Atypical clinical and radiologic findings in a patient with brain metastatic lesions.

We report the case of a 47-year-old man who was admitted to our clinic with an intractable headache, nausea, and sporadic vomiting, as well as speech difficulties and a 'floating' sensation. This man had no prior medical history. MRI of the brain showed evidence of over 20 supra- and infratentorial capsulated ring-enhancing lesions. All other paraclinical investigations done in our clinic were unremarkable and we excluded our first assumption of neurocysticercosis, as well as other parasitic infections. The patient was then referred to the Oral and Maxillofacial Surgery Clinic for an excisional biopsy of a submandibular formation, which was later verified to represent a lymph node metastasis from a poorly differentiated adenocarcinoma. A chest X-ray failed to demonstrate any significant pathology and the immunohistochemical constellation of the lymph node metastasis excluded the possibility of the primary tumor originating in the lung or the prostate. Due to the unresolved diagnostic query, a whole-body PET/CT was performed demonstrating a formation with malignant characteristics in the basal segment of the left lung, reaching the pleura and the left hilum, as well as solitary enlarged mesenteric and mediastinal lymph nodes. Following clinical consultations, it was determined that the patient was inoperable and chemotherapy and palliative CNS irradiation were recommended.

Contribution of Components of Metabolic Syndrome to Cognitive Performance in Middle-Aged Adults.

INTRODUCTION: Metabolic syndrome (MetS) has been associated with impaired cognition in different cognitive domains. This study investigated the association between MetS and cognitive functioning in middle-aged Bulgarians across different definitions of MetS severity. MATERIAL AND METHODS: Our cross-sectional sample included 112 participants (67 free of MetS and 45 with MetS) with a mean age of 50.04 ± 3.31 years. The following MetS variables were considered-presence of MetS, continuously measured MetS components, dichotomized MetS components, number of MetS components present, and Metabolic Syndrome Severity Score (MSSS). Participants' cognitive performance was assessed using the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB). We employed multivariate regression models to investigate the associations between different measures of MetS severity and CERAD-NB total and subtest scores. RESULTS: Bivariate analyses showed that the CERAD-NB total score was significantly higher in women, participants with a university degree, those with normal blood pressure, normal waist circumference, and low triglyceride levels, compared with their counterparts. MetS participants had lower CERAD-NB total score (78.87 ± 6.89 vs. 84.97 ± 7.84) and specifically performed poorer on the subtest Word List Recall (7.16 ± 1.52 vs. 7.99 ± 1.52). These findings persisted after controlling for age, gender, and education. Next, generalized linear regression indicated that the CERAD-NB total score was lower in participants with MetS (ß = -4.86; 95% confidence interval [CI]: -7.60, -2.11), those with more MetS components (ß = -8.31; 95% CI: -14.13, -2.50 for fours vs. 0 components) and with an increase in MSSS (ß = -3.19; 95% CI: -4.67, -1.71). Hypertension independently contributed to lower CERAD-NB total score (ß = -4.00; 95% CI: -6.81, -1.19). CONCLUSIONS: Across several definitions, MetS was associated with lower cognitive functioning, and MetS severity appeared to be a better predictor than most MetS components. Recognizing and reducing severity of MetS components might be helpful in supporting cognitive functioning. Further longitudinal research is needed to shed more light on the relationship between MetS and cognitive functioning across the life span.

A feasibility study on the association between residential greenness and neurocognitive function in middle-aged Bulgarians.

Recent research has indicated that exposure to residential vegetation ("greenness") may be protective against cognitive decline and may support the integrity of the corresponding brain structures. However, not much is known about these effects, especially in less affluent countries and in middle-aged populations. In this study, we investigated the associations between greenness and neurocognitive function. We used a convenience sample of 112 middle-aged Bulgarians and two cognitive tests: the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB) and the Montreal Cognitive Assessment (MoCA). In addition, structural brain imaging data were available for 25 participants. Participants' home address was used to link cognition scores to the normalised difference vegetation index (NDVI), a measure of overall neighbourhood vegetation level (radii from 100 to 1,000 m). Results indicated that higher NDVI was consistently associated with higher CERAD-NB and MoCA scores across radial buffers and adjustment scenarios. Lower waist circumference mediated the effect of NDVI on CERAD-NB. NDVI100-m was positively associated with average cortical thickness across both hemispheres, but these correlations turned marginally significant (P<0.1) after correction for false discovery rate due to multiple comparisons. In conclusion, living in a greener neighbourhood might be associated with better cognitive function in middle-aged Bulgarians, with lower central adiposity partially accounting for this effect. Tentative evidence suggests that greenness might also contribute to structural integrity in the brain regions regulating cognitive functions. Future research should build upon our findings and investigate larger and more representative population groups.

