Progressive multifocal leukoencephalopathy or immune reconstitution inflammatory syndrome after fingolimod cessation? A case report.

BACKGROUND: Fingolimod is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML); however, its discontinuation may cause severe immune reconstitution inflammatory syndrome (IRIS). As both of these conditions (especially fingolimod induced PML) are rarely described in medical case reports distinguishing between PML-IRIS and MS-IRIS may be diagnostically challenging. CASE PRESENTATION: We report a patient with severe clinical decline (Expanded Disability Status Scale (EDSS) increasing from 3.5 to 7.5) and multiple, large, contrast-enhancing lesions on brain magnetic resonance imaging (MRI) a few months after fingolimod withdrawal. The diagnostic possibilities included IRIS due to fingolimod withdrawal versus PML-IRIS. The JC virus (JCV) antibody index was positive (2.56); however, cerebrospinal fluid (CSF) JCV real-time polymerase chain reaction (JCV-PCR) was negative and brain biopsy was not performed. After a long course of aggressive treatment (several pulsed methylprednisolone infusions, plasmapheresis, intravenous dexamethasone, oral mirtazapine) the patient gradually recovered (EDSS 2.5) and MRI lesions decreased. CONCLUSIONS: This case report demonstrates the importance of monitoring patients carefully after the discontinuation of fingolimod for PML-IRIS and rebound MS with IRIS as these conditions may manifest similarly.

Associations between migraine, celiac disease, non-celiac gluten sensitivity and activity of diamine oxidase.

BACKGROUND AND PILOT STUDY: Recent reports reveal a close relationship between migraine and gastrointestinal disorders (GI), such as celiac disease (CD) and non-celiac gluten sensitivity (NCGS). CD is a genetic autoimmune disorder, which affects the mucosa of the small intestine. Gluten, found in various grains, not only plays a major role in the pathophysiology of CD and NCGS, but also aggravates migraine attacks. Another common food component, which can induce migraine headaches, is histamine. Diamine oxidase (DAO) is an enzyme, which degrades histamine. Reduced activity of DAO means reduced histamine degradation, which can cause histamine build-up and lead to various symptoms, including headaches and migraine. In this paper we propose a hypothesis, that in pathogenesis of migraine, low serum DAO activity is related to CD and NCGS. We also conducted our own pilot study of 44 patients with severe migraine in efforts to evaluate the co-presence of decreased serum DAO activity and celiac disease/NCGS in patients. 44 consecutive migraine patients were divided into 2 groups: decreased DAO activity (group 1; n = 26) and normal DAO activity (group 2; n = 18). All patients were screened for celiac disease. The diagnosis of NCGS was made after exclusion of CD, food allergies and other GI disorders in the presence of gluten sensitivity symptoms. Furthermore, dietary recommendations were given to all participants and their effects were assessed 3 months after the initial evaluation via the MIDAS (Migraine Disability Assessment) questionnaire. RESULTS AND CONCLUSIONS: Only 1 patient fit the criteria for celiac disease, rendering this result inconclusive. Pathological findings of the remainder of patients were attributed to NCGS (n = 10). 9 of 10 patients with NCGS belonged to the decreased serum DAO activity group (group 1; n = 26), suggesting a strong relationship between reduced serum DAO activity and NCGS. MIDAS questionnaire revealed, that patients with decreased serum DAO activity were more severely impacted by migraine than those with normal DAO activity, and this remained so after our interventions. Dietary adjustments significantly reduced the impact of migraine on patients' daily activities after 3 months in both groups. We argue, that migraine, celiac disease and NCGS may benefit from treatment with a multidisciplinary approach, involving neurologists, gastroenterologists and dietitians.

[Associations between quality of life and lifestyle peculiarities in stroke survivors: the results of the EROS study]. / Svyaz' mezhdu kachestvom i osobennostyami obraza zhizni lits, perenesshikh tserebral'nyi insul't: rezul'taty issledovaniya EROS.

