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  • Author: S. Ivanov x
  • Clinical Medicine x
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AIM: To suggest diagnostic combinations of symptoms for migraine and tension type headache (TTH), and for differentiation of overlapping headache (classified as either migraine or TTH) through evaluation of the diagnostic value of combinations of characteristics included in the International Headache Society diagnostic criteria for migraine and TTH in children and adolescents.

PATIENTS AND METHODS: The study comprised an epidemiological school-based study (412 of 1029 pupils with chronic / recurrent headache) and a clinical study conducted in the Pediatric Neurology Ward and outpatient clinic at Plovdiv Medical University Hospital (203 patients with chronic / recurrent headache). An inclusion criterion was at least two episodes of headache during the last year. Exclusion criteria were: headache occurring only during acute infections; withdrawal of informed consent. Headache was classified according to the International Classification of Headache Disorders 2nd edition (ICHD-II) The diagnostic value of all combinations of items in criteria C and D for migraine and TTH was measured by sensitivity, specificity, and odds ratio.

RESULTS: The combination “unilateral location, severe intensity, aggravation by physical activity” had 100% specificity for migraine. The combination “bilateral location, pressingtightening

quality, mild intensity, no aggravation by physical activity” had 100% specificity for TTH. The combinations: “migrainous location, severe intensity, aggravation by physical

activity”, “severe intensity, nausea”, “pulsating quality, nausea”, “pulsating quality, migrainous

location, aggravation by physical activity” seemed to pose the greatest risk for developing migraine. These combinations - “no nausea, no photophobia”, “bilateral location, mild intensity and either no aggravation by physical activity or pressing-tightening quality, or no nausea or no photophobia” increased the most the TTH risk. Using these combinations as additional criteria for overlapping headache we classi ed 50% of overlapping headache as TTH and 8.3% as migraine.

CONCLUSIONS: Some combinations of symptoms clarify the diagnosis of migraine and TTH. More than 50% of overlapping headache could be differentiated as TTH or MWA by the proposed combinations.


Background: Development of biomarkers for autism spectrum disorder (ASD) has still remained a challenge to date. Recently, alterations of the expression of microRNAs (miRNAs) in peripheral blood, serum and post-mortem brain tissue have been linked to ASD. miRNAs are known to be secreted by various cell types and can mediate transmission of information into recipient cells and to modulate their physiological functions. On this basis it is assumed that circulating miRNAs could be useful biomarkers for the diagnosis or prognosis of pathological conditions.

Aim: The aim of this study was to test whether circulating miRNAs display differential expression profile in serum of ASD patients.

Patients and methods: The relative expression levels of 42 miRNAs were analyzed by stem-loop qRT-PCR assay in the serum of ASD patients compared to healthy controls.

Results: The results indicated that 11 miRNAs in ASD patients were substantially higher expressed than these in control subjects, and 29 miRNAs were lower expressed, respectively. In addition, target gene analysis displayed that the altered serum miRNAs targeted some important genes like alpha 1C subunit of voltage-dependent calcium channel, L type, (CACNA1C), beta 1 subunit of voltage-dependent calcium channel (CACNB1) and other genes involved in epigenetic processes like dicer 1, coding ribonuclease type III (DICER).

Conclusion: Our results suggested that differentially expressed miRNAs in serum might be involved in ASD molecular pathways, and serum miR-424-5p, miR-197- 5p, miR-328-3p, miR-500a-5p, miR-619-5p, miR-3135a, miR-664a-3p, and miR- 365a-3p might be able to serve as potential biomarkers for ASD because they displayed significant alterations in the expression profile in children diagnosed with ASD.


Background: Most thyroid nodules are benign and do not need intervention. Toxic adenoma and toxic multinodular goiter (MNG) are common causes of hyperthyroidism, second in prevalence only to Graves’ disease. Toxic adenoma and MNG are the result of focal or diffuse hyperplasia of thyroid follicular cells whose functional capacity is independent from regulation by the thyroid stimulating hormone (TSH). When conservative treatment modalities fail to ensure an euthyroid state, surgical intervention is required, typically surgical left or right thyroid lobectomy. Radiofrequency ablation (RFA) is a new percutaneous treatment option that results in thermal tissue necrosis and fibrosis. As a result of this process, the thyroid nodules shrink.

Case presentation: We describe a case of a young woman with a large toxic thyroid adenoma who refused surgery. She was admitted to a one-day surgery unit and underwent radiofrequency ablation under total intravenous anesthesia. Using “moving shot technique” the procedure went uneventfully and the toxic adenoma displayed a significant volume reduction with resolution of the hyperthyroid symptoms. The patient also reported a significant improvement of her neck symptoms (from 7/10 to 1/10 on a Visual Analogue Scale).