Vascular Risk Factors in Bulgarian Volunteers in Middle Adulthood.

The present study in Bulgarian volunteers aged 45-55 years focuses on the type and frequency of some vascular risk factors (VRF); it analyzes physical data and results of instrumental investigations (ophthalmoscopy, electrocardiography, Doppler sonography) as well as magnetic resonance imaging (MRI). The study participants have neither subjective memory complaints nor previous cerebrovascular and cardiovascular incidents. The neurological examination and the mental status is normal and VRF are not considered to aff ect their normal daily living. The arterial hypertension (I degree), dyslipidemia and increased LDL-cholesterol correlate with the pathological findings from Doppler/MRI. The regression model explains 35% of the dispersion in statistics and correctly classifies 76.8% of the observations as independent prognostic factors for the presence of abnormal findings from Doppler/MRI at the age from 45 to 55 years, which corresponds to subclinical cerebrovascular disease.

Cortisol Correlates with Structural Magnetic Resonance Imaging Parameters in Middle Aged Bulgarian Patients with Metabolic Syndrome: A Pilot Study.

BACKGROUND: There is a dose-dependent relationship between chronically increased cortisol levels and the number of metabolic syndrome (MetS) components. Both cortisol and MetS are linked to various brain abnormalities. AIM: To investigate an association of MetS components and salivary cortisol levels with cortical thickness in middle-aged Bulgarian patients with MetS. MATERIALS AND METHODS: We examined 26 healthy volunteers (mean age 50, 16±3.1 yrs) divided into two groups depending on whether or not they were diagnosed with MetS. Salivary cortisol was sampled and tested at two time points -morning and evening. Cortical thickness measures were obtained from structural T1-images using FreeSurfer software. We performed vertex-wise analysis across entire cortex and for preselected brain regions in frontal, temporal and cingulate cortex partial correlation analysis, accounting for gender. RESULTS: The control group consisted of 12 women; in the MetS group there were 6 men and 8 women. The whole brain analysis showed that waist circumference (WC) was negatively correlated with cortical thickness in rostro-lateral area in left frontal lobe and the right lateral orbito-frontal cortex. Morning cortisol levels, accounting for sex and WC, correlated negatively with thickness in left superior temporal area (r = -0.477, p = 0.039) and entorhinal area (r = -0.465, p = 0.045) and left mediotemporal cortex (r = -0.477, p = 0.038). CONCLUSION: Our pilot study confirmed that WC is associated with brain atrophic changes mainly in the frontal lobe. Our finding that cortisol levels negatively correlate with thinning of the cortex in temporal lobe should be further explored in subsequent study.

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).

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, χ2) 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 CVD risk 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.

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.

A case of rheumatoid arthritis presenting with postherpetic neuralgia and abdominal-wall pseudohernia.

Postherpetic neuralgia is a common complication, while the postherpetic abdominal-wall pseudohernia (AWP) is a quite rare complication of herpes zoster (HZ). We report a patient >45 years of age with a history of rheumatoid arthritis (RA) who presented with two chronic HZ complications. A 75-year-old woman was admitted with neuralgia following cutaneous herpes zoster 6 weeks before. She was on long-term glucocorticoid, antimalarial and non-steroidal anti-inflammatory treatment. Confluent ulcers began to fill with granulation tissue, crusts, scars and skin discoloration in the area of the left T12-L2 dermatomes and reducible, painless swelling of the left flank, 20 × 20 cm, without palpable defect in abdominal-wall. There were typical joint deformity and positive rheumatoid factor. On neurological examination superficial abdominal reflexes were diminished in the left side, with hypesthesia of the overlying skin. Needle electromyography revealed denervational changes limited to the left-side muscles (on affected dermatomes T12-L2). Thoracoabdominal CT did not reveal the presence of existing hernia. There was an abdominal distension, the left abdominal-wall was thinner than the right side. The patient was treated with an oral preparation containing benfotiamine and vitamins B6 and B12, carbamazepine, amitriptyline, gabapentin, and local lidocaine. Skin rash left with scarring and pigmentary changes and the abdominal-wall swelling resolved within 8 months, however, the pain still persisted. To our best knowledge, this is the first observation of RA-associated postherpetic AWP. This rare motor complication appears to be self-limited with a good prognosis for recovery, while postherpetic neuralgia may require a combination of treatments for adequate pain relief. Older age, female sex, greater rash and acute pain severity are considered as risk factors associated with severe postherpetic neuralgia. In addition, patients with RA, mainly those treated with oral corticosteroids, are also at increased risk of HZ complications.

