Clinical Neuroscience

[IMPORTANCE OF THE ANALYSIS OF NEUTRALIZING ANTIBODIES TO IMMUNOMODULATORY THERAPY DURING TREATMENT OF MULTIPLE SCLEROSIS]

SERES Erika, VÉCSEI László

MAY 30, 2006

Clinical Neuroscience - 2006;59(05-06)

[Interferon-α, -β, and -γ have been used for the management of several diseases with varying clinical effects. Like many other proteins, all interferon species are potentially immunogenics especially those produced by recombinant gene technologies. A reliable screening assay for anti-interferon-β antibodies is suggested for patients with multiple sclerosis receiving interferon-β therapy. Natural interferon-β is a glycosylated 166 amino acid 25 kDa protein, recombinant interferon-β is available for therapy as 1a and 1b products. Both preparations induce anti-interferon-β antibodies, detectable in the serum of interferon-β-treated patients with multiple sclerosis. The question of wich assay is optimal for testing for antiinterferon- β antibodies in interferon-β-treated patients is unsettled. Two types of antibody assays are generally used: those measuring binding antibodies and those measuring neutralizing antibodies. The findings suggest that high titers of both binding and neutralizing antibodies reduce the clinical efficacy of interferon-β in relapsing-remitting multiple sclerosis, which is important for the long-term efficacy of these drugs. Treatment with glatiramer acetat has also been shown to induce the development of “reactive antibodies” in patients with multiple sclerosis. This article briefly describes some of the findings concerning anti-interferon binding and neutralizing antibodies.]

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[Hungarian Epilepsy League]

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[CHANGES IN EEG-COMPLEXITY AFTER SUBCORTICAL ISCHEMIC BRAIN DAMAGE]

MOLNÁR Márk, CSUHAJ Roland, HORVÁTH Szabolcs, VASTAGH Ildikó, GAÁL Zsófia Anna, CZIGLER Balázs, BÁLINT Andrea, NAGY Zoltán

[Introduction - Complexity analysis of the EEG is a relatively new field in theoretical and cinical electrophysiology. The authors present results of EEG-analysis in a patient with stroke, utilizing the sensitivity of the new procedures with respect to linear and nonlinear synchronization. Participants and methods - The EEG (19 channels) was recorded in a patient with subcortical unilateral ischaemic completed stroke involving the frontoparietal white matter while leaving the cortex intact and in 12 healthy controls in eyes open and in eyes closed conditions. Results - In the patient, increased Omega-complexity was found in slow (delta, theta) and lower alpha frequencies in the side of the stroke and in high frequencies (beta2 in eyes closed, alpha2, beta1 and beta2 in eyes open conditions) in the intact side. Synchronization likelihood was higher in the ischaemic side in the beta2 (eyes closed) and both in the beta1 and beta2 (eyes open) frequencies. Increasing Omega-complexity caused by eyes opening was markedly reduced in the patient in the beta frequencies compared to that seen in the controls. The difference was more conspicuous in the side of the infarct and involved not only the beta but also the alpha frequencies as well. Opening the eyes decreased synchronization likelihood in all frequency bands in the controls and also in the patient except the alpha2, beta1 and beta2 bands in the side of the lesion. Conclusions - The increased Omega-complexity and decreased synchronization likelihood in the slow frequencies in the infarcted side is probably the result of lesioned interneuronal connections lowering the level of cooperation of neuronal systems involved in this type of activity. The increased Omega-complexity and decreased synchronization likelihood caused by eyes opening could not be observed in the beta and alpha frequencies in the side of the lesion, possibly caused by damaged thalamocortical connections.]