OBJECTIVE: To determine relations between quality of life and characteristics of lifestyle in stroke patients and control groups. MATERIAL AND METHODS: The case group consisted of 508 Kaunas citizens, aged 25-84, who had survived their first stroke. The control group consisted of 508 randomly chosen healthy Kaunas citizens age- and sex-matched to the cases. SF-12 questionnaire on the quality of life has been used for the study. The characteristics of lifestyle (alcohol use, smoking, nutrition) were studied. RESULTS: The effect size of alcohol use in the stroke patients was not large (Cohen's d=0.41) compared to the control group (Cohen's d=0.87). Patients who did not use alcohol had lower estimations in the physical health domain of quality of life compared to those who used alcohol. The number of smoking men was significantly higher (p=0.0005) in the stroke patients (29.0%) than in the control group (19.6%). The physical health was best assessed by men belonging to the control group who never smoked compared to men who had quit smoking (p=0.0005) and in the stroke group - by smoking men compared to men who had quit smoking (p=0.049). Nutrition status had significant effect only on the physical health in the control group: the estimate of physical health of obese individuals was lower when compared to the rest participants (p<0.001). CONCLUSION: The number of men who used excessive amounts of alcohol and smoked or had quit smoking was higher in the stroke patients group than in the control group. In the stroke patient group, the effect size of alcohol use was not large. Men who had quit smoking prior to stroke presented poorer evaluations of the quality of life in the general health and mental health domains than did those who had smoked before stroke onset.

Clinical assessment of noninvasive intracranial pressure absolute value measurement method.

OBJECTIVE: To assess prospectively the accuracy and precision of a method for noninvasive intracranial pressure (ICP) measurement compared with invasive gold standard CSF pressure measurement. METHODS: Included were 62 neurologic patients (37 idiopathic intracranial hypertension, 20 multiple sclerosis, 1 Guillain-Barré syndrome, 1 polyneuropathy, and 3 hydrocephalus). The average age was 40 ± 12 years. All patients had lumbar puncture indicated as a diagnostic procedure. ICP was measured using a noninvasive ICP measurement method, which is based on a two-depth high-resolution transcranial Doppler insonation of the ophthalmic artery (OA). The OA is being used as a natural pair of scales, in which the intracranial segment of the OA is compressed by ICP and the extracranial segment of the OA is compressed by extracranial pressure (Pe) applied to the orbit. The blood flow parameters in both OA segments are approximately the same in the scales balance case when Pe = ICP. All patients had simultaneous recording of noninvasive ICP values and invasive gold standard CSF pressure values. RESULTS: Analysis of the 72 simultaneous paired recordings of noninvasive ICP and the gold standard CSF pressure showed good accuracy for the noninvasive method as indicated by the low mean systematic error (0.12 mm Hg; confidence level [CL] 0.98). The method also showed high precision as indicated by the low SD of the paired recordings (2.19 mm Hg; CL 0.98). The method does not need calibration. CONCLUSION: The proposed noninvasive ICP measurement method is precise and accurate compared with gold standard CSF pressure measured via lumbar puncture.

The cost of headache disorders in Europe: the Eurolight project.

BACKGROUND AND PURPOSE: Headache disorders are very common, but their monetary costs in Europe are unknown. We performed the first comprehensive estimation of how economic resources are lost to headache in Europe. METHODS: From November 2008 to August 2009, a cross-sectional survey was conducted in eight countries representing 55% of the adult EU population. Participation rates varied between 11% and 59%. In total, 8412 questionnaires contributed to this analysis. Using bottom-up methodology, we estimated direct (medications, outpatient health care, hospitalization and investigations) and indirect (work absenteeism and reduced productivity at work) annual per-person costs. Prevalence data, simultaneously collected and, for migraine, also derived from a systematic review, were used to impute national costs. RESULTS: Mean per-person annual costs were €1222 for migraine (95% CI 1055-1389; indirect costs 93%), €303 for tension-type headache (TTH, 95% CI 230-376; indirect costs 92%), €3561 for medication-overuse headache (MOH, 95% CI 2487-4635; indirect costs 92%), and €253 for other headaches (95% CI 99-407; indirect costs 82%). In the EU, the total annual cost of headache amongst adults aged 18-65 years was calculated, according to our prevalence estimates, at €173 billion, apportioned to migraine (€111 billion; 64%), TTH (€21 billion; 12%), MOH (€37 billion; 21%) and other headaches (€3 billion; 2%). Using the 15% systematic review prevalence of migraine, calculated costs were somewhat lower (migraine €50 billion, all headache €112 billion annually). CONCLUSIONS: Headache disorders are prominent health-related drivers of immense economic losses for the EU. This has immediate implications for healthcare policy. Health care for headache can be both improved and cost saving.

