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

MARCH 30, 2012

Clinical Neuroscience - 2012;65(03-04)

[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

[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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The applications of transcranial Doppler in ischemic stroke

FINNSDÓTTIR Herdis, SZEGEDI István, OLÁH László, CSIBA László

Background: This overview provides a summary of the applications of transcranial Doppler (TCD) in ischemic stroke. Results: A fast-track neurovascular ultrasound protocol has been developed for detecting occlusion or stenosis. The technique is more reliable in the carotid area than in the posterior circulation. By monitoring the pulsatility index the in­crea­sed intracranial pressure can be diagnosed. TIBI score was developed for grading residual flow. TCD has been shown to accurately predict complete or any recanalization. Regarding recanalization, TCD has a sensitivity of 92%, a specificity of 88%, a positive predictive value of 96%, a negative predictive value of 78% and an overall accuracy of 91%, respectively. Sonothrombolysis seemed to be a promising application but randomized controlled trials have shown that it does not improve clinical outcome. TCD examination can detect microembolic signals (MES) which are associated with an increased risk of stroke. Micro­em­boli were detected in symptomatic and asymptomatic carotid artery stenosis and during carotid endarterectomy. The number of microemboli can be decreased by antithrombotic therapy. Contrast en­chan­ced examination and Valsalva maneuver with continuous TCD monitoring can accurately screen for right-to-left shunt.

Clinical Neuroscience

[Relationships between COVID-19 disease, nutritional status, and dysphagia, particularly in stroke patients ]

KOVÁCS Andrea, SZABÓ Pál Tamás, FOLYOVICH András

[The new coronavirus, SARS-CoV-2, which causes the COVID-19 disease can lead to severe acute respiratory distress syndrome (ARDS). It poses a serious challenge to the health care system, especially intensive care. Neurological patients, usually of advanced age and with a myriad of comorbidities, are at particular risk through the impact of the new coronavirus on their condition and nutritional capacity. Stroke is a leader in morbidity and mortality data, with a focus on dysphagia and its complications due to COVID-19 disease and acute cerebrovascular accident. In the acute phase of stroke, 30-50% of patients suffer from dysphagia, which still shows a prevalence of 10% six months later. Dysphagia results in decreased or insufficient fluid and nutrient uptake, supp­lemented by inactivity, leading to malnutrition and sarcopenia, which worsens overall condition, outcome, and rehabilitation efficiency. Screening and early detection of swallowing disorders is a fundamental issue in order to develop a personalized and timely-initiated nutritional therapy strategy. Nutritional therapy plays a key role in frequent intensive care due to COVID-19 disease, where it increases the chances of recovery and reduces the length of stay in the intensive care unit and mortality. This is especially true in critically ill patients requiring prolonged ventilation. In COVID-19 diagnosed patients, screening for dysphagia, bedside assessment, and instrumental examination, followed by swallowing rehabilitation, are of paramount importance. Stroke can also be a complication of the COVID-19 infection. Care for cerebrovascular patients has also adapted to the pandemic, “triazination” has become systemic, and dysphagia screening for stroke patients and nutritional therapy adapted to it have also shed new light. ]

Lege Artis Medicinae

[The history of acute stroke care in Hungary ]

BERECZKI Dániel

[Stroke is one of the most frequent causes of death and the most important cause of permanent disability worldwide and also in Hungary. The Hungarian medical literature has mentioned this disease and has been giving recommendations for its treatment since 1690. Initially folk medicines, herbal preparations and phlebotomy were used as standard therapy. Later, cooling the head joined these methods. Pharmacy preparations emerged at the middle of the 19th century. From the middle of the 20th century, products of the pharmaceutical industry like blood flow enhancers and neuroprotective drugs were in the frontline of the acute care. Anti­hy­per­ten­sive, antithrombotic and lipid-lowering medications became part of stro­ke prevention. Imaging techniques – mainly computer tomography of the brain and ultrasound examination of the cervical large arteries – have radically changed the diagnostics of cerebrovascular diseases from the middle of the 1980s. Since the 1990s, diagnostic and therapeutic decisions are based on reliable evidence from good quality clinical trials. Since the beginning of the 21st century, reperfusion treatments (intravenous thrombolysis and mechanical thrombectomy) re­present the most effective emergency care. The current direction is the extension of the therapeutic time-window of reperfusion treatments based on sophisticated neruoimaging. This review provides a brief summary of the development of stroke care in the last three and a half centuries as reflected in the Hungarian medical literature. ]

