Peritumor Mucosa in Advanced Laryngeal Carcinoma Exhibits an Aberrant Proangiogenic Signature Distinctive from the Expression Pattern in Adjacent Tumor Tissue.

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the "classical" borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer-the process of tumor neoangiogenesis.

Lower fluorodeoxyglucose positron emission tomography maximum standardized uptake value may show a better response to stereotactic body radiotherapy of adrenals in oligometastatic disease.

Introduction: Stereotactic body radiotherapy (SBRT) is well established for oligometastatic disease, and it is increasingly used to treat adrenal metastases. Material and methods: In this retrospective study we performed an analysis of 75 metastatic adrenal lesions in 64 patients with oligometastatic disease. According to the fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) maximum standardized uptake value (SUVmax) of adrenal metastases, patients were categorized into three groups: low, intermediate, and high SUVmax. Results: For all clinicopathological characteristics we found significant relationships for levels of SUVmax and objective response rate (Kendall Tau-c = 0.290; p = 0.017). Patients who responded to SBRT had a significantly lower SUVmax value than those who did not respond (7.6 ±2.4 vs. 9.7 ±3.8; p = 0.015). At the appropriate SUVmax cut-off values, the biomarker distinguished between patients with and without a response significantly and moderately (area under the curve = 0.670, 95% confidence intervals: 0.540-0.790; p = 0.015). Conclusions: Lower SUVmax is associated with a better response to SBRT in patients whose disease progressed mainly in the adrenal glands.

Ultrasound fusion imaging system in neurology practice.

The ultrasound fusion imaging (UFI) system is a new promising imaging modality that combines live ultrasound investigations with preregistered CT, MRI, or PET images. In this study, we want to present our initial experience with the new method that combines the transcranial color-coded sonography (TCCS) in different insonation planes and the 3T-weighted MRI cerebral images. The study validates the diagnostic capabilities of the system to detect different normal cerebral structures in healthy volunteers. In the present paper, we also discuss the advantages of US fusion imaging technology and its clinical applications in Neurology.

Intraoperative Radiotherapy with Balloon-Based Electronic Brachytherapy System-A Systematic Review and First Bulgarian Experience in Breast Cancer Patients.

(1) Background: We aimed to analyze currently available studies with intraoperative radiotherapy (IORT) as a choice of treatment where the Xoft Axxent® electronic brachytherapy (eBx) system was used as a single-dose irradiation and an exclusive radiotherapy approach at the time of surgery in patients with early breast cancer (EBC). We also compared the results of the systematic review to the Bulgarian experience. (2) Methods and Materials: We performed a systematic review of the studies published before February 2021, which investigate the application of a single-fraction 20 Gy radiation treatment, delivered at the time of lumpectomy in EBC patients with the Xoft Axxent® eBx System. A systematic search in PubMed, Scopus, and ScienceDirect was performed. The results are reported following the PRISMA guidelines. The criteria on patients' selection for IORT (the additional need for EBRT), cosmetic outcomes, and recurrence rate from the eligible studies are compared to the treatment results in Bulgarian patients. (3) Results: We searched through 1032 results to find 17 eligible studies. There are no published outcomes from randomized trials. When reported, the cosmetic outcomes in most of the studies are defined as excellent. The observed recurrence rate is low (1-5.8%). Still, the number of patients additionally referred to postoperative external breast radiotherapy (EBRT) is up to 31%. Amongst the 20 patients treated in Bulgaria, the cosmetic outcomes are also evaluated as excellent, five of which (25%) are referred for EBRT. Within median follow-up of 39 months, there was one local and one distal recurrence. (4) Conclusions: Current evidence demonstrates the Xoft Axxent® eBx system as a safe and feasible technique for IORT delivery in EBC patients. There are no randomized controlled trials conducted at this time point to prove its long-term effectiveness. Better patient selection and a reimbursement strategy have to be proposed to extend the application of this technique in Bulgaria.

Levetiracetam effectiveness as add-on therapy in Bulgarian patients with drug-resistant epilepsy.