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 micromol/l) and lower Se levels (1.3 +/- 0.5 micromol/l). Twice as many IS patients (23%) had optimal Se levels of <1.01 mumol/l. Subjects with hyperhomocysteinaemia (tHCY > or =15 micromol/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 controls.

Cyclic patterns of incidence rate for skin malignant melanoma: association with heliogeophysical activity.

BACKGROUND: Our previous studies revealed cyclicity in the incidence rate of skin malignant melanoma (SMM; ICD9, Dx:172) in the Czech Republic (period T=7.50-7.63 years), UK (T=11.00 years) and Bulgaria (T=12.20 years). Incidences compared with the sunspot index Rz (lag-period dT=+2, +4, +6, +10 or +12 years) have indicated that maximal rates are most likely to appear on descending slopes of the 11-year solar cycle, i.e., out of phase. We summarized and explored more deeply these cyclic variations and discussed their possible associations with heliogeophysical activity (HGA) components exhibiting similar cyclicity. METHODS: Annual incidences of SMM from 5 countries (Czech Republic, UK, Bulgaria, USA and Canada) over various time spans during the years 1964-1992 were analyzed and their correlations with cyclic Rz (sunspot number) and aa (planetary geomagnetic activity) indices were summarized. Periodogram regression analysis with trigonometric approximation and phase-correlation analysis were applied. RESULTS: Previous findings on SMM for the Czech Republic, UK and Bulgaria have been validated, and cyclic patterns have been revealed for USA (T=8.63 years, P<0.05) and Canada (Ontario, T=9.91 years, P<0.10). Also, various 'hypercycles' were established (T=45.5, 42.0, 48.25, 34.5 and 26.5 years, respectively) describing long-term cyclic incidence patterns. The association of SMM for USA and Canada with Rz (dT=+6 and +7 years, respectively) and aa (dT=-10 and +9 years, respectively) was described. Possible interactions of cyclic non-photic influences (UV irradiation, Schumann resonance signal, low-frequency geomagnetic fluctuations) with brain waves absorbance, neuronal calcium dynamics, neuro-endocrine axis modulation, melatonin/serotonin disbalance and skin neuro-immunity impairment as likely causal pathways in melanoma appearance, were also discussed. CONCLUSION: The above findings on cyclicity and temporal association of SMM with cyclic environmental factors could not only allow for better forecasting models but also lead to a better understanding of melanoma aetiology.

Major vascular events after transient ischaemic attack and minor ischaemic stroke: post hoc modelling of incidence dynamics.

