Clinical Neuroscience

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

VALIKOVICS Attila

JULY 30, 2007

Clinical Neuroscience - 2007;60(07-08)

[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.]

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[FUNCTIONAL MRI AT 1 TESLA. BASIC PARADIGMS AND CLINICAL APPLICATION]

SCHWARCZ Attila, AUER Tibor, KOMOLY Sámuel, DÓCZI Tamás, JANSZKY József

[AIM OF THE STUDY - To perform functional MRI experiments at low magnetic field, and to set up routine protocol to help the planning of neurosurgical operations and the examination of epilepsy patients. METHODS - An optimized 2D EPI sequence was applied to yield functional MR images in basic paradigms such as finger tapping and internal word generation. Further, activation was induced also by a task involving mental navigation based on the retrieval of individually familiar visuo-spatial knowledge. RESULTS - Low resolution (matrix of 64×64) functional MR images satisfactorily visualized moto-sensor strip and speech centers. In the mental navigation task bilateral activation of formatio hippocampalis was observed. Determination of motor area was also performed in an epilepsy patient whose seizure focus had been found in the area of pre- and postcentral gyrus. The dislocation of the motor cortex was demonstrated. CONCLUSION - Functional MR images with fine quality can be obtained in basic paradigms even at low magnetic field if MR imaging parameters and paradigms are optimized.]

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[MORTALITY OF HOSPITALIZED STROKE PATIENTS IN HUNGARY; 2003-2005]

GULÁCSI László, MÁJER István, KÁRPÁTI Krisztián, BRODSZKY Valentin, BONCZ Imre, NAGY Attila, BERECZKI Dániel

[The aim of our research was to assess the incidence and the 12- and 24-month mortality of hospitalized stroke in Hungary. We analyzed the rate of mortality after stroke and compared it to the standard mortality rate of the population. To assess the incidence we extracted the data of “new” stroke patients (ICD- 10 diagnoses: I60-64) hospitalized in May 2003 from the database of the National Health Insurance Fund Administration. We regarded those as “new” patients who had not been treated with these primary or secondary diagnoses in the previous 24 months. Data were collected by sex and age (age groups: 25-44, 45-64, 65 and over). We analyzed the patients' survival on the basis of their April 2004 and April 2005 data. The incidence of the “new” hospitalized stroke patients was higher in men than in women; the incidence in the age group of 65 and over was 2112/100.000 in males and 1582/100.000 in females, the corresponding values in the 45-64 age group were 623 vs. 366 per 100.000, respectively. In 2003 more than 42 thousand “new” stroke patients were hospitalized in Hungary of whom over 10 thousand died in the first year, followed by a further 2 thousand in the second year. Women’s survival is more favourable than men's: in the first year it is 71.47% vs. 69.24% (65+ group), and 88.18% vs. 83.16% (45-64 group); in the second year the corresponding values are 66.95% vs. 61.62% (65+), and 85.45% vs. 80.90% (45-64), respectively. The risk of death in the first year after stroke, compared to the standard population, is 5.17- fold in women and 4.70-fold in men in the total sample, and 10-15-fold in the 45-64 group. There are large differences by gender, particularly in men of the working age groups (25-44, 45-64), whose mortality is twice as high as that of women of the same age.]

Clinical Neuroscience

[SOCIAL INSURANCE COSTS OF STROKE HOSPITAL TREATMENTS IN HUNGARY; 2003-2005]

KÁRPÁTI Krisztián, MÁJER István, BONCZ Imre, NAGY Attila, BERECZKI Dániel, GULÁCSI László

