Clinical Neuroscience

[Neurology Editors: Imre Szirmai]

BERECZKI Dániel

MARCH 30, 2012

Clinical Neuroscience - 2012;65(03-04)

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Clinical Neuroscience

[In memoriam András Fazekas MD 1941-2012]

VOLT munkatársai

Clinical Neuroscience

[Study of the effects of vinpocetin on cognitive functions]

VALIKOVICS Attila, CSÁNYI Attila, NÉMETH László

[Introduction - Chronic cerebral hypoperfusion is a risk factor for the development of certain types of dementia. Mild cognitive impairment is a stage of predementia condition, because the symptoms are similar but not as severe as the symptoms in patients with dementia. Vinpocetine, due to its complex mechanism of action, has an important role in the improvement of chronic cerebral hypoperfusion. Objectives - The aim of our study was to determine the severity of the cognitive decline and to investigate the efficacy and safety of per os 18 months vinpocetine treatment in patients with mild cognitive impairment. Methods - We used psychometrical tests (MMSE, ADASCog) to assess the cognitive functions. CGIC-PGIC was used to evaluate the overall change in the disease status. ADL was used to assess the patient’s daily activity and the Hamilton Depression Scale to evaluate the patient’s mood. The assessments were performed at six visits during the 18 months treatment period. Results - At the beginning of the treatment, the stage of our patients’ mild cognitive impairment was moderately severe. Significant improvement was detected in the psychometrical tests after the 18 months treatment period. The overall status of the disease improved significantly according both to the patient and the investigator. Also significant improvement was detected in daily activity. The complex improvement of the clinical symptoms affected the patients’ mood positively. Moreover, vinpocetine was safe and had a good tolerability during the whole study period. Conclusions - Vinpocetine, due its complex mechanism of action, improved significantly the cognitive functions, overall disease status and quality of life in patients with chronic cerebral hypoperfusion. As a result, vinpocetine treatment can be recommended for patients with mild cognitive impairment.]

Clinical Neuroscience

[Botulinum neurotoxin-A therapy in migraine]

TAJTI János, SZOK Délia, TUKA Bernadett, CSÁTI Anett, KURIS Anikó, MAJLÁTH Zsófia, LUKÁCS Melinda, VÉCSEI László

[Although migraine is a common, paroxysmal, highly disabling disorder, the primary cause and the pathomechanism of migraine attacks are enigmatic. Experimental results suggest that activation of the trigeminovascular system is crucial in its pathogenesis. This activation leads to the release of vasoactive neuropeptides (calcitonin gene-related peptide - CGRP, and substance P - SP) and to neurogenic inflammation, and peripheral and central sensitisation are expressed. Botulinum neurotoxin-A (BoNT-A), a potent toxin produced by Clostridium botulinum, affects the nervous system through specific cleavage of the soluble NSF-attachment protein receptor complex (SNARE), like synaptosomal-associated protein of 25 kDa (SNAP-25). The result of this multistage process is blockade of the presynaptic release of pain neurotransmitters such as CGRP, SP and glutamate. A pooled analysis of the data from two programmes of Phase 3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT 1 and 2) with BoNT-A in chronic migraine demonstrated significant benefit of BoNT-A over placebo with regard to the numbers of headache days and migraine episodes. BoNT-A diminished the frequency of acute headache pain medication intake, and resulted in reductions in headache impact and improvements in scores on the Migraine-Specific Quality of Life Questionnaire. The treatments with BoNT-A proved safe and were well tolerated.]

Clinical Neuroscience

[Fingolimod therapy in multiple sclerosis - the issue of the pathomechanism]

TAR Lilla, VÉCSEI László

[Multiple sclerosis is an autoimmune inflammatory disease of the central nervous system with neurodegenerative chararacteristics. The newly discovered per os administrable drug fingolimod (FTY720) has a different mechanism of action than the current disease-modifying therapies. In vivo the drug binds to four out of the five sphingosine-1-phosphate receptors after phosphorylation. Fingolimod-phosphate (FTY720-P) causes internalization and degradation of the sphingosine-1-phosphate receptors in the membrane of lymphocytes thus in contrast to sphingosine-1-phosphate it acts like a functional antagonist. In experimental autoimmune encephalomyelitis - an animal model of multiple sclerosis - fingolimod blocks the sphingosine-1-phosphate gradient controlled lymphocyte egress from the lymph nodes and therefore reduces the peripheral lymphocyte count especially the encephalitogenic Th17 subset is reduced. Modulation of the sinus lining and blood-brainbarrier constructing endothelial cells also contributes to the complex mechanism of action. Additionally due to its liphohilic nature fingolimod is able to penetrate the blood brain barrier thus, beside its peripheral effects the drug can probably modulate the cells of the central nervous system directly. Presumably it can reduce neurodegeneration caused by astrogliosis through modification of astrocyte and oligodendrocyte activity. The results of current clinical studies are holding out with bright prospective in the aspect of either the favourable effects or the well tolerated side effects.]

