Objective:To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)–β treatment in patients with multiple sclerosis (MS).Methods:Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-β treatment were included in this prospective, observational study. Number of relapses and changes in disability were assessed 2 years prior to and 2 years after initiation of treatment. Sera were collected at baseline and after 3 months on therapy. Cytokine levels in sera were assessed by Luminex multiplex assays. Baseline cytokine profiles were grouped by hierarchical clustering analysis. Demographic features, changes in cytokines, and clinical outcome were then assessed in the clustered patient groups.Results:A total of 157 patients were included in the study and clustered into 6 distinct subsets by baseline cytokine profiles. These subsets differed significantly in their clinical and biological response to IFN-β therapy. Two subsets were associated with patients who responded poorly to therapy. Two other subsets, associated with a good response to therapy, showed a significant reduction in relapse rates and no worsening of disability. Each subset also had differential changes in cytokine levels after 3 months of IFN-β treatment.Conclusions:There is heterogeneity in the immunologic pathways of the RRMS population, which correlates with IFN-β response.
Aggregatibacter actinomycetemcomitans is a human pathogen that produces leukotoxin (LtxA) as a major virulence factor. In this study the effect of LtxA on microvascular endothelial cell viability and phenotype was studied. High doses of single LtxA treatment (500 ng/ml to 5 μg/ml) significantly and irreversibly decreased cell proliferation and induced apoptosis, as assessed by tetrazolium salt and annexin V assay, respectively. Apoptosis was partially inhibited by the pan-caspase inhibitor, z-VAD-fmk. LtxA caused a cell cycle arrest in the G2/M phase after 72 h. Between 500 ng/ml and 5 μg/ml, after long- or short-term stimulation LtxA increased the expression of ICAM-1 and VCAM-1, as well as the percentages of endothelial cells expressing these adhesion molecules. Thus, A. actinomycetemcomitans LtxA has substantial pro-inflammatory effects on human brain endothelial cells by upregulation of ICAM-1 and VCAM-1. Furthermore, LtxA in higher concentration was found to decrease proliferation and induces apoptosis in microvascular endothelial cells.
Neutralizing antibodies against interferon-beta are associated with a reduction of the efficacy of this drug. Continuing treatment leads to a decline or even loss of neutralizing antibodies over years. No strategies are currently available to shorten the period of neutralizing antibody positivity. The objective of this study was to investigate the effect of switching between high and low immunogenic interferon-beta products on neutralising antibody titres. Twenty-four patients treated with the subcutaneously administered interferon-beta 1b or 1a and high titres of neutralizing antibodies were included. At baseline interferon-beta therapy was interrupted for 3 months and two pulses of high dose methylprednisolone were applied. Patients were then randomized to receive either the previous interferon-beta preparation or the low immunogenic intramuscular interferon-beta 1a. The primary end-point was the change of neutralizing antibody titres 12 months after randomization. Twelve patients were switched to interferon-beta 1a intramuscularly and 12 patients remained on previous treatment. Median neutralizing antibody titres were 846 NU at baseline and 196 NU at the end of the study. The median change of neutralizing antibody titres did not differ significantly between therapy switchers and non-switchers. Baseline and final neutralizing antibody titres correlated significantly. In conclusion, neither switching nor continuous therapy with any subcutaneous interferon-beta preparation significantly changed neutralizing antibody titres.
SUMMARYSupernumerary phantom limbs, that is, the awareness of an illusory extra limb is a fascinating neurologic symptom that has been described in a number of neurologic diseases including stroke, spinal injury, and epilepsy. Herein we report a case of a 70-year-old male patient with newonset focal seizures with left-sided supernumerary phantom arm and leg as the only seizure manifestation. Ictal single-photon emission computed tomography (SPECT) revealed a hyperperfusion in the right temporoparietal junction and allowed localization of the seizure-onset zone. This report is accompanied by a discussion of phenomenology and terminology in the context of existing literature. KEY WORDS: Supernumerary phantom limb, Epileptic seizure, Parietal lobe epilepsy, Ictal SPECT, Corporal awareness, Body schema.The term ''supernumerary phantom limb'' (SPL) describes the awareness of an illusory extra limb, in addition to the regular limbs. In earlier reports of the same symptoms the terms ''pseudo(poly)melia'' or ''reduplication of body parts'' have been used for the same phenomenon (Weinstein et al., 1954;Brugger, 2003). The symptom has been described in a variety of different neurologic disorders, right hemispheric stroke being the most common (Miyazawa et al., 2004).
Case VignetteA 70-year-old male patient presented with new-onset attacks of ''the feeling to have an additional left arm and/or left leg.'' Figure 1 shows a sketch made by the patient beautifully demonstrating how he felt these supernumerary limbs in a position between his real limbs and the body. The patient further described that the additional limbs accompanied movements of his real limbs synchronously without disturbing his normal movements. Intentional movements with the phantom limbs only were not possible. The attacks occurred up to 10 times per day with duration of few minutes, showing a crescendo and decrescendo of the intensity of the sensation. The patient reported that he could feel but not see the additional limbs and was aware that this feeling was an illusion at all times. He reported no pain or thermal sensations in the phantoms but referred to a slight tingling. During the attacks he never lost consciousness and did not experience any accompanying symptoms. Reports from eyewitnesses confirmed that he seemed absolutely normal during the attacks. Otherwise the patient was in good health both physically and psychically without any relevant medical history or family history.Neurologic examination and extensive neuropsychological testing showed normal results. Repeated routine electroencephalography (EEG) and prolonged video-EEG monitoring did not reveal any epileptic activity during or in between attacks. Recorded attacks did not show any semiology, and ictal testing was utterly normal. Cerebrospinal fluid was normal. Cerebral high-resolution magnetic resonance imaging (MRI) showed very mild frontotemporal atrophy and slightly enlarged lateral ventricles but no focal pathology. Therefore, we performed an ictal technetium-hexamethylpropylene amine...
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