INTRODUCTION: There are no reliable prospective studies on the effectiveness of LEV in Bulgarian adult patients with drug-resistant epilepsy. AIM: The study aimed at conducting an open, prospective study on various aspects of levetiracetam (LEV) effectiveness in Bulgarian patients with drug-resistant epilepsy. MATERIALS AND METHODS: The study was performed with patients with epilepsy recruited from those attending the Department of Neurology at the University Hospital in Plovdiv, Bulgaria. The patients completed diaries about seizure frequency, severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of treatment with LEV and at 6 months afterwards, with dynamic assessment of seizure frequency, severity, adverse events, and EEG recordings. RESULTS: LEV was applied as an add-on therapy in 135 patients (86 males, mean age 35 years). There was a relatively mild and persisting dynamic improvement of seizure severity, a satisfactory seizure frequency reduction in 49.6% of participants, a persisting mean seizure frequency reduction (48-58%) from 6 to 36 months of treatment and a high responder rate (53-60%) during the same period. New seizure types (focal with impaired awareness with /without evolution to bilateral tonic-clonic seizures) occurred in 4 patients. There were adverse events (dizziness, memory impairment, aggressiveness, numbness, non-epileptic seizures, depression, anxiety, speech disturbances, visual hallucinations, sleepiness, pelvic muscles weakness, confusion, sleep disturbances, loss of appetite, unstable gait, hair loss, acne, generalized rash) in 13.33% of patients. CONCLUSIONS: LEV treatment is associated with: low and persisting improvement of seizure severity, a good and persisting improvement of seizure frequency, a possible worsening of seizure control, a possible appearance of new seizure types, a good safety and tolerability.

The role of fibrinogen in acute ischaemic stroke.

AIM: This study aimed to explore associations between fibrinogen and acute ischaemic stroke, neurological impairment, cerebral ischaemia, and clinical evaluation of stroke patients. MATERIALS AND METHODS: The study involved 153 patients categorised into two groups: patients with acute ischaemic stroke, and patients with risk factors but who had not had a stroke. Blood samples were collected to analyse the serum level of fibrinogen. The time from stroke onset to blood test was noted. The National Institutes of Health Stroke Scale was used to determine the neurological disability of the stroke patients upon hospital admission and upon discharge. Cerebral CT was performed on the same group of patients during the first 24 h after stroke onset and evidence of early ischaemic lesions was recorded. The stroke cases were divided into subgroups according to the TOAST classification. RESULTS: Patients with ischaemic stroke had a significantly increased mean level of fibrinogen (> 4g/l). Analysis of stroke subtypes shows that patients with undetermined cause of stroke and patients with atherosclerotic stroke had a significantly higher median level of fibrinogen compared to patients with some other types of stroke. No significant connection was found between fibrinogen level and neurological deficit. A positive linear relationship was established between fibrinogen and blood sample time. A negative relation was established between the clinical evolution of ischaemic stroke patients and fibrinogen level. A significant relation between fibrinogen level and the presence of ischaemic lesions on cerebral CT was observed: patients with a fibrinogen level > 3.41g/l showed a 3.29-times increased risk of ischaemic lesions. CONCLUSION: Fibrinogen is a reliable biomarker that could characterise acute ischaemic stroke.

Various Aspects of Tiagabine Effectiveness as Add-on Therapy in Patients with Refractory Epilepsy.

