Clinical Neuroscience


ZÁDORI Dénes, DATKI Zsolt, PENKE Botond

NOVEMBER 30, 2007

Clinical Neuroscience - 2007;60(11-12)

[In Alzheimer’s disease, which belongs to the neurodegenerative disorders, the ethiopathogenetic role of several risk factors has been proved. A considerable number of them are mainly known as cardiovascular risk factors and can precipitate chronic brain hypoperfusion. Using functional imaging techniques, this hypoperfusion and the resulting hypometabolism become detectable in the watershed areas of the brain as early as in the stage of mild cognitive impairment. Hypoperfusion leads to the degeneration of capillaries in this area causing the deterioration of diffusion. The further reduction of nutrient and oxygen support of neurons is capable to initiate a neurodegenerative process which spreads along the glutamaterg system arising from the neurons of the association cortices. The neuropathological lesions of this neuronal system, such as the neurofibrillary tangles and the β-amyloid plaques, are known to be the characteristic markers of Alzheimer's disease. In our review we present the development of hypoperfusion and its consequences in the watershed areas of the brain and describe the neurodegenerative process of the neuronal system arising from the neurons of the association cortices in the early stage of Alzheimer's disease. Considering the previous hypotheses and the neuropathological lesions of Alzheimer's disease we give a new consensus model to characterize the pathomechanism of the disorder.]



Further articles in this publication

Clinical Neuroscience


AUER Tibor, SCHWARCZ Attila, EZER Erzsébet, CZEITER Endre, ARADI Mihály, HUDVÁGNER Sándor, JANSZKY József, BÜKI András, DÓCZI Tamás

[Aim of the study - Presentation of diffusion tensor imaging (DTI) performed at low magnetic field (1 Tesla) in the algorithm of work-up of a patient suffering from severe traumatic brain injury (TBI). Method - DTI and functional MRI (fMRI) were applied at 1 Tesla for visualization of neural pathways and examination of sensory functions of a patient with severe TBI. DTI-measurement was also performed on a healthy patient for comparison. Results - DTI acquired at low magnetic field yielded appropriate visualization of neural pathways. DTI confirmed the results of the clinical and fMRI examinations in the patient suffering from severe TBI. Conclusion - An optimized DTI can be useful in the examination of patients with TBI, moreover, it may also help in the establishment of diagnoses of other central nervous system diseases affecting neuronal pathways. The presented results suggest that DTI of appropriate quality can be performed at low magnetic field.]

Clinical Neuroscience



[Objective - The standard surgical procedures used in degenerative thoracic and lumbar spinal canal stenosis allows decompression of the neural structures by unroofing the spinal canal, often resulted in destruction or insufficiency of facet joints, sacrifice the interspinosus/supraspinosus ligament complexes and stripping of the paraspinal muscles altering an already pathologic biomechanical milieu causing segmental instability. Various less invasive techniques exists to save the integrity and prevent the instability of the spine and allow decompression of neural structures located in the spinal canal. The authors discusses the experiences with technique of unilateral laminotomy for bilateral decompression. Methods - The unilateral laminotomy for bilateral decompression technique was performed at 60 levels in 51 patients to decompress the symptomatic degenerative stenosis of the thoracic and lumbar spinal canal. The inclusion criteria were used as follows: symptoms of neurogenic claudication and/or radiculopathy, myelopathy, neuroimaging evidence of degenerative stenosis and absence of instability. Symptoms were considered refractory to nonsurgical conservative management or myelopathy was detected. Results - The distribution of mostly affected segments were the L 4-5 (45%) and L3-4 (28.4%). Neurogenic claudication and walking distance improved during the follow up period in all patients. Seven patients (13.73%) reported excellent, 32 (62.74%) good, 12 (23.53%) fair outcome and no patient a poor overall outcome. The low back pain was the major residual postoperative complaint. 25 (49%) patients were very satisfied with their outcome, 23 (45.1%) were fairly satisfied, 2 (3.9%) were not very satisfied and 1 (2%) patients was dissatisfied. Conclusion - The unilateral laminotomy for bilateral microdecompression technique minimizes resection of and injury to tissues not directly involved in the pathologic process, while affording a safe and through decompression of neural structures located in a degeneratively stenotic spinal canal.]

