Functional neurological disorder in Europe: regional differences in education and health policy.

BACKGROUND: Functional neurological disorder (FND) is a common cause of neurological disability. Despite recent advances in pathophysiological understanding and treatments, application of this knowledge to clinical practice is variable and limited. OBJECTIVE: Our aim was to provide an expert overview of the state of affairs of FND practice across Europe, focusing on education and training, access to specialized care, reimbursement and disability policies, and academic and patient-led representation of people with FND. METHODS: We conducted a survey across Europe, featuring one expert per country. We asked experts to compare training and services for people with FND to those provided to people with multiple sclerosis (MS). RESULTS: Responses from 25 countries revealed that only five included FND as a mandatory part of neurological training, while teaching about MS was uniformly included. FND was part of final neurology examinations in 3/17 countries, unlike MS that was included in all 17. Seventeen countries reported neurologists with an interest in FND but the estimated mean ratio of FND-interested neurologists to MS neurologists was 1:20. FND coding varied, with psychiatric coding for FND impacting treatment access and disability benefits in the majority of countries. Twenty countries reported services refusing to see FND patients. Eight countries reported an FND special interest group or network; 11 reported patient-led organizations. CONCLUSIONS: FND is largely a marginal topic within European neurology training and there is limited access to specialized care and disability benefits for people with FND across Europe. We discuss how this issue can be addressed at an academic, healthcare and patient organization level.

Reversible splenial lesion syndrome in patient with acute motor and sensory axonal neuropathy.

Even though the classical clinical concept supports the clear difference between diseases affecting the central and peripheral nervous systems, this difference is becoming less rigid. Here, we report the case of a 50-year-old male patient who presented with acroparaesthesia, headache, and flaccid tetraparesis after febrile diarrhea. Nerve conduction studies indicated action potentials with low amplitudes, which are typical in acute motor and sensory axonal neuropathy. Magnetic resonance revealed a round lesion in the splenium consistent with a diagnosis of reversible splenial lesion syndrome. A polyclonal antiganglioside antibody response was detected. The patient was successfully treated with intravenous immunoglobulins. The coexistence of reversible splenial lesion syndrome and acute motor and sensory axonal neuropathy has not been described in the literature so far. We discuss our diagnostic dilemmas and the possible role of antiganglioside antibodies in the occurrence of simultaneous lesions of the central and peripheral nervous systems.

Risdiplam Real World Data - Looking Beyond Motor Neurons and Motor Function Measures.

BACKGROUND: Risdiplam is an orally administered treatment for spinal muscular atrophy which leads to an improvement in motor function as measured by functional motor scales compared with placebo. Although risdiplam has been registered since 2020, real-world data in adults is still scarce. There have been no new safety signals so far, with some results pointing that risdiplam may be effectiveObjective:The objective was to present real-world data of 31 adult patients with spinal muscular atrophy type 2 and type 3 treated with risdiplam in the Republic of CroatiaMethods:Treatment effects were assessed with motor function tests and patient reported outcome measures, including Individualized Neuromuscular Quality of Life questionnaire, and Jaw Functional Limitation Scale. Side effects, as well as subjective improvements and symptoms, were noted. RESULTS: Majority of patients did not report any side effects. During treatment, we have observed clinically meaningful improvements in some patients, with stabilization of motor functions in the remaining patients. The majority of patients with bulbar function impairment experienced bulbar function improvement, all patients reported an increased quality of life with treatment. An unexpected observed treatment effect was weight gain in a third of all patients with some patients reporting an increase in appetite and subjective improvement in digestion. CONCLUSIONS: Risdiplam treatment was well tolerated with subjective and objective positive outcomes registered as measured by functional motor scales and patient-reported outcomes. Since risdiplam is administered orally and acts as a systemic therapy for a multisystemic disorder, effects in systems other than neuromuscular can be expected and should be monitored. Due to systemic nature of the disease patients need multidisciplinary monitoring.

Transverse myelitis following COVID-19: Insights from a multi-center study and systematic literature review.

INTRODUCTION: We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature. METHODS: The retrospective observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed. RESULTS: We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery. CONCLUSION: Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19.

New-Onset Ocular Myasthenia Gravis After Booster Dose of COVID-19 Vaccine.

