Clinical Neuroscience

[Natalizumab therapy, 2013]


JULY 30, 2014

Clinical Neuroscience - 2014;67(07-08)

[Multiple sclerosis (MS) is the most common chronic disease of the central nervous system in young adults. No curative therapy is known. Currently, six drugs are available that can reduce the activity of MS. The first-line drugs can completely reduce the activity of the disease in nearly two-thirds of the patients. In the remainder, who suffer from breakthrough disease, the condition of the patient worsens, and secondline therapies must be used. The second-line drug natalizumab exhibits almost double efficacy of the first-line drugs, but also have less favourable adverse effects. As a severe side-effect for instance, natalizumab carries the risk of the development of progressive multifocal leucoencephalopathy (PML), caused by a polyoma virus, the JC virus. There are three major risk factors for PML: an anti-JCV antibody status, a long duration of natalizumab treatment and prior immunosuppressant therapy. The lowest-risk group (1:14 286) comprises of patients who are anti-JCV antibody-negative, in whom the prior immunosuppressant use and duration of natalizumab therapy do not influence the risk of PML. With no prior immunosuppressant treatment, the incidence of PML increases to 1 in 192 patients after 2 years among those who are anti-JCV antibody-positive. These data may lead the physician to decide to discontinue natalizumab treatment. The half-life of natalizumab is three months; during this time other therapies can not be administered and the patients encounter the rebound effect: as the patients receiving natalizumab therapy displayed a high disease activity before treatment, the rebound effect can lead to relapses. After the termination of natalizumab secondline disease-modifying therapy with fingolimod may be introduce; no PML cases occur in response to fingolimod treatment. In the large majority of patients taking natalizumab who do not develop PML, this drug is highly effective and can prevent the progression of MS. The benefit of therapy and the risk of PML must be considered on an individual basis, with regard to the disease activity, the progression and the MRI activity, before natalizumab therapy is implemented.]



Further articles in this publication

Clinical Neuroscience

[Depression in Parkinson’s disease]

RIHMER Zoltán, GONDA Xénia, DÖME Péter

[The prevalence of major and minor depression in Parkinson’s disease is around 30-40% but, unfortunately, depression remains frequently underrecognized and often undertreated. However, recognition and appropriate treatment of depression in patients with Parkinson’s disease is essential for improving the cross-sectional picture and longitudinal course. This review focuses on the epidemiology, pathophysiology and different treatment modalities of depression in Parkinson’s disease.]

Clinical Neuroscience

[Maybe it hurts more than you think! - Neonatal pain]

MIKOS Borbála

[Neonatal pain is often undertreated. This is based on the assumption that because of the immature nervous system and the lack of the myelinisation preterm and newborn does not feel pain. It is confirmed by a number of articles that the fetus and neonate can experience and respond to painful events. This publication gives a brief overview of the ontogeny of the pain, short-and long-term postnatal consequences, as well as the perception of the possibility of a particularly frail child population: premature infants and neonates, based on animal and human studies.]

Clinical Neuroscience

[The impact of levodopa-carbidopa intestinal gel on health-related quality of life in Parkinson’s disease]

KOVÁCS Norbert, ASCHERMANN Zsuzsanna, ÁCS Péter, BOSNYÁK Edit, DELI Gabriella, JANSZKY József, KOMOLY Sámuel

[Background - The levodopa/carbidopa intestinal gel (LCIG) therapy can improve the severe fluctuations associated with advanced Parkinson’s disease (PD). Our aim was to assess the improvement in the health related quality of life of PD patients treated with LCIG at University of Pécs. Methods - Eight PD patients were evaluated (age: 68.1±4.4 years, disease duration: 14,5±6,2 years, duration of fluctuations: 8.9±3.1 years). Before the initiation of LCIG treatment and 6 and 12 months later, the health-related quality of life (PDQ-39 and EQ-5D-5L), severity of PDrelated symptoms (MDS-UPDRS, Hoehn-Yahr Scale, Clinical Global Improvement - Severity) and major non-motor symptoms (PD Sleep Scale 2nd version: PDSS-2, Epworth Scale and Beck Depression Inventory: BDI) were assessed. Results - Health-related quality life improved after LCIG treatment measured by both EQ-5D-5L (from 0.257 to 0.662, p=0.009) and PDQ-39 (from 34 to 26 points, p=0.038). Meanwhile PD-related symptoms (MDS-UPDRS total score: from 105 points to 68 points, p<0.05) sleep quality (PDSS-2: from 25 to 22 points, p<0.05), daytime sleepiness (Epworth: from 12 to 7 points, p<0.05) and depression (BDI: from 20 to 15 points, p<0.05) also improved. Median ON time improved form 4.5 hours to 10.0 hours; whereas, the OFF time decreased from 4.5 to 0.5 hours (p<0.05). Conclusion - Both the quality of life and the clinical features of PD can be improved by LCIG treatment in advanced PD.]

