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Background: The neurodegenerative process in Parkinson's disease (PD) affects both dopaminergic and non-dopaminergic structures, which determine the wide range of motor and non-motor symptoms (NMS), including different types of pain. Diverse mechanisms contribute to pain in PD. Abnormal nociceptive processing is considered a distinctive feature of the disease. Objective: In the present study, we used a validated PD-specific pain assessment tool to investigate self-reported pain in PDpatients and to analyze the association with the objective pain threshold. Methods: The RIII component of the nociceptive flexor reflex was assessed in 35 patients with PD and was compared to 40 healthy controls. Self-reported pain was measured using the Bulgarian version of the King's Parkinson's Disease Pain Scale (KPPS-BG). A correlation analysis was used to investigate the relationship between the objective nociceptive threshold and PD pain as assessed by KPPS-BG. Results: PD patients had a significantly lower RIII threshold than control individuals (the mean SD value was 6.24 ± 1.39 vs. 10.33 ± 1.64) when assessed in the "off" state. A statistically significant (p < 0.05) fairly negative Spearman's correlation was observed between the decreased spinal nociceptive threshold and fluctuation-related pain (-0.31). Domain 4, "nocturnal pain" (-0.21), and the KPPS-BG total score (-0.21) showed a weak negative correlation. An insignificant positive correlation was found between domain 6--"discoloration, edema/swelling"--and the RIII threshold. A higher Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score and modified Hoehn and Yahr (H&Y) scale are associated with a decreased nociceptive flexor reflex threshold. Conclusion: The results of the present study demonstrate the important role of increased spinal nociception in the occurrence of pain, which is associated with fluctuations and, to a lesser extent, nocturnal pain. [ABSTRACT FROM AUTHOR]

Depressive disorders are among the most important psychiatric problems. In everyday clinical practice, their symptoms and, respectively, their response to pharmacological treatment are both evaluated and measured subjectively. In the present paper, we apply a new approach for objective monitoring of the pharmacological-treatment response in patients with recurrent depressions. The applied method is user-friendly, easy-to-perform, and not time-consuming (1 test = 1 min), thus allowing repeatable examinations of many patients. The results show that the pre-treatment examination could discriminate between patients and healthy controls by revealing objectively measurable psychomotor retardation (in terms of locomotor hypo-activity and brady-reactivity) in the depressive group. After effective psychopharmacological treatment in a psychiatric clinic, the revealed psychomotor retardation is significantly improved (although not fully normalized) during the post-treatment examination at the time of discharge. The conclusion is that the new approach is reliable and sensitive enough to serve as a surrogate pharmacodynamic biomarker in patients with recurrent depressions. [ABSTRACT FROM AUTHOR]

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Discovery of diagnostic biomarkers for age-related neurodegenerative pathologies (NDDs) is essential for accurate diagnosis, following disease progression and drug development. Blood plasma and blood cells are important peripheral sources for NDDs' biomarkers that, although present in lower concentrations than in cerebrospinal fluid, would allow noninvasive diagnostics. To identify new biomarkers for Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), in this work we have evaluated the modifications in the thermodynamic behavior of blood plasma proteome exploring differential scanning calorimetry. The plasma thermodynamics reflected the complexity and heterogeneity of the two pathologies. The unfolding temperature of the most abundant plasma protein albumin and the weighted average center of the calorimetric profile appeared as the two thermodynamic signatures that reflected modifications of the plasma proteome, i.e., strong thermal stabilization of albumin and plasma proteins' interaction network, related to both pathologies. Based on those two signatures, both PD and ALS patients were stratified in two sets, except several cases with thermodynamic parameters that strongly differed from those of the calorimetric sets. Along with modifications of the plasma thermodynamic behavior, we found altered globulin levels in all PD and ALS patients' plasma (higher level of α- and β-globulin fractions and lower level of γ-globulin fraction than the respective reference values) employing capillary electrophoresis. The presented results reveal the potential of calorimetry to indirectly identify NDDs' biomarkers in blood plasma. [ABSTRACT FROM AUTHOR]

