Clinical Neuroscience

[Change of therapeutic algorithm in sclerosis multiplex based on two case reports]

BIERNACKI Tamás1, BENCSIK Krisztina1, KINCSES Zsigmond Tamás1, SANDI Dániel1, FRICSKA-NAGY Zsanett1, FARAGÓ Péter1, VÉCSEI László1,2

NOVEMBER 30, 2017

Clinical Neuroscience - 2017;70(11-12)

DOI: https://doi.org/10.18071/isz.70.0381

[The aim of our case reports is to demonstrate the therapeutic use and possibilities one has with alemtuzumab, should it be used either as a first or second line therapy. Our first patient's disease in the beginning seemed to be benign. It was not the case however, over several years the diesase showed high activity both radiologically and clinically, she was treated with alemtuzumab as part of an esclationbased therapeutic strategy. The second patient's disease on the other hand showed formidable activity since the very beginning both radiologically and clinically. Therefore we were facing a very disastrous prognosis on the long run, accordingly he received alemtuzumab treatment very early into his illness.]

AFFILIATIONS

  1. Szegedi Tudományegyetem, Általános Orvostudományi Kar, Szent-Györgyi Albert Klinikai Központ, Neurológiai Klinika, Szeged
  2. MTA-SZTE Idegtudományi Kutatócsoport, Szeged

COMMENTS

0 comments

Further articles in this publication

Clinical Neuroscience

A case with reversible neurotoxicity induced by metronidazole

EREN Fulya, ALDAN Ali Mehmet, DOGAN Burcu Vasfiye, GUL Gunay, SELCUK Hatem Hakan, SOYSAL Aysun

Background - Metronidazole is a synthetic antibiotic, which has been commonly used for protozoal and anaerobic infections. It rarely causes dose - and duration - unrelated reversible neurotoxicity. It can induce hyperintense T2/FLAIR MRI lesions in several areas of the brain. Although the clinical status is catastrophic, it is completely reversible after discontinuation of the medicine. Case report - 36-year-old female patient who had recent brain abscess history was under treatment of metronidazole for 40 days. She admitted to Emergency Department with newly onset myalgia, nausea, vomiting, blurred vision and cerebellar signs. She had nystagmus in all directions of gaze, ataxia and incompetence in tandem walk. Bilateral hyperintense lesions in splenium of corpus callosum, mesencephalon and dentate nuclei were detected in T2/FLAIR MRI. Although lumbar puncture analysis was normal, her lesions were thought to be related to activation of the brain abscess and metronidazole was started to be given by intravenous way instead of oral. As lesions got bigger and clinical status got worse, metronidazole was stopped. After discontinuation of metronidazole, we detected a dramatic improvement in patient’s clinical status and MRI lesions reduced. Conclusion - Although metronidazole induced neurotoxicity is a very rare complication of the treatment, clinicians should be aware of this entity because its adverse effects are completely reversible after discontinuation of the treatment.

Clinical Neuroscience

[Alemtuzumab therapy 2017]

BIERNACKI Tamás, BENCSIK Krisztina, SANDI Dániel, VÉCSEI László

[Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system comprising of inflammation, demyelinisation and neurodegeneration. The natural history of MS is heterogenous. Owing to the vast range and severity of the symptoms MS can cause the effect of the disease on one’s cognitive and physical status is unpredictable. According to the new, phenotype based classification two subgroups can be distinguished; relapsing-remitting (RR) and progressive MS. Relapsing-remitting MS can be further divided into active and inactive disease. The activity of the disease can be proven either clinically and/or by radiological means. A patient’s disease is considered inactive, if it fulfills the criteriae set in the “no evidence of disease activity-3” (NEDA-3) concept, meaning that no progression can be seen on the MRI scans, the patient is relapse free and there is no worsening on any disability scale. Nowadays a paradigm shift can be seen in the treatment of MS. The aim of this shift is to provide each and every patient with the most potent medication best suiting his/her illness as soon as possible. Alemtuzumab offers a great option as either a first line treatment or as escalation therapy for patients with a highly active disease. The efficacy of alemtuzumab was proven in two phase III trials (CARE-MS I, II), where it was compared to subcutaneous interferon b-1a, administered three times weekly. In both studies alemtuzumab was superior to subcutaneous interferon b-1a in terms of relapse rate reduction, in all scouted MRI parameters. In the CARE-MS II trial it was found superior in terms of progression slowing. In the studies’ first 2 years 32% and 39% of the alemtuzumab treated patients managed to achieve the NEDA-3 state (data from CARE-MS II and I respectively). At the end of the 4 year extension of both studies these numbers have increased to 60% and 55% respectively. The aim of our synopsis is to suggest neurologists an evidence based guideline, a therapeutic algorithm to be used when they give their MS patients the very best, personalised treatment, and also to appoint the recently introduced alemtuzumab to its proper place in the algorithm.]