Clinical Neuroscience


KAREN Eskesen, TAJTI János, HORTOBÁGYI Tibor, SZOK Délia, VÉCSEI László, LARS Edvinsson

[Calcitonin-like receptor (CL-R) is a functional CGRP1- receptor when complexed with RAMP1 or an adrenomedullin-receptor or when complexed with RAMP2 or RAMP3. This study was carried out 1. to set up a method to examine the relative quantity of mRNA of CL-R, RAMP1, RAMP2 and RAMP3 in human coronary (CA), pulmonary (PA) and middle cerebral arteries (MCA), and 2. to examine the level of mRNA expression in cerebro- and cardiovascular diseases. The method was validated with respect to the use of postmortem tissue and we compared β-actin and GAPDH as housekeeping genes. There was no time-dependent change in total RNA and level of mRNA for β-actin or GAPDH could be detected in vessels removed from 1 and 5 days post mortem. The expression of β-actin appears lower in coronary artery than in pulmonary artery and middle cerebral artery with no significant difference for GAPDH; both worked well. There were some differences in mRNA expression for CL-R (higher) and RAMP3 (lower) in middle cerebral artery compared to coronary artery and pulmonary artery. There was no significant difference in mRNA for RAMP1 and RAMP2 in the three types of arteries. We did not observe any difference in mRNA for CL-R and RAMPs in arteries from patients with hemorrhagic stroke, arteriosclerosis and acute myocardial infarction when compared to patients without these diagnoses. Thus the mRNA expression seems to be unaltered in these disorders.]

Clinical Neuroscience



[One-and-a-half syndrome is characterized by combination of the clinical features of unilateral horizontal gaze palsy and internuclear ophthalmoplegia. The common symptoms are double vision and oscillopsia. The lesion is located in the paramedian pontine reticular formation, involving the centre of horizontal gaze and medial longitudinal fasciculus. More extensive brainstem damage may result in additional neurological signs. The most frequent underlying diseases are vascular insults, multiple sclerosis, and brainstem tumor. We present two cases of one-and-a-half syndrome. Both patients had lacunar infarction in the paramedian pontine tegmentum, revealed by MRI. The first patient had isolated eye movement disorder, while the second had additional nuclear-type facial paresis. In the first case brainstem evoked potentials indicated brainstem damage, in the second patient it was normal. Ocular symptoms improved within some days in both patients.]

Clinical Neuroscience


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Lege Artis Medicinae

[The effects of angiotensin receptor blockers on the nervous system in hypertension and dementia]


[The renin-angiotensin system (RAS) is one of the most important mechanisms regarding the pathomechanism and treatment of hyprtension. The most of the elements of the RAS are found in the nervous system too. The effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ARBs) is based on the inhibition of the RAS. ARBs might have a special role in the central nervous system because they do not decrease the production of angiotensin but inhibit its harmful effects mediated through the AT1 receptor while allowing the stimulation of AT2 receptors with resulting pleiotrophic actions. Hypertension is the most important risk factor for stroke and has a negative effect on cognitive functions. Antihypertensive treatment has an effect on the nervous system; in addition to the consequences of the reduced blood pressure, ARBs might provide additional advantages in stroke and dementia prevention.]

Clinical Neuroscience

Pulmonary physiotherapy and aerobic exercise programs can improve cognitive functions and functional ability

TEKESIN Aysel, TUNC Abdulkadir, GÜNGEN Dogan Belma, AVCI Nalan, BAKIS Muhammed, PERK Seyma

Objective - The increasing prevalence of dementia over the previous decades has been accompanied by numerous social and economic problems. The importance of exercise in the prevention of dementia coupled with the impact of aspiration pneumonia on the mortality and morbidity of dementia patients cannot be overstated. This study investigates the effects of pulmonary rehabilitation combined with aerobic stretching exercises on the cognitive function, life quality, effort capacity, and level of depression in patients with mild cognitive impairment (MCI) in the early stages of dementia. Methods - Sixty-nine patients with MCI diagnosis were routinely monitored, and six were excluded because they did not attend the follow-up appointments. The remaining 63 patients undertook pulmonary physiotherapy (PPT) and extremity exercises for six months. The mini-mental state examination (MMSE), six-minute walk test (6MWT), Nottingham health profile (NHP), and Beck depression inventory (BDI) scores were evaluated before and after exercise. Results - PPT plus extremity exercises appeared to significantly improve the MMSE scores and increase the 6MWT (p < 0.001) by an average of 25 m. No significant improvement was observed in the BDI and NHP scores. Conclusion - PPT and aerobic exercise positively affected the cognitive ability of MCI patients and improved their walking distance. These results underscore the importance of combining medical treatment with physical rehabilitation at the onset of dementia, a disease which exerts a significantly negative impact on the economy.