The aim of the present study was to investigate various aspects of tiagabine (TGB) effectiveness in Bulgarian patients with drug-resistant epilepsy. This open, prospective study recruited the patients with epilepsy attending the Clinic of Neurology at the University Hospital of Plovdiv, Bulgaria. The patients completed diaries about the seizure frequency, severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of treatment with TGB and at 6 months or 1 year afterwards, with dynamic assessment of seizure frequency, severity, adverse events, and EEG recordings. TGB was applied as an add-on treatment in 43 patients (24 males, mean age 39 years). There was relatively mild and transient dynamic improvement of seizure severity, satisfactory seizure frequency reduction in 32.6% of participants, stable mean seizure frequency reduction (40-50%) from month 6 to month 24 and a stable response rate (52.3-50%) during the same period. New seizure types (myoclonic, myoclonic-atonic) occurred in 2 patients. The final clinical efficacy was higher in patients with initial monotherapy. There were adverse events (dizziness/vertigo, sedation, memory impairment, loss of appetite and weight, confusion, psychosis, insomnia, transient diplopia, lymphadenomegaly, rash, nausea, depression, anxiety, tremor of hands, unstable gait, legs edema, thrombocytopenia, cervical muscles tightening) in 26.19% of patients. In conclusion, TGB treatment is associated with low and transient improvement of seizure severity, good and stable improvement of seizure frequency, possible worsening of seizure control, possible appearance of new seizure types, and acceptable safety and tolerability.

Topiramate Effectiveness as Add-on Therapy in Bulgarian Patients with Drug-resistant Epilepsy.

INTRODUCTION: There are no reliable prospective studies on the effectiveness of topiramate in Bulgarian adult patients with drug-resistant epilepsy. AIM: The aim of the study was to conduct an open, prospective study on various aspects of topiramate (TPM) effectiveness in Bulgarian patients with drug-resistant epilepsy. PATIENTS AND METHODS: The study included patients with epilepsy who attended the Clinic of Neurology at the University Hospital in Plovdiv, Bulgaria. Patients completed diaries for seizure frequency, seizure severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of TPM treatment and at 6 months afterwards, with a dynamic assessment of seizure fre-quency, severity, adverse events, and EEG recordings. RESULTS: TPM was used as an add-on treatment in 120 patients (69 males, mean age 37 years). There was a relatively mild and stable dynamic improvement of seizure severity, a satisfactory seizure frequency reduction in 37% of participants, a stable mean seizure fre-quency reduction (47%) from month 6 to month 24 of treatment and a stable responder rate (48-51%) during the same period. New seizure types (focal with impaired awareness with/without evolution to bilateral tonic-clonic seizures) occurred in 5 patients. There were adverse events (dizziness/vertigo, irritability, speech disturbances, memory impairment, concentration problems, tremor, loss of appe-tite and weight, weakness, numbness, bradypsychia, confusion, visual hallucinations, sleepiness, insomnia, headache, itching, unstable gait, nausea, and vomiting) in 20% of patients. CONCLUSIONS: TPM treatment is associated with low and stable improvement of seizure severity, good and stable improvement of sei-zure frequency, possible worsening of seizure control and appearance of new seizure types, good safety and tolerability.

Characteristics of Unstable Carotid Plaques - New Image Modalities.

Ischemic stroke is a socially significant health problem due to high mortality and disability. One of the leading causes for cerebrovascular accidents is the carotid atherosclerosis. The mechanism of its formation presents not only lipid accumulation in the arterial wall but a complex inflammatory disease. The aims of this review are to point the new methods and approaches for diagnostic of the unstable and high-risk carotid plaques. The old plaque imaging modalities emphasized mainly to the degrees of luminal stenosis. The new possibilities reveal plaque morphology so detailed even compared to histological verification. Recent techniques as Shear wave elastography, optical coherence tomography, Superb microvascular imaging, USPIO MRI give information about the pathological mechanisms of carotid atherosclerosis. The efforts are directed to predict the atherosclerotic burden, plaque instability and the occurrence of cerebrovascular events for each patient and to optimize personal management.

Neuromyelitis Optica and Systemic Lupus Erythematosus Association ­ the Chicken or the Egg Dilemma: a Case Repor.

