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This paper deals with thyroid disease that can occur after treatment with alemtuzumab (humanized monoclonal anti-CD52) for relapsing-remitting multiple sclerosis (MS). The 5-year incidence of thyroid adverse events in phase 3 clinical trials is up to 40.7%. In most cases, the thyroid dysfunction is mild and easily manageable and only few serious thyroid adverse events have been reported. The need for patient education on the risk of thyroid dysfunction, as well as regular clinical and biochemical thyroid function screening is well described. However, practical clinical guidance in case of abnormal thyroid-related findings prior to or after alemtuzumab treatment is currently lacking. Therefore, a Belgian taskforce consisting of MS and thyroid experts was created in 2016, with the objective of issuing a clinical thyroid management algorithm based on available scientific evidence and personal experience with regard to alemtuzumab treatment-related thyroid adverse events.

Natalizumab (Tysabri(®)) is highly efficacious in controlling disease activity in relapsing multiple sclerosis (MS) patients. As it is one of the more recent therapies for MS, there remains a need for long-term safety and efficacy data of natalizumab in a clinical practice setting. The Tysabri observational program (TOP) is an open-label, multicenter, multinational, prospective observational study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from Europe, Canada and Australia. The objectives of this study are to collect long-term safety and efficacy data on disease activity and disability progression. We report here the interim results of the 563 patients included in TOP between December 2007 and 2012 from Belgium. This patient cohort was older at baseline, had longer disease duration, higher neurological impairment, and a higher baseline annualized relapse rate, when compared to patients included in the pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was comparable. The annualized relapse rate on treatment was reduced by 90.70 % (p < 0.0001) with a cumulative probability of relapse of 26.87 % at 24 months. The cumulative probabilities of sustained disability improvement and progression at 24 months were 25.68 and 9.01 %, respectively. There were no new safety concerns over the follow-up period. Two cases of progressive multifocal leukoencephalopathy were diagnosed. Our results are consistent with other observational studies in the post-marketing setting.

Background: Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy of natalizumab on disability status and ambulation after switching patients with RRMS from other disease-modifying treatments (DMTs).Methods: A retrospective, observational study was carried out. All patients (n=45) initiated natalizumab after experiencing at least 1 relapse in the previous year under interferon-beta (IFNB) or glatiramer acetate (GA) treatments. The patients also had at least 1 gadolinium-enhancing (Gd+) lesion on their baseline brain MRI. Expanded Disability Status Scale (EDSS) scores, and performance on the Timed 25-Foot Walk Test and on the Timed 100-Metre Walk Test were prospectively collected every 4 weeks during 44 weeks of natalizumab treatment. Brain MRI scans were performed after 20 and 44 weeks of treatment.Results: Sixty-two per cent of patients showed no clinical and no radiological signs of disease activity, and 29% showed a rapid and confirmed EDSS improvement over 44 weeks of natalizumab therapy. Patients with improvement on the EDSS showed similar levels of baseline EDSS and active T1 lesions, but had a significantly higher number of relapses, and 92% of them had experienced relapse-mediated sustained EDSS worsening in the previous year. A clinically meaningful improvement in ambulation speed was observed in approximately 30% of patients.Conclusions: These results indicate that natalizumab silences disease activity and rapidly improves disability status and walking performance, possibly through delayed relapse recovery in patients with RRMS who had shown a high level of disease activity under other DMTs. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

Comment, Letter, info:eu-repo/semantics/published

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Case Reports, Journal Article, info:eu-repo/semantics/published

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Case Reports, Letter, FLWIN, info:eu-repo/semantics/published

Oculomotor nerve disease is a common cause of diplopia. When strabismus is present, absence of diplopia has to induce the research of either uncovering of visual fields or monocular suppression, amblyopia or blindness. We describe the case of a 41-year-old woman presenting with right oculomotor paresis and left object-centred visual neglect due to a right fronto-parietal haemorrhage expanding to the right peri-mesencephalic cisterna caused by the rupture of a right middle cerebral artery aneurysm. She never complained of diplopia despite binocular vision and progressive recovery of strabismus, excluding uncovering of visual fields. Since all other causes were excluded in this case, we hypothesise that the absence of diplopia was due to the object-centred visual neglect. Partial internal right oculomotor paresis causes an ocular deviation in abduction; the image being perceived deviated contralaterally to the left. Thus, in our case, the neglect of the left image is equivalent to a right monocular functional blindness. However, bell cancellation test clearly worsened when assessed in left monocular vision confirming that eye patching can worsen attentional visual neglect. In conclusion, our case argues for the possibility of a functional monocular blindness induced by visual neglect. We think that in presence of strabismus, absence of diplopia should induce the search for hemispatial visual neglect when supratentorial lesions are suspected., Case Reports, Journal Article, info:eu-repo/semantics/published

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Sciatic nerve palsy is an uncommon complication of cardiac surgery and is thought to be induced by a combination of reduced femoral artery blood flow, small vessel vascular disease or prolonged hypoxia. We here describe a new case which is the first described with transient elevation of antiphospholipid antibodies. Although transient elevation of lupus coagulation inhibitor is known to occur frequently in patients treated in an intensive care unit, there are very few data about the possible role of antiphospholipid antibodies in the generation of ischemic neuropathies. We can not prove that the ischemic neuropathy in our case has been favored by the presence of lupus coagulation inhibitor and antiphospholipid antibodies as the occurrence of the symptoms seemed to precede the transient elevation of lupus coagulation inhibitor. This case suggests that antiphospholipid antibodies and lupus coagulation inhibitor should be included in the work up of patients who present nerve damage after cardiac surgery but further studies are needed to ascertain this association., Case Reports, Journal Article, info:eu-repo/semantics/published

