Real-world operation of multiple sclerosis centres in Central-Eastern European countries covering 107 million inhabitants.

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.

Relevance of KFLC quantification to differentiate clinically isolated syndrome from multiple sclerosis at clinical onset.

OBJECTIVE: The objective of the research was to evaluate diagnostic and predictive value for determination of KFLC in cerebrospinal fluid (CSF) compared to the qualitative procedure of OCB determination in patients with CIS who converted to MS during a two-year period. PATIENTS AND METHODS: KFLC, total immunoglobulin G (IgG), serum albumin and CSF albumin were determined with an immunonephelometric method in 151 patients with suspected MS who were admitted to the Neurology Clinic while CSF/serum quotients (QKFLC, QIgG and QAlb) and indexes were calculated with regards to albumin (QCSF/Qserum). Presence of OCBs was determined by isoelectric focusing with immunofixation. Based on their clinical, OCB and magnetic resonance imaging (MRI) findings, 50 patients were classified as other neurological disorder patients (OND), and 101 patients were classified as CIS, 50 of which converted to MS during the two-year period. ROC analysis, ROC curve comparisons and comparison of median KFLC parameters were used to find optimal cut-off with regards to CIS diagnosis and conversion to MS. RESULTS: CSF KFLC median was 2,01 mg/L in MS group contrary to 0,68 mg/L and 0,17 mg/L in CIS and OND group, and KFLC index was 33,52 mg/L contrary to 9,68 mg/L and 3,71 mg/L (p < 0,0001). ROC analysis for accuracy of detection of intrathecal synthesis for QKFLC and KFLC index showed an AUC of 0,891 and 0,839 and the cut-off of 0,027 and 8,82, respectively (sensitivity 73,2% and 71,3%; specificity 96,0% and 98,0%; +PV 97,4% and 98,6%). The diagnostic accuracy of KFLC index for conversion from CIS to MS showed AUC of 0,840 and a cut-off of 9,092 (sensitivity 90,0%; specificity 73,3%; -PV 93,7%). Life age correlates significantly with serum KFLC (r = 0,34; p < 0,0001) and through aging process lower KFLC indexes can be expected, i.e. likelihood of false negative diagnoses. CONCLUSION: KFLC index showed diagnostic value, although it is not more specific and more sensitive than OCB. Application of KFLC might serve as a screening method while OCB could be used in uninterpretted cases only. Patients who converted to MS have significantly higher KFLC which can contribute to an early diagnosis and prompt therapy with its predictive role.

The role of weather conditions and normal level of air pollution in appearance of stroke in the region of Southeast Europe.

We investigated correlation between the normal level of air pollution, weather conditions and stroke occurrence in the region of Southeast Europe with a humid continental climate. This retrospective study included 1963 patients, 1712 (87.2%) with ischemic (IS) and 251 (12.8%) with hemorrhagic stroke (HS) admitted to emergency department. The number of patients, values of weather condition (meteorological parameters) [air temperature (°C), atmospheric pressure (kPa), relative humidity (%)] and concentrations of air pollutants [particulate matter (PM10), nitrogen dioxide (NO2), ozone (O3)], were recorded and evaluated for each season (spring, summer, autumn, winter) during 2 years (July 2008-June 2010). The highest rate of IS was observed during spring (28.9%) (p = 0.0002) and HS in winter (33.9%) (p = 0.0006). We have found negative Spearman's correlations (after Bonferroni adjustment for the multiple correlations) of the number of males with values of relative humidity (%) (day 0, rho = - 0.15), the total number of strokes (day 2, rho = - 0.12), females (day 2, rho = - 0.12) and IS (day 2, rho = - 0.13) with concentrations of PM10 (µg/m3), as well as negative correlations of the number of females (day 2, rho = - 0.12) and IS (day 2, rho = - 0.12) with concentrations of NO2 (µg/m3) (for all p < 0.002). In winter, the number of HS (day 0, rho = 0.25, p = 0.001) positively correlated with concentrations of O3 (µg/m3). The appearance of stroke has seasonal variations, with the highest rates during spring and winter. Positive correlation between the number of HS and values of O3 requires an additional reduction of the legally permitted pollutants concentrations.

