recommendations outlined in these guidelines. We found high quality evidence for good safety and efficacy of anti- CGRP monoclonal antibodies in the preventive treatment of episodic and chronic migraine. These medications may be considered as first-line prophylactic therapy depending on the patient’s history, concomitant diseases, and disease burden. Further real-world studies are needed to elucidate other aspects of their application.

Background Ocrelizumab is the only disease-modifying therapy (DMT) approved for the treatment of people with primary progressive multiple sclerosis (pwPPMS). Objectives To provide real-world evidence of ocrelizumab effectiveness and safety in pwPPMS in Croatian MS centers. Methods A retrospective observational multi-center study of pwPPMS who were started on ocrelizumab in 7 MS centers in Croatia. Results We identified 230 pwPPMS of whom 176 fulfilled the inclusion criteria. The median follow-up of the cohort was 2.73 (0.51-5.77) years. During the follow-up, 50 (28.4%) pwPPMS experienced confirmed disability worsening (CDW) and 19 (10.8%) stopped treatment with ocrelizumab. Baseline EDSS >5 was a statistically significant positive predictor for the development of CDW and/or stop of the treatment due to any cause (OR 2.482, 95% C.I. 1.192-5.166, p=0.015). However, there was no significant difference in the development of CDW and/or stop of the treatment due to any cause if stratifying the patients based on active PPMS, age at treatment start (≤55 years vs >55 years), disease duration at treatment start (≤10 years vs >10 years), or EDSS at treatment start (≤5.0 vs >5.0). During the follow-up, 26 (14.8%) pwPPMS experienced infusion reactions, 64 (36.4%) had an infection and 4 (2.3%) developed a tumor. The percentage of pwPPMS with low levels of IgG was persistently above 10% and with low levels of IgM was persistently above 20% after cycle 4. Conclusion Our real-world data support the use of ocrelizumab in a much broader pwPPMS population than in the original randomized controlled trial.

This study compared the self-assessed health-related quality of life (HRQoL) and degree of depression between patients with chronic neuropathic nonodontogenic orofacial pain (NOFP) and healthy controls using the Short Form Survey (SF-36) health status questionnaire and Beck Depression Inventory II (BDI-II). This controlled cross-sectional study included 100 patients and 119 healthy controls. The diagnostic protocol recorded the following: 1) pain intensity using a visual analog scale for the time of examination and during the one-month prior; 2) evidence for neuropathic pain using the Leeds questionnaire for neuropathic signs and symptoms (LANSS); 3) emotional status using the BDIII; and 4) HRQoL using the SF-36 questionnaire. The mean LANSS score was 17.18 in the patient group and 0.0 in the control group. The mean BDI-II score was 18.31 in the patient group and 5.87 in the control group. The SF-36 scores were shown with Mann-Whitney U testing to have statistically significant differences between the patient and healthy control groups in all categories. Vitality was the only SF-36 category in which the patient group scored higher than the control group. In conclusion, NOFP significantly reduces the self-reported HRQoL. NOFP is also related to the development of depression, but does not affect its severity. There is a significant correlation between depression and low quality of life in patients with NOFP.

BACKGROUND:Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS).OBJECTIVES:To provide real-world evidence of cladribine's effectiveness and safety in people with MS (pwMS).METHODS:A retrospective observational multi-center, multi-national study of pwMS who were started on cladribine tablets in ten centers from five European countries.RESULTS:We identified 320 pwMS treated with cladribine tablets. The most common comorbidities were arterial hypertension and depression. Three patients had resolved hepatitis B infection, while eight had positive Quantiferon test prior to cladribine commencement. There were six pwMS who had malignant diseases, but all were non-active. During year 1, 91.6% pwMS did not have EDSS worsening, 86.9% were relapse-free and 72.9% did not have MRI activity. During the second year, 90.2% did not experience EDSS worsening, 86.5% were relapse-free and 75.5% did not have MRI activity. NEDA-3 was present in 58.0% pwMS in year 1 and in 54.2% in year 2. In a multivariable logistic regression model age positively predicted NEDA-3 in year 1. The most common adverse events were infections and skin-related adverse events. Lymphopenia was noted in 54.7% of pwMS at month 2 and in 35.0% at month 6. Two pwMS had a newly discovered malignant disease, one breast cancer, and one melanoma, during the first year of treatment.CONCLUSION:Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals.