Clinical Neuroscience

[Single dose irradiation of defined region of rat brain with stereotactic BrainLab system]


[Background and purpose of our study was to develop a precise dose delivery technique for partial brain irradiation of two rats simultaneously. Methods - Using a self-developed frame stereotactic radiotherapy with single doses of 30-90 Gy was delivered to the frontal lobe of 22 animals. Tolerability and reproducibility of the method were evaluated and dosimetric measurements were conducted to verify the treatment plans. 2, 4 and 6 months after the irradiation magnetic resonance imaging (MRI) scans and histopathological examinations were performed to detect late radiation induced biological changes. Results - Immobilization device provided excellent reproducibility and tolerability. Dosimetry revealed good corres - pondence with planned dose distribution, but the measured absorbed dose was 30% lower than the planned dose. During the 6 months follow-up period the procedure related death of subject animals after 30 Gy, 70 Gy and 90 Gy were 0%, 20% and 100% respectively. T2 signal and structural changes on MRI scans found to be dose and time dependent. While 30 Gy caused no detectable structural changes, 70 Gy lead to cystic necrosis in 2 cases after 4 month. Histopathology revealed signs of necrosis on macroscopic examination after 70 Gy in the high dose region involving both frontal lobes, and no obvious microscopic changes in the surrounding area were detectable. Conclusion - Our technique of rat cranial irradiation using human stereotactic system provided high accuracy of single dose delivery for a pair of small animals, resulting in brain injury in the defined area. This method proved to be a reproducible model for preclinical studies on radiation effects.]

Clinical Neuroscience

[Examining the diagnostic accuracy of a new migraine screener]

CSÉPÁNY Éva, BOZSIK György, KELLERMANN István, HAJNAL Boglárka, SCHEIDL Erika, PALÁSTI Ágnes, TÓTH Marianna, GYÜRE Tamás, ERTSEY Csaba

[Background - Migraine affects more than 10% of the Hungarian population, causes significant disability and severely affects patients’ generic and condition-specific quality of life. Despite these facts, a significant proportion of patients is not diagnosed and not treated adequately. Headache centres can provide care for only a fraction of all patients. The task of primary care providers would be greatly simplified by a reliable self-administered migraine screening questionnaire. Objective - To develop a short and reliable questionnaire as a migraine screening tool. Methods - Outpatients at the Headache Service, Department of Neurology, Semmelweis University completed a self-administered questionnaire which contained 9 yes/no questions about their headaches’ characteristics. The number of ’yes’ answers (the patients’ total score) was evaluated in connection with the diagnosis based on the International Headache Society criteria. We calculated the sensitivity, specificity, positive and negative predictive value as well as the misclassification rate for each total score value and used these to establish the final cutoff value of the questionnaire. 306 patients (242 females, mean age 39.1±13.3 years) were enrolled. The diagnosis was migraine in 244. Results - Completing the questionnaire did not pose any difficulty for the patients. At a cutoff value of 5 points the questionnaire’s sensitivity was 0.96 and specificity was 0.61. The positive predictive value was 0.91 and the negative predictive value was 0.81. The misclassification rate was 0.11. Discussion - Our results show that the questionnaire may help the diagnosis of migraine. In order to use it in medical practice, its further evaluation is necessary on a large representative sample of the Hungarian population.]

All articles in the issue

Related contents

Clinical Neuroscience

[Health status and costs of ambulatory patients with multiple sclerosis in Hungary]

PÉNTEK Márta, GULÁCSI László, RÓZSA Csilla, SIMÓ Magdolna, ILJICSOV Anna, KOMOLY Sámuel, BRODSZKY Valentin

[Background and purpose - Data on disease burden of multiple sclerosis from Eastern-Central Europe are very limited. Our aim was to explore the quality of life, resource utilisation and costs of ambulating patients with multiple sclerosis in Hungary. Methods - Cross-sectional questionnaire survey was performed in two outpatient neurology centres in 2009. Clinical history, health care utilisation in the past 12 months were surveyed, the Expanded Disability Status Scale and the EQ-5D questionnaires were applied. Cost calculation was conducted from the societal perspective. Results - Sixty-eight patients (female 70.6%) aged 38.0 (SD 9.1) with disease duration of 7.8 (SD 6.7) years were involved. Fifty-five (80.9%) had relapsing-remitting form and 52 (76.5%) were taking immunomodulatory drug. The average scores were: Expanded Disability Status Scale 1.9 (SD 1.7), EQ-5D 0.67 (SD 0.28). Mean total cost amounted to 10 902 Euros/patient/year (direct medical 67%, direct nonmedical 13%, indirect costs 20%). Drugs, disability pension and informal care were the highest cost items. Costs of mild (Expanded Disability Status Scale 0-3.5) and moderate (Expanded Disability Status Scale 4.0-6.5) disease were 9 218 and 17 634 Euros/patient/year respectively (p<0.01), that is lower than results from Western European countries. Conclusion - Our study provides current inputs for policy making and contributes to understanding variation of costof- illness of multiple sclerosis in Europe.]