SOCIOECONOMIC INFLUENCE OF TOBACCO USE AND DENTAL CARIES EXPERIENCE IN DIFFERENT MALE CROATIAN POPULATIONS.

- The purpose was to evaluate dental caries experience in different male subpopulations of Croatian Army recruits and dental students, and subsequently, smoking habits related to the level of education and place of residence. Croatian army recruits (n=248; mean age 20.2) and male dental students (n=56; mean age 21.5) were evaluated according to DMFT and FST indices, divided according to age and place of residence, and interviewed about their dietary habits and smoking of tobacco. In the subpopulation of recruits, the median value of DMFT was 6 and of FST index 25. A statistically significant difference was recorded between DT and FST index (p<0.05) according to dietary role of carbohydrates reflected in caries development. The number of recruits with finished elementary school coming from a rural area who smoked (in total 57.66% of smokers) was significantly larger (p=0.0041). In dental students, the median value of DMFT was 5, with statistical significance in comparison with recruits (p=0.03). There was a difference in FST index (median 28) (p<0.0001). Students were mostly nonsmokers (71.43%) and had urban residence (p<0.0001). FST index was a more specific indicator in the socioeconomically heterogeneous sample of recruits (more subjects coming from rural areas and with a lower level of education) than in the sample of dental students (more subjects coming from urban areas).

AGE AND GENDER DIFFERENCES IN ACUTE STROKE HOSPITAL PATIENTS.

Stroke is the second leading cause of death and the most important cause of adult disability worldwide and in Croatia. In the past, stroke was almost exclusively considered to be a disease of the elderly; however, today the age limit has considerably lowered towards younger age. The aim of this study was to determine age and gender impact on stroke patients in a Croatian urban area during one-year survey. The study included all acute stroke patients admitted to our Department in 2004. A compiled stroke questionnaire was fulfilled during hospitalization by medical personnel on the following items: stroke risk factors including lifestyle habits (smoking and alcohol), pre-stroke physical ability evaluation, stroke evolution data, laboratory and computed tomography findings, outcome data and post-stroke disability assessment. Appropriate statistical analysis of numerical and categorical data was performed at the level of p < 0.05. Analysis was performed on 396 patients, 24 of them from the younger adult stroke group. Older stroke patients had worse disability at hospital discharge and women had worse disabilities at both stroke onset and hospital discharge, probably due to older age at stroke onset. Younger patients recovered better, while older patients had to seek secondary medical facilities more often, as expected. The most important in-hospital laboratory findings in young stroke patients were elevated lipid levels, while older patients had elevated serum glucose and C-reactive protein. Stroke onset in younger patients most often presented with sudden onset headache; additionally, onset seizure was observed more frequently than expected. Stroke risk factor analysis showed that women were more prone to hypertension, chronic heart failure and atrial fibrillation, whereas men had carotid disease more frequently, were more often smokers and had higher alcohol intake. Additionally, age analysis showed that heart conditions and smoking were more prevalent among older stroke patients. In conclusion, considerable differences were established between age and gender stroke patient groups, confirming the need of permanent national stroke registry and subsequent targeted action in secondary care, and prevention with education on risk factors, preferably personally tailored.

BIOFEEDBACK TRAINING AND TENSION-TYPE HEADACHE.