[Our aim was to assess the social insurance costs of hospital treatments for acute stroke in Hungary between 2003 and 2005. We studied how much burden stroke patients impose on the financer (National Health Insurance Fund Administration) in acute and chronic hospital admissions. We extracted the data of “new” stroke patients (ICD-10: I60-64 diagnosis) hospitalized in May 2003 from the database of the financer. We analyzed active and chronic hospital treatment costs of these patients in the period of 12 months before the stroke and in the following first and second 12 months. Data were collected by sex and age (age groups: 25-44, 45-64, over 65). We studied patients hospitalized in May 2003 with the ICD-10: I60-64 main diagnosis but not being treated with the same diagnosis in the previous 24 months. In the first 12 months of the active care the burden of the disease was (male vs. female) 65+: 254.6 vs. 205.8; 45-64: 341.4 vs. 280.5; 25-44: 370.1 vs. 306.1 thousand HUF per patient. In the second 12 months the costs were 50.6 vs. 36.2; 24.2 vs. 32.6; 27.6 vs. 24.8 thousand HUF respectively. In the first year following the episode the costs of the chronic hospital treatment were (age groups as above) 23.3 vs. 31.3; 28.9 vs. 22.2; 22.8 vs. 22.5 thousand HUF. A year later the chronic hospital costs were 9.0 vs. 10.9; 6.7 vs. 12.2; 1.4 vs. 38.1 thousand HUF respectively. Average costs of stroke are higher in the case of males as are in the case of females, 364.8 vs. 303.0 thousand HUF in the first 24 months. The remarkable difference results from active hospital treatment costs (331.5 vs. 262.1 thousand HUF), while the discrepancy is smaller in the chronic hospital care (33.3 vs. 40.9 thousand HUF).]

Clinical Neuroscience

[A CASE OF FRONTOTEMPORAL LOBAR DEGENERATION WITH UBIQUITIN-POSITIVE INTRANEURONAL INCLUSIONS]

LEEL-ŐSSY Lóránt, RÉVÉSZ Tamás, ALMÁSI Kálmán, SZŰCS Iván, SZABÓ Éva

[The case of a 57 year-old-man is reported who has been treated several times because of his relatively expedite mental decline which has begun four years before his death. His first complaints were forgetfulness, mild changes in his behaviour, confusion and difficulty in speech. The neuropsychiatric examinations displayed a mild difficulty in naming and sometimes comprehension of words, although his speech was gramatically correct. Furthermore the patient presented a very severe decrease in short term memory with dementia and confusion. These symptomes together with the results of CT and test examinations established the diagnosis of Alzheimer's disease. Finally pneumonia afflicted the patient during the last hospitalization and he died. Histopathological examinations of the brain showed a severe, mainly temporofrontal atrophy caused by an extensive cortical neuronal loss and gliosis without neurofibrillar degenerations and senile plaques which characterize the Alzheimer's disease. Tau-positivity Pick- and Lewy-bodies may not be found. The loss of neurons associated in some places with spongiosity of laminar form. The ubiquitine-positive intracytoplasmic inclusions proved to be the most characteristic feature in the swollen neurons. These mainly occurred in the gray matter of the mediobasal part of the temporal lobe. The positivity of GFAP immunocytochemistry revealed a definite astrocytosis in the affected parts of the gray matter. In the temporal and frontal cortex scattered ballooned cells (achromatic or Pick cells) were seen in αB-crystallin immunohistochemistry. These findings confirmed the diagnosis of the case of frontotemporal lobar degeneration with ubiquitin-positive intraneuronal inclusions (FTLD-U) without tau-positivity. The separation of the different forms in the group of the frontotemporal dementias is recommended by means of the modern immunocytochemical examinations.]

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[PROTEIN BIOMARKERS IN EXPERIMENTAL MODELS AND IN THE CLINICAL CARE FOR TRAUMATIC BRAIN INJURY]

LÜCKL János, FARKAS Orsolya, PÁL József, KÖVESDI Erzsébet, CZEITER Endre, SZELLÁR Dóra, DÓCZI Tamás, KOMOLY Sámuel, BÜKI András

[Traumatic brain injury is the leading cause of mortality in Hungary in the population under 40 years of age. In Western societies, like the United Sates, traumatic brain injury represents an extreme social-economic burden, expected to become the third leading cause of mortality until 2020. Despite its’ epidemiological significance, experimental therapeutic modalities developed in the last few decades did not prove efficient in the clinical care of severe traumatic brain injury. The reason for such a lack of success in terms of translating experimental results to clinical treatment at least partially could be explained by the paucity and the low sensitivity and specificity of clinical parameters endowing us to monitor the efficacy of the therapy. The drive for finding clinical parameters and monitoring tools that enable us to monitor treatment efficacy as well as outcome focused recent attention on biomarkers (and) surrogate markers that are based on rational pathological processes associated with/operant in traumatic brain injury. This review summarizes those biomarkers that could purportedly be used to monitor the treatment of the severely head injured while also providing information on salvageability facilitating the conduction of more rationally designed clinical studies.]

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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

[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

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

ZAGORKA B. Jovanović, ALEKSANDRA M. Pavlović, TATJANA Pekmezović, MILIJA Mijajlović, 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.]