Clinical Neuroscience

[Stroke prevention - A population screening day in district XII of Budapest]

FOLYOVICH András, BAKOS Mária, KÁNTOR Zita, HERTELENDY Anna, HORVÁTH Eszter, ZSIGA Katalin, LAKATOS Henriette, VADASDI Károly

[Along with advances in the treatment of acute stroke, new efforts have been made to enhance efficiency of the prevention of cerebrovascular diseases. Population screening is a way to contact high-risk patients, and there is an increasing international and national experience with the procedure. However, efforts are associated with high costs, so an efficient method, complying with local features, should be selected from the various methods. A stroke prevention day was organized in Szent János Hospital, localized in district XII, and data were analyzed. Taking advantage of the potentials of a large hospital, a comprehensive risk assessment - within the capacity of health care workers - was performed. Program and contact information of the screening day was published in the local newspaper of the district. Data of 48 residents of the district were analyzed. In addition to neurologists, a radiologist, a cardiologist and an ophtalmologist, as well as health care workers were involved in the project. A data sheet was filled in for all participants, including known risk factors, BMI, blood pressure and serum cholesterol levels. All participants had duplex sonography of the cervical vessels, cardiac evaluation and ophtalmic examination. Data were analyzed anonymously, and - if participants approved - postcode and educational level were also recorded. Among the 48 individuals screened, 35 were female and 13 were male. Average age was 62.86 (±8.57) years, and participants were typically of higher educational level. 5 individuals had no known risk factors, most of them had 2-3 risk factors, and multiple risk factors were not uncommon. Individuals with six and seven risk factors were also found. 20 of 27 patients with known hypertension had target blood pressure levels. By duplex sonography, 36 individuals had mild, 4 had significant atherosclerosis. There was no significant carotid stenosis or occlusion. Based on ophtalmic evaluation, 26 patients had signs of vascular disease (mainly hypertensive fundus changes). Cardiac evaluation detected 14 patients with cardiovascular risk. The high standard of primary care in the district was reflected by the fact that all the 6 highrisk individuals were already taken care of by general practitioners (GP-s). One of the leading conclusions from the evaluation of the data is that local press, family ties and local communities play a major role in recruiting people for a screening day. In order to increase efficiency and cost-efficacy of the program, GP-s should also be involved in the planning process, because efficiency may be increased by pre-selecting high-risk individuals.]

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Clinical Neuroscience

Comparison of pramipexole versus ropinirole in the treatment of Parkinson’s disease

GENCLER Onur Serdar , OZTEKIN Nese , OZTEKIN Fevzi Mehmet

Parkinson’s disease is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. Levodopa is the most effective drug in the symptomatic treatment of the disease. Dopamine receptor agonists provide sustained dopamin-ergic stimulation and have been found to delay the initiation of levodopa treatment and reduce the frequency of various motor complications due to the long-term use of levodopa. The primary aim of this study was to compare the efficacy of potent nonergoline dopamine agonists pramipexole and ropinirole in both “dopamine agonist monotherapy group” and “levodopa add-on therapy group” in Parkinson’s disease. The secondary aims were to evaluate the effects of these agents on depression and the safety of pramipexole and ropinirole. A total of 44 patients aged between 36 and 80 years who were presented to the neurology clinic at Ministry of Health Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey and were diagnosed with idiopathic Parkinson’s disease, were included into this randomized parallel-group clinical study. Dopamine agonist monotherapy and levodopa add-on therapy patients were randomized into two groups to receive either pramipexole or ropinirole. The maximum daily dosages of pramipexole and ropinirole were 4.5 mg and 24 mg respectively. Patients were followed for 6 months and changes on Unified Parkinson’s Disease Rating Scale, Clinical Global Impression-severity of illness, Clinical Global Impression-improvement, Beck Depression Inven­tory scores, and additionally in advanced stages, changes in levodopa dosages were evaluated. Drug associated side effects were noted and compared. In dopamine agonist monotherapy group all of the subsections and total scores of Unified Parkinson’s Disease Rating Scale and Clinical Global Impression-severity of illness of the pramipexole subgroup showed significant improvement particularly at the end of the sixth month. In the pramipexole subgroup of levodopa add-on therapy group, there were significant improvements on Clinical Global Impression-severity of illness and Beck Depression Inventory scores, but we found significant improvement on Clinical Global Impression-severity of illness score at the end of the sixth month in ropinirole subgroup too. The efficacy of pramipexole and ropinirole as antiparkinsonian drugs for monotherapy and levodopa add-on therapy in Parkinson’s disease and their effects on motor complications when used with levodopa treatment for add-on therapy have been demonstrated in several previous studies. This study supports the effectiveness and safety of pramipexole and ropinirole in the monotherapy and levodopa add-on therapy in the treatment of Parkinson’s disease.

