[Show abstract][Hide abstract] ABSTRACT: We analyzed (a) insulin sensitivity (IS), (b) plasma insulin (PI), and (c) plasminogen activator inhibitor-1 (PAI-1) in type 2 diabetes (T2D) patients with (group A) and without (group B) atherothrombotic ischemic stroke (ATIS), nondiabetics with ATIS (group C), and healthy controls (group D). IS was determined by minimal model (Si). Si was lower in A versus B ( versus min−1/mU/L × 104; ) and in C versus D ( versus min−1/mU/L × 104; ). PI and PAI-1 were higher in A versus B (PI: versus mU/L; , PAI-1: versus mU/L; ) and in C versus D (PI: versus mU/L; , PAI-1: versus mU/L; ). Si correlated with PAI-1 in T2D patients and nondiabetics, albeit stronger in T2D. Binary logistic regression identified insulin, PAI-1, and Si as independent predictors for ATIS in T2D patients and nondiabetics. The results imply that insulin resistance and fasting hyperinsulinemia might exert their atherogenic impact through the impaired fibrinolysis.
International Journal of Endocrinology 01/2015; 2015:1-7. DOI:10.1155/2015/934791 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The age of onset of cluster headache (CH) attacks most commonly is between 20 and 40 years old, although CH has been reported in all age groups. There is increasing evidence of CH with early or late onset and a different course of the disorder. The aim of the study was to analyze the influence of the age of onset on clinical features, disorder course, and therapy effectiveness in CH patients.
A retrospective and cross-sectional analysis was performed on 182 CH patients divided into three groups according to the age of onset. The first group consisted of patients with the first CH attack before 20 years of age, the second group was patients with age of onset between 20 and 40 years of age, and the third group was patients with age of onset after 40 years of age. Demographic data, features of CH periods and attacks, and the response to standardized treatment were compared among the groups.
Patients with CH onset after 40 years of age reported a lower number of autonomic features and less frequently had conjunctival injection and nasal congestion/rhinorrhea phenomena during their attacks. Diagnostic delay was the longest in the patients with CH onset before 20 years of age.
The influence of the age of onset of CH is intriguing for further studies and could possibly extend the knowledge about CH pathophysiology. From a clinical point of view, the differences in CH presentation are insufficient to preclude a correct diagnosis and treatment because the same criteria could be applied regardless of patient age.
[Show abstract][Hide abstract] ABSTRACT: Idiopathic intracranial hypertension (IIH) is a pathological state defined as an increase of intracranial pressure in the absence of a causative pathological process. The aim of this study was to evaluate the clinical features of the patients with IIH diagnosed in our Headache Center according to the current knowledge of this disorder. In the retrospective and cross-sectional analysis of 3395 patients we present 12 newly diagnosed IIH patients, ten women and two men, aged from 19 to 51, with obtained values of cerebrospinal fluid pressure between 250 and 680 mm of water. The symptoms of IIH clinical presentation have been headache, reported by 92 % of patients; papilledema, noted in 67 %; and cranial nerve impairment (25 %). The results obtained from presented patients confirmed the presence of headache features that are included in criteria for headache attributed with IIH in majority of them: progressive, daily, diffuse, non-pulsatile headache with aggravation by coughing or straining. Decrease of pain intensity after lumbar puncture was noted in all patients. We notice the relatively small proportion of patients with headache attributed to IIH among the patients treated in our Headache Center. The prevalence of IIH is not low and headache is the most frequent presenting symptom; therefore, we could only conclude that some chronic headache patients refractory for treatment are patients with IIH.
[Show abstract][Hide abstract] ABSTRACT: We analyzed (a) insulin sensitivity (IS) and (b) glutathione peroxidase (GSH-Px), glutathione reductase (GR), and superoxide dismutase (SOD) antioxidant enzyme activity in type 2 diabetic (T2D) patients with atherothrombotic infarction (ATI) (group A), lacunar infarction (LI) (B), or without stroke (C) and in nondiabetics with ATI (D), LI (E), or without stroke (F). ATI and LI were confirmed by brain imaging IS levels were determined by
minimal model (Si index), and the enzyme activity by spectrophotometry. In T2D patients, Si was lower in A and B versus
C (1.14 ± 0.58, 1.00 ± 0.26 versus 3.14 ± 0.62 min−1/mU/l × 104, P < 0.001) and in nondiabetics in D and E versus F (3.38 ± 0.77, 3.03 ± 0.72 versus 6.03 ± 1.69 min−1/mU/l × 104, P < 0.001). Also, GSH-Px and GR activities were lower in A and B versus C (GSH-Px: 21.96 ± 3.56, 22.51 ± 1.23 versus 25.12 ± 1.67; GR: 44.37 ± 3.58, 43.50 ± 2.39 versus 48.58 ± 3.67 U/gHb; P < 0.001) and in D and E versus F (GSH-Px: 24.75 ± 3.02, 25.57 ± 1.92 versus 28.56 ± 3.91; GR: 48.27 ± 6.81, 49.17 ± 6.24 versus 53.67 ± 3.96 U/gHb; P < 0.001). Decreases in Si and GR were significantly related to both ATI and LI in T2D. Our results showed that decreased IS and impaired antioxidant enzymes activity influence ischemic stroke subtypes in T2D. The influence of insulin resistance might be exerted on the level of glutathione-dependent antioxidant enzymes.