Neuropsychological deficits may occur in infratentorial strokes. Only minor cognitive disturbances are reported in unilateral anterior cerebellar lesions. Here, the authors describe a patient with bilateral anterior ponto-cerebellar ischemic lesions associated with major neuropsychological deficits. Cerebral PET and SPECT demonstrated no metabolic defect in supratentorial areas., Case Reports, Journal Article, info:eu-repo/semantics/published

It was observed that interferon beta (IFN-beta) prevents the down-regulation of the interleukin-3 receptor alpha chain (IL-3Ralpha), which spontaneously occurs during culture of human monocytes. The functionality of IL-3R was demonstrated by the fact that IL-3 rescued IFN-beta-treated monocytes from apoptosis. Monocytes cultured in the presence of IFN-beta and IL-3 acquire a dendritic morphology and express high levels of HLA antigen class I and class II and costimulatory molecules. When stimulated by either lipopolysaccharide or fibroblasts expressing CD40 ligand (CD40L) transfectants, dendritic cells (DCs) generated in IFN-beta and IL-3 secreted high levels of IL-6, IL-8, and tumor necrosis factor-alpha but low levels of IL-12 in comparison with DCs generated in IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In mixed leukocyte culture, IL-3-IFN-beta DCs induced a vigorous proliferative response of allogeneic cord blood T cells and elicited the production of high levels of IFN-gamma and IL-5 by naive adult CD4+ T cells. Finally, IL-3-IFN-beta DCs were found to produce much higher levels of IFN-alpha than IL-4-GM-CSF DCs in response to Poly (I:C) but not to influenza virus. It was concluded that monocytes cultured in the presence of IL-3 and IFN-beta differentiate into DCs with potent helper T-cell stimulatory capacity despite their low secretion of IL-12., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Clinical studies have demonstrated beneficial effects of interferon-β (IFN-β) therapy in multiple sclerosis (MS) patients. However, the mechanism of action of IFN-β in MS remains unknown. IFN-β has even been demonstrated to enhance isolated T cell secretion of IFN-γ, a cytokine proven to be deleterious in MS. However, IFN-β inhibits IFN-γ secretion of T cells, when they are stimulated by antigen presenting cells (APC). We therefore decided to study the effects of IFN-β on the in vitro differentiation of dendritic cells (DC), a major class of APC. First, we found that the addition of IFN- β at the initiation of the differentiation did not modify DC morphology, but enhanced the expression of molecules involved in antigen presentation (HLA- DR, B7/1 and B7/2). However, DC, differentiated in the presence of IFN-β, secreted less interleukin-12 (IL-12) both spontaneously and upon activated by CD40-ligand bearing cells. As a consequence, DC differentiated in the presence of IFN-β induced less IFN-γ secretion by alloreactive T cells. We conclude that the direct action of IFN-β on DC results in inhibition of their ability to secrete IL-12 and to elicit Thelper-1 (Th-1) type responses. These results are of particular interest in MS, in which a critical role for IL-12 has recently been suggested by a number of clinical and experimental observations., SCOPUS: ar.j, info:eu-repo/semantics/published

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The idiopathic hypereosinophilic syndrome (HES) is a heterogenous disease entity characterized by persistent unexplained hypereosinophilia generally complicated by end-organ damage. Correct diagnosis and management are important in order to prevent long-term complications. Furthermore, it appears that HES represents a premalignant state in some patients, and close follow-up is necessary to detect early signs of malignant transformation. Previous studies of patient cohorts have led to the identification of a subgroup of patients with various clinical and biological features of primitive myeloproliferative disease. Patients in this subgroup have a clinically more aggressive disease in terms of organ damage and eventually develop acute myeloid leukemia. Among the remaining patients, it appears that some present an underlying T-cell disorder characterized by overproduction of Th2-type cytokines in vivo. Indeed, lymphocytes belonging to the Th2 subset are implicated in the maturation, activation and recruitment of eosinophils, essentially through the production of IL-5. Such patients appear to present a more benign disease at short term; however, they may develop T-cell lymphoma years after initial diagnosis. Therapy of HES includes glucocorticoids, hydroxyurea and more recently, interferon-alpha. Prednisone is generally recommended initially, followed by hydroxyurea in case of treatment failure. Until now, interferon-alpha has been reserved for refractory cases of HES. Our proposal for a new treatment strategy, based on current understanding of the pathogenesis of different subgroups of HES and on the mechanisms of action of the proposed therapeutic agents, which will be discussed in detail. Moreover, prevention of malignant transformation has become a new subject of concern when considering the beneficial effects of drugs., Journal Article, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

Although cerebellar-like ataxia is a well known component of the ataxic hemiparesis (AH), the mechanism of hypermetria in AH has not been established. We describe a patient presenting a left AH following a right pontine infarction. We investigated the ballistic flexion movements of both wrists and the associated agonist and antagonist electromyographic (EMG) activities, before and after addition of inertial loads. At the time of motion analysis, neurological examination showed cerebellar-like dysmetria of the left side but the patient had recovered a normal strength. In the basal state (without addition of loads), movements of the left wrist were hypermetric. The I duration of the agonist EMG activity was prolonged and the onset latency of the antagonist EMG activity was not delayed. Moreover, when a mass was added, the hypermetria was unchanged because the patient was unable to adapt appropriately neither the agonist, nor the g antagonist EMG activity. We suggest that the hypermetria was due to an imbalance between the duration of the agonist EMG activity (the launching force) and the duration of the antagonist EMG activity (the braking force)., SCOPUS: ar.j, info:eu-repo/semantics/published