Objective: To characterize efficacy, safety/tolerability, and pharmacokinetics of padsevonil (PSL) administered concomitantly with ≤3 antiseizure medications (ASMs) for observable focal seizures in adults with drug‐resistant epilepsy in two multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group trials. Methods: The phase 2b dose‐finding trial (EP0091/NCT03373383) randomized patients 1:1:1:1:1 to PSL 50/100/200/400 mg or placebo twice daily (b.i.d.). The phase 3 efficacy trial (EP0092/NCT03739840) randomized patients 1:1:1:1 to PSL 100/200/400 mg or placebo b.i.d. Patients with observable (focal aware with motor symptoms, focal impaired awareness, focal to bilateral tonic–clonic) focal seizures for ≥3 years, experiencing them ≥4 times per 28 days including during the 4‐week baseline period despite treatment with ≥4 lifetime ASMs including current ASMs, were enrolled. Results: In EP0091 and EP0092, 410 and 231 patients, respectively, were randomized and received at least one dose of trial medication. In patients in EP0091 on PSL 50/100/200/400 mg b.i.d. (n = 80/82/81/81, respectively) versus placebo (n = 81), outcomes included percentage reductions over placebo in observable focal seizure frequency during the 12‐week maintenance period: 17.2%, 19.1% (p = 0.128), 19.2% (p = 0.128), 12.4% (p = 0.248); 75% responder rates (p‐values for odds ratios): 13.8%, 12.2% (p = 0.192), 11.1% (p = 0.192), 16.0% (p = 0.124) versus 6.2%; 50% responder rates: 33.8% (p = 0.045), 31.7% (p = 0.079), 25.9% (p = 0.338), 32.1% (p = 0.087), versus 21.0%; TEAEs were reported by 82.7% (67/81), 78.3% (65/83), 74.4% (61/82), 90.1% (73/81) versus 78.3% (65/83). In patients in EP0092 on PSL 100/200/400 mg b.i.d. (n = 60/56/56, respectively) versus placebo (n = 54), outcomes included percentage reductions over placebo: −5.6% (p = 0.687), 6.5% (p = 0.687), 6.3% (p = 0.687); 75% responder rates: 15.3% (p = 0.989), 12.5% (p = 0.989), 14.3% (p = 0.989) versus 13.0%; 50% responder rates: 35.6% (p = 0.425), 33.9% (p = 0.625), and 42.9% (p = 0.125) versus 27.8%; TEAEs were reported by 80.0% (48/60), 78.9% (45/57), 83.1% (49/59) versus 67.3% (37/55). Significance: In both trials, the primary outcomes did not reach statistical significance in any PSL dose group compared with placebo. PSL was generally well tolerated, and no new safety signals were identified. [ABSTRACT FROM AUTHOR]

The imaging and force–distance curve modes of atomic force microscopy (AFM) are explored to compare the morphological and mechanical signatures of platelets from patients diagnosed with classical neurodegenerative diseases (NDDs) and healthy individuals. Our data demonstrate the potential of AFM to distinguish between the three NDDs—Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), and normal healthy platelets. The common features of platelets in the three pathologies are reduced membrane surface roughness, area and height, and enhanced nanomechanics in comparison with healthy cells. These changes might be related to general phenomena associated with reorganization in the platelet membrane morphology and cytoskeleton, a key factor for all platelets' functions. Importantly, the platelets' signatures are modified to a different extent in the three pathologies, most significant in ALS, less pronounced in PD and the least in AD platelets, which shows the specificity associated with each pathology. Moreover, different degree of activation, distinct pseudopodia and nanocluster formation characterize ALS, PD and AD platelets. The strongest alterations in the biophysical properties correlate with the highest activation of ALS platelets, which reflect the most significant changes in their nanoarchitecture. The specific platelet signatures that mark each of the studied pathologies can be added as novel biomarkers to the currently used diagnostic tools. [ABSTRACT FROM AUTHOR]