Conclusions: Radiofrequency ablation is a new, well tolerated, safe and effective treatment option in selected patients with benign thyroid nodules, toxic adenomas of the thyroid gland and multinodular goiter. To the best of our knowledge, this is the first time such treatment modality is used in Bulgaria.


The aim of the study was to explore the impact of oxidative stress on frozen seminal plasma in fertile and infertile men by examining the total antioxidant capacity. Patients: Infertile patients from male infertility clinic with various diagnoses and fertile men. Design: Seminal plasma from proven fertile men [n=50] and infertile patients [n=50] were examined for total antioxidant capacity (TAC) level, semen parameters such as morphology, motility and concentration, and DNA integrity test. Interventions: Seminal plasma TAC measurement by luminometric assay using the TAC assay kit, semen analysis parameters, DNA integrity test. Fertile men showed higher TAC values (median and SD): 1201µM (SD±548), as compared with the infertile patients: 831μM (SD±343). The result from sperm morphology of fertile patients showed a mean percentage of 4.8 % (SD±1.68) whereas the percentage in the infertile group was 2.68% (SD ±1.68). The same group of samples, analyzed for DNA damage showed a mean of DFI 10.38% (SD±5.17%) in fertile men and a mean of DFI 17.22% (SD±7.22%) in infertile men. Total antioxidant capacity of the seminal plasma as measured by the luminоmetric assay is a reliable and simple test for diagnosing and management of male infertility.


Spinal neurofibroma is one of the rarest of the neoplasms involving the spinal cord or roots and occurs much less often than neurinoma, meningioma or glioma. The sixth pediatric case of solitary intramedullary tumor was described in 2013, according to B. Eljebbouri et al. We present a rare, difficult to diagnose and may-be the seventh pediatric case of solitary neurofibroma of the cauda equine in an 11-month-old infant. The patient underwent a laminectomy of T12, L1, L2 and L3, extirpation of intradural, intramedullary and extramedullary spinal cord tumor. The patient is fully recovered for 5 years of monitoring. Although rare, spinal neurofibromas in children should be diagnostically considered and radically treated for a favorable outcome.


Data on cytomegalovirus infection (CMV) prevalence and course in hospitalized infants are rather scarce, obsolete and considerably inconsistent. AIM: to determine the prevalence, rate of clinical manifestations, risk factors and predictive capacity of clinical manifestations of CMV infection in hospitalized infants during their first year of life.

PATIENTS AND METHODS: All 163 infants hospitalized in the Pediatric Ward for Nonrespiratory Pathology in a tertiary hospital were serologically screened for cytomegalovirus infection for 10 months. In infants up to 6 months old that were CMV IgG (+) and CMV IgM (-) we followed up the CMV IgG concentration or compared it with that of their mothers. RESULTS: The CMV prevalence for the entire study sample was 33.1 ± 3.7% (54 seropositive out of 163 examined infants); in newborns it was 19.4 ± 6.7% (7 of 36), in infants aged 1-3 months - 23.8 ± 5.4% (15 of 63), in 4-6-month olds - 28.1 ± 8.1% (9 of 32), and in 7-12-month old - 71.9 ± 8.1% (23 of 32). The rates of clinically apparent infections in the respective groups was 33.3 ± 6.5%, 57.01 ± 20.2%, 53.3 ± 13.3%, 33.3 ± 16.6%, and 13.0 ± 7.17%. The overall rate of clinically apparent CMV infection in all 163 children was between 11.0 ± 2.5% and 17.2 ± 2.9%. The probability of CMV infection increased with age and duration of breastfeeding. Hepatitis, cerebral vasculopathy and pneumonia (alone or combined) turned out to be predictors of CMV infection, but none of these symptoms had a frequency greater than 22%.

CONCLUSIONS: We found a high rate of cytomegalovirus infections in hospitalized infants less than one year of age. This infection is the reason why at least 10% of the newborns and 12% of the children aged 1 to 3 months were hospitalised. The course was clinically apparent in over half of the infected children of up to 3 months of age.