BACKGROUND: Only few follow-up studies have compared the long-term risk of such major vascular events (MVE) as myocardial infarction (MI) and/or stroke following transient ischaemic attack (TIA) or minor ischaemic stroke (MIS). Estimates of relative risk and cumulative long-term occurrence of MVE may provide better information and contribute to the optimization of treatment decisions. METHODS: In the current post hoc modelling study with unique data from Bulgaria, we analysed 183 consecutive patients with TIA (n = 89) or MIS (n = 94), aged >40 years, who were prospectively followed over 36 months for non-fatal or fatal MVE. The cumulative survival, hazard and risks (with 95% confidence intervals) for MVE (combined or by stratification) were calculated by Kaplan-Meier analysis and adjusted (age, sex) by multivariate Cox proportional hazard models. A set of regression models was then applied to MVE incidence (per 100 patients; 4-month intervals). RESULTS: Median follow-up was 36 months (interquartile range 30.8-36.0); no differences by age or sex were found (p > 0.05). The risk of non-fatal or fatal MVE was approximately 28% (stroke 19.7%, MI 8.2%). The adjusted cumulative risk of stroke was 0.21 versus 0.10 for MI. The odds ratio of TIA versus MIS was 0.75 (95% CI 0.43-1.32), i.e. lower for stroke (0.63, 0.31-1.25) than for MI (1.12, 0.40-3.14). The risk of non-fatal MVE was higher in MIS than in TIA (p(Breslow) = 0.0497), especially for non-fatal stroke (p = 0.0325). Time series regression models provided best estimates of the different outcome dynamics in TIA versus MIS (R(2)(TIA) = 0.969 with b(power) = 1.04 vs. R(2)(MIS) = 0.989 with b(linear) = 0.84; p(1-tailed) = 0.04) over the study period. CONCLUSIONS: The age- and sex-adjusted cumulative 36-month hazard of MVE is higher after MIS than after TIA, but MVE fatality was higher after TIA than after MIS. Although stroke incidence was higher (up to 3 times that of MI), with the highest difference between months 8 and 18, MI fatality was always higher in absolute, relative or adjusted terms. The above alarming patterns and increasing, diverging tendencies for MVE indicate a higher long-term cumulative risk after MIS compared with TIA. These results confirm our hypothesis of a differential risk of TIA versus MIS and, at least, point toward equal importance of therapies aimed at preventing MVE in both types of preceding conditions (TIA or MIS) and the increased fatality after MI, in particular in patients with TIA.

Antiphospholipid syndrome and vascular ischemic (occlusive) diseases: an overview.

Antiphospholipid syndrome (APS) is primarily considered to be an autoimmune pathological condition that is also referred to as "Hughes syndrome". It is characterized by arterial and/or venous thrombosis and pregnancy pathologies in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disease or secondary to a connective tissue disorder, most frequently systemic lupus erythematosus (SLE). Damage to the nervous system is one of the most prominent clinical constellations of sequelae in APS and includes (i) arterial/ venous thrombotic events, (ii) psychiatric features and (iii) other non- thrombotic neurological syndromes. In this overview we compare the most important vascular ischemic (occlusive) disturbances (VIOD) with neuro-psychiatric symptomatics, together with complete, updated classifications and hypotheses for the etio-pathogenesis of APS with underlying clinical and laboratory criteria for optimal diagnosis and disease management.

Brain metastases of melanoma--mechanisms of attack on their defence system by engineered stem cells in the microenvironment.

This report gives a better emphasis on the role of targeted effectors (e.g. a combination of 5-FC with CD-NSPCs as compared to the application of NSPCs alone) and how such delivery of pro-drug activating enzymes and other tumor-killing substances may overcome melanocytic defence system, interact with and promote the host defence and immune response modulations not only in melanoma but, potentially, in other highly-metastatic cancers.

Modelling of increased homocysteine in ischaemic stroke: post-hoc cross-sectional matched case-control analysis in young patients.

BACKGROUND & PURPOSE: Hyperhomocysteinaemia has been postulated to participate in pathogenesis of ischaemic stroke (IS). However, especially in young adults, there is possibility of significantly increased IS risk due to increased normal homocysteinaemia, i.e., hidden (pathologically dormant) prevalence within a healthy, normally-defined range. We performed a post-hoc modelling investigation on plasma total homocysteinaemia (THCY) in gender- and age-matched young patients in the acute IS phase. We evaluated relationships between THCY and prevalence of other potential risk factors in 41 patients vs. 41 healthy controls. METHOD: We used clinical methods, instrumental and neuroimmaging procedures, risk factors examination, total plasma homocysteine measurements and other laboratory and statistical modelling techniques. RESULTS: IS patients and healthy controls were similar not only for matching variables, but also for smoking, main vitamin status, serum creatinine and lipid profile. Patients with IS, however, had lower vitamin B6 levels and higher THCY, fibrinogen and triglycerides (TGL). At multivariate stepwise logistic regression only increased THCY and TGL were significantly and independently associated with the risk for stroke (72% model accuracy, p model=0.001). An increase of THCY with 1.0 micromol/L was associated with 22% higher risk of ischaemic stroke [adjusted OR=1.22 (95%CI 1.03?1.44)]. In this way, novel lower cut-off value for HCY of 11.58 micromol/L in younger patients has been revealed (ROC AUC= 0.67, 95CI% 0.55-0.78, p=0.009). CONCLUSION: The new THCY cut-off clearly discriminated between absence and presence of IS (sensitivity>63%, specificity>68%) irrespectively of age and gender and may be applied to better evaluate and more precisely define, as earlier as possible, the young patients at increased IS risk.