Biofeedback is a training method, which connects physiological and psychological processes in a person for the purposes of improving his/her physical, emotional, mental and spiritual health. In biofeedback treatment, an active role of the patient is stressed for him/her to be able to actively control the physiological and emotional processes. The aim of biofeedback is to improve the conscious control of the individual's involuntary physiological activity. Research has shown that biofeedback, either applied alone or in combination with other behavioral therapies (techniques), is an effective treatment for various medical and psychological disorders, from headache and hypertension to temporomandibular and attention deficit disorders. More than 90% of adults experience headache once a year, which makes headache one of the most common symptoms and diagnoses in medicine. Tension-type headaches occur in at least 40% of the population and their impact on the health insurance costs and diminished productivity is significant. Studies have shown that clinical biofeedback training is effective in treating headaches. Moreover, the authors stress the need for additional research and further development of methodology for this kind of research.

PSEUDOBULBAR AFFECT IN MULTIPLE SCLEROSIS PATIENTS.

The aim of the study was to determine the prevalence of pseudobulbar affect (PBA) in patients with multiple sclerosis (MS) and to analyze the link between PBA and patient age, sex, clinical course of MS, disease duration and degree of disability. The study was conducted on 79 MS patients that underwent inpatient rehabilitation at the Lipik Special Hospital for Medical Rehabilitation in the period from August 15, 2014 to February 15, 2015. PBA is a term used for an emotional disinhibition syndrome characterized by sudden and involuntary episodes of crying or laughing which are not in proportion to the stimulus applied or occur without stimulus. The condition can be present in patients with various neurological disorders, such as amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, patients having recovered from stroke, or following traumatic brain injury. The estimated prevalence in patients with MS ranges from 10% to 46.2%. As a measuring instrument in the study, we used the Center for Neurologic Study-Lability Scale (CNS-LS), where a sum 17 denoted positive finding. The total number of respondents was 79, of which 33 (41.8%) met the CNS-LS criteria for the diagnosis of PBA. There was no statistically significant correlation between PBA, age and degree of disability, although PBA was more common in women and in patients with a secondary progressive form of the disease. We found that 42.4% of respondents with positive CNS-LS criteria for PBA did not inform their neurologist on the presence of sudden mood changes. The high frequency of PBA and the fact that a significant proportion of patients did not inform the neurologist on their affective disturbances call for an active approach to diagnosis and treatment.

MIGRAINE, CAROTID STIFFNESS AND GENETIC POLYMORPHISM.

Recently migraine has been associated with increased arterial stiffness, procoagulant state, increased incidence of cerebral white matter lesions (WML) and stroke. Our aim was to compare the characteristics of migraineurs to headache free controls regarding their functional carotid ultrasound parameters. Sixty patients (45 women) with migraine (mean age 40.42 ± 10.61 years) were compared with 45 controls (30 women) with no prior history of repeating headache (mean age 38.94 ± 5.46 years) using E-tracking software on Alpha 10 ultrasound platform. Student's t-test was used on statistical analysis with alpha < 0.05. All tested carotid vascular parameters were worse in patients with migraine including increased intima-media thickness, greater carotid diameter and carotid diameter change, as well as several arterial stiffness indices. Additionally, patients with migraine had greater incidence of homozygous mutations for procoagulant genes (MTHFR (C677T), PAI-1 and ACE I/D) than expected. Computed tomography and magnetic resonance imaging of the brain showed WML in 11 patients, four of them migraine with aura patients. Since we established increased carotid stiffness and higher frequency of procoagulant gene mutations in migraineurs, we propose prospective ultrasound monitoring in such patients, especially those with detected WML, in order to timely commence more active and specific preventive stroke management strategies.

Vascular cognitive impairment in diabetes mellitus: are prevention and treatment effective?

Vascular dementia is caused by progressive atherosclerosis leading to multiple small strokes and subsequent brain damage. Approximately 10%-20% of all cases of dementia are attributed to vascular dementia. The 5-year survival rate is 39% for patients with vascular dementia compared with 75% for age-matched controls. It is a growing public health concern because of the lack of effective curative treatment options and rising global prevalence. Duration of diabetes mellitus of 10 years or longer, onset of diabetes before age 65, treatment with insulin and oral antidiabetic medications, and presence of diabetes complications have an impact on the incidence of vascular dementia. On the other hand, patients who suffered stroke either had or are later diagnosed with diabetes (16%-24%). Treatment of vascular dementia in diabetes patients rests on a two-pronged approach: modification of the underlying disease and prevention and treatment of dementia symptoms.