Coronavirus disease 2019 (COVID-19) vaccines have been reported as possible triggers of the production of antibodies pathogenic to the peripheral nerve and neuromuscular junction. We report on a patient who experienced vertical diplopia three weeks after the booster dose of the Pfizer-BioNTech vaccine (Comirnaty®). The diagnosis of myasthenia gravis (MG) was established based on highly positive antibodies to the nicotinic acetylcholine receptor (nAChR). Treatment with pyridostigmine and prednisone was started with gradually raising doses. On a follow-up exam two months after treatment initiation, clinical improvement was noted with an almost normal bulbomotor examination. The occurrence of diplopia following COVID-19 vaccination should raise suspicion of new-onset ocular MG and testing for anti-nAChR antibodies is advised.

Toward a Better Understanding of the Atypical Features of Chronic Graft-Versus-Host Disease: A Report from the 2020 National Institutes of Health Consensus Project Task Force.

Alloreactive and autoimmune responses after allogeneic hematopoietic cell transplantation can occur in nonclassical chronic graft-versus-host disease (chronic GVHD) tissues and organ systems or manifest in atypical ways in classical organs commonly affected by chronic GVHD. The National Institutes of Health (NIH) consensus projects were developed to improve understanding and classification of the clinical features and diagnostic criteria for chronic GVHD. Although still speculative whether atypical manifestations are entirely due to chronic GVHD, these manifestations remain poorly captured by the current NIH consensus project criteria. Examples include chronic GVHD impacting the hematopoietic system as immune mediated cytopenias, endothelial dysfunction, or as atypical features in the musculoskeletal system, central and peripheral nervous system, kidneys, and serous membranes. These purported chronic GVHD features may contribute significantly to patient morbidity and mortality. Most of the atypical chronic GVHD features have received little study, particularly within multi-institutional and prospective studies, limiting our understanding of their frequency, pathogenesis, and relation to chronic GVHD. This NIH consensus project task force report provides an update on what is known and not known about the atypical manifestations of chronic GVHD while outlining a research framework for future studies to be undertaken within the next 3 to 7 years. We also provide provisional diagnostic criteria for each atypical manifestation, along with practical investigation strategies for clinicians managing patients with atypical chronic GVHD features.

Determinants and Clinical Significance of Musculoskeletal Symptoms in Patients With Chronic Graft-Versus-Host Disease.

Musculoskeletal symptoms in chronic graft-versus-host disease (cGVHD) are rare manifestations contributing to disease burden. This study assesses the frequency of muscle cramps, joint and muscle aches, and muscle weakness in a cohort of patients severely affected by cGVHD. Three hundred thirty-four patients participated in the NCI natural history study of cGVHD (NCT00092235) from October 2004 to March 2017. Five-point Lee cGVHD Symptom Scale was dichotomized (less symptom bother-0, 1, 2; severe symptom bother-3, 4) and tested for associations with: Short Form 36 (SF36), 2-minute walk test, grip strength, joint range of motion, and human activity profile, clinical and laboratory data. Seventy-five point four percent of patients reported joint and muscle aches (36.8% severe, Lee Symptom Scale score 3-4), 74.3% muscle cramps (33.5% severe), and 82.34% muscle weakness (45.51% severe), which were associated with reduced functional capacity (SF36 Physical Component Scale, P < 0.0001). Muscle cramps were associated with limited joint movement (P < 0.0001) and skin manifestations (skin thickening, P = 0.0008; itchy skin, P = 0.0003). Muscle cramps did not show association with potential causative agents, such as concomitant calcineurin inhibitors therapy, statins, or use of antidiabetic drugs. Joint and muscle aches showed associations with multiple variables (including strong associations with mood symptoms and fatigue, P < 0.0001). Muscle weakness was not associated with steroid dose, but was significantly associated with depression (P < 0.0001) and anxiety (P = 0.0009). This study documents a high frequency of musculoskeletal symptoms in a cohort of adult patients with cGVHD. The multivariable logistic regression models showed that a joint set of factors were moderately well associated with musculoskeletal symptoms in this study.

Benign Fasciculation Syndrome and Migraine Aura without Headache: Possible Rare Side Effects of the BNT162b2 mRNA Vaccine? A Case Report and a Potential Hypothesis.

The BNT162b2 (Pfizer BioNTech) mRNA vaccine is an effective vaccine against COVID-19 infection. Here, we report an adverse event following immunization (AEFI) in a 48-year-old female patient who presented with fasciculations, migraine auras without headaches and in an increased discomfort of previously present palpitations, as well as excitation and insomnia. Her fasciculations were intermittently present until the time this paper was written, starting from the 6th day post-vaccination; they changed localization and frequency, but most commonly they were generalized, affecting almost all muscle groups. The patient also suffered from two incidents of migraine auras with visual kaleidoscope-like phenomena without headaches a few months after the vaccination. These symptoms were considered to be AEFI and no causal relation with the vaccine could be proven.