International Journal of Endocrinology 06/2013; 2013:401609. DOI:10.1155/2013/401609 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The early presentation of autonomic dysfunctions at the disease onset has been considered the mandatory clinical feature in adult-onset autosomal dominant leukodystrophy, which is a rarely recognised leukodystrophy caused by duplication of the lamin B1 gene. We report the first family with adult-onset autosomal dominant leukodystrophy and lamin B1 duplication, without the distinguishing early-appearing autonomic dysfunctions. Subjects from three consecutive generations of a multi-generational Serbian family affected by adult-onset autosomal dominant leukodystrophy underwent clinical, biochemical, neurophysiological, neuroradiological, and genetic studies. The patients atypically exhibited late autonomic dysfunctions commencing at the disease end-stages in some. Genetic findings of lamin B1 duplication verified adult-onset autosomal dominant leukodystrophy, which was supported also by neuroimaging studies. Exclusively, proton magnetic spectroscopy of the brain revealed a possibility of neuro-axonal damage in the white matter lesions, while magnetic resonance imaging of the spinal cord excluded spinal myelin affection as a required finding in this leukodystrophy. The detection of lamin B1 duplication, even when autonomic dysfunctions do not precede the other symptoms of the disease, proves for the first time that lamin B1-duplicated adult-onset autosomal dominant leukodystrophy may have a phenotypic variant with delayed autonomic dysfunctions. Prior to this report, such a phenotype had been speculated to represent an entity different from lamin B1-duplicated leukodystrophy. Hereby we confirm the underlying role of lamin B1 duplication, regardless of the autonomic malfunction onset in this disorder. It is the only report on adult-onset autosomal dominant leukodystrophy from Southeastern Europe.
Journal of Neurology 05/2013; 260(8). DOI:10.1007/s00415-013-6958-3 · 3.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
According to the International Classification of Headache Disorders diagnostic criteria, the differences between migraine and cluster headache (CH) are clear. In addition to headache attack duration and pain characteristics, the symptoms accompanying headache represent the key features in a differential diagnosis of these 2 primary headache disorders. Just a few studies of patients with CH exist examining the presence of nausea, vomiting, photophobia, phonophobia, and aura, the features commonly accompanying migraine headache. The aim of this study was to determine the presence of migraine-like features (MF) in patients with CH and establish the significance of these phenomena related to other clinical features and response to treatment. Methods
One hundred and fifty-five patients with CH were studied, and 24.5% of them experienced at least one of MF during every CH attack. Nausea and vomiting were the most frequently reported MF. The clinical presentation between CH patients with and without MF was not significantly different with the exception of aggravation of pain by effort (20.6% vs 4.1%) and facial sweating (13.2% vs 0.85%), both more frequent in CH patients with MF. Conclusion
Inferred from the results of our study, the presence of MF in CH patients had no important influence on the diagnosis and treatment of CH patients. The major differences of these 2 primary headache disorders, attack duration, lateralization, and the nature of associated symptoms, as delineated in the International Classification of Headache Disorders, are still useful tools for effective diagnosis.
Headache The Journal of Head and Face Pain 03/2013; 53(9). DOI:10.1111/head.12077 · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vascular dementia (VaD) is the second most frequent dementia after Alzheimer's disease, and is diagnosed during lifetime in 20% of demented patients. Five-year survival rate in VaD is 39%, while it is estimated to be 75% in healthy persons of the same age. It is therefore important to make correct diagnosis of VaD early in the course of the disease. Risk factors forVaD are identical to stroke risk factors, and there are significant possibilities for the prevention of vascular cognitive decline. Cognitive decline develops acutely or step-by-step within three months after stroke, but more gradual progression of intellectual decline is also possible. Neurological examination can reveal pyramidal and extrapyramidal signs, pseudobulbar palsy, gait disturbance and urinary incontinence. Neuropsychological profile comprises the loss of cognitive set shifting, decline in word fluency, verbal learning difficulties, perseverations, difficulties in complex figure copying, and in patients with cortically located lesions also problems with speech and praxia. The basis of the diagnosis is, besides history, neurological examination and neuropsychological assessment, computed tomography and/ or magnetic resonance brain imaging. Vascular risk factors control is the most important measure in VaD prevention. Modern guidelines for the treatment of cognitive decline in VaD emphasize that donepezil can be useful in the improvement of cognitive status at the level of Class Ila recommendation at the level of evidence A, while memantine may be useful in patients with mixed VaD and Alzheimer's disease dementia.