We present a case report of a 32-year-old woman diagnosed with opticomyelitis of Devic (OMD) and systemic lupus erythematosus (SLE). The onset of neurological symptoms was with optic neuritis. Five months later the neurological deficit progressed within a few days to lower paraplegia and upper paraparesis, retention of urine and faeces, impaired somatic and deep sensation below the level of Th1 dermatome. The results from laboratory investigations confirmed anaemic syndrome, increased urea and creatinine, hypoproteinemia and severe proteinuria. The results from CSF investigations demonstrated hyperproteinorachia with extremely high Ig fractions. Serum and CSF oligoclonal bands and positive serum Aquaporin IgG 32 times higher than the upper referent limit were found. The association with SLE was confirmed by the increased levels of total ANA and anti-ds-DNA ANA. MRT visualized the spinal cord as non-homogenously hypointense on T1 and extremely hyperintense on FLAIR sequences through its whole length up to the bulbar-pontine region. The MRT findings and the serum Aquaporin IgG confirmed the diagnosis OMD. The patient was treated with intravenous immunomodulating agents. We consider the presented case of special interest because of the comorbidity of an aggressive autoimmune systemic and an organ-specific disease of the central nervous system.

Comparative effectiveness of add-on therapy with newer-generation antiepileptic drugs in Bulgarian patients with refractory epilepsy.

OBJECTIVES: The objective of this study is to perform an open, prospective study on various aspects of comparative effectiveness of newer-generation antiepileptic drugs as add-on therapy in Bulgarian patients with drug-resistant epilepsy. METHODS: The study was performed with the participation of 1259 patients with epilepsy who attended the Clinic of Neurology at the University Hospital in Plovdiv, Bulgaria for regular visits and completed diaries about seizure frequency, severity, and adverse events. RESULTS: Oxcarbazepine was used in 82 patients, topiramate in 120 patients, lamotrigine in 73 patients, levetiracetam in 135 patients, pregabalin in 47 patients, tiagabine in 43 patients, gabapentin in 18 patients, lacosamide in 12 patients, and retigabine in 6 patients. During the first 24 months of study, improvement of seizure severity and frequency was most frequent in patients on treatment with pregabalin and levetiracetam and rarest in those on treatment with oxcarbazepine. The retention rate of patients on pregabalin and tiagabine was significantly lower compared to the retention rate of patients on most of the other antiepileptic drugs. The frequency of adverse events was higher in patients on treatment with tiagabine and pregabalin. CONCLUSION: Despite some similar characteristics of newer-generation antiepileptic drugs' effectiveness, levetiracetam stands out with better dynamic improvement of seizure severity and frequency and satisfactory tolerability; typical for pregabalin is a very good dynamic improvement of seizure severity and frequency mainly in patients with focal seizures, but a lower tolerability, and the main advantage of oxcarbazepine is a good tolerability, efficacy, however, is less satisfactory.

25 Hydroxyvitamin D and Cytokines in Multiple Sclerosis.

INTRODUCTION: Clinical trials of patients with multiple sclerosis (MS) have produced inconsistent results for the profile of cytokine secretion in serum and cerebrospinal fluid in patients with multiple sclerosis during periods of relapse and remission. Epidemiological and clinical observations data reveal an association of the changes in vitamin D serum concentration with the risk of developing MS. AIM: To evaluate changes in serum concentrations of 25(OH)D, IL17, IFN-gamma, TGFß1, IL4, IL10 in relapse and remission and their correlation with the severity of disability. PATIENTS AND METHODS: Fifty-three persons (30 clinically healthy controls and 23 patients with relapsing-remitting multiple sclerosis) living between 41° and 42° northern latitude were registered during the astronomical winter period (October 2012- May 2013). -Patients were diagnosed according to Mc Donald 2010 criteria. The degree of neurological deficit was assessed by EDSS. Serum concentrations of 25(OH)D (nmol/l) and cytokines (pg/ml) were tested by ELISA - once for controls and twice for patients (during relapse and remission). RESULTS: In the studied population average levels of 25(OH)D were close to insufficiency, most pronounced in patients in relapse, as differences were not statistically significant. A reverse correlation was found between the levels of 25(OH)D and the deficit in relapse and remission. Concentrations of TGFß1 significantly increased in remission compared with exacerbation and controls. Serum level of IL4 was significantly lower in relapse compared with controls. In remission there was a marked tendency of increase compared with exacerbation. During clinical improvement IL17 and IFN-gamma tended to decrease compared to the average levels in relapse. In both periods, the average concentrations of IFN-gamma in patients were significantly lower compared with controls. No statistically significant differences were found comparing cytokine changes with those of 25(OH)D and deficit. CONCLUSION: Persistent cytokine imbalance in patients compared with controls is a marker for Th1-mediated CNS demyelination. Anti-inflammatory TGFß1, IL4 are indicators of immune response intensity. The deficit severity does not depend on changes of the tested cytokines, but correlates with 25(OH)D levels during periods of relapse and remission.

