Cerebral malaria admissions in Papua New Guinea may show inter-annual cyclicity: An example of about a 1.5-year cycle for malaria incidence in Burundi

Best available descriptions of malaria incidence and mortality dynamics are important to better plan and evaluate the implementation of programs to monitor (e.g., remote sensing) and control the disease, especially in endemic zones. This was stressed recently by Cibulskis et al (2007) in the view of completeness of monthly reporting for cerebral malaria admissions in Papua New Guinea (latitude 6 degree S, 1987-1996). Notably, regardless of the rate of its completeness, the temporal dynamics of admissions was preserved over the years, however, neither raw data nor results on further analyses about eventual inter-annual cyclic components (periods T>1 year) were provided despite obvious graphical patterns for such a specific time structure (chronome). Interestingly, in a recent analysis by Gomez-Elipe et al (2007) on monthly malaria notifications in Burundi, at almost the same latitude (province of Karuzi, >3 degree S, 1997-2001), the data have shown neither trend not periodic oscillations beyond a 6-month (0.5-year) period. Since the graphical representation of both data sets have indicated an eventual existence of inter-annual variations, and because both are located at the same latitude zone, we have further analyzed the data from Burundi for such periodic oscillations. By using a periodogram regression analysis, we discovered a multicomponent cyclic chronome with periods above 12 months (T=17.5-18.0, 27.5 and 65.0-65.5 months, all at p<0.05). Notably, the most strong cyclic pattern at p<0.002 in the periodogram of the detrended malaria rates in Burundi remained only that with a peak at about 1.5 years (period T=17.5-18.0 months, R=0.51, z=5.3). It is possible that likely inter-annual cyclic patterns might exist also in the time structure for cerebral malaria admissions in Papua New Guinea and, if confirmed, these may be found very useful in epidemic forecasting and programs implementation. We explored these cyclic variations and also discussed possible associations with environmental factors exhibiting alike cyclicity

Cerebral Venous Sinus Thrombosis - Diagnostic Strategies and Prognostic Models: A Review

In 1825, Ribes described a case of a 45-year old man who died after a 6-month history of epilepsy, seizures and delirium. The autopsy examination revealed thrombosis of the superior sagittal sinus, the left lateral sinus and a cortical vein in the parietal region. This was probably the first detailed description of extensive cerebral venous sinus thrombosis (CVST). Since then, the literature describing this disease has comprised of case reports, series and some newer prospective studies, including recent reviews and guidelines (statement) on the diagnosis and management of CVST (Siddiqui \u26 Kamal, 2006; Stam, 2005; Saposnik et al, 2011; Brown \u26 Thore, 2011). The cerebral venous sinus thrombosis is a challenging condition and it is most common than previously thought. CVST accounts for 0.5% to 1.0% of all strokes and usually affects young individuals. Important advances have been made in the understanding of the pathophysiology of this vascular disorder. The diagnosis of CVST is still frequently overlooked or delayed as a result of the wide spectrum of clinical symptoms and the often sub-acute or lingering onset. Patients with CVST commonly present with headache, although some develop a focal neurological deficit, decreased level of consciousness, seizures, or intracranial hypertension without focal neurological signs. Uncommonly, an insidious onset may create a diagnostic challenge. The main problem of this disorder is that it is very often unrecognised at initial presentation. In particular, a prothrombotic factor or a direct cause is identified in approximately 66% of the CVST patients (a list of most important causal and risk factors are listed in Table 1). Cerebral venous thrombosis is more common in women than men, with a female to male ratio of 3:1 (cited in Ferro \u26 Canhao, 2011). The imbalance may be due to the increased risk of CVST associated with pregnancy and puerperium and with oral contraceptives. The female predominance in CVST is found in young adults, but not in children or older adults

Metabolic syndrome severity score: range and associations with cardiovascular risk factors