Clinical Neuroscience

To handle the HaNDL syndrome through a case: The syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis

ÇOBAN Eda, TEKER Ruken Serap, SERİNDAĞ Helin, SAKALLI Nazan, SOYSAL Aysun

The syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare entity. This disease has been related to migrainous headaches. It is a benign, self-limited disorder, which is characterized by fluctuating neurological symptoms and cerebrospinal fluid lymphocytosis. We describe a case of a 47 years old man with acute onset of headache and aphasia. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis (25 cells/μl, 100% lymphocytes). Electroencephalogram showed moderate slow rhythm in the left hemisphere, with temporoparietal predominance, and without epileptiform activity. His blood tests as well as magnetic resonance imaging (MRI) results were normal. With the diagnosis of HaNDL syndrome the patient was accepted in the Department of Neurology and discharged with full recovery.

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

Management of bone metabolism in epilepsy

UÇAN TOKUÇ Ezgi Firdevs , FATMA Genç, ABIDIN Erdal, YASEMIN Biçer Gömceli

Many systemic problems arise due to the side effects of antiepileptic drugs (AEDs) used in epilepsy patients. Among these adverse effects are low bone mineral density and increased fracture risk due to long-term AED use. Although various studies have supported this association with increased risk in recent years, the length of this process has not been precisely defined and there is no clear consensus on bone density scanning, intervals of screening, and the subject of calcium and vitamin D supplementation. In this study, in accordance with the most current recommendations, our applications and data, including the detection of possible bone mineralization disorders, treatment methods, and recommendations to prevent bone mineralization disorders, were evaluated in epilepsy patients who were followed up at our outpatient clinic. It was aimed to draw attention to the significance of management of bone metabolism carried out with appropriate protocols. Epilepsy patients were followed up at the Antalya Training and Research Hospital Department of Neurology, Epilepsy Outpatient Clinic who were at high risk for osteoporosis (use of valproic acid [VPA] and enzyme-inducing drugs, using any AED for over 5 years, and postmenopausal women) and were evaluated using a screening protocol. According to this protocol, a total of 190 patients suspected of osteoporosis risk were retrospectively evaluated. Four patients were excluded from the study due to secondary osteoporosis. Of the 186 patients who were included in the study, 97 (52.2%) were women and 89 (47.8%) were men. Prevalence of low bone mineral density (BMD) was 42%, in which osteoporosis was detected in 11.8% and osteopenia in 30.6% of the patients. Osteoporosis rate was higher at the young age group (18-45) and this difference was statistically significant (p=0.018). There was no significant difference between male and female sexes according to osteoporosis and osteopenia rates. Patients receiving polytherapy had higher osteoporosis rate and lower BMD compared to patients receiving monotherapy. Comparison of separate drug groups according to osteoporosis rate revealed that osteoporosis rate was highest in patient groups using VPA+ carbamazepine (CBZ) (29.4%) and VPA polytherapy (19.4%). Total of osteopenia and osteoporosis, or low BMD, was highest in VPA polytherapy (VPA+ non-enzyme-inducing AED [NEID]) and CBZ polytherapy (CBZ+NEID) groups, with rates of 58.3% and 55.1%, respectively. In addition, there was no significant difference between drug groups according to bone metabolism markers, vitamin D levels, and osteopenia-osteoporosis rates. Assuming bone health will be affected at an early age in epilepsy patients, providing lifestyle and diet recommendations, avoiding polytherapy including VPA and CBZ when possible, and evaluating bone metabolism at regular intervals are actions that should be applied in routine practice.

Clinical Neuroscience

[New, innovative prognosis calculator for patients with metastatic spinal tumors]

MEZEI Tamás, BÁSKAY János, POLLNER Péter , HORVÁTH Anna, NAGY Zoltán , CZIGLÉCZKI Gábor , BANCZEROWSKI Péter

[The aim of our research was to create a scoring system that predicts prognosis and recommends therapeutic options for patients with metastatic spine tumor. Increasing oncological treatment opportunities and prolonged survival have led to a growing need to address clinical symptoms caused by meta­stases of the primary tumor. Spinal metastases can cause a significant reduction in quality of life due to the caused neurological deficits. A scoring system that predicts prognosis with sufficient accuracy could help us to achieve personalised treatment options. Methods – We performed a retrospective clinical research of data from patients over 18 years of age who underwent surgery due to symptomatic spinal metastasis at the National Institute of Mental Disorders, Neurology and Neurosurgery between 2008 and 2018. Data from 454 patients were analysed. Survival analysis (Kaplan-Meier, log-rank, Cox model) was performed, network science-based correlation analysis was used to select the proper prognostic factors of our scoring system, such that its C value (predictive ability index) was maximized. Multivariate Cox analysis resulted in the identification of 5 independent prognostic factors (primary tumour type, age, ambulatory status, internal organ metastases, serum protein level). Our system predicted with an average accuracy of 70.6% over the 10-year study period. Our large case series of surgical dataset of patients with symptomatic spinal metastasis was used to create a risk calculator system that can help in the choice of therapy. Our risk calculator is also available online at https://emk.semmelweis.hu/gerincmet.]