Clinical ethics in Croatia: an overview of education, services and research (an appeal for change).

The aim of this paper is to delineate current position of clinical ethics in the Croatian healthcare system by analyzing the following: representation of clinical ethics contents in the curricula of medical and associated schools; composition and role of clinical ethics consultations; and establishment of an ethical/legal framework for the conduct of research. Curriculum investigation, literature review, arid analysis of the Croatian Act on the Protection of Patients' Rights were performed. The contents of clinical ethics are offered through 63 obligatory and elective subjects at 12 institutions. It is wrongly placed either too early or too late within the curriculum. Continuity at all levels of health professional education is needed. Croatian experience with clinical ethics consultations is shaped only by ethics committees. Problematic is the review of research protocols indicated as their main activity. Inclusion of team and individual consultations would increase the availability and facilitate the usage of ethics support services. The Act on the Protection of Patients' Rights is based on the principles of humanity and availability, ensuring the right to protection when participating in clinical trials. Unfortunately, the outdated paradigm of paternalistic medicine aggravates the respect for patients' rights in cure, care and research. A shift towards the patient/person-centered healthcare system would put the Act into everyday practice. Although clinical ethics has entered the Croatian healthcare system in a formal and practical way, the authors wish to emphasize the need to approach the European and other international standards regarding the recent Croatian accession to the European Union.

Factors influencing door-to-imaging time: analysis of the safe implementation of treatments in Stroke-EAST registry.

BACKGROUND: Brain imaging is logistically the most difficult step before thrombolysis. To improve door-to-needle time (DNT), it is important to understand if (1) longer door-to-imaging time (DIT) results in longer DNT, (2) hospitals have different DIT performances, and (3) patient and hospital characteristics predict DIT. METHODS: Prospectively collected data in the Safe Implementation of Treatments in Stroke-EAST (SITS-EAST) registry from Central/Eastern European countries between 2008 and 2011 were analyzed. Hospital characteristics were obtained by questionnaire from each center. Patient- and hospital-level predictors of DIT of 25 minutes or less were identified by the method of generalized estimating equations. RESULTS: Altogether 6 of 9 SITS-EAST countries participated with 4212 patients entered into the database of which 3631 (86%) had all required variables. DIT of 25 minutes or less was achieved in 2464 (68%) patients (range, 3%-93%; median, 65%; and interquartile range, 50%-80% between centers). Patients with DIT of 25 minutes or less had shorter DNT (median, 60 minutes) than patients with DIT of more than 25 minutes (median, 86 minutes; P < .001). Four variables independently predicted DIT of 25 minutes or less: longer time from stroke onset to admission (91-180 versus 0-90 minutes; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.8), transport time of 5 minutes or less (OR, 2.9; 95% CI, 1.7-4.7) between the place of admission and a computed tomography (CT) scanner, no or minimal neurologic deficit before stroke (OR, 1.3; 95% CI, 1.02-1.5), and diabetes mellitus (OR, .8; 95% CI, .7-.97). CONCLUSIONS: DIT should be improved in patients arriving early and late. Place of admission should allow transport time to a CT scanner under 5 minutes.

General recommendations for the management of aneurysmal subarachnoid hemorrhage.

Subarachnoid hemorrhage is a neurologic emergency and a detrimental cerebrovascular event with a high rate of death and complications. Recommendations have been developed and based on literature search, evaluation of the results of large international clinical trials, collective experience of the authors, and endorsed by the Croatian Society of Neurovascular Disorders, Croatian Society of Neurology including Section for Neurocritical Care, Croatian Neurosurgical Society, Croatian Society for Difficult Airway Management and Croatian Medical Association. The aim of these guidelines is to provide current and comprehensive recommendations and to assist physicians in making appropriate decisions in the management of subarachnoid hemorrhage. Evidence based information on the epidemiology, risk factors and prognosis, as well as recommendations on diagnostic work up, monitoring and management are provided, with regard to treatment possibilities in Croatia.