Clinical Neuroscience

Validation of the Hungarian version of Carlson’s Work-Family Conflict Scale

ÁDÁM Szilvia, KONKOLY THEGE Barna

Background and purpose - Work-family conflict has been associated with adverse individual (e.g., cardiovascular diseases, anxiety disorders), organizational (e.g., absenteeism, lower productivity), and societal outcomes (e.g., increased use of healthcare services). However, lack of standardized measurement has hindered the comparison of data across various cultures. The purpose of this study was to develop the Hungarian version of Carlson et al.’s multidimensional Work-Family Conflict Scale and establish its reliability and validity. Methods - In a sample of 557 employees (145 men and 412 women), we conducted confirmatory factor analysis to investigate the factor structure and factorial invariance of the instrument across sex and data collection points and evaluated the tool's validity by assessing relationships between its dimensions and scales measuring general, marital, and job-related stress, depressive symptomatology, vital exhaustion, functional somatic symptoms, and social support. Results - Our results showed that a six-factor model, similarly to that of the original instrument, fit the data best. Internal consistency of the six dimensions and the whole instrument was adequate. Convergent and divergent validity of the instrument and discriminant validity of the dimensions were also supported by our data. Conclusions - This study provides empirical support for the validity and reliability of the Hungarian version of the multidimensional Work-Family Conflict Scale. Deployment of this measure may allow for the generation of data that can be compared to those obtained in different cultural settings with the same instrument and hence advance our understanding of cross-cultural aspects of work-family conflict.

Clinical Neuroscience

Effect of maternal migraine on children’s quality of sleep

GÜNGEN Dogan Belma, YILDIRIM Ahmet, ARAS Guzey Yesim, ARAS Atılgan Bilgehan, TEKESIN Aysel, AYAZ Burcu Ayse

Backround and aim - Sleep disorders are common problems associated with migraine. These sleep disorders are known to have a debilitating impact on daily lives of migraine patients. The purpose of this study is to assess the effects of sleep disorders experienced by individuals suffering from migraine on their children as well as the presence of sleep disorders in their children. Materials and methods - This study included 96 mothers diagnosed with migraine and their 96 healthy children, and a control group formed of 74 healthy mothers and their children. Exclusion criteria were chronic systemic disease or central nervous system disease or a history of smoking/alcohol use for mothers, and chronic disease or regularly occurring headaches or recurrent abdominal pain for children. For maternal evaluation, the Visual Analogue Scale (VAS), Migraine Disability Assessment Scale (MIDAS), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Index (BDI) and Beck Anxiety Index (BAI) were used and for the assessment of the children’s quality of sleep, the Children’s Sleep Habits Questionnaire (CSHQ) was used. The SPSS 21.0 program was employed for statistical analysis, with statistical significance set at p<0.05. Findings - The mean age of the group with migraine was 36.6±7.1 years, while that of the control group was 38.01±4.7. Mood and sleep disorders were more frequently observed in the participants with migraine (p<0.05). Sleep disorders were significantly low in children with migraineur mothers (p=0.02); and child sleep anxiety is significantly high in control group (p=0.048). Maternal BAI scores had a significant influence on their children’s quality of sleep. Discussion and conclusion - In our study, the presence of migraine-type headache in mothers was observed to have a positive effect on reducing sleep disorders in the children. Recurrent headaches of the migraineur mothers with or without sleep disorders and psychiatric comorbidities did not influence the quality of sleep in their children directly, but the sleep anxiety of the children may have had an impact on it.

Clinical Neuroscience

[Role of peginterferon-β-1a in the therapy of multiplex sclerosis]

SIMÓ Magdolna, ILJICSOV Anna

[The subcutaneous peginterferon-b-1a is recently introduced in the therapy of relapsing-remitting multiplex sclerosis (RRMS) patients. Pegylation of IFN b-1a improved pharmacodynamic and pharmacokinetic properties, resulting in, increased biologic activity and a longer half-life. The efficacy of peginterferon-b-1a was proved by the ADVANCE study - a 2-year Phase 3, multicenter, randomized, double-blind study with a 1-year placebocontrolled period evaluating the efficacy and safety of subcutaneous peginterferon-b-1a administered every 2 or 4 weeks in patients with RRMS. Peginterferon-b-1a efficacy was maintained during the two years, with greater effects observed with every 2 week versus every 4 week dosing. Annualized relapse rate and confirmed disability progression was reduced comparing with patients on delayed treatment. Patients treated with continuous peginterferon-b-1a had fewer new or newly enlarging T2 lesions over 2 years than patients in the delayed treatment group. Adverse events were consistent with the known profiles of IFN b therapies in MS. The most commonly reported adverse events were injection site erythema, influenza-like illness. The less frequent administration is associated with fewer flu-like adverse events, which may improve patients’ compliance and adherence. Peginter-feron-b-1a could be an effective and safe treatment option for RRMS patients.]