Background and Purpose: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. Methods: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients–Intervention–Comparator–Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score >6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. Results: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. Conclusions: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs. [ABSTRACT FROM AUTHOR]

Management of Parkinson's disease (PD) is complicated due to its progressive nature, the individual patient heterogeneity, and the wide range of signs, symptoms, and daily activities that are increasingly affected over its course. The last 10–15 years have seen great progress in the identification, evaluation, and management of PD, particularly in the advanced stages. Highly specialized information can be found in the scientific literature, but updates do not always reach general neurologists in a practical and useful way, potentially creating gaps in knowledge of PD between them and neurologists subspecialized in movement disorders, resulting in several unmet patient needs. However, general neurologists remain instrumental in diagnosis and routine management of PD. This review provides updated practical information to identify problems and resolve common issues, particularly when the advanced stage is suspected. Some tips are provided for efficient communication with the members of a healthcare team specialized in movement disorders, in order to find support at any stage of the disease in a given patient, and especially for a well-timed decision on referral. [ABSTRACT FROM AUTHOR]

The present case-control study includes 50 patients with multiple sclerosis, diagnosed according to McDonald criteria, 35 women and 15 men, median age 40.8 years (21-61). Twenty of them had familial history with disease transmitted from the mother. Relapsing-remitting course was noted in 42 of them, relapsing-progressive in 4 and secondary progressive in 4. Statistically significant association with multiple sclerosis was found only for the highest serum levels of EBVCA IgG > 750 U/ml (17 vs. 8, p<0.05) and EBVNA IgG > 1.000 U/ml (23 vs. 3, p<0.05). The subgroup analysis by gender and family history did not reveal significant difference between cases and controls. Two of the sporadic cases were EBVCA IgG and EBVNA IgG negative. In both groups there was identical age-depended increase of the serum levels. The analysis of HLA-G 14bp ins/del polymorphism did not reveal a significant difference between the patients with the EBVCA >750 U/ml и EBVNA > 1.000 U/ml, the entire cohort and controls. In contrast to the literature, we found no convincing evidence for the role of EBV in MS. Except a true association, the highest serum levels may reflect a synergistic influence of other genetic or enviromental factors or may be just a secondary phenomenon. However, the possible role of EBV at the early stages of MS pathogenesis could not be excluded and future and larger studies with a proper design are justified. [ABSTRACT FROM AUTHOR]

Background: The ExtaviJect® 30G autoinjector was developed to facilitate parenteral self-administration of interferon beta-1b (Extavia®), a first-line disease-modifying therapy in patients with multiple sclerosis. Our aim was to assess patient compliance with treatment when using the autoinjector, patients' and nurses' experiences of using the device, its tolerability, and patient satisfaction. Methods: This was a 12-week, real-world, prospective, observational, noninterventional study conducted in nine European countries. Questionnaires were used to measure patient compliance and to assess patients' and nurses' experiences. All adverse events were recorded by severity, including injection site reactions or pain. Patient satisfaction and health-related quality of life were assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) and EuroQol-5 Dimension (EQ-5D) instruments, respectively. Results: Of 582 patients enrolled, 568 (98%) received at least one injection and attended the first follow-up visit at 6 weeks, and 542 (93%) attended the second follow-up visit at 12 weeks. For the whole study, 548 of 568 (97%) patients were compliant with treatment. Among the various questions assessing whether the device was easy and quick to use accurately, without fear of the needle, 56%-98% of patients and 59%-98% of nurses were in agreement. There were nine serious adverse events (four disease-related) reported among the 227 (39%) patients reporting adverse events. Scores increased in the TSQM-9 convenience domain between weeks 6 and 12 (P=0.0009), and in the EQ-5D visual analog scale between baseline and week 12 (P,0.0001), indicating improvement in health-related quality of life. Conclusion: ExtaviJect 30G was convenient to use and was associated with high levels of compliance. [ABSTRACT FROM AUTHOR]

