Clinical Neuroscience

[Vécsei-Komoly (eds.): Sclerosis multiplex]

HARCOS Péter

MARCH 10, 2005

Clinical Neuroscience - 2005;58(03-04)

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Clinical Neuroscience

[Clinical neurosciences for efficient treatment - 2nd Live Issue of Clinical Neuroscience/ Ideggyógyászati Szemle]

RAJNA Péter

[Clinical neurosciences for efficient treatment - 2nd Live Issue of Clinical Neuroscience/ Ideggyógyászati Szemle 2005;58(03-04)]

Clinical Neuroscience

[CLINICO-PATHOLOGY AND DIFFERENTIAL DIAGNOSIS OF BINSWANGER’S DISEASE]

KOVÁCS Tibor, SZIRMAI Imre, PAPP Mátyás

[Pathologically, Binswanger’s disease is subcortical periventricular leucoencephalopathy sparing the U fibers. Clinically it is characterised by executive dysfunction, gait problems, urinary incontinence, pseudobulbar palsy, mood disturbances and dementia. The pathomechanism of Binswanger’s disease is unclear. It is hypothesized that it results from an ischemic-hypoxic injury of the periventricular white matter, which, in turn, can be caused by a sclerotic elongation of the medullary arteries, widening of the perivascular spaces or decreased brain perfusion due to hypotension or heart disease. The symptoms of Binswanger’s disease frequently overlap with those of normal pressure hydrocephalus, vascular parkinsonism and Alzheimer’s disease. A diagnostic criterion of Binswanger’s disease is radiologically demonstrated leukoaraiosis, which, on the other hand, is not equivalent with Binswanger’s disease. A good clinical response after lumbar puncture or shunt implantation might lead to confusion with normal pressure hydrocephalus, which further complicates the clinical diagnosis. It is likely that among the above mentioned disorders there are a number of transitional forms and overlaps, which might be explained by the common pathomechanism of disturbance in cerebrospinal fluid circulation.]

Clinical Neuroscience

[Supplementary sensory-motor seizures - symptomatology, etiology, and surgical management with illustrative case reports]

HALÁSZ Péter, JUHOS Vera, ERÕSS Loránd, TÓTH Szabolcs, BALOGH Attila, GYÖRGY Ilona, BARSI Péter, KELEMEN Anna, BARCS Gábor

[In the past decade, owing to the advance of epilepsy surgery, growing knowledge has accumulated on the role of the supplementary motor area, described by Penfield and coworkers in the early fifties, in movement regulation and on the characteristics of seizures involving this area. In the Hungarian neurological literature this topic - despite its neurophysiological and practical clinical importance - has been hardly touched. The authors, based on their own experience obtained from surgeries performed within the framework of the "Co-operative Epilepsy Surgery Program", describe the electrophysiological features of this area, its role in movement regulation and the symptoms of epileptic seizures stemmed from or spread onto this area. Using cases as illustrations, they demonstrate the reasoning and various algorithms of the multidisciplinary examination necessary to explore the seizure onset zone and the pathways of seizure spread. Details of the surgical solution are also described.]

Clinical Neuroscience

[Primary prevention program of the Hungarian Spine Society - Part I. Scientific background of the posture correction exercise scheme]

GARDI Zsuzsa, FESZTHAMMER Artúrné, DARABOSNÉ Tim Irma, TÓTHNÉ Steinhausz Viktória, SOMHEGYI Annamária, VARGA Péter Pál

[The primary prevention program of the Hungarian Spine Society aims to increase awareness of the need to develop and automatically maintain a biomechanically correct posture for all school children. The biomechanically correct posture is a dynamic balance based on a correct middle position of the pelvis and on muscle balance. In this position three important anatomical points - the left and right anterior superior iliac spines and the upper medial point of the pubic bone - form one frontal plane. From side-view the imaginary weight median of the body crosses the 2nd to 5th lumbar and the 2nd to 5th cervical vertebral bodies. When the muscles involved in posture are in balance, their strength and flexibility are just appropriate for the almost continuous work required against gravity. In case of static and/or dynamic under- or overload tonic muscles become shortened, and phasic muscles become stretched, and are no longer able to work optimally. Since many muscles and muscle parts that are involved in normal posture maintenance are not satisfactorily challenged in regular physical exercises and sport activities, the preventive exercise scheme of the Hungarian Spine Society aimed to involve these rarely used muscles in special strengthening and stretching exercises. The scheme is based on 12 test exercises that assess the strength and flexibility of postural muscles. A person who is able to do all test exercises correctly has no problem with his or her muscle balance. In order to counteract the harm caused by sedentary lifestyle already in childhood, regular use of this posture correction scheme in physical education starting from preschool throughout the school-years is recommended for all children.]