Clinical Neuroscience

[Systemic thrombolysis and endovascular intervention in postpartum stroke]

BERECZKI Dániel Jr., NÉMETH Beatrix, MAY Zsolt, SZAKÁCS ZOLTÁN, GUBUCZ István, SZIKORA István, SZILÁGYI Géza

[Introduction - There are no previously published cases about intravenously applied recombinant tissue plasminogen activator in acute ischemic stroke during puerperium. Case presentation - We report a 40-year-old woman with postpartum acute ischemic stroke caused by multiple cervical artery dissections treated by systemic thrombolysis and endovascular intervention. Discussion - There are only limited data regarding thrombolytic treatment in acute stroke during pregnancy and puerperium. Current acute stroke treatment guidelines - while considering pregnancy as a relative exclusion criterion - do not deal with the postpartum state. Conclusion - As the condition is rare, randomized controlled trials are not feasible, therefore further reports on similar cases could eventually help us suggest guidelines or at least propose recommendations for the acute thrombolytic treatment of strokes occurring in pregnancy and puerperium.]

Clinical Neuroscience

[The role of intravenous thrombolysis before mechanical thrombectomy in the treatment of large vessel occlusion strokes ]

KALMÁR Péter János, TÁRKÁNYI Gábor, KARÁDI Zsófia Nozomi, BOSNYÁK Edit, NAGY Csaba Balázs, CSÉCSEI Péter, LENZSÉR Gábor, BÜKI András, JANSZKY József, SZAPÁRY László

[The efficacy of intravenous thrombolysis (IVT) is moderate in the proximal vascular segments of intracranial arteries, as opposed to mecha­nical thrombectomy (MT). In the management of acute ischemic stroke (AIS) caused by large vessel occlusions (LVO), IVT prior to MT is highly recommended based on the latest guidelines, but the necessity of IVT has been questioned by the latest studies of the past years. The aim of our study was to investigate and compare the efficacy and safety of direct mechanical thrombectomy (dMT) and combined therapy (CT) for patients who suffered an AIS with LVO and were treated in our department. We investigated patients with AIS caused by LVO who were admitted up to 4.5 hours after symptom onset and underwent MT in our department between November 2017 and August 2019. Patients’ data were collected in our stroke register. Patients enrolled in our study were divided into two groups depending on whether dMT or CT was used. Our primary outcome was the 30- and 90- day functional outcome measured by modified Rankin Scale (mRS). Mortality at 30- and 90- day, successful recanalization rates, and symptomatic intracranial hemorrhage were considered as secondary outcomes. A total of 142 patients (age: 68.3 ± 12.6 years, 53.5% female) were enrolled in our study, including 81 (57.0%) dMT cases, and 61 (43.0%) patients who received CT. The vascular risk factors and comorbidities were significantly higher in the dMT-treated group. At day 30, the rate of favorable functional outcomes was 34.7% in dMT vs. 43.6% among those who received CT (p = 0.307), by day 90 this ratio changed to 40.8% vs. 46.3% (p = 0.542). Mortality rates at day 30 were 22.2% and 23.6% (p = 0.851), and at day 90 33.8% and 25.9% (p = 0.343). The rate of effective recanalization was 94.2% for dMT-treated patients and 98.0% for CT-treated patients (p = 0.318). Symptomatic intracranial hemorrhage was detected in 2.5% of dMT-treated patients and 3.4% of CT-treated group (p = 0.757). Our results suggest that CT is associated with a moderately better outcome compared to dMT. IVT prior to MT did not increase the risk of symptomatic intracranial hemorrhages.]