The Eurolight project: the impact of primary headache disorders in Europe. Description of methods.

The Eurolight project is the first at European Union level to assess the impact of headache disorders, and also the first of its scale performed by collaboration between professional and lay organizations and individuals. Here are reported the methods developed for it. The project took the form of surveys, by structured questionnaire, conducted in ten countries of Europe which together represented 60% of the adult population of the European Union. In Lithuania, the survey was population-based. Elsewhere, truly population-based studies were impractical for reasons of cost, and various compromises were developed. Closest to being population-based were the surveys in Germany, Luxembourg, the Netherlands, Italy and Spain. In Austria, France and UK, samples were taken from health-care settings. In addition in the Netherlands, Spain and Ireland, samples were drawn from members of national headache patient organizations and their relatives. Independent double data-entry was performed prior to analysis. Returned questionnaires from 9,269 respondents showed a moderate female bias (58%); of respondents from patients' organizations (n = 992), 61% were female. Mean age of all respondents was 44 years; samples from patients' organizations were slightly older (mean 47 years). The different sampling methods worked with differing degrees of effectiveness, as evidenced by the responder-rates, which varied from 10.8 to 90.7%. In the more population-based surveys, responder-rates varied from 11.3 to 58.8%. We conclude that the methodology, although with differences born of necessity in the ten countries, was sound overall, and will provide robust data on the public ill-health that results from headache in Europe.

[The effect of stroke on health and daily activities].

The purpose of this survey was to compare quality of life between survivors of stroke and the general population with regard to daily activities, health and emotional state. We surveyed a random group of 508 Kaunas residents, aged between 25 and 84 years, who survived the first stroke. The control group was made up of 508 sex- and age-matched stroke-free residents of Kaunas. We used the SF-12 quality of life questionnaire. Logistic regression was applied to evaluate the subjects for quality of life with regard to health, daily routine and mental state. Health was rated as very good by 1% of patients and 24,4% of controls (p = 0,001) and as poor by 78,9% and 26,4%, respectively (p = 0,001). The activities of 35,2% of patients and 3,5% of controls were impaired by their health (p = 0,001). State of health or emotional problems restricted social relationship in 19,3% of patients and in 1,6% of controls (p < 0,05). Social activities were mostly impaired in patients after cerebral stroke (odds ratio (OR = 36,7). Stroke also caused depression (OR = 16) and limited domestic activities (OR = 15,5).

Three-month stroke outcome: the European Registers of Stroke (EROS) investigators.

BACKGROUND: Contemporaneous data on variations in outcome after first-ever-lifetime stroke between European populations are lacking. We compared differences in case fatality rates, functional outcome, and living conditions 3 months after stroke within the European Registers of Stroke Collaboration. METHODS: Population-based stroke registers were established in France (Dijon), Italy (Sesto Fiorentino), Lithuania (Kaunas), the United Kingdom (London), Spain (Menorca), and Poland (Warsaw). All patients with first-ever-lifetime stroke of all age groups from the source population (1,087,048 inhabitants) were included. Data collection took part between 2004 and 2006. The study investigated population variations in outcome at 3 months (death, institutionalization due to stroke, or Barthel Index below 12 points) using multivariable logistic regression analyses adjusted for age, sex, stroke severity, stroke subtype, and comorbidities. RESULTS: A total of 2,034 patients with first-ever-lifetime stroke were included. Median age was 73 years, 52% were female. The mean weighted cumulative risk of death was 21.8% (95% confidence interval 20.0 to 23.6) with a 3-fold variation across populations. The weighted proportion of poor outcome was 41.3% (95% confidence interval 39.0 to 43.7) with a 2-fold variation across populations. CONCLUSION: More than 40% of patients had a poor outcome, defined as being dead, dependent, or institutionalized 3 months after stroke. Substantial outcome variations were found between populations that were explained by case mix variables in this analysis, yet a trend toward a higher risk of poor outcome was present in Kaunas.

