Clinical Neuroscience

[Study of the effects of vinpocetin on cognitive functions]

VALIKOVICS Attila, CSÁNYI Attila, NÉMETH László

MARCH 30, 2012

Clinical Neuroscience - 2012;65(03-04)

[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.]

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[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.]

Clinical Neuroscience

[One year follow-up after stroke. A preliminary feasibility study in Josephtown of Budapest]

SZŐCS Ildikó, SZATMÁRI Szabolcs, FEKETE Klára, ORBÁN-KIS Károly, VASTAGH Ildikó, FOLYOVICH András, AJTAY András, BERECZKI Dániel

[Stroke is a major public health issue in Hungary with considerable regional differences in mortality. We have limited information to explain such regional differences. To assess these differences, we would need comparative followup studies optimally carried out by personal contact with the patient or the carer. According to several epidemiological studies, follow-up can be carried out with significantly lower cost and similar efficiency by telephone contact or regular mail. In this pilot study we intend to assess: 1. the efficacy of telephone follow-up one year after stroke in this geographical region 2. whether the efficacy of follow-up can be further increased with questionnaires sent out by regular mail 3. whether telephone and mail-based assessment is sufficient to perform a larger population based study. We included 135 patients hospitalized consecutively for acute cerebrovascular disease (stroke or TIA) by the Department of Neurology, Semmelweis University in January and February of 2008. Based on residence, patients were divided into three groups: those living in the least wealthy district of Budapest (i.e. District-8); those living in other districts of the city; and those living in suburban areas. One year after the hospital treatment follow-up was possible by telephone in 76%. Further 12 patients could be contacted by questionnaire sent out by regular mail. Efficacy of follow-up was altogether 84%. Even in this small group of patients, we have found a tendency for more severe strokes (p=0.06) and higher acute case fatality (32% vs. 5%, p=0.029) in residents of District-8 of Budapest compared to those residing in more wealthy districts of the city and in suburban areas. Survival rate one year after stroke or TIA was only 39% in those living in District-8, 66% in those living in other districts and 75% in suburban dwellers (p=0.006). Telephone and mail-based questionnaires are insufficient for follow-up in these regions even when applied in combination. These preliminary data raise the possibility that the socio-economical conditions might influence stroke severity and outcome in the population. A larger study to address this issue would require more accurate definition of patient-groups and more efficient follow-up methods.]

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Clinical Neuroscience

[Asymptomatic ischemic cerebrovascular disorders and neuroprotection with vinpocetine]

HADJIEV Dimiter

[The asymptomatic ischemic cerebrovascular disorders (AICVD) is an early manifestation of cerebrovascular disease. It is also known as latent insufficiency of the cerebrovascular circulation or as asymptomatic cerebrovascular disorders. Recently, the term subclinical disease, detected noninvasively, has been introduced by American Heart Association. The diagnosis is based on the following criteria: evidence of vascular risk factors; episodic nonspecific complaints without any focal cerebral symptoms; mild cognitive deficit, detected by neuropsychological tests; carotid ultrasonography often shows intimal-medial thickening, atherosclerotic plaques and carotid stenosis; CT and MRI occasionally reveal silent cerebral infarctions, white matter hyperintensities or cerebral atrophy; regional hypoperfusion above the ischemic threshold is also seen by rCBF measurements. Treatment of the AICVD, modifying the vascular risk factors and using neuroprotective agents, should be the cornerstone of primary prevention of ischemic stroke and cognitive decline, caused by cerebrovascular disorders. Vinpocetine has been found to interfere with various stages of the ischemic cascade: ATP depletion, activation of voltagesensitive Na+- and Ca++-channels, glutamate and free radicals release. The inhibition of the voltage-sensitive Na+- channels appears to be especially relevant to the neuroprotective effect of vinpocetine. Pronounced antioxidant activity of the drug could also contribute to the neuroprotection. PET studies in primates and man showed that 11C labelled vinpocetine passes the blood-brain barrier rapidly. Heterogeneous brain distribution of the compound was observed mainly in the thalamus, basal ganglia, occipital, parietal and temporal cortex, regions which are closely related to the cognitive functions. PET studies in chronic ischemic stroke patients revealed favourable effects of vinpocetine on rCBF and glucose metabolism in the thalamus, basal ganglia and primary visual cortex. It seems, vinpocetine, affecting the multiple mechanisms of the AICVD, could be of benefit for the treatment in this early stage of cerebrovascular disease. Vinpocetine may also become a new therapeutic approach to prophylactic neuroprotection in patients at high risk of ischemic stroke.]