Recommendations for the management of medical complications in patients following aneurysmal subarachnoid hemorrhage.

These are evidence based guidelines for the management of medical complications in patients following aneurysmal subarachnoid hemorrhage, developed and endorsed by the Croatian Society of Neurovascular Disorders, Croatian Society of Neurology including Section for Neurocritical Care, Croatian Neurosurgical Society, Croatian Society for Difficult Airway Management and Croatian Medical Association. They consist of recommendations for best monitoring, medical treatment and interventions based on the literature, evaluation of the results of large international clinical trials, and collective experience of the authors.

Multiple sclerosis registries in Europe - results of a systematic survey.

BACKGROUND: Identification of MS registries and databases that are currently in use in Europe as well as a detailed knowledge of their content and structure is important in order to facilitate comprehensive analysis and comparison of data. METHODS: National MS registries or databases were identified by literature search, from the results of the MS Barometer 2011 and by asking 33 national MS societies. A standardized questionnaire was developed and sent to the registries' leaders, followed by telephone interviews with them. RESULTS: Twenty registries were identified, with 13 completing the questionnaire and seven being interviewed by telephone. These registries differed widely for objectives, structure, collected data, and for patients and centres included. Despite this heterogeneity, common objectives of the registries were epidemiology (n=10), long-term therapy outcome (n=8), healthcare research (n=9) and support/basis for clinical trials (n=8). While physician-based outcome measures (EDSS) are used in all registries, data from patients' perspectives were only collected in six registries. CONCLUSIONS: The detailed information on a large number of national MS registries in Europe is a prerequisite to facilitating harmonized integration of existing data from MS registries and databases, as well as comprehensive analyses and comparison across European populations.

[Guidelines for diagnosis, therapy and follow up of Anderson-Fabry disease]. / Smjernice za dijagnostiku, lijecenje i pracenje Anderson-Fabryjeve bolesti.

Fabry disease (Anderson-Fabry disease) is one of the most common lysosomal storage diseases (after Gaucher disease) caused by deficient activity of the α-galactosidase A (α-Gal A) enzyme, which leads to progressive accumulation of globotriaosylceramide in various cells, predominantly in endothelium and vascular smooth muscles, with multisystem clinical manifestations. Estimates of the incidence range from one per 40,000 to 60,000 in males, and 1:117,000 in the general population. Pain is usually the first symptom and is present in 60%-80% of affected children, as well as gastrointestinal disturbances, ophthalmologic abnormalities and hearing loss. Renal failure, hypertrophic cardiomyopathy, or stroke as the presenting symptom may also be found even as isolated symptoms of the disease. Life expectancy is reduced by approximately 20 years in males and 10-15 years in females, therefore enzyme replacement therapy should be introduced in patients of any age and either sex, who meet treatment criteria for Anderson-Fabry disease.

Pain syndromes in multiple sclerosis patients - patient experience at Lipik Special Hospital for Medical Rehabilitation.

In the study, we evaluated 61 multiple sclerosis patients hospitalized at our hospital in the period from October 1, 2013 to February 15, 2014. The aim of the study was to investigate pain syndromes associated with the underlying disease. Pain in the month preceding assessment was reported by 90% of patients. Most patients suffered from low back pain (52%) and musculoskeletal pain (39%), followed by neck pain (31%), painful tonic spasm (26%), neuropathic extremity pain (23%) and pain due to spasticity (21%). Other types of pain were present in less than 20% of patients. A total of 67% of patients were taking analgesics; the most frequently used were nonsteroidal antiinflammatory drugs, while drugs against neuropathic pain were taken by a smaller number of patients. The high incidence of pain syndromes pointed to the importance of regular physical therapy procedures.