Vitamin D immunomodulatory potential in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of unknown etiology whose treatment is of limited efficiency and therefore has a high social burden. As it has been suggested that myelin destruction model, the clinical manifestation and the potential of therapeutic response in MS are correlated, it is quite justifiable that we study various factors (genetic, hormonal, environmental) that take part in the autoimmune process in order to improve the control over the disrupted immune regulation. Results from epidemiological and clinical studies clearly suggest that changes in vitamin D serum concentrations are correlated with the magnitude of the risk of developing MS, the phases of relapse and remittance and with gender differences in vitamin D metabolism. Experimental and clinical studies also have established that 25-hydroxy vitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)2D) exert an immunomodulatory effect in the central nervous system and peripheral organs of the immune system. The standard reference range of vitamin D concentration in serum is 50-80 nmol/l--it provides normal calcium metabolism. Issues that are discussed include the vitamin D serum concentration needed to suppress the aberrant immune response in MS patients; a subgroup of MS patients suitable for vitamin D treatment, the vitamin D being applied in optimally effective and safe dosage. MS prevalence rate in Bulgaria has increased two-fold in 17 years but this is a rather short interval to be able to assume that the gene pool of the population changes. Thus further studies on possible interactions between different environmental factors and these factors' role in the disease pathogenesis are justified and necessary.

Clinical and laboratory study of pro-inflammatory and antiinflammatory cytokines in women with multiple sclerosis.

UNLABELLED: Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system characterised with a complex system of interactions between proinflammatory and anti-inflammatory cytokines in its course. AIM: The aim of the present study was to investigate the serum levels of cytokines TNF-a, IFN-gamma, IL-4 and IL-10 in female patients with MS and healthy individuals, the changes occurring in the relapse and remission phases of the disease and their correlation with the severity of the neurological deficit. PATIENTS AND METHODS: Thirty-five women with relapsing-remitting MS were examined. The patients' age ranged between 18 and 50 years and MS was verified clinically and by magnetic resonance imaging according to the McDonald criteria. Thirteen of the patients were treated with interferon-beta-1b. The serum concentrations of TNF-a, IFN-y, IL-4 and IL-10 were determined twice - in relapse and in remission - using an enzyme-linked immunosorbent assay (ELISA). The control group consisted of 35 age-matched healthy females. RESULTS: The comparison of cytokine serum concentrations during the two phases of the disease showed significant elevation of the TNF-alpha serum levels in the relapse phase and of IL-4 - in the remission phase. The comparison between the patients and the healthy control subjects demonstrated statistically significant lower concentrations of TNF-a in remission patients and higher concentrations of IL-10 in relapse patients. The patients with interferon-beta-lb treatment showed different profile of cytokine secretion from the patients without interferon-beta-1b treatment. Interferon-beta-1b-treated patients showed significantly lower serum levels of TNF-a and IFN-gamma during the relapse phase and higher TNF-a and IL-10 serum levels during the remission phase compared with the untreated patients. CONCLUSIONS: Serum levels of TNF-a and IL-4 objectively reflect the immune response during relapse and remission of the disease. The severity of neurological deficit as estimated with the expanded disability status scale (EDSS) does not depend on the serum levels of TNF-a, IL-10 and IFN-gamma in the two phases of MS.

Pseudoresistance in patients with epilepsy--characteristics and determining factors.