Isolated abducens nerve palsy following lumbar puncture is a rare complication. In scientific literature, it has been mostly described after performing spinal anesthesia in anesthesiology literature rather than in neurological literature. Isolated abducens nerve palsy usually occurs from one to three weeks after performing lumbar puncture and it is important to connect it with this procedure and exclude other possible etiologies. The actual incidence of this complication is unknown. We describe a 32-year-old male patient who presented with unspecific headache attributed to cavernous malformation and two developmental venous anomalies. While searching for headache etiology, lumbar puncture was performed. Two days after lumbar puncture, the patient presented with isolated abducens palsy of the right eye. Our planned diagnostic evaluation included measuring intracranial pressure by noninvasive optic sheath nerve sonography and repeating brain magnetic resonance imaging. We also planned to treat the patient with epidural blood patch, which is usually successful when performed as soon as the diagnosis is established. Unfortunately, our patient refused diagnostic and therapeutic proposal, so it was impossible to know final outcome. In conclusion, we want to highlight these complications, especially to young doctors and specialists who might see it rarely.

The main objective of this study was to investigate the prevalence of insufficient serum 25-hydroxyvitamin D level in a sample of neurological patients and to compare it to the estimate in the general Croatian population. The secondary aim was to test for the possible significant differences in vitamin D2 insufficiency between the groups of patients according to gender, season, region, vitamin D3 supplementation, and diagnosis of autoimmune disease. This retrospective study involved 371 neurological patients in one-year period. The data collected included gender, age at the time of admission, region, season at the time of admission, main neurological diagnosis at discharge, serum 25-hydroxyvitamin D level at the time of hospitalization, and use of vitamin D3 substitutes prior to hospitalization. The proportion of neurological patients with 25-hydroxyvitamin D insufficiency (<75 nmol/L) was estimated at 74.66% (95% confidence interval, p<0.0001), which is slightly lower than in the Croatian general population. There were no significant differences in 25-hydroxyvitamin D insufficiency according to gender, season and region. Significant differences in 25-hydroxyvitamin D insufficiency were found according to vitamin D3 supplementation and diagnosis of autoimmune disease.

The concentration of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the blood is higher in patients with active multiple sclerosis (MS) compared to those with inactive disease. The concentration of IL-6 and TNF-α in the blood is higher in patients with Hashimoto’s thyroiditis (HT) compared to those with a healthy thyroid. The aim of the study was to assess whether serum IL-6 and TNF-α levels correlated with saliva in patients with inactive MS and whether there was a difference in these groups of patients depending of thyroid status. We also examined the correlation of thyroid stimulating hormone (TSH) levels with thyroid status. The study included 54 patients in the inactive phase of MS. The level of cytokines in the blood was determined by chemiluminescence, and in saliva by ELISA. Blood and saliva IL-6 levels showed positive correlation, while blood and saliva TNF-α levels were not correlated. There was a significantly higher TSH level in patients with inactive MS with positive thyroid antibodies, without therapy, compared with those with negative antibodies.

IntroductionThe health-related quality of life (HRQoL) of people with (Pw) multiple sclerosis (MS) is usually deteriorated. It has been recently suggested that comorbidities may have the negative influence on the quality of life of the PwMS, but according to the best of our knowledge, only one study investigated, although in a very small cohort, the impact of individual comorbidity on the quality of life of PwMS. The aim of our investigation was to assess, in an international, multicentric study, the impact of comorbid seizure/epilepsy on the HRQoL in PwMS.MethodsWe conducted cross-sectional study at numerous neurological centers in Serbia, Croatia, Bulgaria, Montenegro, Northern Macedonia, and Bosnia and Herzegovina (Federation of Bosnia and Herzegovina and Republic of Srpska). For each patient, demographic and clinical data were collected, including Expanded disability status scale (EDSS) score. Beck Depression Inventory (BDI) and the 36-Item Short Form Health Survey (SF-36) questionnaires were administered to all patients.ResultsThe study comprised 326 PwMS in total, 127 PwMS with seizure/epilepsy and 209 PwMS without. Both mean Physical health composite (PHC) and mental health composite (MHC) scores, were statistically significantly higher in PwMS without seizure/epilepsy, implicating worse quality of life in PwMS with comorbid seizure/epilepsy. Presence of seizure/epilepsy in pwMS was statistically significant independent predictor of both PHC and MHC, in multivariate linear regression model after adjustment for potential confounding variables. The hierarchical multivariate regression analysis was performed in order to establish the most important predictors of the PHC and MHC of the SF-36, in PwMS with seizure/epilepsy; older age, higher level of disability, as measured by EDSS, higher depression score, drug-resistant epilepsy and shorter time since last seizure were found to significantly predict worse MHC score in PwMS with seizure/epilepsy.DiscussionOur results point to the possible role of theinterventions related to the adequate control of epilepsy along with improvement of the mental health status to be important in order to reduce MS burden in the PwMS with comorbid seizure/epilepsy.