Srpski arhiv za celokupno lekarstvo 03/2013; 141(3-4):247-55. DOI:10.2298/SARH1304247P · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IntroductionAura occurs in 20-30% of patients with migraine. Some descriptions of aura go far beyond the most frequent visual and sensory symptoms, suggesting the involvement of different cortical areas. The aim of this prospective study was to evaluate the frequency and types of disorders of higher cortical functions (HCF) that occur during visual and/or sensory aura.Methods
We interviewed 60 patients with visual and/or sensory aura about HCF disorders of praxia, gnosia, memory, and speech, during aura. Patients were divided into two groups, with and without HCF disorders, and were compared in terms of demographic data and aura characteristics.ResultsFrom all 60 patients, 65% reported at least one HCF disorder during aura. The patients with HCF disorders had longer-lasting auras (28.51 ± 16.39 vs. 19.76 ± 11.23, p = 0.016). The most common HCF disorders were motor dysphasia (82.05%) and dysnomia (30.74%). Motor dysphasia was more often reported by patients with visual as well as sensory aura (p = 0.002). The number of HCF disorders correlated with the aura duration (p = 0.003).Conclusion
According to our results, HCF disorders during aura occur more often than previously thought. The aura duration has some influence on the HCF disorders.
[Show abstract][Hide abstract] ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common heritable cause of stroke and vascular dementia in adults. We present a family from Serbia presenting with stroke and depression in the lack of vascular risk factors, with brain MRI indicating CADASIL. A novel NOTCH3 Gly89Cys mutation was located in exon 3. This report illustrates that in the setting of a positive family history with typical clinical and MRI features, even with an atypical form of pedigree, a high suspicion of CADASIL should lead to genetic testing.
[Show abstract][Hide abstract] ABSTRACT: Background and aims
The role and importance of insulin sensitivity (IS) and related atherogenic conditions in ischemic stroke have not yet been elucidated. Therefore, our study was aimed to analyze (a) IS and plasma insulin (PI) (b) lipoproteins (c) plasminogen activator inhibitor 1 (PAI-1) levels (d) inflammatory markers, hs-C reactive protein (hs CRP) and interleukin-6 (IL-6) levels (e) abdominal obesity, in 40 type 2 diabetics (T2D) with ischemic stroke (group A), 35 T2D without ischemic stroke (group B), 35 nondiabetics with ischemic stroke (group C) and 34 healthy controls (group D).
Material and Methods
Ischemic stroke was confirmed by clinical and neuroimaging criteria. IS levels were determined by the frequently sampled intravenous glucose tolerance (FSIGT) test with minimal model analysis (Si index). Total cholesterol, HDL-cholesterol (HDL-c), and tryglicerides concentracion were determined with the chromatography metod. LDL-cholesterol (LDL-c) concentrations were calculated using the Friedewald formula. Plasma PAI-1 activity was determined by plasminogen chromogenic plasmin substrate assay. Hs-CRP was determined by Olympus Analyzer and interleukin 6 (IL-6) levels were measured by ELISA method. Waist circumference was measured at the midpoint between the lower border of the rib cage and the iliac crest.
Si levels were significantly lower in group A vs B (1.15+/−0.46 vs 2.81+/−0.65 min-1/mU/lx104; p<0.001) and in C vs D (3.12+/−0.77 vs 6.10+/−1.64 min-1/mU/lx104; p<0.001). However, PI levels were higher in group A vs B (19.96+/−4.10 vs 14.84+/−1.73 mU/l; p<0.001) and in C vs D (16.14+/−2.20 vs 7.76+/−2.08 mU/l; p<0.001). Also, LDL-c and PAI-1 were significantly higher in group A vs B (5.21±0.42vs 4.12±0.53 mmol/l; p<0.001), (7.73+/−1.04 vs 4.58+/−0.66 mU/l; p<0.001) and in C vs D (4.24±0.53 vs 3.66±0.52 mmol/l; p<0.001), (4.60+/−0.64 vs 3.40+/−1.23 mU/l; p<0.001). Simultaneously, hs CRP and IL-6 levels were significantly higher in A vs B [16.02±2.23 vs 9.78 ±1.95 g/l p<0.05; 20.14±4.56 vs 14.98+/−5.04 pg/ml p<0.05] and C vs D [7.54±0.67 vs 2.50±0.32 g/l p<0.01; 11.45±6.26 vs 3.36+/−1.44 pg/ml p<0.01]. Also, waist circumference was higher in group A vs B (103,26 +/−2,56 vs 93,97 +/−9,51; p<0.01), and in C vs D (101,00 +/−1,27 vs 84,19 +/−1,45; p <0.001). The changes in Si significantly correlated with LDL-c, PAI-1, hs-CRP, IL-6 levels and waist circumference, both in T2D (r=−0.388 r=−0.376 r=−0.368 r=−0.413 r=−0.403, p<0.05) and nondiabetics (r=−0.398 r=−0.369 r=−0.372; r=−0.432 r=−0.394, p<0.05).