INTRODUCTION: In pseudorefractory epilepsy (20% of the cases diagnosed with refractory epilepsy) the factors responsible for triggering the seizures are extraneous to epilepsy and the seizures can be controlled after diagnostic and therapeutic re-evaluation. AIM: To determine the factors causing development of pseudoresistance in patients with epilepsy. PATIENTS AND METHODS: Detailed case histories of 191 patients with a diagnosis of drug-resistant epilepsy were collected; the medical records were analyzed retrospectively. Thirty-nine patient (20.42%) were found to be with pseudorefractory epilepsy. The patients were classified by demographic criteria and specific clinical signs, and by laboratory findings. RESULTS: The patients (age range 18 to 72 years, mean duration of disease 27 years) presented with partial (56.41%), generalized (43.59%) and polymorphic seizures (17.95%) with a higher relative percentage of the patients with symptomatic (41.03%) and cryptogenic (35.9%) epilepsy. The main groups of factors that determined pseudoresistance were diagnostic (46.15%) and therapeutic errors (69.23%), poor compliance (33.33%), external factors (5.12%), as well as a combination of these (53.84%). We found that compliance correlated weakly with age and education, but showed high and moderate correlation with duration of epilepsy less than 20 years and male gender. Therapy adjustment had a beneficial effect in 16 of 24 patients (66.67%) in our study. CONCLUSION: The detailed analysis of the causes for pseudoresistance focuses on some pitfalls of the diagnostic and therapeutic process, compliance of the patient and influence of external factors aiming at reduction of the number of cases with pseudorefractory epilepsy and achieving more favourable clinical effect of treatment.

Depressivity, anxiety and quality of life in patients with refractory epilepsy.

INTRODUCTION: Depressive and anxiety disorders are very often comorbid with refractory epilepsy. AIM: To determine the impact of depressivity and anxiety on some aspects of the quality of life of patients with refractory epilepsy. PATIENTS AND METHODS: The present open prospective study included 94 patients (67 women) with refractory epilepsy (mean age 42 years) who were categorised according to their medical history, individual clinical parameters and results of paraclinical studies. Beside these, the patients completed the questionnaires for depression (BDI-II), anxiety (HAS) and quality of life (QOLIE-89). RESULTS: We found different degrees of depressivity in 59 patients (63.44%). Only three of the participants (3.19%) were found to have no depressivity or anxiety. In the remaining 91 patients (96.81%) we diagnosed anxiety in a different degree. The QOLIE-89 showed a low overall assessment of the quality of life in 54 patients (57.45%). We found: 1. A strong correlation between depressivity and the low overall assessment of quality of life as well as the assessment in the subscales for limitations due to physical problems, emotional wellbeing, attention/concentration, and memory. 2. A strong correlation between the increase of severity of depressivity and decrease of the overall assessment of quality of life. 3. A weak correlation between anxiety and the low overall assessment of QOL as well as the assessment in all subscales. CONCLUSIONS: Depressivity is a factor which worsens significantly all aspects of quality of life of patients with refractory epilepsy. This makes the timely diagnosis and treatment of the disease absolute necessity.

A case of encephalocraniocutaneous lipomatosis syndrome with epilepsy (Haberland syndrome).

Encephalocraniocutaneous lipomatosis is a rare congenital neurocutaneous syndrome characterized by scalp, facial, and ocular lesions and multiple intracranial malformations. Approximately 50 cases have been described in the literature. We report a 34-year-old woman with a 6-year history of epilepsy, without mental retardation, with predominantly ipsilateral skin lesions evident at birth, with limbal lipodermoid of the left eye and multiple non-progressive, ipsilateral intracranial structures of soft, cystic components. The described malformations are congenital, mostly unilaterally located and with similar lipomatous structure.

Female sex hormones and multiple sclerosis.

Multiple sclerosis is the most frequent debilitating neurological disease in young subjects. The autoimmune process predominantly affects females. This paper presents a review of experimental and clinical data about the effect of female sex hormones and conditions associated with hormonal alterations on the disease process. Specific consideration is given to the use of estrogens as a remedy influencing the disease course. There haven't been enough studies to indicate presence of either hormonal disbalance in females with multiple sclerosis or peculiarities in the hormone-cytokine profile during disease relapse and remission. Further investigations in this area are needed to provide more profound knowledge of the pathogenesis of this socially significant disease.