Untreated multiple sclerosis (MS) irretrievably leads to severe neurological impairment. In European health care systems, patient access to disease modifying therapies (DMT) is often confined to more advanced stages of the disease because of restrictions in reimbursement. A discrepancy in access to DMTs is evident between West and East European countries. In order to improve access to DMTs for people with MS (pwMS) living in Croatia, the Croatian Neurological Society issued new recommendations for the treatment of relapsing MS. The aim of this article is to present these recommendations. The recommendations for platform therapies are to start DMT as soon as the diagnosis is made. If poor prognostic criteria are present (≥9 T2 or FLAIR lesions on the initial brain and spinal cord magnetic resonance imaging [MRI] or ≥3 T1 lesions with postcontrast enhancement on the initial brain and spinal cord MRI or Expanded Disability Status Scale after treatment of the initial relapse ≥3), high-efficacy DMT should be initiated. If pwMS experience ≥1 relapse or ≥3 new T2 lesions while on platform therapies, they should be switched to high-efficacy DMT. Further efforts should be made to enable early and unrestricted access to high-efficacy DMT with a freedom of choice of an appropriate therapy for expert physicians and pwMS. The improvement of access to DMT achieved by the implementation of national treatment guidelines in Croatia can serve as an example to national neurological societies from other Eastern European countries to persuade payers to enable early and unrestricted treatment of pwMS.

The purpose of the study was to find differences in the parameters of the response to the blink reflex (BR) between patients with idiopathic trigeminal neuralgia (TN) and health volunteers. A prospective cohort study was conducted over 2 years. The TN-subgroup included 15 patients (mean age / SD 62.3 ± 10.7 years). Pain-free and healthy volunteers as a HV-subgroup (mean age / SD: 30.8 ± 8.1 years) were recruited from asymptomatic students of dental medicine. Diagnostic parameters were determined by measuring latency to the onset of the BR components from electric stimulation. The following branches of the trigeminal nerve were affected: maxillary branch only (26.7%), mandibular branch only (20%), combined: ophthalmic branch with maxillary branch (6.7 %), and ophthalmic branch with mandibular branch (6.7%) respectively, combined maxillary and mandibular branch (26.7%) and affected all three branches (13.4%). The latencies of the BR, left and right side together, between subgroups were significantly higher for values R1 (homolateral early response), R2 (homolateral late response), R2c latency (contralaterally expressed response) in the TN-subgroup (p < 0.05). On the basis of the presence of R1c and R3 latencies and upon considering the abnormal findings of the BR, no statistically significant differences were found between the examined subgroups (p > 0.05). Blink-reflex parameters (R1, R2 and R2c) were significantly abnormal comparing TN-patients with healthy volunteers. The R3 component of the BR was related to noxious stimuli, likewise by innocuous stimuli.

