Clinical Neuroscience

[Apoptosis in focal brain ischaemia]


AUGUST 20, 2003

Clinical Neuroscience - 2003;56(07-08)

[Ischaemic stroke is one of the major causes of death and disability in the developed world. It is caused by focal impairment of cerebral blood flow. The subsequent ischaemic cell death is predominantly necrotic in nature. However, a therapeutically important characteristic is the delayed apoptotic cell demise in the border zone of the primary lesion core. Apoptosis is one of the most intensively studied field of current medical and biological research. The better understanding of its mechanism may provide novel and more effective ways of therapy in a wide range of diseases including ischemic stroke. The salient neurological features of focal brain ischaemia and the morphological signs of apoptotic and necrotic cell death are summarized. The mechanism of apoptosis is discussed. It is divided into an early genetic phase of decisionmaking followed by a cellular execution phase. The characteristics of the early shift in the finely tuned balance of proand antiapoptotic genes and their protein products, which is preceded by an inbalance in intracellular ionized calcium homeostasis, energy depletion and mitochondrial dysfunction is discussed. The crucial role of caspases in apoptosis is emphasized. The three possible pathways during the execution phase is described: the intrinsic- and extrinsic caspase activation cascade and the caspase-independent intracellular signal transduction route. The molecular mechanism of neural cell membrane damage in the execution phase is discussed and some examples of altered protein synthesis also known as message-selection are given. The important role of late reperfusion in the execution phase is emphasized. The possible targets of antiapoptotic therapeutic approaches and the results of experimental studies are presented as well as the perspectives of their use in human clinical care.]



Further articles in this publication

Clinical Neuroscience

[Imaging of dopamine transporter with 99mTc-TRODAT-SPECT in movement disorders]

KANYÓ Balázs, ÁRGYELÁN Miklós, DIBÓ György, SZAKONYI Zsolt, VÉCSEI László, FÜLÖP Ferenc, LÁNCZ Adrienn, FORGÁCS Péter, PÁVICS László

[99mTc-TRODAT-1 is a new, technetium based radiopharmaceutical that selectively binds to the dopamine transporters. The aim of the study was to evaluate the dopamine transporter status in movement disorders. Methods - In eight healthy volunteers (age range 22-58 years), 28 patients with Parkinson’s disease (age range 42-80 years), 10 patients with Parkinsonian syndrome (age range 51-79 years) and 13 patients with essential tremor (age range 43-71 years) were 99mTc-TRODAT-SPECT tests performed. The results were evaluated visually and semiquantitatively. Results - The visual assessments were concordant with those of the semiquantitative in each case. The 99mTc- TRODAT uptake of the striatum was referenced to the cerebellum, the frontal and occipital cortex. The best deviation was found in aspect of the occipital cortex. The striatum/occipital ratio was the following: healthy volunteers: 2.12±0.27; Parkinson’s disease: 1.52±0.27; Parkinsonian syndrome: 1.57±0.26; essential tremor: 2.06±0.69. The striatal dopamine transporter availability was significantly lower in subjects with Parkinson's disease or Parkinsonian syndrome compared to the control subjects. There was no difference between healthy volunteers and patients with essential tremor. Using discriminant analysis, the discriminant function had significantly different values in the group of Parkinson’s disease than in Parkinsonian syndrome: f= -3.675×caud/occipit+6.293×put/occipit -2.548. Conclusion - 99mTc-TRODAT-SPECT is able to visualise the presynaptic dopaminergic degeneration. This method itself can be useful in differential diagnosis in some type of movement disorders.]

Clinical Neuroscience

[Two cases of frontotemporal dementia]

SZABÓ Erzsébet, SZABÓ Mihály

[Frontotemporal dementias represent the third most common cause of primer degenerative dementias next to Alzheimer’s disease and Lewy body disease. Frontotemporal dementia constitutes 10-20% of all praesenilis dementias. The authors present the results of the 10 years' clinical, neuropsychological, neuropathological examinations and brain imaging with the examples of two cases. At the early stage of frontotemporal dementia changes of personality and social conduct are prominent, whereas cognitive functions are relativelly well preserved. The usual dementia tests are not sufficiently sensitive to disclose noncognitive symptoms. Clinical diagnosis as well as differentiation from functional psychiatric disorders can be difficult. Brain imaging present the frontal and the anterior temporal lobe atrophy and selective hypometabolism in these areas. The typical onset is between at the age 50 and 65 years. It is very rare under the age of 30. The symptoms of two patients started at the age of 42-44. The first diagnosis was post traumatic stress disorder. Later stereotyped behaviour, mental rigidity, hyperorality, irritability, progressive reduction of speech and vegetative dysfunctions appeared. Besides the affecting of the irresistibly worsening symptoms and the medical care requiring strength and inventiveness, the authentic informing of the relatives is also a challenge. The caregivers have special relationship with the patients and their relatives.]