Highlights: [•] We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. [•] Immunotherapy in RRMS patients reduced the yield of radiation induced MN. [•] The group of treated RRMS accounts for the low radiosensitivity in MS patients. [•] Spontaneous yield of MN was similar in treated and untreated RRMS patients. [ABSTRACT FROM AUTHOR]

Human red blood cells (RBCs) are unique cells with the remarkable ability to deform, which is crucial for their oxygen transport function, and which can be significantly altered under pathophysiological conditions. Here we performed ultrastructural analysis of RBCs as a peripheral cell model, looking for specific signatures of the neurodegenerative pathologies (NDDs)—Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), utilizing atomic force (AFM) and conventional optical (OM) microscopy. We found significant differences in the morphology and stiffness of RBCs isolated from patients with the selected NDDs and those from healthy individuals. Neurodegenerative pathologies' RBCs are characterized by a reduced abundance of biconcave discoid shape, lower surface roughness and a higher Young's modulus, compared to healthy cells. Although reduced, the biconcave is still the predominant shape in ALS and AD cells, while the morphology of PD is dominated by crenate cells. The features of RBCs underwent a marked aging-induced transformation, which followed different aging pathways for NDDs and normal healthy states. It was found that the diameter, height and volume of the different cell shape types have different values for NDDs and healthy cells. Common and specific morphological signatures of the NDDs were identified. [ABSTRACT FROM AUTHOR]

The main trend of current research in neurodegenerative diseases (NDDs) is directed towards the discovery of novel biomarkers for disease diagnostics and progression. The pathological features of NDDs suggest that diagnostic markers can be found in peripheral fluids and cells. Herein, we investigated the thermodynamic behavior of the peripheral red blood cells (RBCs) derived from patients diagnosed with three common NDDs—Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) and compared it with that of healthy individuals, evaluating both fresh and aged RBCs. We established that NDDs can be differentiated from the normal healthy state on the basis of the variation in the thermodynamic parameters of the unfolding of major RBCs proteins—the cytoplasmic hemoglobin (Hb) and the membrane Band 3 (B3) protein. A common feature of NDDs is the higher thermal stability of both Hb and B3 proteins along the RBCs aging, while the calorimetric enthalpy can distinguish PD from ALS and AD. Our data provide insights into the RBCs thermodynamic behavior in two complex and tightly related phenomena—neurodegenerative pathologies and aging, and it suggests that the determined thermodynamic parameters are fingerprints of the altered conformation of Hb and B3 protein and modified RBCs' aging in the studied NDDs. [ABSTRACT FROM AUTHOR]

The phenomenon of cerebellar mutism with subsequent dysarthria is most commonly described as a part of posterior fossa syndrome after surgery for neoplasms in childhood. Pathologic laughter, on the other hand, is observed primarily in various neurologic diseases in adults. In the present case, a child manifested transient mutism and pathologic laughter during a severe cerebellitis. Headache, vertigo, and impaired consciousness developed during an acute respiratory infection. Thereafter, severe ataxia, mutism, and involuntary laughter became the main clinical features, as well as pyramidal signs. Magnetic resonance imaging revealed cerebellar swelling and T2 hyperintensity. During steroid treatment, a gradual vanishing of the pathologic laughter and improvement of the motor and speech functions occurred. Recovery was slow and incomplete, and follow-up magnetic resonance imaging showed cerebellar atrophy. This case confirms that mutism is a rare, but possible, manifestation in acute parainfectious cerebellitis and provides a novel example of pathologic laughter during this disease in childhood. [Copyright &y& Elsevier]