Clinical Neuroscience

[INVESTIGATION OF THE EFFECT OF VINPOCETINE ON CEREBRAL BLOOD FLOW AND COGNITIVE FUNCTIONS]

VALIKOVICS Attila

[Introduction - Vinpocetine has been widely used in the treatment of ischaemic cerebrovascular diseases and dementias of vascular type. Chronic cerebral hypoperfusion plays an important role in the development of certain types of dementia. In consequence of complex mode of action vinpocetine plays a significant role in the improvement of cerebral hypoperfusion. The symptoms of mild cognitive impairment considered as “predementia” are similar to those of dementia, although milder. Aims - The authors investigated the characteristics of the blood flow parameters of patients with ischemic stroke and mild cognitive impairment both in resting conditions or following chemical stimulus as well as they investigated the severity of mental deterioration in the two patient groups. In a pilot study the authors examined the influence of 12-week long oral vinpocetine therapy on the blood flow parameters and cognitive functions in the two patient groups. Methods - The authors studied the blood flow velocity of a. cerebri media in resting conditions and after 30 sec of breath holding with transcranial Doppler before treatment and after a 12-week long oral vinpocetine treatment. At the same time psychometric tests (MMSE, ADAS-Cog) were used in order to examine cognitive functions, while the general condition of the patients were scored by Clinical Global Impression (CGI) scale. Results - After a 12-week long oral vinpocetine treatment the increase of blood flow velocity in resting conditions compared to the baseline values was significant in the vascular group. The percent increase of mean velocity after the breath holding TCD test showed a significant increase compared to the baseline in both patient groups. The authors found a significant improvement of cognitive functions after a 12-week long oral vinpocetine therapy using psychometric tests. The improvement was identical in both groups. The general condition of patients improved significantly according to both the investigator's and the patients' opinion; patients with mild cognitive impairment judged the improvement higher. Conclusions - Vinpocetine improved the cerebrovascular reserve capacity in both patient groups and favourably influenced the cognitive status and general condition of patients with chronic hypoperfusion. The authors recommend the use of vinpocetine for the treatment of patients with mild cognitive impairment.]

Clinical Neuroscience

[Transcranial Doppler assessment of cerebral vasomotor reactivity in evaluating effects of vinpocetine in cerebral small vessel disease: a pilot study]

JOVANOVIC B. Zagorka, PAVLOVIC M. Aleksandra, PEKMEZOVIC Tatjana, MIJAJLOVIC Milija, NADEŽDA Šternić Čovičković

[Background - There are still dilemmas about the vasodilating effect of vinpocetine, a synthetic ethyl alkaloid vincamine. The method of measuring cerebral vasomotor reactivity (VMR) by transcranial Doppler (TCD) technique before and after administration of the medication was used to estimate the degree of arterioles vasodilatation. The aim of this study was to test of the vasodilating effect of vinpocetine in patients with cerebral small vessel disease (SVD) by measuring cerebral VMR. Material and methods - Thirty patients with SVD were on 3-month-long oral treatment with 15 mg vinpocetine daily. Cerebral VMR was determined by breath holding test. The breath holding index (BHI) was calculated in standard manner and values >0.69 were considered normal. At the baseline, before treatment (I), BHI, modified Rankin scale (mRS) score, Mini Mental State Examination (MMSE) score were determined. One month later (II) BHI was assessed again, while after 3 months of treatment (III) we analyzed BHI, mRS score and MMSE score. Results - The average age of patients was 61.4±11.5 years (range 40 to 77 years), 18 (60%) female and 12 (40%) males. Values of BHIs were increased during treatment at the right MCA (I) 1.18±0.53, (II) 1.26±0.54, (III) 1.37±0.41, with statistical significance between I and III measurement (p<0.05). An increase was noted on the left MCA (I) 1.25±0.53, (II) 1.31±0.55 and (III) 1.32±0.42, but it did not reach statistical significance (p>0.05). Mean MMSE score significantly increased from baseline 27.4±2.3 to 28.5±2.0 after three months of treatment (p<0.001). Functional status showed a statistically significant improvement with mRS score increasing from 2.1±1.0 to 1.1±0.6 (p<0.001). Conclusion - This pilot study showed that 3-month-long oral treatment with vinpocetine 15 mg daily had tendency to increase BHI, indicating improvement of cerebral VMR. It is possible that higher doses of vinpocetine are needed to achieve substantial increase of VMR.]