Spinal subdural hematoma caused by lumbar puncture is a rare state of acute blood clot in spinal subdural space, and in some cases, it can be the cause of local compression and consecutive neurological symptoms. We present a 36-year-old female patient who was hospitalized due to persistent headache despite pharmacological therapy. Therefore, we performed lumbar puncture in order to measure intracranial pressure and evaluate cerebrospinal fluid. After lumbar puncture, the patient was complaining of pain in the lumbar region. Emergency magnetic resonance imaging (MRI) of the lumbosacral (LS) region was performed to show acute subdural hematoma of up to 7.3 mm in the dorsal part of the spinal canal at the level of L1 vertebra to the inferior endplate of L4 vertebra. Repeat LS MRI after 3 hours showed unchanged finding. The patient reported gradual regression of pain in the LS region over the next few days, therefore conservative treatment was applied. Patients with a previously known blood clotting disorder and patients on anticoagulation therapy have worse outcome as compared with patients without such disorders. During treatment, it is necessary to monitor patient clinical state and consider the need of surgical treatment.

BACKGROUND In 2018 multiple sclerosis (MS) care unit (MSCU) recommendations were defined. Nevertheless, the information on MS care, and whether MS centres fulfil the international recommendation is limited. Thus our objectives were to assess whether centres meet the MSCU recommendations and gain a comprehensive overview of MS care in Central-Eastern European countries. METHODS A self-report questionnaire assessing aspects of the MSCU recommendations, disease-modifying therapy (DMT) and registry use and the patient number was assembled and sent to nine Central-Eastern European countries. Furthermore, one Danish and one German centre were contacted as a reference. RESULTS In 9/9 countries, MS care was pursued in centres by MS neurologists and MS nurses. In Austria and the Czech Republic, management of MS was conducted under strict regulations displaying a referral centre system, fundamentally similar to but independent of the MSCU criteria. Several centres fulfilled all aspects of the MSCU criteria, while others had similar insufficiencies consisting of a speech therapist, continence, pain and spasticity specialist, neuro-ophthalmologist, and oto-neurologist. In 9/9 countries, DMTs were reimbursed. However, some centres did not provide every available DMT. A national registry was available in 4/9 countries with mandatory registry use only in Austria and the Czech Republic. CONCLUSION In countries where MSCU recommendations are not fulfilled, a strictly regulated centre system similar to the Austrian and Czech model with a registry-based quality control might ensure appropriate care for people with MS.

Parkinson's disease (PD) is generally considered as a primary movement disorder, but the majority of patients also suffer from non-motor oral, salivary symptoms. The most common salivary symptoms, sialorrhea and xerostomia, have a considerable negative impact on the quality of life. Although these symptoms are completely opposite ones, both significantly impair oral health of patients. Sialorrhea is defined as an increased amount of the retaining saliva. It is related to salivary overproduction, or it may be associated with impaired clearance of saliva. Opposed to sialorrhea, xerostomia is subjectively defined as dryness of mouth and it is related to insufficient salivary secretion. Xerostomia promotes imbalance of oral microflora and oral pathology that often leads to malnutrition in PD patients. It is mostly related to autonomic dysfunction, or it might be considered as a side effect of dopaminergic or anticholinergic medication. In PD, different assessments are used for evaluation of sialorrhea and xerostomia, including validated scales for non-motor symptoms and standardized questionnaires on oral health. Consequently, treatment of salivary symptoms includes pharmacological and nonpharmacological approach, and surgical interventions. A multidisciplinary approach in clinical neurology and dental medicine, which includes accurate evaluation of salivary symptoms and effective treatment, indicates successful management of PD patients.

: Previously epilepsy was recognized as part of the multiple sclerosis (MS) disease spectrum and treat-ment with antiepileptic drugs was part of symptomatic MS therapy. These comorbidities in the same patient despite being well known still has not been fully understood. The aim of this study was to evaluate incidence and clinical presentation of epilesy in population of our MS patients. We included in our study 200 patients evaluated in our MS center, 145 females and 55 males. Results: there was no statistically significant difference in mean age, disease duration, EDSS score between MS with and MS without epilepsy groups, no differences in clinical presentation of seizures according to the previous immunomodulatory treatment (p>0,05). We found EEG abnormalities in 50% of patients with MS and seizures, in 35% MS patients without seizures, pooled incidence of epilepsy in 3.5% with peak incidence between 4 and 7 years after the onset of multiple sclerosis. There was difference of seizure incidence according to clinical course of MS. The treatment of epilepsy in patients with multiple sclerosis does not requires specific protocols than the general epileptic population, but requires individualized approach in order to achieve the best treatment for both diseases.