Introduction: The health-related quality of life (HRQoL) of people with (Pw) multiple sclerosis (MS) is usually deteriorated. It has been recently suggested that comorbidities may have the negative influence on the quality of life of the PwMS, but according to the best of our knowledge, only one study investigated, although in a very small cohort, the impact of individual comorbidity on the quality of life of PwMS. The aim of our investigation was to assess, in an international, multicentric study, the impact of comorbid seizure/epilepsy on the HRQoL in PwMS., Methods: We conducted cross-sectional study at numerous neurological centers in Serbia, Croatia, Bulgaria, Montenegro, Northern Macedonia, and Bosnia and Herzegovina (Federation of Bosnia and Herzegovina and Republic of Srpska). For each patient, demographic and clinical data were collected, including Expanded disability status scale (EDSS) score. Beck Depression Inventory (BDI) and the 36-Item Short Form Health Survey (SF-36) questionnaires were administered to all patients., Results: The study comprised 326 PwMS in total, 127 PwMS with seizure/epilepsy and 209 PwMS without. Both mean Physical health composite (PHC) and mental health composite (MHC) scores, were statistically significantly higher in PwMS without seizure/epilepsy, implicating worse quality of life in PwMS with comorbid seizure/epilepsy. Presence of seizure/epilepsy in pwMS was statistically significant independent predictor of both PHC and MHC, in multivariate linear regression model after adjustment for potential confounding variables. The hierarchical multivariate regression analysis was performed in order to establish the most important predictors of the PHC and MHC of the SF-36, in PwMS with seizure/epilepsy; older age, higher level of disability, as measured by EDSS, higher depression score, drug-resistant epilepsy and shorter time since last seizure were found to significantly predict worse MHC score in PwMS with seizure/epilepsy., Discussion: Our results point to the possible role of theinterventions related to the adequate control of epilepsy along with improvement of the mental health status to be important in order to reduce MS burden in the PwMS with comorbid seizure/epilepsy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Drulovic, Pekmezovic, Tamas, Adamec, Aleksic, Andabaka, Basic Kes, Butkovic Soldo, Cukic, Despinic, Dincic, Djelilovic Vranic, Grgic, Habek, Hristova, Ivanovic, Jovanovic, Jovicevic, Krbot Skoric, Kuzmanovski, Maric, Mesaros, Milanov, Miletic Drakulic, Sinanovic, Skarpa Prpic, Sremec, Tadic, Toncev and Sokic.)

Human red blood cells (RBCs) are unique cells with the remarkable ability to deform, which is crucial for their oxygen transport function, and which can be significantly altered under pathophysiological conditions. Here we performed ultrastructural analysis of RBCs as a peripheral cell model, looking for specific signatures of the neurodegenerative pathologies (NDDs)-Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), utilizing atomic force (AFM) and conventional optical (OM) microscopy. We found significant differences in the morphology and stiffness of RBCs isolated from patients with the selected NDDs and those from healthy individuals. Neurodegenerative pathologies' RBCs are characterized by a reduced abundance of biconcave discoid shape, lower surface roughness and a higher Young's modulus, compared to healthy cells. Although reduced, the biconcave is still the predominant shape in ALS and AD cells, while the morphology of PD is dominated by crenate cells. The features of RBCs underwent a marked aging-induced transformation, which followed different aging pathways for NDDs and normal healthy states. It was found that the diameter, height and volume of the different cell shape types have different values for NDDs and healthy cells. Common and specific morphological signatures of the NDDs were identified.

Background: The ExtaviJect® 30G autoinjector was developed to facilitate parenteral self-administration of interferon beta-1b (Extavia®), a first-line disease-modifying therapy in patients with multiple sclerosis. Our aim was to assess patient compliance with treatment when using the autoinjector, patients' and nurses' experiences of using the device, its tolerability, and patient satisfaction., Methods: This was a 12-week, real-world, prospective, observational, noninterventional study conducted in nine European countries. Questionnaires were used to measure patient compliance and to assess patients' and nurses' experiences. All adverse events were recorded by severity, including injection site reactions or pain. Patient satisfaction and health-related quality of life were assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) and EuroQol-5 Dimension (EQ-5D) instruments, respectively., Results: Of 582 patients enrolled, 568 (98%) received at least one injection and attended the first follow-up visit at 6 weeks, and 542 (93%) attended the second follow-up visit at 12 weeks. For the whole study, 548 of 568 (97%) patients were compliant with treatment. Among the various questions assessing whether the device was easy and quick to use accurately, without fear of the needle, 56%-98% of patients and 59%-98% of nurses were in agreement. There were nine serious adverse events (four disease-related) reported among the 227 (39%) patients reporting adverse events. Scores increased in the TSQM-9 convenience domain between weeks 6 and 12 (P=0.0009), and in the EQ-5D visual analog scale between baseline and week 12 (P<0.0001), indicating improvement in health-related quality of life., Conclusion: ExtaviJect 30G was convenient to use and was associated with high levels of compliance.

