Seizure clusters can be observed in patients with epilepsy as well as in individuals without a previous history of epilepsy. However, there are no data on whether seizure clusters differ between these two populations. The purpose of this study was to investigate the clinical presentation, diagnostic findings, presence of seizure triggers, outcomes and complications of seizure clusters in patients with epilepsy and individuals without epilepsy in their medical history. The results indicate that epilepsy history was not independently associated with the number of seizures during cluster; however, increasing age was significantly associated with a lower seizure burden, and pneumonia demonstrated a marginal positive association. Structural brain lesions were prevalent in both groups; particularly chronic post-stroke lesions and frontal lobe lesions were significantly more common among epilepsy patients. Over half of patients without prior epilepsy received a new epilepsy diagnosis following the cluster event. No severe complications, including status epilepticus or postictal psychosis, were observed. Our findings suggest that age, acute comorbidities, and structural brain pathology likely exert greater influence on frequency of seizures during cluster. Chronic post-stroke lesions, which have not yet been reported as a risk factor for seizure clusters, were the most frequent brain pathology in both groups and may thus be considered as an additional risk factor for this clinical entity. Prospective and larger-scale studies are needed to further clarify these associations.

BACKGROUND:Valproate inhibits clearance of lamotrigine and greatly increases its concentrations. We assessed whether this effect was moderated by a polymorphism (ABCG2 c.421C>A) of the breast cancer resistance protein.METHODS:In two consecutive independent studies in adults with epilepsy on lamotrigine monotherapy or cotreated with valproate: (i) Exposure to valproate was considered treatment, (ii) dose-adjusted lamotrigine troughs at steady state were the outcome, and (iii) ABCG2 c.421C>A genotype (wild-type [wt] homozygosity or variant carriage) was the tested moderator. We used entropy balancing (primary analysis) and exact/optimal full matching (secondary analysis) to control for confounding, including polymorphisms (and linked polymorphisms) suggested to affect exposure to lamotrigine (UGT1A4*3 c.142T>G, rs2011425; UGT2B7-161C>T, rs7668258; ABCB1 1236C>T, rs1128503) to generate frequentist and Bayesian estimates of valproate effects (geometric means ratios [GMR]).RESULTS:The two studies yielded consistent results (replicated); hence, we analyzed combined data (total N = 471, 140 treated, 331 controls, 378 ABCG2 c.421C>A wt subjects, 93 variant carriers). Primary analysis: in variant carriers, valproate effect (GMR) on lamotrigine (treated, n = 21 vs. controls, n = 72) was around 60% higher than in wt subjects (treated, n = 119 vs. controls, n = 259)-ratio of GMRs 1.61 (95%CI 1.23-2.11) (frequentist) and 1.63 (95%CrI 1.26-2.10) (Bayes). Similar differences in valproate effects between variant carriers and wt subjects were found in the secondary analysis (valproate troughs up to 364 μmol/L vs. no valproate; or valproate ≥364 μmol/L vs. no valproate). Susceptibility of the estimates to unmeasured confounding was low.CONCLUSION:Data suggest that polymorphism rs2231142 moderates the effect of valproate on exposure to lamotrigine.

Neurological diseases often leave a devastating effect on the quality of life of patients, and their caregivers. Usually, when people are healthy, communication and movement are taken for granted. Unfortunately when disease or trauma happens a disconnection from these basic aspects of life leaves a person stranded with current options still limited in alleviating these devastating situations. That is where Brain-Computer Interfaces come into play, as a novel way of replacing, and treating neurological diseases and injuries. Using advanced computer technologies direct brain activity can be used to issue commands through a computer or a replacement limb, wheelchair, or exoskeleton. Not only replacement but also neuromodulation and neurorehabilitation by way of BCI provide new ways of treating diseases with functional connectivity issues. More and more research is proving its usability, with awe-inspiring prospects for the future treatment of neurological diseases. But as with any technological novelty thorough discussion, and general informing of both the patients and clinicians is needed so as to prevent future worries and disappointment.