Introduction: Metabolic Syndrome Severity Score (MSSS) is a new clinical prediction rule (CPR) for diagnostic and therapeutic decisions and employs available components (sex, age, race, systolic blood pressure, waistline circumference, high-density lipoprotein, triglycerides and fasting blood glucose). The aim of our work was to perform cross-sectional pilot trial on middle-aged healthy volunteers and patients with metabolic syndrome (MetS) with and without type 2 diabetes mellitus (T2DM) for studying feasibility and implementation of MSSS and its associations with cardiovascular risk factors.Material and methods: We approached 64 eligible participants from Bulgaria. The MSSS values, together with demographic, anthropometric, medical history, laboratory findings, CVD risk factors, QRISK2 score for 10-year cardiovascular risk and predicted heart age, were analysed. Descriptive statistics with tests for comparison (e.g., t-test, c2) between groups as well as ANOVA and logistic regression were applied. Results: We analysed data from 56 participants (aged 50.11 ±3.43 years). The MSSS was higher in MetS patients (including 6 T2DM patients) than in controls (n = 29; 51.8%) presented as percentiles (69.97% and 34.41%, respectively) and z-scores (0.60 and –0.45, respectively) (p < 0.05). The logistic regression model of MSSS indicated a positive association with MetS/T2DM cases (correctness > 85%, p < 0.01). For further validation purposes, positive correlations of MSSS with CVDrisk factor as diastolic blood pressure (Rho = 0.399; p < 0.003) and QRISK2 score (Rho = 0.524; p < 0.001) or predicted heart age (Rho = 0.368; p < 0.007) were also found.Conclusions: The pilot study of MSSS in Bulgaria indicated feasibility and consistency of its implementation among patients with metabolic syndrome and/or T2DM and healthy volunteers

Impaired nocturnal melatonin in acute phase of ischaemic stroke: cross-sectional matched case-control analysis

Quantitative data on melatonin in stroke patients are scarce. A gender- and age-matched cross-sectional case–control study in 33 patients with ischaemic stroke was performed and associations between nocturnal melatonin and other factors (e.g. cortisol) were evaluated. Clinical and laboratory (e.g. melatonin and cortisol) measurements (03.00 h and 08.00 h) with statistical techniques [e.g. multifactorial regressions, receiver operating characteristic (ROC) curve and curvilinear estimations] were used. We identified mean value and 95% confidence interval (CI) (69.70 pg/ml; 95% CI = 53.86–85.54) for control levels of nocturnal melatonin in healthy subjects. The patients with stroke had lower melatonin (48.1 ± 35.9 pg/ml) and higher cortisol (297.3 ± 157.8 nmol/l) at 03.00 h (P < 0.05) but not at 08.00 h (P > 0.05). Stroke was the strongest factor of disturbed nocturnal cortisol (P < 0.001), whereas decreased melatonin depended on stroke (P = 0.010) and gender (P = 0.018). At the same time, vice versa, only nocturnal measures were associated with an increased probability of the presence of stroke (accuracy > 75%, Pmodel < 0.001). Thus, a hypothesis that a decrease of melatonin with 1.0 pg/ml might be associated with > 2% increase in the probability of the presence of stroke [adjusted odds ratio (OR) = 1.020; 95% CI = 1.002–1.037] was also suggested. The ROC curve (0.67, P = 0.0119) and optimisation techniques indicated that a novel best cut-off < 51.5 pg/ml for decreased nocturnal melatonin in the view of the presence of stroke (OR = 3.12, P = 0.0463) might exist. The classification performance of such a cut-off might be confirmed by existing nocturnal melatonin and cortisol differences between the sub-groups; potential differences in diurnal melatonin were also suggested. In conclusion, a novel melatonin cut-off of 51.5 pg/ml may be associated with the presence of ischaemic stroke. As a single marker (84% sensitivity, 74% specificity), it is hypothesised that modelling performance was independent of age, gender and cortisol. These new results, including the suggested hypothesis, might be further tested in follow-up (cohort), longitudinal studies and be applied to explore melatonin disturbances as targets in high-risk pre-stroke and post-stroke patient

Associations between serum selenium and total plasma homocysteine during the acute phase of ischaemic stroke

Background/aims: risk of ischaemic stroke (IS) was associated with total homocysteine (tHCY). On the other hand, serum selenium (Se) exhibited anti-aging and cardiopreventive effects. Se and tHCY showed relationships in animals but these were contradictory or inconclusive in humans; therefore, we searched for such associations in acute IS. Methods: ninety-four participants aged around 47 years were identified and 39 patients versus 46 healthy controls were analysed. Clinical, laboratory (blinded) and risk factor questionnaire methods were used. Comparison, correlation and multifactorial regression analyses were applied. Results: IS patients were similar to controls concerning age and gender. IS was prevalent in the carotid system (76.9%); 82.1% had a subacute onset. IS patients expressed higher tHCY (14.65 ± 9.79 ?mol/l) and lower Se levels (1.3 ± 0.5 ?mol/l). Twice as many IS patients (23%) had optimal Se levels of <1.01 ?mol/l. Subjects with hyperhomocysteinaemia (tHCY ?15 ?mol/l) showed lower Se levels during IS; Se accounted for 15.4% of tHCY variations (R = –0.393; p = 0.015) with unit change increasing tHCY by 8.25 units. Se remained predictive of tHCY levels after adjustments (vitamin B6, fibrinogen, triglycerides). Conclusions: lower Se was observed during acute IS, being inversely associated with and predicting increased tHCY levels. Of note, there were more IS patients with suboptimal Se than control