Clinical Neuroscience

[EPILEPSY AND MALE SEXUAL DYSFUNCTION: ETIOLOGY, DIAGNOSIS AND THERAPY]

BÓNÉ Beáta, JANSZKY József

[While 10% of healthy men had sexual dysfunctions, male epilepsy patients experience sexual problems in 40-70%. The cause of sexual dysfunction in epilepsy is multifactorial, but there are three main factors: the epilepsy itself, antiepileptic treatment and psychiatrical/psychic problems. Antiepileptics with hepatic enzyme induction potential (carbamazepine, phenytoin) enhance the metabolism of sexual steroids. Valproic acid as an enzyme inhibitor and drug with high protein binding affinity elevates the free serum levels of androgenes. Certain antiepileptic drugs may have negative cognitive side effects, some of them can induce psychiatric disorders. These drugs can facilitate male sexual dysfunctions through these psychic side effects. The metabolic and endocrine alterations caused by carbamazepin may return to normal level after replacement of carbamazepin with oxcarbazepine. After an oxcarbazepin-carbamazepin replacement, carbamazepin-induced impotency can be cured. According some new data lamotrigine can also help in sexual dysfunction. The therapy of sexual dysfunction in epilepsy depends on its cause. In cases of hormonal alterations, the fist step is a change of antiepileptic regimen. Instead of enzymeinductor antiepileptics and valproate, new antiepileptic drugs should be prescribed. At present, the most investigated antiepileptic drug is the oxcarbazepine with positive effect on antiepileptic-induced male sexual dysfunction, however, lamotrigine seems to be also beneficial. If the hormonal and sexual dysfunctions cannot be eliminated by drug changes, androgenic therapy or bromocriptin may be required. Testosteron may not only be beneficial on sexual functions, but can reduce also the seizure frequency. Independent of etiology, erectile dysfunctions can be successfully treated by sildenafil.]

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[Family planning in multiple sclerosis: conception, pregnancy, breastfeeding]

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[Family planning is an exceptionally important question in multiple sclerosis, as women of childbearing age are the ones most often affected. Although it is proven that pregnancy does not worsen the long-term prognosis of relapsing-remitting multiple sclerosis, many patients are still doubtful about having children. This question is further complicated by the fact that patients – and often even doctors – are not sufficiently informed about how the ever-increasing number of available disease-modifying treatments affect pregnancies. Breastfeeding is an even less clear topic. Patients usually look to their neurologists first for answers concerning these matters. It falls to the neurologist to rationally evaluate the risks and benefits of contraception, pregnancy, assisted reproduction, childbirth, breastfeeding and disease modifying treatments, to inform patients about these, and then together come to a decision about the best possible therapeutic approach, taking the patients’ individual family plans into consideration. Here we present a review of relevant literature adhering to international guidelines on the topics of conception, pregnancy and breastfeeding, with a special focus on the applicability of approved disease modifying treatments during pregnancy and breastfeeding. The goal of this article is to provide clinicians involved in the care of MS patients with up-to-date information that they can utilize in their day-to-day clinical practice. ]

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[Altered rate and absolute count of Th1/Th2 and Tc1/Tc2 lymphocytes in whole blood of patients with psoriasis]

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[BACKGROUND - Psoriasis is a chronic inflammatory skin disorder characterised by an altered rate of interferon (IFN)-γ and interleukin (IL)-4 producing lesional and peripheral blood CD4+ and CD8+ T cells. To further characterise the imbalance of these cells and cytokines the rate and as a novel approach the absolute cell count (ACC) of IFN-γ+, IL-4+ and IL-10+ Thelper and Tcytotoxic cells was determined in the peripheral blood of psoriatic individuals. MATERIALS AND METHODS - Cell-associated cytokine expression was determined using intracellular cytokine staining and flow cytometry, serum cytokine levels were measured by enzyme linked immunosorbent assays (ELISAs) in the samples of 35 psoriatic patients and 15 controls. RESULTS - Significantly elevated rate (p<0.008) and ACC (p<0.009) of CD4+/IFN-γ+ cells was observed in the patients (28.3±8.8% and 237,216±134,154 cells/ml) compared to the healthy controls (21.0+ 6.8% and 135,772±50,212 cells/ml). In contrast the rate and the ACC of CD4+/IL-4+ cells decreased significantly in psoriasis (0.45±0.67% vs. 1.01± 0.48%, p<0.0001; 3,229±3,724 vs. 5,117±4,171 cells/ml, p<0.05). In the case of CD8+ T cells only the rate and the ACC of CD8+/IL-10+ cells increased significantly in patients compared to controls (5.49±5.42% vs. 1.59±0.78%, p<0.003 and 19,799±17,412 vs. 5,564±2,794 cells/ml, p<0.03). Though higher IFN-γ and lower IL-4 and IL-10 serum concentrations were detected in psoriasis these differences between patients and controls were not significant. Comparing the different cytokine parameters the serum cytokine levels showed some correlation only with the ACC and not with the rate of cytokine positive cells. CONCLUSIONS - These results further prove the presence of an altered balance in cytokine regulation towards the Thelper 1 cytokines in psoriasis, besides indicate that application of the ACC of cytokine positive helper and cytotoxic T cells as a novel parameter can help in the characterisation of these changes in different disorders.]

