Clinical Neuroscience

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

SIMÓ Magdolna, ILJICSOV Anna

NOVEMBER 30, 2017

Clinical Neuroscience - 2017;70(11-12)


[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.]



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

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

[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

[Tension-type headache in ulcerative colitis]

TAJTI Jr. János, LÁTOS Melinda, ÁBRAHÁM Szabolcs, SIMONKA Zsolt, PASZT Attila, LÁZÁR György

[Background and purpose - Tension-type headache is a very common disease with a high socio-economic impact as its lifetime prevalence is 30-78% in the general population. The incidence of inflammatory bowel diseases is continuously rising. Limited data are accessible on quality of life in patients with surgically treated ulcerative colitis. The aim of our study is to examine quality of life, concerning headache, among patients who had undergone surgery due to ulcerative colitis. Methods - Between 1 January 2005 and 1 March 2016, surgery was performed due to ulcerative colitis in 75 patients. During this retrospective analysis the average duration of the follow-up was 46 (1-124) months. The pre-sence of headache was evaluated by the use of Brief Illness Perception and Headache Questionnaires. Results - Among the primary headache disorders (n=27), tension-type headache occurred in 19 (70.4%) cases, and 8 (29.6%) patients had migraine (without aura). Among tension-type headache cases 17 (89.5%) patients experienced episodic form and 2 (10.5%) suffered from chronic form. Patients with headache had obtained a significantly higher score on Brief Illness Perception Questionnaire. Conclusions - According to our study tension-type headache is common among patients with ulcerative colitis. This observation raises the question whether stress plays role in the pathogenesis of both diseases, which influences and worsens considerably quality of life. Neurological examination, psychological and psychiatric guidance are worth considering in patients with ulcerative colitis.]

Clinical Neuroscience

Nerve conduction study and gastrocnemius H reflex response in rheumatoid arthritis

EMRE Ufuk, ORTANCIL Özgül, UNAL Aysun, KIRAN Sibel, SAPMAZ Perihan, ATASOY Tugrul

Objectives - We aimed to evaluate nerve conduction studies and gastrocnemius H reflex responses in rheumatoid arthritis (RA) patients and compared to the healthy adult subjects. Materials and methods - Twenty-six RA patients and twenty-two healthy adult subjects were included in the study. The nerve conduction study (NCS) findings and bilateral gastrocnemius H reflex responses were evaluated in all the groups. Age, gender, subcutaneous nodules, joint deformities, laboratory parameters, duration of disease, anti-rheumatic drug and steroid usage were recorded. Activity of disease was assessed using a 28-joint disease activity score (DAS28).The functional status was measured using the health assessment questionnaire (HAQ), pain intensity measured using a visual analog scale (VAS). Results - The rate of electroneuromyographic (ENMG) abnormalities was 73% in RA patients. The most common diagnosis was carpal tunnel syndrome (61.4%). There were no significant correlations between ENMG findings and clinical and laboratory features evaluated. Right H reflex latencies were statistically longer in RA patients (p=0.03). According to calculated cut-off levels, there were more subjects with longer H reflex latencies in RA patients. Conclusions - In this study, entrapment neuropathies were found common as independent identity from duration and severity of disease in RA patients. For H reflex latencies, cut-off values were longer in RA patients. It may provide information about the early neuropathic involvement of long peripheral nerves in RA patients. But this findings are needed to be supported by larger population study.

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[The role of sleep in the relational memory processes ]

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[A growing body of evidence suggests that sleep plays an essential role in the consolidation of different memory systems, but less is known about the beneficial effect of sleep on relational memory processes and the recognition of emotional facial expressions, however, it is a fundamental cognitive skill in human everyday life. Thus, the study aims to investigate the effect of timing of learning and the role of sleep in relational memory processes. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. Our results suggest that the timing of learning and sleep plays an important role in the stabilizing process of memory representation to resist against forgetting.]

Clinical Neuroscience

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Clinical Neuroscience

The etiology and age-related properties of patients with delirium in coronary intensive care unit and its effects on inhospital and follow up prognosis

ALTAY Servet, GÜRDOGAN Muhammet, KAYA Caglar, KARDAS Fatih, ZEYBEY Utku, CAKIR Burcu, EBIK Mustafa, DEMIR Melik

Delirium is a syndrome frequently encountered in intensive care and associated with a poor prognosis. Intensive care delirium is mostly based on general and palliative intensive care data in the literature. In this study, we aimed to investigate the incidence of delirium in coronary intensive care unit (CICU), related factors, its relationship with inhospital and follow up prognosis, incidence of age-related delirium and its effect on outcomes. This study was conducted with patients hospitalized in CICU of a tertiary university hospital between 01 August 2017 and 01 August 2018. Files of all patients were examined in details, and demographic, clinic and laboratory parameters were recorded. Patients confirmed with psychiatry consultation were included in the groups of patients who developed delirium. Patients were divided into groups with and without delirium developed, and baseline features, inhospital and follow up prognoses were investigated. In addition, patients were divided into four groups as <65 years old, 65-75 yo, 75-84 yo and> 85 yo, and the incidence of delirium, related factors and prognoses were compared among these groups. A total of 1108 patients (mean age: 64.4 ± 13.9 years; 66% men) who were followed in the intensive care unit with variable indications were included in the study. Of all patients 11.1% developed delirium in the CICU. Patients who developed delirium were older, comorbidities were more frequent, and these patients showed increased inflammation findings, and significant increase in inhospital mortality compared to those who did not develop delirium (p<0.05). At median 9-month follow up period, rehospitalization, reinfarction, cognitive dysfunction, initiation of psychiatric therapy and mortality were significantly higher in the delirium group (p<0.05). When patients who developed delirium were divided into four groups by age and analyzed, incidence of delirium and mortality rate in delirium group were significantly increased by age (p<0.05). Development of delirium in coronary intensive care unit is associated with increased inhospital and follow up morbidity and mortality. Delirium is more commonly seen in geriatric patients and those with comorbidity, and is associated with a poorer prognosis. High-risk patients should be more carefully monitored for the risk of delirium.

Clinical Neuroscience

A rare entity of acquired idiopathic generalised anhidrosis which has been successfully treated with pulse steroid therapy: Does the histopathology predict the treatment response?

ÖKTEM Özdemir Ece, ÇANKAYA Şeyda, UYKUR Burak Abdullah, ERDEN Simsek Nazan, YULUG Burak

Acquired idiopathic generalised anhidrosis is an uncommon sweating disorder characterized by loss of sweating in the absence of any neurologic, metabolic or sweat gland abnormalities. Although some possible immunological and structural mechanisms have been proposed for this rare entity, the definitive pathophysiology is still un­clear. Despite some successfully treated cases with systemic corticosteroid application, the dose and route of steroid application are controversial. Here, we present a 41-year-old man with lack of genera­lised sweating who has been successfully treated with high dose pulse intravenous prednisolone. We have discussed his clinical and histopathological findings as well as the treatment options in view of the current literature.

Clinical Neuroscience

[Zonisamide: one of the first-line antiepileptic drugs in focal epilepsy ]


[Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term ’epilepsy’ which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level „A”) as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient’s compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.]