Clinical Neuroscience

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

RÓZSA Csilla

[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. ]

Clinical Neuroscience

Matrix metalloproteinases and their tissue inhibitors in relapsing remitting multiple sclerosis: Possible markers and treatment agents


Matrix metalloproteinases (MMPs), which are synthesized by many cell groups and responsible for the destruction of matrix proteins, and endogen tissue inhibitors of MMPs (TIMPs) have a role in the pathogenesis of Multiple Sclerosis (MS) by affecting the blood-brain barrier. We aimed to investigate the role of MMPs and TIMPs in the immunopathogenesis and in the course of multiple sclerosis (MS). We enrolled 25 relapsing remitting MS patients, who had a definite MS diagnosis according to McDonald criteria and 25 healthy subjects similar for age and gender as control group. MMP-9- and TIMP-1 levels were measured twice in patient group (one time during an attack and one in remission) and once in healthy subjects. MMP-9- and TIMP-levels of patients during attack and remission period and MMP-9/TIMP-1 ratio were found significantly higher than in the control subjects. In patient group MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratio during attacks were not significantly different than during remission period. However, when subdivided according to their number of attacks, patients with 2 attacks had significantly higher levels during attack period comparing to remission period (p<0.05); in case of patients with more than 2 attacks did not have a statistically significant difference in attack and remission periods. Matrix metalloproteinases are important actors in MS immunopathogenesis, particularly in the early period and inhibitor agents for these enzymes can be used as a treatment option.

Clinical Neuroscience

[MR imaging of acute disseminated encephalomyelitis and multiple sclerosis in children. A review (in English language)]

PATAY Zoltán

[Inflammatory diseases of the central nervous system (CNS) are relatively rare in children, but their relevance to public health is considerable due to frequent and significant long term morbidity and even mortality. As in adults, acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) and their variants are the most common entities in this group of pathologies in the pediatric patient population. Recent efforts have focused on establishing standardized diagnostic criteria schemes to facilitate the diagnosis and differential diagnosis of these diseases, however especially with multiple sclerosis those have not been fully validated yet for disease occurring in children. In recent decades the role of MRI has been constantly increasing in the diagnostic work-up of suspected inflammatory diseases of the CNS as well as in the follow-up of patients with confirmed disease. Currently, MRI is the first-line diagnostic imaging modality in ADEM and MS and is fully integrated in the most widely used diagnostic criteria schemes, but it has a key role in clinical therapeutic research trials as well. This paper provides an update on the current concepts and strategies of MRI in inflammatory diseases of the CNS, as well as a review of the imaging semiology of the various disease entities and variants with emphasis on clinical and imaging particularities relevant to the pediatric patient population.]

Clinical Neuroscience

[Symptomatic trigeminal autonomic cephalalgia without headache]

RÓZSA Anikó, KOVÁCS Krisztina, GUBA Katalin, GÁCS Gyula

[We report the case of a 60-year-old man who exhibited trigeminal autonomic symptoms on his right side (numbness of the face, reddening of the eye, nasal congestion) occurring several times a day, for a maximum of 60 se­conds, without any pain. The complaints were similar to trigeminal autonomic cephalalgia, just without any headache. Our 60-year-old male patient underwent a craniocervical MRI as part of his neurological workup, which revealed lesions indicative of demyelination. Further testing was guided (ophthalmological examination, VEP, CSF test) by the presumptive diagnosis of multiple sclerosis. It is likely that in his case the cause of these trigeminal and autonomic paroxysms is MS. Here we present an overview of the few cases we found in the literature, although we did not find any similar case reports. Perhaps the most interesting among these is one in which the author describes a family: a 54-year-old female exhibiting the autonomic characteristics of an episodic cluster headache, only without actual headache, her son, who had typical episodic cluster headaches with autonomic symptoms, and the woman’s father, whose short-term periorbital headaches were present without autonomic symptoms. We had not previously encountered a case of trigeminal autonomic cephalalgia without headache in our practice, nor have we had an MS patient exhibiting similar neurologic symptoms. The significance of our case lies in its uniqueness. ]