All articles in the issue

Related contents

Clinical Neuroscience

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

ILLÉS Zsolt, TOBIAS Sejbaek, CSÉPÁNY Tünde

[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.]

Clinical Neuroscience

[Selective ultrastructural vulnerability in the cuprizone-induced experimental demyelination]

ÁCS Péter, KOMOLY Sámuel

[Background and purpose - It has been reported that multiple sclerosis has four different neuropathological subtypes, and two of them (type III and IV) are characterized by primary oligodendrocyte loss. However, the exact pathomechanism that lead to oligodendrocyte apoptosis in human demyelinating diseases is still elusive. The copper chelator cuprizone induces primary oligodendrocyte apoptosis and consequent demyelination in well defined areas of the mouse brain. Nevertheless, the precise subcellular events that result in oligodendrocyte cell death in the cuprizone model are still unknown. We aimed to study the ultrastructural alterations that might induce oligodendrocyte apoptosis in the cuprizone experimental demyelination model. Methods - C57BL/6 mice were given cuprizone for two, 21 and 35 days to induce demyelination to investigate early pathological events, and different stages of demyelination. In addition, mice were given cuprizone for 35 days and were allowed to recover for two or 14 days to study early and late remyelination. After the cuprizone treatment, mice were sacrificed and the corpus callosum, the superior cerebellar peduncle, the optic nerve and the sciatic nerve were studied by electron microscopy. Results - The ultrastructural analysis revealed that cuprizone induced oligodendrocyte apoptosis is accompanied by the formation of giant mitochondria in the affected cells in the corpus callosum and in the superior cerebellar peduncle. Apoptosis of the myelin producing cells was present through the whole cuprizone challenge. Severe demyelination occurred after three weeks of cuprizone administration associated with massive macrophage infiltration and astrocytosis of the demyelinated areas. Axons and neurons remained unaffected. Conclusion - The formation of giant mitochondria in myelin producing oligodendrocytes is the first pathological sign in the cuprizone experimental demyelination. Mitochondrium pathology in the cuprizone challenge might serve as a useful model to study the pathomechanism of multiple sclerosis subtypes (III and IV) characterized by primary oligodendrocyte degeneration.]

Clinical Neuroscience

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

MIKE Andrea, KINCSES Zsigmond Tamás, VÉCSEI László

[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. ]

Lege Artis Medicinae

[How can the fixed-dose atorvastatin/amlodipin combination help better adherence of patients to therapy?]

KIRÁLY Csaba, BENCZÚR Béla

[Among the main risk factors of cardiovascular disease which is the leading cause of death dyslipidemia has a great importance beyond hypertension, diabetes, smoking and obesity. These conditions rarely occure as isolated ones but very often a clustering of major CV risk factors within individual patients can be observed called metabolic syndrome. It’s a great challenge to convince asymptomatic but high-risk adults that they have to take a lot of medicine for a long time period uninterruptedly to prevent future vascular events (eg. MI or stroke) in the primary care settings. Mainly the low statin-adherence means the greatest problem particularly if a subject should take statin beside two or more drugs despite statins have the most prominent evidences in the field of cardiovascular prevention. The efficacy in improving adherence to therapy of fixed-dose atorvastatin/amlodipin combination was investigated in this paper based on the experiences of case reports derived from our clinical practice.]

Clinical Neuroscience

[Benign-onset acute disseminated encephalomyelitis: A report on two cases]

DEGIRMENCI Eylem, ERDOGAN Cagdas, OGUZHANOGLU Attila, BIR Sinan Levent

[The signs and symptoms of acute disseminated encephalomyelitis are heterogeneous and dependent on the location and severity of the inflammatory process. The meningoencephalitic presentation may include meningism, impaired consciousness (occasionally leading to coma), seizures and confusion, or behavioral disturbances. Multifocal neurological features include a combination of optic neuritis, visual field defects, cranial neuropathy, sensorimotor impairment, ataxia, aphasia, and involuntary movements. One definition of acute disseminated encephalomyelitis is “an initial clinical event with a presumed inflammatory and demyelinating cause, with acute or sub-acute onset affecting multifocal areas of the central nervous system”. Patients with acute disseminated encephalomyelitis frequently suffer from seizures, disturbances of consciousness, fever, and headaches, and occasionally there are focal signs and symptoms. Here, we report on two cases who presented with different symptoms, but the clinical findings that the patients showed were benign.]