Modelling of increased homocysteine in ischaemic stroke: post-hoc cross-sectional matched case-control analysis in young patients

BACKGROUND & PURPOSE: Hyperhomocysteinaemia has been postulated to participate in pathogenesis of ischaemic stroke (IS). However, especially in young adults, there is possibility of significantly increased IS risk due to increased ænormalÆ homocysteinaemia, i.e., æhiddenÆ (æpathologically dormantÆ) prevalence within a healthy, normally-defined range. We performed a post-hoc modelling investigation on plasma total homocysteinaemia (THCY) in gender- and age-matched young patients in the acute IS phase. We evaluated relationships between THCY and prevalence of other potential risk factors in 41 patients vs. 41 healthy controls. METHOD: We used clinical methods, instrumental and neuroimmaging procedures, risk factors examination, total plasma homocysteine measurements and other laboratory and statistical modelling techniques. RESULTS: IS patients and healthy controls were similar not only for matching variables, but also for smoking, main vitamin status, serum creatinine and lipid profile. Patients with IS, however, had lower vitamin B6 levels and higher THCY, fibrinogen and triglycerides (TGL). At multivariate stepwise logistic regression only increased THCY and TGL were significantly and independently associated with the risk for stroke (72 percent model accuracy, p model=0.001). An increase of THCY with 1.0 æmol/L was associated with 22 percent higher risk of ischaemic stroke [adjusted OR=1.22 (95 percentCI 1.03?1.44)]. In this way, novel lower cut-off value for HCY of 11.58 æmol/L in younger patients has been revealed (ROC AUC= 0.67, 95CI percent 0.55-0.78, p=0.009). CONCLUSION: The new THCY cut-off clearly discriminated between absence and presence of IS (sensitivity>63 percent, specificity>68 percent) irrespectively of age and gender and may be applied to better evaluate and more precisely define, as earlier as possible, the young patients at increased IS risk.

OBJETIVO: Hiperhomocisteinemia tem sido postulada como um dos fatores de risco na patogênese do acidente vascular cerebral isquêmico (AVCI). Todavia, em adultos jovens existe a possibilidade de aumento significativo de risco de AVCI devido a aumento "normal" da homocisteinemia, "oculta" (patologicamente adormecida) dentro de uma variação definida como normal. Neste trabalho foi investigado um modelo post-hoc de dosagem de homocisteina no plasma (HC) em pacientes jovens com AVCI agudo pareados por gênero e idade. Foi avaliado também relações entre HC e prevalência de outros fatores de risco para AVCI em 41 pacientes e 41 controles normais. MÉTODO: Foi utilizado exame clínico, procedimentos instrumentais e de neuroimagem, exame de fatores de risco, dosagem da homocisteína no plasma, outros exames laboratoriais e análise estatística. RESULTADOS: Não foram encontradas diferenças quanto a presença de fumantes, dosagem de vitaminas, creatinina sérica e perfil lipídico entre os pacientes com AVCI e os controles normais. Todavia os pacientes com AVCI apresentaram diminuição de níveis de vitamina B6 e aumento de homocisteína, fibrinogênio e trigliceridios. A análise multivariada de regressão logística mostrou diferenças significativas apenas para HC e trigliceridios independentemente associadas para fatores de risco para AVCI (72 por cento acuracia, p= 0,001). Um aumento de homocisteína de 1,0 æmol/L estava associado com aumento de 22 por cento de risco de AVCI [OR=1,22 (95 por centoIC 1,03-1,44)]. Foi evidenciado portanto um novo valor de cut-off para HC de 11,58 æmol/L em pacientes jovens com AVCI (ROC auc=0,67, 95 por cento IC 0,55-0,78, p= 0,009). CONCLUSÃO: Este novo valor de cut-offpara a homocisteína discrimina claramente a ausência ou presença de AVCI (sensibilidade >63 por cento, especificidade >68 por cento) independente do gênero ou idade e deve ser aplicado para uma melhor avaliação precoce de pacientes jovens com risco de AVCI.