Clinical Neuroscience

[6th National Congress of the Hungarian Stroke Society]

Clinical Neuroscience

[Report on a research project from abroad (EFNS)]


Clinical Neuroscience


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Clinical Neuroscience

Hyperhomocysteinemia in female migraineurs of childbearing ages


Background and purpose - Migraine is a risk factor for ischemic stroke in women of childbearing ages. Previous researches revealed a higher prevalence of hyperhomocysteinemia in migraineurs. Possible differences on the frequencies of hyperhomocysteinemia between migraine with aura and migraine without aura could contribute the established variances in stroke risk between these migraine types. Therefore, we aimed to search if the frequency of hyperhomocysteinemia was different between these subtypes of migraine or not. Methods - We analyzed the findings of serum homocysteine levels in female migraineurs of 16-49 years old who admitted to our outpatient clinic. Results - Homocysteine level was elevated in 13.3% of study population. There were not any significant differences on median serum homocysteine levels between migraine with aura (8.0 mikromol/L) and without aura (8.5 mikromol/L). (p=0.426) The frequencies of hyperhomocysteinemia were also similar (9.1% versus 16.7%, respectively; p=0.373). Correlation analyses did not reveal any linear correlation between ages and homocysteine levels either in group of migraine with aura or in group of migraine without aura (p=0.417 and p=0.647, respectively). Similarly, any linear correlation between disease ages and homocysteine levels either in group of migraine with aura or in group of migraine without aura was not detected (p=0.359 and p=0.849, respectively). Conclusion - The median serum homocysteine levels and the frequencies of hyperhomocysteinemia are similar between migraine with aura and without aura in women of childbearing ages. Therefore, the variances on stroke risk ratios between these types of migraine are probably not originated from the differences of serum homocysteine status.

Clinical Neuroscience

[Neuroprotection in brain ischemia - doubts and hopes]


[In ischaemic stroke the two major potential therapeutic strategies are aimed at either improving cerebral blood flow or directly interacting with the cytotoxic cascade - a large body of evidence gained from animal studies is in support of them. In clinical trials direct neuroprotection by blocking the neurotoxic cascade remained ineffective, although there are several clinical trials still in progress. We summarize the experimental data and present the results of clinical trials and also discuss why so many drugs, which were effective in animal studies, failed in human trials. It is emphasized, that 1. in most animal studies the reduction of infarct size, i.e. the amount of saved penumbral tissue, was the outcome measure, whereas neurological function remained unassessed; 2. the recovery of intellectual performance and higher cortical functions are of major importance in the future quality of life in stroke victims; however, it is impossible to examine these parameters appropriately in animal studies; 3. in many clinical trials the patient population was rather heterogenous and low in number, the study protocol was not optimal and the critical analysis of the subacute and chronic phase was lacking or insufficient. We present the major experimental stroke models, discuss their similarities, differencies and limitations as compared to the human pathophysiological processes. The pitfalls of extrapolating data from animal studies to clinical practice are also summarized. The complex network of functional and morphological intercellular connections, the long timescale of neurotoxic and reparative events and the lessons learned from clinical trials suggest, that the use of drug combinations (therapeutic cocktails) targeting multiple steps of the neurotoxic cascade would hopefully result in more effective treatment of ischaemic stroke. Strategies to facilitate brain plasticity and regeneration is an additional promising tool to enhance recovery in brain ischaemia.]

Lege Artis Medicinae

[Evidence-based practice guidelines for nursing and rehabilitation of stroke patients]


[Stroke is a common problem, being the third most frequent cause of death in the United Kingdom and Hungary, accounting for about 20% of bed occupancy. It is also an important cause of morbidity and disability mainly for those aged over 65. As a result, stroke care constitutes as an important part of health services use. Home care services working in the field of stroke rehabilitation have not used a unified evidence-based approach and well-described professional principles and protocols. There was little cooperation between the teams working in the institutional rehabilitation and home care rehabilitation services. No agreed rehabilitation processes, and standardised scales and documentation, showing the change of quality of life, were in use. There were no quality indicators and efficiency measures of nursing and no provision of services either. The Hungarian Nursing Association played a pioneering role in the introduction and dissemination of Evidence Based Nursing in Hungary and in adopting it into routine clinical practice. The successful implementation of the Association's project could be a good example for another field of care and nursing in Hungary and other countries in Europe. Our projects are supported by the Department For International Development (UK) in the framework of the TUDOR project. The Hungarian Nursing Association (HNA) developed a postgraduate training programme entitled "Evidence based nursing in practice". The participants were required to be members of the HNA, have a degree in the field of nursing (nurse teacher, degree nurse, nurse director). Members of the target group were all working in the field of stroke rehabilitation at hospitals or out-patient clinics and home nursing. The Hungarian Nursing Association's professional group developed an evidence based practice guideline for rehabilitation of stroke patients, which was published in the Bulletin of the Ministry of Health (11/2002, 23rd May, 2002). These evidence-based stroke rehabilitation guidelines focused on bladder management, position therapy and patient information.]

Clinical Neuroscience



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Hypertension and nephrology

[Stroke incidence and prevalence in the world]


[The incidence and prevalence of ischaemic and haemorrhagic stroke declined continuously from 1970 to 2010. The rate of incidence was the lowest in North America, within Europe in the Mediterranean countries, France and in Asian developed countries. The incidence and prevalence the progress of age have in - creased respectively. The outcome of haemorrhagic stroke is worse everywhere, than that of ischaemic form, rate of mortality/incidence is greater.]