[Risk factors for death after a first-ever stroke].

An aim of the present study is to evaluate the risk factors for death after a first-ever stroke within one year after stroke onset in the Kaunas population. The patient's group consisted of 331 men and women with a first-ever stroke who were treated in two Kaunas hospitals during 1997-1998. The data were collected using a "hot pursuit" approach. The methods used were those applied for the EC BIOMED-2 study. All stroke patients were followed up for one year. The end-point of the present study was death due to any cause. The relative risk estimates were based on the Cox model. Age at disease onset, impaired consciousness and incontinence were the only independent predictors of death during the first 12 months after a first-ever stroke. An increase of the patient's age by one year increased the risk of death by 4%. The impaired consciousness was associated with a 3-fold (relative risk (RR) = 2.76; p = 0.004) and incontinence with a 4-fold (RR = 3.56; p < 0.0001) risk of death during the first year after initial stroke. In addition to the factors relating to the severity of stroke, only age was a predictor of a poor outcome after a first-ever stroke.

[Prognosis of patients with Q wave myocardial infarction of inferior or anterior localization].

The aim of the study was to determine clinical and demographic features that are significant for prognosis after the first-ever myocardial infarction (MI). Kaunas men and women aged 25 - 64 years, admitted to Kaunas hospitals due to their first-ever MI during 1983 - 1992 and with the first coded electrocardiogram (ECG) were enrolled into the study. The Kaunas ischemic heart disease (IHD) register was the source of data, ECGs were coded using the Minnesota Code, and deaths were identified via prospective death s register. Factors significantly increasing the risk of death from IHD during the first year after first-ever inferior MI were age (p=0.01), atrial flutter or fibrillation (p=0.02). In patients with Q wave in anterior site the risk of death from IHD was increased not only by age, but also by acute heart failure - 3.74-fold (p=0.01), history of previous stroke - 3.82 (p=0.046), and history of diabetes - 2.53 (p=0.04).

[Stroke care profile: a study of Lithuania population in Kaunas].

An aim of the study was to evaluate volume of medical care for stroke patients in Kaunas, Lithuania. Patients with first-ever stroke admitted to 2 Kaunas municipal hospitals have been registered. Data have been collected according to the requirements of the EC BIOMED-2 Program "Towards cost-effective stroke care" using standardized questionnaires. In total 331 patients (121 men and 210 women, mean age 69,8 +/- 0,64 years) were studied, 52% being admitted to the hospital during the first 6 h of the illness and over two thirds during the first 24 h. Most of patients (85%) were hospitalized into general neurological wards. Computed tomography of the brain was performed in one third of the patients. More than two thirds did not undergo any of the possible neurodiagnostic procedures. During staying in the hospital, rehabilitation was launched for 53,2% of patients. Out of all patients survived (83,5%), 29,9% were discharged to the rehabilitation unit. The results revealed that the level of medical care for a stroke patient appeared to be rather moderate: delay time for hospital medical care was too long, proportion of diagnostic examinations was too low and the volume of rehabilitation and social services were not sufficient.

A comparison of the costs and survival of hospital-admitted stroke patients across Europe.

BACKGROUND AND PURPOSE: Policy makers require evidence on the costs and outcomes of different ways of organizing stroke care. This study compared the costs and survival of different ways of providing stroke care. METHODS: Hospitalized stroke patients from 13 European centers were included, with demographic, case-mix, and resource use variables measured for each patient. Unit costs were collected and converted into US dollars using the purchasing power parity (PPP) index. Cox and linear regression analyses were used to compare survival and costs between the centers adjusting for case mix. RESULTS: A total of 1847 patients were included in the study. After case-mix adjustment, the mean predicted costs ranged from $466 [95% CI 181 to 751] in Riga (Latvia) to $8512 [7696 to 9328] in Copenhagen (Denmark), which reflected differences in unit costs, and resource use. The mean length of hospitalization ranged from 8.3 days in Menorca (Spain) to 36.8 days in Turku B (Finland). In the 3 Finnish centers at least 80% of patients were admitted to wards providing organized stroke care, which was not provided at the centers in Almada (Portugal), Menorca, or Riga. Patients in Turku A and Turku B were less likely to die than those in Riga, Warsaw (Poland), or Menorca. The adjusted hazard ratios were 0.18 [0.10 to 0.32] for Turku A, 0.18 [0.10 to 0.32] for Turku B, 0.68 [0.48 to 0.96] for Warsaw, and 0.56 [0.33 to 0.96] for Menorca, all compared with Riga. CONCLUSIONS: The cost of stroke care varies across Europe because of differences in unit costs, and resource use. Further research is needed to assess which ways of organizing stroke care are the most cost-effective.