Sexual Dysfunction in Patients with Epilepsy.

BACKGROUND: Patients with epilepsy commonly report sexual dysfunction (SD) and reproductive difficulties. This study aimed to evaluate the relationship between epilepsy, antiepileptic drugs (AEDs) and SD, and its association with the quality of life and depressive symptoms. SUBJECTS AND METHODS: This was a prospective study carried out in a tertiary healthcare centre. SD was evaluated using the internationally acclaimed questionnaire Arizona Sexual Experiences Scale (ASEX) that was successfully translated into Croatian and validated for this purpose. Depressive symptoms and quality of life were evaluated using the Hamilton Rating Scale for Depression (HAM-D17) and Quality of life in epilepsy-31 inventory (QOLIE-31). RESULTS: Of 108 patients (68 (63 %) women, 40 (37 %) men, mean age 39.54±15.91 (range18-80) years) with epilepsy, 16 (14.8%) had focal, 38 (35.2%) generalized and 44 (40.7%) both types of epilepsy. Mean overall total score on the ASEX questionnaire was 11.94±5.61 (mean total score women 12.85±6.00, mean total score men 10.4±4.55), with 48 reporting that they had sexual activity in the past week. Nine (8.33%) patients (7 (6.48%) women, 2 (1.85%) men, mean age 47.66±19.33 (range 25-80) years) had a score 19 and above, 38 (35.18%) patients (27 (25%) women, 9 (8.33%) men, mean age 46.82±17.78 (range 19-80) years) individual score 5 and above on any one item, and 33 (30.55%) patients (26 (24.07%) women, 7 (6.48%) men, mean age 48.87±17.8 (range 19-80) years) had an individual score 4 and above on any three items. Significant correlations were found between SD and older age (p=0.001) and between more pronounced symptoms regarding SD on ASEX and female gender (p=0.000). There were no significant correlations between the type of epilepsy and SD, nor between the AEDs (old generation vs. modern) and SD. Significant correlations were found between the SD and more pronounced depressive symptoms (p=0.003) and between the SD and a lower quality of life (p=0.001). CONCLUSIONS: Results of our study suggest SD is experienced by around one-third of patients in our group, which is similar to the previous percentage of SD reported in the community sample. Women were found to experience more pronounced symptoms of SD on ASEX. Symptoms of SD were found to be significantly correlated with older age, female gender, lower quality of life and depressive symptoms, while no significant correlations were found with the type of epilepsy and the AEDs.

Severe Demyelinating Polyneuropathy and Cranial Neuropathy During Avelumab Treatment of Metastatic Merkel Cell Carcinoma.

INTRODUCTION: Avelumab is a programmed death ligand 1-blocking monoclonal antibody used for the treatment of Merkel cell carcinoma (MCC), urothelial carcinoma, and other solid tumors. It acts as an immune checkpoint inhibitor and prolongs survival of MCC patients. Immune-mediated neurological adverse effects are rare and usually respond well to specific therapy. METHODS AND RESULTS: A case of a 70-year-old man with metastatic MCC is described in this study. The patient developed diplopia after the fourth dose of avelumab, which was then discontinued. Seven months later, therapy was reinitiated and followed by a new adverse neurological event: severe demyelinating polyneuropathy combined with ophthalmoplegia refractory to a plethora of immune suppressive/modulatory treatment regimes. DISCUSSION: This report of severe demyelinating polyneuropathy and cranial neuropathy associated with an anti-programmed death ligand 1 drug refractory to immune suppressive/modulatory treatments sheds a new light to evolving spectrum of immune checkpoint inhibitor immune-related neurological adverse events.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report.

Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Progress in preventing severe morbidity and mortality associated with chronic GVHD is limited by a complex and incompletely understood disease biology and a lack of prognostic biomarkers. Likewise, treatment advances for highly morbid manifestations remain hindered by the absence of effective organ-specific approaches targeting "irreversible" fibrotic sequelae and difficulties in conducting clinical trials in a heterogeneous disease with small patient numbers. The purpose of this document is to identify current gaps, to outline a roadmap of research goals for highly morbid forms of chronic GVHD including advanced skin sclerosis, fasciitis, lung, ocular and gastrointestinal involvement, and to propose strategies for effective trial design. The working group made the following recommendations: (1) Phenotype chronic GVHD clinically and biologically in future cohorts, to describe the incidence, prognostic factors, mechanisms of organ damage, and clinical evolution of highly morbid conditions including long-term effects in children; (2) Conduct longitudinal multicenter studies with common definitions and research sample collections; (3) Develop new approaches for early identification and treatment of highly morbid forms of chronic GVHD, especially biologically targeted treatments, with a special focus on fibrotic changes; and (4) Establish primary endpoints for clinical trials addressing each highly morbid manifestation in relationship to the time point of intervention (early versus late). Alternative endpoints, such as lack of progression and improvement in physical functioning or quality of life, may be suitable for clinical trials in patients with highly morbid manifestations. Finally, new approaches for objective response assessment and exploration of novel trial designs for small populations are required.

B regulatory cells and monocyte subpopulations in patients with chronic graft-vs-host disease.

AIM: To assess the correlations of B regulatory cells (Bregs) and monocyte subsets in peripheral blood with the National Institutes of Health (NIH)-consensus-defined clinical manifestations of chronic graft-vs-host disease (cGvHD), in an attempt to establish their role as cellular biomarkers. METHODS: This multidisciplinary prospective study enrolled adult cGVHD patients treated in the University Hospital Center Zagreb and University of Zagreb School of Medicine. Immunophenotypic subpopulations of CD24highCD38high Bregs (CD27-, CD27+, and total) and monocyte (classical, intermediate, and non-classical) counts were correlated with demographic, transplant, and cGVHD-related data. Bivariate correlation analysis was performed to evaluate the correlations between Bregs and monocytes subsets and cGVHD organ involvement, as well as cGVHD severity and immunosuppression intensity. RESULTS: Twenty-two adult patients (54.5% female) with cGVHD were enrolled. The median (range) age was 44.5 years (24-65). All patients were transplanted for hematologic malignancies and 40.9% had severe NIH cGVHD global score. The median time from cGVHD diagnosis to the analysis was 16.6 months (0-176). The organ most frequently affected with cGVHD were the eyes (68.2%), skin (45.5%), lungs (45.5%), and liver (40.9%). Lower total and CD27-Bregs counts were correlated with worse cGVHD severity, higher immunosuppression intensity, and lung cGVHD, in terms of cell count, but also with skin cGVHD, in terms of percentages. Patients with liver and joint/fascia cGVHD had a lower percentage of non-classical monocytes and patients with more severe global NIH score had a higher classical monocytes count. CONCLUSION: Different organs affected by cGVHD are differently associated with different subpopulations of Bregs and monocytes.

Could Mental and Physical Exercise Alleviate Alzheimer's Disease?

The aim of this review is to emphasize the importance of mental activity and aerobic physical exercise as one of the most important health-related activities which may delay the onset or slow down the progression of Alzheimer's dementia. Studies have shown that the elderly who regularly engage in mental and physical activities have a lower risk of dementia development. Performing mental and physical activities regularly has a synergistic effect on the improvement of cognitive functions. Complex mental activity during life is associated with a reduction in the hippocampal atrophy rate, which is a sensitive early-stage biomarker of dementia while regular physical exercise can slow down the progressive reduction of the cortical brain volume which occurs during aging. Mental activity increases a person's "cognitive reserve" and promotes the formation of new communications between brain cells. Since it is not possible to influence genetic components of Alzheimer's dementia, preventative interventions such as encou¬raging regular engagement in mental and physical activities are extremely important. Activities need to be safe, moderate, comfortable, and adapted as to type, duration, and especially the health and functional status of the patient. In the near future, it is expected that genome analysis in personalized medicine will guide us in the right direction on certain types of physical and mental exercise.

Sexual Dysfunction in Croatian Patients with Obesity.