Pulmonary embolism (PE) is a relatively common cardiovascular emergency, though its exact incidence is difficult to assess. Accurate diagnosis is critical because of the high 30-day mortality in patients in whom the diagnosis is missed on admission. Doubt for PE is often raised by the presence of risk factors for venous thromboembolism (VTE), which are categorized into inherited and acquired. Among these, the importance of inherited/genetic thrombophilic factors is increasingly recognized. The most frequent markers of inherited thrombophilia are Factor V Leiden (FVL) and G2021OA prothrombin gene mutation. Among the inherited factors causal to thrombophilia, the C677T variant in methylentetrahydrofolate reductase (MTHFR) gene as well as factors like P1A1/P1A2 polymorphism in platelet glycoprotein Ilb/IIIa (P1A2) and hypofibrinolytic polymorphism 4G/4G in PAI-1 gene are discussed with controversial results. In our study, thrombophilic and hypofibrinolytic genetic variants were identified in 54.2% of 115 patients with PE. The most common significant genetic defects were FVL- 16.5% in patients versus 6.2% in controls (OR=3.102; p=0.05), G20210A PT 5.7% versus 2.1% (OR=2.983; p>0.05). P1A2 was found in 27.3% patients versus 19.9% in controls (OR= 1.523, p>0.05) and PAM 27.8% versus 22.6% (OR =1.501 p>0.05). MTHFR C677T carriage was inverse: 6.7% in patients versus 13.4% in controls. (OR=0.461 p=0.05). Of all the patients studied, 15.65% had a history of recurrent embolic incidents. The risk of recurrence was higher for the carriers of FVL and G20210A prothrombin gene mutation. The association between carriage of thrombophilic genetic factor and the early onset of the first embolic episode was found in the patients with PE. The awareness of risk factors and risk stratification is a critical issue in treatment and prevention policy. Preventive measures should be taken in particular medical conditions.


Chronic myeloid leukemia (CML) arises from the fusion of the BCR and the ABL1 genes. The BCR gene (chromosome 22q11.2) and the ABL1 gene (chromosome 9q34) fuse together due to reciprocal chromosome translocation forming the Philadelphia chromosome (Ph). This fusion gene codes tyrosine kinase which accelerates the cell division and reduces DNA repair. Imatinib mesylate is a selective inhibitor of this tyrosine kinase. It is the first-line treatment for CML-patients. However, it became clear that Philadelphia-positive (Ph+) cells could evolve to elude inhibition due to point mutations within the BCR-ABL kinase domain. To date more than 40 mutations have been identified and their early detection is important for clinical treatment. With the development of the new tyrosine kinase inhibitors (TKIs), associated with these mutations, the resistance problem seems to diminish, as some of the new drugs are less prone to resistance. The aim of this review is to focus on the diff erent mutations leading to resistance.


AIM: To study the development of children with selectively treated cytomegalovirus infection.

PATIENTS AND METHODS: We studied prospectively a risk group of 12 children with cytomegalovirus infection. These children were diagnosed by serological screening in the first three months after birth and are defined as congenital and perinatal infections. Thirteen infants with no serological evidence of previous or present cytomegalovirus infection at 4 - 12 months of age were used as controls. Ganciclovir in a dose of 10-15 mg/kg/day for at least 2 weeks followed by 5-7.5 mg/kg/day administered intravenously for at least 2 weeks more was given to 4 children from the risk group with PCR confirmed cytomegalovirus infection: to one with suspected congenital infection that presented with encephalitis, to two children with abnormal auditory evoked potentials (AEPs) and other non-neurological symptoms of a suspected congenital infection, and to one child with proven congenital infection with systemic manifestations. There was no infant with cytomegalic inclusion disease in the study. All other children in the risk group that had clinically manifested infection received isoprinosine in a dose of 50 mg/kg for one month.

RESULTS: Psychomotor development delay at age three was found in two children from the risk group and in one child in the control group. There was no difference between the two groups regarding the frequency of paroxysmal events, sensory deficiency or frequent illnesses.

CONCLUSIONS: The prognosis in cases of cytomegalovirus infection diagnosed at three years of age and treated selectively can be similar to that in infection free 3-year-old children (if there are no cases of CMV inclusion disease).


The present study aimed to evaluate the impact of factor V Leiden (FVL) polymorphism within the reproductive problems encountered by patients with polycystic ovary syndrome (PCOS). A total of 92 female patients with PCOS and 101 healthy controls were included in the study. Clinical and laboratory parameters were examined. The full history of each patient was taken. Single nucleotide polymorphism rs6025 in F5 was genotyped in PCOS patients and compared to the genotype frequency of the healthy controls. The data were analysed for correlation with infertility and pregnancy loss in PCOS patients. The prevalence of FVL polymorphism was higher, however not significantly, in PCOS patients compared to that of the control group (respectively OR=2.238, 95 % CI 0.777±6.449, p=0.104). The carriers of FVL polymorphism showed a higher rate of primary infertility (30.0% versus 12.5%, OR=3.143, 9 % CI 0.686±14.388, p=0.047) and their total reproductive failure rate was higher (60.5% versus 47.2%, OR=1.819, 95% CI 0.632±9.259, p=0.117). Carriage of FVL polymorphism in PCOS patients is associated with primary infertility and a presumed cause of the further investigations needed to understand the impact of FVL on PCOS. Carriage of FVL polymorphism in PCOS patients is associated with a higher rate of primary infertility, which draws attention to the role of this factor in the aetiology of the PCOS-related subfertility. Further investigations are needed to understand the impact of FVL on PCOS.