The topic of the paper is to research requirements that appear before users and designers during the planning and programming of laboratory buildings. A part of research conducted in workshop at the Doctoral Scientific Study of Architecture and Urbanism at the Faculty of Architecture in Zagreb is presented: an overview of the development of laboratory buildings, contemporary influences and development trends, and criteria for programming and designing laboratory buildings are included.

Introduction : Our study analysed the prevalence of sleep disorders (primarily insomnia and hypersomnia) in patients who tested positive for Covid 19, as well as the distribution of insomnia/hyper-somnia in different subgroups of these patients (according to their age, gender, BMI, disease severity). Materials and methods: This prospective, noninvasive, cross sectional study was conducted at the Emergency department, Respiratory Center, and Respiratory Intensive care Center of University Hospital Dubrava from December 2020. until March 2021. It included patients whose tested positive for Covid 19 and who reported at least one neurological symptom. Patients were examined, and interviewed face to face using a web – based structured questionnaire designed for the purposes of this study. Results: Of the 337 participants, 109 (32,34%) reported one of two possible symptoms associated with sleep disorder, primarily difficulty sleeping/insomnia ( dubbed „sleep disorder“) or sleepiness/ hypersomnia. Of the 337 participants, 61 (18%) reported sleep disorder while 48 (14%) reported hypersomnia. There was no statistically significant difference in prevalence of sleep disorder between men and women ( ꭓ 2 = 0,113, p = 0,737). Hypersomnia was more prevalent in women ( ꭓ 2 = 8,125, p = 0,004). Patients who had sleep disorder had a lower median age by 5 years compared to patients who did not have a sleep disorder (z = 2,6, p = 0,009). Patients who had hypersomnia had a median of age lower for 9 years than patients who did not have hypersomnia (z = 4,3, p = <0,001). There was no significant difference in BMI between patients with and without hypersomnia (z = 0,157, p = 0,875). There was no association of hypersomnia with the presence of pneumonia ( ꭓ 2 = 0,000, p =1,000). In our study sleep disorder was associated with pneumonia ( ꭓ 2 = 6.4, p = 0.012). Of the patients with a sleep disorder, 59% of them reported dispnea, 78% had pneumonia and72% were hospitalized. Of the admitted patients, only two of them were transferred to the Respiratory intensive care and were treated using mechanical ventilation. In the patient group with hypersomnia, 46% of patients reported dispnea, 64% had pneumonia and 48% were hospitalized, of which one patient was hospitalized in Respiratory intensive care, and did not require treatmeant with mechanical ventilation. Conclusion: Sleep disorders are prevalent in one form or the other in little over a third of patients with a Covid infection. Age, gender, and the presence of pneumonia are associated with different types of sleep disorders. More studies are needed to investigate the potential effect of sleep on the outcome of patients with COVID 19.

To test the hypothesis that the effect of valproate on dose-adjusted lamotrigine troughs was moderated by the ABCG2 c.421C>A (rs2231142) polymorphism, we conducted two studies in adults with epilepsy. Since Study 2 replicated the findings of Study 1, we analysed combined data [total N=471; 140 exposed to valproate (treated), 331 not exposed (controls)]. With adjustment for cotreatments and comorbidities, age, sex, body weight and polymorphisms (and linked polymorphisms) suggested to affect exposure to lamotrigine (UGT1A4*3 c.142T>G, rs2011425; UGT2B7 -161C>T, rs7668258; ABCB1 1236C>T, rs1128503) (by entropy balancing), primary analysis indicated: in variant carriers, geometric means ratio (GMR) [treated (n=21) vs. controls (n=72)] was around 60% higher than in wild-type subjects [treated (n=119) vs. controls (n=259)] – ratio of GMRs 1.61 (95%CI 1.23-2.11) and 1.63 (95%CrI 1.26-2.10), in the frequentist and Bayesian analysis, respectively. Similar differences in valproate effects between ABCG2 c.421C>A variant carriers and wild-type subjects were found in secondary analysis (adjustment by exact matching) when exposure to valproate was defined as valproate troughs up to 364 mol/L or ≥364 mol/L (vs. no exposure to valproate). Susceptibility of the estimates to (hypothetical) unmeasured confounding was low. Data suggests that polymorphism rs2231142 moderates the effect of valproate on exposure to lamotrigine.