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, pressing-tightening 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 classified 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.

Multiple sclerosis (MS) is a neurological disorder characterized by inflammatory demyelination and neurodegeneration in the central nervous system. Until recently, disease-modifying treatment was based on agents requiring parenteral delivery, thus limiting long-term compliance. Basic treatments such as beta-interferon provide only moderate efficacy, and although therapies for second-line treatment and highly active MS are more effective, they are associated with potentially severe side effects. Fingolimod (Gilenya(®)) is the first oral treatment of MS and has recently been approved as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis (RRMS) for adult patients with high disease activity despite basic treatment (beta-interferon) and for treatment-naïve patients with rapidly evolving severe RRMS. At a scientific meeting that took place in Vienna on November 18th, 2011, experts from ten Central and Eastern European countries discussed the clinical benefits and potential risks of fingolimod for MS, suggested how the new therapy fits within the current treatment algorithm and provided expert opinion for the selection and management of patients.

Fingolimod is the first oral treatment of multiple sclerosis. It is the first-in-class sphingosine 1-phosphate receptor modulator that binds to sphingosine 1-phophate receptors on lymphocytes and via downregulation of the receptor prevents lymphocyte egress from lymphoid tissues into the circulation. This mechanism reduces the infiltration of potentially auto-aggressive lymphocytes into the central nervous system. Two large phase III studies with fingolimod have shown superior efficacy of the drug in two dosages compared to placebo and to weekly intramuscular injections of Interferon beta-1a. Among possible side effects of the drug is a transient bradycardia after the first dose of fingolimod including possible AV blockade and therefore monitoring of pulse rate and blood pressure for 6 h following the first application is needed. During treatment, attention has to be given to specific infections, elevated liver enzymes, and ophthalmologic changes. Recommendations on the use of fingolimod including safety aspects are given in this article.

This case report is a detailed description of the clinical, laboratory, imaging and therapeutic characteristics of the sixth patient with neuro-Behçet's disease reported by Bulgarian authors. The diagnosis was made in accordance with the international diagnostic criteria for Behçet's disease and was verified by skin biopsy. Therapeutic response was followed up by clinical and magnetic resonance imaging data for 6 months. Discussed are differences in the classical Behçet's disease presentation and other neuro-Behçet's disease cases found in Bulgaria. The current case supports the wide clinical heterogeneity of the disorder and the variety of therapeutic options.

Objectives: To investigate the prognostic value of median somatosensory evoked potentials (mSSEP) within the "therapeutic window" of ischemic stroke., Materials and Methods: Twenty-two patients (mean age 60.8 +/- 14.8 years) with first ischemic stroke in middle cerebral artery territory without contraindications for thrombolysis underwent mSSEP investigation within 3 hours of onset. Stroke topography was verified within 48 hours by computed tomography. M-SSEP results (presence, amplitude and amplitude ratio, latency and central conduction time) were compared to severity of motor deficit at onset and to recovery at 6 months., Results: M-SSEP were present in 17 patients, 7 of whom had partial and 10--complete motor recovery. Absence of mSSEP was found in 5 persons. None recovered function of the arm and only 2 were ambulatory at 6 months., Conclusions: In the earliest phase of ischemic stroke absence of mSSEP response is reliable predictor of poor functional outcome.