Our results demonstrated that decreased IS are associated with increased LDL-c, decreased PAI-1, together with higher hs-CRP, IL-6 levels and waist circumference, both in T2D and nondiabetics. These results imply that decreased IS in association with compensatory hyperinsulinemia, underlying the development of the ischemic stroke, through potentiation of dislipidemia, hypofibrinolisis, low-grade inflammation and abdominal obesity.
[Show abstract][Hide abstract] ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited vascular disorder caused by Notch3 gene mutations. The main histopathological hallmark is granular osmiophilic material (GOM) deposited in the close vicinity of vascular smooth muscle cells (VSMCs). The authors report the first 7 ultrastructurally and genetically confirmed cases of CADASIL in Serbia. Samples of skin and sural nerve were investigated by transmission electron microscopy. GOM deposits were observed around degenerated VSMCs in all the skin biopsies examined. Sural nerve biopsies revealed severe alterations of nerve fibers, endoneurial blood vessels with GOM deposits, endoneurial fibroblasts, and perineurial myofibroblasts. Total genomic DNA was extracted from peripheral blood leukocytes, and exons 2-6 of the Notch3 gene were amplified by PCR and subsequently sequenced. Four different mutations in exons 2 (Cys65Tyr), 3 (Gly89Cys and Arg90Cys), and 6 (Ala319Cys), which determine the CADASIL disease, were detected among all described patients. A novel missense mutation Gly89Cys involving exon 3 was detected. Due to the difficulties in the determination of the Notch3 mutations, these data suggest that electron microscopic analysis for GOMs in dermal vessel wall provides a rapid and reliable screening method for this disease.
[Show abstract][Hide abstract] ABSTRACT: Stroke is a major medical problem and one of the leading causes of mortality and disability all over in Europe. However, there are significant East-West differences in stroke care as well as in stroke mortality and morbidity rates. Central and Eastern European countries that formerly had centralized and socialist health care systems have serious and similar problems in organizing health and stroke care 20 years after the political transition. In Central and Eastern Europe, stroke is more frequent, the mortality rate is higher, and the victims are younger than in Western Europe. High-risk patients live in worse environmental conditions, and the socioeconomic consequences of stroke further weaken the economic development of these countries. To address these issues, a round table conference was organized. The main aim of this conference was to discuss problems to be solved related to acute and chronic stroke care in Central and Eastern European countries, and also, to exchange ideas on possible solutions. In this article, the discussed problems and possible solutions will be summarized, and introduce 'The Budapest Statement of Stroke Experts of Central and Eastern European countries'.
International Journal of Stroke 09/2012; 8(5). DOI:10.1111/j.1747-4949.2012.00845.x · 4.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The vascular risk factors are associated with an increased risk for vascular cognitive decline (VCD), but also with Alzheimer disease (AD).
To investigate vascular risk factors in relation to AD and VCD, with a non-invasive neurosonological methods in a clinical settings.
A total of 296 patients with AD and 237 patients with VCD were included in the study. Hypertension, hyperlipidemia, diabetes mellitus, stroke, and white matter changes (p<0.001) were significantly more prevalent in VCD, although they were also present in AD patients. No statistically significant differences were obtained between groups regarding coronary disease, atrial fibrillation, average degree of carotid artery stenosis and carotid intima-media thickness (cITM). However, the patients with AD had carotid artery stenosis ">50%" (p=0.007) and present plaques (p<0.001) more frequently compared to vascular group. The significant associations between robust cognitive measure and vascular factors, diabetes mellitus, carotid stenosis, cITM, and type of plaques were identified only in VCD, but not in AD group.
The vascular risk factors were more prevalent in VCD group, although they were also present in AD. With few treatment options available in AD, it may be important not to neglect the vascular risk factors.
Journal of the neurological sciences 08/2012; 322(1-2):166-9. DOI:10.1016/j.jns.2012.07.065 · 2.26 Impact Factor