BACKGROUND: Patients with obesity may have symptoms of sexual dysfunction (SD). Little is known about these symptoms in obese patients in Croatia and the aim of this study was to explore them. SUBJECTS AND METHODS: This was a cross-sectional study carried out in tertiary healthcare centre at the Croatian Obesity Treatment Referral Center in University Hospital Center of Zagreb. 103 patients (72 female, 31 male, mean age 48.7±11.87 years, mean BMI 40.42) were included. SD symptoms were assessed using the internationally acclaimed questionnaire Arizona Sexual Experience Scale (ASEX), that was recently validated for Croatian language. Patients were also administered a questionnaire, prepared for this purpose, that enquired about their previous known chronic disorders. Statistical analyses included t-test, chi-squared test and bivariate Pearson's correlations. RESULTS: Average total response on the questionnaire was 12.4 (women 13.2, range 3-30; men 10.6, range from 5-19). A total score of 19 or more was present in 5 (4.8 %, range from 19-30, average 22.4; 1 man, 4 women), at least one question with a score 5 or greater on any item was found in 36 (34.9 %, 5 men, 31 women), while a score of 4 or more on three items was found in 20 patients (19.4 %, 2 men, 18 women). Overall median response was 3 (range 1-6). Women were found to have more pronounced symptoms of SD (p<0.05). The overall results on ASEX were found to be in significant correlation with regard to depression (r=0.22, p=0.03), as well as anxiety (r=0.2, p=0.04). Significant correlations were also found with regard to age (r=0.31), mobility (r=0.25), and pain/uneasiness (r=0.22) (p<0.05). CONCLUSIONS: This study brings valuable observations on the presence of SD symptoms in obese patients in Croatia. SD symptoms were found to be present in up to one-third of our patients, more pronounced in women, and in significant correlation with depression and anxiety. However, median response on ASEX suggests that overall SD symptoms in our group of patients are not that expressed.

DIAGNOSTIC AND THERAPEUTIC DILEMMAS IN THE MANAGEMENT OF INTRACRANIAL ANEURYSMS.

Intracranial aneurysms have a prevalence of about 2% of the population. They are a common incidental finding of noninvasive neuroimaging methods, raising the question of the necessity of treatment of patients with an asymptomatic intracranial aneurysm. For long, the only treatment option was surgical clipping of aneurysm neck. In the last 25 years, endovascular techniques have been developed as an alternative solution for patients who are not eligible for neurosurgical procedures. Research has shown better results of embolization procedures with lower rates of complications, but a higher rate of recanalization is still a major drawback of endovascular coiling. There are no strict protocols and the treatment of choice for intracranial aneurysms should be agreed upon by both the physician and the patient. This review aims to provide an insight into the management of intracerebral aneurysms with emphasis on the decision making problems faced by clinicians.

A rare case of parasagittal meningioma causing isolated foot drop: case report and review of the literature.

Foot drop represents a very common reason for a neurologist referral and is often first seen in emergency departments or by a general practitioner. This condition is defined as weakness of ankle dorsiflexion (mainly through tibialis anterior muscle weakness). The most common causes include lower motor neuron lesion, with L4-L5 radiculopathy and peroneal neuropathy being the most frequent ones. Classical diagnostic pathway includes a thorough medical history, detailed neurological examination, radiological studies (MRI of the lumbosacral spine), EMG and nerve conduction studies, and a battery of laboratory tests. The absence of abnormal radiological and neurophysiological findings when searching for the most common causes of foot drop, should raise a red flag and broaden the diagnostic yield for central nervous system pathology (upper motor neuron, UMN) as a possible cause of foot drop. Central causes of isolated foot drop are very rare, with less than 20 cases reported in literature so far, and seven of them being a meningioma. We present a case of a 79-year-old female patient with an isolated foot drop (with no UMN signs on the initial examination) and parasagittal meningioma. Central causes of foot drop should be suspected when foot drop is associated with UMN signs on examination (hyperreflexia of the patellar or ankle jerk and extensor plantar reflex) and when standard diagnostic work-up (MRI of the lumbar spine, EMG and NCS, standard laboratory screening for most common causes of foot drop) is negative or inconclusive. Although very rare, central lesions present a far more serious cause of foot drop and require a more urgent diagnostic work up and a potential neurosurgical referral and treatment. Keeping in mind the possible central causes of foot drop would eliminate unnecessary diagnostic work up and avoid delayed diagnosis and treatment.

Immunity in amyotrophic lateral sclerosis: blurred lines between excessive inflammation and inefficient immune responses.