Person-oriented perspectives in neurology.

Person-oriented medicine is characterized by a holistic approach in patient ma- nagement that embraces physical, psychological, social and spiritual aspects of health and dise- ase. It responds to the needs of patients and health care workers to form an effective therapeutic relationship based on trust, empathy, compassion and responsiveness to the individual needs of a patient. Person-oriented perspectives in neurology include active collaborative partnership between a physician and a patient, and intuitive perception, which has a neurobiological correlate in the hu- man mirror neuron system, thus expressing a considerable impact on the quality of the physician's diagnostic and therapeutic activities. On the other hand, personalized approach in medicine implies integration of clinical information and personal genotyping. Personalized neurology provides gene- based preclinical prediction of disease with improved risk assessment, early detection of disease and targeted intervention. The combination of personalized approach and clinical information accelera- tes the translation of genetic discoveries into clinical practice, which ultimately results in improved health care system. Person-oriented perspectives contribute significantly to the growing pluralism of medical science and provide a greater humanization of medicine, individualized treatment and autonomy during therapeutic processes.

Clinical view of the temporomandibular joint disorder.

Temporomandibular pain has a musculoskeletal origin because it occurs as a consequence of masticatory muscle function disorder and temporomandibular joint disorder. Most common diagnoses of disorders are disc displacement and osteoarthritis, but their comorbidity can also occur. Pain is the most common symptom, where chronic temporomandibular pain may con- tribute to the occurrence of psychological disorders in the patient population. Splint is the most widespread dental method of treatment but other, noninvasive methods of musculoskeletal pain treatment are also recommended. Electronic axiography is used for visualization of mandibular movements, in particular pathologic sounds in the joints. Mental health, although not so obvious in dental practice, can influence the need of a multidisciplinary approach to the patient with disorder of the temporomandibular joint.

Quality of life in patients with multiple sclerosis.

Multiple sclerosis is a chronic, immune-mediated disease of the central nervous system that typically strikes young adults. It is often associated with a wide range of functional deficits and progressive disability. Common symptoms of multiple sclerosis include vision problems, spasticity, weakness, ataxia, bladder and bowel dysfunctions, fatigue, pain syndromes, tremors, vertigo, cognitive impairment, and mood disorders. Multiple sclerosis has a major negative impact on patient health-related quality of life (HRQoL). Quality of life (QoL) is a multidimensional construct composed of functional, physical, emotional, social and spiritual well-being. Researches have reported that individuals with multiple sclerosis have lower QoL than non-diseased and diseased populations. The inclusion of HRQoL questionnaires in the patient follow-up is a relevant issue to optimize treatment, facilitate treatment decisions and improve adherence, as well as to reduce the inconveniences derived from medication such as side effects.

Feasibility of transcranial Doppler and single photon emission computed tomography in compound neuroactivation task.

The aim of this study was to test feasibility of transcranial Doppler (TCD) and single photon emission computed tomography (SPECT) during compound neuroactivation task. The study was performed in 60 healthy right-handed volunteers. Cerebral blood flow velocity was measured by TCD in both middle cerebral arteries (MCA) at baseline and during computer game. The same stimulus and response pattern was used in 15 subjects that additionally underwent brain SPECT. Percentage differences between measurements were determined through quantitative result assessment. Both methods detected a statistically significant cerebral blood flow increase during neuroactivation. Correlation of TCD and SPECT showed statistically significant correlation only for the increase of cerebral blood flow velocity in the right MCA and for the right-sided cerebral blood flow increase, demonstrating that both methods partially measure similar cerebral blood flow changes that occur during neuroactivation. Comparison of TCD and SPECT showed TCD to be inadequately sensitive method for evaluation of cerebral blood flow during complex activation paradigm.