Long-term risk of stroke after transient ischaemic attack: a hospital-based validation of the ABCD² rule

Background: The ABCD2 clinical prediction rule is a seven point summation of clinical factors independently predictive of stroke risk. The purpose of this cohort study is to validate the ABCD2 rule in a Bulgarian hospital up to three years after TIA. Methods: All consecutive admissions to an emergency department with symptoms of a first TIA were included. Baseline data and clinical examinations including the ABCD2 scores were documented by neurologists. Discrimination and calibration performance was examined using ABCD2 cut-off scores of ≥3, ≥4 and ≥5 points, consistent with the international guidelines. The Hosmer-Lemeshow test was used to examine calibration between the observed and expected outcomes as predicted by ABCD2 score within the logistic regression analysis. Results: Eighty-nine patients were enrolled to the study with a mean age of 63 years (+/− 12 years). Fifty-nine percent (n = 53) of the study population was male. Seven strokes (7 · 8%) occurred within the first year and six further strokes within the three-year follow-up period. There was no incident of stroke within the first 90 days after TIA. The rule demonstrated good predictive (OR = 1 · 58, 95% CI 1 · 09-2 · 29) and discriminative performance (AUCROC = 0 · 72, 95% CI 0 · 58-0 · 86), as well as a moderate calibration performance at three years. Conclusion: This validation of the ABCD2 rule in a Bulgarian hospital demonstrates that the rule has good predictive and discriminative performance at three years. The ABCD2 is quick to administer and may serve as a useful tool to assist clinicians in the long-term management of individuals with TIA

Early neurological and cognitive impairments in subclinical cerebrovascular disease

Background: The subclinical cerebrovascular disease (SCVD) is an important public health problem with demonstrated prognostic significance for stroke, future cognitive decline, and progression to dementia. The earliest possible detection of the silent presence of SCVD in adults at age at risk with normal functioning is very important for both clinical doctors and scientists.Materials and Methods: Seventy-seven adult volunteers, recruited during the years 2005–2007, with mean age 58.7 (standard deviation 5.9) years, were assessed by four subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB)-Eclipse cognitive assessment system. We used a questionnaire survey for the presence of cerebrovascular risk factors (CVRFs) such as arterial hypertension, smoking and dyslipidemia, among others, as well as instrumental (Doppler examination) and neurological magnetic resonance imaging (MRI) procedures. Descriptive statistics, comparison (t-test, Chi-square) and univariate methods were used as followed by multifactor logistic regression and receiver operating characteristics analyses.Results: The risk factor questionnaire revealed nonspecific symptoms in 44 (67.7%) of the subjects. In 42 (64.6%) of all 65 subjects, we found at least one of the conventional CVRFs. Abnormal findings from the extra- and trans-cranial Doppler examination were established in 38 (58.5%) of all studied volunteers. Thirty-four subjects had brain MRI (52.3%), and abnormal findings were found in 12 (35.3%) of them. Two of the four subtests of CANTAB tool appeared to be potentially promising predictors of the outcome, as found at the univariate analysis (spatial working memory 1 [SWM1] total errors; intra-extra dimensional set 1 [IED1] total errors [adjusted]; IED2 total trials [adjusted]). We established that the best accuracy of 82.5% was achieved by a multifactor interaction logistic regression model, with the role CVRF and combined CANTAB predictor “IED total ratio (errors/trials) × SWM1 total errors” (P = 0.006).Conclusions: Our results have contributed to the hypothesis that it is possible to identify, by noninvasive methods, subjects at age at risk who have mild degree of cognitive impairment and to establish the significant relationship of this impairment with existing CVRFs, nonspecific symptoms and subclinical abnormal brain Doppler/MRI findings. We created a combined neuropsychological predictor that was able to clearly distinguish between the presence and absence of abnormal Doppler/MRI findings. This pilot prognostic model showed a relatively high accuracy of >80%; therefore, the predictors may serve as biomarkers for SCVD in subjects at age at risk (51–65 years)