: Spectacular Shrinking Deficit (SSD) is a term attributed by J.P. Mohr to a rare cerebrovascular event defined by a rapid and dramatic improvement of major hemispheric stroke syndrome. It is presumed to be caused by the migration of initially embolic occlusion of an internal carotid artery or middle cerebral artery to its distal branches. It is only reported in several case reports, and case series with differing criteria of what defies an SSD meaning that its presumed prevalence rate of 7-14% of major hemispheric stroke syndromes could be an overestimation. It is usually associated with the cardioembolic cause of stroke, and it has a higher prevalence rate in younger patients, males, and nondiabetics. Our case is a 58 – year old male who presented to our ER with a major hemispheric stroke syndrome (deviation of head and eyes on the right side, central facioparesis on the left, left hemiplegia, and left hemineglect, NIHSS 16) 30 minutes after symptom onset. He was aggressive, insisting nothing was wrong with him. His initial brain CT showed acute ischemic changes in the right temporooccipital region with an inadequate filling of distal branches of the right MCA shown on CT brain angiography. His symptoms spectacularly improved in our ICU (NIHSS 0) 51 minutes from symptom onset negating the need for thrombolysis. Except for one positive Beta – 2 GPI test his detailed laboratory tests, 24h Holter ECG, TTE, carotid, and vertebral artery ultrasound were noneventful. He had no cognitive or neurological deficit. He denied the possibil-ity of performing TEE and prolonged cardiac monitoring. Control brain MRI 4 days and 4 months later confirmed moderate ischemic changes of the right insular, temporal, and occipital cortex. Studies report that spontaneous recanalization usually happens in 17% of patients but does not correlate with TIA. This is the first report of an SSD with moderate ischemic stroke and no leftover neurological deficit. Other case series report moderate ischemic stroke SSD with a small residual neurological deficit (NIHSS 2-4). Perhaps mood changes can be associated with selective neuronal loss found in animals and patients suf-fering transient occlusion of the brain artery. The cardioembolic cause can in certainty be excluded with TEE and prolonged cardiac monitoring.