Despite wide genetic, environmental and clinical heterogeneity in amyotrophic lateral sclerosis, a rapidly fatal neurodegenerative disease targeting motoneurons, neuroinflammation is a common finding. It is marked by local glial activation, T cell infiltration and systemic immune system activation. The immune system has a prominent role in the pathogenesis of various chronic diseases, hence some of them, including some types of cancer, are successfully targeted by immunotherapeutic approaches. However, various anti-inflammatory or immunosuppressive therapies in amyotrophic lateral sclerosis have failed. This prompted increased scrutiny over the immune-mediated processes underlying amyotrophic lateral sclerosis. Perhaps the biggest conundrum is that amyotrophic lateral sclerosis pathogenesis exhibits features of three otherwise distinct immune dysfunctions-excessive inflammation, autoimmunity and inefficient immune responses. Epidemiological and genome-wide association studies show only minimal overlap between amyotrophic lateral sclerosis and autoimmune diseases, so excessive inflammation is usually thought to be secondary to protein aggregation, mitochondrial damage or other stresses. In contrast, several recently characterized amyotrophic lateral sclerosis-linked mutations, including those in TBK1, OPTN, CYLD and C9orf72, could lead to inefficient immune responses and/or damage pile-up, suggesting that an innate immunodeficiency may also be a trigger and/or modifier of this disease. In such cases, non-selective immunosuppression would further restrict neuroprotective immune responses. Here we discuss multiple layers of immune-mediated neuroprotection and neurotoxicity in amyotrophic lateral sclerosis. Particular focus is placed on individual patient mutations that directly or indirectly affect the immune system, and the mechanisms by which these mutations influence disease progression. The topic of immunity in amyotrophic lateral sclerosis is timely and relevant, because it is one of the few common and potentially malleable denominators in this heterogenous disease. Importantly, amyotrophic lateral sclerosis progression has recently been intricately linked to patient T cell and monocyte profiles, as well as polymorphisms in cytokine and chemokine receptors. For this reason, precise patient stratification based on immunophenotyping will be crucial for efficient therapies.

Lower Urinary Tract Symptoms in Croatian Obese Patients.

BACKGROUND: Patients with obesity may experience lower urinary tract symptoms (LUTS). Little is known about these symptoms in obese patients in Croatia. The aim of this study was to asses LUTS in this group of patients. SUBJECTS AND METHODS: This cross-sectional study was carried out in a tertiary healthcare centre. 111 participants were included (81 women and 30 men, age 23-78 years), with BMI>30 kg/m2. LUTS were evaluated using International consultation on incontinence questionnaires (ICIQ) investigating symptoms of overactive bladder (OAB) and urinary incontinence (UI): ICIQ-OAB and ICIQ-UI Short Form (SF). We evaluated also some of the questions on the EQ-5D-5L questionnaire. RESULTS: On ICIQ-OAB patients most often reported:UI (46.85% (N=52)), nocturia (42.34% (N=47)) and increased frequency of urination (34.23% (N=38)), and on ICIQ-UI SF: UI when coughing and sneezing (44.44% (N=32)), urgency UI (43.06% (N=31)) and UI during exercise/physical activity (22.22% (N=16)). Women were found to be more significantly affected by OAB symptoms (p<0.05). Significant correlations were found between the overall results on ICIQ-OAB and hypertension (r=0.32). CONCLUSIONS: The results of this study confirm that obese patients in Croatia experience LUTS as well. A higher incidence of LUTS was found among women and gender-independent among hypertensive obese patients.

Congenital factor XI deficiency caused by a novel F11 missense variant: a case report.

Hereditary factor XI (FXI) deficiency is a mild bleeding disorder, rare in the general population but relatively common among Ashkenazi Jews. The human F11 gene comprises 15 exons, spanning over 23 kb of the long arm of chromosome 4 (4q35). Homozygotes or compound heterozygotes typically show severe FXI deficiency, whereas heterozygotes show partial or mild deficiency. However, the genotype-phenotype relationship is difficult to establish, even among individuals within the same family. We report on a female patient with a heterozygous variant in F11 and FXI deficiency (49 IU/dL), who suffers from menorrhagia since menarche and easy bruising. She experienced excessive bleeding during thyroidectomy and after a cesarean section. Her younger sister, who carries the same heterozygous variant in F11 and has mild FXI deficiency (47 IU/dL), has menorrhagia without other bleeding difficulties although she has undergone several surgeries. Their father, who carries the same missense variant, has not experienced any bleeding difficulties (but he has not undergone any surgeries either). The family study revealed that the A428C mutation was inherited from the father. This variant has not previously been described in the literature and is the first F11 variant described in the Croatian population. Our study showed that even when family members have the same germline F11 variant, they still may experience phenotypic variability, making disease prognosis more complex.