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.

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.

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.

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.

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.