Clinical Neuroscience

[Application of the Multiple Sclerosis Functional Composite in Debrecen]

MEZEI Zsolt, BERECZKI Dániel, CSIBA László, CSÉPÁNY Tünde

[Introduction - The Multiple Sclerosis Functional Composite (MSFC) has been recommended by the National Multiple Sclerosis Society as a new clinical outcome measure. It is based on measurements in three clinical dimensions: leg function/ambulation (timed 25-foot walk), arm function (9-hole peg test), and cognitive function (paced auditory serial addition test). Scores on component measures are converted to standard scores (Z-scores) that reflect patient performance. This method has not yet been introduced into routine clinical practice. Patients and method - MSFC calculation was applied to 17 patients with relapsing-remitting multiple sclerosis (age mean: 37.4±10.8 years; duration of the disease: 5.5±4.9 years, EDSS: 2.7±1.4) seen at the neuroimmunological outpatient clinic to evaluate its usefulness and its correlation with the traditionally applied Expanded Disability Status Scale (EDSS) and with patient-reported quality of life. Fifteen patients received immunomodulatory treatment (interferon beta and glatiramer acetate). MSFC and EDSS were measured at 0, 3, 6, 9, 12, 18 months, and questionnaires on quality of life were filled in by the patients at 0, 6, 12, 18 months of follow- up. Results - The prospective study confirmed a strong correlation between EDSS and MSFC (Spearman correlation test, p=0.03, 0.004, 0.002, 0.004, 0.0008, 0.002; R=-0.54, -0.66, -0.68, -0.65, -0.73, -0.69) in multiple sclerosis. The MSFC was more sensitive to clinical changes than EDSS. The extent of changes on the two scales correlated only after 18 months (p<0.005, R=-0.65). The arm/hand function was the most sensitive measure for disease progression. There was no correlation between the quality of life and either of the two other clinical parameters. Conclusion - MSFC is a simple method, suitable for followup of multiple sclerosis patients in everyday clinical practice.]

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

SANLI Arzu, OZTURK Musa, SOYSAL Aysun, DOVENTAS Yasemin, BASOGLU Fulya, GOZUBATIK-CELIK R. Gokcen, BAYBAS Sevim

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

[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

[Controversies in neurology: Diagnosis, follow up and therapy of multiple sclerosis with pathomechanismal approach]

VÉCSEI László

[The clinical boundaries between the relapsing and progressive course of multiple sclerosis are often indistinct. Despite the variable patterns of evolution, there are no biological reasons for discerning different multiple sclerosis phenotypes. Indeed, both primary progressive and secondary forms of the disease share similar pathological features in respect of the extent of inflammatory infiltrates, axonal damage, and cortical demyelination. The data indicating that primary progressive multiple sclerosis is preceded by an asymptomatic relapsing remitting phase. The proposed definition of secondary progressive multiple slcerosis, the attainment of at least EDSS of 4 is required to mark the transition to the progressive phase. Therefore, the clinical progress can be uncovered in the early phase of the disease. Furthermore, a continuous progression independent of relapsing activity is commonly observed during the relapsing remitting phase. A continuous smouldering process underpins the subtle clinical deterioration, which stands out as an important unmet treatment target. Concerning cognitive dysfunction of the patients pro-inflammatory cytokines have been associated with worse cognition in active multiple sclerosis, and this inflammatory milieu could also contribute to altered mentation during relapses. Therefore, long before people with multiple sclerosis become physically disabled, they have usually acquired hidden disabilities related to cognitive impairment. Silent progression appears during the relapsing remitting phase and it associates with brain atrophy. This suggests that the same process that underlies secondary progressive multiple sclerosis likely begins far earlier than is generally recognized. This supports a unitary view of multiple sclerosis biology. ]

Clinical Neuroscience

[Current questions of multiple sclerosis: the secunder progressive form of the disease]

VÉCSEI László

[Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.]

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.]