Clinical Neuroscience

[Magnetic resonance imaging in the course of alemtuzumab and teriflunomide therapy]

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[Our work aimed to review the published results of magnetic resonance imaging (MRI) obtained in the course of alemtuzumab and teriflunomide therapy in multiplex sclerosis. In multiplex sclerosis MRI sensitively detects subclinical pathological processes, which do not manifest clinically in the early course of the disease, however have substantial significance from the viewpoint of the long-term disease prognosis. MRI has an increasingly important role in the early monitoring of the therapeutic efficacy. In the last 15 years several clinical trials have been conducted with alemtuzumab and teriflunomide in multiple sclerosis providing evidence about the favourable clinical effect of these drugs. MRI images were acquired in these trials as well, and the results published recently in the scientific literature. These MRI results denote the suppression of the disease activity and the neurodegenerative processes, which may imply a favourable effect on the long-term prognosis of the disease. ]

Clinical Neuroscience

Evaluation of body image perception in multiple sclerosis patients without neurological deficit

SENGUL S Hakan, SENGUL Yildizhan, TAK Zeynel Abidin Ali, KOCAK Müge, TUNC Abdulkadir

Objective - There is a lack of research on the association between body image perception (BIP) and multiple sclerosis (MS). The aim of this study was to evaluate BIP in MS patients and its correlation with depression, anxiety, duration of the disease, and sociodemographic characteristics of the patients. Methods - Fifty patients with MS who applied to our outpatient clinic were examined. Forty-five healthy control were recruited for the study. All patients were diagnosed with MS according to 2010 revisions of McDonald criteria. Expanded Disability Status Scale (EDSS) was performed by the same neurologist for all patients. The participants were asked to complete a sociodemographic form, Body Cathexis Scale (BCS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Results - The mean BCS score was 86.54 ± 32.24 in MS patients and 155.00 ± 20.90 in the healthy subjects (p<0.001). While MS patients had significantly higher anxiety levels, depression scores were similar in both groups. The mean BAI score was 18.50 ± 14.03 for MS patients and 10.06 ± 7.96 in the control group (p=0.001). The BDI score of the patients was 13.77 ± 11.61 and 11.91 ± 8.65 for the controls (p=0.34). Early age of the disease onset, increased number of attacks, increased depressive symptoms, and higher anxiety levels were significantly correlated with higher BCS scores. Age and being single/ divorced/ widowed were also correlated with BCS scores. Conclusions - It is important to preserve the mental well-being of patients. Even in apparently healthy patients, the body perception may be severely impaired.

Clinical Neuroscience

[Alemtuzumab: benefits and challenges of new therapy in multiple sclerosis]

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[The widening spectrum of MS treatment is partially due to increasing knowledge about the pathogenesis of MS. The humanized monoclonal antibody against CD52, alemtuzumab has been approved in Europe for the treatment of MS, which results in long-term depletion of B and T cells due to complement- and antibody-mediated cytotoxicity. Based on phase 2 and 3 clinical trials, alemtuzumab decreases the risk of sustained neurological deficit and progression compared to high-dose subcutaneous interferon- β1a in patients with active relapsing-remitting MS, either treatment-naïve or with breakthrough disease. We review advantages and benefits of the treatment, discuss safety concerns, and present a case to describe practical issues.]