Urinary sodium excretion and cardiovascular mortality in Finland: a prospective study.

BACKGROUND: The evidence that high salt intake increases the risk of cardiovascular disease has been challenged. We aimed to find out whether salt intake, measured by 24 h urinary sodium excretion, is an independent risk factor for cardiovascular disease frequency and mortality, and all-cause mortality. METHODS: We prospectively followed 1173 Finnish men and 1263 women aged 25-64 years with complete data on 24 h urinary sodium excretion and cardiovascular risk factors. The endpoints were an incident coronary and stroke event, and death from coronary heart disease, cardiovascular disease, and any cause. Each endpoint was analysed separately with the Cox proportional hazards model. FINDINGS: The hazards ratios for coronary heart disease, cardiovascular disease, and all-cause mortality, associated with a 100 mmol increase in 24 h urinary sodium excretion, were 1.51 (95% CI 1.14-2.00), 1.45 (1.14-1.84), and 1.26 (1.06-1.50), respectively, in both men and women. The frequency of acute coronary events, but not acute stroke events, rose significantly with increasing sodium excretion. When analyses were done separately for each sex, the risk ratios were significant in men only. There was a significant interaction between sodium excretion and body mass index for cardiovascular and total mortality; sodium predicted mortality in men who were overweight. Correction for the regression dilution bias increased the hazards ratios markedly. INTERPRETATION: High sodium intake predicted mortality and risk of coronary heart disease, independent of other cardiovascular risk factors, including blood pressure. These results provide direct evidence of the harmful effects of high salt intake in the adult population.

Serum gamma-glutamyl transferase, self-reported alcohol drinking, and the risk of stroke.

BACKGROUND AND PURPOSE: There is still conflicting evidence regarding a link between alcohol drinking and the risk of stroke. In most prospective studies, the assessment of the alcohol drinking has been based on self-reporting, which may be unreliable. The aim of the present study was to examine the relationship between stroke and both the self-reported alcohol drinking and the serum gamma-glutamyl transferase (GGT) concentration, which was regarded as a biological marker of alcohol drinking. METHODS: A prospective cohort study of 14 874 Finnish men and women aged 25 to 64 years who participated in a cardiovascular risk-factor survey in 1982 or 1987. The following risk factors, determined at baseline, were included in data analyses: self-reported alcohol drinking, GGT, smoking, blood pressure, serum cholesterol, and body mass index. The cohorts were followed until the end of 1994. Stroke events were identified through the national death registry and hospital discharge registry by computerized record linkage. RESULTS: Serum GGT concentration was associated with the risk of total and ischemic stroke in both genders. There was also a significant association among men between GGT and the risk of intracerebral hemorrhage and among women between GGT and the risk of subarachnoid hemorrhage. The relationships remained statistically significant also after adjustment for other risk factors. Self-reported alcohol drinking did not associate with any type of stroke. CONCLUSIONS: These results support the hypothesis that excessive alcohol drinking is related to an increased risk of stroke. Biological markers of alcohol drinking, such as serum GGT level, are useful for the assessment of risks related to alcohol drinking.

International trends in mortality from stroke, 1968 to 1994.