The World Health Organization declared the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) outbreak a pandemic on March 11, 2020. Consequently, the Croatian Ministry of Healthcare designated University Hospital Dubrava as the primary respiratory intensive center for the treatment of SARS-COV-2 patients from seven administrative regions of central and northwestern Croatia (Peršec 2020). This study aims to assess the impact on emergency neurology department visits after University Hospital Dubrava became the primary respiratory intensive center for the treatment of SARS-COV-2 patients. A retrospective record review study was conducted at emergency neurology department of the University Hospital Dubrava Zagreb and approved by the research ethics committee of University Hospital Dubrava Zagreb. To determin the impact of the COVID-19 pandemic, we evaluated the patients assessed between 1-31 August 2020. It is important to emphasise that during this period hospital was available to all patients who needed medical care, not just to the ones who had COVID-19. Data on the patients observed between 1-31 August 2018 were also collected to provide a control group. Medical records included demographic data, the reason for the visit, methods of patients refferal to ED, number of performed computed tomography brain scans, number of hospitalized patients as well as most common reasons for hospitalisation. We also recorded number of patients who were tested and diagnosed with COVID-19 in August 2020. The differences between groups were tested using the one-tailed independent-samples t-test. The significance threshold was set at 0.05. In this study, 840 patients were included: 358 patients from the pandemic period and 482 patients from the non-pandemic period. During the COVID-19 outbreak in Croatia in 2020, we found a significant decrease in the daily number of patients presenting at the ED with neurological complaints (M=11.55, SD=3.98) compared to the control group (M=15.42, SD=4.66), t(60)=3.52, p<0.001. Other significant results include a smaller share of female patients during COVID-19 period (47.4% during pandemics vrs 55.8% before pandemics). We also witnessed a significant smaller proportion of daily self-referred patients to the ED during COVID-19 period (M=5.97, SD=2.51) vrs ( M=8.71, SD=3.62), t(60)=3.46, p<0.001, while a number of patients referred by general practitioner or brought in by ambulance was not significantlly different. During the COVID-19 period compared to the same time in the year 2018, there was also statistically significant daily decrease in the number of patients who came to ED due to back pain (M=2.74, SD=2.17) vrs (M=4, SD=2.13), t(60)=2.3, p=0.012, general weakness (M=0.13, SD=0.42) vrs (M=0.35, SD=0.49), t(60)=1.94, p=0.028, syncope (M=0, SD=0) vrs (M=0.16, SD=0.37), t(60)=2.4, p=0.009, dizzyness (M=2.1, SD=1.19) vrs (M=2.87, SD=2.04), t(60)=1.82, p=0.037, balance disturbance (M=0.1, SD=0.4) vrs (M=0.58, SD=0.76), t(60)=3.13, p=0.0013. Number of patients who were hospitalized due to stroke, transient ischemic attack, intracerebral hemorrhage, and epilepsy was not significantly different between non-pandemic and pandemic period. During the pandemic period we found a significant decrease in the overall number of performed CT brain scans (M=7.06, SD=2.57) vrs (M=9.06, SD=3.46 ), t(60)=2.58, p=0.006. During August 2020 sixteen patients were tested and only one was SARS-CoV-2 positive. As was seen in other studies, there was a statisticaly significant drop in self-referred patients to the ED. This may be due to public concern of being exposed to the virus in the health institution (Weber et al. 2017). Our assumption is that when patients had symptoms that were not life threatening, fear of being exposed to virus prevented them from coming to ED. Furthermore, our assumption is that the patients were additionally refrained from coming to the ED University Hospital Dubrava because this hospital was specially assigned to treat patients with COVID-19, the fact that presumably raised additional concerns and fear among patients about safety of such visit in terms of exposure to virus and limitation of availability of healthcare services within hospital. Patients define situations worthy of ‘emergency’ ambulance use according to complex socioemotional factors, as well as experienced physical symptoms (Booker et al. 20017). The conditions requiring urgent ED and neurological intervention as well as hospitalisation were not significantly different between non-pandemic and pandemic period which highlights the availability of healthcare resources in our area during healthcare crisis. To conclude, there was a reduction in patient visits to the emergency department in the period of the pandemic. To the best of our knowledge this is the first study to demonstrate the trends of ED attendance of patients with neurological complaints after one tertiary center was designated as the primary respiratory intensive center for the treatment of SARS-COV-2 patients. The extent to which the pandemic affects hospital ED attendance can help healthcare professionals prepare for future such events. Limitations: The study is limited by its focus on a single hospital.

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.

A 20-year-old female with refractory perinatal postischemic catastrophic epilepsy and frequent daily generalized atonic, tonic, tonic-clonic and focal seizures was hospitalized in the progressive phase of illness. The diagnosis was confirmed by semiology, interictal electroencephalogram (EEG), long-term video EEG monitoring, and brain magnetic resonance imaging. Repeated interictal EEG findings showed generalized spike and slow wave complexes with a 2-3 Hz frequency. Interictal EEG showed evidence of electroclinical epileptic status on several occasions. She was treated with various antiepileptic drugs without improvement. After verification of her incompetence for normal autonomous living, which resulted in very low quality of life, this patient with refractory epilepsy underwent implantation of vagus nerve stimulator (VNS). In this case report, we present delayed effect of VNS on interictal epileptiform discharges and pharmacoresistance.