Clinical Neuroscience

[The role of β-amyloid and mitochondrial dysfunction in the pathogenesis of Alzheimer’s disease]


[Alzheimer’s disease is the most common form of dementia in mid- and late life. The 7-10% of the population over 65 and the 50-60% of the population over 85 are affected by this disease. On the contrary of its prevalence the pathogenesis of the disease is not well defined and there is no effective neuroprotective therapeutic agent. Three predominant neuropathological features of the Alzheimer’s disease brain are intracellular neurofibrillary tangles consisting mainly of the hyperphosphorylated protein t; the extracellular amyloid deposits (neuritic plaques) consisting of amyloid b peptide; and the extensive neuronal cell loss in the hippocampus and in portions of the cerebral cortex. The possible reason of the extensive neuronal cell loss can be the mitochondrial dysfunction observed in Alzheimer’s disease. Beyond the unclarified pathogenesis the causality of these characteristic neuropathologic phenomena are still unknown. In this study we would like to deal with two actual hypotheses, with the amyloid cascade and with the mitochondrial cascade hypotheses. We try to give an overview of these two hypotheses and to depict their interrelationship.]

Clinical Neuroscience

[The effect of angiotensin receptor blockers in cerebrovascular disorders and dementia: Bonus in addition to the antihypertensive effect]


[Hypertension and dementia are frequent disorders or rather syndromes. Their incidence is growing with advancing age and hypertension is increasing the risk of cognitive impairment too, while treating hypertension (i.e. the use of antihypertensive medications) is decreasing it. In addition, hypertension is the most important risk factor for stroke. The renin-angiotensin system (RAS) has a special role in the development of hypertension and also involved in the pathogenesis of the most frequent dementia form, namely Alzheimer’s disease. The effect of angiotensin convertase inhibitors and angiotensin receptor blockers (ARB) is based on the inhibition of the RAS, but the ARBs do not inhibit angiotensin formation, just blocking its harmful effects on the AT1 receptor, while allowing the activation of AT2 receptors with pleiotropic effects. Preclinical, epidemiological and clinical therapeutic studies suggest this additional effect of ARBs and these are summarized in this review.]

Clinical Neuroscience

[The role of immobilization stress and sertindole on the expression of APP, MAPK-1 and β-actin genes in rat brain]

KÁLMÁN János, PÁKÁSKI Magdolna, SZŰCS Szabina, KÁLMÁN Sára, FAZEKAS Örsike, SÁNTHA Petra, SZABÓ Gyula, JANKA Zoltán

[Stress, depending on its level and quality, may cause adaptive and maladaptive alterations in brain functioning. As one of its multiple effects, elevated blood cortisol levels decrease the synthesis of the neuroprotective BDNF, thus leading to hippocampal atrophy and synapse loss, and rendering it a possible cause for the Alzheimer’s disease (AD) related neuropathological and cognitive changes. As a result of the stress response, intraneuronal alterations - also affecting the metabolism of β-actin - can develop. These have a role in the regulation of memory formation (LTP), but in pathological conditions (AD) they could lead to the accumulation of Hirano bodies (actin-cofilin rods). According to the dementia treatment guidelines, the behavioural and psychological symptoms of AD can be treated with certain antipsychotics. Therefore, the aim of our study was to examine the effects of sertindole (currently not used in the standard management of AD) on the transcription of some AD associated genes (amyloid precursor protein [APP], mitogen activated protein kinase-1 [MAPK-1], β-actin) in the brain of rats exposed to chronic immobilization stress (CIS). Male Wistar rats were exposed to CIS for three weeks. The four groups were: control (n=16), CIS (n=10), 10 mg/kg sertindole (n=5) and 10 mg/kg sertindole + CIS (n=4). Following transcardial perfusion, the relative levels of hippocampal and cortical mRNA of the previously mentioned genes were measured with real-time PCR. CIS induced hippocampal β-actin (p<0.01), MAPK-1 and APP (p<0.05) mRNA overexpression. The simultaneous administration of sertindole suppressed this increase in β-actin, MAPK-1 and APP expression (p<0.05). Ours is the first report about CIS induced β-actin gene overexpression. This finding, in accordance with the similar results in APP and MAPK-1 expression, underlines the significance of cytoskeletal alterations in AD pathogenesis. The gene expression reducing effect of sertindole suggests that antipsychotic drugs may have a neuroprotective effect.]