BACKGROUND AND PURPOSE: The World Health Organization data bank is an invaluable source of information for international comparison of mortality trends. We present rates and trends in mortality from stroke up to 1994, with a particular emphasis on the last 10-year period. Data are presented for men and women in 51 industrialized and developing countries from different parts of the world. METHODS: We included all deaths from cerebrovascular disease for the population aged 35 to 84 years from all the countries in which death certificates were estimated to be available for at least 80% for the period from 1968 to 1994. Age-standardized mortality rates from stroke were calculated for each country for the last available 5 years. Time trends were calculated by using ordinary linear regression and are presented for the entire study period and for 3 separate time periods: 1968 to 1974, 1975 to 1984, and 1985 to 1994. The last 10-year period was further subdivided into 2 parts of 5 years each. We analyzed data separately for men and women and for groups aged 35 to 74 years and 75 to 84 years. RESULTS: The highest rates at the end of the study period for the population aged 35 to 74 years were observed in eastern Europe and previous Soviet Union countries (309 to 156/100 000 per year among men and 222 to 101/100 000 per year among women), Mauritius (268/100 000 per year among men and 138/100 000 per year among women), and Trinidad and Tobago (185/100 000 per year among men and 134/100 000 per year among women). Relatively low to average rates (<100/100 000 per year among men and <70/100 000 per year among women) were reported for Western Europe, with an exception of Portugal (162/100 000 per year among men and 95/100 000 per year among women). The countries with lowest stroke mortality rates at the end of the study period, such as the United States, Canada, Switzerland, France, and Australia, experienced steep declining trends. However, the slope of the decline was substantially reduced during the last 5 years in these countries. Mortality from stroke increased most in the eastern European countries, especially during the last 5 years. Among other high-risk populations, no change in stroke mortality trends was observed in Mauritius, whereas somewhat declining trends were seen in Trinidad and Tobago. CONCLUSIONS: We observed large differences in mortality rates from stroke around the world together with a wide variation in mortality trends. A widening gap was observed between 2 groups of nations, those with low and declining stroke mortality rates and those with high and increasing mortality, in particular, between western and eastern Europe. Eastern European countries should initiate actions aiming at the reduction of stroke risk, perhaps by looking at the examples of Japan and Finland and the other countries that have been the most successful in reducing previously very high mortality from stroke.

International trends in mortality from stroke, 1968 to 1994

BACKGROUND AND PURPOSE: The World Health Organization data bank is an invaluable source of information for international comparison of mortality trends. We present rates and trends in mortality from stroke up to 1994, with a particular emphasis on the last 10-year period. Data are presented for men and women in 51 industrialized and developing countries from different parts of the world. METHODS: We included all deaths from cerebrovascular disease for the population aged 35 to 84 years from all the countries in which death certificates were estimated to be available for at least 80% for the period from 1968 to 1994. Age-standardized mortality rates from stroke were calculated for each country for the last available 5 years. Time trends were calculated by using ordinary linear regression and are presented for the entire study period and for 3 separate time periods: 1968 to 1974, 1975 to 1984, and 1985 to 1994. The last 10-year period was further subdivided into 2 parts of 5 years each. We analyzed data separately for men and women and for groups aged 35 to 74 years and 75 to 84 years. RESULTS: The highest rates at the end of the study period for the population aged 35 to 74 years were observed in eastern Europe and previous Soviet Union countries (309 to 156/100 000 per year among men and 222 to 101/100 000 per year among women), Mauritius (268/100 000 per year among men and 138/100 000 per year among women), and Trinidad and Tobago (185/100 000 per year among men and 134/100 000 per year among women). Relatively low to average rates (<100/100 000 per year among men and <70/100 000 per year among women) were reported for Western Europe, with an exception of Portugal (162/100 000 per year among men and 95/100 000 per year among women). The countries with lowest stroke mortality rates at the end of the study period, such as the United States, Canada, Switzerland, France, and Australia, experienced steep declining trends. However, the slope of the decline was substantially reduced during the last 5 years in these countries. Mortality from stroke increased most in the eastern European countries, especially during the last 5 years. Among other high-risk populations, no change in stroke mortality trends was observed in Mauritius, whereas somewhat declining trends were seen in Trinidad and Tobago. CONCLUSIONS: We observed large differences in mortality rates from stroke around the world together with a wide variation in mortality trends. A widening gap was observed between 2 groups of nations, those with low and declining stroke mortality rates and those with high and increasing mortality, in particular, between western and eastern Europe. Eastern European countries should initiate actions aiming at the reduction of stroke risk, perhaps by looking at the examples of Japan and Finland and the other countries that have been the most successful in reducing previously very high mortality from stroke.