Pharmacoresistant epilepsy poses a great burden to patients, their families, and the whole healthcare system, with numerous social, economic, physical, and psychical consequences. Hence, it is a diagnosis that has to be made only in cases of high certainty, after all potential causes of epilepsy have been evaluated. One of the important causes of pharmacoresistant epilepsy is false pharmacoresistance, an entity that implies a condition in which poor disease control is not a consequence of the biology of the disease itself, antiepileptic drug inefficacy, and/or patient specificity. It is a consequence of human error and strongly depends on the experience of the treating physician, as well as on the attitude of the patient. Despite its ‘falseness’, this entity is accompanied by real consequences for the patient and his family, and at the same time, it delays appropriate treatment of the actual disease from which the patient is suffering. In order to introduce appropriate treatment and avoid unnecessary and harmful diagnostic procedures, false pharmacoresistance is a condition that has to be ruled out in any patient with difficult-to-treat seizures.

Coronavirus disease 2019 (COVID-19), caused by the late 2019 outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a respiratory disease which could put myasthenia gravis patients at a greater risk of developing severe disease course. This paper presents a single-institution case series of hospitalized myasthenia gravis patients with COVID 19. We identified eight patients previously diagnosed with myasthenia gravis, four of whom presented with clear signs of myasthenia gravis symptom worsening on admission. No form of respiratory support was needed during the complete duration of stay for three patients, oxygen therapy was administered to two patients, while the remaining three patients required mechanical ventilation. Treatment was successful for seven patients, six of whom were discharged without any myasthenia gravis symptoms. One patient died after eleven days of intensive care unit treatment. Although treatment of patients with myasthenia gravis and COVID-19 patients is challenging, case series of myasthenia gravis patients with COVID-19 treated in our institution demonstrates relatively favorable treatment outcome. Our data seem to support the notion that immunosuppressive medication does not seem to result in worse outcomes. Our data also support the notion that intravenous immunoglobulin treatment is safe and should be administered to patients with myasthenia gravis and COVID-19 in case of myasthenia gravis worsening since benefits seem to greatly outweigh the risks.

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.

RAD 547. Medical Sciences 54-55 (2021) : 38-48 www.rad-med.com 38 June 2021 Vol 547 = 54-55 Abstract: Introduction: This study aimed to review the prevalence of NMS in patients with Parkinson’s disease in Split-Dalmatia County and to investigate the effects of other variables on the number and structure of NMS. Materials and Methods: This observational cross-sectional pilot study was conducted at the Department of Neurology, University Hospital of Split. This study lasted from November 2017. to April 2018. and it included 31 patients, hospitalized or treated in the infirmary at the Department of Neurology. By examining medical documentation we acquired necessary demographic and medical information about our subjects. Subjects were then examined and subjected to filling out Parkinson’s disease-specific questionnaires: NMSQuest, Hoehn&Yahr scale, UPDRS, and Schwab&England scale. To analyze given variables we used the Mann-Whitney U test, Kruskal-Wallis test, Spearman’s coefficient of correlation, and ꭓ2 test. Results: On average 12 dwifferent NMS were reported per patient. Most prevalent NMS were reported to be nocturia (67.74%), urinary urgency (61.29%), constipation (61.29%), intense dreams (58.06%), and forgetfulness (58.06%). The least prevalent NMS reported were delusions (6.45%), hallucinations (16.12%), and daytime sleepiness (25.80%). There were neither statistical differences in the total number of NMS nor in demographic variables between men and women. The increased burden of NMS correlated with the disease duration. Prevalence of depression, anxiety, and miscellaneous symptoms rose with the length of disease duration. We established a connection between the number of NMS and the stage of disease according to Hoehn and Yahr. Patients in higher stages of disease (moderate and severe) reported more severe NMS burden than patients in the mild stage of the disease, while patients in the moderate stage had the largest NMS score of all groups. Patients in the mild stage reported urinary, also digestive, and cognitive symptoms, in the moderate stage urinary symptoms, sexual dysfunction, and cardiovascular symptoms were most reported, while in the severe stage of the disease, patients reported cardiovascular symptoms, depression, and anxiety alongside urinary symptoms as most prevalent. Conclusions: Patients are most affected by the autonomic spectrum of NMS, especially urinary symptoms. Duration of the disease and stage of the disease are proven to affect the total number of NMS, while age at onset, current age, and sex have been disproven to have any effect on the total NMS score. Patients in the moderate stage reported the most NMS.